Pain management and sedation/original research
Morphine and Ketamine Is Superior to Morphine Alone for Out-of-Hospital Trauma Analgesia: A Randomized Controlled Trial

https://doi.org/10.1016/j.annemergmed.2011.11.012Get rights and content

Study objective

We 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 (SD 25 mg) of ketamine. Patients allocated to morphine alone received a mean of 14.4 mg (SD 9.4 mg) of morphine. The mean pain score change was −5.6 (95% confidence interval [CI] −6.2 to −5.0) in the ketamine group compared with −3.2 (95% CI −3.7 to −2.7) in the morphine group. The difference in mean pain score change was −2.4 (95% CI −3.2 to −1.6) points. The intravenous morphine group had 9 of 65 (14%; 95% CI 6% to 25%) adverse effects reported (most commonly nausea [6/65; 9%]) compared with 27 of 70 (39%; 95% CI 27% to 51%) in the ketamine group (most commonly disorientation [8/70; 11%]).

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.

Introduction

There is considerable debate about optimal out-of-hospital analgesia for conscious trauma patients and wide variation in practice. Morphine is used commonly; however, there is insufficient evidence about whether this is the optimal analgesic in the out-of-hospital environment.1 Effectiveness of opioid analgesia for patients with severe trauma may be limited by excessive sedation, respiratory depression, and nausea.

Ketamine is a dissociative agent with analgesic properties and has been used extensively in acute care medicine. Compared with opioids, ketamine has a reportedly low frequency of serious adverse effects in doses used for analgesia and has little effect on the blood pressure and pulse rate.2, 3, 4, 5

Ketamine is well suited to the out-of-hospital environment. It effectively provides safe analgesia while simultaneously providing anxiolysis and amnesia.6 A significant benefit of its use is that it has an opioid-sparing effect6, 7, 8 and improves analgesia in patients with severe pain that is poorly controlled by opioids.9 What makes ketamine appealing for use in the out-of-hospital setting is that it is purported to allow patients to maintain their pharyngeal reflexes and maintain their own airway, even when fully dissociated.10

Acute pain is a common presentation to health care clinicians,1, 11, 12, 13 is often associated with injury,14 and is a significant contributor to disability many months or even years after injury. The effective management of pain is of critical importance in both the short and long term, especially for patients after traumatic injury.

This study aimed to determine which therapy was most effective in reducing pain intensity before arrival at the hospital, as measured by the verbal numeric pain rating scale. We also examined the incidence of adverse effects and effects of the agents on vital signs.

Section snippets

Study Design

This study was a prospective, randomized, controlled, open-label, multicenter study to compare the effect of intravenous morphine and ketamine with that of morphine alone in the treatment of moderate (verbal numeric rating score between 5 and 7) to severe (verbal numeric rating score of 8 or greater) traumatic pain before arrival at hospital. The study protocol was approved by Monash University, Victoria, Australia, and the institutional ethics committees at each receiving hospital. The

Results

Sufficient numbers of patients should have been enrolled in 10 months. However, enrollment was far slower than anticipated and as low as 2 patients per month. In July 2010, 30 months after commencement of the study, we chose to undertake an unplanned interim analysis of the 136 patients recruited. A biostatistician, blinded to the intervention allocation, undertook the analysis and recommended that the trial should be discontinued, given that a revised sample size calculation based on the

Limitations

Methoxyflurane, a fast-acting, inhalational analgesic agent, was administered to most but not all patients enrolled in this study. The administration of methoxyflurane was based on the clinician's judgment at the time of managing the patient. Methoxyflurane was administered before the paramedic established intravenous access and therefore before randomization and trial allocation. The proportion of patients who received methoxyflurane and the mean dose administered were equivalent between the 2

Discussion

In this prospective, randomized controlled trial, out-of-hospital use of morphine plus ketamine was superior to that of morphine alone in the reduction of pain intensity in adult patients with moderate to severe pain after trauma. Intravenous ketamine provided safe and effective analgesia to adult patients after injury, conferring an overall pain intensity reduction advantage of 2.4 verbal numeric rating scale points over intravenous morphine alone; patients in the ketamine group had a mean

References (29)

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Supervising editor: Steven M. Green, MD

Author contributions: PAJ, PC, and SB conceived the study. PAJ, PC, SB, TW, MF, and KM designed the trial. PAJ obtained research funding through a TAC research fellowship. PAJ, PC, SB, TW, and KM supervised the conduct of the trial and data collection. PJ undertook recruitment of participating sites and patients and managed the data, including quality control. DJ provided statistical advice and analyzed the data. TW chaired the trial steering committee. PAJ drafted the article, and all authors contributed substantially to its revision. PAJ takes responsibility for the paper as a whole.

Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. This study was funded by the Transport Accident Commission (TAC) Health Research Fellowship.

Please see page 498 for the Editor's Capsule Summary of this article.

Publication date: Available online January 13, 2012.

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