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Veno-Arterial Extracorporeal Membrane Oxygenation for Post- Cardiotomy Shock.

Analysis of the Extra-Corporeal Life Support Organization (ELSO) Registry.

- Veno-Arterial ECMO for Post-cardiotomy Shock - Supplementary material:

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Supplementary Table 1. Endpoints list and definitions.

ECLS code description

101 Mechanical: Oxygenator failure 102 Mechanical: Raceway rupture 103 Mechanical: Other tubing rupture 104 Mechanical: Pump Failure

105 Mechanical: Heat exchanger malfunction 114 Mechanical: Clots: hemofilter

116 Mechanical: Clots: Circuit Component Clots 121 Mechanical: Air in circuit

122 Mechanical: Cracks in pigtail connectors 131 Mechanical: Cannula problems

132 Mechanical: Circuit change

133 Mechanical: Clots and Air Emboli

134 Mechanical: Thrombosis/Clots: circuit component 201 Hemorrhagic: GI hemorrhage

203 Hemorrhagic: Surgical site bleeding

222 Hemorrhagic: Peripheral cannulation site bleeding 223 Hemorrhagic: Mediastinal cannulation site bleeding 301 Neurologic: Brain death

311 Neurologic: Seizures: clinically determined 312 Neurologic: Seizures Confirmed by EEG 321 Neurologic: CNS Infarction (US or CT or MRI)

323 Neurologic: Intraventricular CNS hemorrhage (US or CT or MRI)

324 Neurologic: Intra/extra parenchymal CNS Hemorrhage (US or CT or MRI)

325 Neurologic: CNS diffuse ischemia (CT/MRI)

326 Neurologic: Neurosurgical intervention performed 401 Renal: Creatinine 1.5 - 3.0

402 Renal: Creatinine > 3.0

415 Renal: Renal Replacement Therapy Required 502 Cardiovascular: CPR required

504 Cardiovascular: Cardiac arrhythmia 541 Cardiovascular: Tamponade (blood) 544 Cardiovascular: Tamponade (not blood)

601 Pulmonary: Pneumothorax requiring treatment 602 Pulmonary: Pulmonary hemorrhage

711 Infectious: WBC < 1,500 821 Metabolic: Hyperbilirubinemia 822 Metabolic: Moderate hemolysis 823 Metabolic: Severe hemolysis

901 Limb: Ischemia

902 Limb: Compartment Syndrome

903 Limb: Fasciotomy

904 Limb: Amputation

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ECLS, extra corporeal life support; GI, gastrointestinal; EEG,

electroencephalogram; CNS, central nervous system; US, ultrasound; CT, computed tomography; MRI, magnetic resonance imaging; CPR,

cardiopulmonary resuscitation;

Supplementary Table 2. Mortality rates across years of experience.

Ye ar

Crude observed hospital death

rate

Poisson regression: pre-ECMO variables- adjusted predicted hospital death rate

(95% CIs) 20

10 0.59 0.60 (0.50-0.70)

20

11 0.64 0.63 (0.56-0.72)

20

12 0.60 0.60 (0.54-0.67)

20

13 0.60 0.60 (0.54-0.67)

20

14 0.55 0.55 (0.50-0.60)

20

15 0.55 0.54 (0.50-0.58)

20

16 0.59 0.58 (0.53-0.63)

20

17 0.60 0.59 (0.55-0.63)

20

18 0.57 0.56 (0.52-0.60)

ECMO, extracorporeal membrane oxygenation; CI, confidence interval.

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Supplementary Table 3. Pre-ECMO information and on-ECMO support details.

