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Three Part Question

In [patients poisoned with ethylene glycol] is [methylpyrazole better than ethanol with or without haemodialysis] at [preserving renal function and reducing mortality]?

Clinical Scenario

A 29 year old man attends the emergency department having ingested an unknown quantity of car anti-freeze liquid. His airway, breathing and circulation are satisfactory. He is normoglycaemic. He appears intoxicated, has a depressed level of consciousness with no evidence of injury. You have heard that there is a new treatment available and wonder whether this (methylpyrazole) is better than the standard approach of ethanol and/or haemodialysis.

Search Strategy

Medline 1966-06/02 using the OVID interface.
(exp Ethylene Glycol/ or ethylene glycol.mp OR ethylene.mp OR anti-freeze.mp OR antifreeze.mp) AND (exp ethanol or ethanol.mp OR exp Renal Dialysis/ or haemodialysis.mp OR exp pyrazoles or pyrazoles.mp OR fomepizole.mp OR methylpyrazole.mp OR exp antidotes OR antidote$.mp OR pyrazol$.mp) LIMIT to human AND English.

Search Outcome

524 papers were found of which only 2 looked at newer treatments and none were comparative. These two papers are shown in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Borron SW et al, 1999, France	38 acute poisonings of which 11 patients had plasma ethylene glycol concentrations of 0.20g/l or more.	Prospective observational	Death	1/38 patients died	Simple case series- all patients received fomepizole, no controls Details regarding patient demographics and outcomes inadequate No account taken of confounding alcohol ingestion
			Serum creatinine	0/7 patients who had a normal renal function at presentation had no further deterioration in serum creatinine
			Side effects from fomepizole	4/38 experienced
Brent J et al, 1999, USA	23 acute poisonings of which 19 met inclusion criteria including a plasma ethylene glycol concentration of >20 mg per decilitre.	Prospective observational	Death	1/19 patients died	Simple case series studying the metabolic progress of patients All patients received fomepizole - no controls Authors cannot conclude that fomepizole is safe and effective
			Serum creatinine	17/19 underwent haemodialysis as per study protocol, 3/19 had an elevated serum creatinine at last study reading
			Ethylene glycol metabolites	All patients demonstrated progressive reduction in blood glycolate concentration
			Cranial neuropathies	0/19 patients
			Side effects	2 patients had seizures, 2 patients experienced headaches, 2 patients became bradycardic

Comment(s)

Ethylene glycol poisoning is not common and small number studies are justified. The studies shown above are observational rather than randomised trials with established practice. Furthermore 17 of 19 in the second study patients underwent haemodialysis as well as receiving Fomepizole. A satisfactory randomised trial with Fomepizole and 'non-Fomepizole' arms is needed. Both the studies shown above were supported by grants from the manufacturers of Fomepizole (Antizol).

Clinical Bottom Line

There is no evidence comparing the effectiveness of haemodialysis, ethanol or fomepizole in treating ethylene glycol poisoning. Local guidance should be followed.

References

1. Borron SW, Megarbane B, Baud FJ. Fomepizole in treatment of uncomplicated ethylene glycol poisoning. Lancet 1999;4;354(9181):831.
2. Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of ethylene glycol poisoning. NEJM 1999;340(11):832-838.