ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Methanol and ethylene glycol poisoning: Management

Methanol and ethylene glycol poisoning: Management
Literature review current through: Jan 2024.
This topic last updated: Jan 08, 2024.

INTRODUCTION — Methanol and ethylene glycol poisonings cause scores of fatal intoxications annually, and even relatively small ingestions of these alcohols can produce significant toxicity. Rapid recognition and early treatment, including alcohol dehydrogenase (ADH) inhibition and often hemodialysis, are crucial. A summary table to facilitate emergency management is provided (table 1).

Methanol and ethylene glycol are frequently found in high concentrations in automotive coolant/antifreeze and de-icing solutions, windshield wiper fluid, solvents, cleaners, fuels, and other industrial products. Most serious poisonings occur following ingestion; inhalation and dermal exposures rarely cause toxicity [1]. Patients may ingest toxic alcohols as an ethanol substitute, to inflict self-harm, or by accident (sometimes following transfer from the original container). Multiple victim methanol poisonings can occur with illicit distillation ("moonshine") or occult substitution for ethanol.

The management of methanol and ethylene glycol intoxication is reviewed here. While there are differences between methanol and ethylene glycol poisoning, there is substantial overlap in management, and both the similarities and differences are described. The following related content is discussed in separate topics:

Clinical manifestations, laboratory findings, and diagnosis of methanol and ethylene glycol poisoning (see "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis")

Isopropyl alcohol intoxication (which is considerably different) (see "Isopropyl alcohol poisoning")

The approach to the poisoned adult or child (see "General approach to drug poisoning in adults" and "Approach to the child with occult toxic exposure" and "Initial management of the critically ill adult with an unknown overdose")

OVERVIEW OF MANAGEMENT — Rapid decision-making is critical in the management of the patient poisoned with methanol or ethylene glycol. In most cases, confirmatory toxic alcohol concentration results are delayed and the clinician must make treatment decisions (eg, antidote, hemodialysis) based upon clinical suspicion, bedside assessment of the severity of illness, and readily available surrogate markers (eg, anion and osmolal gaps) of exposure and toxicity. The interpretation of laboratory data in the context of clinical manifestations when evaluating a patient with possible methanol or ethylene glycol exposure is discussed in detail separately. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Laboratory evaluation'.)

We describe an approach based on the most common scenarios encountered (and provide associated algorithms) grouped by the likelihood of a toxic alcohol ingestion, the degree of acidemia, and the severity of end-organ toxicity (see 'Approach based on clinical scenario' below):

Strongly suspected poisoning (eg, witnessed large ingestion or severe metabolic acidosis with/without end-organ toxicity and etiology is most likely a toxic alcohol ingestion) (see 'Strongly suspected poisoning' below)

Possible poisoning (eg, milder manifestations or unlikely to be a toxic alcohol ingestion) (see 'Possible poisoning' below)

Confirmed poisoning (ie, toxic alcohol concentrations available) (see 'Known toxic alcohol serum concentration' below)

Very recent, unintentional, small-volume ingestion without immediate access to confirmatory concentrations, as commonly occurs in children (see 'Accidental small-volume ingestion' below)

The following is an overview of the emergency management of a potentially critically ill patient suspected of toxic alcohol poisoning, including principles and basic rationale regarding immediate testing and treatment decisions (also summarized in the table (table 1)):

Addressing "ABCs" – Assess and address the patient's airway, breathing, and circulation ("ABCs"), and provide appropriate supportive care as needed. If tracheal intubation is required and a significant metabolic acidosis exists or is suspected, the patient should be managed as having a "physiologically difficult airway" because administration of induction medications and neuromuscular blocking agents (NMBAs) may make the apneic phase of rapid sequence intubation (RSI) intolerable and create a risk for circulatory collapse. An approach to intubating the physiologically difficult airway is discussed separately and includes the following strategies (see "Approach to the difficult airway in adults for emergency medicine and critical care", section on 'High-risk physiology present'):

Initiate treatment of the underlying metabolic acidosis prior to intubation. In the case of methanol or ethylene glycol poisoning, this is performed with a sodium bicarbonate infusion and alcohol dehydrogenase inhibition. Some experts will administer intravenous (IV) sodium bicarbonate 7.5 or 8.4% 50 to 100 mL over one to two minutes (ie, one to two ampule pushes) as part of preinduction medication, but this practice is not uniformly accepted. (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' below and 'Sodium bicarbonate' below.)

When possible, perform intubation without an NMBA or deep sedation to avoid a period of apnea. Some experts prefer ketamine in this circumstance because it allows the patient to maintain respiratory drive while providing analgesia, amnesia, and sedation. If an NMBA is administered, the most experienced operator should perform the intubation in order to minimize the apnea time. (See "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care", section on 'Conditions precluding use of a paralytic' and "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care", section on 'Ketamine' and "Awake tracheal intubation".)

Ventilator settings may require a large minute ventilation to prevent profound acidemia in patients with severe intoxication. Arterial and/or venous blood gas analysis should be performed frequently to ensure adequate ventilation. Unless there is ventilator-patient asynchrony or a comparable problem making ventilation extremely difficult, long-acting NMBA and deep sedation should be avoided since they blunt the patient’s ability to breath over the ventilator. If auto-positive end-expiratory pressure (auto-PEEP) develops, it must be recognized and managed quickly since it can prevent adequate ventilation. (See "Mechanical ventilation of adults in the emergency department".)

Bicarbonate to reduce acidemia – In a patient with profound acidemia, sodium bicarbonate IV raises the blood pH and shifts the equilibrium of toxic acids (eg, formic acid, glycolic acid) towards the anion form (eg, formate, glycolate). This protects end-organ tissues including the retina, kidney, and brain since the anion form cannot diffuse across cell membranes. (See 'Sodium bicarbonate' below.)

Alcohol dehydrogenase (ADH) inhibition – Inhibiting the enzyme ADH with either fomepizole (preferred) or ethanol (if fomepizole is unavailable) stops further formation of toxic acid metabolites [2]. Commonly cited indications are provided in the table (table 2) and discussed by clinical scenario below. (See 'Approach based on clinical scenario' below and 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' below.)

Extracorporeal removal – Hemodialysis increases elimination of the parent alcohol and metabolites, corrects acid-base derangements, and prevents end-organ toxicity. In the absence of confirmatory methanol and ethylene glycol serum concentrations, determining the need and timing of hemodialysis based solely on surrogate clinical information (eg, nature and intent of exposure, blood pH, anion gap, serum osmolarity) is often challenging [3]. In general, when the diagnosis is highly likely, the severity of metabolic acidosis guides decisions regarding the urgency and priority of hemodialysis without relying on and waiting for confirmatory toxic alcohol concentrations. (See 'Strongly suspected poisoning' below and 'Possible poisoning' below and 'Extracorporeal removal (hemodialysis)' below.)

Cofactor therapy Folic acid, thiamine, and pyridoxine help optimize metabolic pathways for the elimination of the toxic acid metabolites. (See 'Cofactor therapy' below.)

Obtaining confirmatory alcohol concentrations – Even though management is typically initiated without definitive serum drug concentrations, confirmatory concentrations are important to guide subsequent management. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Additional tests with toxic alcohol exposure'.)

Specialist consultations – We recommend consultation with a medical toxicologist/poison control center and a nephrologist if methanol or ethylene glycol intoxication is suspected or confirmed. (See 'Additional resources' below.)

