This research found that perioperative intravenous S-ketamine could improve sleep quality in patients undergoing thoracoscopic surgery. Moreover, decreased pain intensity, decreased level of serum IL-6, and increased level of serum IL-10 were noticed in patients given S-ketamine. And the S-ketamine use did not increase the incidence of postoperative complications.
Although thoracoscopic surgery is less invasive than traditional thoracotomy, there are still many patients reporting postoperative poor sleep quality and pain, seriously affecting postoperative recovery5,8. PSD and pain can interact with each other. Postoperative pain could induce sleep disturbances including a reduction of total sleep time and higher sleep arousal times10. In turn, sleep can mediate pain through opioid, monoaminergic, immune, and other systems10. Besides, inflammation is also one of the risk factors triggering the incidence of PSD22. Improved sleep quality can enhance immunity, facilitate early motion, accelerate recovery, and improve the quality of life23. A multimodal strategy is recommended to improve transient sleep quality in surgical patients3, but the incidence of perioperative sleep disturbance is still over 40%2. Fortunately, a recent review shed light on a possible application of ketamine for improving sleep quality24. S-ketamine is more efficient and safer than ketamine, so it is speculated that S-ketamine might improve PSD.
Our research suggested that S-ketamine could significantly increase sleep quality in patients after thoracoscopic surgery. The same conclusion was drawn by a recent RCT, in which 0.3 mg/kg/h was used for patients after gynecological laparoscopy surgery18. In addition, another study revealed that ketamine played an important role in achieving better sleep for patients admitted in the intensive care unit25. All these studies demonstrated the efficacy of S-ketamine in improving sleep quality.
A previous study showed that both 0.5 mg/kg and 0.25 mg/kg dosages of S-ketamine provided pain relief effects in cervical carcinoma surgery, and the analgesic effects were dose-dependent26. Therefore, we chose the higher dose of 0.5 mg/kg in our study. On the contrary, another research revealed that S-ketamine's analgesic effects in patients undergoing major lumbar fusion surgery were inapparent27, which could be explained by dramatic surgical trauma covering the analgesic effects. And we also found that S-ketamine reduced the rest and movement pain intensity at postoperative 6, 12, and 24 hours, which was the same conclusion as a meta-analysis published by Wang et al28.
Additionally, researchers established that the high level of pro-inflammatory cytokines was associated with poor sleep quality29,30, while the increased level of anti-inflammation factor IL-10 contributed to the longer sleep duration30. Sleep loss could induce higher levels of TNF-α, IL-6, and C-reactive protein (CRP)31. Furthermore, numerous studies confirmed that surgical trauma and anesthesia could induce the occurrence of PSD by triggering a variety of inflammatory factors and stress responses32,33. S-ketamine could decrease the level of IL-6 and increase the level of IL-10 postoperatively, which was similar to previous studies34,35. By contrast, the anti-inflammatory effects of S-ketamine in patients undergoing colorectal cancer surgery were not obvious, which could be explained by the lower dosage36.
Notably, our results showed that S-ketamine improved sleep quality and reduced pain intensity, which implicated the underlying relationship between sleep and pain. And other mechanisms need to be explored further, including improvement of mood behavioral10. Furthermore, more ways to manage sleep disturbances and postoperative pain should be explored, and it is necessary to consider the interaction effect of sleep and pain in future research.
In our study, the limitations were as followed. Firstly, only a single administration dose of S-ketamine was performed in the thoracoscopic surgery. Additional research should be conducted to find out the optimal administration scheme. Furthermore, the measure of sleep quality in our study was relatively subjective, so more objective measurements such as actigraphy and polysomnography are needed to provide strong evidence. Besides, we only investigated the short-time effect of S-ketamine on sleep quality, future studies should pay attention to the long-term efficacy.