Brain Injury and Neurologic Outcome in Patients Undergoing ...

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Brain Injury and Neurologic Outcome in Patients Undergoing Extracorporeal

Cardiopulmonary Resuscitation: A systematic review and meta-analysis

Supplemental Digital Content

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Table of Contents

Supplemental Table 1: The Cochrane Collaboration Randomization controlled trials quality assessment ................................................................... 2

Supplemental Table 2: The Newcastle-Ottawa Scale to evaluate risk of bias in three domains for observational studies ........................................... 3

Supplemental table 3: Meta-regression analysis for neurologic outcomes based on pre-specified patients’ variables ............................................... 6

Supplemental Table 4: Subgroup analysis by publication year ....................................................................................................................................... 7

Supplemental Figure 1: Meta-analysis of the prevalence of seizures in ECPR ................................................................................................................ 8

Supplemental Figure 2: Meta-analysis of the prevalence of intracerebral hemorrhage in ECPR ................................................................................... 9

Supplemental Figure 3: Meta-analysis of overall survival in ECPR ................................................................................................................................ 10

Supplemental Figure 4: Meta-analysis of the prevalence of brain death in ECPR ........................................................................................................ 11

Supplemental Figure 5: Meta-analysis of the prevalence of good neurological outcomes in ECPR ............................................................................. 12

Supplemental Figure 6: Meta-analysis of early survival in ECPR ................................................................................................................................... 13

Supplemental Figure 7: Meta-analysis of the prevalence of early good neurological outcomes in ECPR .................................................................... 14

Supplemental Figure 8: Meta-analysis of late survival in ECPR ..................................................................................................................................... 15

Supplemental Figure 9: Meta-analysis of the prevalence of late good neurological outcomes in ECPR...................................................................... 16

Supplemental Figure 10: Subgroup Meta-analysis of the prevalence of any neurological complications in ECPR by study design ............................ 17

Supplemental Figure 11: Subgroup Meta-analysis of the prevalence of good neurological outcomes in ECPR by study design ................................ 18

Supplemental Figure 12: Subgroup Meta-analysis of overall survival in ECPR by study design ................................................................................... 19

Appendix A- PubMed Search strategy ........................................................................................................................................................................... 20

Appendix B – References of included articles ............................................................................................................................................................... 24

Appendix C- PRISMA checklist ....................................................................................................................................................................................... 29

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Supplemental Table 1: The Cochrane Collaboration Randomization controlled trials quality assessment

Author Year Randomization

Decision

Allocation Concealmen

t Decision

Are participants blinded? Decision

Are personnel blinded? Decision

Blinding of

Assessors Decision

Incomplete

Outcome Data

Decision

Selective Reportin

g Decision

Other Biases Decisio

n

Criteria "high" no. out

of 8

Criteria "low" no. out of 8

Criteria "unclear" no. out of

8

Comments

Pang 2016

High risk (randomization according to the

day of the month)

Unclear risk Low risk Low risk Low risk Low risk Low risk Low risk

1 5 1 Overall high risk

of bias

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Supplemental Table 2: The Newcastle-Ottawa Scale to evaluate risk of bias in three domains for observational studies

SELECTION COMPARABILITY OUTCOME OR EXPOSURE

Total Score

Studies

Representativeness of exposed cohort (or cases for case-control studies)

Selection of non-exposed cohort (or controls for case-control studies)

Ascertainment of exposure (or case definition for case control studies)

Demonstration that outcome of interest was not present at start of study (or no history of disease for controls in case-control studies)

Comparability of cohorts on the basis of the design or analysis

Assessment of outcome

(or exposure for case-control studies)

Was follow-up long enough for outcomes to occur (for

cohort studies)

Adequacy of follow

up of cohorts (or adequacy

of response rate for case-control studies)

Controls

for X

Controls for Y

Same method of exposure

ascertainment for cases and

controls

Bednarczk 2014

* * * No (None) (None) * * * 6

Cesana 2017

* * * No Age not matched

* (CA time) * * * 7

Wang 2014 * * * No * (Age) * (Initial rhythm,

ischemic duration, ACS) * * * 8

DH Choi 2016

* * * No (None) (None) * * * 6

DS Choi 2016

* * * No * (Age) * (gender, witnessed arrest, arrest location,

CPR duration) * * * 8

Chouihed 2018

* * * No (None) (None) * * * 6

Ellouze 2018

* * * No Age not matched

* (baseline labs, CPR time, systemic complications)

