Modulation of the Inflammatory Response in Bariatric Surgery

Official title

Modulation of the Inflammatory Response to Surgical Trauma: Comparison of Three Anesthetic Techniques in Bariatric Surgery Patients

Overview

This study will evaluate how different anesthesia techniques affect inflammation after bariatric surgery. Patients will be randomly assigned to receive one of three approaches: opioid-free anesthesia, intravenous anesthesia with opioids, or inhalational anesthesia with opioids. The study will measure blood levels of inflammation-related substances (such as IL-6, CRP, cortisol, ESR , WBC and lactate) at several time points before and after surgery. Heart rate variability will also be monitored as an indicator of the body's stress response. The results may help identify anesthesia strategies that reduce inflammation and improve recovery in patients undergoing bariatric surgery.

Detailed description

This is a prospective, randomized, double-blind, comparative observational study designed to assess the perioperative inflammatory response in patients undergoing bariatric surgery under three anesthetic techniques: opioid-free anesthesia (OFA), opioid-based intravenous anesthesia (OBA-IV), and opioid-based inhalational anesthesia (OBA-Inh).

A total of 90 patients scheduled for elective laparoscopic bariatric surgery will be enrolled and randomized using computer-generated allocation into three equal groups (n=30 each). Allocation concealment will be maintained using sealed opaque envelopes. Blinding will involve both the patients and outcome assessors; anesthesiologists administering the interventions will not be blinded due to the nature of the techniques.

The study's primary focus is to evaluate the perioperative modulation of inflammation through quantification of biomarkers including interleukin-6 (IL-6), C-reactive protein (CRP), serum cortisol, leukocyte count (WBC), erythrocyte sedimentation rate (ESR) and lactate. Heart rate variability (HRV) will be continuously monitored as a surrogate marker for autonomic modulation of the inflammatory response.

Biomarkers will be sampled at three time points: preoperative baseline (T0), at the end of surgery (T1), and 24 hours postoperatively (T2). HRV data will be collected from induction to the end of surgical intervention using a non invasive monitoring system with time- and frequency-domain analysis.

Secondary outcomes include intraoperative and postoperative analgesic consumption, pain intensity assessed by visual analog scale (VAS), sedation scores using the Ramsay Agitation-Sedation Scale (RASS), incidence of opioid-related side effects (nausea, vomiting, respiratory depression), patient satisfaction (via validated questionnaire), and length of hospital stay.

Sample size was calculated based on preliminary data detecting a clinically significant difference in IL-6 levels, assuming an alpha of 0.05 and power of 0.8. Data will be analyzed using ANOVA or Kruskal-Wallis test for continuous variables, chi-square for categorical variables, and multivariate regression models to adjust for potential confounders.

This study aims to identify anesthetic strategies that minimize systemic inflammation and autonomic dysregulation in the bariatric surgical population, with potential applications in broader surgical settings.

Interventions

• Procedure Opioid-Free Anesthesia (OFA)
  Opioid-free anesthesia using a multimodal approach, including dexmedetomidine, lidocaine, ketamine, and magnesium sulfate. No intraoperative opioids are administered.
• Procedure Opioid-Based Intravenous Anesthesia (OBA-IV)
  Standard opioid-based intravenous anesthesia using propofol, remifentanil, and neuromuscular blockade.
• Procedure Opioid-Based Inhalational Anesthesia (OBA-Inh)
  Standard opioid-based inhalational anesthesia using sevoflurane, remifentanil, and neuromuscular blockade.

Primary outcome measures

• Serum IL-6 Level [Time frame: Preoperative (baseline), immediately after surgery, and 24 hours post-surgery.]
• C-reactive Protein (CRP) Level [Time frame: Preoperative (baseline), immediately after surgery, and 24 hours post-surgery.]
• Serum Cortisol Level [Time frame: Preoperative (baseline), immediately after surgery, and 24 hours post-surgery.]
• Heart Rate Variability (HRV) as an Inflammatory Marker [Time frame: Collected continuosly from the induction of the anesthesia until the end of surgery]
• Serum Lactate Level [Time frame: Preoperative (baseline), immediately after surgery, and 24 hours post-surgery.]
• Erythrocyte Sedimentation Rate (ESR) [Time frame: Preoperative (baseline), immediately after surgery, and 24 hours post-surgery.]
• Differential White blood Cell count (WBC). [Time frame: Preoperative (baseline), immediately after surgery, and 24 hours post-surgery.]

