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Assuming that a patient with normal or near-normal transaminases has not taken a life-threatening overdose

It is important to understand that AST and ALT are typically unaffected and normal or near-normal in the first 12 hours after a supratherapeutic ingestion. Normal serum AST and ALT levels alone are not predictors of outcome. That being said, AST levels greater than 1,000 IU/L are more likely to result from acetaminophen poisoning than from chronic hepatitis or alcoholic liver disease, and evidence suggests that the acetaminophen level multiplied by the aminotransferase level (calculated at the time of presentation and after several hours of NAC) holds promise as a risk predictor following acetaminophen overdose.⁵ This calculation may be especially useful when the time of ingestion is unknown.

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Failure to recognize the potential value of hyperphosphatemia and elevated arterial lactate in predicting death and the need for liver transplant^6,7

A prospective study looking at serum phosphate levels in patients with acetaminophen toxicity found that hyperphosphatemia was seen only in non-survivors, suggesting that it is a highly accurate predictor of death following acetaminophen overdose.⁸ A retrospective study of acetaminophen-poisoned patients found that when using a threshold of 3.5 mmol/L, arterial lactate drawn early had a positive likelihood ratio of 13, and negative likelihood ratio of 0.35 for death.⁹

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Using the Rumack-Matthew nomogram to inform treatment with NAC in patients with delayed presentations, chronic overdoses, extended-release preparation overdose, or co-ingestions with drugs known to alter the metabolism of acetaminophen (e.g., opioids, phenytoin, carbamazepine, trimethoprimsulfamethoxazole)

The Rumack-Matthew nomogram should only be used in isolated, single, acute overdoses of regular-release acetaminophen within 24 hours of ingestion, which is the minority of patients. Use of the nomogram in other clinical scenarios may be misleading. In one study that looked at patients with significant liver injury as a result of acetaminophen overdose, only 17 percent could be appropriately risk stratified using the nomogram.¹⁰

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Neglecting to administer NAC for late presentations in a timely manner

While it is true that NAC is most effective when given within eight hours of ingestion, a common pitfall is to assume more delayed ingestions do not benefit from administration of NAC.¹¹ There are often significant delays from the time of ordering NAC to the time that the infusion is started. NAC should be given immediately. Indications for NAC include “line crossers” on the Rumack-Matthew nomogram (after an isolated acute ingestion of regular-release acetaminophen within 24 hours) and those patients with elevated transaminases (even in the absence of elevated acetaminophen level) deemed to be as a result of acetaminophen toxicity. If the initial level is not above the nomogram line at the four-hour mark, then an eight-hour and 12-hour level should be drawn.