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.

Methanol-induced optic neuropathy: a still-present problem.

Methanol-induced optic neuropathy (Me-ION) is a serious condition that may result in long-term or irreversible visual impairment or even blindness secondary to damage and loss of function of the optic nerve and retina. Me-ION shows a tendency to occur as mass poisonings around the world with a clear predilection for poor societies in developing countries. The main mechanism underlying the molecular basis of Me-ION is the inhibition of the mitochondrial oxidative phosphorylation process through the binding of the toxic metabolite of methanol-formic acid-with the key enzyme of this process-cytochrome c oxidase. However, other mechanisms, including damage to the eye tissues by oxidative stress causing the intensification of the oxidative peroxidation process with the formation of cytotoxic compounds, as well as an increase in the synthesis of pro-inflammatory cytokines and influence on the expression of key proteins responsible for maintaining cell homeostasis, also play an important role in the pathogenesis of Me-ION. Histopathological changes in the eye tissues are mainly manifested as the degeneration of axons and glial cells of the optic nerve, often with accompanying damage of the retina that may involve all its layers. Despite the development of therapeutic approaches, persistent visual sequelae are seen in 30-40% of survivors. Thus, Me-ION continues to be an important problem for healthcare systems worldwide.

Methanol poisoning during COVID-19 pandemic; A systematic scoping review.

OBJECTIVE: In this systematic scoping review, it was aimed to assess the epidemiology of methanol poisoning, clinical findings and patients' management, causes, and recommendations regarding prevention or reduction of methanol poisoning during COVID-19 pandemic. METHODS: Three Electronic databases [Medline (accessed from PubMed), Scopus, and Science Direct] were searched systematically from December 01, 2019 to September 10, 2020, using MESH terms and the related keywords in English language. Considering the titles and abstracts, unrelated studies were excluded. The full texts of the remained studies were evaluated by authors, independently. Then, the studies' findings were assessed and reported. RESULTS: Total of 86 articles were obtained within the first step of searching, and 64 ones remained after removing the duplications. Through the title and abstract screening, 35 were removed. Finally, after reading the full text of the remained articles, 15 ones included in data extraction. Most of the previous reported evidence (13/15) were letter to editor, commentary and short reports. None of them were interventional, and none of them followed the patients. Findings were summarized in four categories: 1) epidemiology; 2) clinical findings and patients' management; 3) causes; and 4) recommendation regarding prevention or reduction of methanol poisoning during COVID-19 pandemic. CONCLUSION: The recent outbreak is the largest methanol mass poisoning outbreak throughout Iran and the world in recent decades. The causes of methanol poisoning during the COVID-19 pandemic are intertwined, and most of them are modifiable by health policy makers. Building trust, educating and warning, as well as controlling and monitoring are three main recommendation for prevention or reduction of methanol poisoning.

COVID-19 pandemic and methanol poisoning outbreak in Iranian children and adolescents: A data linkage study.

BACKGROUND: During the first wave of COVID-19, many Iranians were poisoned by ingesting hand sanitizers and/or alcoholic beverages to avoid viral infection. To assess whether the COVID-19 pandemic resulted in an increased prevalence of accidental hand sanitizer/alcoholic beverage exposure in children and adolescents, we compared pediatric hospitalization rates during COVID-19 and the previous year. For poisoning admissions during COVID-19, we also evaluated the cause by age and clinical outcomes. METHODS: This retrospective data linkage study evaluated data from the Legal Medicine Organization (reporting mortalities) and hospitalization data from nine toxicology referral centers for alcohol-poisoned patients (age 0 to 18 years) for the study period (February 23 to June 22, 2020) and the pre-COVID-19 reference period (same dates in 2019). RESULTS: Hospitalization rates due to ethanol and methanol exposure were significantly higher in 2020 (n = 375) than 2019 (n = 202; OR [95% CI] 1.9 [1.6, 2.2], p < 0.001). During COVID-19, in patients ≤15 years, the odds of intoxication from hand sanitizers were significantly higher than from alcoholic beverages, while in 15- to 18-year-olds, alcoholic beverage exposure was 6.7 times more common (95% CI 2.8, 16.1, p < 0.001). Of 375 children/adolescents hospitalized for alcoholic beverage and hand sanitizer exposure in 2020, six did not survive. The odds of fatal outcome were seven times higher in 15- to 18-year-olds (OR (95% CI) 7.0 (2.4, 20.1); p < 0.001). CONCLUSION: The Iranian methanol poisoning outbreak during the first wave of COVID-19 was associated with significantly increased hospitalization rates among children and adolescents-including at least six pediatric in-hospital deaths from poisoning. Public awareness needs to be raised of the risks associated with ingesting alcoholic hand sanitizers.

