Comparison of Two Magnesium Sulfate Protocols in Opioid-Free Anesthesia for Bariatric Surgery

Comparison of Two Magnesium Sulfate Protocols in Opioid-Free Anesthesia for Bariatric Surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of Two Magnesium Sulfate Protocols in Opioid-Free Anesthesia for Bariatric Surgery Gregory Contreras-Pérez, Hipólito Labanderya, Alex Carví-Mallo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8632966/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Opioid-free anesthesia has gained increasing interest in bariatric surgery to reduce opioid-related adverse effects. Intravenous magnesium sulfate is commonly used as part of multimodal analgesia in this setting; however, the optimal administration regimen remains unclear. Objective: to compare postoperative morphine requirements between two intravenous magnesium sulfate administration protocols within an opioid-free anesthesia framework in patients undergoing bariatric surgery. Methods This retrospective observational cohort study included adult patients with obesity (ASA II–III) who underwent laparoscopic bariatric surgery under standardized opioid-free total intravenous anesthesia at a single center between June 2022 and December 2023. Patients were allocated into two groups according to the magnesium sulfate regimen received: a single pre-induction bolus of 40 mg/kg (Mg Bolus group) or a pre-induction bolus of 50 mg/kg followed by a continuous intraoperative infusion of 15 mg/kg/h (Mg Bolus + Infusion group). The primary outcome was cumulative postoperative morphine consumption during the first 48 hours. Secondary outcomes included pain scores, postoperative nausea and vomiting, adverse events, and length of hospital stay. Results A total of 110 patients were included (55 per group). Postoperative morphine consumption during the first 48 hours was lower in patients receiving magnesium bolus plus infusion than bolus alone. Pain scores remained low in both groups. No clinically relevant differences were observed in adverse events or length of hospital stay. Conclusion In patients undergoing bariatric surgery under opioid-free anesthesia, a magnesium sulfate regimen consisting of a bolus followed by continuous infusion was associated with reduced postoperative morphine requirements compared with a single bolus strategy. Bariatric surgery Magnesium sulfate Morphine requirements Opioid-free anesthesia Postoperative opioid consumption Figures Figure 1 Figure 2 Introduction Bariatric surgery is an effective treatment for morbid obesity and its metabolic comorbidities, but it poses specific anesthetic challenges related to altered pharmacokinetics, respiratory vulnerability, and postoperative pain management.¹–³ In this population, strategies aimed at minimizing opioid exposure are particularly relevant, given the increased risk of respiratory depression, postoperative nausea and vomiting, ileus, and persistent opioid use after surgery.⁶–⁹ Opioid-free anesthesia (OFA) has emerged as an alternative multimodal approach combining hypnotics and non-opioid analgesic adjuvants to reduce or eliminate intraoperative opioid administration. Randomized trials and meta-analyses suggest that OFA can reduce postoperative opioid requirements and opioid-related adverse effects without compromising analgesic quality.¹⁰–¹² However, despite growing interest, the available clinical evidence remains limited and protocols are highly heterogeneous.¹³ Magnesium sulfate is frequently incorporated into OFA protocols because of its antagonism of N-methyl-D-aspartate (NMDA) receptors, modulation of calcium channels, and anesthetic- and analgesic-sparing effects.¹⁴–¹⁶ Clinical studies have shown that intravenous magnesium, administered as a bolus and/or continuous infusion, can reduce postoperative opioid consumption and early postoperative pain, with a favorable safety profile when appropriately dosed.¹⁷–²⁴ Nevertheless, substantial variability exists regarding dosing regimens, timing of administration, and duration of infusion, particularly in the context of bariatric surgery.²⁵–³⁴ Consequently, the optimal strategy for magnesium administration within OFA protocols remains unclear. Most studies have focused on comparisons between opioid-free and opioid-based anesthesia, whereas data directly comparing different magnesium sulfate regimens within a standardized OFA framework are scarce. The primary objective of this retrospective observational study was to compare postoperative analgesic outcomes between two intravenous magnesium sulfate administration regimens within a standardized opioid-free anesthetic technique in obese patients undergoing bariatric surgery. We hypothesized that a pre-induction magnesium bolus (50 mg·kg⁻¹) followed by a continuous intraoperative infusion (15 mg·kg⁻¹·h⁻¹) would result in lower postoperative opioid consumption compared with a single pre-induction bolus dose (40 mg·kg⁻¹). Methods Study design and population This retrospective observational comparative study was conducted at HM Nou Delfos Hospital (HM Hospitales, Barcelona, Spain). Ethical approval was obtained from the Research Ethics and Medicines Committee (CEIm HM Hospitales, Madrid, Spain; 25.04.2520-GHM), and the study was registered at ClinicalTrials.gov (NCT07077031). Due to the retrospective design, informed consent was waived. Medical records of 110 adult patients (18–65 years) with obesity (BMI ≥ 30 kg·m⁻²) and ASA physical status II–III who underwent elective laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass between June 2022 and December 2023 were reviewed. All patients received opioid-free anesthesia including intravenous magnesium sulfate and were allocated to one of two groups according to the magnesium regimen: a single preoperative bolus of 40 mg·kg⁻¹ (Group A), or a preoperative bolus of 50 mg·kg⁻¹ followed by an intraoperative infusion of 15 mg·kg⁻¹·h⁻¹ (Group B). Exclusion criteria included pregnancy or breastfeeding, chronic opioid use, known allergy to study drugs, significant renal or hepatic dysfunction, uncorrected coagulopathy, active substance abuse, uncontrolled psychiatric disease, preoperative pain (VAS > 0), intraoperative complications requiring protocol deviation, conversion to open surgery, or reoperation. All patients were managed according to ERAS guidelines for bariatric surgery. Surgical procedures were performed by two experienced bariatric surgeons using standardized techniques, and anesthesia was delivered by the same anesthesiologist following a uniform protocol. Mechanical and pharmacological thromboprophylaxis was administered in all cases. Data Collection Data were retrospectively extracted from electronic medical records. Collected variables included demographic data (age, sex, body mass index), ASA physical status, type and duration of surgery, intraoperative and postoperative adverse events, and postoperative recovery parameters. The primary outcome was cumulative intravenous morphine consumption (mg) during the first 48 postoperative hours. Secondary outcomes included postoperative pain intensity assessed using the visual analog scale (VAS, 0–10) at 1, 2, 4, 24, and 48 hours, Ramsay sedation scale scores, time to awakening from anesthesia, and the incidence of adverse events (hypotension, bradycardia, postoperative nausea and/or vomiting). Anesthetic Technique All patients were monitored according to ASA standards, including processed EEG monitoring (qCON and qNOX indices with raw EEG and density spectral array) to assess hypnosis and nociception. Neuromuscular blockade was monitored using train-of-four (TOF) and post-tetanic count (PTC). Premedication included intravenous midazolam, antibiotic prophylaxis, dexamethasone, ondansetron, and non-opioid analgesics. According to group allocation, patients received a preoperative magnesium sulfate bolus of either 40 mg·kg⁻¹ (Group A) or 50 mg·kg⁻¹ followed by a continuous intraoperative infusion of 15 mg·kg⁻¹·h⁻¹ (Group B). After 5 minutes of preoxygenation in the “beach-chair” position, all patients were induced with target-controlled infusion of propofol (TCI, Schnider model, Ce 1–5 µg·ml⁻¹), dexmedetomidine (1 µg·kg⁻¹·h⁻¹) during the first 10 min, ketamine (300 µg·kg⁻¹ IV), lidocaine (1.5 mg·kg⁻¹ IV) and rocuronium (1 mg·kg⁻¹ IV) to facilitate tracheal intubation. Patients assigned to the bolus + infusion group (Group B) received a magnesium sulfate infusion at 15 mg·kg⁻¹·h⁻¹. Patients assigned to the bolus-only group (Group A) did not receive any additional magnesium sulfate during the intraoperative period. General anesthesia was maintained with TCI propofol to keep a qCON (Conox2D®) value between 40 and 60, primarily targeting whenever possible, predominance of alpha and slow-delta patterns on raw EEG and/or DSA and avoiding “burst suppression”, as well as a qNOX between 40 and 60, but mainly identifying disruptive nociceptive stimuli by detecting indicators such as beta arousal, alpha drop-out, or paradoxical delta. As part of our OFA protocol, continuous infusions of ketamine (300 µg·kg⁻¹·h⁻¹), lidocaine (2 mg·kg⁻¹·h⁻¹), and dexmedetomidine (0.25 µg·kg⁻¹·h⁻¹) were also used. Neuromuscular blockade was maintained with rocuronium bromide to keep a TOF ratio of 0 and a post-tetanic count no greater than 8. Reversal was performed with sugammadex at doses of 2–4 mg·kg⁻¹, adjusted according to final PTC or TOF values. All OFA components were administered in an individualized