Skip to main content
Download PDF

Effect of improving sleep quality the night before surgery with zolpidem on postoperative gastrointestinal function in patients undergoing laparoscopic partial colorectal resection: a randomized, double-blind, controlled trial

BMC Anesthesiology volume 25, Article number: 80 (2025) Cite this article

Abstract

Background

Sleep is one of the basic physiological needs of human beings. Preoperative sleep disorders are associated with poor prognosis in surgical patients, and sleep disorders have been shown to be one of the risk factors for gastrointestinal dysfunction. However, there are now few studies to investigate whether improving preoperative sleep disorders can promote the recovery of postoperative gastrointestinal function. This study aimed to investigate the effects and significance of improving preoperative sleep quality with zolpidem on postoperative gastrointestinal function.

Methods

In this prospective, randomized, double-blind clinical trial, 76 patients undergoing elective laparoscopic partial colorectal resection and with a Pittsburgh Sleep Quality Index (PSQI) score > 5, were randomly divided into two groups. The zolpidem group (Group Z, n = 38) was given a capsule containing 10 mg of zolpidem the night before the operation, and the control group (Group C, n = 38) was given an empty capsule the night before the operation. Follow-up visits were performed on the 1st, 3rd, and 7th postoperative days, respectively. The primary outcome of this study was the I-FEED (Intake, Feeling nauseated, Emesis, Physical Exam, and Duration of symptoms) score on the third postoperative day (POD3). Secondary outcomes included time to postoperative first flatus, first feces, and first food intake (semi-liquid diet), I-FEED scores, visual analog scores (VAS) during coughing and at rest, times of patient-controlled intravenous analgesia (PCIA) effective presses, sufentanil dosage, number of remedial analgesia in the 24-hour postoperative period, and changes in inflammatory markers (TNF-α).

Results

Compared with Group C, Group Z had a lower I-FEED score on POD1 (P < 0.05) and shorter time to first flatus and first food intake (P < 0.05); there were significant differences between the two groups in VAS scores during coughing and at rest on POD1, VAS score during coughing on POD3, times of PCIA effective presses and sufentanil dosage in the 24-hour postoperative period, and patient satisfaction (P < 0.05).

Conclusion

For patients with sleep disorders, the use of zolpidem to improve sleep the night before surgery is beneficial in partially improving postoperative gastrointestinal function, relieving postoperative pain, and increasing patient satisfaction.

Test registration

ChiCTR2300077566 November 13, 2023.

Peer Review reports

Introduction

Colorectal cancer is the fourth most deadly cancer in the world, with approximately 900,000 deaths annually, accounting for about 10% of all cancers and cancer-related deaths diagnosed globally each year. Moreover, the incidence of colorectal cancer continues to rise in developing countries. The incidence of colorectal cancer is projected to increase to 2.5 million new cases worldwide by 2035 [1]. Laparoscopic partial colorectal resection is the mainstream treatment for colorectal cancer [2]. Although laparoscopic surgery has the advantages of less trauma and less pain compared with traditional open surgery [3], the effect of carbon dioxide artificial pneumoperitoneum on the physiological function of the patient during laparoscopic surgery cannot be ignored. Artificial pneumoperitoneum can not only cause significant stress reactions in the body, but also have different degrees of impact on postoperative gastrointestinal function. Postoperative ileus (POI) is a manifestation of impaired gastrointestinal function, which is a transient cessation of peristalsis after intestinal resection that prevents efficient transportation of intestinal contents and reduces the tolerance of dietary intake. Patients suffer not only mentally from gastrointestinal dysfunction but also physically due to the pain caused by complications and prolonged postoperative hospitalization [4]. Therefore, it is particularly important to promote the recovery of gastrointestinal function after surgery.

Sleep disorders are defined as clinically significant disturbance in either the quantity, the quality or rhythm of sleep, wakefulness, or the wake-sleep cycle that occurs in an individual [5]. According to the World Health Organization, 27% of the world’s population suffers from sleep disorders. Data from the China Sleep Research Society shows that as many as 300 million Chinese have sleep disorders, with a prevalence rate of 38.2% in adults. Chronic sleep disorders may lead to cognitive dysfunction, prolong postoperative recovery time, and increase the risk of postoperative complications [6]. In addition, it has been found that sleep quality may affect gastrointestinal function through brain-gut axis mechanisms. Specifically, sleep disorders can lead to elevated inflammatory factors in the body, as well as disturbances in the intestinal flora, and the imbalance between pro-inflammatory and anti-inflammatory factors can also exacerbate oxidative stress [7], which can affect gastrointestinal function [8,9,10]. Currently, there are articles confirming the interaction between GI dysfunction and sleep disorders [11], and based on this, melatonin has also been proposed as an adjunctive treatment for gastrointestinal dysfunction [12, 13]. However, no studies have been conducted to investigate whether improving preoperative sleep disorders can promote the recovery of gastrointestinal function after surgery. Therefore, the aim of this study was to investigate the effect of improving sleep quality with zolpidem the night before surgery on postoperative gastrointestinal function, expecting to help clinicians provide such patients with individualized interventions as early as possible in the perioperative period, to improve the quality of postoperative recovery, and to promote rapid postoperative recovery.

