Effects of opioid-free anesthesia on postoperative anxiety in patients undergoing modified radical mastectomy for breast cancer: a randomized controlled trial

Opioid-free anesthesia (OFA) improves somatic recovery after breast cancer surgery, but its effect on postoperative anxiety has not been evaluated. We hypothesized that OFA would reduce postoperative state anxiety in patients undergoing modified radical mastectomy.

In this single-center, randomized, participant- and assessor-blinded trial, 106 patients undergoing modified radical mastectomy were assigned to OFA (n = 53) or opioid-based anesthesia (OA; n = 53). Both groups received a serratus anterior plane block. The OFA group received dexmedetomidine and esketamine intraoperatively and esketamine-based postoperative patient-controlled analgesia; the OA group received intraoperative opioids and sufentanil-based postoperative patient-controlled analgesia. The primary outcome was the State Anxiety Inventory (SAI) score 24 h after surgery. Secondary outcomes were exploratory.

Preoperative SAI scores were comparable between groups. Postoperative SAI scores were significantly lower with OFA at 24 hours (median, 41 vs. 48; P < 0.001) and 72 hours (41.43 ± 4.53 vs. 45.55 ± 4.37; P < 0.001). The QoR-15 score at 24 hours was higher with OFA (median, 104 vs. 99; P < 0.001). NRS pain scores showed a modest rightward distributional shift with OFA at postoperative 24 hours (median, 3[3-4] vs. 3[3-3]; P = 0.014) but were significantly lower at postoperative 72 hours (median, 1 vs. 2; P < 0.001). The incidence of postoperative nausea and vomiting (PONV) was lower with OFA (13.21% vs. 32.08%; P = 0.020). Time to tracheal extubation and PACU length of stay were shorter with OFA (both P < 0.001). Intraoperative hemodynamic parameters and other adverse event rates did not differ significantly between groups.

The evaluated multicomponent opioid-free perioperative regimen reduced early postoperative state-anxiety scores compared with the opioid-based regimen. Because intraoperative drugs and postoperative analgesia differed between groups, the effects of opioid avoidance cannot be disentangled from the direct effects of dexmedetomidine, esketamine, or postoperative PCIA. The clinical importance and longer-term durability of the observed anxiety difference require confirmation.

ChiCTR2500101756, 04/29/2025.