Methanol and Formate Kinetics During Treatment with Fomepizole

Hovda, Knut Erik; Andersson, Kirsti Svendsen; Urdal, Petter; Jacobsen, Dag

doi:10.1081/clt-200058936

Cited by 32 publications

(36 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The variability of the endogenous elimination of formate may in part be explained by its variable renal excretion as also reported in the same patients 27 and in patients not undergoing dialysis. 27 We have previously suggested that this variation in the renal handling of formate is pHdependant; the more acidic the urine becomes, the less formate is excreted: Therefore, the role of dialysis in removing formate most probably becomes more important the more acidotic the patient is because the intrinsic clearance of formate then decreases. 27 We have recently published a fatal case report of a 63-year-old male presenting with a severe metabolic acidosis following methanol poisoning.…”

Section: Comments/discussionmentioning

confidence: 74%

“…27 Again, the benefit may seem marginal, but this is a complex issue: first, the patients where formate kinetics was performed during dialysis were more severely poisoned. That means they were more acidotic on admission, and hence the endogenous formate half-life in these patients would most probably be significantly longer without dialysis.…”

Section: Hemodialysis and Methanolmentioning

confidence: 98%

“…The half-life of methanol during hemodialysis was significantly shortened compared with the mean half-life of 52 h reported in eight patients treated with fomepizole only. 27 Hemodialysis and formate The role of dialysis has been questioned regarding the elimination of formate. Removal of formate with dialysis as such is an efficient process, 11,38 but questions have been raised regarding the effect of dialysis versus the short endogenous half-life of formate often reported.…”

Section: Hemodialysis and Methanolmentioning

confidence: 99%

See 2 more Smart Citations

Expert opinion: fomepizole may ameliorate the need for hemodialysis in methanol poisoning

Hovda

Jacobsen

2008

Hum Exp Toxicol

View full text Add to dashboard Cite

Fomepizole is now the antidote of choice in methanol poisoning. The use of fomepizole may also change the indications for hemodialysis in these patients. We have addressed this change in a review of articles on methanol poisonings. Review of the literature (through PubMed®) combined with our own experiences from two recent methanol outbreaks in Estonia and Norway. The efficiency of dialysis during fomepizole treatment was reported in only a few reports. One recent study challenged the old indications, suggesting a new approach with delayed or even no hemodialysis. Methanol-poisoned patients on fomepizole treatment may be separated into two categories: 1) The critically ill patient, with severe metabolic acidosis (base deficit >15 mM) and/or visual disturbances should be given buffer, fomepizole and immediate hemodialysis: dialysis removes the toxic anion formate, and assists in correcting the metabolic acidosis, thereby also reducing formate toxicity. The removal of methanol per se is not important in this setting because fomepizole prevents further production of formic acid. 2) The stable patient, with less metabolic acidosis and no visual disturbances, should be given buffer and fomepizole. This treatment allows for the possibility to delay, or even drop, dialysis in this setting, because patients will not develop more clinical features from methanol poisoning when fomepizole and bicarbonate is given in adequate doses. Indications and triage for hemodialysis in methanol poisonings should be modified. Delayed hemodialysis or even no hemodialysis may be an option in selected cases.

show abstract

Section: Comments/discussionmentioning

confidence: 74%

Section: Hemodialysis and Methanolmentioning

confidence: 98%

Section: Hemodialysis and Methanolmentioning

confidence: 99%

See 1 more Smart Citation

Expert opinion: fomepizole may ameliorate the need for hemodialysis in methanol poisoning

Hovda

Jacobsen

2008

Hum Exp Toxicol

View full text Add to dashboard Cite

show abstract

“…Methanol is primarily cleared by metabolism, so its half‐life during fomepizole therapy is increased (50–80 h) . Haemodialysis is often used to shorten the duration of therapy and hospital stay , and intermittent haemodialysis has been shown to be superior to continuous dialysis modalities .…”

Section: Treatment With Fomepizolementioning

confidence: 99%

Antidotes for poisoning by alcohols that form toxic metabolites

McMartin

Jacobsen

Hovda

2016

Brit J Clinical Pharma

Self Cite

110

View full text Add to dashboard Cite

The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality. These poisonings have traditionally been treated with ethanol since it competes for the active site of alcohol dehydrogenase and decreases the formation of toxic metabolites. Although ethanol can be effective in these poisonings, there are substantial practical problems with its use and so fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically-toxic alcohol poisonings. Fomepizole has few side effects and is easy to use in practice and it may obviate the need for haemodialysis in some, but not all, patients. Hence, fomepizole has largely replaced ethanol as the toxic alcohol antidote in many countries. Nevertheless, ethanol remains an important alternative because access to fomepizole can be limited, the cost may appear excessive, or the physician may prefer ethanol due to experience.

show abstract

“…In the UK the competitive alcohol dehydrogenase antagonist fomepizole is available for use in ethylene glycol poisoning [186] and methanol poisoning on a named patient basis [187]. This agent may still be required in conjunction with extracorporeal removal as methanol redistribution postdialysis may occur [188, 189].…”

Section: Normal Anion Gap Acidosesmentioning

confidence: 99%

Metabolic acidosis in the critically ill: Part 2. Causes and treatment

2008

View full text Add to dashboard Cite

SummaryThe correct identification of the cause, and ideally the individual acid, responsible for metabolic acidosis in the critically ill ensures rational management. In Part 2 of this review, we examine the elevated (corrected) anion gap acidoses (lactic, ketones, uraemic and toxin ingestion) and contrast them with nonelevated conditions (bicarbonate wasting, renal tubular acidoses and iatrogenic hyperchloraemia) using readily available base excess and anion gap techniques. The potentially erroneous interpretation of elevated lactate signifying cell ischaemia is highlighted. We provide diagnostic and therapeutic guidance when faced with a high anion gap acidosis, for example pyroglutamate, in the common clinical scenario 'I can't identify the acid -but I know it's there'. The evidence that metabolic acidosis affects outcomes and thus warrants correction is considered and we provide management guidance including extracorporeal removal and fomepizole therapy.

show abstract

Methanol and Formate Kinetics During Treatment with Fomepizole

Abstract: Based on our data, methanol-poisoned patients with moderate metabolic acidosis and methanol levels up to 19 mmol/L (60 mg/L) may safely be treated with bicarbonate and fomepizole only, without dialysis.

Cited by 32 publications

References 0 publications

Expert opinion: fomepizole may ameliorate the need for hemodialysis in methanol poisoning

Expert opinion: fomepizole may ameliorate the need for hemodialysis in methanol poisoning

Antidotes for poisoning by alcohols that form toxic metabolites

Metabolic acidosis in the critically ill: Part 2. Causes and treatment

Contact Info

Product

Resources

About