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Acute Continuous Renal

Replacement Therapy

DEVELOPMENTS IN NEPHROLOGY
Cheigh, J.S., Stenzel, K.H., Rubin, A.L., eds.: Manual of Clinical
Nephrology of the Rogosin Kidney Center. 1981. ISBN 90-247-2397-3.
Nolph, K.D., ed.: Peritoneal Dialysis. 1981. ISBN 90-247-2477-5.
Gruskin, A.B. and Norman, M.E., eds.: Pediatric Nephrology. 1981.
ISBN 90-247-2514-3.
Schlick, 0., ed.: Examination of the Kidney Function. 1981.
ISBN 0-89838-565-2.

Strauss, J., ed.: Hypertension, Fluid.,Electrolytes an9.Tubulopathies in


Pediatric Nephrology. 1981. ISBN,'90-247-263j-6.
Strauss, J., ed.: Neonatal Kidney and Fluid-Electrolytes. 1983.
ISBN 0-89838-575-X.
Strauss, J., ed.: Acute Renal Disorders and Renal Emergencies. 1984.
ISBN 0-89838-663-2.
Didio, L.J.A. and Motta, P.M., eds.: Basic, Clinical and Surgical
Nephrology. 1985. ISBN 0-89838-698-5.
Friedman, E.A. and Peterson, C.M., eds.: Diabetic Nephropathy:
Strategy for Therapy. 1985. ISBN 0-89838-735-3.
Dzurik, R., Lichardus, B. and Guder, W., eds.: Kidney Metabolism and
Function. 1985. ISBN 0-89838-749-3.
Strauss, J., ed.: Homeostasis, Nephrotoxicity, and Renal Anomalies in the
Newborn. 1986. ISBN 0-89838-766-3.
Oreopoulos, D.G., ed.: Geriatric Nephrology. 1986. ISBN 0-89838-781-7.
Paganini, E.P., ed.: Acute Continuous Renal Replacement Therapy. 1986.
ISBN 0-89838-793-0.
Cheigh, J.S., Stenzel, K.H. and Rubin, A.L., eds.: Hypertension in Kidney
Disease. 1986. ISBN 0-89838-797-3.

Acute
Continuous
Renal Replacement
Therapy
edited by
Emil P. Paganini, M.D., F.A.C.P.

Head, Section of Dialysis and Extracorporeal Therapy


Department of Hypertension and Nephrology
The Cleveland Clinic Foundation
Cleveland, Ohio, USA

.,
~

Martinus Nijhoff Publishing


a member of the Kluwer Academic Publishers Group
Boston I Dordrecht I Lancaster

Distributors for North America:


Kluwer Academic Publishers
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Library of Congress Cataloging-in-Publication Data


Main entry under title:
Acute continuous renal replacement therapy.
(Developments in nephrology)
I. Renal insufficiency-Treatment. 2. Continuous
arteriovenous hemofiltration. 3. Artificial kidney.
I. Paganini, Emil P. II. Series.
617'.461059
85-32037
RC918.R4A325 1986
ISBN-13: 978-0-89838-793-3
001: 10.1007/978-1-4613-2311-2

e-ISBN-13: 978-1-4613-2311-2

Copyright 1986 by Martinus Nijhoff Publishing, Boston


Reprint of the original edition 1986

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or
transmitted in any form or by any means, mechanical, photography, recording, or otherwise,
without written permission of the publisher, Martinus Nijhoff Publishing, 101 Philip Drive,
Assinippi Park, Norwell, MA 02061.

Second printing

This

book

is dedicated to the memory of

father who introduced me to medicine,


Kramer

whose

filtration,

efforts began continuous

my

physician

to the memory of Peter


arteriovenous

hemo-

and to the continued support of my wife, Loretta

and children, Elizabeth, Stefanie, and Julia.

CONTENTS
ix

LIST OF CONTRIBUTORS

xiii

PREFACE
1.

ULTRAFILTRATION/HEMOFILTRATION OVERVIEW:
CAVH FIT?
Lee W. Henderson, M.D.

2.

CONTINUOUS REPLACEMENT MODALITIES IN ACUTE RENAL DYSFUNCTION


Emil P. Paganini, M.D., F.A.C.P.

3.

TRANSPORT IN CONTINUOUS ARTERIOVENOUS HEMOFILTRATION AND


SLOW CONTINUOUS ULTRAFILTRATION
Michael J. Lysaght, Ph.D. and Daniel Boggs

4.

WHERE DOES

THE PRACTICAL TECHNICAL ASPECTS OF SLOW CONTINUOUS


ULTRAFILTRATION (SCUF) AND CONTINUOUS ARTERIOVENOUS
HEMOFILTRATION (CAVH)
Samuel Swann, C.D.T. and Emil P. Paganini, M.D., F.A.C.P.

43

51

5.

FLUID BALANCE IN CONTINUOUS ARTERIOVENOUS HEMOFILTRATION


H. J. Schurek, M.D.

79

6.

HEMOFILTRATION AND ULTRAFILTRATION: NURSING CONCERNS


Gayle R. Whitman, M.S.N., R.N., C.C.R.N.

91

7.

HYPERALIMENTATION IN ACUTE RENAL FAILURE


Eben I. Feinstein, M.D., F.A.C.P.

8.

CONTINUOUS ARTERIOVENOUS HEMOFILTRATION - THE CONTROL OF


AZOTEMIA IN ACUTE RENAL FAILURE
C. J. Olbricht, M.D.

123

9.

THE PREDILUTION MODE FOR CONTINUOUS ARTERIOVENOUS


HEMOFILTRATION
Andre A. Kaplan, M.D.

143

10.

NUTRITION IN ACUTE RENAL FAILURE: TREATMENT MADE


POSSIBLE BY CONTINUOUS ARTERIOVENOUS HEMOFILTRATION (CAVH)
Robert H. Bartlett, M.D.

173

11.

DRUG KINETICS AND CONTINUOUS ARTERIOVENOUS HEMOFILTRATION


Thomas A. Go1per, M.D., F.A.C.P.

vii

113

185

viii

Contents

12.

CONTINUOUS ARTERIOVENOUS HEMOFILTRATION IN INFANTS


Claudio Ronco, M.D.

201

13.

CONTINUOUS ARTERIOVENOUS HEMODIALYSIS - LABORATORY


EXPERIENCE AND THEORY
Harold Bregman, M.D. and Todd S. lng, M.D.

247

14.

CONTINUOUS ARTERIOVENOUS HEMODIALYSIS - CLINICAL


EXPERIENCE
Robert P. Geronemus, M.D. and Neil S. Schneider, M.D.

255

15.

CONTINUOUS AMBULATORY PERITONEAL DIALYSIS IN ACUTE

16.

RENAL FAILURE
Martin J. Schreiber, Jr., M.D.

CONTINUOUS ARTERIOVENOUS HEMOFILTRATION - APPLICATIONS


OTHER THAN FOR RENAL FAILURE
Ernest WoIner, M.D.

269

283

LIST OF CONTRIBUTORS
Robert H. Bartlett, M.D.
Department of Surgery
University of Michigan
Ann Arbor, Michigan

48109

Daniel Boggs, Engineer Specialist


Material and Membrane Technology Center (RLT-OZ)
Travenol Laboratories
Round Lake, Illinois

60073

Harold Bregman, M.D.


Director, Nephrology Department
Lutheran General Hospital
1775 Dempster Street
Park Ridge, Illinois

60068

Clinical Assistant Professor of Medicine


University of Illinois School of Medicine
18513 West Polk Avenue
Chicago, Illinois

60612

Eben I. Feinstein, M.D., F.A.C.P.


Associate Professor of Clinical Medicine
University of Southern California School of Medicine
Los Angeles, California

90033

Robert P. Geronemus, M.D. - P.A.


4900 West Oakland Park Boulevard, Suite 302
Lauderdale Lakes, Florida

33313

Thomas A. Golper, M.D., F.A.C.P.


Associate Professor of Medicine
Division of Nephrology and Hypertension
Director of Clinical Nephrology, Adult CAPO and Special
Extracorporeal Services
Oregon Health Sciences University
Portland, Oregon

97201

ix

Contributors

x
Lee W. Henderson, M.D.
Professor of Medicine
University of California at San Diego
Veterans Administration Medical Center
San Diego, California

94121

Todd S. lng, M.D.


Chief of Nephrology
Veterans Administration Hospital
Hines, Illinois

60141

Professor of Medicine
Loyola University Stritch School of Medicine
Maywood, Illinois

60153

Andre A. Kaplan, M.D.


Divisions of Nephrology
Departments of Medicine
University of Connecticut School of Medicine
Farmington, Connecticut

06032

Veterans Administration Medical Center


Newington, Connecticut

06111

Michael Lysaght, Ph.D.


Material and Membrane Technology Center (RLT-OZ)
Travenol Laboratories
Round Lake, Illinois

60073

C. J. Olbricht, M.D.
Assistant Professor of Medicine
Center of Internal Medicine
Department of Nephrology
Hannover Medical School
0-3000 Hannover 61, PO 180, FRG

Contributors

xi

Emil P. Paganini, M.D., F.A.C.P.


Head, section of Dialysis and Extracorporeal Therapy
Department of Hypertension and Nephrology
The Cleveland Clinic Foundation
9500 Euclid Avenue
Cleveland, Ohio

44106

Claudio Ronco, M.D.


Associate Professor
Department of Nephrology and Dialysis Unit
St. Bortolo Hospital
Vicenza, Italy
Neil S. Schneider, M.D. - P.A.
4900 West Oakland Park Boulevard, Suite 302
Lauderdale Lakes, Florida

33313

Martin J. Schreiber, Jr., M.D.


CO-Director, Continuous Ambulatory Peritoneal
Dialysis Program
Section of Dialysis and Extracorporeal Therapy
Department of Hypertension and Nephrology
The Cleveland Clinic Foundation
9500 Euclid Avenue
Cleveland, Ohio

44106

H. J. Schurek, M.D.

Center of Internal Medicine


Department of Nephrology
Hannover Medical School
0-3000 Hannover 61, PO 180, FRG

xii

Contributors

Samuel Swann, C.D.T.


Head Dialysis Technician
Hospital Acute Dialysis unit
The Cleveland Clinic Foundation
9500 Euclid Avenue
Cleveland, Ohio 44106

Gayle R. Whitman, M.S.N., R.N., C.C.R.N.


Department Chairman, Cardiac Nursing
Department of Hospital Nursing
The Cleveland Clinic Foundation
9500 Euclid Avenue
Cleveland, Ohio

44106

Professor Ernest Wolner, M.D.


Head, Department of Surgery
University of Vienna
Vienna, Austria

1090

PREFACE
The

initial

brought

from

observations

of

dialytic

the laboratory and confined to

support

were

patients

with

reversible acute renal failure.

The thought at that time was

one of short term maintenance.

It was theorized that removal

of

waste

products from the

inefficient,
damaged

might

tubules

blood,

albeit

incomplete

allow these patients time to

and regain renal function.

appointing earlier experience in survival,

and

regenerate

After

dis-

greater sophisti-

cation and broader practice refined the dialysis skills


reduced mortality.
It
were

also

possible

utilizing

and

this

failure.
who

became apparent that long periods


successful attempts were

technology

of

support

then

in patients with

and

made

chronic

in

renal

These early young patients were a very select group

possessed only renal dysfunction and no

involvement.
survival of
patients on

other

250,000

patients worldwide dependent on artificial

ment.

Mortality

systemic

systemic

Nonetheless, they demonstrated a one year


only 55-64%.
There are presently over 80,000
dialytic support in the United States and over
statistics

vary

but

despite

replacea

20-30%

disease involvement and a fifth decade average

in the North American experience,

the one year survival

age
has

risen to apparently 90%.


Acute
growth
more

failure

support has also

demonstrated

in both its cognitive and technological

aspects.

complete understanding of renal physiology has

prevention
tion

renal

of

of acute dysfunction in many areas,


hybrid intermittent technology has

majority of ARF patients.

led

a
A
to

and applica-

stabilized

the

There still remained, however, an

inability to allow these patients free access to fluid in the


form of hyperalimentation or medications. Further, many were
unable

to

tolerate

the rapid changes

necessary

with

the

intermittent approach.
Thus, the evolution of continuous
renal replacement has been applied to oliguric acute renal
failure.

xiii

xiv

Preface
This

acute

book

has drawn together the world authorities

continuous renal therapy and has asked the

on

questions:

who, what, when, where, and why. Designed for internists,


surgeons, intensivists, nephrologists, allied critical care
nursing,
the

and

technical professions,

the goal is to enhance

knowledge of those already using this

therapy,

and

to

inform and instruct those who are about to begin treatment.


This

text

is

"State

of

the

Art"

compendium

continuous therapies presently available or evolving.


an

of

After

overview of its role in renal replacement (Henderson) and

the

evolution

of continuous therapies over the

past

eight

years (paganini), an insight into the transport of physiology


of the membrane (Lysaght and Boggs) is given.
side

of

the

therapies

are

explained

by

The practical
addressing

the

technical aspects of the system (Swann and Paganini), control


of the fluid (Schurek), and nursing parameter (Whitman).
Theory

and practice is continued in the

evaluation

of

drug handling by CAVH (Golper), and the use of hyperalimentation

in

acute

patients

on

(Olbricht)
round

renal failure (Feinstein) as well


The control of
CAVH (Bartlett)
and variation such as predilution CAVH

out the experience.

hemodialysis
patients'

The introduction

of

as with
azotemia
(Kaplan)
continuous

both from the laboratory (Bregman and Ing)

bedside

(Geronemus),

as well as

application

and
of

access other than renal failure (Wolner) complete the discussion.


In

contrast

continuous
stability,
hospital

renal

to

and

complexity,

therapy

enhances
management,
and

patient

Its future is limited only by our

innova-

simplifies
costs.

rising medical costs

replacement
medical

reduces

tions.
I would like to sincerely thank the artistic and
graphic help of Ann Paladino,
editorial
Louise

assistance
Paskert,

and

photo-

Jim Reed, and Jeff Loerch, the


Henry, Helen Thams, and

of Shannon

especially

the

coordinating

and

secretarial arrangement of Cindy Owens and Jeannie Bongorno.

Acute Continuous Renal


Replacement Therapy

1
ULTRAFILTRATION/HEMOFILTRATION OVERVIEW:
FIT?

WHERE DOES CAVH

L. HENDERSON
University of California, San Diego, California

Hemofiltration
evaluate

the

was

initiated

pathophysiologic

as a

devised
a

stable

in the removal of low

350 daltons) when

"middle

of
end

stage

As originally applied it was recognized to be

disadvantage

solutes

to

As such, the system

for use in the patient with

renal failure.
at

strategy

significance

molecules" for the uremic patient (1,2).


was

test

compared

molecular
with

weight

hemodialysis.

Many changes in how convective mass transport is applied have


occurred since then.
Postdilution versus predilution (3),
hemodiafiltration

(4-6) combining the best of both diffusion

and convection, and continuous low efficiency hemofiltration


for the treatment of acute renal failure (7) are some of the
creative applications to which this ultrafiltration methodology

has

into
to

been put.

In placing this spectrum of

techniques

the perspective of "where does CAVH fit," I would


take

a brief backward look in order to

wish

extrapolate

the

clinical work of Kolff in applying

his

future.
The

pioneering

artificial kidney logically took him first to the application


of

this device in a young woman with chronic

(8)
acute

("malignant
renal

hypertension and

shrunken

failure as has been erroneously

renal

failure

kidneys"),

not

reported

(9).

Her survival of the artificial kidney treatment for more than


four weeks,
if not her uremia, was sufficiently encouraging
to warrant the treatment of 15 more patients suffering from
acute renal failure with but a single survivor (8).
In spite
of these dismal survival statistics, application of the technique continued.

Acute renal failure was the disease entity

UF/HF Overview

to which this new device was applied until the deliberate


application to patients with chronic renal failure by Belding
Scribner in the early 1960's plunged us into
maintenance dialysis (10).
In
first

the

era

like token both hemofiltration and CAVH were


in

the

patient with chronic renal

failure

tested
(11,12).

Peter Kramer must be given full recognition for both


fying

of

identi-

and popularizing CAVH for the treatment of acute renal

failure

in

Europe (7).

His clinical application

of

CAVH

initiated the exponential growth phase of this technique that


we are presently experiencing.
In the United States, attention was focused more on the fluid removal aspects of this
technique (12,13).
I

venture to say that there will be numerous

modifications
as

there

coupling
come

the

failure.

technical

and improvements in the hardware for CAVH just

has

been for hemodialysis.

believe

that

CAVH with parenteral nutrition it will swiftly


"gold

standard"

for

treatment

of

acute

by
be-

renal

A one out of 15 survival rate for the rotating drum

may be considered a success only in the context of a very low


baseline survival.

The monumental efforts of early clinical

investigators such as Bluemle and Teschan (14,15) showed that


hemodialysis,

and

in particular aggressive

application

of

hemodialysis ("prophylactic" rather than "crisis intervention" dialysis), offered an improved mortality in the patient
with acute renal failure.
The dire clinical status of this
population
renders
mortality an insensitive
parameter
requiring

an

exceedingly

large

study

statistically significant information.

number

to

achieve

The failure to report

improved survival statistics with acute renal failure treated


with

CAVH must not be taken than as a negative finding

(16-

19)
I am confident that with time,

CAVH in particular as it

is coupled with parenteral hyperalimentation,


better wound healing,

will result in

improved response to infection,

lower overall morbidity and mortality.

and a

L. Henderson

In the final extrapolation, I would suggest that just as


the

application

eventuated

in

of

hemodialysis

to

acute

renal

its widespread application to

failure

chronic

renal

failure so CAVH will be gradually translated into the chronically


Holy

applied wearable artificial kidney that has

been

Grail of artificial kidney investigators for low

the
these

many years.
It will be necessary to solve the chronic access problem
(deja

vu) and what to do about the large volumes of replace-

ment solution (1-20 L/day)

that will not only be required but

required in portable (potable?) form, as well as the problem


of chronic anticoagulation.
However, investigations are
already
the

ongoing in these areas and will be lent stimulus

very

confess
Figure

success of CAVH in acute renal


to

electrode
combust
gen,

favoring
in

which

compartment

failure.

a closed loop device


electro-oxidation

as

(20)

is

the size of a cigarette

dioxide,

and nitrogen with a small

must

depicted

in

used

(an

package)

to

all organics in the ultrafiltrate to oxygen,

carbon

by

hydro-

amount

of

GOAL
PUMP

~~ F~ILTER~
_____

1-2 LITERS
EXCESS FLU 10
TO DRAIN

VARIABLE
RESISTANCE

_____

DETOXIFICATION
- SORBENT
- LOOSE R.O.
- OTHER

(1)
Fig. 1.
This goal for artificial kidney development
depicts a closed loop for the ultrafiltrate that would inProper filter
clude some means of dialysate reprocessing.
design might obviate the need for a pump on the blood inflow
side.

UF/HF Overview

nonvolatile sulfate and phosphate that could be handled both


by dietary protein and lipid selection and orally administered sorbents. Glucose and bicarbonate would of course have
to

be

replaced,

but

a suitably structured diet

with

periodic ingestion of alkali would not be an onerous


at all.
Lastly,

the loop might be further closed,

the

regimen

so to speak,

by metering out the required amount of "urine" and channeling


it percutaneously to the bladder for storage and its periodic
convective
This

latter

transfer to an appropriate porcelain

receptacle.

event would serve both physiologic and

psycho-

social ends.
May the flux be with you (21).
REFERENCES
1. Henderson LW:
Development of a convective
blood
cleansing technique.
Proc lOth Ann Contractors Conf,
Bethesda, Maryland, 130, 1977.
2. Henderson LW:
The beginning of hemofiltration.
In:
Contributions to nephrology series.
Eds:
Beryne GM,
Giovannetti S, Thomas S, Vol 32, Symposium on Hemofi1tration Volume, Eds: Shaefer K, Koch KM, Quellhorst E,
von Herrath, Publisher, Karger, 1, 1982.
3. Henderson LW:
Pre vs. post dilution hemofiltration.
Clin Nephro1 11:120, 1979.
4. Leber HW, Wizemann V, Goubeaud G, Rawer P, Schutter Ie G:
Simultaneous hemofiltration/hemodialysis:
An effective
alternative to hemofiltration and conventional hemodialysis in the treatment of uremic patients.
Clin
Nephrol 9:115, 1978.
5. Cheung AK, Kato Y, Leypoldt JK, Henderson LW: Hemodiafiltration using a hybrid membrane system for self
generation of diluting fluid. Trans Am Soc Artif Intern
Organs 28:61, 1982.
6. von Albertini B, Miller JH, Gardner PW, Norris KC,
Roberts CE, Shinaberger JH:
High flux hemodiafiltration. Abstract, Am Soc Nephrol 17 Ann Meeting 76, 1984.
7. Kramer P (editor):
Arterio-venous
hemofiltration,
Vandenhoeck & Ruprecht Gottingen, 1982.
8. Kolff WJ: First clinical experience with the artificial
kidney. Ann Intern Med 62:608, 1965.
9. McBride PT:
Genesis of the artificial kidney.
Chpt
3:9, 1979.
10. Quinton WE, Dillard DH, Cole JJ, Scribner BH:
Eight
months experience with cilastic-teflon bypass cannulas.
Trans Am Soc Artif Intern Organs 8:236, 1962.

L. Henderson
11.

12.
13.
14.

15.
16.
17.
18.

19.
20.

21.

Henderson LW, Besarab A, Michaels A, Bluemle LW Jr:


Blood purification by ultrafiltration and fluid replacement (diafiltration).
Trans Am Soc Artif Intern Organs
12:216, 1967.
Silverstein ME, Ford CA, Lysaght MJ, Henderson LW:
Treatment of severe fluid overload by ultrafiltration.
N Engl J Med 291:747, 1974.
paganini EP, Nakamoto S: Continuous slow flow ultrafiltration in oliguric acute renal failure.
Trans Am Soc
Artif Intern Organs 26:203, 1980.
Bluemle LW Jr, Webster GD Jr, Elkinton JR:
Acute
tubular necrosis: Analysis of 100 cases with respect to
mortality complications and treatment with and without
dialysis. Arch Intern Med 104:180, 1959.
Teschan PE, Baxter CR, O'Brien TF, et al: Prophylactic
hemodialysis in the treatment of acute renal failure.
Ann Intern Med 53:922, 1960.
Lauer A, Saccaggi A, Ronco C, Belledonne M, Glabman S,
Bosch J: Continuous arteriovenous hernofiltration in the
critically ill patient. Ann Intern Med 99:455, 1983.
Kramer P, Bohler J, Kehr A, et al:
Intensive care
potential of continuous arteriovenous hemofiltration.
Trans Am Soc Artif Organs 28:28, 1982.
Olbricht C, Mueller C, Schurek HJ, Stolte H: Treatment
of acute renal failure in patients with multiple organ
failure by continuous spontaneous hemofiltration. Trans
Am Soc Artif Intern Organs 28:33, 1982.
Kaplan AA,
Longnecker RE, Folkert VW:
Continuous
arteriovenous hemofiltration.
Ann Intern Med 100:358,
1984.
Wright JC: Electrochemical dialysate regeneration: The
electro-oxidation of urea at the ruthenium titanium
oxide electrode.
Ph.D. Dissertation, Dept of Chern
Engineering, Stanford Univ, 1982.
Kenobi 0: Personal Communication.

2
CONTINUOUS REPLACEMENT MODALITIES IN ACUTE RENAL DYSFUNCTION
E. PAGANINI
The Cleveland Clinic Foundation, Cleveland, Ohio

INTRODUCTION
The

occurrence

hospital

settings,

of

acute renal

generally

failure

being

varies

more

surgical/trauma units than medical areas.

among

frequent

National

in

figures

are lacking and variable incidences can be obtained by merely


changing the definition of acute renal failure.
defining

acute

For example,

renal failure as an acute rise in the

serum

creatinine level to < 3 mg/dL, a 5 to 20% incidence can be


found in all open heart surgical procedures (1).
However,
defining the cutoff serum creatinine level > 5 mg/dL, a 2 to
5% incidence can be seen (2).
If one considers only those
patients who need artificial support then 1.2% incidence has
been reported (3) following open heart surgery.
The

etiology of acute renal failure encountered in

our

intensive care areas occurred in predominantly surgical (70%)


settings,

and

Ischemia

(74%)

the remainder occurred in medical situations.


was by far the

most

frequently

identified

cause; toxic (13%) and other causes (8%) were less prominent.
Patients
multiorgan

needing

support

compromise

of renal failure

frequently

(60%) and thus represented

had

thera-

peutic challenge of major proportions.


Until

recently intermittent forms of therapy

had

been

used for support in renal failure, with isolated ultrafiltration (4,5) being used for fluid management and intermittent
hemodialysis for electrolyte, acid/base, and azotemic control
(6)

Variants

of those basic procedures have brought about

combinations of therapy that enhance patient stability and


allow for greater control of the end product.
Table 1

Continuous Replacement Modalities

Table 1.
therapies.

Working definitions of

Term

available

extracorporeal

Definition

Ultrafiltration (UF)

The removal of plasma water and its


solutes from blood by convective
transport through a semipermeable

membrane.

May be done

alone

or

before, during, or after hemodialysis.


The sole purpose is fluid
removal.

Hemodialysis (HD)

A diffusion-based form of
blood
cleaning using dialysate interfacing
with blood via a semipermeable membrane.
Allows for fluid, electrolyte, and acid-base balance as well
as azotemic control.

Hemofiltration (HF)

A convective mode of blood cleaning


where ultrafiltration accounts for
all solute removal.
Can be viewed
as a plasma water exchange with
sterile fluid replacement.

Hemodiafiltration (HDF)

A hybrid form of therapy combining


both diffusive and convective modalities.

reflects

definitions

the

working

of

these

therapeutic

variations.
Recently,
continuous
extracorporeal
therapeutic
modalities have been applied to these patients (7,8).
These
methods bring a high level of hemodynamic stability, and have
been predominantly applied to the sicker, unstable patient
with multiorgan failure (9).
The systems have also allowed
improved fluid balance, permitting a higher intake to be
achieved
therapies

without

the worry of

become more popular,

fluid

overload.

As

these

greater understanding of the

physiological responses and of indications for such therapy


should occur.
This chapter deals with the experience
obtained

in

continuous

therapies

from

1977

through

the

E. Paganini

present

and

will

give insight into

the

evolution

of

an

integrated system.
ISOLATED ULTRAFILTRATION
Intermittent ultrafiltration.
Fluid

removal

has

always

been a goal

of

all

renal

replacement therapy, however, symptomatic hypotension because


of

fluid

removal during hemodialysis is a

problem.

Although

several

studies

of

common
the

clinical

hemodynamic

instability of uremia have been done (10,11), there still


remains a discordance as to the actual underlying cause.
Kersh et al (12) have implicated autonomic insufficiency;
Zucchelli et al (13) postulated a rapid removal of catecholamine; and Kim et al (14) investigated body fluid volume
changes.
Separating the process of hydrostatic ultrafiltration for fluid removal, i.e., isolated ultrafiltration (UF),
from diffusion dialysis, Bergstrom et al (5) demonstrated a
great de~ree of blood pressure stability.
They attributed
the stability to the lack of osmolar changes. Silverstein et
al (15) noted stable blood pressure in patients with chronic
heart failure while evaluating the stability of isolated
ultrafiltration
noticed

the

in

active participation of the

maintaining blood
central volume.
MacIntyre
nique

of

labelled

chronic hemodialysis patients.


pressure (16,17),

output

(CO)

determination

human serum albumin in animals.

confirmed

the

represented

of

et al (18) first reported in 1951

cardiac

determination

venous

by way

accuracy of radioisotope
in

humans.

To

our

We

had

system

in

maintained
the

tech-

using

131I_

Razzak et al (19)
techniques

knowledge

the first direct measurement of CO

for

our
and

CO

study
cardio-

pulmonary volume (CPV) using radioisotope dilution techniques


in patients subjected to UF (Fig. 1).
co and CPV were
determined from radionuclide dilution curves using an Ohio
Nuclear scintillation camera. Following a bolus injection of
99mTC-labelled
UF,

human serum albumin (99m Tc-HSA)

(4 mCi

pre-

8 mCI post-UF), the bolus passages through the right and

Continuous Replacement Modalities

10

CARDIAC OUTPUT
7.0

RV

LV

6.5

lIJ

:i!

6.0

II::
"-

II::
lIJ

5.5

a..

Ul
I-

0
0

5.0

C)

0
..J

4.5
4.0

3.5

10

20
30
FRAME NO.

40

50

Fig. 1.
Radioisotope technique for the determination of
cardiac output. Actual scan (top). Right and left ventricular time-activity curves (bottom).
left ventricles were defined on the original computer printout and displayed diagrammatically as time-activity curves.
Cardiac output was determined from the formula: F = If C t:" T
where I equals the product of blood volume and blood counts
at the final dilution phase. C~T equals the counts per unit
change of time.
CPV is derived from the formula:
MTT x
CO/60 where MTT equals mean transit time, defined as the time
elapsed between the right and left ventricular output curves.
We had also investigated the changes in body fluid volumes
and compartmental shifts as well as cardiac performance.
As

11

E. paganini

in previous reports (5,15) the mean arterial pressure (MAP)


remained quite stable despite the average removal of 1.6 L of
fluid.
Although extracellular fluid (ECF) and plasma volume
(PV) dropped significantly, the PV/interstitial fluid volume
(IF) ratio remained constant, denoting no disturbance in ECF
partition.

This is in sharp contrast to classic studies

Guyton

al

et

(20)

on

hemorrhage

where

venous

by

return

decreased, resulting in a reduction of CO and MAP.


Stroke volume and the CO/CPV ratio remained unchanged.
This implies no significant alteration in cardiac performance
or function (21) and negates a major role in afterload reduction in maintenance of stable co.
Although no absolute
change was noted in CPV, all but one of our patients showed a
rise in the CPV, CO, and MAP.
Brod (22) has noted that
angiotensin infusion leads to constriction of peripheral
veins

and central redistribution of blood,

rise of central venous pressure.

resulting

in

However, the role of angio-

tensin was not evaluated in our studies.


We

then began looking at the effectiveness of continual

fluid removal with ultrafiltration in an effort to


the

possible

establish

selected use of ultrafiltration in

heart failure.
measurements in

congestive

Magnusson et al (23), using lung water


dogs given oleic acid to induce pulmonary

capillary dysfunction, noted that ultrafiltration was capable


of inducing a marked decrease in lung water.
In fact the
dogs
the

in the ultrafiltration group had a significant drop


lung water content compared with both control

dogs

in
and

dogs

with a diuretic-induced negative fluid balance

greater

than

that achieved via ultrafiltration.

oncotic

pressures
similar,

in
so

Colloidal

the' diuretic and ultrafiltration


greater

group

sodium losses or the removal

of

were
some

"pulmonary factor" with ultrafiltration were postulated.


Magilligan and Oyama (24) reported their use of intermittent ultrafiltration (IUF) during cardiopulmonary bypass
in both mongrel dogs and ten patients. In both groups ultrafiltration was found to be both safe and effective in removal
of excess fluid.
Further, they demonstrated the effective-

continuous Replacement Modalities

12

Fig. 2.
Slow
1500 dialyzer.
ness

of

continuous ultrafiltration using a

ultrafiltration

in removing lung

water

Travenol

in

their

overhydrated patients.
Hemodynamic

stability

was

enhanced

by

efficiency of ultrafiltration during therapy.


required

lowering

longer course of therapy to compensate

lower removal rate.

for

CF

1500

Michigan)
2).

the

Avoiding the "peak and valley" effect of

rapid intermittent removal was originally accomplished


a

the

However, this

Capillary Dialyzer

(Travenol

Labs,

attached in series to a Scribner shunt

This arrangement,

using

Deerfield,
(see

Fig.

however, does not lend itself easily

to continuous ultrafiltration.

Table 2 lists the encountered

difficulties and solutions.


Greater

fluid removal was obtained with the use of

the

high-flux polysulfone membrane (Amicon Diafilter 20, Amicon


Corp., Danvers, Mass.); earlier success with chronic renal
failure
(25-27)
led to its use in unstable patients with
acute renal failure.
The early attempts at use were

E. paganini

13

Table 2.
Difficulties encountered in slow continuous ultrafiltration.
Problem

Clinical Need

Large pressure drop


across dialyzer

Minimal
M.A.P.

Low ultrafiltration
coefficient of membrane:
70 mL/hr without suction
150 mL/hr with suction

Suction-assisted ultrafiltration

Large surface area and


fiber length

High heparin requirement


to avoid clotting

Complicated procedure if
suction assistance is used,
poor nursing acceptance

Nursing training with


equipment not usually
handled

intermittent;
therapy (8).

later

longer sessions

85 mmHg

approached

continuous

Slow continuous ultrafiltration.


Slow continuous ultrafiltration (SCUF) is defined as

continuous method of fluid removal at a rate not exceeding 5


mL/min, with or without peripheral fluid replacement; SCUF
has fluid balance as its sole objective.
Often used as an
adjunct therapy to hemodialysis, it affords a high degree of
stability during fluid removal in patients with acute renal
failure.
The most important consideration in any form of continuous therapy is the selection of an appropriate access, since
this

is the only driving force used in the pumpless

system.

If blood flow is poor because of arterial inadequacy or


venous occlusion, the flow characteristics will be greatly
changed, which might dampen or limit the ultrafiltration
potential.

This

is

of greater importance

when

employing

continuous arteriovenous hemofiltration (CAVH) , where the


emphasis is on high ultrafiltration flows (QF) , but will also
have an impact on SCUF even though the QF is usually less.

continuous Replacement Modalities

14

SCUF/CAUH THERAPY
ACCESS TYPE

.lI.20

90-'

60 J

3 0

J_~ttt--
I

OJ~~~~~~~~--~~~~~
7
9

.PERCUTAH

8
.i.

8
3

8
4

YEAR

~SHUHTS

Fig. 3.
Types of access used for slow continuous ultrafiltration (SCUF) and continuous arteriovenous hemofiltration
(CAVH) therapy.
In general vascular access is obtained either through
surgically created arteriovenous connections (fistula, AV
shunts)
or by percutaneous cannulation of the arterial and
venous systems.
The technical aspects of creating these
accesses are discussed elsewhere.
that

both

percutaneous

and

However it should be noted

surgical

individual advantages and disadvantages.


AV shunts
associated

methods

have

their

For example, while

are certainly easy to use, they are usually


with minimal or no bleeding because of the open
,WII:!
JL60

SCUF/CAVH THERAPY
THERAPY TYPE

"II~~(JI~
Fig. 4.
Use of slow continuous ultrafiltration (SCUF)
continuous arteriovenous hemofiltration (CAVH).

and

15

E. Paganini

They are easily checked for


procedure in their creation.
patency, and are rarely implicated in systemic complications.
They are also the source of local infection, frequently clot,
generally carry lower vessel pressures and flow,
a

future

and destroy

access site for a fistula if the patient

need chronic support.

were

to

Also, the clinical situation may have

resulted in multiple venipunctures with resultant venous flow


compromise, thus having a negative impact on shunt function.
The AV shunt can offer a powerful and useful access site
for

continuous as well as intermittent replacement

Surgical expertise is necessary,

however.

therapy.

Time is needed to

choose appropriate vessels, dilate them when necessary, avoid


vessel damage or tension,
is

nothing

and stabilize the implants.

more than merely following established

This

surgical

procedures and giving appropriate attention to small details.


The

delay

in awaiting the surgeon or

in

establishing

the

access may, at times, be considered a drawback to this method


of entry.
Arteriovenous

cannulation

has

become

increasingly

popular and over the past few years its use has increased in
frequency in our institution as well (Fig. 3).
The details
of

percutaneous technique are outlined elsewhere.

However,

it is of interest that the increased popularity of percutaneous access is accompanied by an increase in the use of CAVH
(Fig. 4).
This is not totally by chance.
The higher circuitry pressures and blood flows achieved with the percutaneous

access

exchanges
improved

allow

higher

more appropriate.
QF

when

QF

and

therefore

Olbricht et al (28)

using femoral

arteriovenous

make

CAVH

noted

an

cannulation

rather than brachial AV shunts as access in performing

CAVH.

However if SCUF is employed, then modest filtration flows are


generally more than adequate.
Table 3 compares AV cannulation of the femoral artery
and vein with brachial AV shunts.
We have been carrying out
a prospective analysis of access complications and have found
an

equal incidence of possible access-related septic

to

either method.

While AV shunts have an increased

events
inci-

Continuous Replacement Modalities

16

Comparison of AV shunt to percutaneous AV cannula-

Table 3.
tion.
Procedure
Blood flow
Hydrostatic
pressure
Rapidity of
access
Bleed ing

Ambulation
Systemic
completion
Clotting of
circuit
Infection
Local
Systemic
Complication
on removal

AV shunt open
Low
Low

AV cannulation closed
High
High

Delay

Immediate

Minimal local

Minimal (potential retroperitoneal hematoma on


removal)
No (strict bed rest)
Infrequent (emboli,
thrombosis)
Infrequent

Yes
Rare
Frequent
Frequent
Rare
Rare

Infrequent
Rare
Infrequent (arterial
cutaneous fistula
hematoma)

dence

of local infections,

and a higher frequency of

clot-

ting,

the femoral cannulation carries a much higher risk

of

bleeding and arteriocutaneous fistula formation.


The

usual

circuitry for SCUF is depicted in Figure

5.

As with all continuous methods, there is no blood pump in the


circuit
tained

and the system's blood flow and pressures are


by the presSure difference between the

main-

arterial

and

venous systems.
If

heparin

apparatus

is

to

be used,

then

delivered by way of an IV infusion pump.


flow is also controlled.
on

second

collection
staff.
fore

continuous

is attached to the arterial line and

drip

heparin

The ultrafiltration

The filtration rate is "dialed in"

IV infusion pump,

without

the

which allows

undue time commitment from

for

accurate

the

nursing

The rate of ultrafiltration during SCUF will


depend upon the rate of intake,

rather than

there-

dictating

the intake rate as in CAVH.


Short

arterial

and venous lines are employed

SCUF and CAVH at The Cleveland Clinic (Fig.

6)

(29).

in

both
These

E. Paganini

17

Fig. 5.
Slow continuous ultrafiltration (SCUF)
with IV infusion pump control.

circuitry

lines were designed to allow for blood sampling, but are of


such a length as to dissipate the systemic pressures only
minimally, delivering the bulk of this pressure to the
filter.
A
full technical description of this circuitry is
found in later chapters (Swann, Whitman).
These lines have
made continuous therapy without heparin possible
(30)
Figure 7 graphically demonstrates differences in reasons for
interruptions of SCUF therapy (when heparin is used or not
While there was a higher incidence of clotting with
used)
heparin than without, this difference was not statistically
significant.

HEMODYNAMICS AND FILTRATION


The

laboratory

work on ultrafiltration efficiency

and

selectivity plus the enhanced hemodynamic stability obtained


with isolated ultrafiltration in our patients undergoing

18

Continuous Replacement Modalities

Fig. 6.
Arterial and venous lines used in SCUF/CAVH at The
Cleveland Clinic Foundation.
chronic dialysis seemed to indicate that continuous ultrafiltration

would be ideal for the oliguric patient

overload.

Many

times

with

these patients are so unstable

they are unable to tolerate standard hemodialysis:

fluid
that

they have

multiple hypotensive episodes during the run and may actually


gain weight.

Early attempts at using a cuprophane

membrane

proved to be unsatisfactory; using a synthetic plastic (po1ysulfone)

would perhaps allow delivery of the required ultra-

filtration at the pressures present within the system without


having to add complicated suction devices to enhance removal.
Early
therapy
stability

hemodynamic

are

data

on

listed in Table 4.

encountered

during

patients

undergoing

Of note was
continuous

the

SCUF

absolute

ultrafiltration.

Twenty-three hemodialysis-resistant patients with acute renal


failure

were placed on SCUF (9).

Hemodynamic stability was

again noted, thus allowing patients to receive needed medication and eventually to stabilize.
Perhaps

the most significant addition to the

treatment

of

acute renal failure has been the ability to remove

in

these highly unstable patients.

We have

reported

fluid
that

E. Paganini
Table 4.

19

Hemodynamic data.
Mean arterial pressure
(mmHg)

No.
Pre-therapy
12 hr
24 hr
36 hr

significant

Cardiac output
(L/min)

24
74.96 + 9.38
76.79 -+ 8.45
74.57 + 8.88
72 .43 +" 11.12

removal

of

6
6.45 + 1.59
6.03 + 0.99
6.13 +" 0.70
6.48 +" 1. 74

fluid with SCUF is

accompanied

by

stable
hemodynamic parameters (8,31) but we are
also
intrigued by the seeming improvement in cardiac function with
this form of fluid mobilization therapy.
Although not significant,
and
5).

definite trend toward increased cardiac

output

diminished systemic vascular resistance was noted (Table


Whether

removal,

or

this
the

is due to

afterload

elimination of

reduction,

"myocardial

volume

depressant

factor" is currently under investigation.


Evaluating oliguric patients with intraaortic balloon
pumping and undergoing SCUF, we found continued hemodynamic
stability, as shown graphically in Figure 8. Direct measurement of left arterial pressure as well as pulmonary artery

i..l.1!lJ:O
60-

SCUF THERAPY
INTERRUPTIONS

45-'

Fig. 7. Interruptions during slow continuous ultrafiltration


(SCUF)
therapy with and without heparin.
(0)
None,
(l)
Clotting, (2) Mechanical, (3) Hemodialysis.

20

Continuous Replacement Modalities

Table 5.

Patient hemodynamic data.


During
SCUF

Pretreatment
Mean arterial
pressure (mmHg)

76.04 + 19.6
-

Cardiac output
Systemic
vascular
resistance
(mL/min)

71.96 -+ 13.9

5.64 + 1.5

5.28 + 1.43

984.5 + 524.3

Cardiac index
SCUF

76.70 -+ 18.3

5.22 + 1.31

(L/min)

2.94

-+

Posttreatment

887 + 310.4

869 + 255.9
-

3.12 + .78

.81

2.87 + .78
-

slow continuous ul trafil tration

pressure,

mean arterial pressure,

insignificant

absolute

changes

and cardiac index


during

fluid

showed

removal

via

continuous ultrafiltration (Table 6).


The
with

ability to remove fluid is important in the patient

excess fluid,

answer

this

membrane

but exactly what are

question

and measured

we continued to use
simultaneous

other

elements.

removing?
the

arterial,

ultrafiltrate samples of electrolytes,


and

we

To

polysulfone
venous,

and

selected amino acids,

As listed in Table 7,

we found

that

measured sieving coefficients for negatively charged elements


were

actually

higher than unity,

Donnan-like effect.
and

Gibbs-

Removal of amino acids such as histidine

and threonine was also enhanced.


coefficient

perhaps due to

the known QF,

Using the measured sieving


one

can

predict

clearance

values and ultimately mass transfer or removal of substances.


This

is helpful when dealing with drug removal or looking at

amino acid balance or urea kinetics.


Figure 9 for
shows the balance of essential amino acids in
receiving hyperalimentation while undergoing SCUF.

example,
patients
There was

E. Paganini

21

1300f
1050

dynes/em 800

----..cz

550
300L-~~~--~~~~

__

~~~~

__

~-L-L

__

LAP

mmHg

c
MAP

mmHg

TIME Hrs.

Fig. 8.
Hemodynamic measurements in patients undergoing
intraaortic balloon pumping while undergoing slow continuous
ultrafiltration (SCUF).
SVR = systemic vascular resistance;
LAP = left arterial pressure; MAP = mean arterial pressure.
a marked positive balance,

ranging from 82.8% for phenylala-

nine to 97.5% for isoleucine.


There is,

however, a time decay in performance for most

hemofilters tested in vitro,


as

well

as

the

Mineshima

et

al (32)

polarization
significantly
when

so that the sieving coefficient

hydraulic

permeability

during therapy.

Leypoldt et al (33)

molecular

for

protein
found

greater sieving of polydisperse neutrodextrans

comparing the effects of various surface

adjusted

decrease.

thought this was secondary to

constant ultrafiltration rates.

that

may

surface

area,

However,
the sieving

sizes were comparable,

areas

during

when the data was


for

all

leading to the

dextran

conclusion

the ratio of filtration rate to surface area is helpful

in evaluating filter performance.

Trudell et al (34)

studied

a nonheparinized system of continuous ultrafiltration with an


AV

shunt

as an access in dogs.

Varying

capillary

configurations seemed to playa major role in the time

of ultrafiltration rates in these pulsatile models.

tubing
decay

22

Continuous Replacement Modalities

Table 6.

Hemodynamic changes induced by SCUF.

Parameter

Change while on SCUF

Cardiac index

.28 + .35 L/min/m2


-

4.0 + 2.6 mmHg


4.6 + 6.0 mmHg

Mean arterial pressure

pulmonary artery pressure

2.4 + 3.0 mmHg


2.4 + 1.5 mmHg
1.5 -+ 1.2 rnrnHg
dynes/ern
107 + 121
sec 2

Central venous pressure


Left arterial pressure
systemic vascular resistance

slow continuous ultrafiltration

SCUF

Although
continuous

therapy

remembered.
for

the

higher

these
The

data

will

help in

hardware,

the

several

evolution

facts

pulsatile nature of

flow

during

be

account

SCUF/CAVH,

blood flows during the investigations then

encountered

must

above approaches either failed to

of

used

generally

in clinical use of continuous therapy (QB 60-100

mL/min versus QB 100-700 mL/min), or used tubing design not


yet available for clinical trials.
Despite these drawbacks,
Table 7.
Measured siev ing coefficients for various elements
and selected amino ac ids. *
Sodium

0.993

Potassium
Chloride
Bicarbonate
Calcium
Albumin

1.019

Leucine

1.014

0.975
1.088

Blood urea
ni trogen
Creatinine
Valine

1.037
1.069

1.089
1.078

1.137
0.677
0.002

Cystine
Methionine
Iso-leucine

1.047
1.000
1.010

Tyrosine
Phenylalanine
Lysine
Histidine
Threonine
UF

Sieving coefficient (SC) =


Art. +
2

] Ven.

1.080
1.109
1.256

E. Paganini

23

13
12
II
10

9
8

(!)

7
6

ILl

U)

::::>

u..

5
4
3
2
1

-2
BALANCE +9'll +85.8 +96.4 +97.5 +89.3 +89.1 +84.5 +82.8 +89.6
(%)

Fig. 9.
Essential amino acid (AA)
balance during slow
continuous ultrafiltration (SCUF).
From Paganini E, et al
Trans ASAIO, 1982.
however,

the

development

of higher solute

efficiency

and

stable membrane hydraulic characteristics are important steps


toward improving clinical performance.
SCUF

can,

adjunctive
for

at

present,

form of therapy.

fluid removal during

be

considered

an

important

It totally eliminates any need

standard

hemodialysis.

Patients

have been able to tolerate the diffusive procedure and uremic


control

has been accomplished.

For those patients who

are

still unable to be supported with standard hemodialysis, CAVH


can be instituted so that both fluid and azotemic control are
achieved.
CONTINUOUS ARTERIOVENOUS HEMOFILTRATION
Since the control of azotemia (Olbricht), drug kinetics
(Golper) ,
and
predilution variants (Kaplan)
are
well
described

in

later chapters of this book,

as well

as

the

24

Continuous Replacement Modalities

technical (Swann), nursing (Whitman), and transport (Lysaght)


characteristics of CAVH,

I will limit this section to intro-

ductory and general remarks.

The original report of arterio-

venous hemofiltration by Kramer et al was in 1977


(7).
Largely due to their continued use of this form of therapy,
and enlightened writing on the subject (35,36), it grew in
popularity in Europe.
Introduced in a variant form in the united States by our
group in 1980 (8),
(37)

later published experience by Lauer et al

and Kaplan (38) made CAVH an important addition to

treatment
renal

of

hemodynamically unstable patients

failure.

reports,

with

the
acute

The hemodynamic stability noted in all

the

as well as the reduction (39) or elimination of the

need for hemodialytic support to control azotemia,

made this

treatment modality ideal for the intensive-care patient.


simplicity

in

design

allowed

staff

not

Its

experienced

in

dialysis

to feel comfortable with its mechanics.

The

only

drawback
both in

initially identified was with replacement fluid,


fluid balance and fluid composition.
Although

convective and conductive forces playa role in standard


hemodialysis techniques, Henderson et al published their work

in

1967 on the use of convective forces alone as a

therapy

for

end-stage

renal

disease

impressed by the large amounts


relatively asymptomatic results.

(40)

mode
They

of
were

of fluid removed
with
To accomplish this, a

special membrane with a high sieving coefficient and ultrafiltration coefficient similar to the glomerular basement
membrane was developed (XM-50).
In

Europe,

(polyacrylonitrile)

membrane
was

with

similar

characteristics

already in use as a

dialysis

mem-

brane.

Quellhorst et al (41), Kramer et al (42), and others

(43-45)

began

using this membrane as

an

ultrafilter,

and

because of its commercial availability, were able to treat a


greater number of patients who were suitable subjects for
hemofil tration.
Intermittent hemofiltration simply employs the application of a high transmembrane pressure to a membrane with a

E. Paganini

25

high ultrafiltration coefficient.


of

In this way, large amounts

fluid are removed as the ultrafiltrate;

of fluid can then be replaced.

a similar amount

This replacement fluid can be

given either predilution or postdilution (before or after the


ultrafiltration).
plasma

water

weight.
amount

The amount of fluid exchanged (acting as a

exchange)

This

is usually based

on

the

patient's

is translated to total body water,

and

that

is exchanged over three separate therapy sessions per

week.
The application of this form of therapy in a
manner

(CAVH)

circuitry
rate

and in a pumpless system requires access

designed

drives.

continuous

to use the

patient's

natural

and

pressure

The fluid exchange still takes place but at a lower

over an indefinite time.

The unrestrained

filtration

rate becomes the guide to therapeutic effectiveness,

with an

of 8 mL/min regarded as minimally effective and

exchange

10

mL/min as the standard.


Postdilution fluid replacement, found to be the simplest
method

of exchange during intermittent

hemofiltration,

perpetuated in continuous hemofiltration.


assistance

was

The use of suction

to enhance the filtration rate led Kaplan to

use

predilution replacement, which resulted in increased urea and


creatinine
efficient

clearances (46).
system,

Since this is a relatively in-

any improvement in urea

clearance

might

reflect a large percentile change but actually represent only


a minor increase in mass transfer.
low

urea clearance,

combined

then continuous hemodialysis (47,48) or

hemodialysis

(continuous

If one is concerned with

and

hemodiafiltration)

postdilution

hemofiltration

(49) might be

better

suited

and less labor-intensive than predilution hemofiltration.


Fluid balance and SCUF/CAVH.
As

pointed out earlier, the two major continuous thera-

pies differ in their goals of treatment.


SCUF is generally
employed for fluid removal, while CAVH promotes an exchange
and

therefore mandates that a fluid infusion

The

types of systems used for these methods are detailed

be

initiated.
in

Continuous Replacement Modalities

26

other areas and include gravity scales, IV infusion pumps, or


hourly manual balancing.
SCUF

is

hyperalimentation
with

used in patients

usually

other fluids,

or

Also,

natural diuresis.

either

iatrogenically

or

who

are

receiving

while having a

problem

patients with fluid

excess,

pathologically

induced,

may

be

undergoing a pure type of ultrafiltration without concomitant

fluid

infusion

prescribed

at

the

time

of

SCUF.

Therefore,

type of fluid and its delivery rate is

upon these patients' clinical needs.

the

dependent

During hemofiltration,

however, it is the system itself that ultimately dictates the


fluid exchange rate.
ment fluid rate.
patient

are

A high QF will mandate a high replace-

After the baseline infusions needed by the

satisfied,

the

excess will then

need

prescribed with a goal of electrolyte and acid-base

to

be

balance.

The composition of this substitution fluid, therefore, should


be

based on the desired serum levels and the losses incurred

during CAVH itself.


The

exaggerated removal of chloride and bicarbonate

the ultrafiltrate require replacement,

in

along with the losses

of ionized calcium, magnesium, and sodium during the process.


Potassium

and such elements as urea or creatinine should

considered
example,

in
by

formulating

the

replacement

fluid.

measuring the urea level in both the

trate and serum,

be
For

ultrafil-

one may calculate the urea appearance

rate

following the formula:


UA
where

(UA)

([Uj uf x Vuf) + VDu ([Uj si -

is urea appearance,

ultrafiltrate, [Uj

(V)

[Uj so)

is timed collection

of

is the concentration of urea in the ultra-

fil trate (UF),


(so) is serum at time 0, and (si) at time of
completion. This may help in adjusting the hyperalimentation
and thus indirectly change the rate of hemofiltrate infusion.
Interactions
sidered

when

among various elements must also

formulating a replacement fluid.

The

be

condirect

mixing of bicarbonate and calcium will form a precipitate and


thus render the solution useless.

Using acetate or

lactate

27

E. Paganini

as the base equivalent will avoid this problem and allow a


mixture similar to that found in hemodialysate. We have used
a bicarbonate-based fluid prepared in our pharmacy.
This
fluid

is

mixed

in a laminar flow room and

delivered

ready

to be infused so that the potential for

bacteriologic

Using this fluid,

contamination can be minimized.

when

has necessitated separate infusion for calcium and

however,
magnesium

and has added labor to the cost of the procedure.


The development of on-line or in-line systems (50-52) of
replacement
runner

in intermittent hemofiltration may be the

to on-site production of fluid for

industry

begins

hemofiltration,

to

CAVH.

Also,

supply fluid at a reasonable

as

cost

for

this procedure will certainly progress at

much faster pace.


Lactated Ringer's solution
saline with appropriate additions is a reasonable
in

fore-

the short run.

However,

or normal
substitute

peritoneal solutions presently

available are best left for intraperitoneal infusions and not


used as hemofiltrate replacement solution.
Clinical practice of SCUF/CAVH.
The patient population described earlier,

resistant

to

intermittent extracorporeal interventions and yet fluid overloaded and oliguric, is typical of many intensive care units.
These
of

same patients are thought to benefit from the delivery

calories and amino acids and frequently require

pressor or antibiotic infusions.


been to limit fluid intake,
practical

nor

advisable

multiple

The classical teaching has

however,

this is frequently not

when to do so

would

also

reduce

needed medications.
For those reasons,
tinuous

therapy

dialytic

it is often judicious to begin

earlier than usual when following

criteria.

Figure

10 shows

the

con-

standard

distribution

of

initial serum creatinine levels in all patients treated with


continuous therapy at our institution.
This group includes
over

200

patients

treated for nearly

1,500

patient-days.

While

close to 90% of the entire population started

prior

to reaching a serum creatinine level of 8

44%

began at levels less than 4 mg/lOO mL.

therapy

mg/100

mL,

Figure 11 shows

continuous Replacement Modalities

28

Per-cent

43.66
45.76
9.66

1..1.6

IHITUAL S.

CREAT.

Fig. 10.
Initial serum creatinine (S. Creat.) levels in
patients
undergoing acute continuous therapies at
the
author's institution.
This group includes more than 200
patients monitored for almost 1,500 patient-days.
SCUF
slow continuous ultrafiltration; CAVH = continuous arteriovenous filtration.
the distribution of creatinine levels between SCUF and
As

might be expected,

levels,

while

CAVH

higher levels.

SCUF was started at lower


was

initiated more frequently

Not infrequently,

CAVH.

creatinine
at

the

the patients may begin to

receive support with a standard hemodialysis run (usually

at

levels of serum creatinine greater than 8 mg/IOO mL) and then


be

placed on CAVH for maintenance.


lll.'i!!.l
S(l-

g
~

SCUF is also frequently

SCUF/CAUH THERAPY
IHITUAL S. CREAT.

MG %

111I2nd

Rx

Fig. 11.
Distribution of starting serum creatinine (S.
Creat.) levels between SCUF (1st Rx) and CAVH (2nd Rx). SCUF
= slow continuous ultrafiltration; CAVH = continuous arteriovenous filtration.

29

E. paganini
SCUF/CAVH THERAPY
SYSTEMS Percen"1:
A:GU
i.8.63
B:RESP
26.66
~~~rE/SKN

E:CNS
F":OI
.J G: IV
H:BOHE/.JT
I I:OTHER
j:ENDOCAR

~f:~J

.56
i..62
2.74
i..62
6.56

2.74

CONCUR

INFECT

Fig. 12.
Concurrent infections (concur. infect.) in
patients undergoing acute continuous therapies.
used for fluid control and the interposition of

all

intermittent

bicarbonate hemodialysis at a reduced schedule.


