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Rational for and strategies of

lung protective ventilation (including


the Open Lung Concept)!

The postnatal pulmonary injury sequence

Prof. Peter C. Rimensberger, MD!


Service of Neonatology and Pediatric Intensive Care!
Department of Pediatrics!
University Hospital of Geneva!
Geneva, Switzerland!

The choices: 1) Try to avoid mechanical ventilation


2) Use gentle lung protective mechanical ventilation

Problem No 1 = Atelectasis: --> Open the lung

Surfactant as a recruitment agent

T --> Surfactant

post

Volume

pre

PEEP

PIP

PEEP

PIP

Pressure

Kelly E Pediatr Pulmonol 1993;15:225-30

mortality

Effects of surfactant
and changes in
ventilator strategies
over time
a retrospective chart review of two
epochs, 1990-1991 and 1999-2000:

bronchopulmonary dysplasia

Group 1: before introduction


of surfactant
Group 2: after introduction
of surfactant
Group 3: ten years later

Soll RF (Cochrane Database) 2002!

Morris S

MJM 2006 9:95-101

Problem No 1 = Atelectasis: --> Open the lung

Group 1: no surfactant
Group 2: + surfactant
Group 3: + lower PIP
T --> Surfactant
P --> positive
pressure:
- CPAP
- CMV / HFO

Morris S

Inborn infants GA <28 weeks


(Boston = 70 and Stockholm
= 102).
Stockholm: 56% CPAP in
the delivery room - 22%
remaind without intubation

MJM 2006 9:95-101

IFDAS trial
% on
mechanical
ventilation

Thomson M Biol Neonate 2002;81(suppl 1):1619

Population: 237 inborn infants 2729 weeks gestational age:

Boston: all infants initially


intubated.

1. Early nCPAP with prophylactic surfactant.

Outcome comparison:

2. Early nCPAP with later rescue surfactant treatment if


needed.

Mortality and moderate/


severe BPD at 36 weeks
were similar; however, at 40
wks oxygen supplementation
was more frequent in Boston.

% on
CPAP

Site was a predictor for


moderate/severe BPD or
death at 40 weeks.

3. Early intermittent positive pressure ventilation (IPPV)


with prophylactic surfactant.
4. Conventional management with rescue IPPV and rescue
surfactant treatment if needed.

Vanpe M Pdiatrica/Acta Pdiatrica 2007:96; 1016

IFDAS trial
Thomson M Biol Neonate 2002;81(suppl 1):1619

The requirement for mechanical ventilation in the first 5


days (120 h) of life was highest in group 3 (CMV +
prophylactic surfactant) and lowest in group 1 (CPAP +
prophylactic surfactant).

COIN-trial
610 infants, 25-to-28-weeks gestation, randomized to
CPAP !" intubation + ventilation
at 5 minutes after birth

Prophylactic surfactant shortens the duration of ventilation.


No difference in total respiratory support (mechanical
ventilation and nCPAP) among the groups.
No difference between groups for oxygen dependency at
28 days or 36 weeks gestational age.

In the year 2008: BPD incidence = 35% < 29 wks "


COIN-trial, NEJM 2008"

SUPPORT- Trial

NCPAP used early or prophylactically for respiratory distress

intubation and
surfactant treatment
(within 1 hour after
birth) or to CPAP
treatment initiated in
the delivery room

NCPAP%vs%no%support%
Finer&2004&
te&Pas&2007&
NCPAP%vs%intuba7on%
Morley&2008&
SUPPORT&2010&

Need for mechanical


ventilation (duration)

Level%of%
Evidence%
&
II&(RCT)&
II&(RCT)&
&
II&(RCT)&
II&(RCT)&

Favors%
CPAP%

Neutral%

Favors%
Alterna7ve%

&
X&
(X)&*&
&
X&
(X)&**&

* reduced intubation rate (37% vs 51%; P=0.04)


