Effect of Lidocaine-Dexmedetomidine on Pain, Inflammation, and Oxidative Stress After Bariatric Surgery.

Official title

Efficacy of Lidocaine-Dexmedetomidine Combination Therapy in Reducing Post-Operative Pain, Inflammatory Response, and Oxidative Stress in Patients Undergoing Bariatric Surgery

Overview

The goal of this randomized clinical trial is to find out whether giving an intravenous lidocaine + dexmedetomidine combination (LIDEX) during laparoscopic bariatric surgery can lower post-operative pain, inflammation, and oxidative stress in adults with obesity. The main questions it aims to answer are: * Pain control: Does LIDEX reduce pain 24 hours after surgery, as measured with the International Pain Outcomes Questionnaire (IPOQ)? * Biomarkers: Does LIDEX lower blood levels of key inflammatory cytokines-interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10)-and oxidative-stress markers-malondialdehyde (MDA), the reduced/oxidized glutathione ratio (GSH/GSSG), superoxide dismutase (SOD), and catalase-compared with the individual drugs or saline placebo? Researchers will compare four groups: lidocaine alone, dexmedetomidine alone, LIDEX, and placebo (saline solution, a look-alike substance that contains no drug) to learn which approach works best. Participants will: * Receive an intravenous infusion of their assigned study drug(s) during surgery. * Provide three small blood samples (before surgery, immediately after, and three hours after). * Complete a short pain questionnaire (IPOQ) 24 hours after surgery.

Detailed description

Obesity is associated with chronic low-grade inflammation and persistent oxidative stress. Laparoscopic bariatric surgery-although highly effective for weight reduction-triggers an acute inflammatory cascade and a burst of reactive oxygen species that can amplify post-operative pain and delay functional recovery.

Intravenous lidocaine stabilises voltage-gated Na+ channels, limits ectopic neuronal firing and inhibits neutrophil priming; it also down-regulates the release of pro-inflammatory cytokines in abdominal procedures. Dexmedetomidine, a highly selective α2-adrenergic agonist, produces sedation and analgesia while attenuating sympathetic outflow, thereby reducing surgical catecholamine surges and cytokine release. Pre-clinical and clinical synergy studies indicate that combining these two agents (LIDEX) can provide additive anti-hyperalgesic, anti-inflammatory and antioxidant effects without increasing cardiovascular risk when each is dosed within its established therapeutic window.

In this protocol, a weight-adjusted intra-operative infusion of lidocaine plus dexmedetomidine is administered during bariatric surgery and compared with each single agent and saline. Peri-operative venous samples are collected for mechanistic profiling of systemic inflammatory and redox responses, and patient-reported pain is captured after surgery using a validated instrument. Haemodynamic parameters are continuously monitored to detect potential lidocaine toxicity or dexmedetomidine-related bradycardia and hypotension; predefined rescue algorithms are applied if thresholds are exceeded.

The study is designed to clarify whether the LIDEX combination can blunt the acute inflammatory-oxidative surge thought to drive sustained pain and metabolic stress after bariatric surgery, thereby informing future enhanced-recovery protocols that integrate multimodal analgesia with metabolic optimisation strategies.

Interventions

• Drug Intravenous Lidocaine infusion + Standard Anesthesia
  Continuous IV infusion of lidocaine 1 % (10 mg mL-¹) at 0.3 mL kg-¹ h-¹ (≈ 1.5 mg kg-¹ h-¹) from induction of anaesthesia to skin closure. No loading bolus, no post-operative infusion.
• Drug Intravenous Dexmedetomidine infusion + Standard Anesthesia
  Continuous IV infusion of dexmedetomidine 1 µg mL-¹ at 0.3 mL kg-¹ h-¹ (≈ 0.3 µg kg-¹ h-¹) without loading dose, started after induction and stopped at skin closure. No post-operative infusion.
• Drug Lidocaine + Dexmedetomidine Combination (LIDEX) + Standard Anesthesia
  Single syringe containing lidocaine 1 % (10 mg mL-¹) + dexmedetomidine 1 µg mL-¹, infused IV at 0.3 mL kg-¹ h-¹ (delivering ≈ 1.5 mg kg-¹ h-¹ lidocaine + 0.3 µg kg-¹ h-¹ dexmedetomidine) from induction to skin closure.
• Drug 0.9 % Saline Placebo + Standard Anesthesia
  Volume-matched IV infusion of 0.9 % normal saline at 0.3 mL kg-¹ h-¹ for the same duration and through the same delivery line as active arms; identical syringe appearance.

Primary outcome measures

• Assessment of postoperative pain patient perception using the Spanish International Pain Outcomes Questionnaire (IPOQ). This questionnaire includes multiple items assessed on a numerical rating scale (NRS) from 0 to 10. [Time frame: 24 hours post-operative]

Secondary outcome measures (2)

• Change in pro-inflammatory cytokine (IL-1β, IL-6, TNF-α) and anti -inflammatory IL-10 panel [Time frame: Day 0 - after anesthesia induction, end of surgery, and 3 hours postoperatively]
• Change in oxidative-stress marker panel (MDA, GSH/GSSG ratio, SOD, catalase, neutrophil respiratory burst) [Time frame: Day 0 - after anesthesia induction, end of surgery, and 3 hours postoperatively]

