Suzetrigine for Postoperative Pain in Head and Neck Free Flap or Transoral Robotic Surgery

Importance: Postoperative pain after head and neck surgery frequently necessitates opioid analgesia despite multimodal pain regimens. Suzetrigine, a selective NaV1.8 inhibitor that was recently approved in the US for acute postoperative pain, may reduce postoperative opioid requirements. However, the current surgical literature regarding suzetrigine use after head and neck surgery is limited. Objective: To evaluate the association of adjunctive suzetrigine use with postoperative opioid consumption after head and neck free flap reconstruction and transoral robotic surgery. Design, Setting, and Participants: This was a retrospective cohort study conducted at a single tertiary academic referral center of adult patients undergoing head and neck free flap reconstruction or transoral robotic surgery from January 1 to December 31, 2025. Patients with chronic high-dose opioid use, chronic pain disorders, liver dysfunction, or unavailable opioid data were excluded. Exposure: Protocolized multimodal analgesic regimen with or without adjunctive suzetrigine. Main Outcomes and Measures: Total inpatient morphine milligram equivalents (MMEs) consumed and MME consumption per hospital day. Secondary outcomes included hospital length of stay, 30-day readmissions, emergency department visits, oral intake consumption, postoperative pain scores, and medication-related adverse events. Results: Of 146 patients (mean [SD] age, 62.8 [13.9] years; 48 female [32.9%] and 98 male [67.1%]) included in the analysis, 41 (28.1%) received suzetrigine plus multimodal analgesia and 105 (71.9%) received standard multimodal analgesia; 114 (78.1%) underwent free flap reconstruction and 32 (21.9%) underwent transoral robotic surgery. Median inpatient opioid use was lower among patients in the free flap group receiving suzetrigine compared with those in the control (109.0 vs 142.1 MMEs; median difference, -50.0; 95% CI, -119.0 to -5.1). Among patients undergoing transoral robotic surgery, suzetrigine was associated with lower inpatient opioid use (29.0 vs 108.9 MMEs; median difference, -56.0; 95% CI, -110.0 to -5.5). Suzetrigine remained independently associated with lower opioid use after multivariable adjustment (adjusted median difference, -76.4 MMEs; 95% CI, -138.8 to -13.9). Postoperative pain scores were similar between groups. No medication-related adverse events were identified. Conclusions and Relevance: In this cohort study, adjunctive suzetrigine use was associated with lower postoperative opioid requirements after head and neck free flap reconstruction and transoral robotic surgery. Given the retrospective, nonrandomized design, these findings should be interpreted as associations warranting prospective confirmation.