Recruitment and PEEP in ALIARDS Paolo Pelosi Department

Recruitment and PEEP in ALI/ARDS Paolo Pelosi Department of Ambient, Health and Safety, University of Insubria, Varese, Italy ppelosi@hotmail. com

Outcomes in ARDS – “In the real life” Esteban, Ferguson, Meade, …. Pelosi et al AJRCCM 2008; 15; 177: 170 -7 1998 (n 135) Duration of intubation, median (IQR), days 2004 (n 198) P Value 8 (5, 15) 10(5, 16) 0. 27 Length of stay in the ICU, median (IQR), days 12 (7, 23) 14 (7, 21) 0. 54 ICU mortality, n (%) 82 (61) 111 (56) 0. 39 Hospital mortality, n (%) 87/126 (69) 117/185(63) 0. 29

The ARDS Lung Gattinoni JAMA 1993, Pelosi AJRCCM 1994, Gattinoni AJRCCM 2002, Gattinoni ICM 2005 Rouby Intensive Care Med 2000 Opening Pressure Superimposed Pressure Normal 0 Small Airway Collapse 10 -20 cm. H 2 O Alveolar Collapse (Reabsorption) 20 -30 cm. H 2 O Consolidation

Ventilator induced lung injury volutrauma zone of overdistension V zone of derecruitment and atelectasis "safe" window LIP atelectrauma P UIP

Ventilator induced lung injury volutrauma zone of overdistension V zone of derecruitment and atelectasis "safe" window LIP atelectrauma P UIP

HOW MUCH TIDAL VOLUME AND INSPIRATORY PLATEAU PRESSURE IN ALI/ARDS PATIENTS ?

Ventilation strategies and outcomes of the ALI/ARDS : a Meta-analysis Ventilation strategies and outcomes of acute respiratory distress syndrome and acute lung injury: a meta-analysis Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P Ann Intern Med 2009; 151: 566 -576 Hospital Mortality: Lower vs Higher VT at the same PEEP Patients, n Low VT Similar PEEP Odds ratio (95% CI) 12/26 1. 17(0. 39 -3. 47) 134/432 171/429 0. 68(0. 51 -0. 90) 30/60 28/60 1. 14(0. 56 -2. 34) Brower, 1998 52 13/26 Brower, 2000 861 Stewart, 1998 120 Summary High VT Similar PEEP 0. 75(0. 58 -0. 96) P<0. 02; I 2 =18. 3

Ventilation strategies and outcomes of the ALI/ARDS : a Meta-analysis Ventilation strategies and outcomes of acute respiratory distress syndrome and acute lung injury: a meta-analysis Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P Ann Intern Med 2009; 151: 566 -576 • Low VT ventilation did not improve outcome when higher VT ventilation resulted in Pei less or equal to 30 cm H 2 O. • Low VT ventilation was associated with greater use of NMBAs • Low VT ventilation may not be beneficial if: - p. H<7. 20 (administering sodium bicarbonate, increasing VT , ECMO) - side effects (hypercapnia/respiratory acidosis) are contraindicated

HOW MUCH RECRUITABLE LUNG IN ALI/ARDS PATIENTS ?

EDEMA – ATELECTASIS IN ALI/ARDS ρxgxh P = 5 cm. H 2 O LESS EDEMA-ATELECTASIS LOWER PEEP P = 10 cm. H 2 O HIGHER EDEMA-ATELECTASIS LOWER PEEP

Paw 45 cm. H 2 O Gattinoni et al NEJM 2006, 354(17): 1775 -86 Non recruiter Weight (grams) 14 12 10 8 Peep 5 cm. H 2 O 6 4 2 0 ov era no ted po rm a lly ae no orl ya rat ed era ted na era ted Peep 5 cm. H 2 O Paw 45 cm. H 2 O

Paw 45 cm. H 2 O Gattinoni et al NEJM 2006, 354(17): 1775 -86 Recruiter Weight (grams) 60 50 40 30 Peep 5 cm. H 2 O 20 10 0 ov no era e rat rm ed all po ya orl era ya no ted era na ted era ted Peep 5 cm. H 2 O Paw 45 cm. H 2 O

Potential for lung recruitment Gattinoni et al NEJM 2006, 354(17): 1775 -86 Frequency [no. of patients] 5 ± 4% (59 ± 51 grams) lower 24 22 20 18 16 14 12 10 8 6 4 2 0 21 ± 10% (374 ± 236 grams) higher ALI patients ARDS patients -80 75 -75 70 -70 65 -65 60 -60 55 -55 50 -50 45 -45 40 -40 35 -35 30 -30 25 -25 20 -20 15 -15 10 0 5 -1 0 -5 0 -5 -5 -10 potential for lung recruitment [% total lung weight]

Mortality at ICU-discharge Gattinoni et al NEJM 2006, 354(17): 1775 -86 mortality [%] lowerpotential 60 higherpotential 50 40 30 20 10 P=0. 006 0 n = 1 st 2 nd 3 rd 4 th 17 17 quartiles of potential for lung recruitment

Possible model Core disease 24% Lower Inflammation spreading 71% 5% 24% Lower severity and mortality Higher 55% 21% 24% Higher severity and mortality

WHICH IS THE “BEST” RECRUITMENT MANEUVER ?