* * * 7

Gil 2017 * * * No * (Age) * (SOFA score, initial rhythm, CPR time)

* * * 8

Kagawa 2012

* * * No (None) (None) * * * 6

Kagawa 2010

* * * No Age not matched

* (OHCA, collapse-to-ECMO time, initial

rhythm) * * * 7

Kim 2014 * * * No *(Age)

*(gender, comorbidity score, witnessed arrest, bystander CPR, initial rhythm, CA etiology,

CPR duration, arrest to

* * * 8

4

CPR time, ROSC during CPR, TH)

Lamhaut 2017

* * * No *(Age)

*(gender, pre-hospital ECPR, CA etiology, VS

prior to ECPR, epinephrine dose)

* * * 8

Lin 2010 * * * No *(Age)

* (gender, CPR duration, initial rhythm,

baseline medical conditions, pre and post

CPR characteristics)

* * * 8

Pang 2017 * * * No Age not matched

*(initial rhythm, systemic complications

* * * 7

Pabst 2018 * * * No (None) (None) * * * 6

Pozzi 2016 * * * No (None) (None) * * * 6

Sakamoto 2014

* * * No (None) (None) * * * 6

Shin 2011-2013

* * * No *(Age)

*(gender, comorbidities, clinical presentation,

cause of CA, location of CA, time period, initial rhythm, CPR duration, post CPR variables)

* * * 8

Siao 2015 * * * No *(Age) *(gender, CPR duration, defibrillation episodes,

hypothermia) * * * 8

Terri 2018 * * * No (None) (None) * * * 6

Maekawa 2013

* * * No *(Age)

*(gender, baseline characteristics, CPR

variables, hypothermia, IABP, PCI)

* * * 8

Grunau 2017

* * * No (None) (None) * * * 6

Tanno 2008

* * * No (None) (None) * * * 6

Ryu 2015-2019

* * * No *(Age)

*(gender, lactic acid and Hgb, OHCA, initial

rhythm, CPR duration, time from CA to ECPR)

* * * 8

Wang 2015 * * * No *(Age) *(CPR duration, PCI, medical conditions, blood gas, fever)

* * * 8

Yukawa 2017

* * * No *(Age) *(gender, initial rhythm, transient ROSC, time from CA to ECMO)

* * * 8

Goto 2018 * * * No *(Age) *(Shockable rhythm, witnessed arrest,

* * * 8

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bystanders CPR, rearrest after ROSC, PH)

Jung 2019 * * * No *(Age)

*(OHCA, pressor use, gender, CPR duration, ventricular fibrillation, Hgb, etc)

* * * 8

Kim 2018 * * * No *(Age)

*(DM, CKD, active malignancy, cardiac cause arrest, arrest time, hypothermia)

* * * 8

Komeyama 2019

* * * No (None) (None) * * * 6

Mandigers 2019

* * * No (None) (None) * * * 6

Matsuoka 2019

* * * No *(Age) *(Time to hospital arrival, witnessed arrest, bystander CPR)

* * * 8

Otani 2018 * * * No Age not matched

*(initial rhythm, low flow time, serum lactate, PH, TTM)

* * * 7

Patricio 2019

* * * No *(Age) *(Gender, bystander CPR, witnessed CA, OHCA, HTN, etc)

* * * 8

Sato 2018 * * * No None None * * * 6

Khan 2018 * * * No None None * * * 6

Schober 2017

* * * No *(age)

*(Gender, low-flow time, shockable rhythm, witnessed CA, PH, lactate, etc)

* * * 8

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Supplemental table 3: Meta-regression analysis for neurologic outcomes based on pre-specified patients’ variables

Variable Estimate

( coefficient)

95% Confidence interval

p value

Age (years) 0.0053 -0.0020 - 0.0127 0.1492

% of OHCA -0.0017 -0.0030 - -0.0005 0.0078

Median CPR time (min) 0.0031 -0.0002 - 0.0063 0.0617

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Supplemental Table 4: Subgroup analysis by publication year

Outcome

Prevalence of outcome by publication year p value 2008-2013 2014-2019

Overall survival 0.22 0.32 0.02

Good neurological outcome 0.21 0.25 0.22

Hypoxic ischemic brain injury 0.15 0.24 0.14

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Supplemental Figure 1: Meta-analysis of the prevalence of seizures in ECPR

