Effects of nitrous oxide on the production of cytokines and chemokines by the airway epithelium during anesthesia with sevoflurane and propofol

Abstract

Abstract. The aim of this study was to evaluate the effects of nitrous oxide (a gaseous anesthetic) on the in vivo production of inflammatory cytokines and chemokines by the airway epithelium, when combined with sevoflurane or propofol. Subjects undergoing simple or segmental mastectomy were randomly assigned to the sevoflurane and nitrous oxide, sevoflurane and air, propofol and nitrous oxide, or propofol and air group (all n=13). Epithelial lining fluid (ELF) was obtained using the bronchoscopic microsampling method prior to and following the mastectomy to enable measurement of the pre-and post-operative levels of certain inflammatory cytokines and chemokines using a cytometric bead array system. Notably, the levels of interleukin (IL)-1β, IL-8 and monocyte chemotactic protein-1 (MCP-1) in the ELF were significantly increased following the operations which involved the inhalation of sevoflurane and nitrous oxide, although the levels of these molecules were not significantly changed by the inhalation of sevoflurane and air. Furthermore, the IL-12p70 levels were significantly reduced in the ELF following the operations that involved the inhalation of sevoflurane and air, although the IL-12p70 levels were not significantly changed by the inhalation of nitrous oxide and sevoflurane. These observations suggest that the combination of sevoflurane and nitrous oxide induces an inflammatory response (increased production of IL-1β, IL-8 and MCP-1) and suppresses the anti-inflammatory response (reduced production of IL-12p70) in the local milieu of the airway. Thus, the combination of these compounds should be carefully administered for anesthesia. IntroductionGlobally, >200 million major surgical procedures are undertaken annually (1), and nitrous oxide is widely used in anesthesia, often administered at an inspired concentration of ~60-70% (2-5). Nitrous oxide has achieved marked longevity as an anesthetic, having been used widely since 1844 (6). However, the low toxicity of modern anesthetic agents and the accumulating evidence on the adverse effects of nitrous oxide render the continued use of nitrous oxide in anesthesia controversial (7-10). A number of the adverse effects of nitrous oxide result from the irreversible inactivation of vitamin B 12 , which inhibits methionine synthase, folate metabolism and deoxyribonucleic acid synthesis (7,8). This mechanism explains the megaloblastic anemia and neurologic toxicity associated with prolonged nitrous oxide administration (11,12), and the possible risk of teratogenicity, immunodeficiency and impaired wound healing (7,13,14). In addition, the inhibition of methionine synthase is associated with increased plasma homocysteine concentrations (15,16) which may increase the risk of post-operative cardiovascular complications (15). Furthermore, nitrous oxide impairs cerebral blood flow-activity coupling (10), and worsens the air space conditions (such as pneumothorax and air embolism) and bowel distension (8,9). Nitrous oxide is also a risk factor for post-operative nausea an...

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