Acute Methanol Poisoning Research Articles

The value of brain CT findings in acute methanol toxicity

Objective Due to depressant effects of methanol on the central nervous system, brain computed tomography (CT) scan has been introduced as a diagnostic device in methanol intoxication. The authors aimed to present brain CT findings in patients with acute methanol intoxication and to determine signs associated with death. Materials and methods This cohort study involved 42 consecutive patients with acute methanol intoxication. Inclusion criteria were consisted of characteristic clinical presentation of methanol poisoning, and metabolic acidosis with increased anion and osmolar gaps. Brain CT scans without contrast medium were obtained. To determine the association between the CT findings and death, the chi-square test or the Fisher's exact test, odds ratio (OR) and its 95% confidence interval (95% CI) were calculated. Results Twenty-eight patients (66.6%) had a total of 55 abnormal findings on brain CT, in which bilateral putaminal hypodense lesions was the most common manifestation (27 cases, 96.4%). Putaminal hemorrhage with varying degrees was observed in 7 patients (25%). Six patients (21.4%) had low attenuation lesions in the subcortical white matter of the insula. A significant association was observed between putaminal hemorrhage (OR = 8, 95% CI = 1.187–53.93, P = 0.018) and subcortical necrosis of the insula (OR = 11, 95% CI = 1.504–80.426, P = 0.007) with death. Conclusion In addition to clinical and laboratory findings, presence of putaminal hemorrhage and insular subcortex white matter necrosis are associated with a poor clinical outcome in patients with methanol poisoning.

Methanol intoxication-induced nigrostriatal dysfunction detected using 6-[18F]fluoro- l-dopa PET

Ingestion of windshield washer liquid resulted with an acute severe methanol intoxication in a 49-year old man. He developed optic atrophy with blindness, and an extrapyramidal syndrome. Putaminal injury and hyperintensity in the subcortical white matter was seen in a brain MRI. PET scanning with 6-[18F]fluoro- l-dopa confirmed symmetrical impaired presynaptic dopaminergic activity in the striatum, indicative of functional impairment of dopaminergic nigrostriatal neurons. The striatal uptake was more markedly impaired in the putamina (40% of controls) than in the caudate nuclei (60% of controls). To our knowledge, this is the first report of an 18F-dopa PET scanning result in a case of an acute methanol poisoning.

MRI findings in methanol intoxication: a report of two cases

Methanol is a highly toxic substance and acute methanol poisoning produces severe metabolic acidosis and serious neurological symptoms, including severe visual impairment, extrapyramidal signs and coma. Its similarity to ethanol in appearance and odour leads to accidental use. We present two cases of accidental methanol intoxication and discuss the MRI findings.

Methanol intoxication: Diffusion MR imaging findings

We present diffusion MR imaging findings and ADC values in acute methanol intoxication in a 32-year-old man. T2-weighted and FLAIR images showed bilateral increased signal in the caudate nuclei, putamen, cerebral peduncle, and centrum semiovale. Diffusion MR showed hyperintensity in same localization, and splenium of corpus callosum. ADC values of these areas were markedly reduced consistent with restricted diffusion.

In vitro and in vivo study of neutrophil functions after acute methanol intoxication in albino rats

Toxicity from methanol (MeOH), a potentially significant problem due to occupational, accidental, or intentional, as well as daily ingestion of small amounts of the agent, only receives considerable attention after severe signs of intoxication have set in or death is imminent. While accidental and intentional exposures usually involve very high doses, the occupational and ingestion forms more often reflect small daily intakes. Still, even at the low levels, little is known about the potential immunotoxic implications (and less so in regard to mechanisms) from these ongoing exposures. This study has been attempted to focus the effects of acute methanol exposure on blood neutrophil functions in both in vitro and in vivo conditions at 30 and 60 min time intervals. Innate immunity of the host defense relies mostly on neutrophils. The blood MeOH levels were determined upon exposing the experimental animals to ¼ of LD50 MeOH. No significant change in the blood methanol level was observed at 30 and 60 min of methanol exposure. The in vitro results showed a decrease in the neutrophil functions of adherence and phagocytic index without affecting the avidity index, followed by an increased nitroblue tetrazolium (NBT) reduction. The in vivo exposures of MeOH showed a decline in neutrophil adherence. However, the other neutrophil functions were found to be significantly increased, which indicates that in vivo results are different from that of the in vitro studies. The present study concludes that MeOH exposure can reconstitute the innate immune status by altering the neutrophil functions. Moreover, the in vivo effects are much pronounced compared to the in vitro effects, which may be due to the formation of the metabolites under in vivo conditions.

