Toxic cocktail: Methanol poisoning in a tourist to Indonesia

Methanol poisoning has become very uncommon in Australasia with regulations that have reduced its retail availability. This report describes a young tourist who developed sudden onset visual failure and rapid breathing 2 days after ingestion of a complimentary local drink called Arrack when travelling in Indonesia. She presented to a hospital in New Zealand with severe metabolic acidosis and a highly toxic methanol level at 17 mmol/L. The cocktail was consumed at a popular tourist bar but is likely to have been mixed from home‐brewed or ‘moonshine’ alcohol tainted with methanol. The aetiology of methanol poisoning, its optic toxicology and therapeutic measures are discussed, as is the concerning number of methanol poisoning cases among tourists to Indonesia over recent years.     

Unexplained drowsiness and progressive visual loss: Methanol poisoning diagnosed at autopsy

A patient was admitted to the emergency department with a reduced level of consciousness and deteriorating vision. Her pupils became fixed and dilated and she developed a third nerve palsy with extensor posturing of her limbs. Biochemistry profile showed an increased serum osmolar gap with a raised anion gap metabolic acidosis. Supportive treatment was instituted, but she made no recovery and brainstem death was later confirmed. Post mortem examination and toxicology screen confirmed the cause of death as methanol poisoning leading to cerebral oedema and transtentorial herniation. We highlight some of the diagnostic difficulties associated with treating a patient with a reduced level of consciousness. The clinical and biochemical findings that are critical in establishing a diagnosis of methanol intoxication are discussed. The definitive management of methanol poisoning is reviewed.     

Methanol poisoning

Methanol ingestion is an uncommon form of poisoning that can cause severe metabolic disturbances, blindness, permanent neurologic dysfunction and death. While methanol itself may be harmless, it is converted in vivo to the highly toxic formic acid. The diagnosis is sometimes elusive and requires a high index of suspicion. Because antidotal treatment is available it is important to recognize methanol poisoning promptly. The presence of metabolic acidosis associated with an increased anion gap and increased osmol gap are important laboratory findings. Specific therapeutic measures include correction of the metabolic acidosis with sodium bicarbonate and administration of enteral or parenteral ethanol to competitively inhibit the metabolic breakdown of methanol to formic acid. Hemodialysis accelerates the elimination of both methanol and formic acid and also assists in correction of the metabolic acidosis. Experimental data suggests that administration of folic acid may be of benefit by hastening the metabolism of formic acid to carbon dioxide. Prompt institution of specific therapy can probably decrease the morbidity and murtality associated with this form of poisoning.     

Fatal methanol poisoning following home distillation of methylated spirits

We present the case report of a 47-year-old man fatally poisoned by ingestion of a home-distilled liquor produced from ‘methylated spirits’ containing 5% methanol and 90% ethanol. Classical signs of severe methanol poisoning, including altered conscious state, shock and profound acidosis were manifest at the time of presentation. Despite an ethanol infusion and haemodialysis he was declared brain dead 36 h after arrival at the emergency department.     

Methanol poisoning: diagnosis and management. A case report

Methanol poisoning is an uncommon but potent central nervous system toxin. The diagnosis and the management of its sequelae remain a challenge to clinicians. A case is hereby presented in which computed tomography of the brain played an important role in making the diagnosis due to poor patient's history and unavailability of methanol assay. Parkinsonism and visual sequelae are well-recognised complications in the survivors. This patient developed parkinsonism in the form of mainly severe tremors and mild rigidity. He benefited from treatment on amantadine.     

Methanol ingestion: prevention of toxic sequelae after massive ingestion

Methanol ingestion, a rare but potentially fatal poisoning, is often difficult to diagnose in the Emergency Department (ED) and historically has been difficult to treat. In this article, we report a methanol ingestion with a blood concentration of 692 mg/dL, which was treated with 4-methylpyrazole (Fomepizole) and dialysis, without sequelae. To our knowledge, such a massive ingestion has never been treated with this modality without development of long-term disability. Another unusual feature of this case is the significantly elevated serum osmolal gap at presentation without elevation in anion gap, demonstrating the effects of co-ingestion of ethanol. Additionally, there was a marked disparity between the patient’s breath alcohol analyzer level and the blood ethanol concentration, illustrating the inability of the breath alcohol analyzer to differentiate between volatile alcohols. Treatment of the methanol-poisoned patient with Fomepizole is discussed.     

