Original Contribution
Management of severe acute pain in emergency settings: ketamine reduces morphine consumption

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Abstract

Objective

The aim of the study was to compare in emergency settings 2 analgesic regimens, morphine with ketamine (K group) or morphine with placebo (P group), for severe acute pain in trauma patients.

Methods

This was a prospective, multicenter, randomized, double-blind, clinical trial. Seventy-three trauma patients with a severe acute pain defined as a visual analog scale (VAS) score of at least 60/100 were enrolled. Patients in the K group received 0.2 mg · kg−1 of intravenous ketamine over 10 minutes, and patients in the P group received isotonic sodium chloride solution. In both groups, patients were given an initial intravenous morphine injection of 0.1 mg · kg−1, followed by 3 mg every 5 minutes. Efficient analgesia was defined as a VAS score not exceeding 30/100. The primary end points were morphine consumption and VAS at 30 minutes (T30).

Results

At T30, morphine consumption was significantly lower in the K group vs the P group, with 0.149 mg · kg−1 (0.132-0.165) and 0.202 mg · kg−1 (0.181-0.223), respectively (P < .001). The VAS score at T30 did not differ significantly between the 2 groups, with 34.1 (25.6-42.6) in the K group and 39.5 (32.4-46.6) in the P group (P = not significant).

Conclusion

Ketamine was able to provide a morphine-sparing effect.

Introduction

Morphine titration infusion usually provides rapid and effective analgesia in severe acute pain [1]. However, adverse effects sometimes occur and may require discontinuation of morphine titration before sufficient pain relief is obtained [2]. The combination of nonopioid analgesics with morphine provides a morphine-sparing effect and should decrease toxicity. This concept is the basis of multimodal analgesia [3].

Small doses of ketamine possess N-methyl-d-aspartate (NMDA) receptor noncompetitive antagonist properties through a magnesium-dependent channel blockade [4]. Several studies demonstrated that it improves opioid analgesia in postoperative settings [5], [6].

Potentiation between opioids and ketamine was demonstrated in animal studies [7] and was suggested in a volunteer study [8], whereas another report favored only an additive association [9]. Furthermore, ketamine attenuates the development of acute analgesic tolerance to opioids in rats [10] and suppresses the rebound hyperalgesia observed after opioid exposure in volunteers [11]. A recent study demonstrated that the combined administration of small-dose ketamine and morphine promptly and satisfactorily resolved pain that was unresponsive to intravenous (IV) morphine alone [12]. In emergency settings, a 0.1-mg · kg−1 dose of IV morphine was not effective for controlling severe acute pain in most patients [13]. There is evidence to suggest that the lack of effectiveness of morphine is due to the activation of NMDA receptors; and if these are not effectively inhibited in time, the process may evolve into a complex change in neural plasticity, resulting in central sensitization [14]. To our knowledge, there is no study assessing the interest of the morphine and ketamine association for trauma patients with severe acute pain in emergency settings.

We tested the hypothesis that the combination of small-dose ketamine and morphine would promptly reduce pain perception and morphine consumption compared with morphine alone in trauma patients with severe acute pain in emergency settings.

Section snippets

Materials and methods

We performed a prospective, multicenter, randomized, double-blind, controlled study. The trial was coordinated by the Avicenne University Hospital (Bobigny, France). Five emergency departments using mobile intensive care units previously described [15] were involved in this study. Mobile intensive care units are staffed by an attending emergency physician, a nurse anesthetist, and an emergency medical technician.

The Human Subjects Committee of the Robert Ballanger Hospital (Aulnay, France)

Patient characteristics

Between January 01, 2004, and June 30, 2005, seventy-three patients were enrolled in the study (Fig. 1). Seven patients (5 in the K group and 2 in the P group) were withdrawn from the analysis because of incomplete data or disrespect of study protocol. One patient was excluded because of an anaphylactoid reaction after antibiotic injection in the P group. Thus, data from 65 patients were completed and analyzed, 33 in the K group and 32 in the P group.

Baseline characteristics were similar

Discussion

In trauma patients with severe acute pain, we found that the association of low-dose ketamine with morphine reduced morphine requirements by approximately 26% within 30 minutes. However, pain intensity measured on a VAS at T30 was not different between the 2 groups. To our knowledge, this is the first study that associated morphine with low-dose ketamine for trauma patients with severe acute pain in emergency settings.

Gurnani et al [20] studied low-dose ketamine in patients with acute pain

Conclusion

This study showed that low-dose ketamine in trauma patients with severe acute pain reduced morphine requirements. We could not demonstrate any reduction in pain intensity with ketamine in this study.

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  • Cited by (0)

    Presented at the European Society of Anaesthesiology Congress in Madrid, Spain, June 3-6, 2006.

    Support was provided solely by institutional and/or departmental sources.

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