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Supplemental Figure 2: Meta-analysis of the prevalence of intracerebral hemorrhage in ECPR

10

Supplemental Figure 3: Meta-analysis of overall survival in ECPR

11

Supplemental Figure 4: Meta-analysis of the prevalence of brain death in ECPR

12

Supplemental Figure 5: Meta-analysis of the prevalence of good neurological outcomes in ECPR

13

Supplemental Figure 6: Meta-analysis of early survival in ECPR

14

Supplemental Figure 7: Meta-analysis of the prevalence of early good neurological outcomes in ECPR

15

Supplemental Figure 8: Meta-analysis of late survival in ECPR

16

Supplemental Figure 9: Meta-analysis of the prevalence of late good neurological outcomes in ECPR

17

Supplemental Figure 10: Subgroup Meta-analysis of the prevalence of any neurological complications in ECPR by study design

18

Supplemental Figure 11: Subgroup Meta-analysis of the prevalence of good neurological outcomes in ECPR by study design

19

Supplemental Figure 12: Subgroup Meta-analysis of overall survival in ECPR by study design

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Appendix A- PubMed Search strategy

("extracorporeal membrane oxygenation"[MeSH Terms] OR (("extracorporeal"[tw] OR "extra-corporeal"[tw] OR "extra corporeal"[tw]) AND "membrane"[tw] AND "oxygenation"[tw]) OR "CardioHelp"[tw] OR "ECLS"[tw] OR "ECMO"[tw] OR "ECPR"[tw] OR "extra corporeal carbon dioxide removal"[tw] OR "extra corporeal cardio pulmonary resuscitation"[tw] OR "extra corporeal cardiopulmonary resuscitation"[tw] OR "extra corporeal CPR"[tw] OR "extra corporeal life support"[tw] OR "extra corporeal membrane oxygenation"[tw] OR "extra corporeal oxygenation"[tw] OR "extra corporeal pump oxygenation"[tw] OR "extra pulmonary oxygenation"[tw] OR "extracorporeal oxygenation"[tw] OR "extracorporeal carbon dioxide removal"[tw] OR "extra-corporeal carbon dioxide removal"[tw] OR "extracorporeal cardio pulmonary resuscitation"[tw] OR "extra-corporeal cardio pulmonary resuscitation"[tw] OR "extracorporeal cardiopulmonary resuscitation"[tw] OR "extra-corporeal cardiopulmonary resuscitation"[tw] OR "extra corporeal cardiopulmonary resuscitation"[tw] OR "extracorporeal cpr"[tw] OR "extracorporeal life support"[tw] OR "extra-corporeal life support"[tw] OR "extracorporeal membrane oxygenation device"[tw] OR "extracorporeal membrane oxygenation"[tw] OR "extra-corporeal membrane oxygenation"[tw] OR "extracorporeal oxygenation"[tw] OR "extra-corporeal oxygenation"[tw] OR "extracorporeal pump oxygenation"[tw] OR "extrapulmonary oxygenation"[tw] OR "Minimax"[tw] OR "Primo2x"[tw] OR "Prolung"[tw] OR "Quadrox PLS Oxygenator"[tw] OR "Rotaflow RF 32"[tw]) AND ("brain death"[mesh] OR "brain edema"[mesh] OR "brain injuries"[mesh:noexp] OR "cavernous sinus thrombosis"[mesh] OR "hematoma, epidural, cranial"[mesh] OR "hypoxia-ischemia, brain"[mesh] OR "intracranial hemorrhage, hypertensive"[mesh] OR "intracranial hemorrhage, traumatic"[mesh:noexp] OR "intracranial hemorrhages"[mesh:noexp] OR "intracranial hypertension"[mesh:noexp] OR "intracranial thrombosis"[mesh] OR "lateral sinus thrombosis"[mesh] OR "sagittal sinus thrombosis"[mesh] OR "seizures"[mesh] OR "sinus thrombosis, intracranial"[mesh] OR "status epilepticus"[mesh:noexp] OR "subarachnoid hemorrhage"[mesh] OR "absence status"[tw] OR "acute stroke"[tw] OR "acute strokes"[tw] OR "anoxic ischaemic encephalopathies"[tw] OR "anoxic ischaemic encephalopathy"[tw] OR "anoxic ischemic encephalopathies"[tw] OR "anoxic ischemic encephalopathy"[tw] OR "arachnoid bleed"[tw] OR "arachnoid bleeding"[tw] OR "arachnoid bleeds"[tw] OR "arachnoid haematoma"[tw] OR "arachnoid haematomas"[tw] OR "arachnoid haemorrhage"[tw] OR "arachnoid haemorrhages"[tw] OR "arachnoid hematoma"[tw] OR "arachnoid hematomas"[tw] OR "arachnoid hemorrhage"[tw] OR "arachnoid hemorrhages"[tw] OR "basal ganglia haematoma"[tw] OR "basal ganglia haematomas"[tw] OR "basal ganglia haemorrhage"[tw] OR "basal ganglia haemorrhages"[tw] OR "basal ganglia hematoma"[tw] OR "basal ganglia hematomas"[tw] OR "basal ganglia hemorrhage"[tw] OR "basal ganglia hemorrhages"[tw] OR "basal ganglionic haematoma"[tw] OR "basal ganglionic haematomas"[tw] OR "basal ganglionic haemorrhage"[tw] OR "basal ganglionic haemorrhages"[tw] OR "basal ganglionic hematoma"[tw] OR "basal ganglionic hematomas"[tw] OR "basal ganglionic hemorrhage"[tw] OR "basal ganglionic hemorrhages"[tw] OR "brain anoxia ischaemia"[tw] OR "brain anoxia ischaemias"[tw] OR "brain anoxia ischemia"[tw] OR "brain anoxia ischemias"[tw] OR "brain arrest"[tw] OR "brain bleed"[tw] OR "brain bleeding"[tw] OR "brain bleeds"[tw] OR

