Medication errors associated with the use of ethanol and fomepizole as antidotes for methanol and ethylene glycol poisoning

Lepik, Katherine J; Sobolev, Boris; Levy, Adrian R.; Purssell, Roy; DeWitt, Chris; Erhardt, Gunnar D.; Baker, Jane L.; Kennedy, James R.; Daws, Derek E.

doi:10.3109/15563650.2011.580754

Cited by 15 publications

(6 citation statements)

References 20 publications

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“…This has historically resulted in frequent delays and errors in achieving therapeutic ethanol concentrations required to provide adequate ADH inhibition. 4 Because of fomepizole's favorable pharmacokinetic profile and ease of use, folate may have been more frequently recommended while ADH inhibition with ethanol was the standard approach.…”

Section: Discussionmentioning

confidence: 99%

Forgoing the Folate?—Contemporary Recommendations for Methanol Poisoning and Evidence Review

Lim

Bryant²

2016

American Journal of Therapeutics

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Methanol poisonings can produce significant toxicity in humans, including acidosis, blindness, and death. The current mainstay of therapy is alcohol dehydrogenase (ADH) inhibition to prevent formation of formic acid and hemodialysis to correct acidosis and remove both parent compound and toxic metabolite. Folate has been recommended as an adjunctive therapy to increase formic acid oxidation into carbon dioxide and water. We retrospectively reviewed recommendation of folate therapy for methanol poisoning by our regional poison center from 2002 to 2012. One hundred two patients met inclusion criteria. Our findings demonstrate a sharp decline in folate recommendation over the course of the study period (48% vs. 12% during the years 2002-2006 and 2007-2012, respectively), despite similar rates of ADH inhibition, hemodialysis, and serious outcomes. This may be related to the approval of the use of fomepizole in methanol poisoning in 2002, which provides a quicker, more reliable means of ADH inhibition than ethanol infusions. We also provide a review of the available evidence of folate use in methanol poisoning.

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Section: Discussionmentioning

confidence: 99%

Forgoing the Folate?—Contemporary Recommendations for Methanol Poisoning and Evidence Review

Lim

Bryant²

2016

American Journal of Therapeutics

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“…Nevertheless, administration of ethanol as an antidote can be associated with some pitfalls, mainly with errors of dosing and adverse reactions 25,26 . It can cause CNS and respiratory depression in the cases of overdose, altering the patients' ability to hyperventilate and thus removing this important compensating mechanism of metabolic acidosis 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Several authors state that ethanol may cause CNS and respiratory depression, hypoglycemia during administration, and generally has a less safe side-effect profile than fomepizole [21][22][23][24] . Ethanol administration is associated with higher risk of medication errors and adverse reactions 25,26 . Higher risk of wrong dosing and adverse reactions is mainly related to the unpredictable pharmacokinetics of ethanol, especially during hemodialysis sessions [27][28][29] .…”

Section: Introductionmentioning

confidence: 99%

Fluctuations in serum ethanol concentration in the treatment of acute methanol poisoning: a prospective study of 21 patients

Zakharov¹,

Navrátil²,

Skalický³

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Objective. During the 2012 outbreak of mass methanol poisonings in the Czech Republic, ethanol, in the main, was used as an antidote. The complex pharmacokinetics of ethanol made it difficult to maintain the requisite 1000-1500 mg/L serum ethanol levels (S-EtOH). The aim of this study was to measure the fluctuations in S-EtOH during the treatment. Methods. A prospective case series in 21 patients, median age 52 (27-79 years), 13 males and 8 females. Serum ethanol, methanol and formate were measured every 2-6 hours during the treatment. Follow-up clinical examination was carried out in 15/18 survivors. Results. The majority of patients (17/21) were late presenters and on admission, almost half (10/21) had suffered a severe grade of intoxication according to the Poisoning Severity Score (PSS). The mean observation time was 90±20 h. The mean period of consistent maintenance of S-EtOH within the recommended therapeutic range lasted 28±7% of the total observation time. For 29±8% of the time, S-EtOH was >1500 mg/L with "peaks" of up to 3500 mg/L. For 44±10% of the observation time, S-EtOH was <1000 mg/L. The mean duration of sub-therapeutic concentration of S-EtOH and toxic serum levels of methanol >200 mg/L or formate >20 mg/L lasted 20±10% and 18±11% of the time of observation, respectively. Complications occurred in 14 (67%) of cases including significant fluctuations of S-EtOH in 9; aspiration pneumonia in 3 and delirium tremens in 2 cases. Other complications included sepsis, bleeding, acidosis rebound, intolerance and set clotting. The outcomes were: 11 survivors free of health impairment, 7 with sequelae and 3 deaths. There was no significant difference in mean duration of sub-therapeutic and supra-therapeutic concentrations of serum ethanol in patients who survived without sequelae and those with poor outcome (P > 0.05). Conclusion. Administration of ethanol according to the present guidelines of the AACT/EAPCCT is effective and relatively safe in the treatment of methanol poisoning during a mass outbreak 31 . Physicians have to be most aware of fluctuations in serum ethanol at the end of short sessions of IHD and after changes in route from intravenous to oral. Rigorous monitoring of serum ethanol concentrations is pivotal for severely poisoned patients with PSS 3 and where there is suspected conversion of significant amounts of methanol to formic acid.

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“…Serious adverse effects of antidotes can result from dosing errors (particularly common with infrequently used antidotes), those requiring reconstitution and dilution, and those generally employed at lower doses for non‐toxic conditions (such as insulin). For example, more errors are made with ethanol than fomepizole for methanol and ethylene glycol poisoning . Ten‐fold dosing errors have led to lethal anaphylaxis with acetylcysteine and excessively high doses for pralidoxime likely explain excess deaths associated with its use in a recent randomized clinical trial .…”

Section: Introductionmentioning

confidence: 99%

Who gets antidotes? choosing the chosen few

Buckley

Dawson

Juurlink

2016

Brit J Clinical Pharma

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An understanding of mechanisms, potential benefits and risks of antidotes is essential for clinicians who manage poisoned patients. Of the dozens of antidotes currently available, only a few are regularly used. These include activated charcoal, acetylcysteine, naloxone, sodium bicarbonate, atropine, flumazenil, therapeutic antibodies and various vitamins. Even then, most are used in a minority of poisonings. There is little randomized trial evidence to support the use of most antidotes. Consequently, decisions about when to use them are often based on a mechanistic understanding of the poisoning and the expected influence of the antidote on the patient's clinical course. For some antidotes, such as atropine and insulin, the doses employed can be orders of magnitude higher than standard dosing. Importantly, most poisoned patients who reach hospital can recover with supportive care alone. In low risk patients, the routine use of even low risk antidotes such as activated charcoal is unwarranted. In more serious poisonings, decisions regarding antidote use are generally guided by a risk/benefit assessment based on low quality evidence.

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Medication errors associated with the use of ethanol and fomepizole as antidotes for methanol and ethylene glycol poisoning

Abstract: Fomepizole was less prone to medication error than ethanol. Error-related harm was most commonly due to excessive antidote dose or delayed antidote initiation.

Cited by 15 publications

References 20 publications

Forgoing the Folate?—Contemporary Recommendations for Methanol Poisoning and Evidence Review

Forgoing the Folate?—Contemporary Recommendations for Methanol Poisoning and Evidence Review

Fluctuations in serum ethanol concentration in the treatment of acute methanol poisoning: a prospective study of 21 patients

Who gets antidotes? choosing the chosen few

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