Of all our patients who have undergone continuous renal
support the majority have also had concurrent infection prior
to initiation of therapy.
of

organ

Figure 12 shows the

distribution

system involvement while Figure 13 gives

specific

differences between patient groups supported on SCUF or CAVH.


Respiratory

infection and blood dyscrasias dominated in

the

SCUF-supported patients, whereas wound and skin infection and


~

so

SCUF/CAUH THERAPY
CONCURR. INFECT.

45-1--~~~--~~--------------------------
I

G
P
SYSTEM

11112nd

Rx

Fig. 13. Concurrent infections (concur. infect.) in patients


undergoing slow continuous ultrafiltration (SCUF)
(1st Rx)
and continuous arteriovenous hemofiltration (CAVH) (2nd Rx).
1) Genitourinary, 2) Respiratory, 3) Wound and skin, 4)
Blood, 5) Central nervous system, 6) Gastrointestinal, 7) IV
site, 8) Bone and joint, 9) Other, 10) Endocarditis.

Continuous Replacement Modalities

30
genitourinary

disturbances were more frequently

in patients receiving CAVH.

encountered

An effort was made to

identify

the infective agents and relate them to either the continuous


procedure

itself or the access necessary for the

procedure.

This retrospective analysis included comparing the culture


results of indwelling catheter tips obtained upon removal
(53) with infective agents isolated prior to initiation of
therapy.
an

Whether long-term indwelling catheters will prolong

already

existing

bacteremia

is

prospective study currently underway.


to

be

no

the

subject

of

However, there seemed

introduction of a new infective

agent

that

was

attributable to the continuous therapy or its access.


Therapy
(Figs.
the

interruptions

14 and 15).

are another

source

of

concern

While these interruptions may be part of

overall scheme of therapy,

there may also be a signifi-

cant compromise in overall clearances because relatively long


periods (4-8 hrs) may pass awaiting reinstitution of therapy.
By far the most frequent cause of interruption is clotting of
the filter.
heparin

The incidence varies enormously depending

usage,

fluid collection,

length

of blood lines employed,

access,

method

and related blood flow.

upon
of

Heparin

usage seemed to playa role in the frequency of clotting with


SCUF,
no

but no difference was found when comparing heparin and

heparin infusion during CAVH (30).

i.iI;~

sa-

We have always

HEPARIN THEIo!:APY
INlfERRUPTIONS

sa J
I

: MECH

:DIAL

REASONS

III1CAUH

Fig. 14.

Therapy interruptions when heparin was used.

used

E. Paganini

31
HO HEPAR!H THERAPY
!HlfERRUPTIOHS

Li1Jlltl
80I
60-'

REASOHS
III1CAUH

Fig. 15.
short

Therapy interruptions when heparin was not used.

blood

produced

lines for our continuous therapy and

fewer

clotting episodes overall

than

with the longer lines (see Swann et al [29]).


by

Kramer et al (36) and Lauer et al (37)

tions,

underlying

related
We

has

As pointed out

filtration

serum protein concentration,

blood flows will all influence

this

encountered
frac-

and access-

clotting

frequency.

have found an overall filter life of 48-55 hours with 10%

of patients able to continue 14 days or longer with the

same

kidney.
Mechanical

interruptions were usually related to device

failure, preparation mistakes, nursing errors or oversights,


or patient-induced disturbances. Membrane rupture was a more
frequent
employs
control.
ment

problem
a

when using the

IV

infusion

plunger-type device mechanism

for

pump,

ultrafiltrate

The sudden withdrawal of fluid from the UF compart-

side of the kidney caused a rapid creation of

pressure.

which

Although

negative

this pressure did not exceed the

facturers's limits for transmembrane pressures,

manu-

the repeated

rapid suction weakened the membrane at its potting site and


rupture ensued.
Also, during preparation of the hemofilter
for

use,

care should be given to assure air removal so that

the

full

potential of the filter can be realized

and

air-

blood interfaces avoided, since this ultimately leads to loss


of surface area and to clotting.

Continuous Replacement Modalities

32

All lines and infusion fluids must be checked


ly.

Unnoticed

(heparin

or

flow

disruption

either

of

frequent-

the

hemofiltration replacement fluid)

infusate

or the

blood

lines or access cannulae, may lead to clotting or decreased


blood flows so that continual therapy would be impossible.
with femoral catheters in place,
to

avoid

flow

catheter kinking,

states

Patients

and

extreme care must be

taken

which will translate into

subsequent

malfunction

of

the

slow

system.

can be mobilized or may actually be able to undergo

surgery while being treated with continuous therapy as long


as close attention is given to the circuitry and system
parameters.
Finally,

baseline

activity is an important

considera-

tion. If patients are entirely uncooperative and incoherent,


the use of continuous therapy should be questioned.
The
unrestrained patient may damage the filter, bend blood lines
or access catheter, remove or disconnect lines, and ultimately cause a great deal of harm.
strongly
circuit
or

In these situations,

recommended that soft restraints be

should be well anchored to the patient,

bedside,

tory.

8 lists the causes

and

outlines

for

manda-

interruptions,

steps to be taken to

is
The

not the bed

and close nursing observation should be

Table

diagnosis,

it

applied.

their

resolve

the

problem.
Morbidity and mortality of SCUF/CAVH.
All therapeutic interventions have risks associated with
their

use

exception.

and

continuous renal replacement therapy

is

no

Although the procedure itself is simple, electro-

lyte balance, fluid control, acid-base considerations, and


the appropriate use of therapy are best left to those well
trained in these areas.
The bicarbonate loss (sieving coefficient 1.069) through the ultrafiltrate, for example, can
be used as a powerful tool in the treatment of acid-base
disturbances in oliguric renal failure (54,55), or may induce
worsening of acidemia if not replaced appropriately.
Electrolyte,
area

where

calcium,

iatrogenic

and magnesium balance is another

morbidity

is

possible.

One

must

separation of
blood in lines

Reduced pulsation
transmission
decreased
calculated QB

Controlled
collection:
- System alarm
- Air in UF line

As per clotting

Access
failure

Loss of transmitted pulsation


to infusion line

unrestricted
collection:
- Decrease rate

Clotting

Blood flow

Ul trafil tration

Diagnosis

Good flush wi th
poor refilling

Increased
clotting
incidence

Inability to
flush clean
carefully with
saline

Dark capillary
and header color

Kidney

Diagnosis and treatment of continuous therapy interruptions.

Interruption

Table 8.

Evaluate vessels

Replace
catheters

Revise shunt

Raise heparin
infusion in new
system

Bolus 1000U
heparin

Replace system

Evaluate access
and lines

Therapy

w
w

::l

....
....

III
::l

1Q

'tI
III

I:'il

If SCUF
maintain QF

Intermittent
dialysis

reduce QF

I f CAVH

Normal

Access
bleeding

Pump generated

In-line setup

Normal

Soaked wrappings

Normal

Decrease rate

Kidney
casing
damage
Normal to low

Normal

Normal

pink to red
color

Membrane
rupture

Kidney

Blood flow

Ultrafiltration

Diagnosis

fluid until Sip


HD

D/C replacement

Follow HD
protocol

Check clotting
parameters
Give protamine
Apply pressure

D/C heparin

Replace kidney

Discontinue
negative
pressure

Replace kidney

Therapy

Diagnosis and treatment of continuous therapy interruptions (continued).

Interruption

Table 8.

.....

CIl

CD

rt

I-'

.....
.....

III

0.

rt

CD

~
::s

III

I-'

'0

il?

CIl

::s

rt

oo
::s

E. paganini

35

realize that the ultrafiltrate contains a sodium level

equal

to that of the serum (sieving coefficient 0.996).

Therefore,

in

14

removing

liters during SCUF or exchanging

liters

during CAVH, a substantial sodium loss occurs that may induce


a true hyponatremia if not appropriately balanced.
reason,

For this

the use of normal saline or lactated Ringer's

solu-

tion is generally recommended as the baseline fluid with


SCUF, and sodium balance is a prime consideration in adjusting the replacement fluid during CAVH.
Calcium (sieving
coefficient 0.6) is also lost in proportion to its ionized
fraction.

This must be replaced either with the hyperalimen-

tat ion or
magnesium.

hemofiltration replacement fluid,


We have experienced the induction

arrhythmias

based

at

least partially on

along with
of cardiac

low

calcium

and

magnesium levels in some patients on CAVH.


are

Fluid
very

balance is another critical issue.


few

therapy,

the

missed.

It

volume

hemodynamic
classical

is,

depletion

tachycardia.

disturbances

signs

for example,
while

related

these

any

patients

hypotension

or
to

unable

as noted above,

assessment

Accurate fluid balance,


necessity

cannot

be

sodium

so that the

laboratory parameters of dehydration are not


physical

this

are

and chloride are removed in proportion to serum,


usual

to

depletion may be
possible to induce a severe

respond to the thirst mechanism and,

Daily

there

of fluid

not observing

Frequently,

Since

helpful.

over-emphasized.

flow charts, and daily weights are a

in evaluating patients on SCUF

and

CAVH.

While

easily correctable, inappropriate fluid adjustments, left


unmonitored, may have a dramatic effect on patient morbidity.
The
this

most frequent morbid event directly associated with

therapy

has

been bleeding.

The

use

of

continuous

heparin infusions has reduced the overall heparin dosage


avoided

the

peak

and

valley

effect

of

an

and

intermittent

regimen.
Nonetheless, 18% of our patient population had
bleeding episodes while undergoing therapy. While monitoring
clotting parameters (PT,
PTT,
ACT) in the
circuit seemed
appropriate, patient monitoring was more effective in de-

continuous Replacement Modalities

36

creasing the bleeding incidence.

Our protocol is to monitor

patient PT and PTT at least every 24 hours, but usually on a


12-hour basis and to adjust the heparin infusion appropriately.

We

have been unable to perform

heparinization,

satisfactory

regional

partially due to the labor-intensive aspects

of this approach.

The inability to adjust heparin/ protamine

flows accurately makes this a less than desirable approach.


The use of prostacycline as a heparin substitute was

considered

but

abandoned

when the anticoagulant

dose

was

found also to induce hypotension.


The use of a lowmolecular-weight heparin may prove beneficial but is still
under

investigation (56).

circuit

by filtration,

Since it can be removed from the

very little entered the patient

and

thus a reduced incidence of hemorrhage was found.


Another
heparin.
to

avoid

episodes

approach

has

been the

total

of

With appropriate patient selection it is

possible

heparin usage (30).

bleeding

while

undergoing

Patients who

treatment

can

therapy with the heparin discontinued.


the

elimination

incidence of clotting may ensue,

have
remain

on

that

A slight increase in
but overall

interrup-

tions of therapy are significant.


Historically,
demonstrated
modalities
prospective
renal

a
are

patients

high

acute renal failure

mortality,

especially

when

have

dialytic

necessary (57-59).

comparison

failure

with

are

Until a well-matched,
of the various therapies of acute

conducted,

the

impact of continuous
on patient mortality will remain unknown.
To our

therapies

knowledge there are no reports that have addressed

mortality

among patients who are unable to undergo dialytic techniques.


Drawn on
tion

anecdotal experience, the mortality in our institu-

has

specific

been

100%.

population

replacement

It
was

treatment.

was for this


identified
We

have

reason

for
managed

that

continuous
to

lower

this
renal
the

mortality to 70% , which we think represents a significant


advance in the management of acute renal failure.
Based
population

on
to

these results, we have since expanded the


include all oliguric intensive care patients

E. Paganini

37
SCUF/CAUH THERAPY
PATIENT MORTALITY

5
~

"Y
C

STATUS

111I2nd

Rx

rl'3"

Rx

Fig. 16. Patient mortality for all acute continuous (1st Rx)
therapies among patients with one, two (2nd Rx) or three or
more separate bouts of acute renal failure (3rd Rx)
requiring fluid,
We

have

also

electrolyte balance,

or azotemic

identified sub-groups of patients

repeated bouts of renal failure during their


and

require subsequent intervention.

control.
that

have

hospitalization

The overall mortality

statistics are summarized in Figure 16.


While mortality
remains high in the hemodynamically unstable population with
multiorgan

failure

(70%),

those patients

who

experienced

repeated bouts of renal failure showed a mortality of 50% and


61%

respectively,

in sharp contrast to the higher mortality

reported among similar patient populations (60,61).


the

true

compromised

impact

of

this

therapy

is

group rather than the stable

with

Perhaps

the

severely

oliguric

patient.

Further data need to be collected to substantiate this trend.


CONCLUSION
This chapter has presented an overview of acute continuous

extracorporeal

treatment modalities for

patients

The hemodynamic stability offered

with

acute

renal failure.

by

these

therapies and the elimination of fluid restrictions in

these patients will open the door to adequate nutrition and


appropriate medication scheduling.
The system's simplicity
will lend itself to ease of implementation but may also allow
significant alteration in patient status if not properly

38
managed.

continuous Replacement Modalities


Finally, mortality seems to have been decreased in

severely compromised patients, but whether this will carry


over into other patient populations remains to be seen.
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In: Acute Renal
Failure,
Brenner
BM,
Stein J
(eds).
Churchill
Livingston, New York, pp 1-16, 1980.
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Magnusson M, Sivak E, Meden G, et al:
The effect of
Furosemide versus ultrafiltration on extravascular lung
water
in
permeability
pulmonary edema
in
dogs
(Abstract). IXth Intern Cong of Nephr, p l75A, 1984.
Magilligan DJ, Oyama C: Ultrafiltration during cardiopulmonary bypass:
laboratory evaluation and initial
clinical experience. Ann Thorac Surg 37:33, 1984.
Lamar J, Briggs WA, McDonald FD:
Effective fluid removal with the Amicon diafilter.
Proc Dial Trans Forum
127, 1978.
Neff MD, Sadjadi S, Slifkin R:
A wearable artificial
glomerulus.
Trans Am Soc Artif Intern Organs 25:71,
1979.
Shaldon S, Beau MC, Deschodt, et al: Continuous ambulatory hemofiltration.
Trans Am Soc Artif Intern Organs
26:210, 1980.
Olbricht C, Schurek HJ, Tytul S, et al: Efficiency of
CAVH in acute renal failure.
Influence of blood pressure, blood flow, vascular access and filter type
(Abstract). Blood Purif 2:14, 1984.
Swann S, Kennedy 0, Paganini EP: Technical aspects of
slow continuous ultrafiltration (SCUF)
and continuous
arterio-venous hemofiltration (CAVH). In preparation.
Smith 0, Paganini EP, Suhoza K, et al:
Non-heparin
continuous renal replacement therapy is possible.

Organs 1986 (In print)

Artif

40
31.
32.

33.
34.
35.
36.
37.
38.
39.
40.

41.

42.
43.
44.
45.

46.
47.

Continuous Replacement Modalities


Desio FJ, Paganini EP:
Evaluation of slow continuous
ultrafiltration in oliguric patients on intraaortic
balloon pumps (Abstract). Blood Purif 2:5, 1984.
Mineshima M, Yamagata K, Era K, et al: Kinetic comparison of hemofilters for continuous arteriovenous hemofiltration (CAVH).
Trans Am Soc Artif Intern Organs, 1985
(In print).
Leypoldt JK, Frigon RP, Henderson LW: Impact of ultrafiltrate
velocity
on
solute clearance
in
CAVH
(Abstract). Blood Purif 2:217, 1984.
Trudell LA, Aebischer P, Panol G, et al: An implantable

continuous ultrafiltration device.

Artif Organs,

1986

(In print).
Kramer P, Schrader J, Bohnsack W, et al:
Continuous
arteriovenous hemofiltration:
A new kidney replacement
therapy. Proc Eur Dial Transplant Assoc 18:743, 1981.
Kramer P, Bohler J, Kehr A: Intensive care potentials
of continuous arteriovenous hemofiltration.
Trans Am
Soc Artif Intern Organs 78:28, 1982.
Lauer A, Saccaggi A, Ronco C, et al:
Continuous
arteriovenous hemofiltration in the critically
ill
patient. Ann Intern Med 99:455, 1983.
Kaplan AP, Longnecker RE, Folkert VW: Suction-assisted
continuous arterio-venous hemofiltration.
Trans Am Soc
Artif Intern Organs 29:408, 1983.
Dodd NJ, O'Donovan RM, Bennett-Jones Div: Arteriovenous
hemofiltration:
A recent advance in the management of
renal failure. Brit Med J 287:1008, 1983.
Henderson LW, Besarab A, Michaels A, et al:
Blood
purification by ultrafiltration and fluid replacement
(diafiltration)
Trans Am Soc Artif Intern Organs
13:216, 1967.
Quellhorst E, Rieger J, Doht B, et al:
Treatment of
chronic uremia by an ultrafiltration artificial kidney-first clinical experience.
Proc Eur Dial Transplant
Assoc 13:134, 1976.
Kramer P, Matthaei C, Fuchs C, et al:
Assessment of
hormone loss through hemofiltration.
Artif Organs
2: 128, 1978.
Schaefer K, Herrath D, Gul1berg H, et al:
Chronic
hemofil tration--a cr i tical evaluation of a new method
for the treatment of blood. Artif Organs 2:386, 1978.
Henderson LW, Colton CK, Ford CA: Kinetics of hemodiafiltration, II. Clinical characterization of a new blood
cleansing modality. J Lab Clin Med 85:372, 1975.
Colton C, Henderson LW, Ford CA, et al:
Kinetics of
herndiafiltration, I. In vitro transport characteristics
of a hollow fiber blood ultrafilter.
J Lab
Clin Med
85:355, 1975.
Kaplan A:
The effect of predilution during continuous
arterio-venous hemofil tration (Abstract).
ASN 17th
annual meeting p 66A, 1984.
Scribner BH, Canez JEZ, Buri R, Quinton W: The technique of continuous hemodialysis.
Trans Am Soc Artif
Intern Organs 6:38, 1960.

E. Paganini
48.

49.

50.
51.

52.
53.
54.
55.

56.

57.
58.
59.
60.
61.

41

Continuous arteriovenous
Geronemus R, Schneider N:
hemodialysis:
A new modality for treatment of acute
renal failure. Trans Am Soc Artif Intern Organs 30:610,
1984.
Ronco C, Brendo1an A, Bragantini L, et al:
Arteriovenous
hemodiafiltration
combined with
continuous
arteriovenous
hemofiltration
(Abstract)
ASAIO
abstracts 14:36, 1985.
Henderson LW, Beans E: Successful production of sterile
pyrogen-free electrolyte solution by ultrafiltration.
Kid lnt 14:522, 1978.
Shaldon S, Bean MC, Deschodt G, et al: Three years of
experience with on-line preparation of sterile pyrogenfree infusate for hemofi1tration. Contr Nephro1 32:161,
1982.
Luehmann D, Hirsch D, Ebben J, et al: Central on-site
preparation of substitution fluid for hemofi1tration.
Trans Am Soc Artif Organs 30:195, 1984.
Cooper GL, Hopkins CC: Rapid diagnosis of intravascular
catheter-associated infection by direct gram staining of
catheter segments. N Eng1 J Med 312:1142, 1985.
Bosch: Acid/base.
Gudis S, Mangi S, Feinroth M, et al: Rapid correction
of
severe
lactic acidosis with massive
isotonic
bicarbonate infusion and simultaneous ultrafiltration
(Abstract). ASN - 14th annual meeting, p 41, 1981.
Moriniere P, Dieua1 J, Renand H, Bene1monfok, et a1:
Comparison of low molecular weight heparin with unfractionated heparin in hemofiltration: same antithrombotic
activity with decreased hemorrhagic risk (Abstract).
Blood Purif 2:56, 1984.
Kje11strand C, Gornick C, David T:
Recovery from acute
renal failure. Clin Exp Dialysis Apher 5:143, 1981.
Hilberman M, Myers BD, Carrie BJ, et a1: Acute renal
failure following cardiac surgery.
J Thorac Cardiovasc
Surg 77:880, 1979.
Gailiunas P, Chawla R, Lazarus JM, et al: Acute renal
failure following cardiac operations.
J Thorac Cardiovasc Surg 79:241.
B1uemle LN Jr, Webster GD Jr, Elkinson JR:
Acute
tubular necrosis. Arch Intern Med 104:18, 1959.
London RE, Burton JR:
Post-traumatic renal failure in
military personnel in southeast Asia.
Am J Med 53:137,
1972.

3
TRANSPORT IN CONTINUOUS ARTERIOVENOUS HEMOFILTRATION AND SLOW
CONTINUOUS ULTRAFILTRATION
M. LYSAGHT
D. BOGGS
Travenol Laboratories, Round Lake, Illinois

This chapter will review the technological basis of


continuous hemofiltration as employed in treating acute renal
failure

and

then

discuss the

physical

factors

governing

filtration rate and solute removal.


MEMBRANES
Figure

1 is a scanning electron micrograph

that

shows

the unique structure of the membranes employed in hemofiltration.

Two

distinct

regions

are

visible:

the

consolidated layer surrounding the fiber lumen,


strate,
of
and

and the sub-

broad microporous region comprising the remainder

the fiber wall.


contains

retain

skin,

plasma

The skin is less than one micron

extremely small pores of a


proteins

size

while passing urea and

thick

suitable
other

to
low-

molecular-weight solutes.
This skin region determines the
transport properties of the membrane;
the substrate simply
provides mechanical strength and support.
If, instead of
being confined to the skin,
the

full

membrane,

the fine pores extended

through

resistance to permeation would be

much

higher and the filtration rate would be far too low to permit
hemofiltration.
Membranes for commercially available CAVH filters are
manufactured from hydrophobic thermoplastics such as polyacrylonitrile,

polyamide, and polysulfone.

(Chemical formu-

lae are included in Table l.)


Such materials are generally
not responsive to the complement system, and the lack of
complement activation is an important feature of
CAVH

43

Transport Characteristics

44

Fig. 1.
Scanning electron micrograph showing a transection
of a hollow-fiber ultrafiltration membrane.
Inner diameter
is 200}J.
(Inset shows skin at higher magnification.)
(continuous

arteriovenous

hemofiltration)

continuous ultrafiltration).

and

SCUF

(slow

Hydrophobic membranes do absorb

proteins

from solution (some are absorbed

absorbed

protein layers influence the infiltration rate

solute

transport

membrane

characteristics of

the

vigorously);
membrane.

and device performance should always

be

the
and
Thus,

evaluated

with plasma or blood as the perfusate.


Membranes are prepared with the use of a phase-inversion
process

(1).

miscible

The

polymer is first dissolved in

solvent to form a viscous dope.

water-

This solution

is

then extruded, as an annulus or as a sheet, around an aqueous


stream.
tates

The polymer directly adjacent to the water precipirapidly,

forming

the skin;

solvent is leached

more

slowly from the remainder of the film, leaving the substrate.


The

properties of the membrane depend to a great

the

kinetics of the precipitation,

extent

on

which can be controlled,

albeit in a semiempirical fashion (2).

45

M. Lysaght and D. Boggs

TABLE I
COMMERCIALLY AVAILABLE OEVICES FOR CAVH AND SCUF
PERFORMANCE'

GEOMETRY

DESIGNATION
OIAFllTER.20
OiAl'llTE~30

FILTRATION POISEUILLE
RAllO
RATE
mmHg-mlf1Jcm
emlmln

.OF

LENGTH

,m

RADIUS
microns

"

06

2500
4800

13
20

100
100

11
17

+iJJJlLiJt
! L! J..! L 1 !..

os

4JOO

19

100

15

~1

"14

"'"
9000

06

6200

AREA

MEMBRANE MATERIAL

MANUFACTURER

{{~

AMICON CORPORATION
LEXINGTON, MAUSA

FIBERS

PRIMING

VOLUME

,m

'83

10

06.

"

'77

"

POLYSULfONE

ULTRAFILTtRCS

ASAHI MEOICAl CO, LTD


TOoo,JAPAN

POLYACAYLONI"TRILE

FRESENIUSAG

AV-<OO

'v<OO

OBERUSEL, fRG

POLYSUlRJNE

GAMBROAB

FH55

LUND, SWEEDEN

-P-A'-~-~-~-jt
"

POLYAMIDE

BIQSPAL 12008

HOSPALLTD

BASlE. SWITZERLAND

"

110

19

OS.

110

21

".

"75

14

100

14

OJ.

27

26

,,,.

15

'13

63

140
140

>10
>20

019

23

""

+WJJlUt
lUUUl

os

~~1

OJ

POLYACRYlOUITRILE

RENARD 025
AE~AFLO

05

RENAL SYSTEMS
MINNEAPOLIS, MN USA

3000
3000

OS

14

22

"
50

OJO

POLYSULFONE

610SPAl 12005 employs

~ parallel plale ~onflgurallon Wllh

15 compartments each 6 5 em wide, 26 em long. and 250 microns apart

F,ltration rates lrom manlJfacturer's literature POl5elllile lallO


P"m'''g vOlume 1$ Irom ma"ula~turer's t'terature

I~

calculated as pressure drop per UM blood flow rate at a deVice average blood VIscosity 01 5 cps

DEVICES
Diafilter R

Hollow

Fiber

Ultrafilters

(Amicon

Corp.,

Lexington, MA, U.S.A.) were utilized in the early development


of CAVH and SCUF (3);
1982,

and

Table

(February 1985)
and

straightforward.

1 describes those available at

(4-7).

hollow-fiber

additional devices were introduced


this

in
time

These devices involve both flat-sheet

geometrics.
Membranes

Design

requirements

are

should not activate complement.

Poiseuille resistance should be low. The product of area and


permeability must be balanced to yield a filtration rate of
10-20 cm 3 jmin under normal operating circumstances.
Lower
rates would be unacceptable to clinicians; higher rates might
lead

to excessive removal of water from the

Priming volume should be minimal.


smooth

flowing

blood.

Flow streamlines should be

and linear to avoid stagnation,

vortices,

separated

flow, and other factors that may result in thrombosis.


FILTRATION RATE
Boundary layer phenomena (e.g.,
tion)

have

concentration polariza-

been shown to be unimportant in

CAVH

and

SCUF

Transport Characteristics

46

(8,9).
Instead, the membrane itself is the controlling
resistance, and filtration rate is determined by the interplay of that resistance and the available driving forces.
Refer to Figure 2 and, for precision, consider filtration at
some

position

filter.

x along the

L,

length,

of

hollow-fiber

The local filtration rate is given by the expression


dJF

(AP x

(Eq. 1)

- TIx) 271 N r dx

cm 3 /min, K is membrane
permeability after exposure to plasma (cm 3/min cm2 mmHg), r

where
is

JF

is

radius,

filtration

rate is

N is the number of fibers,

and

Llp and n

are,

respectively, transmembrane pressure and protein oncotic


pressure in mmHg.
Equation 1 states that the local filtration

rate

will

be zero

until

the

applied

pressure exceeds the oncotic pressure,


increase

transmembrane

and thereafter,

will

in linear proportion to the amount by which applied

pressure exceeds oncotic pressure.

Determining the

tion rate for the full device is more complex.

The simplest

1"'.....1.

filtra-

dx

Differential Element, dx

Full Device

Area:

2 n N r dx

2n NrL

Filtration
Rate:

K (~Px - TTx) 2 n N r dx

K 2 n N r [(~Px -TTx) dx

x = L
x = 0

Fig. 2.
Schematic illustration of local and device average
filtration rates.

47

M. Lysaght and D. Boggs

approach is to assume that P and rI vary linearly from device


inlet

to

device outlet.

Thus,

Equation 1 can

be

simply

integrated to give
QF = K A (/1 P - rI)

(Eq. 2)

where QF is device filtration rate (cm 3 /min and A is membrane


surface area (cm2).
As is shown in Figure 3, Equation 2
gives reasonably satisfactory results when the filtration
fraction is small and JF is'< 20% of inlet blood-flow rate.
At higher filtration fractions, the linear approximation no
longer applies and, to integrate the local rates of viscosity,

derived

pressure
the

filter.

c:::

using Equation 1,

must

be

volumetric flow and

calculated

This

is

along

//

10

a:

3:
iI
0

Q)

15

use

15

Q)

full

possible with the

E
'"E

15

the

:::

/
/.

u:::

//

advanced

25

of

//

of

oncotic

length

50

75

Transmembrane Pressure, mmHg

100

Fig. 3. Filtration rate versus transmembrane pressure under


low filtration-fraction conditions.
Solid line measure
in vivo with fresh whole blood; dotted line is aqueous
filtration rate.
Note x intersect at oncotic pressure
(adapted from reference 8)

Transport Characteristics

48

numerical

methods and empirical relations for viscosity

and

oncotic pressure as a function of hematocrit and protein


concentration.
However, the numerical solutions are valid
only

for a single geometry,

not

and set of inlet conditions

lend themselves to generalization.

rates due,

for example,

logic factors,
device
local

low

blood-flow

to access considerations or physio-

protein concentration along the length of the

increases

approaches

At

do

the point at

which

transmembrane pressure.

As a

filtration

to

oncotic

pressure

consequence,

rate fails asymptotically to

the

zero.

This

particularly interesting case has been extensively treated by


Lauer and Bosch (9) and by Ronco and co-workers (10).
CLEARANCE AND SOLUTE REMOVAL
Even after exposure to plasma, CAVH membranes are freely
permeable to urea,

creatinine,

and uric acid.

Clearance of

these substances may then be determined by using the


tion

rate.

filtra-

When substitution fluid is added downstream

of

the filter,
Cl ~ Qp
where

Cl

expressed

is

clearance

and Qp

(Eq. 3)
is

filtration

rate,

and ~ indicates approximate

in ml/min,

both

equality.

To be more precise, Equation 3 is rewritten as (11,12)


Qp

Cl
(1 -

<Ii)

(1 -

(Eq. 4)
HK)

where > is protocrit (device average protein concentration) , H


is fractional hematocrit, and K is an intracellular/extracellular

distribution

determined

coefficient that

has

been

empirically

to be 0.86 for urea and 0.73 for creatinine (11).

The denominator in Equation 4 is always

<

1.0,

which adjusts

clearance upward to reflect the fact that the cleared solutes


are

more

concentrated

filtrate--than
ignored,

but

in

in plasma

whole blood.

water--and

thus

This correlation is

amounts to 10% to 20% of clearance and

in

the
often

should

M. Lysaght and O. Boggs


probably

49

be more frequently employed in

Kaplan

quantitative

work.

(13) has recently proposed the use of predilution

in

CAVH, in which case the clearance becomes (11)


Cl

(1 - H + HK)

[(1 -

~)

(I -

H)

(Eq. 5)

+ Qol
QB

where

QB and QO are equal to blood replacement solution flow


rates ih cm 3 /min.
Recall that Equations 3 to 5 assume that
the membrane does not sieve out or reject the solutes; treat-

ment for partially rejected solutes is available (11,12), but


is considerably more complex.
FUTURE TRENOS
CAVH

is

the first artificial organ system

satisfactory
This

is,

capable

performance without an external energy

in

itself,

a considerable achievement,

source.
and

natural evolution of the technology promises to be even


impressive.

Membrane

increased,
ence,

and

device

cumulative
probably

geometry

effect

area,

represent

can

certainly

be

in

the

optimized.

design changes such as

header regions.

The
higher

which is

performance,
decreasing

and improving
CAVH

and

ideal applications for nonthrombogenic

those

more

experi-

yielding

The incidence of clotting,

increasing channel gaps~

the

significantly

the limiting factor in current device

streamlines
e.g.,

be

will be smaller devices

be reduced through

surface

can

given present-day understanding and

ultrafiltration rates.
could

permeability

of

SCUF

flow
both

materials,

obtained by the covalent bonding of heparin

to

surfaces coming into contact with blood, which eliminates the


need to use anticoagulants in patients who are often already
at risk of internal bleeding.

Assuming concomitant progress

in percutaneous access, smaller and more thrombosis-resistant


devices could be employed more frequently,

perhaps to reduce

intradialytic hypovolemia or for the generalized treatment of


edema.

Alternatively, the same technology could be employed

Transport Characteristics

50
in

continuously dialyzing,

wearable or implantable

formats

(14,15), which was almost certainly professor Kramer's ultimate intent when he first developed the therapy (16).
REFERENCES
1. Michaels AS:
High flow membrane.
US Patent 3615024:
October 17, 1981.
2. Pusch W, Walch A:
Synthetic membranes:
preparation,
structure, and application.
Angew Chem Int Ed (Engl)
21:660-685, 1982.
3. Kramer P (Brsg): Arterio-venous haemofi1tration--Nieren
(Ersatz) Therapie in Intensivepflegebereich.
Vandenhoeck & Ruprecht, Goettingen, FRG 1982.
4. Gambro AB: Lund Sweden.
5. Fresenius AG, Oberusel, FRG.
6. Castro LA, Banthein CA, Gurlant HJ: Successful clinical experience in the use of a small flat-sheet dialyzer
for continuous AV-hemofiltration. Life Support Systems
1 S-1:275-278, 1983.
7. Heinker W, Kreusser W, Krier C, Just HO, Roeh L: Spontaneous arteriovenous hemofiltration in patients with
acute renal failure.
(Abstract) Kidney Int 26:564,
1984.
8. Lysaght MJ, Schmidt B, Gurland HJ: Filtration rates and
pressure driving forces in AV filtration. Blood Purification 1:178-183, 1983.
9. Lauer A, Saccagi A, Ronco C, Belledone M, Glabman S,
Bosch J: Continuous arteriovenous hemofiltration in the
critically ill patient.
Ann Intern Med 99:455-460,
1983.
10. Ronco C, Brendolan A, Borin D, et al:
Self limited
dehydration during CAVH.
(Abstract) Blood Purification
2:60, 1984.
11. Colton CK, Henderson LW, Ford CA, Lysaght MJ: Kinetics
of hemodiafiltration. I. In vitro transport characteristics of a hollow fiber ultrafilter.
J Lab Clin Med
355-371, 1975.
12. Lysaght MJ, Ford CA, Colton CK, Stone RA, Henderson LW:
Mass transfer in clinical blood ultrafiltration devices.
In:
Technical aspects of renal dialysis.
Ed:
Frost
TH, Pitman Medical, Kent, England, pp 81-95, 1978.
13. Kaplan AA:
The effect of predilution during continuous
arterio-venous hemofiltration.
(Abstract) Arner Soc Neph
17:66A.
14. Neff MS, Sadjadi S, Slifkin R:
A wearable artificial
glomerulus. Proc Ann Dial & Trans Form 26, 1979.
15. Shaldon S, Beau MC, Deschodt G, Lysaght MJ, Ramperez B,
Mion C:
Continuous ambulatory hemofiltration.
Trans
ASAIO 26:210-211, 1980.
16. Kramer P: Gastrointestinal recycling and detoxification
of hemofiltrate. Proc NIAMDD Contractors Conference USA
DHEW Pub #NIH 79-1442, 1978.

4
THE PRACTICAL TECHNICAL ASPECTS OF SLOW CONTINUOUS ULTRAFILTRATION (SCUF) AND CONTINUOUS ARTERIOVENOUS HEMOFILTRATION
(CAVH)
S. SWANN
E. PAGANINI

The Cleveland Clinic Foundation, Cleveland, Ohio

ABSTRACT
Slow continuous ultrafiltration (SCUF) and continuous
arteriovenous hemofiltration (CAVH) have been utilized at The
Cleveland Clinic Foundation, Department of Hypertension and
Nephrology

since

1977

in over 150 patients as

clinical

therapy for the treatment of acute renal failure.


The
the

purpose of this chapter is to instruct and

medical

personnel in direct contact with

educate

patients

who

require SCUF and/or CAVH with regard to the practical set-up,


monitoring,
ment

and management of this continuous renal replace-

therapy.

This

includes the general

design of the extracorporeal circuit,


for

successful

operation

description

including

and management for

and

suggestions
the

on-going

monitoring and regimen involved in this therapy to provide an


easy,

simple,

description

of

yet

effective outline of practical "how

operation.

In

order

to

provide

results and benefit to the patient undergoing SCUF or CAVH


technical

to"

optimal
a

description and understanding is essential for the

success of this modality of treatment.


INTRODUCTION
Slow
means

of

continuous ultrafiltration (SCUF)

is defined as

slow continuous fluid removal in the

patient

a
who

otherwise does not tolerate conventional methods of hemodialysis and related ultrafiltration.
The rate of ultrafiltration is regulated by the desired fluid intake plus

51

Technical Aspects

52

The primary goal of SCUF is the slow

projected weight loss.

continuous removal of plasma free water via an extracorporeal


circuit utilizing a prescribed hemofilter for fluid
while

balance,

avoiding further insult to the already hemodynamically

unstable

patient.

generally

An

controlled

ultrafiltration

rate

for

SCUF

at about 1.5-5 mL/min resulting

is

in

total ultrafiltration removal of approximately 2-7 liters

in

is

given

24-hour

period of

time.

Replacement

volume

generally not required other than by existing nutritional and


intravenous drug administration (1).
Continuous arteriovenous hemofiltration (CAVH)
from

SCUF

generally

in

that

utilizes

ultrafiltration

ranging from 5-16.67 mL/min resulting in

ultrafiltration
given

CAVH

removal

differs
rates

total

of approximately 7-24 liters

24-hour period of time.

in

In addition to the increased

ultrafiltration rates in CAVH versus SCUF,

CAVH also differs

in general purpose.
with SCUF,
removal

only,

control

and

balance

of

basic

the primary purpose is slow continuous fluid


but with CAVH the purpose is not

balance,

components

include

but

electrolytes.
of

the

also azotemic

only

control

fluid

and

the

Both SCUF and CAVH use the


extracorporeal

the same arterial and venous blood

These

circuit.
line

ultrafiltration line, and the same hemofilter.

same

sets,

the

In some cases

in which required ultrafiltration rates exceed 600-700 mL/hr,


a

hemofilter with higher sieving and ultrafiltration coeffi-

cients with more surface area is required.

Proper selection

of hemofilter to facilitate optimal performance required


each

modality

of treatment can be determined from Table

When carefully controlled,


while

1.

fluid removal can be accomplished

in most cases without further insult to the already


patient,

for

unstable

maintaining electrolyte and azotemic balance

(2)

A
SCUF

thorough

and CAVH are vitally

characteristics,
tion

understanding of the technical


important,

including

aspects

hemofilter

arterial/venous blood tubing sets,

methods and devices,

and proper monitoring

of

collec-

equipment.

S. Swann and E. Paganini


Proper

application

clinical

parameters
CAVH.

play

53
and

controlled

clinical

an integral part in the success of SCUF

Vascular

access

and close

monitoring

of

or

clinical

laboratory values ensure safe, yet simple treatment that will


provide optimal results in patients who otherwise would not
tolerate conventional means of dialysis therapy.
TECHNICAL DESIGN OF CIRCUITRY
The selection of the properly prescribed hemofilter
extremely
priming

important.

is

The hemofilter should provide minimal

volume to avoid further

Minimal,

yet

adequate

solute clearance.

intravascular

instability.

adequate surface area is necessary to

provide

Adequate sieving coefficient to

provide required ultrafiltration rates and minimal total size


of hemofilter to minimize pressure drops across the
surface

area are necessary.

membrane

The reduced priming volume (as

compared to conventional dialyzers) and the reduced length of


hollow fibers in the hemofilters will prevent excessive hemoconcentration

within the filter capillaries and

risk of circuit clotting.


tance

reduce

the

Along with this the minimal resis-

across the hemofilter allows for its use even with the

presence of low mean arterial pressures,

low systolic

blood

pressures, both of which result in lower blood flows to the


extracorporeal circuit.
Patients with mean arterial pressures and with subsequent low systolic blood pressures of
about

50-90 mmHg have still been successfully

treated

with

SCUF and CAVH with minimal difficulty.


We

have

experience

designs (Table 1).

with

four

different

hemofilter

They include the Amicon models 20 and 30,

the Gambro model FH-55, and the Biospal plate model 1200S (36)

Arterial
integral

venous

(A-V)

blood tubing sets are

part of the extracorporeal circuit to

be

also

an

employed

for SCUF and CAVH.


A variety of A-V blood tubing sets have
become available at present.
We have designed our own A-V

blood

tubing (Fig.

available

to

1).

provide

Various A-V blood tubing sets


both

prehemofilter

and

are

posthemo

0.2 m2

0.6 m2

0.6 m2

0.5 m2

Amicon
Model 30

Gambro
FH-55

Biospal
1200S

Surface
Area

60 mL

43 mL

35 mL

18-20 mL

Priming
Volume

18
mL/min

8-23
mL/min

60-90
mL/min

20-40
mL/min

U.F.
Rate

PLATE

6,200

6,000

6,000

No. of
Fibers

Less than
60 mmHg

100 mmHg

190 mmHg

100 mmHg

Flow
Resistance

500 mmHg

600 mmHg

500 mmHg

500 mmHg

Max.
Tmp

Hemofilter technical description for SCUF and CAVH applications.

Amicon
Model 20

Hemofilter
Model

Table 1.

Polyacrylonitrile

Polyamide

Polysulfone

Polysulfone

Membrane Material

U1

ro

[J)

rt

()

ro

'd

[J)

i-'

OJ

()

,...-

::s

::l"'

()

..;!

"'"

S. Swann and E. Paganini

"

55

ARTERIAL BLOOD

Fig. 1.
Cleveland Clinic design of AV blood line sets
SCUF/CAVH.

for

filter

A-V

replacement

dilution.

Also integrated on

the

blood tUbing sets are adapters to attach lines to hemofilter,


injection sleeves to withdraw blood samples, or to administer
intravenous solutions,

heparin administration line, and line

clamps (7).
The length of A-V blood lines is an important consideration.

Our experience has lead us to utilize blood lines

minimal
Blood

of

lengths to provide minimal resistance to blood flow.


lines of extensive length can be a hindrance to

flow and enhance clotting within the extracorporeal


Excessive

lengths

can

also

be

awkward

when

blood

circuit.

positioning

circuits for patient comfort and management.


SETTING-UP AND PRIMING PROCEDURE FOR SCUF OR CAVH

NOTE:

This

procedure is recommended when priming the hollow

fiber hemofilters.

(Amicon 20 or 30 and Gambro FH-55)

Technical Aspects

56

Supplies and equipment required to set up and operate SCUF or


CAVH.
1 ea. Hemofilter.
1 ea. Arterial/venous

blood

tubing

set W/ultrafiltra-

tion line.
1 ea. Solution

administration set for intravenous prim-

ing solution.
1 ea. 1,000

mL

NaCl

0.9%

with

5,000

USP

units

of

heparin.
1 ea. Volumetric

urimeter

for ultrafiltration

collec-

tion.
3 ea. Hemostats.

1-3 ea. Intravenous

infusion

pumps to

control

volumes

(i.e., UF, replacement solution, and heparin).


1 ea. Hemochron

400

clotting

device

for

monitoring

activated

times unless equivalent Lee-White

clot-

ting times are done)


Appropriate supplies for access site dressings.
NOTE:

* -

NOTE:

Aseptic technique must be observed throughout

Indicates optional equipment.


priming

procedure.
1.

Properly

remove

hemofilter

and blood

lines

from

appropriate packages.
2.
end

Attach distal ends of A-V blood lines to appropriate

(A or V) of hemofilter.

(On Amicon hemofilters

venous

end is nearest ultrafiltration port.)


3.
4.

Attach tubing to ultrafiltration port and clamp off.


Prime and rinse hemofilter as follows:
a.

Rinse

blood

path of hemofilter

by

connecting

priming solution administration set to

arterial

blood inlet cap.


b.

Administer

approximately 800 mL of

saline

(i.e.,

USP units heparin/L

NaCl

0.9%),

to prime blood path of hemofilter.

The

hemofilter
(venous

must

5,000

heparinized

be in

the

inverted

port on top) during priming

position
procedure.

S. Swann and E. Paganini

57

Allow blood circuit to gravity prime eliminating


all air from circuit.

priming solution must be

elevated

to approximately 3 feet above hemofil-

ter,

facilitate gravity

to

priming

procedure

(Fig. 2).
c.

After
has

approximately 800 mL
primed

arterial
forcep.

the

and

blood

of priming solution

path,

clamp

venous lines with line

off
clamp

both
or

PRIMING SOLUTION Noel 0.9%


WITH 5000 USP UNITS HEPARIN

VENOUS LINE

U.F. PORT (~!$;tlll~![II

HEMOFILTER
PRIMING POSITION

ARTERIAL LINE

v~~~oI-\\------'n"l ISTRATION LINE

Fig.
2.
procedure.

position

of

hemofilter

circuit

for

priming

58

Technical Aspects
d.

CAVH replacement lines and heparin administration lines must also be primed and eliminate all
air prior to patient hook-up.

e.

Simultaneously

with

clamping off blood

lines,

remove clamp from UF port allowing remainder

of

priming solution to prime UF side of hemofilter.


Once

UF side of hemofilter is completely primed

eliminating all air, clamp off UF port tubing.


f.

Hemofilter

circuit

is now

ready

for

hook-up.

I V PUMP
HEPARIN
ADMINIST RATION

I V PUMP
CAVH
REPLACEMENT SOLUTION

I V PUMP
ULT RAFILTRATION
CONTROL

Fig. 3.

Optional IV infusion pump.

patient

59

S. Swann and E. Paganini


PATIENT HOOK-UP AND MONITORING PROCEDURE FOR SCUF OR CAVH
1.

Before patient hook-up, properly prepare and setup:


a.

1 ea. intravenous (IV) pump for heparin infusion


(e.g.,

12,500 USP units heparin in 250 mL

NaC1

0.9%)
b.

1 ea. IV infusion pump for UF collection (optio-

nal screw clamp method may be employed)


c.

ea urimeter collection container for

tion

of

ultrafiltrate removed.

The

collecoptional

Vitalmetrics R Electronic Digital urimeter allows


for accurate collecting and projection of ultrafiltration

while

continuously

current UF rates (9).


ing

device

reading

is extremely useful with the

screw

clamp method of UF control on the SCUF and


where

IV

out

This collection monitor-

pumps are not employed to

CAVH

accurately

control and dictate UF flow rates per hour (Fig.


3)

d.

For
will

CAVH application,
be

solution.

1 ea.

required for infusion

IV infusion
of

pump

replacement

Replacement solution requirements are

prescribed by attending physician.

An

example

of CAVH replacement solution is shown in Table 2


(10)
It

NOTE:

is recommended that the infusion pump be

for
Table 2.

Example of standard CAVH replacement fluid.


Standard CAVH Replacement Solution

Na
K+

utilized

UF control and the urimeter collection container

Acetate
Mg
Ca
Cl
Dextrose

140 mEq/L
0-2 mEq/L
35-40 mEq/L
1.5 mEq/L
3.5 mEq/L
110-120 mEq/L
0-200 mg/dL

Technical Aspects

60

be positioned below patient access to create negative


pressure on UF side of hemofilter to facilitate ultrafiltration (Fig. 4).
2.
according
aseptic

3.

Aseptic
to

technique

standard

must

be

properly

hospital policies

to

adhered
ensure

to

clean

techniques in working around vascular access sites.

with all tubings clamped (i.e.,

A-V lines, UF line,

and heparin infusion line), connect arterial and venous blood


lines to appropriate access connectors.

connect UF line

collection container via IV pump if used.


utilized which is recommended,

to

When IV pumps are

prepare all IV infusion pumps

for immediate hook-up to appropriate connection, heparin pump


to heparin infusion line (Fig.

5), CAVH replacement solution

line to provided CAVH replacement port etc.

Upon connection

of all appropriate lines, unclamp arterial and venous line

POSITION OF HEMOFILTER UPON CONNECTION


TO PATIENT ACCESSES

ARTERIAL LINE ,

Fig. 4.
accesses.

Position of hemofilter upon connection to

patient

61

S. Swann and E. Paganini

CONTROLLED
INFUSION
FLUID

INJECTION PUMP

GRADUATED FILTRATE COLLECTION

Fig. 5. Continuous arteriovenous hemofiltration with utilization of IV pumps.


clamps,

while rotating hemofilter with venous side up, until

hemofilter is completely perfused with patient's blood.

4.

Administer heparin bolus as indicated at this time.

(Recommended

initial

starting

dose of 2,000 USP

units

of

heparin is suggested.)

5.
placement

Set

appropriate

solution

parameters to desired UF

volume rates per hour as

and

prescribed

reby

physician (10).
proper monitoring of
hemochron
activated
6.
For
clotting times or Lee-White equivalents, clotting times

Technical Aspects

62

should

be maintained at between 150-300 seconds

or

between

15-30 minutes.
ANTICOAGULATION REGULATION DURING SCUF AND CAVH
The primary objective of heparinization in SCUF of

CAVH

is to prevent clotting of the extracorporeal circuit.


Of
equal importance is the prevention of over-anticoagulation,
especially
encing

in the postoperative patient or in those

coagulation abnormalities.

with low platelets,


some

type

of

These

include

experipatients

prolonged PT/PTT, and those experiencing

hepatic failure.

patient

with

abnormal

coagulation may require little or no anticoagulation for SCUF


or CAVH.
may

However, patients with hematocrits greater than 30

require large amounts of heparin,


proper

standards

of

so extreme caution is

necessary,

and

monitoring

coagulation

parameters and SCUF or CAVH clotting

patient
parameters

must be strictly adhered to (11,12).


SUGGESTED METHOD FOR ANTICOAGULATION THERAPY
UNDERGOING SCUF OR CAVH
1.

Heparin

during

solution

for

continuous

IN

PATIENTS

anticoagulation

SCUF or CAVH usually consists of 12,500 USP units

heparin in 250 mL NaCl 0.9%.

of

The heparinized saline solution

should then be administered through the appropriate heparinization

port located on the arterial line of the SCUF or CAVH

circuit.
2. It is recommended that heparin administration dosage
begin

at

relation

500

USP units per hour and then

be

to the individual patient's coagulation

titrated

in

laboratory

test results and monitoring of clotting time.


3.

Discontinuing

heparin should be avoided

if at

Initial

of

USP

all

possible.
4.
followed

dose

heparin of

500-2,000

units

by continuous infusion of 500 USP units per hour is

recommended.

63

S. Swann and E. Paganini

SUMMARY OF ANTICOAGULATION THERAPY


It is strongly recommended that heparin be given at
initiation

of

adversely

affects

clotting
the

SCUF or CAVH,
the

since clotting at

overall

outcome.

the

outset

Prevention

early in the procedure also allows longer

extracorporeal circuit.

the
of

life

of

Our recent approach in antico-

agulation therapy with SCUF or CAVH has been the basic


elimination of clotting times, either Lee-White or ACTs in
most cases.
of

This facilitates control and requires less time

nursing

patient

personnel.

without

Our

experience has

shown

bleeding abnormalities can be

that

successfully

maintained with an initial loading dose of 500-2,000 USP


units of heparin followed immediately by the initiating of
continuous
arterial

heparin drip at 500 USP units per hour with


pressures

above 55

mmHg.

Patient's

mean

coagulation

parameters are monitored to avoid over-anticoagulation.

This

approach has seemed to be successful in accomplishing SCUF or


CAVH

patency

and

good membrane life (about

1-3

days

per

hemofilter)
DISCONTINUING SCUF OR CAVH
1.

SCUF

At

or

normal

the completion

CAVH,

treab~ent

of

the hemofilter can be rinsed with 200 mL

of

saline.

clamped
through
corporeal

off
the

First,

arterial access line

and 200 mL of normal saline


arterial
injection sleeve

circuit

is cleared of residual

blood loss is minimal.


disconnecting

the

of the prescribed

must

be

must be injected
until the extrablood.

Residual

Although rinsing the circuit

it from the patient may seem

before

acceptable,

the

risk

of forcing a blood clot trapped in the hemofilter

back

into

the

con-

patient's bloodstream is a risk that must be

sidered.
2.

After

the patient's blood

has been

satisfactorily

retransfused,
arterial venous, and UF lines should be
clamped.
The circuit should be removed from access, and
discarded.
The access site should be cared for according to
hospital procedure.

64

Technical Aspects

3. To change a clotted circuit, follow the same procedure outlined in Discontinuing Hemofilter on SCUF and CAVH.
In addition in changing a clotted circuit, the access catheters

must

patency

be

must

flushed with heparinized

saline,

be ensured before re-starting

and

their

or

CAVH.

SCUF

INTERRUPTING SCUF OR CAVH FOR INTERMITTENT HEMODIALYSIS

Intermittent

hemodialysis is occasionally required in a

patient

who is already on SCUF or CAVH to help correct

temia.

When the SCUF or CAVH circuit appears patent,

possible

to run hemodialysis in series without

this therapy except to make the connection in


hemodialysis

azoit is

interrupting
series.

When

becomes necessary for a patient already on SCUF

or CAVH the following procedure should be followed:


1.

Hemodialysis should be set up and ready for

patient

hook-up before clamping off the SCUF or CAVH circuit.


2.

sterile piece of

silastic tubing or

dialysis

recirculation connector can be used to shunt the venous blood


line

from the SCUF or CAVH circuit and to connect it to

arterial
venous

blood line from the dialysis

machine.

Then,

blood line is connected from the dialysis machine

the patient's venous access line.

the
the
to

Patient hook-up from SCUF

and CAVH in series with dialysis is initiated by clamping the


SCUF

or

CAVH

venous line and the patient's

venous

access

line, followed immediately by connecting or shunting the SCUF


or CAVH venous blood line to the arterial line of the
sis machine.
is

Then,

dialy-

the venous line of the dialysis machine

connected to the venous access line of the patient.

All

lines are immediately unclamped and the blood pump is started


on

the

dialysis machine.

Hemodialysis will

then

proceed

uninterrupted (Fig. 6).


3.
series,

Upon completion of hemodialysis with SCUF or CAVH in


the arterial line is simply clamped off from the

dialysis

machine

in

between

where the

SCUF

or

CAVH

connected,

the dialysis machine arterial blood line is

connected,

the

dialysis

patient's

circuit,

blood

is retransfused

is
dis-

from

the

and the venous lines are clamped off

and

65

S. Swann and E. Paganini

Fig. 6. Slow continuous ultrafiltration in series with hemodialysis.


discarded, leaving the SCUF or CAVH circuit for immediate rehook-up to patient arterial/venous access lines.
CAVH

venous

line

and

The SCUF or

blood line is reattached to the

venous

all clamps are removed allowing SCUF

or

access
CAVH

to

continue once again at previously prescribed parameters.


run

in

series with SCUF or CAVH UF rates may have to be adjusted

It

should

to

compensate

be

for additional obligatory ultrafiltration by

dialysis treatment.
a

noted that when hemodialysis is

the

The operator should be aware that while

patient is on SCUF or CAVH with hemodialysis in series the

patient

must

be

monitored

more

closely

because

of

the

potential further stress to the patient.


The

recent

inclusion of continuous

renal

replacement

therapy
(13) into the nephrologist's armamentarium for
the
care of acute renal failure has led to the resurrection of

by
First described
arterial
cannulation for access.
seldinger (14) as a method for arterial entry in preparation

Technical Aspects

66
for

radiologic procedures,

it was later adapted by

Shaldon

(15) as access for hemodialysis.


The development of various other forms of access (16-18)
as

well

as the use of techniques which. would allow for

pressure

systems

(veno-venous
adaptation;

made

pump

to

be used

assisted

in
flow;

extracorporeal
single

low

therapies

needle

machine

single needle double lumen catheter development)

percutaneou~

undesirous.

arterial entry not only obsolete but

also

Catheter development continued to search for

more durable and less thrombogenic material which would allow


the long term use of the venous system in an acute event,
while

some

other more permanent access was

maturing.

arterial cannulations were left to those who were


in

continuous

monitoring

or
The

interested

of blood pressure or as

an

easy

access for blood testing (19).


with
venous
in

the

description of Kramer's

continuous

arterial

hemofiltration and the subsequent logarithmic

this and similar techniques throughout the

growth

world,

there

has been some renewed interest in percutaneous arterial entry


for the needed pressure difference that drives these systems.
PROCEDURE
Theoretically,

any arterial and venous site can be used

for providing flow.


In practice, however, the main area of
entry has been the femoral artery and vein.
The femoral
technique was well described by Grone and Kramer (20)
and
will be the principal method outlined here.
It should be
noted, however, that both axillary as well as radial arteries
have

been

used as the arterial access for

both

continuous

hemofiltration (CAVH) and ultrafiltration (SCUF).


Supplies.
1.

One (1)
needle.

2.

