Aug 2026· Journal of clinical anesthesia· Vol 114, pp.
112296
· 0 citations· 56 references
Medicine
TL;DR
MMA shows no clear effect on postoperative pain at 24 h but reduces PONV incidence and opioid consumption, and larger, standardized trials are needed to define optimal MMA regimens and patient selection.
Abstract
Background
Multimodal anesthesia (MMA) is widely used to reduce opioid use and improve postoperative recovery. However, evidence for bundled MMA regimens-defined as opioids plus ≥2 adjunct analgesic modalities-has not been systematically synthesized across patient-centered outcomes.
Methods
We performed a systematic review and meta-analysis of randomized controlled trials comparing MMA (opioids plus ≥2 adjuncts, including regional techniques and/or systemic agents such as dexmedetomidine, ketamine, intravenous lidocaine, clonidine, or magnesium) with opioid-based general anesthesia in adults undergoing elective surgery. MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Library were searched to 28 October 2025. Primary outcomes were postoperative pain, PONV, QoR-15, and pulmonary complications. Secondary outcomes included opioid consumption in Morphine Milligram Equivalent (MME) and PACU length of stay. Risk of bias was assessed with RoB 2 and certainty with GRADE. Registered in PROSPERO (CRD42024470056).
Results
Twenty-one RCTs (n = 1828) were included. At 24 h, no clear effect of MMA on pain intensity was observed (10 trials, n = 785; MD -0.6, 95% CI -1.5 to 0.2; very low certainty). MMA reduced PONV incidence (4 trials, n = 352; RR 0.59, 95% CI 0.44 to 0.77; low certainty). For secondary outcomes, MMA reduced opioid consumption (10 trials, n = 915; MD -7.0 mg MME, 95% CI -12.8 to -1.3; moderate certainty), with the opioid-sparing effect persisting at 48 h (MD -14.0 mg MME) and study end (MD -16.0 mg). Data for QoR-15, PACU stay, and pulmonary complications were insufficient for pooling.
Conclusions
MMA shows no clear effect on postoperative pain at 24 h but reduces PONV incidence and opioid consumption. Evidence certainty ranges from moderate to very low. Larger, standardized trials are needed to define optimal MMA regimens and patient selection.
The use of opioids as anesthetic agents is associated with multiple adverse effects, such as delirium. Patients with postoperative delirium (POD) have a higher risk of mortality or major complications. Recently, a multimodal anesthetic technique known as opioid-free anesthesia (OFA) has been developed to minimize or eliminate the use of opioids during anesthesia, which is hypothesized to reduce the incidence of POD. This systematic review aims to compare OFA and opioid-based anesthesia (OBA) to the incidence of POD.
Literature searches were conducted electronically without time restrictions across six databases: PubMed, Cochrane Central Register for Controlled Trials, ProQuest, ScienceDirect, Springer Nature, and PMC Europe. Additional studies were obtained through electronic searches on Google. The inclusion criteria were human studies involving participants aged ≥18 years, interventions of OFA and OBA, and POD as an outcome. Study selection was performed using Rayyan QCRI, and risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) and Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I).
Six studies met the inclusion criteria; three randomized controlled trials (RCTs), two cohort studies, and one case-control study. Five studies demonstrated no significant difference in the incidence of POD between the OFA and OBA groups; one study reported no occurrence of POD in either group. Several factors influencing POD included advanced age, type and duration of surgery, and the pharmacological effects of anesthetic agents such as dexmedetomidine, lidocaine, midazolam, and regional analgesic agents.
OFA has not been shown to clearly reduce the incidence of POD. The occurrence of POD is multifactorial.
Belia O. Jannati, M. I. Lestari, I. Liberty· Journal of Anaesthesiology C...· 0 citations
Introduction: Opioid-Based Anesthesia (OBA) is a common standard; it carries risks like post-operative nausea and vomiting (PONV) and respiratory issues. Opioid-Free Anesthesia (OFA) offers an alternative that may improve recovery quality, but its efficacy relative to OBA requires more evidence.
Objective: This systematic review aims to compare the effectiveness between OFA and OBA on post anesthesia recovery outcomes.
Methods: This systematic review followed the PRISMA 2020. Article searches were conducted via PubMed, ScienceDirect, SpringerLink, and Wiley using appropriate keywords. Five randomized controlled trials meeting the inclusion criteria were analyzed and assessed for risk of bias using the Cochrane RoB 2 tool.
Results: OFA significantly reduced the incidence of PONV across all studies. OFA also demonstrated equivalent or better analgesia quality in the early postoperative period with lower rescue opioid consumption and showed good hemodynamic stability. However, no significant difference was found in the duration of surgery between the two groups.
