PEEP:Bring the Evidence to the Bedside

PEEP: Bringing the Evidence to the Bedside Ira M. Cheifetz MD FAARC Duke Children's Hospital Durham, NC Dean R. Hess PhD RRT FAARC Massachusetts General Hospital Harvard Medical School Boston, MA

19 yo female with Crohn’s Disease Immunosuppressed (once daily 6-mercaptopurine 100 mg po) CMV pneumonia and diffuse alveolar hemorrhage by BAL Febrile and pancytopenic (WBC 2,000; hematocrit 26.2%; reticulocytes 7.1%; platelets 89,000) Intubated for severe hypoxemia with tachypnea and dyspnea Ventilator: VCV, VT 250 mL (≈6 mL/kg PBW), I:E 1:2, rate 26/min, PEEP 14 cm H2O, FiO2 0.6 ABG: pH 7.41, PaCO2 41 mm Hg, PaO2 64 mm Hg

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

Few topics generate more controversy! What is the role of PEEP in reduction / prevention of VILI? What is the role of PEEP with lung protective ventilatory strategies? What is ‘optimal’ PEEP? Does it really exist? 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 have reported reduced mortality with higher levels of PEEP when compared to lower levels of PEEP. A. True B. False

53 patients assigned to conventional or protective mechanical ventilation. Conventional ventilation: lowest PEEP for acceptable oxygenation and VT 12 mL/kg. Protective ventilation: PEEP above the lower inflection point on the PV curve, VT < 6 mL/kg per kilogram, recruitment maneuvers, PCV. 28 day mortality of 38% in the protective-ventilation group and 71% the conventional-ventilation group (P < .001). N Engl J Med 1998;338:347

Control group (n = 50): VT 9–11 mL/kg PBW, PEEP >5 cm H2O Pflex/LTV group (n = 53): VT 5–8 mL/kg PBW and PEEP at Pflex + 2 cm H2O ICU mortality 32% in Pflex/LTV group versus 53% in control group versus (P = .04) Crit Care Med 2006; 34:1311

Was the mortality difference in the Amato and Villar trials due to a 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. Who knows?

861 patients with ALI/ARDS at 10 centers randomized to VT 12 mL/kg PBW or 6 mL/kg PBW (VCV, Pplat ≤ 30 cm H2O) 25% reduction in mortality in patients receiving smaller tidal volume 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) 2 PEEP levels with VT 6 mL/kg PBW Oxygenation and respiratory system compliance better with higher PEEP Stopped at 549 patients for futility No safety concerns N Engl J Med 2004;351:327

Target tidal volume 6 mL/kg PBW Control (n=508): Pplat ≤ 30 cm H2O (VCV), lower PEEP Experimental (n=475): Pplat ≤ 40 cm H2O (PCV), recruitment maneuvers (40 s at 40 cm H2O), initial PEEP 20 cm H2O; higher PEEP No significant difference in hospital mortality, but improved secondary end points related to hypoxemia and use of rescue therapies Meade, JAMA 2008;299:637

Target tidal volume 6 mL/kg PBW Control (n=382): low PEEP (5 - 9 cm H2O) minimal distension strategy Experimental (n=385): PEEP set to reach Pplat of 28 - 30 cm H2O (increased recruitment strategy); PEEP 16 ± 3 cm H2O on day 1 No significant difference in mortality, but improved lung function, reduced duration of mechanical ventilation and duration of 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. who knows?

Benefit of Higher PEEP Offset by Higher Pplat? PPlat or PEEP (cm H20) 6 mL/kg Non- 6 mL/kg recruitable Recruitable (↑Crs, ↓Vd) 6 mL/kg Injury Benefit > > Benefit Injury Lower Higher PEEP PEEP

68 patients with ALI/ARDS underwent CT at airway pressures of 5, 15, and 45 cm H2O. Potentially recruitable lung varied On average, 24% of the lung could not be recruited. Patients with a higher percentage of potentially recruitable lung had poorer oxygenation and respiratory-system compliance, and higher levels of 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↓dead space 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

Which is the best way to select PEEP? A. PV curve B. best compliance C. PEEP/FiO2 table D. stress index E. who knows?