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"brain complication"[tw] OR "brain complications"[tw] OR "brain damage"[tw] OR "brain damaged"[tw] OR "brain damages"[tw] OR "brain dead"[tw] OR "brain death"[tw] OR "brain deaths"[tw] OR "brain edema"[tw] OR "brain edemas"[tw] OR "brain haematoma"[tw] OR "brain haematomas"[tw] OR "brain haemorrhage"[tw] OR "brain haemorrhages"[tw] OR "brain hematoma"[tw] OR "brain hematomas"[tw] OR "brain hemorrhage"[tw] OR "brain hemorrhages"[tw] OR "brain hypoxia ischaemia"[tw] OR "brain hypoxia ischaemias"[tw] OR "brain hypoxia ischemia"[tw] OR "brain hypoxia ischemias"[tw] OR "brain hypoxia"[tw] OR "brain hypoxic"[tw] OR "brain injuries"[tw] OR "brain injury"[tw] OR "brain ischaemia anoxia"[tw] OR "brain ischaemia anoxias"[tw] OR "brain ischaemia hypoxia"[tw] OR "brain ischaemia hypoxias"[tw] OR "brain ischemia anoxia"[tw] OR "brain ischemia anoxias"[tw] OR "brain ischemia hypoxia"[tw] OR "brain ischemia hypoxias"[tw] OR "brain oedema"[tw] OR "brain oedemas"[tw] OR "brain outcome"[tw] OR "brain outcomes"[tw] OR "brain sequelae"[tw] OR "brain sinus thrombosis"[tw] OR "brain stem haemorrhage"[tw] OR "brain stem haemorrhages"[tw] OR "brain stem hemorrhage"[tw] OR "brain stem hemorrhages"[tw] OR "brain swelling"[tw] OR "brain swellings"[tw] OR "brain thromboses"[tw] OR "brain thrombosis"[tw] OR "brain thrombus"[tw] OR "brain vascular accident"[tw] OR "brain vascular accidents"[tw] OR "brain ventricle haemorrhage"[tw] OR "brain ventricle haemorrhages"[tw] OR "brain ventricle hemorrhage"[tw] OR "brain ventricle hemorrhages"[tw] OR "braindead"[tw] OR "brainstem haemorrhage"[tw] OR "brainstem haemorrhages"[tw] OR "brainstem hemorrhage"[tw] OR "brainstem hemorrhages"[tw] OR "cavernous sinus thrombophlebitides"[tw] OR "cavernous sinus thrombophlebitis"[tw] OR "cavernous sinus thromboses"[tw] OR "cavernous sinus thrombosis"[tw] OR "cavernous sinus thrombosis"[tw] OR "caverous sinus septic phlebitis"[tw] OR "cerebellum swelling"[tw] OR "cerebellum swellings"[tw] OR "cerebral anoxia"[tw] OR "cerebral circulatory arrest"[tw] OR "cerebral death"[tw] OR "cerebral edema"[tw] OR "cerebral edemas"[tw] OR "cerebral emboli"[tw] OR "cerebral haematoma"[tw] OR "cerebral haematomas"[tw] OR "cerebral haemorrhage"[tw] OR "cerebral haemorrhages"[tw] OR "cerebral hematoma"[tw] OR "cerebral hematomas"[tw] OR "cerebral