fashion. Patients were extubated in the operating room after sugammadex reversal, once adequate recovery of neuromuscular function was confirmed. All drug doses were calculated according to adjusted total body weight (ATBW). All anesthetic procedures were performed by the same anesthesiologist following a standardized protocol to minimize variability. Postoperative Care After surgery, all patients were admitted to the post-anesthesia care unit (PACU) for 4 hours, where they were monitored according to institutional protocol, including continuous vital signs monitoring, level of responsiveness using the Ramsay Sedation Scale (RSS), and pain assessment using the visual analog scale (VAS). Standard postoperative analgesia included intravenous paracetamol (1000 mg every 8 h), dexketoprofen (50 mg every 8 h) or metamizole (2000 mg every 8 h), ondansetron (4 mg), and omeprazole (40 mg every 24 h). Rescue analgesia with intravenous morphine (2–3 mg every 15 min) was administered for moderate to severe pain (VAS ≥ 4) until adequate pain control was achieved. Pain assessments were performed at 1-hour intervals during the first 4 postoperative hours in the PACU and subsequently at predefined time points (1, 2, 4, 24, and 48 hours after surgery). Patients were discharged from the PACU once discharge criteria were met (Aldrete score > 9). On the surgical ward, morphine was administered via the subcutaneous route when required. Postoperative pain data were collected by members of the anesthesia team in the PACU and by trained nursing staff thereafter. Statistical Analysis Categorical variables were summarized as absolute and relative frequencies, and continuous variables as mean (standard deviation) with 95% confidence intervals. Group comparisons for categorical variables were performed using the chi-squared test. To assess baseline homogeneity between groups, a principal component analysis (PCA) was conducted on demographic and anthropometric variables (age, weight, height, body mass index, and adjusted total body weight), supported by Hotelling’s T² test. Between-group comparisons of continuous outcomes were performed using parametric tests for independent samples. These analyses included postoperative pain scores (VAS at 1, 2, 4, 24, and 48 hours), time from infusion discontinuation to awakening, and cumulative postoperative morphine consumption. All statistical analyses and graphical outputs were performed using R (R Core Team, 2024). Results The study included 110 observations, evenly distributed between the two groups, resulting in a balanced design. The average age was 40.3 (± 11.8) years, the average weight was 118 (± 26.7) kg, height 167 (± 8.6) cm, and BMI 41.9 (± 7.26) (Table 1). Of the 110 patients, 55 were allocated to Group A (single preoperative bolus of 40 mg/kg of intravenous magnesium) and 55 to Group B (preoperative bolus of 50 mg/kg of intravenous magnesium plus a continuous intraoperative infusion of 15 mg/kg/h). Group A included 36 women (65%) and 19 men (35%), while Group B included 43 women (78%) and 12 men (22%). Even though differences were observed in sex proportions between the two groups, the Chi-squared test did not yield significant differences (P-value > 0.05) for this variable or for any of the remaining categorical variables (Supplementary Table 1; Supplementary Fig. 1), suggesting overall homogeneity between the samples. This result was supported by the PCA analysis, which showed both groups largely overlapping in the space defined by the first two principal components, as well as by the non-significant result of Hotelling’s T² test for multivariate mean differences (Supplementary Table 1, Fig. 1 ). Regarding the main variables of interest, the postoperative pain level reported by the patients using the VAS scale was non-significant at one hour after surgery but significantly lower in Group B at the four remaining time points (Table 2, Fig. 2 ). However, none of the recorded time points showed mean values higher than 2.5, suggesting an overall good performance of the anesthetic technique. There were no significant differences in the Ramsay scale between the two groups during the different measurement intervals. Additionally, the time from infusion stopping to awakening was also significantly lower in the group B. Finally, cumulative postoperative morphine consumption during the first 48 hours was significantly lower in Group B, although mean consumption in Group A remained below 2.5 mg (Table 2; Supplementary Fig. 2). In a secondary analysis, postoperative morphine requirements were higher after sleeve gastrectomy than after gastric bypass procedures, regardless of the magnesium regimen (Supplementary Fig. 3). Discussion The present study compared two magnesium sulfate administration regimens within the same opioid-free anesthesia (OFA) protocol in bariatric surgery: a single bolus of 40 mg·kg⁻¹ versus a bolus of 50 mg·kg⁻¹ combined with a continuous intraoperative infusion of 15 mg·kg⁻¹·h⁻¹. In contrast to most published studies, which primarily compare OFA with opioid-based anesthesia (OBA) or placebo/control strategies, our study specifically evaluated the contribution of magnesium as an individual adjuvant within a standardized multimodal OFA regimen. In our cohort of 110 patients, both regimens were associated with very low cumulative morphine consumption during the first 48 postoperative hours (< 2.5 mg), supporting the pronounced opioid-sparing effect of a multimodal OFA strategy combining propofol, dexmedetomidine, ketamine, lidocaine, and magnesium. The bolus-plus-infusion regimen resulted in significantly lower total morphine consumption compared with the single-bolus approach. In addition, patients in this group consistently reported lower pain scores from 2 to 48 hours postoperatively, whereas no significant difference was observed at 1 hour. Taken together, these findings indicate a modest but statistically significant superiority of the bolus-plus-infusion regimen in terms of postoperative analgesia. These results are consistent with previous reports describing magnesium as a modulator of NMDA receptors and an enhancer of multimodal analgesia. Jabbour et al.³⁶ demonstrated that the combination of magnesium and ketamine significantly reduced postoperative morphine consumption in patients undergoing open bariatric surgery. De Oliveira et al.²², in a meta-analysis including more than 20 clinical trials, demonstrated that perioperative magnesium administration is associated with lower pain scores and reduced analgesic requirements in the immediate postoperative period. However, individual randomized studies in bariatric surgery have reported heterogeneous results. Adhikary et al.³⁷, in a randomized trial of 75 patients undergoing laparoscopic sleeve gastrectomy, found no differences in morphine consumption or VAS scores when comparing a single bolus of magnesium (30 mg·kg⁻¹) plus ketamine with ketamine alone or placebo under opioid-free sevoflurane-based anesthesia. In contrast, Ibrahim et al.³⁸ observed significantly lower morphine consumption at 24 hours (5.8 vs 7.2 mg) and reduced early postoperative pain scores in patients undergoing sleeve gastrectomy managed with a comprehensive OFA regimen including ketamine, dexmedetomidine, magnesium, lidocaine, and regional anesthesia. Similarly, a narrative review by Mieszczański et al.³⁹ reported a reduction in opioid requirements predominantly during the early postoperative period, despite substantial variability in magnesium dosing regimens. Notably, the improvement in VAS scores at 2–4 hours described in these studies aligns with the early analgesic benefit observed in our cohort. More recent comparative studies have evaluated OFA strategies incorporating magnesium against opioid-based anesthesia. Dagher et al.⁴⁰ demonstrated lower pain scores and reduced morphine consumption during the first 24 postoperative hours in bariatric patients receiving OFA with magnesium compared with fentanyl-based anesthesia. In contrast, Clanet et al.²⁹, in a multicenter randomized trial of over 300 patients undergoing laparoscopic gastric bypass, found no significant difference in postoperative morphine consumption between OFA and OBA groups, despite the use of similar magnesium dosing ranges. Of note, the absolute morphine consumption reported in that study (15–16 mg in 24 h) was substantially higher than in our cohort (< 2.5 mg in 48 h), suggesting that the overall multimodal analgesic strategy employed in our study may have contributed to a more pronounced opioid-sparing effect. In our study, the superiority of the bolus-plus-infusion regimen, although modest in absolute terms, was statistically significant and extended beyond the immediate postoperative period, as reflected by lower morphine consumption and reduced VAS pain scores from 2 to 48 hours. This pattern is partially consistent with recent reviews on OFA and magnesium, which describe a predominantly early but clinically relevant analgesic benefit. Cheng et al.¹¹ concluded that the advantages of OFA in laparoscopic surgery are mainly concentrated in the early postoperative hours. Regarding safety, none of the patients in our cohort experienced serious adverse events attributable to magnesium. Isolated episodes of bradycardia or hypotension were self-limited, without clinical repercussions, and did not differ significantly between groups. These findings are consistent with previous reports. Ryu et al.