Variable Total

(n=7,185)

Hospital survival (n=2,997)

Hospital death (n=4,188)

p- valu e Pre-ECMO cardiac

arrest 1,707

(23.8) 651 (38.1) 1,056 (61.9) <0.0 01 Pre-ECMO suport

IABP 2,225

(31.0) 904 (40.6) 1,321 (59.4) <0.0 01

CPB 3,442

(47.9) 1,381 (40.1) 2,061 (59.9) <0.0 01 Nitric oxide 818 (11.4) 355 (43.4) 463 (56.6) <0.0 01 Pacemaker 770 (10.7) 275 (35.7) 495 (64.3) <0.0 01

Inotropes 3,253

(45.3) 1,314 (40.4) 1,939 (59.6) <0.0 01 Hand-bagging 435 (6.1) 162 (37.2) 273 (62.8) <0.0 01 Pre-ECMO arterial

blood gases

pH 7.29 ± 0.14 7.31 ± 0.13 7.27 ± 0.14 <0.0 01

PCO2 (mmHg) 42.8 ±

20.73 42.24 ±

20.08 43.2 ±

21.19 0.053 Oxygen partial

pressure (mmHg) 172.06 ±

136.86 175.55 ±

138.51 169.51 ±

135.59 0.065 Bicarbonate levels

mEq/L 20.39 ±

5.79 21.15 ±

5.62 19.84 ±

5.84 <0.0 01

SaO2 (%) 92.82 ±

12.14 93.58 ±

10.69 92.27 ±

13.08 <0.0 01 Ventilator settings

(pre-ECMO)

Respiratory rate

(/min) 16.3 ± 6.3 16.0 ± 6.1 16.6 ± 6.5 <0.0 01 FiO2 (%) 81.5 ± 23.6 80.7 ± 24.0 82.1 ± 23.2 0.013 PIP (cm H2O) 25.8 ± 8.2 24.8 ± 8.0 26.5 ± 8.3 <0.0 01 PEEP (cm H2O) 7.2 ± 4.2 7.0 ± 3.6 7.3 ± 4.6 0.003 Mean AP 15.7 ± 11.0 15.2 ± 10.8 16.0 ± 11.2 0.002 Ventilator settings (24

hours)

Respiratory rate

(/min) 12.7 ± 4.6 12.3 ± 3.9 12.9 ± 5.0 <0.0 01 FiO2 (%) 50.2 ± 19.1 48.8 ± 17.8 51.3 ± 20.0 <0.0 01 PIP (cm H2O) 23.8 ± 6.4 22.7 ± 5.6 24.6 ± 6.9 <0.0

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01 PEEP (cm H2O) 7.6 ± 3.3 7.5 ± 3.0 7.7 ± 3.5 0.011 Mean AP 13.9 ± 10.7 13.4 ± 10.2 14.2 ± 11.1 0.002 Pre-ECMO

hemodynamics

SBP (mmHg) 81.9 ± 26.8 83.8 ± 24.9 80.4 ± 28.0 <0.0 01 DBP (mmHg) 50.2 ± 17.3 52.1 ± 16.1 48.8 ± 18.0 <0.0 01 Mean arterial

pressure (mmHg) 60.4 ± 18.7 62.8 ± 17.2 58.6 ± 19.6 <0.0 01 Venous oxygen

saturation (%) 60.5 ± 17.5 60.4 ± 17.3 60.5 ± 17.7 0.812 Hours on ECMO

Mean (hours) 144.7 ±

148.4 136.5 ±

124.1 148.2 ±

163.4 0.001

0-41 1,308

(18.2) 371 (28.4) 937 (71.6) <0.0 01

42-88 1,626

(22.6) 778 (47.8) 848 (52.2) 0.014

89-161 2,131

(29.7) 1,046 (49.1) 1,085 (50.9) 0.232

>161 2,120

(29.5) 802 (37.8) 1,318 (62.2) <0.0 01 Cannulation

Peripheral 3,888

(54.1) 1,787 (46.0) 2,101 (54.0) <0.0

Central 3,297 01

(45.9) 1,210 (36.7) 2,087 (63.3)

ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; CPB, cardiopulmonary bypass; LVAD, left ventricle assist device;

PCO2, partial pressure of carbon dioxide; SaO2, oxygen saturation; FiO2, fraction of inspired oxygen; PiP, peak inspiratory pressure; PEEP, positive end-expiratory pressure; AP, airway pressure; SBP, systolic blood pressure;

DBP, diastolic blood pressure.

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Supplementary Table 4. Hospital complications during ECMO.

