2025 4080 21 DRAFT Et D vasopressor use Final 12 2 2025Conflict 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 applicable
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 applicable
CoSTR Citation
Kurosawa H, Ong G, Raymond T, Atkins DL, Acworth JP, Scholefield BS on behalf of the International Liaison Committee on Resuscitation Pediatric Life Support Task Force. Vasopressor use during cardiac arrest in children - Pediatric Consensus on Science with Treatment Recommendations [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Pediatric Advanced Life Support Task Force, 2025 January xxxxx. Available from: http://ilcor.org
Methodological Preamble and Link to Published Systematic Review
The continuous evidence evaluation process for the production of Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review of vasopressor use during cardiac arrest in children (Kurosawa 2024 – PROSPERO CRD42024596959), by clinical content experts of the Pediatric Life Support Task Forces of ILCOR, with assistance from Lars Eriksson, Outreach Librarian, University of Queensland, Australia. Evidence was sought and considered by members of the Pediatric Life Support Task Force group. These data were taken into account when formulating the Treatment Recommendations.
Systematic Review
Kurosawa H, Ong G, Raymond T on behalf of the International Liaison Committee on Resuscitation Pediatric Life Support Task Force. Vasopressor use during cardiac arrest in children - Pediatric Consensus on Science with Treatment Recommendations [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Pediatric Advanced Life Support Task Force, 2025 January xxxxx. Available from: http://ilcor.org (in preparation)
PICOST
The PICOST (Population, Intervention, Comparator, Outcome, Study Designs and Timeframe)
Population: Infants and children (excluding newborns) in cardiac arrest who received chest compression in any setting.
Intervention: Any use of vasopressors (epinephrine, vasopressin, combination of vasopressors).
Comparators: No vasopressor use.
Outcomes: Clinical outcomes, including short-term survival and neurological outcomes (eg, hospital discharge, 28 days, 30 days, and 1 month), and long-term survival and neurological outcomes (eg, 3 months, 6months, and 1 year).
Study Designs: Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) and case series with a minimum of 5 cases were eligible for inclusion. Unpublished studies (e.g., conference abstracts, trial protocols) were excluded. All relevant publications in any language were included as long as there was an English abstract.
Timeframe: All years were included. The last search was performed on 30 April 2025.
PROSPERO Registration CRD42024596959
Consensus on Science
Five studies satisfied were eligible for inclusion.. Two propensity score matched observational studies1,5 provided very low- to low-certainty evidence. Both studies were in the out-of-hospital setting and compared outcomes of children who received epinephrine with children who did not. The remaining three observational studies2,3,6 did not adjust for epinephrine administration in their analyses and were therefore excluded from the meta-analysis. None of these provided clinical trial data. No eligible studies were found from the IHCA setting.
Studies comparing no epinephrine to administration of epinephrine in pediatric out-of-hospital cardiac arrest:
Favourable neurological survival at 1 month (Cerebral Performance Category)
For this critical outcome, we identified low certainty data (downgraded for serious risk of bias, and serious indirectness) from 1 propensity-matched cohort study5 involving 608 patients (aged 8-17 years) which showed no significant difference associated when epinephrine was administered compared to when no epinephrine was administered (adjusted Relative Risk (aRR) 1.56 [95% CI 0.61 to 3.96]). There was an absolute risk difference of 15 more patients with favourable neurological survival at 1-month per 1,000 resuscitations [95% CI: 11 fewer to 92 more].
Favourable neurological survival at hospital discharge (Modified Rankin Score)
For this critical outcome, we identified low certainty data (downgraded for serious risk of bias, and serious indirectness) from 1 propensity-matched cohort study1 involving 1426 patients (aged <18 years) which showed no significant difference associated when epinephrine was administered compared to when no epinephrine was administered (aRR 1.23 [95% CI 0.67 to 2.25]). There was an absolute risk difference of 9 more patients with favourable neurological survival at hospital discharge per 1,000 resuscitations [95% CI: 13 fewer to 50 more].
Survival at 1 month
For this critical outcome, we identified low certainty data (downgraded for serious risk of bias, and serious indirectness), from 1 propensity-matched cohort study5 involving 608 patients (aged 8-17 years) which showed no significant difference associated when epinephrine was administered compared to when no epinephrine was administered (aRR 1.13 [95% CI 0.67 to 1.93]). There was an absolute risk difference of 10 more survivors per 1,000 resuscitations [95% CI: 27 fewer to 78 more].
Survival to hospital discharge
For this critical outcome, we identified low certainty data (downgraded serious risk of bias, and serious indirectness), from 1 propensity-matched cohort study1 involving 1426 patients (<18 years) which showed no significant difference associated with survival at hospital discharge when epinephrine was administered compared to when no epinephrine was administered (aRR 1.38 [95% CI 0.87 to 2.19]). There was an absolute risk difference of 19 more survivors per 1,000 resuscitations [95% CI: 7 fewer to 64 more].