Neuroprotective Effects of Citicoline on Methanol-Intoxicated Retina Model in Rats.

Purpose: This study aims to evaluate the effect of citicoline administration in suppressing retinal damage due to methanol intoxication. This study hypothesizes that citicoline will minimize the loss of retinal ganglion cells (RGCs), minimize disruption of photoreceptors, suppress ganglion layer edema, increase expression of bcl-2 as the antiapoptotic protein, and decrease expression of caspase-3 as the proapoptotic protein. Methods: Fifteen Sprague-Dawley rats were divided into 5 groups, including the control group (A); methanol groups, observed on day 3 (B1) and day 7 (B2); and methanol+citicoline groups, observed on day 3 (C1) and day 7 (C2). Rats in groups B and C were placed in an inhalation chamber filled with N2O:O2 during the experiment, then methanol was administered orally. Citicoline, 1 g/kg every 24 h, was orally administered for group C. Enucleation was performed and retinas of rats were prepared for histology and immunohistochemistry examination to evaluate photoreceptor morphology and RGC density, as well as bcl-2 and caspase-3 expression. Results: RGC density of citicoline-treated intoxicated rats was higher than no-citicoline methanol-intoxicated rats on both day 3 (P < 0.001) and day 7 (P < 0.001). The ganglion layer thickness of citicoline-treated intoxicated rats was thinner than no-citicoline intoxicated rats, which means citicoline-treated rats had milder ganglion layer edema. Citicoline-treated rats showed higher bcl-2 and lower caspase-3 expression than no-citicoline rats. No differences were found in photoreceptor findings among groups. Conclusions: This study demonstrated citicoline's potential benefits for management of ocular methanol intoxication. However, more preclinical and clinical trials are needed to obtain a preferred dosage and timing of citicoline administration.

The prognostic value of red cell distribution width for in-hospital mortality in patients with methanol poisoning.

AIM: Red blood cell distribution width (RDW) is a numerical measure of variability in the size of circulating erythrocytes and is routinely reported as a component of a complete blood count panel. It has been shown that higher RDW is associated with increased mortality and morbidity in several types of intoxication. This study was designed to evaluate the prognostic value of RDW for in-hospital mortality and need of invasive mechanical ventilation in patients with methanol poisoning. METHODS: A retrospective chart review of patients with methanol poisoning was performed using data from Adana City Training and Research Hospital obtained between January 2019 and January 2020. Patients' demographics, clinical features, the time elapsed between ingestion and presentation, the treatment applied, blood gas analysis, laboratory measures including RDW on admission, and clinical outcome were obtained. RESULTS: A total of 42 patients with methanol poisoning were included in the study with a mean age of 45 ± 11 years. The overall mortality was 21.4%. Values of RDW on admission were significantly higher in non-survivors than in survivors. The area under the receiver operating curve of RDW was 0.778 (95% CI: 0.567-0.988) for predicting in-hospital mortality and 0.762 (95% CI: 0.592-0.932) for predicting mechanical ventilator requirement. CONCLUSION: This study suggests that increased RDW on the first admission is associated with mortality and with mechanical ventilator requirement in patients with methanol poisoning.

Cognitive changes after methanol exposure: Longitudinal perspective.