Methods

Study design

This double-blind, prospective, randomized, controlled study was conducted at the First People’s Hospital of Lianyungang. The trial was approved by the Ethics Committee of the First People’s Hospital of Lianyungang (KY-20231004002-02) and registered in the China Clinical Trial Registry (ChiCTR2300077566). Eighty-six patients who underwent elective laparoscopic partial colorectal resection under general anesthesia from November 2023 to August 2024 at the First People’s Hospital of Lianyungang were chosen in this study.

The main inclusion criteria were: patients diagnosed primary colorectal carcinoma and with Pittsburgh Sleep Quality Index (PSQI) score > 5, age 18–80 years old, body mass index (BMI) 18–35 kg/m2, the American Society of Anesthesiologists (ASA) class I–III, patients who were tolerant to the drugs in this study, and those who voluntarily participated in this study and signed the informed consent. Patients who met one of the following criteria were excluded: history of oral sedation and analgesia within 14 days before surgery; sleep apnea, drug allergy, drug abuse, combination of severe cardiac, brain, renal, pulmonary, and hepatic impairments or other malignant neoplastic diseases, history of psychoneurological disorders; severe hearing impairment or inability to understand or complete the Pittsburgh sleep quality index (PSQI) questionnaire; refusal to participate in the trial. Written informed consent was obtained from all recruited patients or their authorized family members.

Randomization and blinding

Randomization was performed using a secure web-based system. Based on a computer-generated randomization sequence, patients were divided into two groups, the zolpidem group (Group Z) and the control group (Group C). We kept the grouping information in an opaque envelope sealed, then placed 10 mg of zolpidem in a capsule and assigned a nurse not involved in the study to give zolpidem to patients in Group Z at bedtime and the empty capsule to patients in Group C at bedtime. Thus, the patients were not aware of the grouping. Clinical information collectors, data analysts, surgeons, anesthesiologists, nurses administering medications, and other health care.

personnel were blinded to the grouping.

Methods of intervention

An anesthesiologist not involved in the surgery assessed each patient’s sleep quality the day before surgery using the PSQI, which all patients participating in the trial were asked to complete independently. The PSQI scale was designed by Buysse et al. It consists of 18 items in 7 sections, including subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disorders, use of sleeping pills, and daytime dysfunction. The scale assesses the subject’s sleep quality over the last month, with higher scores on the test indicating poorer sleep quality. A score of 5 is an empirically determined cut-off point [14].

All subjects were assessed by an anesthesiologist, unaware of the grouping, for sleep quality the night before surgery using the Leeds Sleep Evaluation Questionnaire (LSEQ) upon entering the operating room. The LSEQ questionnaire consists of 10 questions covering 4 areas: the ease of getting to sleep (GTS, items 1–3), the quality of sleep (QOS, items 4 and 5), awakening from sleep (AFS, items 6 and 7), and behavior following wakefulness (BFW, items 8–10) [15]. The LSEQ questionnaire allows for a multifaceted assessment of the effects of pharmacological interventions on sleep over a short period of time [16]. Patients’ anxiety levels were also assessed using the Visual Analog Scale for Anxiety (VAS-A), which has been shown to be a reliable indicator for assessing preoperative anxiety [17].

The postoperative management protocol included encouraging the patient to sit up and mobilize out of bed as early as possible four hours after the surgery. On the first postoperative day, patients were advised to begin with water intake. Depending on their tolerance, the diet was progressively advanced from liquids to semi-liquids and eventually to solid foods. Intravenous fluid infusion was discontinued as early as feasible based on oral feeding recovery. Additionally, the urinary catheter was removed on the first postoperative day, with careful monitoring of urinary output.

Methods of anesthesia

All patients were required to fast for 8 h and abstain from drinking for 2 h before surgery. Upon the patient’s admission to the operating room, standard intraoperative monitoring of electrocardiogram (ECG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse oximetry (SpO2) was conducted, and intravenous (IV) access was established. After Allen’s test, radial arterial puncture cannulation was performed and invasive blood pressure was measured.

Anesthesia was induced with sufentanil 0.3 µg/kg, propofol 2 mg/kg, and vecuronium bromide 0.1 mg/kg. Tracheal intubation was performed 3 min after preoxygenation. The respiratory parameters were set to: VT 6–8 mL/kg, I: E = 1:2, FiO2 60%, RR 8–12 times/min (adjust as required), and PETCO2 at 35–45 mmHg. Remifentanil (1.5–6 µg·kg− 1·h− 1) and propofol (4–10 mg·kg− 1·h− 1) were used for maintenance of general anesthesia by a syringe pump to maintain bispectral index (BIS) at 40–60. To maintain muscle relaxation, vecuronium bromide 0.03 mg/kg was administered as needed intravenously. When blood pressure and heart rate fluctuated out of a range of 20% of the basal level, vasoactive drugs were used for adjustment.

