Oxycodone versus Sufentanil for Postoperative Recovery in Obese Patients Undergoing Laparoscopic Bariatric Surgery: A Randomized Controlled Trial

Introduction

Bariatric surgery remains the most effective long-term treatment for morbid obesity, significantly reducing obesity-related comorbidities and mortality risks.^1,2 However, this population presents unique perioperative challenges, particularly in postoperative pain management and early recovery.^3,4 Effective analgesia not only alleviates pain but also directly enhances postoperative recovery quality, which encompasses physical comfort, emotional state, physical independence, psychological support, and pain control—factors particularly critical for obese patients prone to complications such as pulmonary dysfunction, nausea, and vomiting.^5,6 Enhanced Recovery After Surgery (ERAS) protocols advocate multimodal analgesia to minimize opioid-related risks, including respiratory depression, exacerbation of obstructive sleep apnea, and sedation-induced delayed mobilization.^7–9 Thus, careful analgesic selection and dosing in obese patients are essential for improving overall postoperative recovery.

Obesity significantly affects opioid pharmacokinetics and pharmacodynamics.^6,10 Highly lipophilic opioids such as sufentanil demonstrate an increased volume of distribution and prolonged elimination half-life in obese patients, potentially leading to postoperative sedation and respiratory compromise.¹⁰ Furthermore, alterations in hepatic enzyme activities (such as CYP2D6 and CYP3A4) have been reported, influencing opioid metabolism and potentially reducing analgesic predictability and safety in obese individuals.^11,12 Pain perception may also differ in obese patients, with reports indicating heightened sensitivity and lower pain thresholds.¹³ These pharmacological and physiological differences highlight the necessity for analgesic strategies tailored specifically to obese populations, underscoring the importance of using appropriate assessment tools such as the Quality of Recovery-40 (QoR-40) questionnaire to comprehensively evaluate postoperative outcomes.¹⁴

Despite the goal of multimodal analgesia to reduce opioid utilization, opioids remain essential in the analgesic management of bariatric surgery. Among commonly used perioperative opioids, sufentanil offers rapid onset and short duration of action, contributing to its widespread use in bariatric procedures due to its high potency and ease of titration. Nevertheless, its brief analgesic effect may lead to early postoperative pain recurrence. Oxycodone, acting on both µ- and κ-opioid receptors, potentially provides superior visceral analgesia due to κ-receptor agonism, and a longer analgesic duration, possibly bridging the analgesic gap postoperatively.¹⁵ Recent studies comparing oxycodone with other opioids have demonstrated superior analgesic efficacy and improved patient satisfaction across various surgical populations;¹⁶ however, existing research specifically addressing obese patients undergoing bariatric surgery remains sparse, often limited by small sample sizes or a lack of comprehensive recovery evaluation. Thus, this randomized controlled trial aimed to determine whether oxycodone could enhance postoperative recovery quality compared to sufentanil in obese patients undergoing laparoscopic bariatric surgery.

Methods

Ethics and Study Design

This study was a prospective, double-blind randomized controlled trial conducted at a single tertiary hospital (the Affiliated Hospital of Xuzhou Medical University, China). Institutional ethics committee approval was obtained (no. XYFY2024-KL475-01) on October 18, 2024, and the trial was registered at ClinicalTrials.gov (Registration no: ChiCTR2500095380; Principal investigator: Xiangyu Yao; Date of registration: January 6, 2025). This trial was conducted in strict compliance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines and adhered to the ethical principles established by the Declaration of Helsinki. All enrolled patients provided written informed consent.

Patient Selection

Eligible participants were adults aged 18–60 years, classified as American Society of Anesthesiologists (ASA) physical status II–III, with obesity defined as a body mass index (BMI) ≥30 kg/m², who were scheduled for elective laparoscopic bariatric surgery (including sleeve gastrectomy or sleeve gastrectomy with transit bipartition). Exclusion criteria included severe cardiovascular disease or hepatic/renal dysfunction, history of open abdominal surgery, psychiatric disorders, chronic opioid or alcohol abuse, known allergy to the study drugs, inability or unwillingness to comprehend the scoring scales or refusal to participate, and severe obstructive sleep apnea-hypopnea syndrome (OSAHS).

