Pain management and sedation/original research
A Randomized Controlled Trial of Ketamine/Propofol Versus Propofol Alone for Emergency Department Procedural Sedation

https://doi.org/10.1016/j.annemergmed.2010.11.025Get rights and content

Study objective

We compare the frequency of respiratory depression during emergency department procedural sedation with ketamine plus propofol versus propofol alone. Secondary outcomes are provider satisfaction, sedation quality, and total propofol dose.

Methods

In this randomized, double-blind, placebo-controlled trial, healthy children and adults undergoing procedural sedation were pretreated with intravenous fentanyl and then randomized to receive either intravenous ketamine 0.5 mg/kg or placebo. In both groups, this procedure was immediately followed by intravenous propofol 1 mg/kg, with repeated doses of 0.5 mg/kg as needed to achieve and maintain sedation. Respiratory depression was defined according to any of 5 predefined markers. Provider satisfaction was scored on a 5-point scale, sedation quality with the Colorado Behavioral Numerical Pain Scale, and propofol dose according to the total number of milligrams of propofol administered.

Results

The incidence of respiratory depression was similar between the ketamine/propofol (21/97; 22%) and propofol-alone (27/96; 28%) groups, difference 6% (95% confidence interval −6% to 18%). With ketamine/propofol compared with propofol alone, treating physicians and nurses were more satisfied, less propofol was administered, and there was a trend toward better sedation quality.

Conclusion

Compared with procedural sedation with propofol alone, the combination of ketamine and propofol did not reduce the incidence of respiratory depression but resulted in greater provider satisfaction, less propofol administration, and perhaps better sedation quality.

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

References (35)

  • K. Wilbur et al.

    Is propofol an optimal agent for procedural sedation and rapid sequence intubation in the emergency department?

    CJEM

    (2001)
  • T.W. Hui et al.

    Additive interactions between propofol and ketamine when used for anesthesia induction in female patients

    Anesthesiology

    (1995)
  • H.P. Frizelle et al.

    A comparison of propofol with a propofol-ketamine combination for sedation during spinal anesthesia

    Anesth Analg

    (1997)
  • E. Tomatir et al.

    Effects of low dose ketamine before induction on propofol anesthesia for pediatric magnetic resonance imaging

    Paediatr Anaesth

    (2004)
  • Z. Morse et al.

    Effects of a propofol-ketamine admixture in human volunteers

    Pacific Health Dialog

    (2003)
  • R.F. Mortero et al.

    The effects of small-dose ketamine on propofol sedation: respiration, postoperative mood, perception, cognition, and pain

    Anesth Analg

    (2001)
  • G. Andolfatto et al.

    A prospective case series of pediatric procedural sedation and analgesia in the emergency department using single-syringe ketamine-propofol combination (ketofol)

    Acad Emerg Med

    (2010)
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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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