Combining ketamine and propofol ("ketofol") for emergency department procedural sedation and analgesia: a review. (2008)

R eview A rticle Combining Ketamine and Propofol (“Ketofol”) for Emergency Department Procedural Sedation and Analgesia: A Review Sanjay Arora, MD Department of Emergency Medicine, Keck/USC School of Medicine, Los Angeles, CA Submission history: Submitted May 24, 2007; Accepted November 1, 2007 Reprints available through open access at www.westjem.org [WestJEM. 2008;9:20-23.] INTRODUCTION Emergency physicians must be comfortable and confident in providing safe and effective procedural sedation and analgesia (PSA). Goals of PSA include providing an adequate level of sedation while minimizing pain and anxiety, maximizing amnesia, minimizing the potential for adverse drug-related events, controlling behavior, and maintaining a stable cardiovascular and respiratory status. The ideal pharmacologic agent for PSA would accomplish all of these goals, and would have a quick onset and offset, be safe in all age groups, be inexpensive, and be equally efficacious in multiple routes of administration. Unfortunately, at this time no single agent exists that has all of the aforementioned qualities, so physicians must use combinations of different drugs at varying does to achieve as many of the desired goals as possible. The most recent PSA combination to be described in the literature is that of low-dose ketamine and propofol (“ketofol”). In this article we attempt to describe the postulated benefits of using these two agents together and examine the safety and efficacy of the combination. Background Ketamine was developed in the 1960s as a safer and more predictable anesthetic than its precursor phencyclidine (PCP). It is a unique agent in procedural sedation and analgesia (PSA) in that it is a “dissociative” anesthetic that functions by blocking communication between the thalamic and limbic regions of the brain, thereby preventing the brain from processing external stimuli. 1 It provides excellent amnesia and analgesia, and preserves muscle tone maintaining protective airway reflexes and spontaneous respiration. 2,3 Despite its obvious advantages over other agents, some practitioners are hesitant to use ketamine alone secondary to its propensity to cause vivid and frightening emergenct reactions. 4 Additional significant adverse effects include sympathomimetic effects and vomiting when administered in sedating doses. 5 Propofol is a non-barbiturate sedative hypnotic developed in Europe in the 1970s and was gradually utilized Western Journal of Emergency Medicine by anesthesiologists in the United States over the next two decades. Relatively recently its use has spread into the Emergency Department (ED) as a part of PSA. Its popularity as a PSA agent is growing rapidly due mainly to its favorable pharmacokinetic profile as the lipid solubility confers a quick onset and short recovery time. 6 It also has the advantages of functioning as an antiemetic, an anticonvulsant, and an amnestic agent. 7 Although extremely effective and potent, propofol use is limited by a relatively high incidence of dose- dependant hypotension and respiratory depression. 7,8,9 It is postulated that combining these two agents for PSA may preserve sedation efficacy while minimizing their respective adverse effects. This is due partly to the fact that many of the aforementioned potential adverse effects are dose-dependant, and when used in combination the doses administered of each can be reduced. 10 Also, the cardiovascular effects of each are opposing in action, thus theoretically balancing each other out when used together. This theoretical advantage of ketofol producing a more stable hemodynamic and respiratory profile was tested and found to be true in a group of healthy patients receiving general anesthesia. 11 Although there is a significant amount of literature describing the use of ketofol in infusion form, in this article we attempt to review all the published literature describing the use of ketofol in bolus form as would be applicable for PSA in the ED. METHODS Both MEDLINE and Pubmed were searched using ketamine, propofol, ketofol, conscious sedation, and procedural sedation as search terms. This resulted in the identification of 31 abstracts. All abstracts were reviewed and those that described the use of the combination of ketamine and propofol in intravenous bolus form were included for review. Those that described studies in animals, in healthy volunteers, or that described the administration of propofol and ketamine either in isolation, in infusion form, or for general anesthesia were excluded. An ancestral search of Volume IX, no . 1 : January 2008