EXTRACORPOREAL LIFE SUPPORT FOR REFRACTORY IN-HOSPITAL AND OUT-OF-HOSPITAL CARDIAC ARREST: ARE THE OUTCOMES REALLY DIFFERENT? A 10-YEAR EXPERIENCE

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EXTRACORPOREAL LIFE SUPPORT FOR REFRACTORY IN-HOSPITAL AND OUT-OF-HOSPITAL CARDIAC ARREST: ARE THE OUTCOMES REALLY DIFFERENT? A 10-YEAR EXPERIENCE Pozzi M 1, Armoiry X 2, Koffel C 3, Pavlakovic I 3, Lavigne F 3, Schweizer R 3, Fellahi JL 3, Hugon-Vallet E 4, Flagiello M 1, Adamou K 1, Grinberg D 1, Generali T 1, Obadia JF 1 1 Department of Cardiac Surgery, Louis Pradel Cardiologic Hospital, Lyon, France 2 University of Warwick, Warwick Medical School, Division of Health Sciences, Coventry, England 3 Department of Anesthesia and ICU, Louis Pradel Cardiologic Hospital, Lyon, France 4 Department of Cardiology, Louis Pradel Cardiologic Hospital, Lyon, France

CONFLICT OF INTEREST DISCLOSURE CONFLICT OF INTEREST TO DISCLOSE: None

INTRODUCTION Refractory cardiac arrest is defined by the lack of return of spontaneous circulation within a period of at least 30 min of CPR under medical direction in the absence of pre-existing hypothermia Riou et al. Ann Fr Anesth Reanim 2009;28:182-90 IN-HOSPITAL CARDIAC ARREST (IHCA) OUT-OF-HOSPITAL CARDIAC ARREST (OHCA)

INTRODUCTION Extracorporeal CPR (ecpr) should be considered as a rescue therapy for those patients in whom initial ALS measures are unsuccessful and/or to facilitate specific interventions (e.g. coronary angiography and percutaneous coronary intervention (PCI) or pulmonary thrombectomy for massive pulmonary embolism). Soar et al. Resuscitation 2015;95:100-47

INTRODUCTION ECPR Abrams et al. Intensive Care Med 2018 [Epub ahead of print]

BACKGROUND ECLS for IHCA Author [Reference] Patients (n.) Survival CPC 1-2 Massetti Ann Thorac Surg 2005;79:178-83 35 20.0% Chen Lancet 2008;372:554-61 59 23.7% Shin Crit Care Med 2011;39:1-7 85 28.2% Bednarczyk Resuscitation 2014;85:1713-9 22 45.4% Peigh J Thorac Cardiovasc Surg 2015;150:1344-9 23 30.4% Ellouze Artif Organs 2018;42:15-21 43 20.9% Satisfactory Outcomes of ECLS for IHCA Encouraging Homogeneous Survival CPC 1-2: 20-45%

BACKGROUND ECLS for OHCA Author [Reference] Patients (n.) Survival CPC 1-2 Le Guen Crit Care 2011;15:R29 51 3.9% Mégarbane Resuscitation 2011;82:1154-61 47 2.1% Maekawa Crit Care Med 2013;41:1186-96 53 15.1% SAVE-J Study Resuscitation 2014;85:762-8 234 13.7% Pozzi Int J Cardiol 2016;204:70-6 68 4.4% CHEER Trial J Thorac Cardiovasc Surg 2015;150:1344-9 11 45.4% Choi Resuscitation 2016;99:26-32 320 9.1% Rousse Artif Organs 2016;40:904-9 32 3.1% Outcomes of ECLS for OHCA Survival CPC 1-2: Disappointing results

OBJECTIVE To evaluate the results of ECLS support for refractory cardiac arrest and compare the outcomes between IHCA and OHCA patients at a single-centre experience

MATERIALS and METHODS Study design - Patient population Observational analysis of our prospective database Adult patients supported with ECLS for witnessed, refractory IHCA or OHCA 01/01/1997-31/12/2016 449 ECLS 131 (29.2%) ECLS for refractory cardiac arrest 45 (34.4%) IHCA 86 (65.6%) OHCA

