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

Wendy Campos-Pérez, Lilia Ramírez-Plascencia, Mariana Pérez-Robles, Juan J Rivera-Valdés, Patricia Sánchez-Muñoz, Liliana Pérez-Vargas, Dulce González-Landeros, Juan Heberto Muñoz Cuevas, Erika Martínez-López, Wendy Campos-Pérez, Lilia Ramírez-Plascencia, Mariana Pérez-Robles, Juan J Rivera-Valdés, Patricia Sánchez-Muñoz, Liliana Pérez-Vargas, Dulce González-Landeros, Juan Heberto Muñoz Cuevas, Erika Martínez-López

Abstract

Background: Opioid anesthetic agents can modulate the impaired immune response in obese patients through mechanisms that involve the expression and release of cytokines. For this reason, anesthetic care for obese patients remains controversial. Therefore, the aim of the study was to compare the effect of opioid-containing anesthesia (OCA) vs opioid-free anesthesia (OFA) using the Cortínez-Sepúlveda model on IL-6, IL-1β and TNF-α serum levels before and after surgery in obese patients undergoing bypass surgery.

Methods: This randomized cross-sectional study conducted among 40 unrelated obese adults was performed in 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: OCA (n = 20) or OFA (n = 20). Fentanyl was the opioid used in the OCA group. The Cortínez-Sepúlveda pharmacokinetic model was used to characterize the disposition of intravenous propofol for the target-controlled infusion technique in obese patients. Body mass was determined to the nearest 0.05 kg using a balance scale (Seca 703; Seca, Hamburg, Germany). Blood samples were taken before and immediately after surgery and cytokine concentrations were determined by ELISA. Pain was assessed using a numerical pain rating scale. Adverse effects were collected within the first 24 h after surgery.

Results: A total of 6 men and 34 women were included (37.9 ± 10.6 years). Pre-surgery IL-6 and TNF-α serum levels were not detected in study subjects. However, IL-1β levels significantly decreased after surgery (49.58 pg/mL (18.50-112.20)-before surgery vs 13 pg/mL (5.43-22)-after surgery, p = 0.019). IL-6 concentrations were significantly higher in subjects who received OCA (with fentanyl) compared to subjects with OFA (224.5 pg/mL (186.3-262.8) vs 99.5 pg/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 correlated positively with IL-6 serum levels in obese patients undergoing bypass surgery. This finding could have clinical relevance when an appropriate anesthetic management plan is selected for bariatric surgical patients.

Trial registration: The study was retrospectively registered at ClinicalTrials.gov Identification Number: NCT04854252, date 22/04/2021.

Keywords: Cortínez-Sepúlveda model; Fentanyl; IL-6; Opioid free anaesthesia.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of study subjects. BMI: Body Mass Index, OCA: Opiod-containing anesthesia, OFA: Opiod-free anesthesia

