Kidney outcomes after methanol and ethylene glycol poisoning: a systematic review and meta-analysis.

INTRODUCTION: Ingestions with methanol, ethylene glycol, diethylene glycol, propylene glycol, and isopropanol are rare yet exceedingly dangerous conditions that may require emergent management with kidney replacement therapy. Little is known regarding short- and long-term kidney outcomes post-ingestion. OBJECTIVES: To comprehensively synthesize existing evidence regarding short- and long-term kidney and other outcomes of adult patients following these poisonings. METHODS: We developed a search strategy in MEDLINE via OVID and then translated it into other databases including EMBASE (via OVID), PubMed, CENTRAL (via OVID). The databases were searched from their dates of inception to 29 July 2021. A grey literature search was conducted in the International Traditional Medicine Clinical Trial Registry and ClinicalTrials.gov. All interventional and observational studies and case series with ≥ five participants that reported on the outcomes of toxic alcohol (methanol, ethylene glycol, diethylene glycol, propylene glycol and isopropanol) poisonings in adult patients ≥18 years old were included. Studies that reported mortality, kidney outcomes and/or complications attributed to toxic alcohol poisoning were eligible. RESULTS: The search strategy identified 1,221 citations. Sixty-seven studies (13 retrospective observational studies, one prospective observational study, 53 case series) met inclusion criteria (total N = 2,327 participants). No randomized controlled trials were identified per our prespecified criteria. Generally, included studies had small sample sizes (median of 27 participants) and were of low quality. Methanol and/or ethylene glycol poisoning made up 94.1% of included studies, whereas one study reported on isopropanol and none reported on propylene glycol. Results of the 13 observational studies of methanol and/or ethylene glycol poisoning were pooled for meta-analyses. The pooled in-hospital mortality estimates amongst patients with methanol and ethylene glycol poisoning were 24 and 11%, respectively. A more recent year of publication, female sex and mean age were associated with lower in-hospital mortality amongst individuals with ethylene glycol poisoning. Although hemodialysis was the most frequently employed kidney replacement therapy, the indications for initiation of this therapy were not reported in the majority of studies. At hospital discharge, kidney recovery occurred in 64.7-96.3% of patients with ethylene glycol poisoning. In studies of methanol and/or ethylene glycol poisoning, 2-3.7% of individuals required ongoing dialysis. Only one study reported post-discharge mortality. Furthermore, long-term toxic alcohol-mediated sequelae, such as visual and neurologic outcomes, were scarcely reported. DISCUSSION: Ingestions of methanol and ethylene glycol were associated with a significant short-term risk of mortality. Although a wealth of literature in the form of case reports and case series exists, high-quality evidence regarding kidney outcomes after these poisonings is lacking. We identified a paucity of standardized reporting in clinical presentations, therapeutics and outcomes amongst adults with toxic alcohol poisoning. Amongst the included studies, there was substantial heterogeneity encompassing study type, outcomes, duration of follow-up and treatment modalities. These sources of heterogeneity restricted our ability to perform comprehensive meta-analyses of all outcomes of interest. An additional limitation is the lack of studies pertaining to propylene glycol and the paucity of data on isopropanol. CONCLUSIONS: The indications for hemodialysis, long-term kidney recovery and long-term mortality risk vary widely in these poisonings and are inconsistently reported in the literature. This highlights the need for further research with standardized reporting of baseline kidney function, indications for initiation of kidney replacement therapy and short-term and long-term kidney outcomes. REGISTRATION: This systematic review protocol is registered at PROSPERO, CRD42018101955.

Folate as an Adjuvant Therapy in Methanol Poisoning.

Folate and its derivatives have long been used as an adjunctive treatment in methanol poisoning. Methanol is ultimately metabolized to formate, the toxic compound. The accumulation of formate can lead to acidemia, retinal damage, visual impairment, and death. Formate is converted to carbon dioxide and water in a folate-dependent manner, and folate is often given in cases of methanol poisoning. In this paper, the evidence for folate as an adjunctive therapy in methanol poisoning is reviewed.

