The feasibility of perioperative methadone in older hip fracture patients: A pilot continual reassessment trial (MetaHip trial)

Background: Hip fractures cause extreme pain, primarily affecting the older and frail. The necessity of sufficient pain relief in combination with a lower tolerance for drugs makes the analgesic treatment of older patients difficult. A single dose of methadone might reduce postoperative pain and opioid consumption. However, the safety of using methadone for older and fragile patients is unknown. Aim: Determine the maximal tolerable dose (MTD) of perioperative methadone in older hip fracture patients and assess the feasibility of this protocol for future clinical trials. Methods: Hip fracture patients ≥60 years old were consecutively included at the hospital in the winter/spring of 2023. An adaptive algorithm allocated 0.10 mg/kg, 0.15 mg/kg, or 0.20 mg/kg of methadone to each patient, administered intravenously at the induction of anesthesia. The primary outcome was respiratory depression, which was monitored continuously. Occurrence required a dosage decrease, while absence allowed an increase. Registered Nurses at the orthopedic ward collected data using observation charts completed 6, 24, and 72 hours after surgery. Secondary outcomes include time spent in the post-anesthesia care unit (PACU), verbal rating pain score (VRS), opioid consumption, and nausea/vomiting. Results: 30 patients completed the study. Nine received 0.10 mg/kg, and 21 received 0.15 mg/kg. Three patients experienced respiratory depression in PACU, all receiving 0.15 mg/kg methadone and undergoing general anesthesia. None of the spinal anesthesia patients or those receiving 0.10 mg/kg experienced respiratory depression. Conclusion: Methadone is an effective analgesic for hip fracture surgery. The data suggests that the maximal tolerable dose of methadone in older hip fracture patients is 0.10 mg/kg. This study proves the feasibility of our trial setup and provides a foundation for future randomized controlled trials. Additionally, the findings suggest that the tolerability of methadone may vary depending on the type of anesthesia used, which merits further investigation.