Background Acutely agitated patients are common in the emergency department (ED). Given the myriad aetiologies of the clinical conditions that can produce agitation, such a high prevalence is unsurprising. Agitation is a symptomatic presentation, not a diagnosis, secondary to a psychiatric, medical, traumatic, or toxicological condition. Most literature on the emergency management of agitated patients is from psychiatric populations, not generalised to EDs. Benzodiazepines, antipsychotics, and ketamine have been used to treat acute agitation. However, a clear consensus is lacking. Objectives The objectives are to study the effectiveness of intramuscular (IM) olanzapine as a first-line treatment for rapid tranquillisation in undifferentiated acute agitation in the ED and compare the effectiveness of sedatives to control agitation in etiologically divided groups per the following preassigned protocols: Group A: Alcohol/drug intoxication (olanzapine vs haloperidol), Group B: Traumatic brain injury (TBI) with or without alcohol intoxication (olanzapine vs haloperidol), Group C: Psychiatric conditions (olanzapine vs haloperidol and lorazepam), and Group D: Agitated delirium, organic causes (olanzapine vs haloperidol). Methods This 18-month prospective study included acutely agitated ED patients between 18 and 65. Results A total of 87 patients between 19 and 65 were included, all with a Richmond Agitation Sedation Scale (RASS) score between +2 and +4 at presentation. Nineteen of the 87 patients were managed as acute undifferentiated agitation, and 68 were assigned to one of the four groups. In acute undifferentiated agitation, IM olanzapine 10 mg effectively sedated 15 (78.9%) patients within 20 minutes, whereas the remaining four (21.1%) were sedated with a repeat IM olanzapine 10 mg over the next 25 minutes. In 13 patients with agitation due to alcohol intoxication, zero out of three with olanzapine and four out of 10 (40%) with IM haloperidol 5 mg were sedated within 20 minutes. In patients with TBI, two out of eight (25%) receiving olanzapine and four out of nine (44.4%) receiving haloperidol were sedated within 20 minutes. In acute agitation secondary to psychiatric disease, olanzapine sedated nine out of 10 (90%), and haloperidol with lorazepam sedated 16 out of 17 (94.1%) within 20 minutes. In patients with agitation secondary to organic medical conditions, olanzapine rapidly sedated 19 out of 24 (79.1%), whereas haloperidol sedated one out of four (25%). Interpretation and conclusion IM olanzapine 10 mg is effective for rapid sedation in acute undifferentiated agitation. Olanzapine is superior to haloperidol in agitation secondary to organic medical conditions and is as efficacious as haloperidol with lorazepam in agitation due to psychiatric diseases. However, in agitation due to alcohol intoxication and TBI, haloperidol 5 mg is slightly better, although not statistically significant. Olanzapine and haloperidol were well tolerated by Indian patients in the current study, with minimal side effects.

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