Minutes Matter: The Power of Timely Opioids in Sickle Cell Pain Relief

Children with sickle cell disease (SCD) frequently suffer acute painful episodes (“pain crises”) that bring them to emergency departments (EDs). Expert guidelines from the National Heart, Lung, and Blood Institute (NHLBI) and the American Society of Haematology (ASH) recommend that the first parenteral (injectable) opioid be given within 60 minutes of ED arrival, with subsequent doses every 30-60 minutes until pain control is achieved.¹ Prior to this study, evidence that earlier opioid administration actually leads to fewer hospital admissions was limited.²

Nemours Children’s Health in Wilmington, Delaware conducted a study to assess whether timely administration of opioids—specifically the time to first dose and the interval to the second dose—is associated with lower odds of hospitalization among children under age 19 who present to EDs with uncomplicated SCD pain (i.e., pain crises without other SCD complications).³

The study conducted was a multicenteric, cross-sectional study over a period of 2 years from 2019 to 2021. The data source was the Paediatric Emergency Care Applied Research Network (PECARN) registry.⁴ About 2538 children younger than 19 years were part of this study across 12 children's hospitals with comprehensive SCD centres. Time from ED arrival to first opioid dose ≤ 60 min vs > 60 min was evaluated. The time interval between the first and second opioid dose was also evaluated at cutoff thresholds of ≤30, ≤45, and ≤60 minutes. And the outcome was measured in terms of the requirement for hospitalization versus discharge. The study showed that administering the first opioid dose on time, when analyzed in isolation, was associated with fewer hospital admissions (odds ratio [OR], 0.84). Among the 7,853 visits (85.1%) in which children received at least two opioid doses, timely delivery of the first dose still lowered the likelihood of hospitalization even if the second dose was delayed beyond 30 minutes (OR, 0.85) or 45 minutes (OR, 0.84). The greatest reduction in admission risk occurred when the first dose was timely and the second dose followed quickly: within 30 minutes (OR, 0.62), within 45 minutes (OR, 0.70), or within 60 minutes (OR, 0.78).

Hence, the study concluded that timely opioid administration in the ED for children with uncomplicated SCD pain is significantly associated with a lower likelihood of hospital admission. The greatest reduction in admissions comes when both the first dose is given within 60 minutes of arrival and the second dose within 30 minutes of the first. However, even when the second dose is delayed beyond these thresholds (45 or 60 minutes), there is still a measurable benefit.

These findings lend empirical support to existing guidelines (NHLBI, ASH) that have recommended rapid initial and subsequent dosing guidelines that, prior to this, were based largely on expert opinion and smaller single‐site studies.

References:

1. Brandow AM, Carroll CP, Creary S, Edwards-Elliott R, Glassberg J, Hurley RW, Kutlar A, Seisa M, Stinson J, Strouse JJ, Yusuf F. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood advances. 2020 Jun 23;4(12):2656-701.
   
   
2. Ballas SK. Update on pain management in sickle cell disease. Hemoglobin. 2011 Oct 1;35(5-6):520-9.
   
   
3. Gwarzo I, Coleman KD, McKinley K, et al. Opioid Timeliness in the Emergency Department and Hospitalizations for Acute Sickle Cell Pain. JAMA Pediatrics. 2025. DOI:10.1001/jamapediatrics.2025.2967
   
   
4. Brousseau DC, Alpern ER, Chamberlain JM, et al; Pediatric Emergency Care Applied Research Network (PECARN). A multiyear cross-sectional study of guideline adherence for the timeliness of opioid administration in children with sickle cell pain crisis. Ann Emerg Med. 2020;76(3S):S6-S1