Trifluorinated ether anesthetic lethality in rats: the role of bacterial infection

The lethal effects of the fluorinated ether anesthetics fluroxene (2,2,2-trifluoroethyl vinyl ether) and its ethyl (TFEE) and allyl analogues in male Wistar rats have previously been demonstrated to be potentiated by specific hepatic microsomal cytochromes P-450, and mediated by the common metabolite 2,2,2-trifluoroethanol (TFE). We report here that administration of lethal combinations of anesthetic and cytochrome P-450-inducing agents or of lethal doses of TFE (0.21 g/kg and higher) to rats caused decreased white blood cell counts, necrosis of sternum bone marrow cells and lymphocytes in the thymic cortex, and resulted in Escherichia coli contamination of the blood, lungs, liver, and kidneys of treated rats. Control animals in identical environments were free of bacterial contamination. Pretreatment of rats with the antibiotic tetracycline-HCl in the drinking water (0.6 g/liter) from 24 hr before anesthetic or TFE administration significantly diminished the mortality. With TFEE and beta-naphthoflavone induction, mortality was reduced from 85 to 30% by the antibiotic. However, the antibody plaque assay following immunization with sheep erythrocytes indicated that the primary humoral immune response to a thymus-dependent antigen was not impaired in treated rats. These results considered together indicate that metabolic formation of TFE from the anesthetic agents produced a decreased host resistance with subsequent increased susceptibility to bacterial infection. If not administered the antibiotic, the animals succumbed to the infection.