Eligibility criteria

Inclusion criteria

• Adults aged 18 - 60 years
• Male or female
• Elective laparoscopic bariatric surgery
• Post-operative pathway: post-anaesthesia care unit (PACU) followed by standard ward, with an expected in-hospital stay ≥ 24 h
• ASA physical-status II or III

Exclusion criteria

• Use of any loco-regional anaesthetic technique during the peri-operative period (transversus abdominis plane, paravertebral, spinal, epidural, erector spinae, or other abdominal wall blocks).
• Current substance abuse or illicit drug use.
• Previous abdominal surgery within the last 6 months.
• Known hypersensitivity or allergy to lidocaine, dexmedetomidine, amide local anaesthetics, or α₂-adrenergic agonists.
• Congestive heart failure, significant bradyarrhythmia, second- or third-degree atrio-ventricular block without pacemaker, severe hypotension, or current therapy with Class I/III anti-arrhythmic drugs.
• Estimated glomerular filtration rate (eGFR) < 60 mL min-¹ 1.73 m-² (moderate-to-severe renal impairment).
• Severe hepatic impairment (Child-Pugh C).
• Pregnancy or lactation.
• Chronic opioid consumption > 30 mg oral morphine equivalents per day for > 4 weeks
• Active seizure disorder, myasthenia gravis, or other neurologic disease contraindicating lidocaine infusion.
• Patient cannot communicate
• Patient does not want to fill in the questionnaire
• Participation in another interventional study within the past 30 days.
• Intra-operative conversion to open surgery.
• Insufficient biological sample for biomarker analysis.
• Premature discontinuation of the study drug during surgery for any reason that, in the judgement of the treating anaesthesiologist or investigators, prevents adequate exposure or assessment of safety variables (e.g., major haemorrhage > 200 mL, anaphylactic shock, failed intubation, inability to extubate, severe metabolic/respiratory acidosis, transfer to ICU while intubated).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Mexico · 2 centers

• Hospital de Especialidades Centro Medico Nacional Siglo XXI — Mexico City
• Unidad Médica de Alta Especialidad Hospital de Especialidades del Centro Médico Nacional S — Mexico City

Publications

• Xie D, Wang F, Wen W, Li H. Postoperative analgesic effect of intravenous coinjection of lidocaine and dexmedetomidine in gynaecological surgery: a systematic review and meta-analysis. BMJ Open. 2024 Dec 11;14(12):e091904. doi: 10.1136/bmjopen-2024-091904. PMID 39663167
• Rekatsina M, Theodosopoulou P, Staikou C. Effects of Intravenous Dexmedetomidine Versus Lidocaine on Postoperative Pain, Analgesic Consumption and Functional Recovery After Abdominal Gynecological Surgery: A Randomized Placebo-controlled Double Blind Study. Pain Physician. 2021 Nov;24(7):E997-E1006. PMID 34704710
• Zhang Y, Zhou Y, Hu T, Tong X, He Y, Li X, Huang L, Fu Q. Dexmedetomidine reduces postoperative pain and speeds recovery after bariatric surgery: a meta-analysis of randomized controlled trials. Surg Obes Relat Dis. 2022 Jun;18(6):846-853. doi: 10.1016/j.soard.2022.03.002. Epub 2022 Mar 9. PMID 35422388
• de Oliveira CMB, Coelho LMG, Valadao JA, Moura ECR, da Silva AAM, de Lima RC, Brunialti MKC, Salomao R, da Cunha Leal P, Sakata RK. Assessment of the Effect of Perioperative Venous Lidocaine on the Intensity of Pain and IL-6 Concentration After Laparoscopic Gastroplasty. Obes Surg. 2020 Oct;30(10):3912-3918. doi: 10.1007/s11695-020-04748-1. Epub 2020 Jun 12. PMID 32533519
• Xu S, Hu S, Ju X, Li Y, Li Q, Wang S. Effects of intravenous lidocaine, dexmedetomidine, and their combination on IL-1, IL-6 and TNF-alpha in patients undergoing laparoscopic hysterectomy: a prospective, randomized controlled trial. BMC Anesthesiol. 2021 Jan 6;21(1):3. doi: 10.1186/s12871-020-01219-z. PMID 33407156
• Lai Y, Chen Q, Xiang C, Li G, Wei K. Comparison of the Effects of Dexmedetomidine and Lidocaine on Stress Response and Postoperative Delirium of Older Patients Undergoing Thoracoscopic Surgery: A Randomized Controlled Trial. Clin Interv Aging. 2023 Aug 3;18:1275-1283. doi: 10.2147/CIA.S419835. eCollection 2023. PMID 37554513
• Chen X, Chen Q, Qin Z, Alam A, Zhao H, West R, Liu X, Li J, Li X, Yi B, Ma D, Gu J. Dexmedetomidine Attenuates Inflammation in Elderly Patients Following Major Hepatobiliary and Pancreatic Surgery: A Randomized Clinical Trial. Clin Interv Aging. 2024 May 29;19:981-991. doi: 10.2147/CIA.S455987. eCollection 2024. PMID 38827237
• Ohta Y, Miyamoto K, Kawazoe Y, Yamamura H, Morimoto T. Effect of dexmedetomidine on inflammation in patients with sepsis requiring mechanical ventilation: a sub-analysis of a multicenter randomized clinical trial. Crit Care. 2020 Aug 10;24(1):493. doi: 10.1186/s13054-020-03207-8. PMID 32778146

Identifiers

NCT: NCT07073846 · R-2025-3601-197

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