Clinical analysis of severe visual loss caused by inhalational methanol poisoning in a chronic process with acute onset:a retrospective clinical analysis.

BACKGROUND: To analyze the clinical features and prognosis of the visual loss resulted from inhalational methanol poisoning in 8 Chinese patients. METHODS: Eight consecutive patients seen at the Beijing Tongren Hospital of Capital Medical University, Beijing, China between January 2003 to August 2017, with complains of vision loss in both eyes, identified as inhalational methanol poisoning. Detailed medical history was extracted. All patients underwent optic nerve and brain magnetic resonance imaging (MRI) scan, laboratory tests, and visual function analysis. Treatment protocols were large dosage of methylprednisolone and B vitamins over 3 months. Patients were seen at 3-month intervals until a year. RESULTS: Eight patients with optic neuropathy caused by inhalation toxicity of methanol were under observation, whose methanol-contact time spans were form 4 days to 5 years for occupational exposure. All the patients had acute onset, transient systemic symptoms on early stage, both eyes involved with severe visual impairment (visual acuity 0.1 or even worse). Retrobulbar optic nerves (ONs) were the major sites involved. Optic nerve MRI scan showed increased signal of bilateral ONs in the orbit and the canal parts, with enhancement. After treatment, the visual function of these patients got improved in different degree in a year follow-up, but not satisfactorily. CONCLUSIONS: Inhalational methanol toxicity may lead to serious damage to ON in a process of chronic intoxication with acute attack, and with poor prognosis.

Association between acute methanol poisoning and subsequent mortality: a nationwide study in Taiwan.

BACKGROUND: Methanol poisoning (MP) often causes acute mortality and morbidities; however, the association between MP and subsequent mortality has not been well studied. METHODS: We conducted a nationwide population-based cohort study by identifying 621 participants with MP from the Nationwide Poisoning Database and 6210 participants without MP from the Longitudinal Health Insurance Database 2000 by matching the index date at a 1:10 ratio between 1999 and 2012. Comparison of the mortality rate between the two cohorts was performed by following up until 2013. RESULTS: A total of 249 (40%) participants with MP and 154 (2.5%) participants without MP died during the follow-up (p < 0.001). Statistic analysis showed that participants with MP had a higher risk for mortality than did the participants without MP (adjusted hazard ratio [AHR]: 13.48; 95% confidence interval [CI]: 10.76-16.88). The risk of mortality was highest in the first 6 months after MP (AHR: 480.34; 95% CI: 117.55-1962.75). Hypertension, chronic obstructive pulmonary disease, liver disease, malignancy, drug abuse, and lower monthly income also predicted mortality. CONCLUSIONS: MP was associated with increased subsequent mortality. Close follow-up for comorbidity control and socioeconomic assistance are suggested for patients with MP.

Cupping of the optic disk after methanol poisoning.

PURPOSE: To assess the frequency and significance of optic disk cupping after methanol poisoning. METHODS: We retrospectively reviewed the medical records of 50 consecutive patients with methanol poisoning, including visual acuity, pupillary reaction, and optic disk features such as the presence and degree of cupping. All patients were examined in the chronic phase after optic nerve damage. RESULTS: Optic disk cupping ≥0.8 c/d was present in at least one eye of 22 of these 50 patients (43/100 eyes). Severity of cupping was statistically symmetric in the two eyes, and increasing severity of cupping was correlated with worse visual acuity (p=0.007) and increasing visual field loss. Degree of cupping was significantly correlated with increasing patient age but not with putaminal necrosis. CONCLUSIONS: Optic disk cupping after methanol poisoning may be more common than previously recognised. Cupping in this setting may reflect toxicity of methanol metabolites to axons and glial cells in the prelaminar, laminar and retrolaminar regions, and seems to be important as a marker for worse optic nerve damage.

