Is intravenously administered, subdissociative-dose KETAmine non-inferior to MORPHine for prehospital analgesia (the KETAMORPH study): study protocol for a randomized controlled trial

Clément Le Cornec, Said Lariby, Vivien Brenckmann, Jean Benoit Hardouin, Claude Ecoffey, Marion Le Pottier, Philippe Fradin, Hélène Broch, Amine Kabbaj, Yannick Auffret, Florence Deciron, Céline Longo, François Javaudin, Quentin Le Bastard, Joël Jenvrin, Emmanuel Montassier, Clément Le Cornec, Said Lariby, Vivien Brenckmann, Jean Benoit Hardouin, Claude Ecoffey, Marion Le Pottier, Philippe Fradin, Hélène Broch, Amine Kabbaj, Yannick Auffret, Florence Deciron, Céline Longo, François Javaudin, Quentin Le Bastard, Joël Jenvrin, Emmanuel Montassier

Abstract

Background: Acute pain is a common condition among prehospital patients and prompt management is pivotal. Opioids are the most frequently analgesics used in the prehospital setting. However, opioids are highly addictive, and some patients may develop opioid dependence, even when they are exposed to brief opioid treatments. Therefore, alternative non-opioid analgesia should be developed to manage pain in the prehospital setting. Used at subdissociative doses, ketamine, a noncompetitive N-methyl-D-aspartate and glutamate receptor antagonist, provides analgesic effects accompanied by preservation of protective airway reflexes. In this context, we will carry out a randomized controlled, open-label, multicenter trial to compare a subdissociative dose of ketamine to morphine to provide pain relief in the prehospital setting, in patients with traumatic and non-traumatic pain.

Methods/design: This will be a multicenter, single-blind, randomized controlled trial. Consecutive adults will be enrolled in the prehospital setting if they experience moderate to severe, acute, non-traumatic and traumatic pain, defined as a numeric rating scale score greater or equal to 5. Patients will be randomized to receive ketamine or morphine by intravenous push. The primary outcome will be the between-group difference in mean change in numeric rating scale pain scores measured from the time before administration of the study medication to 30 min later.

Discussion: This upcoming randomized clinical trial was design to assess the efficacy and safety of ketamine, an alternative non-opiate analgesia, to manage non-traumatic and traumatic pain in the prehospital setting. We aim to provide evidence to change prescribing practices to reduce exposition to opioids and the subsequent risk of addiction.

Trial registration: ClinicalTrials.gov, ID: NCT03236805 . Registered on 2 August 2017.

Keywords: Ketamine; Morphine; Pain; Traumatic and non-traumatic.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol and patient-informed consent procedures were approved and received Sud-Méditerranée 2 Institutional Review Board approval (IRB sudmed 2, approval number 217 R26).

Consent for publication

Consent forms for the trial include consent for publication of results in peer-reviewed journals.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Figure for the KETAMORPH trial. Schedule of enrollment, interventions, and assessments