Optimal PEEP by Compliance 15 normovolemic patients requiring mechanical ventilation for ARF PEEP resulting in maximum oxygen transport and the lowest dead-space fraction resulted in highest compliance Optimal PEEP varied from 0 to 15 cm H2O Mixed venous PO2 increased from 0 PEEP to the PEEP resulting in maximum oxygen transport, but then decreased at higher PEEP Conclusion: 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 normal volume above FRC (liters) 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 PV Curves Requires sedation/paralysis Difficult to identify “inflection points” (Harris et al, AJRCCM 2000; 161:432) May require esophageal pressure to separate lung from chest wall effects (Mergoni et al, AJRCCM 1997; 156:846 Ranieri et al, AJRCCM 1997; 156:1082) Deflation limb may be more useful than inflation limb (Holzapfel et al, Crit Care Med 1983;11:561; Hickling, AJRCCM 2001;163:69) Pressure-volume curves of individual lung units not known (Hickling, AJRCCM 1998;158:194) Role of 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

Stress Index Tidal Recruitment Over-Distention Am J Respir Crit Care Med 2007;176:761

AJRCCM 2007;176:761 In all 15 patients, the stress index revealed hyperinflation with the ARDSnet PEEP strategy PEEP decreased to normalize the stress index Compliance higher and plasma cytokines lower using the stress index compared with ARDSnet

Pulmonary vs. Extrapulmonary ARDS Gattinoni, Am J Respir Crit Care Med 1998;158:3

N Engl J Med 2008;359:2095

Esophageal Balloon Catheter Benditt, Respir Care 2005; 50:68

Setting PEEP for Acute Lung Injury 0 cm H2O: likely harmful 8 – 15 cm H2O: appropriate in most patients >20 cm H2O: seldom necessary PEEP should be selected in the context of prevention of ventilator-induced lung injury 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 O2 Supply = O2 Delivery = DO2 DO2 = cardiac output x oxygen content O2 content = (1.34 x Hgb x O2 sat) + (0.003 x PaO2)

Determinants of Oxygen Delivery Preload Stroke Volume Afterload Contractility Cardiac Output Heart Rate O2 Delivery Hgb (O2 capacity) Oxygen Content O2 binding (SaO2) O2 dissolved (PaO2)

Right Ventricular Filling Effects on RV positive pressure RA thorax ventilation RV PA

Systemic Venous Return RV Preload P SV RAP= mean systemic venous pressure PPV increases right atrial pressure Right Atrial spontaneous breathing Pressure 0 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 Atelectasis PVR Large Vessels Lung Volume

Effect of Lung Volume on PVR Overexpansion Atelectasis PVR 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 overdistend 600 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

PaO2 vs. PEEP Optimize O2 delivery 600 600 500 500 400 400 300 300 200 200 100 100 DO2 vs. PEEP 0 0 0 5 10 15 20 25 0 5 10 15 20 25

‘Optimal’ PEEP

Ventilator-Induced Gas Exchange Lung Injury Setting the Ventilator Patient Comfort Hemodynamics

20 yo female with ALL Immunosuppressed – last ChemoTx 10 days ago Adenoviral pneumonia Febrile and pancytopenic (WBC 2K; hematocrit 25; platelets 89K) Intubated for severe hypoxemia with tachypnea and dyspnea Vent: PCV, PIP 32 cm H2O, VT ≈6 mL/kg PBW, I:E 1:2, PEEP 14 cm H2O, rate 26, FiO2 0.6 ABG: pH 7.41, PaCO2 41 mm Hg, PaO2 64 mm Hg

The goal of PEEP in this patient is to: A. increase PaO2 B. decrease FiO2 C. decrease risk of VILI D. provide a good excuse for a 90 min lecture

Ventilator-Induced Gas Exchange Lung Injury Setting the Ventilator Patient Comfort Hemodynamics

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PEEP:Bring the Evidence to the Bedside

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PEEP:Bring the Evidence to the Bedside — Presentation Transcript