PEEP: Bringing the

Evidence to the Bedside

Ira M Cheifetz MD
Duke Children's Hospital
Durham, NC

Dean R Hess PhD RRT

Massachusetts General Hospital
Harvard Medical School
Boston, MA
y 16 yo with Crohn’s Disease
y Immunosuppressed
(mercaptopurine)
y CMV pneumonia and diffuse
alveolar hemorrhage by BAL
y Febrile and pancytopenic (WBC
2K; HCT 26%; Plt 89K)
y Intubated for severe hypoxemia
with tachypnea and dyspnea
y Ventilator: VCV, VT 250 mL
(≈6 mL/kg PBW), I:E 1:2, rate 26,
PEEP 14 cm H2O, FiO2 0.60
y ABG: pH 7.41, PaCO2 41 torr,
PaO2 64 torr
The goal of PEEP in this patient is to:

A. Increase PaO2
B. Decrease FiO2
C. Decrease risk of VILI
 Preventing Overdistention and
Collapse Injury

‘Lung Protective’ Ventilation

Add
Add PEEP
PEEP
V
O
L
U
M
Limit Distending Pressure
E Limit Vt

Pressure
Few topics generate more controversy!

y What is the role of PEEP in the reduction /

prevention of VILI?
y What is the role of PEEP with lung protective
ventilatory strategies?
y What is ‘optimal’ PEEP? Does it really exist?
y How do you select the ‘best’ PEEP for your
patient?
Edema in Rat Lungs after Ventilation

14/0 45/10 45/0

Webb HH et al. Am Rev Respir Dis. 1974;110:556-565.

Does PEEP recruit alveoli?
Or, just prevent de-recruitment
 Zone of
Overdistention

ion
lat
ha
Ex

tion
i ra
p
Ins
Ideal
PEEP
Zone of
Atelectasis
Studies report reduced mortality with
higher levels of PEEP when compared
to lower levels of PEEP?

A. True
B. False
y 53 patients: conventional vs. protective ventilation
y Conventional: lowest PEEP for acceptable
oxygenation and VT 12 mL/kg
y Protective: PEEP above the lower inflection point
on the PV curve, VT < 6 mL/kg, recruitment
maneuvers, PCV
y 28 day mortality: protective-ventilation 38% vs.
conventional-ventilation 71% (p < 0.001).

N Engl J Med 1998;338:347

y Control (n = 50): VT 9–11 mL/kg PBW,
PEEP > 5 cm H2O
y Pflex / LTV (n = 53): VT 5–8 mL/kg PBW,
PEEP at Pflex +2 cm H2O
y ICU mortality: 32% in Pflex/LTV group vs. 53% in
control group (p = 0.04)

Crit Care Med 2006; 34:1311

Was the mortality difference in the
Amato and Villar trials due to lower
tidal volume, higher PEEP, or both?

A. Lower tidal volume only

B. Higher PEEP only
C. Combined effect of PEEP and tidal
volume
D. Unknown
y 861 ALI/ARDS patients (10 centers)
y 6 vs. 12 mL/kg PBW (VCV, Pplat ≤ 30 cm H2O)
y 25%↓in mortality with smaller tidal volume
y Number-needed-to-treat: 12 patients

N Engl J Med 2000; 342:1301

 ALVEOLI (Assessment of Low tidal Volume and
elevated End-expiratory volume to Obviate Lung Injury)

y 2 PEEP levels; VT 6 mL/kg PBW

y Oxygenation and respiratory system compliance
were improved with↑PEEP
y Stopped at 549 patients for futility
y No safety concerns

N Engl J Med 2004;351:327

y Target VT 6 mL/kg PBW
y Control (n=508): Pplat ≤ 30 cm H2O (VCV), lower PEEP
y Intervention (n=475): Pplat ≤ 40 cm H2O (PCV),
recruitment maneuvers (40 s at 40 cm H2O),
initial PEEP 20 cm H2O
y No significant difference in hospital mortality

Meade, JAMA 2008;299:637

y Target VT 6 mL/kg PBW
y Control (n=382): low PEEP (5-9 cm H2O)
minimal distension strategy
y Experimental (n=385): PEEP set to achieve Pplat
28-30 cm H2O (recruitment strategy);
PEEP 16±3 cm H2O on day 1
y No significant difference in mortality, but
improved lung function; reduced duration of
mechanical ventilation and organ failure
Mercat, JAMA 2008;299:646
Why did these studies fail to show a
mortality benefit?
A. They were underpowered
B. Higher PEEP does not help
C. PEEP strategies were incorrect
D. Harm from higher Pplat offsets benefit of
PEEP
E. Unknown
Benefit of Higher PEEP Offset by Higher Pplat?

PPlat or PEEP (cm H20)

6 mL/kg
Non-
recruitable 6 mL/kg
Recruitable
6
mL/kg
Injury Benefit
> >
Benefit Injury

Lower Higher
PEEP PEEP
y 68 ALI/ARDS patients; chest CT at airway
pressures of 5, 15, and 45 cm H2O
y Potentially recruitable lung varied
y On average, 24% lung could not be recruited
y Patients with a higher percent of potentially
recruitable lung had↓oxygenation and
respiratory-system compliance, and↑dead space

N Engl J Med 2006;354:1775

N Engl J Med 2006;354:1775
FiO2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0
PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 20-24

no

Assess ‘lung recruitability’

PaO2/FiO2 < 150 on 5 cm H2O PEEP
↑compliance or↓deadspace with↑PEEP?