References

    1. McLean SA, Maio RF, Domeier RM. The epidemiology of pain in the prehospital setting. Prehospital Emerg. Care. 2002;6:402–405. doi: 10.1080/10903120290938021.
    1. Jennings PA, Cameron P, Bernard S. Epidemiology of prehospital pain: an opportunity for improvement. Emerg Med J. 2011;28:530–531. doi: 10.1136/emj.2010.098954.
    1. Galinski M, Ruscev M, Gonzalez G, Kavas J, Ameur L, Biens D, et al. Prevalence and management of acute pain in prehospital emergency medicine. Prehospital Emerg. Care. 2010;14:334–339. doi: 10.3109/10903121003760218.
    1. Murphy AP, Hughes M, McCoy S, Crispino G, Wakai A, O’Sullivan R. Intranasal fentanyl for the prehospital management of acute pain in children. Eur J Emerg Med. 2017;24:450–454. doi: 10.1097/MEJ.0000000000000389.
    1. Bohnert ASB, Valenstein M, Bair MJ, Ganoczy D, McCarthy JF, Ilgen MA, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305:1315–1321. doi: 10.1001/jama.2011.370.
    1. Herzig SJ, Rothberg MB, Cheung M, Ngo LH, Marcantonio ER. Opioid utilization and opioid-related adverse events in nonsurgical patients in US hospitals. J Hosp Med. 2014;9:73–81. doi: 10.1002/jhm.2102.
    1. Brennan MJ, Stanos S. Strategies to optimize pain management with opioids while minimizing risk of abuse. PM R. 2010;2:544–558. doi: 10.1016/j.pmrj.2010.03.011.
    1. Chang AK, Bijur PE, Napolitano A, Lupow J, Gallagher EJ. Two milligrams i.v. hydromorphone is efficacious for treating pain but is associated with oxygen desaturation. J Opioid Manag. 2009;5:75–80. doi: 10.5055/jom.2009.0008.
    1. Motov S, Rosenbaum S, Vilke GM, Nakajima Y. Is there a role for intravenous subdissociative-dose ketamine administered as an adjunct to opioids or as a single agent for acute pain management in the emergency department? J Emerg Med. 2016;51:752–757. doi: 10.1016/j.jemermed.2016.07.087.
    1. Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, et al. Opioid complications and side effects. Pain Physician. 2008;11:S105–S120.
    1. Butler MM, Ancona RM, Beauchamp GA, Yamin CK, Winstanley EL, Hart KW, et al. Emergency department prescription opioids as an initial exposure preceding addiction. Ann Emerg Med. 2016;68:202–208. doi: 10.1016/j.annemergmed.2015.11.033.
    1. Guirimand F, Dupont X, Brasseur L, Chauvin M, Bouhassira D. The effects of ketamine on the temporal summation (wind-up) of the R(III) nociceptive flexion reflex and pain in humans. Anesth Analg. 2000;90:408–414.
    1. Schmid J, Tortorano AM, Jones G, Lazzarini C, Zhang N, Bendall MJ, et al. Increased mortality in young candidemia patients associated with presence of a Candida albicans general-purpose genotype. J Clin Microbiol. 2011;49:3250–3256. doi: 10.1128/JCM.00941-11.
    1. Motov S, Rockoff B, Cohen V, Pushkar I, Likourezos A, McKay C, et al. Intravenous subdissociative-dose ketamine versus morphine for analgesia in the emergency department: a randomized controlled trial. Ann Emerg Med. 2015;66:222–229.e1. doi: 10.1016/j.annemergmed.2015.03.004.
    1. Svenson JE, Abernathy MK. Ketamine for prehospital use: new look at an old drug. Am J Emerg Med. 2007;25:977–980. doi: 10.1016/j.ajem.2007.02.040.
    1. Galinski M, Dolveck F, Combes X, Limoges V, Smaïl N, Pommier V, et al. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. Am J Emerg Med. 2007;25:385–390. doi: 10.1016/j.ajem.2006.11.016.
    1. Smith DC, Mader TJ, Smithline HA. Low dose intravenous ketamine as an analgesic: a pilot study using an experimental model of acute pain. Am J Emerg Med. 2001;19:531–532. doi: 10.1053/ajem.2001.27152.
    1. Losvik OK, Murad MK, Skjerve E, Husum H. Ketamine for prehospital trauma analgesia in a low-resource rural trauma system: a retrospective comparative study of ketamine and opioid analgesia in a ten-year cohort in Iraq. Scand J Trauma Resusc Emerg Med. 2015;23:94. doi: 10.1186/s13049-015-0176-1.
    1. Tran KP, Nguyen Q, Truong XN, Le V, Le VP, Mai N, et al. A comparison of ketamine and morphine analgesia in prehospital trauma care: a cluster randomized clinical trial in rural Quang Tri province, Vietnam. Prehospital Emerg Care. 2014;18:257–264. doi: 10.3109/10903127.2013.851307.
    1. Schulz KF, Altman DG, Moher D, CONSORT Group CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Trials. 2010;11:32. doi: 10.1186/1745-6215-11-32.
    1. Adnet F, Lapostolle F. International EMS systems: France. Resuscitation. 2004;63:7–9. doi: 10.1016/j.resuscitation.2004.04.001.
    1. Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009;374:293–300. doi: 10.1016/S0140-6736(09)60949-1.
    1. Société française d’anesthésie et de réanimation (SFAR), Société française de médecine d’urgence. Vivien B, Adnet F, Bounes V, Chéron G, et al. Sedation and analgesia in the emergency context. Ann Fr Anesth Reanim. 2010;29:934–949. doi: 10.1016/j.annfar.2010.10.005.
    1. Chang AK, Bijur PE, Esses D, Barnaby DP, Baer J. Effect of a single dose of oral opioid and nonopioid analgesics on acute extremity pain in the emergency department: a randomized clinical trial. JAMA. 2017;318:1661–1667. doi: 10.1001/jama.2017.16190.
    1. Chang AK, Bijur PE, Holden L, Gallagher EJ. Comparative analgesic efficacy of oxycodone/acetaminophen versus hydrocodone/acetaminophen for short-term pain management in adults following ED discharge. Acad Emerg Med. 2015;22:1254–1260. doi: 10.1111/acem.12813.
    1. Chang AK, Bijur PE, Munjal KG, John GE. Randomized clinical trial of hydrocodone/acetaminophen versus codeine/acetaminophen in the treatment of acute extremity pain after emergency department discharge. Acad Emerg Med. 2014;21:227–235. doi: 10.1111/acem.12331.
    1. Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med. 2017;376:663–673. doi: 10.1056/NEJMsa1610524.
    1. Jennings PA, Cameron P, Bernard S. Ketamine as an analgesic in the pre-hospital setting: a systematic review. Acta Anaesthesiol Scand. 2011;55:638–643. doi: 10.1111/j.1399-6576.2011.02446.x.

Source: PubMed

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