Target Temperature Management Following Pediatric Cardiac Arrest: A Systematic Review and Network Meta-Analysis to Compare the Effectiveness of the Length of Therapeutic Hypothermia

We aimed to compare the efficacy of therapeutic hypothermia for 24, 48, and 72 h, and normothermia following pediatric cardiac arrest. We searched the Cochrane Central Register of Controlled Trials, MEDLINE via Ovid, World Health Organization International Clinical Trials Platform Search Portal, and ClinicalTrials.gov. from their inception to December 2021. We included randomized controlled trials and observational studies evaluating target temperature management (TTM) in children aged < 18 years with the return of spontaneous circulation (ROSC) after cardiac arrest. We compared four intervention groups (normothermia, therapeutic hypothermia for 24 h (TTM 24h), therapeutic hypothermia for 48 h (TTM 48h), and therapeutic hypothermia for 72 h (TTM 72h)) using network meta-analysis. The outcomes were survival and favorable neurological outcome at 6 months or more. Seven studies involving 1008 patients and four studies involving 684 patients were included in the quantitative synthesis of survival and neurological outcome, respectively. TTM for 72 h was associated with a higher survival rate, compared to normothermia (RR 1.75 (95% CI 1.27-2.40)) (very low certainty), TTM 24h (RR 1.53 (95% CI 1.06-2.19)) (low certainty), and TTM 48h (RR 1.54 (95% CI 1.06-2.22)) (very low certainty). TTM for 72 h was also associated with favorable neurological outcomes compared with normothermia (RR 9.36 (95% CI 2.04-42.91)), or TTM 48h (RR 8.15 (95% CI 1.6-40.59)) (all very low certainty). TTM for 24 h was associated with favorable neurological outcome, compared with normothermia (RR 8.02 (95% CI 1.28-50.50)) (very low certainty). In the ranking analysis, the hierarchies for efficacy for survival and favorable neurological outcome were TTM 72h > TTM 48h > TTM 24h > normothermia. Although prolonged therapeutic hypothermia might be effective in pediatric patients with ROSC after cardiac arrest, the evidence to support this result is only weak to very weak. There is no conclusive evidence regarding the effectiveness and length of therapeutic hypothermia and high-quality RCRs comparing long-length therapeutic hypothermia to short-length hypothermia and normothermia are needed.