Protective Effects of N-Acetylcysteine and Vitamin E Derivative U83836E on Proteins Modifications Induced by Methanol Intoxication

Methanol is oxidized into the formaldehyde and formate and these processes are accompanied by free radicals' generation. Formaldehyde and free radicals induce chemical modifications of proteins, leading to changes in their structure and function. The aim of this paper has been to evaluate the effect of N-acetylcysteine and vitamin E derivative U83836E on free radicals' generation and protein modifications induced during acute methanol intoxication. U83836E is an analog of α-tocopherol and similarly protects cells against oxidative damage. Moreover, this compound has hydrophilic properties and can be dissolved in an aqueous phase of blood and interstitial fluid, and next, membranes readily take it up. This compound belonging to the benzopyran family contains the reactive trolox ring and possesses antioxidant properties. The ESR determination indicates the increase in free radicals' signal 6 and 12 h after intoxication. Methanol ingestion causes a significant decrease in GSH level (by about 35%) and a significant increase in the lipid peroxidation product malondialdehyde (by about 25%). During methanol metabolism the aromatic amino acids of proteins are modified—the amount of carbonyl groups is increased (by about 42%) and fluorescence intensity of tryptophan is statistically decreased (by about 30%). The increase (by about 200%) in bityrosine fluorescence is also observed. Moreover, a significant decrease in free sulphydryl (by about 40%) and amino groups (by about 30%) in liver proteins is observed during intoxication. This is accompanied by the loss of lysosomal protease-cathepsin B activity (by about 25%). N-acetylcysteine (in dose 150 mg/kg body weight) and U83836E (in dose 10 mg/kg body weight) prevent free radicals' generation to a similar degree. U83836E protects membrane phospholipids against peroxidation a little stronger than N-acetylcysteine (concentration of MDA is decreased by 9 to 20% in the U83836 group and by 7 to 14% in the N-acetylcysteine group compared to methanol group). However after treating methanol-intoxicated rats with N-acetylcysteine, the changes in protein modification parameters are significantly smaller than in the group receiving methanol alone and they are a little smaller than after U83836E application.These findings suggest that N-acetylcysteine and to a smaller degree U83836E protect protein from modification in methanol intoxication, which can prevent liver pathologies.

Kinetics, dialysis systems, adequacy Postdialysis rebound in a case of acute methanol poisoning

Introduction: Methanol poisoning can lead to complications that include metabolic acidosis, visual impairment and death. Treatment options include ethanol, fomepizole, and hemodialysis (HD). Objective: To report on the occurrence of post dialysis methanol rebound during treatment. Method and Findings: A 40‐year‐old male with a history of schizophrenia and suicide attempts presented to the emergency room after reportedly ingesting 1 quart of windshield washer fluid. The patient presented with a preliminary blood chemistry of methanol 390 mg/dL, ethanol 48 mg/dL, glucose 93 mg/dL, Na 138 meq/L, K 3.8 meq/L, Cl 98 mmol/L, CO2 26 mmol/L, urea 16 mg/dL, creatinine 1.2 mg/dL, and an anion gap of 14 mmol/L. The patient was started on 1360 mg of fomepizole (12:50 AM) followed by HD for 4 hours. A second dose of fomepizole (900 mg) was administered at 8:00 AM. In addition, another HD session was started at 12:00 PM and continued for 4 hours. A third dose of fomepizole (700 mg) was administered at 8:50 PM. Finally, a third HD session was started the next day at 3:05 PM and lasted 3 hours. Table 1 illustrates methanol levels in relation to each HD session. Findings: Methanol concentration after the first HD increased from 100 mg/dL to 127 mg/dL (27%) in 5 h 20 m. It also increased from 35 mg/dL to 50 mg/dL (43%) 14 h 45 m after the second HD. Conclusions: Close attention must be paid to the potential for post dialysis methanol rebound. It is recommended that methanol levels continue to be monitored for several hours after HD. Methanol levels before and after each hemodialysis Start HD #1 (2:40 AM) End HD #1 (6:40 AM) Start HD#2 (12:00 PM) End HD#2 (4:00 PM) Next Day (6:45 AM) Methanol (mg/dL) 324 100 127 35 50 Rebound 27% 43%

