Over the past 15 years, utilization of ketamine as an analgesic in the emergency department (ED) has significantly increased, generating an extensive body of clinical research. Ketamine, as an NMDA antagonist, alleviates pain primarily by reducing central sensitization, hyperalgesia, and the “wind-up” phenomenon within the central nervous system (CNS) and at the spinal cord [1,2]. Sub-dissociative ketamine (SDK) administered alone or in combination with opioids and non-opioid analgesics, demonstrated nearly 40 % pain reduction from the baseline, both in the ED and prehospital settings [[3], [4], [5], [6]].

The most common routes of ketamine administration for analgesia are intravenous, intranasal, and less frequently, subcutaneous injections [[7], [8], [9]]. An alternative method, nebulized ketamine inhalation, has emerged as a promising route for analgesia in emergency care.

Initial data supporting the analgesic use of nebulized ketamine originated from the anesthesia literature on postoperative sore throat management where nebulized ketamine demonstrated up to 50 % greater pain reduction than placebo without significant adverse events [[10], [11], [12]]. Additionally, inhalation of ketamine at escalating doses in healthy volunteers resulted in a systemic bioavailability ranging from 20 % to 40 % of the intravenous route, with an inhalation duration between 20 and 40 min. Peak plasma concentrations rose by approximately 77 % from the lowest to the highest inhaled dose, with no absence of serious adverse events reported [13].

More recently, several studies have explored nebulized ketamine's effectiveness in managing acute pain within emergency settings, utilizing both conventional nebulizers and breath-actuated nebulizers, the latter delivering medication triggered by the patient's inspiratory effort [14,15]. This systematic review aimed to evaluate the analgesic efficacy and incidence of adverse events associated with nebulized ketamine in prehospital and ED environments.