Complications^a Total (n=7,185

)

Hospital survival (n=2,997

)

Hospital death (n=4,188

)

p-value Limb complications^b 456 (6.3) 129 (28.3) 327 (71.7) <0.001 Ischemia 312 (4.3) 88 (28.2) 224 (71.8) <0.001 Limb compartment

syndrome 106 (1.5) 24 (22.6) 82 (77.4) <0.001 Fasciotomy^c 143 (2.0) 38 (26.6) 105 (73.4) <0.001 Amputation^c 43 (0.6) 22 (51.2) 21 (48.8) 0.209 Hematologic/bleeding^b 3,052

(42.5) 1,056

(34.6) 1,996

(65.4) <0.001 DIC^c 200 (2.8) 39 (19.5) 161 (80.5) <0.001 Hemolysis^c 290 (4.0) 85 (29.3) 205 (70.7) <0.001 Surgical site

bleeding 1,897

(26.4) 637 (33.6) 1,260

(66.4) <0.001 Cannulation site

bleeding 1,130

(15.7) 427 (37.8) 703 (62.2) 0.004 Mediastinal

cannulation bleeding 98 (1.4) 32 (32.7) 66 (67.3) 0.068 Cardiac tamponade^c 547 (7.6) 194 (35.5) 353 (64.5) 0.002 GI bleeding^c 298 (4.1) 72 (24.2) 226 (75.8) <0.001 Neurologic^b 654 (9.1) 115 (17.6) 539 (82.4) <0.001

Diffuse ischemia^c confirmed by

US/CT/MRI 7 (0.1) 1 (14.3) 6 (85.7) 0.157

Hemorrhage^c confirmed by

US/CT/MRI 122 (1.7) 14 (11.5) 108 (88.5) <0.001 Infarction confirmed

by US/CT/MRI 326 (4.5) 79 (24.2) 247 (75.8) <0.001 Intra/extra

parenchymal Hemorrhage^c confirmed by

US/CT/MRI 19 (0.3) 19 (100.0) 0.005

Intraventricular hemorrhage^c confirmed by

US/CT/MRI 7 (0.1) 7 (100.0) 0.069

Neurosurgical intervention

performed 1 (0.0) 1 (100.0) 0.635

Seizures: confirmed

by EEG 32 (0.4) 9 (28.1) 23 (71.9) 0.121

Seizures: clinically

determined 78 (1.1) 22 (28.2) 56 (71.8) 0.016

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Brain death^c 181 (2.5) 181

(100.0) 0.022 Sepsis^b 871 (12.1) 332 (38.1) 539 (61.9) 0.057

Culture-proven

infection^c 771 (10.7) 297 (38.5) 474 (61.5) <0.001 Kidney failure^b 3,510

(48.9) 1,126

(32.1) 2,384

(67.9) <0.001

sCr 1.5-3 1,591

(22.1) 576 (36.2) 1,015

(63.8) <0.001 sCr >3 715 (10.0) 203 (28.4) 512 (71.6) <0.001

CRRT^c 2,593

(36.1) 724 (27.9) 1,869

(72.1) <0.001 Cardiovascular^b 3,894

(54.2) 1,488

(38.2) 2,406

(61.8) <0.001 Cardiac arrhythmia 1,141

(15.9) 384 (33.7) 757 (66.3) <0.001 CPR required^c 206 (2.9) 38 (18.4) 168 (81.6) 0.005 Hypertension

requiring

vasodilators 222 (3.1) 113 (50.9) 109 (49.1) <0.001 Inotropes on ECMO 3,196

(44.5) 1,213

(38.0) 1,983

(62.0) <0.001

Metabolic^b 1,934

(26.9) 636 (32.9) 1,298

(67.1) <0.001 Glucose < 40 104 (1.4) 6 (5.8) 98 (94.2) 0.143 Glucose > 240 758 (10.5) 335 (44.2) 423 (55.8) <0.001 Hyperbilirubinemia 941 (13.1) 248 (26.4) 693 (73.6) <0.001 pH < 7.20 620 (8.6) 108 (17.4) 512 (82.6) 0.001 pH > 7.60 208 (2.9) 111 (53.4) 97 (46.6) <0.001 Pulmonary 271 (3.8) 85 (31.4) 186 (68.6) <0.001 Pneumothorax 91 (1.3) 34 (37.4) 57 (62.6) 0.397 Pulmonary