Short- and long-term success of organs transplanted from acute methanol poisoned donors.

The shortage of organs for transplantation has made it necessary to extend the criteria for the selection of donors, among others including those patients who die because of toxic substances such as methanol. Methanol is a toxic which is distributed through all the systems and viscera of the organism and tends to cause a severe metabolic acidosis. It can specifically cause serious or irreversible lesions of the central nervous system (CNS) and retina, and ultimately brain death. We present our experience with 16 organ donors who died as a result of acute methanol intoxication in 10 Spanish hospitals over the last 14 yr. Between October 1985 and July 1999, 16 organ donors with brain death caused by acute methanol intoxication, 13 females and three males with a mean age of 38.4 +/- 7.6 yr (interval: 26-55 yr), allowed 37 elective transplants to be performed: 29 kidneys, four hearts and four livers for 37 recipients, and one urgent liver transplantation to a recipient with fulminant hepatitis. The immediate postoperative period was favourable for the 38 graft recipients. None of the graft recipients presented gap anion metabolic acidosis in the immediate postoperative period, nor symptomatology or lesions of the CNS characteristic of methanol intoxication. Two patients died during the first month post-transplantation, a liver recipient and a heart recipient, at 16 and 24 days, respectively, because of acute rejection of the graft. At 1 month after transplantation 35 of the 36 recipients had been discharged from hospital with normal-functioning grafts. The last of the recipients, a kidney recipient, was discharged at 6 wk with normal-functioning graft. Actuarial survival of the graft and patient of kidney recipients at 1, 3 and 5 yr was 92.6, 77.8, and 75%, and 100, 88.9 and 83.3%, respectively; with average serum creatinines of 139.9 +/- 42.9, 150.4 +/- 42.8, and 164.4 +/- 82.5 micromol/L, respectively. At 1 yr after transplantation the three heart recipients and two of the three liver recipients had normal-functioning graft. Methanol intoxication is not transferred from the donor to the recipient. The survival of the graft and kidney, heart and liver recipients using organs from donors who die because of methanol does not differ in the short- and long-term from the transplants performed with organs from donors who die from other causes.

Epidemic poisoning with methanol in Estonia: experience of intensive care

In September 2001, 147 patients were admitted to Parnu county hospital in Estonia with suspicion of acute methanol poisoning due to consumption of illegal alcohol. From these patients, 35 (22 male and 13 female, age from 19 to 74, mean 41 years) were transferred into Tartu University Clinics for further intensive care, particularly for hemodialysis. Most of the transferred patients appeared in coma, 29 were in shock. First-line therapy (before and during transport) consisted of artificial ventilation, fluid resuscitation, vasopressors, if needed, and i.v. infusion of 10% ethylalcohol as an antidote. Arterial pH prior to transport was in range from 6.49 to 7.29, and base excess from -12 to -30. In average 690 mmoles (from 200 to 1700 mmoles) of sodium bicarbonate was administered before dialysis for management of acidemia. In our department, 30 patients were treated with single hemodialysis for 6 hours, while three patients underwent continuous venovenous hemodialysis for 12 to 16 hours. The blood level of methanol was in range from 0.24 to 5.9 (mean 1.67) mg/dl before dialysis. After discontinuation of the dialysis, the methanol level remained between 0.05 and 1.6 (mean 0.59) mg/dl, and infusion of 10% ethyl alcohol was continued until methanol level below 0.3 mg/dl was detected. Neurological impairment was evident in seven patients after dialysis. In CT-scans, intracerebral haemorrhages, white-matter lesions, and severe brain oedema were the common findings. Four patients, who complained visual disturbances in immediate post-dialysis period, were treated with hyperbaric oxygenation, and in three of them the symptoms were effectively reversed. Overall, from 35 patients six died (mortality 17%), two remained with persistent neurological disability (encelopathy, coma), while 27 patients (77%) were discharged from hospital in normal health status. In conclusion, our experience demonstrates the importance of intravenous ethanol administration, hemodialysis, and hyperbaric oxygenation in the management of acute methanol poisoning.

