Original Contribution
Comparing the analgesic efficacy of morphine plus ketamine versus morphine plus placebo in patients with acute renal colic: A double-blinded randomized controlled trial

https://doi.org/10.1016/j.ajem.2018.09.004Get rights and content

Abstract

Objectives

Renal colic (RC) is a common cause for emergency department visits. This study was conducted to compare the analgesic efficacy of morphine plus ketamine (MK) versus morphine plus placebo (MP) in patients with acute renal colic.

Method

Using a single center, double-blind, two-arm, parallel-group, randomized controlled trial, 200 patients were equally and randomly divided to receive 0.1 mg/kg morphine plus normal saline and 0.1 mg/kg morphine plus 0.2 mg/kg ketamine. The severity of renal colic was assessed by VAS at baseline, 20 and 40 min after drug injection. The number of adverse events also was recorded.

Results

Totally, 200 patients completed the study. Mean age of the patients was 35.60 ± 8.17 years. The patients were mostly men (68.5%). The severity of pain between the groups was not significantly different at baseline. Both groups showing a significant reduction in VAS scores across the three time points. The main effect comparing the two types of intervention was significant (F = 12.95, p = 0.000), suggesting a significant reduction in pain severity of patients in the MK group. The number of patients who suffered from vomiting was significantly higher in MP group than that of MK group (13 and 3, respectively (P = 0.009)). However, the risk of dizziness in the MK group was >2 times higher than MP group (relative risk: 2.282, 95% CI: 1.030–5.003, P = 0.039). The number of patients who needed rescue analgesia was significantly lower in the MK group (OR, 0.43 (0.22–0.83)).

Conclusion

Adding 0.2 mg/kg ketamine to 0.1 mg/kg morphine can reduce the renal colic pain, nausea and vomiting more than morphine alone; however, it was associated with higher number of patients with dizziness.

Introduction

Renal colic (RC) is a common cause for emergency department (ED) visits, worldwide [1]. Renal colic is caused by an increase in pressure within the upper urinary system or due to the dilatation of the kidney and pelvic capsules above the blockage site, which is often caused by stones. This pain is suddenly felt on the patient's flank and radiates to the groin and genital area [1]. Due to the severe and intermittent nature of renal colic, one of the main priorities in the ED is to provide quick and effective analgesia for patients. However, several factors such as efficacy, safety, the ease of rapid administration, and availability must be considered in analgesia selection [2]. In most clinical settings, the choice of medication to reduce pain is determined by the local policies of the given health care system and there is no consensus guideline regarding the best analgesic option for patients presenting with renal colic to the ED [1,[3], [4], [5]].

Several medications are available for the treatment of renal colic pain, including, but not limited to, NSAIDs, antidepressants, anesthetic agents, anti-epileptics and opioids [[3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]]. As frequent therapies, both non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are usually used for the prompt pain relief of patients in the ED. However, due to the unwanted adverse events of opioids, NSAIDs, particularly in intravenous forms, become very attractive agents for acute pain relief in the ED [5]. In this regard, a recent Cochrane review of non-opioid analgesia for acute renal colic showed that NSAIDs could improve pain control compared with placebo [3].

Regarding the management of acute pain in ED, finding alternatives to opioids has become increasingly interesting, both in practical applications and in theoretical studies, for emergency medical professionals. Ketamine, a noncompetitive N-methyl-d-aspartate receptor antagonist, is recently used at sub-anesthetic doses as a supplementary medication for treatment of various therapy-resistant pain syndromes [14]. A number of studies have evaluated the effects of ketamine for reducing pain in patients with renal colic and found some promising results that ketamine may be effective to reduce the severity of pain in renal colic as well as morphine consumption and therefore, it can reduce the number of opioid-related adverse events [11,12,[15], [16], [17], [18]]. Accordingly, based on the available evidence, we hypothesized that the combination of morphine and ketamine can reduce the pain intensity and the number of adverse events better than that of morphine alone in patients with renal colic. Therefore, the aim of this study was to compare the analgesic efficacy morphine plus ketamine versus morphine alone in patients with acute renal colic in the ED.

Section snippets

Design and study setting

This study was a single-center, double-blind, two-arm, parallel-group, randomized controlled trial, which was performed in the ED of Imam Khomeini Hospital, Sari, Iran, between 20 September 2015 and 22 May 2017. This study was carried out according to the Helsinki Declaration on ethical principles for research involving human subjects. The Ethics Committee of Mazandaran University of Medical Sciences approved the study on 09 April 2017 (ID: IR.MAZUMS.REC.94-1719). Written informed consent was

Participants' characteristics

230 participants were assessed for eligibility criteria and finally, 200 patients completed the study (Fig. 1).

Mean age of the patients was 35.60 ± 8.17 years. The patients were mostly men (68.5%). The MP and MK groups exhibited roughly similar demographic and clinical characteristics. However, the number of patients with gross hematuria was significantly higher in the MP group compared with the MK group (p = 0.007). In addition, the respiratory rate of patients in the MP group was

Discussion

The results from this single-center, randomized controlled trial showed that the combination of ketamine with morphine compared to morphine alone could better reduce the severity of renal colic pain at both 20 and 40 min after drug injection. In addition, this combination reduced the need for rescue analgesia such that the number of patients in MK group who needs for extra doses of rescue analgesia was lower at both 20 and 40 min after the start of the intervention. Moreover, using this

Conclusion

Adding 0.2 mg/kg ketamine to 0.1 mg/kg morphine appears to reduce the renal colic pain, nausea, and vomiting as well as the requirements for additional rescue analgesia. However, this combination increased the risk of dizziness. Further well-designed studies are needed to identify the optimal adjuvant analgesia, the optimal dose, duration, and timing of ketamine administration.

Conflicts of interest

None.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgments

This study was done at and supported by the Mazandaran University of Medical Science, Sari, Iran.

References (22)

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RCT registration number: The study was registered at the Iraninan registry of clinical trial with ID: IRCT2015080523517N1.

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