²⁴ demonstrated that intravenous magnesium reduces anesthetic requirements and improves postoperative analgesia without increasing major complications in patients undergoing total intravenous anesthesia. Interestingly, the time to awakening after cessation of the infusions was significantly shorter in Group B (Table 3), while Ramsay sedation scores were comparable between groups (mean 2.2 in Group A vs 2.0 in Group B). A continuous infusion, unlike a bolus-only strategy, is more likely to maintain relatively stable plasma concentrations throughout pneumoperitoneum and surgical stimulation, thereby providing sustained attenuation of central sensitisation and sympathetic activation. This may translate into lower hypnotic requirements and fewer “catch-up” increases in anesthetic depth in response to intermittent nociceptive surges, ultimately facilitating a faster and clearer emergence. Evidence from randomised data indicates that different magnesium regimens can reduce propofol requirements during induction and maintenance, supporting the concept that dosing strategy influences anesthetic exposure 17,19,24. Overall, our results confirm that both bolus and bolus-plus-infusion magnesium regimens are safe within an OFA framework. An additional finding was the difference in opioid consumption according to the type of surgery: patients undergoing sleeve gastrectomy required more morphine than those undergoing gastric bypass, regardless of the magnesium regimen. This pattern, previously described by Berlier et al.¹⁰, may be explained by greater diaphragmatic distension and referred shoulder pain typically associated with sleeve procedures. This observation suggests that the analgesic benefit of magnesium may be particularly relevant in shorter procedures, where preventive analgesia and modulation of central hyperalgesia play a key role. The remarkably low absolute amount of morphine observed in our study (< 2.5 mg over 48 hours in both groups) is substantially lower than that reported in most previous studies,²⁹ and may reflect a highly effective perioperative multimodal analgesic strategy at our institution, as well as differences in rescue analgesia protocols or patient populations. In our view, several factors may have contributed to this finding, including the use of a fully intravenous anesthetic technique with propofol as the principal GABAergic hypnotic agent, combined with dexmedetomidine, lidocaine, ketamine, and magnesium. All drugs were calculated according to adjusted total body weight and administered as boluses followed by individualized infusions under deep neuromuscular blockade, with attention to the pharmacokinetic profiles of each agent to maximize synergistic effects. In addition, the low-dose fentanyl used at induction and the concomitant administration of non-opioid analgesics (NSAIDs and dexamethasone) may have further enhanced analgesic efficacy. Furthermore, anesthetic management guided by qCON/qNOX indices and electroencephalographic monitoring (raw EEG and density spectral array) may have optimized hypnosis and antinociception, reducing the risk of under or overdosing.¹¹ , ²² In the context of contemporary bariatric surgery, where ERAS guidelines emphasize multimodal analgesia and opioid minimization,¹¹ , ¹² our findings suggest that magnesium administration either as a single bolus or as a bolus-plus-infusion regimen—is a useful and safe component of OFA. The bolus-plus-infusion strategy provides an additional statistically significant benefit, although its absolute clinical magnitude remains limited given the very low baseline opioid requirements achieved with both approaches. This study has several limitations that should be acknowledged. Its retrospective, non-randomized design is inherently associated with a risk of selection bias and limits causal inference. Although the sample size was balanced between groups, the relatively small number of patients (55 per group) may have reduced the statistical power to detect small differences between regimens. Serum magnesium concentrations were not routinely measured, precluding a direct correlation between administered dose, efficacy, and safety. In addition, follow up was limited to the first 48 postoperative hours, without evaluation of longer-term outcomes such as opioid consumption at 30 days, functional recovery, or quality of life. Finally, this was a single-center study in which all anesthetic procedures were performed by a single anesthesiologist; while this approach enhanced protocol standardization, it may limit the generalizability of the findings to other institutions and practice settings. In bariatric surgery performed under opioid-free anesthesia, magnesium administration either as a single bolus or as a bolus plus infusion regimen was associated with very low postoperative opioid requirements and adequate pain control. The bolus-plus-infusion strategy resulted in significantly lower morphine consumption and reduced postoperative pain scores compared with the single bolus approach, while both regimens were safe and well tolerated, with no serious adverse events. The analgesic benefit of magnesium was most evident in the early postoperative period and may be particularly relevant in procedures such as sleeve gastrectomy. Abbreviations ASA – American Society of Anesthesiologists BMI – Body mass index EHR – Electronic health records ERAS – Enhanced Recovery After Surgery IV – Intravenous MgSO₄ – Magnesium sulfate NMDA – N-methyl-D-aspartate OFA – Opioid-free anesthesia PACU – Post-anesthesia care unit PONV – Postoperative nausea and vomiting SD – Standard deviation TIVA – Total intravenous anesthesia VAS – Visual analog scale OFA–Mg Bolus – Opioid-free anesthesia with magnesium sulfate bolus OFA–Mg Bolus + Infusion – Opioid-free anesthesia with magnesium sulfate bolus plus continuous qCON : Quantium Consciousness Index qNOX : Quantium Nociception Index DSA : Density Spectral Array TOF : Train-of-Four PTC : Post-Tetanic Count TCI: Target-Controlled Infusion ATBW : Adjusted Total Body Weight Ce : Effect-site concentration Declarations Acknowledgements Assistance with the study: none Financial support and sponsorship: none Conflicts of interest: none Presentation: none Authors Contributorship Gregory Contreras-Pérez Contribution: This author participated in study design, data analysis, and manuscript preparation. Attestation: Contreas-Pérez approved the final manuscript. Conflicts of Interest: None Hipolito Labandeyra Contribution: This author participated in study design, data analysis, and manuscript preparation. Attestation: Labandeyra approved the final manuscript. Conflicts of Interest: None Alex Carví-Mallo Contribution: This author participated in study design and data analysis. Attestation: Alex-Mallo approved the final manuscript. Conflicts of Interest: None Conflicts of Interest: The authors declare no conflicts of interest. Funding : This study was conducted at Hospital HM Nou Delfos (Barcelona, Spain). The authors received no external funding for this work. References World Health Organization. Obesity and overweight. Fact sheet. World Health Organization; 2025. Published May 7, 2025. Accessed May 2025. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight Rubino F, Cohen RV, Mingrone G, Arterburn DE, le Roux CW, Mechanick JI, et al. 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Anesth Pain Med. 2014; 4 (1):e12750. doi:10.5812/aapm.12750 Bhatia A, Kashyap L, Pawar DK, Trikha A. Effect of intraoperative magnesium infusion on perioperative analgesia in open cholecystectomy. J Clin Anesth. 2004; 16 (4):262-265. doi:10.1016/j.jclinane.2003.11.006 Clanet M, Touihri K, El Haddad C, Goldsztejn N, Himpens J, Fils JF, et al. Effect of opioid-free versus opioid-based strategies during multimodal anesthesia on postoperative morphine consumption after bariatric surgery: a randomized double-blind clinical trial. BJA Open. 2024; 9 (C):100263. doi:10.1016/j.bjao.2024.100263 Duarte-Medrano G, Nuño-Lámbarri N, Cabal-Ruiz V, Minnuti-Palacios M, Domínguez-Franco A, Domínguez-Cherit JG. Magnesium sulfate: an essential adjuvant in anesthesiology. Rev Chil Anest. 2024; 53 (5):488-494. Kizilcik N, Koner O. Magnesium sulfate reduced opioid consumption in obese patients undergoing sleeve gastrectomy: a prospective randomized clinical trial. Obes Surg. 2018; 28 (9):2783-2788. doi:10.1007/s11695-018-3284-4 Contreras-Pérez G, Avendaño CF, Cortínez LI, Giménez Crouseilles J, Carví Mallo A. Postoperative lidocaine and ketamine effects on morphine requirement in bariatric surgery. Obes Surg. 2025. doi:10.1007/s11695-025-07689-9 Contreras-Pérez G, Avendaño CF, Carví A, Giménez Crouseilles J. Opioid-free anesthesia in a patient with extreme morbid obesity undergoing intestinal bipartition: is it worth the challenge? Rev Chil Anest. 2024; 53 (4):437-439. Bataller Bassols A, Quintero Moreno D, Colina Vargas YA, Santaliestra Fierro J, Rivero Novoa E, Ballesta C, Ramirez-Paesano C. Total intravenous opioid-free anesthesia/analgesia for a morbidly obese patient with a body mass index of 99 kg/m² undergoing gastric bypass: a case report. J Med Case Rep. 2025; 19 :404. doi:10.1186/s13256-025-0404-x Cortínez LI, De la Fuente N, Eleveld DJ, Oliveros A, Crovari F, Sepúlveda P, et al. Performance of propofol target-controlled infusion models in the obese: pharmacokinetic and pharmacodynamic analysis. Anesth Analg. 