Randomization and Blinding

Patients were randomized in a 1:1 ratio into either the oxycodone group (Group O) or sufentanil group (Group S) using a computer-generated randomization sequence. Random allocation was concealed using opaque, sealed envelopes opened immediately before anesthesia induction by an anesthesia provider who did not participate in patient care or outcome assessment. This unblinded provider prepared the assigned study drugs (oxycodone or sufentanil) in identical syringes to ensure that the appearance and volumes were indistinguishable. Patients, surgeons, anesthesiologists (except the drug-preparing provider), outcome assessors, and postoperative nursing staff were all blinded to group allocation throughout the study. All surgical procedures were performed by the same surgical team.

Anaesthesia Protocol

All patients underwent a standardized anesthesia protocol, differing only in the opioid administered (oxycodone or sufentanil). Upon entering the operating room, standard monitoring was established, including electrocardiography (ECG), pulse oximetry (SpO₂), invasive arterial blood pressure, bispectral index (BIS), and train-of-four (TOF) monitoring. After adequate preoxygenation (FiO₂ 100% for 3 min), anesthesia induction was performed using intravenous propofol (2 mg/kg), rocuronium bromide (0.9 mg/kg), and dexamethasone (8 mg). Analgesic induction differed between groups: patients in the oxycodone group (Group O) received oxycodone (0.3 mg/kg), whereas the sufentanil group (Group S) received sufentanil (0.3 µg/kg). Five minutes after induction, tracheal intubation was performed.

Mechanical ventilation was initiated with pressure-controlled ventilation–volume guaranteed (PCV-VG) mode, characterized by a tidal volume of 6 to 8 mL/kg, an inspiratory-to-expiratory (I:E) ratio of 1:2, an initial inspired oxygen fraction (FiO₂) of 80%, a positive end-expiratory pressure (PEEP) of 5 cm H₂O, and an airway pressure limit of < 30 cm H₂O. The respiratory rate was adjusted to maintain end-tidal CO₂ (PETCO₂) between 35 and 45 mm Hg. After intubation, bilateral ultrasound-guided transverse abdominis plane (TAP) blocks (20 mL of 0.375% ropivacaine each side) and rectus sheath blocks (10 mL of 0.375% ropivacaine each side) were performed on all patients.

Anesthesia maintenance consisted of intravenous infusions of propofol and remifentanil combined with inhaled sevoflurane (1–2%). Rocuronium infusion was titrated based on quantitative TOF monitoring to maintain a TOF ratio of 0. Hemodynamic stability was maintained by adjusting the infusion rates of propofol and remifentanil and administering vasoactive drugs as needed, ensuring mean arterial pressure (MAP) fluctuations remained within 30% of baseline values and heart rate (HR) between 45–100 beats/min.¹⁷

Approximately 20 minutes before the anticipated end of surgery, sevoflurane and rocuronium infusions were discontinued, and tropisetron (2 mg IV) was administered. Propofol infusion was discontinued at the beginning of skin closure. The skin closure procedure generally takes approximately 10 minutes to complete. Group O received oxycodone (0.1 mg/kg IV) and Group S received sufentanil (0.1 µg/kg IV). At the end of skin closure, remifentanil was discontinued, and neuromuscular blockade was reversed with sugammadex (2 mg/kg IV). The tracheal tube was removed once standard extubation criteria were met, and patients received supplemental oxygen via face mask for at least 5 minutes before transfer to the post-anesthesia care unit (PACU).

Intervention and Postoperative Management

Patients in Group O received intravenous oxycodone (0.3 mg/kg at anesthesia induction, supplemented with 0.1 mg/kg 10 min before surgery completion). Group S received intravenous sufentanil (0.3 μg/kg at induction, supplemented with 0.1 μg/kg 10 min before surgery completion). Upon arrival in the PACU, patients continued to receive supplemental oxygen to maintain SpO₂ >94%. Pain intensity was routinely assessed using the Numeric Rating Scale (NRS), ranging from 0 (no pain) to 10 (worst imaginable pain). If moderate-to-severe pain occurred (NRS >4), intravenous fentanyl (100 µg) was administered as rescue analgesia and documented. Postoperative nausea and vomiting (PONV) were treated with intravenous metoclopramide (10 mg) and recorded as necessary. Intravenous infusions of flurbiprofen axetil (routine analgesia) and tramadol (100 mg; rescue for NRS >4 breakthrough pain) were administered in the surgical ward.