Limited role for gastrointestinal decontamination – With the exception of the rare patient presenting within 60 minutes of ingesting a large volume (discussed below), there is no role for gastrointestinal decontamination in methanol or ethylene glycol poisoning. Most alcohols are rapidly and completely absorbed within one hour. Activated charcoal, gastric lavage, and syrup of ipecac have no role in the management of toxic alcohol exposures. (See 'Strongly suspected poisoning' below and "Gastrointestinal decontamination of the poisoned patient".)

APPROACH BASED ON CLINICAL SCENARIO

Strongly suspected poisoning — We strongly suspect ethylene glycol or methanol poisoning in a patient who meets any of the following criteria:

A patient with a witnessed or compelling history of intentional ingestion of product known to contain >10% methanol or ethylene glycol for self-harm or mistaken for ethanol. If a patient presents within two hours of ingestion, the blood pH can still be normal.

A patient linked to an outbreak of toxic alcohol poisoning involving one or more severely poisoned victims.

Presence of severe elevated anion gap metabolic acidosis (eg, pH <7.1) without clear alternative etiology, such as diabetic ketoacidosis (DKA), uremia, sepsis, tissue or bowel ischemia, or poisoning with acetaminophen, salicylate, iron, or isoniazid (table 3). (See "Approach to the adult with metabolic acidosis", section on 'Causes of elevated anion gap metabolic acidosis'.)

A patient with a possible ingestion and end-organ toxicity (see "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Clinical features of overdose'):

Methanol: new-onset blindness (including "snowfield" blindness but also marked decrease in visual acuity, central scotoma, or afferent pupillary defect) or coma

Ethylene glycol: acute kidney injury or urine with large amount of needle-shaped or envelope-shaped crystals

Presence of osmolal gap ≥25 mOsm/kg after correction for measured serum ethanol concentration (calculator 1 and calculator 2). (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Plasma osmolal gap'.)

Initial management — Our initial approach to management is the following:

Assess and address the patient's airway, breathing, and circulation ("ABCs"), provide appropriate supportive care as needed, and obtain consultation with a medical toxicologist/poison control center and a nephrologist as discussed above. (See 'Overview of management' above.)

We recommend immediately administering alcohol dehydrogenase (ADH) inhibitor therapy. The dosing, duration, and rationale for ADH inhibitor therapy are presented below. (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' below.)

Obtain confirmatory toxic alcohol serum concentrations. Since these tests are not commonly ordered, it is often helpful to convey to laboratory personnel the urgency of obtaining timely results. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Testing for methanol and ethylene glycol'.)

Although rare, for a patient presenting within 60 minutes of ingestion, we recommend performing gastric aspiration via small-bore (8 to 14 French) flexible nasogastric tubing. Immediate gastric aspiration has the potential to limit absorption in such highly selected cases. Small-bore tube gastric aspiration is sufficient, easier to perform, and has fewer complications compared with large-bore orogastric lavage.

Further management — In a patient with a strong suspicion for ethylene glycol or methanol poisoning, further management depends on whether they have a metabolic acidosis or end-organ toxicity:

Patient with moderate-severe acidosis or end-organ toxicity — In a patient with a strong suspicion and a moderate-severe metabolic acidosis (eg, blood pH <7.25, anion gap >24) and/or evidence of end-organ toxicity, in addition to ADH inhibitor therapy, we recommend urgent hemodialysis and sodium bicarbonate and suggest cofactor therapy [2]. (See 'Extracorporeal removal (hemodialysis)' below and 'Sodium bicarbonate' below and 'Cofactor therapy' below.)

Patient without a metabolic acidosis or with a mild acidosis and without end-organ toxicity — In a patient with a strong suspicion without a metabolic acidosis (or with only a mild acidosis) and without evidence of end-organ toxicity, there is less urgency to perform hemodialysis provided ADH inhibition is adequate and metabolic acidosis does not develop or worsen. Our approach is the following:

Repeat basic electrolytes, creatinine, blood urea nitrogen (BUN), venous (or arterial) blood gas, ethanol concentration (until undetectable), and serum osmolality every two hours until the osmolal gap ≤10 mOsm/kg.

Continue ADH inhibitor therapy until the estimated ethylene glycol or methanol concentration (table 4) ≤20 mg/dL or the confirmatory concentration is ≤20 mg/dL. If the confirmatory concentration is >20 mg/dL, follow the approach discussed below. (See 'Concentration >20 mg/dL' below.)

We recommend hemodialysis if prolonged ADH inhibitor therapy is impractical (eg, administering ethanol because fomepizole is unavailable) or for any large methanol ingestion. Hemodialysis accelerates removal of the parent alcohol and can be performed semi-urgently as long as a metabolic acidosis is not developing. Hemodialysis is generally needed following large methanol ingestions since it has a very slow elimination half-life once ADH is inhibited [3,4]. (See 'Extracorporeal removal (hemodialysis)' below.)

Intentional ingestions (whether for self-harm or inadvertently as an ethanol substitute) tend to involve larger volumes than accidental ingestions, although the ingested amount reported by history may be inaccurate. If the history is compelling, administering fomepizole to inhibit ADH is generally advisable as this antidote is well tolerated and will halt any ongoing production of toxic acid metabolites, thus slowing the progression of end-organ toxicity. In a patient with concerning symptoms or even a moderate metabolic acidosis, we provide ADH inhibition, ideally with fomepizole unless co-ingested ethanol is present, while the confirmatory toxic alcohol serum concentrations are pending.

However, clinical judgement is needed when the only indication for ADH inhibitor therapy is a history of ingestion, especially when the intent was self-harm [2]. In the absence of overt signs or symptoms of toxic alcohol poisoning, obtaining an anion gap and osmolal gap will help establish the role and urgency of empiric ADH inhibition. The absence of a metabolic acidosis or raised anion gap excludes the accumulation of toxic acid metabolites and affords additional time to confirm or exclude the diagnosis. Additionally, a patient with a serum ethanol concentration >50 mg/dL (10 mmol/L) does not require immediate empiric administration of fomepizole (nor additional ethanol) since the serum ethanol provides a temporary degree of ADH inhibition.  

In a patient with an extremely elevated anion gap or osmolal gap, unless an alternative cause is apparent, we generally initiate empiric ADH inhibition. Fomepizole is preferred as the empiric ADH inhibitor in such cases since it is safer compared with ethanol. (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' below.)

Metabolic acidosis develops as toxic acid metabolites begin to accumulate. An anion gap ≥28 mmol/L is strongly suggestive that substantial amounts of the parent alcohol have already been metabolized to either formate (methanol poisoning) or glycolate (ethylene glycol poisoning) and retinal, neurologic, or kidney toxicity is expected [2,5,6]. Few poisons (eg, toxic alcohols, salicylates, metformin, iron) cause a profound metabolic acidosis (eg, pH <7.0) in the absence of seizures or tissue asphyxia. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Pharmacology and cellular toxicology'.)

A patient with an extremely elevated osmolal gap (≥25 mOsm/kg after correction for measured serum ethanol concentration) in the appropriate clinical context (eg, suspected ingestion for self-harm) can be presumed to have ingested an alcohol (including ethanol). Few substances other than alcohols cause a very high osmolal gap (table 5). (See "Serum osmolal gap", section on 'Major causes of an elevated serum osmolal gap'.)

