Literature Review: Morphine vs. Morphine/Ketamine

Jennings PA, Cameron P, Bernard S, et al. Morphine and ketamine is superior to morphine alone for out-of-hospital trauma analgesia: A randomized controlled trial. Ann Emerg Med, Jan 11, 2012 [e-pub ahead of print].

Abstract

Objective—To assess the efficacy of intravenous ketamine compared with intravenous morphine in reducing pain in adults with significant out-of-hospital traumatic pain. Methods—This study was an out-of-hospital, prospective, randomized, controlled, open-label study. Patients with trauma and a verbal pain score of greater than 5 after 5 mg intravenous morphine were eligible for enrollment. Patients allocated to the ketamine group received a bolus of 10 or 20 mg, followed by 10 mg every 3 minutes thereafter. Patients allocated to the morphine alone group received 5 mg intravenously every 5 minutes until pain free. Pain scores were measured at baseline and at hospital arrival.

Results—A total of 135 patients were enrolled between December 2007 and July 2010. There were no differences between the groups at baseline. After the initial 5-mg dose of intravenous morphine, patients allocated to ketamine received a mean of 40.6 mg of ketamine. Patients allocated to morphine alone received a mean of 14.4 mg of morphine. The mean pain score change was -5.6 in the ketamine group compared with -3.2 in the morphine group. The difference in mean pain score change was -2.4 points. The intravenous morphine group had 9 of 65 adverse effects reported (most commonly nausea) compared with 27 of 70 in the ketamine group (most commonly disorientation). Conclusion—Intravenous morphine plus ketamine for out-of-hospital adult trauma patients provides analgesia superior to that of intravenous morphine alone but was associated with an increase in the rate of minor adverse effects.

Comment

Morphine and other opioid analgesics are very effective in treating pain, but their use is often limited by side effects, such as sedation, hypotension, respiratory depression and nausea. Ketamine is a “dissociative agent”—providing analgesia and amnesia with minimal effect on blood pressure and respiration. In higher doses it is has been used extensively as a general anesthetic, including in combat surgery, where patients appear awake and continue breathing but do not respond to procedures. In lower doses it has an “opioid-sparing” effect—reducing the dose of opioid needed for adequate pain relief—and has the additional benefit of reducing anxiety. A limitation of ketamine is the “emergence phenomenon” seen in many patients—delirium, excitement, disorientation and confusion.

In this study from Australia, all patients received 5 mg of morphine, then half received ketamine and the other half more morphine. After treatment, the ketamine group had a lower pain score, but also had a higher incidence of side effects, mostly disorientation. One limitation of the study is that most patients received methoxyflurane (the inhaled analgesic recently used on Survivor), which may have affected their response to other medications.

Ketamine may be a useful medication in EMS. It will need further study, but may have a role in treating patients with significant trauma, especially those at risk for hypotension or respiratory compromise.

Angelo Salvucci, Jr., MD, FACEP, is medical director for the Santa Barbara County and Ventura County (CA) EMS agencies and a member of the EMS World editorial advisory board.