Journal of Clinical Toxicology
Open Access

Fomepizole and Concomitant Hemodialysis Regimen is Effective in Overdue Methanol Poisoning

Sinan Yavuz^1*, Selman Kesici¹, Gorkem Abdikan², Nesrin Tas³, Ali Duzova³ and Benan Bayrakci^{1 *}Correspondence: Sinan Yavuz, Department of Pediatric Critical Care Medicine, Life Support Practice and Research Center, Hacettepe University, Ankara, Turkey, Email:

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Introduction

Methanol (CH₃OH) is also known as wood alcohol and its intake may cause severe metabolic acidosis and visual impairments, which can be permanent despite aggressive treatment [1]. It is used in as a synthetic precursor in laboratories and as a solvent in industry. It is used for some plastic materials, synthetic textile products and paints as a precursor. Methanol intoxication is most often caused by the intake of methanol containing commercial products and consuming alcoholic beverages containing these products. Intentional use may also occur when desperate alcoholics who could not reach ethanol (C₂H₅OH) containing beverages, either don’t know the substance is toxic or know it is toxic [2]. In this case report, we will present a methanol poisoning case presenting with visual complaints.

Case Presentation

A 17-year-old male patient was admitted to the Pediatric Intensive Care Unit with the complaint of blurred vision. It was learned that he drank 200 ml of homemade drink two days ago and spent the night sleeping. In physical examination, bilateral mydriasis and nystagmus with normal vital signs were recorded. His visual acuity and optic disc margins were indistinct. Blood gas analysis revealed severe metabolic acidosis (pH 7.17, CHCO₃ 11.2 mmol/L, anion gap 15 mmol/L). One-session emergency hemodialysis was started because of ongoing acidosis despite bicarbonate infusion. After hemodialysis, 15 mg/kg/dose fomepizole was administered, followed by a dose of 10 mg/kg 12 hours later. Venous blood gas was found as (pH 7.38, HCO₃ 23.4 mmol/L, anion gap 10 mmol/L) at the fourth hour of the follow-up. Acidosis and blurred vision were improved after hemodialysis. Eye drops including coenzyme Q and vitamin E TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) were started with the diagnosis of optic neuritis due to methanol intoxication. The patient’s vision was completely recovered and he was discharged on the fourth day (Figure 1).

Figure 1: In the case of methanol intoxication prompt treatment with fomepizole are used.

Results and Discussion

Methanol intoxication mostly occurs due to oral intake while dermal absorption and inhalation can also cause intoxication. Methanol is rapidly absorbed from the gastrointestinal tract. The volume of distribution after absorption is similar to that of body water, reaches a peak concentration in the blood within 30-40 minutes. Its half-life is 14-30 hours when taken alone, 43-96 hours when taken with ethanol [3]. Since the price of methanol is cheaper than ethanol, it has caused an outbreak of poisoning even in Libya and Kenya, where alcohol consumption rates are low [4]. Regardless of the price of ethanol, bulk methanol can be bought cheaper, which has led to outbreaks in countries such as Estonia, the Czech Republic, Finland, and Poland.

Methanol toxicity has been extensively studied since it is considered as a serious neurotoxin in humans. It is well known that the nervous system and especially the visual system are vulnerable to methanol poisoning [5]. Alcohol is converted into formate by Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase Enzymes [6]. Retinal and optic nerve neurons are particularly sensitive to the harmful effects of formate due to the difference in their mitochondria density [7]. An oral intake of 3.16-11.85 g/person of pure methanol could cause blindness and onset of optic neuritis and blindness has been demonstrated at a concentration of 228.5-1103 mg/ml for 12- hour exposure [8]. Basal ganglia, especially putamen and subcortical white matter are also more sensitive to formate toxicity. Our case had already the complaint of blurred vision.

As formate accumulates, the most characteristic and often the most obvious symptom is vision impairment. This visual finding can range from mild impairment in visual acuity to complete blindness. In the survivors, visual findings may be permanent or recover partially or completely [2]. When enough methanols are metabolized severe metabolic acidosis and secondary hyperpnea may be seen. Our patient had severe metabolic acidosis on admission. Apart from the initial inebriation, CNS findings such as headache, confusion and stupor; in severe cases, coma, brain edema, brain damage, and herniation may be seen. Severe heart failure and shock have also been reported.

