Abstract
BACKGROUND: Acute pain accounts for 60-90% of presentations to the emergency department (ED), with 20-40% of patients reporting severe pain. Current management practices, including simple analgesics, opiates and anti-inflammatory drugs, are often inadequate or slow to reach peak effect, necessitating the exploration of alternative analgesics. Ketamine, acting primarily through N-methyl-D-aspartate (NMDA) receptor antagonism, presents a promising alternative due to its rapid onset. However, its nebulised form remains underutilised in clinical practice. AIMS AND OBJECTIVES: This review evaluates the efficacy of nebulised ketamine in reducing pain in adult ED patients, alongside its side effect profile, optimal dosing, and potential as an alternative or adjunctive analgesic compared to other treatments. METHODS AND DESIGN: A systematic review utilising the PRISMA guidelines was conducted. Searches were carried out in Medline, Embase, PubMed, Science Direct, google scholar and Ovid databases from 2010 to May 2024, including studies containing objective analysis of pain control with nebulised ketamine. A two-sample t-test was used to assess statistical significance. Quality assessment was performed using the CASP tool, and bias was evaluated using the ROBINS-I and ROB2 tool. RESULTS: Of 99 articles, 9 (5 randomised controlled trials, 3 case series and 1 case report) totalling 453 patients were included. All studies suggested improvement in pain scores with nebulised ketamine, with an average reduction of 42.5% and 70.4% over a 15 and 120-minute period respectively (p < 0.0001). Higher doses (1 mg/kg, 1.5 mg/kg) did not significantly improve pain compared to lower doses (0.7 mg/kg 0.75 mg/kg), with similar overall reductions reported across all four dosing regimens (p < 0.0003 or 0.0001). Nebulised ketamine was non-inferior to intravenous (IV) morphine, IV ketamine, nebulised dexmedetomidine, and Entonox, and had fewer side effects. CONCLUSION: Nebulised ketamine offers a viable alternative for pain management in emergency settings, providing effective analgesia with a favourable safety profile. Further multicentre trials with larger populations are recommended to confirm these findings and establish standardised dosing protocols for consideration in national guidance.