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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2007  |  Volume : 18  |  Issue : 1  |  Page : 117-122
Methanol Intoxication with Brain Hemorrhage: Catastrophic outcome of late presentation


Division of Nephrology, Department of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia

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How to cite this article:
Askar A, Al-Suwaida A. Methanol Intoxication with Brain Hemorrhage: Catastrophic outcome of late presentation. Saudi J Kidney Dis Transpl 2007;18:117-22

How to cite this URL:
Askar A, Al-Suwaida A. Methanol Intoxication with Brain Hemorrhage: Catastrophic outcome of late presentation. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2020 Jan 22];18:117-22. Available from: http://www.sjkdt.org/text.asp?2007/18/1/117/31859

   Introduction Top


Methanol (CH3OH) is a highly toxic alcohol with a smell and taste similar to ethanol. It is found in a variety of commercial paint thinners, gasoline anti-freeze, windshield products, organic solvents, shellac varnish, washer fluid, photocopying fluids, perfumes, and in some eau de cologne. [1],[2] The lethal dose of methanol is 50-100 ml. [1] Methanol intoxication occurs after accidental or suicidal ingestion of the above mentioned liquids or, occasionally, it is due to the fraudulent adulteration of wine or other alcoholic beverages; [3] it is also frequently taken as an alcohol substitute, especially during times of ethanol restriction (wartime or prohibition). Its ingestion causes high anion gap metabolic acidosis from the production of formic and lactic acids and CNS disturbances ranging from inebriation and drowsiness to obtun­dation, seizure and coma. Selective toxicity of the optic nerve and basal ganglia are well­known features. [4], [5] When large amounts of methanol are ingested, death usually occurs within three days. [6] We report on a young patient with methanol intoxication who presented with severe high anion gap metabolic acidosis and massive intracerebral bleeding.


   Case Report Top


A 26-year-old man was brought to our hospital 60 hours after ingestion of a heavy dose of an adulterated, poor quality, alcoholic beverage mixed with eau de cologne/perfume. Twenty-four hours after ingestion, the patient started to complain of abdominal pain, nausea and vomiting. Forty-eight hours later, he complained of blurred vision then lapsed into a coma. On admission, he was comatose with a Glascow coma scale of 6/15 with dilated pupils and sluggish reaction. His blood pressure was 80/35 mmHg, heart rate was 83/min, respiratory rate was 30/min, and temperature was 36 0 C. Hyperemia and edema of the optic discs were observed with fundoscopy. An examination of the chest, heart and abdomen was unremarkable. There were multiple injection sites at the arms. His chest radiograph, electrocardiograph, urina­lysis, complete blood count, and blood glucose level were normal. The patient had severe high anion gap metabolic acidosis with an arterial blood pH of 6.89, HCO3 1.6 mmol/L, paCO2 18 mmHg. Serum electrolytes included Na 145 mmol/L, K+ 6.2 mmol/L, Cl- 106ml/L. Urea was 7.2 ml/L, creatinine 191 µmol/L, sugar 8.5mmol/L, osmolality 296 mosmol/L and anion gap 37. The initial blood level of methanol was 14.6 mg/dl, formic acid 30 mg/L, and the salicylates and paracetamol were negative.

A CT scan of the brain without contrast that was performed soon after intubation and stabilization of the patient demonstrated bilateral, symmetrical areas of low density in the putaminal region [Figure - 1]A, large hyperdense areas due to hemorrhage in the regions of right basal ganglia, external capsule and right ventricule] [Figure - 1]B. With a presumed diagnosis of methanol poisoning, the patient was started on intravenous sodium bicarbonate to correct acidosis. Ethanol was added to block formic acid production, while a hemodialysis session without heparin was initiated to help correct the severe acidosis and eliminate both ethanol and its metabolites - formic acid.

The next morning, the patient had two episodes of cardiac arrest, which were rapidly responded to. His life was maintained on inotropes, dopamine and noradrenaline, but remained severely acidotic (pH 6.79, HCO 3 6.4, PaCo 2 43.8) with a high anion gap of 29. Because he was hemodynamically unstable, continuous venovenous hemofiltration (CVVH) was applied for 24 hours with high volume replacement fluid and no heparin.

On the third day after admission, the metabolic acidosis (pH 7.35, HCO 3 25.6, PaCO 2 47.6, AG 13), urea, and creatinine levels were corrected, but the patient was hypernatremic (Na 155mmol/L) with polyuria 10300 ml/24 (fluid intake was 9,550 ml/24 hours). A diagnosis of central diabetes insipidus versus high fluid intake was considered. Accordingly, the infusion of sodium bicarbonate and ethanol were discontinued and the patient was maintained on half normal saline.

On the 4 th day after admission. The patient's state was poor as he had dilated fixed pupils, no gag reflex, and a flat electroencepha­logram (EEG). A CT scan of the brain was repeated and revealed massive intracerebral bleeding. There was a hemorrhage in both lateral ventricles as well as the 3 rd and 4 th ventricles, in addition to subarachnoid hemorrhage and midline shift to the left side with cerebral edema, [Figure - 2]. At this stage, brain death with central diabetes insipidus was diagnosed and the patient received desmo­pressin with dextrose water 5%.

