Inclusion of infants, children, and adolescents in Public Access Defibrillation programs.

Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest: None

The following Task Force members and other authors declared an intellectual conflict of interest and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest committees: None

CoSTR Citation

Atkins DL, Acworth J, Chung SP, Reis A, Van de Voorde P, on behalf of the International Liaison Committee on Resuscitation Pediatric and Basic Life Support Task Forces.

Application of Automated External Defibrillators in Infants, Children and Adolescents in Cardiac Arrest Consensus on Science with Treatment Recommendations [Internet] Brussels, Belgium: International Committee of Resuscitation (ILCOR) Pediatric and Basic Life Support Task Forces XXX. Available from: http//ilcor.org

Methodological Preamble

The continuous evidence evaluation process for the production of Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review {Ashoor, 2017, 50300} – PROSPERO citation) conducted by Damien Ihrig (IS) and Dianne Atkins (TF member) with involvement of clinical content experts. Three databases were searched: PubMed, EMBASE and Cochrane. Evidence from the pediatric literature was sought. Two members of the writing group did an initial review of the author/title review of the citations. The final selection of included articles was done by the entire writing group. The search identified (initial search on Jan 25, 2021, repeated on 11/3/2021) 1,163 unique articles of which 76 were selected for full text review. Of these 4 satisfied all inclusion and exclusion criteria. Inclusion criteria included all age < 18, application of an AED or shock delivered by a lay rescuer. Exclusion criteria included age > 18, combined adult and pediatric data, and combined lay rescuer and first responder response,

Three papers {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126} were from the CARES database in the United States. The data reported did not correspond to the PICOST question in a usable manner. The CARES database provided the raw data encompassing the dates of the papers and we calculated the RR from these data. There were several studies from the Japanese FDMA with overlapping dates for data inclusion. The most time inclusive study was chosen to avoid duplication of data. {Kiyohara 2018 122}

PICOST

Inclusion of Infants, Children, and Adolescents in Public Access Programs

The PICOST (Population, Intervention, Comparator, Outcome, Study Designs and Timeframe)

Population: Infants, children and adolescents with non-traumatic out-of-hospital cardiac arrest (OHCA)

Intervention: Application of or shock delivery from an automated external defibrillator (AED) by lay rescuers.

Comparators: Standard care by lay rescuer without AED application.

Outcomes: Improve ROSC, hospital discharge and neurologic status, all other outcomes as available.

Study Designs: Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) are eligible for inclusion. Unpublished studies (e.g., conference abstracts, trial protocols) are excluded

Timeframe: All years and all languages were included as long as there was an English abstract.

PROSPERO Registration CRD42017080475

Consensus on Science

Meta-analysis Not Possible Option:

• Unadjusted relative risks were calculated from the raw data provided by the CARES database from 2013-2017. These are the data reported in 3 studies {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126}, but were not reported in a manner that answered the PICOST. From the raw data, we calculated unadjusted RRs for survival to hospital discharge with CPC 1-2 and survival to hospital discharge.
• The data from the CARES registry {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126} reported AED application, while the data from the Japanese FDMA reported AED shock delivery by lay rescuers {Kiyohara 2018 122}.

For the critical outcome of one month survival with a CPC of 1-2, in children 6-17 years of age

For the critical outcomes of CPC 1-2 at 1 month (n=1 study) {Kiyohara 2018 122}, we identified only observational studies. The overall quality of evidence was rated as very low for all outcomes primarily due to a serious risk of bias and serious imprecision. The study was at a serious risk of bias due to confounding and selection bias. Because of this availability of only unadjusted RR, no meta-analyses could be performed. The unadjusted RR of one month survival with a CPC of 1-2 in children 6-17 years was 12.12 (95% C 4.97-17.12), resulting in 537 more per 1000 (absolute 95% CI 192 more to 778 more).

For the critical outcome of survival to hospital discharge with a CPC of 1-2, in children 1-12 years of age

For the critical outcomes of survival to hospital discharge (n=3 studies) with a CPC of 1-2 {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126}, we identified only observational studies. The overall quality of evidence was rated as very low for all outcomes primarily due to a serious risk of bias and serious imprecision. The individual studies were all at a serious risk of bias due to confounding and selection bias. Because of this availability of only unadjusted RR, no meta-analyses could be performed. The unadjusted RR of survival to hospital discharge with a CPC of 1-2 age 1-12 years was 3.85 (95% C 2.69-5.5), resulting in 335 more per 1000 (absolute 95% CI 199 more to 529 more).

For the critical outcome of survival to hospital discharge with a CPC of 1-2 in children 13-18 years of age

For the critical outcomes of survival to hospital discharge with CPC 1-2 in children 13-18 years of age (n=3 studies) {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126}, we identified only observational studies. The overall quality of evidence was rated as very low for all outcomes primarily due to a serious risk of bias and serious imprecision. The individual studies were all at a serious risk of bias due to confounding and selection bias. Because of this availability of only unadjusted RR, no meta-analyses could be performed. The unadjusted RR of survival to hospital discharge with CPC of 1-2 in children 13-18 years of age was 3.75 (95% CI 2.97-4.72), resulting in 444 more/1000 (absolute 95% CI 319 more to 602 more).

