ECMO for Refractory Septic Shock Prof. Alain Combes

ECMO for Refractory Septic Shock Prof. Alain Combes Service de Réanimation ican, Institute of Cardiometabolism and Nutrition Hôpital Pitié-Salpêtrière, AP-HP, Paris Université Pierre et Marie Curie, Paris 6 www.reamedpitie.com alain.combes@psl.aphp.fr

Conflict of Interest Principal Investigator: EOLIA trial VV ECMO in ARDS NCT01470703 Sponsored by MAQUET, Getinge Group Received honoraria from MAQUET, Baxter, ALung

Reversible myocardial dysfunction during sepsis Parker MM, Ann Intern Med 1984

Reversible myocardial dysfunction during sepsis Parrillo et al., JCI 1985

Reversible myocardial dysfunction during sepsis Circulating Myocardial Depressant Substance (MDS) Endotoxine? TNF-α? IL-1β? IL-6? NO? Parrillo et al., JCI 1985

Reversible myocardial dysfunction during sepsis Half of the nonsurvivors developed a decreasing cardiac index, with no change in heart rate or ejection fraction, (..) and become those nonsurvivors who die of a cardiogenic shock-like state. Parker MM, J Crit Care 1989

Continuum in several consecutive phases Early phase: Low-flow state related to hypovolemia Volume expansion increases cardiac output and improves patient s perfusion Second phase: Hyperdynamic state High cardiac output Low systemic vascular resistance Third phase: Decreased cardiac output Increased systemic vascular resistance Progressive metabolic acidosis

Understanding cardiac failure in sepsis Antoine Vieillard-Baron M. Cecconi ICM, 2014

Reversible myocardial dysfunction during sepsis Role of catecholamines? Reversible Left Ventricular Dysfunction Takotsubo Cardiomyopathy Related to Catecholamine Cardiotoxicity Akashi, Journal of Electrocardiology 2002

ECMO & Sepsis Pediatric data

ECMO & Sepsis Pediatric data Publication Beca, Pediatrics 94 Goldman, Lancet 1997 Luyt, Acta Paediatr 2004 MacLaren, Pediatr Crit Care Med 2007 MacLaren, Pediatr Crit Care Med 2011 MacLaren, Anaesth Intensive Care 2004 Vohra, Ann Thorac Surg 2009 Firstenberg, Am Surg 2010 Age Nb of patients, context ECMO type Pre-ECMO myocardial dysfunction Survival, n (%) ECMO duration, median Child 9, septic shock PVA? 5 (55%) 5,7 (2,4-9,6) Child 12, meningococcemia 10 PVA, 2 VV? 8 (66%) 3,2 (0,8-10,9) Child 6, meningococcemia PVA? 1 (17%) 4,3 (3-7,2)? Child 45, septic shock PVA (76%) & central (24%)? 21 (47%) 3,5 (1,3-5,6) ICU stay median 32 (17-38) 12 (7-35) 9 (3,5-14) Child 23, septic shock Central VA? 17 (74)% 3,9 (1,8-4,9) 9,7 (7,8-15,7) Adult 1, bacteriemia MSSA PVA + 1/1 7 25 Adult Adult 1, septic shock after cardiac surgery 2, necrotizing dermatitis PVA + 1/1 3 26 PVA + 2/2 4 (3-5) 51 (47-55), hospital stay

McLaren, Ped Crit Care Med 07 45 pts (17 M/ 28 F) Mean age 2,5-12 Refractory septic shock BC+91%, MOF>3 All on catecholamine Dopa 12 μg/kg/min (5-20), n=32 Dobu 17,3μg/kg/min (10-25), n=14 Norepi 1 μg/kg/min (0,02-4), n=33 Epi 1,85 μg/kg/min (0,05-10), n=33 18 (40%) CPR-ECMO

McLaren, Ped Crit Care Med 07 ECMO support 34 (76%) peripheral VA-ECMO 22 (6,5-38) hours after shock onset Durations, days ECMO: 3.5(1-5) ICU: 9(3.5-14) Hospital 16(3.6-36) 21/45 (47%) SURVIVAL

McLaren, Ped Crit Care Med 07 Long-term Outcomes 5 years (0.3-14) No death Disability 13 (62%) no disability 5 (24%) minor disability 3 (14%) moderate None had severe disability