Conclusion: OFA shows potential as a superior anesthetic strategy compared to OBA in aspects of postoperative recovery, particularly in reducing PONV and additional opioid consumption without compromising analgesia quality. The implementation of OFA has the potential to be integrated into Enhanced Recovery After Surgery (ERAS) protocols. Further studies with larger samples and standardized protocols are needed to strengthen these findings.
Dewi Ainur Rohmah, M. Lestari, Emma Novita· Indonesian Journal of Anesth...· 0 citations
BACKGROUND AND OBJECTIVES
Perioperative intravenous lidocaine infusion has been proposed as an opioid-sparing analgesic adjunct in spine surgery, but previous meta-analyses pooled heterogeneous procedures and may have obscured procedure-specific treatment effects. We evaluated the analgesic and opioid-sparing effects of perioperative intravenous lidocaine in adult spine surgery and whether efficacy differs by procedure type.
METHODS
We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception through June 2026 for randomized controlled trials comparing perioperative intravenous lidocaine infusion with placebo or standard care in adults undergoing spine surgery. The primary outcome was postoperative pain intensity at 24 hours. Secondary outcomes were opioid consumption, postoperative nausea and vomiting (PONV), and hospital length of stay (LOS). Random-effects meta-analyses, a post hoc subgroup analysis by procedure type, and meta-regression were performed.
RESULTS
10 randomized trials were included. Intravenous lidocaine reduced postoperative pain at 24 hours (9 trials, 655 patients; mean difference (MD), -0.83; 95% CI -1.36 to -0.30; p=0.002; I²=89%, 95% CI 81% to 93%; prediction interval, -2.69 to 1.02; moderate certainty) and opioid consumption (9 trials; MD, -11.64 mg intravenous morphine equivalents; 95% CI -16.14 to -7.14; p<0.001). In a post hoc exploratory analysis, the analgesic effect differed by procedure type (test for subgroup differences, p=0.005): the reduction was clinically meaningful after instrumented fusion or complex spine surgery (MD, -1.23; 95% CI -1.81 to -0.64), exceeding the minimal clinically important difference of 1.0 point, but minimal after decompression (MD, -0.20; 95% CI -0.61 to 0.21). Baseline pain severity explained approximately 53% of between-study heterogeneity, whereas lidocaine infusion rate did not modify the treatment effect (p=0.97). No significant effects were observed for PONV or LOS.
CONCLUSIONS
There is moderate-certainty evidence that perioperative intravenous lidocaine reduces postoperative pain and opioid consumption after adult spine surgery. Its analgesic benefit appeared procedure-specific, with the greatest benefit after instrumented fusion and complex procedures; this difference emerged from a post hoc, exploratory analysis and should be regarded as hypothesis-generating.
Unknown authors· Regional anesthesia and pain...· 0 citations
BACKGROUND CONTEXT
Spinal fusion is associated with substantial early postoperative pain and opioid exposure. Both ketamine and pregabalin are widely incorporated into Enhanced Recovery After Surgery (ERAS) protocols as opioid-sparing adjuncts. However, their comparative efficacy and safety in this specific setting remain uncertain. Our objective was to compare ketamine and pregabalin indirectly for early postoperative opioid consumption, pain, and adverse events in adults undergoing spinal fusion.
METHODS
Pubmed, Embase, and Cochrane Trials were searched from inception through October 2025. Eligible studies were randomized trials enrolling adults undergoing instrumented spinal fusion, randomized to perioperative ketamine, pregabalin, or control, and reported extractable 24-hour opioid consumption or pain outcomes. Continuous outcomes were pooled as mean differences in MME or VAS units, and adverse events were reported descriptively. A connected treatment network was analyzed using random-effects models. Risk of bias (RoB) was assessed with the Cochrane RoB 2 tool.
RESULTS
Thirteen trials (n=879) were included: ketamine (n=210), pregabalin (n=271), and control (n=398). Six trials contributed opioid data (3 ketamine, 3 pregabalin). Using pregabalin 150 mg as reference, ketamine was associated with lower 0-24-hour opioid use (MD -56.99 mg MME; 95% CI -99.56 to -14.43). Control (MD +21.31; 95% CI -1.05 to +43.66) and pregabalin 300 mg (MD -13.22; 95% CI -40.41 to +13.96) did not significantly differ from pregabalin 150 mg. Seven trials contributed 24-hour VAS data, with control being associated with higher pain versus pregabalin 150 mg (MD +0.84; 95% CI +0.01 to +1.66), while ketamine and pregabalin 300 mg were not k significantly different. Adverse events were generally infrequent and similar to control.
