Question 21.3 from the first paper of 2015 presents us with a story of a foreign sailor who was found unconscious. Immediately a sour flavour of intoxication and despair permeates through the case scenario. Prior to his descent into coma, he complained of visual disturbance. A "snowstorm", you might wonder. A gas is then offered, and the high anion gap found therein helps to form the impression of a methanol overdose. In a much less oblique fashion, Question 18.3 from the first paper of 2019 directly asked the trainees to list the biochemical features of methanol toxicity and discuss its specific management.
Toxic alcohols receive a more enthusiastic treatment elsewhere (Methanol and the other toxic alcohols, from the Acid-Base Disturbances collection of notes). This brief revision chapter is focused on answering CICM SAQs on toxic alcohol ingestion, or wherever a high anion gap metabolic acidosis raises such a differential. Kraut and Kurtz give this topic a thorough treatment in their 2008 article, which is probably the only thing you ever need to read on the subject. This article (as well as the relevant chapter from Goldfranks' ) formed the basis for this summary chapter.
Toxic alcohol toxidromes
|Disorder||Toxin||Clinical and Laboratory Abnormalities|
|Ethylene glycol intoxication||
|Diethylene glycol intoxication||
|Propylene glycol intoxication||
|Isopropyl alcohol intoxication||
Features common to toxic alcohol poisonings
- High anion gap (all except isopropyl acohol)
- High osmolar gap (all). Methanol is the alcohol molecule with the lowest molecular weight (32.04), and therefore a glass of methanol will raise the osmolar gap more than ethanol (MW= 46) or any of the others.
- Rapidly absorbed from the GI tract
- Volume of distribution similar to that of body water
- Metabolized in the liver
- Metabolites and unchanged drug are readily cleared by the kidneys
- All cause inebriation: the higher the molecular weight, the more intoxicating the alcohol.
- Methanol is the only one which causes "snowblindness", because of the retinal toxicity of formate.
Management of toxic alcohol poisoning
- Activated charcoal is useless. Absorption is too rapid.
- Haemodialysis: toxic alcohols and their metabolites are rapidly cleared in this manner
- Thiamine enhances metabolism of ethylene glycol to alpha-hydroxy-beta-ketoadipate
- Pyridoxine enhances metabolism of ethylene glycol to glycine (and ultimately hippuric acid).
- Folate and leucovorin enhance the clearance of formate; specifically formate binds with tetrahydrofolate to produce 10-formyl-tetrahydrofolate, which is then incorporated into purine metabolism (Morrow et al, 2015)
- Alkalinization of urine with a bicarbonate infusion promotes dissociation of formic acid (it is less toxic in its ionised state) and improves its clearance by ion trapping in the urine
- Alcohol - the precise use of this substance in overdose is discussed in the chapter on ethylene glycol and its toxic acid metabolytes.
- In brief, one should sustain a blood ethanol concentration of 20 to 30 mmol/L (100 to 150 mg/dL) - this equates to a blood alcohol level of 0.1-0.15%.
- Fomepizole as it is known, is basically a competitive antagonist to alcohol dehydrogenase. It does what ethanol would do, except it does so with great expense, and without ethanol intoxication. The advantage of using it is its lack of CNS effects - if the patient is confused already you do not want to add alcohol into the mix.
- Boring supportive care is all that is required.
- Airway control and mechanical ventilation: the patient may be uncooperative and with a foul manner.
- Circulatory support in case of significant haemodynamic collapse
- Sedation and analgesia with short acting substances