hemorrhage^c 187 (2.6) 54 (28.9) 133 (71.1) <0.001

a Complications with their pertinent definitions are listed in the Supplementary Table 1

b Total n of patients with complications per group

c Declared as major complications

DIC, disseminated intravascular coagulation; GI, gastrointestinal; US, ultrasound; CT, computed tomography; MRI, magnetic resonance imaging;

EEG, electroencephalogram; sCr, serum creatinine; CRRT, continuous renal replacement therapy; CPR, cardiopulmonary resuscitation; ECMO,

extracorporeal membrane oxygenation.

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Supplementary Table 5. Multivariable predictors of death (binary logistic regression). Pre-ECMO and on-ECMO variables.

Variable Coeffici

ent SE OR Lower

CI Upper

CI P-value pH (24) -3.939 0.518 0.019 0.007 0.054 <0.001 PO2 (24) 0.002 0.000 1.002 1.002 1.003 <0.001 HCO3 (24) -0.045 0.009 0.956 0.939 0.973 <0.001 Hypertensi

on 0.319 0.101 1.375 1.129 1.675 0.002

CABG 0.309 0.083 1.362 1.157 1.603 <0.001

Heart transplanta

tion -0.548 0.103 0.578 0.472 0.707 <0.001 Thoracic

aorta

aneurysm 0.728 0.317 2.071 1.113 3.855 0.022

PPI 0.287 0.110 1.332 1.074 1.653 0.009

CRRT 0.446 0.139 1.562 1.190 2.051 0.001

iv.

bicarbonat

es 0.290 0.097 1.336 1.106 1.615 0.003

iv.

dobutamin

e -0.176 0.086 0.838 0.708 0.993 0.041

iv.

nitroprussid

e -0.763 0.331 0.466 0.244 0.892 0.021

Peripheral

cannulation -0.351 0.127 0.704 0.549 0.904 0.006 SE, standard error; OR, odds ratio; CI, confidence interval; CABG, coronary artery bypass grafting; PPI, permanent pacemaker implantation; CRRT, continuous renal replacement therapy

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Supplementary Table 6. Multivariable predictors of death (binary logistic regression). Pre-ECMO, on-ECMO variables and on-ECMO complications.

Variable Coeffici

CI Upper

CI P-value pH <7.20 0.611 0.133 1.843 1.419 2.394 <0.001 HCO3 (24) -0.058 0.006 0.944 0.932 0.956 <0.001

CABG 0.241 0.072 1.273 1.106 1.465 0.001

Heart

transplantati

on -0.452 0.090 0.636 0.533 0.760 <0.001

Thoracic aorta

aneurysm 0.314 0.134 1.370 1.052 1.783 0.019

CRRT 0.831 0.064 2.296 2.027 2.601 0.000

iv.

bicarbonates 0.240 0.083 1.272 1.080 1.498 0.004 Limb:

Ischemia 0.471 0.147 1.601 1.200 2.136 0.001

Hemorrhagic:

Disseminated intravascular coagulation (DIC)

0.922 0.232 2.515 1.596 3.964 <0.001

Hemorrhagic:

Surgical site

bleeding 0.233 0.068 1.262 1.105 1.443 0.001

Hemorrhagic:

GI

hemorrhage 0.609 0.167 1.838 1.324 2.551 <0.001 Neurologic:

CNS

hemorrhage by US/CT

1.309 0.334 3.702 1.925 7.117 <0.001 Neurologic:

CNS

Infarction (US or CT or MRI)

0.659 0.155 1.933 1.426 2.619 <0.001 Cardiovascul

ar: Cardiac

arrhythmia 0.167 0.083 1.182 1.005 1.391 0.043 Metabolic:

Glucose < 40 1.987 0.614 7.297 2.191 24.305 0.001 Metabolic:

