Pain management and sedation/original researchKetamine-Propofol Combination (Ketofol) Versus Propofol Alone for Emergency Department Procedural Sedation and Analgesia: A Randomized Double-Blind Trial
Introduction
Procedural sedation and analgesia is used in the emergency department (ED) to efficiently and humanely perform necessary painful procedures.1 Ketamine and propofol are 2 medications commonly used for this purpose because they possess many characteristics deemed desirable by clinicians.2, 3 However, ketamine use is limited by its propensity to cause emesis and recovery agitation, and by its prolonged recovery time compared with that of propofol.4, 5 Propofol itself is limited by dose-dependent hypotension and respiratory depression,6, 7, 8 especially when combined with opioids.9, 10, 11, 12, 13 The opposing physiologic effects of ketamine and propofol suggest the potential for synergy, and this has led to interest in their combined use, commonly termed “ketofol,” to facilitate ED procedural sedation.14, 15, 16 The use of ketofol has been described in numerous non-ED settings,17, 18, 19, 20, 21 and its use for ED procedural sedation has been accomplished with each drug in separate syringes, as well as mixed in the same syringe.22, 23, 24, 25, 26, 27 The combination has been demonstrated to be chemically stable and physically compatible when mixed in polypropylene syringes.28, 29
The potential advantages of ketofol over propofol alone include the provision of deep sedation with lower doses of propofol, thus potentially limiting propofol-associated adverse respiratory effects; the provision of ketamine analgesia without the increased adverse respiratory effects associated with concomitant opioid administration; and the mitigation of propofol-induced hypotension.30, 31 The potential advantages of ketofol over ketamine-alone procedural sedation include shorter recovery time and a lower incidence of ketamine-associated emesis and recovery agitation.26, 32
The potential synergy of ketamine and propofol used in combination may result in fewer adverse respiratory events than when propofol is used alone for ED procedural sedation.
Our goal was to determine whether a single-syringe mixture of ketamine and propofol in a 1:1 ratio for ED procedural sedation in patients aged 14 years or older results in a 13% or more absolute reduction in adverse respiratory events as described by predefined criteria (the Quebec Criteria)33 when compared with propofol alone.
Section snippets
Study Design
This was a randomized, double-blind trial approved by the University of British Columbia Clinical Research Ethics Board. Before study launch, the methods were registered with ClinicalTrials.gov (NCT01211158), and a “no objection letter” was obtained from Health Canada (file no. 9427-2649-21C).
Subjects were assigned to receive either propofol or ketofol by a computer-generated block randomization schedule, with variable block sizes to a maximum of 10.
Setting and Selection of Participants
The study was performed between December 2010
Characteristics of Study Subjects
The flow of study subjects is illustrated in Figure 1, which represents all patients sedated during the study period. There were no cases of sedations occurring with agents other than ketofol or propofol. The 2 groups were similar with regard to demographic characteristics and procedures performed (Table 2). The most commonly performed procedures were orthopedic, comprising 60% of each group. Fifty-nine ketofol patients (41%) and 50 propofol patients (35%) received preprocedural analgesia. No
Limitations
The use of the Quebec Criteria for reporting adverse events is limited by the fact that the decision to intervene is based on the judgment of the clinician. Different clinicians may have different intervention thresholds in the face of a potentially adverse event.
The variety of procedures performed had differing requirements for sedation and analgesia. The use of the same weight-based dosing schedule for procedures of varied painfulness may have affected the incidence of adverse events.
Discussion
To our knowledge, this study is the largest reported randomized double-blind comparison of ketamine-propofol combination versus propofol alone for ED procedural sedation and analgesia. Using the widely accepted intervention-based Quebec Criteria,33 we found that, when targeting deep sedation, the incidence of adverse respiratory events is not lessened when a 1:1 single-syringe mixture of ketamine and propofol is used compared with using propofol alone.
Ketamine is known to preserve respiratory
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Supervising editor: Steven M. Green, MD
Author contributions: GA, RBA-L, and EW conceived the study. GA, RBA-L, PJZ, and EW performed the background literature review and designed the study. GA, SMS, SS, and SM supervised conduct of the trial and data collection. EW tabulated data and provided statistical analyses. GA drafted the article, and all authors contributed substantially to its revision and approved the final version of the article. GA takes responsibility for 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 as per ICMJE conflict of interest guidelines (see www.icmje.org). Dr. Andolfatto is supported by a Vancouver Coastal Health Research Institute Mentored Clinical Scientist Award (FAS # F09-05828).
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Please see page 505 for the Editor's Capsule Summary of this article.
Publication date: Available online March 7, 2012.