Outcomes After Recurrent Intentional Methanol Exposures Not Treated With Alcohol Dehydrogenase Inhibitors Or Hemodialysis

BackgroundRelying on a treatment threshold for methanol poisoning of 20 mg/dL (6.2 mmol/L) as a stand-alone criterion may lead to unnecessary and invasive treatment because it is likely too conservative, especially for patients with repeated, intentional methanol exposures.ObjectiveWe investigated how often patients with recurrent intentional methanol exposures above this threshold developed biochemical or overt clinical toxicity despite not being treated with either an alcohol dehydrogenase inhibitor (ADHi) or hemodialysis.MethodsWe identified patients with ≥3 methanol-related emergency visits from 2002 to 2015 and selected every visit in which neither ADHi nor hemodialysis were administered despite serum methanol >20 mg/dL but neither metabolic acidosis nor end organ toxicity at presentation. The primary outcome was the incidence of visual deterioration or death.ResultsFour patients accounted for the 17 visits that met inclusion criteria. All exposures were intentional substance misuse, and 7 of 17 were via inhalation (i.e., huffing). Initial methanol concentrations ranged from 22 mg/dL to 35 mg/dL (7–11 mmol/L). Four of these 17 visits had undetectable initial ethanol concentrations at presentation, including 1 with an initial methanol concentration of 35 mg/dL. No patients developed visual deterioration, and all were known to have survived the exposure.ConclusionFollowing recurrent, intentional methanol exposure, isolated serum methanol concentrations as high as 35 mg/dL (11 mmol/L) appear to be well-tolerated without treatment in the absence of metabolic acidosis or end-organ toxicity. To better define the methanol treatment threshold, prospective studies are warranted in which patients are followed closely while fomepizole is withheld.     

早期血液灌注与血液滤过治疗甲醇中毒的疗效观察

目的:探讨早期血液透析联合血液灌注治疗甲醇中毒的治疗效果。方法:回顾性分析早期血液与延迟血液的甲醇中毒患者的死亡率、住院天数及并发症发生率。结果:早期血液透析及滤过与延迟血液透析及滤过的甲醇中毒患者的死亡率及并发症发生率分别为8.33%,16.67%及24.07%,51.85%。两组的死亡率及并发症发生率比较差异均有统计学意义(P<0.05)。结论:早期血液透析联合血液灌注治疗甲醇中毒可以降低患者的死亡率及并发症的发生率,改善预后。     

A novel bedside diagnostic test for methanol poisoning using dry chemistry for formate

Abstract

Background. The standard diagnostic approach to methanol poisoning is chromatographic measurement of methanol on centrally placed stationary equipment. Methanol poisoning in places where such equipment is unavailable is thus often not diagnosed. Methanol is metabolized to a toxic metabolite, formate; the presence of this compound indicates methanol poisoning. We have developed an enzymatic test for formate and modified it into a portable dry chemistry system that could be used anywhere. Methods. The method consists of two enzymatic steps: Formation of NADH from NAD by formate dehydrogenase, and subsequent use of NADH as a reductant of a tetrazolium into a formazan dye that can be quantified photometrically or visually. Results. The photometer gave a good correlation of R² = 0.9893 in serum and R² = 0.9949 in whole blood, showing an instrumental detection limit of less than 1 mM (4.5 mg/dL). The visual readings showed a correlation of R² = 0.8966. Users experienced some difficulty in separating the negative control from the low positives. Conclusions. We have documented the feasibility of an affordable formate strip test for bedside diagnosis of methanol poisoning and for screening of metabolic acidosis of unknown origin. Visual reading is possible, but a reader will improve reliability at lower levels of formate. Future studies are necessary to study the sensitivity and specificity towards other causes of metabolic acidosis and other acids present in human blood.     

Acute methanol poisoning with bilateral diffuse cerebral hemorrhage: A case report

BACKGROUNDAcute methanol poisoning (AMP) is a systemic disease that mainly affects the central nervous system and is characterized by ocular damage and metabolic acidosis. If appropriate treatments are inadequate or delayed, the mortality can exceed 40%. As the most serious complication, cerebral hemorrhage is rare with reported prevalence of 7%-19%.CASE SUMMARYA 62-year-old man drank liquor mixed with 45% methanol and 35% alcohol. His vision blurred 10 h later and he fell into coma in another 9 h. Serum toxicological tests were performed immediately, and continuous renal replacement therapy (CRRT) was carried out as the lactic acid exceeded 15 mmol/L and blood pH was 6.78. In addition, the toxicological report revealed 1300.5 μg/mL of methanol in serum and 1500.2 μg/mL in urine. After 59 h of CRRT, the methanol level decreased to 126.0 μg/mL in serum and 151.0 μg/mL in urine. However, the patient was still unconscious and his pupillary light reflex was slow. Computed tomography showed hemorrhage in the left putamen. After 16 d of life support treatment, putamen hemorrhage developed into diffuse symmetric intracerebral hemorrhage. In the end, his family gave up and the patient was discharged, and died in a local hospital.CONCLUSIONCerebral hemorrhage requires constant vigilance during the full course of treatment for severe cases of AMP.     