** requirement for intubation, postnatal use of corticosteroids for BPD, days of mechanical
ventilation, and mechanical ventilation by day 7 but no difference for death or BPD (at 36 wks)

Survival w/o need for


mechanical ventilation

Adapted form SE Courtney in Neonatal and Pediatric Mechanical Ventilation:


From Basics to Clinical Practice, ed. Rimensberger, Springer (2015)

Postnatal steroids
therapy for BPD

Levels of Evidence
Level
Level
Level
Level
Level
Level

From CPAP group


83 % intubated later
NEJM 2010: 362;1970-9

40 years ago"
Bendixen

NEJM"1963; 269:991-996!

I
II
III
IV
V
VI

Systematic review of randomized controlled trials


Randomized controlled trial
Cohort study
Case-control study
Case series or historical controls
Animal or mechanical model study

Barotrauma is not "


only gross airleak"

Derecruitment (poor oxygenation and ventilation ) with shallow tidal


volumes"
"

Recruitment (good oxygenation and ventilation) with large tidal volumes"

Ventilator induced lung injury:


Experimental data
Non
ventilat
ed lung"

PIP 45
cmH2O"
for 5
min"

Parker JC et al. Crit Care Med 1993;21:131-143!

Effect of ventilation at peak airway pressures of 45 cmH2O on:"


Pulmonary edema"

Permeability"

Albumin distribution"

PIP 45
cmH2O"
for 20
min"

Dreyfuss D AJRCCM 1998;157:294-323!


Dreyfuss D et al. ARRD 1985;132:880-884!

Biotrauma:
cytokines

Vt
PEEP

Control
7 ml/kg
3 cm H2O

MVHP
15 ml/kg
10 cm H2O

MVZP
15 ml/kg
0 cm H2O

HVZP
40 ml/kg
0 cm H2O

Surfactant conversion from large to small aggregates


" surfactant inactivation
1) high Vt (15 ml/kg)/ PEEP 3.5
2) normal Vt (10 ml/kg) / PEEP 3.5
3) low Vt (5 ml/kg)/ PEEP 3.5

Ito Y AJRCCM 1997; 155:493-499


Tremblay L J Clin Invest 1997; 99:944-952

Manual ventilation with a few large breath"


The classical inflation breaths in the labor room!
Surfactant before first breath!

Small Vt-Ventilation or

Bagging before surfactant!

Peak Pressure Limitation"

(Permissive Hypercapnia)"
Bjorklund LJ Ped Research 1997; 42:348-55!

Darioli R, Perret C. Am Rev Respir Dis 1983; 129:385-387

1985: Management of infants with severe respiratory failure

15 infants (2000 - 4800 g/bw); PPHN and severe respiratory failure


(FiO2 1.0)
PaCO2 allowed to increase to 60 mmHg
maximum PIP 25 to 35 cmH2O (increased ventilatory rates);
no paralysis
--> all survived, 1 infant with CLD
Wung J-T Pediatrics 1985;76:488-494

1994: Low mortality rate in adult respiratory distress


syndrome using low-volume, pressure-limited
ventilation with permissive hypercapnia
Hickling KG. Crit Care Med 1994;22:1568-1578

Permissive hypercapnia in preterm infants


PaCO2 pH
(mmHg)

Birth weight 601-1250 gm


RDS requiring ventilation

Permissive
hypercapnia

Postnatal age less than 24 hours

Normocapnia

Infants on MV (%)

1984: Controlled hypoventilation in status asthmaticus

45 - 55

> 7.20

35 - 45

> 7.25

RESPIRATORY OUTCOMES

100

Normocapnia
Hypercapnia
Normocapnia
Permissive hypercapnia
p = 0.002 Log rank test
Days on MV
2.5 (1.5 - 11)
9.2 (2 - 22)
Days on O2

80
60
40
20
0

12 24 36 48 60 72 84 96

Duration of MV (hours)

15 (4 - 53)

32 (17 - 50)

O2 at 28 days (%)

43

64

O2 at 36 weeks (%)

10

Reintubation (%)

67

54

Air leaks (%)

16

Steroids (%)

12

24

all differences between groups did not reach significance

Mariani G, Cifuentes J, Carlo WA Pediatrics 1999;104:1082-1088

Minimal ventilation
to prevent BPD

Minimal ventilation
to prevent BPD

PCO2 target >52 mm Hg


vs.
PCO2 target <48 mm Hg

Carlo W et al.

