Remimazolam Mitigates Oxidative Stress Response in Patients Undergoing One-lung Ventilation

Overview

Journal Front Surg

Specialty General Surgery

Date 2025 Mar 10

PMID 40060219

Authors

Shanshan Li

Siriguleng Sana

Dan Wang

Affiliations

Soon will be listed here.

Abstract

Introduction: The effectiveness of remimazolam in suppressing oxidative stress, inflammatory reactions, and its lung-protective effects in patients undergoing thoracic surgery with one-lung ventilation (OLV) remains unestablished. This study aimed to investigate the protective effects of remimazolam against oxidative stress and inflammatory damage in such patients.

Methods: This randomized controlled trial evaluated 88 patients with lung tumors who underwent single-lung ventilation for thoracoscopic lobectomy under general anesthesia. Patients were randomly divided into an experimental group (R group) and a control group (Con group), with 44 patients in each group. The R group received an intravenous injection of 0.2 mg/kg of remimazolam during anesthesia induction. During anesthesia maintenance, a continuous intravenous infusion of remimazolam at a rate of 0.2 mg/kg/h was administered. The Con group received routine anesthesia. Preoperative and postoperative levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6 were detected. Changes in blood pressure and heart rate were recorded at four time points: upon entering the operating room (T1), immediately after tracheal intubation (T2), immediately after incision (T3), and immediately after surgery completion (T4). The postoperative awakening time, post-anesthesia care unit (PACU) stay time, and frequency of adverse reactions were also recorded.

Results: Postoperatively, the R group exhibited significantly higher levels of SOD and GSH-Px, and significantly lower levels of TNF-α and IL-6 compared to the Con group ( < 0.01). At T2, the blood pressure and heart rate in R group were significantly higher than those in Con group ( < 0.01), whereas no differences were found between the two groups at other time points. There were no significant differences between the two groups in postoperative awakening time, PACU stay time, or incidence of adverse reactions.

Discussion: Low-dose remimazolam (0.2 mg/kg) can provide protective effects against oxidative stress and inflammatory injuries in patients undergoing OLV, without affecting awakening time or PACU time.

References

Liu T, Lai T, Chen J, Lu Y, He F, Chen Y . Effect of remimazolam induction on hemodynamics in patients undergoing valve replacement surgery: A randomized, double-blind, controlled trial. Pharmacol Res Perspect. 2021; 9(5):e00851. PMC: 8363771. DOI: 10.1002/prp2.851. View

Zhu T, Zhang W, Wang D, Huang N, Bo H, Deng W . Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by inhibiting the gamma-aminobutyric acid type A receptor. Chin Med J (Engl). 2012; 125(8):1457-64. View

Lohser J . Evidence-based management of one-lung ventilation. Anesthesiol Clin. 2008; 26(2):241-72, v. DOI: 10.1016/j.anclin.2008.01.011. View

Marret E, Cinotti R, Berard L, Piriou V, Jobard J, Barrucand B . Protective ventilation during anaesthesia reduces major postoperative complications after lung cancer surgery: A double-blind randomised controlled trial. Eur J Anaesthesiol. 2018; 35(10):727-735. DOI: 10.1097/EJA.0000000000000804. View

Goudra B, Singh P . Propofol alternatives in gastrointestinal endoscopy anesthesia. Saudi J Anaesth. 2014; 8(4):540-5. PMC: 4236943. DOI: 10.4103/1658-354X.140893. View

Lapenna D, Ciofani G, Pierdomenico S, Giamberardino M, Cuccurullo F . Reaction conditions affecting the relationship between thiobarbituric acid reactivity and lipid peroxides in human plasma. Free Radic Biol Med. 2001; 31(3):331-5. DOI: 10.1016/s0891-5849(01)00584-6. View

Doi M, Morita K, Takeda J, Sakamoto A, Yamakage M, Suzuki T . Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial. J Anesth. 2020; 34(4):543-553. DOI: 10.1007/s00540-020-02788-6. View

Jacob T, Moss S, Jurd R . GABA(A) receptor trafficking and its role in the dynamic modulation of neuronal inhibition. Nat Rev Neurosci. 2008; 9(5):331-43. PMC: 2709246. DOI: 10.1038/nrn2370. View

Oka S, Satomi H, Sekino R, Taguchi K, Kajiwara M, Oi Y . Sedation outcomes for remimazolam, a new benzodiazepine. J Oral Sci. 2021; 63(3):209-211. DOI: 10.2334/josnusd.21-0051. View

10.

Liao Y, Min J, Wu Z, Hu Z . Comparison of the effects of remimazolam and dexmedetomidine on early postoperative cognitive function in elderly patients with gastric cancer. Front Aging Neurosci. 2023; 15:1123089. PMC: 10277633. DOI: 10.3389/fnagi.2023.1123089. View

11.

Brohan J, Goudra B . The Role of GABA Receptor Agonists in Anesthesia and Sedation. CNS Drugs. 2017; 31(10):845-856. DOI: 10.1007/s40263-017-0463-7. View

12.

Caldeira D, Souza M, Gomes M, Picinato M, Fina C, Feres O . Effects of hyperbaric oxygen (HBO), as pre-conditioning in liver of rats submitted to periodic liver ischemia/reperfusion. Acta Cir Bras. 2013; 28 Suppl 1:66-71. DOI: 10.1590/s0102-86502013001300013. View

13.

Lohser J, Slinger P . Lung Injury After One-Lung Ventilation: A Review of the Pathophysiologic Mechanisms Affecting the Ventilated and the Collapsed Lung. Anesth Analg. 2015; 121(2):302-18. DOI: 10.1213/ANE.0000000000000808. View

14.

Liu X, Lin S, Zhong Y, Shen J, Zhang X, Luo S . Remimazolam Protects Against LPS-Induced Endotoxicity Improving Survival of Endotoxemia Mice. Front Pharmacol. 2021; 12:739603. PMC: 8641375. DOI: 10.3389/fphar.2021.739603. View

15.

Bellani G, Laffey J, Pham T, Fan E, Brochard L, Esteban A . Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016; 315(8):788-800. DOI: 10.1001/jama.2016.0291. View

16.

Chintagari N, Liu L . GABA receptor ameliorates ventilator-induced lung injury in rats by improving alveolar fluid clearance. Crit Care. 2012; 16(2):R55. PMC: 3681384. DOI: 10.1186/cc11298. View

17.

Karzai W, Schwarzkopf K . Hypoxemia during one-lung ventilation: prediction, prevention, and treatment. Anesthesiology. 2009; 110(6):1402-11. DOI: 10.1097/ALN.0b013e31819fb15d. View

18.

Zhu Z, Shi Z, Xie C, Gong W, Hu Z, Peng Y . A novel mechanism of Gamma-aminobutyric acid (GABA) protecting human umbilical vein endothelial cells (HUVECs) against HO-induced oxidative injury. Comp Biochem Physiol C Toxicol Pharmacol. 2018; 217:68-75. DOI: 10.1016/j.cbpc.2018.11.018. View

19.

Xiang Y, Wang S, Liu M, Hirota J, Li J, Ju W . A GABAergic system in airway epithelium is essential for mucus overproduction in asthma. Nat Med. 2007; 13(7):862-7. DOI: 10.1038/nm1604. View

20.

Kozian A, Schilling T, Freden F, Maripuu E, Rocken C, Strang C . One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung: an experimental study. Br J Anaesth. 2008; 100(4):549-59. DOI: 10.1093/bja/aen021. View