Hyperbilirubi

nemia 0.460 0.096 1.585 1.314 1.911 <0.001 Peripheral

cannulation -0.356 0.129 0.700 0.544 0.903 0.001

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SE, standard error; OR, odds ratio; CI, confidence interval; CABG, coronary artery bypass grafting; CRRT, continuous renal replacement therapy; DIC, disseminated intravascular coagulation; GI, gastrointestinal; CNS, central nervous system; US, ultrasound; CT, computed tomography; MRI,

magnetic resonance imaging;

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Supplementary Table 7. Multivariable predictors of weaning from ECMO (binary logistic regression). Pre-ECMO variables.

Variable Coeffici

CI Upper

CI P-value

Age -0.021 0.003 0.979 0.974 0.985 <0.001

Initial PCO2 0.014 0.003 1.014 1.007 1.021 <0.001 Heart

transplanta

tion 0.438 0.132 1.549 1.195 2.008 0.001

SE, standard error; OR, odds ratio; CI, confidence interval.

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Supplementary Table 8. Multivariable predictors of weaning from ECMO (binary logistic regression). Pre-ECMO and on-ECMO variables.

Variable Coeffici

CI Upper

CI P-value

Age -0.020 0.003 0.980 0.975 0.986 <0.001

Initial pH 1.744 0.330 5.720 2.993 10.931 <0.001 Initial PCO2 0.007 0.003 1.007 1.001 1.012 0.013

pH (24) 1.013 0.378 2.754 1.313 5.776 0.007

PO2 (24) -0.003 0.000 0.997 0.996 0.998 <0.001 HCO3 (24) 0.044 0.011 1.045 1.021 1.068 <0.001

PIP -0.023 0.005 0.977 0.967 0.987 <0.001

Heart transplanta

tion 0.311 0.123 1.365 1.073 1.735 0.011

PPI -0.271 0.119 0.763 0.603 0.964 0.023

iv.

bicarbonat

es -0.257 0.100 0.773 0.635 0.942 0.011

SE, standard error; OR, odds ratio; CI, confidence interval; PIP, peak inspiratory volume; PPI, permanent pacemaker implantation.

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Supplementary Table 9. Multivariable predictors of weaning from ECMO (binary logistic regression). Pre-ECMO, on-ECMO variables and on-ECMO complications.

Variable Coeffici

CI Upper

CI P-value

Age -0.022 0.002 0.978 0.974 0.982 <0.001

Weight -0.004 0.001 0.996 0.994 0.999 0.009

pH < 7.20 -0.666 0.136 0.514 0.394 0.670 <0.001 PO2 (24) -0.002 0.000 0.998 0.997 0.998 <0.001 HCO3 (24) 0.059 0.007 1.060 1.047 1.074 <0.001

CABG -0.199 0.073 0.820 0.710 0.946 0.007

Heart

transplantati

on 0.555 0.091 1.743 1.458 2.084 <0.001

CRRT -0.822 0.065 0.440 0.387 0.499 <0.001 iv. bicarbonates -0.277 0.084 0.758 0.643 0.895 0.001 iv.

nitroprusside 0.640 0.290 1.897 1.075 3.347 0.027 Limb:

Ischemia -0.502 0.149 0.605 0.452 0.811 0.001 Hemorrhagic:

Disseminated intravascular coagulation (DIC)

-0.828 0.233 0.437 0.277 0.690 <0.001

Hemorrhagic:

Surgical site

bleeding -0.186 0.069 0.830 0.725 0.951 0.007 Hemorrhagic:

GI

hemorrhage -0.583 0.169 0.558 0.401 0.778 0.001 Neurologic:

CNS

hemorrhage by US/CT

-1.395 0.332 0.248 0.129 0.476 <0.001 Neurologic:

CNS

Infarction (US or CT or MRI)

-0.730 0.157 0.482 0.355 0.656 <0.001 Metabolic:

Glucose < 40 -2.080 0.614 0.125 0.038 0.416 0.001 Metabolic:

Hyperbilirubi

nemia -0.471 0.097 0.624 0.517 0.755 <0.001 Peripheral

cannulation 0.397 0.061 1.488 1.320 1.676 <0.001

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SE, standard error; OR, odds ratio; CI, confidence interval; CABG, coronary artery bypass grafting; CRRT, continuous renal replacement therapy; DIC, disseminated intravascular coagulation; GI, gastrointestinal; CNS, central nervous system; US, ultrasound; CT, computed tomography; MRI,

magnetic resonance imaging;

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Supplementary Table 10. Baseline characteristics of 1:1 PS-matched patients for comparison peripheral vs central cannulation. Adjustment for pre-ECMO variables.

