A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
While on a teaching sabbatical in Uruguay, a pathologist examined the excised liver of an 18-year-old otherwise healthy female who passed away due to massive hepatic necrosis 5 days after she underwent general anesthesia to repair a fractured femur. Which of the following is a general anesthetic most likely responsible for her death?
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A
LidocaineIncorrect. Lidocaine is a local/regional anesthetic (Na+ channel blocker), not a general anesthetic, and does not cause massive hepatic necrosis.
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B
MidazolamIncorrect. Midazolam is a benzodiazepine used for procedural sedation; it does not cause idiosyncratic hepatitis with massive necrosis.
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C
HalothaneCorrect. Halothane (still used in low-resource settings) causes idiosyncratic immune-mediated centrilobular hepatic necrosis with a 2-5 day latency after exposure, exactly matching this case.
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D
DesfluraneIncorrect. Desflurane can rarely cause halothane-like hepatitis through similar TFA-protein adduct mechanisms but at vastly lower rates than halothane, and halothane is the textbook answer.
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E
IsofluraneIncorrect. Isoflurane is a halogenated inhalational anesthetic that can rarely cause hepatitis through TFA adduct formation but at vastly lower rates than halothane; halothane is the classic culprit for massive hepatic necrosis with this latency.
↑ Tap an answer to reveal the reasoning
Answer: C. Massive hepatic necrosis several days after general anesthesia in a young, otherwise healthy patient is the classic presentation of halothane hepatitis. Halothane is a volatile halogenated anesthetic that, in rare cases (especially with repeated exposures), causes fulminant hepatic failure with a typical 2-5 day latency. The mechanism involves oxidative metabolism of halothane to a trifluoroacetyl (TFA) intermediate by CYP2E1, which haptenizes hepatic proteins; an immune response against these TFA-protein adducts produces severe hepatocellular necrosis.
Halothane has been largely phased out of high-income countries because of this hepatotoxicity but remains in use in resource-limited settings (consistent with the Uruguay setting of this question). Histology shows centrilobular (zone 3) necrosis. Mortality from halothane hepatitis can exceed 50%.
Desflurane and other newer halogenated agents (sevoflurane, isoflurane) can rarely cause similar reactions but at far lower rates than halothane. Midazolam is a benzodiazepine used for sedation/induction; it is not hepatotoxic in this way. Lidocaine is a local/regional anesthetic and is not a general anesthetic. The age (18), recent surgical exposure, and severe hepatic necrosis 5 days after anesthesia are signature halothane.
**Why each option:**
**A.** Lidocaine is a local/regional anesthetic (Na+ channel blocker), not a general anesthetic, and does not cause massive hepatic necrosis.
**B.** Midazolam is a benzodiazepine used for procedural sedation; it does not cause idiosyncratic hepatitis with massive necrosis.
**C.** Correct. Halothane (still used in low-resource settings) causes idiosyncratic immune-mediated centrilobular hepatic necrosis with a 2-5 day latency after exposure, exactly matching this case.
**D.** Desflurane can rarely cause halothane-like hepatitis through similar TFA-protein adduct mechanisms but at vastly lower rates than halothane, and halothane is the textbook answer.