Opioid‐Free Versus Opioid‐Based Anesthesia in Laparoscopic Surgery: Systematic Review and Meta‐Analysis Across Multiple Perioperative Outcomes

Patients who undergo laparoscopic bariatric surgery (LBS) are susceptible to postoperative nausea and vomiting (PONV). Opioid-free anesthesia (OFA) or opioid-sparing anesthesia (OSA) protocols have been proposed as solutions; however, differences between the 2 alternative opioid protocols for anesthesia maintenance in obese patients remain uncertain. A network meta-analysis was conducted to compare the impacts of OFA and OSA on PONV. Systematic searches were conducted using Embase, PubMed, MEDLINE, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing OFA and OSA strategies. After screening according to the inclusion and exclusion criteria, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the credibility of the evidence. The main concern of this review was the difference between OFA and OSA in reducing PONV. The primary outcome was any PONV occurrence within 24 hours. Secondary outcomes included postoperative pain intensity, opioid consumption, opioid-related adverse events, and length of hospital stay. Fifteen RCTs involving 1310 patients were identified for a network meta-analysis from 1776 articles that compared OFA, OSA, and traditional opioid-based anesthesia (OBA) strategies in LBS. Twelve RCTs (80%) with 922 participants (70%) were eligible for the occurrence of PONV. These included 199 (22%) patients who received OFA and 476 (52%) and 247 (27%) patients who received OSA and OBA, respectively. OFA was more effective at reducing PONV (relative risks [RR], 0.6, 95% confidence interval [CI], 0.5-0.9, moderate-quality evidence) compared to OSA. No differences were observed in postoperative pain control or opioid consumption between the OFA and OSA strategies (very low-to high-quality evidence). Notably, OFA is associated with a higher risk of bradycardia than OSA (RR, 2.6, 95% CI, 1.2-5.9, moderate-quality evidence). OFA is more effective than OSA in reducing the occurrence of PONV during the early postoperative period of LBS, although it may associate with an increased risk of bradycardia. Patients who received either opioid-alternative strategy demonstrated similar effects in reducing postoperative opioid consumption and alleviating pain intensity.

BackgroundBreast cancer is the most common malignancy among women, and patients require rapid transition to adjuvant therapy post-surgery. Opioid-based anesthesia (OBA) is widely used but carries risks such as postoperative nausea and vomiting (PONV), immunosuppression, and hyperalgesia, which may delay recovery. Opioid-sparing anesthesia (OSA) and opioid-free anesthesia (OFA) may reduce these risks, but their effects on postoperative quality of recovery (QoR) are unclear. This study compares the effects of these three anesthetic strategies on early postoperative QoR in breast cancer surgery using a Bayesian network meta-analysis.MethodsFollowing PRISMA guidelines (PROSPERO ID: CRD420251065588), a systematic search was conducted in PubMed, Cochrane Library, EMBASE, and Web of Science from inception to June 1, 2025. Included were randomized controlled trials (RCTs) comparing OSA, OFA, and OBA in adult breast cancer surgery that reported QoR scores. Risk of bias and evidence quality were assessed using the Cochrane tool and GRADE system. Bayesian random-effects analysis was performed with the R package gemtc. Continuous data were reported as mean differences, and categorical data as odds ratios.ResultsSeventeen RCTs with 1,254 patients were included. Bayesian network meta-analysis showed that OSA significantly outperformed OBA in 24-hour postoperative QoR (d = 0.050, 95% CrI: 0.038–0.062; SUCRA = 85.3%), and OFA was also superior to OBA (d = 0.044, 95% CrI: 0.020–0.068; SUCRA = 64.7%). No significant difference was found between OSA and OFA (d = −0.006, 95% CrI: −0.029–0.018). Secondary outcomes SUCRA showed that OFA was most effective in controlling postoperative nausea and vomiting (99.4%) and pain management (81.4%), while OSA excelled in emotional well-being (96.2%) and physical comfort (76.6%). For physical independence, OFA (85.1%) outperformed OSA (63.5%), with no differences in psychological support. Intraoperative opioid reduction showed an inverted U-shaped relationship with QoR improvement (p = 0.0004).ConclusionOSA is the optimal strategy for enhancing overall quality of recovery within 24 hours after breast cancer surgery. Although OFA excels in PONV reduction and pain control, OSA offers more balanced benefits across multiple QoR dimensions. An individualized anesthetic approach is recommended, aiming for opioid minimization rather than complete elimination.

