4/28/2010

UPDATE & MANAGEMENT

OF
PEDIATRIC SEPTIC SHOCK
Abdul-Rahman Abu-Taleb, MD
Pediatric Intensivist
Chairman, Pediatric Department, KKNGH
KAMCR -Jeddah

INCIDENCE & MORTALITY RATE

Mortality has decreased from 97 % in the mid 60s
to 9% in children before 2002
(better than in adults 9% vs 28%)

Reported outcomes associated with implementation of the

best clinical practices MR 0%-5% in previously healthy
and 10% in chronically ill children

Crit Care Med 2009 Vol. 37, No.2

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INCIDENCE & MORTALITY RATE

Sepsis still is a major killer. It kills more people
than lung cancer, bowel and breast cancer put
together.
Cost over $30 billion.
billion

Br J Nurs. 2008 Jan 1010-23

23;;17(
17(1):16
):16--21

SURVIVING SEPSIS CAMPAIGN

Guidelines for Management of Severe Sepsis
and Septic Shock.

Reduce mortality rates

in severe sepsis
by 25 % in 5 years
Crit Care Med 2004 Vol.32.No.11 (suppl.)

4/28/2010

SURVIVING SEPSIS CAMPAIGN

Randomized clinical trails

in pediatric critical care
are rarely done but
desperately needed

SURVIVING SEPSIS CAMPAIGN

Evidence-based medicine (EBM) is an important strategy
for assessing the vast amount of published data and
applying them appropriately to our patients. However, in
pediatric intensive care, there is a shortage of "gold
standard therapy" randomized controlled trails (RCT) to
support "or not support" therapeutic decisions. This is
because, most of the therapies delivered to patients with
sepsis/severe sepsis and septic shock in the PICU are
life saving (e. g, IV antibiotics, vasopressor agents) and
could not ethically be put to the RCT test.

4/28/2010

Large well conducted RCT in 2001 & 2004 will have impact
on ICU practice

TV for
ALI
Anti-TNF
Antiin sepsis

Activated
protein C

St id
Steroids
in sepsis

Renal dose
dopamine

British Journal of Anesthesia. 2001 Sep; 87(3): 377

Anesth Analg, Volume 99(2). Aug; 2004.566-572

International pediatric sepsis consensus

conference 2005
The definitions for systemic inflammatory response
syndrome (SIRS), sepsis, severe sepsis, and septic
shock, in adults
were recently modified for children

Pediatr Crit Care Med 2005 Vol. 6, No. 1

4/28/2010

International pediatric sepsis consensus

conference 2005

Definitions for sepsis and organ

dysfunction in pediatrics

Brahm Goldstein, MD; Brett Giroir, MD; Adrienne Randolph, MD; and the
Members of the International Consensus Conference on Pediatric Sepsis

Pediatr Crit Care Med 2005 Vol. 6, No. 1

Definitions of SIRS, Infection, Sepsis, Severe Sepsis & Septic Shock

SIRS
(systemic inflammatory response syndrome)

The presence of at least two of the following four criteria, one of which
must be:

Abnormal temperature
or
Leukocyte count

Core temperature of > 38.5 C or < 36 C.

Tachycardia / Bradycardia.
Mean respiratory rate 2 SD above normal for age or mechanical
ventilation.
Leukocyte count elevated or depressed for age. Pediatr Crit Care Med 2005 Vol. 6, No. 1

4/28/2010

DEFINITION OF SEPSIS

Sepsis
SIRS in the presence of or as a
result of suspected or proven
infection.

Age-specific vital signs and laboratory variables

Age Group

Tachyc
Tachyc.

Bradyc
Bradyc.