The concept of PEEP and Recruitment Pelosi P et al. Crit Care. 2010 Mar 9; 14(2): 210 -218 optimal-PEEP recruited vol.

Old and new recruitment maneuvers in ALI/ARDS Pelosi P et al. Crit Care. 2010 Mar 9; 14(2): 210 -218 ICM 2003, 29: 218 45% 23% CCM 2001, 1255: 1260 20%

Recruitment Maneuvers for Acute Lung Injury: A Systematic Review Fan E et al. Am J Respir Crit Care Med Vol 178. pp 1156– 1163, 2008 Hypotension 10% Desaturation 8%

Respiratory and hemodynamic changes during decremental open lung PEEP titration in ARDS Gernoth W, et al Critical Care 2009, 13: R 59; Epub 2009 Apr 17 Before Right ventricular Tei index [%] During RM After 39± 11 42± 10 36± 11

Recruitment maneuver: RAMP versus CPAP pressure profile in a model of ALI Riva M et al Respiratory Physiol & Neurobiol 2009; 169: 62 -68

HOW TO PREDICT “RECRUITERS” AT BEDSIDE ?

Oxygenation and collapsed tissue Borges et al Am J Respir Crit Care Med 174; 268 -278, 2006 Pa. O 2 / Fi. O 2 < 150 at PEEP 5 cm. H 2 O

Assessment of Pulmonary Morphology in ALI Absence of Lower Inflection Point in the P-V Curve Vieira et al. Am J Resp Crit Care Med 1999; 159: 1612 -1623. Overdistension ZEEP PEEP 10 cm. H 2 O PEEP 15 cm. H 2 O

Assessment of Pulmonary Morphology in ALI Significance of Lower Inflection Point in the P-V Curve Vieira et al. Am J Resp Crit Care Med 1999; 159: 1612 -1623. Overdistension ZEEP LIP + 2 cm. H 2 O LIP + 7 cm. H 2 O

OXYGENATION OR MECHANICS TO SET “OPTIMAL” PEEP ?

Is ∆Pa. O 2 is assocated with recruitment ? Malbouisson et al Am J Respit Crit Care Med 2001; 163: 32 -40

Elastance to titrate PEEP in ALI/ARDS Carvalho AR et al. Intensive Care Med. 2008 Dec; 34(12): 2291 -9

The stress index: is it useful to set TV ? Grasso et al Crit Care Med. 2004 Apr; 32(4): 1018 -27 Ranieri et al. Am J Respir Crit Care Med. 1994 Jan; 149(1): 19 -27. Carvalho, Pelosi, Abreu et al Intenisve Care Med 2008 ( on line)

THE IMPORTANCE OF ESOPHAGEAL PRESSURE TO SET “OPTIMAL” PEEP ?

Esophageal Pressure vs SP gradient Pelosi P et al Am J Respir Crit Care Med. 2001 Jul 1; 164(1): 122 -30. PEEP (Intraalveolar P) >= Pes, exp ( Extraalveolar P)

IAP and Respiratory Function in ALI/ARDS Krebs J, Pelosi P, Luecke T. Crit Care 2009 Oct 5; 13(5): R 160

Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury Talmor D et al. N Engl J Med 2008; 359: 2095 -104.

Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury Talmor D et al. N Engl J Med 2008; 359: 2095 -104.

Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury Talmor D et al. N Engl J Med 2008; 359: 2095 -104.

CLINICAL EVIDENCE FROM RCTs: - High vs Low PEEP (7 -10 vs 15 -20 cm. H 2 O) - Neuromuscular blockade (48 hrs) - Prone position - ECMO

Higher vs lower positive end-expiratory pressure in patients with ALI/ARDS : systematic review and meta-analysis Briel M et al. JAMA. 2010; 303(9): 865 -873

Ventilation strategies and outcomes of the ALI/ARDS : a Meta-analysis Ventilation strategies and outcomes of acute respiratory distress syndrome and acute lung injury: a meta-analysis Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P Ann Intern Med 2009; 151: 566 -576 Rescue Therapies and ICU Mortality: Lower vs Higher PEEP at the same VT Patients, n Low PEEP At Low VT High PEEP At Low VT Odds ratio (95% CI) Meade, 2008 983 45/508 20/475 0. 45(0. 26 -0. 78) Mercat, 2008 767 62/382 37/385 0. 55(0. 36 -0. 85) Summary 0. 51(0. 36 -0. 71) P<0. 01; I 2 =0