On the morning of the fifth day, the patient went into cardiac arrest and, 45 min. later, was pronounced dead. One hour before cardiac arrest, the blood investigations revealed Na + 164 mmol/L, K + 4.2 mmol/L urea 4 mmo/L, creatinine 91 µmol/L, pH 7.31, HCO3 27.5 mmol/L, PaCO2 55.8 mmHg.


   Discussion Top


The clinical features of methanol intoxi­cation usually occur after a latent period of 12-24 hours following methanol ingestion. The latent period corresponds to the time period in which methanol is converted by alcohol dehydrogenase in the liver to formic acid, the metabolite that is responsible for the acidosis and the toxic effects. [7],[8]

Early manifestations of methanol toxicity include inebriation, nausea, vomiting, abdo­minal pain, headache, dizziness and weakness. While the late manifestations (after 24 hours of ingestion) are due to the toxic effects of formic acid on brain (seizure, coma, death), on eyes (blurred vision, light flashes, central scotomas and blindness or optic atrophy), and high anion gap metabolic acidosis. Optic nerve atrophy is due to the demyelination that results from the inhibitory effect of formic acid on mitochon­drial ATP production as well as from anoxia secondary to disc hyperemia/edema. [7],[9],[10]

Brain injury in methanol toxicity is characterized by lesions affecting both basal ganglia and sub-cortical regions. [3],[11] These lesions could be ischemia/necrosis or hemorrhage, selectively affecting the putamenal area bilaterally.[12] The basis for the selective vulnerability in these regions remains unknown. It has been suggested that the putamen is at particular risk because of its high metabolic demand and location in an end zone of vascular perfusion. [3], [13]

The coincident putamen hemorrhagic necrosis and hemorrhagic white matter lesions were first described in 1953 by Orthner. [2], [14] However, the clinical syndrome of these lesions was not described until 1988 by Phang et al [15] who observed extensive necrosis and hemorrhagic necrosis in the basal ganglia, and hemorrhage into the ventricles of the brain in six of 21 patients with methanol intoxication who had a CT scan of the brain.

The precise mechanism of necrosis and hemorrhage in the case of methanol toxicity remains a matter of debate. [11] It may represent a direct toxic effect of methanol and its metabolite "formic acid" as well as injury which is secondary to anoxia and acidosis. [11], [15] Moreover, Phang et al [15] suggested that systemic heparinization during hemodialysis may well contribute to the hemorrhage observed in the necrotic areas of the brain. However, more recently, a study in the State University of New York demonstrated that methanol elevates cystolic calcium ions in cultured canine cerebral vascular muscle cells. These results suggest that methanol-induced cerebral vasospasm may be a consequence of a large rise in intracellular calcium. These events could play a crucial role in methanol-induced cerebral edema, brain ischemia/necrosis and hemorrhage. [16]

Treatment of methanol toxicity is directed toward achieving two goals: first, a decrease the metabolism of methanol into formic acid by inhibiting the alcohol dehydrogenase using either the specific antidote "Fomipizole" intravenously or ethanol intravenous/orally; Second, remove both parent and toxic metabolites from the blood and correct metabolic acidosis by hemodialysis and sodium bicarbonate infusion. Hemodialysis is usually continued until plasma levels fall below the toxic range and metabolic acidosis is corrected; hence continuous renal replacement therapy (CRRT) maybe preferred.

Our patient suffered from a severe methanol intoxication and presented very late, 60 hours after ingestion, to medical attention with a high anion gap metabolic acidosis and brain hemorrhage that resulted in the death of the patient.


   Questions and Answers Top


Dr. Ramesh Kumar, chairman of the club (Riyadh Medical Complex): Now the presen­tation is open for discussion.

Dr. Al-Suwaida (King Khaled University Hospital, KKUH): The aim of our presen­tation is to shed light on the possibility of alcohol intoxication that should be included in our differential diagnosis when we are confronted with high anion gap acidosis.

Dr. Askar: We see more and more such cases related to adulteration of alcohol produced illegally and sold to addicts, so it is not an uncommon case scenario.

Dr. Ramesh Kumar: I agree with you. We see such cases at Riyadh Medical Complex, which is a community hospital. Also we hear about it from other areas in the kingdom.

Dr. Nauman Tarif (KKUH): Such episodes usually occur in clusters. So, when you see one case you know another one is coming soon and, as you said, it is related to bad alcohol made locally and sold to the addicts. We used to see such a pattern in India and Pakistan.

Audience: What about isopropyl Alcohol? Some addicts use it instead of ethanol.

Dr. Askar: Isopropyl alcohol is also toxic but does not cause anion gap acidosis. Rather, it only causes osmolar gap acidosis.

Prof. Jamal Al-Wakeel (KKUH): The etiology of the intracerebral hemorrhage is still intriguing to me. Is it possible that thepatient was hypertensive and, after the bleeding, he became hypotensive?