Beats/min

RR
Breaths/min

Leukocyte C
Leucosytes x 103

>34

Sys
Sys. BP
mm HG

0 days to 1 wk

> 180

< 100

> 50

< 65

1 wk to 1 mo

> 180

< 100

> 40

>19.5 or < 5

< 75

1 mo to 1 yr

> 180

< 90

> 34

>17.5 or < 5

<100

5 yrs
y
25

> 140
0

NA

> 22

>15.5
5 5 or
o <6

< 94
9

612 yrs

> 130

NA

> 18

>13.5 or < 4.5

<105

13 to 18 yrs

> 110

NA

> 14

>11 or < 4.5

<117

Lower values for heart rate, leukocyte count, and systolic blood pressure are for the 5th
and upper values for heart rate, respiration rate, or leukocyte count for the 95th percentile.
Pediatr Crit Care Med 2005 Vol. 6, No. 1

4/28/2010

PEDIATRIC CONSIDERATIONS
Goal directed Endpoints in the management of sepsis are based on
evidence-based adult studies and the extrapolation to the pediatric
patient remains unvalidated.
1.
3.
5.
7.
8.
9.
10.
11.
12.

Mechanical Ventilation
2.
Fluid Resuscitation
Vasopressors / Inotropes
4.
Steroids
Blood/ and blood products
6.
Sedation / Analgesia
prophylaxis
p y
Stress ulcer p
Renal replacement therapy
Extracorporeal membrane oxygenation (ECMO)
Glycemic control
DVT
Protein C & activated protein C
Pediatr Crit Care Med 2005 Vol. 6, No. 1

MECHANICAL VENTILATION

Mechanical Ventilation:
Due to low functional residual capacity (FRC) in
neonates and young infants with severe sepsis early
intubation and mechanical ventilation may be required.

Lung protective strategies are applied to children as

th are tto adults.
they
d lt

Avoiding hyperoxemia in premature infants to prevent

retinopathy.

4/28/2010

MECHANICAL VENTILATION
Max O2
extraction

VO2

Max O2
extraction

VO2
Critical DO2

DO2

Normal
VO2 = DO2 x O2ER

Critical DO2

DO2

Septic Shock/ARDS
ScvO2 < 70%
70%

ScvO2 > 70%

70%
OXYGEN DELIVERY (DO
DO2)
OXYGEN CONSUMPTION (VO2)
OXYGEN EXTRACTION RATIO (O2ER)

INTIAL RESUSCITATION

The initial resuscitation of septic

patients is of utmost importance and
should start in the ED or wards prior
t ttransfer
to
f tto th
the PICU
PICU.

4/28/2010

Early Goal-Directed Therapy (EGDT) for Sepsis Induced

Hypoperfusion
Standard therapy N=133

EGDT N=130

Mortality %

60
P=0.009

50
40
30

56.9
49.2

46.5

44.3
35.1
30.5

20
10
0
In-hospital mortality
(all ptients)

28-day mortality

60-day mortality

Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;
345:1368-1377

The new recommendation 2007 indicate

the following:
g
proportionally larger quantities of fluid than in
adult
first hour fluid resuscitation and inotrope therapy
directed to goals of threshold heart rates, normal
blood pressure, and capillary refill < 2 secs.

Crit Care Med 2009 Vol. 37, No.2

4/28/2010

FLUID RESUSCITATION DURING

INITIAL MANAGEMENT

Aggressive fluid resuscitation with boluses of 20 ml/kg

over 5-10 min
Initial resuscitation usually requires up to 60 ml/kg,
but more may be required
Blood pressure by itself is not a reliable endpoint for
resuscitation
Physical exam, urine output, and pulse response are
the primary response monitors.

HEMODYNAMIC SUPPORT

H
Hemodynamic
d
i profile
fil may be
b variable
i bl
1.

CO and

SVR

22%

2.

CO and

SVR

58%

3.

CO and

SVR

Vasopressors/Inotrops:

Shock
Ceneviva et al: Hemodynamic support in
fluid refractory pediatric septic shock.

Pediatrics 1998; 102:e19

Should only be used after appropriate volume Resuscitation.