All patients received intravenous sufentanil 0.1 µg/kg and acetaminophen mannitol injection 500 mg 30 min before the end of surgery to prevent postoperative pain, as well as intravenous dolasetron mesylate 12.5 mg and dexamethasone 10 mg to prevent postoperative nausea and vomiting. Propofol and remifentanil were discontinued while stitching the skin. The endotracheal tube was removed when the indications for extubation were met, and then the patients were admitted to the post-anesthesia care unit. Ramsay sedation score was measured 30 min after extubation, and patients were transferred to the ward when the relevant standard was met.

A patient-controlled intravenous analgesia (PCIA) pump was used postoperatively. The analgesic pump formulation was 2 µg/kg of sufentanil and 100 mg of dolasetron, with a total fluid volume of 100 mL. The analgesic pump infusion rate was 2 mL/h, and the self-administered dose was 1.5 mL.

Clinical data collection

Clinical data were collected by an anesthesiologist who was unaware of grouping. Preoperative demographic characteristics of the patients were collected, including gender, age, BMI, past medical history, ASA classification, PSQI score, and LSEQ score. Intraoperatively, mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO2) were recorded upon admission to the operating room, after anesthesia induction, at the time of skin incision, at the end of the procedure, and after extubation; intraoperative medications, anesthesia, length of surgery, and surgical complications were also recorded.

Patients were followed up on days 1, 3, and 7 postoperatively and the number of PCIA effective press times and sufentanil dosage in the 24-hour postoperative period, as well as the number of times of remedial analgesia, the intake, feeling nauseated, emesis, physical examination, and duration of symptoms (I-FEED) scores and visual analog scores (VAS) (with a score of 0 for no pain and a score of 10 for maximal pain) during coughing and at rest on these three days were recorded. The I-FEED scoring system assigns 0 to 2 points for each of 5 components, which include intake, feeling nauseated, emesis, physical examination, and duration of symptoms, then categorizes patients as having normal gastrointestinal function (scores of 0–2), postoperative gastrointestinal intolerance (scores of 3–5), or postoperative ileus (scores of ≥ 6) [18]. The time to postoperative first flatus, first feces, and first food intake (semi-liquid diet), as well as the occurrence of postoperative complications were also recorded.

Whole blood specimens (approximately 4 mL) were collected from patients using serum separator tubes on the day before surgery (T0), before anesthesia induction (T1), immediately after the operation (T2), and 24 h after surgery (T3). The blood samples were left at room temperature for 2 h, centrifuged at 1000 × g for 15 min, and then the supernatants were stored at − 80 °C. Serum concentrations of TNF-α were measured by enzyme-linked immunosorbent assay (ELISA).

Outcome measures

The primary outcome was the I-FEED score of POD 3. Secondary outcomes included preoperative demographic characteristics of the patients including gender, age, BMI, past medical history, ASA classification, PSQI score and LSEQ score, MAP and HR upon admission to the operating room, intraoperative medications, anesthesia, length of surgery and surgical complications, the time to postoperative first flatus, first feces and first intaking, the occurrence of postoperative complications and pain scores, I-FEED score and serum TNF-α concentrations at different time points.

Statistical analysis

Before this study, a preliminary study was conducted on each of the two groups to determine the sample size. The primary outcome of this study was the I-FEED score of POD 3. Based on the pre-test results, the I-FEED score of POD 3 in Group Z is 4.0 ± 0.632 (n = 6), and the I-FEED score of POD 3 in Group C is 4.5 ± 0.837 (n = 6). And G*power 3.1 statistical software was applied to calculate sample size. Based on 80% power, α = 0.05 and Cohen´s d effect size = 0.674, a total of 72 patients were needed. We anticipated a 20% dropout rate in patients, and given the 1:1 ratio, 86 patients were ultimately enrolled in the study.

The SPSS 25.0 statistical software was applied for analysis. A total of 76 patients in this trial could be evaluated for the per-protocol analysis. Shapiro-Wilk test was used to analyze the normality of the variables, and the measurement data conforming to normal distribution were expressed as mean ± standard deviation (x ± s), with the t-test used for comparison between groups. The data not conforming to normal distribution were described by median and quartiles, and a non-parametric test was used for comparison between groups. Count data were expressed as rates and the X2 test was used for comparison between groups, while the rank-sum test was used for rank data. P < 0.05 is considered as a statistically significant difference.

Results

A total of 120 patients were screened for participation in the trial, and 34 patients were excluded according to the inclusion criteria. After enrollment, 10 patients were eliminated, including 3 patients with data loss during follow-up, 5 patients who were transferred to the ICU postoperatively, and 2 patients who were converted to open surgery during the procedure. Thus, a total of 76 patients were finally included in the trial and randomized into 2 groups: the control group (Group C, n = 38) and the zolpidem group (Group Z, n = 38) (Fig. 1).

Fig. 1
figure 1

CONSORT flow diagramfor the study

Full size image

Abbreviations: Group C, control group; Group Z, zolpidem group; ICU, Intensive Care Unit.

