Combination of Dexamethasone and Pregabalin for Postoperative Pain After Laminectomy: A Randomized Controlled Trial

Combination of Dexamethasone and Pregabalin for Postoperative Pain After Laminectomy: A Randomized Controlled Trial | 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 Combination of Dexamethasone and Pregabalin for Postoperative Pain After Laminectomy: A Randomized Controlled Trial Ali Sadighi, Aran Nikpay, Sajjad Valizadeh, Mehrdad Zamani This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8457462/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Apr, 2026 Read the published version in European Spine Journal → Version 1 posted 12 You are reading this latest preprint version Abstract Purpose Multimodal analgesia is standard for post-laminectomy pain. This study evaluated two intravenous dexamethasone doses, with or without oral pregabalin, within this framework. Methods In this randomized, double-blind, placebo-controlled trial, 800 adult patients undergoing elective 2–3 level lumbar laminectomy were allocated to: Group A (8 mg IV dexamethasone + 150 mg oral pregabalin), Group B (8 mg IV dexamethasone + oral placebo), Group C (4 mg IV dexamethasone + 150 mg oral pregabalin), or Group D (4 mg IV dexamethasone + oral placebo). Drugs were given preemptively. Primary outcome was pain scores (Visual Analogue Scale, VAS) over 24 hours. Secondary outcomes included 24-hour opioid consumption (morphine equivalents), time to first rescue analgesia, hemodynamics, and adverse events. Results All patients completed the protocol. Statistically significant differences in VAS scores were observed among groups at all time points (p < 0.001), with Group A reporting the lowest scores. Twenty-four-hour opioid consumption was also significantly different (p < 0.001), being lowest in Group A. A formal factorial analysis indicated a statistically significant interaction effect (p = 0.012) between the higher dexamethasone dose and pregabalin. Sedation/dizziness was more frequent in pregabalin groups (A: 22.5%; C: 20.0%) versus placebo groups (B & D: 5.0% each; p < 0.001). No significant differences in surgical site infections or hyperglycemia were noted. Conclusion In a selected cohort of patients undergoing elective laminectomy, preemptive administration of 8 mg IV dexamethasone combined with 150 mg oral pregabalin was associated with statistically significant reductions in pain scores and opioid requirements over 24 hours compared to lower doses or monotherapy, alongside greater hemodynamic stability but increased neurosedative effects. This combination represents a potential option within multimodal analgesia protocols for spinal surgery, though its generalizability to broader patient populations requires further study. Level of evidence: 1 Laminectomy Postoperative Pain Multimodal Analgesia Dexamethasone Pregabalin Randomized Controlled Trial Figures Figure 1 1. Introduction Postoperative pain following lumbar laminectomy is often severe, resulting from extensive tissue dissection, muscle retraction, and potential neural element manipulation. Inadequately managed acute pain can lead to a cascade of adverse outcomes, including delayed mobilization, increased risk of thromboembolic events, prolonged hospital stay, higher opioid consumption with its attendant side effects, and may contribute to the development of chronic post-surgical pain—a significant concern in spine surgery populations[1, 2] The pursuit of effective analgesia while minimizing opioid-related complications, such as respiratory depression, ileus, nausea, and the potential for long-term dependence, remains a paramount objective in perioperative care.[3] This has led to the widespread adoption of multimodal analgesic strategies, which combine medications with distinct mechanisms of action to target multiple pain pathways simultaneously. The goal is to achieve synergistic or additive effects, allowing for lower doses of individual agents and an improved side-effect profile, aligning with Enhanced Recovery After Surgery (ERAS) principles.[4] Dexamethasone, a potent glucocorticoid, is a well-established adjunct in multimodal regimens. Its perioperative analgesic and opioid-sparing effects are attributed to its potent anti-inflammatory properties, primarily through the inhibition of phospholipase A2 and the subsequent suppression of prostaglandin and cytokine synthesis at the surgical site [5, 6] Meta-analyses support its efficacy in reducing pain scores and opioid requirements across various surgical procedures.[7] Pregabalin, a gabapentinoid, modulates neuropathic pain and central sensitization by binding to the α2-δ subunit of presynaptic voltage-gated calcium channels in the central nervous system. This action reduces the release of excitatory neurotransmitters (e.g., glutamate, substance P), thereby attenuating postoperative hyperalgesia[8, 9] Its use in acute postoperative pain management, particularly in surgeries with a significant neuropathic component like spinal procedures, has been extensively studied, though with variable conclusions regarding its risk-benefit ratio..[10, 11] While the individual roles of dexamethasone and pregabalin are recognized, a significant knowledge gap exists regarding their combined use, specifically in lumbar laminectomy. Furthermore, the optimal dose of perioperative dexamethasone in this context is not well-defined, with common clinical practice oscillating between 4 mg and 8 mg. It is plausible that a higher anti-inflammatory dose of dexamethasone might interact more effectively with the central neuromodulatory action of pregabalin, potentially yielding superior outcomes compared to either drug alone or lower-dose combinations. This study was therefore designed to investigate the efficacy and safety of two different doses of intravenous dexamethasone (4 mg versus 8 mg), each combined with or without a single preoperative dose of oral pregabalin (150 mg), in patients undergoing elective lumbar laminectomy. We hypothesized that the combination of 8 mg dexamethasone with pregabalin would provide more effective analgesia and greater opioid-sparing effects over the first 24 postoperative hours compared to lower-dose combinations or monotherapy. 2. Methods 2.1. Study Design and Ethical Approval This single-center, prospective, randomized, double-blind, placebo-controlled trial was approved by the Institutional Ethics Committee (IR.TBZMED.REC.1403.156) and registered (IRCT20190325043107N11). Written informed consent was obtained. The manuscript adheres to CONSORT guidelines. 2.2. Participants 800 adult patients (ASA I-II) scheduled for elective 2–3 level lumbar laminectomy were recruited. Key exclusion criteria were: emergency surgery; drug hypersensitivity; BMI > 40 kg/m²; uncontrolled diabetes mellitus or hypertension; significant renal/hepatic impairment; substance abuse; chronic opioid/gabapentinoid use; major psychiatric disorders; glaucoma; active infection; or previous spinal surgery within 6 months. These criteria aimed to ensure homogeneity and initial safety but limit generalizability. 2.3. Sample Size Calculation Based on a pilot study anticipating a 20% difference in 24-hour opioid consumption with an SD of 25 mg morphine equivalents, 160 patients per group provided 90% power (α = 0.05). Accounting for minimal attrition, 200 per group were recruited. 2.4. Randomization and Blinding Patients were randomized 1:1:1:1 via computer-generated blocks (size 8). Allocation was concealed using sequentially numbered, opaque, sealed envelopes opened by a research pharmacist who prepared the study drugs. All IV solutions and oral capsules were identical. The administering anesthesiologist, postoperative caregivers, outcome assessors, and data analyst were blinded to group assignment. 