Pain management and sedation/original researchA Randomized Controlled Trial of Ketamine/Propofol Versus Propofol Alone for Emergency Department Procedural Sedation
Introduction
Drugs administered for emergency department (ED) procedural sedation and analgesia include propofol, ketamine, benzodiazepines, opioids, and barbiturates,1, 2, 3, 4 with propofol being particularly popular despite its potential for respiratory depression and hypotension.5 Preliminary research suggests that adding ketamine to propofol might enhance hemodynamic stability,6, 7, 8 decrease respiratory depression,9 and stabilize respiratory drive.10, 11 Three observational series of ED ketamine/propofol procedural sedation suggest that the combination is safe and effective.12, 13, 14
If the combination of ketamine/propofol is safer or more effective than propofol alone, then it would be preferred.
We wished to compare the incidence of respiratory depression between ketamine/propofol and propofol alone for ED procedural sedation. Our secondary objectives were to compare provider satisfaction, sedation quality, and total propofol dose.
Section snippets
Study Design and Setting
We conducted a randomized, double-blind, placebo-controlled trial of children and adults receiving procedural sedation from April 2007 until July 2009 in the ED of a 274-bed university teaching hospital with an annual census of greater than 40,000 patient visits. The study was approved by the University of Missouri institutional review board, and informed consent was obtained from all participants or their parents.
Selection of Participants
ED attending physicians participating in the study enrolled patients selected for
Results
Patient flow is shown in Figure 1. Baseline characteristics were similar between groups, except more men were in the propofol-alone group (Table 2). Young children were unable to tolerate the sunglasses 2 times in the ketamine/propofol group and 4 times in the propofol-alone group.
For our primary outcome, the incidence of respiratory depression was similar between groups (Table 3; P=.38), including comparisons of the individual markers (Table 4). In the ketamine/propofol group, 2 subjects
Limitations
The principal limitation to our study was the challenge of maintaining blinding with ketamine. Although we used sunglasses to obscure nystagmus, 3% of subjects could not tolerate them and were thus likely unblinded. We did not find that the glasses impaired monitoring, as has been described elsewhere.19 We observed that some subjects became quiet after receiving the study intervention, potentially unblinding them. We did not count how often this occurred, nor did we have providers attempt to
Discussion
To our knowledge, we report the first randomized controlled trial of ketamine/propofol versus propofol alone in the ED setting. Although both regimens demonstrate similar evidence of safety according to our primary outcome of respiratory depression, we observed differences in our secondary outcomes favoring the ketamine/propofol group.
First, we observed that sedation could be maintained with significantly less propofol in the ketamine/propofol group. This finding may lack clinical importance
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Supervising editor: Steven M. Green, MD
Author contributions: HD and JS conceived the study, designed the protocol, obtained departmental funding for the trial, and supervised the conduct of the trial and its data collection, including quality control. HD analyzed the data and drafted the article. Both authors contributed substantially to its revision. HD 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 that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement.
Publication date: Available online January 21, 2011.
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