Methanol poisoning: predictors of visual outcomes.

OBJECTIVE: To determine whether laboratory markers of methanol ingestion and subsequent toxicity can serve as predictors of visual outcomes in patients. METHODS: Retrospective medical record review of 122 patients in a cluster outbreak of methanol poisoning. Data collected included history, complete ocular and systemic examination details, time to presentation, amount of alcohol ingested, and results of laboratory investigations, such as hemogram, glucose levels, hematocrit level, arterial pH, methanol levels, potassium and bicarbonate levels, and anion and osmolar gap determination, as well as hepatic and renal function tests. Therapy administered consisted of ethyl alcohol, sodium bicarbonate, and nutritional supplements, with hemodialysis in severe cases. Visual acuity (VA), pupillary reaction, and optic disc findings were assessed at presentation and 3 months after discharge. Patients were classified according to their visual disturbance: transient (group 1) or permanent (group 2). Appropriate statistical analysis was performed. Outcome measures included determining the association between biochemical markers of methanol poisoning and final VA. RESULTS: A total of 122 patients (1 female and 121 male) were admitted for treatment; of these, 10 died. Only 1 patient showed a 2-line drop in VA. pH was the strongest predictor of final VA and improvement in VA among all markers. The odds that a patient with an initial pH greater than 7.2 would have only transient visual disturbances were high (odds ratio, 31; 95% CI, 6-149). CONCLUSIONS: The degree of acidosis at presentation appears to determine final VA; early presentation and treatment did not seem to significantly alter the visual outcome, especially in severe poisoning.

A case of optic nerve atrophy with severe disc cupping after methanol poisoning.

We report a rare case of optic nerve atrophy with severe disc cupping resulting from methanol poisoning. A 30-year-old man presented to the hospital complaining of decreased visual acuity in both eyes a day after drinking alcohol containing methanol. His initial visual acuity allowed for only visualizing hand motion and not corrected in either eye. Initial intraocular pressure was within normal limits in both eyes. Initial fundus examination showed optic disc swelling in both eyes. Four years later, he visited our hospital for an eye evaluation. Visual acuity in both eyes still only allowed for visualizing hand motion. No nystagmus was observed in either eye during the optokinetic nystagmus test, and no waves were found in a visual evoked potential test. No specific change was noted on brain magnetic resonance imaging. On fundus examination, there was disc pallor in both eyes and disc cupping with a high cup/disc (C/D) ratio above 0.9 in the left eye. C/D ratio of the right eye was 0.5. Methanol poisoning may induce glaucomatous disc cupping in the late stage as well as optic atrophy. One possible mechanism of disc cupping is ganglion cell loss due to acute demyelination of the retrobulbar optic nerve. This report is the first photographic evidence of methanol induced optic disc cupping in Korea.

Letter to the Editor: A Case of Optic Nerve Atrophy with Severe Disc Cupping after Methanol Poisoning

No abstract available.

A Case of Optic Nerve Atrophy with Severe Disc Cupping after Methanol Poisoning

We report a rare case of optic nerve atrophy with severe disc cupping resulting from methanol poisoning. A 30-year-old man presented to the hospital complaining of decreased visual acuity in both eyes a day after drinking alcohol containing methanol. His initial visual acuity allowed for only visualizing hand motion and not corrected in either eye. Initial intraocular pressure was within normal limits in both eyes. Initial fundus examination showed optic disc swelling in both eyes. Four years later, he visited our hospital for an eye evaluation. Visual acuity in both eyes still only allowed for visualizing hand motion. No nystagmus was observed in either eye during the optokinetic nystagmus test, and no waves were found in a visual evoked potential test. No specific change was noted on brain magnetic resonance imaging. On fundus examination, there was disc pallor in both eyes and disc cupping with a high cup/disc (C/D) ratio above 0.9 in the left eye. C/D ratio of the right eye was 0.5. Methanol poisoning may induce glaucomatous disc cupping in the late stage as well as optic atrophy. One possible mechanism of disc cupping is ganglion cell loss due to acute demyelination of the retrobulbar optic nerve. This report is the first photographic evidence of methanol induced optic disc cupping in Korea.