2014; 119 (2):302-310. doi:10.1213/ANE.0000000000000243 Jabbour H, Jabbour K, Abi Lutfallah A, Abou Zeid H, Nasser-Ayoub E, Abou Haidar M, et al. Magnesium and ketamine reduce early morphine consumption after open bariatric surgery: a randomized double-blind study. Obes Surg. 2020; 30 (4):1452-1458. doi:10.1007/s11695-019-04379-3 Adhikary SD, Liu WM, Memtsoudis SG, Davis JJ, Liu J, Wu CL. Analgesic efficacy of ketamine and magnesium after laparoscopic sleeve gastrectomy: a randomised, double-blind, placebo-controlled trial. Anaesthesia . 2021; 76 (12):1669-1677. Ibrahim M, Elnabtity AM, Hegab A, Alnujaidi OA, El Sanea O. Combined opioid-free and loco-regional anaesthesia enhances the quality of recovery in sleeve gastrectomy done under ERAS protocol: a randomized controlled trial. BMC Anesthesiol . 2022; 22 (1):29. Mieszczański P, Malczak P, Rogala T, Wysocki M, Major P, Budzyński A. Opioid-free anesthesia in bariatric surgery: is it the one-size-fits-all? Healthcare (Basel) . 2024; 12 (14):1422. Dagher C, Bou Chebl R, Khoury M, Abou Mrad R, Sleiman E, Maaliki H, et al. Opioid-free versus opioid-based anesthesia in bariatric surgery: a randomized controlled trial. Eur J Med Res . 2025; 30 :320. Tables Table I. Demographic characteristics. Values are presented as mean (standard deviation). ATBW: adjusted total body weight; BMI: body mass index. Group A Group B Variable Mean SD Mean 95% CI Mean SD Mean 95% CI Age 40.3 11.8 37.1-43.5 45.5 12.8 42-48.9 Weight 118 26.7 111-126 118 22.2 112-124 Height (cm) 167 8.6 165-170 165 7.8 163-167 ATBW 87.8 14.5 83.9-91.7 86.3 12 83.1-89.6 BMI 41.9 7.26 40-43.9 43.1 6.78 41.3-45 Table II. Postoperative outcomes, including pain scores assessed using the visual analog scale (VAS) at predefined time points, time from infusion discontinuation to awakening, and cumulative postoperative morphine consumption during the first 48 hours. Null Hypothesis Variable Statistic DF P-value µ A - µ B = 0 VAS after 1 Hr t = -0.18 108 0.86 VAS after 2 Hr t = 2.92 108 <0.05 VAS after 4 Hr t = 4.71 92 <0.05 VAS after 24 Hr t = 4.47 108 <0.05 VAS after 48 Hr t = 3.87 108 <0.05 Time from Infusion Stopping to Awakening (min) t = 6.09 104.6 <0.05 Total Postoperative Morphine (mg) t = 2.15 101 <0.05 Additional Declarations No competing interests reported. Supplementary Files Table1DescriptiveStatistics.docx Table2HomogeneityTest.docx Table3ComparativeTest.docx Fig1CualitativeVariables.png Fig4TotalMorphineComparison.png FigXXXXTotalMorphinebySurgicalIntervention.png Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8632966","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":579204740,"identity":"bfb7cf71-14e2-4c5d-8705-c17c9cb94501","order_by":0,"name":"Gregory Contreras-Pérez","email":"","orcid":"","institution":"Delfos Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gregory","middleName":"","lastName":"Contreras-Pérez","suffix":""},{"id":579204743,"identity":"96e0d78e-3aa1-42fc-acfe-3482983e487c","order_by":1,"name":"Hipólito Labanderya","email":"data:image/png;base64,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","orcid":"","institution":"Delfos Hospital","correspondingAuthor":true,"prefix":"","firstName":"Hipólito","middleName":"","lastName":"Labanderya","suffix":""},{"id":579204746,"identity":"857d2783-0878-4261-8e85-16d080ecf397","order_by":2,"name":"Alex Carví-Mallo","email":"","orcid":"","institution":"Delfos Hospital","correspondingAuthor":false,"prefix":"","firstName":"Alex","middleName":"","lastName":"Carví-Mallo","suffix":""}],"badges":[],"createdAt":"2026-01-18 17:53:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8632966/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8632966/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101275101,"identity":"643406a3-41fb-4c53-9b2f-0e03dad85045","added_by":"auto","created_at":"2026-01-28 03:16:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":84327,"visible":true,"origin":"","legend":"\u003cp\u003ePrincipal component analysis (PCA) of baseline demographic and anthropometric variables, including age, weight, height, body mass index, and adjusted total body weight, showing the distribution of patients in Groups A and B across the first two principal components.\u003c/p\u003e","description":"","filename":"PCA.png","url":"https://assets-eu.researchsquare.com/files/rs-8632966/v1/8b758a61a6adf9df2545d43f.png"},{"id":101275102,"identity":"b2333784-1d12-4783-a47e-40ccd477a293","added_by":"auto","created_at":"2026-01-28 03:16:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":117721,"visible":true,"origin":"","legend":"\u003cp\u003ePostoperative pain scores assessed using the visual analog scale (VAS) at 1, 2, 4, 24, and 48 hours after surgery in Groups A and B.\u003c/p\u003e","description":"","filename":"VASComparison.png","url":"https://assets-eu.researchsquare.com/files/rs-8632966/v1/09633b65d840d0177d225485.png"},{"id":104397117,"identity":"1b992c3e-0100-46b1-9b48-646687ba5405","added_by":"auto","created_at":"2026-03-11 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03:16:09","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":125930,"visible":true,"origin":"","legend":"","description":"","filename":"Fig1CualitativeVariables.png","url":"https://assets-eu.researchsquare.com/files/rs-8632966/v1/3f216312f7e17abbec757fb9.png"},{"id":101297870,"identity":"c9f60ec6-1b2d-4d1e-b8f9-337b6fbcca90","added_by":"auto","created_at":"2026-01-28 09:29:09","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":71518,"visible":true,"origin":"","legend":"","description":"","filename":"Fig4TotalMorphineComparison.png","url":"https://assets-eu.researchsquare.com/files/rs-8632966/v1/f962c7292f35a4b63ff754d8.png"},{"id":101297697,"identity":"89e27509-ea94-45ee-a750-61720d56ecc7","added_by":"auto","created_at":"2026-01-28 09:28:38","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":83389,"visible":true,"origin":"","legend":"","description":"","filename":"FigXXXXTotalMorphinebySurgicalIntervention.png","url":"https://assets-eu.researchsquare.com/files/rs-8632966/v1/e7d43e3874008e9437d0a96f.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of Two Magnesium Sulfate Protocols in Opioid-Free Anesthesia for Bariatric Surgery","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBariatric surgery is an effective treatment for morbid obesity and its metabolic comorbidities, but it poses specific anesthetic challenges related to altered pharmacokinetics, respiratory vulnerability, and postoperative pain management.\u0026sup1;\u0026ndash;\u0026sup3; In this population, strategies aimed at minimizing opioid exposure are particularly relevant, given the increased risk of respiratory depression, postoperative nausea and vomiting, ileus, and persistent opioid use after surgery.⁶\u0026ndash;⁹\u003c/p\u003e \u003cp\u003eOpioid-free anesthesia (OFA) has emerged as an alternative multimodal approach combining hypnotics and non-opioid analgesic adjuvants to reduce or eliminate intraoperative opioid administration. Randomized trials and meta-analyses suggest that OFA can reduce postoperative opioid requirements and opioid-related adverse effects without compromising analgesic quality.\u0026sup1;⁰\u0026ndash;\u0026sup1;\u0026sup2; However, despite growing interest, the available clinical evidence remains limited and protocols are highly heterogeneous.\u0026sup1;\u0026sup3;\u003c/p\u003e \u003cp\u003eMagnesium sulfate is frequently incorporated into OFA protocols because of its antagonism of N-methyl-D-aspartate (NMDA) receptors, modulation of calcium channels, and anesthetic- and analgesic-sparing effects.\u0026sup1;⁴\u0026ndash;\u0026sup1;⁶ Clinical studies have shown that intravenous magnesium, administered as a bolus and/or continuous infusion, can reduce postoperative opioid consumption and early postoperative pain, with a favorable safety profile when appropriately dosed.\u0026sup1;⁷\u0026ndash;\u0026sup2;⁴ Nevertheless, substantial variability exists regarding dosing regimens, timing of administration, and duration of infusion, particularly in the context of bariatric surgery.\u0026sup2;⁵\u0026ndash;\u0026sup3;⁴\u003c/p\u003e \u003cp\u003eConsequently, the optimal strategy for magnesium administration within OFA protocols remains unclear. Most studies have focused on comparisons between opioid-free and opioid-based anesthesia, whereas data directly comparing different magnesium sulfate regimens within a standardized OFA framework are scarce.\u003c/p\u003e \u003cp\u003eThe primary objective of this retrospective observational study was to compare postoperative analgesic outcomes between two intravenous magnesium sulfate administration regimens within a standardized opioid-free anesthetic technique in obese patients undergoing bariatric surgery. We hypothesized that a pre-induction magnesium bolus (50 mg\u0026middot;kg⁻\u0026sup1;) followed by a continuous intraoperative infusion (15 mg\u0026middot;kg⁻\u0026sup1;\u0026middot;h⁻\u0026sup1;) would result in lower postoperative opioid consumption compared with a single pre-induction bolus dose (40 mg\u0026middot;kg⁻\u0026sup1;).\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and population\u003c/h2\u003e \u003cp\u003eThis retrospective observational comparative study was conducted at HM Nou Delfos Hospital (HM Hospitales, Barcelona, Spain). Ethical approval was obtained from the Research Ethics and Medicines Committee (CEIm HM Hospitales, Madrid, Spain; 25.04.2520-GHM), and the study was registered at ClinicalTrials.gov (NCT07077031). Due to the retrospective design, informed consent was waived.