BACKGROUND: From 2012 to 2013, there was a mass methanol poisoning outbreak in the Czech Republic. Methanol metabolites can cause specific lesions in the basal ganglia, subcortical white matter, and optic nerve. However, long-term sequelae of methanol poisoning on cognitive functioning have not yet been explored. The current study aimed to delineate the cognitive changes observed in methanol poisoning survivors in the seven years since 2012. METHODS: We conducted longitudinal research with repeated measurements in 2013, 2015, 2017 and 2019 to evaluate the development of cognitive changes after acute methanol poisoning. A complex neuropsychological battery consisted of tests of global cognitive performance, auditory and visual attention, executive functioning, learning and memory, working memory and language. Motor performance measures and depression scale were also included. RESULTS: Repeated measures ANOVA of four measurements with post-hoc tests showed a significant decline in the Mini-Mental State Examination (p = 0.007); however, other parameters were not significantly decreasing. In comparison to normative values, the z-scores for each test measure, in the memory domain, in particular, ranged from 43 to 60 % of participants below 1.5 SD. Mild to severe depression levels from the onset of poisoning improved during the seven years, returning to normal in up to 27 % of participants. CONCLUSION: In the longitudinal perspective, methanol poisoning survivors manifest progressive global cognitive decline and overall persistent below-average cognitive performance with some improvements in the frequency of depressive symptoms.

Formate test for bedside diagnosis of methanol poisoning.

Methanol poisoning kills thousands of people every year and remains a diagnostic challenge, especially where the resources are scarce, but also in high-income countries worldwide. We are in the course of developing a bedside strip to detect formate - the toxic metabolite of methanol. We hereby present the first clinical methanol case where formate was detected bedside from a drop of blood: The patient, a 61-year-old male, was admitted with a suspect methanol poisoning and severe metabolic acidosis. The test strip was positive after 3 minutes. Sodium bicarbonate (500 mmol/L), fomepizole, dialysis and folinic acid were given based on the positive test. The diagnosis was some hours later confirmed by GC-MS, showing a methanol concentration of 62 mmol/L (200 mg/dL) and a formate concentration of 19 mmol/L. Implementation of this technology into routine clinical use can potentially offer an opportunity for a step change in the management of methanol poisoning.

Death by hand sanitizer: syndemic methanol poisoning in the age of COVID-19.

BACKGROUND: The advent of COVID-19 increased attention to hand hygiene in prevention of disease transmission. To meet the increased demand for hand sanitizer during the pandemic, the US FDA issued an Emergency Use Authorization allowing new manufacturers and importers to enter the market. Some of the newly introduced hand sanitizer products contained methanol in lieu of ethanol or isopropanol. We describe five patients with fatal methanol poisoning resulting from hand sanitizers improperly containing methanol. CASE SUMMARY: Comparing a 5-month period from 2019 to the same time frame in 2020, the Arizona Poison and Drug Information Center has seen an increase of 124% in exposures to hand sanitizer. Of these cases, 28% involved methanol-contaminated hand sanitizer. Five of these patients died from methanol poisoning. All five cases had similar clinical features with severe high anion gap metabolic acidosis and, in four patients, elevated osmolal gap. Methanol concentrations were consistently very elevated, but these results were not available before the patients succumbed. Four of the patients received fomepizole and adjunctive care. Two patients received emergency extracorporeal therapy. All five died despite maximal treatment efforts. CONCLUSION: During the pandemic in 2020, there was a proliferation of alcohol-based hand sanitizers which contained methanol. Exposure to these products, which failed to meet regulatory standards, led to increased harm and death. Challenges to treatment of methanol poisoning, especially in rural areas, include lack of access to timely laboratory measurement of methanol concentrations and lack of available emergency hemodialysis without transfer of the patient.

A Geographically Distinct Case of Fatal Methanol Toxicity from Ingestion of a Contaminated Hand Sanitizer Product During the COVID-19 Pandemic.

The COVID-19 pandemic has triggered outbreaks of unanticipated toxicities, including methanol toxicity. Multiple methanol outbreaks have been described, including contaminated hand sanitizer in the southwest USA. In this case, we describe a fatal case of methanol toxicity from hand sanitizer ingestion, geographically separated from the outbreak in the southwest USA and prior to the announcement of nationwide warnings by the Food and Drug Administration (FDA). The product was identified as one later recalled by the FDA for methanol contamination. Additionally, the consumption in this case was related to a desire to conceal alcohol consumption from family members. This case of methanol toxicity should increase awareness of the ease of which contaminated products can be widely distributed and of the use of alternative ethanol-containing products to obscure relapse in alcohol use disorder.

