Ye Zhang,* Xiaotong Xian,* Furui Wang,* Bochong Zhou, Yuwen Wang, Penglei Wang, Yun Li, Yun Wu

Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yun Wu, Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, People’s Republic of China, Tel +86– 551– 63869485, Email wuyunanyi@163.com Yun Li, Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, People’s Republic of China, Email yunli_001@aliyun.com

Background: Opioid-free anesthesia (OFA) is increasingly being adopted to provide effective analgesia and reduce opioid-related adverse events. However, existing literature on OFA remains contentious, and its impact on postoperative recovery following thyroidectomy has not been evaluated. Therefore, we examined the hypothesis that OFA enhances the early quality of recovery in patients undergoing thyroid surgery.
Methods: In this randomized controlled trial, 204 adult patients undergoing thyroidectomy were randomly assigned to receive either OFA (esketamine, dexmedetomidine, and bilateral superficial cervical plexus blocks) or opioid-based anesthesia (OBA, sufentanil and remifentanil). The primary outcome was the quality of recovery on the first postoperative day, assessed using the quality of recovery-15 scale. Secondary outcomes included sleep quality score, area under the curve of pain intensity. Anesthesia-related complications were also recorded.
Results: On the first postoperative day, the OFA group had a significantly higher quality of recovery-15 score versus the OBA group (137.6 [5.6] vs 128.2 [10.5], mean difference = 9.4, 95% CI, 7.0– 11.7, P < 0.001). Patients in the OFA group also had better sleep quality (mean difference = 7.8, P < 0.001), lower area under the curve of pain intensity versus those in the OBA group. The incidence of postoperative nausea and vomiting was lower (1.0% vs 18.6%, P < 0.001) in the OFA group versus the OBA group. Patients receiving OFA had a delayed extubation and prolonged postanesthesia care unit stay.
Conclusion: We showed that with a pre-emptive and preventive analgesia effect, OFA improved quality of recovery, sleep quality, pain, and postoperative nausea and vomiting after thyroidectomy. However, a prolonged emergence recovery was observed when patients receiving OFA strategy, warranting further investigation to optimize agent design and monitoring method to balance the intraoperative anesthesia depth.
Name of Trial Registry: Chinese Clinical Trial Registry.
Registration Number: ChiCTR2300070794; URL: https://www.chictr.org.cn/showproj.html?proj=196152.
Plain Language Summary: Thyroid surgery is increasingly performed as day case procedures. With the goal of enhanced recovery, it is important to assess outcomes from the patient’s perspective. This double blind, randomized controlled trial aimed to examine the effect of opioid-free anesthesia (OFA) on subjective quality of recovery (QoR) in patients undergoing thyroid surgery compared to those receiving opioid-based anesthesia. Importantly, we found that OFA improved QoR, sleep quality, pain, and postoperative nausea and vomiting after thyroid surgery, although it was associated with an increased risk of prolonged emergence recovery. Although cumulative effects of OFA has been shown to potentially enhance the overall postoperative QoR after different surgeries, such as orthopedic and thoracoscopic surgeries, our results showed that the advantages of OFA for QoR, particularly for thyroid surgery, remains limited and contentious. It warrants further investigation to optimize agent design of OFA.

Keywords: opioid-free anesthesia, dexmedetomidine, esketamine, quality of recovery, thyroid surgery