Clinical judgement is also needed to establish the urgency of empiric hemodialysis (ie, prior to confirmatory toxic alcohol serum concentrations). We reserve immediate hemodialysis for a patient who is severely poisoned and toxic alcohol ingestion is the most likely working diagnosis, given the greater morbidity of hemodialysis compared with ADH inhibitor therapy. In general, immediate hemodialysis is likely required for survival in a patient with an anion gap >24 or blood pH <7.1 since ADH inhibitor therapy alone is insufficient to treat profound metabolic acidosis from a toxic alcohol [2]. Early nephrology involvement is imperative since delays to starting hemodialysis are common, even in hospitals capable of emergency hemodialysis.

However, precise thresholds for hemodialysis are not algorithmic, and additional considerations impact this complex decision. In a patient with early and adequate ADH inhibition (and thus without acidemia or with only mild acidemia), hemodialysis may still be appropriate but can be performed less urgently. As examples, hemodialysis may be necessary to remove remaining parent alcohol (as suggested by an osmolal gap >10 mOsm/kg), especially in the setting of a methanol ingestion or when fomepizole is not available and prolonged therapy with ethanol is impractical.  

Possible poisoning — A patient who does not meet any of the criteria for strongly suspected poisoning (see 'Strongly suspected poisoning' above) and has any of the following can possibly have poisoning with ethylene glycol or methanol  :

Presence of elevated anion gap metabolic acidosis without clear etiology (table 3), and the following have been ruled out: DKA, uremia, sepsis, tissue or bowel ischemia, and poisoning with acetaminophen, salicylate, iron, or isoniazid.

Patient more likely has ingested another alcohol (eg, ethanol, isopropyl alcohol, propylene glycol), but the exact product or amount is uncertain. The sole clinical manifestations may be sedation or inebriation, and the serum ethanol concentration may be nondetectable or lower than expected. A mild to moderate metabolic acidosis (eg, blood pH >7.1) may or may not be present.

Serum osmolal gap 10 to 24 mOsm/kg after correction for measured serum ethanol concentration (calculator 1 and calculator 2).

Patient self-reports mild visual impairment and concern for alcohol ingestion.

Urine has needle-shaped or envelope-shaped crystals (ie, oxalate) and urine output is preserved.

A moderately elevated anion gap is often the initial warning that a patient may have ingested a toxic alcohol when an ingestion cannot be excluded by history (eg, confused patient). In a patient with an alcohol use disorder and recent cessation of active drinking (such as from abdominal pain, nausea, or vomiting) in whom a toxic alcohol ingestion is unlikely (eg, ready access to ethanol products, no suspicion of concealed ingestion for self-harm), it is reasonable to treat for alcoholic ketoacidosis (AKA) and defer empirically starting ADH inhibitor therapy unless the acidosis worsens. (See "Fasting ketosis and alcoholic ketoacidosis", section on 'Treatment'.)

A moderately elevated osmolal gap can be seen in patients with methanol or ethylene glycol poisoning but also in patients with AKA, DKA, isopropyl alcohol ingestion, diethylene glycol ingestion, large ethanol ingestion, and other serious illnesses (eg, sepsis, ischemic bowel, shock) (table 5). (See "Serum osmolal gap", section on 'Major causes of an elevated serum osmolal gap'.)

An elevated anion gap metabolic acidosis should not be attributed to methanol or ethylene glycol ingestion if co-ingested ethanol is still present since substantial metabolism of the toxic alcohol is unlikely in the presence of ethanol. In the rare patient who co-ingested ethanol and a toxic alcohol (eg, methanol substituted for ethanol after initially drinking ethanol), the metabolic acidosis typically takes many hours to manifest. This can be a challenging scenario to identify and manage, especially if the patient is substituting other products such as handwashing solution or mouthwash presumed to contain ethanol. A patient with an unexpectedly low serum ethanol concentration or who develops worsening acidemia after the ethanol has been metabolized should be strongly suspected of having methanol or ethylene glycol poisoning and treated as discussed above. (See 'Strongly suspected poisoning' above.)

Initial management — While awaiting results of confirmatory serum ethylene glycol and methanol concentrations, our approach to the patient with possible poisoning is the following:

Do not initially start ADH inhibitor therapy or sodium bicarbonate. Clinicians should be wary of initiating ADH inhibitor therapy based solely on a minor abnormality of the anion gap or osmolal gap without at least circumstantial evidence of toxic alcohol ingestion, especially when ethanol therapy is contemplated.

If the differential diagnosis includes a ketosis or ketoacidosis (ie, starvation or alcoholic), treat with thiamine 100 mg, folate 1 mg, multivitamin, and food/fluids/dextrose (can be given orally or intravenously [IV]). A ketoacidosis can be confirmed by detecting the presence of ketone bodies (eg, acetone, beta-hydroxybutyrate). (See "Fasting ketosis and alcoholic ketoacidosis".)

Repeat basic electrolytes, creatinine, BUN, venous or arterial blood gas, serum ethanol concentration (if initially detectable), and serum osmolality with osmolal gap calculation after two to four hours.

Subsequent management — Further management is based on the trajectory of the patient’s clinical status as follows:

Improving clinical status – If the anion gap and osmolal gap are decreasing, the creatinine is stable or decreasing, and the metabolic acidosis (if initially present) is resolving, then the patient may have a ketoacidosis or isopropyl alcohol ingestion rather than methanol or ethylene glycol poisoning and should be treated appropriately. (See "Fasting ketosis and alcoholic ketoacidosis", section on 'Treatment' and "Isopropyl alcohol poisoning", section on 'Management'.)

Worsening clinical status – If the anion gap is increasing, the metabolic acidosis is worsening, the creatinine is increasing, or the patient is developing other severe manifestations of toxic alcohol poisoning, our approach is the following:

We recommend starting ADH inhibitor therapy and suggest administering cofactors. The dosing, duration, and rationale for ADH inhibitor therapy are presented below. (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' below and 'Cofactor therapy' below.)

Obtain confirmatory toxic alcohol serum concentrations (if not obtained already and testing is available). We convey to laboratory personnel the urgency of obtaining timely results and inquire when the results will be available as that may change further management. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Testing for methanol and ethylene glycol'.)

When toxic alcohol concentrations become available, the results can be used to guide further management. (See 'Known toxic alcohol serum concentration' below.)

However, if the patient develops a moderate to severe metabolic acidosis (eg, blood pH <7.25, anion gap >24) or signs of end-organ damage, the likelihood of toxic metabolites accounting for the acidosis outweighs the risk of hemodialysis; thus, we generally recommend hemodialysis and sodium bicarbonate as described above in the strongly suspected poisoning scenario. (See 'Further management' above.)

Accidental small-volume ingestion — In a patient with an accidental small-volume ingestion of a product known or suspected to contain either methanol or ethylene glycol, we rule out absorption of a toxic dose by frequent, serial measurements of serum chemistries, osmolality, and venous blood gases. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Laboratory evaluation'.)

Such accidental ingestions tend to be of a smaller volume/dose than intentional ingestions. These also typically occur in young children but can occasionally occur in adults if the product was left in an unmarked container. Additionally, these patients commonly present for care within one to two hours of the ingestion, at which time the absence of a metabolic acidosis does not reliably exclude a substantial ingestion. (See 'Younger children' below.)

Our approach is the following for a reliable, asymptomatic patient who presents within four hours of an unintentional small-volume ingestion:  

Attempt to identify the toxic alcohol that was actually ingested (eg, some antifreeze products contain isopropyl alcohol or propylene glycol rather than ethylene glycol) and the concentration (commonly expressed as percent by volume). The evaluation and management of these other alcohols are discussed elsewhere. (See "Isopropyl alcohol poisoning" and "Household nonpharmaceutical product ingestions", section on 'Propylene glycol ("non-toxic" antifreeze)'.)