All medication dosages, expressed in mg/kg or µg/kg, were calculated based on corrected body weight (CBW), where ideal body weight (IBW) was defined as height (cm) minus 100 for males or height (cm) minus 105 for females, and CBW was calculated as IBW + [0.4 × (actual weight – IBW)].¹⁸

Outcome Measures

Primary Outcome

The primary endpoint was the quality of postoperative recovery assessed by the 40-item Quality of Recovery questionnaire (QoR-40) at 24 h after surgery. QoR-40 is a validated instrument widely used to measure patient-reported recovery quality across dimensions including physical comfort, emotional state, physical independence, psychological support, and pain.^14,19 Higher QoR-40 scores indicate better recovery quality.

Secondary Outcomes

Secondary endpoints included postoperative pain intensity, functional recovery milestones, sedation, analgesic requirements, and adverse events. Postoperative pain intensity was assessed using the numeric rating scale (NRS, ranging from 0 = no pain to 10 = worst imaginable pain) at 0.5, 2, 6, and 24 h post-surgery. Functional recovery milestones recorded were awakening time (defined as the duration from anesthetic discontinuation to patient responsiveness) and extubation time (interval from anesthetic discontinuation to removal of the endotracheal tube). Additionally, postoperative sedation was evaluated using the Ramsay sedation scale upon arrival in the PACU. The rates of rescue analgesia, PONV, administration of rescue antiemetics, and hypoxemia (defined as SpO₂ <90% persisting for more than 10 seconds) were documented. Duration of PACU stay, time to first flatus, time to first ambulation, and length of postoperative hospital stay were also recorded and compared between groups.

All outcome data were collected by an investigator blinded to group allocation. Pain and sedation scores were directly obtained from patient self-reports and nursing assessments, while clinical events and recovery milestones were recorded from medical charts and anesthesia records.

Sample Size Calculation

Sample size estimation was based on a preliminary study demonstrating a standard deviation of 15 for the QoR-40 total score at 24 h postoperatively. A difference of 10 points on the QoR-40 scale represents a clinically meaningful improvement in recovery quality following surgery.²⁰ Assuming an α-error of 0.05 and β-error of 0.20 (power = 80%), the calculated required sample size was 37 patients per group. To account for a potential dropout rate of approximately 10%, we planned to enroll 42 patients in each group, resulting in a total of 84 patients.

Statistical Analysis

All statistical analyses were performed using SPSS software (version 25.0, IBM Corp., Armonk, NY, USA). Data distribution normality was assessed by the Kolmogorov–Smirnov test. Continuous data with normal distribution were presented as mean (standard deviation, SD) and analyzed using independent-samples t-tests. Non-normally distributed continuous data were expressed as median (interquartile range, IQR) and analyzed with Mann–Whitney U-tests. Categorical variables were reported as numbers and percentages (%) and compared using Chi-square tests or Fisher’s exact tests, as appropriate. For repeated measures data (such as postoperative NRS scores at multiple time points), generalized estimating equations (GEE) were applied. A two-tailed p-value < 0.05 was considered statistically significant.

Results

Patient Enrollment and Baseline Characteristics

Between January and September 2025, 100 patients scheduled for elective laparoscopic bariatric surgery were screened. Among these, 84 met eligibility criteria, provided informed consent, and were randomized equally to the oxycodone group (n = 42) or sufentanil group (n = 42). All patients received the assigned interventions, completed the study protocol and were discharged uneventfully, with no instances of loss to follow-up (Figure 1). Baseline demographic and clinical characteristics were comparable between groups with no statistically significant differences (Table 1).

Table 1 Patient Characteristics

Figure 1 Study flow diagram. Abbreviations: BMI, body mass index; OSHAS, Obstructive Sleep Apnea-Hypopnea Syndrome.

Primary Outcome

The oxycodone group demonstrated significantly higher global QoR-40 scores at 24 hours postoperatively compared to the sufentanil group (median [IQR]: 187.0 [178.8–190.3] vs 173.0 [164.8–184.3]; estimated median difference: 11; 95% CI: 6–17; P<0.001), indicating a clinically and statistically significant improvement in recovery quality. Specifically, patients in the oxycodone group had significantly better scores in physical comfort (P < 0.001), emotional status (P = 0.006), physical independence (P = 0.033), and pain control dimensions (P < 0.001). Psychological support scores showed no significant difference (Table 2).