MATERIALS and METHODS Study protocol WITNESSED REFRACTORY CARDIAC ARREST OHCA Location IHCA 1) INCLUSION CRITERIA - Absence of absolute contraindications - Age 18-55 years - No-flow time 5 minutes - Low-flow time 75 minutes - E T CO 2 10 mmhg ECLS 1) INCLUSION CRITERIA - Absence of absolute contraindications - Age 18 years - No-flow time 5 minutes - Low-flow time 75 minutes 2) CARDIAC RHYTHM AT EMERGENCY MEDICAL SERVICE TEAM ARRIVAL SHOCKABLE RHYTHM 3) CARDIAC RHYTHM AT ECLS IMPLANTATION SHOCKABLE RHYTHM NON-SHOCKABLE RHYTHM Transfer to the operatory theatre NON-SHOCKABLE RHYTHM ECLS Non heart-beating organs donation criteria Yes Non heart-beating organs donation criteria Yes No Transfer to the operatory theatre No Transfer to the operatory theatre Cardiopulmonary resuscitation discontinuation ABDOMINAL NORMOTHERMIC OXYGENATED RECIRCULATION Cardiopulmonary resuscitation discontinuation ABDOMINAL NORMOTHERMIC OXYGENATED RECIRCULATION

MATERIALS and METHODS Implantation technique

RESULTS Baseline characteristics 131 patients Mean age: 43.2 ± 12.8 (18-76) years Male sex: 71.8% OVERALL IHCA OHCA p-value a Cardiac rhythm at ECLS implantation was not recorded in 5 patients

RESULTS Baseline biological profile IHCA OHCA p-value BUN, mmol/l 11.2±6.9 6.3±2.3 0.001 Bilirubin, µmol/l 30.8±36.2 9.5±6.5 0.034 ASAT, U/l 1353.3±2537.0 821.8±788.8 <0.001 ALAT, U/l 851.3±1462.7 459.5±456.2 <0.001 Low-flow time, min 46.9±19.0 85.3±23.0 <0.001 Lactates 7.1±5.2 16.0±5.5 <0.001 ph 7.32±0.13 7.08±0.21 <0.001

RESULTS Cause of cardiac arrest OVERALL IHCA OHCA p-value

RESULTS Outcomes ECLS for refractory cardiac arrest n = 131 IHCA n=45 OHCA n=86 Cannulation failure n = 2 (4.4%) Death on ECLS n = 34 (79.1%) p=0.479 Death on ECLS n = 69 (84.1%) Cannulation failure n = 4 (4.7%) Unsuccessful weaning n = 1 (2.2%) Successful weaning n = 8 (18.6%) p=0.565 Successful weaning n = 12 (14.6%) Unsuccessful weaning n = 1 (1.2%) Cardiac transplantation n=1 Survival to discharge n = 5 (11.6%) p=0.745 Survival to discharge n = 8 (9.8%) Long-term MCS n=1 Death Survival to discharge CPC 1-2 n = 3 (7.0%) p=1.00 Survival to discharge CPC 1-2 n = 5 (6.1%)

S U R V I V A L Survival CPC 1-2 10-15% Maekawa et al. 49 min. (15.4%) Kagawa et al. 59 min. (10.2%) DISCUSSION ECLS for OHCA Survival CPC 1-2 5-10% Avalli et al. 77 min. (5.5%) C P C 1-2 Pozzi et al. 85 min. (6.1%) Survival CPC 1-2 < 5% Rousse et al. 110 min. (3.1%) Le Guen et al. 120 min. (3.9%) Mégarbane et al. 155 min. (2.1%) < 60 minutes 60-90 minutes LOW-FLOW > 90 minutes

DISCUSSION ECLS for IHCA Lower survival to hospital discharge CPC 1-2 than previous published series Severe impairment of the renal and hepatic functions Heterogeneous cardiac arrest etiologies Underlying long-standing illness Drug intoxication (4.4%) Acute coronary syndrome (15.6%) Cardiomyopathies (15.6%) PCS with unclear cause (13.3%)

DISCUSSION ECLS for IHCA vs. OHCA Author [Reference] Survival CPC 1-2 p-value IHCA vs. OHCA Kagawa Resuscitation 2010;81:968-73 26.3% vs. 10.2% 0.07 Wang Resuscitation 2014;85:1219-24 25.1% vs. 25.8% >0.05 Dennis Int J Cardiol 2017;231:131-6 69% vs. 31% 0.87 Ellouze Artif Organs 2018;42:15-21 20.9% vs. 27.2% 0.76 Avalli Resuscitation 2012;83:579-83 45.8% vs. 5.5% 0.005

CONCLUSION ECLS could be considered an ultimate solution in refractory cardiac arrest patients who failed conventional cardiopulmonary resuscitation IHCA and OHCA patients experienced the same survival to hospital discharge with good neurological outcome after ECLS support The results of ECLS for refractory OHCA are mainly limited by the low-flow duration In the setting of refractory IHCA, a better selection of patients is mandatory to improve outcomes and avoid futile support