Obtain venous blood gas, serum chemistry, and serum osmolarity (and a serum ethanol concentration if indicated).

Provided that the blood pH and anion gap are normal:

If the serum osmolal gap >10 mOsm/kg, we recommend starting ADH inhibitor therapy and obtaining confirmatory toxic alcohol serum concentrations. Continue ADH inhibition until the confirmatory serum toxic alcohol concentration results are received from the laboratory. The dosing and rationale for ADH inhibitor therapy is presented below. (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' below.)

When toxic alcohol concentrations become available, the results can be used to guide further management. (See 'Known toxic alcohol serum concentration' below.)

If the serum osmolal gap ≤10 mOsm/kg, then further testing is required because the plasma osmolal gap is not sufficiently sensitive to exclude a small ingestion that could still lead to toxicity. Limitations of the osmolal gap are discussed separately. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Plasma osmolal gap'.)

Under these circumstances, our approach is to perform serial testing as follows:  

-Do not initially start ADH inhibitor therapy. Obtain a venous blood gas and serum electrolytes every one to two hours. Toxic alcohol poisoning can be excluded if a metabolic acidosis or increasing anion gap does not develop within eight hours of the ingestion. In this approach, ADH inhibition with fomepizole or ethanol should not be initiated during observation since it will prevent the development of metabolic acidosis.

-If the serum toxic alcohol concentration can be obtained within a few hours and the laboratory confirms a negligible concentration, this serial testing and observation strategy can be halted early. (See 'Known toxic alcohol serum concentration' below.)

If the serum osmolal gap ≤10 mOsm/kg but ethanol is present or fomepizole has already been administered, then confirmatory testing of toxic alcohol serum concentrations is usually necessary to exclude a small ingestion. The serial testing strategy is impractical since it requires the observation and testing to be prolonged after the ADH inhibition of either the ethanol or fomepizole has disappeared.

Hemodialysis, cofactors, and sodium bicarbonate are only very rarely necessary in these situations.

If the patient develops a progressive metabolic acidosis or any signs of end-organ damage, we immediately initiate ADH inhibitor therapy, obtain confirmatory toxic alcohol serum concentrations (if not obtained already), and follow the approach for a patient with a strongly suspected ingestion described above. (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' below and 'Further management' above.)

Known toxic alcohol serum concentration — A detectable ethylene glycol or methanol serum concentration (performed by gas chromatography) confirms the diagnosis and guides treatment in combination with other laboratory (eg, blood pH, kidney function) and clinical findings. Whenever a detectable serum concentration is brought to the attention of a clinician, attempt to confirm the timing, source, and route of exposure and immediately proceed with the approach described here based on the severity of poisoning and the concentration.

Whenever a detectable methanol or ethylene glycol concentration is reported by a clinical laboratory, immediate consultation with a medical toxicologist is recommended. (See 'Regional poison control centers' below.)

In addition to manifestations of metabolic acidosis, end-organ toxicity of methanol includes visual blurring, scotomata, "snowfield vision," and afferent pupillary defect; end-organ toxicity of ethylene glycol includes acute kidney injury, oxalate crystalluria, and cerebral edema. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Clinical features of overdose'.)

Patient with metabolic acidosis or end-organ toxicity — In a patient with any detectable ethylene glycol or methanol serum concentration in the presence of a metabolic acidosis or evidence of end-organ toxicity, we recommend ADH inhibitor therapy and hemodialysis, and we suggest cofactor therapy. If the patient has a moderate-severe metabolic acidosis (eg, blood pH <7.25), we also recommend sodium bicarbonate. The dosing, duration, and rationale for these therapies are presented below. (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' below and 'Extracorporeal removal (hemodialysis)' below and 'Sodium bicarbonate' below and 'Cofactor therapy' below.)

Patient without metabolic acidosis and no end-organ toxicity — This situation may occur if a patient presents to care and/or has received ADH inhibitor therapy within one to two hours of the ingestion, if only a small dose of the toxic alcohol was ingested, or if ethanol was co-ingested (temporarily inhibiting ADH). The decision to administer ADH inhibitor therapy or perform hemodialysis depends on the toxic alcohol concentration, but other factors (eg, timing of ingestion, time interval until laboratory report of concentrations, expected adequacy of ADH inhibition) may influence this decision.

Concentration >20 mg/dL — In a patient with an ethylene glycol or methanol concentration >20 mg/dL (methanol SI equivalent 6.2 mmol/L; ethylene glycol SI equivalent 3.2 mmol/L), we recommend ADH inhibitor therapy with either fomepizole (preferred) or ethanol (if fomepizole is unavailable). The dosing, duration, and rationale for ADH inhibitor therapy is presented below. (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' below.)

The American Academy of Clinical Toxicology's (AACT) minimum treatment threshold of 20 mg/dL for ADH inhibition is intentionally conservative [4,7-9]. Parent alcohol concentrations must be interpreted in clinical context. As an example, a patient with a methanol concentration of 25 mg/dL (or 7.8 mmol/L) and a normal acid-base status may only require one or two doses of fomepizole, whereas a patient with the same concentration but a significant metabolic acidosis and vision deficits may require fomepizole, alkalinization, and hemodialysis. Making such determinations can be difficult, and we recommend consultation with a regional poison control center or medical toxicologist in such cases. (See 'Additional resources' below.)

Methanol concentration >50 mg/dL – In a patient with a methanol concentration >50 mg/dL (SI equivalent 15.6 mmol/L) without metabolic acidosis or end-organ toxicity, we recommend hemodialysis because serum methanol elimination becomes extremely slow when ADH is inhibited [10-12]. (See 'Extracorporeal removal (hemodialysis)' below.)

Ethylene glycol concentration >50 mg/dL – In a patient with an ethylene glycol concentration >50 mg/dL (SI equivalent 8.1 mmol/L) without metabolic acidosis or end-organ toxicity, hemodialysis may not be required but can be used to remove the unmetabolized ethylene glycol and shorten the course of ADH inhibitor therapy [5,6,13,14]. In order to forgo hemodialysis, sufficient fomepizole should be available (prolonged ethanol therapy is impractical) and the blood pH and serum creatinine should remain near normal. Patients with ethylene glycol concentrations >300 mg/dL (48 mmol/L) have been successfully treated without hemodialysis when fomepizole was initiated before metabolic acidosis developed.

Methanol or ethylene glycol concentration 21 to 50 mg/dL – Hemodialysis is not required but can be used to remove the parent alcohol and shorten the course of ADH inhibitor therapy.

The AACT treatment threshold of 50 mg/dL (methanol SI equivalent 15.6 mmol/L; ethylene glycol SI equivalent 8.1 mmol/L) for hemodialysis is similarly conservative and must also be interpreted in clinical context [2]. Importantly, there is less urgency to perform immediate hemodialysis if ADH inhibition is adequate and metabolic acidosis is not developing since the goal is to remove the parent alcohol and not the toxic acid metabolites. (See 'Extracorporeal removal (hemodialysis)' below.)

Concentration ≤20 mg/dL — In a patient with an ethylene glycol or methanol concentration ≤20 mg/dL (methanol SI equivalent 6.2 mmol/L; ethylene glycol SI equivalent 3.2 mmol/L) without metabolic acidosis or end-organ toxicity, no further treatment is required. Any therapies (eg, fomepizole) that the patient was receiving while awaiting results of the toxic alcohol concentrations can be stopped as long as the blood pH remains normal.