CONCLUSIONS
Both ketamine and pregabalin provide early opioid sparing with comparable 24-hour analgesia. Ketamine showed a larger opioid-sparing point estimate, but indirect comparisons are imprecise. Adequately powered head-to-head trials with standardized protocols and adverse event reporting are needed.
Michael Coffin, Muhammad Zain Azhar, Walker Shepherd et al.· Journal of clinical neurosci...· 0 citations
BACKGROUND
Postoperative nausea and vomiting (PONV) is common after video-assisted thoracoscopic surgery (VATS). Opioid-free anesthesia (OFA) may reduce PONV; however, procedure-specific evidence remains limited. This review evaluated the effects of OFA versus opioid-inclusive anesthesia (OIA) on PONV, pain, and recovery after VATS lung resection.
METHODS
Randomized controlled trials (RCTs) involving adults who underwent VATS lung resection and compared OFA, defined as no intraoperative opioid use, with OIA, were included. MEDLINE, Embase, and Cochrane Central were searched until January 18, 2026, and ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched on January 19, 2026. The risk of bias was assessed using the RoB 2 tool. Random-effects meta-analyses were performed, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation framework. The primary outcomes were PONV and pain at 24 h.
RESULTS
Eleven RCTs involving 1183 participants were included, all of which used regional anesthesia. Most studies were conducted in China (n = 8), with one study each conducted in Poland, Turkey, and South Korea. Across the included studies, the mean age of participants ranged from 44.6 to 67.8 years. OFA was associated with reduced PONV within 24 h compared with OIA (eight studies; risk ratio, 0.58; 95% confidence interval [CI], 0.41-0.81; moderate certainty). Pain scores at 24 h were lower with OFA (eleven studies; mean difference, - 0.30; 95% CI, - 0.54 to - 0.07), although the difference did not reach the minimally important difference. OFA improved the quality of recovery (QoR) at 24 h (three studies; standardized mean difference, 0.40; 95% CI, 0.07 to 0.72; moderate certainty). No meaningful difference was observed in postoperative opioid consumption, and adverse event findings were inconsistent.
CONCLUSIONS
In selected patients undergoing VATS lung resection within multimodal pathways including regional analgesia, OFA protocols probably reduce PONV and improve early QoR compared with heterogeneous OIA regimens, while having little or no clinically important effect on acute postoperative pain. However, the independent contribution of intraoperative opioid avoidance remains uncertain owing to heterogeneity in regional analgesia, comparator opioid exposure, antiemetic strategies, and anesthetic management.
TRIAL REGISTRATION
PROSPERO CRD420261292925.
Shosaburo Jotaki, Norio Yamamoto, E. Imai et al.· BMC Anesthesiology· 0 citations
Background: Intravenous magnesium sulfate has been proposed as an adjuvant analgesic in perioperative care; however, its effects on postoperative pain and related analgesic outcomes remain uncertain. Methods: A systematic search of the literature was conducted from 1 January 2015 through 19 January 2026 to identify randomized controlled trials comparing intravenous magnesium sulfate with placebo in adults undergoing general anesthesia. Pain intensity was harmonized to a 0–10 scale. Primary outcomes were early postoperative pain (0–6 h), pain at 12 h, and pain at 24 h. Secondary outcomes were postoperative opioid consumption, expressed as intravenous morphine equivalents, and time to first rescue analgesia. Random-effects meta-analyses were performed. Risk of bias was assessed using RoB 2, and certainty of evidence using GRADE. Results: A total of 24 randomized controlled trials were included in the qualitative synthesis, of which 22 provided data for quantitative meta-analysis, yielding 23 comparisons and a total of 1750 participants. Intravenous magnesium reduced early postoperative pain (mean difference [MD] −0.90, 95% confidence interval [CI] −1.33 to −0.47; I2 = 96.27%) and pain at 24 h (MD −0.59, 95% CI −1.00 to −0.18; I2 = 66.36%), but not pain at 12 h (MD −0.52, 95% CI −1.15 to 0.11; I2 = 77.38%). Magnesium also reduced postoperative opioid consumption (MD −6.28 mg morphine equivalents, 95% CI −8.94 to −3.61; I2 = 95.93%) and prolonged time to first rescue analgesia (MD 85.61 min, 95% CI 40.11 to 131.10; I2 = 79.37%). Certainty of evidence ranged from very low to moderate, with the highest certainty observed for pain at 24 h. Conclusions: Intravenous magnesium was associated with reduced postoperative pain, particularly at 24 h, and with opioid-sparing effects. However, substantial heterogeneity across outcomes and generally low-to-moderate certainty of evidence warrant cautious interpretation. Magnesium may be considered as part of multimodal analgesia in appropriately selected patients.
L. Tomaszek, W. Mędrzycka-Dąbrowska, S. Lange et al.· Pharmaceuticals· 0 citations
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