A comparison of opioid-containing anesthesia versus opioid-free anesthesia using the Cortínez-Sepúlveda model on differential cytokine responses in patients undergoing gastric bypass surgery: a randomized controlled trial

Background: Anesthetic agents, including opioids can modulate the altered immune function in patients with obesity through mechanisms that involve the expression and release of cytokines. For this reason, anesthetic care in patients with obesity remains controversial. Therefore, the aim of the study was to compare the effect of opioid-containing anesthesia vs opioid-free anesthesia using the Cortínez-Sepúlveda model on serum levels of IL-6, IL-1β and TNF-α before and after surgery in obese patients undergoing bypass surgery. Methods: : A randomized cross-sectional study of 40 unrelated obese adults was performed at the Civil Hospital of Guadalajara “Dr. Juan I. Menchaca”. Before undergoing laparoscopic Roux-en-Y gastric bypass, patients were randomly assigned to two anesthesia groups: opiod-containing (n=20) or opiod-free (n=20). The opioid used in the opioid-containing anesthesia group was fentanyl. To characterize the disposition of intravenous propofol for the target-controlled infusion technique in obese patients, the Cortínez-Sepúlveda pharmacokinetic model was used. Body mass was determined to the nearest 0.05kg using a balance scale (Seca 703; Seca, Hamburg, Germany). Blood samples were taken before and immediately after surgery and cytokine serum levels were determined with ELISA kits. Pain was assessed using a numerical pain rating scale. Adverse effects were collected 24 h after surgery. Results: : 6 men and 34 women were included in this study (37.9±10.6 years). Pre-surgery IL-6 and TNF-α serum levels were not detected in all participants. However, IL-1β levels significantly decreased after surgery (49.58pg/mL (18.50-112.20)-before surgery vs 13pg/mL (5.43-22)-after surgery, p=0.019). IL-6 concentrations were significantly higher in subjects who received opioid-containing anesthesia (with fentanyl) compared to subjects with opioid-free anesthesia (224.5pg/mL (186.3-262.8) vs 99.5pg/mL (60.8-138.2), respectively, p<0.001; adjusted by age, gender, and BMI). In addition, the use of opioids confers an increased risk for higher IL-6 levels in obese patients (OR=2.95, 95% CI: 1.2-7.2, p=0.010). A linear regression model showed that the operative time (in hours) of bypass surgery and anesthetic technique were positively correlated with IL-6 levels. Conclusion: Anesthesia with opioids was positively related to IL-6 serum levels in obese patients undergoing bypass surgery. This finding could have clinical relevance when choosing an appropriate anesthetic management plan for bariatric surgical patients. Trial registration: The study was retrospectively registered at ClinicalTrials.gov Identification Number: NCT04854252, date 22/04/2021.