2.5. Intervention and Standardization One hour preoperatively, patients received oral pregabalin 150 mg or placebo. In the operating room, IV dexamethasone (4 mg, 8 mg) or volume-matched saline was given. A standardized anesthetic protocol was mandated: induction with propofol (2-2.5 mg/kg) and fentanyl (2–3 µg/kg), muscle relaxation with atracurium, maintenance with sevoflurane (1-1.5 MAC). No other intraoperative analgesics (e.g., ketamine, lidocaine, NSAIDs) were permitted. Intraoperative fentanyl boluses (0.5-1 µg/kg) were allowed at the anesthesiologist's discretion and recorded. Postoperative mobilization followed a standardized protocol (sitting at 4h, standing at 6h, ambulating with assistance at 8h). 2.6. Postoperative Management and Data Collection Rescue analgesia was IV morphine 2 mg boluses, then PCA morphine (1 mg bolus, 10-min lockout). Data collected by a blinded researcher included: Primary Outcome : Pain VAS (0–10) at PACU discharge, and 1, 2, 4, 6, 12, 24h post-discharge. Secondary Outcomes : Time to first rescue analgesia; total 24-hour morphine consumption (all boluses + PCA); hemodynamics (SBP, DBP, HR) at baseline, induction, PACU discharge, and serial times; adverse events (sedation/dizziness, PONV, pruritus, headache, respiratory depression, hyperglycemia > 180 mg/dL, surgical site infection at 30 days). Assessor Training: All nursing and research staff collecting VAS and sedation scores underwent standardized training before the study to ensure consistent assessment. 2.7. Statistical Analysis Data analyzed using SPSS v26 and R. Normally distributed continuous data (mean ± SD) compared with one-way ANOVA (Tukey's post-hoc). Longitudinal data (pain, hemodynamics) analyzed with two-way repeated-measures ANOVA. A pre-specified 2x2 factorial ANOVA assessed main and interaction effects on 24-hour opioid consumption. Categorical data compared with Chi-square/Fisher's exact test. Intention-to-treat analysis. P < 0.05 significant. 3. Results 3.1. Participant Flow and Baseline Characteristics During the study period, 1025 patients were assessed for eligibility. Of these, 225 were excluded (145 did not meet inclusion criteria, 80 declined to participate). The remaining 800 patients were randomized (200 per group). All randomized patients received the intended intervention and completed the 24-hour follow-up, with no dropouts or protocol deviations, resulting in 800 patients included in the ITT analysis (Fig. 1). The four groups were well-balanced with respect to all baseline demographic and clinical characteristics (p > 0.05 for all comparisons) (Table 1). Table 1 Baseline Demographic and Clinical Characteristics of the Study Groups Characteristic Group A (n = 200) Group B (n = 200) Group C (n = 200) Group D (n = 200) p-value Age (years) 43.9 ± 8.9 43.4 ± 6.2 44.7 ± 8.1 43.6 ± 8.6 0.642 Sex (Male/Female) 115/85 120/80 105/95 110/90 0.792 BMI (kg/m²) 27.4 ± 3.8 27.6 ± 4.1 27.3 ± 3.7 27.5 ± 3.9 0.824 ASA I/II 85/115 82/118 88/112 84/116 0.901 Surgery Duration (min) 102.3 ± 14.5 104.9 ± 13.1 103.5 ± 14.0 104.2 ± 14.2 0.703 Anesthesia Duration (min) 128.5 ± 16.1 130.2 ± 15.8 129.1 ± 15.9 129.8 ± 16.0 0.815 Laminectomy Levels (2/3) 135/65 130/70 140/60 132/68 0.745 Intraop. Fentanyl (µg) 225.5 ± 35.5 230.1 ± 36.2 228.3 ± 34.9 231.4 ± 37.1 0.558 3.2. Postoperative Pain Scores Pain VAS scores differed significantly among groups across all time points (p < 0.001 for group effect, time effect, and group*time interaction in repeated-measures ANOVA). Group A (8 mg Dex + PGB) consistently reported the lowest pain scores, followed by Group C (4 mg Dex + PGB). Groups B and D (without pregabalin) reported higher pain, with Group D (4 mg Dex alone) showing the highest scores at most time points (Table 2). Table 2 Comparison of Postoperative Pain Scores (VAS, mean ± SD) Time Point Group A (n = 200) Group B (n = 200) Group C (n = 200) Group D (n = 200) p-value PACU Discharge 3.42 ± 1.12 4.71 ± 1.32 4.10 ± 1.20 5.02 ± 1.41 < 0.001 1-hour 2.80 ± 1.00 3.41 ± 1.10 3.05 ± 1.00 3.81 ± 1.21 < 0.001 2-hour 2.40 ± 0.90 3.10 ± 1.00 2.80 ± 1.00 3.41 ± 1.11 < 0.001 4-hour 1.89 ± 0.78 2.56 ± 0.89 2.12 ± 0.84 2.89 ± 0.93 < 0.001 6-hour 1.45 ± 0.67 2.01 ± 0.78 1.78 ± 0.72 2.34 ± 0.81 < 0.001 12-hour 0.89 ± 0.45 1.45 ± 0.67 1.12 ± 0.56 1.78 ± 0.69 < 0.001 24-hour 0.45 ± 0.23 1.01 ± 0.34 0.78 ± 0.29 1.45 ± 0.45 < 0.001 3.3. Postoperative Opioid Consumption and Analgesia Duration The 24-hour cumulative opioid consumption differed significantly among groups (p < 0.001). Group A required the least amount of morphine (177.0 ± 25.5 mg, 95% CI: 173.5-180.5), which was significantly lower than all other groups. The order of consumption was: Group A < Group C (204.0 ± 29.5 mg, 95% CI: 200.0-208.0) < Group B (228.5 ± 31.5 mg, 95% CI: 224.1-232.9) < Group D (250.5 ± 33.5 mg, 95% CI: 245.8-255.2) (Table 3). The time to first rescue analgesia was longest in Group A (125.4 ± 45.6 min) and shortest in Group D (68.3 ± 32.1 min) (p < 0.001). Formal 2x2 factorial ANOVA on 24-hour opioid consumption revealed significant main effects for dexamethasone dose (p < 0.001) and pregabalin administration (p < 0.001), as well as a statistically significant interaction effect (p = 0.012), indicating a synergistic interaction between the higher dose of dexamethasone (8 mg) and pregabalin. Table 3 Comparison of 24-hour Cumulative Opioid Consumption (Morphine Equivalents, mg) Group n 24-hour Opioid Consumption (mg) Mean ± SD 95% Confidence Interval p-value (vs. Group D) Group A 200 177.0 ± 25.5 173.5–180.5 < 0.001 Group B 200 228.5 ± 31.5 224.1–232.9 < 0.001 Group C 200 204.0 ± 29.5 200.0–208.0 < 0.001 Group D 200 250.5 ± 33.5 245.8–255.2 Reference 3.4. Hemodynamic Stability Groups receiving pregabalin (A and C) exhibited greater hemodynamic stability, with significantly less fluctuation in SBP, DBP, and HR over the 24-hour period compared to groups B and D (p 160 mmHg) and tachycardia (HR > 100 bpm) in response to pain. 3.5. Adverse Events The overall adverse event profile is summarized in Table 4. Sedation and dizziness were significantly more common in the pregabalin groups (A & C) during the first 6–8 hours post-dose. No episodes of severe respiratory depression occurred. The incidence of postoperative nausea and vomiting (PONV) was significantly lower in groups receiving dexamethasone (A, B) compared to groups C and D. There were no statistically significant differences among groups in the rates of surgical site infection (assessed at 30-day follow-up) or significant hyperglycemia requiring intervention. Discussion This large, randomized controlled trial demonstrates that a preemptive multimodal regimen combining 8 mg intravenous dexamethasone with 150 mg oral pregabalin provides superior analgesic outcomes for patients undergoing elective laminectomy. The combination resulted in the lowest pain scores, a 29.3% reduction in 24-hour opioid consumption compared to the weakest regimen (4 mg dexamethasone alone), the longest time to first rescue analgesia, and the most stable hemodynamic profile. The formal finding of a statistically significant interaction effect supports a synergistic, rather than merely additive, benefit from combining the higher-dose steroid with the gabapentinoid. Effective pain management after lumbar laminectomy is critical, as poorly controlled acute pain can impede early mobilization—a key factor in preventing complications like deep vein thrombosis and aiding functional recovery.