Case report: Severe brain hypoxic damages after acute methanol poisoning

Methanol poisoning is a challenging clinical situation with irreversible neurologic complication mainly encountered in developed countries. We report a case of a 50‐year‐old patient who presented with methanol poisoning, symptomatic of respiratory and neurologic failure. In this context, cerebral magnetic resonance imaging concluded entangled injury mechanisms leading to neurologic failure.     

Serum osmolal gap in clinical practice: usefulness and limitations

Background: Although serum osmolal gap can be a useful diagnostic tool, clinicians are not familiar with its use in clinical practice.

Objectives: The review presents in a series of questions-answers and under a clinical point of view the current data regarding the use of osmolal gap.

Discussion: The definition and the best formula used for the calculation of osmolal gap, the main causes of increased osmolal gap with or without increased anion gap metabolic acidosis, as well as the role of concurrent lactic acidosis or ketoacidosis are presented under a clinical point of view.

Conclusions: The calculation of osmolal gap is crucial in the differential diagnosis of many patients presenting in emergency departments with possible drug or substance overdose as well as in comatose hospitalized patients.     

Leukotriene-mediated neuroinflammation,toxic brain damage,and neurodegeneration in acute methanol poisoning

Context: The role of neuroinflammation in methanol-induced toxic brain damage has not been studied.

Objective: We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors.

Methods: Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88?±?20?h). In 36 survivors, control LT measurements were performed 2 years after discharge.

Results: The acute maximum (C_max) LT concentrations were higher than concentrations in survivors: C_max for LTC4 was 80.7?±?5.6 versus 47.9?±?4.5?pg/mL; for LTD4, 51.0?±?6.6 versus 23.1?±?2.1?pg/mL; for LTE4, 64.2?±?6.0 versus 26.2?±?3.9?pg/mL; for LTB4, 59.8?±?6.2 versus 27.2?±?1.4?pg/mL (all p?p?p?p?p?The follow-up LT concentrations in survivors with and without CNS sequelae did not differ (all p?>?0.05). The mean decrease in LT concentration was 30.9?±?9.0?pg/mL for LTC4, 26.3?±?8.6?pg/mL for LTD4, 37.3?±?6.4?pg/mL for LTE4, and 32.0?±?8.8?pg/mL for LTB4.

Conclusions: Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.     

MPTP诱导猴偏侧帕金森病模型的制作

目的探讨偏侧帕金森病恒河猴动物模型的成模率及影像、病理的对比。方法经一侧颈内动脉注入1甲基4苯基1,2,3,6四氢吡啶(MPTP)后,对实验组猴的行为表现及影像学表现:包括MRI、PET及SPECT进行检测及酪氨酸羟化酶(TH)免疫组化染色。结果注射MPTP后第5～7天逐渐出现偏侧帕金森病症状,肌注阿朴吗啡后动物向左侧快速旋转;PET检查示实验组猴右侧(患侧)18F脱氧葡萄糖平均标准摄取值较左侧明显减低,SPECT检查示多巴胺转运蛋白(DAT)显像右侧纹状体放射性摄取明显减低,二者均与对侧及给药前对比统计学上差异有显著性差异(P<0.05)。TH免疫组化染色示右侧黑质多巴胺能神经元明显减少。结论经一侧颈内动脉注射MPTP制作偏侧帕金森病猴模型安全、简单、成模率高,是研究帕金森病的一种理想的帕金森病动物模型。     

Efficiency of acidemia correction on intermittent versus continuous hemodialysis in acute methanol poisoning

Context: Acidemia is a marker of prognosis in methanol poisoning, as well as compounding formate-induced cytotoxicity. Prompt correction of acidemia is a key treatment of methanol toxicity and methods to optimize this are poorly defined.

Objective: We studied the efficiency of acidemia correction by intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) in a mass outbreak of methanol poisoning.

