Fomepizole for the Treatment of Ethylene Glycol Poisoning

Brent, Jeffrey; McMartin, Kenneth E.; Phillips, Scott E.; Kk, Burkhart; Donovan, JW; Wells, Mike; Kulig, Ken

doi:10.1056/nejm199903183401102

Cited by 321 publications

(143 citation statements)

References 22 publications

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“…A large number of patients with methanol or ethylene glycol intoxication have developed these intoxications after ingesting contaminated ethanol-based products, and, in these cases, serum ethanol levels are high (55,57). In this regard, increased levels of ketones in the blood or urine have been found in from 2 to 20% of patients with methanol intoxication (52,56), consistent with AKA.…”

Section: Epidemiologymentioning

confidence: 71%

“…Because clinical and laboratory abnormalities are due to metabolites of ethylene glycol, co-ingestion of ethanol can delay their appearance by several hours (13,37,57). In the multicenter study examining the use of fomepizole in ethylene glycol intoxication (57), 12 (60%) of 19 had measurable blood ethanol levels, and four of the 12 had blood levels Ͼ100 mg/dl.…”

Section: Pathophysiologymentioning

confidence: 99%

“…The signs and symptoms of ethylene glycol have been reported to develop in three distinct stages: First there are neurologic abnormalities, followed by cardiopulmonary dysfunction, and finally renal dysfunction (13,37,57). However, it is not uncommon for neurologic, cardiopulmonary, and renal failure to be present together (37).…”

Section: Clinical Findingsmentioning

confidence: 99%

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Toxic Alcohol Ingestions

Kraut¹,

Kurtz²

2008

Clinical Journal of the American Society of Nephrology

370

326

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Alcohol-related intoxications, including methanol, ethylene glycol, diethylene glycol, and propylene glycol, and alcoholic ketoacidosis can present with a high anion gap metabolic acidosis and increased serum osmolal gap, whereas isopropanol intoxication presents with hyperosmolality alone. The effects of these substances, except for isopropanol and possibly alcoholic ketoacidosis, are due to their metabolites, which can cause metabolic acidosis and cellular dysfunction. Accumulation of the alcohols in the blood can cause an increment in the osmolality, and accumulation of their metabolites can cause an increase in the anion gap and a decrease in serum bicarbonate concentration. The presence of both laboratory abnormalities concurrently is an important diagnostic clue, although either can be absent, depending on the time after exposure when blood is sampled. In addition to metabolic acidosis, acute renal failure and neurologic disease can occur in some of the intoxications. Dialysis to remove the unmetabolized alcohol and possibly the organic acid anion can be helpful in treatment of several of the alcohol-related intoxications. Administration of fomepizole or ethanol to inhibit alcohol dehydrogenase, a critical enzyme in metabolism of the alcohols, is beneficial in treatment of ethylene glycol and methanol intoxication and possibly diethylene glycol and propylene glycol intoxication. Given the potentially high morbidity and mortality of these intoxications, it is important for the clinician to have a high degree of suspicion for these disorders in cases of high anion gap metabolic acidosis, acute renal failure, or unexplained neurologic disease so that treatment can be initiated early. Table 1. Methanol, ethylene glycol, diethylene glycol, and propylene glycol intoxication and alcoholic ketoacidosis can produce hyperosmolality and metabolic acidosis (3-9). Isopropanol intoxication is usually associated with hyperosmolality alone (4,5). Importantly, several of these disorders can be fatal or produce irreversible tissue damage if they are not quickly recognized and treated appropriately (4 -15). Effect of Alcohols on Serum Osmolality and the Osmolal GapThe normal serum osmolality of 285 to 290 mOsm/L is due to sodium and its counterbalancing ions, bicarbonate and chloride, and glucose and urea. It can be calculated using the following equation:Serum osmolality (mOsm/L) ϭ 2 ϫ Na ϩ ϩ blood urea nitrogen (mg/dl)/2.8 ϩ glucose (mg/dl)/18. The serum osmolality measured by freezing point depression is usually within 10 mOsm/L of the calculated serum osmolality (16). Accumulation of low molecular weight substances in the serum (such as each of the alcohols) will raise the measured serum osmolality above that of the calculated serum osmolality, producing an osmolal gap (4,5,16 -18). The effect of each of the alcohols on serum osmolality is shown in Table 2. Methanol gives rise to the greatest increment in serum osmolality, followed by ethanol, isopropanol, ethylene glycol, propylene glycol, and diethylene glycol in that...

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Section: Epidemiologymentioning

confidence: 71%

Section: Pathophysiologymentioning

confidence: 99%

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Toxic Alcohol Ingestions

Kraut¹,

Kurtz²

2008

Clinical Journal of the American Society of Nephrology

370

326

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“…Consequently, fomepizole has greater ease of administration compared with ethanol and is potentially safer as well. 2,19,20 Methanol poisoning in the pediatric population is rare, with reports of intoxication limited to infants. [12][13][14][15]21 Methanol intoxication in other pediatric age groups is described less frequently.…”

