Ketamine Safety and Use in the Emergency Department for Pain and Agitation/Delirium

A Health System Experience

Hanjie Mo, PharmD; Matthew J. Campbell, PharmD; Baruch S. Fertel, MD, MPA; Simon W. Lam, PharmD; Elizabeth J. Wells, PharmD; Elizabeth Casserly, PharmD; Stephen W. Meldon, MD


Western J Emerg Med. 2020;21(2):272-281. 

In This Article

Abstract and Introduction


Introduction: Two protocols were developed to guide the use of subdissociative dose ketamine (SDDK) for analgesia and dissociative sedation ketamine for severe agitation/excited delirium in the emergency department (ED). We sought to evaluate the safety of these protocols implemented in 18 EDs within a large health system.

Methods: We conducted a retrospective chart review to evaluate all adult patients who received intravenous (IV) SDDK for analgesia and intramuscular (IM) dissociative sedation ketamine for severe agitation/excited delirium in 12 hospital-based and six freestanding EDs over a one-year period from the protocol implementation. We developed a standardized data collection form and used it to record patient information regarding ketamine use, concomitant medication use, and any comorbidities that could have impacted the incidence of adverse events.

Results: Approximately 570,000 ED visits occurred during the study period. SDDK was used in 210 ED encounters, while dissociative sedation ketamine for severe agitation/excited delirium was used in 37 ED encounters. SDDK was used in 83% (15/18) of sites while dissociative sedation ketamine was used in 50% (9/18) of sites. Endotracheal intubation, non-rebreather mask, and nasal cannula ≥ four liters per minute were identified in one, five, and three patients, respectively. Neuropsychiatric adverse events were identified in 4% (9/210) of patients who received SDDK.

Conclusion: Patients experienced limited neuropsychiatric adverse events from SDDK. Additionally, dissociative sedation ketamine for severe agitation/excited delirium led to less endotracheal intubation than reported in the prehospital literature. The favorable safety profile of ketamine use in the ED may prompt further increases in usage.


Ketamine is an N-methyl-D-aspartate receptor antagonist that exhibits dissociative sedation and analgesic properties and is commonly used in procedural sedation and induction settings.[1–3] Additionally, ketamine has been explored as novel therapy for analgesia and severe agitation/excited delirium. Multiple studies have described the efficacy and safety of subdissociative-dose ketamine (SDDK) for analgesia in the emergency department (ED), typically with dosing regimens of 0.1–0.3 milligrams per kilogram (mg/kg) administered intravenously (IV).[4–9] Dissociative sedation ketamine, typically defined as 3–5 mg/kg given intramuscularly (IM),[10–12] has been studied for severe agitation/excited delirium in the prehospital setting.[12–14] Ketamine use for this indication has also been studied in a limited number of patients in single-center EDs.[15,16] Adequate sedation is necessary to prevent severe agitation/excited delirium complications such as metabolic abnormalities, cardiac arrest, and death.[11]

However, ketamine administration may contribute to serious respiratory, cardiovascular, and neuropsychiatric adverse events.[8,10,12] Cole et al. reported intubation rates of 39% for severely agitated patients who received ketamine 5 mg/kg IM vs 4% for those who received haloperidol 10 mg IM in the prehospital setting.[13] These authors also reported intubation rates of 57% in profoundly agitated patients who received ketamine in the prehospital setting.[14] SDDK use may also lead to neuropsychiatric adverse events such as mood changes, dysphoria, confusion, and hallucinations.[4–6,16] To assist emergency medicine (EM) prescribers in safely using ketamine, our emergency services attending physicians and pharmacists developed two ED ketamine protocols for these two indications.

Previous single-center studies have described the benefits and risks of SDDK for analgesia and dissociative sedation ketamine for severe agitation/excited delirium, but the optimal dosing range and administration method of SDDK to minimize adverse effects is unclear.[8–9,17–18] Additionally, limited, single- center studies have assessed the safety of IM ketamine for severe agitation/excited delirium in the prehospital setting and ED.[12–16] We designed this multicenter study to provide further insight into the safety of ketamine use in the ED for these two novel indications across a broad spectrum of EDs in a variety of settings.

Our goal was to evaluate the safety of SDDK for analgesia and dissociative sedation ketamine for severe agitation/excited delirium in patients at 18 EDs of a large, integrated health system. The primary objective of this study was to describe the incidence of serious respiratory and cardiovascular adverse events requiring intervention within two hours after ketamine administration. Secondary objectives included describing the incidence of neuropsychiatric adverse events after SDDK administration during the ED encounter; determining the percentage of ketamine orders in the ED for analgesia or severe agitation/excited delirium that were adherent to the approved protocols; and evaluating real-world ketamine use in a large, integrated health system with a diverse group of providers.