Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department

Stacy L Reynolds, Jonathan R Studnek, Kathleen Bryant, Kelly VanderHave, Eric Grossman, Charity G Moore, James Young, Melanie Hogg, Michael S Runyon, Stacy L Reynolds, Jonathan R Studnek, Kathleen Bryant, Kelly VanderHave, Eric Grossman, Charity G Moore, James Young, Melanie Hogg, Michael S Runyon

Abstract

Introduction: Fentanyl is the most widely studied intranasal (IN) analgesic in children. IN subdissociative (INSD) ketamine may offer a safe and efficacious alternative to IN fentanyl and may decrease overall opioid use during the emergency department (ED) stay. This study examines the feasibility of a larger, multicentre clinical trial comparing the safety and efficacy of INSD ketamine to IN fentanyl and the potential role for INSD ketamine in reducing total opioid medication usage.

Methods and analysis: This double-blind, randomised controlled, pilot trial will compare INSD ketamine (1 mg/kg) to IN fentanyl (1.5 μg/kg) for analgesia in 80 children aged 4-17 years with acute pain from a suspected, single extremity fracture. The primary safety outcome for this pilot trial will be the frequency of cumulative side effects and adverse events at 60 min after drug administration. The primary efficacy outcome will be exploratory and will be the mean reduction of pain scale scores at 20 min. The study is not powered to examine efficacy. Secondary outcome measures will include the total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the ED stay, number and reason for screen failures, time to consent, and the number and type of protocol deviations. Patients may receive up to 2 doses of study drug.

Ethics and dissemination: This study was approved by the US Food and Drug Administration, the local institutional review board and the study data safety monitoring board. This study data will be submitted for publication regardless of results and will be used to establish feasibility for a multicentre, non-inferiority trial.

Trial registration number: NCT02521415.

Keywords: PAIN MANAGEMENT; ketamine; pediatric orthopaedics.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

