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Leucovorin (calcium folinate) in “antifreeze” poisoning
  1. Angaj Ghosh, Senior Clinical Fellow,
  2. Russell Boyd, Consultant
  1. Emergency Department, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK; kevin.mackway-jones{at}


    A short cut review was carried out to establish whether the addition of intravenous calcium folinate to standard (ethanol) therapy reduced the visual complications of antifreeze (methanol and ethyleny glycol). Altogether 12 papers were found using the reported search, of which one animal study presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.

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    Report by Angaj Ghosh,Senior Clinical FellowChecked by Russell Boyd, Consultant

    Clinical scenario

    A man attends the emergency department having deliberately taken 150 ml of “antifreeze”. The can of antifreeze has conveniently been brought along and you find it consists of a mixture of methanol and ethylene glycol. The Poisons Centre is contacted. In addition to treatment with ethanol it is suggested that intravenous Leucovorin (calcium folinate) is given. You wonder if there is any evidence to support this recommendation.

    Three part question

    In [an adult with methanol/ethylene glycol poisoning] is [the addition of intravenous calcium folinate better than ethanol alone] at [reducing the incidence of reduced acuity and retinal oedema)]?

    Search strategy

    Medline 1996–06/03 using the OVID interface. [exp leucovorin OR folinic OR Calcium] AND [exp methanol OR OR exp ethylene glycol OR ethylene OR] LIMIT to English.

    Search outcome

    Altogether 12 papers were found, none of which were relevant to humans. One paper published in two different journals described studies on monkeys and suggested that the results could be extrapolated to humans (table 3).

    Table 3


    In humans methanol toxicity is characterised by a metabolic acidosis and an ocular toxicity that occur coincident with an accumulation of formate in blood. After experimental studies on monkeys, Noker and Tephly hypothesised that folate compounds could decrease formate accumulation after methanol by stimulating formate oxidation or utilisation and suggested a possible use for folates in the treatment of certain cases of human methanol poisoning.


    There is no direct evidence of the usefulness of folates in methanol poisoning in humans. Local policy should be followed.

    Report by Angaj Ghosh,Senior Clinical FellowChecked by Russell Boyd, Consultant


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