[2, 11]Furthermore, severe acute postoperative pain is a known risk factor for the development of chronic neuropathic pain after spinal surgery.[1]Our findings align with and extend the growing literature on multimodal analgesia in spine surgery. The significant opioid-sparing effect (approximately 73.5 mg less morphine over 24 hours in Group A vs. Group D) is clinically meaningful, as it directly correlates with a lower risk of opioid-related side effects such as respiratory depression, ileus, and sedation, potentially facilitating faster recovery and earlier discharge.[3, 12] The mechanism behind the observed synergy is plausible. Dexamethasone acts peripherally and centrally to blunt the inflammatory cascade and cytokine-mediated sensitization following surgical trauma.[5, 7] Pregabalin modulates central pain processing by attenuating neuronal hyperexcitability and dampening the neuropathic component common in spine surgery patients.[8, 13] Their concurrent use thus targets multiple pain pathways—inflammatory, somatic, and neuropathic—simultaneously. The greater efficacy of the 8 mg dose over the 4 mg dose, particularly when combined with pregabalin, suggests a dose-dependent effect for dexamethasone in this context, consistent with some studies in other surgical models.[14] The improved hemodynamic stability in pregabalin groups likely stems from its anxiolytic properties and a more effective mitigation of the sympathetic stress response triggered by surgical trauma and pain.[15]However, this benefit must be weighed against the increased incidence of transient sedation and dizziness, which, while not leading to serious complications in our relatively healthy cohort, warrants caution, especially in elderly patients or those with balance disorders. This study has important limitations that must be acknowledged. First, the stringent exclusion criteria, while ensuring internal validity and patient safety for this initial evaluation, created a homogenous cohort of relatively healthy, younger adults. Consequently, the generalizability of these findings to the broader, often older and comorbid, population undergoing spinal surgery is significantly limited. Patients with diabetes, hypertension, or those on chronic medications were not represented. Second, the single-center design and highly standardized protocol, which contributed to the lack of dropouts and protocol deviations, may not reflect real-world variability in practice. The absence of attrition, while strengthening the ITT analysis, is unusual in large surgical trials and should be considered when interpreting feasibility for other settings. Third, the 24-hour follow-up period does not inform on longer-term outcomes like chronic pain development or functional recovery. Fourth, despite assessor training, the subjective nature of pain scoring retains inherent measurement bias potential. Finally, while the factorial analysis indicated interaction, confirming true clinical synergy requires dedicated dose-ranging studies. Conclusion Within the constraints of its design and patient population, this trial demonstrates that preemptive combination of 8 mg IV dexamethasone and 150 mg oral pregabalin provides effective analgesia and opioid-sparing in the first 24 hours after elective laminectomy, albeit with increased sedation. These results support the potential utility of this combination within multimodal analgesic protocols for spinal surgery. However, caution is advised in extrapolating these results to typical, more comorbid surgical populations. Future multi-center studies with broader inclusion criteria and longer follow-up are warranted to confirm these findings and establish external validity. Table 4 Incidence of Adverse Events within 24 Hours Postoperatively, n (%) Adverse Event Group A (n = 200) Group B (n = 200) Group C (n = 200) Group D (n = 200) p-value Sedation/Dizziness 45 (22.5%) 10 (5.0%) 40 (20.0%) 10 (5.0%) < 0.001 Nausea/Vomiting 20 (10.0%) 22 (11.0%) 50 (25.0%) 55 (27.5%) < 0.001 Pruritus 15 (7.5%) 18 (9.0%) 20 (10.0%) 25 (12.5%) 0.275 Headache 10 (5.0%) 12 (6.0%) 8 (4.0%) 14 (7.0%) 0.521 Hyperglycemia 30 (15.0%) 28 (14.0%) 25 (12.5%) 22 (11.0%) 0.612 Surgical Site Infection 2 (1.0%) 3 (1.5%) 1 (0.5%) 2 (1.0%) 0.823 Declarations Author Contribution Credit Author StatementMehrdad Zamani : Conceptualization, Methodology, Supervision, Review & Editing. Writing - Original Draft. Ali Sadighi: Data curation , Validation Writing - Review & Editing. Resources, SoftwareAran Nikpay: Data curation, Investigation, Methodology, Supervision. Supervision ,Sajjad Valizadeh: Formal analysis, Investigation, Project administration,All authors: Read and approved the final manuscript. Acknowledgement The authors would like to thanks clinical research development unit , Shohada hospital, Tabriz university of medical science, Tabriz, Iran for kind support. References Clarke, H., et al., Acute pain after total hip arthroplasty does not predict the development of chronic postsurgical pain 6 months later. J Anesth, 2010. 24 (4): p. 537 − 43. Gerbershagen, H.J., et al., Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology, 2013. 118 (4): p. 934 − 44. Sun, E.C., et al., Incidence of and Risk Factors for Chronic Opioid Use Among Opioid-Naive Patients in the Postoperative Period. JAMA Intern Med, 2016. 176 (9): p. 1286-93. Wick, E.C., M.C. Grant, and C.L. Wu, Postoperative Multimodal Analgesia Pain Management With Nonopioid Analgesics and Techniques: A Review. JAMA Surg, 2017. 152 (7): p. 691–697. De Oliveira, G.S., Jr., et al., Perioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology, 2011. 115 (3): p. 575 − 88. Waldron, N.H., et al., Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis. Br J Anaesth, 2013. 110 (2): p. 191–200. Liu, L., et al., Efficacy and Safety of First-Line Immunotherapy Combinations for Advanced NSCLC: A Systematic Review and Network Meta-Analysis. J Thorac Oncol, 2021. 16 (7): p. 1099–1117. Mishriky, B.M., N.H. Waldron, and A.S. Habib, Impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis. Br J Anaesth, 2015. 114 (1): p. 10–31. Zhang, J., K.Y. Ho, and Y. Wang, Efficacy of pregabalin in acute postoperative pain: a meta-analysis. Br J Anaesth, 2011. 106 (4): p. 454 − 62. Koç, S., D. Memis, and N. Sut, The preoperative use of gabapentin, dexamethasone, and their combination in varicocele surgery: a randomized controlled trial. Anesth Analg, 2007. 105 (4): p. 1137-42, table of contents. Kim, S.I., K.Y. Ha, and I.S. Oh, Preemptive multimodal analgesia for postoperative pain management after lumbar fusion surgery: a randomized controlled trial. Eur Spine J, 2016. 25 (5): p. 1614–1619. Soffin, E.M., et al., An enhanced recovery after surgery pathway: association with rapid discharge and minimal complications after anterior cervical spine surgery. Neurosurg Focus, 2019. 46 (4): p. E9. Doleman, B., et al., A systematic review and meta-regression analysis of prophylactic gabapentin for postoperative pain. Anaesthesia, 2015. 70 (10): p. 1186 − 204. Lou, Y., et al., Efficacy of Dexamethasone Injection at Different Sites on Postoperative Sequelae After Extracting Mandibular Impacted Third Molars: A Randomized Controlled Trial. J Oral Maxillofac Surg, 2024. 82 (9): p. 1129–1138. Buvanendran, A., et al., Perioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg, 2010. 