18-gauge

cutting edge

1/2

inch

flexible guide wire small enough to pass

long

through

the needle, and long enough to allow for the passage


of

the catheter without losing sight of the

free end.

wire's

67

S. Swann and E. Paganini

.!fi

Fig. 7. Arterial catheter size = 10 Fr (top), venous return


catheter is polyurethane material and is 9 1/2 inches long
(center), guide wire 100 cm x .035 inches (bottom).
3.

1%

4.

One

lidocaine

without

epinephrine

and

10

cc

syr inge.
(1) 20-gauge 1 1/2 inch,

one (1) 22-gauge

1/2

inch, and one (1) IS-gauge 1/2 inch needle.


5.

Heparinized saline solution and a 20 cc syringe.

6. One (1) #11 surgical scalpel blade.


7. Good supply of 4 x 4 (sterile).
S. Arterial and venous catheters.
Technique.
1. Evaluate arterial pulsation at all levels of the
leg, but especially distally to the proposed site of entry
(Figs. Sand 9).
2. Once the femoral artery course is established,
choose a site approximately 2 em below the inguinal
as entry.
3. Shave and prep the groin in the usual
manner.

ligament
surgical

6S

Technical Aspects

4. Wear sterile gloves, mask, and gown.


5. Infiltrate the area of entry for both the venous
(medial)
and the arterial (lateral) puncture site with lidocaine.
6. Use the *11 blade to make a puncture wound in the
skin to allow for entry of both catheters.
(Wound should be
large enough for easy entry, but not so large as to leave a
gaping hole)

(Fig. 10).

7. Enter the venous system first, using the IS-gauge


needle to puncture the vessel, and feeding the guide wire
through the needle and into the vein (Figs. 11 and 12)
S. Withdraw the puncture needle while leaving the wire
in place, making sure there is constant pressure applied over
the entry site to reduce the bleeding (Fig. 13).
9.

Advance

the venous catheter over the guide

with

continuous twisting motion and once placed, withdraw the wire


(Figs. 14, 15, and 16).
10.
saline

Flush

the

and clamp,

catheter

immediately

with

heparinized

leaving it filled with the heparin

(Fig.

17)
11.

Repeat steps 7-10 while entering the arterial system

(DO NOT puncture the artery through and through,

and be sure

to apply appropriate pressure to ensure bleeding control).


12. DO NOT force either wire into the vessel.
resistance is met, abandon the attempt and begin again.
13.

If

Suture both catheters in place using 3-0 silk

(make

doubly sure the catheters are SECURELY fastened to the

skin)

(Fig. IS).
14.

Apply

a GENEROUS supply of polyvidone-iodine

oint-

ment to the sites and redo the dressing daily.


DISCUSSION
The major complications for the procedure are listed in
Table 3.

with careful entry techniques and with

catheter care during therapy,


avoided.
the

meticulous

many of these drawbacks can be

The site of entry may well determine the success of

procedure itself.

For example,

Olbricht (21) reported

S. Swann and E. Paganini

69

Fig. 8

Fig. 9

Fig. 10

Fig. 11

Fig. 12

Fig. 13

70

Technical Aspects

Fig. 14

Fig. 15

Fig. 16

Fig. 17

Fig. 18

S. Swann and E. Paganini


the

outcome

71

of CAVH comparing femoral

artery

percutaneous

entry and the use of brachial artery shunt, showing favorable


exchange

rates

approach.
CAVH

even at lower pressures

using

the

femoral

Lauer (22) also reported higher blood flows in the

circuit

with a femoral artery access when compared

to

other accesses at a similar mean arterial pressure.


Infection continues to be a main concern with the use of
any

long

Although we

term indwelling catheter.

impressed by any increased incident of

were

infection,

not

complica-

tions in the acute renal failure population since our move to


CAVH as the main method of support,
completed

infections

and

retrospective
found

no

we nonetheless have just

analysis

related

of

access

sepsis,

nor

related
increased

morbidity related to the catheters., We are presently looking


at

the

same data-points in a prospective

identified

manner

and

have

infrequent local inflammation as our only finding

(23)
Femoral

cannulation

will restrict the patient to

bed.

There have been several incidences of patients being moved to


a sitting position while having the catheters in
have

found

place.

blood flow through the external circuit

compro-

mised because of kinking of the catheter or the blood


We

lines.

have experienced no catheter erosion of either artery

vein

secondary

to patient mobilization.

It must

We

be

or
also

emphasized that patients who are hyperactive should either be


Table 3.

Complications of AV cannulation.

Radial
Thrombosis
Embolism
Aneurysm
Necrosis of
overlying skin

Femoral
Thrombosis
Embolism
Compromised flow
Infection (local, systemic)
Bleeding (hematoma, oozing,
retroperitoneal)
Fistula formation
False aneurysm

Technical Aspects

72

restrained

or other access obtained,

since they may require

constant supervision.
Patients

with

moderate

to

atherosclerosis

severe

especially with already compromised flow to a limb should not


be subjected to percutaneous arterial cannulation.

The risk

of embolization as well as thrombosis is greatly increased in


this type of patient.

Catheter removal is also more compli-

cated in this setting.


Bleeding
being

both

episodes

can also complicate

the

superficial and retroperitoneal.

procedure,

The first

is

usually identifiable and can be easily stopped with appropriate

pressure applied to the entry site of the

more dangerous is retroperitoneal bleeding,


be

a drop in hematocrit,

hip,

back or buttocks,

loss

(hypotension,

occur

The
only

sudden severe pain in the abdomen,


and hemodynamic signs of rapid blood

rapid heart rate)

spontaneously,

vessel.

identified

careful

Although

this

entry techniques as

well

may
as

judicious withdrawal procedures will lessen the likelihood of


a traumatic etiology.
SUMMARY
The

technique of arteriovenous cannulation has

allowed

for the use of pumpless extracorporeal systems in the care of


the acutely ill patient.
both

the

cannulation

therapy which it allows,


minimum.

If sufficient attention is given to


procedure as well as

the

continuous

then complications can be kept to a

As with all invasive procedures, a search for less

thrombogenic,

more biocompatible material should continue to

be undertaken.
BLOOD FLOW IMPORTANCE
the

Blood flow is perhaps the most important variable for


success of SCUF or CAVH.
Inadequate blood flow will

result
and

in thrombosis to the hemofilter and attached

circuit

may even result in thrombosis of access catheters or

shunt.

AV

Blood flows of approximately 30-200 mL/min have been

measured in both the AV shunt and the percutaneous catheters.

S. Swann and E. Paganini


Blood

73

flows have been consistently higher with

accesses

versus AV shunts.

advantageous

Therefore,

percutaneous

it is perhaps

to utilize percutaneous femoral accesses

more
where

possible.
It is also necessary to realize that since blood flow is
so vital for CAVH or SCUF success, that AV shunts due to
lower blood flows may only work on SCUE where lower ultrafiltration rates are mandated.
L/24

hr is acquired,

On CAVH where volumes up to

24

it may be necessary to limit access to

femoral percutaneous route.

Our experience has proved

that

the higher the blood flow the greater the success of the SCUE
or CAVH.

Blood flow determination can be calculated by using

the following formula:

Blood flow (mL/min)

Blood
mL/min,
with

UF rate mL/min x venous hematocrit


venous hematocrit - arterial hematocrit

flows have been measured at approximately

with mean arterial pressures of 50-60

a patient's blood pressure this low,

mmHg.

30-100
Often

it will be almost

impossible to run SCUE or CAVH using an AV shunt,

whereas in

these same instances femoral percutaneous accesses will still


provide adequate blood flow rates.
We can summarize our evaluation of blood flow rates by
emphasizing once again that without adequate blood flow from
vascular accesses the chance of circuit and hemofilter thrombosis is greatly enhanced.
WARNINGS AND PRECAUTIONS
1.

Aseptic

preparation

technique

MUST be strictly

of and use of SCUF or CAVH

adhered to

extracorporeal

in
cir-

cuits.
2.

When priming a SCUE or CAVH circuit it is

necessary

that all air has been properly eliminated from the blood path
circuit.
3. Proper monitoring of ACT or Lee-White clotting times
should be done to prevent inadequate or excessive anticoagu-

Technical Aspects

74

(Lab PT/PTT's should be drawn at least


lation.
nursing shift.)
4. The patient's blood pressure must be
throughout
cardiac

treatment.

Drops

once

per

monitored

in mean arterial pressure

output will create a drop in blood flow through

or
the

circuit and subsequent clotting will most likely occur.


5.

Proper

monitoring of ultrafiltration and fluid (IV)

administration must be observed to prevent hypovolemic

shock

or overhydration.

6.

If red or pinkish color in the ultrafiltrate,

indi-

cates a rupture in hemofilter membrane and hemofilter must be


changed at once.

7.
tration

Air bubbles continuously drawn through the ultrafilline

are an initial indicator that the

circuit

is

clotting or that there is a kink in a line or even mechanical


failure of one of the IV pumps.
of

Air in the UF port and line

the hemofilter will occur if the ultrafiltration rate

higher than blood flow will allow to be removed,


appears in the circuit,

is

If clotting

the circuit must be changed at once.

If a question arises as to the validity of the clotting,

the

circuit

the

may

be

checked

by flushing the

circuit

via

arterial sleeve after clamping the arterial access line


50-100 mL of normal saline.

with

When doing this caution must be

used to prevent clots from breaking loose from the hemofilter


to the patient.
that

only

If the circuit appears clear,

partial surface area has been lost and it may

necessary to decrease the ultrafiltration rate.


not

it is likely
be

If this does

correct the problem or the circuit appears clotted

when

flushed, then the circuit must be changed.

8.

If

blood

in the circuit becomes extremely dark

or

appears to be separated (plasma from cells), clotting has


occurred and replacement of the hemofilter circuit must be
done at once to prevent access devices from also clotting.
SUMMARY
Understanding
and

the

practical technical aspects of

CAVH is essential to derive optimal benefit

from

SCUF
these

S. Swann and E. Paganini

75

procedures.

on

many

experience in performing SCUF and CAVH

patients including unstable patients in an ICU

has

afforded us a simple yet effective means of

fluid
By

Our

controlling

and electrolyte imbalance and correction of

utilizing

the

SCUF or CAVH with IV

setting

pumps

azotemia.

to

regulate

ultrafiltration, CAVH replacement and heparin administration,


once the circuit is set up and started, is virtually
automatic, requiring only monitoring.
Strict monitoring of patient coagulation times
is
important in regulating heparin therapy to prevent overanticoagulation
have

and clotting of circuit.

bleeding abnormalities,

without heparin.
or

azotemia

In

patients

SCUF and CAVH can be attempted

In an acute situation where fluid

correction is required in acute renal

SCUF or CAVH without heparin can be performed.


run

SCUF

or

CAVH without heparin,

remain

patent

for hours

or

even

days.

removal
failure,

In order

the circuit

connected to the patient and run until clotting


may

who

is

to

simply

occurs.

It

predilution

methods of CAVH versus posthemofilter dilution have also been


used

to

prevent excessive hemoconcentration and to

blood flow.

enhance

Although I do not recommend this method, it has

been known to aid in SCUF and CAVH without heparin.

Another

method is to periodically flush the blood circuit with 50-200


mL of normal saline to help prevent clotting.

This could be

done routinely as necessary.


Naturally, higher ultrafiltration rates will greatly hemoconcentrate blood and will
increase risk of clotting.
Good vascular access with optimal blood flow and minimal
resistance
providing

is

blood

critical factor to the

procedure

flows that allow high fluid

with optimal CAVH.

and

removal

in

rates

Internal resistance across the hemofilter

membrane is minimal and in most cases does not hinder

ultra-

filtration blood flow.


utilizing
of

SCUF and CAVH has greatly reduced the

individualized

Whereas

dialyses

intermittent

necessary, the

performed in

diffusion dialysis

an
may

lCU

number
setting.

sometimes

be

frequency of conventional methods of dialysis

Technical Aspects

76

can be limited, and replaced by SCUF or CAVH.


This frees
personnel and aids in fluid and electrolyte imbalance corrections, as well as correcting azotemia.
When intermittent
dialysis becomes necessary for patients who are already
undergoing
patent

and

dialysis.
CAVH

SCUF or CAVH,

if the hemofilter circuit

is running well,
This

it may be run in

appears

series

allows simple reconnection of the

SCUF

circuit after dialysis without requiring another

filter

and

circuit

set,

with
or

hemo-

and is therefore much more

cost

While clotting of the circuit occurs periodically,

SCUF

effective.
and

CAVH have become routine procedures for the

hemodynami-

cally unstable patient and the patient with acute renal


failure in an ICU setting.
When properly managed SCUF and
CAVH

offer

intermittent

more physiological
therapeutic

dia1ytica1

approaches.

therapy

The ease of

lends itself nicely to respond to the rapidly changing


of

the

patient,

than

control

while eliminating the labor intensive

needs
and

cumbersome intermittent approach.


REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.

pagani~i EP,
Nakamoto S:
Continuous slow ultrafiltration 1n oliguric acute renal failure.
Trans Am Soc
Artif Intern Organs 26:201, 1980.
Kramer P, Buhler J, Kehr A, et a1:
Intensive care
potential of CAVH.
Trans Am Soc Artif Intern Organs
28:28, 1982.
Amicon Corp., Danvers, MA, 01923. Amicon Models 20 & 30
hemofi1ters & A-V blood lines.
Gambro Inc., Barrington, IL, 60010.
Ref. for FH-55
hemofi1ters & A-V blood lines.
Hospal Med Corp., E. Brunswick, NJ,
08816.
Ref for
Biospal 1200 S Plate Dialyzer used for SCUF/CAVH & A-V
blood tubing sets.
Castro LA, Banthien F, Gurland HJ: Successful clinical
experience in use of small filter sheet dialyzer for
CAVH.
Lifemed Corp., Ref. for A-V blood tubing sets for
SCUF/CAVH, Compton CA, 90220.
International Technidyne Corp., Metuchen, NJ,
08840.
Ref. for Hemochron 400 for activated clotting time
control.
Vitalmetrics Inc., San Diego, CA, 92121.
Ref for
Electronic digital urinary monitoring system.

S. Swann and E. Paganini


10.
11.

12.
13.

14.
15.

16.

17.
18.
19.
20.

21.

22.
23.

77

Travenol Labs, Deerfield IL, 60015.


Ref for CAVH
replacement solution kits.
Schriever HG,
Epstein SE,
Mintz MD:
Statistical
correlation and heparin sensitivity of activated PTT,
whole blood coagulation time, and an automated coagulation time. Am J Clin Path 60(3):323-329,1973.
Shanillin N, ploth OW:
Evaluation of an activated
clotting time technique for use in hemodialysis.
Dial
Transpl 9(10) :955-957, 1980.
Kramer P, Wigger W, Rieger J, et al:
Arteriovenous
hemofiltration:
A new and simple method of treating
overhydrated patients resistant to diuretics.
Klin
Wschr 55:1121, 1977.
Seldinger SI:
Catheter replacement of the needle in
percutaneous
arteriography.
Acta Radiol
(Stockh)
20:368-376, 1939.
Shaldon S, Chiandussi L, Higgs B:
Hemodialysis by
percutaneous catheterization of the femoral artery and
vein with regional heparinization.
Lancet 2:857-859,
1961.
Brescia MJ, Cimino JE, Appel K, Hurwich BJ:
Chronic
dialysis
using venipuncture and surgically created
arteriovenous fistula.
N Engl J Med 275:1089-1092,
1966.
Wellington JL:
Expanded polytetrafluoroethylene prosthetic grafts for blood access in patients on dialysis.
Surgery 21:42-422, 1978.
Cohen PG:
Circulatory access for extracorporeal blood
modification. Plasma Therapy 2:235, 1982.
Kaye W:
Invasive monitoring techniques: Arterial cannulation, bedside pulmonary artery catheterization, and
arterial puncture. Heart Lung 12:395, 1983.
Grone HJ, Kramer P: Puncture and long term cannulation
of the femoral artery and vein in adults in continuous
arterio-venous hemofiltration.
Vandenhoeck & Ruprecht,
1982.
Olbricht C, Schnrek HJ, Tytul S, et all
Efficacy of
CAVH in acute renal failure influence of blood pressure,
blood
flow,
vascular
access,
and filter
type.
(abstract). Blood Purification 2:57, 1984.
Lauer A, Saccaggi A, Ronco C, et all
Continuous
arteriovenous hemofiltration in the critically
ill
patient. Ann Intern Med 99:450, 1983.
Paganini EP: Unpublished data.

5
FLUID BALANCE IN CONTINUOUS ARTERIOVENOUS HEMOFILTRATION
H. SCHUREK
Hannover Medical School, Hannover, FRG

Despite
venous

the numerous advantages of continuous

hemofiltration (CAVH),

arterio-

a major disadvantage that has

restricted worldwide adoption of the method is the problem of


manual control of the large fluid volumes of 12 to 20 L daily
necessary to control azotemia.

An exact manual balance is a

time-consuming and often grossly inaccurate procedure (1).


Different procedures and methods have been developed
overcome

this

systematic

problem

balance

(2).

These include

protocol,

infusion control

simple
systems

to
but
by

means of simple mechanical in-line dripping control (Isoflux R


system,

van Leer Medical;

I.V. Master FLOW system, Master

Medical Corporation), control by means of infusion pump, or


electronic
scales used as an infusion control
system
(Infusart R , Sartorius, Gottingen, FRG). Though all of these
aids

have been developed to enable fluid exchange with exact

balance, they are not self-regulating systems, which regulate


substitution fluid volume by measuring filtrate volume.
During
systems

have

including
(1,3)
systems

the
a

last

years,

different

self-regulation

been developed for

automatic

fluid

very simple gravity-operated mechanical

and more or less sophisticated


(4).

These

systems include

electrically
both

balance,
device
operated

microprocessor-

controlled systems
(2) and computer-based systems (5)
that
are based on techniques similar to those used in mechanical
intermittent hemofiltration.

79

80

Fluid Balance in CAVH

SYSTEMS WITHOUT SELF-REGULATION


Types of systems.
Conventional drip infusion systems are inadequate for
the control of the large daily fluid volumes of 12 to 20 L
involved in CAVH because of the large variation in flow rates
(1,2)
Systems such as the Isoflux R system prevent the
problem of slipping clamps (and thus changing flow rates) and

reduce the variation in flow to less than 5% of the set point


(2).

disadvantage

of the system is the upper limit

accurate delivery of about 400 mL/hr which is even less

for
than

Delivery
that achieved with the I.V. Master Flow system.
of fluids for parenteral nutrition by a second system or two
sets

in

parallel is a means of overcoming

this

limitation

(2)
Iloflux Iystem

tntu rt

lue' lock

manual filling
pump

extra Infulon

Idluaament
of delivery

~1iii'iI~ru.

dripping
chamber

extra Intullon
non return valve

luer lock

Fig. 1.
Schematic representation of the Isoflux R fluid
delivery system on the left and the infusion control system
Infusart R on the right.
In the latter, two systems control
both substitution fluid and filtrate.

81

H. Schurek
A

spring

control

balance with a range of 5 kg may be

used

to

the remaining fluid of the substitution fluid bag in

one-hour intervals.

A more expensive but elegant way is the


infusion control unit Infusart R (Sartorius, Gottingen, FRG).
An electronic display reset to zero on starting the infusion

gives the absolute change of fluid weight and


substitution rate/min or rate/hr as required.
For
urine

the

bags

measurement

of filtrate

either

or more advanced systems may be

calculates
conventional

used

including

graduation and overflow (UreofixR, Braun Melsungen, FRG).


Schunemann and Kramer recommended the exact
of

filtrate

measuring
used

to

prior

to its disposal by

cylinders (2).
measure

measurement

means of two-liter
R
The Infusart system can also be

filtrate collected in a

large

fluid

bag

(upper weight limit 5 kg)


Protocol for manual fluid balance.
The daily fluid balance should be subdivided into

6- or

After starting CAVH, the filtration rate,


8-hr intervals.
measured in minute intervals, may be used to calculate the
hourly

production of filtrate,

which in turn gives a

measure of the set point for delivery of substitution


using this method,

however,

rough
fluid.

the balance must be re-adjusted

every hour.
For a time period of 6 or 8 hours, ultrafiltrate, urine,
and

other fluid losses should be measured in adequate gradu-

ated containers and an exact balance calculated, including


all fluids substituted (caloric intake + substitute for hemofiltrate)
Schunernann
during

It is our advice (1) and also the experience of


and Kramer (2) to calculate not only the balance

each

balance.
achieved

nursing

shift

The best control


by the use of bed

but

also

cumulative

of manual fluid
scales or, even

daily

balance
better,

is
by

weighing the patient daily.


The
are
error

above-mentioned measurement and nursing

subject
(2).

to

many sources of both systematic

techniques
and

human

Our own experience with these techniques

since

Fluid Balance in CAVH

82

January 1980 provided us with the impetus to develop a simple


mechanical device for automatic fluid balance in CAVH (l).
SYSTEMS WITH AUTOMATIC FLUID BALANCE
The Hannover system.
When

we started to use CAVH as a tool in the

treatment

of acute renal failure in 1980 a satisfying and simple method


for automatic fluid exchange was not available (l), especial-

ly in the treatment of patients with multiorgan failure

(6).

Kramer

tank

developed a system consisting of a water-filled

containing substitution bags.


closed

The filtrate was led into the

tank and a weight on top of the tank was connected by

a pin to a plate inside the tank.


the bags,
(7).

This plate, by compressing

was used to drive substitution fluid into the vein

From a practical point of view the system was unmanage-

able.
Our system, now commercially available from Gambro
(l,3), uses for substitution a conventional gravity-operated

substitution
fluid 4.5L

Fig. 2.

Scheme of the Hannover balancing system.

H. Schurek
dripping

83
infusion;

tube clamp regulates

the

mechanical

feedback between filtrate and substitution fluid.


depicts the system schematically.
Two mechanically coupled cross-beams
roller

bearings

on a vertical stand.

are

Figure

mounted

by

A bag with 4.5 L

of

substitution fluid is suspended from the upper beam and is


balanced by an integrated weight within the connecting square
bar coupling the horizontal beams.

The working point of the

balance can be adjusted by a taring wheel, which may be moved


along a screw projecting from the lower beam.
trate

starts

hanging

at the lower beam,

tube clamp,

container

the growing imbalance opens

the

thereby mechanically adjusting the rate of fluid

substitution
balance
balance

When hemofil-

to drip into the graduated filtrate

to

that

of

filtration.

be required
(usually in the
during parenteral nutrition),

Should

negative

regulation of fluid
the hanging point of

the filtrate container may be set in preselectable positions


at the start of a cycle.
This allows for an exact negative
balance of up to 2 L in 500-mL steps.
The imbalance introduced by changing the hanging point of the empty filtrate
container

at the start of a cycle can be compensated for

by

adjustment of the taring wheel.


The
sum

balance

system operates on the principle that

of the products of leverage lengths and hanging

is constant for both the upper and the lower beam.


cycle the center of gravity moves from the shrinking
tution
trate.

bag
The

calculated

weights
During a
substi-

to the container that gradually fills with


position

of the notches at the lower

the

fil-

beam

is

from the law of the lever so that the product

of

length and force remains constant.


the

When the fluid exchange during one cycle is complete and


SUbstitution bag is empty, the now-filled filtration

container moves the beams to a position that stops filtration


automatically by means of a security clamp (Fig. 3).
Only under these circumstances is it necessary to
control the weight of the filtrate at the end of a cycle for
the balance protocol, as an excess of 160 to 200 mL of

Fluid Balance in CAVH

84

Fig. 3.
Schematic representation of the security clamp,
which stops filtration should a change of bag be overlooked.
filtrate

is required to close the security clamp (should the

filtrate

container not be in a negative

This

balance

position).

amount of extra filtrate is proportionately higher when

a negative balance position is used.


When
balance

the bag is changed punctually,


for one cycle is less than

the

50 mL.

variation

of

The regulating

accuracy of the running system per se is less


mL/4.5 L exchange (l).

than

10

Differences in the filling volume of bags used from


different suppliers can amount to 100 mL, but this results in
a balance
selectable

error of only about 40 mL when the highest prenegative balance position of -2 L is used (6.5 L

filtrate versus 4.5 L substitution fluid).


For practical purposes,
method

is

balance calculation using

simple when compared with manual

cycle takes about 8 hours,

handling.

which corresponds to one

this
One

nursing

shift.
If a negative balance of 1 L is preselected, at the
end of one cycle 4.5 L of substitution fluid is balanced by
5.5 L of filtrate.
(urine

Thus conventional balance of fluid losses

and other drained fluids) versus parenteral nutrition

fluid can be calculated and used to adjust the volume of CAVH


fluid necessary to achieve fluid balance.

85

H. Schurek
During
measured
enable
per

a running cycle,

using

the amount of filtrate may

graduation of the

filtrate

container.

an approximative measurement of the

minute,

plastic

filtrate

tube (syringe cylinder),

To

filtration

is allowed to drip into

be
rate

graduated

the outlet of which can be

blocked, e.g., for one minute.


Our

system

period,

can

be handled,

after

short

training

by the staff of a general intensive care unit.

For

better handling during transport two wheels are mounted under


two arms of the five-armed pedestal of the stand (3).
Procedure to start a cycle.
When

CAVH

is running,

a 4.5-L bag

with

substitution

fluid is suspended, the infusion line is prefilled, and a


Silastic tube segment of the line is placed into the tube
clamp.

Then the empty filtrate container is suspended in its

preselected
filter

position.

The

filtration line from the

is placed into the security clamp,

syringe

cylinder.

Fluid

hem 0-

its end into

exchange can now

be

started

the
by

adjusting the dripping rate of the substitution fluid roughly


to

that of the filtrate by means of the taring wheel.

this

point

on the system spontaneously reaches

its

From
steady

state after a short time span (some minutes)


Since the preselected negative balance cannot be changed
during a cycle,

the selected value should be adequate, as it

is never a problem to reach a positive balance.


prototype (1),
infusion

to

In our first

negative balance was achieved by allowing


drip

into a 2-L container

hanging

below

an
the

connecting square bar; this procedure also allowed for adaptation of negative balance during a cycle.
This may be used
by skillful nurses or physicians in addition to or instead of
regulation using preselected balance positions.
Clinical experience.
The

newly developed mechanical balance system (1,3) has

been used since April 1982 as an aid in CAVH in six different


intensive care units in which quite different frequencies
acute

renal

advanced

failure occur.

system

has

Since the summer of

been used as described

above

1984

of
the

without

Fluid Balance in CAVH

86

In contrast to sophisticated electronically


problems (3).
regulated systems our method simplifies CAVH and eliminates
its greatest disadvantage, i.e., the need for manual balancing.
The basic system can also be used for the purpose of
forced

diuresis

when

adequate

hypo-osmolar

substitution

fluids are used.


For special purposes the "Hannover balancing system" can
be

combined

(Sartorius,
ducer

with

the

infusion

control

Infusart R

unit

Gottingen, FRG) by interposing the weight trans-

between

the bag and the bag hook on the

upper

The weight of the transducer must be compensated by a


of 400 g on the counterbalance side.

beam.
weight

In this way, the amount

of delivered fluid can be displayed continuously,

the amount

of sUbstitution fluid delivered per minute or per hour can be


displayed also, and an alarm function can be programmed to be
activated after substitution of 4.5 L.
(Table

1)

with a simple

it is possible also to read the amount of

sponding filtered fluid.

table
corre-

Though it is not necessary for the

balancing device, this allows an exact hourly balance display


for

control

purposes.

This is especially

useful

when

negative balance is sel ected


Table 1.

Hannover balancing system conversion table.


Fil trate at preselected
negative balance

Substitution
fluid
- 0

- 500

- 1000

- 1500

- 2000

500
1000
1500
2000
2500
3000
3500
4000
4500

555
1111
1666
2222
2777
3333
3888
4444
5000

611
1222
1833
2444
3056
3667
4278
4889
5500

667
1333
2000
2667
3333
4000
4667
5333
6000

727
1444
2167
2889
3661
4333
5056
5778
6500

87

H. Schurek
In

principle,

it

is possible to suspend larger

fluid

units for exchange, however, it is more practical to restrict


the balance period to 6-8 hours, as the clinical situation of
the patient often requires frequent revision of the target
balance.
OTHER SYSTEMS WITH AUTOMATIC FLUID BALANCE
System for controlled cyclic sUbstitution.
Schultheiss et al (4) developed an electrically powered
system mounted on a trolley that uses an electromechanical
sensor to give a signal to a magnetic valve within the infusion line when the sum of infusion fluid and filtrate is
increased
magnetic

by

amounts of 25 to 50 mL.

The opening

of

valve is cyclically operated by the imbalance

the
pro-

duced by filtration of this amount.

A negative
pump,

which

balance is achieved by an

electric

roller

draws fluid from the filtrate container into

Fig.
4.
Schematic system for controlled cycle substitution
developed by Schultheiss et al (4):
1) Extracorporeal cir-

cuit.
2) Heparin pump.
3) Hemofilter.
4) Filtrate to be
substituted.
5) Filtrate for negative fluid balance.
6)
Roller pump.
7) Magnetic valve. 8) substitution fluid. 9)
Electromechanical sensor.
10) Container suspension.
11)
Control unit.

Fluid Balance in CAVH

88

graduated cylinder.

The system is designed with an

optical

and acoustic malfunction alarm.


Programmable electronic balancing systems.
Sartocare R system.
One step away from

these

simple

techniques is the fully automatic balancing Sartocare R system


(2), (Sartorius, Gottingen, FRG).
an

and substitution fluid.


as

This system is composed of

electronic balance that also controls the sum of filtrate


parenteral

fluids,
fluid

may

In principle, all other fluids, such

nutrition fluid and urine or


also be collected and

other

balanced.

drainage

Substitution

for CAVH is pumped by a roller pump through

bubble

catcher monitored by an air detector and a pressure control.


A total balance can be programmed for up to 24 hr.
main

The

drawback is that critically ill intensive care patients

with multiple organ failure demonstrate an array of


individual

problems,

thus,

changing

therapeutic decisions may often

need to be revised at short notice.


computer-assisted monitoring.
The
computer-assisted
intensive care unit, usually the cardiac surgery unit, provides

the possibility of integrating the balance problem

CAVH into the available facilities.


with
and

Electronic force gauges

adequate range limits can be used to follow

filtration

substitution rates and adapt them by means of an

interface to the desired balance.

of

analog

Thus substitution rate can

be regulated by a computer program.


The

computer system demonstrated by Mason et al (5)

of

a high technical standard and provides graphic

of

24-hr

placed

balance.

printouts

The authors state "that their

on 'user friendliness' has been

readily

is

emphasis

assimilated

into the nursing process and has fulfilled their expectations


of successful operation by non-specialist nurses
only a few minutes tuition."
The

system

is not a closed-loop system

that

following
provides

automatic substitution with respect to measured filtration.


These authors'
experience as well as ours was that the
relationship

between

outflow

and

replacement

requires

H. Schurek
frequent

89
revision

in

order to take account

of

clinically

determined events such as transfusions and feeding.


ACKNOWLEDGMENT
Dr. Paul Cullen gave me valuable criticism and
linguistic advice in preparing this chapter.

expert

REFERENCES
1.
2.
3.
4.
5.
6.
7.

Blood purification 1:189-196,


Schurek HJ, Biela JD:
1983.
Schunemann B, Kramer P:
In: Arterio-venose haemofiltration,
Kramer
P (ed),
Vandenhoeck & Ruprecht,
Gottingen, Zurich, pp 99-108, 1982.
Schurek HJ, Biela JO, Bergmann KH:
In:
Continuous
arteriovenous hemofiltration (CAVH), Sieberth HG, Mann H
(eds), Karger, Basel, pp. 67-75, 1985.
schultheiss R, Brings W, Glockner WM, Sieberth HG: In:
Continuous arteriovenous hemofiltration (CAVH), Sieberth
HG, Mann H (eds), Karger, Basel, pp 64-66, 1985.
Mason JC, Cowell TK, Hilton PJ, Wing AJ:
In: Continuous arteriovenous hemofiltration (CAVH), Sieberth HG,
Mann H (eds), Karger, Basel, pp 37-44, 1985.
Olbricht C, Muller C, Schurek HJ, Stolte H: Trans Am
Soc Artif Intern Organs 28:33-37, 1982.
Kramer P: In: Arterio-venose haemofiltration, Kramer P
(ed), Vandenhoeck & Ruprecht, Gottingen, zurich, pp
inside cover, 1982.

6
HEMOFILTRATION AND ULTRAFILTRATION:

NURSING CONCERNS

G. WHITMAN
The Cleveland Clinic Foundation, Cleveland, Ohio

In the past two decades,


extracorporeal

therapy

new methods and techniques

have brought about vast

and concurrent expansion of its clinical


dialysis
therapy

role.

Previously,

and isolated ultrafiltration had been the


for

Dialysis,

patients

from

with acute

oliguric

clinical standpoint,

of

improvement

renal

is the

mainstay
failure.

removal

of

endogenous and exogenous toxins and other harmful substances


from the body fluids by differential diffusion across a
semipermeable membrane.
able

membrane

is

ultrafiltration.

Mass transfer

based on two

across a

mechanisms,

diffusion

and

Diffusion, a conductive process, is a pas-

sive transfer of solutes across a membrane.


is

semiperme-

Ultrafiltration

convective process in which simultaneous

transfer

of

solutes and solvent across the membrane occurs.

In the past,

ultrafiltration

in

procedures were performed only

isolated

fashion; either predialysis or postdialysis, ultrafiltration


was used to remove significant amounts of fluid in relatively
small periods of time,
of

i.e.,

2-6 hours.

This rapid removal

2-3 liters of fluid could produce hemodynamic instability

in acutely ill patients.


Another technique of extracorporeal therapy is
ous

ultrafiltration.

and

solutes

Continuous
and

continu-

This is a method whereby plasma water

are removed over a prolonged


ultrafiltration can remove

period

water,

of

time.

electrolytes,

some other substances from the vascular system at

rates

that do not effect hemodynamic stability,


since the 2-3
liters of fluid is removed over a 24-hour period or longer.
This continuous removal of excess fluid and solutes also
allows therapeutic regimen requiring fluid administration,

91

92

Nursing Aspects

such as vasoactive support or nutritional therapy, to be


undertaken in oliguric patients without the danger of hypervolemia, congestive heart failure, and pulmonary edema.
within

the general technique of

two distinct methods have arisen:


tration

(SCUF)

continuous

ultrafiltration

slow continuous ultrafil-

and continuous arteriovenous

hemofiltration

(CAVH)
SLOW CONTINUOUS ULTRAFILTRATION
Slow continuous ultrafiltration (SCUF)

is a

technique

whereby fluid
(plasma water) is removed continuously and
slowly from a patient over a prolonged period of time. Fluid
removal
uses

an

is accomplished via an ultrafiltration process


ultrafiltration membrane attached to some

vascular access (Fig. 1).

Fig. 1.

form

that
of

Vascular access for this procedure

Schematic representation of the SCUF circuitry.

G. Whitman

93

can be achieved via a Scribner shunt, Shaldon catheters, or a


The

fistula.
arterial

ultrafiltration

and

membrane is attached to

venous lines of the vascular

access

the

so

that

arterial blood flows through the ultrafiltration membrane and


returns
enters
used

to
the

to

the patient via the venous arm.


arterial end,

prevent

parameters

clotting

As

the

blood

a continuous heparin infusion


at

the

membrane.

are measured from the venous

arm.

is

Coagulation
The

heparin

infusion is then titrated to maintain these parameters within


designated

ranges.

Coagulation parameters that can be used

are activated clotting time (ACT) or Lee White clotting

time

(LWCT).
Plasma water or ultrafiltration fluid exits via the
sideport.
The rate of flow or the rate of removal of the
ultrafiltrate may be controlled by a volumetric pump or a
screw clamp on the sideport. with the SCUF system, ultrafiltration flow is usually maintained at 150-200 mL/hr and may
continue for 24-72 hours or longer.
It is usually only
discontinued
the therapy.

for diffusion dialysis or at the termination of

Various ultrafiltration membranes exist.


illustrated

in

Figure

1,

has the capability

The Amicon-20,
of

removing

approximately 40 mL/min of ultrafiltrate if the flow rate


the

sideport is not controlled by a screw clamp or an

of

infu-

sion pump. The surface area of this membrane is approximately 0.2 m2 and the membrane has a priming volume of 25 mL. As
a consequence of this low priming volume,
evacuation
(as

can

hypotension due to

of a large volume of fluid from the vascular tree


be seen in normal initiation of dialysis is

not

problem)
Control of the heparin infusion and the ultrafiltrate flow is the responsibility of the individual bedside
nurse.
Specific nursing guidelines for the initiation and
maintenance of the SCUF system can be found in Appendix 1.
CONTINUOUS ARTERIOVENOUS HEMOFILTRATION
Continuous arteriovenous hemofiltration (CAVH)
is a
technique whereby fluid
(plasma water)
and solutes are
removed

On

a slow continuous basis via

large-volume

fluid

Nursing Aspects

94

exchanges.
The technique used to accomplish this is very
similar to the technique described above for SCUF.
CAVH is
performed with an ultrafiltration membrane attached to a
vascular

access site.

heparin

infusion

Administration and titration of

and control of the ultrafiltrate

similar to that used with SCUF.


niques

flow

the
is

The difference in the tech-

is that in addition large volumes of sterile pyrogen-

free

electrolyte solutions are administered via

port

on the vascular access device.

In

the

general,

infusion

rates for this CAVH fluid average 400-600 mL/hour.


tration

rates

venous

Ultrafil-

will then either equal or exceed the

infused

volume in order to maintain a negative fluid balance,


accomplishing the fluid removal.
Solute removal is achieved
because infusion of these quantities of CAVH solution assists
in

providing

solute
that

a dilutional solute

removal

composition of the ultrafiltrates


of

the patient's plasma.

mechanism.
generally

Therefore,

The

mirrors

by

withdrawing

infusing

replacement

large

amounts of ultrafiltrate and by

fluid

the patient's serum levels of the non-replaced solutes

declines.
tively

This form of dilutional solute removal can effec-

limit

Specific

or

take

the

place

of

diffusion

nursing guidelines for the initiation

dialysis.

and

mainte-

nance of the CAVH system can be found in Appendix 2.


The
bility

bedside nursing practitioner assumes the


for

s~tems

patient.

maintaining

and monitoring the

as well as providing nursing care to the


Appendices

and 2 provide some

maintaining these devices.


diagnoses

SCUF

provides

responsiand

CAVH

individual

guidelines

for

The following section on nursing

framework to assist in

planning

and

implementing nursing care for these patients.


NURSING DIAGNOSES
Potential for alteration in cardiac output related to
inappropriate volume status.
Patient outcomes.
symptoms
evidenced

of
by:

The

patient will exhibit signs

adequate cardiac output and

volume

status

adequate cardiac output/cardiac index,

and
as
ade-

G. Whitman
quate

95

filling pressure,

normotension,

signs and symptoms of hypovolemia or

absence of

physical

hypervolemia,

adequate

electrolyte profiles, maintenance of prescribed ultrafiltrate


removal and infusion rates.
Nursing orders.
1. Identify and describe mechanism or
factors that contribute to alteration in volume status during
SCUF or CAVH.
Hypovolemia

can

develop

due

to

ultrafiltrate

fluid than prescribed,

ultrafiltrate

fluid at prescribed amounts,

ultrafiltration membrane,

removal

long-term

of

more

removal

of

leaking from the

and inadequate replacement rate of

CAVH infusion.
Factors
sion

of

responsible for hypervolemia include

CAVH fluid,

a decrease

in

overinfu-

ultrafiltration

rate,

and/or a worsening of the patient's underlying condition.


decrease
that

in

the ultrafiltration rate may be the first

clotting

decrease

is occurring at the

membrane.

in flow may occur after an episode of

A
sign

transient

hypotension.

Normal flow should resume once the blood pressure returns

to

normal.
These complications are usually precipitated by
technical problems with the SCUF/CAVH systems or infusion
pumps.

When these problems develop, assessment of the equip-

ment is the first priority.


Alterations in electrolyte concentrations can also occur
and

may assist in altering the volume status.

This

has

greater potential of occurring with the CAVH system than with


SCUF due to the removal of larger fluid volumes.
2.

Monitor and assess the SCUF/CAVH systems.


Infusion pumps:
a.

Monitor pump function at frequent intervals.

b.

Maintain all pump alarms in "on" position.

c.

Record

the

intake and output parameters

every

hour and otherwise as necessary.


d.

Maintain

infusion and ultrafiltrate removal at


by the physician.
Notify
physician if parameters cannot be maintained. A
levels

20%

or

determined

greater fall

in

ultrafiltration

flow

Nursing Aspects

96

should be brought to the physician's


attention.
Ultrafiltrate membrane:
a.

immediate

Observe frequently for disconnections, cracks,


increasing air bubbles in the ultrafiltrate
fluid,

clotting at membrane,

or a decrease

in

ultrafiltration flow.

b.

Observe

color

of

ultrafiltrate

at

frequent

intervals.
c.

Document appearance of ultrafiltrate on

nurses'

notes every eight hours.


Ultrafiltrate should
normally appear pale yellow.
If pink ultrafiltrate or frank bleeding is noted, rupture of the
ultrafiltration membrane is present and the
membrane must be immediately removed or changed.
Vascular access sites:
a.

Observe

b.

During

dressing

and

bedding

frequently

for

wetness or dampness.
dressing

changes and access

site

care

routines, check for leakage.


c.

Observe

vascular

clotting,
tube.
d.
3.

such

access tubing

for

as separation of plasma in

of
the

This occurs most frequently on the venous

side.
Auscultate and document the status of
bruits near the access site.

Monitor,

signs

assess,

and

vascular

record signs and symptoms of

hypovolemia.
a.

b.

Decreased cardiac output/cardiac index: cardiac


output less than 5 liters per minute and cardiac
index less than 2.7 liters/minute m2
Inadequate
dynamic

filling pressures:

variables

less

than

monitored hemotheir
expected

ranges.
c.

Fluctuations in the baseline of the right atrial


pressure
tion.

tracing

with inspiration and

expira-

97

G. Whi tman
d.

mean arterial pressure less

Hypotension:
60

mmHg.

than

The arterial wave configuration in a

hypovolemic

state

is characterized by

slow

upstroke, a prolonged peak, and a dicrotic notch


that is less than one-third of the height of the

4.

e.

curve.
Tachycardia:
per minute.

f.

Weak, thready pulses.

g.

Decreased level of consciousness.

h.

Prolonged peripheral filling time.

i.

Poor skin turgor.

Monitor,

access,

heart rate greater than 110 beats

and record signs and symptoms

of

hypervolemia.
a.
b.

Decrease in ultrafiltration rate.


Overinfusion of CAVH fluid.

c.

Decreased cardiac output/cardiac index:

cardiac

output less than 5 liters per minute and cardiac


index less than 2.7 liters/minute/m 2
d.
e.

Elevated filling pressures.


Presence

of "v" waves on atrial pressure waves.

These waves develop when the ventricle


is
dilated.
This dilatation prevents the cusps of
the

mitral

each

and tricuspid valves from

other during closing.

regurgitant
during

touching
of

this,

flow back into the atria can

occur

systole.

This

Because

regurgitation

creates

exaggerated "v" waves on the atrial tracings.


f.

Hypotension:

g.

60 rnmHg.
Tachycardia:

mean
heart

arterial pressure less than


rate

than

llO

obliterated

with

greater

beats/minute.
h.

Bounding

pulses

not

easily

i.
j.

pressure.
Peripheral edema.
Weight gain greater than 0.5 kg per day.

98

Nursing Aspects
k.
5.

Engorgement of peripheral veins.

1. Pulmonary rales.
Monitor and assess for signs and symptoms

of elec-

trolyte abnormalities.
6. Implement strategies according to nursing judgement,
physician's order, or standing unit policies to assist in
controlling volume status or technical problems.
a.

Ruptured

membrane.

Diagnosis

is

made

by

presence of pink-tinged or bloody ultrafiltrate.


Membrane should be changed immediately.
filtrate
stopped
b.

flow
to

should be slowed

Ultra-

completely

prevent blood loss during

tions for membrane change.


Decrease of 20% or greater
rate.

or

in

prepara-

ultrafiltration

This is usually indicative of clotting at

the membrane.
Assess systems to assure proper
functioning.
If flow remains low despite corrective
changed.

measures,

the

membrane

needs

to

be

Depending on the degree or severity of

the clotting the membrane may require immediate


changing or change may be delayed for brief
The latter may be appropriate if, for
periods.
example, the system has been scheduled for discontinuation soon.
Administration of a heparin
bolus may assist in maintaining or extending the
patency
result

of the membrane.

Clotting may be

of inadequate heparinization,

the

prolonged

hypotension, or prolonged membrane usage.


c.

Air

withdrawal from

the

could indicate clotting at the membrane.


all

Assess

connections to assure that there is no leak

or kink in the system.


and

This

ultrafiltrate.

If these are

corrected

their correction does not halt the entrance

of air into the ultrafiltration tubing clotting


may be beginning and the membrane may need to be
changed. This is more likely to occur with CAVH
than

with

SCUF.

The condition is due to

the

99

G. Whitman
large

volumes

the membrane is clearing

on

an

hourly basis and to the levels of negative pressure the infusion pump is generating.
d.

Hypovolemia.
of

This most often reflects the loss

intravascular

fluids

is

the

volume.

Administration

treatment

of

choice.

of

Normal

sterile saline is the preferred replacement


solution.
Decreasing the ultrafiltration rate
is usually not performed. Iatrogenic blood loss
from

frequent blood sampling for various

can also contribute to hypovolemia.


electrolyte
are

values

identical,

of serum and

samples

of

the

tests

Because the
ultrafiltrate
ultrafiltrate

rather than the serum can be sent to the laboratory for analysis.
filtrate

levels

phosphorus,

However, because the ultraof

and

total

protein,

enzymes do not

calcium,

reflect

serum

values, serum samples are required for laboratory analysis of these substances.
e.

Hypervolemia.

Treatment for this can consist of

increasing the rate of the ultrafiltrate flow or


decreasing the infusion rate of the CAVH fluid.
The underlying cause should also be treated.
f.

Electrolyte
electrolytes

imbalances.

Replacement

of

lost

can be achieved by adding them

to

either the CAVH solution or the patient's hyperalimentation formula.

Again,

commonly with the CAVH system,

this occurs more


due to the

mas-

sive fluid exchange.


g.

Oozing

of vascular access site.

This requires

immediate notification of the physician.


sion

or

reinsertion of lines is

usually

Reviper-

formed.

h.

Leaking
casing

membrane.
of

splintered.

the

This occurs when the

membrane

Depending

becomes

outer

cracked

or

on the severity of

the

leak and the interval of time before a previous-

100

Nursing Aspects
ly

scheduled termination,

the membrane mayor

may not be changed immediately.


Potential for volume loss or hemorrhage related to
anticoagulation.
Patient outcomes.
adequate
prescribed
200

The

patient

anticoagulation as evidenced

will exhibit signs


by:

clotting times (activated clotting times of

seconds;

Lee-White

of

maintenance

clotting times of

25-40

of
150-

minutes),

absence of occult or obvious bleeding.


Nursing orders.
predispose

1.

Identify

risk

factors that

the patient to excessive bleeding or

may

hemorrhage.

Patients with previous histories of gastrointestinal bleeding


or hepatic involvement are at a high risk for bleeding
tendencies.

Patients

with moderate hepatic involvement may

not require anticoagulation with heparin as auto-anticoagulation

may

be

sufficient to allow the

systems

to

function

heparin to maintain prescribed

clotting

without clotting.
2.

Administer

times.
3.

Monitor

and assess

the patient for signs and symp-

toms of over-anticoagulation.
a.

Oozing from intravascular lines.

b.

Guaiac-positive nasogastric drainage.

c.

Hematuria.

d.

Oral or nasal mucosal drainage.

e.

Neurological changes.

f.

Melena.

g.

Coagulation

values greater than the

prescribed

parameters.
4.

Avoid

insertion

or removal of

central

venous

arterial lines during periods of anticoagulation.

or

If inser-

tion or removal is necessary, transient removal from the SCUF


or CAVH systems and reversal of the heparin with protamine
sulfate are required.
Potential alteration in physical mobility related to
ultrafiltration device.
Patient outcomes.
adequate

mobility

as

The

patient will exhibit

evidenced by:

maintenance

signs
of

of
pre-

101

G. Whitman

procedure range of motion of involved extremities; absence of


complications

of

immobility such as

decubiti

or

thrombo-

phlebitis.
Nursing orders.
with

Kerlix

1.

Attach device to involved extremity

providing padding or cushion between

patient's

skin and the device.


2.
nections

Assure that the wrapping allows easy access to

con-

and the ultrafiltration port and avoid kinking

and

excessive bending of the lines.


3. Provide passive range-of-motion therapy to the

ex-

tremity

every

two hours while awake or QID.

Turn

patient

every two hours.


4.
If device is attached to an upper extremity, and the
patient

is capable of ambulating,

ambulate the patient

routine of the underlying disease.

per

Use IV pole to assist in

equipment movement.
5.
patient
disease.

If the device is attached to lower extremity,


out

of bed in a chair per

routine

for

place

underlying

Keep lower extremity elevated to the hip level.

6. Assess and document the status of the patient's


range of motion, skin integrity, and pulses in the involved
extremity.
Potential for infection related to prolonged vascular access.
Patient outcomes.
absence
thermia,
sites.

The

patient

will exhibit signs

of infection as evidenced by:

normal

WBC,

of

normo-

lack of erythema, drainage, or exudate at insertion

Nursing orders.

1.

Observe

and document

status

of

vascular access insertion sites during dressing changes.


2.

Perform vascular access site care per unit routines.

3.

Obtain and record temperature QID.

4.
5.

Observe WBC.
Monitor routine culture reports.

102

Nursing Aspects

APPENDIX 1
Nursing guidelines for the initiation and maintenance of the
SCUF system.
Equipment:
Two volumetric infusion pumps and cassette tubing
250 mL bag or bottle of patient's base IV solution
Vial of heparin
Roll of Kerlix
1/2 inch adhesive tape
Urinary drainage bag
Hemochron
ACT tubes or tubes for LWCT
Amicon

diafilter

20 with attached arterial and

venous

sleeves (supplied by dialysis technicians)


IV extension tubing
Tuberculin syringes
20-g needles
Alcohol wipes
Nursing actions and rationale.
1. Obtain a written order
the procedure.
rate
will

prior to the initiation

of

This should include the desired ultrafiltrate

per hour, as well as the ACT or LWCT parameters that


govern the titration of the heparin infusion by the

bedside

nurse.

Normal

ACT levels will most frequently

ordered to be maintained at 150-250 seconds.

be

If the LWCT is

used, it will generally be maintained at 25-40 minutes.


2.

Explain the procedure to the patient and the family.

Explanations will assist in decreasing anxiety and

enhancing

compl iance.
3.

Weigh

the

patient.

This is not necessary if

the

patient has been weighed in the last twenty-four hours.


4.

Prepare two volume infusion pumps.


A.

Add

12,500

units of heparin to 250 mL

patient's base IV solution.

Connect it

priately to the first infusion pump.


first

infusion

pump with a "HEPARIN"

of

the

appro-

Label this
sticker.

103

G. Whi tman

Once the system is initiated, this infusion will


be attached to the Luer-lok arterial port.
B.

Connect
pump,
of

cassette tubing to the second

infusion

attach an 18-g needle to the infusion end

that tubing and then insert the needle

into

the rubber tubing on top of the urinary drainage


bag.
Label this second infusion pump with an
"ULTRAFILTRATE" sticker.
This infusion pump
uses the ultrafiltrate membrane as the reservoir
of fluid, Le., the IV bag.
Once an infusion
rate is set on the infusion pump, it will remove
that

much

fluid per hour

ultrafiltration

membrane

from

the

patient's

and empty

the

fluid

into the urinary drainage bag.


(1).

Attach extension tubing to the inflow port


of the cassette.

(2).

The

distal

end of this extension

tubing

will be attached to the ultrafiltrate port


of the membrane once SCUF has been

initi-

ated.
5.

Provide

any assistance needed to the dialysis

per-

sonnel as they establish the SCUF system.


6. As soon as the membrane is attached obtain a blood
sample from one of the arterial ports in order to measure a
baseline
Only at

determination of the patient's ACT or LWCT levels.


the initiation of the procedure is the clotting

parameter obtained from the arterial port.


for heparin
port.

All other samples

regulation should be obtained from

the

venous

To obtain ACT level:


A.

Cleanse the port with an alcohol wipe.

B.

withdraw

1/4-1/2 mL of blood using a TB syringe

and 20-g needle.


C.
D.
E.

Place blood into the ACT tube.


Depress timer switch on Hemochron.
Place tube into the Hemochron and rotate tube
clockwise until green indicator light comes on.

104

Nursing Aspects
F.
G.
H.

Then turn tube another 360 degrees.


Machine will sound an audible alarm when ACT
level is calculated.
The number depicted on the digital display after
the

alarm

sounds is the ACT level

and

should

then be transcribed to the nurses' notes.


To obtain LWCT:
A.

Cleanse the port with an alcohol wipe.

B.

withdraw

1/4-1/2 mL of blood using a TB syringe

with a 20-g needle.


C.
D.

Place blood in a test tube and allow to sit in


an upright position.
Every 5 minutes gently pick up the tube and
slightly

tilt it to the side.

formation

Observe for the

of a clot on the bottom of

the

and the separation of plasma to the top.

tube
Avoid

shaking or unnecessary agitation of the tube, as


this will cause the forming clot to lyse and the
LWCT will be inaccurate.
E.

The

time

it takes for this clot

formation

to

occur is the LWCT.


7. Set the ultrafiltrate pump at the rate ordered by
the physician.
This should initiate withdrawal of ultrafiltrate from the membrane into the urinary drainage bag.
8.
of

Administer

2,000 units of heparin IV bolus into one

the arterial ports.

"loading"

dose

This bolus of heparin serves

as

to assist in maintaining the patency of

a
the

ultrafiltrate membrane.
9. Attach
arterial port.

the

heparin infusion pump to

the

Luer-lok

10. Initiate the administration of heparin solution


the rate of 10 mL/hour or 500 unit/hour.
11. Obtain ACT or LWCT samples from the venous port

at
60

minutes after the initiation of the heparin infusion.


12.

Titrate the heparin infusion to achieve the

ACT or LWCT levels.

desired

Titration in 1-2-mL increments is usual-

G. Whitman

105

ly adequate to achieve control of the clotting

times,

since

each mL contains 50 units of heparin.


13.

Continue

to measure the prescribed clotting

param-

eters hourly until they have remained stable for three


consecutive hours and have thus required no further adjustment of the heparin infusion.
After this point has been
reached, the clotting times can be measured every 8 hours.
If at any time the levels alter such that a manipulation of
the heparin infusion is required, measuring of the clotting
times

should

patient's
hours.
14.
notes.
reflect

be

resumed

clotting

at

hourly

intervals

until

status has again remained stable

the

for

Record the ACT and LWCT results on the nurses'


An ACT or LWCT level above the prescribed limit may
excessive anticoagulation.
Signs of clotting dis-

orders include oozing of blood from IV sites, hematuria,


neurological
changes,
or
guaiac-positive
nasogastric
drainage.
Bleeding when the levels are within the accepted
range can occur, particularly in patients with a history of
gastrointestinal bleeding or hepatic dysfunction.
15.
quency

Record
rate

the

heparin dosage hourly or with the

changes

on

the

nurses'

notes.

fre-

Indicate

volume/dose, i.e., 10 mL/500 units.


16.
the

Measure ultrafiltrate volume hourly,

nurses'

flow

sheet in a column

and record

designated

on

"ultrafil-

trate".
Continue to monitor the flow rate of ultrafiltrate
every 15-20 minutes to assure that the correct amount is
being withdrawn.
17. Record the amount of ultrafiltrate on the 24-hour I
& 0 sheet in a separate column from urine output.
Recording
ultrafiltration output in the urine output column could cause
a misleading assessment of the patient's renal status.
18.
separate
included
19.
is being

Record the amount of heparin solution infused in a


column on the 24-hour I & 0 sheet.
Heparin is
in the hourly fluid total.
Continue to perform the above functions while SCUF
used.

