Feasibility, Safety and Effectiveness of Intranasal Fentanyl in the Treatment of Acute Pain Episodes Among Adults with Sickle Cell Disease: A Retrospective Single Center Study

Introduction: The management of acute moderate to severe pain episodes (APE) in patients with sickle cell disease (SCD) involves the rapid administration of opioid analgesia within 60 minutes of presentation, as recommended by the National Heart, Lung, and Blood Institute, and the American Society of Hematology. Intranasal fentanyl (INF) is therefore an appealing option for its non-invasive administration, bypassing the need for IV access, as well as for its rapid onset of action (<10 min). The use of INF has been widely adopted in the pediatric SCD population, where it has been associated with more rapid administration of analgesia and early discharge from the ED. Despite this, there is currently a paucity of evidence to support its use in adults with SCD. Since 2020, the CHUM (Centre Hospitalier de l’Université de Montréal) has instituted a standardized INF protocol for the management of patients with severe non-complicated APE referred to the medical day hospital (MDH).

Objective: The aim of this study is to describe the feasibility, safety and effectiveness of INF in managing APE in adults with SCD at our center.

Methods: A retrospective chart review was conducted at the CHUM (Montréal, Canada), a tertiary care center treating 586 patients with SCD. An administrative list was used to identify patients with at least one visit to the MDH for management of APE between March 2020 and June 2024, and patients who were managed with INF were identified. Electronic medical records were accessed to extract patient characteristics, variables pertaining to the process (time to first dose of analgesia, duration of stay in MDH), safety (respiratory depression, hypotension, or bradycardia) and effectiveness (serial pain scores and admission rate).

Results: Between March 2020 and June 2024, 23 patients with SCD were treated with INF in the MDH over a total of 38 visits. INF was administered as a fixed dose of 100 mcg, via a Mucosal Atomizer Device. Seventeen (74%) patients were female, and the median age at presentation was 26 years (range: 18-58). Genotype distribution was as follows: 15 (66%) of patients with HbSS, 5 (21%) with HbSC, and 3 (13%) with HbSβ⁺. Twenty (86%) patients were receiving treatment with hydroxyurea, and 5 (21%) were undergoing regular erythrapheresis. Virtually all patients had previous exposure to opioids, and 3 (13%) patients had chronic exposure to long-acting opioids.

On presentation, all patients received co-analgesia with non-steroidal anti-inflammatory drugs, and all received subsequent doses of parenteral opioids, with a median dose of 12.5 mg (5-50 mg) morphine equivalents. The median time to administration of INF from presentation was­­ 48 minutes (10-125 min). The median duration of stay in MDH was 4 hours (1.5-6.7 hours). No patients experienced cardiorespiratory adverse events, nor alterations in mental status. The most common side effects reported were nausea and pruritus resulting in the administration of antiemetics or antihistamines in 7 (18%) and 4 (10%) of visits, respectively.

The median pain score on presentation was 7 (4-10) and pain scores at 1 hour after INF and at discharge from MDH were 6 (1-8) and 3 (0-8), respectively. This represented a median 60% (0-100%) reduction in pain score at the time of discharge and only 4 (11%) visits resulted in hospital admission due to inadequate pain control. Ten patients (43%) had more than 1 visit during the observation period, and 50% of these patients received INF again on their subsequent visits.

Conclusion: To our knowledge, this is the first study reporting on the use of INF in adults with SCD in a MDH setting. In this small cohort, INF appeared to be feasible, safe, and effective in the management of APE in adults with SCD presenting to the MDH and was acceptable among patients. Administration of INF was rapid, respecting recommended delays, and very few visits required admission or ED referral for additional analgesia. The use of INF has been widely accepted in the pediatric population with SCD and it has been shown to be effective in adults with chronic and cancer related pain. Standardized protocols which incorporate INF should therefore be considered in the management of adults with SCD, and further research on its relative effectiveness compared to traditional parenteral routes of administration, as well as patient preferences, are needed.