Subcellular Localization Of Trifluoroacetylated Liver Proteins In Association With Hepatitis Following Isoflurane

Anesthesiology:
March 2002 - Volume 96 - Issue 3 - pp 757-761
Case Reports

Subcellular Localization of Trifluoroacetylated Liver Proteins
in Association with Hepatitis following Isoflurane
Njoku, Dolores B. M.D.*; Shrestha, Sanjeeb M.D.†; Soloway , Roger M.D.‡; Duray, Paul R. M.D.§;
Tsokos, Maria M.D.∥; Abu-Asab, Mones S. Ph.D.#; Pohl, Lance R. Pharm.D., Ph.D.**; West, A. Brian
M.D.††Author Information
IDIOPATHIC, volatile anesthetic –associated hepatitis has been documented with halothane, 1–
3enflurane, 4 isoflurane, 5–7 and desflurane. 8 Among these, halothane -associated hepatitis has
been best characterized, and evidence suggests that this type of hepatitis may be caused by an
immune reaction induced by liver cell proteins that have been covalently trifluoroacetylatedby the
trifluoroacetyl chloride metabolite of halothane. It is also believed that hepatitis after the use of
enflurane, isoflurane, and desflurane may be caused by a similar mechanism, although the evidence
for this idea is not as compelling as that reported for halothane. 9 In this case report, we provide
clinical, histochemical, and immunohistochemical evidence supporting a possible role oftrifluoroacetyl-modified proteins (TFAMPs) in hepatitis associated with isoflurane.
Case Report
A 66-yr-old man with type II diabetes mellitus, chronic obstructive pulmonary disease, hypertension,
and coronary artery disease underwent an uneventful carotid endarterectomy during which
anesthesia was conducted with the use of oxygen (30–100%), isoflurane (0.4–1.0%, 135 min),
fentanyl, andthiopental. Two months later, he presented with chest pain and underwent three -vessel
coronary artery bypass graft. His preoperative medications were morphine sulfate, diazepam,
scopolamine, cefazolin, and gentamicin. During this surgery, the patient received fentanyl,
pancuronium, ϵ-aminocaproic acid, mannitol, and heparin in addition to isoflurane and 100%
oxygen. The cardiopulmonarybypass time was 110 min, and the cross -clamp time was 89 min. The
patient had a postbypass hemoglobin concentration of 8.2 g/dl and received 400 ml pump blood.
There were no intraoperative episodes of hypotension, although approximately 15 min after incision,
norepinephrine (45 min) and nitroglycerin (60 min) were administered to the patient. Moreover, his
cardiac output was 3.7 (onnorepinephrine and nitroglycerin) before bypass and 5.0 after bypass
without these medications. In addition, his arterial blood gases before, during, and after
cardiopulmonary bypass were all within normal range:p H 7.39, partial pressure of carbon dioxide
(Pco2) 46, partial pressure of oxygen (Po2) 157, HCO3 28 (before);p H 7.41, Pco2 44, Po2 405,
HCO3 27 (during);p H 7.38, Pco2 45, Po2 346, HCO3 26(after). His immediate postoperative
recovery was unremarkable except for a mild fever of 38.1–38.3°C that developed 7 h after the
completion of surgery, which was taken as time 0 (fig. 1). He was transferred from intensive care to
the surgical floor at 23 h. That night, his temperature fluctuated betwee n 36.8 and 38.0°C, and mild
icterus developed. At 45 h, his temperature increased to 38.6°C,and he became more severely
icteric. Examination revealed that he had tender hepatomegaly, and he became progressively
drowsier until he was able to be aroused only with painful stimuli. His serum aspartate

aminotransferase concentration, measured at 38 h, was 3,973 U/l. At 52 h after surgery, liver
biochemistry testing revealed alanine aminotransferase of 10,394 U/l; aspartateaminotransferase of
25,515 U/l; total bilirubin of 3.8 mg/dl, and alkaline phosphatase of 55 U/l. The prothrombin time
peaked at 20.6 s, and total bilirubin peaked at 10.9 mg/dl. Serologic assays for hepatitis A, B, and C
were negative. An ultrasound image showed a normal gallbladder and common bile duct. At 50 h, the
patient was transferred back to the intensive care unit, where he had a transient...