\u003c/p\u003e \u003cp\u003eMedical records of 110 adult patients (18\u0026ndash;65 years) with obesity (BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg\u0026middot;m⁻\u0026sup2;) and ASA physical status II\u0026ndash;III who underwent elective laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass between June 2022 and December 2023 were reviewed. All patients received opioid-free anesthesia including intravenous magnesium sulfate and were allocated to one of two groups according to the magnesium regimen: a single preoperative bolus of 40 mg\u0026middot;kg⁻\u0026sup1; (Group A), or a preoperative bolus of 50 mg\u0026middot;kg⁻\u0026sup1; followed by an intraoperative infusion of 15 mg\u0026middot;kg⁻\u0026sup1;\u0026middot;h⁻\u0026sup1; (Group B).\u003c/p\u003e \u003cp\u003eExclusion criteria included pregnancy or breastfeeding, chronic opioid use, known allergy to study drugs, significant renal or hepatic dysfunction, uncorrected coagulopathy, active substance abuse, uncontrolled psychiatric disease, preoperative pain (VAS\u0026thinsp;\u0026gt;\u0026thinsp;0), intraoperative complications requiring protocol deviation, conversion to open surgery, or reoperation.\u003c/p\u003e \u003cp\u003e All patients were managed according to ERAS guidelines for bariatric surgery. Surgical procedures were performed by two experienced bariatric surgeons using standardized techniques, and anesthesia was delivered by the same anesthesiologist following a uniform protocol. Mechanical and pharmacological thromboprophylaxis was administered in all cases.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eData were retrospectively extracted from electronic medical records. Collected variables included demographic data (age, sex, body mass index), ASA physical status, type and duration of surgery, intraoperative and postoperative adverse events, and postoperative recovery parameters.\u003c/p\u003e \u003cp\u003eThe primary outcome was cumulative intravenous morphine consumption (mg) during the first 48 postoperative hours. Secondary outcomes included postoperative pain intensity assessed using the visual analog scale (VAS, 0\u0026ndash;10) at 1, 2, 4, 24, and 48 hours, Ramsay sedation scale scores, time to awakening from anesthesia, and the incidence of adverse events (hypotension, bradycardia, postoperative nausea and/or vomiting).\u003c/p\u003e\n\u003ch3\u003eAnesthetic Technique\u003c/h3\u003e\n\u003cp\u003eAll patients were monitored according to ASA standards, including processed EEG monitoring (qCON and qNOX indices with raw EEG and density spectral array) to assess hypnosis and nociception. Neuromuscular blockade was monitored using train-of-four (TOF) and post-tetanic count (PTC).\u003c/p\u003e \u003cp\u003ePremedication included intravenous midazolam, antibiotic prophylaxis, dexamethasone, ondansetron, and non-opioid analgesics. According to group allocation, patients received a preoperative magnesium sulfate bolus of either 40 mg\u0026middot;kg⁻\u0026sup1; (Group A) or 50 mg\u0026middot;kg⁻\u0026sup1; followed by a continuous intraoperative infusion of 15 mg\u0026middot;kg⁻\u0026sup1;\u0026middot;h⁻\u0026sup1; (Group B).\u003c/p\u003e \u003cp\u003eAfter 5 minutes of preoxygenation in the \u0026ldquo;beach-chair\u0026rdquo; position, all patients were induced with target-controlled infusion of propofol (TCI, Schnider model, Ce 1\u0026ndash;5 \u0026micro;g\u0026middot;ml⁻\u0026sup1;), dexmedetomidine (1 \u0026micro;g\u0026middot;kg⁻\u0026sup1;\u0026middot;h⁻\u0026sup1;) during the first 10 min, ketamine (300 \u0026micro;g\u0026middot;kg⁻\u0026sup1; IV), lidocaine (1.5 mg\u0026middot;kg⁻\u0026sup1; IV) and rocuronium (1 mg\u0026middot;kg⁻\u0026sup1; IV) to facilitate tracheal intubation. Patients assigned to the bolus\u0026thinsp;+\u0026thinsp;infusion group (Group B) received a magnesium sulfate infusion at 15 mg\u0026middot;kg⁻\u0026sup1;\u0026middot;h⁻\u0026sup1;. Patients assigned to the bolus-only group (Group A) did not receive any additional magnesium sulfate during the intraoperative period.\u003c/p\u003e \u003cp\u003eGeneral anesthesia was maintained with TCI propofol to keep a qCON (Conox2D\u0026reg;) value between 40 and 60, primarily targeting whenever possible, predominance of alpha and slow-delta patterns on raw EEG and/or DSA and avoiding \u0026ldquo;burst suppression\u0026rdquo;, as well as a qNOX between 40 and 60, but mainly identifying disruptive nociceptive stimuli by detecting indicators such as beta arousal, alpha drop-out, or paradoxical delta. As part of our OFA protocol, continuous infusions of ketamine (300 \u0026micro;g\u0026middot;kg⁻\u0026sup1;\u0026middot;h⁻\u0026sup1;), lidocaine (2 mg\u0026middot;kg⁻\u0026sup1;\u0026middot;h⁻\u0026sup1;), and dexmedetomidine (0.25 \u0026micro;g\u0026middot;kg⁻\u0026sup1;\u0026middot;h⁻\u0026sup1;) were also used. Neuromuscular blockade was maintained with rocuronium bromide to keep a TOF ratio of 0 and a post-tetanic count no greater than 8. Reversal was performed with sugammadex at doses of 2\u0026ndash;4 mg\u0026middot;kg⁻\u0026sup1;, adjusted according to final PTC or TOF values. All OFA components were administered in an individualized fashion. Patients were extubated in the operating room after sugammadex reversal, once adequate recovery of neuromuscular function was confirmed.\u003c/p\u003e \u003cp\u003eAll drug doses were calculated according to adjusted total body weight (ATBW). All anesthetic procedures were performed by the same anesthesiologist following a standardized protocol to minimize variability.\u003c/p\u003e\n\u003ch3\u003ePostoperative Care\u003c/h3\u003e\n\u003cp\u003eAfter surgery, all patients were admitted to the post-anesthesia care unit (PACU) for 4 hours, where they were monitored according to institutional protocol, including continuous vital signs monitoring, level of responsiveness using the Ramsay Sedation Scale (RSS), and pain assessment using the visual analog scale (VAS).\u003c/p\u003e \u003cp\u003eStandard postoperative analgesia included intravenous paracetamol (1000 mg every 8 h), dexketoprofen (50 mg every 8 h) or metamizole (2000 mg every 8 h), ondansetron (4 mg), and omeprazole (40 mg every 24 h). Rescue analgesia with intravenous morphine (2\u0026ndash;3 mg every 15 min) was administered for moderate to severe pain (VAS\u0026thinsp;\u0026ge;\u0026thinsp;4) until adequate pain control was achieved.\u003c/p\u003e \u003cp\u003ePain assessments were performed at 1-hour intervals during the first 4 postoperative hours in the PACU and subsequently at predefined time points (1, 2, 4, 24, and 48 hours after surgery). Patients were discharged from the PACU once discharge criteria were met (Aldrete score\u0026thinsp;\u0026gt;\u0026thinsp;9). On the surgical ward, morphine was administered via the subcutaneous route when required.\u003c/p\u003e \u003cp\u003ePostoperative pain data were collected by members of the anesthesia team in the PACU and by trained nursing staff thereafter.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were summarized as absolute and relative frequencies, and continuous variables as mean (standard deviation) with 95% confidence intervals. Group comparisons for categorical variables were performed using the chi-squared test.\u003c/p\u003e \u003cp\u003eTo assess baseline homogeneity between groups, a principal component analysis (PCA) was conducted on demographic and anthropometric variables (age, weight, height, body mass index, and adjusted total body weight), supported by Hotelling\u0026rsquo;s T\u0026sup2; test.\u003c/p\u003e \u003cp\u003eBetween-group comparisons of continuous outcomes were performed using parametric tests for independent samples. These analyses included postoperative pain scores (VAS at 1, 2, 4, 24, and 48 hours), time from infusion discontinuation to awakening, and cumulative postoperative morphine consumption. All statistical analyses and graphical outputs were performed using R (R Core Team, 2024).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included 110 observations, evenly distributed between the two groups, resulting in a balanced design. The average age was 40.3 (\u0026plusmn;\u0026thinsp;11.8) years, the average weight was 118 (\u0026plusmn;\u0026thinsp;26.7) kg, height 167 (\u0026plusmn;\u0026thinsp;8.6) cm, and BMI 41.9 (\u0026plusmn;\u0026thinsp;7.26) (Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003eOf the 110 patients, 55 were allocated to Group A (single preoperative bolus of 40 mg/kg of intravenous magnesium) and 55 to Group B (preoperative bolus of 50 mg/kg of intravenous magnesium plus a continuous intraoperative infusion of 15 mg/kg/h). Group A included 36 women (65%) and 19 men (35%), while Group B included 43 women (78%) and 12 men (22%). Even though differences were observed in sex proportions between the two groups, the Chi-squared test did not yield significant differences (P-value\u0026thinsp;\u0026gt;\u0026thinsp;0.05) for this variable or for any of the remaining categorical variables (Supplementary Table\u0026nbsp;1; Supplementary Fig.