References

    1. Panuganti KK, Nguyen M, Kshirsagar RK. Obesity. Treasure Island: StatPearls Publishing; 2020.
    1. Encuesta Nacional de Salud y Nutrición. (2018). . Accessed 6 Apr 2021.
    1. Nudel J, Sanchez VM. Surgical management of obesity. Metab Clin Exp. 2019;92:206–216. doi: 10.1016/j.metabol.2018.12.002.
    1. Heil LBB, Silva PL, Pelosi P, Rocco PRM. Immunomodulatory effects of anesthetics in obese patients. World J Crit Care Med. 2017;6:140. doi: 10.5492/wjccm.v6.i3.140.
    1. Rossaint J, Margraf A, Zarbock A. Perioperative inflammation. Anaesthesist. 2019;68:421–427. doi: 10.1007/s00101-019-0596-9.
    1. Campbell L, Engbers FHKG. Total intravenous anesthesia. Anesthesia. 2001;3:109–119.
    1. Sultana A, Torres D, Schumann R. Special indications for opioid free anaesthesia and analgesia, patient and procedure related: including obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, opioid addiction and cancer surgery. Best Pract Res Clin Anaesthesiol. 2017;31:547–560. doi: 10.1016/j.bpa.2017.11.002.
    1. Liang X, Liu R, Chen C, Ji F, Li T. Opioid system modulates the immune function: a review. Transl Perioper pain Med. 2016;1:5–13.
    1. Gilliland HE, Armstrong MA, Carabine U, McMurray TJ. The choice of anesthetic maintenance technique influences the antiinflammatory cytokine response to abdominal surgery. Anesth Analg. 1997;85:1394–1398. doi: 10.1213/00000539-199712000-00039.
    1. Schneemilch CE, Ittenson A, Ansorge S, Hachenberg T, Bank U. Effect of 2 anesthetic techniques on the postoperative proinflammatory and anti-inflammatory cytokine response and cellular immune function to minor surgery. J Clin Anesth. 2005;17:517–527. doi: 10.1016/j.jclinane.2004.12.017.
    1. Heller A, Heller S, Blecken S, Urbaschek R, Koch T. Effects of intravenous anesthetics on bacterial elimination in human blood in vitro. Acta Anaesthesiol Scand. 1998;42:518–526. doi: 10.1111/j.1399-6576.1998.tb05160.x.
    1. Loop T, Scheiermann P, Doviakue D, Musshoff F, Humar M, Roesslein M, et al. Sevoflurane inhibits phorbol-myristate-acetate-induced activator protein-1 activation in human T lymphocytes in vitro: potential role of the p38-stress kinase pathway. Anesthesiology. 2004;101:710–721. doi: 10.1097/00000542-200409000-00020.
    1. Roussabrov E, Davies JM, Bessler H, Greemberg L, Roytblat L, Yardeni I-Z, et al. Effect of ketamine on inflammatory and immune responses after short-duration surgery in obese patients. Open Anesthesiol J. 2008;2:40–45. doi: 10.2174/1874321800802010040.
    1. Obesity. . Accessed 6 Apr 2021.
    1. Cortínez LI, Sepúlveda P, Rolle A, Cottin P, Guerrini A, Anderson BJ. Effect-site target-controlled infusion in the obese: model derivation and performance assessment. Anesth Analg. 2018;127:865–872. doi: 10.1213/ANE.0000000000002814.
    1. Haefeli M, Elfering A. Pain assessment. Eur Spine J. 2006;15(SUPPL. 1):S17. doi: 10.1007/s00586-005-1044-x.
    1. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–867. doi: 10.1038/nature05485.
    1. Jawa RS, Kulaylat MN, Baumann H, Dayton MT. What is new in cytokine research related to trauma/critical care. J Intensive Care Med. 2006;21:63–85. doi: 10.1177/0885066605284325.
    1. Cruickshank AM, Fraser WD, Burns HJG, Van Damme J, Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci. 1990;79:161–165. doi: 10.1042/cs0790161.
    1. Brandacher G, Hoeller E, Fuchs D, Weiss H. Chronic immune activation underlies morbid obesity: is IDO a key player? Curr Drug Metab. 2007;8:289–295. doi: 10.2174/138920007780362590.
    1. Winkler G, Lakatos P, Salamon F, Nagy Z, Speer G, Kovács M, et al. Elevated serum TNF-α level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients. Diabet Med. 1999;16:207–211. doi: 10.1046/j.1464-5491.1999.00052.x.
    1. Hirano T. Interleukin 6 and its receptor: ten years later. Int Rev Immunol. 1998;16:249–284. doi: 10.3109/08830189809042997.
    1. Jaber S, Amraoui J, Lefrant JY, Arich C, Cohendy R, Landreau L, et al. Clinical practice and risk factors for immediate complications of endotracheal intubation in the intensive care unit: a prospective, multiple-center study. Crit Care Med. 2006;34:2355–2361. doi: 10.1097/01.CCM.0000233879.58720.87.
    1. Kamimura D, Ishihara K, Hirano T. IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev Physiol Biochem Pharmacol. 2003;149:1–38.