hemorrhage"[tw] OR "cerebral hemorrhages"[tw] OR "cerebral hypertension"[tw] OR "cerebral hypertensions"[tw] OR "cerebral hypertensive"[tw] OR "cerebral hypoxia"[tw] OR "cerebral hypoxic"[tw] OR "cerebral ischaemia anoxia"[tw] OR "cerebral ischaemia anoxias"[tw] OR "cerebral ischaemia hypoxia"[tw] OR "cerebral ischaemia hypoxias"[tw] OR "cerebral ischemia anoxia"[tw] OR "cerebral ischemia anoxias"[tw] OR "cerebral ischemia hypoxia"[tw] OR "cerebral ischemia hypoxias"[tw] OR "cerebral microbleed"[tw] OR "cerebral oedema"[tw] OR "cerebral oedemas"[tw] OR "cerebral performance categories"[tw] OR "cerebral performance category"[tw] OR "cerebral performance"[tw] OR "cerebral sinus thrombosis"[tw] OR "cerebral sinus vein thrombosis"[tw] OR "cerebral swelling"[tw] OR "cerebral swellings"[tw] OR "cerebral thromboses"[tw] OR "cerebral thrombosis"[tw] OR "cerebral thrombus"[tw] OR "cerebral venous sinus thromboses"[tw] OR "cerebral venous sinus thrombosis"[tw] OR "cerebral venous thromboses"[tw] OR "cerebral venous thrombosis"[tw] OR "cerebro vascular accident"[tw] OR "cerebro vascular accidents"[tw] OR "cerebro vascular stroke"[tw] OR "cerebro vascular strokes"[tw] OR "cerebrovascular accident"[tw] OR "cerebrovascular accidents"[tw] OR "cerebrovascular stroke"[tw] OR "cerebrovascular strokes"[tw] OR "cerebrovenous thromboses"[tw] OR "cerebrovenous thrombosis"[tw] OR "convulsion"[tw] OR "convulsions"[tw] OR "corpus callosum bleeding"[tw] OR "CPC"[tw] OR "cranial epidural haemorrages"[tw] OR "cranial epidural haemorrhage"[tw] OR "cranial epidural hemorrages"[tw] OR "cranial epidural hemorrhage"[tw] OR "cranial extradural haemorrhage"[tw] OR "cranial extradural haemorrhages"[tw] OR "cranial extradural hemorrhage"[tw] OR "cranial extradural hemorrhages"[tw] OR "cranial haematoma"[tw] OR "cranial haematomas"[tw] OR "cranial hematoma"[tw] OR "cranial hematomas"[tw] OR "cranial hypertension"[tw] OR "cranial hypertensions"[tw] OR "cranial hypertensive"[tw] OR "cranial sinus thromboses"[tw] OR "cranial sinus thrombosis"[tw] OR "cranial sinus thrombosis"[tw] OR "cranial thromboses"[tw] OR "cranial thrombosis"[tw] OR "cranial thrombus"[tw] OR "cva"[tw] OR "cvas"[tw] OR "dura mater sinus thrombosis"[tw] OR "dural sinus thrombosis"[tw] OR "elevated intracranial pressure"[tw] OR "embolic infarction"[tw] OR "embolic infarctions"[tw] OR "embolic