Acute kidney injury in hospitalized patients with methanol intoxication: National Inpatient Sample 2003-2014.

BACKGROUND: This study aimed to 1) determine the incidence of acute kidney injury (AKI), 2) identify risk factors for AKI, and 3) evaluate the impact of AKI on in-hospital outcomes in hospitalized patients for methanol intoxication. METHODS: We searched the National Inpatient Sample Database for hospitalized patients from 2003 to 2014 with a primary diagnosis of methanol intoxication. We excluded patients with end-stage kidney disease. We identified the AKI using a discharge diagnosis code. We compared clinical characteristics, in-hospital treatment, outcomes, and resource use between AKI and non-AKI patients. RESULTS: A total of 603 hospital admissions for methanol intoxication were analyzed. AKI developed in 135 (22.4%) admissions. Anemia (OR 3.43 p < 0.001), hypertension (OR 1.86; p = 0.02), volume depletion (OR 3.46; p = 0.001), sepsis (OR 6.91; p < 0.001), rhabdomyolysis (OR 6.25; p = 0.003), and acute pancreatitis (OR 5.30; p = 0.004) were independent risk factors for AKI development. AKI was significantly associated with increased risk of in-hospital mortality and organ failure. AKI patients needed more mechanical ventilation, and extracorporeal therapy, had longer length of hospital stay, and higher hospitalization costs. CONCLUSION: Over one-fifth of methanol intoxication patients developed AKI during hospitalization. AKI was associated with higher morbidity, mortality, and resource utilization.

Distinguishing between toxic alcohol ingestion vs alcoholic ketoacidosis: how can we tell the difference?

CONTEXT: Anion gap metabolic acidosis (AGMA) is common in patients presenting for emergency care. While some disease processes and ingestions are easily excluded, diagnosing toxic alcohol (TA) ingestion can be challenging. This is especially true if drug concentrations are not readily available, which forces clinicians to rely on surrogate markers. Like TA ingestion, alcoholic ketoacidosis (AKA) produces an elevated osmol gap and an AGMA. The aim of this study was to identify risk factors suggestive of AKA when TA ingestion was the primary alternative differential diagnosis. We hypothesized that the odds of an AKA diagnosis would increase as ethanol concentration increased. METHODS: This was a retrospective analysis of data from 2000 through 2019 from a single US Poison Control Center. Records were reviewed to identify cases coded as "methanol" or "ethylene glycol"; or coded as "alcohol" or "ethanol with acidosis." The case definition for AKA required: (1) documented alcohol use disorder; (2) urine or serum ketones or elevated blood beta-hydroxybutyrate concentration; (3) anion gap ≥ 14 mmol/L. The inclusion criterion for TAs was a detectable methanol or ethylene glycol concentration. RESULTS: Of 699 patients screened, 86 were diagnosed with AKA and 36 were diagnosed with TA ingestion. As ethanol concentration increased, the odds of an AKA diagnosis significantly increased (OR = 1.016, 95% CI 1.002-1.031, p = .03). CONCLUSIONS: In this retrospective analysis, the odds of diagnosing AKA instead of TA ingestion increased as ethanol concentration increased. The limited ability of common clinical factors to differentiate these diagnoses highlights the need to obtain quantitative TA concentrations in real time. Until prospective validation, interpretation of ketone concentrations and toxic alcohol concentrations (when available) will continue to guide decision making.

Efficiency of 123I-ioflupane SPECT as the marker of basal ganglia damage in acute methanol poisoning: 6-year prospective study.