Demographic data such as age, gender, BMI, ASA classification, type of surgery, past medical history, and PSQI score were similar in both groups. In addition, there were no significant differences in intraoperative data, intraoperative medications, intraoperative fluid intake and output, and other parameters between the two groups (Table 1).

Table 1 Basic information and surgical data
Full size table

The LSEQ scores on the night before surgery and the VAS-A scores after entering the operating room are shown in Table 2. Group Z’s ease of getting to sleep and sleep quality scores were significantly better than those of Group C. However, there was no significant difference between the two groups in terms of awakening and behavior following wakefulness. Group Z’s VAS-A score was significantly lower than that of Group C after entering the operating room.

Table 2 LSEQ and VAS-A scores
Full size table

The postoperative I-FEED scores are shown in Table 3. The I-FEED score on POD1 in Group Z was 4 (1), lower than in Group C (5 [2]; P = 0.001). As for the I-FEED scores on POD3 and POD7, there was no difference between the two groups.

Table 3 Postoperative I-FEED scores
Full size table

Table 4 shows the comparison of VAS scores at rest and during coughing between the two groups. At any time point, VAS scores were lower in Group Z than in Group C. On POD1, patients in Group Z had lower VAS scores compared to Group C (resting: 2 [1] vs. 3 [1]; P < 0.01, coughing: 4.5 [1] vs. 5 [0.25]; P < 0.05). On POD3, patients in Group Z had lower VAS scores during coughing compared to Group C (3 [1] vs. 4 [1]; P < 0.001). However, the difference between the groups at rest was not significant (P = 0.141). There was also no statistically significant difference in VAS scores at rest and during coughing between the two groups on POD7 (rest: P = 0.089, coughing: P = 0.158).

Table 4 Postoperative VAS scores
Full size table

There was no difference in the baseline data of TNF-α at T0 between the two groups. At T1, T2, and T3, the TNF-α values in Group Z were smaller than those in Group C. However, the difference was statistically significant only at T3 (5.68 ± 1.69 vs. 6.99 ± 3.26; P = 0.031), and the difference was not statistically significant at the remaining time points. (Table 5)

Table 5 Serum TNF-α-concentrations
Full size table

Table 6 documents the postoperative follow-up. According to patient self-report, the median time to first flatus (63.5 [22.75] vs. 74 [24.5], P = 0.010) and the median time to first intaking (121 [16.75] vs. 130 [19.25], P = 0.021) were significantly lower in Group Z than in the control group. The patient satisfaction was also higher in Group Z (P = 0.008). In terms of postoperative analgesia, on the first postoperative day, the times of effective press with the PCIA (1 [1] vs. 2 [1], P = 0.000) and the consumption of sufentanil (64.21 ± 8.78 vs. 68.12 ± 8.01, P = 0.046) were significantly reduced in Group Z compared with Group C. There were no significant differences between the two groups in terms of postoperative complications, length of hospitalization,30 readmission rate, and rescue analgesia.

Table 6 Postoperative outcomes
Full size table

Discussions

This randomized controlled trial investigated the effect of improving preoperative sleep quality with zolpidem on the recovery of gastrointestinal function in patients undergoing laparoscopic partial colorectal resection. The results of this study showed that the zolpidem group had a shorter time to first flatus and food intake and lower I-FEED score on the first postoperative day compared to the control group, but no statistically significant differences were found in postoperative gastrointestinal function as measured by the I-FEED scores on the third postoperative day and the seventh postoperative day. In addition, pain scores on the first postoperative day and patient satisfaction were significantly better in the zolpidem group than in the control group.

With the development of medical technology, the current status of rapid perioperative recovery of patients has received increasing attention. The concept of ERAS (Enhanced Recovery After Surgery) is to promote the postoperative recovery of patients by alleviating the stress caused by surgical trauma and other management measures. Rapid recovery of gastrointestinal function after surgery is a key element of ERAS [19], and it is gaining more attention from surgeons and anesthesiologists. Sleep is one of the basic physiological needs of humans, and sleep disorders affect a large number of patients undergoing surgery, which can adversely affect their recovery. One study reported that nearly 40% of colorectal cancer patients in China had preoperative insomnia [20]. Therefore, in order to promote the rapid recovery of patients after surgery, we should also pay more attention to the preoperative sleep quality of surgical patients, which is in line with the recent European guidelines on the preoperative assessment of adults undergoing elective noncardiac surgery that emphasize the importance of comprehensive preoperative assessment and optimization to improve surgical outcomes [21].

