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Journal Scan: Benzodiazepines Reduce Ketamine-Related Emergence Reactions in Adults

Waxman, Matthew MD; Lovato, Luis M. MD

doi: 10.1097/01.EEM.0000398959.94031.f5

    Of the many drugs stocked in modern emergency departments, ketamine is one of the most fascinating. While most emergency physicians reflexively administer ketamine for the wailing 3-year-old with a complex head laceration, many are apprehensive about sending a business professional with a broken hip on the equivalent of an acid trip.

    Developed in 1962 by Parke-Davis as a safer alternative to the related compound phencyclidine (PCP), ketamine is less likely to cause seizures or neurotoxicity. American soldiers in Vietnam having emergent surgery were some of the first patients to receive ketamine. Today, ketamine remains a convenient “anesthesiologist in a bottle” in the developing world because it provides a true dissociative state while safely maintaining airway reflexes and blood pressure.

    More than likely, a few members of your ED group have been comfortable sedating adults with Special K for years. As a self-described ketaphile, the lead author of this month's column has trained medics on the Thai-Burmese border to use ketamine sedation safely and successfully for extremity amputations done in relatively unsophisticated, makeshift environments. Conversely, ketaphobes roll their eyes when ketamine crusaders wax poetic about their psychedelic marvel.

    This study and the accompanying editorial attempt to answer the question of whether the administration of benzodiazepines with ketamine can reduce the incidence of emergence reactions in adult patients undergoing procedural sedation in the emergency department.

    Ketamine With and Without Midazolam for Emergency Department Sedation in Adults: A Randomized Controlled Trial

    Sener S, Eken C, et al

    Ann Emerg Med


    The Taming of Ketamine —

    40 Years Later

    Green S, Krauss B

    Ann Emerg Med


    The study by Sener et al was a double-blind randomized controlled trial of adults between 18 and 50 undergoing procedural sedation in the ED. Notably excluded were patients with severe systemic disease (ASA physical status III or above); those with significant cardiovascular, neurologic, thyroid or psychiatric disorders; those with acute pulmonary infections, and patients who were pregnant. Of 548 eligible patients, 200 were randomized into one of four groups: IM ketamine (4 mg/kg) with or without IV midazolam (0.03 mg/kg) and IV ketamine (1.5 mg/kg) with or without IV midazolam (0.03 mg/kg).

    The majority of procedures were orthopedic (fractures, dislocation reductions) or wound-related (lacerations, burn care, incision and drainage). Primary outcome measures in this study were recovery agitation and adverse events. The authors used a broad definition of recovery agitation, which included everything from mild moaning to severe agitation requiring further sedation.

    Consistent with previous studies (Am J Emerg Med 2008;26[9]:985), this study found an overall incidence of recovery agitation of 16 percent after ketamine sedation. Overall, there was significantly more recovery agitation in those who did not receive midazolam (22%) than those who did (8%), representing a 17 percent absolute decrease in recovery agitation in groups receiving midazolam. Remarkably, there was no incidence of laryngospasm, oxygen desaturation, or apnea in any of the groups.

    Some notable limitations of this study should be pointed out. Due to a variety of factors, a rather substantial 60 percent (348/548) of eligible patients ultimately were not enrolled in the study. As a general principle, as the proportion of eligible patients excluded from a study increases, so does the potential for some unintended or unknown selection bias to affect the validity of the study conclusions in other populations (external validity).

    Recovery agitation also was reported as a binary result: either it occurred or not. Unfortunately, the authors provided no information about the severity of each episode. To better gauge the clinical impact of adding midazolam, it would have been more helpful to know how many of these episodes were clinically significant. If, for example, the midazolam benefit was limited to merely preventing a groan or two, there very well might be a statistically significant effect, even though it had no significant clinical relevance.

    What should the front-line emergency physician take home from this column? Ketamine is a relatively safe and viable option for adult procedural sedation in the ED. If it isn't already, ketamine should be part of your adult sedation arsenal. It is true that other sedation alternatives like propofol, etomidate, and fentanyl/midazolam also have low rates of respiratory depression, but in this study, respiratory depression from ketamine sedation was completely nonexistent. There were absolutely no incidents of hypoxia or apnea reported in this study! Keeping other contraindications in mind, this might actually make ketamine sedation preferable in adults in whom you would anticipate falling on the far right of the difficult airway spectrum.

    Secondly, while IM ketamine is the preferred route in children, the IV route is likely preferable in adults. In addition to the pharmacodynamic benefits of more rapid onset and shorter duration of action from the IV route, it is also important to have IV access readily available so that benzodiazepines can be administered. If you prefer minimizing the chance of any emergence reaction, no matter how trivial that reaction may be, administer midazolam routinely with adult ketamine sedation. On the other hand if you prefer minimizing the administration of medication, have midazolam immediately available, and use it only if there is a reaction deemed significant.

    And make sure the patients you choose for ketamine sedation are similar to the ones in this study: under 50, ASA physical status II or less, no significant cardiovascular disease, and no significant neuropsychiatric disorders, a population at higher risk of developing severe emergence agitation.

    Comments about this article? Write to EMN at[email protected].

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    Dr. Waxmanis an assistant clinical professor of medicine at the David Geffen School of Medicine at the University of California at Los Angeles, and an emergency physician and hospitalist at UCLA-Olive View Medical Center.Dr. Lovatois an associate professor at the David Geffen School of Medicine at UCLA, the director of critical care in emergency medicine at Olive View-UCLA Medical Center, the co-chair for the Emergency Medicine Best Practices Committee for the Los Angeles County Department of Health Services, and an instructor for the National MegaLLSA Review Course (

    © 2011 Lippincott Williams & Wilkins, Inc.