Abstract and Introduction
A 42-year-old man was brought to the emergency department with ethylene glycol intoxication. He was hemodynamically stable and had normal renal function. His serum ethylene glycol concentration was 284 mg/dl approximately 1 hour after ethylene glycol consumption. The patient was treated with fomepizole and forced diuresis. Elimination of ethylene glycol in this patient followed first-order pharmacokinetics. Elimination pharmacokinetics in this patient were compared with that in a patient who received fomepizole and hemodialysis. Fomepizole monotherapy can be given in patients without renal failure or metabolic acidosis even with serum ethylene glycol concentrations greater than 50 mg/dl. However, cost estimates based on this case suggest that if the patient is treated adequately with a single hemodialysis session and 24-hour hospitalization, then fomepizole monotherapy may be more expensive than the combination regimen of fomepizole and hemodialysis.
Ethylene glycol is an odorless volatile alcohol found in automotive products such as antifreeze. Adults generally ingest ethylene glycol as a source of inebriation or as a means of attempted suicide.
In 2001, 5833 ethylene glycol exposures were reported to the American Association of Poison Control Centers. Of these, 850 occurred in children younger than 6 years. Seven hundred eighty-six exposures occurred in individuals aged 6-19 years, and 4131 exposures occurred in adults older than 19 years. Age of the individual was not reported for 66 of the exposures. Two hundred twenty-two individuals (3.8%) experienced a major outcome, defined as signs or symptoms resulting from the exposure that were life-threatening or caused significant residual disability or disfigurement. Thirty-four individuals died as a result of the exposure or related complications.
Treatment recommendations for ethylene glycol intoxication include inhibition of alcohol dehydrogenase (ADH) with or without accelerated blood clearance by hemodialysis. Hemodialysis is recommended if severe metabolic acidosis (pH < 7.3) unresponsive to therapy or renal failure exists, or if the ethylene glycol concentration is greater than 50 mg/dl unless fomepizole is being administered and the patient is asymptomatic with a normal arterial pH.
Traditionally, ethanol has been administered to inhibit ADH. The target plasma ethanol concen-tration that provides ADH inhibition is 100-125 mg/dl. The serum ethanol concentration must be measured frequently, as the rate of ethanol metabolism is unpredictable. Ethanol therapy may result in inebriation, hypoglycemia, obtundation, or myocardial depression; hence, patients must be monitored closely in an intensive care unit. In addition, patients with ethylene glycol toxicity may have underlying alcoholic cardiomyopathy or liver disease, both relative contraindications for therapy with ethanol.
Fomepizole (4-methylpyrazole, Antizol; Orphan Medical, Minnetonka, MN) is a competitive inhibitor of ADH and was approved by the United States Food and Drug Administration in 1997 for the treatment of ethylene glycol poisoning. Alcohol dehydrogenase has an 8000-fold greater affinity for fomepizole than for ethanol. The presence of ethanol has no significant effect on the elimination of ethylene glycol in the presence of fomepizole, demonstrating the high degree of competitive inhibition of ADH by fomepizole.
Ethylene glycol follows first-order elimination pharmacokinetics in the presence of ADH inhibition, with an elimination half-life of 16.8 hours in patients with normal renal function. Renal clearance is proportional to creatinine clearance, with a fractional excretion of ethylene glycol of 26%, which allows the use of serum creatinine level on presentation to determine which patients may need hemodialysis to accelerate elimination.
Hemodialysis clears ethylene glycol but imposes risk, such as that of hypotension or dialyzer reactions, as well as expense. Hemodialysis traditionally has been recommended for patients with plasma ethylene glycol concentrations greater than 50 mg/dl. However, recent pharmacokinetic evaluations suggest that hemodialysis may not be necessary in all patients with serum ethylene glycol concentrations in this range. We report a case of acute ethylene glycol intoxication in a 42-year-old man who at presentation had a serum concentration of 284 mg/dl, hemodynamic stability, normal renal function, and absence of metabolic acidosis. The patient demonstrated resolution of toxicity with fomepizole monotherapy. This clinical experience exemplifies the efficacy of fomepizole monotherapy for ethylene glycol toxicity in selected patients.
The elimination pharmacokinetics of ethylene glycol from a similar patient treated with both fomepizole and hemodialysis are given for comparison and highlight the expected rapidity of blood clearance of ethylene glycol with hemodialysis. The accelerated blood clearance by hemodialysis provides for a shorter hospital stay and fewer required doses of ADH inhibitors. Cost estimates of these differences based on our patient reveal lower expense when hemodialysis is given with ADH inhibition if hospitalization and ADH inhibition are required for only 24 hours and if a single session of hemodialysis adequately clears the blood of ethylene glycol.
Pharmacotherapy. 2003;23(12) © 2003 Pharmacotherapy Publications
Copyright © 1999, Pharmacotherapy Publications, Inc., All rights reserved.
Cite this: Ethylene Glycol Intoxication: Case Report and Pharmacokinetic Perspectives - Medscape - Dec 01, 2003.