ABSTRACT
BACKGROUND: Three cases of drug-induced liver injury (DILI) have been reported after desflurane anesthesia. However, no previous reports have detected serum autoantibodies such as that reported with DILI from halothane or isoflurane. METHODS AND RESULTS: We describe the first documentation of cytochrome P450 2E1 IgG4 autoantibodies, as well as 58 kDa endoplasmic reticulum protein and trifluoroacetyl chloride hapten-specific IgG4 antibodies, in a patient who developed DILI after desflurane anesthesia. CONCLUSIONS: These findings suggest that allergic and autoimmune mechanisms have critical roles in the development of desflurane DILI.
Subject(s)
Autoantibodies/biosynthesis , Autoantigens/immunology , Chemical and Drug Induced Liver Injury/immunology , Haptens/immunology , Immunoglobulin G/blood , Isoflurane/analogs & derivatives , Adult , Autoantibodies/blood , Autoantigens/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Desflurane , Female , Haptens/adverse effects , Humans , Isoflurane/adverse effects , Isoflurane/immunologyABSTRACT
This report is of a case of a previously fit 65-year-old woman who developed postoperative liver dysfunction following an anaesthetic involving isoflurane. Biliary ultrasound demonstrated gallstones. However, serum antibodies to trifluoroacetylated proteins were detected, suggesting that immune sensitisation to the anaesthetic could have contributed to the impaired liver function.
Subject(s)
Anesthetics, Inhalation/adverse effects , Cholelithiasis/complications , Hepatitis/etiology , Isoflurane/adverse effects , Postoperative Complications , Aged , Anesthetics, Inhalation/immunology , Chemical and Drug Induced Liver Injury/etiology , Drug Hypersensitivity/etiology , Female , Humans , Isoflurane/immunologySubject(s)
Anesthetics, Inhalation/adverse effects , Kidney/drug effects , Liver/drug effects , Methyl Ethers , Anesthetics, Inhalation/metabolism , Anesthetics, Inhalation/toxicity , Animals , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/immunology , Chloroform/adverse effects , Chloroform/metabolism , Chloroform/toxicity , Disease Models, Animal , Enflurane/adverse effects , Enflurane/immunology , Ethers/adverse effects , Ethers/metabolism , Ethers/toxicity , Halothane/adverse effects , Halothane/immunology , Halothane/toxicity , Humans , Isoflurane/adverse effects , Isoflurane/immunology , Methoxyflurane/adverse effects , Methoxyflurane/toxicity , Sevoflurane , Trichloroethylene/adverse effects , Trichloroethylene/toxicity , Vinyl Compounds/adverse effects , Vinyl Compounds/toxicityABSTRACT
Two halogenated anesthetics, enflurane and isoflurane, have been associated with an allergic-type hepatic injury both alone and following previous exposure to halothane. Halothane hepatitis appears to involve an aberrant immune response. An antibody response to a protein-bound biotransformation product (trifluoroacetyl adduct) has been detected on halothane hepatitis patients. This study was performed to determine cross-reactivity between enflurane and isoflurane with the hypersensitivity induced by halothane. The subcellular and lobular production of hepatic neoantigens recognized by halothane-induced antibodies following enflurane and isoflurane, and the biochemical nature of these neoantigens was investigated in two animal models. Enflurane administration resulted in neoantigens detected in both the microsomal and cytosolic fraction of liver homogenates and in the centrilobular region of the liver. In the same liver, biochemical analysis detected fluorinated liver adducts that were up to 20-fold greater in guinea pigs than in rats. This supports and extends previous evidence for a mechanism by which enflurane and/or isoflurane could produce a hypersensitivity condition similar to that of halothane hepatitis either alone or subsequent to halothane administration. The guinea pig would appear to be a useful model for further investigations of the immunological response to these antigens.
Subject(s)
Anesthetics, Inhalation/immunology , Anesthetics, Inhalation/metabolism , Antigen-Antibody Reactions , Liver/metabolism , Animals , Antibody Formation/immunology , Cross Reactions/immunology , Enflurane/immunology , Enflurane/metabolism , Guinea Pigs , Halothane/immunology , Halothane/metabolism , Isoflurane/immunology , Isoflurane/metabolism , Male , Rats , Rats, Sprague-DawleyABSTRACT
This paper reviews the approach to pain during surgery in the newborn under five general headings: (1) current attitudes to pain in the newborn during anaesthesia and intensive care; (2) current evidence on the response of the newborn to pain; (3) current approaches to the management of pain in the newborn; (4) the complications of these approaches; (5) the resultant principles of the management of anaesthesia in the newborn.
