Intentional or Inadvertent Acetaminophen Overdose-How Lethal It Really Is?

Acetaminophen, the ubiquitous over-the-counter analgesic and antipyretic, is the most common drug used in intentional overdoses in the United States. Inadvertent self-poisoning is also a surprisingly common unintended consequence of acetaminophen misuse for pain management.

The primary goal of this naturalistic study was to substantiate outcomes that were previously described in other large cohorts of patients with acetaminophen overdoses.

The Rochester Epidemiology Project yielded a cohort of 207 patients of age 18 years or older treated at the Mayo Clinic between January 1, 2004 and December 31, 2010 for excessive acetaminophen exposure. Patients with a diagnosis of acetaminophen overdose, acetaminophen ingestion, and/or acetaminophen toxicity were characterized according to demographics, treatment location, overdose intentionality, identities of the drugs and amounts taken, mental health and addiction history, previous suicide attempts, and current alcohol intake. Outcomes included N-acetylcysteine treatment, emergence of serious clinical syndromes, and admission to the liver transplant unit (LTU), liver transplant, and death. Data were analyzed using the JMP statistical program.

Of 140 females and 67 males treated in the emergency department (ED), 184 (89%) were admitted, including 116 (56%) to the intensive care unit, 26 (13%) to medicine services, 18 (9%) directly to LTU, 23 (11%) directly to psychiatry services, and 1 (0.5%) to off-campus detox. The consultation-liaison (C-L) psychiatry service evaluated 175 patients (85%). Eighteen intensive care unit/medicine patients were eventually transferred to the LTU, and 104 of the 184 patients not immediately admitted to psychiatry were ultimately transferred there. Of all, 158 (76.3%) overdoses were intentional, but in the chronic pain subset of 14 patients, only 4 (29%) were. One hundred twenty-seven (61%) patients had no previous suicide attempt history. Twenty-one percent of the intentional overdose group versus 12.5% of the unintentional overdose group was intoxicated at the time of overdose. One hundred thirty-five (65%) patients received N-acetylcysteine, but barely a third (33%) were treated within the recommended 8 hours of overdose. Nonetheless, most outcomes were benign: only 36 (17.6%) required LTU admission because of serious medical complications. Only 12 received consideration for transplant, and only 5 (2.7%) were listed for transplant. Three (1.5%) ultimately received new livers. Two (1.0%) died awaiting transplant. Two of the 3 transplanted patients had unintentionally overdosed while treating chronic pain.

A vast majority of patients survived and recovered without lasting medical sequelae, including liver transplant. Half of the patients received N-acetylcysteine, and only a third received it within the recommended 8-hour window after ingestion. Serious medical consequences were concentrated in the 17% of patients requiring LTU admission. With a transplant rate of 1.5% and a death rate of less than 1%, we conclude that the risk of serious medical outcomes from this frequent overdose modality is rare, even as the majority of both intentional and unintentional overdose patients received both inpatient medical and psychiatric treatment.