J Pediatr 2002;141:370-5

ARDS network trial (Vt 6 vs. 12 ml/kg)

Carlo W et al.

Mechanism 1:

J Pediatr 2002;141:370-5

Excessive end-inspiratory volume

"

Overdistension!
Volume

n = 861

Mortality: 31 vs. 38
(p < 0.007)
PIP:
32 vs. 39 cmH2O
Pplat: 25 vs. 33 cmH2O

Pressure
NEJM 2000;342:1301-1308!

Concept of low Vt or peak pressure limitation

1967 - 1975: PEEP and the Oxygenation Concept!


Investigators

Title

Asbaugh

Acute respiratory distress syndrome

Lancet 1967; 2:319-323

The lower end:


PEEP

Gregory
NEJM 1971; 284:1332-1340

Treatment of idiopathic respiratory distress "


syndrome with continuous positive airway "
pressure

1975- 1990: PEEP and Dynamic Compliance / Shunt!


Investigators

End points

Terminology

Suter et al.,

Maximum compliance

Best PEEP

NEJM 1975; 292:284-289

Kirby et al.,

Reduction of shunt to 15% Super-PEEP

Chest 1975; 67:156-163

PEEP

"
Intratidal collapse "
and decollapse "
(opening)"
Mechanism 2:

and lung function


assessment
to prevent VILI
during small Vt
ventilation

PEEP = 0

PEEP = 4

PEEP > Pinf

Control

Pinf (LIP)

Muscedere AJRCCM 1994;149:1317-1334

Biotrauma:
Protection
by PEEP

Vt
PEEP

Control
7 ml/kg
3 cm H2O

MVHP
15 ml/kg
10 cm H2O

MVZP
15 ml/kg
0 cm H2O

HVZP
40 ml/kg
0 cm H2O

Effects of Ventilation with Different PEEP: on Cytokine


Expression in the Preterm Lamb Lung!

Naik AS Am J Respir Crit Care Med 2001; 164:494498!


Tremblay L J Clin Invest 1997; 99:944-952

PEEP preserves surfactant function in


preterm lambs!
!

Ventilator induced lung injury (VILI)

LA-pool size recovery!

Volume

surfactant alone!

Atelectasis
0

12

15

18

21

24

27

30

transpulmonary pressure (cmH2O)

Michna J

AJRCCM 1999;160:634639!

Atelectrauma:

Concept of high PEEP

QuickTime et un dcompresseur
Photo - JPEG sont requis pour visualiser
cette image.

LIP"

The combination of Low Vt + High PEEP "

Biotrauma:
Combined
Vt and PEEP
effects

MVHP
15 ml/kg
10 cm H2O

identical
end-inspiratory
distension

HVZP
40 ml/kg
0 cm H2O

Tremblay L J Clin Invest 1997; 99:944-952

Lung heterogeneity

VILI
Tidal Breath
Overdistention

Tidal Breath
Recollapse

Tidal Breath
Recruitment

28800 times/day"

In heterogeneous lung injury inflation behavior is heterogeneous

57600 times/day"

86400 times/day"
Courtesy from Niemann G

Lung protective mechancial ventilation:


Concept of low Vt or peak pressure limitation and
high PEEP

Lung Opening:
Experience from
the adults

How much is
too much or
how high is too
high ?

