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

Not Applicable

Not yet recruiting

• Conditions: Postoperative Adjuvant Treatment; Morbid Obesity Requiring Bariatric Surgery; Postoperative Analgesia; Postoperative Pain; Postoperative Pain Management; Postoperative Inflammatory Markers; Postoperative Inflammatory Response
• Interventions: Drug: Intravenous Lidocaine infusion + Standard Anesthesia; Drug: Intravenous Dexmedetomidine infusion + Standard Anesthesia; Drug: Lidocaine + Dexmedetomidine Combination (LIDEX) + Standard Anesthesia; Drug: 0.9 % Saline Placebo + Standard Anesthesia

• Registration Number: NCT07073846
• Lead Sponsor: Instituto Mexicano del Seguro Social

Brief Summary

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.

Study Timeline

• Study First Submitted: 2025-06-30
• Status Verified: 2025-07
• Study First Submitted QC: 2025-07-16
• Last Update Submitted: 2025-07-16
• Study First Posted: 2025-07-18
• Last Update Posted: 2025-07-18
• Study Start: 2025-08-01
• Primary Completion: 2026-02-01
• Study Completion: 2027-05-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 104

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lidocaine Infusion (LID)	Intravenous Lidocaine infusion + Standard Anesthesia	Intra-operative IV lidocaine 1 % at ≈ 1.5 mg·kg-¹·h-¹ (0.3 mL·kg-¹·h-¹). Infusion starts after induction and stops at skin closure; no post-operative infusion.
Dexmedetomidine Infusion (DEX)	Intravenous Dexmedetomidine infusion + Standard Anesthesia	Intra-operative IV dexmedetomidine ≈ 0.3 µg·kg-¹·h-¹ (0.3 mL·kg-¹·h-¹) without loading dose, from induction to skin closure.
Lidocaine + Dexmedetomidine (LIDEX)	Lidocaine + Dexmedetomidine Combination (LIDEX) + Standard Anesthesia	Concurrent IV lidocaine 1 % (1.5 mg·kg-¹·h-¹) plus dexmedetomidine (0.3 µg·kg-¹·h-¹) in the same syringe, administered from induction to skin closure.
Saline Placebo	0.9 % Saline Placebo + Standard Anesthesia	IV 0.9 % saline at 0.3 mL·kg-¹·h-¹ for the same duration as active arms; syringe identical in appearance.

Primary Outcome Measures

Name	Time	Method
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.	24 hours post-operative	* For most items (e.g., pain intensity, interference with activities, emotional impact), \*\*higher scores indicate worse outcomes\*\*.; * For items such as pain relief and satisfaction, \*\*higher scores indicate better outcomes\*\*.; Items include: * Highest and lowest pain intensity experienced since surgery; * Proportion of time spent in pain; * How pain limited physical activities (e.g., coughing, moving, walking); * Impact of pain on mood and emotional well-being; * Adverse effects attributed to pain medication (e.g., nausea, dizziness); * Overall degree of pain relief obtained; * Desire for additional analgesic treatment; * Clarity and usefulness of information received about pain therapy; * Extent of patient involvement in treatment decisions; * Global satisfaction with pain management; * Use of non-pharmacological methods for pain relief; * Presence of pre-existing pain before hospital admission

Secondary Outcome Measures

Name	Time	Method
Change in pro-inflammatory cytokine (IL-1β, IL-6, TNF-α) and anti -inflammatory IL-10 panel	Day 0 - after anesthesia induction, end of surgery, and 3 hours postoperatively	Serum concentrations of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α) measured by multiplex ELISA (pg mL-¹). The primary comparison is the change from baseline and the area-under-curve (AUC₀-₃ h) across the four treatment arms; lower values indicate a reduced systemic inflammatory response.
Change in oxidative-stress marker panel (MDA, GSH/GSSG ratio, SOD, catalase, neutrophil respiratory burst)	Day 0 - after anesthesia induction, end of surgery, and 3 hours postoperatively	Plasma malondialdehyde (MDA, µmol L-¹; TBARS assay), glutathione redox ratio (GSH/GSSG), superoxide-dismutase activity (SOD, U mL-¹) and catalase activity (U mL-¹) will be quantified with spectrophotometric/enzymatic methods. Neutrophil respiratory burst (reactive oxygen-species production) will be assessed by flow cytometry using DCFH-DA and expressed as mean fluorescence intensity (MFI). Change from baseline and the area-under-the-curve (AUC₀-3 h) will be compared across the four study arms; lower MDA/MFI and higher antioxidant indices indicate less oxidative stress.

Trial Locations

Locations (1)

Unidad Médica de Alta Especialidad Hospital de Especialidades del Centro Médico Nacional Siglo XXI; 🇲🇽 Mexico City, Mexico