Perioperative pregabalin within an enhanced recovery pathway and postoperative quality of recovery after head and neck cancer surgery with free-flap reconstruction: A pilot study.

OBJECTIVE: Patients undergoing major head and neck cancer surgery with free tissue transfer reconstruction (HNS-FTTR) frequently experience impaired postoperative quality of recovery (QoR) despite implementation of Enhanced Recovery After Surgery (ERAS) pathways. Pregabalin has been reported to reduce postoperative pain and opioid consumption and may exert beneficial effects beyond conventional analgesia. This pilot study evaluated the association between perioperative pregabalin administration and postoperative recovery following HNS-FTTR. METHODS: This retrospective observational cohort study included 179 patients who underwent HNS-FTTR between January 2022 and June 2026. Twenty-four patients received perioperative pregabalin and were compared with 155 historical controls. To address potential temporal bias, a sensitivity analysis was performed using a contemporary control cohort of 24 patients treated after April 2025. Because this was an exploratory pilot study, no single confirmatory primary endpoint was prespecified. Postoperative recovery was evaluated using the Japanese version of the Quality of Recovery-40 questionnaire (QoR-40J), with global and domain scores assessed on postoperative days (PODs) 2, 4, and 7. Additional exploratory outcomes included pain and postoperative nausea and vomiting (PONV) visual analogue scale (VAS) scores, postoperative analgesic requirements, and serum C-reactive protein levels. RESULTS: In the historical cohort analysis, QoR-40J global scores were significantly higher in the pregabalin cohort on POD2 (150.7 ± 21.9 vs. 140.5 ± 21.4, p = 0.039) and POD7 (164.9 ± 19.9 vs. 154.5 ± 18.0, p = 0.013). Improvements were observed in the Physical Comfort, Emotional State, Physical Independence, and Patient Support domains. No significant differences were identified in postoperative pain or PONV VAS scores. In the sensitivity analysis, improvements in global QoR on POD7 (164.9 ± 19.9 vs. 153.8 ± 16.4, p = 0.048), as well as in the Physical Comfort and Physical Independence domains, were reproduced despite the absence of significant differences in postoperative pain scores. Differences in postoperative analgesic consumption were inconsistent between the historical and contemporary cohort analyses. CONCLUSION: Perioperative pregabalin administration was associated with improved postoperative QoR following HNS-FTTR, particularly in the domains of physical comfort and physical independence, despite limited effects on postoperative pain intensity. Given the retrospective design, small sample size, and potential for residual confounding, these findings should be considered preliminary and hypothesis-generating and warrant confirmation in prospective randomized controlled trials.