Section: Discussionmentioning

confidence: 99%

Childhood Methanol Ingestion Treated With Fomepizole and Hemodialysis

et al. 2001

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ABSTRACT. Fomepizole (4-methylpyrazole; Antizol) is used increasingly in the treatment of methanol toxicity in adults. Little experience exists with this drug in the pediatric population, however. We present a case of methanol poisoning in a child in whom the use of fomepizole averted intravenous ethanol infusion and the attendant side effects of this therapy. Pediatrics 2001;108(4). URL: http://www.pediatrics.org/cgi/content/full/108/4/e77; 4-methylpyrazole, fomepizole, Antizol, methanol, pediatric.ABBREVIATION. ADH, alcohol dehydrogenase. M ethanol may produce severe morbidity and mortality if undetected or treated improperly. In 1999, more than 970 methanol exposures were reported to poison centers in the United States, with 363 exposures occurring in the pediatric population. 1 Formerly, treatment for methanol poisoning required intravenous ethanol infusion, hemodialysis, or both. Fomepizole (4-methylpyrazole, Antizol) was approved recently by the Food and Drug Administration as an antidote for methanol poisoning in adults. 2 In 1 case series of patients who were poisoned with methanol, fomepizole eliminated the need for ethanol therapy, although many still required hemodialysis. 2 Although clinical experience with fomepizole has been expanding, its use in children remains uncommon and is limited to cases of ethylene glycol toxicity. [3][4][5][6] We report a case of methanol poisoning in a child who was treated with fomepizole. Fomepizole obviated the need for intravenous ethanol infusion, prevented metabolic acidosis as well as neurotoxicity, and produced no discernible adverse effects. CASE REPORTA 5-year-old male ingested an unknown amount of windshield washer fluid (40% solution of methanol) that was stored improperly in a sports drink bottle. He was brought to a local emergency department within 60 minutes of the ingestion. Initial vital signs were as follows: temperature, 37°C; pulse, 101 beats per minute; blood pressure, 101/59 mm Hg; respiratory rate, 22 breaths per minute. He weighed 24.5 kg. Physical examination was normal with no signs of intoxication or ophthalmologic abnormality.Initial laboratory evaluation revealed a normal complete blood count. Serum chemistries were as follows: sodium, 134 mEq/L; potassium, 3.7 mEq/L; chloride, 110 mEq/L; bicarbonate, 23 mEq/dL; blood urea nitrogen, 12 mg/dL; creatinine, 0.5 mg/dL; and glucose, 136 mg/dL. Anion gap was 4.7 mEq/dL. The serum osmolality was 320 mOsm/kg H 2 O; the calculated serum osmolarity was 284 mOsm/kg H 2 O, yielding an osmolal gap of 36 mOsm/kg H 2 O. Plasma aspirin, acetaminophen, and ethanol were negative. Serum methanol concentration measured by gas chromatography was 35 g/dL.Transfer to a tertiary care center was arranged. On arrival to the referral intensive care unit, he complained of intermittent abdominal pain, was slightly confused, and was tachypneic. An arterial blood gas was as follows: pH, 7.43; Pco 2 , 36 mm Hg; Po 2 , 137 mm Hg. Serum bicarbonate was 20. Eight hours after the ingestion, the child received a 15 mg/kg intrav...

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“…1 Toxic effects include metabolic acidosis, cardiovascular instability, visual impairment, and renal failure. 2,3 Standard treatment for methanol or ethylene glycol ingestion involves inhibition of alcohol dehydrogenase using either ethanol or fomepizole. In addition, hemodialysis may be indicated.…”

Section: Ré Sumémentioning

confidence: 99%

The safety of ethanol infusions for the treatment of methanol or ethylene glycol intoxication: an observational study

Wedge

Natarajan

Johanson

et al. 2012

CJEM

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Background: Methanol or ethylene glycol ingestion may result in significant morbidity or death without prompt treatment. Despite traditional and widespread use of intravenous ethanol as an antidote, its safety is not well described. An evaluation of the safety and ease of titrating ethanol infusions is necessary given the availability of an alternative antidote. Objective: To evaluate the safety and ease of titrating ethanol infusions for the treatment of methanol or ethylene glycol ingestion. Methods: We reviewed the hospital records of adults treated with ethanol at The Ottawa Hospital for methanol or ethylene glycol ingestion over a 9-year period. Using a standardized case report form, a single reviewer identified prespecified adverse events that developed after the start of ethanol therapy and classified dose adjustments during ethanol therapy as appropriate or inappropriate based on a priori criteria. Results: Forty-nine cases of methanol or ethylene glycol ingestion treated with ethanol were included in the analysis, of which 45 underwent hemodialysis, 38 were admitted to the intensive care unit, and 4 died. At least one adverse event was identified in 45 (92%) cases, including 35 (71%) with agitation requiring chemical or physical restraints and 10 (20%) with a depressed level of consciousness treated with intubation. The median number of ethanol concentration measurements per treatment course was 6 (range 0-24), of which only 27% were within the target range of 22 to 30 mmol/L and 47% were below. When measured concentrations were outside the target, the adjustment in ethanol dosing (or lack thereof) was deemed inappropriate 59% of the time, including 69% of the time during hemodialysis. Conclusion: Based on actual practice in a large academic centre, adverse events occur frequently with intravenous ethanol infusions, and ethanol titration is inefficient. The

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Fomepizole for the Treatment of Ethylene Glycol Poisoning

Abstract: In patients with ethylene glycol poisoning, fomepizole administered early in the course of intoxication prevents renal injury by inhibiting the formation of toxic metabolites.

Cited by 321 publications

References 22 publications

Toxic Alcohol Ingestions

Toxic Alcohol Ingestions

Childhood Methanol Ingestion Treated With Fomepizole and Hemodialysis

The safety of ethanol infusions for the treatment of methanol or ethylene glycol intoxication: an observational study

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