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stroke"[tw] OR "embolic strokes"[tw] OR "endocranial hypertension"[tw] OR "endocranial hypertensions"[tw] OR "endocranial hypertensive"[tw] OR "epidural haematoma"[tw] OR "epidural haematomas"[tw] OR "epidural hematoma"[tw] OR "epidural hematomas"[tw] OR "epilepsia partialis continua"[tw] OR "epilepsies"[tw] OR "epilepsy"[tw] OR "epileptic state"[tw] OR "extradural haematoma"[tw] OR "extradural haematomas"[tw] OR "extradural hematoma"[tw] OR "extradural hematomas"[tw] OR "foix syndrome"[tw] OR "foix syndromes"[tw] OR "haemorrhagic apoplexy"[tw] OR "haemorrhagic stroke"[tw] OR "haemorrhagic strokes"[tw] OR "hemorrhagic apoplexy"[tw] OR "hemorrhagic stroke"[tw] OR "hemorrhagic strokes"[tw] OR "hie"[tw] OR "hypoxic brain"[tw] OR "hypoxic ischaemic encephalopathies"[tw] OR "hypoxic ischaemic encephalopathy"[tw] OR "hypoxic ischemic encephalopathies"[tw] OR "hypoxic ischemic encephalopathy"[tw] OR "hypoxic ischemic injuries"[tw] OR "hypoxic ischemic injury"[tw] OR "ich"[tw] OR "increased intracranial pressure"[tw] OR "intra cerebral bleeding"[tw] OR "intra cerebral bleeds"[tw] OR "intra cerebral haemorrhage"[tw] OR "intra cerebral haemorrhages"[tw] OR "intra cerebral hemorrhage"[tw] OR "intra cerebral hemorrhages"[tw] OR "intra cranial bleed"[tw] OR "intra cranial bleeding"[tw] OR "intra cranial haematoma"[tw] OR "intra cranial haematomas"[tw] OR "intra cranial haemorrhage"[tw] OR "intra cranial haemorrhages"[tw] OR "intra cranial hematoma"[tw] OR "intra cranial hematomas"[tw] OR "intra cranial hemorrhage"[tw] OR "intra cranial hemorrhages"[tw] OR "intra cranial thromboses"[tw] OR "intra cranial thrombosis"[tw] OR "intra parenchymal haemorrhage"[tw] OR "intra parenchymal haemorrhages"[tw] OR "intra parenchymal hemorrhage"[tw] OR "intra parenchymal hemorrhages"[tw] OR "intracerebral bleed"[tw] OR "intracerebral bleeding"[tw] OR "intracerebral bleeds"[tw] OR "intracerebral haemorrhage"[tw] OR "intracerebral haemorrhages"[tw] OR "intracerebral hemorrhage"[tw] OR "intracerebral hemorrhages"[tw] OR "intracerebral hypertension"[tw] OR "intracerebral hypertensions"[tw] OR "intracerebral hypertensive"[tw] OR "intracranial bleed"[tw] OR "intracranial bleeding"[tw] OR "intracranial bleeds"[tw] OR "intracranial edema"[tw] OR "intracranial edemas"[tw] OR "intracranial haematoma"[tw] OR "intracranial haematomas"[tw] OR "intracranial haemorrhage"[tw] OR "intracranial haemorrhages"[tw] OR "intracranial hematoma"[tw] OR "intracranial hematomas"[tw] OR "intracranial hemorrhage"[tw] OR "intracranial hemorrhages"[tw] OR "intracranial hypertension"[tw] OR "intracranial hypertensions"[tw] OR "intracranial hypertensive"[tw] OR "intracranial oedema"[tw] OR "intracranial oedemas"[tw] OR "intracranial pressure elevation"[tw] OR "intracranial pressure increase"[tw] OR "intracranial pressure increases"[tw] OR "intracranial sinus thrombophlebitides"[tw] OR "intracranial sinus thrombophlebitis"[tw] OR "intracranial sinus thromboses"[tw] OR "intracranial sinus thrombosis"[tw] OR "intracranial thromboses"[tw] OR "intracranial thromboses"[tw] OR "intracranial thrombosis"[tw] OR "intracranial thrombosis"[tw] OR "intracranial thrombus"[tw] OR "intracranial venous thromboses"[tw] OR "intracranial venous thrombosis"[tw] OR "intraparenchymal haemorrhage"[tw] OR "intraparenchymal haemorrhages"[tw] OR "intraparenchymal hemorrhage"[tw] OR "intraparenchymal hemorrhages"[tw] OR "intraventricular haemorrhage"[tw] OR "intraventricular haemorrhages"[tw] OR "intraventricular hemorrhage"[tw] OR "intraventricular hemorrhages"[tw] OR "iph"[tw] OR "irreversible coma"[tw] OR "irreversible comas"[tw] OR "ischaemic hypoxic encephalopathies"[tw] OR "ischaemic hypoxic encephalopathy"[tw] OR "ischemic hypoxic encephalopathies"[tw] OR "ischemic hypoxic encephalopathy"[tw] OR "ischemic stroke"[tw] OR "ischemic strokes"[tw] OR "kojewnikow s syndrome"[tw] OR "kojewnikow syndrome"[tw] OR "kozhevnikov s syndrome"[tw] OR "kozhevnikov syndrome"[tw] OR "lateral sinus thrombophlebitis"[tw] OR "lateral sinus thrombophlebitis"[tw] OR "lateral sinus thromboses"[tw] OR "lateral sinus thrombosis"[tw] OR "lateral sinus thrombosis"[tw] OR "neurologic complication"[tw] OR "neurologic complications"[tw] OR "neurologic damage"[tw] OR "neurologic damages"[tw] OR "neurologic deficit"[tw] OR "neurologic deficits"[tw] OR "neurologic injuries"[tw] OR "neurologic injury"[tw] OR "neurologic insult"[tw] OR "neurologic insult"[tw] OR "neurologic insults"[tw] OR "neurologic outcome"[tw] OR "neurologic outcomes"[tw] OR "neurologic prognoses"[tw] OR "neurologic prognosis"[tw] OR "neurologic sequelae"[tw] OR "neurological complication"[tw] OR "neurological complications"[tw] OR "neurological damage"[tw] OR