\u0026nbsp;1), suggesting overall homogeneity between the samples. This result was supported by the PCA analysis, which showed both groups largely overlapping in the space defined by the first two principal components, as well as by the non-significant result of Hotelling\u0026rsquo;s T\u0026sup2; test for multivariate mean differences (Supplementary Table\u0026nbsp;1, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRegarding the main variables of interest, the postoperative pain level reported by the patients using the VAS scale was non-significant at one hour after surgery but significantly lower in Group B at the four remaining time points (Table\u0026nbsp;2, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, none of the recorded time points showed mean values higher than 2.5, suggesting an overall good performance of the anesthetic technique. There were no significant differences in the Ramsay scale between the two groups during the different measurement intervals. Additionally, the time from infusion stopping to awakening was also significantly lower in the group B. Finally, cumulative postoperative morphine consumption during the first 48 hours was significantly lower in Group B, although mean consumption in Group A remained below 2.5 mg (Table\u0026nbsp;2; Supplementary Fig.\u0026nbsp;2). In a secondary analysis, postoperative morphine requirements were higher after sleeve gastrectomy than after gastric bypass procedures, regardless of the magnesium regimen (Supplementary Fig.\u0026nbsp;3).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study compared two magnesium sulfate administration regimens within the same opioid-free anesthesia (OFA) protocol in bariatric surgery: a single bolus of 40 mg\u0026middot;kg⁻\u0026sup1; versus a bolus of 50 mg\u0026middot;kg⁻\u0026sup1; combined with a continuous intraoperative infusion of 15 mg\u0026middot;kg⁻\u0026sup1;\u0026middot;h⁻\u0026sup1;. In contrast to most published studies, which primarily compare OFA with opioid-based anesthesia (OBA) or placebo/control strategies, our study specifically evaluated the contribution of magnesium as an individual adjuvant within a standardized multimodal OFA regimen.\u003c/p\u003e \u003cp\u003eIn our cohort of 110 patients, both regimens were associated with very low cumulative morphine consumption during the first 48 postoperative hours (\u0026lt;\u0026thinsp;2.5 mg), supporting the pronounced opioid-sparing effect of a multimodal OFA strategy combining propofol, dexmedetomidine, ketamine, lidocaine, and magnesium. The bolus-plus-infusion regimen resulted in significantly lower total morphine consumption compared with the single-bolus approach. In addition, patients in this group consistently reported lower pain scores from 2 to 48 hours postoperatively, whereas no significant difference was observed at 1 hour. Taken together, these findings indicate a modest but statistically significant superiority of the bolus-plus-infusion regimen in terms of postoperative analgesia.\u003c/p\u003e \u003cp\u003eThese results are consistent with previous reports describing magnesium as a modulator of NMDA receptors and an enhancer of multimodal analgesia. Jabbour et al.\u0026sup3;⁶ demonstrated that the combination of magnesium and ketamine significantly reduced postoperative morphine consumption in patients undergoing open bariatric surgery.\u003c/p\u003e \u003cp\u003eDe Oliveira et al.\u0026sup2;\u0026sup2;, in a meta-analysis including more than 20 clinical trials, demonstrated that perioperative magnesium administration is associated with lower pain scores and reduced analgesic requirements in the immediate postoperative period. However, individual randomized studies in bariatric surgery have reported heterogeneous results. Adhikary et al.\u0026sup3;⁷, in a randomized trial of 75 patients undergoing laparoscopic sleeve gastrectomy, found no differences in morphine consumption or VAS scores when comparing a single bolus of magnesium (30 mg\u0026middot;kg⁻\u0026sup1;) plus ketamine with ketamine alone or placebo under opioid-free sevoflurane-based anesthesia.\u003c/p\u003e \u003cp\u003eIn contrast, Ibrahim et al.\u0026sup3;⁸ observed significantly lower morphine consumption at 24 hours (5.8 vs 7.2 mg) and reduced early postoperative pain scores in patients undergoing sleeve gastrectomy managed with a comprehensive OFA regimen including ketamine, dexmedetomidine, magnesium, lidocaine, and regional anesthesia. Similarly, a narrative review by Mieszczański et al.\u0026sup3;⁹ reported a reduction in opioid requirements predominantly during the early postoperative period, despite substantial variability in magnesium dosing regimens. Notably, the improvement in VAS scores at 2\u0026ndash;4 hours described in these studies aligns with the early analgesic benefit observed in our cohort.\u003c/p\u003e \u003cp\u003eMore recent comparative studies have evaluated OFA strategies incorporating magnesium against opioid-based anesthesia. Dagher et al.⁴⁰ demonstrated lower pain scores and reduced morphine consumption during the first 24 postoperative hours in bariatric patients receiving OFA with magnesium compared with fentanyl-based anesthesia. In contrast, Clanet et al.\u0026sup2;⁹, in a multicenter randomized trial of over 300 patients undergoing laparoscopic gastric bypass, found no significant difference in postoperative morphine consumption between OFA and OBA groups, despite the use of similar magnesium dosing ranges. Of note, the absolute morphine consumption reported in that study (15\u0026ndash;16 mg in 24 h) was substantially higher than in our cohort (\u0026lt;\u0026thinsp;2.5 mg in 48 h), suggesting that the overall multimodal analgesic strategy employed in our study may have contributed to a more pronounced opioid-sparing effect.\u003c/p\u003e \u003cp\u003eIn our study, the superiority of the bolus-plus-infusion regimen, although modest in absolute terms, was statistically significant and extended beyond the immediate postoperative period, as reflected by lower morphine consumption and reduced VAS pain scores from 2 to 48 hours. This pattern is partially consistent with recent reviews on OFA and magnesium, which describe a predominantly early but clinically relevant analgesic benefit. Cheng et al.\u0026sup1;\u0026sup1; concluded that the advantages of OFA in laparoscopic surgery are mainly concentrated in the early postoperative hours.\u003c/p\u003e \u003cp\u003eRegarding safety, none of the patients in our cohort experienced serious adverse events attributable to magnesium. Isolated episodes of bradycardia or hypotension were self-limited, without clinical repercussions, and did not differ significantly between groups. These findings are consistent with previous reports. Ryu et al.\u0026sup2;⁴ demonstrated that intravenous magnesium reduces anesthetic requirements and improves postoperative analgesia without increasing major complications in patients undergoing total intravenous anesthesia. Interestingly, the time to awakening after cessation of the infusions was significantly shorter in Group B (Table\u0026nbsp;3), while Ramsay sedation scores were comparable between groups (mean 2.2 in Group A vs 2.0 in Group B). A continuous infusion, unlike a bolus-only strategy, is more likely to maintain relatively stable plasma concentrations throughout pneumoperitoneum and surgical stimulation, thereby providing sustained attenuation of central sensitisation and sympathetic activation. This may translate into lower hypnotic requirements and fewer \u0026ldquo;catch-up\u0026rdquo; increases in anesthetic depth in response to intermittent nociceptive surges, ultimately facilitating a faster and clearer emergence. Evidence from randomised data indicates that different magnesium regimens can reduce propofol requirements during induction and maintenance, supporting the concept that dosing strategy influences anesthetic exposure 17,19,24. Overall, our results confirm that both bolus and bolus-plus-infusion magnesium regimens are safe within an OFA framework.\u003c/p\u003e \u003cp\u003eAn additional finding was the difference in opioid consumption according to the type of surgery: patients undergoing sleeve gastrectomy required more morphine than those undergoing gastric bypass, regardless of the magnesium regimen. This pattern, previously described by Berlier et al.\u0026sup1;⁰, may be explained by greater diaphragmatic distension and referred shoulder pain typically associated with sleeve procedures. This observation suggests that the analgesic benefit of magnesium may be particularly relevant in shorter procedures, where preventive analgesia and modulation of central hyperalgesia play a key role.\u003c/p\u003e \u003cp\u003eThe remarkably low absolute amount of morphine observed in our study (\u0026lt;\u0026thinsp;2.5 mg over 48 hours in both groups) is substantially lower than that reported in most previous studies,\u0026sup2;⁹ and may reflect a highly effective perioperative multimodal analgesic strategy at our institution, as well as differences in rescue analgesia protocols or patient populations. In our view, several factors may have contributed to this finding, including the use of a fully intravenous anesthetic technique with propofol as the principal GABAergic hypnotic agent, combined with dexmedetomidine, lidocaine, ketamine, and magnesium. All drugs were calculated according to adjusted total body weight and administered as boluses followed by individualized infusions under deep neuromuscular blockade, with attention to the pharmacokinetic profiles of each agent to maximize synergistic effects. In addition, the low-dose fentanyl used at induction and the concomitant administration of non-opioid analgesics (NSAIDs and dexamethasone) may have further enhanced analgesic efficacy. Furthermore, anesthetic management guided by qCON/qNOX indices and electroencephalographic monitoring (raw EEG and density spectral array) may have optimized hypnosis and antinociception, reducing the risk of under or overdosing.