For the critical outcome of survival to hospital discharge with a CPC of 1-2, in children < 1 year of age

For the critical outcomes of survival to hospital discharge with a CPC of 1-2 in children < 1 year of age (n=3 studies) {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126}, we identified only observational studies. The overall quality of evidence was rated as very low for all outcomes primarily due to a serious risk of bias and serious imprecision. The individual studies were all at a serious risk of bias due to confounding and selection bias. Because of this availability of only unadjusted RR, no meta-analyses could be performed. The unadjusted RR of survival to hospital discharge with CPC of 1-2 in children < 1 year of age was 1.82 (95% CI 0.28-11.96), resulting in 38 more per 1000 (absolute 95% CI 33 fewer to 501 more).

For the critical outcome of survival to hospital discharge, in children age 1-12 years of age

For the critical outcomes of survival to hospital discharge in children 1-12 years of age (n=3 studies) {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126}, we identified only observational studies. The overall quality of evidence was rated as very low for all outcomes primarily due to a serious risk of bias and serious imprecision. The individual studies were all at a serious risk of bias due to confounding and selection bias. Because of this availability of only unadjusted RR, no meta-analyses could be performed. The unadjusted RR of survival to hospital discharge in children 1-12 years of age was 3.04 (95% CI 2.18-4.25), resulting in 240 more/1000(absolute 95% CI 138 more to 382 more).

For the critical outcome of survival to hospital discharge, in children age 13-18 years of age

For the critical outcomes of survival to hospital discharge in children age 13-18 years of age (n=3 studies) {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126}, we identified only observational studies. The overall quality of evidence was rated as very low for all outcomes primarily due to a serious risk of bias and serious imprecision. The individual studies were all at a serious risk of bias due to confounding and selection bias. Because of this availability of only unadjusted RR, no meta-analyses could be performed. The unadjusted RR of survival for hospital discharge 13-18 years of age was 3.38 (95% CI 2.74-4.16), resulting in 338 more/1000(absolute 95% CI 248more to 450 more).

For the critical outcome of survival to hospital discharge, in children < 1 year of age

For the critical outcomes of survival to hospital discharge in children < 1 year of age (n=3 studies) {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126}, we identified only observational studies. The overall quality of evidence was rated as very low for all outcomes primarily due to a serious risk of bias and serious imprecision. The individual studies were all at a serious risk of bias due to confounding and selection bias. Because of the availability of only unadjusted RR, no meta-analyses could be performed. The unadjusted RR of survival to hospital discharge < 1 year of age was 1.43 (95% CI 0.22-9.37), resulting in 25 more/1000(absolute 95% CI 46 fewer to 488 more).

For the critical outcome of CPC 1-2 at hospital discharge of Bystander CPR associated with AED use in children of 0-17 years of age

For the critical outcomes of survival to hospital discharge with CPC 1-2 for children 0-17 years of age who received bystander CPR as well as AED application (n=1 study) {Naim 2017 113}, we identified only observational studies. The overall quality of evidence was rated as very low for all outcomes primarily due to a serious risk of bias and serious imprecision. Because of this availability of only unadjusted RR, no meta-analyses could be performed. The unadjusted RR of survival for hospital discharge with CPC 1-2 with bystander CPR and AED use, age 0-17, the RR was 1.49 (95% CI 1.11-1.97) resulting in 51 more/1000 (absolute 95% CI 11-101 more).

For the critical outcome of survival to hospital discharge of Bystander CPR associated with AED use in children 0-17 years of age

For the critical outcomes of survival to hospital discharge in children 0-17 years of age who received bystander CPR as well as AED application (n=1 study) {Naim 2017 113}, we identified only observational studies. The overall quality of evidence was rated as very low for all outcomes primarily due to a serious risk of bias and serious imprecision. Because of this availability of only unadjusted RR, no meta-analyses could be performed. The unadjusted RR of survival for hospital discharge with bystander CPR and AED use, age 0-17, the RR was 1.55 (95% CI 1.12-2.12) resulting in 46 more/1000 (absolute 95% CI10-93 more).

Table 1 summarizes the relative risks for the critical outcomes CPC 1-2 at one month, CPC 1-2 at Hospital Discharge and Hospital Discharge and Bystander CPR with AED.

TABLE 1 Summary of RR for all Outcomes

*{Naim 2017 113; Naim 2019 e012637; Griffis 2020 126}

^ {Naim 2017 113}

# {Kiyohara 2018 122}

Treatment Recommendations

We suggest the use of an AED by lay rescuers for all children over age 1 year suffering non-traumatic out-of-hospital cardiac arrest (weak recommendation, very low certainty evidence).

