Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity

Abstract

The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were studied, giving special attention to alcohol history, time between overdose and intravenous N-acetylcysteine (NAC) treatment ("time to NAC"), and other data available at the time of admittance. Up until 72 hours after ingestion, time to NAC was the single most important independent risk factor. With a time to NAC less than 12 hours, the mortality rate was 0.42% (95% CI, 0.05-2.7). When time to NAC exceeded 12, 24, and 48 hours, the mortality rate increased to 6.1%, 13%, and 19%, respectively. Chronic alcohol abuse was an independent risk factor of mortality (odds ratio [OR], 3.52; 95% CI, 1.78-6.97). Acute alcohol ingestion was an independent protective factor regarding mortality in alcoholic patients (OR, 0.08; 95% CI, 0.01-0.66) but not in nonalcoholic patients (OR, 0.21; 95% CI, 0.03-1.67). Patient age and quantity of acetaminophen were independent risk factors. In conclusion, time to NAC was confirmed as the major risk factor in acetaminophen-induced hepatotoxicity and mortality. Chronic alcohol abuse was an independent risk factor that could be counteracted by concomitant acute alcohol ingestion. We suggest that patients with chronic alcoholism and suspected acetaminophen poisoning due to an increased risk of developing hepatotoxicity should be treated with NAC regardless of risk estimation. (HEPATOLOGY 2002;35:876-882.)

Acetaminophen‐induced acute liver failure

“…Compared with nonabusers, alcohol abusers had lower acetaminophen levels (15 g/dL [range, 0-315] vs. 34 g/dL [0-644]; P ϭ .003), were less likely to use antidepressants (24% vs. 40%; P ϭ .03) or compound narcotics (31% vs. 50%; P ϭ .009), and were less likely to present with severe (grades 3 and 4) hepatic encephalopathy (34% vs. 53%; P ϭ .02). Clinically, there were no other differences between those who were abstinent and those who abused alcohol with regard to INR, ALT, bilirubin, body mass index (BMI), APACHE II score, MELD score, or overall survival (data not shown).…”

Acetaminophen Poisoning: an Evidence-Based Consensus Guideline for Out-of-Hospital Management

“…The smallest reported doses associated with evidence of hepatic injury have ranged from 3.25 to 10 g (2,34-46). A cohort analysis (level 2b) described several patients in whom acute doses of less than 12 g were associated with hepatotoxicity, but the exact doses were not specified (47). This same study reported deaths in patients with reported doses as low as 15 g. In contrast, some reports have described large single ingestions with documented serum concentrations of acetaminophen above the possible or probable toxicity nomogram lines that did not result in toxicity (48).…”

“…Patients with acute co-ingestion of acetaminophen with alcohol or gastrointestinal antimotility agents and patients taking cimetidine chronically have been reported to be at decreased risk of liver injury (levels 2b and 4) (31,47,50,53,77,78). Other authors have found no correlation between acute alcohol consumption and severity of toxicity (level 2b) (46).…”

“…Other authors have found no correlation between acute alcohol consumption and severity of toxicity (level 2b) (46). Schmidt et al (47) reported that acute ingestion of benzodiazepines exacerbated hepatic encephalopathy after acute acetaminophen overdose but that acute use of opiates was protective against hepatotoxicity (level 2b). Schmidt et al also reported that chronic use of opioids, benzodiazepines, and acetaminophen increased the risks of various negative outcomes after acute acetaminophen overdoses.…”

“…In a large cohort analysis (level 2b), Schmidt et al (47) found that mortality after acute acetaminophen overdose depended on time to acetylcysteine treatment, with mortality rates for the 0-12, 12-24, 24-48, and more than 48 hour groups of 0.4%, 6%, 13%, and 19%, respectively. One study (level 2b) found no difference in survival between small treated and untreated cohorts (43).…”