Dr. Askar: according to the family who brought the patient to the hospital, there was no history of hypertension. I agree with you that one should not label the case as hemorrhage secondary to methanol intoxi­cation without entertaining the other causes of intracerebral bleed. On the contrary, we believe that we should include the methanol intoxication in the differential diagnosis of the intracerebral bleed.

Dr. Nauman Tarif: The hypertensive episode could be due to other recreational drugs, such as cocaine or heroine, which the addicts may combine with alcohol intake. The hyper­tension may be induced by these drugs and may result in intracerebral bleed.

Dr. Askar: Our initial attempt to explain the intracerebral bleed was the possible transiently severe hypertension. However, we did not find any clue to other drugs in our patient.

Prof. Al-Wakeel: Regarding dialysis, do you not think the hemodialysis would be more efficient than CRRT at removing alcohol readily?

Dr. Askar: The hemodialysis is efficient but, when the patient is unstable, as in our patient, the CRT would become a better option.

Audience: what would the sequellae be if the patient had survived? Dr. Asker: According to the literature review, the sequellae are usually related to the nervous system, including blindness that may not recover due to damaged optic nerve as well as variable extrapyramidal symptoms and signs due to damaged putamen.

 
   References Top

1.Burton DR, James FW. Methanol and ethylene glycol intoxication, Up to Date, Jan. 2006.  Back to cited text no. 1    
2.Likosky D, Rutchik JS, Talavera F, Jimenez NG. Methanol. e-Medicine, March 2005.  Back to cited text no. 2    
3.Blanco M, Casado R, Vazquez F, Pumar JM. CT and MR imaging findings in methanol intoxication. AJNR Am J Neuroradiaol 2006; 27:452-4.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Koopmans RA, Li DK, Patry DW. Basal ganglia lesion in methanol poisoning: MR appearance. J Comput Assist Tomogr 1988;12:168-9.  Back to cited text no. 4    
5.Pelletier J, Habib MH, Khalil R, Salamon G, Bartoli D, Jean P. Putaminal necrosis after methanol intoxication. J Neurol Neurosurg Psychiatry 1992;55(3):234-5.  Back to cited text no. 5    
6.Younger DS. Pollutants and industrial hazards. In Lewis P Rowland (Ed): Merritt's Textbook of Neurology. Ninth edition. Baltimore: Williams and Wilkins, 1995; pp 992-3.  Back to cited text no. 6    
7.Boz C, Velioglu SK, Bulbul I, Ozmenoglu M. Bilateral putaminal hemorrhagic infarction and optic atrophy caused by methanol intoxication. J Neurol Sciences (Turkish) 2000; 17:4.  Back to cited text no. 7    
8.Liesivuori J, Savolainen H. Methanol and formic acid toxicity; biochemical mechanisms pharmacol toxical 1991; 69:157-63 (Abstract).  Back to cited text no. 8    
9.Sharpe JA, Hostovsky M, Bilbao JM, Rewcastle NB. Methanol optic neuropathy: a histopathological study. Neurology 1982; 32:1093-100 (Abstract)  Back to cited text no. 9    
10.Cursiefen C, Bergua A. Acute bilateral blindness caused by accidental methanol intoxication during fire "eating". British J Ophthalmol 2002; 86:1064-5.  Back to cited text no. 10    
11.Feany MB. Anthony DC, Frosch MP, Zane W, De-Girolami U. August 2000: two cases with necrosis and hemorrhage in putamen and white matter. Brain Pathol 2001;11(1):121-5.  Back to cited text no. 11    
12.Gaul HP, Wallace CJ, Auer RN, fong TC. MR Findings in Methanol Intoxication. AJNR Am J Neuroradiol 1995;16: 1783-6.  Back to cited text no. 12    
13.Hsu HH, Chen CY, Chen FH, et al. Optic atrophy and cerebral infarcts caused by methanol intoxication: MRI, Neuroradiology 1997; 39:192-4.  Back to cited text no. 13    
14.Kuteifan K, Oesterle H, Tajahmady T, Gutbub AM, Laplatte G. Necrosis and haemorrhage of the putamen in methanol poisoning shown on MRI. Neuroradiology 1998; 40(3): 158-60.  Back to cited text no. 14    
15.Phang PT, Passerini L, Mielke B, Berendt R, king EG. Brain hemorrhage associated with methanol poisoning. Crit Care med 1988; 16(2):137-40.  Back to cited text no. 15    
16.Li W, Zheng T, Wang J, Altura BT, Altura BM. Methanol elevates cystolic calcium ions in cultured canine cerebral vascular smooth muscle cells: possible relation to CNS toxicity. Alcohol 1999; 18(203): 221-4 (abstract)  Back to cited text no. 16    

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Correspondence Address:
Akram Askar
Division of Nephrology, Department of Medicine, King Khalid University Hospital, P.O. Box 2925, Riyadh 11461
Saudi Arabia
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PMID: 17237904

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    Introduction
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    References
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