Methods: The study was designed as observational cohort study. The mean time for an increase of 1?mmol/L HCO₃^–, 0.01 unit arterial blood pH, and the total time for correction of HCO₃^– were determined in IHD- and CRRT-treated patients.

Results: Data were obtained from 18 patients treated with IHD and 13 patients treated with CRRT. At baseline, CRRT group was more acidemic than IHD group (mean arterial pH 6.79?±?0.10 versus 7.05?±?0.10; p?=?0.001). No association was found between the rate of acidemia correction and age, weight, serum methanol, lactate, formate, and glucose on admission. The time to HCO₃^– correction correlated with arterial blood pH (r=??0.511; p?=?0.003) and creatinine (r?=?0.415; p?=?0.020). There was association between the time to HCO₃^– correction and dialysate/effluent and blood flow rates (r=??0.738; p?r=??0.602; p?The mean time for HCO₃^– to increase by 1?mmol/L was 12?±?2?min for IHD versus 34?±?8?min for CRRT (p?p?=?0.024). The mean increase in HCO₃^– was 5.67?±?0.90?mmol/L/h for IHD versus 2.17?±?0.74?mmol/L/h for CRRT (p?Conclusions: Our study supports the superiority of IHD over CRRT in terms of the rate of acidemia correction.     

Ethylene glycol poisoning treated by intravenous 4-methylpyrazole

A 19-year-old woman was admitted 45 min after ethylene glycol (EG) ingestion. The initial serum EG concentration was 1.34 g/l (21.6 mmol/l), the anion gap 14.5, and the osmolal gap 24. Renal function was preserved (serum creatinine 75.1 μmol/l). As the patient was seen soon after poisoning, before the development of metabolic acidosis, therapy with 4-methylpyrazole (4-MP) was proposed as an antidote. 4-MP was administered via the intravenous route (7 mg/kg as loading dose, followed by 3.6, 1.2, 0.6, and 0.6 mg/kg at intervals of 12 h). 4-MP alone was effective in preventing EG biotransformation to toxic metabolites (absence of metabolic acidosis and renal injury). Ethanol therapy, hemodialysis, and sodium bicarbonate administration were not required. The half-life of EG during 4-MP therapy was 11 h, with a mean EG renal clearance of 26.9 ml/min, and a total of 65.3 g EG was eliminated unchanged in the urine. 4-MP therapy was also well tolerated. Received: 25 August 1997 Accepted: 9 April 1998     

Anion gap‐opening metabolic acidosis and urinary findings in the early diagnosis of ethylene glycol poisoning: A case report

Causative agent identification is important in the treatment of poisoning. We report the case of a patient who presented with an altered level of consciousness after drinking a fluorescent pink liquid. Upon measuring the anion gap and urinary calcium oxalate level, the patient was diagnosed with early ethylene glycol poisoning.     

Two cases of acute methanol poisoning partially treated by oral 4-methylpyrazole

Objective: Since the use of 4-methylpyrazole (4-MP) in the treatment of humans with methanol poisoning is poorly documented, we report two cases of acute methanol intoxication partially treated by this potent alcohol dehydrogenase (ADH) inhibitor. Setting: Intensive Care Unit in a university hospital. Patients: A 56-year-old man and an 18-year-old woman were observed, respectively, 41 and 16 h after the voluntary ingestion of an unknown amount of methanol. Intervention: In both cases, ethanol was used as the first antidote. In the first patient, hemodialysis was also performed on admission because a high methanol level (0.72 g/l) and visual impairment were noted. In the second patient, ethanol therapy was withdrawn after 12 h when clinical and biological signs of acute pancreatitis became evident. Both patients received multiple oral doses of 4-MP. No recurrence of metabolic acidosis occurred and the 4-MP therapy was well tolerated. Conclusion: While the use of 4-MP is better documented in cases of ethylene glycol poisoning, it could also become an accepted option for the management of methanol poisoning since 4-MP offers advantages over ethanol therapy. Received: 5 November 1998 Final revision received: 18 February 1999 Accepted: 24 February 1999     

4-Aminopyridine (fampridine) effectively treats amlodipine poisoning: a case report

A case of a serious poisoning with the calcium entry blocker amlodipine is described, which was treated effectively with 4-aminopyridine. Calcium is suggested as general treatment of poisoning with calcium entry blockers in many guidelines. The use of intravenous 4-aminopyridine is theoretically useful to treat poisoning from calcium entry blockers and was demonstrated in this case report.