Nausea and vomiting are common gastrointestinal discomforts. Nausea is the unpleasant sensation of having the urge to vomit, whereas vomiting is a physical event and is the forceful expulsion of intestinal and gastric contents through the mouth (Zhong et al., 2021). From the beginning of the use of general anesthesia in the 1840s, it was recognized that postoperative nausea and vomiting (PONV) is a common side effect after surgery (Horn et al., 2014). PONV is an unpleasant experience that affects 20%–30% of surgical patients after general anesthesia, and in patients with high-risk factors, the incidence of PONV in the absence of preventive measures is as high as 80% (Eberhart et al., 2000; Apfel et al., 2012a). PONV decreases patient comfort and satisfaction and may cause dehydration and electrolyte imbalances, aspiration of gastric contents, esophageal rupture, suture dehiscence, and bleeding (Visser et al., 2001; Veiga-Gil et al., 2017).

The mechanism of PONV is complex, and there are many influencing factors. Being female, nonsmoking, having a history of motion sickness, having a history of PONV and taking opioids are regarded as risk factors (Apfel et al., 2012b). In addition, the type of surgery, duration of anesthesia, use of volatile anesthetics, nitrous oxide, and age under 50 years are also important factors related to PONV(Horn et al., 2014).

Thoracic surgery has the characteristics of a strong stress response and systemic inflammatory response, unstable circulation, a high risk of postoperative pulmonary complications, and a high demand for opioid drugs (Huang et al., 2017). With the development of minimally invasive technology, thoracoscopic surgery, which has the advantages of less trauma and fast recovery, has now become the most common surgical method in thoracic surgery. However, the incidence of PONV after thoracoscopic surgery remains high (Zha et al., 2021; Sertcakacilar et al., 2022; Vijitpavan et al., 2022). Vijitpavan’s study showed that the incidence of PONV within 48 h after thoracoscopy was 68.42%–73.68%, and 57.89% of patients needed drug intervention treatment (Vijitpavan et al., 2022).

Researchers have tried various methods to prevent and treat PONV. Among them, medication, such as 5-hydroxytryptamine (5-HT3) receptor antagonists, dopamine receptor antagonists, glucocorticoids, and anticholinergic drugs, is one of the important methods (Gan et al., 2020). However, due to the different pharmacokinetics, efficacy, and side effects of these drugs, as well as controversies regarding the route of administration and dosage, it is necessary to find suitable medications for better prevention and treatment of PONV.

Dexmedetomidine (Dex) is a highly selective α-2 adrenergic receptor agonist (Afonso and Reis, 2012). Dex possesses analgesic, anxiolytic, sympatholytic, organ-protective, and sedative properties similar to natural sleep, and it is now widely used in clinical practice (Chima et al., 2022). The effect of Dex in preventing PONV has been continuously investigated. On the one hand, Dex exerts analgesic effects and reduces the perioperative use of opioid drugs, thereby decreasing the incidence of PONV caused by postoperative pain and opioid use (Bao and Tang, 2020; Tian et al., 2022). On the other hand, Dex has been found to inhibit the release of norepinephrine in the locus coeruleus and reduce the release of 5-HT3 in the median raphe nucleus and dorsal raphe nucleus, thereby reducing the incidence of PONV(Hopwood and Stamford, 2001; Sugino et al., 2021). Wang’s study demonstrated that for adult lung cancer patients undergoing lobectomy, the intravenous infusion of Dex can reduce the incidence of PONV and decrease the use of opioid drugs (Wang et al., 2016). Other studies have shown that the intraoperative use of Dex can reduce the pain visual analog scale (VAS) scores within 48 h after cholecystectomy and orthopedic surgery and decrease the use of postoperative antiemetic drugs and opioids, thereby accelerating patient surgical recovery (Shin et al., 2019; Choi et al., 2021). However, previous studies have the following limitations: 1. No studies have specifically focused on adult female patients who are at high risk for PONV. The effects of Dex on adult females are still unclear. 2. The dosage range of Dex in previous studies has been highly variable, and the appropriate dosage for treating PONV remains unclear. 3. The incidence of PONV may vary depending on the type of surgery. To date, few studies have focused on radical thoracoscopic lung cancer resection, which accounts for an important proportion of thoracic surgeries.