Dopamine for hypotension

Epinephrine or norepinephrine for dopaminerefractory shock
Dobutamine for low cardiac output state

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4/28/2010

HEMODYNAMIC SUPPORT
In cases were epinephrine-resistant low CO & high SVR shock is present
management should include as first-line therapy:

Nitrosovasodilators (nitroprusside & nitroglycerin)

When pat remain in a low CO & high SVR resistant state,

despite of epi. + nitros. therapy
use of
phosphodiesterase inhibitor (milrinone) should be
strongly considered.
MR 1985 vs 1998 was reduced from 58% down to 18% in fluid-refractory, dopamine
resistant septic shock since aggressive volume resuscitation & goal-directed therapy
(CI 3.3-6.0 L/min/m2) were applied.

HEMODYNAMIC SUPPORT
Catecholamine-resistant shock
Draw baseline cortisol level
At risk of adrenal insufficiency
Give hydrocortisone (50mg/kg)
Normal BP

Cold shock

CV O2 sat < 70 %
Add vasodilator or
type III PDE inhibitor
with volume loading

Not at risk
dont give hydrocortisone
Low BP

Cold shock

CV O2 sat < 70 %
Titrate volume
and
Epinephrine

Low BP

Warm shock

CV O2 sat 70 %
Titrate volume
and
Norepinephrine

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4/28/2010

Hemodynamic support guidelines by ACCM/PALS

for pediatric septic shock with & without monitoring ScvO2

(End point 70%)

Parameter
n
28 days MR
Crystalloid (ml/kg)
Inotrops in first 6
hours

With
ScvO2
51
11.8%
28 (20-40)
(20 40)

Without
ScvO2
51
39.2%
5 (0-20)
(0 20)

29.4%

7.8%

P - Value

0.002
< 0.001
0 001
0.01

Resulted in significant & additive impact on the outcome.

Intensive Care Med. 2008 Jun;
Jun;34
34((6):991
):991--3.

Early and Late stage of septic shock

Early Stage (hyperdynamic)

Hyperthermia
Tachycardic
Tachypnea
Warm extremities
Bounding pulse
Normal capillary refill time
Hypertensive / Normotensive
Hypoxia
Polyuria
Increased cardiac output
Decreased SVR
Normal CNS
Respiratory alkalosis
Hyperglycemia
Normal coagulation

Late Stage (cardiogenic)

Hypothermia
Tachycardic
Bradypnea
Cold mottled extremities
Weak, thready pulse
Prolonged capillary refill time
Hypotensive
Hypoxia
Oliguria / anuria
Decreased cardiac output
Increased SVR
Obtunded, comatose
Metabolic acidosis
Hypoglycemia
Disseminated intravascular
coagulopathy (DIC)

12

4/28/2010

Historical informations and clinical signs in different shock forms

Cardiogenic
shock

Hypovolemic
shock
History:

Trauma, Vomiting
and /or Diarrhea

CHD, Cardiac surgery,

poor feeding and
respiratory distress

Distributive
shock
Fever, Lethargic,
poor skin color
and irritability

Clinical signs :
Increased

Increased

Increased

1 Heart size
1-

S ll
Small

Large

Small

2- Lungs

Clear

Wet

Clear
(in the early stage)

Gallop rhythm

Not present

Present

Not present

Capillary refill

Prolonged

Prolonged

Normal (in the early stage)

Heart rate
Chest x-ray :

time

Clinical practice parameters for hemodynamic support of pediatric and

neonatal septic shock
2007 update from the American College of Critical Care Medicine

The updated 2007 guidelines continue to recognize an increased

likelihood that children with septic shock, compared with adults, require:

proportionally larger quantities of fluid

inotrope and vasodilator therapies
hydrocortisone for absolute adrenal insufficiency
(ECMO for refractory shock).

The major new recommendation in the 2007 update is earlier use

of inotrope support through peripheral access until central
access is attained.

