Use of Out-of-Hospital Ethanol Administration to Improve Outcome in Mass Methanol Outbreaks

Zakharov, Sergey; Pelclová, Daniela; Urban, Pavel; Navrátil, Tomáš; Nurieva, Olga; Kotikova, Katerina; Diblik, Pavel; Kurcová, Ivana; Běláček, Jaromír; Komarc, Martin; Eddleston, Michael; Hovda, Knut Erik

doi:10.1016/j.annemergmed.2016.01.010

Cited by 34 publications

(20 citation statements)

References 48 publications

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“…This fact supports the recommendation on the potential benefit of the pre-hospital administration of ethanol on outcome during an on-going outbreak of methanol poisoning [21]: given a standard regimen, a worst-case scenario would mean that a certain number of patients will be given a limited amount of ethanol unnecessarily, which can be considered acceptable from a risk–benefit point of view.…”

Section: Resultssupporting

confidence: 81%

“…Its wide availability in the community makes it suitable antidote for a pre-hospital ‘first aid’ in the cases of suspicious toxic alcohol ingestion. We addressed this question during a recent methanol mass poisoning in the Czech Republic [20, 21]. In this study, we aimed to evaluate serum ethanol concentration on admission to hospital as the factor predictive of treatment outcome in patients with acute methanol poisoning during a methanol epidemic.…”

Section: Introductionmentioning

confidence: 99%

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Positive serum ethanol concentration on admission to hospital as the factor predictive of treatment outcome in acute methanol poisoning

et al. 2016

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Mass methanol poisonings present a serious problem for health systems worldwide, with poor outcome associated with delayed treatment. Positive pre-hospital serum ethanol concentration may have predictive value as the prognostic factor of the treatment outcome. We studied the effect of positive serum ethanol level on admission to hospital on survival in patients treated during the Czech methanol outbreak during 2012–2014. Cross-sectional cohort study was performed in 100 hospitalized patients with confirmed methanol poisoning. Pre-hospital ethanol was administered in 42 patients (by paramedic/medical staff to 30 patients and self-administered by 12 patients before admission); 58 patients did not receive pre-hospital ethanol. Forty-two patients had detectable serum ethanol concentration on admission to hospital [median 18.3 (IQR 6.6–32.2) mmol dm−3]. Pre-hospital ethanol administration by paramedic/medical staff had a significant effect on survival without visual and CNS sequelae when adjusted for arterial blood pH on admission (OR 8.73; 95 % CI 3.57–21.34; p < 0.001). No patients receiving pre-hospital ethanol died compared with 21 not receiving (p < 0.001). Positive serum ethanol concentration on admission to hospital was a predictor for survival without health sequelae when adjusted for arterial blood pH (OR 8.10; 95 % CI 2.85–23.02; p < 0.001). The probability of visual and CNS sequelae in survivors reduced with increasing serum ethanol concentration on admission.Graphical abstract

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Section: Resultssupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Positive serum ethanol concentration on admission to hospital as the factor predictive of treatment outcome in acute methanol poisoning

et al. 2016

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“…In animal models of cerebral, renal, liver, and cardiac ischemia, alcohol exposure was shown to reduce ischemia reperfusion injury and prevent post-ischemic adhesive interactions between leukocytes and endothelial cells which can lead to organ dysfunction and death [51,52]. The patients who received pre-hospital ethanol as a "first aid antidote" before admission to hospital had higher serum LTC4 concentration and had better outcome of poisoning than those with negative serum ethanol on admission, as was shown in our earlier studies [53,54]. Finally, the patients treated with IHD had higher concentration of cys-LTs than those treated with CRRT.…”

Section: Discussionsupporting

confidence: 59%

Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning

Zakharov

Kotikova

Nurieva

et al. 2017

Clinical Toxicology

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Context: The role of neuroinflammation in methanol-induced toxic brain damage has not been studied. Objective: We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors. Methods: Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge. Results: The acute maximum (C max ) LT concentrations were higher than concentrations in survivors: C max for LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p < 0.001). The patients who survived had higher LT concentrations than those who died (all p < 0.01). Among survivors, patients with CNS sequelae had lower LTE4 and LTB4 than did those without sequelae (both p < 0.05). The LT concentrations increased at a rate of 0.4-0.5 pg/mL/h and peaked 4-5 days after admission. The patients with better outcomes had higher cys-LTs (all p < 0.01) and LTB4 (p < 0.05). More severely poisoned patients had lower acute LT concentrations than those with minor acidemia. The follow-up LT concentrations in survivors with and without CNS sequelae did not differ (all p > 0.05). The mean decrease in LT concentration was 30.9 ± 9.0 pg/mL for LTC4, 26.3 ± 8.6 pg/mL for LTD4, 37.3 ± 6.4 pg/mL for LTE4, and 32.0 ± 8.8 pg/mL for LTB4. Conclusions: Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.ARTICLE HISTORY

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“…In humans, up to 30% of the consumed methanol is excreted through the respiratory tract, 3% to 5% are excreted unchanged through the sweat and urine . The majority (~60%) of the consumed methanol is, due to its structural similarity to ethanol, metabolised through the same pathway as ethanol (as long as ADH1B activity is not saturated by ethanol, which has a higher affinity to this enzyme than methanol) …”

Section: Introductionmentioning

confidence: 99%

Aldehyde dehydrogenase 2 polymorphism affects the outcome of methanol poisoning in exposed humans

et al. 2018

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As the susceptibility of humans to xenobiotics often depends on genetic factors, we assumed that ADH1B and ALDH2 genetic variants may affect susceptibility to the acute methanol exposure. To evaluate the role of genetic variants of enzymes involved in methanol catabolism in humans, we analysed ADH1B (rs1229984) and ALDH2 (rs441) polymorphisms in 50 adults who survived acute methanol poisoning, 246 individuals with alcoholic liver cirrhosis, and in 545 healthy controls. GG homozygotes of ADH1B were more common among methanol-poisoned patients (98%) and among patients with alcoholic liver cirrhosis (98%) than among healthy controls (90%) (P = 0.08 and < 0.001, respectively). Minor C allele carriers of the ALDH2 were significantly more common among methanol-poisoned persons (46%) than among patients with alcoholic liver cirrhosis or healthy controls (31% in both groups, P < 0.05 and 0.025, respectively); the odds ratios were 1.89 (95% CI 1.02-3.52) and 1.94 (1.08-3.48), respectively. As there was a substantial amount of subjects with alcohol abuse between both groups of patients, ADH1B is unlikely to affect the susceptibility to methanol poisoning. By contrast, the genetic variant of the ALDH2 enzyme seems to specifically affect the susceptibility to methanol in acutely exposed humans and potentially plays a role in the outcome of methanol poisoning.

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Use of Out-of-Hospital Ethanol Administration to Improve Outcome in Mass Methanol Outbreaks

Abstract: We found a positive association between out-of-hospital ethanol administration and improved clinical outcome. During mass methanol outbreaks, conscious adults with suspected poisoning should be considered for administration of out-of-hospital ethanol to reduce morbidity and mortality.

Cited by 34 publications

References 48 publications

Positive serum ethanol concentration on admission to hospital as the factor predictive of treatment outcome in acute methanol poisoning

Positive serum ethanol concentration on admission to hospital as the factor predictive of treatment outcome in acute methanol poisoning

Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning

Aldehyde dehydrogenase 2 polymorphism affects the outcome of methanol poisoning in exposed humans

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