110 (1): p. 199–207. Footnotes From repeated-measures ANOVA (group effect). p-values from one-way ANOVA with Tukey's post-hoc test. All inter-group comparisons were significant (p 180 mg/dL Reported at 30-day follow-up. Additional Declarations No competing interests reported. Supplementary Files LaminectomyPainData.csv Cite Share Download PDF Status: Published Journal Publication published 20 Apr, 2026 Read the published version in European Spine Journal → Version 1 posted Editorial decision: Revision requested 25 Mar, 2026 Reviews received at journal 10 Mar, 2026 Reviews received at journal 26 Feb, 2026 Reviews received at journal 19 Feb, 2026 Reviewers agreed at journal 13 Feb, 2026 Reviewers agreed at journal 11 Feb, 2026 Reviewers agreed at journal 10 Feb, 2026 Reviewers agreed at journal 10 Feb, 2026 Reviewers invited by journal 08 Jan, 2026 Editor assigned by journal 29 Dec, 2025 Submission checks completed at journal 29 Dec, 2025 First submitted to journal 26 Dec, 2025 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. 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1","display":"","copyAsset":false,"role":"figure","size":195845,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT Flow Diagram\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8457462/v1/ce63c9e657de77dfc130ec6c.jpg"},{"id":107928042,"identity":"6f039f8d-6a4b-40e6-b763-e6866a8c402e","added_by":"auto","created_at":"2026-04-27 16:06:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":488338,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8457462/v1/af285d96-eccc-4f8a-95e8-f1d0151dc455.pdf"},{"id":100360966,"identity":"3e380c69-8d09-4685-96ad-a3dcb6cd4beb","added_by":"auto","created_at":"2026-01-16 07:44:15","extension":"csv","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":55739,"visible":true,"origin":"","legend":"","description":"","filename":"LaminectomyPainData.csv","url":"https://assets-eu.researchsquare.com/files/rs-8457462/v1/686527d09970478058189a84.csv"}],"financialInterests":"No competing interests reported.","formattedTitle":"Combination of Dexamethasone and Pregabalin for Postoperative Pain After Laminectomy: A Randomized Controlled Trial","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePostoperative pain following lumbar laminectomy is often severe, resulting from extensive tissue dissection, muscle retraction, and potential neural element manipulation. Inadequately managed acute pain can lead to a cascade of adverse outcomes, including delayed mobilization, increased risk of thromboembolic events, prolonged hospital stay, higher opioid consumption with its attendant side effects, and may contribute to the development of chronic post-surgical pain\u0026mdash;a significant concern in spine surgery populations[1, 2]\u003c/p\u003e \u003cp\u003eThe pursuit of effective analgesia while minimizing opioid-related complications, such as respiratory depression, ileus, nausea, and the potential for long-term dependence, remains a paramount objective in perioperative care.[3] This has led to the widespread adoption of multimodal analgesic strategies, which combine medications with distinct mechanisms of action to target multiple pain pathways simultaneously. The goal is to achieve synergistic or additive effects, allowing for lower doses of individual agents and an improved side-effect profile, aligning with Enhanced Recovery After Surgery (ERAS) principles.[4]\u003c/p\u003e \u003cp\u003eDexamethasone, a potent glucocorticoid, is a well-established adjunct in multimodal regimens. Its perioperative analgesic and opioid-sparing effects are attributed to its potent anti-inflammatory properties, primarily through the inhibition of phospholipase A2 and the subsequent suppression of prostaglandin and cytokine synthesis at the surgical site [5, 6] Meta-analyses support its efficacy in reducing pain scores and opioid requirements across various surgical procedures.[7]\u003c/p\u003e \u003cp\u003ePregabalin, a gabapentinoid, modulates neuropathic pain and central sensitization by binding to the α2-δ subunit of presynaptic voltage-gated calcium channels in the central nervous system. This action reduces the release of excitatory neurotransmitters (e.g., glutamate, substance P), thereby attenuating postoperative hyperalgesia[8, 9] Its use in acute postoperative pain management, particularly in surgeries with a significant neuropathic component like spinal procedures, has been extensively studied, though with variable conclusions regarding its risk-benefit ratio..[10, 11]\u003c/p\u003e \u003cp\u003eWhile the individual roles of dexamethasone and pregabalin are recognized, a significant knowledge gap exists regarding their combined use, specifically in lumbar laminectomy. Furthermore, the optimal dose of perioperative dexamethasone in this context is not well-defined, with common clinical practice oscillating between 4 mg and 8 mg. It is plausible that a higher anti-inflammatory dose of dexamethasone might interact more effectively with the central neuromodulatory action of pregabalin, potentially yielding superior outcomes compared to either drug alone or lower-dose combinations.\u003c/p\u003e \u003cp\u003eThis study was therefore designed to investigate the efficacy and safety of two different doses of intravenous dexamethasone (4 mg versus 8 mg), each combined with or without a single preoperative dose of oral pregabalin (150 mg), in patients undergoing elective lumbar laminectomy. We hypothesized that the combination of 8 mg dexamethasone with pregabalin would provide more effective analgesia and greater opioid-sparing effects over the first 24 postoperative hours compared to lower-dose combinations or monotherapy.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study Design and Ethical Approval\u003c/h2\u003e \u003cp\u003eThis single-center, prospective, randomized, double-blind, placebo-controlled trial was approved by the Institutional Ethics Committee (IR.TBZMED.REC.1403.156) and registered (IRCT20190325043107N11). Written informed consent was obtained. The manuscript adheres to CONSORT guidelines.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Participants\u003c/h2\u003e \u003cp\u003e800 adult patients (ASA I-II) scheduled for elective 2\u0026ndash;3 level lumbar laminectomy were recruited. Key exclusion criteria were: emergency surgery; drug hypersensitivity; BMI\u0026thinsp;\u0026gt;\u0026thinsp;40 kg/m\u0026sup2;; uncontrolled diabetes mellitus or hypertension; significant renal/hepatic impairment; substance abuse; chronic opioid/gabapentinoid use; major psychiatric disorders; glaucoma; active infection; or previous spinal surgery within 6 months. These criteria aimed to ensure homogeneity and initial safety but limit generalizability.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Sample Size Calculation\u003c/h2\u003e \u003cp\u003eBased on a pilot study anticipating a 20% difference in 24-hour opioid consumption with an SD of 25 mg morphine equivalents, 160 patients per group provided 90% power (α\u0026thinsp;=\u0026thinsp;0.05). Accounting for minimal attrition, 200 per group were recruited.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Randomization and Blinding\u003c/h2\u003e \u003cp\u003ePatients were randomized 1:1:1:1 via computer-generated blocks (size 8). Allocation was concealed using sequentially numbered, opaque, sealed envelopes opened by a research pharmacist who prepared the study drugs. All IV solutions and oral capsules were identical. The administering anesthesiologist, postoperative caregivers, outcome assessors, and data analyst were blinded to group assignment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Intervention and Standardization\u003c/h2\u003e \u003cp\u003eOne hour preoperatively, patients received oral pregabalin 150 mg or placebo. In the operating room, IV dexamethasone (4 mg, 8 mg) or volume-matched saline was given.