Nursing Aspects

106
20. Provide any assistance necessary to
sonnel when they terminate the SCUF system.

dialysis

per-

APPENDIX 2
Nursing guidelines for initiation and maintenance of the CAVH
system
Equipment:
Three volumetric infusion pumps and cassette tubing
CAVH replacement fluid
250 mL bag or bottle of patient's base IV solution
Vial of heparin
Roll of Kerlix
1/2 inch adhesive tape
Urinary drainage bag
Hemochron
ACT tubes or tubes for LWCT
Amicon

diafilter

20 with attached arterial and

venous

sleeves (supplied by dialysis technician)


IV extension tubing
Tuberculin syringes
20-g needles
Alcohol wipes
Nursing actions and rationale
1.
the

Obtain

procedure.

written order prior to the initiation


This should include the infusion

constituents of the CAVH solution,


rate

per

will

govern

bedside

hour,

as well as the ACT or LWCT parameters


Normal

of
and

the desired ultrafiltrate

the titration of the heparin

nurse.

rate

infusion

by

ACT levels will most frequently

ordered to be maintained at 150-250 seconds.

that
the
be

If the LWCT is

used, it will generally be maintained at 25-40 minutes.


2.

Explain the procedure to the patient and the family.

Explanation

will assist in decreasing anxiety and

enhancing

compliance.
3.
patient

Weigh the patient.


This is not necessary if the
has been weighed in the last twenty-four hours.

G. Whi tman
Daily

107

weight should be measured while the patient is

under-

going CAVH.
4.

Prepare the three volume infusion pumps.


A.

Add

12,500

patient's

units of heparin to 250 mL


base IV solution.

of

the

Connect it appro-

priately to the first infusion pump.

Label this

first infusion pump with a "HEPARIN" sticker.


Once the system is initiated, this infusion will
B.

be attached to the Luer-lok arterial port.


Connect cassette tubing to the second infusion
pump,

attach an 18-g needle to the infusion end

of that tubing,

and then insert the needle into

the rubber tubing on top of the urinary drainage


bag.

Label

this second infusion pump with

"ULTRAFILTRATE"

sticker.

This

infusion

an
pump

uses the ultrafiltrate membrane as the reservoir


of fluid,

i.e.,

the IV bag.

Once an infusion

rate is set on the infusion pump, it will remove


that

much

fluid

per hour from

the

patient's

ultrafiltrate membrane and empty the fluid

into

the urinary drainage bag.


(1).

Attach extension tubing to the inflow port


of the cassette.

(2).

The

distal

end of this extension

tubing

will be attached to the ultrafiltrate port


of the membrane once CAVH has been initiated.
C.

Obtain

CAVH

fluid

from

pharmacy

and

attach

appropriately to the third infusion pump.

Label

this infusion pump with a "CAVH" sticker.

Once

the

system is initiated,

this infusion will be

attached to the Luer-lok venous port.


5.

Provide

any assistance needed to the dialysis

per-

sonnel as they establish the CAVH system.


6.

sample
baseline

As

soon as the membrane is attached obtain a

blood

from one of the arterial ports in order to measure


determination of the patient's ACT or LWCT

levels.

108

Nursing Aspects

Only at the initiation of the procedure


parameter obtained from the arterial port.
for heparin
port.

is the clotting
All other samples

regulation should be obtained from

the

venous

To obtain ACT level:


A.

Cleanse the port with an alcohol wipe.

B.

Withdraw 1/4-1/2 mL of blood using a TB

syringe

and 20-g needle.


C.

Place blood into the ACT tube.

D.

Depress timer switch on Hemochron.

E.

Place

tube

into the Hemochron and rotate

tube

clockwise until green indicator light comes on.


F.

Then turn tube another 360 degrees.

G.

Machine

H.

The number depicted on the digital display after

will

sound an audible alarm

when

ACT

level is calculated.
the

alarm

sounds is the ACT level

then be transcribed to the nurses'

and

should

notes.

To obtain LWCT:
A.

Cleanse the port with an alcohol wipe.

B.

Withdraw 1/4-1/2 mL of blood using a TB

syringe

with a 20-g needle.


C.

Place

blood in a test tube and allow to sit

in

an upright position.
D.

Every 5 minutes gently pick up the tube


slightly tilt it to the side.
Observe for
formation

of

and
the

a clot on the bottom of the

and the separation of plasma to the top.

tube
Avoid

shaking or unnecessary agitation of the tube, as


this will cause the forming clot to lyse and the
LWCT will be inaccurate.
The time it takes for this clot
occur is the LWCT.

E.

7.
of

the

"loading"

formation

Administer 2,000 units of heparin IV bolus into


arterial ports.

This bolus of heparin serves as

dose to assist in maintaining the patency

ultrafiltrate

ma~brane.

of

to
one
a
the

G. Whitman

109

8. Set the CAVH pump at the rate ordered by the physician and begin the infusion.
This should initiate infusion
of the CAVH fluid into the venous port of the system.
9.
the

Set

the u1trafi1trate pump at the rate

physician and begin withdrawal.

withdrawal of ultrafi1trate
urinary drainage bag.
10. Attach
arterial port.

the

from

This
the

ordered

should

initiate

membrane

heparin infusion pump to

by

into

the

the

Luer-lok

11. Initiate the administration of heparin solution


the rate of 10 mL/hour of 500 units/hour.

at

12. Obtain ACT or LWCT samples from the venous port 60


minutes after the initiation of the heparin infusion.
13. Titrate the heparin infusion to achieve the desired
ACT or LWCT levels. Titration in 1-2-mL increments is usually adequate to achieve control of the clotting times,
each mL contains 50 units of heparin.

since

14. Continue to measure the prescribed clotting parameters hourly until they have remained stable for three
consecutive
ment

of

reached,
If

hours and have thus required no further

the heparin infusion.


the

After this point

adjusthas

clotting times can be measured every 8

been
hours.

at any time the levels alter such that a manipulation

the

heparin infusion is required,

times

should

patient's

be

clotting

resumed

at

of

measuring of the clotting

hourly

intervals

until

status has again remained stable

the

for

hours.
15.
notes.

Record the ACT and LWCT results on the nurses'


An ACT or LWCT level above the prescribed limit may

reflect

excessive anticoagulation.

Signs of clotting

dis-

orders include oozing of blood from IV sites, hematuria,


neurological
changes,
or
guaiac-positive
nasogastric
drainage.
Bleeding when the levels are within the accepted
range

can occur,

particularly in patients with a history of

gastrointestinal bleeding or hepatic dysfunction.

Nursing Aspects

110

16. Record the heparin dosage hourly or with


quency of rate changes on the nurses'
notes.

the freIndicate

volume/dose, i.e., 10 mL/500 units.


17.

Record

record

the infusion volume of CAVH fluid hourly and

on the nurses' notes in a column

Continue

designated

"CAVH".

to monitor the infusion rate every 15-20 minutes to

assure the correct amount is being withdrawn.

Careful moni-

toring of infusion and withdrawal rates is crucial since such


large volumes of fluid are involved.
18.
the

Measure

nurses'

trate".
every

ultrafiltrate volume hourly and

flow sheet in a

Continue
15-20

column

record

designated

on

"ul trafil-

to monitor the flow rate of ultrafiltrate

minutes to assure that the

correct

amount

is

solution

on

being withdrawn.
19.
the

Record

the amount of CAVH replacement

24-hour I & 0 sheet in a separate column from

other

IV

solutions.
20.

Record the amount of ultrafiltrate on

the 24-hour I

& 0 sheet in a separate column from urine output.

Recording

ultrafiltrate output in the urine output column could cause a


misleading assessment of the patient's renal status.
2l.

Record

separate

column

the amount of heparin solution infused in


on

the 24-hour I

& 0

sheet.

Heparin

a
is

included in the hourly fluid total.


22.

At the termination of therapy provide any assistance

necessary to dialysis personnel.


REFERENCES
1.
2.
3.
4.
5.

Continuous arteriovenous hemofiltration clinical protocol.


Ann Arbor:
University of Michigan printing
Services, 1984.
Earley S, Gottschalk B (eds):
In: Strauss and Welt's
Diseases of the Kidney,
Boston, Little and Brown
Company, 1979.
Henderson AE, et al: Clinical use of the Amicon diafilter. Dial Transpl 12:7, 532, 1983.
Kiely MA:
Continuous arteriovenous hemofiltration.
Critical Care Nurse 4:4, 39, 1984.
Kramer P, et al:
Management of anuric intensive care
patients with arteriovenous hemofiltration. Int J Artif
Organs 3:4, 225, 1980.

G. Whitman
6.
7.
8.

9.
10.
11.

111

Lauer A, et al: Continuous arteriovenous hemofiltration


in the critically ill patient.
Ann Intern Med 99:4,
455, 1983.
Paganini EP, Nakamoto S:
Continuous slow ultrafiltration in oliguric acute renal failure.
Trans Am Soc
Artif Organs 26:201, 1980.
Paganini EP, et al: Amino acid balance in patients with
acute renal failure undergoing slow continuous ultrafiltration. Scientific Sessions of the 27th Annual Meeting
of ASAIO, 11:1, 76, 1982.
Whitman G:
Continuous slow ultrafiltration.
Procedures:
Nursing Reference Library, Springhouse, PA,
Nursing 83 Series, 662, 1983.
Williams V, Perkins L:
Continuous ultrafiltration: A
new ICU procedure for the treatment of fluid overload.
Critical Care Nurse 4:4, 44, 1984.
Zbylut T, Nolph K:
Blood purification in acute renal
failure. Ann Intern Med 100:3, 447, 1984.

7
HYPERALIMENTATION IN ACUTE RENAL FAILURE
E. FEINSTEIN
University of Southern California School of
Angeles, California

In
acute

Medicine,

Los

recent years, nutritional therapy of patients with


renal failure (ARF) has become increasingly important.

This is especially true in patients with ARF related to, or


following surgery, trauma, or sepsis. It is these patients
who are most likely to demonstrate increased net protein
breakdown with malnutrition and wasting. These complications
contribute to impaired wound healing and decreased resistance
to infection.
Since the mortality rate in patients with ARF
and sepsis is very high (l), it is conceivable that provision
of

optimal

restore

nutrient intake may improve

the immune response.

wound

healing

and

This chapter will discuss the

reasons for the accelerated protein breakdown in ARF, analyze


the results of nutritional therapy,

and suggest some

future

approaches to therapy.
The degree of catabolism in patients with ARF is variable.
A major reason for this is the nature of the underlying disease(s}.
When ARF is due to uncomplicated radiocontrast media or aminoglycoside toxicity, it is usually not
associated with marked catabolism; whereas in the septic or
postoperative situation, significant elevations in catabolic
rate

are frequent.

In non-uremic patients with the

latter

condition, recent evidence points to the importance of


circulating proteases in promoting protein breakdown. Clowes
et al have demonstrated a circulating proteolytic peptide in
postoperative patients (2).
Baracos et al have implicated
interleukin
proteases

and

prostaglandin

E2

in

the

from the heart and skeletal muscles of

sepsis and fever (3).

release
rats

of
with

Disturbances in hormone metabolism are

also present in the septic and postoperative patients.


113

Blood

Hyperalimentation in ARF

114
concentrations
elevated
been

of

catecholamines (4) and glucagon

in these patients.

able

(5)

are

Bessey and co-workers (6) have

to reproduce many of the

catabolic

features

of

injured patients by infusion of hydrocortisol, epinephrine,


and glucagon into normal subjects.
They developed negative
nitrogen balance, increased energy expenditure, and augmented
protein catabolism.
In

patients with ARF and increased catabolism,

pathophysiologic
proteolytic

mechanisms may be

factors

have

been

operative.

demonstrated

similar

Circulating
by

Horl

Heidland in the sera of catabolic ARF patients (7).


also

associated

which

have

with many hormonal

Insulin resistance,
both

disturbances,

been implicated as important catabolic

glucose

and

and

growth

amino

acids (8,9),

is

release
sion

of

reasons

some

of

hormone (12) are also found in

ARF

is associated with

in

(10),

amino acids to urea and glucose

ARF.

ARF,

but

in

the

role

increased
(14,15).

does not increase in the rat with ARF

muscle
converProtein

(16).

for the failure of muscle protein synthesis to

include insulin resistance (16),

acid uptake (9),

of

glucagon

of amino acids (13) and accelerated hepatic

synthesis
may

is

factors.

common

further study is necessary to elucidate their


catabolic process.
Experimental

ARF

manifested by impaired muscle uptake

Elevated blood levels of parathyroid hormone


(11),

and

impaired muscle

and circulating inhibitors of protein

The
rise
amino
syn-

thesis (17)
Other factors which contribute to the wasting seen in
patients with ARF include the loss of protein from wounds and
fistulae; the removal of amino acids via hemodialysis, and
proteins and amino acids via peritoneal dialysis; and nausea,
vomiting,

and ileus which limit the amount of enteral nutri-

tion received.

In the past, the risk of fluid overload from

the large quantities of intravenous solutions required for


nutrition in catabolic, oliguric patients has led to insufficient nutritional intake.

115

E. Feinstein

The aims of nutrition in ARF have expanded since the


widespread use of dialysis.
No longer is the major goal one
of

limiting protein,

potassium,

control uremic toxicity.


hemofiltration

are

NOw,

and fluid intake so as


in many cases,

the usual methods of controlling

toxicity and fluid balance.

to

dialysis and
uremic

These treatment modalities allow

the administration of larger quantities of fluids and greater


amounts of protein than in the past.
the

It remains unclear what

optimal nutritional prescription in ARF should

date,

no

total parenteral nutrition (TPN)

conclusively
the

response,

To

regimen has

shown to reduce the morbidity of

catabolic

be.

ARF,

been

control

and improve the survival

rate

of

patients with ARF associated with trauma, surgery, or sepsis.


One
tion

major issue concerns which type of amino acid solu-

is

preferable,

essential amino acids alone

(EAA)

or

essential and nonessential amino acids (ENAA). Dudrick et al


(18)
and Abel et al (19) advocated the use of hypertonic
glucose and small amounts of EAA.
of

rise of serum potassium,

were

phosphorus,

and urea

nitrogen

reduced when compared to treatment with glucose

Wound

healing

prospective

was

EAA

also

controlled

glucose alone,
the

They showed that the rate

reported to
trial

of

be

EAA

alone.

improved.

and

In

glucose

versus

the recovery of renal function was greater in

group

(20).

Other

investigators

have

assessed

similar regimens but have not found similar results.


reports of Leonard et al (21) and Feinstein et al
degree
improved
treated

of

negative nitrogen balance was


in

the

patients.

not

EAA treated patients compared

In the

(22),

the

significantly
to

glucose

Serum protein concentrations and

plasma

amino acid remained below normal (22).


Another

nutritional regimen which has been evaluated in

ARF entails the use of ENAA and glucose.


approach

Advocates of

this

argue that the rationale for using small amounts of

EAA along--that they promote reutilization of urea


for synthesis of protein--has been disproven (23).

nitrogen
Further-

more, in the face of marked protein breakdown, it is likely


that all of the amino acids, essential and nonessential,

Hyperalimentation in ARF

116

would be required to promote synthetic processes.


of Toback and co-workers (24)
ENAA

and

The

work

in rats with ARF has shown that

glucose infusions promote the synthesis

cell membrane phospholipid synthesis.

of

renal

In the few studies in

which EAA and ENAA have been compared, the results have
differed. Mirtallo et al reported no difference in estimated
nitrogen balances or urea nitrogen appearance rates in two
groups of patients who were given about 5 gm of nitrogen
daily from either EAA or ENAA (25).

These patients, however,

had mild renal failure with creatinine clearances of about 12


mLjmin and were not receiving hemodialysis.
of

Feinstein et al (22,26),

and

15

In the

studies

patients who received between 5

gm of nitrogen from ENAA had

significantly

greater

urea nitrogen appearances and more negative nitrogen balances


than

those who received 2.0 to 2.5 gm of nitrogen from

EAA.

Serum proteins and plasma amino acids remained abnormally low


in the ENAA group (22).
As

to

reported
the

the

survival

with

ARF,

several

groups

have

improvement with EAA therapy and ENAA therapy.

prospective

controlled trial of Abel

et

aI,

In

hospital

survival was improved in those patients who had other serious


complications

such

as pneumonia (20).

In

the

controlled

trials of Leonard et al (21) and Feinstein et al (22),


was

no

significant difference in

receiving
there
with

glucose

survival

alone versus glucose and

among

patients

EAA.

Although

are retrospective studies reporting improved


ENAA

(27,28),

neither

Feinstein et

there

al

survival

(22,26)

Mirtallo et al (25) found any difference in survival

nor

between

ENAA and EAA therapy.


There
results

in

are

several reasons for the lack

the clinical trials.

Because ARF

of

consistent
comprises

heterogeneous group of patients who exhibit a range of


bolic

responses,

it is reasonable to assume that

cata-

different

quantities and different proportions of amino acids may be


required depending upon the individual patient.
Another
important consideration is that a greater intake of

calories

E. Feinstein
than

has

117

been provided until now may be needed in the

most

stressed patients (29).


Further research efforts should be directed towards
evaluation

of

formulations

with

branched-chain amino acids in ARF.


that

higher

proportions

the
of

Also, it may be possible

pharmacological intervention to control catabolism with

antiprostaglandin agents, with protease inhibitors, and with


insulin will prove beneficial.
The use of continuous
arteriovenous hemofiltration or slow continuous hemodialysis
is likely to obviate the problems of fluid overload which
were seen in past years.
THERAPEUTIC CONSIDERATIONS
The
beneficial

foregoing
effect

data suggest that there is


of parenteral nutrition

patients with acute renal failure.

on

However,

no

definite

survival

of

in view of the

frequently marked catabolism seen in this condition, the need


for nutritional support is clear.
The goals of nutritional
therapy are to improve nutritional status without causing
worsening of uremic toxicity.

In recent years, the emphasis

has been on the former objective.


frequent hemodialysis,

Most nephrologists rely on

ultrafiltration, or hemofiltration to

control the positive fluid balance and the rise in blood urea
nitrogen which may result from the nutritional therapy.
The nutritional strategy must take into account

the

level of catabolism of the patient and the ability of the


patient to be fed via the gastrointestinal tract.
The level
of catabolism can be determined from an assessment of the
patients clinical condition,
failure,

presence

i.e., underlying cause of renal

of associated catabolic

from laboratory data.

conditions;

and

The rate of rise of blood urea nitro-

gen (> 30 mg/dL/day) can be an important indication of increased protein breakdown in acute uremia.
A better method
of assessment is the calculation of the urea nitrogen appearance rate (UNA) using the following equations:

Hyperalimentation in ARF

118
UNA (g/day)

change in body urea nitrogen content

+ urinary urea nitrogen


(Eq. 1)

+ dialysate urea nitrogen (where applicable)


change in body urea nitrogen (g/day
[change in BUN (giL)

x body weight x 0.6 L/kg]

+ [change in body weight x final SUN (giL)]

UNA of greater than 5 g/day in a patient

renal

(Eq. 2)
with

acute

failure receiving no protein intake indicates a hyper-

catabolic state.

Also, because the UNA correlates well with

nitrogen output, it can be used for the bedside approximation


of nitrogen balance.
For the patient who is mildly catabolic,
tion

or

peripheral intravenous supplemental

suffice.
diet

enteral nutri-

If the patient can eat,

(0.5-0.5

Restriction

g/kg

of

body

salt

nutrition

may

then a restricted protein

weight)

should

and potassium

are

be

prescribed.

usually

required.

Fluid intake allowance will depend on the daily urine volume.


all

In

many cases,

the patient will not be able to

of

the required nutrition by mouth due to anorexia

episodic nausea and vomiting.


mented
as

ingest

The diet can then be

and

supple-

with enteral formulas specific for renal failure such

Amin-Aid

(American McGaw) or Travasorb

Renal

Labs)

which contain amino acids and carbohydrate.

quate

calorie

intake is the main problem,

supplement such as Polycose (Ross)

then

(Travenol
If
a

ade-

caloric

or Controlyte (Coyle)

may

be prescribed.
An

alternate

peripheral

route for supplementary

intravenous infusion.

Lipid emulsion and

acid solutions can be given in this way.


Table 1.
failure.

Peripheral

nutrition

amino

The 20% concentra-

intravenous nutrition in acute

Amino acids
essential amino acids or essential
essential amino acids
Lipid emulsion

is

and

renal

non-

E. Feinstein

119

tion of intravenous lipids, Intralipid (Cutter Labs)


or
Liposyn (Abbott Labs), contain 1,100 cal/500 mL.
Infusion of
essential amino acids (up to 21 g/day)
can be given to
patients

who are not markedly catabolic,

particularly those

for whom dialysis therapy is not required.


Patients

with evidence of marked catabolism are

to require intravenous alimentation;

likely

usually in the form

of

total parenteral nutrition (TPN).


The preferable source of
calories for patients with acute renal failure receiving TPN
is 70% dextrose/water, which provides 2.4 kcal/mL.
Calorie
needs will vary from 30 to 50 kcal/day depending upon the
extent

and

procedure.
essential

nature
Amino

of

the

traumatic

injury

or

surgical

acids should be given as a formulation of

and nonessential amino acids;

the

maximum

quantity currently recommended is 1 g/kg body weight.


emulsions

can

also be used but they should

not

daily
Lipid

contribute

more than one third of the daily calorie requirement.


The

requirements

for

vitamins,

minerals,

metals in acute renal failure are not well

and

trace

established.

It

is routine practice to administer a multiple vitamin preparation

containing the water soluble

vitamins.

However,

the

long term use of ascorbic acid in TPN regimen has been


Of the fat
reported to cause widespread oxalate deposition.
soluble vitamins, it is important to give vitamin K parenterally at least weekly during TPN therapy.
Vitamin A and D
supplementation are usually not required during the treatment
of

acute

renal

failure.

Electrolyte

supplementation

is

frequently needed, particularly for potassium, phosphate, and


magnesium.
Table 2.

The

daily

amounts of these electrolytes to

be

TPN in acute renal failure.

Amino acids - essential and nonessential amino acids: 1 gm/kg


body weight
Major calorie source: hypertonic dextrose (70% dextrose/water
yields 2.4 kcal/mL)
Lipid emulsion as a supplementary calorie source

Hyperalimentation in ARF

120
given

are

determined from close monitoring of

their

serum

Specific recommendations for trace metals are not


levels.
available, but it is prudent to administer these substances
during long term TPN to patients with extensive wounds.
The maintenance of fluid balance during TPN in acute
renal failure has been greatly facilitated in recent years by
the use of intensive hemodialysis, continuous arteriovenous
hemofiltration, slow continuous ultrafiltration, and slow
continuous
cussed
using

hemodialysis.

These

modes of therapy are

dis-

in detail elsewhere in this book.

A new innovation
slow continuous hemodialysis involves the addition of

nutrients to the dialysate.


At reduced dialysate flow rate,
(25 mL/min), Feinstein et al (30) reported uptakes of 49
grams

of glucose/hour and 4 grams of amino

the dialysate.

acids/hour

from

This technique allows for efficient adminis-

tration of nutrients during hemodialysis without the need for


fluid.
in

The major drawback of this technique is the reduction

clearances

Recently,
described

in

sorbent system.
reduction

that occurs when dialysate flow

another

in

which

variation
the

in

this

is

approach

nutrients are added

to

reduced.
has

been

the

REDY

Efficient uptake of glucose occurred without


the

usual

dialysate

flow

rate

using

this

technique (31).
REFERENCES
1.
Stott RB, Cameron JS, Ogg CS et al: Why the persistently high mortality in acute renal failure?
Lancet 2:7578, 1972.
2.
Clowes GHA Jr, George BC, Villee CA Jr: Muscle proteolysis induced by a circulating peptide in patients with
sepsis or trauma. N Engl J Med 308:545-552, 1983.
3.
Baracos V, Rodermann HP, Dinarello CA, Goldberg AL:
Stimulation and prostaglandin E2 release by leukocyte
pyrogen:
A mechanism for the increased degradation of
muscle proteins during fever. N Engl J Med 308:553-558,
1983.
4.
Jaatela J, Alho A, Avikainen V, et al:
Plasma catecholamines in severely injured patients.
A prospective
study on 45 patients with multiple injuries.
Br J Surg
62:177-181, 1975.
5.
Meguid MM, Brennan MF, Aoki TT:
Hormone-substrate
interrelationships following trauma. Arch Surg 109:776783, 1974.

E. Feinstein
6.
7.
8.
9.
10.

11.

12.
13.

14.

15.
16.
17.
18.

19.

20.

21.

121

Bessey PQ, Watters JM, Aoki TT, Wilmore OW: Combined


hormonal infusion stimulates the metabolic response to
injury. Ann Surg 200:264-280, 1984.
Horl WH, Heidland A:
Enhanced proteolytic activity cause of protein catabolism in acute renal failure.
Am
J Clin Nutr 33:1423-1426, 1980.
Mondon CE, Dolkas CB, Reaven GM:
The site of insulin
resistance in acute uremia. Diabetes 27:571-576, 1978.
Arnold WE, Halliday MA:
Tissue resistance to insulin
stimulation of amino acid uptake in acutely uremic rats.
Kidney Int 16:124-129, 1979.
Massry SG, Arieff AI, Coburn JW: Divalent ion metabolism in patients with acute renal failure:
Studies on
the mechanism of hypocalcemia.
Kidney Int 5:437-445,
1974.
Kokot F:
The endocrine system in patients with acute
renal failure.
In:
Robinson BHB, Hawkins JB, Davison
AM (eds), Proceedings of E.D.T.A. Vol 18, Pitman,
London, pp 617-629, 1981.
Kokot F, Kuska J: The endocrine system in patients with
acute renal insufficiency. Kidney Int 10:S26-S3l, 1976.
Flugel-Link RM,
Salusky IB, Jones MR, Kopple JD:
Protein and amino acid metabolism in the posterior hemicorpus of acutely uremic rats.
Am J Physiol 244:E6l5623, 1983.
Frohlich J, Hoppe-seyler G, Schollmeyer P, et al: Possible sites of interaction of acute renal failure with
amino acid utilization for gluconeogenesis in isolated
perfused rat liver. Eur J Clin Invest 7:261-268, 1977.
Lacy WE:
Effect of acute uremia on amino acid uptake
and urea production by perfused rat liver. Am J Physiol
216:1300-1305, 1969.
Clark AS, Mitch WE: Muscle protein turnover and glucose
uptake in rats with acute uremia. J Clin Invest 72:836845, 1983.
Delaporte C, Gros F:
In vitro inhibition of protein
synthesis by dialysates of plasma from uremic patients.
Eur J Clin Invest 11:139-143, 1981.
Dudrick SJ, Steiger E, Long JM:
Renal failure in
surgical patients. Treatment with intravenous essential
amino acids and hypertonic glucose. Surgery 68:180-186,
1970.
Abel RM, Abbott WM, Fischer JE: Intravenous essential
L-amino acid and hypertonic dextrose in patients with
acute renal failure.
Effects on serum potassium, phosphate and magnesium. Am J Surg 123:632-638, 1972.
Abel RM, Beck CH Jr, Abbott WM, et al: Improved survival from acute renal failure after treatment with intravenous essential L-amino acids and glucose.
Results of
a prospective double-blind study. N Engl J Med 288:695699, 1973.
Leonara CD, Luke RG, Siegel RR: Parenteral essential amino acids in acute renal failure. Urology 6:154157, 1975.

122

Hyperalimentation in ARF

22.

Feinstein EI, Blurnenkrantz MJ, Healy M, et al: Clinical


and metabolism responses to parenteral nutrition in
acute renal failure - a controlled double-blind study.
Medicine 60:124-137, 1981.
Varcoe R, Halliday 0, Carson ER, Richards P, Tavill AS:
Efficiency of utilization of urea nitrogen for albumin
synthesis by chronically uremic and normal man.
Clin
Sci Mol Med 48:379-390, 1975.
Toback FG, Havener LJ, Dodd RC, Spargo BH: Phospholipid
metabolism during renal regeneration after acute tubular
necrosis. Am J Physiol 232:E216-E222, 1977.
Mirtallo JM, Schneider PJ, Mavko K, Ruberg RL, Fabri PJ:
A comparison of essential and general amino acid infusions in the nutritional support of patients with
compromised renal functions. JPEN 6:109-113, 1982.
Feinstein EI, Kopple JD, Silberman H, Massry SG: Total
parenteral nutrition with high or low nitrogen intake in
patients with acute renal failure.
Kidney Int 26:S319S323, 1983.
Baek SM, Makabali GG, Bryan-Brown CW, et al:
The
influence of parenteral nutrition on the course of acute
renal failure. Surg Gynec Obstet 141:405-408, 1975.
McMurray SO, Luft FC, Maxwell DR, et al:
Prevailing
patterns and predictor variables in patients with acute
tubular necrosis. Arch Intern Med 138:950-955, 1978.
Mault JR, Bartlett RH, Dechert R, et al: Starvation: A
major contributor to mortality in acute renal failure.
Trans Am Soc Artif Intern Organs 29:390-394, 1983.
Feinstein EI, Collins JF, Blumenkrantz MJ, et al:
Nutritional hemodialysis.
In: Progress in Artif Organs
- 1983, Atsumi K, Makawa M, Ota K (eds), Cleveland, ISAO
Press, pp 421-426, 1984.
Friedman P, Feinstein EI, Roberts H, et al: Administration of glucose during hemodialysis using the Redy
Sorbent
System
(Abstract)
Fourth
International
Congress on Nutrition and Metabolism in Renal Disease,
1985.

23.

24.
25.

26.

27.
28.
29.
30.

31.

8
CONTINUOUS ARTERIOVENOUS HEMOFILTRATION
AZOTEMIA IN ACUTE RENAL FAILURE

- THE

CONTROL

OF

C. OLBRICHT
Hannover Medical School, Hannover, FRG

INTRODUCTION
In patients with acute renal failure the central goal of
all

therapeutic efforts is the control of fluid balance

the

control of azotemia.

and

continuous arteriovenous hemofi1-

tration (CAVH) has been advocated as an excellent measure


achieve

these

therapeutic goals in intensive care

with acute renal failure (ARF).


This chapter will review the available data and the
to-date

experience

concerning

the control of

intensive care patients with ARF.


patients
by

CAVH,

since

fluid

up-

azotemia

It is the critically

who may benefit most of all from renal


removal and control of

agree

replacement

ill

azotemia

renal

that the major indication for CAVH

therapy

failure

includes

The term "intensive

may

evaluation

of

vary from hospital


the

to

renal

with

acute

care

more

its

For

the

and

for

defini tion

of

hospital.

precise

patients"
and

therapeutic efficiency of CAVH

compar isons

by
Most

is

broad spectrum of different conditions

definition
meaningful

in intensive care patients

(1-6).

in

replacement

regular dialysis may be limited by severe hypotension.


authors

to

patients

"intensive care patient" is needed, since the control of


azotemia depends not only on CAVH but also on the patient's
cond i tion.
In

our

daily

practice

CAVH

was

applied

mainly

in

patients with ARF and one or more of the following criteria:


1. polytrauma/postsurgery; 2. multiple organ failure;
3.
severe cardiovascular instability with fluid overload and
with disturbances of pulmonary diffusion;
calorie parenteral nutrition.

123

4.

need of

high-

124

CAVH in ARF

Table 1.

Clinical background of 36 patients on CAVH.

Condition

On
respirator
n

Total
n

Open heart surgery


Aortic aneurysmectomy
Abdominal surgery
Poly trauma

18
6
9

Vasopressor
support
n

18
6
7

18
6
9
3

CONTROL OF AZOTEMIA
To

investigate

the therapeutic potential

of

CAVH

patients who fulfilled the above criteria were studied.

36
The

patients were treated exclusively by CAVH and had a treatment


time

exceeding

48 hr.

Shorter treatment periods

may

not

allow a meaningful assessment of the efficiency of CAVH.


The
Table 1.
the

clinical

required

of the patients is

shown

in

All patients needed vasopressor support to maintain

systolic

indicates

background

blood pressure at or

severe

above

100

cardiovascular instability.

mechanical ventilation.

mmHg.

This

All but

The majority of

two

patients

underwent cardiovascular or abdominal surgery.


The technique of CAVH was standardized for all patients
and is shown in Figure 1.
Quinton-Scribner shunts were used
as vascular access. The vessel tip with the largest possible
diameter was implanted.
Most vessel tips had diameters
between 1.9 and 2.4 mm.

In 29 patients the shunt was on the

lower leg and in 7 patients the forearm was used for vascular
access.

However,

the

mean filtration rate was similar

both groups and a significant difference could not be

in

found.

Hence, all patients were referred to one group.


The
(Amicon
tubes
shunt.

Amicon hemofilter 0-30 was applied in all


Corp.,

Danvers,

MA).

It was connected via

with the arterial and the venous line of the


The

potassium-free

filtrate

tube

substitution

patients

had a length

of

40

solution was infused

venous line as previously described (7).

short

Scribner
cm.

The

into

the

The filtration rate

125

C. Olbricht
FEMORAL
CATHETERS

SUBSlllUTlON FLUID mmol/l


Na
142
K
0
Ca
2
Mg
0.75
CI
103
Lactate 44.5

SCRIBNER

ARTERIAL INLET

SHUNT

NO PUMPS

ALTRATE

I =I

Technique

Fig. l.
tion.

NO MONITORING

of continuous arteriovenous hemofiltra-

was measured every hour.

Serum urea, creatinine, potassium,

and acid-base status were determined three times daily.


The

results

replacement

of

this standardized

approach

of

renal

by CAVH in a well-defined group of patients

given in Table 2 and Figure 2.

are

The total treatment time

of

all patients was 289 days with a median duration of treatment


of

8 days.

hr

with

lifetime

The lifetime of one filter ranged from 4 to 171

a mean of 43 hr.
depends

coagulation.

In our

experience,

the

primarily on careful monitoring

filter

of

anti-

Other factors influencing the lifetime are the

hematocrit and the blood flow.


The
mL/min)
times
and

filtration rate was 13.7

4.4 1/24 hr (9.5

of interruption due to filter changes,


repeated surgery.

actual

3.1

This is a mean value and it includes, for example,

filtration

rate

filter may be higher.

resuscitation,

It is important to notice
during the running
However,

period

that

the

of

the

significant for the control

of azotemia is the mean filtration rate during the course of


the total treatment time.
Despite various interruptions and despite severe cardiovascular

instability this artificial glomerulus was so effi-

126

CAVH in ARF

Table 2.

Treatment of 36 patients by CAVH.

Total treatment time


Range
Median treatment time
Fil ter life time, mean
Filtration rate, mean + SD

289
2 - 57
8
43
13.7 + 4.4

days
days
days
h
1/24 h

cient as to deliver a filtration rate equivalent to a GFR


about 10 mL/min.

by others and in our previous studies (1-6,8,9).


seems

of

Similar filtration rates have been measured


Hence,

it

to be an approximate value for what we can expect from

CAVH.
The steady state concentration of creatinine was
530 pmol/L (Fig.
inine
and

2).

around

This is in good agreement with creat-

values measured in patients with chronic renal failure


with a kidney function reduced to a

rate.

This

comparison

similar

indicates a similar

filtration

production

of

creatinine in acute and in chronic renal failure.


In

contrast,

was rather high.

the steady state serum urea concentration


After 3 days of CAVH,

the urea concentra-

tion was about 40 mmol/L (= BUN 112 mg/lOO mL)


Under the given adverse conditions it is somewhat difficult to assess whether or not this is an adequate control of
azotemia.
It is important to consider that in most of these
patients a renal replacement therapy by conventional dialysis
would be difficult or impossible.
Controlled studies relating the levels of serum urea and
outcome of the patients in acute renal failure are not available.

However,

past studies correlated an increased

serum

urea concentration with delayed wound healing (10,11).

This

may be of importance for most of the presented patients.

In

addition, for chronic dialysis patients, higher levels of


serum urea are correlated with a higher morbidity of the
patients (12).
It seems safe to conclude that a steady state serum urea
level

of

40 mmol/L (BUN 112 mg/lOO mL)

is rather

high

certainly does not represent optimal control of azotemia.

and

c.

Olbricht

60

127
.pa

..J

""-o
E
E

40

"""

!.

'po

,...

CO 20

....

"""

,... l-

.~

50~

CI)

'-

::J

OJ

C
100 Z

36

35

26

17

Q.

Mean! SO
800

...

..J

""- 600

,... I-

a>400

c:
c:

'po

.~

,... !-

P'"

....

,... t-

..

.10

.~

36

35

26

17

Days

Fig. 2.
Serum creatinine and serum urea during the first six
days of continuous arteriovenous hemofiltration.
The values
are mean + SO; ~ denotes the number of patients.
Other indicators of the efficiency of renal
are the
incidence
metabolic acidosis.

of hyperkalemia and
A total of 12% of all

the

replacement
presence of
days was

trea~~ent

complicated by hyperkalemia above 6.0 mmol/L.

Serious hyper-

CAVH in ARF

128
kalemia

above 7.0 mmol/L was present on 2% of the

treatment

days.
The

control of hyperkalemia is limited to steady

conditions.

Acute

dialysis.

CAVH

dangerously

hyperkalemia

is

not

must be treated

an appropriate

state

by

measure

hemo-

to

lower

high potassium concentrations within the

neces-

sary short period of time.


The

renal
A

synopsis of the results allows the conclusion

that

replacement was suboptimal under the given conditions.

steady state BUN was achieved in most patients.

But

level of BUN was around 110 mg/IOO mL and lower values

the
would

be better.
Besides the filtration rate,
depends

the steady state BUN level

on the generation rate of urea.

In order to design

adequate removal rates of urea we should know the quantity of


urea generated per day in the multiple organ-failure patient.
We therefore measured the generation rate of urea during
CAVH

in 9 patients with a clinical background quite

similar

to the 36 patients.
These 9 patients were treated 39 days by CAVH and during
this
The

the mean filtration rate was 15.1 + 5.2 1/24

time
mean

daily urea production was 48 g (urea

g/24 hr).

nitrogen

22

The group of patients was not homogeneous and six

patients were septic.


higher

hr.

urea

These six patients had a considerably

production of 53

10 g per day

(24.2

urea

nitrogen),

whereas the non-septic patients generated only 20

hr (urea).

g/24

normal control values.

The latter value is

slightly

In the septic patients,

Table 3.
Urea production in 9 patients with
acute renal failure.

Total
9

Urea, mmol/day
Urea,
g/day

812 + 399
48 + 24

Septic
6
850 + 177
53 + 10

above

the protein
postoperative

Non septic
3
338 + 87
20 + 5

C. Olbricht

.c

129

1400

40

C'<I

30

"- 1000
C

E
E

'It

XI

c:[

cc
"-

".

a::

600

1'1)

10

200

DAYS ON CAVH
Fig. 3. Generation rate of urea during six days of continuous arteriovenous hemofiltration. Values are given as mean +
SD; E represents number of patients.
catabolism

was

increased two to three

times

above

normal

levels (Table 3).


It
were

was interesting to notice that the production

initially high and decreased significantly during

(Fig. 3).
due

to

was

CAVH

or

due to therapy

for

sepsis

and

uncontrolled

parenteral
was

not

inducing

changed before

urea

that

protein

responsible
high

sepsis.

significant

nutrition is not very likely,

hypothesize

and

removal
of

of

during
a

CAVH.

circulating,

low molecular weight by


rate

in septic

of

regimen
we

proteolysisCAVH

for the decrease of urea production


production

died

influence
Therefore,
may

be

(13).

The

(and

most

patients

is not expected.

is well recognized that protein catabolism


to

they

since the

patients undergoing CAVH suffer from sepsis)


three

adequate

However, successful therapy for sepsis

not achieved in five of the six patients and

with

CAVH

It remains an open question whether this effect is

parenteral nutrition.

It

rates

is

five times above normal values in septic

increased
patients

(13-16)
Hence, the first step in the appropriate control of
azotemia is the control of urea production.
This involves

CAVH in ARF

130

the proper management of the underlying disease, adequate


therapy for sepsis, and sufficient parenteral nutrition. It
is

important

to

include these measures in the

control

of

azotemia, during CAVH and before CAVH.


The topic of adequate parenteral nutrition is

discussed

elsewhere in this book.


INCREASING THE FILTRATION RATE
The

second

optimize
rates,

step

in

the control

the urea removal by CAVH.


the urea removal increases.

of

azotemia

with higher
Hence,

is

to

filtration

the therapeutic

goal should be the highest possible filtration rate under the


particular conditions of the individual patient.
achieve

this

goal?

filtration rate?
filtration

What are the options to

How can we
increase

the

Table 4 shows the determinants of the mean

rate by CAVH under the aspect of the daily clini-

cal practice.

We will discuss each of these determinants and

we will evaluate the influence on the filtration rate


Hematocrit.
The
viscosity.

hematocrit is an important determinant of the blood


Increasing viscosity increases the flow

resist-

For CAVH, there is an inverse relation


ance of the blood.
between hematocrit and filtration rate, as demonstrated in
Figure 4.
Thus, CAVH with postdilution is 1 imi ted to
patients with a hematocrit lower than 45 Vol%
(2,17)
In
our experience, the overwhelming majority of intensive care
patients

with

acute

between 25 and 40%.


Table 4.
1.
2.
3.
4.
5.
6.
7.
8.

renal failure have

hematocrit

values

In general it is our policy to maintain

Determinants of the mean filtration rate in CAVH.

Hematocrit
Plasma protein
Interruptions of CAVH
Blood pressure
Vascular access
Filter
Filtrate column/suction
predilution/postdilution

131

C. 01bricht
30

....

'.........

Z
:Ii

'.

.....

E
u,;-20

..........

!i
a:

.
...~......... ....... .,:
..
.. . . ..:........ .......

. ............


.....
.....

'.

".

...
""a:~ 10

u.

....

...............>. :

HEMATOCR IT. %

i
35

i
30

25

20

45

40

Fig. 4. Filtration rate in relation to hematocrit (modified


from Kramer P, Seegers A, DeVivie R, Matthaei D, Scheler F:
Therapeutic potential of continuous arteriovenous hemofi1tration. C1in Nephro1 11:145, 1979.
the

hematocrit between 30 and 35 Vo1%

during

CAVH.

values may be beneficial for the filtration rate,

Lower

but detri-

mental for the patient. It should not exceed 40%, since with
higher values blood flow and filtration rate may decrease too
much.
Plasma protein.
The plasma protein concentration determines the
pressure.
filtration
decrease
this

At

a given hydrostatic pressure,

pressure

and

hence

the

the

filtration

with increasing protein concentration.

relation

has been studied by Lauer et al

hydrostatic pressure of 100 mmHg,

oncotic
effective

rate
For
(5).

will
CAVH,
At

for instance, the decrease

of plasma protein from 8 g/100 mL to 6 g/100 mL has increased


the filtration rate from 20 to 33 mL/min.
In vitro experiments with CAVH by Eisenhauser
(17)
demonstrated that the albumin concentration affects both the

132

CAVH in ARF

blood flow rate and the filtration rate.


under controlled
conditions, the filtration rate decreased linearly with increasing plasma albumin and ceased at a total protein concentration

of 12 g/lOO mL (blood pressure 120/64 mmHg,

crit

35 Vol%)

flow

and an almost linear decrease of the

tion.

These

loid

This was due to a linear decrease of

by

In order to get optimal

CAVH the plasma protein

around 6 g/lOO mL.


by

albumin

blood

filtration

frac-

results demonstrate the importance of the col-

osmotic pressure.

rates

hemato-

filtration

concentration

be

should

A substantial increase of plasma protein

infusion or by hemoconcentration may reduce

the

filtration rate by 50% or more, as previously reported


and as expected from the in vitro data.

(18)

Interruption of CAVH.
Interruptions
filter changes,
ever,

of

CAVH are inevitable,

resuscitation,

mainly

due

and repeated surgery.

to
How-

it should be kept in mind that every hour of interrup-

tion

decreases

interval

the mean daily filtration rate by

between

possible;

replaced

use of two filters should be as

filter

that

is clotted at

10

pm

4%.

as

should

be

An

at 11 pm and not the next day at 8 am.

The

short

appro-

priate organization for 24-hr service should be available.


It may be even better to define a lower limit of filtration.

An

acceptable lower limit of the filtration rate may

be 450 mL/hr.
limit,

Whenever the filtration rate falls below this

the filter should be changed,

Clotting

is the common cause for filter change and prior


the

of

the

blood

tubes

are

blood

or

dismounting

kinks

except when low

pressure

responsible.

filter a short saline flush should be

to
per-

formed to confirm this.


Blood pressure, vascular access, and filter.
Blood pressure is certainly the major determinant of
filtration in CAVH. It is determined by the condition of the
patient

and we have not many options to increase

pressure.
conduit

The
to

arterial

blood must have a

the filter in order to supply the

pressure that drives filtration.

low

the

blood

resistance

transmembrane

The vascular access may be

133

C. Olbricht

Table 5. CAVH with different filters and with different vascular access
Group

Patients , n

11

11

Filter (surface)

0-20 (0.25 m2 )

0-30 (0.55 m2 )

0-30 (0.55 m2 )

Vascular access

Scribner shunt

Scribner shunt

femoral catheters

Hematocrit , %

31 + 4

31 + 5

33 + 3

Plasma protein , gil

56 + 5

56 + 7

57 + 9

Filtration rate ,1/24h

* denotes a p value
one

14.2 + 4.6 *

8.0 + 4.1

16.6 + 6.9 *

< 0.05 against group A

of the major resistances in the CAVH circuit and

appro-

priate selection is important.


The characteristic of the filter is another
of the filtration rate.
these

determinant

In order to examine the influence of

three determinants on filtration we studied the

rela-

tion among blood pressure, blood flow, and filtration rate in


three groups of patients (19) as depicted in Table 5.
Groups

and B had Scribner shunts as vascular

access

and group C had large-bore femoral artery and vein catheters.


Group A was treated with Amicon D-20 hemofilters and groups B
and C with Amicon D-30 filters.

The mean hematocrit

values

and the mean plasma protein concentrations are not different.


This

excludes the influence of these variables on

different

filtration rates in the three groups.


In all three groups the arterial inlet blood flow ranged
from 30 to 135 mL/min and the mean blood pressure ranged from
50 to 125 mmHg.
within this range, the correlation between
mean

blood

pressure and blood flow was

strated in Figures 5 and 6.


twice

as

steep

linear,

as

demon-

The slope of line C was

almost

as the slope of lines A and

B.

In

other

words, at a given blood pressure, the blood flow was almost


two times higher in patients with femoral vascular access,
compared with Scribner shunts.
It should be emphasized here
that the blood pressure was measured in the radial artery.

CAVH in ARF

134

125

c:
E
.......

0-20

100

75

LL

50

'0

0
0

iii

25

0
0

0
0

o~~~--~-,---~--------~

25

50

75

100 125 150

Mean Blood Pressure, mm Hg


blood

Correlation between mean blood pressure and


Fig. 5.
flow. Correlation coefficient 0.69; slop 0.68.
There are two explanations for this difference:
blood

1. The

flow in the femoral artery is much higher than in

any

peripheral artery commonly used for Scribner shunts.


2. The
vessel tip of the Scribner shunt causes a significant drop in
blood pressure.
The

second explanation may be more important.

patients

with

pressure

between

Scribner shunt the average drop


femoral artery and arterial

tube

In
of

the
blood

of

the

C. Olbricht

135

140
120
c

"e
'-

100

80

60

"'CI

o
o

:a
iii

40

";:

GI

1:

20

20

40

60

80

120

100

Mean arterial blood pressure (mm Hg )

Correlation between mean blood flow pressure and


Fig. 6.
Regression line B:
correlation coefficient
blood flow.
Regression line c:
correlation coeffi0.64, slope 0.99.
cient 0.84, slope 1.86 (from Olbricht et al [19]).
extracorporeal circuit was 22 mmHg,

whereas in patients with

femoral catheters virtually no decrease of blood pressure was


measured.
The
was

correlation between blood flow and filtration

also linear within the measured range (Figs.

At a given blood flow,


20

filters.

pressure,

blood

Similar
flow,

rate

7 and

8).

the filtration rate was lower with 0linear

correlations

among

blood

and filtration rate have been demon-

strated before by in vitro experiments (1,2,17).


In vivo measurements by Lauer et al (5) demonstrated
almost
blood

linear

correlation within the given small

pressure and blood flow.

With higher blood

range

an
of

pressure

and higher blood flow, the correlation may be different (5).

136

CAVH in ARF

30

~
-

20

G)

IV

0:

---...

.-0
IV

10
0

.u.

o~~~--~--~--~--

25

50

75

100 125

Blood Flow, ml/min


Fig. 7. Correlation between blood flow and filtration rate.
Regression Line A: correlation coefficient 0.64, slope 0.13.
Regression line B:
correlation coefficient 0.92, slope 0.29
(from Olbricht et al [19]).
These
blood

data

pressure,

have important implications.


the

At

vascular access by large-bore

given
femoral

artery and vein catheters may be the best choice in order


achieve a high filtration rate.
on

blood

flow

filters tested.

The influence of the filter

seems to be of minor importance in


However,

to

at a given blood flow,

the
the

two
0-30

137

C. Olbricht
30

20
c

'......E

E
II
lIS

...

.....
c
0

10

lIS

ii:

O+---~~----r-----~--~~---'

25

50

Arterial blood flow

75

100

125

mllmin)

Fig. 8. Correlation between blood flow and filtration rate.


Correlation coefficient 0.84, slope 0.26 (from Olbricht et al
[19] )

filter was more effective.


the

different

(Table

5).

mean

This experience was confirmed by

filtration rates in

the

three

groups

Patients with 0-20 filters and Scribner

shunts

had the lowest filtration rates and patients


filters had significant higher filtration rates.

with

0-30

Filtrate column/suction.
Suction
on

and filtrate columns exert "negative

pressure"

the filtrate side and increase the hydrostatic

transmem-

brane
the

pressure.
filter

with

We routinely connect the filtrate port


a tube of 40 cm length that

filtrate to the collecting device.


as

possible

conducts

of
the

This is positioned as low

on the patient's bedstead in order to

exert

138

CAVH in ARF

"negative pressure" of 40 cm H20. This increases the fil tration rate by approximately 30%.
Suction on the filtrate port may further increase the
filtration

rate.

Suction-assisted CAVH has been studied by

Kaplan et al (20).

The suction was set at 200 mmHg and they

reported a significant increase of filter output.


Hence, suction may be a valuable tool to increase

the

filtration

was

rate.

different.
was

However,

our

initial

experience

We applied suction in two patients.

a short increase of filter output,

than a

The result
decrease

of

blood flow, and finally clotting at the filter occurred.


The
rience

difference responsible for this heterogeneous expewas probably the different

patients
is

hematocrit

values.

of Kaplan et al (20) had hematocrits of 25%,

characteristic for chronic renal failure

The
which

patients.

Our

patients had hematocrits of 35 and 37%.


According
increases
patients

to

the

data of Kaplan et

al

(20)

the filtration fraction to roughly


with

suction

38%.

higher pre-filter hematocrits,

In

such

our
high

filtration fraction would result in a postfilter hematocrit


of above 45%.
The result is a high blood viscosity, a
decrease of blood flow, and finally clotting may occur.
The course of suction-assisted CAVH in the two
demonstrates

patients

the importance of the hematocrit in this

nique.
The success of suction depends on
hematocrit and, of course, on the magnitude
pressure applied at the filtrate side.

tech-

the "right"
of negative

The routine adminis-

tration of suction without consideration of the hematocrit


may be detrimental, except when the predilution technique is
appl ied.
In patients with lower hematocrits,

suction

assistance

may be very helpful to increase the filtration rate, as shown


by Kaplan et al (20).

With higher hematocrits, we suggest an

increase

in

monitoring

of

suction

of blood flow.

small

increments

This may prevent

and

careful

"over-suction"

with the resulting decrease of blood flow and clotting at the


filter, as experienced in our two patients.

C. Olbricht

139

Predilution/postdilution
Replacement
arterial

line

tion)
net

fluids can be administered either into


(predilution)

or the venous

line

(postdilu-

The predilution mode has been shown to increase

urea

clearance in machine-driven

Predilution

hemofiltration

investigated recently by a crossover study (22).

(21).

Predi1ution

Despite the

dilution

b160d and a consecutive lower urea concentration,

18% increase of the urea clearance has been observed.


predilution
of

azotemia by CAVH.
the

net

Hence,

is an effective measure of improving the control


Furthermore,

pre-filter hematocrit and eliminates


with

the

versus postdilution replacement in CAVH has been

increased the filtrate output by 22%.


of

the

filtration

predilution lowers
potential

fraction that can

suction assistance is used with CAVH.

be

the

difficulties

generated

when

We have addressed this

problem above.
The present data suggest that CAVH with predilution
suction

assistance

can increase substantially the

output and the net urea clearance by CAVH.

and

filtrate

Further

studies

are needed to determine the optimal rate of predilution under


conditions

of

varying blood flows in order to increase

the

net urea clearance.


The

main disadvantage of predilution is

the

increased

cost of providing larger volumes of substitution fluid.


SUMMARY
The

effective control of azotemia by CAVH in

care patients requires high filtration rates.


1/24

hr

is

intensive

A total of 14

mandatory and higher filtration

rates

may

be

necessary to control BUN in hypercatabolic patients.


Whenever lower filtration rates are encountered a careful check according to the above mentioned determinants
should be helpful to increase the filtration rate.
The
sure.
for

first check should be on the patient's blood

pres-

In our experience the minimum blood pressure required


a filtration rate of 14 1/24 hr is 50 mmHg

sure),

even under optimal conditions (19).

(mean

pres-

The second check

CAVH in ARF

140
should

be

the measurement of blood flow and the

whether it is appropriate or not,


blood pressure.
flow

considering the

estimation
patient's

As discussed above, inappropriate low blood

(and hence low filtration rates) may be due to a vascu-

lar access of high resistance, to a high hematocrit, to


clotting of filter capillaries (inappropriate anticoagulation) or to a kink in the tubes.
Predilution should be done routinely.
Whenever

patient's blood pressure is very low

the

the blood flow is appropriately low,

suction can be

and

applied

in combination with predilution.


Following these guidelines,
kidney

function

by

a sufficient replacement of

CAVH should be possible

in

the

over-

whelming majority of intensive care patients with acute renal


failure.
REFERENCES
1. Kramer P, Kaufhold G, Grone HJ, et al:
Int J Artif
Organs 3:225-230, 1980.
2. Kramer P, Seegers A, DeVivie DR, et al: Clin Nephrol
11:145-149, 1979.
3. Kramer P, Boehler J, Kehr A, et al: Trans Am Soc Artif
Intern Organs 28:28-32, 1982.
4. Olbricht C, Mueller C, Schurek HJ, Stolte H: Trans Am
Soc Artif Intern Organs 28:33-37, 1982.
5. Lauer A, Saccaggi A, Ronco C, et al:
Ann Intern Med
99:455-460, 1983.
6. Kaplan AA, Longnecker RE, Folkert VW:
Ann Intern Med
100:358-367, 1984.
7. Schurek HJ, Biela 0:
Blood Purification 1:189-196,
1983.
8. Isemer FE, Hoelscher M, Hildebrand HH, Siewert R:
In:
Arterio-venoese haemofiltration. Nieren-(Ersatz)-Therapie im Intensivpflegebereich, Kramer P (ed).
9. Olbricht C, Mueller C, Schurek HJ, Stolte H:
In:
Arterio-venoese haemofiltration. Nieren-(Ersatz)-Therapie im Intensivpflegebereich.
Kramer P (ed), Vandenhoeck und Ruprecht, Goettingen, Zurich, pp 201-219,
1982.
10. Bluemle LW, Webster GO, Elkinton JR:
Arch Intern Med
104:180-197, 1959.
II. Teschan PE, Post RS, Smith LH, et al: Am J Med 18:172186, 1955.
Laird NN,
Lowrie EG:
Kidney Intern
12. Parker TF,
23:Supple, 13 S42-S49, 1983.
13. Clowes GHA, Georege BC, Villee CA, Saravis CA: N Engl J
Med 308:545-552, 1983.

C. 01bricht
14.
15.
16.
17.
18.

19.

20.
21.
22.