Based on the above considerations, this study intends to observe the effects of different doses of dexmedetomidine on PONV in female patients undergoing thoracoscopic radical lung cancer surgery. We aimed to clarify its clinical efficacy and explore its optimal dose, providing evidence for reducing the incidence of PONV in thoracic surgery patients.

To the best of our knowledge, our study is the first to reveal the dynamic effect of different dosages of dexmedetomidine on PONV in female patients undergoing thoracoscopic radical lung cancer surgery. In general, PONV mainly occurred during the first 24 h after surgery. The protective effect of dexmedetomidine on PONV in female patients was verified in our study. Dexmedetomidine (0.4 μg/kg) was preferable to the other two Dex groups. Our study also found that the PONV grade, PONV_AUC and POV were improved by dexmedetomidine. In addition, PCA frequencies and the time to first postoperative oral intake were also affected by dexmedetomidine. Finally, based on our results, we constructed a regression model for the risk factors for PONV. Dexmedetomidine (0.4 μg/kg/h) was a protective factor against PONV.

Research by Wang et al. demonstrated that 0.5 μg/kg/h dexmedetomidine during thoracoscopic lung lobectomy reduced the incidence of PONV within 6 h postoperatively compared to saline infusion (Wang et al., 2016). Mohta et al. also found that 0.6 μg/kg dexmedetomidine alleviated postoperative pain and maintained hemodynamic stability on laparoscopic cholecystectomy with a surgical duration of approximately 1 h (Mohta et al., 2016). Tufanogullari et al. conducted a study on reduced-port laparoscopic surgery and found that intravenous infusion of dexmedetomidine at doses of 0.2–0.8 μg/kg/h reduced the consumption of fentanyl, postoperative antiemetics, and the length of stay in the PACU (Tufanogullari et al., 2008). Based on previous studies and our preliminary experiments, this study ultimately selected three different doses of 0.2 μg/kg/h, 0.4 μg/kg/h, and 0.8 μg/kg/h for investigation.

Studies have shown that the risk of PONV decreases with increasing age in adults (Eberhart et al., 2000; Apfel et al., 2012a). The subjects of this study are restricted to adult women who are a high-risk population for PONV. Patients aged 18–65 years were selected as the study population, while more elderly patients and children were excluded. The average age of the four groups of patients ranged from 51 to 54 years, aiming to minimize the impact of age on the experimental results. Furthermore, there were no differences in smoking history, history of PONV, history of motion sickness, or other general characteristics. To reduce the influence of anesthesia factors on the results of this study, this study uniformly used total intravenous general anesthesia (Visser et al., 2001) and no volatile anesthetics, which increased the comparability of this study. Studies have indicated that serotonin receptor antagonists (such as ondansetron) and/or corticosteroids (such as dexamethasone) are the preferred medications for preventing vomiting (Golembiewski and Tokumaru, 2006; Sridharan and Sivaramakrishnan, 2019). Therefore, to maximize the protection of patient rights and interests, we administered 5 mg of dexamethasone to each patient before induction and a prophylactic dose of 5 mg of ondansetron 15 min before the end of surgery.

The incidence of PONV is a dynamic process; therefore, based on previous literature and the preliminary experiment, we selected four time points within 48 h postoperatively for evaluation. Luo’s study showed that after administering a loading dose of 1 μg/kg of dexmedetomidine during surgery, followed by a maintenance dose of 0.6 μg/kg/h of dexmedetomidine, it can effectively reduce the pain scores at 1 h, 2 h, and 4 h after submucosal dissection of gastric endoscopy and decrease the severity of PONV (Luo et al., 2023). Lee’s study showed that 0.4 μg/kg/h dexmedetomidine reduced the incidence of PONV and alleviated postoperative pain in patients undergoing laparoscopic hysterectomy within 24 h postoperatively (Lee et al., 2022). Similar to the above experimental results, our study revealed that 0.4 μg/kg/h dexmedetomidine could effectively reduce the incidence of PONV. In addition, compared with the method of simply selecting a fixed postoperative time point, the area under the curve can reflect the dynamic trend of different postoperative time points. The PONV_AUC can reflect the severity of PONV over a period of time. Our study shows that the PONV_AUC was lower in the Dex2 group than in the Control group, and dexmedetomidine could improve the PONV_AUC for a period of time after surgery.