Guidelines Crit Care Med 09

ECMO and Septic Shock Data in Adult Patients

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Venoarterial extracorporeal membrane oxygenation support for refractory cardiovascular dysfunction during severe bacterial septic shock Venoarterial ECMO n=222 Venoarterial ECMO n=222 Bréchot et al, Crit Care Med, 2013 Refractory septic shock n = 14 Refractory septic shock

14 septic shock patients 7 M/ 7 F, 45 years (28-66) 6 Immunocompromised 12 CA, 2 nosocomial 11/14 severe bacterial pneumonia 8/14 ECMO via Mobile team

6/14 Streptococcus pneumonia 2 Legionella pneumophila 2 Staphylococcus aureus

Venoarterial extracorporeal membrane oxygenation support for refractory cardiovascular dysfunction during severe bacterial septic shock Bréchot et al, Crit Care Med, 2013 Patients n=14 Value Age, yr, median (range) 45 (28 66) ECMO implantation by UMAC, n 8 Shock onset-to-ecmo interval, hrs, median 24 (3 108) Femoral ECMO, n 14 Left ventricular ejection fraction (%), median 16 (10 30) Catecholamine dose, g/kg/min, median Dobutamine, n= 4 17.5 (6 30) Norepinephrine, n= 9 2.0 (0.5 4.9) Epinephrine, n=13 1.25 (0.1 4.2) Pre-ECMO mean arterial pressure, mmhg, median 72 (53-105) Pre-ECMO central venous pressure, mmhg, median 18 (10-35) Pre-ECMO cardiac index, L/min/m 2, median 1.3 (0.7 2.2) Pre-ECMO systemic resistance vascular index, 3162 (2047-7685) SOFA score, median 18 (8 21) ph, median 7.16 (6.68 7.39) Blood lactate, median 9 (2 17) N-Terminal pro-brain natriuretic peptide, pg/ml 29,788 (1,843 35,000)

Venoarterial extracorporeal membrane oxygenation support for refractory cardiovascular dysfunction during severe bacterial septic shock Bréchot et al, Crit Care Med, 2013 Patients n=14 Value Age, yr, median (range) 45 (28 66) ECMO implantation by UMAC, n 8 Shock onset-to-ecmo interval, Very hrs, median specific 24 (3 108) Femoral ECMO, n 14 Left ventricular ejection fraction (%), median 16 (10 30) hemodynamic profile Catecholamine dose, g/kg/min, median Dobutamine, n= 4 17.5 (6 30) Norepinephrine, n= 9 2.0 (0.5 4.9) Low LVEF Epinephrine, n=13 1.25 (0.1 4.2) Pre-ECMO mean arterial pressure, mmhg, median 72 (53-105) Pre-ECMO central venous pressure, mmhg, median 18 (10-35) Low Pre-ECMO cardiac index, L/min/m 2 CI, median 1.3 (0.7 2.2) Pre-ECMO systemic resistance vascular index, 3162 (2047-7685) SOFA score, median 18 (8 21) High vascular resistance ph, median 7.16 (6.68 7.39) Blood lactate, median 9 (2 17) N-Terminal pro-brain natriuretic peptide, pg/ml 29,788 (1,843 35,000)

Peripheral VA-ECMO cannulation

Peripheral cannulation

The ECMO circuit: Centrifugal pump Electrical Centrifugal pump 0->4000 RPM Can deliver flows up to 8 L/min Very reliable Up to 21 days

The ECMO circuit: Central Unit Controller Flow alarms

The ECMO circuit: Membrane Oxygenator Hollow fiber membrane oxygenator Polymethylpentene Heparin-coated High performance CO2 elimination Blood oxygenation Low pressure drop Long duration 15-21 d

The case of a 54 yrs old patient with severe CA pneumonia Had VA-ECMO for septic shock and evolution towards cardiogenic shock

At ECMO initiation

On Day one

On day 5

On day 7

Peripheral VA ECMO is not indicated for ARF because Flow competition in the aorta Heart vs. ECMO pump If pulmonary function is impaired The Harlequin syndrome Blue head : deoxygenated blood directed to the upper part of the body Red legs : hyperoxygenated blood in the lower part of the body Not possible to rest the lungs Vt, Pplat and FiO2 cannot be reduced

Long-term HRQL

Conclusion Cardiogenic shock Rare but life-threatening complication of severe septic shock Low CI, Low LVEF, High Catecho, High SVR VA-ECMO to rescue these dying patients 70% survival if treated early Rapid recovery of LV function Severe ARDS may require switch to VV-ECMO Good long-term HRQL Network of hospitals, Mobile ECMO team+++