141

Surgery
Bartlett RH, Deckert RE, Mault JR, et al:
92:771-779, 1982.
Cameron JS, Ogg C, Trounce JR:
Lancet 1:1188-1191,
1976.
Duke JH, Jorgensen SB, Broell JR, et al: N Engl J Med
282:668-675, 1970.
Eisenhauser T:
In:
Continuous Arteriovenous Hemofi1tration (CAVH), Sieberth HG, Mann H (eds), S. Karger,
Basel, Muenchen, New York, pp 1-13, 1985.
Roesick F, Boehler J, Kramer P:
In: Arterio-venoese
Haemofiltration.
Nieren-(ErsatZ)-Therapie im Intensivpflegebereich. Vandenhoeck und Ruprecht, Goettingen,
zurich, pp 131-134, 1982.
01bricht C,
Schurek HJ, Stolte H, Koch KM:
In:
Continuous Arteriovenous Hemofiltration (CAVH), Sieberth
HG, Mann H (eds), S. Karger, Basel, Muenchen, New York,
pp 14-24, 1985.
Kaplan AA, Longnecker RE, Folkert VW:
Trans Am Soc
Artif Intern Organs 29:408-413, 1983.
Henderson LW: Clin Nephrol 11:120-124 1979.
Kaplan AA:
Abstract.
Am Soc Artif Intern Organs 31st
Annual Meeting, p 52, 1985.

9
THE PREDILUTION
TRATION

MODE FOR CONTINUOUS ARTERIOVENOUS

HEMOFIL-

A. KAPLAN
University of
Connecticut

Connecticut School of

Medicine,

Farmington,

We have been using the predilution mode as the exclusive


method of fluid replacement during CAVH. Our experience with
this

technique

has shown an enhanced filtrate output and

net increase in urea clearance when compared to the postdilution

mode.

This chapter will offer a brief outline of

background

and theory related to predilution and a

the

detailed

description of .its use in clinical practice.


INTRODUCTION
CAVH is a useful alternative to conventional dialysis in
the intensive-care setting.
lyte,

and

acid-base

patients.

In particular,

balance

In hypotensive patients,

with marginal vascular access,


to

fluid, electro-

are easily achieved


however,

in

most

and in

those

blood flows may be inadequate

generate sufficient output to control uremia.

To offset

this difficulty we have proposed the use of vacuum suction on


the

filtrate

approach
outputs

that

the

assist,
with

port (1).

In

clinical

an approximate doubling

trials

of

obtained without suction (Table 1).

however,
that

output

yielded

the

this

filtrate

It was

noted,

the patients studied had low hematocrits

high

filtration fractions generated

by

and

suction-

approaching 50%, might be less tolerated by patients

higher

blood

suggested that,
hematocrits

counts

(2).

Furthermore,

even without suction-assist,

above

Kramer

has

patients

with

45% could not be adequately treated

with

CAVH (3).
The predilution mode,
filter

(Figure

1),

with infusion of fluid before the

has been found to be a solution to


143

the

144

Predilution CAVH

Table 1.
Filter

Filter outputs with and without vacuum suction.

without Suction

1
2

450
270
240
210

Means

With Suction

mL/hr
mL/hr
mL/hr
mL/hr

293 mL/hr

-+ S.D.

mL/hr
mL/hr
mL/hr
mL/hr

700
450
500
600

563 mL/hr

108

111

Vacuum suction set at 200 mmHg


(Adapted from reference 1)
above-mentioned
blood
the

difficulties.

The

immediate

before entering the filter significantly

dilution
lowers

for continued filtration despite what would

wise be prohibitively high filtration fractions.


under isovolumetric conditions (i.e.,
equals filtrate removal),
systemic blood.

thus
other-

In effect,

when fluid replacement

the hematocrit and protein concen-

tration in the postfilter blood equals that of the


the

both

hematocrit and the plasma's protein concentration,

allowing

of

patient's

Furthermore, several studies have shown that

predilution of pre-filter plasma causes a disequilibrium

between

intraerythrocytic and plasma urea

levels,

allowing

intraerythrocytic urea to leave the cell and became available


for removal in the filtrate.
BACKGROUND
Henderson

has long advocated the use of predilution

as

the preferred method of fluid replacement with machine-driven


hemofiltration

(4).

intraerythrocytic

and

Detailed

calculations,

extraerythrocytic solutes,

contrasting
show

theoretical potential for increased solute removal with


dilution
using

(5).

As originally proposed,

the postdilution mode.

CAVH was

under these

the
pre-

performed

conditions,

the

filtrate output is virtually identical to the urea clearance,

A. Kaplan

145

limb

Fig. 1. CAVH using the predilution mode. The arterial limb


of the shunt is attached with tubing to the hemofilter.
The
filtered blood is returned to the patient via the venous
limb.
The resultant filtrate is collected in a standard
urine bag. A continuous heparin infusion is connected to the
arterial tubing.
The replacement fluid is infused into the
arterial tubing before the blood's passage through the
fil ter.
since plasma and filtrate urea concentrations are similar (68).

With the predilution mode, however, a varying percentage

of the replacement fluid escapes into the filtrate,


the
of

filtrate urea concentrations.


filtrate

increase
net

urea

urea

can be offset

in total filtrate output,


clearance.

diluting

This percentage dilution


by

greater

percentage

yielding an increase

Using a machine-driven

system,

in
with

blood flows of 300 mL/min, Geronemus and colleagues varied


the predilution rate and found that 20 mL/min was optimum for
increasing net urea removal (9).
The optimum rate of pre-

146

Predilution CAVH

dilution infusion during CAVH, under conditions of


blood flows, has yet to be investigated.

varying

THEORY
Lauer

and colleagues have studied the

postdilution

hemodynamics

arteriovenous hemofiltration (7).

of

They calcu-

lated that rising oncotic pressures, the result of increasing


protein

concentrations,

provided
causes

by

can negate the

hydrostatic

the patient's blood pressure.

This

forces

situation

net filtration to cease well before the blood

leaves

the filter, thus decreasing the efficiency of the CAVH


system.
In effect, calculations by Landis and pappenheimer
suggest that the same effect occurs in the glomerulus of

the

kidney, governing the filtration fraction and, ultimately the


glomerular filtration rate (10).
Recently, we compared the net effect
versus

postdi1ution

for CAVH (11).

of

predilution

Data from that

study,

combined with results of Lauer's work, allow the construction


of a model depicting the conditions within the filter (Figure
2).

During CAVH,

pressures

without suction-assist,

within the filter are low,

to be between 30 and 45 mmHg (7).


static

pressure

is

the

hydrostatic

having been calculated

In the figure, this hydro-

contrasted with

the

oncotic

pressure

generated by either the postdilution or the predilution mode.


The

hydrostatic pressure provides the force to propel

through

the

pressure

membrane to form

tends

the

filtrate.

to hold the fluid within

decreasing the formation of filtrate.


hydrostatic

oncotic

fibers,

thus

In essence,

when the

pressure exceeds the oncotic pressure,

net fil-

tration occurs.
the

the

The

fluid

When,

however, the oncotic pressure equals

hydrostatic pressure,

filtration

ceases.

Note

that,

under conditions of postdilution replacement, the pre-filter


protein concentration is 6 g/dL, which generates an oncotic
pressure of 20
the

blood

mmHg.

Thus,

with postdilution, even before

enters the filter,

hydrostatic pressure is negated.


passes

towards

a significant amount
Furthermore,

the venous end of the

filter,

of

the

as the blood
the

protein

147

A. Kaplan

1
60
50

HP

0'1

IE

during
CAVH

40

w-

30

~
en
w

20

a..

10

a:
a:

/f-------

oncotic
pressure
during
postdilution

O~--r_~---.--.---.-_.--_+

10

12

14

PLASMA PROTEIN CONCENTRATION


(gm/100 ml)
Fig. 2.
Range of oncotic pressures seen during the passage
of blood through the filter during CAVH.
The conditions
generated by the postdilution mode are contrasted with the
conditions generated by the predilution mode.
These oncotic
pressures can then be compared to the hydrostatic pressures
(HP), demonstrated to exist within the filter
(7).
Note
that, during the postdilution mode, the oncotic pressures
generated by increasing protein concentrations attain levels
provided by the hydrostatic pressures.
This would, in some
cases, totally abolish the net filtration pressure before the
blood leaves the filter.
During the predilution mode, however, the oncotic pressures generated are more modest, and
allow for a continued net filtration pressure throughout the
blood's passage through the filter.
(HP = hydrostatic pressure, defined as (pre-filter + postfilter pressures)/2 +
negative pressure within filtrate tubing).
Adapted from
Landis E (10).
concentration increases to 9 g/dL,
advantageous conditions.

causing increasingly dis-

This increase in protein concentra-

tion generates an oncotic pressure which,

in some cases, can

filtration.
completely oppose the forces favoring
contrast, under conditions of predilution replacement,
filter

protein

generating

concentrations

are

diluted

to

more modest oncotic pressure of only 12

In

preg/dL,
mmHg.

predilution CAVH

148

Subsequently, at the venous end of the system, the protein


concentration is only 6.5 g/dL, allowing for a continued net
filtration pressure throughout the passage of blood through
the

filter.

shifts

In essence,

the predilution mode

effectively

the protein concentrations to the left,

operating

conditions

away

from the

greater

setting

the

increases

oncotic pressure obtained during the postdilution mode.

in
(The

above calculations of oncotic pressure assume a normal plasma


protein

composition,

and globulin [10].

with roughly equal amounts of

Under these conditions, the oncotic pres-

sure can be calculated using the formula:


0.009 C3.

albumin

2.1 c + 0.16 C2 +

Where "c" equals the plasma protein concentration

in g/dL.)
As is clear from the above sample,

the diluting

effect

of predilution can be of significant advantage during CAVH


without suction-assist. with suction-assist, however, transmembrane pressures can approach 250 mmHg, the result of
adding the 200 mmHg "negative" pressure (provided by the
vacuum suction)

to the hydrostatic pressure (provided by

patient's blood pressure).

Thus, given these high pressures,


would

seem

that

the

favoring

fil tration,

increases

in oncotic pressure would not assume as

importance.
high

with

pressures,

suction-assist,

fractions greater than 50%,


in

depicted
great

an

However, the combination of low blood flows and

transmembrane

performed

it

the

postfilter

protein

suction-assist,

a situation unique
can

generate

to

CAVH

filtration

leading to substantial increases

concentrations.

Thus,

even

with

the diluting effect of predilution can be of

particular benefit.
Several

authors

have investigated the extent to

which

urea can move across red-cell membranes in response to extracorporeal renal replacement techniques. Katz and Hull demonstrated that there was a complete and rapid shift of intraerythrocytic urea into the plasma compartment in response

to

standard hemodialysis (12).


However, Nolph, Bass, and Maher
found a substantial and persistent disequilibrium between
intraerythrocytic and plasma urea levels (13).

Subsequently,

149

A. Kaplan
::::::;)-PREDILUTION FLUID

/,11\
000

000

o
o

0000

PLASMA

00 0

00

000

0000 0

0000

000

0
0

0000

RED

CEll MASS

o : UREA
Fig. 3. Urea kinetics during predilution. A. Arterial blood
tubing before the infusion of replacement fluid:
note that
urea concentrations in both plasma and red-cell water are
approximately equal.
B. Tubing during the addition of predilution fluid:
the predilution fluid, containing no urea,
dilutes the urea in the plasma compartment.
C. Prefilter
tubing after the infusion of predilution fluid:
the disequilibrium, created by the decrease in plasma urea concentrations, causes intraerythrocytic urea to enter the plasma
compartment.
D. Filter: having entered the plasma compartment, urea, which was previously intraerythrocytic, is now
available for removal in the filtrate. The predilution fluid
is an electrolyte solution that generates an osmotic pressure
roughly equal to that of plasma;
thus, despite the substantial decreases in urea concentration, there is only a modest
change in the plasma's "concentration" of water, accounting
for the fact that significant amounts of water do not pass
into the red-cell mass.
Cheung

and

colleagues,

using more

sensitive

radioisotope

techniques, found a rapid and complete equilibrium, with urea


moving freely between red-cell and plasma in response to both
standard

hemodialysis

predilution
indications,

and hemofiltration performed

mode (14).
the

weight

Thus,

in

the

despite the previous contra-

of the

currently

available

data

supports the concept that urea does move freely from the redcell

to the plasma compartments,

to occur within 6 seconds (12,14).

the effect being estimated


Thus, a major benefit of

the predilution mode, especially with low-flow systems, where

Predilution CAVH

150

mixing would be maximal, is the immediate pre-filter dilution


of the plasma urea concentration and an almost immediate
movement

of intraerythrocytic urea to the plasma compartment

in order to establish a new equilibrium.


This process
renders intraerythrocytic urea available for removal in the
fil trate (Fig. 3).
Thus, during CAVH,

the predilution mode increases

net

urea clearance by decreasing the negative effects of increasing oncotic pressures and by rendering intraerythrocytic urea
available for filtration.
predilution

mode

Despite the demonstration that the

increases net urea clearance

during

CAVH

(see below), there is little information concerning the relative

contribution of each of the above-mentioned effects

to

the production of this increase.

100

Mean
Arterial

PresstJ'e
rrmHg

50

2
1000
Output

m/tv' 500

U"ea

Clearance

m/m

Hou's

10

12

14

16

15

PostdlJtion
X'
75.6
$EM =':2.3
PredlJtion
X'
74.9
$EM =':2.1
N.S.
Postclution
X'
678
$EM=': 25
PredUtion
X'
825
SEM=': 14
p<O.05
Postclution
X'
10.6
SEM Z 0.3
PredlJtion
12.5
ll'
SEM Z 0.3
p<Q.05

Fig. 4. A 16-hour crossover study comparing predilution and


postdilution during CAVH.
The study was performed in two
periods of 8 hours each, separated by 24 hours. The predilution and postdilution mode was alternated each hour.
The
results from both studies are combined to yield the mean
values.
(Reproduced with permission from ASAIO [11].)

151

A. Kaplan
EXPERIMENTAL EVIDENCE
net

Keeping in mind the above mentioned considerations,

the

effect of predilution was studied during CAVH (11).

To

best contrast the two methods of fluid replacement,


was

constructed

administered,
dilution)

that allowed the replacement

alternatively,

fluid

to

be

into the arterial tubing (pre-

or the venous tubing (postdilution).

demonstrated a 22% increase in filtrate output


the

a system

The results
and,

obligatory dilution of filtrate urea with some

despite
predilu-

4,
Table 2).
In conjunction, a one-hour crossover trial was
performed using vacuum suction to increase net filtration
pressures.
The predilution mode yielded an 88% increase in
tion

an 18% net increase in urea clearance (Fig.

fluid,

filtrate

output

However,

these

CAVH treatment,
mL/min)

60% increase in

net

urea

clearance.

where blood flows were particularly low

Other

increases

and

results are representative of only one given


observations

revealed

that

the

(30

percent

in filtrate output and urea clearance are variable

(8,15,16).

Thus, as with machine-driven hemofiltration, the

net benefit of the predilution mode with CAVH will depend


the

system's

infusion.
with

blood flow and the rate of

predilution

fluid

In contrast to machine-driven treatments, however,

CAVH,

the

blood

flows

are not

controlled

and

replacement fluid rate is dictated by the desired net


of

the

on

treatment (i.e.,

either net fluid removal

the

effect
or

iso-

volumetric toxin dilution)


OPERATING CHARACTERISTICS
Several
with

the

importance

particular
filtrate
filters

observations

predilution
by

can be made from

mode in
is

that

the
the

percent

predilution fluid increases with

become

our

clinical

partially occluded (Table 3).

experience

setting.

Of

dilution
t~e

The

of
the

as

percent

decrease in filtrate urea, when compared to the systemic


plasma levels, increases as filter use is prolonged.
Thus,
on the first day of use there was only a 10% dilution,

while

on the fourth day the percent dilution more than doubled.

As

678
+ 26

Mean
+ SEM

<

.001

825
+ 14

800

875

800

825

900

800

800

800

Predilution

(Adapted from reference 11)

650

750

700

700

800

600

625

600

Postdilution

15
16

14

9
10
11
12
13

3
4
5

1
2

Hr

FILTRATE
OUTPUT
mL/hr

Table 2.
16-hour crossover
arteriovenous hemofiltration.

study:

10.61
+ 0.33

10.46

11. 46

11.08

10.19

12.33

9.80

9.78

9.79

Postdilution

< .001

12.49
+ 0.22

12.18

12.61

12.64

12.38

13 .92

12.07

12.07

12.05

Predilution

UREA
CLEARANCE
mL/min

predilution versus

during

continuous

76
+ 2

80

76

81

67

81

77

84

76

Postdilution

NS

75
+ 2

66

75

74

76

78

70

70

76

Predilution

MEAN ARTERIAL
PRESSURE
mmHG

postdilution

I--'

::r:

::l

......

rt

I--'
C

......

0..

C1J

'1::l
H

U1
N

153

A. Kaplan
Table 3.
Change in predilution percentage over time:
nitrogen (mg/dL).

Day
Day
Day
Day

Plasma (Up)

Filtrate ( Uf)

% Decrease*

130
125
79
72

117
103
64
57

10
17.6
19
20.8

1
2
3

* % decrease

urea

(Up-Uf) /Up

(Adapted from reference 11)


filter

life

is extended,

partial occlusion of

the

fibers

present an increasing resistance to blood flow.


Thus, the
progressive increases in percent dilution may be a result of
a

progressive

decrease in plasma

logical since,
plasma

flow,

the

treatments

between

greater the degree of

In support of this concept,

plasma.
CAVH

flow.

This

would

seem

at any given predilution rate, the slower the

show

dilution

of

that

data obtained during 5

significant

negative

correlation

the plasma flow and the percent dilution of filtrate

urea (Fig. 5).


Since
using

this

replacement
procedures

our first trials with predilution,


technique

as

the

exclusive

during CAVH treatments (8).


(17)

include daily

we have

method

of

been
fluid

Standard operating

measurements

of

pre- fil ter

plasma and filtrate chemistry studies (the plasma samples are


taken

from

a port in the arterial blood tubing

infusion of predilution fluid and are,

before

the

therefore, indicative

of the patient's systemic levels)


Thirty-one of these
samples taken during 5 consecutive treatments are depicted in
the

following

two graphs.

In Figure 6,

the

plasma

urea

levels are contrasted with the filtrate urea levels, showing


a relatively close correlation.
In Figure 7, the same
samples are depicted in decreasing order of percent filtrate
dilution.
The majority of filtrate samples are diluted by

154

Predilution CAVH
100

.E

y =86.3 - 2.15x
R=.8699
P<.05

80

40

10

15

20

25

30

% Dilution Urea Nitrogen (plasma vs. filtrate)


Fig. 5.
Plasma flow versus percent dilution urea nitrogen.
Percent dilution of urea nitrogen was correlated with the
plasma flow during 5 CAVH treatments.
The results demonstrate a significant negative correlation between the two
parameters
(r
.8699, p < 0.05).
Percent dilution is
defined as:
pre-filter plasma urea concentration (Up) minus
the ureal concentration in the filtrate (Uf), divided by the
plasma concentration:
(Up-Uf)/Up.
(Reproduced with permission from ASAIO [11].)
30% or less,

thus supporting the concept that only a

modest

amount of the predilution fluid escapes into the filtrate.


Clinically,

the

determination of the percent

dilution assumes importance in two situations.

filtrate

First is for

the proper estimate of the treatment's net urea clearance and


second is to provide an estimate of drug clearance.
CALCULATING SOLUTE CLEARANCE
Normally,
filtrate

under

conditions of postdilution

CAVH,

the

urea concentrations are virtually identical to

the

plasma levels such that the total filtrate output per day, in

A. Kaplan

155

110

88

Filtrate 66
Urea
Nitrogen
mg/dl 44

.,..

22 .

".

20

40

60

80

120

100

BUN mg/dl
Fig. 6. Filtrate urea versus plasma urea during predilution
CAVH. The plasma urea samples blood urea nitrogen (BUN) were
obtained from a point in the arterial tubing before the
infusion of predilution fluid and are, therefore, indicative
of the patient's systemic levels

O~-~I-~I~-r'-~II~r-T~T~T~T-T-I~I-~'-~'~~'~"~-~'-~'~

Paired Samples
Fig. 7.
Percent filtrate dilution during predilution CAVH.
The paired samples depicted in Figure 6 are calculated for
percent dilution and ranked in decreasing order.
The predilution percentage was calculated using the formula:
(UpUf)/Up, where Up equals the urea concentration in plasma and
up equals the urea concentration in filtrate.

Predilution CAVH

156
milliliters,

divided by 1,440 (minutes/day),

will give

the

net urea clearance in milliliters per minute.


With predilution, however, the degree of dilution of filtrate urea must
be

taken

into

account such that the day's

total

filtrate

output is decreased by the percent dilution of urea.


using Uf to represent the urea level in the filtrate and
Up as the urea level in plasma,

then the percent dilution of

filtrate urea, when compared to plasma samples, can be determined as follows:


(Up-Uf)/Up = % filtration dilution
A "corrected" filtrate output, which accounts for this
percent dilution, can be calculated by multiplying the actual
total

output

by the percent dilution and

subtracting

this

number from the total output:


Corrected filtrate output
Total filtrate output/day (total filtrate output/day x % filtration dilution)
The

corrected filtrate output is then divided by

1,440

in order to arrive at the day's true urea clearance in milliliters per minute.

An example of the calculations are given

below:
Suppose

that the day's total output was 15

liters

and

the plasma's urea level (Up) was 80 mg/dL, while the filtrate
urea level,

determined at the same time,

was 60 mg/dL.

The

percent dilution of filtrate would then be 25% as follows:


(80 - 60)/80 = 20/80 = 25%
The corrected filtrate output would be 11,250 mL:
15,000

(15,000 x .25)

15,000 - 3,750 = 11,250


The treatment's true urea clearance is than 7.8 mL/min:
11,250/1,440 = 7.8 mL/min
Alternatively,

the

net urea clearance with predilution

can be calculated using a simple modification of the standard

A. Kaplan

157
day

is

multiplied by the filtrate urea concentration and divided

by

clearance

formula.

The

total filtrate output per

the plasma urea levels:


Total filtrate output/day x Uf
Up
As

with the previous formula,

the result is divided by

1,440 to arrive at the net urea clearance in milliliters

per

minute.
Although
perform,

the

above calculation is

clearly

easier

to

it has the disadvantages of not providing the day's

percent

filtrate

dilution,

number that is

estimating clearances of other solutes,

useful

such as

when

medications

(see below)
Either
that

has

of

'the above formulas is valid for

a sieving coefficient of one

any

(18,19)

solute

(i.e.,

any

solute, which, under conditions of postdilution hemofiltration, is found in equal concentrations in the plasma and the
filtrate
(6-8)
and which is not present in the predilution
Using

fluid.

the amount of urea to calculate this

percent

dilution introduces a certain error, in as much as there is a


variable amount of urea that leaves the red-cell in
to

predilutioni

than
the

thus,

response

the percent dilution of urea is less

that of a solute that is purely extraerythrocytic


section

on Theory)

extent of this movement.


and filtrate,
approximate

It is difficult to

across

the

In effect, paired samples of plasma

20% increase in filtrate dilution of

that

creatinine

We have interpreted this to

creatinine does not move as quickly

red-cell membranes (16) and,

indicator

quantify

measured for both urea and creatinine, show an

when compared to urea (Table 4).


indicate

(see

as such,

of the percent filtrate dilution of

is

as
a

urea
better

extraerythro-

cytic solutes.
This conclusion is supported by the results
of Katz and Hull (12) who also found that a disequilibrium
for creatinine occurs in response to standard hemodialysis.
However, Cheung and colleagues did not find a difference in
the permeability of creatinine and urea (14) and the issue

131
79
82
79
72
70
65
62
62
68
63
60
64
24
19
2
38
24
9
17
16
15
16
5
17
28
17
3

99
64
80
49
55
64
54
52
53
57
60
50
46

Means
+ S.D.

(Up-Uf)/Up

% Dilution:

6.6
4.3
9.2
10.1
10.5
9.8
9.5
8.9
7.6
8.2
8.0
6.7
7.0

<

Prefil ter
Plasma (Cp)*

0.01

4.8
3.3
7.9
6.1
8.0
8.7
7.6
7.6
6.2
6.7
6.6
5.4
4.7

Filtrate
( Cf)

CREATININE

22
8

27
23
14
40
24
11
20
15
18
18
18
19
33

the

(Cp-Cf)/Cp

% Dilution:

* Prefilter plasma samples were taken from a point in the arterial tubing prior to
infusion of predilution fluid, and are indicative of the patient's systemic levels.

1)
2)
3)
4)
5)
6)
7)
8)
9)
10)
11)
12)
l3)

Fil trate
(Uf)

UREA NITROGEN

Filtrate dilution of urea and creatinine in response to predilution.

Prefilter
Plasma (Up)*

Table 4.

::c

::l

1-'-

rt

I-'

1-'-

'0
Ii

co

lJ1

I-'

159

A. Kaplan
must

be

considered

as

unresolved.

In

any

event,

when

calculating drug clearances, which, for the most part, can be


considered to be extraerythrocytic solutes,
to

use

it is preferable

creatinine instead of urea in order to

determine

more accurate estimate of percent filtrate dilution.


ESTIMATING DRUG CLEARANCE
Bennett and colleagues have collected data
clearances in patients with impaired renal function

on drug
(20,21)

data are listed under three broad ranges of residual


function, with glomerular filtration rates of 50

Their
renal
mL/min,

10 to 50 mL/min, and less than 10 mL/min.

They also

list whether or not a given drug is dialysable by hemodialysis or peritoneal dialysis. Data related to hemofiltration,

however, is not presented.

Although simplified, their

recommendations have proved to be enormously valuable in


clinical

the

setting and have become the standard of drug dosing

regimens in renal failure.

Kaplan et al discuss the pitfalls

of using the data of Bennett et al for estimation of drug


removal by hemodialysis or peritoneal dialysis (22). Recently,
with

Golper
CAVH

et al have studied the kinetics of drug


(23-25).

These calculations

another chapter of this volume.


new data was not available,
estimating

drug

are

removal

presented

in

In most cases, however, this

and we have devised a method for

clearance that is relatively easy

and

yet

still valid in the clinical setting.


To estimate the approximate dosing schedule of any drug,
one must first determine the treatment's true solute clearThis is done in the manner described above (see
ance.
section on Calculating Solute Clearance) except that creatinine is used instead of urea in order to calculate the
percent filtrate dilution.
Since most drugs in their nonprotein

bound

fraction

are less than

10,000

daltons

and

since, for molecules less than 10,000 daltons, hemofiltration


yields
sieving
coefficients approaching that
of
the
glomerular basement membrane (26,27), the calculated clearance during CAVH is approximately equal to that of a

Predilution CAVH

160

Thus, if the calculated clearglomerular filtration rate.


ance equals glomerular filtration rate, then this number can
be used in the context of Bennett's recommendations (20,21).
In

essence,

if

the calculated clearance is

20

mL/min,

reasonable dosing schedule can be determined by consulting


Bennett's table under the heading "GFR = 10 to 50 mL/min."
As more drugs are investigated under conditions of CAVH,

the

estimate

with

of drug removal with predilution can

more precision.

calculated

for

decreased

In essence,

be

made

once a drug's removal is

the postdilution mode,

this amount

can

be

by the percent filtrate dilution brought about

by

the predilution mode.


Again, the percent filtrate dilution
should be calculated using creatinine instead of urea, and
even

this solute may be imperfect in determining the

"true"

percent filtrate dilution.


In clinical practice, however,
this consideration is probably of little importance.
Regardless of the method used for estimating drug-dosing
schedules,

when

feasible,

obtaining blood levels is always

preferable to any calculation.


the

filter

cutoff
has

(This discussion assumes that

membrane used for CAVH has

of 10,000 daltons or more.

been

almost

exclusively limited to

generally

equal,

filters

Corporation,
daltons,
Minn] ,

Danvers,

[28-30],

Mass.],

with

the

use

the Amicon
a

and the Renaflo [Renal Systems,


with

molecular

weight

Our experience with CAVH

cutoff of 17,000 daltons.

cutoff

of

20

two,

[Amicon

of

10,000

Inc., Minneapolis,
Using either

these membranes yields sieving coefficients which,

for

of
non-

protein-bound drugs, are essentially equal to that of the


human glomerulus.
If other membranes are used, caution
should be exercised in making this assumption.
Leypoldt and
colleagues have studied the sieving characteristics
of
several membranes under conditions of hemofiltration.
data, especially with protein-containing solutions,
some surprising results [31]).

Their
yields

A. Kaplan

161

CALCULATING FLUID BALANCE


Some

confusion still exists concerning the

calculation

of fluid balance using the predilution mode, a holdover from


the experience with predilution during machine-driven hemofiltration, where enormous amounts of fluid may be infused.
With CAVH, however, no adjustment is necessary.
In brief,
the

predilution fluid infused is charted as "input" and

the

amount of filtrate removed is charted as "output."


ANTICOAGULATION
During CAVH,

the use of continuous anticoagulation

can

present difficulties for patients with hemorrhagic tendencies


(8)

As

such,

methods for reading or eliminating the need

for anticoagulation have been sought.

In this

regard,

predilution mode may offer a potential advantage.

the

In effect,

the addition of predilution fluid lowers the concentration of


platelets and clotting factors entering the filter.
seems

reasonable

Thus, it

to expect that the predilution mode

decrease or eliminate the need for heparin therapy.

could

In fact,

our experience has suggested that this is indeed the case


and, in some patients, we have been able to eliminate heparin
therapy and still maintain a reasonable prolonged effective
filter life.

In a retrospective study,

however, Eisele and

Paganini did not find a significant advantage to


during heparin-free treatments (32).
will

remain

unresolved

until a

The issue,

well-designed

predilution
therefore,
prospective

study is undertaken.
INITIATING TREATMENT
Since the predilution mode yields a significant increase
in filtrate outputs, it seems logical, therefore, to use this
technique at the start of treatment.
treatment's

With CAVH, however, the

filtrate output cannot be controlled (at

least,

in its uppermost limits).


Thus, we have devised a system of
fluid balance that allows the replacement fluid rate to be
determined
the

by the previous hour's filtrate output (17).

first hour of any treatment,

or when a new

filter

In
re-

predilution CAVH

162
places a clotted filter,

determining the rate of predilution

requires an estimate of the first hour's output.


This
calculation is useful with all methods of CAVH treatment,
with

predilution

suction-assist.

or

postdilution

and

the first hour of filter use, which


estimate of successive efficiency.
A

rough

with

and

without

However, this estimate need only be made in

estimate

gives

of the first hour's

reasonable

output

can

be

calculated using the following technique.


The total volume
capacity of the CAVH system is determined (for the Amicon 20
and its standard tubing,
and its tubing, 50 mL).

this equals 35 mL,

for the Renaflo

When the treatment is initiated, the

time

it takes for the blood to travel from the

the

venous

example,
minute,
30
the

access

mode,

"circuit time."

For

if the circuit time is

with blood flows of

less

Using

800

mL/hr

suction-assist

is

of

filtrate

with blood flows exceeding 100

filtrate

used (1),

100

than

reasonable estimate of the first hour's

output would be about 400 mL.

to

if the circuit time is 1

the blood flow is 100 mL/min and so on.

predilution

mL/min,

the

the blood flow is 50 mL/min,

seconds,

mL/min,

represents

using the Renaflo system,

arterial

should

be

expected.

the above estimates

If

should

be

These values are only rough guides for the first


doubled.
hour's rate of predilution infusion, which can be adjusted as
the CAVH treatment continues.
CLINICAL EXPERIENCE
The predilution mode, especially when used with suctionassist, substantially increases the efficiency of the CAVH
treatment, allowing its use in situations that would be
inadequately handled by postdilution
histories are detailed below.
Case 1.
74-year-old

Rapid fluid removal:


man

aneurysmectomy.

CAVH.

Several

The patient was an obese

who

had acute renal failure

The

operative

difficult and prolonged,

case

procedure

was

after

aortic

technically

requiring massive amounts of intra-

venous solutions to maintain adequate filling pressures.

The

163

A. Kaplan
postoperative
25

management was difficult because of the

liters of fluid.

Conservative management for

extra

one

week

failed to relieve the fluid overload.


An attempt at extubation failed and renal replacement therapy was initiated. The
newly placed aortic graft and obesity made peritoneal dialysis unacceptable.
Although conventional hemOdialysis could
have been used for solute removal, the continued need for
intravenous fluids and the rather modest amount of fluid
removal possible per treatment indicated that daily hemodialysis would take almost 2 weeks to remove the extra fluid.
It

was

decided that CAVH,

assist,

would

providing

allow

using predi1ution

continuous net

fluid

sufficient clearance to control

significant

edema and obesity,

by femoral cannu1ations.
Figure 8.

and

suction-

removal,
uremia.

while
Despite

adequate access was obtained

The treatment course is depicted in

Filtrate outputs averaged 1,354 mL per hour, which

yielded not only a 20-liter net fluid removal in 2 days,


also a net ureal clearance of 21.5 mL/min.
the

patient

respirator.
patient

was

After two

successfully removed from

Soon after,

the

but
days,

artificial

having achieved "dry" weight,

the

underwent intermittent hemodialysis until return

of

adequate renal function. The results achieved by this treatment are most likely representative of the most efficient
fluid removal documented for any renal replacement therapy
and, in any case, must be considered to be highly successful.
It is also reasonable to assume that standard CAVH, in the
postdi1ution mode and without suction-assist,
would be
incapable of providing the same results.
The

treatment course depicted in Figure 8 illustrates a

common operating characteristic of suction-assisted CAVH (1).


Two

points in the MAP graph depict significant decreases

blood

pressure (indicated by the arrows)

decreases

are

the result of

significant

(Fig.

8).

filtrate

in

These
removal

without the concomitant infusion of predilution fluid.


In
fact, hypotensive episodes should be anticipated any time
suction-assisted

whether

CAVH

is used

without

replacement

in the predilution or postdilution mode.

fluid,

Normally,

164

Predilution CAVH

Weight
Kg.

::~
1251--------=::::=::=====_-1

M.A.P.
rrmHg

Filtrate
Output
ml/hr

Input

ml/hr
12

24

H
36
ours

60

48

Fig. 8.
Rapid fluid removal during predilution CAVH.
The
treatment was performed using vacuum suction on the filtrate
output port.
Net fluid removal totalled 20 liters.
Note
arrows depicting decreases in mean arterial pressure (M.A.P).
These decreases occur at periods when significant fluid
removal was not matched with appropriate amounts of predilution fluid. Vacuum suction was set at 200 mmHg.
when CAVH is used without suction-assist,
decreases,
an

as blood

pressure

filtrate output also decreases, thus allowing for

automatic

control against net fluid removal that is

aggressive.

too

with suction-assist, however, net fluid removal

continues despite a decrease in blood pressure.


In patients
undergoing isovolumetric treatments, where replacement fluid
equals filtrate removal,
suction-assist
patients
suction

undergoing
should

replacement
order

to

serve
be

fluid,
attenuate

the increased filtrate outputs with

only to
net

enhance

fluid

net

removal,

clearance.
however,

used in conjunction with at


preferably in the predilution
the

effect

on

the

In

vacuum

least

some

mode,

patient's

in

blood

A. Kaplan

165

pressure.

The need for diligent blood pressure monitoring is

intensified if suction-assist is used.


Case 2.

Enhanced urea clearance:

The patient was a 67-

year-old man admitted with the acute onset of


uremic
symptomatology.
After hydration and conservative treatment,
urea levels remained high.
developed, which, in view

A pericardial rub subsequently


of the results of laboratory

studies, was considered to be secondary to uremic pericardi tis. The patient was being treated in an intensive care
unit

and

CAVH was chosen as the most cost-efficient way

deliver renal replacement therapy (33).


was

provided

Vacuum
trate

by femoral arterial

suction,

set at 200 mmHg,

output port.

and

The vascular access


venous

cannulation.

was connected to the fil-

Filtrate outputs were

averaged 1,615 mL/hr (Fig. 9).

to

substantial

and

The percent filtrate dilution

125

Blood 100
Urea 75
Nitrogen 50
mg/dl

25
0

Filtrate 2000
Outout
ml/hr

1000

o
o

Input
mI/hr

1000
2000
3000~----~----~----~----~----~--~

Hours
Enhanced urea clearance during predilution CAVH.
Fig. 9.
Filtrate outputs averaged 1,615 mL/hr.
Net urea clearance
was 21. 5 mL/min.
Vacuum suction, set at 200 mmHg, was
connected to the filtrate output port.

Predilution CAVH

166

averaged 22%, thus yielding a net urea clearance of 21 mL/min


(see section on Calculating Solute Clearance)
This efficient rate of urea removal, combined with a generous replacement

of predilution fluid,

urea

levels.

findings

were

apparent.
made

After

We

possible
was

blood

laboratory

study

normal and the pericardial rub was no


believe that the rapidity of solute
by

vacuum suction,
treatment

led to a rapid decline in

2 days of treatment

the concomitant use

of

removal,

predilution

helped reverse the pericarditis.


subsequently

longer

discontinued

and

and

The
the

CAVH

patient

regained adequate renal function.


The
ance,

above treatment,

also

Previous

resulted

experience

with its excellent solute

clear-

in a decreased serum magnesium

level.

with

CAVH suggested that

this

is

an

unusual occurrence (8), especially if patients are maintained


on

regular oral feedings.

nutritional
clearances
event,

intake
yielded

In this

was poor,

and

patient,
the

however,

significant

a substantial magnesium

loss.

the

solute
In

any

when predilution and suction are used in conjunction,

significant

clearances

should be anticipated and levels

magnesium and phosphate should be closely monitored in


to determine the necessity for replacement.
Case

3.

Rapid toxin removal:

year-old man who,

like his brother,

order

The patient was a


had irreversible

27renal

failure secondary to type 1 primary hyperoxaluria (34).


brother
the
the

His

had recently received a renal transplant that failed

in the immediate post-transplant period.


failed

calcium

of

transplant

oxalate.

result

revealed

Biopsy specimen of

disseminated

deposits

It was believed that these deposits

of increased oxalate levels present

during

post-transplant episode of acute renal failure (35,36).

of
were
the
When

this patient received his transplant, he too developed acute


renal failure, and it was feared that continued exposure of
his

new

graft to high levels of calcium oxalate would

also

lead to premature calcinosis.


It was clear from the brother's experience that in order
to

save the transplanted kidney a renal replacement

therapy

A. Kaplan

167

providing

significant

solute clearance would

be

required.

Although daily hemodialysis would provide the most

efficient

method of oxalate clearance,

a calculation of this patient's

oxalate production rate suggested that precipitable levels of


calcium oxalate would be attained during the interdialytic
period (37).
As such, a continuous method of solute removal
would be required and it was clear, from simple calculations,
that peritoneal dialysis would be insufficient. Furthermore,
the presence of the renal graft would make this technique
difficult at best.
with these considerations in mind, CAVH,
using

predilution and suction to enhance

solute

clearance,

was used as the method of renal replacement therapy.


in Figure 10,

the l2-day treatment allowed for 245 liters of

fluid exchange.
irrto

account,

liters,

or

As seen

When the percent filtrate dilution was taken


the treatment's net solute clearance was

17 liters per day.

208

The ultimate return of

the

graft's function attests to the adequacy of the treatment.


ADVANTAGES AND DISADVANTAGES
Advantages.
As detailed above,
tion

the major advantage of the

predilu-

mode is in obtaining enhanced solute clearance and

net

fluid removal.
In particular, the use of predilution allows
for a more liberal use of suction-assisted CAVH, without the
generation of prohibitively high postfilter protein concentrations or hematocrits.
Our experience demonstrates that
the efficiency of the predilution mode allows CAVH to replace
conventional
therapy.

dialysis

Although
would

seem

as

complete

renal

replacement

it is yet to be convincingly demonstrated,


logical that the predilution mode

effective filter life and,


for

will

at least in some patients,

decreased need for anticoagulation

(see

it

prolong
allow

section

on

Anticoagulation)
Disadvantages.
The

major disadvantages to the predilution mode is

increased cost of replacement fluid.

the

This, however, is only

168

Predilution CAVH
27 Y.O. c!
TYPE I PRIMARY HYPEROXALURIA
POST - TRANSPLANT
RENAL FAILURE
TOTAL OUTPUT:
245 LITERS

I-

::J
Q.

I::l

I::l
Q.

~=NEWFILTER

Fig.
10.
continuous arteriovenous hemofiltration
for
continuous oxalate removal.
The treatment was performed in
the predilution mode, which led to an approximate 15% dilution of filtrate constituents. Thus, the 245 liters of total
output represents 208 liters of actual clearance, or 17
liters per day.
Filter replacement is indicated by the
inverted arrows.
The first filter clotted immediately after
a dose of antilymphocyte globulin (ALG); subsequent doses of
ALG were preceded by a bolus of 5,000 IU if heparin.
No
bleeding problems ensued, and this clotting problem did not
recur.
(Reproduced with permission from Ann Intern Med [8].)
of a modest nature,

approximating a 10 to 30% increase

over

the postdilution needs. with a total output of 20 liters per


day this would represent approximately 6 liters.
In the
manner in
represents

which we prepare our fluid (Table 4)


(8)
an increase of only 10 dollars per day.

this
This

modest increase in replacement fluid costs must be contrasted


with the potential for increased filter life, the replacement
of

which

represents

Furthermore,
modest
increase

therapy

(33).

and perhaps of greater importance, is that this

increase
in

the major cost of CAVH

urea

in daily fluid costs yields


clearance,

especially

a
when

substantial
used

with

169

A. Kaplan
suction-assist,

thus

eliminating the need for

intermittent

hemodialysis and the costs it incurs.


Another

minor

disadvantage to the predilution mode

that the filtrate chemistry studies can no longer be used


monitor

the

patient's plasma values

(38).

Although

is
to
this

technique has the potential to substantially lower the amount


of

blood

drawn for the purpose of

early experience
filtrate
values

chemical

analysis,

our

with the postdilution mode suggests that


are rarely considered adequate by the

attending medical staff.


Furthermore, it is now general
practice to draw all blood samples in pediatric chemistry
tubes,

thus

greatly decreasing the amount of blood required

during each evaluation.

In this regard it should be kept in

mind that the generally available autoanalyzers,


in

most

hospitals,

now in

allow for chemical evaluation of

use
serum

with as little as 1 mL of serum.


CONCLUSION
Our experience with the predilution mode has shown it to
substantially

enhance the efficiency of the CAVH

Considering all the advantages,


advantages,

we

have

chosen

treatment.

and the seemingly minor disthe predilution

mode

as

the

Tenukas,

for

exclusive method of fluid replacement for CAVH.


ACKNOWLEDGMENTS
The author
assistance
Steinmetz

in

would

like to

thank

Linda

preparing the illustrations and

and Bruce Koeppen,

for their helpful

Drs.

Philip

suggestions

concerning this chapter.


REFERENCES
1.
2.
3.
4.

Kaplan AA, Longnecker RE, Folkert VW: Suction-assisted


continuous arteriovenous hemofiltration.
Trans Am Soc
Artif Intern Organs 29:408-412, 1983.
Kramer P: Discussion, ibid, p 413.
Kramer P, Kaufhold G, Grone HJ, et al: Management of
anuric intensive-care patients with arteriovenous hemofiltration.
lnt J Artif Organs 3:225-230, 1980.
Henderson LW:
Hemofiltration.
Kidney lnt 13 Supple:
S145-Sl49, 1978.

170

Predilution CAVH

5.

Henderson LW:
Pre vs. post dilution hemofiltration.
C1in Nephrol 11:120-124, 1979.
Paganini EP, Flaque J, Whiteman G, Nakamoto S: Amino
acid balance in patients with oliguric acute renal
failure
undergoing slow continuous
ultrafiltration
(SCUP)
Trans Am Soc Artif Intern Organs 28:615-620,
1982.
Lauer A, Saccaggi A, Ronco C, et al:
Continuous
arteriovenous
hemofiltration in the critically ill
patient. Ann Intern Med 99:455-460, 1983.
Kaplan AA,
Longnecker RE, Folkert VW:
Continuous
arteriovenous hemofi1tration:
a report of six months'
experience. Ann Intern Med 100:358-367, 1984.
Geronemus R, Von Albertini B, Glabman S, et al:
Enhanced small molecular clearances in hemofiltration.
Proc Clin Dial Transplant Forum 8:147-151, 1978.
Landis E, Pappenheimer JR: Circulation. In: Handbook
of Physiology, Sec 2, Vol II, Hamilton WP, Dow P (eds),
American Physiological Society, Washington, D.C., 2:972974.
Kaplan AA: Predilution versus postdilution for continuous arterio-venous hemofiltration.
Trans Am Soc Artif
Intern Organs 31:
In Press.
Katz MA, Hull AR: Transcellular creatinine disequilibrium and its significance in hemodialysis. Nephron 12:171177, 1974.
Nolph KD, Bass OE, Maher JF: Acute effects of hemodialysis on removal of intracellular solutes.
Trans Am
Soc Artif Intern Organs 20:622-627, 1974.
Cheung AK, Alford MF, Wilson MW, et al: Urea movement
across erythrocyte membrane during artificial kidney
treatment. Kidney Int 23:866-869, 1983.
Kaplan AA: The predilution mode for continuous arteriovenous hemofi1tration (CAVH) (abstract).
Presented at
the
Scientific Symposium of the American
Israeli
Nephrology Association, September 8-10, Tel-Aviv.
Kaplan AA:
The effect of predilution during continuous
arterio-venous hemofiltration (abstract).
Presented at
the 17th Annual Meeting of the ~~erican Society of
Nephrology, December 9-12, Washington, D.C., p 66A.
Kaplan AA: Procedure manual: Continuous arterio-venous
hemofiltration. Clinical protocol from the John Dempsey
Hospital,
University of Connecticut Health Center,
Farmington, CT (copies available from the author).
Colton CK, Henderson LW, Pord CA, Lysaght MJ: Kinetics
of hemodiafi1tration:
I. In vitro transport characteristics of a hollow-fiber blood ultrafilter.
J Lab Clin
Med 85:355-371, 1971, 1975.
Henderson LW, Colton CK, Ford CA: Kinetics of hemodiafiltration:
II. Clinical characterization of a new
blood cleansing modality.
J Lab Clin Med 85:372-391,
1975.

6.

7.
8.
9.
10.

11.
12.
13.
14.
15.

16.

17.

18.

19.

A. Kaplan
20.

21.

22.
23.
24.

25.
26.
27.

28.

29.

30.

31.
32.
33.

171

Bennett WM, Muther RS, Parker RA, et al: Drug therapy


in renal failure:
dosing guidelines for adults:
Part
I. Antimicrobial agents, analgesics.
Ann Intern MEd
93:(1 pt 1)62-89,1980.
Bennett WM, Muther RS,
Parker RA, et al: Drug therapy
in renal failure:
dosing guidelines for adults:
Part
II. Sedatives, hypnotics, and tranquilizers; cardiovascular,
antihypertensive
and
diuretic
agents;
miscellaneous agents. Ann Intern Med 93:286-325, 1980.
Kaplan AA, Longnecker RE, Folkert VW: Continuous hemofiltration.
Letters to the Editor.
Ann Intern Med
101:145-146, 1984.
Golper TA, Pulliam J, Bennett WM:
Removal of therapeutic drugs by continuous arteriovenous hemofiltration.
Arch Intern Med 145:1651-1652, 1985.
Golper TA, Wedel SK, Kaplan AA, et al:
Drug removal
during continuous arteriovenous hemofiltration:
theory
and clinical observations.
Int J Artif Intern Organs
(in press)
Golper TA, Saad AM:
Gentamicin and phenytoin in vitro
sieving characteristics through hollow-fiber polysulfone
hemofilters. Submitted for publication.
Henderson LW, Silverstein ME, Ford CA, Lysaght MJ:
Clinical
response to maintenance hemodiafiltration.
Kidney Int 7 Supple 2:S58-S63, 1975.
Man NK, Funck-Brentano JL: Hemofiltration, an alternative method for treatment of end-stage renal failure.
In: Hamburger J (ed) , Advances in Nephrology, Vol. VII,
Chicago: Yearbook Medical Publishers, pp 293-310, 1978
Kaplan AA, Toueg S, Merrow M, Kennedy TL: First clinical trials of anew polysulphone membrane for use with
continuous
arteriovenous hemofiltration
(abstract)
presented at the Third Annual Meeting of the International Society of Hemofiltration, October 9-10, New
York, NY, 1985.
Kaplan AA, Toueg S, Merrow M, Kennedy TL: Biocompatibility and efficiency of a new polysulphone membrane for
use with continuous arteriovenous hemofiltration. To be
presented at the VI Annual Symposium of Hemoperfusion
and Blood Detoxification, September 29 - October 2,
1985, Mexico City, Mexico.
Kaplan AA, Toueg S., Merrow M, Kennedy TL: Complement
kinetics during continuous arteriovenous hemofiltration:
studies with a new polysulphone membrane (abstract). Am
Soc Nephrol, 1985.
Leypoldt JK, Frigon RP, Henderson LW: Dextran sieving
coefficients of hemofiltration membranes.
Trans Am Soc
Artif Intern Organs 29:678-683, 1983.
Eisele G, Paganini EP:
Heparin-free continuous acute
renal replacement therapy (abstract).
Am
Soc Artif
Intern Organs 14:46, 1985.
Kaplan AA:
Continuous arteriovenous hemofiltration
(CAVH) :
an alternative to dialysis in the intensive
care setting. VA Practitioner 1:34-38, 1984.

172

Predilution CAVH

34.

Williams HE:
Oxalic acid and the hyperoxaluric syndromes. Kidney Int 13:410-417, 1978.
Jacobsen E, Mosbaek N:
primary hyperoxaluria treated
with haemodialysis and kidney transplantation.
Dan Med
Bull 21:72-76, 1974.
Rosier JGMC, Baadenhuijsen H, Koene RAP:
Long-term
survival of a renal allograft in a patient with primary
hyperoxa1uria (type I). Neth J Med 24:179-184, 1981.
Kaplan AA, Longnecker RE, Folkert VW: Continuous hemofiltration.
Letters to the Editor.
Ann Intern Med
101:146-147, 1984.

35.
36.
37.

38.

Kramer P, Bohler J, Kehr A, et al:


Intensive care
potential of continuous arteriovenous hemofiltration.
Am Soc Artif Intern Organs 28:28-32, 1982.

10
NUTRITION IN ACUTE RENAL FAILURE: TREATMENT MADE POSSIBLE BY
CONTINUOUS ARTERIOVENOUS HEMOFILTRATION (CAVH)
R. BARTLETT
The University
Michigan

of

Michigan

t1edical

Center,

Continuous

AV

hemofiltration provides an exciting

Ann

Arbor,

new

approach to acute renal failure because of its simplicity and


ability
but

to handle large volume of fluids

primarily

and

electrolytes,

because of the possibility of providing

nutritional support for renal failure patients.

full

It is possi-

ble to feed patients using dialysis as a renal support system


to be sure,
and

other

but the hypermetabolic effects of


limitations

hemodialysis,

of this technique have

resulted

in

limiting protein and energy supply to critically ill patients


with renal failure.

With the advent of continuous

arterio-

venous hemofiltration (CAVH), full nutritional support is now


possible, and several groups are just beginning to explore
the effects of the feeding

(and conversely the effects of our

current treatment - starvation)


Patients
metabolic

in

acute

in acute renal failure (1).

renal failure

and protein catabolic,

are

usually

hyper-

using body stores to

meet

metabolic needs at a time when the exogenous supply of energy


and protein is severely curtailed by the basic disease or
the physician caring for the patient.
the

fact

major

This phenomenon,

that simple starvation and malnutrition may

contributing

renal failure,

factor

to the high mortality

in

by
and

be

acute

has led us to the study of energy balance

in

acute renal failure (2,3).


The

hypermetabolism

and catabolism

which

accompanies

acute renal failure is caused by the inherent disease process


which leads to the renal failure, and is not a consequence of
the renal failure itself.
Acute renal failure rarely occurs
in

an

isolated

fashion (at least

173

in

surgical

patients).

Nutrition in ARF by CAVH

174

Rather, it is one component of a multiple organ system


failure syndrome which frequently has localized or systemic
bacterial infection as the underlying pathogenetic mechanism.
Hence, although we focus in this chapter on renal failure and
its management, it is important to remember that treatment of
the underlying ischemic or infected tissue (usually by excision or surgical drainage) is far more important in management

in these patients than any method of

supporting

renal

function or nutrition.
Having said that, we will devote the
remainder of the chapter to metabolism and nutrition.
Studies of metabolism in postoperative or critically ill
patients have usually focused on protein metabolism since
nitrogen balance is relatively simple to measure.
Protein
metabolism is only one component of nutrient
Energy

metabolism

metabolism,
do

is not directly proportional

however.

to

protein

and conclusions drawn regarding nitrogen balance

not necessarily apply to carbohydrates,

balance

flow,

in general.

fats,

This suggests that general

or energy
metabolism

and protein metabolism are subject to different mediators and


each

component may be elevated or depressed

independent

of

the other.

Typical energy and protein metabolism is outlined

in

1.

Figure

metabolism

Note that under maximal

increases

only

50-100%

stimulation

above

normal,

energy
whereas

protein catabolism may be three or four times the normal


rate.
This suggests that different mediators are at work.
Indeed metabolism is controlled primarily by catecholamines
and protein catabolism is probably controlled primarily by
white cell messengers.
Under
130
lism

normal conditions (4) the metabolic rate is

cc of oxygen STPD per square meter per minute.


is measured as oxygen consumption,

which

100-

Metabo-

converts

to

700-900 calories per square meter per minute when expressed


as calories of energy (the proper expression of energy is
joules,

but this method of measurement has not found its way

into medical practice).

20%

for

The metabolic rate increases by 10-

day or two following a major operation

and

may

increase as much as 50% with severe systemic sepsis of a type

175

R. Bartlett

~Oa

1m2

eel/dey
(70Kg)

Energy

200
180
120
100
Om/Kg

0
2

normal

l1'

operation

atarvatlon

l'

aepala

Fig. 1. Energy and protein metabolism in typical conditions.


Normal is shown in the shaded area (from Sieberth and Mann,
CAVH, Karger, 1985).
associated
metabolic

with

multiple organ failure.

Very

rate may reach twice normal under

rarely

maximum

the

physi-

ologic stress combined with septicemia.


The

normal protein catabolic rate (5)

is 0.5 to 1

gram

of protein (or one sixth that amount of nitrogen) catabolized


per
rate

day.

Unlike the metabolic rate,

may

increase

two to four

physiologic stress and sepsis.

the protein catabolic

times

normal

levels

with

A major part of this protein

catabolism is related to the fact that endogenous protein may


be mobilized as an energy source if external nutrition is not
provided,
rate

hence

appears

critically

to

the observation that the protein


go

down when

ill patients.

nutrition

However,

is

catabolic

provided

that phenomenon is

to
not

enough to explain the disparity between metabolic rate and


protein catabolic rate. It now appears that the mediator for
overall metabolism is primarily catecholamines combined
thyroid

hormone,

whereas the mediator for abnormal

with

protein

catabolism in ischemia and sepsis is a material derived from


activated granulocytes, probably a member of the interleukin
family of molecules.
This finding by Clowes (6) and others

Nutrition in ARF by CAVH

176
(7)

would explain why we see patients with active

inflamma-

tion but not sepsis (a drained abscess with bowel fistula for
example)

who

metabolic.

are severely protein catabolic but not

hyper-

Wherever these mechanisms are, it is important to

consider energy metabolism and protein catabolism as

related

but

manage-

separate items in the metabolic and nutritional

ment of the critically ill patients.


primarily

with

energy

This chapter will deal

metabolism with

some

reference

to

protein catabolism.
Measurement of energy metabolism.
Metabolism
consumption

is most easily measured by measuring

and

C02

production.

This

straightforward in healthy patients breathing air,


difficult

oxygen

technique

is

but it is

in patients with respiratory failure on mechanical

ventilators.

Commercially available "metabolic carts" which

analyze mixed exhaled gas in order to measure oxygen consumption cannot be used for ventilator patients because of slight
fluctuations in the Fi02 and volume of ventilating

gas.

We

addressed

this problem by redeveloping a closed circuit

re-

breathing

spirometer system which can be used for

ously

spontane-

breathing patients or ventilator patients with

respiratory

failure (8).

ventilator respirometer.
oxygen

We call this device a

severe

volumetric

With this apparatus we can measure

consumption and C02 production in any critically

patient.

The

calculations

ill

values are converted to STPD and a variety of


and conclusions can be based on these

measure-

ments.
Indirect

calorimetry

is the process of converting

measurements to energy expressed as calories.

Each class of

foodstuffs has its own caloric equivalent - 5.0 calories


liter

of oxygen consumed for carbohydrate,

and 4.7 for fat.

Similarly,

C02
per

4.8 for protein,

each class of foodstuffs has a

characteristic respiratory quotient (ratio of C02 produced to


oxygen consumed) when metabolized.

