For acute overdoses, in which an acetaminophen level is available within 8 hours of the time of ingestion, the emergency physician has the luxury of time. Smilkstein et al., demonstrated that NAC administration within the first 8 hours is essentially 100% effective at preventing hepatotoxicity.⁴ This does not imply that physicians should unnecessarily delay NAC administration; rather, this knowledge should reassure the clinician that an acetaminophen level can be checked and plotted on the nomogram without negative consequences.

Because patients are at greater risk of morbidity and mortality if they are not treated with NAC within 8 hours of ingestion, all patients with delayed presentations should be empirically treated with NAC prior to any laboratory evaluation. If the acute ingestion occurred within the past 24 hours, the acetaminophen level should be plotted on the nomogram. If the patient’s level is above the toxic level, NAC should be continued, and the patient should be admitted for further treatment.

Likewise, all patients with ingestions that occurred more than 24 hours before presentation and those with chronic or multiple ingestions should be empirically treated with NAC. These patients with acetaminophen levels of more than 10 mcg/mL or AST levels above 50 IU/mL should be presumed to have toxicity and should be admitted for continuation of treatment.⁵ Remember that patients who smoke and chronically consume alcohol, those who are fasting or debilitated, and those who take medicines that delay gastric emptying (opiates, anticholinergics) or induce liver enzyme activity (phenytoin, phenobarbital, carbamazepine, rifampin, and isoniazid) are more susceptible to acetaminophen toxicity.

Even patients who present in fulminant hepatic failure benefit from NAC.^6,7 Keays et al demonstrated that patients with fulminant hepatic failure who received NAC had improved survival rates (48% versus 20%), a lower incidence of cerebral edema (40% versus 68%), and fewer episodes of hypotension requiring pressor support (48% versus 80%).⁶

If there is any doubt, err on the side of caution and administer NAC until the case can be discussed with the local poison control center. Activated charcoal (1g/kg up to 50 grams) should be administered within 4 hours of an ingestion for decontamination.

CRITICAL DECISION

Which patients should be transferred to a liver transplant center following an acetaminophen overdose?

Although patients with fulminant hepatic failure still benefit from NAC administration, it is important to identify which patients will require a liver transplant for survival. The King criteria predict death from fulminant hepatic failure if the patient does not receive a liver transplant.^8-10 The King criteria are a serum pH below 7.3 after adequate fluid resuscitation; creatinine above 3.3 mg/dL; INR above 6.5, and grade III or IV encephalopathy. If any of the above criteria are met, serious consideration should be given to transferring the patient to a regional liver transplant center for definitive management.

Case Resolution

The young woman who attempted suicide with acetaminophen was treated with intravenous NAC and admitted to a monitored bed. The following morning, repeat liver enzymes showed improvement: AST of 540 and ALT of 616. The NAC was continued for an additional 20 hours, and the following day the patient’s liver enzymes had normalized. She was discharged from the hospital, and outpatient followup with a psychiatrist was scheduled.

Summary

Toxic exposures are a growing threat; it is essential that emergency physicians be able to diagnose and treat these patients effectively. Failure to recognize these subtle poisonings in the emergency department could lead to further morbidity and mortality.