\u003c/p\u003e \u003cp\u003eA standardized anesthetic protocol was mandated: induction with propofol (2-2.5 mg/kg) and fentanyl (2\u0026ndash;3 \u0026micro;g/kg), muscle relaxation with atracurium, maintenance with sevoflurane (1-1.5 MAC). No other intraoperative analgesics (e.g., ketamine, lidocaine, NSAIDs) were permitted. Intraoperative fentanyl boluses (0.5-1 \u0026micro;g/kg) were allowed at the anesthesiologist's discretion and recorded.\u003c/p\u003e \u003cp\u003ePostoperative mobilization followed a standardized protocol (sitting at 4h, standing at 6h, ambulating with assistance at 8h).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6. Postoperative Management and Data Collection\u003c/h2\u003e \u003cp\u003eRescue analgesia was IV morphine 2 mg boluses, then PCA morphine (1 mg bolus, 10-min lockout). Data collected by a blinded researcher included:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003ePrimary Outcome\u003c/em\u003e: Pain VAS (0\u0026ndash;10) at PACU discharge, and 1, 2, 4, 6, 12, 24h post-discharge.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eSecondary Outcomes\u003c/em\u003e: Time to first rescue analgesia; total 24-hour morphine consumption (all boluses\u0026thinsp;+\u0026thinsp;PCA); hemodynamics (SBP, DBP, HR) at baseline, induction, PACU discharge, and serial times; adverse events (sedation/dizziness, PONV, pruritus, headache, respiratory depression, hyperglycemia\u0026thinsp;\u0026gt;\u0026thinsp;180 mg/dL, surgical site infection at 30 days).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAssessor Training: All nursing and research staff collecting VAS and sedation scores underwent standardized training before the study to ensure consistent assessment.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7. Statistical Analysis\u003c/h2\u003e \u003cp\u003eData analyzed using SPSS v26 and R. Normally distributed continuous data (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) compared with one-way ANOVA (Tukey's post-hoc). Longitudinal data (pain, hemodynamics) analyzed with two-way repeated-measures ANOVA. A pre-specified 2x2 factorial ANOVA assessed main and interaction effects on 24-hour opioid consumption. Categorical data compared with Chi-square/Fisher's exact test. Intention-to-treat analysis. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003e3.1. Participant Flow and Baseline Characteristics\u003c/h2\u003e\n \u003cp\u003eDuring the study period, 1025 patients were assessed for eligibility. Of these, 225 were excluded (145 did not meet inclusion criteria, 80 declined to participate). The remaining 800 patients were randomized (200 per group). All randomized patients received the intended intervention and completed the 24-hour follow-up, with no dropouts or protocol deviations, resulting in 800 patients included in the ITT analysis (Fig.\u0026nbsp;1).\u003c/p\u003e\n \u003cp\u003eThe four groups were well-balanced with respect to all baseline demographic and clinical characteristics (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05 for all comparisons) (Table\u0026nbsp;1).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eBaseline Demographic and Clinical Characteristics of the Study Groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup A (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup B (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup C (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup D (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e43.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e43.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e44.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e43.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e0.642\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSex (Male/Female)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e115/85\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e120/80\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e105/95\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e110/90\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e0.792\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI (kg/m\u0026sup2;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e27.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e27.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e27.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e27.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.824\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eASA I/II\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e85/115\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e82/118\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e88/112\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e84/116\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.901\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery Duration (min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e102.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e104.9\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e103.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e104.2\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.703\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnesthesia Duration (min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e128.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e130.2\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e129.1\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e129.8\u0026thinsp;\u0026plusmn;\u0026thinsp;16.0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.815\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaminectomy Levels (2/3)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e135/65\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e130/70\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e140/60\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e132/68\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.745\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntraop. Fentanyl (\u0026micro;g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e225.5\u0026thinsp;\u0026plusmn;\u0026thinsp;35.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e230.1\u0026thinsp;\u0026plusmn;\u0026thinsp;36.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e228.3\u0026thinsp;\u0026plusmn;\u0026thinsp;34.9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e231.4\u0026thinsp;\u0026plusmn;\u0026thinsp;37.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.558\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003e3.2. Postoperative Pain Scores\u003c/h2\u003e\n \u003cp\u003ePain VAS scores differed significantly among groups across all time points (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for group effect, time effect, and group*time interaction in repeated-measures ANOVA). Group A (8 mg Dex\u0026thinsp;+\u0026thinsp;PGB) consistently reported the lowest pain scores, followed by Group C (4 mg Dex\u0026thinsp;+\u0026thinsp;PGB). Groups B and D (without pregabalin) reported higher pain, with Group D (4 mg Dex alone) showing the highest scores at most time points (Table\u0026nbsp;2).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparison of Postoperative Pain Scores (VAS, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTime Point\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup A (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup B (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup C (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup D (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePACU Discharge\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e4.