Should a Lower Treatment Line Be Used When Treating Paracetamol Poisoning in Patients with Chronic Alcoholism?

Abstract

The widespread practice of using a lower plasma paracetamol (acetaminophen) concentration threshold for the treatment of paracetamol poisoning in patients with chronic alcoholism has been introduced on the basis of anecdotal case reports. In animals, acute alcohol loading inhibits toxic metabolic activation of paracetamol whilst chronic alcohol administration results in cytochrome P450 (CYP) 2E1 induction with increased toxic metabolic activation of paracetamol by CYP2E1 and increased hepatotoxicity. However, due to species differences in CYP expression, activity and induction, it is not possible extrapolate the results of these animal studies to clinical situations in humans. Isoenzymes are also responsible for the metabolic activation of paracetamol in humans and human studies to date have not convincingly demonstrated increased toxic metabolic activation of paracetamol in patients with chronic alcoholism. Acute alcohol ingestion at the time of a paracetamol overdose is probably protective and the timing and chronicity of alcohol intake is therefore crucial in the interpretation of the effects of alcohol on paracetamol overdose. One of the problems in the interpretation of the literature to date is that insufficient information is available on the timing of alcohol intake in relation to the ingestion of paracetamol. Whilst it is possible that chronic exposure to excessive amounts of alcohol does predispose patients with paracetamol overdose to hepatotoxicity, a critical review of the literature reveals that the evidence to date does not support this. A prospective, controlled study is required. On the basis of the scientific evidence to date, use of the 100 line for patients with chronic alcoholism, in countries where the 200 line represents the standard treatment line, is unjustified.

Acute Ethanol Coingestion Confers a Lower Risk of Hepatotoxicity after Deliberate Acetaminophen Overdose

“…16,[20][21][22] However, there is some uncertainty about the significance of chronic ethanol consumption as an independent risk factor, because the association is confounded by delayed presentation to hospital and initiation of NAC. [23][24][25][26] Exclusion of patients who presented more than 24 hours after ingestion does not allow us to address whether chronic ethanol excess might influence the development of hepatotoxicity in patients who present late. Induction of cytochrome 2E1 requires chronic exposure to ethanol concentrations >250 mg ⁄ dL, which might be encountered only in patients with extremely heavy drinking patterns.…”

A Risk Quantification Instrument for Acute Acetaminophen Overdose Patients Treated With N-Acetylcysteine

“…4 Initiating antidote therapy based on the Rumack-Matthew nomogram has withstood the test of time, with only rare failures reported using the 150 mg/ mL (1,000 mmol/L) treatment line. 15,25,26 Which N-acetylcysteine protocol to initiate, however, is less clear. Without the ability to identify low-risk patients at presentation, clinicians must follow an ''all or none'' approach, in which all patients at some risk are admitted to the hospital and prescribed the same antidote regimen.…”

“…Our findings refute the suggestion that the apparent susceptibility of alcoholics is merely due to greater delays to presentation or larger doses ingested. 14,15,43 In conclusion, we propose a risk prediction instrument expressing the first dose-response curve for hepatotoxicity after acute acetaminophen overdose treated with N-acetylcysteine. This instrument uses pretreatment exposure to predict hepatotoxicity.…”

“…3,6,7,13,14 Moreover, the effects of postulated risk modifiers such as alcoholism and acute ethanol ingestion are poorly quantified. 15,16 Therefore, only a rough approximation of risk is possible for patients treated with N-acetylcysteine, despite the frequency of this occurrence.…”

Oral Presentations

“…Conclusion: Male aged patients receiving aspirine at low dose, as antiplatelet drug therapy, combined with other drugs, specially NSAID or COX2 inhibitors seem to be at a higher risk of suffering GIH. Although avoiding aspirin plus NSAID is recommended in the summarized data sheet of these two drugs, a specific reference to the risk of suffering GIH by combining aspirin with COX2 inhibitors, (Dargan & Jones, 2002;Buckley & Srinivasan, 2002). Aims: This study aimed to examine whether acute ethanol co-ingestion influences the risk of hepatotoxicity after acute paracetamol ingestion.…”