A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation

Abstract

Background: Inhaled anesthetics, including halothane, iso- and sevoflurane induce proinflammatory cytokine release. Halothane is an inhaled anesthetic agent that is metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which can react endogenously to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct is formed by acetaldehyde and malondialdehyde reacting with endogenous proteins and is found in both patients and animals post-consumption of alcohol. These TFA and MAA-adducts have been shown to cause the release of proinflammatory cytokines by endogenous inflammatory cells. If both adducts share a similar mechanism of cell activation, receiving general anesthesia following alcohol ingestion could exacerbate the inflammatory response caused by the inhaled general anesthetic halothane and lead to solid organ (including liver and brain) injury. Methods: Control diet and alcohol-fed rats were randomized to receive halothane pretreatments by intraperitoneal injection mixed in sesame oil. Following the intraperitoneal injections, the intact heart was removed, HECs were isolated and stimulated with unmodified bovine serum albumin (Alb), MAA-modified Alb (MAA-Alb), Hexyl-MAA, or lipopolysaccharide (LPS), and supernatant concentrations of TNF-α were determined. Results: Halothane pre-treated rat HECs demonstrated significantly greater TNF-α concentration following MAA-adduct and LPS stimulation than the non-halothane pre-treated in both pair and alcohol-fed rats, but was significantly greater in the alcohol-fed groups. Conclusion: These results demonstrate that halothane and MAA-adduct pre-treatment will increase the inflammatory response (TNF-α release) in rat HECs following LPS and MAA stimulation in vitro. Also, these results suggest that halothane exposure may increase the risk of alcohol-induced solid organ injury secondary to TNF-induced inflammation. Other investigators have reported similar proinflammatory cytokine release with other (isoflurane and sevoflurane) inhaled anesthetic exposure, suggesting inhaled anesthetics should be used with caution in alcohol consuming humans.