Dallas 2015

TFQO: Anne-Marie Guerguerian # 97EVREV1: Anne-Marie Guerguerian # 97EVEREV2: Ericka Fink # 83Taskforce: PEDS

Peds 407 : ECMO for pediatric cardiac arrest

Dallas 2015COI Disclosure specific to this systematic review

Anne-Marie Guerguerian # 97Commercial/industry• None

Potential intellectual conflicts• None

Ericka Fink # 83Commercial/industry• None

Potential intellectual conflicts• None

Dallas 20152010 CoSTR

“ECPR may be beneficial for infants and children with cardiac arrest if they have heart disease amenable to recovery or transplantation and the arrest occurs in a highly supervised environment such as an ICU with existing clinical protocols and available expertise and equipment to rapidly initiate ECPR. There is insufficient evidence for any specific threshold for CPR duration beyond which survival with ECPR is unlikely. ECPR may be considered in cases of environmentally induced severe hypothermia (temperature 30°C) for pediatric patients with out-of-hospital cardiac arrest if the appropriate expertise, equipment, and clinical protocols are in place.”

Dallas 2015C2015 PICO

Population:infants and children in cardiac arrest in the in-hospital setting

Intervention:does the use of ECMO with resuscitation (ECPR)

Comparison:compared to standard resuscitative treatment (resuscitation without the use of ECMO)

Outcomes:Critical (9): survival to 180 days with good neurological outcome Critical (7): survival to hospital discharge Important (5): survival to intensive care discharge

Dallas 2015

Inclusion/ExclusionIncluded: studies with infants or children populations, with cardiac arrest where comparative interventional or observational studies designs were available.

Excluded: studies without a comparator group (case series, case reports), studies that did not report separate outcomes for infants and children, studies reporting cardiopulmonary arrest in out-of-hospital such as in the context of drowning events.

Dallas 20152015 Proposed Treatment Recommendations - 1

We suggest ECMO with resuscitation (ECPR) compared to standard resuscitation without ECMO for infants and children with cardiac disease with in-hospital cardiac arrest (weak recommendation, very low quality evidence) in settings that allow for the resources, systems, and expertise to optimize the use of ECMO during resuscitation.

Dallas 20152015 Proposed Treatment Recommendations -2

We recommend that there is insufficient evidence to suggest for or against the routine use of ECMO with resuscitation (ECPR) in comparison to standard resuscitation without ECMO in infants and children in general with in-hospital cardiac arrest (weak recommendation, very low quality evidence).

Dallas 2015

Articles found & Data Set selected

The search yielded a total of 2834 citations. Of these, five observational studies were included for bias assessment.Two additional studies’ data were retrieved, the public dataset used in Moler 2009, p 2259, and author query to Doherty 2009, p 1492; unpublished analysis of the former was selected.

Dallas 2015

Risk of Bias in published studies non-RCT

Study Year Page Design PopulationIHCA

subjects Industry Eligibility Exposure/Outcome Confounding Follow up

De Mos 2006 1209 Retrospective cohort IHCA 91 no Low High High High

Wu 2009 443 Retrospective + prospective single center cohort study IHCA 316 non Low Low Low Low

Ortmann 2011 2329 Retrospective registry IHCA cardiac disease 1274 no Low High Low High

Lowry 2013 1422 National administrative registry IHCA & ECMO same day 9000 no High High High high

Odegard 2013 175 Retrospective single center IHCA Cath lab only 70 no Low Low High High

Public dataset 2015 NA Retrospective multicenter

cohort study IHCA selected 491 no Low Low High Low

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Evidence profile table - 1Quality assessment № of patients Effect

Quality Importance№ of

studiesStudy design

Risk of bias Inconsistency Indirect-

nessImpreci-

sionOther

considera-tions

ECPRStandard resuscita-

tionRelative95% CI

Absolute95% CI

Critical outcome: Survival at 180 days with good neurological outcome or follow up at one year as reported in Wu et al 2009 p 443:

1

Wu

2009

Retro & prospective single center

cohort – outcome at one

year

Serious Not serious Serious No serious Residual confounding 12/64 39/252

1.21

95% CI

0.67 to 2.17

0.03

95% CI

-0.07 to 0.13

Very Low Critical

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Evidence profile table - 2Quality assessment № of patients Effect

Quality Importance

№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations ECPRStandard

resuscitationRelative95% CI

Absolute95% CI

Critical outcome:Survival to hospital discharge 5 studies Observational Serious Serious Serious Not serious Residual

confoundingVery Low Critical

De Mos 2006p1209

Retrospective cohort single center

Serious Not serious Serious Serious Residual confounding 2/5 21/86 RR 1.63 95% CI 0.53 to 5.1

0.15 95% CI - 0.28 to 0.59

Low Critical

Wu 2009p443

Retrospective and prospective single center cohort

Not serious Not serious Serious Not serious Residual confounding 16/64 50/252 RR 1.26 95% CI 0.77 to 2.06

0.05 95% CI - 0.06 to 0.17

Low Critical

Ortmann 2011p 2329

Registry, multicenter, Surgical and Medical Cardiac

Not serious Not serious Serious Not serious Residual confounding but adjusted odds ratio of survival reported