Table 2 Postoperative QoR-40 Scores at 24 Hours

Secondary Outcomes

Patients receiving oxycodone reported lower postoperative NRS pain scores compared with sufentanil at 0.5 h, 2 h, 6 h (all P < 0.001), and 24 h (P = 0.003) after surgery. The rate of rescue analgesia was lower in the oxycodone group than in the sufentanil group both in the PACU (16.7% vs 50%; P = 0.001) and on the ward (23.8% vs 64.3%; P < 0.001). Incidences of PONV (47.6% vs 69.1%; P = 0.046), antiemetic usage (14.3% vs 35.7%; P = 0.023), and hypoxemia events (19.1% vs 50%; P = 0.003) were also lower in the oxycodone group. The oxycodone group demonstrated earlier extubation time (P=0.048), first flatus (P=0.024), and first ambulation (P=0.040) compared to the sufentanil group. Patients in the oxycodone group required lower intraoperative total doses of propofol (P = 0.025) and remifentanil (P < 0.001) compared to those in the sufentanil group (Tables 3 and 4).

Table 3 Postoperative Outcomes

Table 4 Hemodynamic Data and Respiratory Adverse Events

Hemodynamic Outcomes

No significant differences in mean arterial pressure (MAP) or heart rate (HR) were observed between the two groups. (P > 0.05). (Table 4).

Discussion

In this randomized trial, we found that an oxycodone-based analgesic regimen improved postoperative pain control and recovery outcomes compared with sufentanil in obese patients undergoing laparoscopic bariatric surgery. Patients receiving oxycodone exhibited lower pain scores, reduced total opioid consumption, and achieved earlier recovery milestones, such as first ambulation and return of bowel function. These benefits were attained without an increase in opioid-related complications and were reflected in significantly higher QoR-40 scores, representing clinically meaningful improvements in the quality of recovery.

With the increasing adoption of multimodal analgesia and ERAS protocols in bariatric surgery, postoperative complications have decreased. Consequently, the assessment of postoperative recovery quality has shifted its focus toward patient-centered self-evaluation.²¹ The QoR-40, as a comprehensive and validated instrument, is widely used as an outcome measure in clinical trials.¹⁹ In this study, the total QoR-40 score on postoperative day 1 was significantly higher in the oxycodone group compared to the sufentanil group, with notable improvements in physical comfort, emotional state, activity independence, and pain management. This suggests that oxycodone-based multimodal analgesia may enhance early postoperative recovery. A similar trend has been observed in other surgical populations: Hao et al reported higher QoR-15 scores in the oxycodone group after thoracic surgery, and Wang et al found superior early recovery in the oxycodone group following Da Vinci robot-assisted nephrectomy.^22,23 These findings support the potential of oxycodone to improve early postoperative recovery. Our study extends this by focusing on a high-risk group—obese patients undergoing bariatric surgery, a population less studied in the existing literature. To our knowledge, this is one of the few studies in this field using QoR-40 as the primary outcome measure, providing a more comprehensive assessment of recovery quality than the QoR-15. Higher QoR-40 scores not only align with the ERAS concept but also indirectly reflect better patient recovery experiences, enhanced overall satisfaction, and increased confidence in their rehabilitation.²⁴

Accumulating evidence indicates κ-opioid receptor activation as a peripherally restricted strategy for visceral pain management, mechanistically mediated through heightened nociceptive thresholds and suppression of afferent pain transmission.^25–27 The superior analgesia observed with oxycodone aligns with its pharmacological profile, characterized by dual µ- and κ-opioid receptor agonism, providing robust visceral pain relief. This is particularly relevant in laparoscopic bariatric surgery, where pneumoperitoneum and visceral traction contribute significantly to postoperative discomfort. Consistent with previous studies, oxycodone provided effective relief from postoperative visceral pain, thereby encouraging deep breathing and early ambulation.^28–30 By comparison, sufentanil primarily exerts its analgesic effects through μ-opioid receptors in the central nervous system. Its relatively short duration of action, combined with rapid redistribution and elimination, contributes to higher early postoperative pain scores. Therefore, the intraoperative use of sufentanil may require supplemental analgesia to achieve effective postoperative pain control.

The need for higher intraoperative remifentanil and propofol doses in the sufentanil group, as observed in our study, suggests that sufentanil’s shorter duration may lead to compensatory increases in other anesthetics. This could contribute to postoperative hyperalgesia or delayed recovery.³¹ In contrast, oxycodone, administered at induction and skin closure, provided sustained analgesia and helped reduce the need for additional intraoperative opioids and hypnotics.

