Ketamine for Pharmacological Management of Aggression and Agitation in Pre-Hospital Settings: A Review of Comparative Clinical Effectiveness, Safety and Guidelines

Rapid stabilization of patients with acute aggression and agitation using either pharmacological or physical restraint is frequently needed to prevent injury of patients, bystanders and providers. Pharmacological restraint need to have quick onset of action, be easily administered, and be safe for patients. Benzodiazepines and antipsychotics such as haloperidol are probably the most often used medication to control acutely agitated patients. However, these drugs have slow onsets of action (in 15 to 30 min) when given intramuscularly, and have significant adverse events including respiratory failure, cardiac dysrhythmias, and prolongation of the QTc interval that may result in cardiac death.Ketamine, an N-methyl-D-aspartate receptor antagonist, has been used in the emergency department for many indications including local anesthesia, procedural sedation, pain management, asthma and depression.– Ketamine can be administered via intramuscular (IM), intravenous (IV), subcutaneous, or intranasal route. It has been suggested that ketamine may be useful for the control of agitated patients due to its short onset of action (less than 5 minutes), duration of 30 min, and having few hemodynamic changes. In 2017, the American College of Emergency Physicians endorsed the use of ketamine for sedation of agitated patients in the emergency department (ED), despite limited evidence. The literature is also relatively sparse regarding the effectiveness and safety of ketamine for sedation of agitated patients in the prehospital settings, in which a physician is absent.The aim of this report is to review the comparative clinical effectiveness and safety of ketamine for pharmacological management of aggression and agitation in pre-hospital settings or any setting. The report also reviews evidence-based guidelines regarding the pharmacological management of aggression and agitation in prehospital settings.