Major spine surgery is associated with severe postoperative pain and increased opioid consumption. Opioid-free anesthesia (OFA) is thought to provide adequate intraoperative analgesia with reduced postoperative opioid consumption. The aim of this study is to compare the impact of intraoperative OFA approach to the conventional opioid-based anesthesia (OBA) on postoperative pain, opioid consumption, and related side effects in patients undergoing multilevel spinal fusion surgery. Forty-eight patients undergoing elective major spine surgery were randomly allocated to either receive intraoperative dexmedetomidine and lidocaine (OFA group) or fentanyl during induction and intraoperative remifentanil (OBA group). All patients received intraoperative sevoflurane, propofol, rocuronium, ketamine, dexamethasone, ondansetron and postoperative paracetamol and patient-controlled analgesia device set to deliver intravenous morphine for 48 hours after surgery. Postoperative pain was measured using numerical rating scale. Opioid side effects were documented, when present. OFA group required less morphine in the first 24 hours post-surgery (17.28±12.25 mg versus 27.96±19.75 mg, P<0.05). The incidence of postoperative nausea and vomiting (PONV) was significantly lower in the OFA group. More patients in the OFA group required antihypertensive medications compared to patients in the OBA group (P<0.05). In the post anesthesia care unit, OFA patients had a significantly longer stay than OBA patients (114.1±49.33 min versus 89.96±30.71 min, P<0.05). OFA can be an alternative to OBA in patients undergoing multilevel spine fusion surgery. OFA reduces opioids consumption in the first 24 hours and PONV.

Breast cancer is the most common malignancy among women, and patients require rapid transition to adjuvant therapy post-surgery. Opioid-based anesthesia (OBA) is widely used but carries risks such as postoperative nausea and vomiting (PONV), immunosuppression, and hyperalgesia, which may delay recovery. Opioid-sparing anesthesia (OSA) and opioid-free anesthesia (OFA) may reduce these risks, but their effects on postoperative quality of recovery (QoR) are unclear. This study compares the effects of these three anesthetic strategies on early postoperative QoR in breast cancer surgery using a Bayesian network meta-analysis. Following PRISMA guidelines (PROSPERO ID: CRD420251065588), a systematic search was conducted in PubMed, Cochrane Library, EMBASE, and Web of Science from inception to June 1, 2025. Included were randomized controlled trials (RCTs) comparing OSA, OFA, and OBA in adult breast cancer surgery that reported QoR scores. Risk of bias and evidence quality were assessed using the Cochrane tool and GRADE system. Bayesian random-effects analysis was performed with the R package gemtc. Continuous data were reported as mean differences, and categorical data as odds ratios. Seventeen RCTs with 1,254 patients were included. Bayesian network meta-analysis showed that OSA significantly outperformed OBA in 24-hour postoperative QoR (d = 0.050, 95% CrI: 0.038-0.062; SUCRA = 85.3%), and OFA was also superior to OBA (d = 0.044, 95% CrI: 0.020-0.068; SUCRA = 64.7%). No significant difference was found between OSA and OFA (d = -0.006, 95% CrI: -0.029-0.018). Secondary outcomes SUCRA showed that OFA was most effective in controlling postoperative nausea and vomiting (99.4%) and pain management (81.4%), while OSA excelled in emotional well-being (96.2%) and physical comfort (76.6%). For physical independence, OFA (85.1%) outperformed OSA (63.5%), with no differences in psychological support. Intraoperative opioid reduction showed an inverted U-shaped relationship with QoR improvement (p = 0.0004). OSA is the optimal strategy for enhancing overall quality of recovery within 24 hours after breast cancer surgery. Although OFA excels in PONV reduction and pain control, OSA offers more balanced benefits across multiple QoR dimensions. An individualized anesthetic approach is recommended, aiming for opioid minimization rather than complete elimination.