Pre-hospital return of spontaneous circulation (ROSC)
For this important outcome, we identified very low certainty data (downgraded for serious risk of bias, very serious inconsistency, and serious indirectness), from the two cohort studies1,5, involving 2034 patients ( <18 years) which showed a significant association with ROSC when epinephrine was administered compared to when no epinephrine was administered (Relative Risk of 1.64 [95% CI 1.26 to 2.13], p<0.001).
Summary of findings
Acknowledging the very low- to low-certainty evidence, the currently available data suggest that the critical outcomes (favourable neurological survival, and survival to discharge or at 1 month) were not significantly better or worse when epinephrine was given in pediatric out-of-hospital cardiac arrest. However, the administration of epinephrine in pediatric out-of-hospital cardiac arrest was significantly associated with improved ROSC.
Treatment Recommendations
We suggest the use of epinephrine in pediatric out-of-hospital cardiac arrest. [weak recommendation, very low-certainty evidence].
We suggest the use of epinephrine in pediatric in-hospital cardiac arrest. [good practice statement]
Justification and Evidence to Decision Framework Highlights
While there is limited evidence in pediatric out-of-hospital cardiac arrest, administration of epinephrine was associated with improved ROSC but not with other neurological and survival outcomes. While there was no data available for the IHCA setting, the Task Force considered that the OHCA data should be used as indirect evidence.
The task force acknowledged that the included studies were from settings with advanced Emergency Medical Services. In similar settings, the administration of epinephrine as part of advanced pediatric life support for pediatric out-of-hospital cardiac arrest should be continued but also further evaluated.
However, there is a paucity of studies looking at the resources required to train, maintain skillsets, and provide the necessary equipment for EMS systems to administer epinephrine in pediatric out-of-hospital cardiac arrests. Future studies should be undertaken to evaluate the ability of EMS systems to provide advanced care in pediatric out-of-hospital cardiac arrest, to better inform equity issues of such systems in both resource-rich healthcare but also resource-limited countries.
Knowledge Gaps
Specific undesirable effects (outside of the lack of reported neurological or survival benefits) were not reported in the studies identified. Adverse outcomes from administration of epinephrine have previously been reported.4
Further studies should address whether specific sub-populations might potentially benefit (or not) from the administration of epinephrine in pre-hospital settings.
The cost-effectiveness and feasibility of the provision of advanced pediatric life support in pre-hospital settings to facilitate the administration of epinephrine in pediatric out-of-hospital cardiac arrest, (while ensuring high-quality basic life support) should be explored in all healthcare settings, including in LMICs.
Future studies would benefit from including outcome measures consistent with the P-COSCA recommendations.
Attachment: EtD 2025 4080 21 DRAFT Et D vasopressor use Final 12 2 2025
References
1. Amoako J, Komukai S, Izawa J, Callaway CW, Okubo M. Evaluation of Use of Epinephrine and Time to First Dose and Outcomes in Pediatric Patients With Out-of-Hospital Cardiac Arrest. JAMA Netw Open. 2023;6:e235187. doi: 10.1001/jamanetworkopen.2023.5187
2. Banerjee P, Ganti L, Stead TG, Vera AE, Vittone R, Pepe PE. Every one-minute delay in EMS on-scene resuscitation after out-of-hospital pediatric cardiac arrest lowers ROSC by 5. Resusc Plus. 2021;5:100062. doi: 10.1016/j.resplu.2020.100062
3. Dieckmann RA, Vardis R. High-dose epinephrine in pediatric out-of-hospital cardiopulmonary arrest. Pediatrics. 1995;95:901-913.
4. Eriksson CO, Bahr N, Meckler G, Hansen M, Walker-Stevenson G, Idris A, Aufderheide TP, Daya MR, Fink EL, Jui J, et al. Adverse Safety Events in Emergency Medical Services Care of Children With Out-of-Hospital Cardiac Arrest. JAMA Netw Open. 2024;7:e2351535. doi: 10.1001/jamanetworkopen.2023.51535
5. Matsuyama T, Komukai S, Izawa J, Gibo K, Okubo M, Kiyohara K, Kiguchi T, Iwami T, Ohta B, Kitamura T. Pre-Hospital Administration of Epinephrine in Pediatric Patients With Out-of-Hospital Cardiac Arrest. J Am Coll Cardiol. 2020;75:194-204. doi: 10.1016/j.jacc.2019.10.052
6. Rodriguez-Nunez A, Lopez-Herce J, Garcia C, Carrillo A, Dominguez P, Calvo C, Delgado MA, Spanish Study Group for Cardiopulmonary Arrest in C. Effectiveness and long-term outcome of cardiopulmonary resuscitation in paediatric intensive care units in Spain. Resuscitation. 2006;71:301-309. doi: 10.1016/j.resuscitation.2005.11.020