Ventilation strategies and outcomes of the ALI/ARDS : a Meta-analysis Ventilation strategies and outcomes of acute respiratory distress syndrome and acute lung injury: a meta-analysis Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P Ann Intern Med 2009; 151: 566 -576 • Based on available evidence from a limited number of RCTs routine use of low VT tends to be beneficial in all ALI/ARDS patients (if potential side effects of hypercapnia and respiratory acidosis are not contraindicated) • Higher PEEP strategies during lower VT ventilation did not improve hospital mortality and cannot be recommended in unselected ALI/ARDS patients. • Higher PEEP strategies during lower VT ventilation may be suggested in severe ARDS (Pa. O 2/Fi. O 2 <150 at PEEP 5) and to prevent life threatening hypoxemia

Effect of prone ventilation on mortality (hospital discharge or longest follow-up) Sud S et al. Intensive Care Med. 2010 Apr; 36(4): 585 -99

Prone position reduces mortality in pts with ARF and severe hypoxemia: systematic review & meta-analysis Sud S et al. Intensive Care Med. 2010 Apr; 36(4): 585 -99 Other “effects” of Prone position RR(95%CI) P Reduction in VAP 0. 81 (0. 67 -1. 00) 0. 05 Increase in ET obstruction 1. 58 (1. 24 -2. 01) 0. 01 Increase in pressure ulcers 1. 29 (1. 16 -1. 44) 0. 01 Increase in thoracostomy tube dislodgment 3. 14 (1. 02 -9. 69) 0. 05

Prone position reduces mortality in patients with ARF and severe hypoxemia: systematic review & meta-analysis. Sud S et al. Intensive Care Med. 2010 Apr; 36(4): 585 -99 PP is an effective rescue maneuver for hypoxemia In ALI and moderate ARDS (likely low recruiters) PP does not influence mortality In severe ARDS (Pa. O 2/Fi. O 2 < 150 at PEEP 5 cm. H 2 O), likely higher recruiters, the available data strongly suggest that PP may provide survival benefits (about 10%)

Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial Peek JL et al. Lancet 2009; 374: 1351– 63 • Murray score > 3 • Fi. O 2>90% needed to to maintain Sa. O 2>90% • Respiratory metabolic acidosis p. Ha<7. 2 • Haemodynamically unstable Transfer to a centre with an ECMO-based management protocol

CONCLUSIONS: HOW TO VENTILATE ALI/ARDS PATIENTS

Low VT (6 ml/Kg) and Pplat < 27 -30 cm. H 2 O FOR ALL ALI/ARDS PATIENTS !! YES!

Patient targetted MV strategy in ALI/ARDS ? Rocco PR, Abreu GM, Pelosi P Expert Review 2010 (Epub ahead of print) • If: Pa. O 2/Fi. O 2 > 150 mm. Hg at PEEP 5 Lobar Chest X ray densities - Assisted MV (VT 6 -8 ml/kg; Pplat 27 -30 cm. H 2 O) - PEEP 7 -10 cm. H 2 O, no RM - Supine position • If: Pa. O 2/Fi. O 2 < 150 mm. Hg at PEEP 5 Patchy/Diffuse Chest X ray densities - CMV (VT 6 -8 ml/kg; Pplat 27 -30 cm. H 2 O) - SRM, PEEP 15 -20 cm. H 2 O - Prone position, NMBAs (48 hrs)

VCV or PCV VT=6 ml/kg IBW and PEEP=5 cm. H 2 O Pa. O 2/Fi. O 2 > 150 mm. Hg Pa. O 2/Fi. O 2 ≤ 150 mm. Hg Chest X-ray Patchy or Diffuse densities Chest X-ray Lobar dependent densities CT scan whole lung at PEEP 5 cm. H 20 No Recruitment Maneuver PEEP= 7 -10 cm. H 2 O Patchy or diffuse densities Lobar dependent densities CT scan 2 slices (5 and 45 cm. H 20) at apex, hilus and base No evident decrease of nonaerated tissue Rocco PR, Abreu GM, Pelosi P Expert Review 2010 (Epub ahead of print) PEEP=7 -10 cm. H 2 O Evident decrease of nonaerated tissue Slow and Prolonged Recruitment Maneuver, decremental PEEP trial

How to perform a PEEP trial in most severe ARDS patients ? Pressure (cm. H 2 O) Pelosi P, Abreu GM, Rocco PR Crit Care 2010 (Epub ahead of print) PEEP to achieve the “best” Cst, rs VT 6 ml/Kg IBW 40 35 30 25 20 15 10 5 5 min 1 -2 min 5 -10 min per step Time

How to perform a PEEP trial in most severe ARDS patients ? Pressure (cm. H 2 O) Pelosi P, Abreu GM, Rocco PR Crit Care 2010 (Epub ahead of print) Maximal PEEP to achieve VT 6 ml/Kg IBW, with Pplat, rs = 30 -27 cm. H 2 O 40 35 30 25 20 15 10 5 5 min 1 -2 min 5 -10 min per step Time

“Sometimes, it’s the simple things that work best” (Jeremy Laurance, The Independent, 15 January 2009) Thanks