Ovarian cysts are common gynecological diseases that can occur at any age but are most seen during the reproductive years. These cysts are mostly benign and generally do not demonstrate specific symptoms, except in cases of acute abdomen caused by torsion or rupture in some cases. The estimated global incidence of ovarian cysts is approximately 7% [1]. The current clinical treatment for ovarian cysts involves a combination of surgery, mostly laparoscopic, and medication. Laparoscopic surgery is often used as the preferred surgical procedure owing to its advantages of shorter hospital stays, faster recovery, and less postoperative pain and bleeding [2, 3]. Postoperative nausea and vomiting (PONV) is more common in gynecological laparoscopic surgery under general anesthesia, and up to 80% of patients have postoperative nausea, and 30% of patients have postoperative vomiting [4, 5, 6]. It is the second most common postoperative complication after surgical pain [7]. PONV is a complex phenomenon involving the interaction of various receptors, neural pathways, and both peripheral and central nervous systems. Therefore, the incidence of PONV has a greater effect on the associated risk factors. Common risk factors for PONV include being a female, a nonsmoker, having a history of Multiple Sclerosis (MS), prolonged duration of anesthesia, younger age, and postoperative use of opioids [8, 9]. As the number of risk factors increases, the incidence of PONV also increases. Apfel et al. [10] and Son and Yoon [11] reported that being a female, a nonsmoker, having a history of MS or PONV, postoperative opioid use, receiving general anesthesia and the use of nasogastric tubing are independent risk factors for PONV. Xu et al. [12] reported that the incidence of PONV in patients receiving total intravenous anesthesia was lower than that in patients receiving composite anesthesia by static inhalation. Remimazolam reduces the incidence of PONV after gynecologic laparoscopic surgery [13].

Opioid-free anesthesia (OFA) is a multimodal approach for anesthesia induction and involves the use of hypnotics, N-methyl-D-aspartate receptor antagonists, local anesthetics, anti-inflammatory drugs, and $\alpha$-2 agonists [14]. The use of opioids during the intraoperative or postoperative period is an important factor leading to PONV, and opioids are widely used in clinical practice for inducing general anesthesia. Opioids primarily produce intestinal dysfunction and inhibit sphincter function by agonizing mu (µ) receptors in the intestine [15], thereby inhibiting intestinal mobility. This results in clinical symptoms such as abdominal distension, constipation, nausea, and vomiting. Opioid avoidance may exacerbate postoperative pain after laparoscopic surgery, which, in turn, may lead to or worsen PONV. Conversely, the use of opioids to alleviate pain can also contribute to or exacerbate PONV [16, 17, 18, 19, 20, 21]. A meta-analysis investigating the effects of opioids versus opioid avoidance on postoperative pain and incidence of postoperative PONV showed that opioids provided better analgesia 2 h after surgery, but the incidence of postoperative PONV increased by about 20% [22]. The use of opioids is a high-risk factor for PONV in children undergoing adenotonsillectomy and strabismus repair [23]. Zero-opioid general anesthesia is administered for head and neck tumor resection and breast cancer surgery [24, 25], and this approach significantly reduces postoperative Visual Analogue Scale/Score (VAS), the need for analgesics, and PONV incidence [26].

However, only a few reports are available on PONV incidence and its associated risk factors after laparoscopic benign ovarian cyst debulking, and detailed reports on the effectiveness of the zero-opioid general anesthesia technique in reducing PONV occurrence are scarce. Therefore, the present study investigated risk factors influencing PONV occurrence and the effectiveness of zero-opioid general anesthesia in reducing PONV in patients undergoing laparoscopic benign ovarian cyst debulking.

As one of the common complications after general anesthesia, PONV usually occurs within 6 to 24 hours after surgery. It will not only aggravate the patient’s discomfort and dissatisfaction with the treatment but also contribute to increased healthcare costs due to extended hospital stays. Given these implications, anesthesiologists need to prioritize the prevention and management of PONV to enhance patient outcomes and reduce unnecessary healthcare expenditures [28]. In this study, a history of PONV, history of MS, postoperative use of analgesic pumps, and insufficient amount of preoperative intravenous rehydration showed significant differences between patients with and without PONV. Apfel et al. [10] reported that the incidence of PONV in patients with a history of PONV and MS was relatively high, consistent with the results of the present study. Additionally, the results of this study indicated that a history of PONV, history of MS, postoperative use of analgesic pumps, preoperative intravenous fluid volume, and 5-HT usage are independent risk factors for PONV occurrence after surgery. For patients who had a history of PONV and MS, their nausea and vomiting threshold was low, and thus, the incidence of PONV was high [28]. In addition, there is a study showing that certain patients with a previous history of MS may have the same mechanism for PONV development as that of MS [29]. Analgesic drugs slow down the peristalsis of the patient’s gastrointestinal tract, inhibit gastrointestinal tract function, and may trigger vomiting by stimulating various receptors involved in the transmission of vomiting information, including 5-HT3 receptors, 5-HT4 receptors, opioid receptors, cholinergic receptors, and dopamine receptors [30], which, in turn, causes nausea, vomiting, and other side effects. The patient’s anxiety and psychological stress can activate a stress response, leading to an increase in the release of catecholamines including serotonin (5-HT) and dopamine. This, in turn, results in delayed gastric emptying, which can contribute to nausea and vomiting. Additionally, the elevated levels of these neurotransmitters may exert central emetogenic effects further exacerbating the symptoms. Additionally, the use of carbon dioxide for artificial pneumoperitoneum during laparoscopic surgery causes physical and chemical stimulation of the septal muscle and septal nerve, which induces nausea and vomiting. Furthermore, prolonged intraoperative lithotomy causes prolonged compression of the gastrointestinal mucosa, leading to ischemia of the intestinal mucosa and release of 5-HT3 and resulting in PONV [31]. The study has shown that hypoperfusion of organs is also the cause of PONV [32]. Preoperative fluid infusion can reduce the occurrence of hypotension after induction and avoid splanchnic hypoperfusion. In addition, preoperative intravenous fluid infusion can supplement the body fluid loss caused by intestinal preparation and diet prohibition, maintain the stability of the internal environment, reduce stress response, and reduce the incidence of postoperative insulin resistance. Therefore, preoperative fluid infusion can reduce the incidence of postoperative PONV [33, 34, 35].

