Opioid-Sparing Versus Opioid-Based Analgesia for Craniotomy: A Multicenter Randomized Controlled Trial

INTRODUCTION: Pain control remains a challenge after neurosurgery. Opioid-sparing analgesia may provide better pain relief without opioid-related side effects after craniotomy. We aimed to compare analgesia requirement and postoperative pain between opioid-sparing and opioid-based analgesia for craniotomy. METHODS: This investigator-initiated, multicenter randomized controlled trial was conducted at 5 Indian centers from October 19, 2022, to September 5, 2024, in adult patients undergoing elective craniotomy for brain tumors, following trial registration (CTRI/2022/09/045705, September 20, 2022). Patients received fentanyl 1 µg.kg-1.h-1 or dexmedetomidine 0.5 µg.kg-1.h-1 in a 1:1 allocation ratio after anesthetic induction until dural closure as the primary systemic analgesic. In addition, patients received intraoperative loco-regional analgesia. Our primary outcomes were intraoperative rescue opioid consumption and incidence of moderate-to-severe pain on the numerical rating scale (NRS) in the postanesthesia care unit (PACU). Secondary outcomes were pain on the first 2 postoperative days, drug-associated harms, recovery profile, patient satisfaction, quality of sleep, hospital stay duration, and persistent pain at 3 and 6 months. RESULTS: There was no difference between fentanyl (n=252) and dexmedetomidine (n=248) groups for rescue fentanyl (38.0±63.1 vs. 44.6±81.7 μg, P=0.327) or moderate-to-severe pain in the PACU (145/242 vs. 138/233, P=0.559). Intraoperative hypotension was more common with dexmedetomidine (100/248 vs. 75/252, P=0.015), while shivering was lower than with fentanyl (9/241 vs. 22/251, P=0.026). Other outcomes were similar between groups. CONCLUSIONS: Both opioid-based and opioid-sparing regimens were similar regarding rescue analgesia, postoperative pain, and other in-hospital outcomes in patients undergoing craniotomy. Dexmedetomidine increased the occurrence of intraoperative hypotension and reduced postoperative shivering compared with fentanyl.