Efficacy of Lidocaine-Dexmedetomidine Combination Therapy in Reducing Post-Operative Pain, Inflammatory Response, and Oxidative Stress in Patients Undergoing Bariatric Surgery
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 104
- 试验地点
- 2
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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).
研究组 & 干预措施
Lidocaine Infusion (LID)
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.
干预措施: Intravenous Lidocaine infusion + Standard Anesthesia (Drug)
Dexmedetomidine Infusion (DEX)
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.
干预措施: Intravenous Dexmedetomidine infusion + Standard Anesthesia (Drug)
Lidocaine + Dexmedetomidine (LIDEX)
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.
干预措施: Lidocaine + Dexmedetomidine Combination (LIDEX) + Standard Anesthesia (Drug)
Saline Placebo
IV 0.9 % saline at 0.3 mL·kg-¹·h-¹ for the same duration as active arms; syringe identical in appearance.
干预措施: 0.9 % Saline Placebo + Standard Anesthesia (Drug)
结局指标
主要结局
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.
时间窗: 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
次要结局
- 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)
- 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)
研究者
Dulce Maria Rascon Martinez
Clinical Research Physician
Instituto Mexicano del Seguro Social