The Safety of Methoxyflurane for Emergency Pain Relief in Children and Adolescents: A Retrospective Cohort Study.

Objectives: The use of methoxyflurane is becoming increasingly popular in the treatment of pain in an emergency setting, in part due to its ease of administration. However, little is known about the risk of serious adverse events in children and adolescents. The aim of this study was to examine the safety of methoxyflurane in a pediatric population.

Methods: The study was a retrospective cohort study of pediatric prehospital events using probabilistic linked health data. All ambulance transfers in Western Australia between 1990 and 2016 involving children and adolescent patients were identified. Patients were categorized based on administered analgesia: methoxyflurane, an opioid analgesic, both methoxyflurane and an opioid analgesic, or no analgesic. Hospital and mortality data were linked to transferred patients to identify deaths, adverse drug reactions, liver and kidney toxicity, and re-admissions to hospital following ambulance transfer. Generalized linear models, adjusting for sociodemographic and ambulance transfer characteristics, were used to compare outcomes between children exposed to methoxyflurane and the other three groups.

Results: The study cohort consisted of 37,211 children, including 9,472 patients (25.5%) treated with methoxyflurane alone, 2,764 (7.4%) treated with an opioid analgesic, 1,235 (3.3%) treated with both methoxyflurane and an opioid analgesic, and 23,740 (63.8%) treated with no analgesic. Death in children and adolescents was uncommon, with less than five deaths (<0.1%) observed in the 12 months following treatment with methoxyflurane and no deaths in those treated with both methoxyflurane and an opioid analgesic. Adverse drug reaction was rare (<0.1%) in patients treated with methoxyflurane, as was liver and kidney toxicity with no case observed. At 90-days follow-up, there was no significant difference in hospitalization in patients treated with methoxyflurane and those treated with methoxyflurane and an opioid analgesic (adjusted OR:1.01, 95%CI:0.85-1.21). Compared with methoxyflurane treated patients, patients treated with an opioid analgesic were more likely to be hospitalized (aOR:1.23, 95%CI:1.09-1.39), while patients treated with no analgesic were less likely to be hospitalized (aOR:0.85, 95%CI:0.79-0.92).

Conclusions: In children and adolescents transported by ambulance, the use of methoxyflurane was not associated with an increased risk of hospitalization, death, serious adverse drug reactions or liver and kidney toxicity.