Ketamine in Emergency Medicine

Ketamine is a potent dissociative analgesic and anesthetic that has gained popularity in emergency medicine over the last decade. It contains an asymmetrical carbon atom, leading to two optical isomers (the S-(+) isomer and the R-(-) isomer) that have different pharmacologic profiles. S-(+)-ketamine is two-fold more effective and longer acting than the racemic mixture of both isomers.¹ However, S-(+)-ketamine is only available in some countries.¹ 

Ketamine is suitable for administration via multiple routes, making it adaptable to many clinical scenarios.^1,3 Racemic ketamine is commonly available in three different concentrations: 10, 50, and 100 mg/mL. The 50 mg/dL solution is most commonly stocked because it can be easily injected intravenously and intramuscularly. S-(+)-ketamine is available in two concentrations: 5 and 25 mg/mL. The S-(+)-ketamine solution is preservative-free, which may decrease neurotoxicity. Patients often report fewer side effects and a shorter recovery with S-(+)-ketamine.¹ The variable dosing of ketamine allows it to serve as an induction agent with a good hemodynamic profile at higher doses, or as a sedative or analgesic drug at lower doses.³ 

The use of ketamine and propofol mixed in a single syringe, known as “ketofol,” has become a popular sedative agent in emergency medicine. The opposing physiological effects of ketamine and propofol can be used to clinical advantage as ketamine mitigates propofol-induced hypotension, and propofol mitigates ketamine-induced vomiting and recovery agitation.¹ Ketamine and propofol can also be administered in separate syringes to achieve desired effects.^1,2 For example, small doses of propofol can be given following ketamine administration to relieve muscle rigidity.² 

Ketamine has been used in emergency medicine as an alternative to rapid sequence intubation (RSI), the most common method of facilitating endotracheal intubation (ETI). ETI is a high-risk procedure frequently performed in emergency departments that is associated with considerable patient mortality and morbidity. Traditional RSI involves the simultaneous administration of an induction agent and paralytic, which can result in harmful consequences in patients who have challenging airway anatomy, severe hypoxia, acidemia, or hypotension. Ketamine can be used as an alternative to traditional RSI by delaying intubation, which allows time for proper airway preparation and preoxygenation. Additionally, it can be administered without a paralytic, allowing for ETI while the patient continues to breathe spontaneously.² 

Some studies have also suggested that ketamine is effective for acute agitation in the emergency medicine setting.⁴ Common causes of acute agitation are varying combinations of alcohol, drugs, medical issues, and psychiatric episodes.⁵ When surveyed, nearly half of emergency department staff reported experiencing physical assault by a patient.⁴ Traditional agents such as benzodiazepines and antipsychotics have several disadvantages.⁵ Benzodiazepines increase the risk of respiratory failure when combined with alcohol or other central nervous system depressants. Moreover, the onset of action of benzodiazepines and antipsychotics is 15-30 minutes after administration. Ketamine is a more effective alternative, as it readily crosses the blood-brain barrier and has a typical onset of action of less than 5 minutes.⁵ 

Furthermore, ketamine is considered to have a very good safety profile. Ketamine overdose is uncommon when administered appropriately and only a few cases of severe respiratory depression have been linked to ketamine administration.³ However, healthcare providers must carefully consider the risks associated with ketamine and when its use is indicated. According to the British National Formulary, absolute contraindications to ketamine are hypertension, cardiovascular disease, stroke, elevated intracranial pressure, porphyria, and thyroid disorder. Ketamine is also not recommended for patients less than 3 months in age and patients with schizophrenia.^1,3 Common adverse events associated with ketamine sedation include recovery agitation, muscular hypertonicity, emesis, laryngospasm, and hypersalivation.¹  

Ketamine is a promising agent for induction of anesthesia and analgesia in emergency medicine. Increased availability of solutions of pure S-(+)-ketamine may help to increase its use.³ As ketamine usage increases in emergency medicine, healthcare providers should remain cognizant of its side effects and limitations.^1,3 

References 

1. Marland, S., Ellerton, J., Andolfatto, G., et al. (2013). Ketamine: use in anesthesia. CNS Neuroscience & Therapeutics, 19(6), 381-389. doi:10.1111/cns.12072 

2. Merelman, A. H., Perlmutter, M. C., & Strayer, R. J. (2019). Alternatives to rapid sequence intubation: contemporary airway management with ketamine. Western Journal of Emergency Medicine, 20(3), 466. doi:10.5811/westjem.2019.4.42753 

3. Gales, A., & Maxwell, S. (2018). Ketamine: Recent evidence and current uses. Education for Anesthesia Providers Worldwide, 43. 

4. Sullivan, N., Chen, C., Siegel, R., Ma, Y., Pourmand, A., Montano, N., & Meltzer, A. (2019). Ketamine for emergency sedation of agitated patients: A systematic review and meta-analysis. The American Journal of Emergency Medicine. doi:10.1016/j.ajem.2019.11.007 

5. Mankowitz, S. L., Regenberg, P., Kaldan, J., & Cole, J. B. (2018). Ketamine for rapid sedation of agitated patients in the prehospital and emergency department settings: a systematic review and proportional meta-analysis. The Journal of Emergency Medicine, 55(5), 670-681. doi:10.1016/j.jemermed.2018.07.017