\u0026sup1;\u0026sup1;\u003csup\u003e,\u003c/sup\u003e\u0026sup2;\u0026sup2;\u003c/p\u003e \u003cp\u003eIn the context of contemporary bariatric surgery, where ERAS guidelines emphasize multimodal analgesia and opioid minimization,\u0026sup1;\u0026sup1;\u003csup\u003e,\u003c/sup\u003e\u0026sup1;\u0026sup2; our findings suggest that magnesium administration either as a single bolus or as a bolus-plus-infusion regimen\u0026mdash;is a useful and safe component of OFA. The bolus-plus-infusion strategy provides an additional statistically significant benefit, although its absolute clinical magnitude remains limited given the very low baseline opioid requirements achieved with both approaches.\u003c/p\u003e \u003cp\u003eThis study has several limitations that should be acknowledged. Its retrospective, non-randomized design is inherently associated with a risk of selection bias and limits causal inference. Although the sample size was balanced between groups, the relatively small number of patients (55 per group) may have reduced the statistical power to detect small differences between regimens. Serum magnesium concentrations were not routinely measured, precluding a direct correlation between administered dose, efficacy, and safety. In addition, follow up was limited to the first 48 postoperative hours, without evaluation of longer-term outcomes such as opioid consumption at 30 days, functional recovery, or quality of life. Finally, this was a single-center study in which all anesthetic procedures were performed by a single anesthesiologist; while this approach enhanced protocol standardization, it may limit the generalizability of the findings to other institutions and practice settings.\u003c/p\u003e \u003cp\u003eIn bariatric surgery performed under opioid-free anesthesia, magnesium administration either as a single bolus or as a bolus plus infusion regimen was associated with very low postoperative opioid requirements and adequate pain control. The bolus-plus-infusion strategy resulted in significantly lower morphine consumption and reduced postoperative pain scores compared with the single bolus approach, while both regimens were safe and well tolerated, with no serious adverse events. The analgesic benefit of magnesium was most evident in the early postoperative period and may be particularly relevant in procedures such as sleeve gastrectomy.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul\u003e\n \u003cli\u003eASA \u0026ndash; American Society of Anesthesiologists\u003c/li\u003e\n \u003cli\u003eBMI \u0026ndash; Body mass index\u003c/li\u003e\n \u003cli\u003eEHR \u0026ndash; Electronic health records\u003c/li\u003e\n \u003cli\u003eERAS \u0026ndash; Enhanced Recovery After Surgery\u003c/li\u003e\n \u003cli\u003eIV \u0026ndash; Intravenous\u003c/li\u003e\n \u003cli\u003eMgSO₄ \u0026ndash; Magnesium sulfate\u003c/li\u003e\n \u003cli\u003eNMDA \u0026ndash; N-methyl-D-aspartate\u003c/li\u003e\n \u003cli\u003eOFA \u0026ndash; Opioid-free anesthesia\u003c/li\u003e\n \u003cli\u003ePACU \u0026ndash; Post-anesthesia care unit\u003c/li\u003e\n \u003cli\u003ePONV \u0026ndash; Postoperative nausea and vomiting\u003c/li\u003e\n \u003cli\u003eSD \u0026ndash; Standard deviation\u003c/li\u003e\n \u003cli\u003eTIVA \u0026ndash; Total intravenous anesthesia\u003c/li\u003e\n \u003cli\u003eVAS \u0026ndash; Visual analog scale\u003c/li\u003e\n \u003cli\u003eOFA\u0026ndash;Mg Bolus \u0026ndash; Opioid-free anesthesia with magnesium sulfate bolus\u003c/li\u003e\n \u003cli\u003eOFA\u0026ndash;Mg Bolus + Infusion \u0026ndash; Opioid-free anesthesia with magnesium sulfate bolus plus continuous\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eqCON\u003c/strong\u003e: Quantium Consciousness Index\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eqNOX\u003c/strong\u003e: Quantium Nociception Index\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eDSA\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e Density Spectral Array\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTOF\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e Train-of-Four\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePTC\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e Post-Tetanic Count\u003c/li\u003e\n \u003cli\u003eTCI: Target-Controlled Infusion\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eATBW\u003c/strong\u003e: Adjusted Total Body Weight\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCe\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e Effect-site concentration\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAcknowledgements\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAssistance with the study:\u0026nbsp;none\u003c/p\u003e\n\u003cp\u003eFinancial support and sponsorship: none\u003c/p\u003e\n\u003cp\u003eConflicts of interest: none\u003c/p\u003e\n\u003cp\u003ePresentation: none\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAuthors Contributorship\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGregory Contreras-P\u0026eacute;rez\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContribution: This author participated in study design, data analysis, and manuscript preparation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAttestation: Contreas-P\u0026eacute;rez approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConflicts of Interest: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHipolito Labandeyra\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContribution: This author participated in study design, data analysis, and manuscript preparation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAttestation: Labandeyra approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConflicts of Interest: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAlex Carv\u0026iacute;-Mallo\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContribution: This author participated in study design and data analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAttestation: Alex-Mallo\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eapproved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConflicts of Interest: None\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest: \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was conducted at Hospital HM Nou Delfos (Barcelona, Spain). The authors received no external funding for this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWorld Health Organization.\u0026nbsp;\u003cstrong\u003eObesity and overweight.\u003c/strong\u003e Fact sheet. World Health Organization; 2025. Published May 7, 2025. Accessed May 2025.\u003cbr\u003ehttps://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight\u003c/li\u003e\n \u003cli\u003eRubino F, Cohen RV, Mingrone G, Arterburn DE, le Roux CW, Mechanick JI, et al. Bariatric and metabolic surgery during and after the COVID-19 pandemic: DSS recommendations for management of surgical candidates and postoperative patients. \u003cem\u003eLancet Diabetes Endocrinol.\u003c/em\u003e 2020;\u003cstrong\u003e8\u003c/strong\u003e(7):640-648. doi:10.1016/S2213-8587(20)30157-1\u003c/li\u003e\n \u003cli\u003eOgunnaike BO, Jones SB, Jones DB, Provost D, Whitten CW. 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Magnesium can decrease postoperative physiological ileus and postoperative pain in major nonlaparoscopic gastrointestinal surgeries: a randomized controlled trial. \u003cem\u003eAnesth Pain Med.\u003c/em\u003e 2014;\u003cstrong\u003e4\u003c/strong\u003e(1):e12750. doi:10.5812/aapm.12750\u003c/li\u003e\n \u003cli\u003eBhatia A, Kashyap L, Pawar DK, Trikha A. Effect of intraoperative magnesium infusion on perioperative analgesia in open cholecystectomy. \u003cem\u003eJ Clin Anesth.\u003c/em\u003e 2004;\u003cstrong\u003e16\u003c/strong\u003e(4):262-265. doi:10.1016/j.jclinane.2003.11.006\u003c/li\u003e\n \u003cli\u003eClanet M, Touihri K, El Haddad C, Goldsztejn N, Himpens J, Fils JF, et al. Effect of opioid-free versus opioid-based strategies during multimodal anesthesia on postoperative morphine consumption after bariatric surgery: a randomized double-blind clinical trial. \u003cem\u003eBJA Open.\u003c/em\u003e 2024;\u003cstrong\u003e9\u003c/strong\u003e(C):100263. doi:10.1016/j.bjao.2024.100263\u003c/li\u003e\n \u003cli\u003eDuarte-Medrano G, Nu\u0026ntilde;o-L\u0026aacute;mbarri N, Cabal-Ruiz V, Minnuti-Palacios M, Dom\u0026iacute;nguez-Franco A, Dom\u0026iacute;nguez-Cherit JG. Magnesium sulfate: an essential adjuvant in anesthesiology. \u003cem\u003eRev Chil Anest.\u003c/em\u003e 2024;\u003cstrong\u003e53\u003c/strong\u003e(5):488-494.\u003c/li\u003e\n \u003cli\u003eKizilcik N, Koner O. Magnesium sulfate reduced opioid consumption in obese patients undergoing sleeve gastrectomy: a prospective randomized clinical trial. \u003cem\u003eObes Surg.\u003c/em\u003e 2018;\u003cstrong\u003e28\u003c/strong\u003e(9):2783-2788. doi:10.1007/s11695-018-3284-4\u003c/li\u003e\n \u003cli\u003eContreras-P\u0026eacute;rez G, Avenda\u0026ntilde;o CF, Cort\u0026iacute;nez LI, Gim\u0026eacute;nez Crouseilles J, Carv\u0026iacute; Mallo A. Postoperative lidocaine and ketamine effects on morphine requirement in bariatric surgery. \u003cem\u003eObes Surg.