History
Most patients who have taken an overdose of acetaminophen will initially be asymptomatic, as clinical evidence of end-organ toxicity often does not manifest until 24-48 hours after an acute ingestion.
However, because antidotal therapy is most effective when initiated within 8 hours after an ingestion, it is important to obtain an accurate history of the time(s) of ingestion, the quantity, and the formulation of acetaminophen ingested. Knowledge of the maximum recommended and minimum toxic dosages, as well as underlying conditions that increase susceptibility, can help the clinician determine the risk for hepatotoxicity (see Etiology). In addition, the history should include any co-ingestants, such as salicylates or medications that may delay gastric emptying and acetaminophen absorption (eg, anticholinergic drugs or opioids).
Physical Examination
The clinical course of acetaminophen toxicity generally is divided into 4 phases. Physical findings vary, depending on the degree of hepatotoxicity.
In phase 1 (0.5-24 hours after ingestion), patients may be asymptomatic or report anorexia, nausea or vomiting, and malaise. Physical examination may reveal pallor, diaphoresis, malaise, and fatigue. It is during this phase, if the ingestion is unknown, that patients may be given an APAP-containing medication to alleviate their nonspecific symptoms.
In phase 2 (18-72 h after ingestion), patients generally develop right upper quadrant abdominal pain, anorexia, nausea, and vomiting. Right upper quadrant tenderness may be present. Tachycardia and hypotension may indicate volume losses. Some patients may report decreased urine output (oliguria).
Phase 3 (72-96 h after ingestion), is also called the hepatic phase. Patients may have continued nausea and vomiting, abdominal pain, and a tender hepatic edge. Hepatic necrosis and synthetic dysfunction manifest as jaundice, coagulopathy, hypoglycemia, and hepatic encephalopathy. Acute renal failure develops in some critically ill patients. Death from multiorgan failure may occur.
Phase 4 is the recovery phase (4 d to 3 wk after ingestion). Patients who survive critical illness in phase 3 have complete resolution of symptoms and resolution of organ failure. Clinical recovery may take up to 21 days; however, complete hepatic histologic recovery requires several months.
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Semilogarithmic plot of plasma acetaminophen levels vs time. Courtesy of Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Original_Nomogram_Rumack_BH_Matthew_H,_Acetaminophen_Pediatrics_1975_(55)_871_-_876.pdf).
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Acetaminophen metabolism. Courtesy of Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Acetaminophen_metabolism.jpg).