By measuring the respira-

tory

protein

quotient

and

the amount of

indicated by nitrogen excretion)


the amount of fat,

catabolized

it is possible to

(as

determine

protein, and carbohydrate metabolized and

R. Bartlett
therefore

177
to

convert 02 consumption to calories

using

the

conversion factors listed above (4).


For

practical

excretion

is

purposes,

since a measure

generally not available when the

of

nitrogen

calculations

must be made, it is most convenient to use a conversion


factor
of
5 calories per liter of oxygen consumed
for
planning
nutritional regimens.
This overestimates the
metabolic rate slightly, but this is within the range of
error of measurement of metabolism.
ness,

Hence, in critical ill-

including acute renal failure, we measure V02 and VC02

once

or twice daily and calculate the metabolic

rate.

The

caloric value of nutrients given to the patient can be easily


calculated, and the caloric balance is the difference between
the

caloric intake minus the caloric

expenditure.

Caloric

balance is calculated daily, and the running total of caloric


balance is accumulative caloric balance.
balance

is

convenient way to

Cumulative caloric

characterize

course of energy metabolism and nutrition,

the

overall

and has proven to

be a useful prognostic number in our experience (3,8,9).


renal

Measurement of nitrogen balance is complicated in acute


failure because the disease interferes with nitrogen

excretion.
A reasonable approximation of protein catabolism
in the anuric patient is calculation of the urea generation
rate (5).
The rise in blood urea nitrogen in 24 hours is
measured and the extracellular fluid space is estimated. The
amount of urea generated can be calculated, assuming that the
urea

is

contained in the extracellular space.

Of

course,

urea and creatinine loss via dialysis or hemofiltration,


other

protein

loss

through

included in this calculation.


niques

drains

or

fistulas

and

must

with these measurement

be

tech-

it is possible to characterize the metabolic rate and

energy balance,

and the protein catabolic rate and

nitrogen

balance.
Energy balance in critical illness.
We
patients

have
with

made

these

measurements

multiple organ failure

in
(8,9),

critically
chest

ill

trauma

(IO), renal failure (1-3), and a variety of other conditions.

Nutrition in ARF by CAVH

178

In patients selected because of multiple organ failure,


increasing mortality correlates with increasing
caloric
deficit.
Specifically, patients with a 10,000 calorie
cumulative

deficit

had 86% mortality,

whereas patients

in

positive cumulative balance had only a 27% mortality (8).


In another study we compared early feeding (one to two
days after admission to ICU) with conventional feeding (five
to seven days)

In this study, the mortality of patients in

positive cumulative caloric balance on day seven was 27%


compared to 54% for those patients in negative balance on day
seven (7).
Hence, the evidence is gradually increasing that
nutritional support,

or at least the energy component of the

nutritional support,

improves the possibility of survival in

critical illness.
lipid)
of

The source of energy substrate (glucose or

is less important than the timing and the total amount

caloric support.

tive

randomized

feeding

We are currently engaged in a prospec-

study

of

immediate

versus

regimens in critically ill patients,

conventional
but all of the

information assembled to date suggests that matching measured


energy requirements with feeding is desirable in these
patients.
The energy requirements are lower than those that
predicted in the past.
It is very rarely necessary to

were
give

more

give

than 3,000 calories to a patient,

more than 2,000.


be

just as dangerous as starvation.

excess

and unusual to

Grossly exceeding caloric requirements can


Carbohydrate given

in

of metabolic requirements is simply converted to fat,

causing fatty infiltration in the liver and


carbon dioxide
failure (11).

disproportionate

generation which may exacerbate

respiratory

Amino acids or other protein given to patients should be


supplied

for protein anabolism,

overall

nutritional

protein

breakdown must be considered,

will

continue

planning

not as energy sources.


the

during a course of

caloric

equivalent

In
of

and protein breakdown

exogenous

feeding.

Our

usual practice is to give the full daily requirement of


energy as glucose or lipid, and to supply approximately one

R. Bartlett

gram

179

per kilogram of protein in addition,

caloric

value

of substrates given to

so that the total

the

patient

exceeds

measured requirement by 200-400 calories per day.


Metabolism in acute renal failure.
Critically

ill patients with multiple organ failure are

usually hypermetabolic.
In our study of patients in acute
renal failure (1,2) the average metabolic rate was approximately

150 cc per kg cc oxygen per square meter per

which

is about 20% above normal.

before

If sepsis

the renal failure resolves,

to the normal range.

is

minute,

controlled

the metabolic rate drops

In fact, daily measurement of metabolic

rates has become the most effective way to track infection,


response to drainage or antibiotics, etc., in our Intensive
Care

unit.

often

This

moderate elevation of metabolic

accompanied by a major elevation in protein

rate (2-4 gm of protein per kg per day)


patients
sources
that

in

caloric

acute renal failure will

require

recovery and survival is

balance

is

established

is

catabolic

As a group,

and more protein than normal.

renal

rate

then,

more

energy

Our studies indicate


better

(Fig.

2).

when

positive

The

studies

described in this figure include patients with polyuric renal


failure
Results

and
in

later.
Asbach
decreased

anuric

patients

patients

treated

with

hemodialysis.

treated with CAVH

will

be

discussed

(12)
demonstrates that protein catabolism
when calorie support (as glucose) was provided

is
to

renal failure patients.


These relationships were further
studied by Kopple's group (13,14).
They found that renal
recovery was better in patients with higher calorie intake.
This
dialysis.

elevated

by

hemo-

within minutes of the first exposure of blood to a

hemodialysis
30-40%,

metabolic rate is exacerbated

circuit,

oxygen consumption increases

and this exaggerated hypermetabolic state

another
continues

throughout dialysis and for a few hours thereafter (2).

This

phenomenon is illustrated in Figure 3. This primary increase


in metabolic rate appears to be the cause of hemodynamic
The baseline
instability in acute renal failure patients.

Nutrition in ARF by CAVH

180

Cumulative Caloric Balance


Positive

Negative

20

J.

Outcome

Survivors

G~

~= DIED

'-----"'--'

Polyuric

0= SURVIVED

Anurlc

Fig.
2.
Outcome in acute renal failure related to
balance (from Trans ASArO [3]).
metabolic
cardiac

rate

is

already

output

to

meet

elevated

the

requiring

metabolic

energy

increased

demands.

During

dialysis

the metabolic rate goes even higher requiring

more

systemic

oxygen

this

delivery.

I f the heart cannot

meet

need, either because of myocardial disease or because cardiac


output
supply,

is already maximal,
the

the metabolic demand exceeds the

patient becomes acidotic and apparently

quately perfused,

and eventually bradycardia and hypotension

follow.

To those caring for the patients,

dialysis

was

it appears

started and within an hour or two

instability followed,

that

hemodynamic

but simple arithmetic detects that the

problem is not related to volume shifts.


the

inade-

acute renal patient is made even more

Hence,

feeding of

difficult,

since

hemodialysis used to remove the fluid associated with feeding


adds considerably to the feeding requirements.
It
the

should be stated that the simplest way to deal

hypermetabolism

and hemodynamic instability

and

with
acute

181

R. Bartlett

il00

Baaeline

15'

30'

120'

180"

24

48

TIme

Fig. 3.
Increased oxygen consumption associated with hemodialysis in acute renal failure (from Trans ASAIO [2]).
renal failure is to assure adequate oxygen delivery by
keeping the hematocrit normal (15).
Renal failure patients
tend to be anemic,
further comprising systemic oxygen
Establishing
a normal hematocrit (above 40) with
delivery.
red blood cell transfusion will allow the patient to deal
with hypermetabolism at a lower cardiac output and in general
eliminate
the problems of vascular instability
during
dialysis.
CAVH
volume,

provides excellent control of extracellular

fluid

and adequate control of solutes and acid/base status

(16-18).

This

technique provides us with the mechanism

study the variations of timing,


nutrition in acute renal failure.

dose,

and

components

to
of

We have used CAVH in the treatment of 32 surgical


patients with acute renal failure, measuring metabolic rate,
caloric

fluid,

parenteral

and electrolyte balance.

nutrition during the period of CAVH and

positive caloric balance on these patients.


balance

We provided

full

achieved

positive protein

was not achieved because protein requirements

often

exceeded 1-2 g/kg/day.


Nine of these 32 patients survived
acute renal failure (28%).
This is in comparison to 18

182

Nutrition in ARF by CAVH

previous patients treated with hemodialysis.


Only 11% of
those patients survived which had been our usual experience
with acute renal failure.
One of the major differences
between these groups of patients is the ability to provide
nutrition to the patients on CAVH.
Hence, we are beginning
to see from our own data that CAVH will have an impact on the
outcome in acute renal failure.
It

should be noted that parenteral nutrition should

given separately from the filtration replacement


is

fluid.

be
It

tempting to design a replacement fluid which supplies the

electrolyte

and the nutrition requirement from the

However,

because

variable

hourly infusion of filtrate replacement

patient.

of the variable level of filtrate and


fluid

the
the

best plan is to give continuous infusion of nutrients, and


simply include that infusion in the calculation related to
replacement fluid.
In
treat

summary,

CAVH

provides us with a simple

renal failure which allows full

support.

Our

parenteral

means

to

nutrition

early data suggests that this will result

in

improved survival in the patient with acute renal failure.


REFERENCES
1.
Mault JR, Kresowik TF, Dechert RE, Arnoldi DK, Swartz
RD, Bartlett RH:
Continuous arteriovenous hemofiltration:
The answer to starvation in acute renal failure?
Trans Am Soc Artif Intern Organs 30: In press, 1984.
2.
Mault JR, Dechert RE, Bartlett RH, Swartz RD, Ferguson
SK:
Oxygen consumption during hemodialysis for acute
renal failure. Trans Am Soc Artif Intern Organs 28:514,
1982.
3.
Mault JR, Bartlett RH, Dechert RE, Clark SF, Swartz RD:
Starvation:
A major contributor to mortality in acute
renal failure? Trans Am Artif Intern Organs 29:390-394,
1983.
4.
Wilmore DW:
The metabolic management of the critically
ill. Plenum Medical Book Co., New York, 1977.
5.
Sargent J, Gotch F, Borah M, et al: Urea kinetics: A
guide to nutritional management of acute renal failure.
Am J Clin Nutr 31(9) :1696-1702, 1978.
6.
Clowes GH Jr, George BC, Villee CA Jr, Saravis CA:
Muscle proteolysis induced by a circulating peptide in
patients with sepsis or trauma.
N Engl J Med 308:545588, 1983.

R. Bartlett
7.

8.
9.
10.
11.
12.

13.
14.
15.

16.

17.

18.

183

Baracos V, Rodemann HP, Dinarello CA, Goldberg AL:


Stimulation of muscle protein degradation and prostaglandin E2 release by leukocyte pyrogen (interleukin-l).
N Engl J Med 308:553-558.
Bartlett RH, Dechert RE, Mault JR, Ferguson SK, Kaiser
AM, Erlandson EE: Measurement of metabolism in multiple
organ failure. Surgery 92:771-778, 1982.
Kresowik TF, Dechert RE, Mault JR, Arnoldi DK, Whitehouse WM Jr, Bartlett RH:
Does nutritional support
affect survival in critically ill patients?
Surg Form
35:108 1984.
Bartlett RH, Dechert RE, Mault JR, Clark SF: Metabolic
studies in chest trauma. J Thor Cardio Surg 87:503-508,
1984.
Askanazi J, Nordenstrom J, Rosenbaum SH, et al: Nutrition for the patient with respiratory failure.
Glucose
vs fat. Anesthesiology 54:1373-1377, 1981.
Asbach HW, Stoeckel H, Schuler HW, et al: The treatment
of hypercatabolic acute renal failure by adequate nutrition and haemodialysis. Acta Anaesthesiol Scand 18:225260, 1974.
Feinstein EI, Blumenkrantz MJ, Healy M, et al: Clinical
and metabolic responses to parenteral nutrition in acute
renal failure. Medicine 60:124-137, 1981.
Blumenkrantz MJ, Kopple JD, Koffler A, et al:
Total
parenteral nutrition in the management of acute renal
failure. Am J Clin Nutr 31:1831, 1978.
Bartlett RH:
A critical carol:
Being an essay on
anemia, suffocation, starvation, and other forms of
intensive care, after the manner of Dickens.
Chest
85:687-693, 1984.
Kramer P, Wigger W, Rieger J, Matthaei D, Scheler F:
Arteriovenous hemofiltration:
A new and simple method
for treatment of over-hydrated patients resistant to
diuretics. Klin Wschr 55:1121-1122, 1977.
Lauer A, Saccaggi A, Ronco C, Belledonne M, Glabman S,
Bosch JP:
continuous arteriovenous hemofiltration in
the critically ill patient.
Ann Intern Med 99:450-460,
1983.
Kaplan AA,
Longnecker RE, Folkert VW:
Continuous
arteriovenous hemofiltration.
Ann Intern MEd 100:358367, 1984.

n
DRUG KINETICS AND CONTINUOUS ARTERIOVENOUS HEMOFILTRATION
T. GOLPER

Oregon Health Sciences University, Portland, Oregon

INTRODUCTION
Since Kramer's initial description of the procedure
called
its

continuous

role in the management of acute renal failure

considerably

expanded (2-4).

medications

(1),

has

Because most patients

going CAVH are critically ill,


rent

been
under-

optimal management of concur-

is a necessity.

Only recently

has

drug

handling during CAVH been studied in any detail (4-8).


the

It is

purpose of this chapter to review the factors related to

drug handling during CAVH,


and

he

arteriovenous hemofiltration (CAVH)

to establish uniform

methodology for drug data collection,

terminology

to summarize

the

available data concerning specific drugs, and to recommend an


approach to drug administration in patients undergoing CAVH.
PHARMACOKINETIC BACKGROUND
Vd.
The

apparent volume of distribution of a drug at steady

state (Vd) is the amount of drug in the body (mg/kg)


divided
by the plasma drug concentration (mg/L)
when plasma and
tissue equilibrium is reached.
Its units are (mg/kg)/(mg/L)
or L/kg. The Vd does not necessarily correspond to a particular

anatomic

mathematical
homogeneous

compartment
relationship

or
that

reservoir of water.

fluid space
assumes

but
the

denotes
body

The Vd is that

is

amount

of

water that the administered drug must have been dissolved in


to give the observed steady-state plasma concentration.
A
drug highly bound to certain tissues (e.g. digoxin, tricyclic
antidepressants, metoclopramide) will frequently have a large
Vd

while

drugs highly bound to circulating

185

proteins

(e.g.

Drug Kinetics

l86

)xacillin,

phenytoin)

will

be restricted to

space, and thus will have a small Vd.


(such

as uremia)

important

only

the

vascular

Certain disease states

change the Vd but this


when the Vd is small

becomes
0.7

clinically

L/kg).

During

changing rates of fluid replacement in CAVH, the Vd is likely


to vary,

especially for drugs whose Vd is predominantly

extracellular fluid space,

no

studies

e.g.

aminoglycosides.

the

There are

that investigate the Vd of drugs during CAVH

or

intermittent high flux hemofiltration.


T 1/2.
Most
kinetics,

drugs are eliminated from the body by first


which

means that a constant fraction of the

present is eliminated per unit time.


tion

process is saturated,

wherein
per

following

of ~ime.

does zero order kinetics

In practical

clinical

apply,

eliminated

terms,

first order kinetics will have its plasma


drop by a constant fraction per unit of time.

removal

rate is conventionally expressed as the

body
first
plasma

Drug

elimination

the time required for the amount of total

drug burden to decrease by half.

For drugs

following

order kinetics this also means that in the T


drug levels fall by half.

dependent on its clearance (renal,


filter, other)

drug

concen-

tration

half-life (T 1/2),

drug

Only when the elimina-

a constant amount of the drug present is

unit

order

1/2

the

The T 1/2 for any drug is


hepatic,

dialytic, hemo-

and its Vd by the formula:

T 1/2

0.693 x Vd

(Eq. 1)

clearance

Thus for a given clearance, the larger the Vd, the longer the
T 1/2.

Conversely, a reduction in clearance prolongs T 1/2.

When maintenance doses are administered,

steady-state plasma

levels

half-lives.

are achieved after three to five

If

loading dose is administered, a steady-state level is reached


within minutes. Without further doses, after five half-lives
- only 3% of the drug rema ins.

T. Golper

187

Clearance.
Total

body clearance is the sum of the regional

clear-

ances,

which include renal, hepatic, other endogenous clear-

ances,

and any exogenous techniques, such as hernofiltration,

hemoperfusion,

or

dialysis.

A procedure that improves the

uremic condition (e.g. dialysis, hemofiltration) may alter an


endogenous clearance.
of

all

these events.

clearance
drug
by

The body recognizes the total


This discussion addresses

by the hemofiltration procedure.

only

the

The concept

clearance through a hemofilter is similar to


glomerular filtration,

effect
of

clearance

where U now represents the ultra-

filtrate concentration (noted hereafter as UF) and P is still


the

plasma concentration in the retentate.

view

Another way

hernofilter clearance is described in the section

discussing
cc/min,

sieving coefficients.

The units

of

to

below

clearance,

are awkward and of limited use in the acute clinical

setting.

Absolute

drug removal per unit of time (usually 6

to 24 hour increments)

is more applicable to CAVH.

FACTORS AFFECTING DRUG REMOVAL DURING HEMOFILTRATION


(TABLE 1)
Hemofiltration removes solutes by convective mass transfer, i.e. solutes dissolved in the plasma water component are
removed

with the plasma water.

binding,

In the absence

of

protein

the solute concentration in whole plasma is related

to the concentration in plasma water by:


conc. in whole plasma

conc. in plasma water

where

g/dL (9).
unbound

(1 -

(Eq. 2)

~)

0.0107 times plasma total protein concentration in


For solutes that are partially protein bound

fraction is contained in the plasma water and Eq.

the
2

should be modified to:

plasma water conc.


(Eq. 3)

conc. in whole plasma x unbound fraction

(1 -

~)

Drug Kinetics

188
For practical clinical purposes
and

is usually between .03

.08 and the denominator can be considered to

be

unity.

Then Eq. 3 is reduced to


plasma water conc. = conc. in whole plasma x unbound fraction
(Eq. 4)
The

rest of the discussion on factors affecting drug removal

will

address the delivery of plasma water to the

filter,

particular drug's unique ultrafiltration properties,


dependency

of

drug removal on

ultrafiltration

and the

rate

(UFR)

(Table 1).
Table
tion.

1.

Factors affecting drug removal during hemofiltra-

1.

Delivery of drug to hemofilter membrane


Volume of distribution
Blood flow - macro
micro
Protein concentration polarization

2.

The drug's unique ultrafiltration properties


Drug - protein binding
Drug - membrane interaction
Molecular size
Sieving coefficient

3.

Ultrafiltration rate
Hydrostatic pressure (blood pressure, blood flow, blood
access, UF column height, UF suction)
Oncotic pressure
Viscosity
Length and width of blood lines
Venous resistance
Filter surface area and intrinsic membrane properties

An

adequate

blood flow to the filter is

maximum performance,

necessary

thus flow to peripheral blood

for

vessels,

vascular access, blood lines, and perfusion pressure must be


optimal
(2).
At the microscopic level the hemofilter blood
pathways must be patent.
All of these factors also affect
UFR (see below). In addition to blood flow, delivery of drug

T. Golper

189

to the hemofilter is dependent on the drug's Vd.


A reasonable fraction of the body's drug burden must be in the blood
compartment (or in equilibrium with it) such that delivery to
the filter may result in significant removal. Drugs that are
highly
not
such

tissue bound and have a large Vd (e.g.

delivered to the hemofilter in large

digoxin)

enough

that hemofiltration removal is clinically

are

quantities
significant.

Because of the rapid turnover of extracellular fluid


(which
is in equilibrium with intracellular fluid)
during fluid
replacement in CAVH, a drug's Vd may actually vary. Unfortunately, there are no studies of drug Vd during hemofiltration.
Another factor affecting delivery of the unbound
(plasma water) drug to the hemofilter membrane is the
potential

for protein layers to build up along the

membrane

in a process called protein concentration polarization.


may

decrease

pressure

at

ultrafiltrate flux by increasing


the membrane and/or by offering

the
an

osmotic

additional

solute hydrodynamic resistance barrier to flow (9).


tration

This

Concen-

polarization is not a function of intrinsic membrane

properties

and is actually determined by the mass

characteristics of the entire hemofilter (10).

transport

Its effect on

solute transport appears to be real


(11), but based on
in vitro experiments its clinical significance will probably
be minor (12).
There may be additional minor interactions
between proteins and membranes that may impair drug
(solute)
movement across hemofilters (11,12).

Again,

it is unlikely

that these effects will have clinical significance in CAVH.


The second group of factors affecting drug removal during
hemofiltration

relate

to properties unique to the

drug

in

question. Foremost among these is the binding of the drug to


the
large nonultrafilterable macromolecular proteins in
plasma, especially, but not exclusively, albumin.
bound to these proteins will remain with the protein

Drugs
during

transit through the hemofilter.


Only the unbound fraction
has the potential for removal by ultrafiltration.
Many
factors affect the degree of drug protein binding including
uremia,

acidosis,

presence

of

elevated free

fatty

acids

190

Drug Kinetics

(FFA),

the molar ratios of drug to protein, hyperbilirubine-

mia,

the presence of other displacing drugs and heparin (13-

21).

The clinical significance of drug-protein binding will

vary from case to case.


The possibility clearly exists that
during CAVH, drug displacement will occur and u1trafi1trative
losses will be increased.
Furthermore, when displacement
occurs, the drug's clinical effect will be enhanced since the

unbound

drug

Alter.ed

protein binding may become clinically

the

is

setting

index.

of

the

pharmacologically

active

highly bound drugs with a

component.

important

low

in

therapeutic

To further point out the complexity of the issue

of

drug protein binding, it has been shown that elevated FFA's


may displace a drug like cefamando1e, but may actually
enhance the binding of other cephalosporins like
or

cefoxitin (21).

induced
when

by

cephalothin

The displacement (or enhanced

binding)

elevated FFA's is particularly relevant in

intravenous fat emulsions may be used during

mentation.
lipase,

Heparin,

through

activation

produces a rapid increase in FFA.

drug-protein

binding in uremia,

of

CAVH

hyperalilipoprotein

For a review

of

readers are referred to the

discussion of this subject by Gulyassy and Depner (19).


There are limited data regarding the interaction
drugs

and

the hemofi1ter membrane.

experiments,

we

insignificant

observed

po1yacrynitril
on

ultrafiltration

as

polysulfone

daltons
The

found

membrane transport
but

or

has

been

extensively

Membrane composition has an effect on


in saline solutions molecules

less

easily

traverse

most

weighing
hemofilter

presence of protein in the solvent (usually

of these test molecules (11,27).


on

hemo-

The role of molecular size (weight + steric


a

plasma or whole blood) decreases the transmembrane

ment

pilot

Kraft and Lode noted gentamicin binding to a

studied (9-11, 23-26).


6,000

of

clinically

membrane during intermittent high flux

filtration (22).

membranes.

probably

interaction between phenytoin and

membranes (12).

hindrance)

In a series

a small and

between

two occasions tha t Vi t.

Dodd and

B12 (1,400

inulin (5,200 daltons) easily traversed Amicon's

move-

associates

dal tons)

and

polysulfone

T. Golper

191

membranes

Virtually all drugs in

in patients on CAVH (28).

clinical use have a molecular size less than that of


Whether
size

inulin data can be extrapolated to large

drugs is not known.

content

using a cuprophan

hemofilter membrane,

inulin.

molecular-

high-cellulose

Pauls et al could not

predict

drug elimination by molecular size and water solubility (29).


In studying drug movement across a membrane,
of

sieving coefficient is appropriate.

the concept

The sieving coeffi-

cient

(S) of a solute is the concentration in the

trate

(UF)

divided

by

the

concentration

of the retentate (9).

in

ultrafilthe

water

S is a mathematical
expression of the solute's ability to permeate a membrane. A
solute that freely passes has an S of 1.0 and a solute
completely rejected by the membrane has an S of zero.
In the
case
of plasma the solute concentration in the water
component will relate to the concentration in whole plasma as
described in Eq. 2 above. At any point along the membrane S
component

OF/[retentate]
coefficient
entire

must

A rigorous expression for the


include the integrations of

membrane.

Colton,

Thus,

As

Henderson,

such this concept


and

associates

becomes

have

shown

sieving

along

the

unwieldy.
that

the

rigorous expression can be reasonably approximated to


OF
A + V

2UF

(A

V)

(Eq. 5)

where A is the plasma water concentration at the filter inlet


and

V is the plasma water concentration at the filter outlet

(9)

For a particular membrane and solute, S will generally be


constant.
Major changes in transmembrane pressure (which
changes transmembrane volumetric flux and ultrafiltration
rate)

will

dextran (11).

inversely

change

sieving

coefficient

of

This is consistent with the membrane transport

theories of Klein et al (23).


volumetric

the

fluxes

generate

Presumably high pressures and


retarding

protein

layers

or

Drug Kinetics

192

protein-membrane interactions, which decrease solute sieving.


This

only

occurs

at elevations of pressure

experienced clinically in CAVH.

hemofilter

not
inde-

is

the

Since the sieving coeffi-

cient for a particular membrane and solute is


constant, clearance is dependent on the UFR (30).
the

are

Sieving is generally

pendent of blood flow (11,12).


The clearance of a solute across a
sieving coefficient times the UFR.

that

important way to describe a drug's

relatively
Therefore,

convective

movement

across a hemofilter is to define its sieving coefficient.


The

last

category

of factors affecting

drug

removal

during hemofiltration are those that directly affect the UFR.


As noted above drug clearance is S x UFR.
and membrane, S is constant.

For any given drug

Therefore, any factor affecting

UFR will impact on the clearance of the drug.

These factors

are listed in Table 1.


For

a more extensive discussion of

this

subject,

the

reader is referred to several recent reviews (2,31).


DRUG REMOVAL DURING CAVH
Molecules the size of inulin (5,200
traverse

polysulfone

daltons)

membranes (10,11,28).

readily

Virtually

therapeutic agents have a molecular weight less than that


inulin

so

permeate
protein

one can reasonably assume that these

binding.

will

Only the unbound free fraction is

ultra-

Protein binding data for many drugs are cited in

extensive

review by Bennett and

associates

(32).

possible alterations in drug-protein binding during


illnesses

of

these membranes limited only by the extent of their

filterable.
an

drugs

all

were discussed in the section above.

The

critical

The data of

Bennett et al were predominantly gathered from the literature


describing protein-binding in normal humans.

Therefore, some

discrepancies may be noted when comparing the Bennett data to


observations in the critically ill patient.
In our experience these discrepancies are rarely clinically significant
(Tables 3 and 4).

T. Colper

193

For practical purposes, one can measure the removal of a


drug

in CAVH by simply measuring the concentration in the UF

and mUltiplying by the UFR.


are

usually

calculate

required

Since (arterial)

for clinical

plasma

management,

levels

one

the UF concentration from the arterial

could

concentra-

tion (A) by the formula

=A

UF
where

protein

review

by

binding

water.

exclusively,
from it.

Equation 6

stated
is

in

the

essentially

4 where the ultrafiltrate represents plasma


2 summarizes the technique to

Table
removal

(Eq. 6)

is assumed to be as

Bennett et al (32).

identical to Eq.
drug

x unbound fraction

during

CAVH using the plasma

determine
arterial

the
level

and calculating the ultrafiltrate concentration

If this approach is used, the arterial plasma level

must be a steady-state level.


The ideal timing of such a
sample is halfway between maintenance doses, after three to
five

half-lives.

Again

the review by Bennett et al

cites

T 1/2 data (32).

CLINICAL OBSERVATIONS
The
drug

above discussion recommended using arterial

concentrations

However,

Eq.

to

and

calculate

the

UF

plasma

concentrations.

4 describe the conversion of

arterial

whole plasma drug concentrations to plasma water drug concentrations.

To be as precise as possible,

necessary.

However,

to 97% of whole plasma,


two

is

that conversion is

since plasma water is almost always 92


the clinical difference between

insignificant.

In addition,

the

the

Colton-Henderson

abbreviated formula for sieving coefficient

2 UF

A + V

Eq. 5 can be further abbreviated by the exclusion of the venous component to

UF

(Eq. 7)

194

Drug Kinetics

Table 2.
1.
2.

Drug removal in CAVH using arterial levels.

Determine steady-state arterial concentration (A).


Determine fraction not bound to protein (Bennett et
[32] )
Determine ultrafiltration rate (UFR) from flow sheet.
Amount removed = A x unbound fraction x UFR.

3.
4.

These

recommendations

arterial,

venous,

are

and

based on analyzing

whole plasma and plasma water concentrations.


S

34

ultrafiltrate drug levels

sets
by

al

of

using

variations in

of + 0.1 can be noted when plasma water and venous

levels

are used compared to whole plasma and only using the arterial
component.
sieving

Regardless

of whether the S is high or

low,

coefficient variation of 0.1 for a drug will not

clinically significant.

a
be

Therefore, for practical purposes we

recommend that S be described by Ui and that A represents the


whOle

plasma

drug level in the arterial side of the

filter

Table 3.
Antibiotic drug-sieving coefficients in CAVH with
Amicon (R) Polysulfone Hollow-Fiber Hemofil ters.

Drug
Amikacin
Ampicillin
Gentamicin
Metronidazole
Mezl ocill in
Nafcillin
Tobramycin
vancomycin
Amphotericin
Cefoperazone
Cefotaxime
Ceftr iaxone
Cephapirin
Clindamyc in
Erythromycin
Oxacillin
Streptomyc in

S (UF/A)
S.E.M.

X+

.88
.69
.81
.80
.68
.55
.78
.76

+ .03

"+

.21
+ .02
+ .11
"+ .11
+ .13
"+ .06
"+ .04

.32 + .08
.27
1.10 + .44
.71
1. 48 + .36
.98
.37
.02
.30

Predicted

8
4

.95
.80
.95
.80
.68
.20
.95
.90

l3

6
4
6
6
11
2
1
4
1
3
1
1
1
1

.10
.10
.62
.10
.55
.40
.30
.05
.65

T. Golper

195

Table 4.
Miscellaneous drug-sieving coefficients in
with Amicon (R) Polysulfone Hollow-Fiber Hemofilters.
S (UF/A)
S.E.M.

CAVH

Drug

x -+

Digoxin
N-acety1
procainamide
Phenobarbital
Phenytoin
Procainamide
Th eophyll i ne

.96 + .06
-

12

.80

.92 + .02
.86 +" .01
.44 +" .05
.86 +" .02
.85 + .01

9
2
15
9
2

.90
.60
.10
.86
.47

(in

Predicted

the absence of predilution fluid

Figure

replacement).

one describes the correlation between the Colton-Henderson


for
abbreviated sieving coefficient formula and ours, UF

A'

five high-sieving drugs.


that

In vitro work in our lab indicates

Ui accurately reflects S for low-sieving drugs as

well

(12)
Tables

3 and 4 list drug-sieving coefficients that have

been

observed

clinically at four centers

performing

CAVH.

Also

noted are the expected sieving coefficients from

known

protein binding data (32).


S

and

Differences between the observed

that expected are infrequent but may be due

placement,

enhanced

binding,

assay

to

inaccuracies,

dis-

altered

Protein binding, or major variations in UFR in these very ill


patients.

The

number

of observations are

also

noted

in

Tables 3 and 4.
SUPPLEMENTAL DOSES IN CAVH
There

are two general approaches to supplementing drugs

in patients on CAVH.

One approach is to replace the quantity

of drug removed in the ultrafiltrate.


to

The other approach is

administer the amount needed to achieve a desired

plasma

level.
To replace the quantity removed in the ultrafiltrate one
would determine UF by either direct measurement or by calculating it from the steady-state arterial
concentration

Drug Kinetics

196

Plot of UF vs 2 UF

1.4

A+V

Digoxin

1.3

.0. Gentamicin

N.. acetylprocalnamlde

1.2

Procainamide

Tobramycin

1.1
1.0

2 UF
A+V.9

.8

r=.98041
p=.00001
y=.97363 x+.02516

.7

.6

ol,,""~r'---L----~--~--~~~~--~
:s
.7

.8

.9

1.0

1.1

1.2

UF
A

The Colton-Henderson abbreviated formula for S


is plBrted on the vertical axis against our simpler
aooeviation -X on the horizontal axis. For these five highsieving drugs the correlation is excellent.
In vitro data
shows that this correlation can be extended t8F the origin,
demonstrating that for low-sieving drugs, S = -X (12).
1~gOF)1.
A~

(Eq.

6,

Table 2).

removed.
strategy

One

could

UF times the UFR is the absolute amount


amount.

This

ignores drug elimination by means other than

simply administer this

hem 0-

fil tration.
Alternatively,

one could ignore measurements of drug in

the ultrafiltrate and follow arterial plasma levels, boosting


them when necessary.
employed.

Subtract

To this end the following strategy


the present arterial plasma drug

is

level

from the desired level, yielding the difference level.


The
required supplemental dose is determined by the following
formula:

197

T. Golper
supplemental dose

difference level x Vd x body weight


(Eq. 8)

where

Vd

is

kilograms.
level

to

volume of distribution and body weight


This

supplemental dose will boost

the

the desired level and will replace the

drug removed by hemofiltration,


or metabolized.

is

in

present

amount

of

eliminated by other pathways

The Bennett reference cites the Vd of common

As mentioned earlier when there


drugs in clinical use (32).
are large volumes of replacement fluid there may be alterations in the Vd.

As of this writing, it is not known whether

this effect will be clinically significant.


SUMMARY
We

have

discussed

the basic principles

of

pharmaco-

kinetics and convective solute removal in the context of each


other.

Clinical observations appear to follow the theoreti-

cal expectations.
and
drug

For practical purposes clinically, plasma

plasma water are not different.


sieving,

venous

In the calculation

samples do not contribute

warrant their extra costs.


data

Recommendations

of
to

We recommend that drug removal in

hemofiltration be expressed by the sieving


Drug-sieving

enough

coefficient,

in humans undergoing CAVH are

for supplemental dosing are

U!.

tabulated.

discussed

that

are applicable to any clinical setting.


The alterations in
Vd that occur during CAVH may be clinically significant and
should be evaluated.
ACKNOWLEDGMENT
The author is grateful to Gloria Ellis and Rick Delk for
their transcription, William M. Bennett for his advice and to
the

housestaff and nurses who helped us collect the data

Oregon

Health

(Baltimore,

now

Sciences

Drs.

Suzanne

at

Wedel

Andre Kaplan (Farmington CT)

and

Emil paganini (Cleveland) provided data used in Figure 1

and

Tables 3 and 4.

Boston),

University.

Drug Kinetics

198
REFERENCES
1.

2.
3.

4.
5.
6.

7.
8.

9.

10.
11.
12.

13.
14.
15.
16.

Kramer P, Wigger W. Rieger J, et a1:


Arteriovenous
hemofi1tration:
a new and simple method for treatment
of overhydrated patients resistant to diuretics.
Klin
Wochenschr 55:1121-2, 1977.
Go1per TA:
Continuous arteriovenous hemofiltration in
acute renal failure. Am J Kid Dis 1985 (In press).
Kaplan AA,
Longnecker RE, Folkert VW:
Continuous
arteriovenous hemofiltration.
Ann Intern Med 100:358367, 1984.

Paganini

EP,

O'Hara P,

Nakamoto S:

Slow

continuous

ultrafiltration in hemodialysis resistant oliguric acute


renal failure patients.
Trans Am Soc Artif Intern
Organs 30:173-177, 1984.
Kaplan AA, Longnecker RE, Folkert VW: Continuous hemofiltration:
in response (Letters).
Ann Intern Med
101:145-146, 1984.
Ossenkopp1e GJ, Van der Muel1en J, Bronsve1d W, et a1:
Continuous arteriovenous hemofi1tration as an adjunctive
therapy for septic shock.
Crit Care Med 13:102-104,
1985.
Golper TA, Pulliam J, Bennett WM:
Removal of therapeutic drugs by continuous arteriovenous hemofiltration.
Arch Intern Med 145:1651-1652, 1985.
Golper TA, Wedel SK, Kaplan AA, Saad A-M, Donta ST,
paganini EP:
Drug removal during continuous arteriovenous hemofi1tration:
theory and clinical observations. Intern J Artif Organs 1985 (In press)
Colton CK, Henderson LW, Ford CA, et a1: Kinetics of
hemodiafiltration.
I.
In vitro transport characteristics of a hollow fiber blood ultrafilter.
J Lab C1in
Med 85:355-371, 1975.
Leypoldt JK, Frigon RP, Henderson LW: Dextran sieving
coefficients of hemofilter membranes.
Trans Am Soc
Artif Intern Organs 29:678-683, 1983.
Frigon RP, Leypoldt JK, Alford MF, et a1: Hemofilter
solute sieving is not governed by dynamically polarized
protein. Ibid. 486-490, 1984.
Golper TA, Saad A-M: Gentamicin and phenytoin in vitro
sieving characteristics through polysulfone hemofilters:
effect of flow rate, drug concentration, and solvent
hemofilters:
effect of flow rate, drug concentration,
and solvent systems (submitted for review)
Reidenberg MM, Affrime M:
Influence of disease on
binding of drugs to plasma protein.
Ann NY Acad Sci
226:115-126, 1973.
Dayton PG, Israili ZH, Perel JM: Influence of binding
on drug metabolism and distribution.
Ibid.
226:172194, 1973.
Anton AH:
Increasing activity of sulfonamides with
displacing agents. Ibid. 226:273-292, 1973.
Reidenberg MM:
The binding of drugs to plasma protein
and the interpretation of measurements of plasma concentration of drugs in patients with poor renal function.
Am J Med 62:460-470, 1977.

T. Golper
17.
18.
19.
20.

21.
22.
23.
24.
25.
26.
27.
28.
29.
30.

31.
32.

199

Tillement JP, Lhoste F, Fiudicelli TF:


Diseases and
drug protein binding. Clin Pharmacokin 3:144-154, 1978.
McNamara PJ, Lalka 0, Gibaldi M: Endogenous accumulation products and serum protein binding in uremia.
J
Lab Clin Med 98:740, 1981.
Gulyassy PF, Depner TA:
Impaired binding of drugs and
endogenous ligands in renal disease.
Am J
Kid Dis
2:578-601, 1983.
Keller F, Wilms H, Schulte G, et a1: Effect of plasma
protein binding, volume of distribution and molecular
weight on the fraction of drugs eliminated by hemodialysis. Clin Nephro1 19:201-205, 1983.
Suh B, Craig WA, England AC, et a1: Effect of the free
fatty acids on protein binding of antimicrobial agents.
J Infect Dis 143:609-616.
Kraft 0, Lode H:
Elimination of ampicillin and gentamicin by hemofiltration.
Klin Wochenschr 57:195-196,
1979.
Klein E, Holland FF, Eberle K: Rejection of solutes by
hemofiltration membranes. ASAIO J 1:15-23, 1978.
Rockel A, Gi1ge U, Liewa1d A, et al: Elimination of low
molecular weight proteins during hemofiltration.
Artif
Organs 6:307-311, 1982.
Michaels AS:
Analysis and prediction of sieving curves
for ultrafiltration membranes: a universal correlation?
Separation Sci and Tech 15:1305-1322, 1980.
Feldhoff P, Tunham T, Klein E:
Effect of plasma proteins on the sieving spectra of hemofi1ters.
Artif
Organs 8:186-192, 1984.
Jaffrin MY, Vantard G, Granger A:
A concentration
polarization model of hemofiltration with highly permeable membranes. ASAIO J 2:73-85, 1985.
Dodd NJ, O'Donovan RM, Bennett-Jones ON: Arteriovenous
haemofiltration:
a recent advance in the management of
renal failure. Br Med J 287:1008-1010, 1983.
Pauls A, Grigoleit H-G, Von Herrath 0, Schaefer K:
Comparison of drug elimination by current methods of
blood purification. Blood Purification 2:14-22, 1984.
Zarowitz BJM, Anandan JV, Jayashankar J, et al: Ultrafiltration
clearance of aminoglycoside antibiotics.
Drug Intel1 Clin Pharm 19:459, 1985.
Lauer A, Saccaggi A, Ronco C, et al:
Continuous
arteriovenous hemofiltration in the critically
ill
patient. Ann Intern Med 99:455-460, 1983.
Bennett WM, Aronoff GR, Morrison G, et al:
Drug
prescribing in renal failure:
dosing guidelines for
adults. Am J Kid Dis 3:155-193, 1983.

CONTINUOUS ARTERIOVENOUS HEMOFILTRATION IN INFANTS


C. RONCO
St. Bortolo Hospital, Vicenza, Italy

INTRODUCTION
Acute renal
several
renal

in infancy may occur due

to

pathologic events leading to a sudden impairment

failure (ARF)

of

function.

decrease

in

newborn)

and

The

urine
a

syndrome is generally

output (less than 1

defined

mL/kg/hour

parallel increase in blood levels

by
in

of

a
the

urea

nitrogen, creatinine, and other waste products.


renal

The main cause of acute renal failure in infancy is


hypoperfusion, which can be due to acute dehydration,

perinatal asphyxia, severe hypotension, or various medical or


surgical complications.

As noted in Table 1,

other

condi-

tions such as renal vein thrombosis, urinary tract infections


and congenital uropathies, hemolytic uremic syndrome, cardiac
failure, and septic shock may provoke acute renal failure and
subsequent dangerous clinical derangements.
The treatment of acute renal failure in infants requires
not

only wide experience in the management of patients

renal

disease,

but also a deep knowledge of the

with

functional

characteristics of the kidney during the first days of life.


The
only

kidney

20%

of the newborn has a

cellular

deficiency;

of the number of cells that will be functional

the adult is functioning at birth.

in

Cortical nephrons are not

functionally mature and the glomerular filtration rate which


ranges from 20 to 30 mL/min/I.73 m2 at birth, is mainly due
to juxtarnedullary nephrons.
On the contrary, the metabolic
rate related to body weight or surface area is higher in the
newborn

than

functional

in

demand

the adult,

and

consequently

is also greater than in the

the
adult.

kidney
All

these factors plus the small size of the newborn render acute

201

202

Pedia tric CAVH

Table 1.

Causes of acute renal failure in infants.

Renal hypoperfusion
acute dehydration
septic shock
post-surgical
hemorrhagic shock
vascular diseases
gastroenteritis
pyloric stenosis
cardiac failure
burns

renal

failure

treatment
acidosis

an even more complicated

becomes

electrolyte

Renal vein thrombosis


Urinary tract infections
Congenital obstructive uropathy
Perinatal asphyxia
Hemolytic uremic syndrome
Cortical necrosis
Miscellaneous

difficult

and

syndrome,

problematic.

imbalances are frequently present and

and

its

Fluid

and

metabolic

is often associated with metabolic alterations

and

various degrees of the catabolic state.


Conservative treatment with drugs and diet can be useful
to

maintain a patient's steady state,

overload

and

solute intoxication may

but

sometimes

require

fluid

substitutive

therapy to maintain adequate control.


Recent advances in technology have made possible the use
of hemodialysis even in such small patients,
of

this

technique

beyond the clinical routine.


in

however the use

is difficult and problematic and


Special equipment is

it

is

employed

order to minimize possible complications associated

with

the extracorporeal circulation, and a specially trained staff


is required to carry out the dialysis session.
Peritoneal dialysis has been used for blood purification
in

infancy

and has produced satisfactory clinical

results.

This technique is simpler than hemodialysis, it can be safely


used in a large number of pediatric departments,

and it does

not require specialized nurses or machinery.


Acute

renal failure in infancy is generally

associated

with severe cardiovascular instability, respiratory problems,


or
use

other medical complications.

Under those conditions the

of hemodialysis can be precluded or contraindicated

not

only for technical reasons but also for medical problems

and

C. Ronco

203

the patient's clinical safety.


peritoneal
surgery,

dialysis

On the other hand, the use of

can be discouraged by recent

abdominal

skin infections, and technical problems.

Moreover,

severe fluid overload cannot always be removed or


by

osmotic

agents

such as glucose added

to

controlled

the

dialysis

solution.
The peritoneal blood flow in the newborn is very
low and the surface area of the peritoneal membrane is also
limited.
In those conditions, even when high filtration
fraction is obtained by the ultrafiltration of the blood
circulating in the peritoneal capillary network, the amount
of fluid removal might be inadequate to maintain the body
fluid balance.
Finally, in the newborn risk of peritonitis
is higher than in adults and may limit the application of
this kind of treatment.
In all these conditions,

an alternative

required,

not

but

to avoid dangerous derangement in the

also

treatment

only to maintain adequate metabolic

is

control,

body

fluid

balance and composition (Fig. 1).


Continuous
simple

method

arteriovenous

hemofiltration

for blood purification and

(CAVH)

fluid

is

withdrawal

that was originally described by Kramer et al in 1977 (3).

small hemofilter is connected to an artery and a vein and the

ACUTE RENAL FAILURE

II

FLUID OVERLOAD

II

ELECTROLYTE DERAHG.

~ ~ /~~.Iaa"'11iq

_ _ Suraer7

Infections

Poor Ultrft'iltrat.

HEMODIALYSIS. Bleeding risk

PERIT.DIAL.

Lack of equipJBeDts

Technical Problems

Technical problems

C.A.V.H.

Fig. 1.
Conditions leading to use of continuous
venous hemofiltration (CAVH).

arterio-

204

Pediatric CAVH

simple
heart

arteriovenous hydrostatic gradient generated


moves

the blood through the circuit,

by

producing

the
slow

continuous ultrafiltration.
The plasma depuration is mainly
obtained by convection replacement of the ultrafiltrate by
substitution solutions contributed to lower solute levels in
the blood. No pumps are used and transmembrane pressures are
very low.

In recent years CAVH has been widely used as an alternative treatment for critically ill patients when
or

peritoneal

problems
this

or

dialysis

precluded

clinical conditions.

procedure are its simplicity,

good clinical tolerance.


for

were

infants and children;

technique

may

characteristics
circuit,

low

continuous

to

rapid

application,

CAVH is also a reliable


in those patients,

as low priming volume of the


heparinization,

low

technical

The known advantages

be even more useful because of

removal

hemodialysis

due

blood

of
and

treatment

in fact,

the

such special
extracorporeal

flow,

of fluid with a composition

and
similar

slow
to

plasma water (Table 2)


The

following paragraphs will describe the

principles
born.

theoretical

and the clinical application of CAVH in the

Special care will be given to the description of

newthe

procedures and the technical aspects of the treatment in such


small patients.
Table 2.

The results obtained in our population will

CAVH in the newborn:

advantages.

Generic
Continuous therapy
Easy technique and procedure
No machinery
Low heparinization
Specific
Low prlmlng volume of the circuit
Low blood flow
Low pressures operating in the system
Slow continuous ultrafiltration
possible manipulation of extracellular fluid composition
Adequate plasma refilling

C. Ronco
also

205

be discussed in order to point out the role of CAVH

as

an alternative therapy in the infant.


VASCULAR ACCESS
The
the

vascular

access in CAVH is not only the source

blood for the extracorporeal circulation,

but also

key point in the generation of the hydrostatic gradient

of
the
that

moves the blood through the circuit.


The objectives of vascular access for CAVH should be the
achievement of the best arteriovenous hydrostatic pressure
gradient, choice of length and diameter of the cannulas and
catheters to achieve a good blood flow while avoiding unnecessary pressure loss, flexibility without reduction of the
inner

lumen

of

the cannula,

and finally a

good

clinical

tolerance since the treatment is generally carried out over a


prolonged period of time.

Fig. 2.
Sequence of procedures for arterial and venous
cannulation after the section of the umbilical cord in the
neonate.

206

Pediatr ic CAVH

25 em

LENGTH OF ARTERIAL AND VENOUS CATHE1ERS


REQUIRED TO REACH THE DIAPHRAGM LEVEL VIA
UMBILICAL VESSELS ACCORDING TO PATIENT'S
LENGTH IN em.

til

s..

20

OJ

.....

OJ
.<::

.....

'"

15

Diaphragm
Level

Ql
.<::

.....

....o

Lines

10

.<::

.....

'"s::

Ql
...J

O;-____~----__~----~----~------~----~
40
45
50
55
60 em
30
35

Length of the neonate


Fig. 3. Nomogram for the determination of catheter length to
reach diaphragm level via the umbilical vessels in patients
undergoing continuous arteriovenous hemofiltration.
Several
fants;

the

clinical
infant

vascular access routes can be utilized

in

in-

choice should be made according to the patient's

condition and the local situation.

In

the

small

the umbilical vessels are still open and they can

be

safely used for both arterial and venous access.


Figure 2
shows an umbilical cord section with the umbilical vessels (2
arteries and I vein) open and ready to be cannulated.
using
Dunn's
the

nomograms

catheter

depending

on

it is possible to calculate the length

to use for arterial

and

venous

of

cannulation,

the length of the neonate and on the point

the systemic circulation the catheter should reach.

of

Figure 3

shows the modified nomogram used as a guideline for umbilical


vessel cannulation in patients undergoing CAVH.
The use of umbil ical vessels (Fig.
easy
used
more

in the neonate,
for

4)

is qui te safe and

however this type of access cannot

a long time and cannot be used at all in

be

patients

than 4-5 days old.


Special care should be taken in
order to avoid possible complications such as air embolism or

207

c. Ronco

UMBILICAL VESSELS CANNULATION


Fig. 4.
continuous arteriovenous hemofiltration circuit
applied to a patient, using umbilical vessel cannulation (A =
arterial; V = venous).
infections.
catheters
particular,

A control radiograph showing the position of the


is helpful to confirm the
the

correct

position.

In

venous catheter should be placed beyond the

Arantius duct in the sovrahepatic veins or in the vena

cava.

When umbilical vessel cannulation is not possible alternative

access can be obtained by brachial artery or

artery cannulation.

femoral

This procedure should be performed by a

pediatric surgeon, preferably after surgical isolation of the

artery in order to avoid hematoma, hemorrhagic complications,


and accidental disconnection of the cannula from the

artery.

208

Pediatric CAVH

Fig. 5.
Surgical isolation
neonate undergoing continuous
treatment.
For

of the brachial artery in a


arteriovenous hemofiltration

this purpose the use of small flexible Teflon

25-35 mm long,
should

cannulas,

size 18-20 gauge is suggested.

The cannulas

be fixed to the skin in order to avoid

disconnection

and

to maintain an adequate blood flow even when changes

the

patient's

Figure

surgical

position

might partially fold

shows the insertion of a

20-gauge

the

of

cannula.

cannula

after

isolation of the right brachial artery in a patient

undergoing CAVH treatment.


In Figure 6 a complete CAVH
circuit applied to a neonate via femoral artery and jugular
vein is depicted.

According to the mean arterial pressure of

the newborn (generally ranging from 35 to 50 mmHg) , the blood


flow

achievable with this type of cannula ranges from 15

to

50 mL/min.
Figure 7 depicts the results obtained in vitro with the
18 and 20-gauge cannulas used for CAVH.
Blood flows allowed
by the cannulas were measured under conditions of several
different applied hydrostatic pressures obtained by gravity

209

C. Ronco

FEMORAL ARTERY
Fig. 6.
Continuous
applied to a patient,
cannulation.
(the

arteriovenous hemofiltration circuit


using femoral artery and jugular vein

blood bags were raised to different heights

cannulas;
pressure
this

CANNULATIOI~

cm

= 0.74 mmHg).

above

the

It is evident that the

produces blood flows higher in vitro than in

same
vivo;

can be explained by the resistances of the circuit

and

of the venous return in the patient.


The risks of peripheral artery cannulation are linked to
the possibility of reducing blood flow to the arm or to the
leg, producing ischemic lesions or even causing complete
thrombosis of the vessel.
tion

For this reason, periodic inspec-

of the cannulation site and of the regional tissues

strongly recommended.

is

Pediatric

210

100

CAVH

BLOOD ACCESS

90
80
70

60

0....

II.

50

0
0
....co

40
30
20
10

10

20

30

40

50

60

70

80 90

100

MEAN ARTERIAL PRESSURE (mmHg)


Fig. 7. In vitro blood flow obtained with 18- and 20-gauge
cannulas under conditions of different hydrostatic pressure.
For the venous return the jugular vein is certainly the
most commonly used path, however, the standard connections
for

jugular infusion (such as those for intravenous

and

central venous pressure measurement) are extremely

thin

and

too

with

quite

long for the purposes of CAVH.

large

Short

feeding

lines

inner diameter (18 gauge) are useful to

reduce

undesired resistance in the extracorporeal circuit.


If

venous

access

is

used

for

prolonged

period,

peripheral vein cannulation should be avoided because of the


high risk of thrombosis, a quite common occurrence in this
condi tion.
The subclavian vein can also be used
but

the

for

cannulation,

jugular vein is safer and easier for returning

blood to the patient.

Furthermore,

since the

the

substitution

fluid may sometimes by hyperosmotic, the peripheral


could be seriously damaged but reinfusion in a central
would provide rapid dilution of the hyperosmotic fluid.

vein
vein

C. Ronco

211

When the patient is older than a neonate and the body


weight exceeds 4-5 kg, a procedure for blood access similar
to that for adults can be used.

Figure 8 shows the sequence

of a femoral artery percutaneous cannulation according to the


seldinger technique in a 3-month-old girl who underwent
because

of

postoperative ARF.

In this patient the

CAVH
venous

return was provided by jugular vein cannulation.

The femoral

catheter

significant

was

used

for 72

hours

without

any

complication and the blood flow recorded ranged from 30 to 36


mL/min.
EXTRACORPOREAL CIRCUIT
0.3

Standard

pediatric

cm)

be modified in order to

venous

can
lines

hemodialysis lines (inner

adequate for CAVH.

obtain

diameter

arterial

Figure 9 shows

the

and
full

system.
The

arterial

line

should be as short as

possible

order to avoid unnecessary pressure drops along the

in

circuit.

Since CAVH operates at low pressures, a loss of 5-10 mmHg may


seriously

affect

the ultrafiltration rate and

the efficacy of the treatment.


filter
short

with

consequently

For the same reason, a hemo-

very low end-to-end pressure drop is

connections with adequate diameter should be

between

the venous line and the


should

jugular

have a port

for

used

cannulation.
continuous

and

employed

arterial

line

infusion

and another port for arterial blood sampling.

The

heparin

sampling could also be used for pressure measurements or

The
for

the use of the filter in a predilutional mode.


The

venous

line must have a port for the

infusion

of

replacement solutions and a venous blood sampling port, which


can be used also for pressure measurements.

At the inlet and

outlet of the circuit three-way stopcocks should be placed in


order to exclude the patient's circulation during lavage of
the filter and circuit with heparinized saline solution. The
stopcocks also make change of the system easier if the filter
is obstructed by clotting.
Special care must be taken to
avoid possible folding of the arterial and venous lines that

212

Pediatric CAVH

Fig. 8. Sequence of femoral artery percutaneous cannulation


according to the Seldinger Technique.

c.

Ronco

213

Fig. 8. Sequence of femoral artery percutaneous cannulation


according to the Seldinger Technique.
(continued)

214

Pediatric CAVH

8.
Sequence of femoral artery percutaneous cannulation
according to the Seldinger Technique.
(continued)

Fig.

C. Ronco

215

Fig. 9. A complete continuous


system applied to a neonate.

arteriovenous

hemofiltration

may produce dangerous reductions of the blood flow inside the


circuit.
The ultrafiltration line is connected to the ultrafilter
port of the hemofilter and generally ends in a graduated
for

collection and measurement of the

line

should

This

ultrafiltrate.

be maintained as long as possible in

bag

order

to

maximize the negative pressure exerted by the ultrafiltration


column
where

on the membrane.
a

This effect is clear in Figure

standard pressure profile in a CAVH circuit in

newborn is depicted.
ultrafiltration

10
the

The negative pressure generated by the

column is critical in the generation of

the

final transmembrane pressure and contributes to the ultrafiltrate

production.

provided
order

to

The ultrafiltration line should also


with a port for drawing ultrafiltrate samples,
determine

calculations,

solute

concentration,

and study sieving coefficient.

make

clearance

Figure 11 sum-

marizes the focal points of a CAVH system in a neonate.


low

resistance

of the circuit and the

low

be
in

priming

The
volume

Pediatric CAVH

216

PRESSURES PROFILE

100

::~:::::I

80

-en

60

40

J:

Hydrostatic Pro
Fi Itrate Neg. Pro

20

Artery

Inlet

Outlet

Vein

MINIFILTER CAVH CIRCUIT


Fig. 10.
Pressure profile along a continuous arteriovenous
hemofiltration (CAVH) circuit in a neonate.