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"neurological damages"[tw] OR "neurological deficit"[tw] OR "neurological deficits"[tw] OR "neurological injuries"[tw] OR "neurological injury"[tw] OR "neurological insults"[tw] OR "neurological outcome"[tw] OR "neurological outcomes"[tw] OR "neurological prognoses"[tw] OR "neurological prognosis"[tw] OR "neurological sequelae"[tw] OR "petit mal status"[tw] OR "petrous sinus thrombophlebitides"[tw] OR "petrous sinus thrombophlebitis"[tw] OR "petrous sinus thromboses"[tw] OR "petrous sinus thrombosis"[tw] OR "pituitary apoplexies"[tw] OR "pituitary apoplexy"[tw] OR "posterior fossa haematoma"[tw] OR "posterior fossa haematomas"[tw] OR "posterior fossa haemorrhage"[tw] OR "posterior fossa haemorrhages"[tw] OR "posterior fossa hematoma"[tw] OR "posterior fossa hematomas"[tw] OR "posterior fossa hemorrhage"[tw] OR "posterior fossa hemorrhages"[tw] OR "putamen haematoma"[tw] OR "putamen haematomas"[tw] OR "putamen haemorrhage"[tw] OR "putamen haemorrhages"[tw] OR "putamen hematoma"[tw] OR "putamen hematomas"[tw] OR "putamen hemorrhage"[tw] OR "putamen hemorrhages"[tw] OR "putaminal haematoma"[tw] OR "putaminal haematomas"[tw] OR "putaminal haemorrhage"[tw] OR "putaminal haemorrhages"[tw] OR "putaminal hematoma"[tw] OR "putaminal hematomas"[tw] OR "putaminal hemorrhage"[tw] OR "putaminal hemorrhages"[tw] OR "sagittal sinus septic phlebitis"[tw] OR "sagittal sinus thrombophlebitis"[tw] OR "sagittal sinus thromboses"[tw] OR "sagittal sinus thrombosis"[tw] OR "sah"[tw] OR "sdh"[tw] OR "seizure"[tw] OR "seizures"[tw] OR "sigmoid sinus thromboses"[tw] OR "sigmoid sinus thrombosis"[tw] OR "sigmoid sinus thrombosis"[tw] OR "sinus thromboses"[tw] OR "sinus thrombosis"[tw] OR "status epilepticus"[tw] OR "sub arachnoid haemorrhage"[tw] OR "sub arachnoid haemorrhages"[tw] OR "sub arachnoid hemorrhage"[tw] OR "sub arachnoid hemorrhages"[tw] OR "sub dural acute haematoma"[tw] OR "sub dural acute haematomas"[tw] OR "sub dural acute haemorrhage"[tw] OR "sub dural acute haemorrhages"[tw] OR "sub dural acute hematoma"[tw] OR "sub dural acute hematomas"[tw] OR "sub dural acute hemorrhage"[tw] OR "sub dural acute hemorrhages"[tw] OR "sub dural chronic haematoma"[tw] OR "sub dural chronic haematomas"[tw] OR "sub dural chronic haemorrhage"[tw] OR "sub dural chronic haemorrhages"[tw] OR "sub dural chronic hematoma"[tw] OR "sub dural chronic hematomas"[tw] OR "sub dural chronic hemorrhage"[tw] OR "sub dural chronic hemorrhages"[tw] OR "sub dural haematomas"[tw] OR "sub dural haematomas"[tw] OR "sub dural haemorrhage"[tw] OR "sub dural haemorrhages"[tw] OR "sub dural hematoma"[tw] OR "sub dural hematoma"[tw] OR "sub dural hemorrhage"[tw] OR "sub dural hemorrhages"[tw] OR "subarachnoid bleed"[tw] OR "subarachnoid bleeding"[tw] OR "subarachnoid bleeds"[tw] OR "subarachnoid haemorrhage"[tw] OR "subarachnoid haemorrhages"[tw] OR "subarachnoid hemorrhage"[tw] OR "subarachnoid hemorrhages"[tw] OR "subdural acute haematoma"[tw] OR "subdural acute haematomas"[tw] OR "subdural acute haemorrhage"[tw] OR "subdural acute haemorrhages"[tw] OR "subdural acute hematoma"[tw] OR "subdural acute hematomas"[tw] OR "subdural acute hemorrhage"[tw] OR "subdural acute hemorrhages"[tw] OR "subdural chronic haematoma"[tw] OR "subdural chronic haematomas"[tw] OR "subdural chronic haemorrhage"[tw] OR "subdural chronic haemorrhages"[tw] OR "subdural chronic hematoma"[tw] OR "subdural chronic hematomas"[tw] OR "subdural chronic hemorrhage"[tw] OR "subdural chronic hemorrhages"[tw] OR "subdural haematoma"[tw] OR "subdural haematomas"[tw] OR "subdural haemorrhage"[tw] OR "subdural haemorrhages"[tw] OR "subdural hematoma"[tw] OR "subdural hematomas"[tw] OR "subdural hemorrhage"[tw] OR "subdural hemorrhages"[tw] OR "swelling brain"[tw] OR "swelling brains"[tw] OR "swollen brain"[tw] OR "swollen brains"[tw] OR "swollen cerebellum"[tw] OR "swollen cerebellums"[tw] OR "transverse sinus thromboses"[tw] OR "transverse sinus thrombosis"[tw])