How low is too


low ?
Froese A
Crit Care Med 1997;25:906-8

Anatomical Recruitment
during increasing PEEP steps

Radford: in Respiratory Physiology (eds. Rahn and Fenn)

Lung volume
recruitment
and
higher PEEP

Barbas C Crit Care Med 2003; 31[Suppl.]:S265S271


Gattinoni L

AJRCCM 2001; 164:17011711

Courtesy from Niemann G

normal poorly areated

Lung opening and closing

CT-aeration
At ZEEP and
2 PEEP levels
= turning up
the PEEP
approach

Behavior of the whole lung: Hysteresis

Diffuse CT-attenuations

normal

poorly areated

Pressure

Focal CT-attenuations

Rouby JJ AJRCCM
2002;165:1182-6

Radford: in Respiratory Physiology (eds. Rahn and Fenn)

Factors that influence the efficiency of RM

PEEP is an end-expiratory phenomenon

1) Recruiting pressure (CPAP, SI or Pplat)


Recruitment occurs over the whole PV-range

It does not recruit


It does maintain

Rimensberger PC Crit Care Med 1999; 27:1946

Gattinoni L

A JRCCM 2001; 164:17011711


Rimensberger PC Crit Care Med 1999; 27:1946

small tidal volume ventilation (5 ml/kg)

small tidal volume ventilation (5 ml/kg)

Pression

30

Pression

30

8
Optimal PEEP

Oxygenation

Optimal PEEP

Gradient PaO2/FiO2

600
500
400

Recruited vol

Recruited vol

300
200
100
0

Rimensberger PC

Crit Care Med 1999; 27:1946

Rimensberger PC

Postlavage

60

120
180
Time (min)

240

Crit Care Med 1999; 27:1946

small tidal volume ventilation (5 ml/kg)


Pression

30

Optimal PEEP

Recruited vol

Rimensberger PC

Crit Care Med 1999; 27:1946

Rimensberger PC
Crit Care Med 1999; 27:1940

Optimal = Maximum dynamic compliance and


best oxygenation at the least pressure required

Factors that
influence the
efficiency of RM

after RM

before RM

alveoli per field


inspiration

Volume effect of various levels of PEEP


(In- and decremental PEEP steps)

expiration

PEEP after
IE

Courtesy from David Tingay, Melbourne

Hickling KG et al. AJRCCM 2001; 163:69-78

Halter JM

Rimensberger PC Crit Care Med 1999; 27:1946

Common RM-Techniques

Common RM-Techniques

CPAP-Recruiting Maneuver (Sustained Inflation)

CPAP-Recruiting Maneuver (Sustained Inflation)

CPAP to 40 60 cmH2O
for 20 to 60 secondes

AJRCCM 2003, 167:1620-6

CPAP to 40 60 cmH2O
for 20 to 60 secondes
Individuel PEEP level

45/20

Lapinsky SE Intensive Care Med 1999; 25: 1297-1301

Lapinsky SE Intensive Care Med 1999; 25: 1297-1301

Lung opening and closing


Behavior of the whole lung: Hysteresis

Volume
derecruitment
throughout
deflation

Pclosing

UIPdefl

Frequency distribution of
opening and closing pressure
in patients with ARDS

Use of dynamic
compliance for open
lung positive endexpiratory pressure
titration in an
experimental study

UIPinfl
Alveolar
recruitment
throughout
inflation

LIP

Radford: in Respiratory Physiology (eds. Rahn and Fenn)

Crotti S AJRCCM 2001;164: 131140

F Suarez-Sipman
Crit Care Med 2007; 35:214221

10

PEEP 6

PEEP 24

PEEP 18

PEEP 14

PEEP 10

PEEP 6

Effects of descending positive end-expiratory pressure on lung


mechanics and aeration in healthy anaesthetized piglets
end-inspiration

end-expiration

PEEP 14 = level of best


compliance

Volume controlled ventilation

end-inspiration
end-expiration

PEEP 14

A Roncally S Carvalho et al.