ULTRAFILTRATION RATE

<

AVERAGE HYDROSTATIC
PRESSURE (p)

MEMBRANE~~~:~:~:I~~:~

COEFF.

TRANSMEMBRANE PRESSURE (TMP)

~ l~

NEGATIVE PRESSURE
BY UF COLU (PC)

AVERAGE ONCOTIC PRESSURE (n)


(gi yen by plasma proteins)

Fig. 11. Scheme of the determinants of ultrafiltration (UF)


in continuous arteriovenous hemofiltration.

C. Ronco

217

Fig. 12. The Amicon Minifilter for continuous arteriovenous


hemofiltration in infants.
(less than 15 mL) minimize any modification of cardiac output
and contribute to clinical tolerance of the treatment.
FILTER
There are no commercially available hemofilters especially made for CAVH in infants and children, however,
the
clinical trials have been carried out with devices originally
designed

for

other purposes.

One such device is

polyarea)
(Fig.

sulfonic

hollow fiber hemofilter (0.005 m2 of surface

made

by

Amicon Corporation and called a "Minifilter"

12).

This filter was originally designed to be placed within

hemodialysis

filter

is

hollow

fibers

appears

line to obtain plasma

water

about 2 cm thick and 10 ern long and


with an inner diameter of

in Figure 13,

900

samples.

The

contains

25

As

it

m.

these fibers are much larger than the

normal fibers used for hernofiltration,

allowing the

end-to-

218

Pediatric CAVH

Fig. 13.

Cross-sectional view of the Amicon Minifilter.

end pressure drop in the filter to be very low.

Figures 14-

16

experiments

report

results

obtained by some

in

vitro

carried out to test the Minifilter performance


Figure

14 depicts the filter inlet pressure at

blood flow rates.

various

The resistance of the filter appears to be

low and the inlet pressure begins to rise significantly


for blood flow rates higher than 100 mL/min.
This

very
only

observation

is

supported

by the graph shown in

where the ultrafiltration rate (Qf)

Figure

is plotted against

15

blood

flow (Qb).
The effect of Qb on Qf appears to be very low
under Qb values of 100 mL/min, showing the importance in vivo
of

the

negative pressure generated by

column.

For

the

ultrafiltration

Qb values higher than 100 mL/min (blood


Qf shows a progressive

flows

never

achievable in CAVH),

increase

until

it reaches a plateau determined by the limiting effect

of the surface area.


It must be noted that such high blood
flow rates can be achieved only with a blood pump.
Furthermore,

the

blood flow rates obtained spontaneously with

above

described

cannulas appear to be adequate

to

the

perform

C. Ronco

219

AMICON MINIFILTER

20
0)

J:

.........

16

...
w

::I

12

V)
V)

~
Q..

....w
z

8
4
0

Venous Pressure =0

200

100

300

BLOOD FLOW (ml/min)


Fig. 14.
Behavior of the Minifilter inlet pressure at different blood flow rates.

-E

IN VITRO EXPERIMENT

r::::

.........

.E.

....w

u.:

......

t-

::I

100

200

300

400

BLOOD FLOW {ml/min}


Fig. 15.

Effect of blood flow on ultrafiltration rate

Pediatric CAVH

220

CAVH

in the newborn.

80-90
the

Higher spontaneous blood flow (up

mL/min) might be achieved using larger


effect on ultrafiltration rate,

would be very small,


ultrafiltration

rates

according to Figure

obtained by

transmembrane pressures (TMP).


70 mmHg,
ance
those

Figure 16
applying

the

spontaneous

by

different

hydrostatic

negligible.

to obtain an adequate Qf in

tional pressure must be applied to the membrane;


obtained

shows

Since the resist-

generated by the blood flow is

cond i tions I

15

For TMP values between 20 and

Qf ranges from 0.5 to 2 mL/min.

ot the til ter is so low,

gradient

but

while the risk of thrombosis and hemor-

rhagic complications would be much higher.


the

cannulas,

to

Under

vivo,

addi-

this can be

lowering the ultrafiltrate collecting

bag

and

filter

are

from those of the standard filters

for

maximizing the column height.


The

operational

partially

different

characteristics

of

this

AMICON MINIFllTER

-e
c

"-

..
1.1-

o~~--~--~--~~~~--~--~--~---

10

20

30 40

50

60

70

80

90

100

TRANSMEMBRANE PRESSURE (mmHg)


Fig. 16.
Effects of different transmembrane pressures on
ultrafiltration rate (Qf) with the Amicon Minifilter
(Qb
blood flow)

C. Ronco

221

CAVH used in adults.


ance to blood flow,

The main difference is the low resistthe low ultrafiltration rates achievable

with spontaneous pressures in the absence of additional pressures,

and

finally the low filtration

fractions

generally

obtained during the treatment.


In classic hemodialysis or hemofiltration, TMP levels as
high as 300-400 mmHg can be achieved with mechanical devices,
while
mmHg.

in

CAVH the system operates with TMP levels of

It

is

evident that factors generally

standard hemodialysis,

in

such as plasma protein concentration,

may become very important in this system.


generated

10-30

neglected

The oncotic force

by plasma proteins might in fact act against

fil-

tration, reducing the average TMP.


As the blood moves through the filter,

water is removed

from the blood and the protein concentration increases,


a parallel increase in the oncotic force.
with

the

hydrostatic gradient and

process.
not

In adults treated

CAVH and standard D-20 hemofilters this force may

equal

Many

with

the

arrest

the

even

filtration

In the newborn treated with the Minifilter this is


case because of the low resistance of

the

filter.

experiments have demonstrated that an increase in blood

flow does not result in a parallel increase in Qf,


tration

fraction

in

fact

progressively

and

fil-

decreases.

This

observation suggests that the Minifilter does not operate in


conditions of filtration pressure equilibrium, and this is
clearly
istic

depicted in Figure 10.

This particular

should also offer some advantages in terms

duration

characterof

filter

and clotting in the fibers (less frequent when

low

filtration fractions are achieved inside the filter).


In summary ultrafiltration rate in CAVH can be described
as follows:
Qf = A K TMP
where K is the permeability coefficient of the membrane
A is the surface area of the membrane
TMP is the transmembrane pressure gradient,
expressed by the following equation:

and can be

222

Pediatric CAVH

TMP
where

Pi + Po
2

71 i + 11

+ Pf -

pi

and Po are the hydrostatic pressures at the


and outlet of the filter

Pf

is the negative pressure exerted by the

inlet

ultrafil-

trate column

11 i and fI 0 are the oncotic pressures at the inlet and


outlet of the filter, respectively
All

variables in the equation are dependent on

several

factors, which are summarized in Figure 17.


This equation, however, represents a schematization of a
more complex phenomenon,

which could be summarized more cor-

rectly as follows:
TMP

In

this

equation the average pressures in

expressed

by

the integrals of the curves

TMP=Pi+PO

Arterial pressure,
blood flow,
protein oollC8ntretion
Type and site
of vascular
acc:ass

filter

are

representing

the

Pf- "i+"o
2

Length of the
arterial line

the

Heart/filter
position

Length of the
venous line

Resistance of
the hemofilter

Type of access
venous pressure

+
Diameter of venous line

Diameter of
arterial line

Height of the U F column

Diameter of
UF port

UF-coliecting bag,

position

Fig. 17. Factors affecting ultrafiltration rate in continuous arteriovenous hemofiltration.

c.

223

Ronco

values of hydrostatic and oncotic pressures along each hollow


fiber.
For

practical

purposes Table 3 lists

the

operational

parameters of the filter recorded in seven patients aged 1 to


12

days and treated with CAVH for acute renal

all

failure.

In

the patients the filtration fractions obtained are

low,

even

in

the

presence of adequate blood flow

very

in

the

circuit.
SOLUTE REMOVAL AND MEMBRANE CHARACTERISTICS
An
is

asymmetric synthetic polysulfonic membrane 0.005

employed in the Minifilter utilized for CAVH

(Fig.

18).

in

m2

infants

In addition to the special physical properties,

this synthetic material (commonly used in adults for hemofiltration)

has

cellulosic
activation

passed

and
nor

all

the

safety

tests

and,

other membranes,
it produces no
leukopenia even over a 36-hour

unlike

complement
period of

treatment.
This
ability
The

membrane

extr~~ely

high

hydraulic

perme-

and a molecular weight cut-off below 50,000 daltons.

internal

uniform

has an

surface is IJlm thick and

diameter surrounded by a

macro-porous

65-~m

contains

pores

of

thick mantle layer of

support material with extremely low

resistance

to flow.
Table 3.
Patient
No.
1
2
3
4

5
6
7

Minifilter operational parameters.


Blood Flow
mL/min

Plasma Flow
mL/min

28.0
25.2
15.4
22.0
31. 3
21.5
19.4

19.6
18.7
9.8
14.3
22.4
13.6
10.9

+ 3.1

1'"

-+"+
+
+

2.4
4.2
3.3
3.1
1.4
2.0

+ 2.6

2.0
"+ 3.9
+" 3.0
2.9
-++ 0.9
"+ 1.2

1'"

UF Rate
mL/min
1.1
1.0
0.8
0.7
1.0
0.9
0.9

+ 0.2

0.1
"+ 0.3
+" 0.2
-++ 0.2
0.2
"+ 0.2
:f"

Fi ltr. Fr.
%

6.0
5.2
8.0
5.3
4.4
6.6
8.2

+ 1.3

:f"

0.1

"+ 1.6

"+ 1.0

-++
"+

0.9
0.7
0.6

Pediatric CAVH

224

Fig. 18.

Section of the polysulfonic membrane.

Unlike

the

diffusive

transport

in

dialysis,

where

solutes move through a network of various-sized channels at a


rate

inversely

proportional to their

molecular

size,

the

convective transport of solutes in CAVH is determined by the


diameter of the pores on the internal surface of the membrane.

The

function

solute concentration in the ultrafiltrate is

of the membrane permeability to the solute.

plasma solute freely passes through the membrane,


case with urea,

the "rejection" coefficient ()

If

as is
is

o.

a
a
the

When

the solute does not pass at all, as with proteins, the rejection
and

coefficient is 1.

The ratio between the ultrafiltrate

the plasma concentrations in absence of a

diffusion
rej ection

is

called

coefficient

the "sieving
for

coefficient"

given

solute

calculated as follows:

I - 8

1 -

gradient

[xl

[xl p

(x)

(8).

can

for
The
be

C. Ronco

225

Accordingly, the concentration of a solute in the


trate will be:
[xlf = [xlp

(1

-E)

ultrafil-

[xlp S

Therefore solute clearance in CAVH (Cx) can be calculated

as

follows:
Cx

UF

[xl

Qf

[xl p

since S is generally near 1 the clearance value is nearly


identical to the rate of ultrafiltration. The rate of ultrafiltration per unit of area can be calculated from the
following equation:
Qf/A

= Jf = K

~p

-1l7t)

Accordingly the removal of a solute small enough


through the membrane can be calculated as follows:
Jx

[xl f

to

pass

UF

Finally when the removal is related to a period of time the


obtained value corresponds to the mass transfer rate (MTR)
and can be calculated as follows:
MTRx

= J xl t = [xl f

Qf

This process of convective transport is quite similar to the


physiological function of the human glomeruli; the clearances
of solutes with molecular weight lower than the membrane's
cut-off point do not vary significantly between the two.
In
CAVH this property results in the generation of an ultrafiltrate with the same characteristics as plasma water (Table
4)

However, there is a slight difference of solute concentration in the ultrafiltrate due to the presence of anionic
proteins in the blood rejected at the internal surface of the
Here, Donnan's equilibrium prevails, exerting a
membrane.

Pediatric CAVH

226
Table 4.
Solute sieving coefficients
arteriovenous hemofiltration.

Solute

Plasma
Concentration

Ul trafi 1 trate
Concentration

137.2
4.1

136.3

Sodium
Potassium
Chloride

Bicarbonate

Sieving
Coefficient
0.9B3

99.3

0.985
1. 046

79.1
B.5
7.3
3.9
B.B

BO.9
B.6
7.5
4.1
5.5

1. 023
1. 020
1.015
1.043
0.635

24.0

modest effect on solute passage.


reduction

continuous

4.0
103.6

21.5

BUN
Creatinine
Uric acid
Phosphate
Calcium

no

during

1.124

In our experience with CAVH

in permeability has been noted after up to

B6

hours of treatment.
This

observation plus the consideration of the low

and steady ultrafiltration rates suggest that the


of

"concentration

phenomenon

polarization" is less important

than in classic mechanical hemofiltration.

TMP

in

CAVH

However, periodic

lavage of the filter's fiber pathways with only small quantities

of

effect.
with

isotonic

fluid will further minimize

the

protein

Additionally, complete replacement of ultrafiltrate

substitution will prevent the effects due to

increased

blood viscosity.
HEPARINIZATION
The

preparation

extremely

important

of

the filter for CAVH

for the function and

treatment

duration

of

is
the

filter during therapy (Table 5).


The filter and circuit, after assembly, should be rinsed
with

2,000

heparin/L).

mL of heparinized saline solution (5,000

IU

During the washing procedure the venous line and

the ultrafiltration lines should be clamped periodically


order to remove all the air bubbles from the system.
The
in

of

membrane is a sponge-like tissue and operates

conditions of maximal hydration.

Permeability and

in
best
bio-

C. Ronco

227

Table 5.

Heparin administration.

a)

Wash the filter with 2,000 mL saline containing


(5,000 IU/L)

b)

Determinate patient's coagulative status

c)

Starting bolus:

d)

Start continuous heparin infusion:

heparin

100 IU/kg body weight

5-15 IU/kg body weight/hour


or
0.5 IU/mL blood flow in filter
e)

Control circuit and patient's whole blood clotting


during treatment

compatibility

are

time

directly related to the water content

of

the membrane-surrounding layer.


Since

population treated with CAVH

the

some hemorrhagic problems or risks,


administration
anticoagulant

the treatment should be

during
effect

might

present

the main goal of heparin


an

adequate

in the extracorporeal circuit

without

any systemic consequence on the whole-blood clotting time and


partial

thrombin

time.

After the determination

of

parameters under baseline conditions in the patient,


are

within

normal

ranges,

a bolus of

heparin

if they

should

be

This

is

administered at the rate of 100 IU/kg body weight.


quite

these

large dose but the neonate metabolizes the

heparin

rapidly and the coagulation parameters return to normal after


less

than

maximal

hour;

on the other hand

this

anticoagulant

one

effect during the

first

ensures
minutes

the
of

contact between blood and membrane, which is critical for the


successive function of the filter.
After

these

procedures

have

been

complete,

the

continuous heparin infusion should be provided. Two criteria


can be followed:
a)
administration of 5-15 IU/kg body
weight/hour of heparin; b) administration of 0.05 IU/mL of
blood flow in the filter. Both criteria are designed to give
the minimal dose of heparin adequate to maintain the function
of

the filter without systemic effects.

The blood flow

in

Pediatric CAVH

228

the extracorporeal circuit can easily be calculated with


formula reported at the end of this chapter.
flows

the

Since the blood

recorded in CAVH generally range from 15 to 30 mL/min,

the heparin infusion, regulated by a pump or drop counter,


ranges between 45 and 90 IU/hour.
Although this amount of
heparin is enough to maintain the hollow fibers,

the rate of

metabolism in the newborn is such as to avoid significant


alterations in blood partial thromboplastin time or clotting
time during the treatment.
heparin

Figure 19 reports the effects of

infusion in different points of the system in

patients

treated

with CAVH.

It should be noted

seven

that

maximal

anticoagulation is achieved inside the filter

normal

values are restored in the systemic circulation.

Patient

heparin

treatment

values

the levels are higher because he

were

treatment,

for recent

open

heart

was

In

surgery.

These
the
whole

treatment time.
The dose of heparin required by the Minifilter is

lower

the

showed a stable trend over

of

the

than

they

while

undergoing

recorded two hours after the beginning

but

the

one generally given during the treatment with

standard hemofilters.

The reason is the different

of the blood flow inside the Minifilter's fibers,

the

geometry
which have

a much larger diameter.


The blood travels faster in the
fibers so that lower filtration fractions are achieved, with
a reduction of the
protein/membrane
interactions
and
secondary layer aggregation.
the survival of the filter;

All these factors contribute to


we have never found it necessary

to change one during the treatment of a single patient.


Sometimes

it

can be helpful to wash the

circuit

heparinized solution to make sure the filter is clean and


detect the complete absence of clots.
be
and

at

overload.

the

end

of the circuit in

to

This procedure should

done via the three-way stopcocks placed at the

patient's

with

order

to

beginning

exclude

the

circulation and to avoid unnecessary patient fluid


Once the procedure is completed,

can be continued.

CAVH

treatment

c. Ronco

229

BLOOD PTT DURING CAVH


_

Before Treatment

Systemic eire.

em Filter Inlet

100

80
VI

o
z

60

ou
w

VI

PA TIENTS STUDIED
Fig. 19. Blood partial thromboplastin time during continuous
'arteriovenous hemofiltration.
SUBSTITUTION FLUID
The
patient

removal of large amounts of ultrafiltrate from


(1 mL/min = about 1.5 L/day ) requires the

adminis-

tration of substitution fluid to maintain the body


balance under adequate control.
The amount to be given depends on the preferred
balance to be obtained in that patient.
trate can be replaced in part,
The

in whole,

the
fluid
fluid

The hourly ultrafilor even in excess.

composition of the solutions can be varied according

to

the patient's needs.


The

replacement solution can be administered by manual,

semiautomatic,
the

or completely automated

systems,

rate of replacement on the basis of the

regulating

ultrafiltration

rate of the antecedent period of 15 minutes.


The

use

of this equipment is generally discouraged

in

adults to avoid possible complications of a simple treatment.


In

the newborn particular care has to be taken in

obtaining

the exact fluid balance desired because of the extreme sensi-

230

Pediatric CAVH

Table 6.

Substitution fluids in the newborn.

The amount of replacement fluid depends on the wanted


fluid balance
The
composition
requirements:

should

be

adapted

to

the

body

clinical

Normal saline (control the sodium and water intake)


Ringer lactate (check possible lactic acidosis)
Sodium bicarbonate (2
mM/kg
increase
serum
sodium
bicarbonate of about 5 mM/Li consider sodium load)
If necessary give sodium gluconate supplement
Hyperalimentation solutions (glucose and amino acids solutions; control fluid balance and
caloric intake-nitrogen balance
stud ies)
possible use of biofiltration or hemofiltration solutions

tivity of the neonate to even small variations in body


balance and composition.
solution
to

fluid

THe composition of the replacement

should be adapted to the metabolic requirements and

the electrolyte imbalances recorded at the

the treatment.

beginning

of

The correction or the maintenance of a steady

acid-base balance is also important.


Table 6 summarizes some of the criteria for substitution
CAVH.

Further

details will be given in the section concerning the

clinical

fluid

administration

in the newborn during

management of the treatment.


CAVH IN INFANTS:
CAVH
therapies

is

not

already

INDICATIONS AND CLINICAL MANAGEMENT


a substitute for any
in

use,

of

of

the

monitoring,
peritoneal

technique
even

allows

rapid

as

The s impl ic i-

application

and

easy

in those departments where hemodialysis or

dialysis cannot be used because of

logistic problems.

depurative
them

but it complements

further modality of renal replacement therapy.


ty

the

technical

or

231

C. Ronco
On

the

other

hand

the

clinical

tolerance

and

the

peculiar

operational characteristics of the technique permit

the

of CAVH under clinical conditions

use

types

of

treatment

might be dangerous

(severe cardiovascular instability,

in

or

which

other

contraindicated

polytraurnatisrns,

multi-

organ failure, abdominal surgery, septic shock).


Table
hospital
from

the

The age of our

patients

was less than 1 mL/kg/hour.

The

causes

renal failure are reported in Table 7 and for all

patients

hemodialysis

or peritoneal dialysis

were

our

ranged

to 12 days and the urine output at the beginning

treatment

acute

shows the population treated with CAVH in

until June 1985.

of
of
the

contra-

indicated or precluded due to clinical or technical problems.


In the majority of the patients acute renal
failure
developed after abdominal surgery (pyloric stenosis, necrotizing
dialysis
of

enteritis,

peritonitis)

and the use

The other

Table 7.
Population treated with continuous
hemofil tration.

Age
(Days)

No.

Sex

12

ARF

peritoneal

under those conditions was contraindicated

the risk of leakage and infections.

Patient

of

Diagnosis
Postoperative
ARF
postoperative
ARF
Cardiac surgery
ARF
Septic shock
ARF
Perinatal
asphyxia ARF
Abruptio
placentae ARF
Postoperative
ARF

acute renal failure

because
patients

arteriovenous

Duration of
Treatment
(hours)

Outcome

86

Recovery

78

Recovery

30

Death

48

Death

46

Recovery

32

Death

70

Death

232

Pediatric CAVH

were

affected

use

by severe cardiovascular instability and

of peritoneal dialysis or hemodialysis

was

the

contraindi-

In all patients the treatment was well tolerated and


cated.
The treatment duration
the treatment monitoring was easy.
varied from 30 to 86 hours and no complication related to the
treatment

occurred

recovered

renal function and regular diuresis was

with

dur ing

the

therapy.

Three

patients
restored,

a parallel return to normal of the solute blood concen-

tration.
According to the patient's clinical condition and to the
body fluid and solute abnormalities special strategies
used to obtain effective correction of the symptoms.
Fluid overload.
Fluid

overload

with pulmonary vascular

pulmonary edema may occur in the newborn,


acute renal failure but also because of
excessive
reduced

in

which

or absent.

therapy,

the response to

congestion

and any

diuretic

of

dialysis

control.

Under

the

therapy

is

When oliguria is refractory to diuretic

body fluid balance may be difficult to control

peritoneal

or

not only due to


cardiac failure,

fluid intake during operations,

situations

were

is

those

not

always able

to

provide

conditions the use of

CAVH

and
this

allowed

reduction of overhydration, maintaining a negative balance of


fluid

during

several hours of

of replacement solution

In

words,

the

period

was constantly less than the amount of fluid

from

amount

ultrafiltration.

the body by ultrafiltration.

removal
produces

of

given

The slow and

isotonic fluid is generally well

other

in

this

removed

continuous

tolerated

and

marked decrease in ventricular after load and a


The latter is probably responsible
negative sodium balance.
for a decrease in peripheral vascular resistance and a consequent increase in cardiac index.
In Figures 20 and 21 the
cardiovascular response to CAVH treatment in four patients is
shown in terms of arterial pressure and heart rate.
Removal
of fluid is well tolerated and no significant modifications
in

the

ment.

cardiovascular activity are noted during the


Note

that Patient 3 had altered values

of

treatarterial

C. Ronco

233

80

MEAN ARTERIAL PRESSURE

68
0)

::I:

E
E

56

44
32

HOURS
Fig. 20.
Mean arterial pressure during continuous arteriovenous hemofiltration in four neonates.

200

HEART RATE

180

E
"CO
W

I-

DI:
I-

DI:

:J:

Patient n2
1000

40

60

80

100

HOURS
Fig. 21. Cardiovascular response to continuous arteriovenous
hemofiltration treatment in four neonates.

Pediatric CAVH

234

pressure and heart rate since the beginning of the treatment,


but

this was due to the cardiac malformation (left ventricu-

lar hypoplasia)
fluid

allows

present from birth.


for

continuous plasma refilling

oncotic effect of proteins;


when

extravascular

present.
during

The removal of isotonic

Finally,

overhydration
the

due

to

this can be particularly


or

cerebral

cardiovascular

the

useful

edema

are

stability

obtained

treatment enhances the possibility of rapid

restora-

tion of normal renal blood perfusion.


Electrolyte and acid-base derangements.
The easy manipulation of extracellular fluid
with

CAVH

permits

derangements.
and
of

the

treatment

Hyponatremia,

several

hypernatremia,

electrolyte

hypercalcemia,

hyperkalemia can be managed by changing the


the

replacement

depends,

of

course,

solution.

liters

of ultrafiltrate,

circulating

The

speed

kg

vary

not only the concentration but also the

body

times
weight.

high turnover of fluid can also be used

of some electrolytes.
in

correction

which represents about five

volume in a neonate of 3

relatively

useful

of

During a day CAVH may produce 1.5

This

content

composition

on the ultrafiltration rate and on the

amount of exchanged fluid.


the

of

achievable

absolute

This effect is

body

particularly

the treatment of the edematogenic syndromes

involve increased total body sodium,

to

that

where a negative sodium

balance is required.
Hyperkalemia can also be corrected with CAVH:
ciency

of

amount

of ultrafiltrate generated throughout the

removing

potassium is directly

the effi-

related

to

the

treatment.

CAVH is also reliable in the treatment of hypercalcemia or in


some

conditions

of

acute

renal

failure

associated

alkalosis in which hemodialysis or peritoneal dialysis

with
might

worsen the clinical condition of the patient.


In

all these procedures not only should the

electrolyte losses of the ultrafiltrate be


also gastrointestinal losses,
increased

associated with prematurity or other conditions,


of overhead heating canopies.

fluid

and

considered, but
insensible loss
and the use

Hypocalcemia may occur in the

C. Ronco

235

newborn
due to immaturity of the parathyroid
glands,
especially during an exchange transfusion using acid-citratedextrose.

In

those

conditions

convulsion may

calcium administration is urgent.

occur

and

Because calcium solutions

are irritant, CAVH is a good method for administering calcium


supplementation

because the replacement solution is

rapidly

diluted by the blood returning to the venous circulation.


the absence of convulsions calcium gluconate
can
a

In

supplementation

be scheduled in addition to the replacement solution and


continuous

infusion

mg/kg/hour.

Of

can be provided at

the

rate

solutions are incompatible with sodium bicarbonate.


nesemia may occur in association with
exchange

tr~nsfusion

hydantoin

to

pregnancy.
exceed

of

course it should be considered that calcium

the

Hypomagfollowing

hypocalce~ia

or following administration of diphenyl-

mother for the treatment

Treatment

of

toxemia

with 1% magnesium sulfate should

5-19 mL at the rate of 0.5-1 mL/min.

The losses

in
not
in

the ultrafiltrate should be considered.


In
be

acid-base derangements,

considered.

measured

different situations should

Bicarbonate loss during CAVH can easily

directly

in

the ultrafiltrate

or

by

using

be
the

formula:
HC03(f)
where:

UF x HC03(s) x 1.124

is the bicarbonate
HC03 (f)
ul trafil tra te
HC03 (s)

is

the

concentration

in

the

bicarbonate concentration

in

the

serum
UF is the total amount of ultrafiltrate
1.124

is the average sieving coefficient for bicarbonate

When

CAVH is applied without substitution fluid in order

reduce the patient's fluid overload,


compensated

bicarbonate losses

to
are

by the reduction of the body volume distribution

for the buffer,


s ig ni ficantly.

and the serum concentration does not

change

236

Ped ia tr ic CAVH
On

the

other

hand,

when

replacement

infused to maintain the body fluid balance,

solutions
the same

are

amount

of bicarbonate lost in the ultrafiltrate must be administered


to achieve stable serum levels of the buffer.

Finally, when

CAVH is used to correct metabolic acidosis (Fig. 22)


the
amount of bicarbonate in the replacement solution must exceed
the

amount lost in the ultrafiltrate,

providing a

positive

balance of the buffer.


In conclusion,

when a correction of water, electrolyte,

or acid-base derangement is required,


tration,

the rate of reinfusion,

trations,

the

ultrafil-

the initial plasma concen-

the rate of metabolic production,

in the ultrafiltrate,
content

the rate of

the amount lost

the amount lost in other ways, and the

of the replacement solutions must be considered

different solutes in order to achieve the desired

for
final

balance and the plasma concentration.

30

'E

26

22

SERUM BICARBONATE
Patient nl

_ ..............-- Patient n4

:::I:

en

0::
::J

:::I:

10

100
HOURS

Fig. 22.
Correction of metabolic acidosis in four neonates
using sodium bicarbonate in the replacement solution.

C. Ronco

237

BUN LEVELS DURING CAVH


CAVH Discontinued
~ _ Patient 1
III Patient2
CJ Patient 3
f'llJ Patient 4

50
-0

........

40

30
20
10

o o

10

20

30

40

50

60

70

80

HOURS OF TREATMENT
Fig. 23. BUN levels in four neonates treated with continuous
arteriovenous hemofiltration.
Solute removal and metabolic balance.
The operational characteristics of CAVH result in the
treatment not being particularly efficient in removing waste
products.

This

is mainly due to the identical

between ultrafiltrate and plasma water.


depurative

efficiency

depurative

therapy

other

substitutive

problems.

Despite this limited

CAVH can be used

as

an

in patients who cannot be


therapies

composition

because

of

alternative
treated

with

their

medical
Furthermore, CAVH can be applied as a first-choice

treatment when soft fluid removal and continuous blood


purification over a prolonged period of time are required.
This is the case in patients with multiorgan failure, cardiovascular instability, cerebral edema, and other conditions in
which hemodialysis or peritoneal dialysis may even worsen the
patient's clinical condition.
Despite

the

achievable in CAVH,
cient
Figure

to

control

remarkable

amount

of

ul trafil tration

the treatment may sometimes be


the

metabolic balance

of

23 reports the BUN levels recorded in

insuffi-

the

patient.

four

newborns

Pediatric CAVH

238

treated

with

appeared

The

CAVH for acute renal failure.

treatment

to be effective in removing urea nitrogen in

patients,

while

in

Patient

the

BUN

levels

three

increased

progressively despite the depurative therapy.


The limited
efficiency of the treatment can be evident in patients with a
severe catabolic state and high rates of urea generation.
Several strategies can be applied in order to increase the
treatment

efficiency

1.2-1.8 g/day.
tration

rate

however,

when the urea generation rate

Of course the maximal increase in


should be the first approach to

special

exceeds
ultrafil-

the

problem;

care must be taken in the reduction of the

protein catabolic rate and urea generation in order to obtain


a

positive nitrogen balance.

studies

in

Considering the urea

Patients land 4,

reported in Table

kinetic
it

8,

is

evident that the efficiency of the treatment depends not only


on

the

ultrafiltration

rate,

but

also

on

the

rate

of

metabolism and urea production.


In an attempt to achieve a
positive nitrogen balance and to control the BUN level, early
institution
of
parenteral hyperalimentation should
be
scheduled.
Hyperalimentation

must

be carried out in

the

newborn

with special attention to the patient's fluid and electrolyte


Glucose

requirements.

solutions

and mixed

essential

and

nonessential amino acid solutions should be provided in order


to obtain an energy intake ranging from 100 to 150 Cal/kg/day
and

to prevent cellular protein breakdown.

however,

even

In some

cases,

these strategies are insufficient to maintain

the BUN level under adequate control,

and further depuration

is required to treat those patients.

In those conditions the

low efficiency of the technique may limit its application and


other

treatments

should be used,

even in the

presence

of

technical or clinical problems.


New developments.
Because of these limitations, partially linked to
relatively low rate of ultrafiltration achievable with

the
the

Minifilter,

the

original

0-20

we

developed
hemofilter,

new

devices

derived

from

with special characteristics

of

239

C. Ronco
Table 8.
Urea kinetic study (48 hours)
arteriovenous hemofiltration.

during

continuous

Patient 1
Treatment time (min)
Ultrafiltration rate (mL/min)
Replacement (mL/min)
Urea generation (mg/min)
Total urea generation (mg)
Urea removal (mg/min)
Total urea removed (mg)
BUN concentration (mg/dL)

Patient 4

2880
1.1
1.1
0.7
2016
0.5
720
+ 4

2880
0.7
0.7
1.2
3446
0.5
720
+ 30

resistance and priming volume.


The new hemofilter
is a
hollow fiber polysulfonic device with 0.13 m2 of surface area
in

which the fiber length is 7 cm and the resistance is very

low.

This device,

shown in Figure 24 along with the

filter and the Standard 0-20,

Mini-

allowed the treatment of small

patients with severe catabolism and permitted an ultrafiltration

rate

low

blood

patients

of about 4 mL/min even in the presence of a


flow.
during

However,
treatment

some problems

arose

because of the

high

those

filtration

fractions

achieved

necessary

to reduce the length of the ultrafiltration column

in

to

order

(45-50%).

very

in

In these conditions

decrease the transmembrane

pressure

it
and

was
the

filtration fraction; this procedure avoided further complications

due to the high viscosity of the blood in

the

filter

and the patient was safely treated (Fig. 25).


Treatment monitoring.
The
ty.
a

main feature of the CAVH treatment is its simplici-

Once the circuit and the filter are assembled and primed
final

check should be

performed;

the

following

should be controlled:
arterial and venous blood access
connections between lines and the filter
heparin infusion system
replacement solution infusion system
ultrafiltrate collecting system

points

240

Pediatric CAVH

Fig. 24.
Hemofilters for continuous arteriovenous hemofiltration (left to right):
Minifilter, prototype 0-10, normal
0-20.

Fig.
25.
A three-month-old girl undergoing continuous
arteriovenous hemofiltration with the 0-10 hemofilter.

C. Ronco

241

Table 9.

Key formulas.

Blood flow (Qb):

Qb

Plasma flow (Qp):

Qf

Qp = Qb - Red cell mass


Red cell mass = 1 - Ht/100

Filtration fraction (FF):

FF%

Qf/Qp
Pi + Po

Transmembrane pressure (TMP):


Solute (x) removal (J):

Mass transfer rate (MTR):


Clearance (C):

Once

[Prot] i

1 -

[Prot]

+ Pf -

= UF

[x] f

MTR

= J/t =

11 i + 11
2

Qf [X]f

where S = [X]f/[X]p

C = Qf S

these checks have been performed the treatment

initiated
plastin
taken

and
time,

from

samples

baseline blood samples for


clotting time,
hematocrit

and

partial

can

be

thrombo-

and blood chemistry should be

the arterial line.

for

Arterial and
total

protein

venous

blood

concentration

determinations should be taken 15 minutes after the beginning


of the treatment in order to calculate the blood flow and
filtration

fraction

Table

An

9.

according to the formulas

reported

accurate reading of the ultrafiltration

in
rate

should be carried out every 15 minutes and ultrafiltrate


samples can be drawn from the collecting bag in order to make
sieving coefficient calculations.

The patient's vital signs

should be recorded (heart rate, arterial pressure, breathing,


etc.)
avoid

and body temperature should be controlled in order to


dangerous hypothermia.
If necessary a heating system

should be applied to the extracorporeal circuit.


Throughout
the treatment hourly monitoring of these parameters is
generally adequate to maintain the patient under steady
conditions.

Progressive measurements of the blood

chemical

Pediatric CAVH

242
levels

and

regulate

the

ultrafiltration

rate

should

be

used

the rate of replacement and the composition of

substitution

fluid.

An additional check of the body

to
the

fluid

balance can be made with a graduated bed scale.


The maximal efficiency of the treatment is related to
the ultrafiltration rate achieved.
A periodic inspection of
the blood access and of the blood lines should be made in
order

to

gradient.

maintain
The

an

adequate

blood

flow

and

ultrafiltrate line should be

pressure

maintained

as

long as possible to maximize the negative pressure exerted on


the membrane by the ultrafiltration column (Figs. 26 and 27).
Complications.
Although CAVH is a safe and simple method,

technical or

clinical complications may occur during the treatment.


Clinical complications.
specific loss of vitamins,

Depletion

syndromes

or

non-

amino acids,

hormones,

etc., as

well as hypophosphatemia, can occur throughout the treatment.


In

our

probably

experience

these

complications

never

because specific parenteral nutrition

occurred,
support

provided during the treatment.


Electrolyte and
imbalances can occur if inappropriate replacement
are prescribed.
sive
made
the

may

acid-base
solutions

Bleeding episodes can be observed if exces-

doses of heparin are given.

hydration

was

Hyperhydration

or

hypo-

be observed when errors in fluid balance

due to inadequate control of ultrafiltration


rate of replacement solution infusion.

are

rate

and

We suggest

the

use of micromethods for the blood chemistry determinations in


order to avoid significant reductions in the patient's
hematocrit due to excessive blood sample drawing.
When
necessary,

blood

transfusions

can

replacement solution infusion port.


must

be

taken

be

provided

Finally,

with drug administration

via

special

according

to

the
care
the

plasma concentrations, the protein binding, and the molecular


size of
process.

the drug,

all of which affect the

ultrafiltration

Technical complications.
Blood loss can occur if a
hollow fiber develops a leak.
This potential problem is

c.

243

Ronco

Fig. 26. The continuous arteriovenous hemofiltration system;


the ultrafiltration column allows the maximal transmembrane
pressure gradient.
quite

negligible because of the low pressures

the system.

operating

in

Should it occur, the high visibility of the red

blood cells in the filtrate render the problem rapidly


detectable and a rapid exchange of the filter can be
scheduled.
When ultrafiltration rates drop below 0.5 mL/min
a

general

inspection of the

filter,

blood

access,

blood

lines, and patient arterial pressure should be carried out.


If clotting
in the fibers
is suspected
lavage can be

performed

using

50-100 mL of heparinized solution

via

the

Pediatric CAVH

244

Fig. 27.
Continuous arteriovenous hemofiltration system.
Filter and lines primed and connected to the patient and
ready to start the treatment.
three-way
If

this

Finally,

stopcocks,
is

excluding the

unsuccessful,

patients'

the filter should

circulation.
be

it must be noted that air embolisms are

replaced.
impossible

in this system, which operates under conditions of positive


pressure.
Special care must therefore be taken when the
umbilical vessels are used for blood access.
CONCLUSIONS
Continuous
an

arteriovenous hemofiltration can be used

as

alternative treatment in infants and children as well

as

in the adult. The small size of the patients may represent a


problem and special supplies are required.
However, the
clinical

experience

so

far

suggests

that

the

technical

problems of technique can be overcome. Clinical tolerance is


well demonstrated and the simple and safe use of CAVH in
those conditions in which hemodialysis or peritoneal dialysis
are

precluded

or contraindicated make this treatment a

new

C. Ronco

245

development of substitutive therapy in the neonate.


Further
studies must be performed to obtain statistically meaningful
data.
for

Finally

an accurate study of the materials necessary

the performance of CAVH in such small patients

carried

out;

as

must

long as new devices and supplies are

vided, safer and more reliable use of the


certainly be ensured.

technique

be
prowill

REFERENCES
1.
Donckerwolcke RA, Chantler C, Broyer MJC:
Paediatric
dialysis, replacement of renal function by dialysis,
edited by Drukker W, Parsons FM, Maher JF, Boston,
Martinus Nijhoff Publishers, pp 514-535, 1983.
2.
Lauer A, Saccaggi A, Ronco C, et al:
Continuous
arterio-venous hemofiltration in the critically ill
patient. Ann Intern Med 99:455-460, 1983.
3.
Kramer P, wigger W, Rieger J, tal:
Arterio-venous
hemofiltration:
a new and simple method for treatment
of overhydrated patients resistant to diuretics.
Klin
Wochenschr 55:1121-1122, 1977.
4.
Ronco C, Biasioli S, Brendolan A, et al:
Aspetti
teorici ed applicazione clinica della ultrafiltrazione
artero-venosa continua.
Minerva Nefrol 30:195-206,
1983.
5.
Sargent JA, Gotch FA:
Mathematic modeling of dialysis
therapy. Kidney lnt 18 (supple 10):S2-S10, 1980.
6.
Pappenheimer AM Jr: Passage of molecules through capillary walls. Physiol Rev 33:387-423, 1953.
7.
Lieberman KV, Nardi L, Bosch JP:
Treatment of acute
renal failure in an infant using continuous arteriovenous hemofiltration. J Pediatr 106:646-649, 1985.
8.
Ronco C, Bragantini L, Brendolan A, et al: Treatment of
acute renal failure in the newborn by
continuous
arteriovenous hemofiltration. Kidney lnt (in press).
9.
Ronco C, Brendolan A, Bragantini L, et al: Treatment of
acute renal failure in newborns by continuous arteriovenous hemofiltration. ASAIO 1985 (in press)

CONTINUOUS ARTERIOVENOUS HEMODIALYSIS - LABORATORY EXPERIENCE


AND THEORY
H. BREGMAN
T. ING
Lutheran General Hospital, Niles, Illinois
Administration Hospital, Hines, Illinois

The
(CAVHD)

concept
was

of continuous

arteriovenous

and

Veterans

hemodialysis

first suggested in 1960 by Scribner et al

(1).

Since then, various forms of continuous renal fluid replacement therapy such as continuous ambulator peritoneal dialysis
(CAPD)
and continuous arteriovenous hemofiltration (CAVH)
have been developed.
As we will describe, the original
concept of continuous hemodialysis may prove to be the treatment

of choice for continuous therapy in the critically

ill

patient with renal failure.


HISTORICAL PERSPECTIVE
Scribner et al (1) described CAVHD, whereby blood,
obtained from an arteriovenous shunt, was driven by the
patient's own blood pressure, rather than by a blood pump,
through

a cuprammonium cellulose

spontaneous

between 30 and 135 mL/min.


prevent

plate

hemodiaiyzer.

blood flow rate through the hemodialyzer

clotting.

The
ranged

Heparin was given continuously to

Dialysate was cooled to 0 0

C to prevent

bacterial overgrowth and dialyzed blood was rewarmed


being returned to the patient.

before

Eighteen patients were dialyzed continuously in this


manner for a total of 68 days, with the duration of treatment
for

each

patient varying from 1/2 to 14 days.

Serum

urea

nitrogen levels stabilized at or below 100 mg/dL through


removal of 20 or more grams of nitrogen per 24 hours.
The
goal

of

the

procedure was to achieve a urea

247

clearance

of

CAVHD - Lab

248

about 14 mL/min, a value approximately 10% of that obtained


with present-day, intermittent hemodialysis.
Subsequently, the development of more efficient hemodialyzer membranes has markedly reduced dialysis treatment
time (2).
However,
critically ill patients generally
tolerate modern, short-duration hemodialysis treatments (in
association with ultrafiltration)
poorly because of the
deyelopment of hypotension as a result of cardiovascular
instability.
In 1981,
ment

in an attempt to devise a renal fluid replace-

therapy for patients who are seriously ill and

hemody-

namically unstable, Kramer et al (3) pioneered the concept of


CAVH,

patient

technique

uniquely suited to

the

critically

with renal failure and overhydration.

elsewhere

in

hemofilter
cannulas

this book,

connected

to

functioning

CAVH utilizes a
large-bore

As described

highly

arterial

as vascular conduits.

ill

permeable

and
By

venous

virtue

of

convective

forces derived from the hydrostatic pressure (and

ultimately

the blood pressure) and applied across the

hemo-

filter membrane, an ultrafiltrate of blood is formed.


The
higher the blood pressure and hence the hydrostatic pressure,
the

greater

the

convective force and

the

ultrafiltration

rate.
Since the concentrations of ultrafilterable solutes
(including most waste products) in an ultrafiltrate of plasma
are closely similar to those in plasma water, the higher the
rate

of ultrafiltration,

the greater the removal

of

these

solutes from the blood.


The purpose of CAVH is to get rid of waste products from
the
to

body,

although it is understood that a secondary aim is

maintain or achieve euvolemia (4).

adequate

In order

to

remove

amounts of waste products from a patient with renal

failure, high rates of ultrafiltration (12 tp 15 L/day)


are
generally needed (3).
Such a large volume of ultrafiltrate
greatly exceeds the quantity of any available excess fluid in
a

given

patient.

substitution
volemia.

Administration

of

plasma-resembling

fluid is therefore necessary to

prevent

hypo-

H. Bregman and T. lng


The

249

high rate of ultrafiltration required with CAVH has

rekindled

interest

in

CAVHD.

It

was

reasoned

that

exposing the nonblood side of a hemodialyzer/hemofilter

by
mem-

brane to a dialysate solution, the process of diffusion would


occur, and solute removal would take place. Moreover, since
blood pressure in the device will generate a transmembrane
pressure gradient, an element of ultrafiltration would automatically
could be

be added.
The magnitude of this ultrafiltration
tailored to an individual patient's particular

needs.
MORE RECENT DEVELOPMENTS
Recently, lng et al incorporated the concept of
sion

into

their design of CAVHD (5).

These

diffu-

investigators

successfully performed CAVHD in an experimental animal for 24


hours,

using an arteriovenous shunt, conventional nonsterile

hemodialysate, and a highly permeable hemodialyzer/hemofilter


made

of polysulfone membrane.

The animal's blood

propelled the blood through the device.


monitor

An

pressure

ultrafiltration

was used for precise control of fluid removal during

dialysis.

These

intensive-care

investigators

clinical

were

able

to

mimic

setting by infusing four liters

an
of

physiologic saline and removing an equal volume of

ultrafil-

trate during a 24-hour period, at the same time


substantial waste-product removal.

achieving

Geronemus and Schneider (6) modified Scribner's basic


principle of CAVHD and performed the improved procedure on
their
highly

patients.

These

permeable),

regenerated

cellulose.

artery

the

and

workers used

conventional

(not

O.6-m 2 hollow-fiber hemodialyzer made of

femoral

For vascular
vein

were

access,

the

cannulated

femoral

(Fig.

1).

Dialysate consisted of standard sterile peritoneal dialysate,


Gontaining 1.5 g/dL glucose buffered with lactate.

Being at

room temperature, the dialysate was administered by an infusion pump at a rate of 15-20 mL/min (22-29 L/day)
in a
single-pass, countercurrent fashion, i.e., in a direction
opposite to that of blood flow.
Ten patients were studied

CAVHD - Lab

250

Peritoneal
dialysate

~-------------------------"
-----===~,,/

eparin

=
Fig. 1. Schematic of vascular access via the femoral artery
and femoral vein.
for

23-108

levels

hours of therapy.

of

After stabilization

blood waste products in 1 to 2 days,

of

mean

the
serum

values of urea nitrogen and creatinine were 44 mg/dL and


mg/dL,

respectively.

stated

that

membranes

More

recently,

these

4.5

investigators

they believed that the use of highly

allowed a higher ultrafiltration rate (up

permeable
to

322

mL/hr) than conventional hemodia1yzers (7).


Ronco et a1 (9) modified the dialysate side of the basic
CAVHD system.
ing

CAVH

combination

In patients with renal failure already receiv-

treatment
of

(in other words,

with a

highly

permeable

CAVH and CAVHD was performed

membrane,

intermittently

hemodiafiltration, or simUltaneous hemofi1-

tration and hemodialysis) by additionally infusing peritoneal


dialysate into the nonb1ood

compartment of the hemodia1yzer/

hemofi1ter so as to augment solute removal with fair success.

H. Bregman and T.

251

Ing

CLINICAL APPLICATIONS
At present,
principles

for patients who require CAVHD, the general

underlying the method of Geronemus and

(6) should be followed.


or

cannulate

access.

a large artery and a large vein

A highly permeable plate

hemofilter

should

be

Schneider

One can use an arteriovenous

used.

for

shunt

vascular

or capillary hemodialyzer/

Heparin

is

usually

infused

continuously at'between 500 to 1,000 units per hour.

Sterile

peritoneal dialysate containing 1.5 g/dL glucose, and lactate


should
into
aid

ordinarily be used.

The dialysate can be introduced

the nonblood compartment either by gravity or with


of

a volumetric pump.

inflow

into

obtained.
every

and

Accurate

the outflow from the

measurements
dialyzer

The tubings and the dialyzer (6)

2 days.

of

should

the
the
be

should be changed

Since glucose in the dialysate diffuses into

the blood, frequent measurements of blood glucose values


should be carried out.
Serum electrolytes and phosphate
levels should also be monitored often. Addition of potassium
supplements to the dialysate should be determined on an
individual basis.
COMPARISONS AMONG CONVENTIONAL HEMODIALYSIS, CAVH, AND CAVHD
In the case of conventional acute hemodialysis, vascular
access requires either cannulation of a large vein (e.g., the
femoral

or the subclavian)

shunt.

or creation of

an

conventional

hemodialysis is an intermittent,

replacement

therapy

staff.

critically ill patients with renal

In

overhydration,
removal,
with

arteriovenous

with each session lasting no longer than a few hours,

in

requiring

specially

intense renal

trained

and

order to achieve optimal solute and fluid

daily conventional hemodialysis treatments

dialytic

dialysis

failure

ultrafiltration

(ultrafiltration

coupled
during

dialysis)
or with isolated ultrafiltration is often necessary.
Overhydration occurs in these patients because they
frequently receive large volumes of intravenous fluids in the
form of parenteral nutrition mixtures, blood and blood
products, blood substitutes, electrolyte solutions, antibi-

CAVHD - Lab

252

otics, vasopressors, and other medications.


However, as
mentioned earlier, these patients may be too ill to stand the
vigor of conventional hemodialysis.
In the case of CAVH and CAVHD, a large-bore (usually 810

F)

be

used in order to provide sufficient inlet pressure to the

femoral artery cannula or an arteriovenous shunt

hemofilter/hemodialyzer.

Both procedures require close moni-

toring by critical-care personnel.


dialysis,

Unlike conventional hemo-

both CAVH and CAVHD allow,

volume-overloaded patients,
fluid

must

in the gravely ill and

the continuous removal of excess

and waste products in a slow and smooth manner over

prolonged period of time.


Thus complications that are often
associated with conventional hemodialysis in the critically
ill

patient

will be minimized.

superior to CAVH (5,9).

We believe that

Firstly,

CAVH requires the

venous infusion of large volumes of expensive,


sterile substitution fluid.
sate

CAVHD

with CAVHD,

is

intra-

high-quality,

the sterile dialy-

does not have to meet the stringent criteria of

fluids

for intravenous administration and hence is less expensive to


prepare.

In

fact,

such

dialysate

can

be

produced

inexpensively with automated dialysate delivery machines that


are ordinarily used
peritoneal dialysis.

to make dialysates for intermittent


Secondly, because no fluid is given

intravenously during CAVHD, the risks of air embolism


intravenous therapy are eliminated.
Although
clinical
needed.

CAVHD

experience
For example,

is

theoretically

and

improvements

appealing,
in

further
technology are

an ultrafiltration monitor that could

handle sterile dialysate would facilitate removal of a


quantity of ultrafiltrate during CAVHD.
with

cardiovascular

given

Also, since patients

instability may be susceptible

development of lactic acidosis,


sate

from

to

the

systems for producing dialy-

buffered with bicarbonate (10) rather than with lactate

or acetate are needed.

H. Bregman and T. Ing

253

REFERENCES
1.
2.
3.
4.
5.
6.

7.

8.

9.
10.

Scribner BH, Caner JEZ, Buri R, et al: The techniques


of continuous hemodialysis.
Trans Am Soc Artif Intern
Organs 6:88, 1960.
Cambi V, Savazzi G, Arisi L, et al:
Short dialysis
schedules (SDS) - finally ready to become a routine?
Proc Eur Dial Transplant Assoc 11:112, 1974.
Kramer P, Schrader J, Bohnsack W, et al:
Continuous
arteriovenous hemofiltration.
A new kidney replacement
therapy. Proc Eur Dial Transplant Assoc 18:743, 1981.
Ing TS, Daugirdas JT, Chandran KGP, et al: Continuous
arteriovenous ultrafiltration versus continuous arteriovenous hemofiltration. Int J Artif Organs 7:165, 1984.
Ing TS, Purandare VV, Daugirdas JT, et al:
Slow
continuous hemodialysis. Int J Artif Organs 7:53, 1984.
Geronemus R, Schneider N:
Continuous arteriovenous
hemodialysis:
A new modality for treatment of acute
renal failure. Trans Am Soc Artif Intern Organs 30:610,
1984.
Geronemus R, Schneider N: Further studies with continuous arteriovenous hemodialysis (CAVHD) in acute renal
failure (ARF).
Abstract, Am Soc Artif Intern Organs
14:54, 1985.
Ronco C, Brendolan A, Bragantini L, et al:
Arteriovenous
hemodiafiltration
(AVHDF)
combined
with
continuous
arteriovenous
hemofiltration
(CAVH)
Abstract, Am Soc Artif Intern Organs 14:36, 1985.
Ing TS, Daugirdas JT, Bregman H, et al:
Continuous
arteriovenous hemodialysis.
Int J Artif Organs 8:117,
1985.
Ing TS, Daugirdas JT, Nawab ZM, et al: Preparation of a
bicarbonate-buffered, plasma-resembling parenteral solution. Int J Artif Organs 1985 (In press)

CONTINUOUS ARTERIOVENOUS HEMODIALYSIS - CLINICAL EXPERIENCE


R. GERONEMUS
N. SCHNEIDER
Florida Medical Center, Lauderdale Lakes, Florida

Acute

renal

failure,

especially in the

patient

with

multiorgan failure, still carries a substantial mortality and


morbidity

despite the recent technological

medicine.

The

goals

advancements

for the adequate treatment

of

in

acute

renal failure require:


1.

Adequate removal of waste products

2.

Correction and maintenance of acid-base balance

3.

Treatment

of electrolyte disorders,

especially hy-

perkalemia
4.

Treatment of volume-overloaded states

5.

Nutritional support

In addition,

these goals should be accomplished without

further destabilization of an already unstable patient.


Numerous approaches to the treatment of these patients
have been utilized (1).
These include bicarbonate dialysis,
high sodium dialysis,
various
slow

forms

cool

of peritoneal dialysis.

dialysate,

(CAVH) was originally proposed by

approach

and

The alternative

continuous treatment by continuous arteriovenous

filtration
this

hemofiltration,

Kramer

is discussed in other chapters in this

of

hemo(2-4);
book.

Based upon the concept of continuous treatment in CAVH and on


earlier
dialysis,
proposed

work

by

Scribner (5) with

continuous
as

form

of

continuous

arteriovenous hemodialysis (CAVHD) was

an alternative treatment of

renal

failure

in

critically ill patients (6).


This treatment borrows the
passive-flow system (no blood pump) from CAVH, but utilizes
diffusion as the major method of toxin removal and electrolyte exchange.

255

CAVHD - Clinical

256
Numerous

unit

setting

have been treated with CAVHD over a 24-month period.

In the

initial

studies,

rected

in the intensive care

volume removal was limited;

in later studies with dialyzers with

membranes.
than

patients

In the initial studies,

adequate;

the

this was cormore

permeable

urea clearance was more

later studies showed an improvement

in

has been our goal in developing CAVHD to provide

an

this area as well.


It

effective,

stable

treatment modality for renal failure that

meets the above-mentioned criteria and, that does not require


expensive equipment nor sophisticated nursing capabilities.
GENERAL METHODS OF OPERATION
schematic

Figure 1.
arterial

in

Short arterial tubing is connected to the femoral


cannula and to the dialyzer;

completed
venous

of the extracorporeal circuit is shown


the blood circuit

with short venous tubing connected to the

cannula.

Direction

is

femoral

of blood flow is shown

in

the

figure.

Care is exercised to avoid kinks in the tubing

and

cannulas

during the procedure to ensure high blood flow

and

to prevent clotting.
in

the

Ideally, the dialyzer should be placed

patient's bed rather than on an intravenous pole

or

bedside table to avoid accidental disconnections.


Dialysate

is administered in countercurrent fashion

in standard hemodialysis (Fig.

1).

as

In these studies, inlet

dialysate flow was controlled by an IV infusion pump generally

at 15 mL/min.

fluid

in

follows:
calcium,

2- to
1.5
1.5

Dialysate fluid was


5-liter plastic bags

g/dL dextrose,
mEq/L magnesium,

peritoneal
with

composition

132 mEq/L sodium,


96 mEq/L chloride,

lactate with a final osmolality of 346 mOsm/L.

dialysis
3.5

as

mEq/L

35 mEq/L

KCl was added

as required in amounts of 0-4 mEq/L.


Special dialysate
fluids were used for certain conditions such as hyperkalemia
or severe acidosis.

Prescription dialysate for the metabolic

requirements of the patient can be modified as required.

R. Geronemus and N. Schneider

257

Fig. 1. Schematic diagram of continuous arteriovenous hemodialysis system.


1) Arterial line with sampling port.
2)
Hollow-fiber or flat-plate dialyzer.
3) Venous tubing with
sampling port.
4) Heparin syringe pump with tubing connecting to arterial line.
5) Dialysate bag and tubing.
6)
Dialysate pump
(optional).
7) Dialysate outlet line and
collection container.
Several

dialyzers were tested.

Both hollow-fiber

and

flat-plate geometries were evaluated and synthetic as well as


cellulosic membranes have been utilized.
Table 1.

Dialyzers.
Surface Area (m 2 )

Membrane
Regenerated cellulose
Cellulose acetate
PAN

In

the initial studies,

cannulas were Shaldon-type


femoral dialysis catheters.