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4/28/2010

Clinical practice parameters for hemodynamic support of pediatric and

neonatal septic shock
2007 update from the American College of Critical Care Medicine

CONCLUSIONS
1. first hour fluid resuscitation and inotrope therapy
directed to goals of threshold heart rates, normal blood
pressure, and capillary refill < 2 secs.
2. subsequent intensive care unit hemodynamic support
directed to goals of central venous oxygen saturation
>70% and cardiac index 3.36.0 L/min/m2

CONCLUSIONS

THERAPEUTIC ENDPOINTS
Physical exam findings indicating successful
resuscitation include:

Capillary refill < 2 sec

Warm extremities
N
Normal
l mental
t l status
t t
Urine output >1 ml/kg/hr
Central venous O2 sat 70 % (as in adult)
Normalization of lactate (more in adult)

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4/28/2010

THANK YOU

HEMODYNAMIC SUPPORT

Inhaled NO useful in neonates with persistent

pulmonary hypertension (PPHN) and sepsis.
Pentoxifylline (an immunomodeliating agent)
improved outcome in premature neonates with sepsis
when
h given
i
for
f 6 hrs/day
h /d for
f 5 days
d
in
i a randomized
d i d
controlled trail.

15

4/28/2010

OTHER THERAPIES

Steroids: Recommended for children with catecholamine

resistant shock and suspected or proven adrenal insufficiency
(as in adults).

Activated protein C: Not studied adequately in pediatric

severe sepsis yet.

G M - C S F : Shown to be of benefit in neonates with sepsis

and neutropenia (unlike adults).
adults)
DVT: Most DVTs in young children are associated with CVL,
around 25% of children with a femoral CVL will develop DVT.
There are no data on use of heparin prophylaxis to prevent
DVT in children.

OTHER THERAPIES

Stress ulcer p
prophylaxis:
p y
Commonlyy used in mechanicallyy
ventilated children, usually with H2 blockers. No studies
analyzing the effect of stress ulcer prophylaxis in children.

Renal replacement therapy: Continuous venovenous

hemofiltration (CVVH) may be clinically useful in children with
anuria/severe oliguria and fluid overload, but no large RCTs
have been performed.

Glycemic control: There are no studies in pediatric patients

analyzing the effect of rigid glycemic control using insulin.

Sedation/Analgesia: Appropriate sedation and analgesia

for children who are mechanically ventilated is the standard
care, although there are no data supporting any particular
drugs or drug regimens.

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4/28/2010

OTHER THERAPIES

Blood p
products: In the absence of data,, it is reasonable to
maintain Hb at 10 g/dl in children with severe sepsis and
septic shock.

Intravenous immunoglobulin (IVIG): Therapy with

monoclonal IVIGs in children remains experimental. All trails
have been small to support strong conclusion of benefit.

Extracorporeal membrane oxygenation (ECMO): May be

considered
id d in
i children
hild
with
ith refractory
f t
shock
h k or respiratory
i t
failure (not recommended in adults).
ECMO for refractory shock in children.
Pediatr Crit Care Med 2007 Vol. 8, No. 5
ECMO rescue for CPR in pediatric patient.
Crit Care Med 2008 Vol.36, No. 5
Crit Care Med 2009 Vol. 37, No.2

ECMO-CPR

Huang, et al Crit Care Med. 2008

In a retrospective study from the year 1999-2006.

Included all p
patients <18 yyears old how received ECMO during
g active
CPR.

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4/28/2010

ECMO-CPR
Morris and Nadkarni reported 66 children who
were placed on ECMO during CPR over 7
years period
Median time of CPR prior to ECMO was 50
min
23/66 (35%) survived to hospital discharge
These children had a brief period of no flow
phase and excellent CPR during the low flow
phase

ECMO-CPR
How dose this ECMO-CPR experience relate to
post-resuscitation care?
Potential advantage of ECMO come from its
ability to maintain tight control of physiologic
parameters
t
after
ft resuscitation
it ti (e.g.
(
flow
fl
rate,
t
oxygenation, temperature control)
If not available may be we could imitate
ECMO goals by maintaining adequate SvO2?

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THANK YOU

19