The sleep aid used in this study was zolpidem, a non-benzodiazepine hypnotic that belongs to a new class of psychotropic drugs called imidazopyridines. It enhances the GABAA receptor by selectively binding to omega-1 receptor subtypes [22]. Zolpidem is a proven safe and effective drug characterized by rapid onset of action and minimal drug residuals and rebound effects. In clinical applications, zolpidem is used to treat transient episodic insomnia and chronic insomnia by increasing the ratio of rapid eye movement (REM) sleep to slow-wave sleep (SWS) to repair sleep disruption [23, 24]. Its side effects include ataxia or poor motor coordination and difficulty in maintaining balance. It has been shown that the side effects of zolpidem are related to the dose used, which is commonly associated with the use of more than 20 mg per day [22]. In contrast, in this trial, only a single 10mg [25,26,27] (It is also the recommended dose in the drug description.) was given and the LSEQ scores showed no significant difference in AFS and BFW between the two groups, so statistically no relevant side effects were found.

Most of the primary outcomes in previous studies of perioperative use of zolpidem to improve sleep quality were postoperative pain. Types of surgery include hip and knee replacements [26], knee arthroscopy [28], rotator cuff repair [29], spine surgery [30], and laparoscopic partial colorectal resection [31]. These articles suggest that improved sleep with pre- or postoperative use of zolpidem reduces postoperative pain and decreases postoperative opioid use. Our study yielded similar results. There are also articles stating that the use of rescue analgesia can be reduced, which is inconsistent with the results of our study.

A study confirmed a significant relationship between sleep disturbances and gastrointestinal symptoms, including epigastric discomfort, nausea, dysphagia, reflux symptoms, diarrhea, and constipation [32]. Poor nighttime sleep can lead to worsening gastrointestinal symptoms the following day [33]. These gastrointestinal symptoms may be associated with an inflammatory response due to sleep disorders. A review has indicated that sleep disorders are associated with systemic inflammatory responses [34] and that sleep disruption activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). In particular, the activation of β-adrenergic signaling induces an increase in nuclear factor κB (NF-κB), inflammatory gene expression, pro-inflammatory cytokine production, and systemic inflammatory markers [35, 36]. In addition to this, studies have confirmed that normal nighttime sleep is associated with decreased sympathetic excitability [37]. Whereas, abnormal sleep leads to abnormal sustained activation of sympathetic pathways, which could plausibly explain the correlation between sleep disorders and inflammatory markers. These inflammatory markers include tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO). Tumor necrosis factor (TNF) plays a central role in coordinating the inflammatory response in mammals [38]. It also plays a key role in maintaining intestinal integrity and has been implicated in the pathogenesis of intestinal inflammation [39]. TNF-α has been shown to increase intestinal epithelial cell shedding and apoptosis, and to induce changes in tight junction morphology and intestinal permeability [40, 41]. In addition, TNF-α-mediated signaling plays an important role in maintaining the colonic epithelial barrier and wound healing [39]. In summary, lower levels of postoperative TNF-α may be able to promote the recovery of gastrointestinal function, which needs to be confirmed by further studies. Our results showed that improved sleep resulted in lower levels of TNF-α, lower I-FEED scores, and shorter time to postoperative first flatus and first food intake on POD1 compared with the control group. Interestingly, we found that improved sleep quality favored patients’ recovery of postoperative gastrointestinal function.

The results of this trial showed that improved preoperative sleep relieved pain on POD1 and reduced the use of sufentanil in the analgesic pump, a result similar to that of a randomized controlled trial [31]. Opioids are one of the most commonly used analgesics for the treatment of acute postoperative pain and mediate their effects mainly through interactions with three G-protein-coupled receptors: µ-opioid receptors, δ-opioid receptors, and κ-opioid receptors, which are expressed by central and peripheral (including intestinal) neurons. It has been found that chronic stimulation of µ-opioid receptors may be involved in esophageal motility disorders and is associated with sphincter of Oddi dysfunction. The κ-opioid receptors mediate responses such as analgesia, sedation, and bowel dysfunction. Although δ-opioid receptors are mainly localized in the central nervous system and mediate analgesia and respiratory depression, they are also present in the intermuscular plexus and submucosal plexus of the intestines, exerting inhibitory effects on gastrointestinal motility and secretion [42]. Therefore, a decrease in opioid use after surgery may have a certain effect on the recovery of gastrointestinal function.

In addition, this study found that improved sleep the night before surgery was effective in relieving patient anxiety, and it has been demonstrated that preoperative anxiety delays the recovery of postoperative gastrointestinal function. Anxiety leads to the activation of the HPA axis and an increase in the body’s stress response; it also causes dysregulation of the brain-gut axis, which leads to different intestinal disorders and affects the recovery of gastrointestinal function in the postoperative period. Kim et al. found that the application of buspirone in mice significantly suppressed stress-induced anxiety or depression behaviors and altered the composition of the intestinal microbiota of the mice [43]. Besides, anxiety may lead to a shift in gut flora, which can worsen intestinal inflammation. It may also reduce specific intestinal epithelial tight junction proteins in the intestinal epithelium, compromising its integrity. This disruption can affect intestinal motility and lead to alterations in microbial composition and intestinal permeability [44, 45].