DOSING, DURATION, AND RATIONALE OF THERAPIES DISCUSSED ABOVE

Alcohol dehydrogenase inhibition (fomepizole or ethanol) — Fomepizole is superior to ethanol for alcohol dehydrogenase (ADH) inhibition [9,15-21]. Both agents effectively inhibit ADH, but fomepizole is easier to administer and has less toxicity. Inhibition of ADH blocks bioactivation of the parent alcohol to its toxic acid metabolites. Early treatment is crucial since ADH inhibition does not prevent toxicity if sufficient metabolism to acid species has already occurred.

The American Academy of Clinical Toxicology (AACT) practice guideline provides indications for ADH inhibitor therapy, which are presented in the table (table 2) [10,13]. A clinical scenario-based approach that expands upon the AACT indications is discussed above. (See 'Approach based on clinical scenario' above.)

In a patient with an ethanol co-ingestion and a serum ethanol concentration >100 mg/dL, we delay starting ADH inhibitor therapy until the measured or estimated serum ethanol concentration is ≤100 mg/dL. The rate of ethanol clearance is discussed elsewhere. (See "Ethanol intoxication in adults", section on 'Mild ethanol intoxication and ethanol clearance'.)

Fomepizole – The loading dose of fomepizole is 15 mg/kg intravenously (IV), followed by 10 mg/kg every 12 hours, with adjustments for hemodialysis or after more than two days of therapy. (See 'Extracorporeal removal (hemodialysis)' below.)

Fomepizole is an effective ADH competitive inhibitor and antidote for methanol and ethylene glycol poisoning. It is easy to dose and administer, and clinically significant adverse effects are rare [9,15-19,21-23]. Its main disadvantage is cost. However, the cost of fomepizole compares favorably with the total cost of managing patients treated with ethanol, including need for titration, frequent monitoring, intensive care unit admission, and possibly hemodialysis in selected cases [20,24,25].

There is no benefit to adding ethanol therapy to fomepizole in a patient poisoned with methanol or ethylene glycol.

Ethanol — Historically, ethanol has been administered as a competitive inhibitor of ADH since ADH has greater affinity for ethanol than for methanol or ethylene glycol. Although effective, IV ethanol treatment creates several problems [26,27]:

Ethanol is difficult to dose, and appropriate concentrations are difficult to maintain; as a result, frequent testing and infusion adjustments are often required.

Ethanol requires compounding by the hospital pharmacy, irritates veins when infused, and can complicate fluid balance in oliguric patients.

The sedative and behavioral effects of ethanol (eg, obtundation) increase the risk of aspiration and other complications (eg, agitation, hypotension) [22].

Ethanol therapy may pose risks in certain patients (eg, upper gastrointestinal bleeding, first trimester pregnancy).

In the rare circumstance in which ethanol therapy must be used, many sources cite an absolute ethanol concentration of 100 mg/dL (22 mmol/L) as the therapeutic target. However, the target ethanol concentration should be based on the estimated concentration of methanol or ethylene glycol since ADH inhibition is competitive. The appropriate target for antidotal therapy with ethanol is a concentration of at least one-fourth to one-third the serum methanol or ethylene glycol concentration expressed as mg/dL rather than a single, arbitrary concentration of 100 mg/dL. As an example, a modest ethanol concentration of 20 mg/dL will effectively inhibit the metabolism of 60 to 80 mg/dL of methanol or ethylene glycol. When ethanol is the only available ADH inhibitor, it is reasonable to reduce the dosing intensity given ethanol's antidotal potency.

Due to the risks associated with ethanol therapy, patients should be treated in a critical care setting in order to closely monitor mental and respiratory status. Whenever possible, ethanol should be administered by central venous catheter using an infusion pump to limit venous irritation.

Dosing of IV ethanol – We use a simplified approach to the loading and adjustment of IV ethanol, which aims to reduce confusion and the potential for dosing errors that can occur when making precise calculations for an antidote used infrequently and under time pressure. A table summarizing the dilution, dosing, and titration of IV ethanol is provided (table 6). An IV loading dose of 10 mL/kg of a 10% ethanol (volume/volume) solution in D5W (ie, 800 mg/kg of ethanol) will raise serum ethanol concentrations by about 100 mg/dL. The loading dose should be given over 60 minutes to avoid excessive side effects (eg, hypotension, respiratory depression, somnolence). When treating patients who have co-ingested ethanol, this loading dose can be scaled back in proportion to their current serum ethanol concentration. A maintenance infusion of the 10% ethanol solution, starting at 1 mL/kg per hour, is appropriate to maintain any current ethanol concentration, as metabolism is zero order.

Dosing of oral ethanol – If both fomepizole and pharmaceutical-grade IV ethanol are unavailable, ethanol can also be administered orally, both to load and to maintain serum ethanol concentrations as described above. Distilled spirits (40 to 50% volume/volume) intended for human consumption can be diluted to a 20% solution and administered orally or via nasogastric tube at one-half the volumes recommended above (ie, 5 mL/kg of a 20% solution to raise serum concentrations by 100 mg/dL, and 0.5 mL/kg per hour for the initial maintenance dose). Gastritis and vomiting, in addition to the other adverse effects of ethanol, are occasionally encountered when using the enteral route for antidotal ethanol therapy.

Ethanol concentrations should be measured every one to two hours initially, following any change in dose or infusion rate, during and after hemodialysis, and every two to four hours otherwise. The maintenance rate can be adjusted based on the serial ethanol concentrations. The rate should also be adjusted during hemodialysis. (See 'Extracorporeal removal (hemodialysis)' below.)

Duration of ADH inhibitor therapy — Once begun, ADH inhibition with fomepizole or ethanol should be continued until the blood pH is normal and one of the following criteria are met:

The diagnosis of methanol or ethylene glycol exposure has been excluded by more accurate or newly obtained history (eg, definitive identification of the product ingested).

The methanol or ethylene glycol serum concentrations are ≤20 mg/dL (SI units: methanol 6.2 mmol/L and ethylene glycol 3.2 mmol/L). In a patient with severe toxicity, most experts recommend treating until the methanol or ethylene glycol concentrations are below the assay’s limit of quantification (ie, “negative”).

If the confirmatory concentrations cannot be obtained, then we repeat serum electrolytes, venous blood gas, ethanol (until undetectable), and osmolality every two hours until the osmolal gap ≤10 mOsm/kg  and the estimated methanol or ethylene glycol concentrations are <20 mg/dL. We stop the ADH inhibitor as long as metabolic acidosis or signs of end-organ toxicity do not develop.

Sodium bicarbonate — We initially administer 1 to 2 meq/kg of sodium bicarbonate via IV bolus. A maintenance infusion is then prepared by mixing approximately 133 meq of sodium bicarbonate in 1 liter (L) of D5W. Infusion rates may range from 150 to 250 mL/hour in adults or one to two times the maintenance fluid rate in children. The appropriate rate depends upon the initial pH and parameters such as fluid status and serum sodium concentration. The goal is to maintain an arterial or venous pH >7.35. The infusion can be discontinued when the pH has normalized and no further acid production is expected.

Bicarbonate therapy shifts the equilibrium towards deprotonation of acid metabolites, which are less likely to penetrate end-organ tissues and more likely to be excreted in the urine [10,13]. Methanol is metabolized to formate and ethylene glycol to glycolate, glyoxylate, and oxalate. Acidemia leads to protonation of these species to uncharged molecules (eg, formic acid), making them more likely to penetrate end-organ tissues (such as the retina) and more likely to be reabsorbed across the renal epithelium from the urine. Thus, patients with methanol or ethylene glycol poisoning fare worse when systemic acidemia is present [9,28]. However, despite this clear rationale, no clear evidence exists to determine how bicarbonate should be given.