We cannot make a recommendation for or against the use of an AED by lay rescuers for all children below age 1 year suffering non-traumatic out-of-hospital cardiac arrest

Justification and Evidence to Decision Framework Highlights

• This topic was chosen because of a growing literature on the inclusion of children in Public Access Defibrillation programs, the growing use of AEDs for children generally, and the increasing availability of AEDs in the community.
• In reviewing the literature for this topic, we noted that there were several papers arising from the same data source (Japanese FDMA) with differing sub-populations but overlapping time intervals. We chose the most inclusive study for this systematic review.
• Unadjusted relative risks were calculated from the data provided by the CARES database from 2013-2017. These are the data reported in 3 studies {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126}, but were not reported in a manner that answered our PICOST. , We calculated unadjusted RR for survival from the raw data

In making these recommendations, the PLS Task Force considered the following:

AED vs no AED by lay rescuers > 1 year

• We did not identify any RCTs, only observational data.
• We considered the large number of patients (7591) in the CARES database {Naim 2017 113; Naim 2019 e012637; Griffis 2020 126} who suffered cardiac arrest but the very small number of patients who had an AED applied (120). Similar findings were apparent in the Japanese FDMA study {Kiyohara 2018 122}: 5,899 total patients and 220 received a bystander AED shock. The RRs in favor of AED application by a lay rescuer was strongly in favor of use of the AED for children > age 1.
• In making a weak recommendation, we considered the strongly positive RR and the number needed to treat for improved hospital discharge and favorable neurologic outcomes at hospital discharge or 30 days, but recognized the small numbers of patients who had an AED applied. There may be significant selection bias in those children who had the AED applied. The rescuers who applied the AED may be those with a greater skillset and provide higher quality CPR, than those with less experience.
• In addition to treating shockable rhythms, AEDs provide instructions about CPR which may aid lay rescuers in performing CPR even if a shock is not required and dispatch instructions are not available.
• We did not evaluate outcomes with chest compression only versus chest compressions with rescue breaths because of the low numbers of children who had AEDs applied.
• The TF had substantial discussion about the potential for harm in applying an AED by delaying CPR and increasing the number and duration of pauses. In making a final recommendation, we acknowledged that the data were from non-selected rescuers and those events likely occurred, but the RR were still significantly in favor of AED application.

AED vs no AED by lay rescuers < 1 year

• The Task Force had a robust discussion about this treatment recommendation. In making no recommendation about the use of AEDs in children < 1, we considered the RR which was not statistically significant. The very few patients (12) and poor survival (only 1) was insufficient to make any recommendation and likely resulted created a Type II error.
• The TF recognized that there is a small population of infants who do have shockable rhythms, mainly those with inherited arrhythmia syndromes or as a result of hypoxia. These infants could benefit from AED application.
• In the absence of dispatch CPR instructions, AEDs assist lay rescuers by providing CPR instructions which could increase survival in infants without shockable rhythms.

Knowledge Gaps

• There are no randomized controlled trials of AED use in children.
• There are limited data on the interaction between high-quality CPR with and without AED application. This is particularly y important in light of the importance of rescue breaths with chest compressions in pediatric cardiac arrest.
• There are limited data on whether AED application alters outcomes based on the type of CPR provided, i.e., chest compression only or standard CPR with compressions and rescue breathing.
• Only short term/surrogate outcomes were evaluated, future studies should document survival/neurologically intact survival beyond 30 days.
• There is no information about possible advantages of using the pediatric modifications for the younger children, especially those < 8 years or 25 kg
• The application of an AED may be beneficial beyond shock delivery, such as directing the rescuer to the appropriate actions and performing AED. The mechanisms potential human factors and behavioral change are not understood.

Attachment

Evidence-to-Decision Table: Should Automatic external defibrillators application vs. no application be used for pediatric cardiac arrest by lay rescuers?

References

Griffis H, Wu L, Naim MY, Bradley R, Tobin J, McNally B, et.al. Characteristics and outcomes of AED use in pediatric cardiac arrest in public settings: The influence of neighborhood characteristics. Resuscitation. 2020;146:126-131.

Kiyohara K, Masahiko N, Sata Y, Kojimahara N, Yamaguchi N, Iwami T, etal. Ten-year trends of public access defibrillation in Japanese School-aged patients having neurologically favorable survival after out-of-hospital cardiac arrest. AM J Cardiol. 2018;122:890-897.

Naim MY, Burke RV, McNally BF, Song L, Griffis HM, Berg RA, etal. Association of bystander cardiopulmonary resuscitation with overall and neurologically favorable survival after pediatric out-of-hospital cardiac arrest in the United States. JAMA Pediatr.2017;171:133-141.

Naim MY, Griffis HM, Burke RV, McNally BF, Song L, Berg RA. Race, ethnicity and neighborhood characteristics are associated with bystander cardiopulmonary resuscitation I pediatric out-of-hospital arrest in the United States: A study from CARES. JAHA. 2019;8 e012637, 1-12.