The statistical results of this trial showed that the difference in I-FEED scores on POD3 between the two groups was not statistically significant, but the difference in I-FEED scores on POD1 was statistically significant. We speculated several reasons for this. First, as discussed previously, TNF-α values can have an effect on gastrointestinal function, and the difference in serum TNF-α values on POD 1 between the two groups was statistically significant. However, due to the limitation of conditions, our protocol did not collect blood samples from patients on POD 3. Future studies could consider collecting such data to supplement the lack of evidence. Secondly, there was a significant difference in pain scores between the two groups on POD1, whereas there was little difference in pain scores on POD3. There is evidence that the gut microbiome is associated with the development of postoperative pain [46], which may affect the recovery of gastrointestinal function. Finally, since this was a single-center, small-sample trial, the results were susceptible to some individual differences. This suggests that future studies with large sample sizes are needed for further validation.

There are some limitations in this study. First, this trial did not use objective indicators such as polysomnography to monitor sleep, nor did it differentiate between types of sleep disorders, which may have varying effects on gastrointestinal function. Second, due to the lack of uniform criteria for assessing postoperative gastrointestinal function, only the I-FEED score and conventional gastrointestinal function indicators were used for validation, and future studies are needed to establish more reliable assessment indicators to assess the recovery of gastrointestinal function. Third, the sample size of this trial was relatively small. Fourth, in order to maintain the consistency of the surgical approach, we excluded patients who were converted to open surgery intraoperatively, which may have had some impact on the results of the trial. Fifth, due to certain reasons, there are shortcomings in our postoperative management. We did not initiate early feeding for patients on the day of surgery, which may potentially impact the recovery of gastrointestinal function postoperatively. Finally, the specific mechanism of action of improved sleep on the recovery of gastrointestinal function is unclear, which requires more in-depth basic research.

Conclusion

In patients with pre-existing sleep disorders, improved sleep preoperatively reduced the I-FEED score on POD1 and contributed to the reduction of acute postoperative pain, the decreased need for analgesic medications, and improved patient satisfaction.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

Group Z:

Zolpidem group

Group C:

Control group

ERAS:

Enhanced recovery after surgery

VAS-A:

Visual analog scale for anxiety

ASA:

American Society of Anesthesiologists

ECG:

Electrocardiogram

SBP:

Systolic blood pressure

DBP:

Diastolic blood pressure

SpO2 :

Pulse oximetry

IV:

Intravenous

BIS:

Bispectral index

POD 1:

The first postoperative day

POD 3:

The third postoperative day

POD 7:

The seventh postoperative day

I-FEED:

Intake, response to nausea treatment, emesis, exam, and duration

GABA:

Gamma-amino-butyric acid

VAS:

Visual analog scores

PCIA:

Patient-controlled intravenous analgesia

POI:

Postoperative intestinal obstruction

BMI:

Body mass index

PSQI:

Pittsburgh sleep quality index

LSEQ:

Leeds sleep evaluation questionnaire

GTS:

The ease of getting to sleep

QOS:

The quality of sleep

AFS:

Awakening from sleep

BFW:

Behavior following wakefulness

ELISA:

Enzyme-linked immunoassay

POD:

Postoperative day

HPA:

Hypothalamic-pituitary-adrenal

SNS:

Sympathetic nervous system

NF-κB:

Nuclear factor κB

TNF-α:

Tumor necrosis factor-α

IL-6:

Interleukin-6

NO:

Nitric oxide

References

  1. Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer[J]. Lancet. 2019;394(10207):1467–80.

    Article  PubMed  Google Scholar 

  2. Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies[J]. Nat Reviews Gastroenterol Hepatol. 2019;16(12):713–32.

    Article  Google Scholar 

  3. M B, A V, L G, et al. Laparoscopic versus open colorectal surgery: a randomized trial on short-term outcome[J]. Annals of surgery, Ann Surg, 2002, 236(6).

  4. B B, N S. Postoperative ileus: etiologies and interventions[J]. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association. Clin Gastroenterol Hepatol, 2003, 1(2).

  5. Gauld C, Wakefield JC, Micoulaud-Franchi J-A. Proposing a definition for sleep disorders: an epistemological review[J]. Sleep Med Rev. 2024;79:102028.

    Article  PubMed  Google Scholar 

  6. Bp O, L G, Er M, et al. Sleep, Pain, and Cognition: modifiable targets for optimal perioperative Brain Health[J]. Anesthesiology, Anesthesiology; 2021;135:6.

  7. Lavalle S, Masiello E, Iannella G, et al. Unraveling the complexities of oxidative stress and inflammation biomarkers in obstructive sleep apnea syndrome: a comprehensive review[J]. Life (Basel Switzerland). 2024;14(4):425.

    CAS  PubMed  Google Scholar 

  8. Pj P, Ec O, Da J. Wake-up call to clinicians: the impact of Sleep Dysfunction on Gastrointestinal Health and Disease[J]. Journal of clinical gastroenterology. J Clin Gastroenterol, 2018, 52(3).

  9. M Z GK. Y L. The relationship between gut microbiota and inflammatory response, learning and memory in mice by sleep deprivation[J]. Frontiers in cellular and infection microbiology. Front Cell Infect Microbiol, 2023, 13.