Opioid-free anaesthesia for anterior total hip replacement under general anaesthesia: the Observational Prospective Study of Opiate-free Anesthesia for Anterior Total Hip Replacement trial

ObjectiveThis study aimed to examine the effect of opioid-free anesthesia (OFA) on postoperative outcome indicators and explore its application in thoracoscopic or laparoscopic as well as non-thoracoscopic or laparoscopic surgeries, providing a scientific basis for clinical decision-making.MethodA systematic search was conducted for clinical studies comparing OFA and opioid-based anesthesia (OBA) published from the establishment of the databases to May 2025 using databases such as PubMed, Web of Science, Embase, and Cochrane Library. The primary outcome was the incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included perioperative recovery indicators, the need for postoperative emergency analgesia, postoperative pain score (VAS, NRS), and adverse reactions.ResultsA total of 3,766 relevant studies were initially identified, and 68 randomized controlled trials involving 5,426 patients were ultimately included. Compared with OBA, OFA significantly reduced the risks of PONV (RR = 0.50, 95% CI: 0.39–0.64), nausea alone (RR = 0.34, 95% CI: 0.25–0.46), vomiting alone (RR = 0.34, 95% CI: 0.25–0.46), and the need for postoperative emergency analgesia (RR = 0.61, 95% CI: 0.51–0.72). OFA was also associated with lower 24 h postoperative NRS pain scores (SMD = −0.32, 95% CI: −0.53 to −0.10). For outcomes with high heterogeneity (I2 > 75%), the systematic review showed that most studies did not find a significant reduction in postoperative VAS pain scores with OFA. However, over two-thirds of the studies have shown that OFA can improve the quality of postoperative recovery (QoR-40). Approximately half of the studies suggested that OFA may prolong extubation time, while most found no significant difference in PACU stay time.ConclusionIn summary, OFA not only significantly reduces postoperative PONV, but also lowers the demand for analgesic drugs and improves the quality of postoperative recovery. However, its effect on some postoperative recovery indicators is limited, and further high-quality studies are required to confirm these findings. OFA is expected to serve as a safe and effective anesthesia strategy to optimize the perioperative outcomes of patients.

Opioid-free anaesthesia reduces postoperative nausea and vomiting after thoracoscopic lung resection: a randomised controlled trial

Opioid-free anesthesia (OFA) provides adequate analgesia minimizing opioids. OFA has not been evaluated in laparoscopic radical prostatectomy (LRP). Our aim was to evaluate OFA feasibility and its effectiveness in LRP. A quasi-experimental retrospective study of 55 adult patients undergoing LRP was performed from September 2020 until December 20223. Predefined protocols for either opioid-based anesthesia (OBA; with continuous remifentanil infusion) or OFA (continuous lidocaine, dexmedetomidine, and ketamine infusion) were followed. In both groups, wound infiltration was performed before skin incision. Primary outcome was postoperative pain management (numerical rating scale [NRS]) in the first 24 postoperative hours. Secondary outcomes were opioid consumption, start to sitting and ambulation, postoperative complications, and length of hospital stay. OFA protocol patients had better median pain scores during movement at 1, 18 and 24 h, that is, 1 (interquartile range [IQR] 0-3) versus 2.5 (IQR 0-4), P = 0.047; 0 (IQR 0-1) versus 1 (IQR 0-2), P = 0.017; and 0 (IQR 0-0.25) versus 1 (IQR 0-2), P = 0.013, respectively. At 6 and 12 h, there were no statistically significant differences, that is, 0.5 (IQR 0-2) versus 1 (IQR 0-2), P = 0.908 and 1 (IQR 0-2) versus 0.5 (IQR 0-2), P = 0.929, respectively. Lower morphine requirements were recorded in the first 18 and 24 postoperative hours, that is, 0 (IQR 0-0) versus 1 (IQR 0-2.75) mg, P = 0.028 and 0 (IQR 0-2) versus 1.5 (IQR 0-3) mg, P = 0.012, respectively. Start to sitting and ambulation occurred earlier in the OFA group (P = 0.030 and P = 0.002, respectively). Linear regression showed that ambulation was independently associated with the analgesic technique (P = 0.034). Only one patient had postoperative nausea and vomiting (PONV) and belonged to the OBA group. There was no difference in total complications or the length of stay. In this study, OFA strategy was found to be safe, feasible, and provided adequate analgesia, minimizing the use of postoperative opioids, and was independently associated with earlier ambulation.