Extracorporeal removal (hemodialysis) — Hemodialysis is fundamental in treating severely poisoned patients and is the best method to rapidly remove both toxic acid metabolites and the parent alcohol [2,10,13,29]. Hemodialysis also corrects the acidemia, if present. An arterial or venous blood gas helps triage the urgency and likelihood that hemodialysis will be required. We consult a nephrologist immediately if a patient is suspected to have a toxic alcohol ingestion and has evidence of end-organ dysfunction or acidemia, especially if transfer to a hemodialysis center may be necessary. Consultation should not be delayed until confirmatory methanol or ethylene glycol concentrations have resulted.  

The hemodialysis prescription should include a large surface area dialyzer (>1.5 m²), a blood flow rate in excess of 300 mL/min, and a bicarbonate bath. (See "Acute hemodialysis prescription".)

Peritoneal dialysis, hemoperfusion, and plasma exchange are not recommended since they are inefficient at clearing toxic alcohols and their metabolites [2,3]. When intermittent, high-efficiency hemodialysis is unavailable or impractical, continuous kidney replacement techniques (or hybrid techniques such as sustained low-efficiency hemodialysis) permit a modest amount of toxin clearance and are preferable to no renal replacement therapy [2].

In a patient without metabolic acidosis or end-organ toxicity, hemodialysis can be used to remove the parent unmetabolized alcohol and abbreviate the course of antidotal therapy. (See 'Patient without metabolic acidosis and no end-organ toxicity' above.)

Adjusting ADH inhibitors during hemodialysis — The frequency of fomepizole dosing should be increased to every four hours during hemodialysis. An additional dose should be given at the beginning of hemodialysis if six or more hours have elapsed since the prior dose. Fomepizole is removed by hemodialysis, thus warranting these adjustments.

If ethanol is used for ADH inhibition, adjustments in the dose must be made during hemodialysis. A fall in ethanol concentrations can be avoided or ameliorated by increasing the rate of ethanol infusion by about 50 percent during hemodialysis or possibly by adding ethanol directly to the dialysate [30,31]. In one such case, a dialysate ethanol concentration of 100 mg/dL was achieved by adding a 95% ethanol solution into the dialysate inlet tubing at a rate of 40 mL/h via an infusion pump. The dialysate flow rate was maintained at 500 mL/min, and the dialyzer blood flow averaged 280 mL/min. An average plasma ethanol concentration of 90 mg/dL was maintained during the six-hour hemodialysis session.

Duration of hemodialysis — Hemodialysis should continue until the blood pH is normal and parent alcohol concentrations (confirmed or estimated (table 4)) are ≤20 mg/dL (methanol 6.2 mmol/L; ethylene glycol 3.2 mmol/L), similar to the duration of ADH inhibitor therapy [2]. (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' above.)

It is often impractical to obtain frequent parent toxic alcohol concentrations. The long turnaround time to obtain results may cause unnecessarily prolonged hemodialysis sessions when targeting a confirmed (ie, resulted) concentration <20 mg/dL.

The duration of hemodialysis can be better estimated using the following formula [32-34]:

                                      -V ln (5/A)
    Duration (hours)  =   ─────────  
                                         0.06 k

              Units: V in L, A in mmol/L, and k in mL/min

V is total body water from the Watson formula, ln is the natural logarithm function, A is the initial alcohol concentration, k is 80 percent of the dialyzer urea clearance at the observed blood flow rate, and the term 0.06 converts units from mL to L and minutes to hours. The estimated total duration of hemodialysis based on this formula for an individual of average size, using either the toxic alcohol concentration or the increase in osmolal gap, is provided in the table (table 7). This formula provides only an estimate, and the efficacy of hemodialysis can decrease after several hours. The patient's clinical condition will also affect the duration of hemodialysis; when possible, we prefer to eliminate nearly all of the parent alcohol in patients who have substantial end-organ toxicity.

The term "ln (5/A)" in the formula targets a final concentration of 5 mmol/L provided A is also expressed in mmol/L. To target 20 mg/dL instead, use the term "ln (20/A)" with A expressed in mg/dL. The Watson formula for V (total body water) is discussed in detail separately. (See "Incorporating residual kidney function into the dosing of intermittent hemodialysis", section on 'The prescription of incremental hemodialysis'.)

We generally remeasure the blood gas, osmolal gap, and serum alcohol concentration near the end of the estimated hemodialysis duration and again two hours post-hemodialysis to ascertain the adequacy of treatment [3]. The duration estimate (using the above formula or table) should be updated during hemodialysis based on the most recent confirmed or estimated concentration as new measurements become available during the hemodialysis session.

More than one hemodialysis session may be necessary in large overdoses since it may be impractical to perform one session of hemodialysis for the total estimated duration. The first session of hemodialysis should be long enough to correct any acidemia, and repeat sessions can be performed afterwards in discussion with the nephrologist.

Survivors of ethylene glycol poisoning who have sustained severe acute kidney injury may need renal replacement therapy for months, but renal function will often recover.

Cofactor therapy — We provide cofactor therapy as follows [10,35,36]:

In a methanol-poisoned patient, we administer either leucovorin 50 mg IV or folic acid 50 mg IV every six hours.

In an ethylene glycol-poisoned patient, we administer thiamine 100 mg IV and pyridoxine 100 mg IV daily.

If toxic alcohol poisoning is possible or suspected but the exact alcohol is unknown, especially in the presence of a metabolic acidosis, it is reasonable to empirically administer all three cofactors.

Cofactors may increase elimination of the toxic alcohol metabolites, especially for methanol. Cofactors may also benefit patients who are nutritionally deficient or have a starvation/alcoholic ketoacidosis.

PRETERMINAL CARE — Severely poisoned patients who present with coma and profound acidemia (pH <6.74) may not survive despite maximum intensive therapy [28,37,38]. In a patient with severe methanol poisoning, consideration should be given to organ harvesting prior to withdrawal of support. Formate is a highly specific neurotoxin, and case series support the viability of organs harvested from such patients [39,40]. (See "Evaluation of the potential deceased organ donor (adult)".)

However, adequate time should be provided prior to withdrawing support in a patient with coma and cerebral edema because recovery is possible despite a poor initial neurologic examination. Even though cerebral edema from ethylene glycol poisoning is often lethal, case reports exist of complete neurologic recovery [41,42]. Cerebral edema can cause seizures, encephalopathy, and coma and can be detected in the basal ganglia (putamen), thalamus, midbrain, and pons on computed tomography (CT) and magnetic resonance imaging (MRI).  

MULTIVICTIM OUTBREAKS

Methanol — Outbreaks with multiple methanol-poisoned victims are rare but continue to occur around the globe [28,38,43-46]. When the supply of "alcohol" (ie, ethanol) is contaminated, especially with methanol, a cluster of victims can easily overwhelm available critical care and hemodialysis resources. The timing and severity of presentation and geographic range of victims will depend on the nature, distribution, and consumption of the contaminated product.

A 2019 consensus statement from an international panel of clinical toxicologists recommends that as few as three cases within 72 hours appearing in the same city or town should be considered a methanol-poisoning outbreak, triggering active case-finding by public health and government authorities [38]. Triage elements should include level of consciousness, visual disturbances, and blood gas testing, if possible. An arterial or venous blood gas is an important triage tool, especially with limited hemodialysis capability [26,47]. Antidotal and extracorporeal therapies should be allocated according to the severity of illness. The combination of coma at presentation with a pH <6.74 is strongly associated with death or severe neurologic sequelae in almost all cases [37,38]. On the other hand, a pH >7.2 at the time of initial treatment is rarely associated with subsequent deterioration [48].

