TITLE:
A Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation
AUTHORS:
Gary E. Hill, Irina Gasanova, Geoffrey M. Thiele
KEYWORDS:
Anesthetic-Induced; Solid Organ; Inflammation; Halothane; MAA
JOURNAL NAME:
Open Journal of Anesthesiology,
Vol.4 No.3,
March
4,
2014
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 endogenousproteins 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 proinflammatorycytokines 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 that inhaled anesthetics should be used with caution in alcohol consuming
humans.