• Per Kristian Hyldmo, Marius Rehn, Kristian Dahl Friesgaard, Leif Rognås, Lasse Raatiniemi, Jouni Kurola, Robert Larsen, Poul Kongstad, Mårten Sandberg, Vidar Magnusson, and Gunn Elisabeth Vist.
• Division of Prehospital Care, Sørlandet Hospital Trust, Kristiansand, Norway.
• Acta Anaesthesiol Scand. 2024 Sep 26.

BackgroundMany prehospital emergency patients receive suboptimal treatment for their moderate to severe pain. Various factors may contribute. We aim to systematically review literature pertaining to prehospital emergency adult patients with acute pain and the pain-reducing effects, adverse events (AEs), and safety issues associated with inhaled analgetic agents compared with other prehospital analgesic agents.MethodsAs part of an initiative from the Scandinavian Society of Anaesthesia and Intensive Care Medicine, we conducted a systematic review (PROSPERO CRD42018114399), applying the PRISMA guidelines, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and Cochrane methods, searching the Cochrane Library, Epistemonikos, Centre for Reviews and Dissemination, PubMed, and EMBASE databases (updated March 2024). Inclusion criteria were the use of inhaled analgesic agents in adult patients with acute pain in the prehospital emergency care setting. All steps were performed by minimum of two individual researchers. The primary outcome was pain reduction; secondary outcomes were speed of onset, duration of effect, and relevant AEs.ResultsWe included seven studies (56,535 patients in total) that compared inhaled agents (methoxyflurane [MF] and nitrous oxide [N2O]) to other drugs or placebo. Study designs were randomized controlled trial (1; n = 60), randomized non-blinded study (1; n = 343), and randomized open-label study (1; n = 270). The remaining were prospective or retrospective observational studies. The evidence according to GRADE was of low or very low quality. No combined meta-analysis was possible. N2O may reduce pain compared to placebo, but not compared to intravenous (IV) paracetamol, and may be less effective compared to morphine and MF. MF may reduce pain compared to paracetamol, ketoprofen, tramadol, and fentanyl. Both agents may be associated with marked but primarily mild AEs.ConclusionWe found low-quality evidence suggesting that both MF and N2O are safe and may have a role in the management of pain in the prehospital setting. There is low-quality evidence to support MF as a short-acting single analgesic or as a bridge to IV access and the administration of other analgesics. There may be occupational health issues regarding the prehospital use of N2O.© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

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