SGEM#473: Did You Ever Have To Make Up Your Mind – Midazolam or Ketamine for Acute Agitation in the Pre-Hospital Setting

Reference: Muldowney et al. A Comparison of Ketamine to Midazolam for the Management of Acute Behavioral Disturbance in the Out-of-Hospital Setting. Ann Emerg Med. 2025  Date: April 24, 2025 Guest Skeptic: Dr. Howie Mell received his Medical Doctorate (MD) from the University of Illinois at Chicago, College of Medicine at Rockford. Prior to that, he received a Master of Public Health (MPH) degree emphasizing Environmental and Occupational Health from the University of Illinois at Chicago, School of Public Health, while serving as a firefighter/paramedic in the Chicago suburbs. He completed his residency in emergency medicine at the Mayo Graduate School of Medicine, Rochester, Minnesota. Dr. Mell is board-certified by the American Board of Emergency Medicine in both Emergency Medicine (EM) and Emergency Medical Services (EMS) Medicine. He is a Fellow of the American College of Emergency Physicians (FACEP). Dr. Mell serves as an Ambassador Emergency Physician for Vituity (formerly CEP-America), and he is currently assigned to Schneck Medical Center in Seymour, Indiana (John Cougar Mellencamp’s “Small Town”). Case: You’re an experienced paramedic working a busy night shift in an urban EMS system. Dispatch sends you to a call for a 35-year-old male found acting erratically in a public park. Upon arrival, you find him disoriented, agitated, and combative. Bystanders report that he has been using methamphetamine and alcohol. The patient is uncooperative, making verbal de-escalation ineffective. Physical restraint is needed for transport. Your EMS protocol allows for pharmacologic sedation with either midazolam (1 to 5 mg IV/IM, repeat every 2 to 5 minutes as needed) or ketamine (5 mg/kg IM, max 500 mg). The patient is tachycardic (HR 122 bpm), hypertensive (BP 156/96 mmHg), and has a Glasgow Coma Scale (GCS) score of 12. You need to act quickly for scene safety and the patient's well-being. Background: Acutely agitated patients in the pre-hospital setting present a unique challenge for emergency medical services (EMS). Agitation can stem from various underlying conditions, including psychiatric disorders, substance intoxication, metabolic disturbances, traumatic brain injury, or postictal states​. If not managed appropriately, severe agitation can escalate, leading to self-harm, harm to others, or interference with necessary medical care. Initial management emphasizes verbal de-escalation techniques, which should always be attempted first. However, when these strategies fail, pharmacologic sedation may be necessary to ensure the safety of both the patient and pre-hospital providers. The choice of sedative agent is a critical decision. The paramedic must balance the need for rapid sedation with the risk of adverse effects, including respiratory depression and cardiovascular instability​. Benzodiazepines, such as midazolam, have historically been used for pre-hospital sedation due to their anxiolytic and muscle-relaxant properties. However, their use is associated with risks such as respiratory depression and paradoxical agitation. In recent years, ketamine has gained popularity due to its rapid onset, potent dissociative properties, and preservation of airway reflexes​. Despite its advantages, ketamine is not without concerns, including the potential for emergence reactions, increased blood pressure, and the need for airway management in some cases. Current guidelines lack consensus on the optimal pharmacologic approach, leading to significant variation in practice across EMS systems. The ongoing debate surrounding the best sedation strategy highlights the need for robust clinical research to guide evidence-based practice. A newly published study aims to address this knowledge gap by comparing ketamine and midazolam in the out-of-hospital setting, shedding light on their relative efficacy and safety. Clinical Question: In prehospital patients requiring pharmacologic sedation for acute behavioural disturbance,...