In the current study, the use of opioids for anesthesia was identified as an independent risk factor for the occurrence of PONV in patients following surgery. Opioid agonists activate opioid-like activity at intestinal peripheral receptors, inhibit acetylcholine release from the mesenteric plexus, and stimulate µ receptors. This combination leads to decreased muscle tone and peristaltic activity. Consequently, delayed gastric emptying and gastric dilation occur, activating visceral mechanoreceptors and chemoreceptors. This process triggers PONV through the serotonergic signaling pathways [36]. Similarly, a recent study highlighted that remifentanil dosage and the use of neostigmine were risk factors for PONV in patients undergoing gynecologic laparoscopic surgery [37]. In this context, the use of OFA not only prolonged the time to the first dose of rescue analgesia but also decreased pain scores, minimized the need for antiemetic medications, and enhanced the quality of postoperative recovery for patients [38]. In the present study, the incidence of PONV in the treatment group was significantly lower than that in the control group, with the treatment group experiencing less than half the incidence of PONV. Moreover, the postoperative quality of life scores of patients in the treatment group were significantly higher than those of patients in the control group, consistent with the findings from previous research [38].

In addition to anesthesia, a crucial element in preventing PONV occurrence involves conducting a thorough assessment of risk factors, identifying patients with high-risk profiles, and implementing appropriate preventive measures [39, 40]. For those identified as high-risk, perioperative guidelines for PONV prevention and treatment [41] recommend the combined use of multiple medications. In cases where prophylaxis has not been administered, the initial occurrence of PONV can be treated with a small dose of 5-HT3 receptor antagonists [42]. Conversely, for patients who have received prophylaxis, the first occurrence of PONV can be managed through a combination of different medications. Following treatment, it is important to evaluate the effectiveness of antiemetic drugs and monitor for any adverse reactions. Furthermore, greater emphasis should be placed on several key areas (i) addressing the patient’s psychological well-being through effective communication, which can help alleviate anxiety and depression; (ii) implementing proper postoperative dietary care, to enhance the patient’s recovery; (iii) incorporating acupuncture as an adjunct to assist anesthesia [43]; (iv) ensuring completion of the surgical procedure by effectively aspirating gas and fluids from the abdominal cavity, followed by abdominal compression to facilitate the expulsion of CO₂ gas from the body, thereby minimizing its irritation of the septal muscle. These methods can yield significant benefits and help reduce the incidence of PONV.

This study has certain limitations that must be considered. It is a retrospective analysis, and although the indicators were sourced from the same hospital data, the timeframe for data collection was restricted. Additionally, the sample collection was confined to China, which may lead to varying results in different countries and among diverse ethnic groups. Future studies addressing these limitations are necessary to validate the findings of this study.

In conclusion, this study demonstrated that the zero-opioid general anesthesia technique significantly reduced postoperative complications. Additionally, it identified independent risk factors for nausea and vomiting after laparoscopic surgery for benign ovarian cysts by analyzing the clinical characteristics of patients in the treatment and control groups and in the PONV and non-PONV groups. These findings are expected to provide a reference for reducing PONV occurrence in patients after gynecological laparoscopy and improving their postoperative quality of life.

PONV occurrence in patients with ovarian cysts is associated with a history of PONV and motion sickness, and the zero-opioid general anesthesia technique can significantly reduce PONV occurrence, which will aid in improving patient prognosis.

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Conception and design: JC; Administrative support: JS; Provision of study materials or patients: JC; Collection and assembly of data: XYJ and XHZ; Data analysis and interpretation: JC, XYJ, XHZ and JS. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Informed consent was obtained from all patients. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Rudong Clinical College affiliated with Yangzhou University (Rudong Hospital of Traditional Chinese Medicine) (RDXZYY-PA-20221109).

This study was supported by the Nantong Municipal Health Commission scientific research project (No. MSZ2022096).

The authors declare no conflict of interest.