  10. Matenchuk BA, Mandhane PJ, Kozyrskyj AL. Sleep, circadian rhythm, and gut microbiota[J]. Sleep Med Rev. 2020;53:101340.

    Article  PubMed  Google Scholar 

  11. Vernia F, Ruscio MD, Ciccone A, et al. Sleep disorders related to nutrition and digestive diseases: a neglected clinical condition[J]. Int J Med Sci. 2021;18(3):593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gao T, Wang Z, Dong Y, et al. Role of melatonin in sleep deprivation-induced intestinal barrier dysfunction in mice[J]. J Pineal Res. 2019;67(1):e12574.

    Article  PubMed  Google Scholar 

  13. Wz L, Ka G et al. S M,. Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: A double-blind placebo-controlled study[J]. Alimentary pharmacology & therapeutics, Aliment Pharmacol Ther, 2005, 22(10).

  14. Buysse DJ, Reynolds CF, Monk TH, et al. The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research[J]. Psychiatry Res. 1989;28(2):193–213.

    Article  CAS  PubMed  Google Scholar 

  15. Ac P. I H. The Leeds sleep evaluation questionnaire in psychopharmacological investigations - a review[J]. Psychopharmacol Psychopharmacol (Berl), 1980, 71(2).

  16. N Z ML. Subjective assessment of the effects of CNS-active drugs on sleep by the Leeds sleep evaluation questionnaire: a review[J]. Human psychopharmacology, Hum Psychopharmacol, 2003, 18(1).

  17. Facco E, Stellini E, Bacci C et al. Validation of visual analogue scale for anxiety (VAS-A) in preanesthesia evaluation[J]. Minerva Anestesiol, 2013, 79(12).

  18. Pp YL, Yq F et al. Y,. Effect of Intraoperative Dexmedetomidine on Recovery of Gastrointestinal Function After Abdominal Surgery in Older Adults: A Randomized Clinical Trial[J]. JAMA network open, JAMA Netw Open, 2021, 4(10).

  19. Uo G, Mj S et al. M H,. Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations: 2018[J]. World journal of surgery, World J Surg, 2019, 43(3).

  20. Gw S, Yl Y, Xb Y et al. Preoperative insomnia and its association with psychological factors, pain and anxiety in Chinese colorectal cancer patients[J]. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer. Support Care Cancer, 2020, 28(6).

  21. Lamperti M, Romero CS, Guarracino F, et al. Preoperative assessment of adults undergoing elective noncardiac surgery: updated guidelines from the European Society of Anaesthesiology and Intensive Care[J]. Eur J Anaesthesiol. 2025;42(1):1–35.

    Article  PubMed  Google Scholar 

  22. Pv ADAG. R. Role of zolpidem in the management of insomnia[J]. CNS neuroscience & therapeutics, CNS Neurosci Ther, 2011, 17(5).

  23. X DL. H, Y S, Perioperative Sleep disorder: a Review[J]. Frontiers in medicine. Front Med (Lausanne), 2021, 8.

  24. Kd V, Sm RH et al. T,. Lower doses of sublingual Zolpidem are more effective than oral Zolpidem to anticipate sleep onset in healthy volunteers[J]. Sleep medicine, Sleep Med, 2013, 14(1).

  25. Roehrs TA, Roth T. Gender differences in the efficacy and safety of chronic nightly zolpidem[J]. Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine, 2016;12(3):319.

  26. L K, P J, H K. Postoperative sleep disturbances after zolpidem treatment in fast-track hip and knee replacement[J]. Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine. J Clin Sleep Med, 2014, 10(3).

  27. Mg K, M H, Sk V et al. Zolpidem does not serve as reinforcer in humans subjected to simulated shift work[J]. Drug and alcohol dependence, Drug Alcohol Depend, 2010, 112(1–2).

  28. Rz T, Mp RB. B, Zolpidem reduces postoperative pain, fatigue, and narcotic consumption following knee arthroscopy: a prospective randomized placebo-controlled double-blinded study[J]. The journal of knee surgery. J Knee Surg, 2006, 19(2).

  29. Ch C, Sw L, Yk L et al. Effect of a sleep aid in analgesia after arthroscopic rotator cuff repair[J]. Yonsei medical journal. Yonsei Med J, 2015, 56(3).

  30. H M, E M, A M, et al. The pain control efficacy of zolpidem versus melatonin after intervertebral disc herniation surgery under general anaesthesia: a randomised clinical trial[J]. J West Afr Coll Surg J West Afr Coll Surg, 2022, 12(2).

  31. Z X. B L, Z Z. The Effect of Improving Preoperative Sleep Quality on Perioperative Pain by Zolpidem in Patients Undergoing Laparoscopic Colorectal Surgery: A Prospective, Randomized Study[J]. Pain research & management, Pain Res Manag, 2022, 2022.

  32. F C, Ar MC et al. Z,. Sleep disturbances are linked to both upper and lower gastrointestinal symptoms in the general population[J]. Neurogastroenterology and motility, Neurogastroenterol Motil, 2009, 21(2).