CONTEXT: Investigate whether 123I-ioflupane SPECT (DaT SPECT) has the potential as a marker of basal ganglia damage in acute methanol poisoning. METHODS: Prospective, single-centre, cohort study of patients with confirmed methanol poisoning was conducted. DaT SPECT was performed twice with semi-quantification using DaTQUANTTM and MRI-based volumetry was calculated. Specific binding ratios (SBR) of striatum, caudate nucleus, and putamen were correlated with laboratory parameters of outcome, volumetric data, and retinal nerve fibres layer (RNFL) thickness measurements. RESULTS: Forty-two patients (mean age 46.3 ± 4.2 years; 8 females), including 15 with MRI-detected putamen lesions (group I) and 27 patients with intact putamen (group II), underwent DaT SPECT. Volumetry was calculated in 35 of the patients assessed. SBR values for the left putamen correlated with putamen volume (r = 0.665; p < 0.001). Decreased bilateral SBR values were determined for the striatum and the putamen, but not for the nucleus caudate, in group I (p < 0.05). Significant correlation was observed between the SBR of the posterior putamen and arterial blood pH (r = 0.574; p < 0.001) and other toxicological parameters of severity of poisoning/outcome including serum lactate, glucose, and creatinine concentrations (p < 0.05). The SBR of the posterior putamen positively correlated with the global RNFL thickness (p < 0.05). ROC analysis demonstrated a significant discriminatory ability of SBR of the posterior putamen with AUC = 0.753 (95%CI 0.604-0.902; p = 0.007). The multivariate regression model demonstrated that arterial blood pH, age, and gender were the most significant factors associated with SBR of the posterior putamen. CONCLUSION: DaT SPECT demonstrates significant potential for the diagnosis of methanol-induced basal ganglia damage.

The Toxic Effects of Ethylene Glycol Tetraacetate Acid, Ferrum Lek and Methanol on the Glutathione System: correction Options.

Objectives: The purpose of this study was to measure the level of lipid peroxidation and investigate the response of the glutathione system to toxic doses of ethylene glycol tetraacetate acid (EGTA), Ferrum Lek, methanol, and Depakine (valproate sodium). Methods: This study focused on analyzing the toxic effects of EGTA, Ferrum Lek and methanol on lipid peroxidation processes and glutathione levels in animals. The study involved 375 outbred adult mice, of both sexes, weighing 28-31 g, and 100 outbred rats, weighing 180-200 g. Results: After 14 days of valproate sodium/ademethionine treatment, the GR (glutathione reductase) activity in experimental animals continued to be higher than in controls. Using EGTA enhanced glutathione reductase and glutathione S transferase activities in the liver and kidney. The activity of glutathione peroxidase, however, increased only in the kidney (2.1-fold, p ≤ 0.001), while in the liver, a 31% drop was observed (p ≤ 0.05). The 15-mg and 30-mg doses of Ferrum Lek caused the liver level of thiobarbituric acid reactive substances to grow 3- and 3.5-fold, respectively (p ≤ 0.001). Conclusion: The results of the study indicate that poisoning affected practically all components of the glutathione system. The oxidative stress was likely to result from an increased generation of reactive oxygen species against the background of inhibited antioxidant protection.

Atypical presentation of COVID-19; an observational retrospective study.

BACKGROUND: COVID-19 infection may present with atypical signs and symptoms and false negative polymerase chain reaction (PCR) tests predisposing healthy people and health care workers to infection. The aim of the current study is to evaluate the features of atypical presentations in COVID-19 infection in a referral center in Tehran, Iran. METHODS: Hospital database of inpatients admitted to Loghman Hakim hospital between February 20th and May 11th, 2020 was reviewed and all patients with final diagnosis of COVID-19 infection were evaluated for their presenting symptoms. Patients with chief complaints of "fever", "dyspnea", and/or "cough" as typical presentations of COVID-19 were excluded and those with other clinical presentations were included. RESULTS: Nineteen patients were included with a mean age of 51 ± 19 years, of whom, 17 were males (89%). Median [IQR] Glasgow coma scale (GCS) was 14 [13, 15]. Almost 10 had referred with chief complaint of methanol poisoning and overdose on substances of abuse. Only 8 cases (42%) had positive COVID-19 test. Nine (47%) needed invasive mechanical ventilation, of whom, two had positive COVID-19 test results (p = ns). Eight patients (42%) died with three of them having positive PCRs. CONCLUSIONS: In patients referring to emergency departments with chief complaint of poisoning (especially poisonings that can result in dyspnea including substances of abuse and toxic alcohols), gastrointestinal, and constitutional respiratory symptoms, attention should be given not to miss possible cases of COVID-19.