Since methanol is absorbed very quickly, decontamination with gastric lavage or activated charcoal is not recommended. Sodium bicarbonate is recommended to correct severe acidosis [9]. An antidote to block ADH metabolism due to severe morbidity and potential mortality should be started quickly. Before fomepizole was available, ethanol was routinely used to treat toxic methanol intake. Today, fomepizole is used as a first-line antidote in North America and Western European countries due to its effectiveness and reliability [10]. Fomepizole and ethanol are more effective in the early stage of intoxication before toxic metabolites reach a significant level. There are several reasons why fomepizole is preferred as an antidote rather than ethanol. Fomepizole is more potent with longer duration of action in a ADH inhibition. The administration regimen is easy and there is no need to monitor fomepizole concentration in the blood, it is generally well tolerated. In oral or intravenous ethanol treatment, blood ethanol concentration monitoring and frequent dose adjustments are required. In our case we started immediately sodium bicarbonate infusion and fomepizole treatment.

Hemodialysis (HD) is indicated in case of significant metabolic acidosis, visual abnormality, vital signs deteriorated despite intensive supportive treatment, renal failure or electrolyte imbalance that does not respond to conventional treatment [11]. Methanol molecular size is 0.45 nm and formate molecular size is 0.43 nm and they can be easily removed with HD [12]. These procedures contribute to clinical recovery with direct removal of toxin, correction of acidosis, or both. Since the inhibition of ADH significantly increases the half-life of methanol by an average of 54 hours, the removal of methanol with HD shortens the treatment time [13].

Conclusion

Since our patient had blurred vision and severe metabolic acidosis, hemodialysis was started immediately. As a conclusion we would like to draw attention to the effectiveness of fomepizole and concomitant HD for reversing the visual complications of methanol even if applied during the late stages of the intoxication.

References

1. Suit PF, Estes ML. Methanol intoxication: Clinical features and differential diagnosis. Cleve Clin J Med. 1990;57(5):464-471.

   [Crossref] [Google Scholar] [PubMed]

2. Kruse JA. Methanol and ethylene glycol intoxication. Crit Care Clin. 2012;28(4):661-711.

   [Crossref] [Google Scholar] [PubMed]

3. Kraut JA, Kurtz I. Toxic alcohol ingestions: Clinical features, diagnosis, and management. Clin J Am Soc Nephrol. 2008;3(1):208-225.

   [Crossref] [Google Scholar] [PubMed]

4. Rostrup M, Edwards JK, Abukalish M, Ezzabi M, Some D, Ritter H, et al. The methanol poisoning outbreaks in Libya 2013 and Kenya 2014. PloS One. 2016;11(3):e0152676.

   [Crossref] [Google Scholar] [PubMed]

5. Meyer RJ, Beard ME, Ardagh MW, Henderson S. Methanol poisoning. N Z Med J. 2000;113(1102):11.
6. McLean DR, Jacobs H, Mielke BW. Methanol poisoning: A clinical and pathological study. Ann Neurol. 1980;8(2):161-167.

   [Crossref] [Google Scholar] [PubMed]

7. Sharpe JA, Hostovsky M, Bilbao JM, Rewcastle NB. Methanol optic neuropathy: A histopathological study. Neurology. 1982;32(10):1093-1100.

   [Crossref] [Google Scholar] [PubMed]

8. Moon CS. Estimations of the lethal and exposure doses for representative methanol symptoms in humans. Ann Occup Environ Med. 2017;29(1):1-6.

   [Crossref] [Google Scholar] [PubMed]

9. Rietjens SJ, De Lange DW, Meulenbelt J. Ethylene glycol or methanol intoxication: Which antidote should be used, fomepizole or ethanol. Neth J Med. 2014;72(2):73-79.
10. Mégarbane B. Treatment of patients with ethylene glycol or methanol poisoning: Focus on fomepizole. Open Access Emerg Med. 2010;2:67.

    [Crossref] [Google Scholar] [PubMed]

11. Barceloux DG, Randall Bond G, Krenzelok EP, Cooper H, Allister Vale J. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol. 2002;40(4):415-446.

    [Crossref] [Google Scholar] [PubMed]

12. Sharma N, Sharma N, Srinivasan P, Kumar S, Rayappan JB, Kailasam K. Heptazine based organic framework as a chemiresistive sensor for ammonia detection at room temperature. J Mat Chem. 2018;6(38):18389-18395.

    [Crossref] [Google Scholar]

13. Roberts DM, Yates C, Megarbane B, Winchester JF, Maclaren R, Gosselin S, et al. Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: A systematic review and consensus statement. Crit Care Med. 2015;43(2):461-472.

    [Crossref] [Google Scholar] [PubMed]