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e4.10\u0026thinsp;\u0026plusmn;\u0026thinsp;1.20\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e5.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e1-hour\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3.81\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e2-hour\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.10\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e4-hour\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.84\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e6-hour\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e12-hour\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e24-hour\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\"\u003e\n \u003ch2\u003e3.3. Postoperative Opioid Consumption and Analgesia Duration\u003c/h2\u003e\n \u003cp\u003eThe 24-hour cumulative opioid consumption differed significantly among groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Group A required the least amount of morphine (177.0\u0026thinsp;\u0026plusmn;\u0026thinsp;25.5 mg, 95% CI: 173.5-180.5), which was significantly lower than all other groups. The order of consumption was: Group A\u0026thinsp;\u0026lt;\u0026thinsp;Group C (204.0\u0026thinsp;\u0026plusmn;\u0026thinsp;29.5 mg, 95% CI: 200.0-208.0)\u0026thinsp;\u0026lt;\u0026thinsp;Group B (228.5\u0026thinsp;\u0026plusmn;\u0026thinsp;31.5 mg, 95% CI: 224.1-232.9)\u0026thinsp;\u0026lt;\u0026thinsp;Group D (250.5\u0026thinsp;\u0026plusmn;\u0026thinsp;33.5 mg, 95% CI: 245.8-255.2) (Table\u0026nbsp;3). The time to first rescue analgesia was longest in Group A (125.4\u0026thinsp;\u0026plusmn;\u0026thinsp;45.6 min) and shortest in Group D (68.3\u0026thinsp;\u0026plusmn;\u0026thinsp;32.1 min) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n \u003cp\u003eFormal 2x2 factorial ANOVA on 24-hour opioid consumption revealed significant main effects for dexamethasone dose (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and pregabalin administration (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as well as a statistically significant interaction effect (p\u0026thinsp;=\u0026thinsp;0.012), indicating a synergistic interaction between the higher dose of dexamethasone (8 mg) and pregabalin.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparison of 24-hour Cumulative Opioid Consumption (Morphine Equivalents, mg)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e24-hour Opioid Consumption (mg) Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% Confidence Interval\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value (vs. Group D)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup A\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e177.0\u0026thinsp;\u0026plusmn;\u0026thinsp;25.5\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e173.5\u0026ndash;180.5\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup B\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e228.5\u0026thinsp;\u0026plusmn;\u0026thinsp;31.5\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e224.1\u0026ndash;232.9\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e200\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e204.0\u0026thinsp;\u0026plusmn;\u0026thinsp;29.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e200.0\u0026ndash;208.0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup D\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e200\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e250.5\u0026thinsp;\u0026plusmn;\u0026thinsp;33.5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e245.8\u0026ndash;255.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eReference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003e3.4. Hemodynamic Stability\u003c/strong\u003eGroups receiving pregabalin (A and C) exhibited greater hemodynamic stability, with significantly less fluctuation in SBP, DBP, and HR over the 24-hour period compared to groups B and D (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for group*time interaction in repeated-measures ANOVA). Group A showed the most stable profile, with the lowest incidence of hypertension (SBP\u0026thinsp;\u0026gt;\u0026thinsp;160 mmHg) and tachycardia (HR\u0026thinsp;\u0026gt;\u0026thinsp;100 bpm) in response to pain.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3.5. Adverse Events\u003c/strong\u003eThe overall adverse event profile is summarized in Table\u0026nbsp;4. Sedation and dizziness were significantly more common in the pregabalin groups (A \u0026amp; C) during the first 6\u0026ndash;8 hours post-dose. No episodes of severe respiratory depression occurred. The incidence of postoperative nausea and vomiting (PONV) was significantly lower in groups receiving dexamethasone (A, B) compared to groups C and D. There were no statistically significant differences among groups in the rates of surgical site infection (assessed at 30-day follow-up) or significant hyperglycemia requiring intervention.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis large, randomized controlled trial demonstrates that a preemptive multimodal regimen combining 8 mg intravenous dexamethasone with 150 mg oral pregabalin provides superior analgesic outcomes for patients undergoing elective laminectomy. The combination resulted in the lowest pain scores, a 29.3% reduction in 24-hour opioid consumption compared to the weakest regimen (4 mg dexamethasone alone), the longest time to first rescue analgesia, and the most stable hemodynamic profile. The formal finding of a statistically significant interaction effect supports a synergistic, rather than merely additive, benefit from combining the higher-dose steroid with the gabapentinoid. Effective pain management after lumbar laminectomy is critical, as poorly controlled acute pain can impede early mobilization\u0026mdash;a key factor in preventing complications like deep vein thrombosis and aiding functional recovery.[2, 11]Furthermore, severe acute postoperative pain is a known risk factor for the development of chronic neuropathic pain after spinal surgery.[1]Our findings align with and extend the growing literature on multimodal analgesia in spine surgery. The significant opioid-sparing effect (approximately 73.5 mg less morphine over 24 hours in Group A vs. Group D) is clinically meaningful, as it directly correlates with a lower risk of opioid-related side effects such as respiratory depression, ileus, and sedation, potentially facilitating faster recovery and earlier discharge.[3, 12] The mechanism behind the observed synergy is plausible. Dexamethasone acts peripherally and centrally to blunt the inflammatory cascade and cytokine-mediated sensitization following surgical trauma.[5, 7] Pregabalin modulates central pain processing by attenuating neuronal hyperexcitability and dampening the neuropathic component common in spine surgery patients.[8, 13] Their concurrent use thus targets multiple pain pathways\u0026mdash;inflammatory, somatic, and neuropathic\u0026mdash;simultaneously. The greater efficacy of the 8 mg dose over the 4 mg dose, particularly when combined with pregabalin, suggests a dose-dependent effect for dexamethasone in this context, consistent with some studies in other surgical models.[14] The improved hemodynamic stability in pregabalin groups likely stems from its anxiolytic properties and a more effective mitigation of the sympathetic stress response triggered by surgical trauma and pain.