Acute methanol intoxication generates free radicals in rats: an ESR spin trapping investigation

Electron spin resonance (ESR) spectroscopy has been used to investigate free radical generation in rats with acute methanol poisoning. The spin trapping technique was used where a spin trapping agent, α-(4-pyridyl 1-oxide)- N- tert-butylnitrone (POBN), reacted with the corresponding alcohol-derived or alcohol-dependent radical to form radical adducts. One radical adduct was detected in both bile and urine samples 2 h after acute methanol poisoning in male Sprague Dawley rats. The hyperfine coupling constants for the radical adduct from [ 13C]-labeled methanol detected in the bile were a N = 15.58, a β H = 2.81 G, and a β 13C = 4.53 G, which unambiguously identified this species as POBN/ CH 2OH. The same radical adduct was detected in urine. The identification of a methanol-derived radical adduct in samples from bile and urine provided strong direct evidence for the generation of the alcohol-derived radicals during acute intoxication by methanol. Simultaneous administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole and methanol resulted in an increase in the generation of the free radical metabolite detected in the bile. This is the first ESR evidence of methanol-derived free radical generation in an animal model of acute methanol intoxication.

Short and long-term success of organs transplanted from donors dying of acute methanol intoxication

Short and long-term success of organs transplanted from donors dying of acute methanol intoxication

Successful Double Lung Transplantation With a Graft Obtained From a Methanol-Poisoned Donor

A 25-year-old woman developed "brain death" 48 h after acute methanol poisoning. After the elimination of methanol and the correction of metabolic disorders, organ donation was discussed. The lungs were transplanted into a 46-year-old woman suffering from cystic "emphysematous-like" lesions as a complication of lymphangioleiomyomatosis. The procedure was not complicated, and we have an uneventful follow-up of > 12 months. In addition to the lungs, the kidneys and the liver were also removed and transplanted with success.

Treatment of acute methanol intoxication with hemodialysis using an ethanol-enriched, bicarbonate-based dialysate

A patient poisoned with methanol was successfully hemodialyzed with an ethanol-enriched, bicarbonate-based dialysate. Along with a concomitant intravenous infusion of ethanol, the ethanol-enriched dialytic procedure was able to maintain an intradialytic plasma ethanol level of 80 to 102 mg/dL. The patient recovered without any sequelae of methanol intoxication.

Antioxidant status of liver, erythrocytes, and blood serum of rats in acute methanol intoxication

SOD, CAT, GSH-Px, GSSG-R, ascorbic acid, α-tocopherol, nonprotein- and protein-bound sulfhydryl compounds, and TBA-rs content in the liver, erythrocytes, and blood serum of rats treated with methanol after 6, 12, and 24 h and 2, 5, and 7 days were investigated. Furthermore, hematological parameters of erythrocytes were analysed. GSH-Px, GSSG-R, sulfhydryl compounds, and ascorbic acid in the liver, erythrocytes, and in blood serum were significantly decreased. In addition, Cu,Zn-SOD and tocopherol in erythrocytes were diminished, whereas TBA-rs in the three biological materials was enhanced. Simultaneously, erythrocytes amount, hemoglobin level, hematocrit, and MCV were reduced. These results indicate that methanol in rats leads to the impairment of antioxidant mechanisms in the liver, erythrocytes, and blood serum.