Secondary outcome measures (4)

• Postoperative Pain Evaluation Using Visual Analog Scale (VAS) [Time frame: hourly during the first 4 hours post surgery in the recovery area, and at 12 and 24 hours in the hospitalization ward]
• Postoperative Sedation Level Using Ramsay Sedation Scale [Time frame: immediately after surgery, and hourly during the first 4 hours in the recovery area, and at 12 and 24 hours in the hospitalization ward]
• Incidence of Postoperative Complications [Time frame: 24 hours post-surgery.]
• Patient Satisfaction with Anesthetic Technique [Time frame: 24 hours post-surgery.]

Eligibility criteria

Inclusion criteria

• Patients scheduled for bariatric surgery.
• Age 18-65 years.
• BMI ≥ 30 kg/m².
• ASA physical status II-III.

Exclusion criteria

• Pregnancy or breastfeeding.
• Chronic opioid use before surgery.
• Severe renal or hepatic failure.
• Uncontrolled psychiatric disorders.
• Significant intraoperative complications requiring protocol deviation.

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

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Spain · 1 center

• Hospital HM Nou Delfos — Barcelona

Publications

• Heil LBB, Silva PL, Pelosi P, Rocco PRM. Immunomodulatory effects of anesthetics in obese patients. World J Crit Care Med. 2017 Aug 4;6(3):140-152. doi: 10.5492/wjccm.v6.i3.140. eCollection 2017 Aug 4. PMID 28828299
• Alsumali A, Eguale T, Bairdain S, Samnaliev M. Cost-Effectiveness Analysis of Bariatric Surgery for Morbid Obesity. Obes Surg. 2018 Aug;28(8):2203-2214. doi: 10.1007/s11695-017-3100-0. PMID 29335933
• Lin YT, Wu HT, Tsao J, Yien HW, Hseu SS. Time-varying spectral analysis revealing differential effects of sevoflurane anaesthesia: non-rhythmic-to-rhythmic ratio. Acta Anaesthesiol Scand. 2014 Feb;58(2):157-67. doi: 10.1111/aas.12251. PMID 24410106
• Bonhomme V, Uutela K, Hans G, Maquoi I, Born JD, Brichant JF, Lamy M, Hans P. Comparison of the surgical Pleth Index with haemodynamic variables to assess nociception-anti-nociception balance during general anaesthesia. Br J Anaesth. 2011 Jan;106(1):101-11. doi: 10.1093/bja/aeq291. Epub 2010 Nov 4. PMID 21051493
• Wennervirta J, Hynynen M, Koivusalo AM, Uutela K, Huiku M, Vakkuri A. Surgical stress index as a measure of nociception/antinociception balance during general anesthesia. Acta Anaesthesiol Scand. 2008 Sep;52(8):1038-45. doi: 10.1111/j.1399-6576.2008.01687.x. PMID 18840101
• Lisowska B, Jakubiak J, Siewruk K, Sady M, Kosson D. Which idea is better with regard to immune response? Opioid anesthesia or opioid free anesthesia. J Inflamm Res. 2020 Nov 5;13:859-869. doi: 10.2147/JIR.S275986. eCollection 2020. PMID 33177861
• Campos-Perez W, Ramirez-Plascencia L, Perez-Robles M, Rivera-Valdes JJ, Sanchez-Munoz P, Perez-Vargas L, Gonzalez-Landeros D, Cuevas JHM, Martinez-Lopez E. A comparison of opioid-containing anesthesia versus opioid-free anesthesia using the Cortinez-Sepulveda model on differential cytokine responses in obese patients undergoing gastric bypass surgery: a randomized controlled trial. BMC Anesthesiol PMID 36114460
• Ahmed SA, Abdelghany MS, Afandy ME. The effect of opioid-free anesthesia on the post-operative opioid consumption in laparoscopic bariatric surgeries: A randomized controlled double-blind study. J Opioid Manag. 2022 Jan-Feb;18(1):47-56. doi: 10.5055/jom.2022.0694. PMID 35238013

Identifiers

NCT: NCT06915558 · 25.02.2467-GHM

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