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Appendix B – References of included articles

1. Avalli, L. et al. Favourable survival of in-hospital compared to out-of-hospital refractory cardiac arrest patients treated with extracorporeal membrane oxygenation: An Italian tertiary care centre experience. Resuscitation 83, 579–583 (2012).

2. Bednarczyk, J. M. et al. Resuscitative extracorporeal membrane oxygenation for in hospital cardiac arrest: a Canadian observational experience. Resuscitation 85, 1713–9 (2014).

3. Blumenstein, J. et al. Extracorporeal life support in cardiovascular patients with observed refractory in-hospital cardiac arrest is associated with favourable short and long-term outcomes: A propensity-matched analysis. Eur. Hear. journal. Acute Cardiovasc. care 5, 13–22 (2016).

4. Casadio, M. C. et al. Organ donation in cardiac arrest patients treated with extracorporeal CPR: A single centre observational study. Resuscitation 118, 133–139 (2017).

5. Cesana, F. et al. Effects of extracorporeal cardiopulmonary resuscitation on neurological and cardiac outcome after ischaemic refractory cardiac arrest. Eur. Hear. journal. Acute Cardiovasc. care 7, 432–441 (2018).

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Appendix C- PRISMA checklist

Section/topic # Checklist item Reported on page #

TITLE

Title 1 Identify the report as a systematic review, meta-analysis, or both. 1

ABSTRACT

Structured summary 2 Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.

3-4

INTRODUCTION

Rationale 3 Describe the rationale for the review in the context of what is already known. 5

Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

5

METHODS

Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.

6

Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered,

language, publication status) used as criteria for eligibility, giving rationale. 6, 7

Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

6

Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

6

Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

6, 7

Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

7

Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

7

Risk of bias in individual studies

12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

8

30

Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means). 8

Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis.

8

Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

7, 8

Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

8

RESULTS

Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

9

Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

9

Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). 10

Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

10-12

Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency. 10-12

Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15). 10

Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]). 11, 12

DISCUSSION

Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

13

Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

15

Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research. 16

FUNDING

Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.

17