Acute methanol poisonings: Folates administration and visual sequelae

Zakharov, Sergey; Nurieva, Olga; Navrátil, Tomáš; Diblik, Pavel; Kuthan, Pavel; Pelclová, Daniela

doi:10.1016/j.jab.2014.04.001

Cited by 40 publications

(22 citation statements)

References 37 publications

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“…Folates were administered to substitute the internal pool (folinic or folic acid) [35]. No corticosteroids and nonsteroid anti-inflammatory drugs were administered.…”

Section: Selection Of Participants and Treatmentmentioning

confidence: 99%

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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“…Folates were administered to substitute the internal pool (folinic or folic acid) [35]. No corticosteroids and nonsteroid anti-inflammatory drugs were administered.…”

Section: Selection Of Participants and Treatmentmentioning

confidence: 99%

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

Zakharov

Kotikova

Nurieva

et al. 2017

Clinical Toxicology

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“…These poisonings generally occur either intentionally through abuse, attempted suicide or unintentionally through misuse or accident 3 . It is a medical emergency where rapid administration of antidotes, fomepizole or ethanol, preventing toxic metabolite formic acid formation by blocking alcohol dehydrogenase (ADH) is crucial for successful treatment 4,5 . Formate anions as the products of methanol metabolism have a strong cytotoxic effect by inhibition of mitochondrial respiration 6,7 .…”

Section: Introductionmentioning

confidence: 99%

“…Thus, it effectively blocks the enzyme when its concentration in blood serum is between 1000-1500 mg/L (22-33 mmol/L) (ref. 5,14 ). Fomepizole (4-methylpyrazole) is another effective antidote with affinity for ADH several thousand times higher than of methanol [15][16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

Fomepizole in the treatment of acute methanol poisonings: Experience from the Czech mass methanol outbreak 2012-2013

Zakharov¹,

Navrátil²,

Pelclová³

2014

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Objective. During an outbreak of mass methanol poisonings in the Czech Republic in 2012-2013, fomepizole was applied as an alternative antidote to ethanol. We present the laboratory data, clinical features, adverse reactions, and treatment outcomes in all patients treated with fomepizole. Methods. Combined retrospective and prospective case series study in 25 patients, median age 50 (16-73) years, 18 males and 7 females. Results. There were 24% fatalities, 36% survivors without health impairment, and 40% survivors with sequelae. All the patients who died were comatose on admission; the mortality was 50% among patients in a coma. The median intensive care unit length of stay was six (2-22) days. The median total dose of fomepizole was 2 (1-9) g. Complications were observed in 7/25 cases: aspiration pneumonia (4), sepsis (2), bleeding (2), malignant arrhythmia (1), delirium tremens (1), and rebound of acidosis (1). The patients who survived without impairment were less acidotic than those who died or survived with sequelae (P<0.01). No difference in serum methanol and formate was found between the three groups. Conclusion. There is no evidence whether fomepizole is a more efficient antidote than ethanol with regards to the hospital mortality. The possibility of delirium tremens in the patients with a history of chronic alcohol abuse has to be taken in consideration. The benefits of fomepizole were indirect: no need to monitor serum ethanol's level during the hemodialysis in severely poisoned patients and less working overload on ICU doctors treating several poisoned patients simultaneously.

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“…The normal blood serum concentration of formate in healthy human subjects is 0.033 AE 0.013 mmol/L [11,12]. In cases of methanol poisoning, formate anions accumulate due to the saturation of their folate-dependent elimination, resulting in the gradual accumulation of this metabolite and subsequent delayed toxic effects [13][14][15].The formate anions as the products of methanol metabolism have a strong cytotoxic effect, inhibiting mitochondrial respiration [16,17]. The accumulation of formic acid results in metabolic acidosis, lactacidaemia, visual impairment and damage to the basal ganglia in the brain [18,19].…”

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confidence: 99%

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confidence: 99%

Is the Measurement of Serum Formate Concentration Useful in the Diagnostics of Acute Methanol Poisoning? A Prospective Study of 38 Patients

Zakharov

Kurcová

Navrátil

et al. 2014

Basic Clin Pharma Tox

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The aim of this article was to study the role of serum formate (S-formate) in diagnosing methanol poisoning. A prospective study was undertaken of 38 patients from the Czech methanol mass poisoning in 2012 -median age 51 [interquartile range (IQR) 37-62] years with confirmed methanol poisoning. S-formate was measured enzymatically. The receiver operating characteristics (ROC) curve was used to examine the predictive ability of S-formate. Asymptomatic patients had median S-formate of 1.9 (IQR 1.5-2.4) mmol/L. The median S-formate was 15.2 (IQR 13.9-17.6) mmol/L in symptomatic subjects with visual disturbances, 15.4 (12.1-18.0) mmol/L in subjects with dyspnoea and 15.7 (IQR 12.8-18.5) mmol/L in comatose patients. The differences in serum formate concentrations in symptomatic patients depending on clinical features were not significant (all p > 0.05). Patients with long-term visual sequelae of poisoning had median S-formate of 16.1 ) mmol/L; with central nervous system (CNS) sequelae, patients had 15.9 (IQR 14.2-19.5) mmol/L. In lethal cases, the median S-formate was 15.2 (IQR 13.8-15.9) mmol/L. The probability of a poor outcome (death or survival with sequelae) was higher than 90% in patients with S-formate ≥17.5 mmol/L, S-lactate ≥7.0 mmol/L and/or pH <6.87. The ROC analysis showed that the corresponding areas under the curve (AUC) were 0.64 (0.44-0.85 CI 95%) for S-formate, 0.75 (0.56-0.93 CI 95%) for 'S-formate+S-lactate' and only 0.54 (0.38-0.69 CI 95%) for serum methanol, which is lower than for S-formate (p < 0.05). The measurement of S-formate is an important tool in the laboratory diagnostics and clinical management of acute methanol poisoning. S-formate ≥3.7 mmol/L can lead to the first clinical signs of visual toxicity, indicating haemodialysis. S-formate ≥11-12 mmol/L is associated with visual/CNS sequelae and a lethal outcome.Acute methanol poisoning remains a challenge for healthcare providers throughout the world because of its high mortality rate and serious health sequelae [1][2][3]. This poisoning generally occurs either intentionally through abuse or attempted suicide or unintentionally through misuse or accident [4,5]. It is a medical emergency in which the rapid administration of antidotes preventing formic acid formation as a toxic metabolite of methanol by blocking alcohol dehydrogenase (ADH) and the enhanced elimination of formate and methanol are crucial for successful treatment [6][7][8].Nevertheless, in cases of poisoning with toxic spirits containing mixtures of methanol and ethanol in adulterated strong alcoholic beverages, timely diagnosis is difficult due to the long latency period and late presentation to hospitals. Therefore, the onset of treatment is often delayed [7,9]. Serum concentrations of methanol in late-presenting patients can be low and even under the level of detection due to its biotransformation. On the other hand, serum concentrations of formic acid rise high above the upper reference limit of 0.4 mmol/L [9].Formate is one of the normal intermediates in human...

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Acute methanol poisonings: Folates administration and visual sequelae

Cited by 40 publications

References 37 publications

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

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

Fomepizole in the treatment of acute methanol poisonings: Experience from the Czech mass methanol outbreak 2012-2013

Is the Measurement of Serum Formate Concentration Useful in the Diagnostics of Acute Methanol Poisoning? A Prospective Study of 38 Patients

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