\u003c/em\u003e 2025. doi:10.1007/s11695-025-07689-9\u003c/li\u003e\n \u003cli\u003eContreras-P\u0026eacute;rez G, Avenda\u0026ntilde;o CF, Carv\u0026iacute; A, Gim\u0026eacute;nez Crouseilles J. Opioid-free anesthesia in a patient with extreme morbid obesity undergoing intestinal bipartition: is it worth the challenge? \u003cem\u003eRev Chil Anest.\u003c/em\u003e 2024;\u003cstrong\u003e53\u003c/strong\u003e(4):437-439.\u003c/li\u003e\n \u003cli\u003eBataller Bassols A, Quintero Moreno D, Colina Vargas YA, Santaliestra Fierro J, Rivero Novoa E, Ballesta C, Ramirez-Paesano C. Total intravenous opioid-free anesthesia/analgesia for a morbidly obese patient with a body mass index of 99 kg/m\u0026sup2; undergoing gastric bypass: a case report. \u003cem\u003eJ Med Case Rep.\u003c/em\u003e 2025;\u003cstrong\u003e19\u003c/strong\u003e:404. doi:10.1186/s13256-025-0404-x\u003c/li\u003e\n \u003cli\u003eCort\u0026iacute;nez LI, De la Fuente N, Eleveld DJ, Oliveros A, Crovari F, Sep\u0026uacute;lveda P, et al. Performance of propofol target-controlled infusion models in the obese: pharmacokinetic and pharmacodynamic analysis. \u003cem\u003eAnesth Analg.\u003c/em\u003e 2014;\u003cstrong\u003e119\u003c/strong\u003e(2):302-310. doi:10.1213/ANE.0000000000000243\u003c/li\u003e\n \u003cli\u003eJabbour H, Jabbour K, Abi Lutfallah A, Abou Zeid H, Nasser-Ayoub E, Abou Haidar M, et al. Magnesium and ketamine reduce early morphine consumption after open bariatric surgery: a randomized double-blind study. \u003cem\u003eObes Surg.\u003c/em\u003e 2020;\u003cstrong\u003e30\u003c/strong\u003e(4):1452-1458. doi:10.1007/s11695-019-04379-3\u003c/li\u003e\n \u003cli\u003eAdhikary SD, Liu WM, Memtsoudis SG, Davis JJ, Liu J, Wu CL. Analgesic efficacy of ketamine and magnesium after laparoscopic sleeve gastrectomy: a randomised, double-blind, placebo-controlled trial. \u003cem\u003eAnaesthesia\u003c/em\u003e. 2021;\u003cstrong\u003e76\u003c/strong\u003e(12):1669-1677.\u003c/li\u003e\n \u003cli\u003eIbrahim M, Elnabtity AM, Hegab A, Alnujaidi OA, El Sanea O. Combined opioid-free and loco-regional anaesthesia enhances the quality of recovery in sleeve gastrectomy done under ERAS protocol: a randomized controlled trial. \u003cem\u003eBMC Anesthesiol\u003c/em\u003e. 2022;\u003cstrong\u003e22\u003c/strong\u003e(1):29.\u003c/li\u003e\n \u003cli\u003eMieszczański P, Malczak P, Rogala T, Wysocki M, Major P, Budzyński A. Opioid-free anesthesia in bariatric surgery: is it the one-size-fits-all? \u003cem\u003eHealthcare (Basel)\u003c/em\u003e. 2024;\u003cstrong\u003e12\u003c/strong\u003e(14):1422.\u003c/li\u003e\n \u003cli\u003eDagher C, Bou Chebl R, Khoury M, Abou Mrad R, Sleiman E, Maaliki H, et al. Opioid-free versus opioid-based anesthesia in bariatric surgery: a randomized controlled trial. \u003cem\u003eEur J Med Res\u003c/em\u003e. 2025;\u003cstrong\u003e30\u003c/strong\u003e:320.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable I. Demographic characteristics. Values are presented as mean (standard deviation). ATBW: adjusted total body weight; BMI: body mass index.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"115%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup B\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean 95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean 95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eAge\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e40.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e37.1-43.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e45.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e42-48.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eWeight\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e26.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e111-126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e22.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e112-124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eHeight (cm)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e167\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e165-170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e165\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e163-167\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eATBW\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e87.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e14.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e83.9-91.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e86.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e83.1-89.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eBMI\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e41.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e7.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e40-43.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e43.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e6.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e41.3-45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable II. Postoperative outcomes, including pain scores assessed using the visual analog scale (VAS) at predefined time points, time from infusion discontinuation to awakening, and cumulative postoperative morphine consumption during the first 48 hours.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNull Hypothesis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStatistic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026micro;\u003csub\u003eA\u003c/sub\u003e - \u0026micro;\u003csub\u003eB\u003c/sub\u003e = 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eVAS after 1 Hr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003et = -0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eVAS after 2 Hr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003et = 2.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eVAS after 4 Hr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003et = 4.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eVAS after 24 Hr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003et = 4.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eVAS after 48 Hr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003et = 3.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eTime from Infusion Stopping to Awakening (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003et = 6.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e104.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eTotal Postoperative Morphine (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003et = 2.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bariatric surgery, Magnesium sulfate, Morphine requirements, Opioid-free anesthesia, Postoperative opioid consumption","lastPublishedDoi":"10.21203/rs.3.rs-8632966/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8632966/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOpioid-free anesthesia has gained increasing interest in bariatric surgery to reduce opioid-related adverse effects. Intravenous magnesium sulfate is commonly used as part of multimodal analgesia in this setting; however, the optimal administration regimen remains unclear. Objective: to compare postoperative morphine requirements between two intravenous magnesium sulfate administration protocols within an opioid-free anesthesia framework in patients undergoing bariatric surgery.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective observational cohort study included adult patients with obesity (ASA II\u0026ndash;III) who underwent laparoscopic bariatric surgery under standardized opioid-free total intravenous anesthesia at a single center between June 2022 and December 2023. Patients were allocated into two groups according to the magnesium sulfate regimen received: a single pre-induction bolus of 40 mg/kg (Mg Bolus group) or a pre-induction bolus of 50 mg/kg followed by a continuous intraoperative infusion of 15 mg/kg/h (Mg Bolus\u0026thinsp;+\u0026thinsp;Infusion group). The primary outcome was cumulative postoperative morphine consumption during the first 48 hours. Secondary outcomes included pain scores, postoperative nausea and vomiting, adverse events, and length of hospital stay.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 110 patients were included (55 per group). Postoperative morphine consumption during the first 48 hours was lower in patients receiving magnesium bolus plus infusion than bolus alone. Pain scores remained low in both groups. No clinically relevant differences were observed in adverse events or length of hospital stay.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn patients undergoing bariatric surgery under opioid-free anesthesia, a magnesium sulfate regimen consisting of a bolus followed by continuous infusion was associated with reduced postoperative morphine requirements compared with a single bolus strategy.\u003c/p\u003e","manuscriptTitle":"Comparison of Two Magnesium Sulfate Protocols in Opioid-Free Anesthesia for Bariatric Surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-28 03:16:01","doi":"10.21203/rs.3.rs-8632966/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a271ff18-cb5f-4bb3-ae54-8282c410386d","owner":[],"postedDate":"January 28th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-14T23:53:21+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-28 03:16:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8632966","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8632966","identity":"rs-8632966","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}