Opioid-free Anesthesia: Time to Regain Our Balance.

Laparoscopic inguinal hernia repair (LIHR) is increasingly performed as a day surgery procedure under enhanced recovery after surgery (ERAS) protocol. While opioid-based anesthesia (OA) remains standard, its adverse effects may impair postoperative recovery. This randomized controlled non-inferiority trial assessed whether opioid-free anesthesia (OFA) provides non-inferior postoperative pain control to OA for day surgery LIHR under ERAS protocol and evaluated comprehensive recovery outcomes. This single-center, prospective, randomized non-inferiority trial enrolled 90 patients scheduled for day surgery LIHR who were randomly allocated to receive either lidocaine-dexmedetomidine-based OFA (n = 45) or sufentanil-remifentanil-based OA (n = 45). The primary outcome was postoperative 24-h time-weighted average visual analog scale (TWA-VAS) pain score at rest. Secondary outcomes included extended pain assessment, quality of recovery indicators, day surgery pathway efficiency, and perioperative hemodynamic stability. The 24-h TWA-VAS scores were 1.84 ± 1.02 in the OFA group and 1.77 ± 0.88 in the OA group (mean difference: 0.07; 95% CI: -0.33-0.47), establishing non-inferiority. The OFA group experienced significantly lower rates of intraoperative hypotension (8.9% vs. 53.3%; relative risk: 0.17; P = 0.001) but longer laryngeal mask airway removal time (20 vs. 15min; P = 0.034) and post-anesthesia care unit stay (50 vs. 45min; P = 0.018). No significant differences were observed in Quality of Recovery-15 scores, rescue analgesia requirements, postoperative urinary retention (POUR), postoperative nausea and vomiting (PONV), or 24-h discharge success rates. Under ERAS protocol, lidocaine-dexmedetomidine-based OFA provided non-inferior analgesic efficacy to OA for day surgery LIHR, while delivering superior hemodynamic stability. Despite modestly prolonged emergence times, OFA maintained comparable recovery quality and discharge success rates. These findings establish OFA as a valuable alternative anesthetic strategy for day surgery LIHR under ERAS protocol, particularly for patients at risk of opioid-related adverse effects. ChiCTR2500098054, registered on February 28, 2025, retrospectively registered.