Antidotes for alcohol and glycol toxicity: translating mechanisms into treatments.

Translational toxicology can be defined as the movement of potential antidotes for the treatment of poisonings from basic mechanistic research to the marketplace. Because poisonings are infrequent, the clinical development of antidotes is fraught with trials and tribulations. Academic scientists often conduct basic mechanistic work with antidotes but are infrequently involved in further drug development. This article presents the development of 4-methylpyrazole (4MP) (fomepizole) as an antidote against toxic alcohol poisonings, particularly by methanol and ethylene glycol (EG).

Phosphorus-enriched hemodialysis for the treatment of patients with severe methanol intoxication.

Severe methanol poisoning requires treatment with prolonged and intensive hemodialytic therapy. Such treatment can engender either the de novo development of hypophosphatemia or the worsening of pre-existing hypophosphatemia. Phosphorus-enriched hemodialysis therapy can prevent the occurrence of this complication. We report three patients with severe methanol poisoning who were treated with phosphorus-enriched hemodialysis. Prevention or treatment of hypophosphatemia was successfully achieved with this dialytic technique.

[Specific drug therapy of acute poisoning]. / Spetsificheskaia farmakoterapiia ostrykh otravlenii.

Antidote therapy is an important component of urgent treatment of acute poisonings. However, due to high specificity of the antidote action they can be effectively and safely used only under certain conditions. According to Ye. A. Luzhnikov's classification, 4 main groups of antidotes are distinguished: toxicotropic, toxicokinetic, symptomatic, and antitoxic immunopreparations. The use of individual antidotes, mainly symptomatic and some toxicotropic and toxicokinetic, is determined by the presence of typical clinical signs of poisoning and the anamnesis. In the rest cases the diagnosis is to be confirmed by laboratory findings, which is particularly important in poisoning with alcohol substitutes and metal compounds. Antidotes can cause side effects and complications, and therefore cannot be used in some cases.

MR enhancing brain lesions in methanol intoxication.

Methanol intoxication can cause necrosis of the putamen and subcortical white matter that is evident on neuroimaging. We report a 47-year-old man with significant methanol intoxication who had enhancing lesions in the caudate nuclei, putamina, hypothalamus, and subcortical white matter by MRI. This case demonstrates that contrast enhancement of brain lesions can be observed after methanol poisoning.

Partly reversible visual failure with methanol toxicity.

Methanol is a highly toxic substance which is used as an industrial solvent and in automotive antifreeze. If accidentally ingested blindness or death may result. The case of a young woman who developed sudden onset of visual failure following ingestion of a methanol-fortified beverage is presented. Although she failed to seek immediate medical help visual function improved. Acute changes of bilateral optic disc hyperaemia and venous engorgement were present at initial examination. She subsequently developed optic disc atrophy together with glaucomatous-like cupping of the optic discs. The aetiology of visual failure in methanol poisoning is discussed, as are the current therapeutic guidelines in the management of acute cases.

The alcohols: ethanol, methanol, isopropanol, ethylene glycol.

More than 6 per cent of poisonings involve alcohols and glycols, reflecting their availability in a wide range of household products, including aftershave, brake fluid, gas line antifreeze, model airplane fuel, mouthwash, rubbing alcohol, and windshield washing solution. Diagnosis involves recognition of an osmolal gap and variable degrees and delays in development of an anion gap metabolic acidosis. Therapeutic modalities are similar for methanol and ethylene glycol, both cases requiring ethanol-blocking of alcohol dehydrogenase and hemodialysis. More often, treatment of ethanol and isopropanol poisoning is limited to supportive care.