0.6
0.9
0.5

both the arterial

Geometry
Hollow fiber
Hollow fiber
Flat plate

and

venous

catheters intended for use as


Recently, larger cannulas of 8

258

CAVHD - Clinical

Fr diameter without side holes have been utilized for the


arterial access.
Tubing sets consisted of short arterial and venous
tubing

originally

manufactured for

CAVH.

Tubing

lengths

varied from 50-106 cm.


Blood

sampling was performed every 4-8 hours

on the clinical situation.


the
in

depending

Blood samples were obtained from

arterial and venous tubing from the sampling ports shown


Figure 1.

Dialysate samples were taken

simultaneously.

All samples were analyzed for BUN and creatinine; arterial


line samples were additionally analyzed for electrolytes and
hematocrit.

Outlet dialysate volume was measured hourly and

net

ultrafiltration was calculated by simple subtraction

the

inlet dialysate volume from the measured outlet

In the studies with permeable membranes,


ment

fluid

needed;

(other

than

of

volume.

additional replace-

hyperalimentation)

was

at

times

in these cases replacement solution was generally 5%

dextrose in Ringer's lactate.


Urea and creatinine clearance were calculated from

CI
outlet dialysate flow rate

where Qd
Cd

concentration in the dialysate

Cp

concentration in the plasma (arterial line)

Anticoagulation
corporeal
u/L)

the

extra-

circuit was primed with heparinized saline

(5,000

follows:

An initial bolus of heparin was administered at onset

(2,000-4,000
tubing

was

clotting
and

was achieved as

u) and a continuous infusion into the


maintained

with

syringe

pump_

arterial
Activated

time was determined at the bedside every 2-4

heparin infusion was adjusted accordingly.

requiring extremely low-dose heparinization,

hours

In patients

pretreatment

clotting time was taken and only a small initial bolus (1,000
to

2,000

patients,

heparin)

was given

if

necessary.

a flat-plate dialyzer was used and,

In

these

if necessary,

R. Geronemus and N. Schneider


small

259

intermittent doses of heparin were given instead of

continuous infusion to achieve extremely low dose heparinization.


Priming and initiating CAVHD.
The
procedure

following instructions are a capsule summary of the


that has been utilized for preparing the

and initiating the treatment.

This procedure is

dialyzer
applicable

to both hollow-fiber and plate devices.


1.
ized

Attach blood tubing

to dialyzer.

saline bag to arterial line.

Connect heparin-

Connect dialysate

inlet

line from dialysate bag to dialyzer and dialysate outlet line


to collection bag.
2.

Prime dialysate side first with at

least 200 cc

of

dialysate, purge all air from the dialysate side, keeping the
arterial end of the dialyzer up (I).
3.
arterial

Reverse

the position of

the dialyzer so

that

end is at the bottom and prime the blood side

the
with

Fig. 2.
priming and initiating CAVHD (see text).
I) Priming
the dialysate compartment.
II) Priming the blood compartment.
III)
Connecting to the patient and initiating blood
flow.
IV) Initiation of dialysate flow and running position.

CAVHD - Clinical

260

1-2 liters of heparinized saline, being certain to purge all


air from the system.
The heparin infusion line and the
substitution fluid side port should also be primed at this
point

so

as

not to introduce air into

the

system

later.

Remember that there is no bubble trap (II).


4.
the

To initiate CAVHD,

arterial

line

arterial cannula.

and

disconnect the priming bag from

connect the arterial

line

to

the

start the blood flow through the circuit,

either giving or wasting the prime,

with the dialyzer

in the vertical position (arterial end down)


air bubbles at onset (III).

still

Observe

for

5. After blood flow has been established, initiate


dialysate flow at the desired rate and place the dialyzer in
the horizontal running position (IV).
Identification of clotted dialyzer.
Nursing

personnel

were trained to identify

clotted

dialyzer by several different clinical and laboratory signs:


1.

A decrease in

hourly ultrafiltration may be a

sign

of clotting.
2.
touch

An
of

early sign of clotting is relative


the

venous

tubing as compared

to

coolness
the

to

arterial

tubing. Under such circumstances, anticoagulation is checked


by clotting time, and obstruction to blood flow such as
tubing kinks are looked for.
3.
(BUN)

The ratio of dialysate to plasma blood urea nitrogen


or

creatinine can be estimated and a decline in

this

ratio may be a sign of dialyzer clotting.


4.
An advanced sign of clotting is gravity separation
of blood into cells and plasma in the tubing. At this stage,
the extracorporeal circuit must generally be replaced.
OVERALL RESULTS AND DISCUSSION
Continuous arteriovenous hemodialysis was well tolerated
with

all devices.

hemodynamic
tensive,

In no patient did CAVHD

induce

further

instability even though many patients were hypo-

requiring vasopressors.

There was no difference in

patient tolerance with use of any of the hemodialyzers listed

261

R. Geronemus and N. Schneider


in

Table 1.

Patients who could not tolerate regular

hemo-

dialysis tolerated CAVHD.


The

duration of CAVHD depended upon the clinical situa-

tion and varied from 16-126 hours.


Clotting of the dialyzer
was infrequent and in general occurred when the blood flow
was interrupted accidently or after a period of time approximating

two days of continuous use of a single dialyzer.

In

12 patients randomly selected from those patients

undergoing

CAVHD

CAVHD

during

evaluated
plate

the

past two years,

for heparin usage.

dialyzers

were

460 hours of

Both hollow-fiber

utilized

in

these

was

and

flat-

patients.

Mean

heparin dosage was .88 mL/hr of 1,000 unit per mL heparin


(880 units per hour).
The original studies with the 0.6 m2
hollow-fiber dialyzer resulted in fluid removal rates of 25100 mL/hr.
In the more recent studies with dialyzers with
more

permeable

membranes,

the

fluid

removal

rates

were

considerably greater as shown in Table 3, particularly with


the 0.5 m2 PAN membrane dialyzer yielding an ultrafiltration
rate of 33 mL/hr.
Table 2.

Urea clearance - Qd

15 mL/min.

Dialyzer

Clearance
(mL/min)

0.6 m2 regenerated cellulose


0.9 m2 cellulose acetate
0.5 m2 PAN

13.3 + 1.0
14.2 + 2.5
16.9
2.3

41
17
28

Rate
(mL/hr)

Table 3.

Ultrafiltration.

Dialyzer
0.9 m2 cellulose acetate
0.5 m2 PAN

128 + 102
322 + 159

17
28

CAVHD - Clinical

262

Plasma urea clearance at the standard dialysate flow of


15 mL/min is depicted in Table 2. The initial studies, which
utilized
the 0.6 m2 regenerated cellulose hollow-fiber
dialyzer, yielded a mean clearance of 13.3 mL/min.
Later
studies of 0.9 m2 cellulose acetate hollow-fiber dialyzer and
the 0.5 m2 PAN membrane dialyzer yielded higher clearances as
shown.

These

solute

removal rates generally

resulted

steady-state values of urea and creatinine after 24-48

of CAVHD treatment.
versus

time

in

hours

The typical course of BUN and creatinine

in patients undergoing the treatment

is

shown

below.
Continuous arteriovenous hemodialysis as applied in the
intensive care setting has proved to be an effective treat200
180
180
140

aUN

120
100

80
80
40
20
0

Fig. 3.

12

24

38
TIME-

48

72

80

BUN versus time in one patient.

7
8

CREAnNINE

5
4

3
2

Fig. 4.

12

24

38
TIME-

48

10

72

Creatinine versus time in one patient.

263

R. Geronemus and N. Schneider


ment

for

renal

failure during the

past

two

years.

technique relies on the same principles as does


hemodialysis.
with

an

exchange of solutes occurs by

additional

transport.
much

The

smaller

due

to

diffusion
convective

The difference is that the apparatus for CAVHD is

simpler

than that for conventional

blood pump is required.


low

component

The

conventional

hemodialysis.

No

The hallmarks of the treatment

are

blood flow and slow dialysate flow rate of less than

of that used in regular hemodialysis.

5%

Slow continuous treat-

ment leads to the high degree of stability of patients undergoing continuous arteriovenous hemodialysis.
experience

with this therapy,

In 24 months of

no patient was identified who

became more unstable as a result of CAVHD.


contrast to conventional hemodialysis,

This is in marked

in which acutely

ill

patients commonly have adverse symptoms during the treatment.


Furthermore,
dialyzed

patients

were identified who were unable to be

via conventional hemodialysis but were able

to

be

treated with CAVHD.


Furthermore,

the

treatment satisfies the

requirements

for the treatment of uremia that were mentioned in the introduction to this paper.
kept
In

All patients' acid-base balance

was

under good control and hyperkalemia was easily treated.


general,

sufficient

several
to

treat

hours of potassium-free
hyperkalemia.

For

dialysis

the

most

was
part,

patients could be treated with a bath containing 3 to 4 mEq/L


of

potassium.

The

use of dialyzers

with

more

permeable

membranes corrects an important deficiency noted in the early


studies

CAVHD with the 0.6 m2 device.

of

studies,

In the

original

the dialyzers used resulted in fluid removal

rates

of 25-100 mL/hr.
Thus,
if a patient was initially volume
overloaded, continuous ultrafiltration had to be applied
before CAVHD could be initiated.
volume
to

Then, if the patient became

overloaded during the course of CAVHD,

the CAVHD had

be interrupted and continuous ultrafiltration once

started

for several hours to correct

state.

Also

limitation

the

again

volume-overloaded

the low ultrafiltration capacity resulted in a

of the amount of hyperalimentation that could

be

264

CAVHD - Clinical

applied in certain cases, thus limiting the attempts at


nutritional support.
with the more permeable membranes
utilized in the more recent studies, especially with the
flat-plate

PAN

membrane device,

ultrafiltration

both solute clearance

are carried out simultaneously.

and

Therefore,

large volumes of hyperalimentation, lipid emulsion, transfusions, and other intravenous solutions can be administered to
these

acutely ill patients on CAVHD without fear

overload.
hourly.

of

volume

The volume state of such patients can be adjusted


Therefore, CAVHD as modified with the more permeable

membranes now satisfies the criteria for treatment of volurneoverloaded states and for the maintenance of good nutritional
support.
toxic

CAVHD

waste

creatinine
devices
state.

products.
values

are

Excellent
obtained.

control

of

The clearance

urea

in clearance,

and

with

is more than adequate for the control of the


with the more permeable membranes, there

improvement
tion

also provides more than adequate removal of


all

uremic
is an

probably as a result of the addi-

of convective transport to a significant degree to

diffusion transport already present.

When applied on a

hour basis, the clearance is quite remarkable.

the
24-

The clearance

per 24 hours is depicted in Figure 5 for various treatments


of renal failure. CAVHD compares favorably with conventional
hemodialysis for which the daily clearance is calculated as a
mean value of every-other-day hemodialysis treatment.
The
24

25

20
UTERS

15
10

o
Fig. 5.
ties.

HD

CAYH

CAYHD

CAPO

Daily urea clearance with different dialysis modali-

265

R. Geronemus and N. Schneider


clearance
CAVH.

of

CAVHD

is far superior to that

obtained

with

The CAVH clearance is calculated from a mean ultrafil-

tration

rate of 500 mL/hr.

Other investigators have

noted

the limitation of CAVH in certain catabolic patients (7).

It

was found that certain patients on CAVH required intermittent


hemodialysis to make up the deficit in solute removal. Since
these patients tend to be unstable to begin with, the use of
hemodialysis may not be possible or may result in further
cardiovascular instability. It would appear to be preferable
to apply CAVHD to these unstable patients and obtain adequate
solute

removal without inducing cardiovascular

Twenty-four-hour clearance
Figure as a benchma"rk.

of

CAPD is also

instability.
shown

in

the

As stated above, the major benefits of CAVHD, aside from


excellent patient tolerance,

are the treatment's simplicity.

The procedure can be performed in any facility,

even without

hemodialysis machines or trained hemodialysis nurses.


ment

can

initiated or carried out by a nurse

be

experience

who has been trained for several hours in

This

of

lack

need for dialysis nurses was

patients on slow,
failure

also

ICU

CAVHD.

noted

continuous ultrafiltration in acute

This is true because there is no

(8).

Treat-

with

in

renal

complicated

The treatment is therefore applicable to


machine to learn.
small hospitals and also to hospitals in relatively underdeveloped countries.
nurses

and

substantial
of
to

The lack of need for specially trained

expensive machinery leads,

in

cost savings for the hospital.

addition,

to

The high degree

stability of patients during the treatment may also


substantial

reduction

and

time

commitment

by

lead
the

physicians caring for the patient.


CONCLUSIONS
1.

CAVHD

is an effective treatment

for renal

failure

with adequate clearance even in catabolic patients.


2.
The use of high permeability membranes improves the
efficiency of CAVHD by combining diffusion with convection.

CAVHD - Clinical

266

3. CAVHD appears to be superior to regular hemodialysis


in terms of cardiovascular stability.

4.

CAVHD

is

superior

to

CAVH in

terms

of

solute

removal.

5.
The high ultrafiltration rates available with the
high permeability membranes permit the treatment of volumeoverloaded states and the administration of sufficient hyperalimentation and other intravenous medications.
SUMMARY
In

summation

then,

CAVHD would appear at the

time to be the ideal form of therapy in acute renal


especially

in

those

instability.
the
and,

patients who

demonstrate

current
failure,

hemodynamic

The pure simplicity of the technique

broadens

horizons of availability of acute dialysis in the world,


additionally,

constraints,

in

the

face

of

increasing

economic

offers a viable alternative to the treatment of

acute renal failure.


ACKNOWLEDGMENTS
The authors thank the nurses of the Renal Intensive Care
unit

at

Florida

Medical Center,

Donna

Leopold

for

data

collection, and Rhoda Smolian for secretarial assistance.


REFERENCES
1. Twardowski ZJ, Nolph KD:
Blood purification in acute
renal failure. Ann Intern Med 100:447, 1984.
2. Kramer P, Wigger W, Rieger J, Matthaei D, Scheler F:
teriovenous hemofiltration:
a new and simple method for
treatment
of
overhydrated
patients
resistant
to
diuretics. Klin Wochenschr 55:1121, 1977.
3. Kramer P, Kaufhold G, Grone HJ, et al:
Management of
anuric intensive-care patients with arteriovenous hemofiltration. Int J Artif Organs 3:225, 1980.
4. Kramer P, Bohler J, Kehr A, Grone HJ, Schrader J,
Matthaei D, Scheler F: Intensive care potential of continuous arteriovenous hemofiltration. Trans Am Soc Artif
Intern Organs 28:28, 1982.
5. Scribner BH, Caner JEZ, Buri R, Quinton W: The technique
of continuous hemodialysis.
Trans Am Soc Artif Intern
Organs 6:88, 1960.

R. Geronemus and N. Schneider


6.
7.

8.

267

Geronemus R, Schneider N: Continuous arteriovenous hemodialysis:


a new modality for treatment of acute renal
failure. Trans Am Soc Artif Intern Organs 30:610, 1984.
Dodd NJ, O'Donovan RM, Bennett-Jones ON, Rylance PB ,
Bewick M, Parsons V, weston MJ: Arteriovenous haemofiltration:
a recent advance in the management of renal
failure. Br Med J 287:1008, 1983.
Paganini EP, Nakamoto S: Continuous slow ultrafiltration
in oliguric acute renal failure.
Trans Am Soc Artif
Intern Organs 26:201, 1980.

CONTINUOUS AMBULATORY PERITONEAL DIALYSIS IN ACUTE


FAILURE
M. SCHREIBER
The Cleveland Clinic Foundation, Cleveland, Ohio

RENAL

INTRODUCTION
Continuous

ambulatory

peritoneal dialysis

(CAPD)

and

continuous cycling peritoneal dialysis (CCPD) have evolved as


standard

forms of home peritoneal dialysis.

three

to five exchanges,

day,

while

exchanges
Both

CCPD

during

CAPD

each four to six hours during

utilizes

multiple

chemistry

dialysate

diurnal

exchange.

the night and one long

acceptable

levels,

fluid balance,

dialysis
uremia,

and

maintaining
achieving

quality of life in patients with end-stage

disease requiring dialytic support.


be
but

incorporated

into

the

automated

dialysis systems have proved successful in

blood

requires

an

renal

Not only can peritoneal

the

treatment

of

chronic

also offers the potential for the treatment

of

acute renal failure and has been used for years.


Specific clinical situations have been preferentially
treated
cardiac

with peritoneal dialysis such as states of altered


output, inadequate vascular access, severe head

trauma (1), and severe coronary atherosclerosis (2).


different techniques of peritoneal dialysis such as
automated intermittent peritoneal dialysis (IPD) ,
equilibrium
continuous

peritoneal
peritoneal

dialysis
dialysis

(CEPD)

(4),

and

(3) ,
CAPO

utilized in the setting of acute renal failure.


of

modified

multiple exchange CAPO

protocol

Several
machine-

continuous
low-flow
have

been

The results
with

high

ultrafiltration volumes have been successful in treating


acute renal failure in our clinical experience.
Although
there are specific technical
differences
between
the various techniques the general
principles

269

CAPD in ARF

270

modulating peritoneal factors which govern solute removal and


ultrafiltration generation are common to all methods.
The
following review discusses both the anatomic and the dynamic
physical factors involved in peritoneal dialysis,
nique of modified multiple exchange CAPD,
complications

the

tech-

patient selection,

of peritoneal dialysis and an overall

assess-

ment of peritoneal dialysis in acute renal failure.


PERITONEAL DIALYSIS SYSTEM
Anatomical.
Solutes moving into the peritoneum during peritoneal
dialysis move from the peritoneal capillary through the
peritoneal
interstitium, mesothelium, and stagnant fluid
films into the peritoneal cavity (Fig. 1).
Each anatomic
site in the peritoneal dialysis system plays a role in
regulating solute and water removal (5).
Capillary circulation.
solute
from

removal

During peritoneal dialysis, net

results mostly from the movement

of

solute

the capillaries in the peritoneal membrane by means

of

diffusion and osmotically generated ultrafiltration (convective transport) (6).


Although small solutes readily move
across capillary walls, both the actual number of capillaries
in the peritoneum and the low pore density of capillaries
determine the rate at which small solutes are removed. Vasodilators such as nitroprusside improve peritoneal clearances
mainly by increasing vascular permeability in the distal

end

of the capillary rather than increasing effective blood flow.


Also,

dialysate itself can result in vasodilatation, but not

to the extent of actual pharmacological vasodilators.

Wide-

spread use of vasodilators to increase solute removal is not


practical but may have applications in specific clinical
settings.
Seemingly, peritoneal dialysis is most likely not
limited by blood flow, as capillary blood flow is approximately

two

times

peritoneal cycling.
collapse
affected.

the maximum urea clearance


However,

during

rapid

in settings of severe cardiac

(shock) peritoneal dialysis systems

are

adversely

M. Schreiber

271

CAPILLARY

Fig. 1.

Schematic representation of solute removal.

Peritoneum interstitium.

Solutes

diffuse from

capil-

laries, enter the interstitium, and then traverse both the


interstitial cell layer and another cell layer, the mesothelium, before entering the dialysis solution.
Surface
charges, mucopolysaccharide and collagen cells, and the fluid

272

CAPO in ARF

status of the interstitium affect solute removal.

is,

stitium

in essence,

The inter-

a fluid network dispersed

mucopolysaccharide and collagen gels (8) as well as


surface

changes.

between
collagen

The movement of solute through the inter-

stitium is dependent upon the stability of the aforementioned


network.
Hypertonic peritoneal dialysis solutions may in actuality

dehydrate

the interstitium,

thus

causing

contraction,

alterations in fluidity, and changes in surface charges.


actual

dimensions

directly

of these

interstitial

impact on solute and water

aqueous

transport.

The

pathways

Therefore,

severe volume contraction predialysis or the attainment of a


"dehydrated state" during peritoneal dialysis theoretically
leads to interstitial dehydration, which adversely affects
transport flow. Thus, the status of the interstitium becomes
of paramount importance during aggressive peritoneal dialysis
with

large ultrafiltration

volume

generation.

Continuous

intravenous water repletion in patients undergoing aggressive


dialysis is essential in preventing interstitial dehydration.
Crystalloid

may

be

needed to ensure

settings of hypotension.
disease-associated

stable

hydration

in

Little is known regarding specific

interstitial abnormalities or medications

that may directly affect structures in the interstitium.


Peritoneal mesothelium.
is

lined

(9)

The surface of the

by mesothelial cells with

villi-like

peritoneum
projections

While the integrity of the mesothelium can change with

chronic dialysis and infection,


fungal,
acute

these alterations are theoretically less relevant in


peritoneal

infection.
ever,

especially gram-negative and

With

dialysis

with a

decreased

incidence

disruption of mesothelial integrity,

significant protein is potentially lost in the

of
how-

dialy-

sate and undergoes abnormal back absorption of glucose,


resulting in an overall decrease in net ultrafiltration. The
intact mesothelium may act as a barrier against glucose and
solute back diffusion into the interstitium, thus preserving
an

osmotic pressure gradient,

on ultrafiltration generation.

which has a beneficial effect

M. Schreiber

273

Stagnant fluid films.

within

the

peritoneal

cavity,

stagnant fluid films may restrict small solute removal


(10)

These

resistant

rates

films tend to be more operative

in

chronic dialysis and longer dwell cycles where there is less


fluid mixing compared to rapid cycling in a modified multiple
exchange CAPO technique.
DYNAMIC PHYSICAL FACTORS
Dialysate volume.
Solute
(11),

are

creased

as

suggested by Twardowski

augmented by high-volume dialysis.


with

et

al

This has in-

the use of 3-liter dialysis volumes in a

patients
The

clearances,

number

high urea generation and greater

body

of

size.

modulating factor of high-volume dialysis is an increase

in the solute concentration gradient, which thereby increases


both solute transport and water removal.
of

significant

And yet the absence

changes in protein losses

with

high-volume

dialysis argues against there being an increase in membrane


fluid contact area.
Incremental changes in dialysate volume
could

be

used to increase small solute

long-dwell and short-dwell cycling.


optimal

removal

both

with

Therefore, utilizing the

volume of dialysate will improve solute removal in a

number of clinical settings.


Dialysate flow.
Differences
large

part

rates

in solute clearances can be

to dialysis solution flow

differ

in

hemOdialysis

and

attributed

rates.

Solute

peritoneal

contributing to small solute removal in each.

dialysis

with CAPO, the

clearance of urea approximates the dialysis drainage


caused

by

changes.
do

not

dialysis

the

equilibration of urea during

However,
approach
cycles,

The

and

the

volumes
CAPO

ex-

larger molecular weight solutes (inulin)


equilibration
and

during

routine

peritoneal

clearances tend to be less than

dicted by drainage volumes.


Larger molecules are more dependent on
area

in
flow

permeability for removal than

total

smaller

pre-

membrane
molecules.

loss of membrane surface area that occurs with peritoni-

CAPD in ARF

274

tis or chronic exposure to dialysate will reduce large solute


clearances proportionately more than small solute clearances.
For smaller solutes such as urea, both blood flow and dialysate flow will be higher per unit area of effective membrane
than larger solutes.
Techniques employing rapid cycling of
peritoneal
CCPD,

dialysis,

such as IPD or the nocturnal phase

allow for maximum urea clearance,

mL/min at any flow.

of

which approaches 30

Because of the limited

number of capil-

laries involved in dialysis and other membrane resistance


factors,
the effect of increasing dialysate flow will
eventually reach a plateau. Therefore, a rapid infusion time
with increased dialysate flow is desirable for peritoneal
dialysis. It is essential that the most efficient peritoneal
catheters

are utilized to optimize infusion,

dialysis

flow

rates, and drainage times.


Osmotic ultrafiltration.
Glucose in a number of different concentrations (1.5%,
2.5%, and 4.25%) allows for multiple degrees of osmolality
and

ultrafiltration.

creases

capillaries
sures

Ultrafiltration

is achieved

by

in permeability from proximal capillaries to


and venules.

in-

distal

Both hydraulic and osmotic

pres-

favor ultrafiltration through a tight membrane in

proximal

capillaries.

Distal

capillaries

have

the
lower

hydraulic pressure with increased potential for glucose to


cross vascular membranes, resulting in less effective osmotic
pressure and ultrafiltration.
The lower the hydraulic pressure, the greater the degree of reabsorption will be.
Seemingly,

the integrity of the mesothelium cells lining the

peritoneal cavity is important in preventing rapid fluxes

of

glucose

In

patients

from
with

the
low

peritoneum

into

the

ultrafiltration

interstitium.

rates,

there

is

high

peritoneal permeability to glucose, which results in accelerated

osmotic

equilibrium

and

premature

plateauing

of

maximal ultrafiltration (12).


Evaluating dialysate/plasma
solute levels during time cycles can help differentiate
abnormalities
~eneration.

in

solute

removal

and

ultrafiltration

M. Schreiber
with

2-liter exchanges,

approached
patient

275

after 4 hours;

this may differ from

in the setting of acute renal failure.

the volume of body water,


will

osmotic equilibrium is usually


patient

to

The greater

the greater the removal of

solute

be over time as a factor of ultrafiltration and

solute

drag.

Intraperitoneal

volume

increases

at

exponentially

diminishing rates as solute equilibration is reached;

as the

osmotic gradient decreases, net ultrafiltration will also


decrease.
Therefore, the use of high-concentration glucose
solutions, optimal flow rates, and dialysate volume tend to
provide a significant stimulus for osmotic ultrafiltration.
Mechanical

problems with

( osmotic

blunting) ,

catheter

and

function,

severe

volume

hyperglycemia

contraction

may

adversely affect ultrafiltration volumes.


Convective Transport (solute drag)
As

water

is drawn across the

osmotic forces (ultrafiltration),

peritoneal

into the dialysate (solute drag) occurs.


higher

molecular weight than water,

brane

impedes

water

movement

refer

to

membrane

by

transport of small solutes


and the peritoneal mem-

the convective transport


by acting as a sieve;

Most solutes have a


of

solutes

sieving

a characteristic of the peritoneal

during

coefficients
membrane

that

limits solute movement from capillaries into the dialysate.


Water flow rates and molecular charge are also important
in

solute

molecule

clearance.
may

significant

The charged property of

explain the net sieving effect


water

the

sodium

observed

removal without proportional

sodium

with
re-

moval.
Therefore, ultrafiltration proportionately increases
small noncharged solute removal by convection.
Larger
charged molecules have lower sieving coefficients
behind water in removal.
Maintaining an optimal osmotic gradient with a

and

lag

hydrated

interstitium will allow for optimal fluid and solute removal


both through ultrafiltration as well as convective transport.
It is important to avoid interstitial dehydration as well
depletion of body water to the point of hypernatremia.

as

276

CAPD in ARF

Determining which specific pharmacologic agents beneficially change baseline membrane charge might improve solute
removal in the future.

However,

little is known

regarding

how to effectively alter peritoneal membrane charge.


MODIFIED MULTIPLE EXCHANGE CAPD
Technique.
A shorter exchange high-ultrafiltration method of
is

utilized

Cleveland
dynamic

Clinic.

the

utilize

the

solute

At the same time the patient is kept well hydrated

through
This

The shorter exchange times

portion of the equilibration curve for small

removal.

CAPD

in the treatment of acute renal failure at

intravenous administration of water or

prevents

hypernatremia

and

theoretical

crystalloid.
interstitial

dehydration, while preserving the high ultrafiltration flows.


By maintaining the optimal fluid status, we have been able to
remove 50% of the urea load in 24 to 36 hours in most individuals, while preserving hemodynamic stability.

Crystalloid

has been incorporated in the treatment of hypotension,


continuing

to

Hypotension
stopped,

maintain increased

ultrafiltration

while

volumes.

does not mean that peritoneal dialysis should be

but

rather alludes to the need of increased

fluid

repletion.
A

l2-prong

incorporated
placement

manifold setup using

Dianeal

solution

in this dialysis teChnique (Figure


of

temporary

peritoneal

2).

dialysis

(surgically or percutaneously at the bedside),

is

After
catheter

the patient's

ultrafiltration ability is assessed by the first two exchange


cycles;

2.5

and 4.25 two-liter exchange cycles are utilized

in succession and ultrafiltration volumes evaluated after the


completion of a 2-hour cycle for each concentration.

If the

patient's total ultrafiltration volume after 4 hours is


greater than 300 cc, then aggressive ultrafiltration and
water

supplementation are initiated.

pressure,

The

patient's

blood

body weight, and drainage volumes are evaluated at

each cycle.
A period of 2 hours for infusion transit time
and dwell is adhered to. Intravenous fluid flow rates of 100

277

M. Schreiber

Fig. 2. Modified multiple exchange CAPO - high ultrafiltration techniques.


to

150

cc/hr balanced are against ultrafiltration

In the setting of decreases in blood pressure,

volumes.

as alluded to

before, patients are given crystalloid or colloid as dictated


by their clinical setting.

For urea values greater than 150

mg/dL, the usual time interval from initiation to 50% removal


is 36 hours in most patients.
It
ating

is important to continue water hydration


adequate ultrafiltration volumes.

in

gener-

Concentrations

of

dialysate 2.5% to 4.25% are utilized throughout the 12 cycles


in

24 hours in most patients.

avoiding hypernatremia,

Attention should be given to

hyperkalemia,

and/or

hyperglycemia

during peritoneal dialysis for acute renal failure.


The theoretical advantage of high ultrafiltration CAPO
is to ensure optimal water movement through the interstitium,
accelerate solute removal through osmotic and convective
transport, obviate the need for hemodialysis stations, and
incorporate

the assistance of existing personnel in treating

renal failure.

CAPD in ARF

278

If the patient's renal function does not show signs of


improvement after 72 hours, a permanent Tenckhoff catheter is
placed either surgically in a patient with previous abdominal
surgery or at the bedside, utilizing a trochar or peritoneoscope in patients with no evidence of bowel obstruction,
or

ileus,

significant

surgical

history.

Tenckhoff

catheter

that

catheter cannot be removed in

the

recovery,

The

permanent

is really a misnomer and does not

Tenckhoff

catheters

the

future.

can be removed

morbidity provided that they are


within the peritoneum.

not

imply
with

with

surgically

little
attached

Patients may be dialyzed on a regular nursing floor, or


if necessary, in an intensive care facility. This technique
provides

rapid removal of both fluid and solute in

who have acute renal failure.


some patients,
to

the

can be adequately treated by adding potassium

dialysate in a dosage of 6 to 8 mEq per 2 liters

dictated by the serum level.


Patient selection.
Peritoneal dialysis has
majority
1)

patients

Hypokalemia, which develops in

a broad

application

to

of patients who develop acute renal failure

as

the

(Table

Prior abdominal surgery is not considered a contraindi-

cation

to peritoneal dialysis but

peritoneoscopic

dialysis

or

surgical

catheter.

peritoneal

pathology,

effective

form

of

In

potentially

placement

the absence of
peritoneal

acute

of

the

peritoneal

significant

dialysis

dialytic

necessitates

support

is

an
with

intraequally
a

more

physiologic and gradual removal of solutes.


The

peritoneum may provide a means of delivering

amino

acids during periods of increased catabolism and decreased


dietary intake that may present with acute renal failure.
Comparisons
between intravenous nutrition versus intraperitoneal nutritional support in decreasing the mortality of
acute renal failure are warranted.
Most patients can undergo bedside placement of a
cath

and

term

dialysis

then a more permanent Silastic catheter for


with

relatively

little

morbidity.

stylolongBefore

279

M. Schreiber
Table 1.

CAPO in acute renal failure (ARF)

Indications

Contraindications

Blood access difficulty


Hemodialysis instability
Postcardiac surgery
Pancreatic postsurgery
Children
Low cardiac output status
Hemodynamic instabilities
Anticoagulant contraindication
Lactic acidosis
Hyperuricemia with cancer
treatment

Postoperative bowel
surgery
Aortic graft patient
Respiratory compromise
Scleroderma
Burn or hypercatabolic
patient
Diaphragmatic tear

initiating dialytic support,

the patient should be

clinically with respect to weight gain,

followed

hemodynamic stabili-

ty, and levels of electrolytes and glucose.


Complications.
A

number

follow-up
major

of

complications

may be

avoided

of patients undergoing peritoneal

complications,

as listed in Table

by

close

dialysis.

2,

deserve

The
close

attention and treatment.


Hypernatremia.
lyte

Hypernatremia

can result from electro-

sieving and states of prolonged

water

removal

Thus,

large

ultrafiltration.

does not correlate with

net

Net

sodium

losses.

imbalances in water and sodium removal

through

the extracellular fluid space during rapid cycling can occur,


resulting
likely,
capillary
removal

in

clinically

since

significant

ultrafiltration

walls,
of sodium.

the

low
Also,

hypernatremia.

occurs across

permeability

area

the

Most

proximal

impedes

intracellular water pathways

the
or

transcellular specific surface charges can impede the removal


Table 2.

Complications:

Hypernatremia
Pleural effusion

CAPD in acute renal failure


Hyperglycemia
Dehydration

Infection

CAPD in ARF

280

of the charged sodium molecule.


Both osmotic pressure and
transport pathways may thus restrict solute removal allowing
for electrolyte sieving.
By monitoring the sodium level and
balancing water intake with net ultrafiltration, one can
avoid clinically significant hypernatremia.
may

Hyperglycemia. Hyperglycemia during peritoneal dialysis


occur in individuals with already diagnosed diabetes or

those patients with abnormal glucose tolerance tests.

Since

hyperglycemia may impede ultrafiltration and solute removal,


attention should be given to this abnormality.
The majority
of patients who have hyperglycemia can be controlled with
intraperitoneal insulin.
There have been a few patients in
our clinical experience who have necessitated an insulin
drip,

which

range

of

glucose

has

stabilized the blood glucose level in

110-140 mEg/dL.
levels,

regulates

the

blood

If patients

constant

glucose

have

low-dose

smoother

labile

insulin

than

the
blood

infusion

intraperitoneal

insulin.
Infection.
support

do

Most

patients

undergoing

acute

not develop peritonitis provided

dialysis proceeds in a sterile fashion.

dialytic

initiation

of

In those who become

febrile shortly after initiating dialysis, cultures are taken


of the dialysate, and antibiotic regimens are begun for gramnegative and gram-positive coverage.

While gram stains have

been

with

disappointing

disease,
Our

they

in CAPD patients

end-stage

renal

tend to be more helpful in the acute setting.

preferential approach for treating gram-positive

infec-

tions relies on vancomycin, 1 gm, intravenously, administered


initially

and aminoglycoside loading regimen until

are clarified.

cultures

Monitoring drug levels and the slow infusion

of vancomycin initially have decreased the incidence of


vestibular and ototoxicity seen with antibiotic combinations.
Pleural effusion. Patients undergoing peritoneal dialysis

postoperatively,

experience
pleural

movement

especially

postcardiac

surgery,

of fluid from the peritoneum

space resulting in pleural effusions.

due to a tear in the diaphragm,

extension of the

into

This may

may
the
be

midsternal

281

M. Schreiber
incision

at

horizontal

the time of surgery,

or by patients kept in

position during peritoneal dialysis,

diffusion

into the pleural space.

with

water

Patients should be in

45- to 60-degree angle position during dialysis.


Dehydration.
dialysis
water,

and
one

By

monitoring hemodynamic

responses

utilizing colloid and crystalloid as


can

avoid significant dehydration

undergoing multiple exchange CAPO.


Hypoalbuminemia.
In patients

well

in

to
as

patients

with significant

hypo-

albuminemia (albumin less than 1.9 g/dL and low total protein
concentrations, it may not be possible to generate adequate
amounts

of

ultrafiltration

until

these

deficiencies

are

corrected.
The intravascular compartment must be expanded
before successful dialytic therapy in patients with clinically significant hypoalbuminemia.
OVERVIEW

Peritoneal dialysis performed by several different techniques can achieve efficient removal of solute and water.
understanding

peritoneal physiology,

a clinical approach to

treating acute renal failure with peritoneal dialysis can


formulated.

Most

acute

failure develops are candidates for

renal

dialysis.
peritoneal

patients

Previous
dialysis.
the

in a hospital setting

abdominal
The

rate

surgery
of

By

does

in

be
whom

peritoneal
not

complications

negate
is

prohibitive,

and

acceptable.

Attention to a multiple-exchange technique

overall success of solute removal

not
is
and

optimal degrees of ultrafiltration may add to the success of


CAPO in treating acute renal failure.
REFERENCES
1.
Sipkins JH, Kjellstrand CM:
Severe head trauma and
acute renal failure. Nephron 28:36-41, 1981.
2.
Ash SR, wimberly AL, Mertz SL: Peritoneal dialysis for
acute and chronic renal failure: an update. HOsp Pract
18(1):179-210, 1983.
3.
Posen GA, Luisce110 J: Continuous equilibration peritoneal dialysis in the treatment of acute renal failure.
Dial Bull 1:6, 1980.

282

CAPO in ARF

4.

Gastaldi L, Barate11i L, Cassani 0, Cinquepalmi M, et


a1:
Low flow continuous peritoneal dialysis in acute
renal failure. Nephron 29:101-102, 1981.
No1ph KD, Miller F, Rubin J, popovich R: New directions
in
peritoneal dialysis concepts and
applications.
Kidney Int 18(S10):S111-116, 1980.
Nolph KD:
Solute and water transport during peritoneal
dialysis. Perspect Peritoneal Dial 1:4-8, 1983.
Aune S:
Transperitonea1 exchange.
II.
Peritoneal
blood flow estimated by hydrogen gas clearance. Scand J
Gastroentero1 5:99-104, 1970.
Wayland H: Transmural and interstitial molecular transport.
Action of histamine.
In:
Legrain M (ed) ,
Continuous Ambulatory Peritoneal Dialysis, Amsterdam.
Exerpta Medica 20, 1980.
Tsi1ibary EC, Wissig SL: Absorption from the peritoneal
cavity:
SEM study of the mesothelium covering the
peritoneal surface of the muscular portion of the
diaphragm. Am J Anat 149:127-133, 1977.
McGary TJ, Nolph KD, Rubin J:
In vitro simulations of
peritoneal dialysis.
A technique for demonstrating
limitations on solute clearances due to stagnant fluid
films and poor mixing. J Lab Clin Med 96:148-157, 1980.
Twardowski ZJ, Nolph KD, Prowant BF, Moore HL: Efficiency of high volume low frequency continuous ambulatory peritoneal dialysis (CAPD).
Trans Am Soc Artif
Intern Organs 29:53-57, 1983.
Verger C, Brunschvicg 0, Le Charpentier Y, Lavergne A,
Vante10n T:
Structural and ultrastructural peritoneal
membrane changes and permeability alterations during
continuous ambulatory peritoneal dialysis.
Proc Eur
Dial Transplant Assoc 18:199-205, 1981.
Diaz-Buxo JA, Burgess WP:
Comparison of kinetics CAPD
and CCPD. Perspect Peritoneal Dial 3(1):37-41, 1985.

5.
6.
7.
8.

9.

10.

11.

12.

13.

CONTINUOUS ARTERIOVENOUS HEMOFILTRATION - APPLICATIONS OTHER


THAN FOR RENAL FAILURE
E. WOLNER
University of Vienna, Vienna, Austria

Hemofi1tration has been used in the past mainly for the


treatment of renal failure (12,14). Recently, application of
hemofi1tration other than for renal failure, such as cardiac
failure, septic shock, and intoxications has been evaluated
(3-5).
the
that

The main mode of action is the dehydration along with

elimination

of toxic substances.

various shock states,


to

It has been

proved,

especially during extracorporea1 circulation (ECC)


the

circulation.

inqtropic

humoral toxic substances are


These

substances

cause

and

released
negative

effect on the heart and have also been claimed

contribute

to

pulmonary

paralysis (5,20).

dysfunction and

peripheral

to

vaso-

I will discuss hemofiltration in relation

to this pathophysiological mechanism,

during cardiac surgery

(both during and after ECC), in cardiomyopathy, and in sepsis


with acute respiratory failure.
HEMOFILTRATION DURING EXTRACORPOREAL CIRCULATION
During ECC, blood is delivered from the arterial line of
the heart-lung-machine to the filtration coil.
filtration

prophylactically

failure with lung congestion.

in

patients

who

We used hemohad

cardiac

Most of these patients were in

cardiogenic shock from endocarditis or complication of

acute

myocardial infarction, such as rupture of papillary muscle or


poor left ventricular function.
In more than 2,000 operations using ECC, we used hemofiltration in 34 cases. In a retrospective study we compared
two

similar

groups of patients that did or did not

receive

hemofiltration during cardiopulmonary bypass, comparing fluid


balance, urinary output, and hematocrit.
283

284

Other Applications
In

the

during

hemofiltration group,

the mean urinary

ECC was 583 mL and the mean amount of

output

hemofiltration

was 2.853 mL, resulting in a mean total fluid output of 3.436


mL.

During

the same time,

the mean fluid input

including

2.00 mL prime volume amounted to 2.459 mL, resulting


mean fluid balance of 977 mL (Tables la and b)

The difference of mean fluid balance between the groups


2.809 mL,
meaning that the hemofil tration-treated

wa,s

patients

were 2.809 rnL less hydrated than the control

patients after ECC.


groups
2.8

in

The difference in hematocrit between the

was negligible.

The treated patients had a loss

mL in the fluid balance,

decrease

group

which shows that there

is

of
no

of intravascular volume and that this fluid derives

from the extravascular space.


In

a second group of patients,

during
group

ECC

we used

for problems in weaning from

we used the HF only,

if,

hemofiltration

bypass.

In

thi s

in spite of pharmacological

support, control of metabolic disorders, and the intra-aortic


balloon pump (IASP), the patients could not be weaned from
the bypass because of low cardiac output syndrome.
There
were 32 males and 12 females ranging from 31 to 68 years.
The following procedures were performed:
replacements,

mitral valve replacements,

6 aortic valve
16 ACS,

and 14

combined procedures.
No patients responded to high catecholamine dosage.
addition

19

patients received IASP assistance

and

In
were

attached to an extracorporeal left ventricular assist device.


These patients could not be weaned from ECC despite all these
therapeutic efforts.

Hemofiltration was installed for 1 to 2

hours, excreting a mean of 2.700-mL hemofiltrate; 42 patients


were

weaned

from ECC;

however,

only 29 patients could

be

discharged.
In

this group,

the following hemodynamic results

were

observed:
the left atrial pressure, 33 ~ 66 mmHg before and
17 + 4 mmHg after hemofiltration (p < 0.001);
the mean
arterial

pressure,

hemofil tration.

49 mmHg + 7 before and 33 + 8 mmHg after

2853 + 1192

HF

839 + 219

3436 + 897

35.9 + 4.8

35.6 + 4.8

HF Group
n = 34

Control
Group
n = 30

Before ECC

22.5 + 3.5

22.9 + 3.6

5 Min.
After Start

21.9 + 4.1

22.4 + 4.2

15 Min.
ECC

Hematocrit change during ECC (%).

839 + 599

Control
Group
n = 30

Table lb.

583 + 415

urine

ECC

30 Min.

22.0 + 3.9

Balance

1837 + 1312

-997 + 1363

25.8 + 2.3

27.6 + 2.5

ECC End

2671 + 1047

2459 + 966

Total
Fluid Input

23.4 + 4.8

Total
Fluid Output

Fluid balance during hemofiltration.

HF Group
n = 34

Table lao

1.8%

Hematocrit

2809

Balance

N
CXl
U1

I"'C

::s
fl)

I-'

::E:

tzJ

Other Applications

286
HEMOFILTRATION
AFTER
INTENSIVE CARE UNIT
The

main

EXTRACORPOREAL

indication

CIRCULATION

for this group

was

IN

low

THE

cardiac

output syndrome (LCOS)


in the postoperative period.
We
treated 29 patients, 27 of whom survived the acute episode
and recovered from shock.
survivors.
One patient
multiple

However, only 19 were long-term


died 10 days after recovery from

cerebrovascular insults,

2 patients died after six

weeks from gastrointestinal hemorrhage, 2 of sepsis following


pneumonia,

of

recurrent

myocardial

infarction,

and

patient of progressive myocardiopathia.


The cardiac index, the mean atrial pressures, stroke
volume index, and left ventricular stroke work index increased

significantly after 2 hours and after 24 hours (p


Left

0.001)

atrial

pressure as well

as

central

<

venous

pressure and pulmonary arterial pressure declined immediately


after

the

two

decreased

from

peripheral

hours of

hemofiltration.

95 to 84 beats after 24

resistance (TPR) a baseline

The

and

rate

The

total

reading of 571 + 321

dyn.sec.cm-5 indicated severe paralysis.


hemofiltration,

heart

hours.

After two hours of

the TPR increased to 791 + 363 dyn.sec.cm.-5

after 24 hours was 728

275 dyn.sec.cm-5.

At the same

time the pulmonary vascular resistance (PVR) was rather high.


A

significant decrease of this high resistance was

our

patients,

seen

in

indicating an oxygen diffusion improvement of

the lung (Table 2).

All these patients were still intubated

and conventionally ventilated with volume-controlled respirators using a 10 cm H 2 0 positive end expiratory pressure. The
arterial

oxygen

partial pressure was

low

before

hemofil-

tration despite a high oxygen supply (Fi02 = 0.86), indicating a secondary concomitant with increased arterial pressure
values despite hours of hemofiltration (Table 3).
At the
same
could

time it was observed that the dosage of


be

reduced stepwise,

meani~g

catecholamines

that the efficiency

of

catecholamines was increased during the period of hemofiltration (3,5).

25.0 + 2

Left atrial
pressure (LAP)

Student's Test for Paired Data:

Total per ipheral


resistance (dyn.sec./cm 5 )

791. 0 + 363

20.0 + 5**

31.0 + 1**

66.0 + 4**

33.0 + 1*

39.0 + 3

86.0 + 3**
3.1 + I n s

After 2 hours

741. 0 + 320

19.0 + 3**

28.0 + 7**

67.0 + 3**

40.0 + 4

46.0 + 4

3.5 + 0.8*

85.0 + 3**

After 8 hours

(CAVH)

728.0 + 275

19.0 + 6**

26.0 + 4**

77.0 + 4**

45.0 + 9**

47.0 + 2**

3.7 + 0.7**

84.8 + 3

After 24 hours

hemofil tration

* p < 0.05 as Level for Statistical Significance

571. 0 + 321

37.0 + 3

Mean pulmonary
arterial pressure (mmHg)

(mmHg)

52.0 + 3

25.0 + 10

Mean arterial
pressure (mmHg)

Left ventricular stroke


Work index (g .m/m 2 )

31.9 + 3

3.1 + 0.7

95.0 + 4

Heart rate (beat/min)

Cardiac index (L/min .m 2 )


Stroke volume index (ml/m2)

Baseline

measurements during continuous arteriovenous

Measurements

Hemodynamic
Table 2.
treatment (n = 29).

N
00
-.J

ro

:J

I-'

:<:

t<:1

454.0 + 33

Alveolo arterial oxygen


difference ( AaDo 2) mmHg

Oxygen utilization

Right to left shunt


Qs/Qt %

Arteriovenous oxygen
difference (a- vDo 2)

0.26 + 0.7

30.0 -+ 2.1

3.8 + 0.33

16.4 + 0.7

93.0 + 7

Arterial oxygen Tension


( PA02l mmHg

Arterial oxygen content


(mL/dL)

0.86 + 0.03

Baseline

29)

0.28 + 0.08

20.7 + 2%

5.3 + 0.74

17.1 + 0.7**

370.0 + 38**

136.0 + 7**

0.79 + 0.04

2 Hours

Blood oxygenation and related metabolic measurement (n

Oxygen supply ( F1 02)

Table 3.

0.28 + 0.09

15.0 -+ 2.3**

4.83 + 0.4

17.9 + 8**

278.0 + 35**

141.0 + 11**

0.66 + 0.04**

24 hours

IT

rn

0
::l

IT

.....

PJ

(J

I-'
.....

'U
'U

;I>'

(f)

::t

IV
OJ
OJ

E. Wolner

2B9

Undoubtedly, hemofiltration achieves this improvement


mainly through withdrawal of fluid, especially in such
patients as those with critical heart disease,
overload

is a severe problem.

in whom fluid

preoperative heart

failure,

long ECC, a large volume of cardioplegic solution, and a considerable


crease

amount

of catecholamine bypasses lead to

in heart work,

particularly if there was

an

in-

concurrent

impaired renal function.


but

The dehydration not only reduces the load on the heart,


also leads to an improvement of the gas exchange by

reducing the interstitial edema of the lung.

This

improves

the oxygen delivery to the heart.


It is not known if these mechanisms alone improve hemodynamics or how the increased sensibility to catecholamines
during hemofiltration in patients with Leos can be explained?
One explanation could be the elimination of toxic-receptorblocking peptides by hemofiltration.
It could be shown that during cardiogenic
peptides,

such

pulmonary

lesion factor,

leased

from

as

the myocardial

ischemic

shock,
factor,

the

and other shock mediators are

re-

organs,

depressant

toxic

which,

at least

in

animal

experiments caused not only reduction of heart contractility,


increase of pulmonary artery pressure,

and a lowering of the

atrial pressure, but also an extreme peripheral vasoparalysis


with
low
receptors.

peripheral resistance by blocking


vasoactive
From this point of view we did chemical examina-

tions of the filtrated fluid.


column chromatography and ion

By bioassay methods after


exchange chromatography we

found that the B-fraction highly increased.


This fraction
resembles the high concentration of toxic substances with a
molecular weight of BOO.OOO Daltons.
In comparison to that,
the concentration of the B-fraction of the hemofiltrate in
normal individuums was low.
We proved these results in a
biological standard model using the isolated papillary muscle
of guinea pigs.
An B9-percent decrease of contractility can
be demonstrated, when the hemofiltrate shows a high concentration of toxic peptides.

No contractility changes of

the

Other Applications

290
guinea

pig muscle were noticed by using hemofiltrate samples

from healthy individuums.


These preliminary results indicate that other mechanisms
such as dehydration are also responsible for
effects of hemofiltration.

the

favorable

HEMOFILTRATION IN CARDIOMYOPATHY
Encouraged
surgery,

we together with the Cardiology

hemofiltration
opathy:

the results of hemofiltration in

by

in

patients

Department,

in the end stage

of

tried

cardiomy-

Group IV according to the New York Heart Association

Classification.
therapy,

All

patients were resistant

to

pharmaco-

diuretics, digitalis, and catecholamines.

tration was usually applied at weekly intervals.


was

cardiac

reduced about 20 percent at each session.

patients

died within eight weeks;

Hemofil-

Body weight
However,

15 others survived for

longer period with a mean survival time of five months.


patient

with

severe cardiac failure caused

by

15
a
One

myocarditis

survived 2.5 years.

It was observed that the central venous

pressure

pulmonary

and

decreased,
fraction

the

whereas
did

not

capillary

the cardiac index

wedge

pressure

increased.

Ejection

show significant changes

despite

38-

percent increase of stroke volume index.


These preliminary results indicate that the early use of
hemofiltration

in

cardiomyopathy may

treatment in order to prolong life.

offer

an

acceptable

However, the underlying

disease could not be changed.


SEPSIS WITH ACUTE RESPIRATORY FAILURE
In this group, 40 patients were evaluated retrospectively.

There were two groups of patients; group I with younger

patients
trauma

suffering
and

from

periobstetric

acute diseases
complications

such

as

multiple

developing

acute

respiratory failure at still low blood urea nitrogen


(BUN)
and serum creatinine levels.
A second group consists of
higher-aged patients, usually with septic complications after
abdominal surgery and acute respiratory failure.
In both

291

E. Wolner

groups respiratory failure could be controlled.


However,
lethality in the second group was much higher than in group
I.

It

can be stated that a group of younger acute-diseased

patients

with symptoms of interstitial lung edema

unrespon-

sive to high doses of diuretics but still low levels of BUN


and serum creatinine benefit most from
hemofil tration.
Better conductance of terminal airways could serve as an
explanation for increased arterial oxygenation.
However,
hemofiltration remains, despite its simplicity, a major
ingression in the physiologic regulation systems of the body.
Close observation, intensive care monitoring including SwanGanz

catheters,

and

proper nursing staff are required

for

this highly specialized therapy.


REFERENCES
1.

2.

3.

4.

5.

6.
7.

8.

Addonizio VP, Strauss JF, Chang LF, Fischer CA, Colman


RW, Edmunds LH: Release of lysosomal hydrolases during
simulated
extracorporeal
circulation.
J
Thorac
Cardiovasc Surg 84:28, 1982.
Blanke H, Rentrop P, Karsch KR, Hellberg T, Kirchhof PO,
Kreuzer
H:
Invasive diagnostik und therapie
im
kardiogenen schock:
Kreislaufschock.
Anaesth und
Intensivmedizin 125:373, 1980.
Coraim F, Binder B, Laczkovics, Pauser G, Stellwag F,
Wolner E:
Additional hemofiltration in the weaning off
cardio-pulmonary bypass phase.
J Europ Soc Artif Organ
189-191, 1984.
Coraim F, Khan H, Stellwag F, Zimpfer Wolner E:
Der
einflub der kontinuierlichen haemofiltration auf die
haemodynamik bei kardiogenem schock nach herzoperationen. Anaesthesist 32:374, 1983.
Coraim F, Spiss CH, Zimpfer M: Effekte kontinuierlicher
arteriovenoser hamofiltration bei akutem lungenversagen
nach
kardiochirurgischen
eingriffen.
Anaesthesist
32:181, 1983.
De Santis 0, Phillips P, Spath MA, Lefer AM: Delayed
appearance of a circulating myocardial depressant factor
in burn patients. Ann Ernerg Med 10:22-24, 1981.
Erdmann N:
Pathophysiologie der zellularen sauersoffversorgung im schock.
In:
Frey R, Stossek K (Hrsg.):
Der schock und seine behandlung. Fischer, Stuttgart-New
York, 91, 1982.
Glenn TM, Lefer AM, Martin JM, Lovett WL, Morris IN,
Wangensteen SL:
Production of myocardial depressant
factor in cardiogenic shock. Am Heart J 82:78, 1971.

292

Other Applications

9.

Gnanadurai TU, Branthwaite MA, Colbeck JF, WeIman E:


Lysosomal enzyme release during cardiopulmonary bypass.
Anaesthesia 32:743-748, 1977.
Gnanadurai TU, Branthwaite MA, Colbeck JF, WeIman:
Lysosomal enzyme release from the lungs after cardiopulmonary bypass. Anaesthesia 33:227-231, 1978.
Heine H, Trenkel K, Arbogast R, Eisenbach J: Funktionelle morphologie von endstrombahn und transitstrecke.
Probleme beim schock. Med Welt 15:558, 1980.
Henderson LW, Ford CA, Lysaght MJ, Grossman RA, Silverstein ME:
preliminary observations on blood pressure
response to maintenance diafi1tration.
Kidney Int
7:413, 1975.
Holloway E, Stinson EA, Derby CC, Harrison DC: Action
of drugs in patients early after cardiac surgery.
I.
Comparison of isoproterenol and dopamine. Am J Cardiol
Kramer P, Wigger PW, Rieger J, Matthaei D, Scheler F:
Arteriovenous hemofiltration:
A new and simple method
for treatment of overhydrated patients resistant to
diuretics. Wien Klin Wschr 55:1121, 1977.
Lefer AM:
Blood-borne humoral factor in the pathophysiology of circulatory shock. Circ Res 32, 1973.
Mann H, Schultes R, Homburg A, Raguse T, Rantenbach R:
Hamofiltration in der intensivmedizin. Intensivtherapie
2:15, 1978.
Mathieu D, Gosselini B, Paris J, Dantrevaux M, Wattel F:
Hemofiltration continue dans Ie traitment de l'encephalopathie hepatique. Nouv Presse Med 11:1921, 1982.
Okuda M, Yamada T, Hosono K: Activity of a myocardial
depressant factor and associated lysosomal abnormalities
in experimental cardiogenic shock.
New Aspects of
Trasylol Therapy 8:183, 1975.
Reichart B, Turk R, Alt B, Kemkes B, Kreuzer E, Holtz J,
et al:
Treatment of acute left heart failure using
dobutamine and intra-aortic counter-pulsation.
Intens
Care Med 3:133, 1981.
Stokke T, Burchardi H, Schlier F: Management of anuric
intensive care patients with arteriovenous hemofiltration.
International J Artific Organs Vol 3, No. 4:225230, 1980.
Wolner E:
Die mechanische kreislaufunterstutzung in
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10.
11.
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13.
14.

15.
16.
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19.

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