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The Efficacy of Ketamine Administration in Prehospital Pain Management of Trauma Patients; a Systematic Review and Meta-Analysis

Mahmoud Yousefifard, Shaghayegh Askarian-Amiri, Seyedeh Niloufar Rafiei Alavi, Mostafa Sadeghi, Peyman Saberiana, Alireza Baratloo, Mohammad Taghi Talebian



Introduction: Although previous articles and reviews suggest that ketamine might effectively manage pain in trauma patients, these articles have serious limitations. Accordingly, the current meta-analysis aims to investigate the efficacy of ketamine administration in prehospital pain management of trauma patients.

Method: In the present meta-analysis, controlled human studies were included. An extensive search was conducted in electronic databases including Medline (via PubMed), Embase, Central, Scopus, Web of Science, and ProQuest, gathering data to the end of 2018. The efficacy and side effects of ketamine administration in pre-hospital pain management were compared with those of opioid analgesics based on standard mean difference (SMD) and odds ratio (OR) calculations with 95% confidence interval (95% CI).

Results: Data from seven articles were included in the present meta-analysis. Ketamine administration was not more effective than administrating morphine or fentanyl in prehospital pain management of trauma patients (SMD = -0.56, 95% CI: -1.38 to 0.26, p = 0.117). However, co-administration of ketamine+morphine was considerably more effective than ketamine alone, in alleviating pain in prehospital settings (SMD = -0.62, 95% CI: -1.12 to -0.12, p = 0.010). Finally, it was concluded that ketamine alone had less side effects than morphine alone (OR = 0.25, 95% CI: 0.11 to 0.56, p = 0.001). However, co-administration of ketamine+morphine increases the risk of side effects to 3.68 times compared to when morphine is prescribed solely (OR=3.68, 95% CI: 1.99 to 6.82, p<0.001).

Conclusion: For the first time, findings of the current meta-analysis demonstrated that ketamine, being administered alone, is an effective and safe medication in prehospital pain management in trauma patients, and can be considered as an acceptable alternative to opioid analgesics.


Pain Management; Analgesics, Opioid; Analgesics, Non-Narcotic; Emergency Medical Services; Ketamine


Demling R, Youn Y. The stress response to injury and critical illness. Surgical Critical Care Philadelphia: WB Saunders. 1996;286.

Moore E, Mattox KL, Feliciano DV. Trauma Manual. New York, McGraw-Hill; 2003:110–12.

Villanueva MT. Analgesia: Designing out opioid side effects. Nature Reviews Drug Discovery. 2017;16(5):311.

Baratloo A, Mirbaha S, Delavar Kasmaei H, Payandemehr P, Elmaraezy A, Negida A. Intravenous caffeine citrate vs. magnesium sulfate for reducing pain in patients with acute migraine headache; a prospective quasi-experimental study. The Korean journal of pain. 2017;30(3):176-82.

Dolatabadi AA, Memary E, Kariman H, Gigloo KN, Baratloo A. Intranasal desmopressin compared with intravenous ketorolac for pain management of patients with renal colic referring to the emergency department: a randomized clinical trial. Anesthesiology and pain medicine. 2017;7(2).

Baratloo A, Rouhipour A, Forouzanfar MM, Safari S, Amiri M, Negida A. The role of caffeine in pain management: a brief literature review. Anesthesiology and pain medicine. 2016;6(3).

Dameni S, Janzadeh A, Yousefifard M, Nasirinezhad F. The effect of intrathecal injection of irisin on pain threshold and expression rate of GABAB receptors in peripheral neuropathic pain model. Journal of chemical neuroanatomy. 2018;91:17-26.

Mojarad N, Yousefifard M, Janzadeh A, Damani S, Golab F, Nasirinezhad F. Comparison of the antinociceptive effect of intrathecal versus intraperitoneal injection of paracetamol in neuropathic pain condition. Journal of Medical Physiology. 2016;1(1):10-6.

Nasirinezhad F, Hosseini M, Karami Z, Yousefifard M, Janzadeh A. Spinal 5-HT3 receptor mediates nociceptive effect on central neuropathic pain; possible therapeutic role for tropisetron. The journal of spinal cord medicine. 2016;39(2):212-9.

Abdolrazaghnejad A, Banaie M. Fentanyl-midazolam vs. midazolam-ketamine regarding patient sedation analgesia for emergency orthopedic procedures. Bangladesh Journal of Pharmacology. 2017;12(2):30-2017.

Yang C, Shirayama Y, Zhang J, Ren Q, Yao W, Ma M, et al. R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Translational psychiatry. 2015;5(9):e632.

Riva-Posse P, Reiff CM, Edwards JA, Job GP, Galendez GC, Garlow SJ, et al. Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions. Journal of affective disorders. 2018;236:291-7.

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 Emergency Care. 2014;18(2):257-64.

Baekgaard JS, Eskesen TG, Sillesen M, Rasmussen LS, Steinmetz J. Ketamine as a Rapid Sequence Induction Agent in the Trauma Population: A Systematic Review. Anesthesia and analgesia. 2018.

Lee EN, Lee JH. The effects of low-dose ketamine on acute pain in an emergency setting: a systematic review and meta-analysis. PloS one. 2016;11(10):e0165461.

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine. 2009;151(4):264-9.

Furlan AD, Pennick V, Bombardier C, van Tulder M. 2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group. Spine. 2009;34(18):1929-41.

Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629-34.

Bronsky ES, Koola C, Orlando A, Redmond D, D'Huyvetter C, Sieracki H, et al. Intravenous Low-Dose Ketamine Provides Greater Pain Control Compared to Fentanyl in a Civilian Prehospital Trauma System: A Propensity Matched Analysis. Prehospital Emergency Care. 2019;23(1):1-8.

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. The American journal of emergency medicine. 2007;25(4):385-90.

Jennings PA, Cameron P, Bernard S, Walker T, Jolley D, Fitzgerald M, et al. Morphine and ketamine is superior to morphine alone for out-of-hospital trauma analgesia: a randomized controlled trial. Annals of emergency medicine. 2012;59(6):497-503.

Johansson P, Kongstad P, Johansson A. The effect of combined treatment with morphine sulphate and low-dose ketamine in a prehospital setting. Scandinavian journal of trauma, resuscitation and emergency medicine. 2009;17:61.

Shackelford SA, Fowler M, Schultz K, Summers A, Galvagno SM, Gross KR, et al. Prehospital pain medication use by U.S. Forces in Afghanistan. Military medicine. 2015;180(3):304-9.

Wiel E, Zitouni D, Assez N, Sebilleau Q, Lys S, Duval A, et al. Continuous Infusion of Ketamine for Out-of-hospital Isolated Orthopedic Injuries Secondary to Trauma: A Randomized Controlled Trial. Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors. 2015;19(1):10-6.

Häske D, Böttiger BW, Bouillon B, Fischer M, Gaier G, Gliwitzky B, et al. Analgesia in Patients with Trauma in Emergency Medicine: A Systematic Review and Meta-analysis. Deutsches Ärzteblatt International. 2017;114(46):785.

DOI: https://doi.org/10.22037/aaem.v8i1.479

DOI (PDF): https://doi.org/10.22037/aaem.v8i1.479.g657

DOI (HTML): https://doi.org/10.22037/aaem.v8i1.479.g699