Introduction: The use of intranasal fentanyl for pain relief in children’s emergency departments is gaining popularity following the publication of a randomised controlled trial showing intranasal fentanyl to be as effective as intravenous morphine while being easier to administer1. Unfortunately, intranasal fentanyl is being used with younger children, higher doses, and with a different formulation to the one studied. A randomised controlled study to compare intranasal versus intravenous fentanyl and the two formulations has been proposed. The design is based on a study comparing intravenous fentanyl to nebulised fentanyl2 and an adult study comparing intranasal fentanyl to intravenous fentanyl.3 Important PKPD questions remain unanswered.
Aim: To present the proposed study design and investigate study designs that may help elucidate the PKPD of intranasal fentanyl in children.
Methods: Setting will be a tertiary children’s hospital emergency department. A double-arm, double-blind, double-dummy, crossover design study is proposed. Concentrated fentanyl (150µg/ml) will be compared to standard concentration fentanyl (50µg/ml). Children aged 6-18 with forearm fractures will be randomised to receive concentrated or standard fentanyl intranasal. They will then be randomised to first receive intranasal fentanyl (1.5µg/kg) or intravenous fentanyl (1µg/kg). Primary outcome measure is a visual analog pain score (0-100). When pain scores clinically fail to decrease sufficiently or increase again, further fentanyl, via the cross-over route, will be given.
Discussion: A critique of the study design and its ability to provide meaningful results will be asked of the PAGANZ attendees. Can PKPD studies be incorporated or should they be separate? Do we need to collect intranasal and intravenous drug levels in the same child? Can baseline parameters from Foster3 be used to help optimise studies?4. How many samples, how many participants, when should samples be taken? Future study should include younger children, using an observational pain measure. Studies into fentanyl analogues may have value.
- Borland M, Jacobs I, King B, O’Brien D. A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med. Mar 2007;49(3):335-340.
- Miner JR, Kletti C, Herold M, Hubbard D, Biros MH. Randomized clinical trial of nebulized fentanyl citrate versus i.v. fentanyl citrate in children presenting to the emergency department with acute pain. Acad Emerg Med. Oct 2007;14(10):895-898.
- Foster D, Upton R, Christrup L, Popper L. Pharmacokinetics and pharmacodynamics of intranasal versus intravenous fentanyl in patients with pain after oral surgery. Ann Pharmacother. Oct 2008;42(10):1380-1387.
- Duffull S, Waterhouse T, Eccleston J. Some considerations on the design of population pharmacokinetic studies. J Pharmacokinet Pharmacodyn. Aug 2005;32(3-4):441-457.