    1. Høgevold HE, Lyberg T, Kähler H, Haug E, Reikerås O. Changes in plasma IL-1β, TNF-α and IL-6 after total hip replacement surgery in general or regional anaesthesia. Cytokine. 2000;12:1156–1159. doi: 10.1006/cyto.2000.0675.
    1. Liu YM, Zhu SM, Wang KR, Feng ZY, Chen QL. Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain. J Zhejiang Univ Sci B. 2008;9:895–902. doi: 10.1631/jzus.B0820039.
    1. Nagahiro I, Andou A, Aoe M, Sano Y, Date H, Shimizu N. Pulmonary function, postoperative pain, and serum cytokine level after lobectomy: a comparison of VATS and conventional procedure. Ann Thorac Surg. 2001;72:362–365. doi: 10.1016/S0003-4975(01)02804-1.
    1. Raeburn CD, Sheppard F, Barsness KA, Arya J, Harken AH. Cytokines for surgeons. Am J Surg. 2002;183:268–273. doi: 10.1016/S0002-9610(02)00781-X.
    1. Taylor NM, Lacoumenta S, Hall GM. Fentanyl and the interleukin-6 response to surgery. Anaesthesia. 1997;52:112–115. doi: 10.1111/j.1365-2044.1997.65-az0063.x.
    1. Kaufmann KB, Heinrich S, Staehle HF, Bogatyreva L, Buerkle H, Goebel U. Perioperative cytokine profile during lung surgery predicts patients at risk for postoperative complications—A prospective, clinical study. PLoS ONE. 2018;13(7):e0199807. 10.1371/journal.pone.0199807.
    1. Loskutov O, Maruniak S, Dryzhyna O, Malysh I, Kolesnykov V, Korotchuk N. Influence of low-opioid anesthesia in cardiac surgery on dynamics of pro-inflammatory interleukin-6. Kardiochirurgia i Torakochirurgia Pol = Polish J Cardio-Thoracic Surg. 2020;17:39. doi: 10.5114/KITP.2020.94190.
    1. De Gennaro L, Brunetti ND, Montrone D, De Rosa F, Cuculo A, Di Biase M. Subacute inflammatory activation in subjects with acute coronary syndrome and left ventricular dysfunction. Inflammation. 2012;35:363–370. doi: 10.1007/S10753-011-9326-4/Figures/6.
    1. Brix-Christensen V, Tønnesen E, Sørensen IJ, Bilfinger TV, Sanchez RG, Stefano GB. Effects of anaesthesia based on high versus low doses of opioids on the cytokine and acute-phase protein responses in patients undergoing cardiac surgery. Acta Anaesthesiol Scand. 1998;42:63–70. doi: 10.1111/j.1399-6576.1998.tb05082.x.
    1. Miller KM, Anderson JM. Human monocyte/macrophage activation and interleukin 1 generation by biomedical polymers. J Biomed Mater Res. 1988;22:713–731. doi: 10.1002/jbm.820220805.
    1. Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev. 2011;22:189–195. doi: 10.1016/j.cytogfr.2011.10.001.
    1. Haga Y, Beppu T, Doi K, Nozawa F, Mugita N, Ikei S, et al. Systemic inflammatory response syndrome and organ dysfunction following gastrointestinal surgery. Crit Care Med. 1997;25:1994–2000. doi: 10.1097/00003246-199712000-00016.
    1. Sarbinowski R, Arvidsson S, Tylman M, Öresland T, Bengtsson A. Plasma concentration of procalcitonin and systemic inflammatory response syndrome after colorectal surgery. Acta Anaesthesiol Scand. 2005;49:191–196. doi: 10.1111/j.1399-6576.2004.00565.x.
    1. Hsing CH, Wang JJ. Clinical implication of perioperative inflammatory cytokine alteration. Acta Anaesthesiol Taiwan. 2015;53:23–28. doi: 10.1016/j.aat.2015.03.002.
    1. Dominguini D, Steckert AV, Michels M, Spies MB, Ritter C, Barichello T, et al. The effects of anaesthetics and sedatives on brain inflammation. Neurosci Biobehav Rev. 2021;127:504–513. doi: 10.1016/J.Neubiorev.2021.05.009.
    1. Boysen PG, Pappas MM, Evans B. An evidence-based opioid-free anesthetic technique to manage perioperative and periprocedural pain. Ochsner J. 2018;18:121–125. doi: 10.31486/TOJ.17.0072.
    1. 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;13:859–869. doi: 10.2147/JIR.S275986.
    1. Eisenach JC, De Kock M, Klimscha W. α2-adrenergic agonists for regional anesthesia a clinical review of clonidine (1984 - 1995) Anesthesiology. 1996;85:655–674. doi: 10.1097/00000542-199609000-00026.
    1. Kamibayashi T, Maze M. Perioperative use of alpha-2 adrenergic agonists. Curr Opin Anaesthesiol. 1996;9:323–327. doi: 10.1097/00001503-199608000-00011.
    1. Li B, Li Y, Tian S, Wang H, Wu H, Zhang A, et al. Anti-inflammatory effects of perioperative Dexmedetomidine administered as an adjunct to general anesthesia: a meta-analysis. Sci Rep. 2015;5. 10.1038/SREP12342.
    1. Cortínez LI, Anderson BJ. Advances in pharmacokinetic modeling: target controlled infusions in the obese. Curr Opin Anaesthesiol. 2018;31:415–422. doi: 10.1097/ACO.0000000000000619.

Source: PubMed

Подписаться