Early vs delayed opioid administration for pediatric sickle cell vaso-occlusive crisis: A systematic review and meta-analysis.

IMPORTANCE: Sickle cell disease is frequently complicated by vaso-occlusive events, which represent one of the leading causes of acute pain and emergency care utilization in pediatric patients. However, there is limited and inconsistent data about the time to administer opioids in pediatric patients with sickle cell vaso-occlusive episodes (VOE).

OBJECTIVE: We aim to conduct a systematic review and meta-analysis to compare early and delayed opioid administration in pediatric patients with VOE.

DATA SOURCES: We systematically searched PubMed, Embase, and Cochrane Library from inception to November 2025.

STUDIES SELECTION: Randomized controlled trials or observational studies comparing early and delayed opioid administration in pediatric patients with sickle cell VOE. Five reviewers independently screened titles and abstracts, followed by full-text evaluation of potentially eligible articles. Disagreements were resolved through discussion and adjudication by a third reviewer.

DATA EXTRACTION AND SYNTHESIS: We followed PRISMA guidelines. Data were independently extracted by multiple reviewers.

MAIN OUTCOMES AND MEASURES: Our main endpoint was hospital admission from the index emergency department (ED) visit. Additional endpoints included ED discharge, ED length of stay, and pain reassessment. Risk ratios (RRs) were calculated for binary outcomes and mean differences (MDs) or standardized mean differences (SMD) for continuous outcomes with 95% confidence intervals (CIs). We performed a random-effect meta-analysis for all outcomes using R software (version 4.3.2).

RESULTS: Six studies comprising 3367 patients were included, of whom 67% received early and 32% delayed opioid. The mean age was 9-16 years, and males accounted for 50% of participants. There was no significant difference when comparing early vs delayed opioid administration for hospital admission (RR 0.96; 95% CI 0.85 to 1.10), ED discharge (RR 1.04, 95% CI 0.89 to 1.22), ED length of stay (MD -6.02 min; 95% CI -1.22,45 to 110.42) and pain reassessment (SMD 0.85; 95% CI -1.92 to 3.63). A subgroup analysis comparing ≤60 min with ≥60 min of opioids administration also showed no difference between intervention arms. Individual studies showed potential benefits with timely repeat opioid dosing and the use of intranasal fentanyl (INF).

CONCLUSIONS AND RELEVANCE: Our analysis showed no difference comparing early and delayed opioid administration in pediatric patients with sickle cell related VOE across hospital admission, ED discharge, ED length of stay, and pain reassessment.