Reduced opioid requirements (less rescue analgesia) observed with oxycodone treatment are consistent with prior literature and reinforce the clinical significance of its opioid-sparing effects. Wang et al similarly reported that oxycodone decreased total opioid consumption compared to sufentanil after abdominal surgery.³² This opioid reduction translated into fewer adverse effects and facilitated an earlier return of gastrointestinal function, a critical ERAS milestone.

Additionally, patients in the oxycodone group demonstrated lower rates of postoperative nausea and vomiting (PONV), aligning with previous studies.^33,34 This observed advantage may be attributed to reduced supplemental opioid use and oxycodone’s milder emetogenic potential compared to sufentanil.

Opioid-induced respiratory depression represents a primary safety concern. Previous studies observed a numerically lower incidence of respiratory depression with oxycodone compared to sufentanil. However, this difference lacked statistical significance due to limited event numbers, suggesting comparable safety profiles between these opioids.^22,30,33,35 However, this statistically non-significant difference may potentially magnify in higher-risk cohorts such as obese populations where postoperative respiratory depression risk is elevated. Our study demonstrated a significantly lower incidence of hypoxemia in the oxycodone group compared to the sufentanil group—a critical advantage for obese patients. Respiratory depression, primarily mediated by μ-opioid receptor activation, was attenuated with oxycodone due to its low lipophilicity (reducing central nervous system penetration) and reduced μ-receptor affinity.^28,36,37 Furthermore, oxycodone’s superior visceral analgesia facilitated sustained deep breathing, improving respiratory mechanics and thereby counterbalancing partial respiratory depression effects.

An intriguing finding was the shorter extubation time in the oxycodone group, which is consistent with findings reported in previous studies of other surgical procedures.^22,30 This seemingly counterintuitive finding may be associated with the lower total burden of intraoperative sedative and analgesic medications in the oxycodone group, as well as the milder respiratory depression associated with oxycodone. Although both sufentanil and oxycodone exert some sedative effects at the time of extubation, the sedative effects of opioids at conventional doses typically do not impede extubation when adequate neuromuscular blockade reversal with sugammadex is achieved.³⁸ The less pronounced central respiratory depression induced by oxycodone likely constitutes a key contributing factor to its shorter extubation time.

It is also worth comparing our opioid-based approach with the emerging concept of opioid-free anesthesia (OFA) in bariatric surgery. OFA typically uses alternatives like infusions of dexmedetomidine, ketamine, lidocaine, etc., to avoid opioids entirely.^39–41 Studies and meta-analyses on OFA in bariatric patients have shown mixed results: some report improved immediate postoperative pain scores and reduced PONV, while others find no difference in overall opioid consumption postoperatively.^42,43 In practice, many OFA patients still require opioids for postoperative pain, so total avoidance is challenging.⁴⁴ Our trial was not an OFA study, but the strong performance of oxycodone raises an argument that a carefully managed opioid-inclusive strategy can be just as effective for recovery.

These findings support the integration of oxycodone into multimodal analgesia protocols within ERAS pathways for bariatric surgery. Although current anesthetic and analgesic approaches for bariatric surgery increasingly favor ultra-short-acting opioids or opioid-free multimodal regimens to minimize the risk of opioid-induced respiratory depression, an optimal analgesic strategy should balance efficacy with safety. Our results demonstrate that the prudent use of potent, long-acting opioids like oxycodone not only effectively alleviates postoperative pain in obese patients but also reduces postoperative opioid requirements and related adverse events. This approach accelerates patient recovery and significantly enhances the early postoperative experience for bariatric surgery patients.

Several limitations warrant acknowledgment. This single-center study had a moderate sample size, limiting generalizability. Patients with severe obstructive sleep apnea or chronic opioid use were excluded, so findings may not extend to these high-risk subgroups. Additionally, our analysis focused on in-hospital recovery outcomes; longer-term endpoints such as chronic pain development or persistent opioid use were not assessed.

Conclusion

In conclusion, oxycodone provided superior visceral pain relief, reduced opioid requirements, enhanced recovery quality metrics, and demonstrated a more favorable safety profile compared with sufentanil in obese patients undergoing laparoscopic bariatric surgery. These findings support using oxycodone as the primary opioid within multimodal analgesic regimens for this high-risk surgical population to enhance recovery outcomes in bariatric surgical patients undergoing ERAS pathways.