BackgroundEnhanced recovery after surgery (ERAS) is now widely used in various surgical fields including gynecological laparoscopic surgery, but the advantages of opioid-free anesthesia (OFA) in gynecological laparoscopic surgery under ERAS protocol are inexact.AimsThis study aims to assess the effectiveness and feasibility of OFA technique versus traditional opioid-based anesthesia (OA) technique in gynecological laparoscopic surgery under ERAS.MethodsAdult female patients aged 18 ~ 65 years old undergoing gynecological laparoscopic surgery were randomly divided into OFA group (Group OFA, n = 39) with esketamine and dexmedetomidine or OA group (Group OA, n = 38) with sufentanil and remifentanil. All patients adopted ERAS protocol. The primary outcome was the area under the curve (AUC) of Visual Analogue Scale (VAS) scores (AUCVAS) postoperatively. Secondary outcomes included intraoperative hemodynamic variables, awakening and orientation recovery times, number of postoperative rescue analgesia required, incidence of postoperative nausea and vomiting (PONV) and Pittsburgh Sleep Quality Index (PSQI) perioperatively.ResultsAUCVAS was (Group OFA, 16.72 ± 2.50) vs (Group OA, 15.99 ± 2.72) (p = 0.223). No difference was found in the number of rescue analgesia required (p = 0.352). There were no between-group differences in mean arterial pressure (MAP) and heart rate (HR) (p = 0.211 and 0.659, respectively) except MAP at time of surgical incision immediately [(Group OFA, 84.38 ± 11.08) vs. (Group OA, 79.00 ± 8.92), p = 0.022]. Times of awakening and orientation recovery in group OFA (14.54 ± 4.22 and 20.69 ± 4.92, respectively) were both longer than which in group OA (12.63 ± 3.59 and 18.45 ± 4.08, respectively) (p = 0.036 and 0.033, respectively). The incidence of PONV in group OFA (10.1%) was lower than that in group OA (28.9%) significantly (p = 0.027). The postoperative PSQI was lower than the preoperative one in group OFA (p = 0.013).ConclusionIn gynecological laparoscopic surgery under ERAS protocol, OFA technique is non-inferior to OA technique in analgesic effect and intraoperative anesthesia stability. Although awakening and orientation recovery times were prolonged compared to OA, OFA had lower incidence of PONV and improved postoperative sleep quality.Trial registrationChiCTR2100052761, 05/11/2021.

Patient preference for intraoperative opioid use and early recovery after noncardiac surgery: protocol for a randomised factorial design trial of opioid-free versus opioid-based anaesthesia (the PERFECT trial)

Introduction: Intravenous opioids have been frequently used to provide analgesia and supplemental sedation during general anaesthesia or monitored anaesthesia care. Opioid Free Anaesthesia (OFA) is a multimodal approach which combines different drugs likes lignocaine, dexamethasone, paracetamol and dexmedetomidine with different techniquessuch as hypnosis, sedation, analgesia and sympatholysis. Thus, reducing and avoiding opioids perioperatively will lead to decrease in opioid related adverse effects with better postoperative outcomes. Aim: To compare OFA and Opioid-based Anaesthesia (OBA) in terms of haemodynamic stability, speed and quality of recovery, postoperative pain score and analgesic requirement. Material and Methods: The present study was a randomised study conducted over a period from June 2021 to September 2022, in which 90 patients of American Society of Anaesthesiologists (ASA) Grade I,II, 20-60 years of age undergoing elective Laparoscopic Cholecystectomy (LC) were divided into OBA fentanyl and OFA-lignocaine and dexmedetomidine. A standard general anaesthesia protocol of the institute was followed. OBA group received fentanyl (2 μg/kg) over 10 minutes before induction of anaesthesia and OFA group received lignocaine (2 mg/kg) and dexmedetomidine (0.5 μg/kg) both intravenously over 10 minutes before induction of anaesthesia. In OFA group analgesia was maintained by infusion of lignocaine 2 mg/kg/hr and dexmedetomidine 0.5 μg/kg/hr whereas in OBA group fentanyl 0.5 μg/kg was given whenever required till the gallbladder was resected. Postoperative intraperitoneal instillation of gallbaldder fossa was done with 20 mL 0.5% bupivacaine. Intraoperative mean Heart Rate (HR) and Mean Arterial Pressure (MAP) were recorded. Postoperative speed and quality of recovery, pain score, analgesic requirements and incidence of Postoperative Nausea and Vomiting (PONV) were noted. Paracetamol 15 mg/kg was given intravenously whenever Numerical Rating Scale (NRS) score was ≥6. Comparison of means between the two groups was done using unpaired t-test, association between two non parametric variables was done using Pearson Chi-square (χ2 test) test. Results: The mean age, sex, weight, ASA and duration of surgery were comparable in both the groups. The mean HR and mean MAP were significantly lower in OFA group compared to the OBA group at all the time points (p-value=0.001). Although postoperative speed of recovery was slower in OFA group, the overall quality of recovery was better (p-value=0.001). The postoperative pain score, analgesic requirement and incidence of nausea and vomiting were all significantly less in OFA group as compared to OBA group with p-values of 0.02, 0.001 and 0.02, respectively. Conclusion: OFA is new anaesthetic approach that provides better perioperative haemodynamic stability, postoperative pain control with less PONV and thus can be used safely and successfully

