Morbid Obesity Requiring Bariatric Surgery, Postoperative Adjuvant Treatment, Postoperative Analgesia, Postoperative Inflammatory Markers, Postoperative Inflammatory Response, Postoperative Pain, Postoperative Pain Management
Conditions
Keywords
Bariatric Surgery, Laparoscopic Sleeve Gastrectomy, Laparoscopic Gastric Bypass, Pain Management, Lidocaine-Dexmedetomidine, Multimodal Analgesia, Inflammatory Cytokines, Oxidative Stress, Opioid-sparing Anesthesia, Enhanced Recovery (ERAS), Postoperarive Oxidative Stress
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.
Interventions
DRUGIntravenous 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.
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.
DRUGLidocaine + 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.
DRUG0.9 % 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.
Sponsors
Instituto Mexicano del Seguro Social
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Randomisation codes are generated in 13 permuted blocks of eight by an independent investigator who is not involved in patient care or outcome assessment. The codes are printed, placed in sequentially numbered, opaque, sealed envelopes, and handed to the study nursing team. Immediately before anaesthetic induction, a research nurse opens the next envelope and communicates the allocation to a second nurse-preparer (also independent from clinical care). This nurse draws up a visually identical 50 mL syringe containing lidocaine, dexmedetomidine, the fixed-dose combination (LIDEX), or 0.9 % saline, according to the code. Each syringe is labelled only with the participant ID and infusion rate. Emergency unblinding is allowed solely for patient-safety reasons and must be reported immediately to the Data and Safety Monitoring Board.
Intervention model description
Randomized, quadruple-masked, four-arm parallel design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Mexico
Contacts
Primary ContactDulce M Rascón Martínez, Prof MD, MSc
Backup ContactArnulfo Calixto Flores, Prof MD, PhD
Outcome results
None listed