We concur with the consensus statement and recommend a "use what you have" approach to antidotal therapy in such outbreaks [38]. We prefer fomepizole when both fomepizole and ethanol are available. When there is insufficient fomepizole to treat all victims, we suggest using fomepizole preferentially for patients who are more seriously ill, pregnant, or younger than 14 years of age. Prehospital distribution of ethanol to suspected victims has been used successfully in Estonia [45].

By increasing the fomepizole dosing interval, partitioning the loading dose, and avoiding doses during hemodialysis, a greater number of victims can be treated and additional time obtained to prioritize hemodialysis and to confirm the diagnosis. The effective duration of alcohol dehydrogenase (ADH) inhibition after the initial 15 mg/kg loading dose of fomepizole likely lasts longer than 24 hours in the absence of hemodialysis [49]. Also, fomepizole can be administered orally when obtaining intravenous (IV) access is delayed or impossible since it has excellent oral bioavailability [49,50]. The expert panel did not reach consensus on the difficult issue of allocating scarce fomepizole during such disasters; thus, ultimately, individual circumstances need to be considered.

While many factors will determine the optimal approach, experience suggests that mobilizing and transferring resources to increase the critical care, antidotal, and hemodialysis capacity in a health care facility overwhelmed with multiple sick patients is usually preferable to the interfacility transport of critically ill patients [38]. Mildly poisoned patients (ie, alert, lack of visual symptoms, higher pH) are more suitable candidates for redistribution to other health care facilities during an outbreak. Consultation with medical toxicologists with specific expertise in methanol poisoning will be particularly important in guiding management decisions during these rare events. (See 'Additional resources' below.)

Diethylene glycol — Diethylene glycol (DEG; ethylene diglycol) is similar in some respects to ethylene glycol, with similar toxicity but also with unique aspects. Given their similar names, DEG is often confused for ethylene glycol. Other glycols (eg, propylene glycol, ethylene glycol monobutyl ether, ethylene glycol monomethyl ether, polyethylene glycol, etc) can also be confused for ethylene glycol, highlighting the need for exact product identification when possible and consultation with a medical toxicologist if dealing with such compounds.

DEG has caused numerous and tragic outbreaks of acute kidney failure and death following substitution for propylene glycol (a common pharmaceutical solvent) in medications such as cough syrup or liquid acetaminophen formulations [51,52]. Outbreaks continue to occur and are associated with a high mortality rate [53,54]. DEG is a viscous, colorless, sweet-tasting liquid and less expensive than pharmaceutical-grade propylene glycol or glycerine (other common pharmaceutical solvents). DEG is also found in antifreeze, brake fluids, cosmetics, lubricants, wallpaper strippers, artificial fog solutions, ink, heating and cooking fuel, adhesives, plasticizers, and other sources. The toxic dose is approximately 0.1 mg/kg following acute ingestion.

Clinical manifestations of DEG poisoning include nausea, vomiting, abdominal pain, diarrhea, acute liver injury, and inebriation followed many hours later by an elevated anion gap metabolic acidosis and acute kidney injury [53]. Nephrotoxicity, the hallmark manifestation, starts with progressive oliguria followed by anuria and death within two to seven days if untreated. Patients who survive often do not recover complete kidney function and may remain dialysis dependent. Survivors can also develop delayed neurologic toxicity several days after exposure, notably cranial neuropathies (specifically bilateral facial paralysis), peripheral neuropathy (primarily axonal), dysphonia, dilated and unreactive pupils, quadriparesis, seizures, and coma.

Similar to methanol and ethylene glycol, DEG is metabolized by alcohol dehydrogenase followed by aldehyde dehydrogenase [53]. The precise mechanism of toxicity is unknown, but the metabolite diglycolic acid is believed to be the primary nephrotoxin and neurotoxin [55]. Even though DEG consists of two ethylene glycol molecules, the connecting ether bond is very stable, and human metabolism does not produce ethylene glycol, glycolate, or oxalate. Similar to poisoning with methanol and ethylene glycol, the osmolal gap can be used to estimate the DEG serum concentration in a patient who presents early after ingestion (table 4), and the degree of acidemia helps confirm the accumulation of acid metabolites. In a patient with a DEG ingestion and elevated osmolal gap, we recommend ADH inhibition with fomepizole (or ethanol if fomepizole is not available) followed by hemodialysis if metabolic acidosis or kidney failure is present. Evidence is limited to case reports and animal models [55-58].  

PEDIATRIC CONSIDERATIONS

Younger children — A child who may have swallowed one or two mouthfuls of a concentrated methanol or ethylene glycol solution should be referred to an emergency department and not managed at home [59].

Most children with unintentional exposure present for evaluation shortly after ingestion and do not initially manifest significant metabolic acidosis or evidence of end-organ dysfunction. Ideally, measurement of the serum concentration of the specific alcohol would quantify the absorbed dose and predict the clinical course. Unfortunately, results of such concentrations are unlikely to be available within a few hours of the ingestion. Also, the plasma osmolal gap is not sufficiently sensitive to exclude a small ingestion, and absence of urinary oxalate crystals does not definitely rule out ethylene glycol ingestion. Thus, children pose a diagnostic and therapeutic dilemma. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Pitfalls in laboratory testing'.)

We follow the approach for accidental small-volume ingestion discussed above (see 'Accidental small-volume ingestion' above), provided that all of the following criteria are satisfied and that toxic alcohol concentrations are not immediately available:

The ingestion was unintentional and of small volume

The product is accurately identified

The patient is asymptomatic

The patient has a normal pH and normal anion gap

There is no co-ingestion or treatment with ethanol or fomepizole

The co-ingestion of ethanol or treatment with either ethanol or fomepizole invalidates this approach as it relies on close observation and frequent, serial laboratory testing to exclude progression to metabolic acidosis over several hours.

In a pediatric patient who develops manifestations of methanol or ethylene glycol poisoning, or who does not meet all of the criteria listed above, the approach to diagnosis and treatment is the same as an adult patient. Fomepizole is safe and effective in children using the same dosing protocol as presented above [60]. (See 'Strongly suspected poisoning' above.)

In all cases, parents, patients, and/or caregivers should be counseled about safe storage of household products and pharmaceuticals prior to discharge. (See "Prevention of poisoning in children".)

Occasionally, infants with inherited metabolic disorders such as methylmalonic acidemia present with features that resemble ethylene glycol poisoning, and vice versa [61,62]. The clinician should obtain organic acid testing in an infant presenting with unexplained metabolic acidosis. (See "Organic acidemias: An overview and specific defects".)

Adolescents — Whenever treating an adolescent for a possible toxic alcohol ingestion, the possibility of multiple victims should be entertained. Groups of adolescents may consume toxic alcohols inadvertently when intending to drink ethanol. If the ingestion is likely to have been a recreational misadventure, establish whether other individuals may be affected. Other high-risk groups for multivictim inadvertent poisonings include prisoners and residents of areas where ethanol is not readily available.

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Toxic alcohol poisoning".)

SUMMARY AND RECOMMENDATIONS

Overview of management – Methanol and ethylene glycol poisonings are potentially fatal. Rapid recognition and early treatment are crucial. The clinician must often make treatment decisions without definitive serum drug concentrations, based only upon clinical suspicion and readily available laboratory data. Algorithms for confirmed poisoning (ie, known toxic alcohol concentration), strongly suspected poisoning, possible poisoning (ie, metabolic acidosis without clear cause), and a summary table (table 1) to facilitate emergency management are provided. (See 'Overview of management' above.)