Variable

Central cannulati

on (n=931)

Peripher al cannulati

on (n=931)

P-value Mean age, years

18-38 111 (11.9) 119 (12.8) 0.573

39-52 186 (20.0) 180 (19.3) 0.726

53-62 170 (18.3) 133 (14.3) 0.020

63-70 231 (24.8) 290 (31.1) 0.002

≥71 233 (25.0) 209 (22.4) 0.191

Gender

Male 635 (68.2) 658 (70.7) 0.247

Female 296 (31.8) 273 (29.3) Race

White 722 (77.6) 693 (74.4) 0.116

Black 64 (6.9) 94 (10.1) 0.013

Asian 40 (4.3) 56 (6.0) 0.094

Hispanic 56 (6.0) 59 (6.3) 0.773

Other 49 (5.3) 29 (3.1) 0.021

Diabetes melitus 89 (9.6) 95 (10.2) 0.641 Uncontrolled

hypertension 100 (10.7) 85 (9.1) 0.245 Dyslipidemia 88 (9.5) 79 (8.5) 0.465

COPD 34 (3.7) 32 (3.4) 0.802

Obstructive sleep

apnea 18 (1.9) 16 (1.7) 0.729

Asthma 18 (1.9) 16 (1.7) 0.729

Chronic kidney disease 41 (4.4) 55 (5.9) 0.143 Atrial fibrillation 74 (7.9) 77 (8.3) 0.799 Acute coronary

syndrome 104 (11.2) 134 (14.4) 0.037 Unstable angina 35 (3.8) 50 (5.4) 0.096

STEMI* 16 (1.7) 25 (2.7) 0.156

Cardiomyopathy 50 (5.4) 53 (5.7) 0.761 Heart failure 86 (9.2) 87 (9.3) 0.936 Pulmonary

hypertension 19 (2.0) 24 (2.6) 0.441 Pulmonary embolism 9 (1.0) 8 (0.9) 0.808 Bacterial endocarditis 56 (6.0) 53 (5.7) 0.767 Cancer diagnosis 7 (0.8) 7 (0.8) 1.000

*Last 90 days

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COPD, chronic obstructive pulmonary disease; STEMI, ST-segment elevation myocardial infarction.

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Supplementary Table 11. Pre-ECMO information and on-ECMO support details of 1:1 PS-matched patients for comparison peripheral vs central cannulation. Adjustment for pre-ECMO variables.

Variable Central

cannulation (n=931)

Peripheral cannulation

(n=931)

P- value Pre-ECMO cardiac arrest 131 (14.1) 154 (16.5) 0.139 Pre-ECMO suport

IABP 247 (26.5) 243 (26.1) 0.833

Hand-bagging 58 (6.2) 64 (6.9) 0.574

Pre-ECMO arterial blood gases

pH 7.31 ± 0.12 7.31 ± 0.12 1.000

PCO2 (mmHg) 40.0 ± 12.7 40.3 ± 13.3 0.619 Oxygen partial

pressure (mmHg) 184.7 ± 141.4 179.5 ± 141.4 0.428 Bicarbonate levels

mEq/L 21.0 ± 8.4 21.0 ± 8.5 1.000

SaO2 (%) 93.4 ± 10.5 93.6 ± 9.5 0.666

Ventilator settings (pre- ECMO)

Respiratory rate (/min) 16.0 ± 4.4 16.2 ± 4.8 0.349

FiO2 (%) 80.5 ± 25.6 80.3 ± 25.8 0.867

PIP (cm H2O) 25.0 ± 8.5 25.4 ± 8.5 0.310 PEEP (cm H2O) 7.3 ± 4.3 7.3 ± 4.2 1.000

Mean AP 14.7 ± 8.2 15.2 ± 8.8 0.205

ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump;

PCO2, partial pressure of carbon dioxide; SaO2, oxygen saturation; FiO2, fraction of inspired oxygen; PiP, peak inspiratory pressure; PEEP, positive end-expiratory pressure; AP, airway pressure.