[15]However, this benefit must be weighed against the increased incidence of transient sedation and dizziness, which, while not leading to serious complications in our relatively healthy cohort, warrants caution, especially in elderly patients or those with balance disorders. This study has important limitations that must be acknowledged. First, the stringent exclusion criteria, while ensuring internal validity and patient safety for this initial evaluation, created a homogenous cohort of relatively healthy, younger adults. Consequently, the generalizability of these findings to the broader, often older and comorbid, population undergoing spinal surgery is significantly limited. Patients with diabetes, hypertension, or those on chronic medications were not represented. Second, the single-center design and highly standardized protocol, which contributed to the lack of dropouts and protocol deviations, may not reflect real-world variability in practice. The absence of attrition, while strengthening the ITT analysis, is unusual in large surgical trials and should be considered when interpreting feasibility for other settings. Third, the 24-hour follow-up period does not inform on longer-term outcomes like chronic pain development or functional recovery. Fourth, despite assessor training, the subjective nature of pain scoring retains inherent measurement bias potential. Finally, while the factorial analysis indicated interaction, confirming true clinical synergy requires dedicated dose-ranging studies.\u003c/p\u003e "},{"header":"Conclusion","content":"\u003cp\u003e Within the constraints of its design and patient population, this trial demonstrates that preemptive combination of 8 mg IV dexamethasone and 150 mg oral pregabalin provides effective analgesia and opioid-sparing in the first 24 hours after elective laminectomy, albeit with increased sedation. These results support the potential utility of this combination within multimodal analgesic protocols for spinal surgery. However, caution is advised in extrapolating these results to typical, more comorbid surgical populations. Future multi-center studies with broader inclusion criteria and longer follow-up are warranted to confirm these findings and establish external validity.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIncidence of Adverse Events within 24 Hours Postoperatively, n (%)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse Event\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup A (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup B (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup C (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGroup D (n\u0026thinsp;=\u0026thinsp;200)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSedation/Dizziness\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (22.5%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (5.0%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (20.0%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (5.0%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea/Vomiting\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (10.0%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (11.0%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (25.0%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55 (27.5%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePruritus\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e15 (7.5%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e18 (9.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e20 (10.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e25 (12.5%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.275\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHeadache\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e10 (5.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e12 (6.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e8 (4.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e14 (7.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.521\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHyperglycemia\u003c/b\u003e\u003ca class=\"FNLink\" href=\"#Fn3\" id=\"#FNLinkFn3\"\u003e\u003c/a\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e30 (15.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e28 (14.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e25 (12.5%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e22 (11.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.612\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgical Site Infection\u003c/b\u003e\u003ca class=\"FNLink\" href=\"#Fn4\" id=\"#FNLinkFn4\"\u003e\u003c/a\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e2 (1.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e3 (1.5%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e1 (0.5%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e2 (1.0%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.823\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eCredit Author StatementMehrdad Zamani : Conceptualization, Methodology, Supervision, Review \u0026amp; Editing. Writing - Original Draft. Ali Sadighi: Data curation , Validation Writing - Review \u0026amp; Editing. Resources, SoftwareAran Nikpay: Data curation, Investigation, Methodology, Supervision. Supervision ,Sajjad Valizadeh: Formal analysis, Investigation, Project administration,All authors: Read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors would like to thanks clinical research development unit , Shohada hospital, Tabriz university of medical science, Tabriz, Iran for kind support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eClarke, H., et al., \u003cem\u003eAcute pain after total hip arthroplasty does not predict the development of chronic postsurgical pain 6 months later.\u003c/em\u003e J Anesth, 2010. \u003cb\u003e24\u003c/b\u003e(4): p. 537 − 43.\u003c/li\u003e\n\u003cli\u003eGerbershagen, H.J., et al., \u003cem\u003ePain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures.\u003c/em\u003e Anesthesiology, 2013. \u003cb\u003e118\u003c/b\u003e(4): p. 934 − 44.\u003c/li\u003e\n\u003cli\u003eSun, E.C., et al., \u003cem\u003eIncidence of and Risk Factors for Chronic Opioid Use Among Opioid-Naive Patients in the Postoperative Period.\u003c/em\u003e JAMA Intern Med, 2016. \u003cb\u003e176\u003c/b\u003e(9): p. 1286-93.\u003c/li\u003e\n\u003cli\u003eWick, E.C., M.C. Grant, and C.L. Wu, \u003cem\u003ePostoperative Multimodal Analgesia Pain Management With Nonopioid Analgesics and Techniques: A Review.\u003c/em\u003e JAMA Surg, 2017. \u003cb\u003e152\u003c/b\u003e(7): p. 691–697.\u003c/li\u003e\n\u003cli\u003eDe Oliveira, G.S., Jr., et al., \u003cem\u003ePerioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials.\u003c/em\u003e Anesthesiology, 2011. \u003cb\u003e115\u003c/b\u003e(3): p. 575 − 88.\u003c/li\u003e\n\u003cli\u003eWaldron, N.H., et al., \u003cem\u003eImpact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis.\u003c/em\u003e Br J Anaesth, 2013. \u003cb\u003e110\u003c/b\u003e(2): p. 191–200.\u003c/li\u003e\n\u003cli\u003eLiu, L., et al., \u003cem\u003eEfficacy and Safety of First-Line Immunotherapy Combinations for Advanced NSCLC: A Systematic Review and Network Meta-Analysis.\u003c/em\u003e J Thorac Oncol, 2021. \u003cb\u003e16\u003c/b\u003e(7): p. 1099–1117.\u003c/li\u003e\n\u003cli\u003eMishriky, B.M., N.H. Waldron, and A.S. Habib, \u003cem\u003eImpact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis.\u003c/em\u003e Br J Anaesth, 2015. \u003cb\u003e114\u003c/b\u003e(1): p. 10–31.\u003c/li\u003e\n\u003cli\u003eZhang, J., K.Y. Ho, and Y. Wang, \u003cem\u003eEfficacy of pregabalin in acute postoperative pain: a meta-analysis.\u003c/em\u003e Br J Anaesth, 2011. \u003cb\u003e106\u003c/b\u003e(4): p. 454 − 62.