In the prehospital setting, undifferentiated patients presenting with hyperactive delirium with severe agitation (HDSA) may be acutely disoriented, restless, aggressive, hyperthermic, and a risk to themselves or others [1,2]. These patients may initially require sedating medications for stabilization and transport to the hospital [3]. Antipsychotics and benzodiazepines, often considered first-line medications for sedation, may not be optimal for such patients because of their time of onset and potential adverse effects, including respiratory depression and loss of airway control [1,3,4].

Ketamine has been shown to more rapidly provide sufficient sedation within three-to-five minutes when administered via intramuscular (IM) injection, when compared to midazolam and haloperidol [3,[5], [6], [7]]. Ketamine is a schedule III non-narcotic that can be used to provide rapid sedation with preserved respiratory function through antagonism of glutamate N-methyl-d-aspartate receptors in the central nervous system, inducing a dissociated state resulting in analgesia and amnesia [8,9]. Use of ketamine for patients exhibiting signs of HDSA in the prehospital environment is considered off-label, therefore no standardized FDA approved dosing scheme exists for this indication [6,10]; however, a weight-based dose of 3–5 mg/kg of ketamine is commonly cited in the literature [6,9,11,12].

The prehospital use of ketamine in patients with altered mentation or for behavioral conditions is rare; a systematic review reported ketamine use for profound agitation in 6 out of every 10,000 patients [13]. Assessing a patient's weight and calculating the correct weight-based dose may be challenging, especially during an emergency [11,[14], [15], [16]]. Much of the existing literature regarding weight-based dosing is based on the pediatric population [15,[17], [18], [19]]. The requirement for emergency medical services (EMS) personnel to ascertain adult weights and administer appropriate weight-based dosages arises less frequently but remains equally demanding [14,20].

Paramedics faced with patients displaying signs of HDSA contend with multiple stressors, which may result in task saturation. Conventional dosing protocols may exacerbate this cognitive strain by requiring weight estimation and arithmetic computations [11,15,16,20]. To reduce cognitive load, certain medication administration protocols have the potential to be refined for time-sensitive emergencies to accelerate delivery speed and alleviate the cognitive burden on EMS personnel [15,21]. Refined protocols have the potential to enhance patient safety, mitigate the risk of medication dosing errors, and streamline the administration of therapeutic medications [15,21].

The New York State Collaborative EMS Protocols call for a fixed dose of 250 mg IM on standing order for the treatment of agitated adult patients who are extremely combative and are at immediate risk of causing physical harm to themselves and/or others [22]. The primary objective of this study was to determine the safety of a 250 mg fixed dose protocol by evaluating the frequency of adverse events following pre-hospital ketamine administration for HDSA. The secondary objectives were to describe the characteristics of these ketamine-related adverse events, to assess their impact on patient outcomes, and to determine the corresponding weight-based dose in a cohort of prehospital patients with severe agitation.