(ORLANDO, Dec. 6, 2025) A new study finds that only one in three patients visiting emergency departments (EDs) for severe pain associated with sickle cell disease received appropriate opioid-based pain-relieving medications within the first hour as recommended by the American Society of Hematology (ASH) and National Heart, Lung, and Blood Institute (NHLBI) .
Based on data from several hundred medical centers across the United States, the research represents the first large, national study to assess guideline adherence across diverse EDs. It shows substantially lower guideline adherence than has been reported in smaller studies focused on pediatric specialty EDs.
The results suggest that a majority of patients experience prolonged suffering while waiting to receive opioids as recommended for pain. Patients over age 19, female patients, and those with public health insurance were less likely to receive guideline-adherent care compared with younger patients, male patients, and those with private health insurance.
"We want to call attention to the fact that there is huge room for improvement across the board, particularly in general EDs that primarily attend to adults," said lead study author Ibrahim Gwarzo, MD, DrPH, MBBS, research scientist at Nemours Children's Health, Delaware Valley and research assistant professor Sidney Kimmel Medical College at Thomas Jefferson University. "Some strategies for improvement include greater dissemination of the guidelines, integration of the sickle cell care protocol into general EDs, and continued advocacy for this population."
Sickle cell disease causes red blood cells to become sickle-shaped, and when these misshapen blood cells accumulate in a vessel, they can cause episodes of severe pain, known as vaso-occlusive crises. ASH and NHLBI guidelines recommend that patients experiencing vaso-occlusive crises receive opioid pain medication within 60 minutes of arrival at a hospital ED. After the initial dose, ASH guidelines recommend evaluating the patient's pain level and administering further doses as needed at intervals of 30-60 minutes, while NHLBI guidelines recommend subsequent evaluations and doses at intervals of 30 minutes.
To study the implementation of these guidelines in practice, researchers analyzed electronic health records on 398,895 ED visits for vaso-occlusive crises between 2019 and 2024 in which at least one opioid pain medication was administered. These visits occurred among 41,547 unique patients at 233 medical centers.
The results showed that the first opioid dose was given within 60 minutes of arrival in just 32.5% of visits. Among the approximately three-quarters of visits in which multiple doses of opioid medications were administered, the timing of the second dose also failed to meet guideline recommendations in most instances. In these cases, the second dose was administered within 60 minutes after the first dose (in accordance with ASH guidelines) 36% of the time, while the second dose was administered within 30 minutes after the first dose (in accordance with NHLBI guidelines) just 9% of the time.
Researchers found that patients younger than 19 received guideline-adherent care far more often – in 52% of cases – compared with older patients, who received timely treatment in just 30% of cases. They suggested that clinicians' familiarity with sickle cell treatment protocols may play a role in this disparity.
"Generally, pediatric EDs might be more familiar with sickle cell disease because those are typically near more academic sites and may have more specialized care, as opposed to freestanding adult or general EDs in more remote locations where the exposure to sickle cell disease is pretty limited," said Dr. Gwarzo.
As a result of the ongoing epidemic of opioid dependence, ED clinicians sometimes encounter patients who request opioid medications as a result of their dependence but are not actually experiencing severe pain. Given this context, researchers suggested that some clinicians may be concerned about giving opioid medications to people they suspect of opioid dependence.
"One of the challenges of identifying sickle cell disease pain is that there is no biomarker for it, and as a provider, you rely on what the patient tells you about how severe the pain is," said Dr. Gwarzo. "Providers are more likely to be hesitant to administer opioids for the adult population than for little kids." He added that implicit bias may also influence a clinician's decision on whether to give opioids when a patient visits the ED for pain.
The study found that guideline adherence was higher when patients were male, with 37% of male patients receiving their first dose within 60 minutes compared with 29% of female patients. Adherence was also higher among the one-quarter of patients who were privately insured compared with those on public insurance. Arriving at the ED overnight was also associated with higher adherence, perhaps because patient volumes are generally lower at night.
Opiate medications can be administered orally, injected, or infused. The study showed no difference in guideline adherence by route of administration for the first dose, but adherence was significantly higher for the second dose when medications were given orally (which showed guideline adherence in 24% of cases) compared with injection or infusion (less than 8%).
Overall, researchers said that the findings underscore the importance of improving clinician training and awareness to ensure people living with sickle cell disease receive recommended treatments in a timely manner, wherever they receive treatment. Dr. Gwarzo added that further studies could assess interventions to improve guideline adherence and elucidate the benefits of compliance, such as potential reductions in hospitalization.
Dr. Ibrahim Gwarzo, of Nemours Children's Health, Delaware Valley and Sidney Kimmel Medical College at Thomas Jefferson University, will present this study on Saturday, December 6, 2025, at 9:30 a.m. Eastern time in W311E-H of the Orange County Convention Center at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.