\u003c/li\u003e\n\u003cli\u003eKoç, S., D. Memis, and N. Sut, \u003cem\u003eThe preoperative use of gabapentin, dexamethasone, and their combination in varicocele surgery: a randomized controlled trial.\u003c/em\u003e Anesth Analg, 2007. \u003cb\u003e105\u003c/b\u003e(4): p. 1137-42, table of contents.\u003c/li\u003e\n\u003cli\u003eKim, S.I., K.Y. Ha, and I.S. Oh, \u003cem\u003ePreemptive multimodal analgesia for postoperative pain management after lumbar fusion surgery: a randomized controlled trial.\u003c/em\u003e Eur Spine J, 2016. \u003cb\u003e25\u003c/b\u003e(5): p. 1614–1619.\u003c/li\u003e\n\u003cli\u003eSoffin, E.M., et al., \u003cem\u003eAn enhanced recovery after surgery pathway: association with rapid discharge and minimal complications after anterior cervical spine surgery.\u003c/em\u003e Neurosurg Focus, 2019. \u003cb\u003e46\u003c/b\u003e(4): p. E9.\u003c/li\u003e\n\u003cli\u003eDoleman, B., et al., \u003cem\u003eA systematic review and meta-regression analysis of prophylactic gabapentin for postoperative pain.\u003c/em\u003e Anaesthesia, 2015. \u003cb\u003e70\u003c/b\u003e(10): p. 1186 − 204.\u003c/li\u003e\n\u003cli\u003eLou, Y., et al., \u003cem\u003eEfficacy of Dexamethasone Injection at Different Sites on Postoperative Sequelae After Extracting Mandibular Impacted Third Molars: A Randomized Controlled Trial.\u003c/em\u003e J Oral Maxillofac Surg, 2024. \u003cb\u003e82\u003c/b\u003e(9): p. 1129–1138.\u003c/li\u003e\n\u003cli\u003eBuvanendran, A., et al., \u003cem\u003ePerioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial.\u003c/em\u003e Anesth Analg, 2010. \u003cb\u003e110\u003c/b\u003e(1): p. 199–207.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Footnotes","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e \u003cb\u003eFrom repeated-measures ANOVA (group effect).\u003c/b\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e p-values from one-way ANOVA with Tukey's post-hoc test. All inter-group comparisons were significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Blood glucose\u0026thinsp;\u0026gt;\u0026thinsp;180 mg/dL\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e Reported at 30-day follow-up.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-spine-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"esjo","sideBox":"Learn more about [European Spine Journal](http://link.springer.com/journal/586)","snPcode":"586","submissionUrl":"https://submission.springernature.com/new-submission/586/3","title":"European Spine Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Laminectomy, Postoperative Pain, Multimodal Analgesia, Dexamethasone, Pregabalin, Randomized Controlled Trial","lastPublishedDoi":"10.21203/rs.3.rs-8457462/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8457462/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eMultimodal analgesia is standard for post-laminectomy pain. This study evaluated two intravenous dexamethasone doses, with or without oral pregabalin, within this framework.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this randomized, double-blind, placebo-controlled trial, 800 adult patients undergoing elective 2\u0026ndash;3 level lumbar laminectomy were allocated to: Group A (8 mg IV dexamethasone\u0026thinsp;+\u0026thinsp;150 mg oral pregabalin), Group B (8 mg IV dexamethasone\u0026thinsp;+\u0026thinsp;oral placebo), Group C (4 mg IV dexamethasone\u0026thinsp;+\u0026thinsp;150 mg oral pregabalin), or Group D (4 mg IV dexamethasone\u0026thinsp;+\u0026thinsp;oral placebo). Drugs were given preemptively. Primary outcome was pain scores (Visual Analogue Scale, VAS) over 24 hours. Secondary outcomes included 24-hour opioid consumption (morphine equivalents), time to first rescue analgesia, hemodynamics, and adverse events.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAll patients completed the protocol. Statistically significant differences in VAS scores were observed among groups at all time points (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with Group A reporting the lowest scores. Twenty-four-hour opioid consumption was also significantly different (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), being lowest in Group A. A formal factorial analysis indicated a statistically significant interaction effect (p\u0026thinsp;=\u0026thinsp;0.012) between the higher dexamethasone dose and pregabalin. Sedation/dizziness was more frequent in pregabalin groups (A: 22.5%; C: 20.0%) versus placebo groups (B \u0026amp; D: 5.0% each; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant differences in surgical site infections or hyperglycemia were noted.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn a selected cohort of patients undergoing elective laminectomy, preemptive administration of 8 mg IV dexamethasone combined with 150 mg oral pregabalin was associated with statistically significant reductions in pain scores and opioid requirements over 24 hours compared to lower doses or monotherapy, alongside greater hemodynamic stability but increased neurosedative effects. This combination represents a potential option within multimodal analgesia protocols for spinal surgery, though its generalizability to broader patient populations requires further study.\u003c/p\u003e\u003ch2\u003eLevel of evidence: 1\u003c/h2\u003e","manuscriptTitle":"Combination of Dexamethasone and Pregabalin for Postoperative Pain After Laminectomy: A Randomized Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 05:25:31","doi":"10.21203/rs.3.rs-8457462/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-25T18:00:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-11T00:11:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-26T13:52:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-19T09:52:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"160189489521435076430056133593835075591","date":"2026-02-13T09:27:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"209948361268238262385616703312376727355","date":"2026-02-12T02:24:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"284263026905227301686852408982505511239","date":"2026-02-11T04:34:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"219572705844914438974166837689046145108","date":"2026-02-11T03:55:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-08T17:58:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-29T06:15:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-29T06:14:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Spine Journal","date":"2025-12-26T19:53:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-spine-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"esjo","sideBox":"Learn more about [European Spine Journal](http://link.springer.com/journal/586)","snPcode":"586","submissionUrl":"https://submission.springernature.com/new-submission/586/3","title":"European Spine Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"e8f00720-bf38-4249-b4d0-40bb73f1eeda","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-27T16:04:39+00:00","versionOfRecord":{"articleIdentity":"rs-8457462","link":"https://doi.org/10.1007/s00586-026-09954-6","journal":{"identity":"european-spine-journal","isVorOnly":false,"title":"European Spine Journal"},"publishedOn":"2026-04-20 15:57:17","publishedOnDateReadable":"April 20th, 2026"},"versionCreatedAt":"2026-01-12 05:25:31","video":"","vorDoi":"10.1007/s00586-026-09954-6","vorDoiUrl":"https://doi.org/10.1007/s00586-026-09954-6","workflowStages":[]},"version":"v1","identity":"rs-8457462","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8457462","identity":"rs-8457462","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}