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Mix up ketamine and propofol and you get a PSA cocktail that just might give you the best of both worlds.

In October’s EMRAP, Dr. Sanjay Arora discussed procedural sedation and analgesia (PSA) with Mel Herbert. Their discussion centered on ketofol, the combination of ketamine and propofol, which has been proposed as an ideal agent for PSA. The question of the hour: Could Ketofol be the perfect drug?
Sedation does not equal analgesia. Propofol provides excellent sedation but no analgesia. Ketamine provides both good sedation and analgesia but many EPs are hesitant to use it outside of the pediatric population. Adding ketamine to propofol makes up for propofol’s lack of analgesic effect while permitting a lower dose of each agent. Moreover, the two agents are complementary in their adverse effect profiles – propofol lowers blood pressure and pulse whereas ketamine raises both.

To highlight the role of ketofol, Drs. Arora and Herbert considered three specific cases. In the first case, a 6-year-old boy sustains a laceration from a dog bite to the cheek. Which agent should be used to sedate him? Many of us would say ketamine. It’s fast, provides good analgesia, decreased respiratory depression, and we know its side effect profile well.

But what about a 45-year-old male in atrial fibrillation with rapid ventricular response rate? The patient reports no chest pain, only palpitations for the past 20 minutes, and you feel confident that cardioversion is the best treatment. The patient asks, “Is this going to hurt?” You think “Yes it is!” What do you use to sedate him? Some EPs are hesitant to use ketamine on a patient with a cardiac issue because ketamine increases myocardial oxygen demand. As this effect is dose related, the use of ketofol in this situation will result in a lower dose of ketamine and thus mitigate the risk.

In the third case, a 67-year-old female in a motor vehicle collision presents with chest pain and a hip dislocation. You notice a dusky blue, pulseless leg. As you consider procedural sedation agents, you realize that although very effective, full dose propofol could easily cause her to become hypotensive and apneic. You briefly consider etomidate but then remember that it often results in vomiting and myoclonus, which can make orthopedic procedures difficult. You would love to give ketamine, because it will not lower her blood pressure, but the biggest fear that you have is of an emergence reaction, which you have seen before and would prefer not to see again. These reactions can range from a dream-like state with vivid hallucinations to emergence delirium. As it happens, the incidence and severity of emergence reactions can be reduced by using lower doses of ketamine. Again, it appears that the combination of ketamine and propofol, each in doses low enough to mitigate the other’s worst side effects, might be ideal.

The concept of ketofol has been around for many years, with anesthesiologists mixing their own cocktail combinations in the operating rooms, titrating different agents to achieve optimal results. But beyond the OR, there are already several convincing papers on the use of ketofol in the emergency department.

The first article on ketofol in the ED came in 2007. The authors, from University of British Columbia in Vancouver, coined the term ketofol and used 0.5mg/kg of each ketamine and propofol, mixing it in one syringe, on 114 patients requiring procedural sedation. Their reported success rate was about 97% with a short time to recovery, only 3 patients developing hypoxia, and 3 developing an emergence reaction. They concluded that ketofol provides potent sedation, analgesia, and amnesia with a short duration of action, supporting hemodynamic and respiratory stability when used in the emergency room (1).

Shah et. al. evaluated ketofol versus ketamine alone for procedural sedation in children. In this study, 136 kids were given a 1:1 ketamine/propofol mixture versus ketamine alone for orthopedic procedures. They reported procedural sedation success rates of 97% with ketofol versus 100% with ketamine alone. Sedation and recovery times were also comparable. Their conclusion was that no great advantage was realized by using both agents together, but that nothing bad happened either.

David and Shipp, changed how ketofol was given. Instead of mixing a 1:1 mixture in one syringe, the patients were given a pre-dose of 0.5mg/kg of ketamine, followed by 0.5mg/kg of propofol titrated to sedation. This randomized, controlled study looked at ketofol versus propofol alone for emergency department procedural sedation and included both children and adults. They observed that the total dose of propofol administered was less in the ketofol group, which also demonstrated a trend toward better sedation quality overall. This trial provided the most compelling evidence to date that the sedative effects of propofol and subdissociative ketamine are indeed synergistic, with ketamine bridging the gaps of sedation with propofol to provide a more consistent sedation depth (3).

Although in general it is better to use one drug than two, these studies support the safety of ketofol in both adult and pediatric patients. Moreover, in the properly selected patient, it may even be the ideal solution.

Dr. Lopez is a fourth year emergency medicine resident at Los Angeles County/USC Medical Center.
Dr. Swadron is an Associate Professor of Clinical Emergency Medicine at the Keck School of Medicine of the University of Southern California. EM:RAP (Emergency Medicine: Reviews and Perspectives) is a monthly audio program that can be found at www.EMRAP.org


References
1. Willman EV, Andolfatto G. A prospective evaluation of “ketofol” (ketamine/propofol combination) for procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2007;49(1):23-30.
2. Shah A, Mosdossy G, McLeod S, Lehnhardt K, Peddle M, Rieder M. A blinded, randomized controlled trial to evaluate ketamine/propofol versus ketamine alone for procedural sedation in children. Ann Emerg Med. 2011;57(5):425-33.
3. David H, Shipp J. A randomized controlled trial of ketamine/propofol versus propofol alone for emergency department procedural sedation. Ann Emerg Med. 2011;57(5):435-41.




 

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