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Supplementary Table 12. Propensity scores of 1:1 PS-matched patients for comparison peripheral vs central cannulation. Adjustment for pre- ECMO variables.

Variable Wald/

χ² Scor

e Odds

ratio 95% Confidence

interval P value

Initial pH 56.188 -

3.793 0.023 0.008 to 0.061 <0.001 Initial PO2 56.577 0.002 1.002 1.002 to 1.003 <0.001 Initial HCO3 28.784 -

0.047 0.954 0.938 to 0.971 <0.001 Hypertension 11.887 0.349 1.418 1.163 to 1.730 0.001

CKD 3.951 0.272 1.313 1.004 to 1.717 0.047

Heart

transplantation 28.773 -

0.542 0.582 0.477 to 0.709 <0.001 CABG 12.796 0.293 1.340 1.141 to 1.573 <0.001 Thoracic aorta

aneurysm 5.276 0.706 2.025 1.109 to 3.698 0.022 CKD, chronic kidney disease; CABG, coronary artery bypass grafting.

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Supplementary Table 13. Subgroup analysis of 1:1 PS-matched patients for comparison peripheral vs central cannulation. Adjustment for pre-ECMO variables.

Variable Odds Ratio

(95%CIs) P-value

Overall hospital death 0.48 (0.40-0.58) <0.001

Overall weaning from ECMO* 2.07 (1.72-2.48) <0.001

Demographic

Diabetes 0.98 (0.65-1.47) 0.917

Uncontrolled hypertension 0.63 (0.44-0.90) 0.011

Chronic kidney disease 0.56 (0.34-0.93) 0.026

Atrial fibrillation 0.61 (0.40-0.93) 0.021

Cardiomyopathy 0.68 (0.41-1.12) 0.129

Heart failure 0.45 (0.29-0.70) 0.000

Pulmonary hypertension 0.50 (0.21-1.16) 0.107

Pre-ECMO support

Pre-ECLS cardiac arrest 0.90 (0.66-1.22) 0.481

Intra-aortic balloon pump 0.66 (0.51-0.86) 0.002

Hand-bagging 1.93 (1.38-2.69) <0.001

Surgery

CABG 0.70 (0.54-0.91) 0.008

Valve 0.78 (0.60-1.00) 0.049

CABG+valve 1.53 (0.97-2.41) 0.070

Thoracic aorta aneurysm 2.02 (0.86-4.73) 0.107

Aortic dissection 0.03 (0.00-0.50) 0.014

Heart transplantation 0.49 (0.30-0.80) 0.005

VAD 0.91 (0.67-1.23) 0.538

0.01 0.1 1 10

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 Favours peripheral cannulation Favours central cannulation  *interchanged arrow indicators

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Supplementary Figure 1. Trends in average age and major

complications during ECMO: cardiopulmonary resuscitation, cardiac tamponade, disseminated intravascular coagulation, gastrointestinal bleeding, mediastinal bleeding, culture-proven sepsis, limb amputation or fasciotomy for ischemia, pump or oxygenator failure, severe hemolysis, brain death, diffuse brain ischemia or hemorrhage, pulmonary

hemorrhage and renal replacement therapy. ECMO, extracorporeal membrane oxygenation; SD, standard deviation.

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Supplementary Figure 2. Receiver operating curves (ROC) along with areas under curve (AUCs) for in-hospital death. Curves stratified on 1) pre- ECMO variables; 2) pre-ECMO- and on-ECMO variables; 3) pre-ECMO-, on- ECMO variables and on-ECMO complications. ECMO, extracorporeal membrane oxygenation.