Treatment of Methanol and Ethylene Glycol Poisoning: DISCUSSION
To the authors’ knowledge, this study represents the largest case series on the use of IV ethanol therapy for the management of methanol or ethylene glycol poisoning. Despite difficulty in achieving target serum ethanol concentrations, treatment with IV ethanol therapy and hemodialysis was associated with favourable patient outcomes. Of the 27 patients, 25 (93%) survived, and the 2 deaths occurred in patients with evidence of severe central nervous system damage who presented late after ingestion. Only one patient was discharged with renal dysfunction induced by ethylene glycol, and this patient may have had pre-existing kidney disease. No visual disturbances associated with methanol were reported.
Brent and others recently published 2 case series describing the results of treatment of methanol and ethylene glycol poisoning with fomepizole. The patient characteristics in those studies, including demographic characteristics, severity of intoxication, and use of hemodialysis, were similar to those in the study reported here. The outcomes of treatment were also similar. Among patients with ethylene glycol poisoning, 1 (9%) of 11 in the current series and 3 (16%) of 19 patients in one of the fomepizole studies were discharged with elevated serum creatinine concentration. Overall survival was 93% in the current study and 90% (27/30) in the 2 fomepizole studies.
Two other case series reporting the use of fomepizole in methanol and ethylene glycol poisoning indicate that this drug can be effective without concomitant hemodialysis. If these results receive further confirmation, fomepizole therapy may have an advantage over ethanol treatment, especially in centres where expedient hemodialysis is not available for patients with poisoning.
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Because of the lack of direct comparative trials, there is limited information on potential differences in effectiveness between IV ethanol therapy and fomepizole. Each treatment has advantages and disadvantages. The recommended fomepizole dose regimen is advantageous in situations where frequent laboratory monitoring or continuous IV infusion is not feasible. Fomepizole is the only drug that has received regulatory approval for use in methanol and ethylene glycol poisoning. However, the higher acquisition cost of fomepizole is a significant consideration, especially in view of limited data to suggest its superiority over ethanol. The cost of ethanol for IV administration is lower, but the requirement for continuous IV infusion is inconvenient, achieving recommended serum concentrations can be problematic, and monitoring may be costly. Although hypoglycemia has been cited as a potential consequence of IV ethanol use, no patients in this series exhibited this adverse effect, despite frequent monitoring of blood glucose concentrations. It is possible that hypoglycemia was avoided by use of dextrose solution as the diluent for the ethanol. In summary, the lack of comparative trials and formal pharmacoeconomic analyses makes it difficult to choose between fomepizole and ethanol for the management of methanol or ethylene glycol poisoning.
Concurrent hemodialysis was used for all but one patient in the series reported here. It could be argued that the favourable outcomes observed here, which were evident despite the fact that serum ethanol concentration targets were not consistently achieved, were due in large part to timely and adequate hemodialysis. Ethanol can prevent metabolism of the parent compounds methanol and ethylene glycol to their toxic metabolites, but provides no protection once those metabolites have formed; therefore, hemodialysis appears to be an essential component of appropriate management.
The results of this study raise questions regarding the traditional target serum ethanol concentration of 22 mmol/L in patients undergoing hemodialysis. An animal study has suggested that lower-dose ethanol therapy has results comparable to those achieved with the traditional higher doses. This, together with the current results demonstrating good clinical outcomes in spite of inconsistency in reaching target ethanol concentrations, suggests that lower, fixed-dose ethanol infusions in combination with hemodialysis may be an effective alternative for the treatment of methanol or ethylene glycol poisoning.
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The limitations of this study’s design, a retrospective examination of medical records, must be acknowledged. The treatment protocol for IV ethanol administration was not standardized, and the reporting of subjective outcome data such as visual disturbances associated with methanol and adverse effects caused by ethanol were incomplete. Nonetheless, these results do provide insight into the “real world” effectiveness and safety of IV ethanol therapy and hemodialysis in the management of methanol and ethylene glycol poisoning.
In conclusion, IV ethanol administration combined with hemodialysis appears to be effective and safe for the management of patients with methanol or ethylene glycol poisoning. This continues to be the preferred therapeutic approach at the authors’ institution.