Opioid anesthesia is commonly employed in minimally invasive surgeries but is associated with adverse effects, including postoperative nausea and vomiting (PONV). Opioid-free anesthesia aims to mitigate these issues. We conducted a systematic review, meta-analysis, and trial sequential analysis (TSA) comparing opioid and opioid-free anesthesia in minimally invasive abdominal surgeries. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for randomized controlled trials (RCTs) comparing these approaches. Our primary outcomes were adverse effects (PONV, bradycardia), while secondary outcomes were pain, opioid consumption, and postanesthesia care unit (PACU) length of stay (LOS). We performed a TSA to investigate the conclusiveness of the results. We included 26 RCTs encompassing 2,025 patients, with 1,009 (49%) in the opioid-free anesthesia group. Opioid-free anesthesia reduced PONV significantly (risk ratio, 0.55; 95% confidence interval [CI], 0.40 to 0.74; P < 0.001), but we found no significant differences in bradycardia rates. We found nonclinically relevant higher pain scores for opioid anesthesia (mean difference [MD], -0.9; 95% CI, -1.7 to -0.2; P = 0.01) and opioid consumption at 2hr post surgery (MD, -5.4mg oral morphine equivalents; 95% CI, -9.1 to -1.8; P = 0.004). We also noted a reduced time to first analgesia (MD, 88min; 95% CI, 18 to 159; P = 0.01). We found no differences in PACU LOS. The TSA confirmed the sample size's adequacy in showing PONV reduction with opioid-free anesthesia. Opioid-free anesthesia showed a significant reduction in PONV and a decrease in opioid consumption during the first 2hr postoperatively, suggesting it can be an alternative to opioid anesthesia in minimally invasive abdominal surgeries. PROSPERO ( CRD42023492385 ); first submitted 18 December 2023.

Study objectiveTo evaluate all available evidence thus far on opioid based versus opioid-free anesthesia and its effect on acute and chronic postoperative pain. DesignSystematic review and meta-analysis of randomized clinical trials. SettingOperating room, postoperative recovery room and ward. PatientsPatients undergoing general anesthesia. InterventionsAfter consulting MEDLINE, EMBASE and Cochrane database, studies which compared opioid free anesthesia (OFA) with opioid based anesthesia (OBA) were included (last search April 15th 2022). MeasurementsPrimary outcomes were acute and chronic pain scores in NRS or VAS. Secondary outcomes were quality of recovery and postoperative opioid consumption. Risk of bias was assessed using the RoB2 tool and a random effects model for the meta-analysis was conducted. Main resultsWe identified 1245 citations, of which 38 studies met our inclusion criteria. There is moderate quality evidence showing no clinically relevant difference of Numeric Rating Scale (NRS) scores or opioid consumption in the postoperative period (pooled mean difference of 0.39 points with a CI of 0.19–0.59 and 4.02 MME with a CI of 1.73–6.30). We found only one small-sized study reporting no effect of opioid-free anesthesia on chronic pain. The quality of recovery was superior in patients with opioid-free anesthesia (mean difference of 8.26 points), however, this pooled analysis was comprised of only two studies. Postoperative nausea and vomiting (PONV) occurred less in opioid-free anesthesia, but bradycardia was more frequent. ConclusionsWe concluded that we cannot recommend one strategy over the other. Future studies could focus on quality of recovery as outcome measure and adequately powered studies on the effects of opioid-free anesthesia on chronic pain are eagerly awaited.