Xingyu Geng,1,2,* Yutian Pu,1,2,* Ziwei Hu,1,2 Heling Zhang,1,2 Maosan Wang,1,2 Can Fang,1,2 Gaochao Lv,1,2 Wanting Li,1,2 Xinyue Zhang,1,2 Xiaoxuan Fan,1,2 Su Liu,1,2 Xiuxia Chen,1,2 Jingru Wu1,2 

1Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiuxia Chen, Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, No. 99 huaihai West Road, Xuzhou, Jiangsu, 221002, People’s Republic of China, Tel +86-15205200798, Email cxxlxy@sina.com Jingru Wu, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China, Email wujingr5810@sina.com

Objective: Postoperative sleep disturbance(POSD) is a problem in breast cancer patients after surgery. Little is known about the differences in the treatment of POSD with esketamine combined with dexmedetomidine under the same circumstances. We investigated the effects of intraoperative esketamine combined with intravenous dexmedetomidine on the incidence of POSD and postoperative sleep architecture.
Methods: A single-center, randomized, double-blind controlled trial was conducted. A total of 100 participants were randomly assigned to four groups: the esketamine group (Group E), the dexmedetomidine group (Group D), the esketamine combined with dexmedetomidine group (Group ED), and the control group (Group S) (n=25 each). The intervention drugs were continuously infused until the placement of the drainage tube. The primary outcome measure was the incidence of POSD, defined as an Athens Insomnia Scale (AIS) score > 6 on at least one of the first three postoperative days. The secondary outcome measure was the duration of sleep structure, which was collected using the Fitbit Charge 2® smartwatch (Fitbit, Inc. San Francisco, California, USA).
Results: In the first three postoperative days, the incidence of POSD was similar across the four groups (P=0.947). However, on postoperative day 3 (POD3), there was a significant interaction between esketamine and dexmedetomidine (P=0.004). Further simple effect analysis revealed that, in the absence of esketamine, dexmedetomidine had a significant effect on POSD on POD3 (OR=0.196, [0.056– 0.691]; P=0.019). In the absence of dexmedetomidine, esketamine had a significant effect on POSD on POD3 (OR=0.248, [0.074– 0.833]; P=0.042). Dexmedetomidine reduced rapid eye movement (REM) sleep on postoperative day 1 (P=0.042). Esketamine reduced nighttime awakening time on POD1 (P=0.036) and POD3 (P=0.020).
Conclusion: Intraoperative infusion of esketamine combined with dexmedetomidine had no significant effect on POSD, but dexmedetomidine reduced REM sleep, and esketamine reduced the nocturnal awakening time.

Keywords: breast cancer, sleep disturbance, esketamine, dexmedetomidine