As methanol and ethylene glycol are metabolized, the osmolar gap decreases and a high anion gap metabolic acidosis (HAGMA) develops. Observing that ethanol consumption often delayed the clinical features of methanol poisoning, Röe 48 postulated that ethanol could be a treatment, along with sodium bicarbonate, for methanol poisoning. The rationale for this treatment is that ethanol has at least 10 times the affinity for ADH compared to methanol 49 and 20‐fold more than ethylene glycol 50. Ethanol occupies the active site of the enzyme, thereby reducing production of toxic metabolites as demonstrated in many case reports/series on methanol or ethylene glycol poisoning 29, 30, 51, 52, 53. Because most patients were also treated with bicarbonate and dialysis, conclusions regarding the efficacy of ethanol therapy alone are limited. Another problem with ethanol is the potential for adverse effects, especially CNS depression.
Antidotes for poisoning by alcohols that form toxic metabolites
One of the most common medications used alcohol overdose to reverse alcohol overdose is metadoxine. This drug is used for acute alcohol intoxication, alcohol overdose, and for chronic intoxication, which may be seen in alcohol addiction. Once the person experiencing alcohol poisoning makes it to the hospital or other care facility, there are a few ways healthcare professionals may work to treat the overdose. Treatment for alcohol use disorder may include inpatient and outpatient services. Alcohol poisoning is the result of drinking excessive amounts of alcohol (ethanol) faster than the body can process it.
Hemodialysis
An osmolar gap and anion gap may be present simultaneously, but as more of the toxic alcohol is metabolized, osmolality will start to fall and anion gap will continue to rise2. Treatment with an alcohol dehydrogenase inhibitor should commence expeditiously when there is a strong suspicion of toxic alcohol poisoning or when metabolic acidosis of unknown cause is present3. Fomepizole (4‐methylpyrazole (4MP)) is a potent competitive inhibitor of ADH activity with an affinity more than 1000 times that of the toxic alcohols 65. Fomepizole was shown to reduce the formation of toxic metabolites in lethal methanol and ethylene glycol poisonings in animal models 66, 67. In these studies, fomepizole reversed an already‐developed metabolite accumulation and severe metabolic acidosis without dialysis.
Isopropyl alcohol poisoning
- Treatment for alcohol poisoning depends on the severity of the symptoms and typically involves supportive care to stabilize the person until their body metabolizes the excess alcohol.
- Fomepizole (or 4-methylpyrazole) is a strong inhibitor of alcohol dehydrogenase with an affinity for alcohol dehydrogenase 8,000 times that of ethanol.
- Some glycol ethers are also metabolized to intermediates, but their poisonings are less severe with few common features, so are not discussed.
- Each individual’s reaction to alcohol varies based on factors like body weight, metabolism, hydration, age, and overall health.
- Although Paasma and coworkers did not find a significantly better overall outcome with fomepizole, methanol‐poisoned patients that could hyperventilate had a significantly better survival with fomepizole compared to ethanol 95.
- An educated estimate is that the maintenance ethanol dose be doubled during intermittent haemodialysis (see Table 3).
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. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality. Fomepizole only prevents formation of toxic metabolites, while hemodialysis is effective at removing toxic alcohols and their toxic metabolites. Hemodialysis should be used in patients with significant acidosis, elevated anion gap, or evidence of end-organ injury. It can also be used in patients with or without severe side effects to reduce length of fomepizole therapy in patients with very high initial toxic alcohol concentrations. In the presence of hemodialysis, the half-lives of toxic alcohols are cut dramatically, methanol down to approximately 2.5 hours and ethylene glycol to approximately 2.7 hours3.
Steps to Take If Someone Shows Signs of Alcohol Poisoning
Even so, one animal study indicates that ethanol treatment can block the acidosis and renal histopathology produced by a large dose of diethylene glycol (16.8 g kg−1) 55. Guidelines suggest that fomepizole should be the main antidote for methanol or ethylene glycol poisoning 37, 38, while ethanol can be used when fomepizole is unavailable. The preference for fomepizole in most countries is based on its efficacy and lower degree of adverse effects compared with ethanol, 95, 108 and its major drawback is the perceived high cost. Believe it or not, it’s possible to overdose on alcohol without drinking alcoholic beverages. This is because the ingestion of other products and household items such as antifreeze and solvents can cause methanol or ethylene glycol poisoning. Even as the person’s BAC gradually drops, they can still experience after-effects or complications of alcohol poisoning, such as dehydration, low blood sugar, or altered mental status.
Alcohol Poisoning Treatment in Hospitals
The most important is that the compounds themselves are relatively nontoxic 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 poisonings, from either unintentional or intentional ingestion. Although relatively infrequent, toxic alcohol poisonings do unfortunately occur in outbreaks and can result in severe morbidity and mortality. Although ethanol can be an effective antidote, there are substantial practical problems with its use. Therefore fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically toxic alcohol poisonings.
- As methanol and ethylene glycol are metabolized, the osmolar gap decreases and a high anion gap metabolic acidosis (HAGMA) develops.
- Methanol and ethylene glycol poisonings share many clinical and biochemical features, including metabolite‐induced metabolic acidosis.
- Two large studies have tried to compare the effects of ethanol and fomepizole 94, 95.
- Adverse events reported with the use of fomepizole include mild irritation at the i.v.
Treatment criteria
- Although clinical evidence is lacking for a therapeutic effect of ethanol alone, several studies have demonstrated that ethanol treatment alters the kinetics of toxic alcohols 56, 57.
- The Food and Drug Administration (FDA)-approved regimen of fomepizole is an i.v.
- In a retrospective review of adverse events in methanol and ethylene glycol‐poisoned cases, CNS symptoms were reported in half of the cases treated with ethanol, while only in 2% treated with fomepizole 98.
- In ethylene glycol poisoning, thiamine and pyridoxine shunt metabolism of glyoxylic acid away from oxalate and favor the formation of less toxic metabolites.
- Even as the person’s BAC gradually drops, they can still experience after-effects or complications of alcohol poisoning, such as dehydration, low blood sugar, or altered mental status.
Although it varies from person to person, a BAC above 0.30% can lead to severe complications, including unconsciousness and death. Antidotes for toxic alcohol poisoning are not required for isopropyl alcohol poisoning. Fomepizole appears to reduce the need for haemodialysis, at least in ethylene glycol exposures. The use of fomepizole simplifies management of many patients, and potentially reduces the use of intensive care beds 14, 15, 19. Two large studies have tried to compare the effects amphetamine addiction treatment of ethanol and fomepizole 94, 95.