yes

FiO2 0.3 0.3 0.3 0.3 0.3 0.4 0.4 0.5 0.5 0.5 0.6 0.7 0.8 0.9 1.0
PEEP 5 8 10 12 14 14 16 16 18 20 20 20 20 20 20-24

Ramnath, Clin Chest Med 2006;27:601

 Optimal PEEP by Compliance

y 15 normovolemic ventilated patients

with acute lung injury
y ↑O2 transport and↓deadspace
correlated with ↑compliance
y Optimal PEEP varied; 0-15 cm H2O
y PMVO2 increased from PEEP 0 to the
PEEP resulting in maximum O2
transport, but then↓at higher PEEP
y Compliance may be used to indicate
the PEEP likely to result in optimum
cardiopulmonary function.
↑ PEEP
Suter, N Engl J Med 1975;292:284
Pressure-Volume Curve

1.6
volume above FRC (liters) normal
1.2

ARDS
0.8

upper inflection
point
0.4

lower inflection
point
0

0 10 20 30 40
airway pressure (cm H2O)
Rotta, J Pediatr (Rio J) 2003;79(Suppl 2):S149
Owens, Stigler, Hess; Clin Chest Med 2008; 29:297
 Issues with Static PV Curves
y Requires sedation / paralysis
y Difficult to identify ‘inflection points’ (Harris, AJRCCM, 2000)
y May require esophageal pressure to separate lung
from chest wall effects (Mergoni, AJRCCM, 1997;
Ranieri, AJRCCM, 1997)
y Deflation limb may be more useful than inflation limb
(Holzapfel, Crit Care Med, 1983; Hickling, AJRCCM, 2001)
y Pressure-volume curves of individual lung units not
known (Hickling, AJRCCM, 1998)

Role of static PV curve for setting PEEP

currently unknown!
 Decremental PEEP Trail

Theoretically attractive, but unproven!

Hickling, AJRCCM 2001;163:69 Richard, Critical Care 2004, 8:163
Esophageal Balloon Catheter

Benditt, Respir Care 2005; 50:68

 Setting PEEP for Acute Lung Injury

y 0 cm H2O: likely harmful

y 8-15 cm H2O: appropriate in most patients
y > 20 cm H2O: seldom necessary

y PEEP should be selected in the context of

prevention of ventilator induced lung injury.
y The benefit of precise setting of PEEP is
unproven.
PEEP adversely affects cardiac output
by which of the following?

A. Decreased RV preload
B. Increased RV preload
C. Increased LV afterload
D. Decreased LV afterload
E. None of the above
 Cardiorespiratory Economics

y O2 Supply = O2 Delivery = DO2

y DO2 = cardiac output x oxygen content

O2 content = (1.34 x Hgb x O2 sat) + (0.003 x PaO2)
 Determinants of Oxygen Delivery

Preload
Afterload Stroke Volume
Contractility
Cardiac Output
Heart Rate
O2 Delivery
Hgb (O2 capacity)
O2 binding (SaO2) Oxygen Content
O2 dissolved (PaO2)
 Right Ventricular Filling
Effects on RV

positive
RA pressure
thorax RV ventilation

PA
 Systemic Venous Return

RV Preload
P
SV RAP= mean systemic venous pressure

PPV increases right atrial pressure

Right Atrial
Pressure spontaneous breathing

0 Max
Systemic Venous Return
How does increasing PEEP affect PVR?

A. Increases PVR
B. Decreases PVR
C. Either is possible
 Effect of Lung Volume on PVR

PVR Atelectasis

Large Vessels

Lung Volume
 Effect of Lung Volume on PVR

Overexpansion

PVR Atelectasis

Small Vessels

Lung Volume
 Effect of Lung Volume on PVR

PVR
Total PVR

Lung Volume
 Overdistention and PVR
5000
4500 PEEP 5 PEEP 10

PVR 4000

(d-sec/cm5) 3500
3000
2500
2000
1500
1000
10 15 20
Cheifetz. CCM. 1998.
Tidal Volume (mL/kg)
 Overdistention and PVR
1000
950
PEEP 5 PEEP 10
900
Cardiac 850

Output 800
750
(mL/min) 700
650
600
550
500
10 15 20

Cheifetz. CCM. 1998. Tidal Volume (mL/kg)

 PaO2 vs. PEEP

600 overdistend
PaO2 (torr)

500

400

300
collapse
200

100

0
0 5 10 15 20 25

PEEP (cm H2O)

 Cardiac Output vs. PEEP

5.5

5
CO (l/min)

4.5
collapse
4

3.5

3
overdistend
2.5

2
0 5 10 15 20 25

PEEP (cm H2O)

DO2 vs. PEEP
600
600 PaO2 vs. PEEP Optimize O2 delivery
500
500

400
400

300
300

200
200

100
100

00
00 55 10
10 15
15 20
20 25
25
DO2 vs. PEEP
‘Optimal’ PEEP
Ventilator-Induced
Gas Exchange
Lung Injury

Setting the Ventilator

Patient Comfort Hemodynamics

y 20 yo female with ALL
y Immunosuppressed – last
ChemoTx 10 days ago
y Adenoviral pneumonia
y Febrile and pancytopenic (WBC
2K; hematocrit 25; platelets 89K)
y Intubated for severe hypoxemia
with tachypnea and dyspnea
y Vent: PCV, PIP 32 cm H2O,
VT 6 mL/kg PBW, I:E 1:2, PEEP
14 cm H2O, rate 26, FiO2 0.60
y ABG: pH 7.41, PaCO2 41 torr,
PaO2 64 torr
The goal of PEEP in this patient is to:

A. Increase PaO2
B. Decrease FiO2
C. Decrease risk of VILI
Ventilator-Induced
Gas Exchange
Lung Injury

Setting the Ventilator

Patient Comfort Hemodynamics