Our study demonstrates that dexmedetomidine can significantly reduce the incidence of PONV. We speculate that the reason partially lies in its analgesic properties (Afonso and Reis, 2012; Chima et al., 2022). According to the studies conducted by Zhang and Kaye (Kaye et al., 2020; Zhang et al., 2022), intraoperative administration of dexmedetomidine can alleviate postoperative pain. Pain is an independent risk factor for the incidence of PONV. Our study shows dexmedetomidine reduces the PCA press frequencies through its synergistic analgesic effect, as the latter has been identified as a risk factor for PONV(Mauermann et al., 2019). The PCA press frequency in the treatment group was lower than that in the Control group. Therefore, we speculate that dexmedetomidine reduces the incidence of PONV through its synergistic analgesic effect by reducing the number of postoperative PCA presses.

Compared to the Dex1 and Dex3 groups, the Dex2 group showed significant efficacy in preventing and treating PONV and POV. Patients in the Dex3 group, who received a higher dose of dexmedetomidine, had a significantly longer dwell time in the PACU compared to the Dex1 group (low-dose dexmedetomidine) and the Control group. This is unfavorable for patient recovery and reduces the efficiency of the PACU. According to previous studies (Choi et al., 2017), the use of a loading dose of 1 μg/kg followed by a larger dose of 0.3–0.5 μg/kg/h of dexmedetomidine during surgery resulted in delayed recovery during the initial few hours after extubation. In addition, side effects associated with dexmedetomidine mainly include hypotension and bradycardia (Weerink et al., 2017). The dose of the vasoactive drug norepinephrine used in the Dex3 group was significantly higher than that in the Control group, suggesting that 0.8 μg/kg/h dexmedetomidine may have contributed to intraoperative hemodynamic instability.

Comprehensive optimization of the perioperative period based on evidence-based medicine aims to reduce surgical stress and complications and achieve rapid patient recovery (Simpson et al., 2019). Early oral intake and early mobilization after surgery are important components of enhanced recovery after surgery (ERAS). Studies have shown that early oral intake can maintain the intestinal mucosa, nourish the intestines, promote portal venous circulation, and accelerate gastrointestinal motility recovery (Terashima, 2014). Our study demonstrated that the time for the first postoperative oral intake in the Dex2 group was shorter than that in the other groups. This may be attributed to the good preventive effect of dexmedetomidine at a dose of 0.4 μg/kg/h on PONV and its analgesic action, which helps facilitate early postoperative diet and accelerate early patient recovery.

Our study further analyzed the risk factors for PONV through regression analysis. The results showed that intraoperative infusion of 0.4 μg/kg/h dexmedetomidine was a protective factor against PONV. Preoperative anxiety scores, intraoperative consumption of remifentanil, and history of motion sickness were found to influence the incidence of PONV, serving as risk factors for PONV, which is consistent with previous research findings. Laufenberg-Feldmann et al. found a close correlation between preoperative anxiety and PONV, with preoperative anxiety increasing the odds ratio of PONV by fivefold in nonsmoking women, suggesting that preoperative anxiety may be an important indicator for predicting PONV (Laufenberg-Feldmann et al., 2019). Roh et al. proposed that this phenomenon may be attributed to increased sympathetic nervous system activity in anxious patients, leading to increased release of catecholamines (Roh et al., 2014). Additionally, anxious patients tend to swallow excessive air, increasing gastric capacity, which may be associated with an increased incidence of POV. Opioid drugs can inhibit the release of acetylcholine in the mesenteric plexus and stimulate μ receptors, thereby reducing muscle tone and motility and triggering PONV through the serotonergic signaling pathway (de Boer et al., 2017). A history of motion sickness has been identified as a risk factor for predicting PONV, although the specific mechanisms are unclear and may be related to abnormal sensitivity of the vestibular organ (Momeni et al., 2006).

For female patients undergoing thoracoscopic radical lung cancer surgery, infusion of dexmedetomidine during total intravenous general anesthesia can reduce the incidence of PONV, reduce perioperative opioid use, improve postoperative analgesic effect, shorten the time for first postoperative oral intake, and promote early recovery of patients after surgery. Compared with the other two dosages, 0.4 μg/kg/h dexmedetomidine is preferable.