References

    1. Kircher J, Drendal AL, Newton AS et al. . Pediatric musculoskeletal pain in the emergency department: a medical record review of practice variation. CJEM 2014;16:449–57.
    1. Stang AS, Hartling L, Fera C et al. . Quality indicators for the assessment and management of pain in the emergency department: a systematic review. Pain Res Manag 2014;19:e179–90. 10.1155/2014/269140
    1. Iyer SB, Schubert CJ, Schoettker PJ et al. . Use of quality improvement methods to improve timeliness of analgesic delivery. Pediatrics 2011;127:e219–25. 10.1542/peds.2010-0632
    1. Dong L, Donaldson A, Metzger R et al. . Analgesic administration in the emergency department for children requiring hospitalization for long-bone fracture. Pediatr Emerg Care 2012;28:109–14. 10.1097/PEC.0b013e3182442c25
    1. Gausche-Hill M, Brown KM, Oliver ZJ et al. . An evidence-based guideline for prehospital analgesia in trauma. Prehosp Emerg Care 2014;18(Suppl 1):25–34. 10.3109/10903127.2013.844873
    1. Truba N, Hoyle J. Pediatric pain. J Pain Manag 2014;7:235–48.
    1. Weisman SJ, Bernstein B, Schechter NL. Consequences of inadequate analgesia during painful procedures in children. Arch Pediatr Adolesc Med 1998;152:147–9. 10.1001/archpedi.152.2.147
    1. Borland M, Jacobs I, King B et al. . A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med 2007;49:335–40. 10.1016/j.annemergmed.2006.06.016
    1. Swor R, McEachin CM, Seguin D et al. . Prehospital pain management in children suffering traumatic injury. Prehosp Emerg Care 2005;9:40–3. 10.1080/10903120590891930
    1. Williams DM, Rindal KE, Cushman JT et al. . Barriers to and enablers for prehospital analgesia for pediatric patients. Prehosp Emerg Care 2012;16:519–26. 10.3109/10903127.2012.695436
    1. Andolfatto G, Willman E, Joo D et al. . Intranasal ketamine for analgesia in the emergency department: a prospective observational series. Acad Emerg Med 2013;20:1050–4. 10.1111/acem.12229
    1. Mudd S. Intranasal fentanyl for pain management in children: a systematic review of the literature. J Pediatr Health Care 2011;25:316–22. 10.1016/j.pedhc.2010.04.011
    1. Panagiotou I, Mystakidou K. Intranasal fentanyl: from pharmacokinetics and bioavailability to current treatment applications. Expert Rev Anticancer Ther 2010;10:1009–21. 10.1586/era.10.77
    1. Saunders M, Adelgais K, Nelson D. Use of intranasal fentanyl for the relief of pediatric orthopedic trauma pain. Acad Emerg Med 2010;17:1155–61. 10.1111/j.1553-2712.2010.00905.x
    1. Malinovsky JM, Servin F, Cozian A et al. . Ketamine and norketamine plasma concentrations after i.v., nasal and rectal administration in children. Br J Anaesth 1996;77:203–7. 10.1093/bja/77.2.203
    1. Yanagihara Y, Ohtani M, Kariya S et al. . Plasma concentration profiles of ketamine and norketamine after administration of various ketamine preparations to healthy Japanese volunteers. Biopharm Drug Dispos 2003;24:37–43. 10.1002/bdd.336
    1. Uprety D, Baber A, Foy M. Ketamine infusion for sickle cell pain crisis refractory to opioids: a case report and review of literature. Ann Hematol 2014;93:769–71. 10.1007/s00277-013-1954-3
    1. Kerr C, Holahan T, Milch R. The use of ketamine in severe cases of refractory pain syndromes in the palliative care setting: a case series. J Palliat Med 2011;14:1074–7. 10.1089/jpm.2010.0424
    1. Neri CM, Pestieau SR, Darbari DS. Low-dose ketamine as a potential adjuvant therapy for painful vaso-occlusive crises in sickle cell disease. Paediatr Anaesth 2013;23:684–9. 10.1111/pan.12172
    1. Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev 2012;11:CD003351 10.1002/14651858.CD003351.pub2
    1. Mabry R, McManus JG. Prehospital advances in the management of severe penetrating trauma. Crit Care Med 2008;36:S258–66. 10.1111/pan.12172
    1. Graudins A, Meek R, Egerton-Warburton D et al. . The PICHFORK (Pain in Children Fentanyl or Ketamine) trial: a randomized controlled trial comparing intranasal ketamine and fentanyl for the relief of moderate to severe pain in children with limb injuries. Ann Emerg Med 2015;65:248–54. 10.1016/j.annemergmed.2014.09.024
    1. Shikanai H, Hiraide S, Kamiyama H et al. . Subanalgesic ketamine enhances morphine-induced antinociceptive activity without cortical dysfunction in rats. J Anesth 2014;28:390–8. 10.1007/s00540-013-1722-5
    1. Yeaman F, Oakley E, Meek R et al. . Sub-dissociative dose intranasal ketamine for limb injury pain in children in the emergency department: a pilot study. Emerg Med Australas 2013;25:161–7. 10.1111/1742-6723.12059
    1. Motov S, Rockoff B, Cohen V et al. . Intravenous subdissociative-dose ketamine versus morphine for analgesia in the emergency department: a randomized controlled trial. Ann Emerg Med 2015;66:222–9. 10.1016/j.annemergmed.2015.03.004
    1. Tsze DS, Hirschfeld G, von Baeyer CL et al. . Clinically significant differences in acute pain measured on self-report pain scales in children. Acad Emerg Med 2015;22:415–22. 10.1111/acem.12620
    1. Tsze DS, von Baeyer CL, Bulloch B et al. . Validation of self-report pain scales in children. Pediatrics 2013;132:e971–9. 10.1542/peds.2013-1509
    1. Bulloch B, Tenenbein M. Assessment of clinically significant changes in acute pain in children. Acad Emerg Med 2002;9:199–202. 10.1111/j.1553-2712.2002.tb00244.x
    1. Bailey B, Bergeron S, Gravel J et al. . Comparison of four pain scales in children with acute abdominal pain in a pediatric emergency department. Ann Emerg Med 2007;50:379–83. 10.1016/j.annemergmed.2007.04.021
    1. Moore CG, Carter RE, Nietert PJ et al. . Recommendations for planning pilot studies in clinical and translational research. Clin Transl Sci 2011;4:332–7. 10.1111/j.1752-8062.2011.00347.x
    1. Harris PA, Taylor R, Thielke R et al. . Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81. 10.1016/j.jbi.2008.08.010

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner