Intranasal Fentanyl: A Breath of Fresh Air in Sickle Cell Pain Management

Introduction

Sickle cell disease (SCD) and the associated vaso-occlusive episodes (VOEs) remain a significant health challenge, particularly among children. Additionally, the National Heart, Lung, and Blood Institute recommended that parenteral opioids be given within 30 minutes from triage or 60 minutes from emergency department (ED) registration. Realistically, these are challenging benchmarks to meet, partly because of the delays caused by ED crowding and understaffing challenges. 

Intranasal fentanyl has grown in popularity in care of pediatric and adult patients. The pharmocokinetics demonstrate a fast onset and effective means for short-term pain relief. Specifically, therapeutic levels are seen in approximately 2 minutes with analgesia lasting approximately 2-3 hours [1, 2].

Intranasal fentanyl is an excellent strategy to better adhere to the National Heart, Lung, and Blood Institute guidelines of rapid delivery of pain medication for children suffering from sickle cell related vaso-occlusive pain. While not intended to replace IV pain medications, since it is very short acting, it is an excellent bridge to provide immediate pain relief while obtaining IV access.

Dr. Claudia Morris, senior investigator
Professor of Pediatrics and Emergency Medicine at Emory University

A 2023 multicenter PECARN publication by Rees et al. suggests that intranasal fentanyl may offer a promising strategy to expedite early pain relief, because it does not require IV placement [3].

Study question

Are pediatric patients in a SCD-VOE more likely to be discharged home from the ED if they received an initial dose of intranasal fentanyl?

Study design

This multicenter, cross-sectional study, conducted across 20 academic pediatric EDs in the United States and Canada, enrolled 400 patients with a median age of 14.6 years. The primary outcome measure was the time to discharge home from the emergency department. 

Notable exclusion criteria from the study:

• Current upper respiratory tract infection
• Concern for stroke
• Altered mental status
• Head injury
• Acute chest syndrome

Intranasal dosing protocol

Because this was a cross-sectional study, the fentanyl dosing regimen was not standardized across sites. A typical formulary recommendation range is 1-2 mcg/kg. Intranasal fentanyl was available at concentrations of 50 mcg/mL with a maximum of 1 mL to each nostril (maximum 100 mcg). 

Notably, one site had a nursing-driven protocol to administer 2 doses of intranasal fentanyl at a dose of 1.5 mcg/kg/dose (max 100 mcg/dose), given 5 minutes apart. The 180 patients who received intranasal fentanyl did not experience any adverse events [4]. 

Primary finding

Children who received an initial dose of intranasal fentanyl were 9 times more likely to be discharged from the ED, compared to those who did not. This remained true despite adjusting for potential confounders, which might influence ED discharge rates, such as presenting pain scores, changes in pain scores, and opioids received in the ED. Interestingly when narrowing the analysis to only the 10 hospitals that used intranasal fentanyl, this statistic rose to 40 times more likely, based on adjusted odds ratio calculations. Both groups (with and without intranasal fentanyl) had similar median ED lengths of stay of 3 hours.

The magnitude of the benefit of intranasal fentanyl on discharge to home, even when controlling for pain scores and other potentially contributory factors, was astounding. In medicine, we are often impressed by 50% to 60% improvements, but here we saw more than a 900% greater likelihood of being discharged to home with intranasal fentanyl.

Dr. Chris A. Rees, primary investigator
Assistant Professor of Pediatrics and Emergency Medicine, Emory University School of Medicine

Caution

• Because this cross-sectional study was a post-hoc analysis, findings may be confounded by retrospective bias. Association does not equate to causation. For example, healthcare providers may have given patients with less severe pain intranasal fentanyl instead of IV opioids in the hopes of the patient not needing an IV for more doses. A prospective randomized study is needed to assess causality further.
• Dose intranasal fentanyl carefully, especially for patients with an upper respiratory infection, head injury, or potential for altered consciousness.

Why is this important for patients and caregivers

Quick Relief in the Hospital: This study shows that a medication, given as a nose spray (intranasal fentanyl) can help kids with sickle cell disease feel better faster when they have a pain crisis. It can be given in the ambulance or emergency department. It works so well that many kids can go home sooner instead of staying in the hospital. This means less time waiting for pain relief and more comfort for kids.

References

1. Serra S, Spampinato MD, Riccardi A, et al. Intranasal Fentanyl for Acute Pain Management in Children, Adults and Elderly Patients in the Prehospital Emergency Service and in the Emergency Department: A Systematic Review. J Clin Med. 2023;12(7):2609. Published 2023 Mar 30. PMID 37048692
2. Murphy A, O’Sullivan R, Wakai A, et al. Intranasal fentanyl for the management of acute pain in children. Cochrane Database Syst Rev. 2014;2014(10):CD009942. Published 2014 Oct 10. doi:10.1002/14651858.CD009942.pub2. PMID 25300594
3. Rees CA, Brousseau DC, Ahmad FA, et al. Intranasal fentanyl and discharge from the emergency department among children with sickle cell disease and vaso-occlusive pain: A multicenter pediatric emergency medicine perspective. Am J Hematol. 2023;98(4):620-627. doi:10.1002/ajh.26837. PMID 36606705
4. Akinsola B, Hagbom R, Zmitrovich A, et al. Impact of Intranasal Fentanyl in Nurse Initiated Protocols for Sickle Cell Vaso-occlusive Pain Episodes in a Pediatric Emergency Department. Am J Hematol. Published online May 17, 2018. doi:10.1002/ajh.25144. PMID 29770479