Original ContributionManagement of severe acute pain in emergency settings: ketamine reduces morphine consumption☆
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.
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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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Presented at the European Society of Anaesthesiology Congress in Madrid, Spain, June 3-6, 2006.
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