  33. Kc MJMH. C, Sleep disturbance influences gastrointestinal symptoms in women with irritable bowel syndrome[J]. Digestive diseases and sciences, Dig Dis Sci, 2000, 45(5).

  34. Mr I, Je RO, Sleep Disturbance C. Sleep duration, and inflammation: a systematic review and Meta-analysis of Cohort studies and experimental sleep Deprivation[J]. Biological psychiatry. Biol Psychiatry, 2016, 80(1).

  35. Mr I, Sw C. Reciprocal regulation of the neural and innate immune systems[J]. Nat Reviews Immunol Nat Rev Immunol, 2011, 11(9).

  36. Yang D-F, Huang W-C, Wu CW, et al. Acute sleep deprivation exacerbates systemic inflammation and psychiatry disorders through gut microbiota dysbiosis and disruption of circadian rhythms[J]. Microbiol Res. 2023;268:127292.

    Article  CAS  PubMed  Google Scholar 

  37. M I, J T, C M, et al. Effects of sleep and sleep deprivation on catecholamine and interleukin-2 levels in humans: clinical implications[J]. The Journal of clinical endocrinology and metabolism. J Clin Endocrinol Metab, 1999, 84(6).

  38. Huyghe J, Priem D, Bertrand MJM. Cell death checkpoints in the TNF pathway[J]. Trends Immunol. 2023;44(8):628–43.

    Article  CAS  PubMed  Google Scholar 

  39. B R. R A, C B. Tumour Necrosis Factor Alpha in Intestinal Homeostasis and Gut Related Diseases[J]. International journal of molecular sciences. Int J Mol Sci, 2019, 20(8).

  40. Marchiando AM, Shen L, Graham WV, et al. Caveolin-1–dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo[J]. J Cell Biol. 2010;189(1):111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Am M, Wv LS. G, The epithelial barrier is maintained by in vivo tight junction expansion during pathologic intestinal epithelial shedding[J]. Gastroenterol Gastroenterol, 2011, 140(4).

  42. Farmer AD, Holt CB, Downes TJ, et al. Pathophysiology, diagnosis, and management of opioid-induced constipation[J]. The Lancet Gastroenterology & Hepatology; 2018;3(3):203–12.

  43. Kim J-K, Han S-K, Joo M-K et al. Buspirone alleviates anxiety, depression, and colitis; and modulates gut microbiota in mice[J]. Sci Rep, 2021, 11.

  44. Ca S, C D-A DE et al. The gut microbiota in anxiety and depression - A systematic review[J]. Clinical psychology review. Clin Psychol Rev, 2021, 83.

  45. S V, S L, B J, et al. Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals[J]. Scientific reports, Sci Rep, 2020, 10(1).

  46. A M, S S. Gut microbiome in anesthesiology and pain medicine[J]. Anesthesiology Anesthesiology, 2022, 137(1).

Download references

Acknowledgements

The authors acknowledge The Affiliated Lianyungang Hospital of Xuzhou Medical University staff, and study participants for their support.

Funding

No funding was received for this study.

Author information

Author notes

  1. Ruijia Gao and Yu Huang contributed equally to this work and are co-first author.

Authors and Affiliations

  1. Department of Anesthesiology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 6 Zhenhua East Road, Lianyungang, 222002, Jiangsu, China

    Ruijia Gao, Shimeng Mao, Hongyan He, Jinliang Yao & Jiying Feng

  2. Department of Anesthesiology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, No.6 Zhenhua East Road, Lianyungang, 222002, Jiangsu, China

    Yu Huang

  3. Department of Gynecology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 6 Zhenhua East Road, Lianyungang, 222002, Jiangsu, China

    Ying Wang

Authors
  1. Ruijia Gao
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Yu Huang
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Shimeng Mao
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Hongyan He
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Jinliang Yao
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Jiying Feng
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Ying Wang
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Ruijia Gao: contributed to the design, analysis, interpretation, and drafting of the manuscript, Yu Huang: contributed to the design, analysis, interpretation, and drafting of the manuscript, Shimeng Mao: contributed to the analysis, interpretation, and drafting of the manuscript, Hongyan He: contributed to the interpretation and drafting of the manuscript, Jinliang Yao: contributed to the analysis, Jiying Feng: contributed to study conception and design, data collection, and drafting of the manuscript, and Ying Wang: contributed to study conception and design and data collection.

Corresponding authors

Correspondence to Jiying Feng or Ying Wang.

Ethics declarations

Ethics approval and consent to participate

This study was approved by The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu Province, China (registration number: KY-20231004002-02). Written informed consent was signed by the patients.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gao, R., Huang, Y., Mao, S. et al. Effect of improving sleep quality the night before surgery with zolpidem on postoperative gastrointestinal function in patients undergoing laparoscopic partial colorectal resection: a randomized, double-blind, controlled trial. BMC Anesthesiol 25, 80 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12871-025-02959-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12871-025-02959-6

Keywords

BMC Anesthesiology

ISSN: 1471-2253

Contact us