Authors: Brandon Reynolds, PharmD: UMKC School of Pharmacy Class of 2018 and Kerra Cissne, PharmD: PGY-2 Pharmacy Resident at Truman Medical Center
Ketamine was first described as an anesthetic and “chemical derivative” of phencyclidine (PCP) in 1965 by the American Society for Clinical Pharmacology and Therapeutics.1 Ketamine, like PCP, has the capability of inducing a state of dissociative anesthesia as well as producing a strong analgesic and amnestic effect.2,3 Unlike PCP, ketamine demonstrates a shorter duration of action and less pronounced psychotomimetic effects than its parent drug, vastly improving its clinical properties as an anesthetic.4 In contrast to other medications employed for analgesia and procedural sedation, ketamine preserves respiratory function and hemodynamic stability.5 In the emergency department, ketamine has several uses, including acute pain management, procedural sedation, limb reduction, and anesthesia in patients with diminished or worsening respiratory drive.6
Ketamine has multiple mechanisms of action. The most studied mechanism is the drug’s ability to block glutamate receptors, such as the N-methyl-D-aspartate (NMDA) receptor and the non-NMDA glutamate receptors.4 Although there are several other proposed mechanisms related to analgesia such as µ-opioid receptor agonism,7 NMDA receptor antagonism is expected to induce the characteristic properties of ketamine use such as amnesia, analgesia, and psychosensory effects.4 Interestingly, the dissociative anesthesia induced by ketamine is proposed to be caused by a disconnect between the thalamo-neocortical and limbic systems, which may also be associated with the emergence phenomenon8 afflicting an estimated 23% of patients that do not receive adjunctive benzodiazepines.8,9 This phenomenon, however, is still relatively poorly understood and is described in a heterogeneous manner throughout the literature.
Subanesthetic analgesia: A prospective, randomized, double-dummy trial of IV ketamine use for subdissociative analgesia in the emergency department (ED) was published in the American Journal of Emergency Medicine in August 2017 by Motov et al12
Procedural sedation and analgesia: Ferguson I et al 14 published the POKER study in the Annals of Emergency Medicine in 2016. POKER is the largest randomized, double-blind, prospective clinical trial to date comparing propofol to ketofol, a 1:1 mixture of ketamine and propofol, for procedural sedation in adults
Dissociative sedation for excited delirium: A prospective, single-center, observational study evaluated different treatment modalities for emergency department patients with excited delirium, a condition is characterized by violent outbursts oftentimes due to acute psychosis or intoxication15
Ketamine has a multitude of uses and beneficial effects due to its unique pharmacology, and it harbors significant advantages over current mainstream therapies. It is an opioid-sparing pain-relieving agent6, it preserves respiratory drive while facilitating painful procedures13,14, and can very rapidly dissociate a patient experiencing excited delirium.15,16 Of note, ketamine does have drawbacks, including an increase in nausea and vomiting as well as the risk of emergence phenomenon in higher dosages.17 Research continues to be published on the use of ketamine in several situations, as evidenced by the recent surge of literature for esketamine, the active S-enantiomer of ketamine, for treatment of major depressive disorder with an imminent suicide risk.18 With new research and the overarching threat of opioid addiction in the United States, ketamine may present itself as an old drug with new tricks.