Get that Man a Ladder! – Helping patients out of the K-hole
Written by Dr. Luke Lin, Edited by Dr. Sunny Elagandhala
Your patient, a 35-year-old, overweight male presents to the ED, intoxicated, with an open right ankle dislocation. He states he “fell off a ladder.” His dorsalis pedis pulse is intact and the articular surface of his right tibia is visibly extruded. He is sedated with 200mg IV Ketamine. Ankle reduction is performed in the ED and his right foot is splinted. While the ketamine wears off, the patient becomes agitated, confused and thrashes his right leg. He kicks apart his Orthoglass splint and re-dislocates his ankle. Then the patient is sedated again with 200mg IV Ketamine. His ankle is reduced once more and splinted. The patient wakes up from the Ketamine agitated and again he fights staff to get out of bed and kicks apart his splint, re-dislocating his ankle a third time.
Unfortunately, this is a real case. The patient eventually had his right foot amputated. This tragedy could have been avoided if the doctors were more prepared to manage the negative side effects of ketamine, namely emergence reaction/ recovery agitation.
Ketamine is an NMDA receptor antagonist and a dissociative anesthetic that is commonly used for procedural sedation. It is probably the most common sedative that we use when we need to reduce fractures and dislocations. We prefer ketamine over other sedatives because its onset is only 1 minute, duration lasts up to 20 minutes and it is the only induction agent that causes hypertension rather than hypotension. Ketamine is considered relatively benign and the adverse effects are generally short lived. [1] However, adverse reactions can be disastrous, as illustrated in the case above.
Remember that Ketamine A.K.A “Special K” is also a recreational street drug that is structurally related to PCP. Although agitation and other psychiatric disturbances caused by ketamine are much less common and less severe than those caused by PCP, Emergency Physicians should exercise caution when using ketamine for procedural sedation. This is especially true in schizophrenics and patients with an unknown psychiatric history. Furthermore, ketamine is a sympathomimetic and also has effects on opioid receptors so its overall effect can be unpredictable. Side effects can include laryngospasm as well as cardiovascular, respiratory, CNS effects. In the streets, the hallucinogenic emergence reaction is referred to as “coming out of the K-hole.” Users may experience vivid dreams, fear, euphoria and “out of body” experiences.
In this post, we aim to better prepare emergency physicians to deal with the potential for recovery agitation/emergence reactions by having benzodiazepines ready at bedside. Benzodiazepines are the mainstay of treatment for psychomotor agitation, muscle rigidity and hallucination caused by ketamine. Lorazepam may be used in 1 to 2 mg IV doses until the desired level of sedation is achieved. Alternatively, diazepam in 5 to 10 mg IV doses may be used.
There has also been research suggesting that pre-treatment with benzodiazepines is beneficial. [2][3][4] According to a 2011 study by Sener et al. “Coadministered midazolam [0.3mg/kg IV or 4 mg/kg IM] significantly reduces the incidence of recovery agitation after ketamine procedural sedation and analgesia.” [5] The study by Sener and colleagues was a double-blind randomized controlled trial of adults undergoing procedural sedation in the ED. 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). One of the primary outcome measures was a binary result of recovery agitation. Recovery agitation included everything from mild moaning to severe agitation requiring further sedation. This study found that 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 reduction in recovery agitation in groups receiving midazolam.
According to another study published in 2018 by Akhlaghi et al. “premedication with either midazolam 0.05 mg/kg or haloperidol 5 mg intravenously significantly reduces ketamine-induced recovery agitation while delaying recovery.” [6] The study by Akhlaghi was also a double-blind randomized controlled trial of adults undergoing procedural sedation in the ED. The trial enrolled 185 subjects that were randomized into receiving one of three interventions 5 minutes before receiving IV ketamine at 1mg/kg: IV distilled water, IV midazolam at 0.05 mg/kg, IV haloperidol at 5 mg. The study showed that the maximum Pittsburg Agitation Scale score was significantly less with midazolam compared with placebo (with a difference of 3) and with haloperidol compared with placebo (with a difference of 3). However, recovery times were also longer in those treated with Haldol. The Richmond Agitation Scale scores at 5, 15, and 30 minutes trended lower with the active agents.
Despite its potential adverse effects, we still believe Ketamine is relatively safe and it should be used routinely for procedural sedation. Disastrous side effects are rare. The findings published by Sener’s 2011 study were reinforced by Akhlaghi’s 2018 study after the latter publication stratified the results based on the severity of the recovery agitation. It is uncommon for agitation from ketamine to result in a foot amputation, like the case above. However, in order to prevent emergence agitation, we should either pretreat patients with Midazolam/Haloperidol before Ketamine or keep Midazolam/Haloperidol available at bedside before procedural sedation with Ketamine.
References
1. Green, S. M., & Sherwin, T. S. (2005). Incidence and severity of recovery agitation after ketamine sedation in young adults. The American journal of emergency medicine, 23(2), 142-144. https://www.ncbi.nlm.nih.gov/pubmed?term=15765332
2. Chudnofsky, C. R., Weber, J. E., Stoyanoff, P. J., Colone, P. D., Wilkerson, M. D., Hallinen, D. L., ... & Perry, M. A. (2000). A combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department patients. Academic emergency medicine, 7(3), 228- 235. https://www.ncbi.nlm.nih.gov/pubmed?term=10730829
3. Somashekara, S. C., Govindadas, D., Devashankaraiah, G., Mahato, R., Deepalaxmi, S., Srinivas, V., & Murugesh, J. V. (2010). Midazolam premedication in attenuating ketamine psychic sequelae. Journal of basic and clinical pharmacy, 1(4), 209. https://www.ncbi.nlm.nih.gov/pubmed/24825990
4. Perumal, D. K., Adhimoolam, M., Selvaraj, N., Lazarus, S. P., & Mohammed, M. A. R. (2015). Midazolam premedication for ketamine-induced emergence phenomenon: a prospective observational study. Journal of research in pharmacy practice, 4(2), 89. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418142/
5. Sener, S., Eken, C., Schultz, C. H., Serinken, M., & Ozsarac, M. (2011). Ketamine with and without midazolam for emergency department sedation in adults: a randomized controlled trial. Annals of emergency medicine, 57(2), 109-114. https://www.sciencedirect.com/science/article/abs/pii/S0196064410015362
6. Akhlaghi N., Payandemehr P., Yaseri Mehdi., Akhlaghi A. (2018). Premedication with Midazolam or Haloperidol to Prevent Recovery Agitation in Adults Undergoing Procedural Sedation with Ketamine: A Randomized Double-Blind Clinical Trial. Pain Management and Sedation/ Original Research 73(5), 463