Formate-Induced Alterations in Retinal Function in Methanol-Intoxicated Rats

Formic acid is the toxic metabolite in methanol poisoning. Permanent visual damage in methanol-intoxicated humans and nonhuman primates has been associated with prolonged exposures (>24 hr) to blood formate concentrations in excess of 7 mM; however, little information is available on the toxicity associated with chronic low-level or repeated exposure to methanol. The present studies compared the effects on retinal function and structure of rapidly increasing formate concentrations typical of acute methanol intoxication with low-level plateau formate concentrations more likely to be generated by subacute or chronic methanol exposure. Rats that accumulated formate concentrations of 8–15 mMdeveloped metabolic acidosis, retinal dysfunction, and retinal histopathologic changes. Retinal dysfunction was measured as reductions in thea- andb-waves of the electroretinogram that occurred coincident with blood formate accumulation. Histopathologic studies revealed vacuolation in the retinal pigment epithelium and photoreceptor inner segments. Rats exposed to formate concentrations ranging from 4 to 6 mMfor 48 hr showed evidence of retinal dysfunction in the absence of metabolic acidosis and retinal histopathology. These data indicate that formic acid generated from methanol oxidation acts as a direct retinal toxin. Formate-induced retinal dysfunction in methanol-intoxicated rats can be produced by steadily increasing concentrations of formate and importantly can also be produced by prolonged exposure to lower concentrations of formate. Our findings substantiate evidence based on clinical case reports and a small number of epidemiological studies and support the hypothesis that the visual system toxicity produced by acute, subacute, or chronic methanol poisoning share a common mechanism.

Acute methanol toxicity in minipigs

The pig has been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Average maximum methanol concentrations in plasma, of 3100 +/- 700 (SD), 6200 +/- 2300, and 15,200 +/- 900 micrograms/ml were reached within 0.5 to 4 hr following methanol administration in animals given 1.0, 2.5, or 5.0 g methanol/kg, respectively. The mean initial elimination half-lives of methanol were 9.0 +/- 1.6, 22.4 +/- 6.1, and 18.9 +/- 4.3 hr, for 1, 2.5, and 5.0 g/kg doses, respectively. In 3 minipigs, a transient increase in plasma formate concentration (1.74-3.40 mEq/liter vs control = 0.5 +/- 0.3 mEq/liter) occurred 4 to 30 hr following methanol administration. Methanol- and formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuro-ocular toxicosis.

Acute Methanol Toxicity in Minipigs

The pig has been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Average maximum methanol concentrations in plasma, of 3100 ± 700 (SD), 6200 ± 2300, and 15,200 ± 900 μg/ml were reached within 0.5 to 4 hr following methanol administration in animals given 1.0, 2.5, or 5.0 g methanol/kg, respectively. The mean initial elimination half-lives of methanol were 9.0 ± 1.6, 22.4 ± 6.1, and 18.9 ± 4.3 hr, for 1, 2.5, and 5.0 g/kg doses, respectively. In 3 minipigs, a transient increase in plasma formate concentration (1.74–3.40 mEq/liter vs control = 0.5 + 0.3 mEq/liter) occurred 4 to 30 hr following methanol administration. Methanol- and formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuroocular toxicosis.

Treatment of methanol intoxication by hemodialysis.

THE effectiveness of the artificial kidney in removing a wide variety of ingested poisons has been demonstrated in recent years.1 , 2 Studies by Marc-Aurele and Schreiner3 have shown the feasibility of artificial dialysis in the treatment of acute methanol intoxication. They demonstrate the removal of methanol from the laboratory animal and suggest that the metabolic by-products — namely, formic acid and formaldehyde — are theoretically dialyzable substances. At this writing we are unable to find case reports of patients with acute methanol intoxication treated by hemodialysis. Case Report A 32-year-old dockhand was admitted to the Maine Medical Center on September 15, . . .