F Suarez-Sipman
Crit Care Med 2007; 35:214221

Critical Care 2006, 10:R122

Get the lung as much homogeneous as possible

Volume
distribution

Frerichs I et al. J Appl Physiol 2002; 93: 660666

Tidal volume
distribution

Volume
distribution

Frerichs I, Dargaville P, Rimensberger PC

Intensive Care Med 2003; 29:2312-6

Frerichs I, Dargaville P, Rimensberger PC

Intensive Care Med 2003

Regional homogeneity on the deflation limb


right lung non-dependent region

Delivered tidal volume


(% of maximal Vt)

right lung dependent region

normal lung

normal lung

injured lung

injured lung

ventral

Regional ventilation (R)

median
dorsal

post surfactant lung

post surfactant lung

Dargaville P, Frerichs I, Rimensberger PC

Regional ventilation (L)

Dargaville P, Rimensberger PC, Frerichs I

Intensive Care Med 2010

11

Normal lung / recruited lung


at optimal lung volumes

ARDS / RDS lung


(Heterogeneous)

PEEP titration vs. recruitment maneuvers


Recruitment maneuvers:

C=2

Vt=2.5ml/kg

Vt=4ml/kg
Vt=5ml/kg

Vt=5ml/kg

How high, and what afterwards ?

Alveolar
C=2
Rupture!

Intermittently
increased VT

?
C=1

C=2

VT= 1ml/kg

Vt=2.5ml/kg

=
/=

=
3

=
2

=
/=

From the lab to the bedside: The principal concepts

Sustained inflation

Intermittently
increased PEEP

Stepwise
PEEP increase

Lung Recruitment Using Oxygenation during Open


Lung High-Frequency Ventilation in Preterm Infants

Adapted from Suzuki H


Acta Pediatr Japan 1992

Adapted from Suzuki H Acta Pediatr Japan 1992; 34:494-500


De Jaegere Ann et al.

Lung Recruitment Using Oxygenation during Open


Lung High-Frequency Ventilation in Preterm Infants

Am J Respir Crit Care Med 2006: 174; 639645

Lung Recruitment Using Oxygenation during Open


Lung High-Frequency Ventilation in Preterm Infants
before surfactant

after surfactant

Adapted from Suzuki H


Acta Pediatr Japan 1992

De Jaegere Ann et al.

Am J Respir Crit Care Med 2006: 174; 639645

De Jaegere Ann et al.

AJRCCM 2006: 174; 639645

12

Ventilation efficiency during optimal CDP finding


Diffusion coefficient of CO2 (DCO2) = alveolar ventilation
Alveolar Ventilation during HFV is defined as:
f x Vt

Vmineff

or

DCO2 )

CMV: Optimal = Maximum dynamic


compliance and best oxygenation at
the least pressure required

pO2
pCO2
Cdyn

pO2
pCO2
Cdyn

Optimal O2 = Paw 19
Optimal Vt = Paw 10.5
Optimal CO2 = Paw 8

RIP PV-curve in
RSV pneumonitis
on HFOV

Optimal lung expansion (the most


homogeneous one) adapted to the lung
pathology assures best oxygenation and
ventilation

David Tingay,
Melbourne, 2004

HFOV: Optimal = Maximum DCO2


(f x Vt2) and best oxygenation at the
least pressure required

pO2

pO2
pCO2
Cdyn

Setting PEEP and lung volume recruitment

pCO2
Vt (VCO2)

)3

= 2

1 =

Suzuki H Acta Pediatr Japan 1992; 34:494-500

pO2

pCO2

/ /

/
=

/
=

Vt (VCO2)

3 3
=3 / /

= =
3 3
=

Optimal lung expansion (the most


homogeneous one) adapted to the lung
pathology assures best oxygenation and
ventilation

2=

/ /

pO2
pCO2
Vt (VCO2)

13