Unadjusted Not reported

Unadjusted Not reported

Surgical Cardiac OR 2.5

95%CI 1.3 to 4.5 p 0.007

Medical Cardiac OR 3.8

95%CI 1.4 to 5.8 p 0.011

Not estimated Low Critical

Lowry 2013p 1422

National administrative dataset (KID Inpatient Database)

Serious Serious Serious Serious Residual confounding but propensity matched odds ratio of survival reported

Propensity matched

34.1%

Propensity matched 43.3%

Propensity matched OR 0.7

95% CI 0.4 to 1.3

Not estimated Very low Critical

Odegard 2013 p 175

Retrospective cohort single center (cardiac interventional diagnostic unit)

Serious Serious Serious Serious Residual confounding 10/18 45/52 0.6495% CI 0.48 to 0.98

-0.3195% CI -0.55 to 0.06

Very Low Critical

Public dataset Retrospective multicenter cohort study

Very serious Serious Not serious Serious Residual confounding 19/38 206/453 1.0995% CI 0.78 to 1.56

0.0595% CI -0.12 to 0.21

Very Low Critical

Dallas 2015Proposed Consensus on Science statements -1

In infants and children with in-hospital cardiac arrest for the critical outcome of survival at 180 days with favorable outcome we have identified no difference in outcomes, with very low quality evidence (downgraded for indirectness and imprecision) from an observational study (Wu 2009, p443) with RR 1.21 (95% CI 0.67 - 2.17) at one year, and very low quality evidence from unpublished secondary data analyses from another study's public dataset (Moler 2009, p2259) with RR 0.74 (95% CI 0.45 - 1.25) on hospital discharge (downgraded for serious risk of bias with residual confounding).

Dallas 2015Proposed Consensus on Science statements -2

In infants and children with in-hospital cardiac arrest for the critical outcome of survival to hospital discharge, we identified very low quality evidence from five observational studies (Wu 2009, p443; De Mos 2006, p1209; Ortmann 2011, p2329; Lowry 2013, p1422, Odegard 2014, p175) (downgraded for indirectness, inconsistency, and residual confounding) and very low quality evidence from an unpublished analysis of a public dataset (RR 1.09 95%CI 0.78- 1.56; used in Moler 2009, p2259) showing no benefit, or some benefit among children with cardiac diseases (downgraded for residual confounding) (Ortmann 2011, p 2329; Lowry 2013, p 1422).

Dallas 20152015 Proposed Treatment Recommendations - 1

We suggest ECMO with resuscitation (ECPR) over standard resuscitation without ECMO for infants and children with cardiac disease with in-hospital cardiac arrest (very low quality evidence) in settings that allow for the resources, systems, and expertise to optimize the use of ECMO during resuscitation.

Dallas 20152015 Proposed Treatment Recommendations -2

We recommend that there is insufficient evidence to suggest for or against the routine use of ECMO with resuscitation (ECPR) in comparison to standard resuscitation without ECMO in infants and children in general with in-hospital cardiac arrest (weak recommendation, very low quality evidence).

Dallas 2015

Knowledge Gaps -1

Comparative studies in pediatric in-hospital cardiac arrest or out-of-hospital cardiac arrest receiving resuscitation with and without ECMO are lacking. 1.The quality of CPR i.e., quality of perfusion of cerebral and systemic circulations, during ECMO cannulation has not been studied in the pediatric resuscitation setting.2.The optimal timing of initiation of ECMO cannulation during pediatric resuscitation measures has been not studied - both minimal interval and maximal interval. The optimal timing of ECMO initiation during resuscitation measures of select populations such as deep hypothermic out-of-hospital arrest, pulmonary emboli, and high risk complex congenital heart disease (e.g., in single ventricle physiology) has not been studied.3.The anatomical preferred location for ECMO cannulation during resuscitation for optimal neuro and cardio-protection has not been studied.

Dallas 2015Knowledge Gaps -2

4. The effect of co-interventions delivered during ECMO initiation and circulatory support is not reported in the pediatric in-hospital cardiac arrest population; such interventions that warrant further evaluation are the following: temperature targeted therapy, hypothermia therapy and rate of rewarming, blood flow rate on reperfusion, oxygenation and carbon dioxide targets, hemodilution (associated with crystalloid circuit prime), hemofiltration, concurrent mechanical ventilation, inotropes and vasoactives strategies, steroids.

5. Studies incorporating functional outcomes are urgently needed.6. Alternatives to patient-level-randomization study designs to evaluate benefit are

urgently needed. Several enters have adopted the use of ECMO in resuscitation as standard practice in pediatric in-hospital cardiac arrest in selected pediatric populations. Random allocation of ECMO for resuscitation at an individual patient level presents several challenges which decreases the feasibility of traditional randomized control trials designs and suggests that alternatives need to be considered to minimize bias in order to compare interventions and generate clinical evidence to inform practice.

7. Studies on the ethical frameworks applied or informed consent processes used with ECMO for resuscitation are also missing.

Dallas 2015

Additional comments – Resources and costs

We found in one study that studied the costs associated with in-hospital charges in children with cardiopulmonary events and found that these were different and increased with the use of ECMO compared to no ECMO ( Lowry 2013, p 1422).

Dallas 2015Next Steps

This slide will be completed during Task Force Discussion (not EvRev) and should include:

Consideration of interim statementPerson responsibleDue date