Pediatric emergency medicine trisk 3062 3062
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been associated with low morbidity, although occasional cases of hepatotoxicity
occur, particularly in the context of inadvertent repetitive overdosing.
The primary toxicity of APAP is hepatocellular damage. Acetaminophen is
metabolized in three ways by the liver: (i) glucuronidation, (ii) sulfation, and (iii)
metabolism through the cytochrome P-450 pathway to form a potentially toxic
intermediate, which conjugates with glutathione. In a massive overdose,
glutathione becomes depleted, thus allowing the undetoxified intermediate to bind
to hepatocytes, leading to cellular necrosis. This damage is reflected by rising
levels of liver enzymes, by hepatic dysfunction, and in severe poisonings, by
hepatic failure and death. The use of N -acetylcysteine as an antidote relates in
part to this molecule’s ability to act as a glutathione precursor.
Clinical Considerations
Initially, the signs and symptoms of APAP ingestion are vague and nonspecific
but can include nausea and vomiting, anorexia, pallor, and diaphoresis. These
manifestations usually resolve within 12 to 24 hours, and the patient appears well
for 1 to 4 days. During this latent period, levels of liver enzymes may rise, and
jaundice with liver tenderness may ensue. Most patients have a gradual resolution
of their hepatic dysfunction, although without antidotal treatment about 2% to 4%
of intoxications that develop toxic plasma levels will go on to hepatic failure and
death. Such patients with severe toxicity develop further clinical evidence of
hepatic disease at 3 to 5 days after ingestion, and some develop renal damage.
Anorexia, malaise, and abdominal pain may progress to signs of fulminant liver
failure with hepatic encephalopathy, coagulopathy, and multisystem organ
dysfunction.
Key components of the history include estimated amount ingested, formulation
ingested, time of ingestion, and the presence of coingestants. The potential
severity of an acute intoxication may be predicted by the amount ingested, if
accurately known, and the plasma level of APAP. A single acute overdose of less
than 200 mg/kg of APAP in young children is unlikely to cause significant
toxicity. Severe toxicity in adolescents or adults usually occurs with overdoses of
at least 7.5 to 10 g. Initial GI symptoms, although vague, are generally more
pronounced when the overdose is large, and with massive ingestions patients may
demonstrate altered mental status and metabolic acidosis soon after ingestion.
However, the only reliable indication of the potential severity of the hepatic
damage is the plasma APAP level, taken at least 4 hours after ingestion.
Basic toxicologic principles of preventing absorption apply to APAP
overdoses, and it is important to note that there are both immediate- and
