Abstract
During the 2012 outbreak of mass methanol poisonings in the Czech Republic, ethanol, in the main, was used as an antidote. The complex pharmacokinetics of ethanol made it difficult to maintain the requisite 1000-1500 mg/L serum ethanol levels (S-EtOH). The aim of this study was to measure the fluctuations in S-EtOH during the treatment. A prospective case series in 21 patients, median age 52 (27-79 years), 13 males and 8 females. Serum ethanol, methanol and formate were measured every 2-6 hours during the treatment. Follow-up clinical examination was carried out in 15/18 survivors. The majority of patients (17/21) were late presenters and on admission, almost half (10/21) had suffered a severe grade of intoxication according to the Poisoning Severity Score (PSS). The mean observation time was 90±20 h. The mean period of consistent maintenance of S-EtOH within the recommended therapeutic range lasted 28±7% of the total observation time. For 29±8% of the time, S-EtOH was >1500 mg/L with "peaks" of up to 3500 mg/L. For 44±10% of the observation time, S-EtOH was <1000 mg/L. The mean duration of sub-therapeutic concentration of S-EtOH and toxic serum levels of methanol >200 mg/L or formate >20 mg/L lasted 20±10% and 18±11% of the time of observation, respectively. Complications occurred in 14 (67%) of cases including significant fluctuations of S-EtOH in 9; aspiration pneumonia in 3 and delirium tremens in 2 cases. Other complications included sepsis, bleeding, acidosis rebound, intolerance and set clotting. The outcomes were: 11 survivors free of health impairment, 7 with sequelae and 3 deaths. There was no significant difference in mean duration of sub-therapeutic and supra-therapeutic concentrations of serum ethanol in patients who survived without sequelae and those with poor outcome (P > 0.05). Administration of ethanol according to the present guidelines of the AACT/EAPCCT is effective and relatively safe in the treatment of methanol poisoning during a mass outbreak(31). Physicians have to be most aware of fluctuations in serum ethanol at the end of short sessions of IHD and after changes in route from intravenous to oral. Rigorous monitoring of serum ethanol concentrations is pivotal for severely poisoned patients with PSS 3 and where there is suspected conversion of significant amounts of methanol to formic acid.
Highlights
Methanol in illicit alcoholic drinks remains an important cause of outbreaks of mass poisonings throughout the world, resulting in high mortality and serious health damage1-4
In our study despite the wide fluctuations in serum ethanol concentration during the treatment, we found no association between serum ethanol fluctuations and treatment outcome
Rigorous monitoring of the serum ethanol concentrations is pivotal for the severely poisoned patients with Poisoning Severity Score (PSS) 3 and for patients where it is suspected that significant amounts of methanol will be converted to formic acid
Summary
Methanol in illicit alcoholic drinks remains an important cause of outbreaks of mass poisonings throughout the world, resulting in high mortality and serious health damage. Formate anions as the products of methanol metabolism have a strong cytotoxic effect by inhibition of mitochondrial respiration. The accumulation of formic acid results in metabolic acidosis, lactacidemia, visual impairment, and damage of basal ganglia. Ethanol or fomepizole, prevents toxic metabolite formation by blocking the alcohol dehydrogenase (ADH) enzyme. The role of ethanol in the treatment of acute methanol poisonings is well-established. Ethanol has approximately ten times higher affinity to ADH than methanol, so it blocks effectively the enzyme when its concentration in the blood serum is between 1000-1500 mg/L (2233 mmol/L) (ref.). Fomepizole (4-methylpyrazole) is another effective antidote with affinity to ADH several thousand times higher than that of methanol
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