We encourage consultation with a medical toxicologist or a regional poison center for all suspected exposures and for cases in which fomepizole, ethanol, or hemodialysis therapy may be used. A nephrologist should be immediately consulted for an acidotic patient in whom the diagnosis appears likely. (See 'Regional poison control centers' above.)

Supportive care – Address the patient's airway, breathing, and circulation ("ABCs") and provide appropriate supportive care as needed. If mechanical ventilation is required, large minute ventilation may be needed to prevent profound acidemia (eg, pH <7.1) in patients with severe poisoning. (See 'Overview of management' above.)

Gastrointestinal decontamination – In a patient known to have ingested a large amount of methanol or ethylene glycol who presents within 60 minutes of the ingestion, we recommend gastric aspiration via flexible nasogastric tubing (Grade 1C). Otherwise, activated charcoal, gastric lavage, and syrup of ipecac have no routine role in the management of toxic alcohol exposures. (See 'Overview of management' above and 'Initial management' above.)

Alcohol dehydrogenase (ADH) inhibition – In a patient with strong suspicion or confirmed ethylene glycol or methanol poisoning, we recommend administering fomepizole (Grade 1B). Fomepizole is an ADH inhibitor and prevents bioactivation of the parent alcohol to its toxic acid metabolites. (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' above.)

Criteria for strong suspicion or confirmed poisoning include those in the table (table 2) and the algorithms. (See 'Strongly suspected poisoning' above.)

The loading dose of fomepizole is 15 mg/kg intravenously (IV), followed by 10 mg/kg every 12 hours, with adjustments for hemodialysis and after more than two days of therapy.

In a patient who requires ADH inhibition but fomepizole is unavailable, we recommend treatment with ethanol (Grade 1B). (See 'Alcohol dehydrogenase inhibition (fomepizole or ethanol)' above.)

Sodium bicarbonate infusion – In a patient with a blood pH <7.25 and a strong suspicion or confirmed ethylene glycol or methanol poisoning, we recommend treatment with sodium bicarbonate (Grade 1C). We begin treatment with 1 to 2 meq/kg of sodium bicarbonate via IV bolus followed by an infusion. (See 'Sodium bicarbonate' above.)

Cofactor therapy – In a patient with metabolic acidosis or end-organ toxicity from methanol poisoning, we suggest administering leucovorin 50 mg IV or folic acid 50 mg IV every six hours (Grade 2C). In a patient with metabolic acidosis or end-organ toxicity from ethylene glycol poisoning, we suggest administering thiamine 100 mg IV and pyridoxine 100 mg IV daily (Grade 2C). (See 'Cofactor therapy' above.)

Hemodialysis – In a patient with any of the following, we recommend hemodialysis (Grade 1B) (see 'Known toxic alcohol serum concentration' above and 'Strongly suspected poisoning' above):

Serum methanol concentration greater >50 mg/dL (SI equivalent 15.6 mmol/L)

Serum ethylene glycol concentration >50 mg/dL (SI equivalent 8.1 mmol/L) and presence of metabolic acidosis

Confirmed or strong suspicion for methanol or ethylene glycol ingestion and any of the following:

-Elevated moderate-severe anion gap metabolic acidosis (eg, pH <7.25, anion gap >24), regardless of toxic alcohol concentration

-Evidence of end-organ damage (eg, visual changes, afferent pupillary defect, acute kidney injury, large amount of urinary oxylate crystals, cerebral edema)

-Prolonged ADH inhibitor therapy is impractical (eg, administering ethanol because fomepizole is unavailable)

-Strong suspicion for large methanol ingestion

Unexplained moderate-severe anion gap metabolic acidosis (eg, pH <7.25, anion gap >24) and significant osmolal gap elevation (≥25 mOsm/kg), even in the absence of history of ingestion

Hemodialysis rapidly removes both toxic acid metabolites and the parent alcohols and corrects the acidemia, if present. (See 'Extracorporeal removal (hemodialysis)' above.)

Hemodialysis may not be necessary in a patient with elevated ethylene glycol concentration, provided their blood pH is near normal, their kidney function is normal, and fomepizole is given. (See 'Patient without metabolic acidosis and no end-organ toxicity' above.)

Accidental small-volume ingestion (eg, young child) – An asymptomatic patient (young child or adult) suspected of accidentally swallowing a small volume of methanol or ethylene glycol with a normal blood pH, anion gap, and osmolal gap can be monitored without the administration of fomepizole or ethanol with serial blood gases and electrolytes to ensure no developing metabolic acidosis. (See 'Pediatric considerations' above and 'Accidental small-volume ingestion' above.)

Diethylene glycol – This glycol is often confused for ethylene glycol. Its toxicity includes an elevated anion gap metabolic acidosis, acute kidney injury, and neurotoxicity (eg, cranial neuropathies, peripheral neuropathy, dysphonia, quadriparesis, seizures, and coma). In a patient with a diethylene glycol ingestion and elevated osmolal gap, we recommend ADH inhibition with fomepizole (or ethanol if fomepizole is not available) (Grade 1C). Hemodialysis may also be required if metabolic acidosis or kidney failure are also present. (See 'Diethylene glycol' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges James Winchester, MD, who contributed to an earlier version of this topic review.

  1. Wallace EA, Green AS. Methanol toxicity secondary to inhalant abuse in adult men. Clin Toxicol (Phila) 2009; 47:239.
  2. Ghannoum M, Gosselin S, Hoffman RS, et al. Extracorporeal treatment for ethylene glycol poisoning: systematic review and recommendations from the EXTRIP workgroup. Crit Care 2023; 27:56.
  3. Roberts DM, Yates C, Megarbane B, et al. Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement. Crit Care Med 2015; 43:461.
  4. Kostic MA, Dart RC. Rethinking the toxic methanol level. J Toxicol Clin Toxicol 2003; 41:793.
  5. Beaulieu J, Roberts DM, Gosselin S, et al. Treating ethylene glycol poisoning with alcohol dehydrogenase inhibition, but without extracorporeal treatments: a systematic review. Clin Toxicol (Phila) 2022; 60:784.
  6. Roberts DM, Hoffman RS, Brent J, et al. The serum glycolate concentration: its prognostic value and its correlation to surrogate markers in ethylene glycol exposures. Clin Toxicol (Phila) 2022; 60:798.
  7. Porter WH, Rutter PW, Bush BA, et al. Ethylene glycol toxicity: the role of serum glycolic acid in hemodialysis. J Toxicol Clin Toxicol 2001; 39:607.
  8. De Leacy EA, Moxon LN, Ellis VM, et al. A report of accidental ethylene glycol ingestion in 2 siblings. Pathology 1995; 27:273.
  9. McMartin K, Jacobsen D, Hovda KE. Antidotes for poisoning by alcohols that form toxic metabolites. Br J Clin Pharmacol 2016; 81:505.
  10. Barceloux DG, Bond GR, Krenzelok EP, et al. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol 2002; 40:415.
  11. Burns MJ, Graudins A, Aaron CK, et al. Treatment of methanol poisoning with intravenous 4-methylpyrazole. Ann Emerg Med 1997; 30:829.
  12. Bekka R, Borron SW, Astier A, et al. Treatment of methanol and isopropanol poisoning with intravenous fomepizole. J Toxicol Clin Toxicol 2001; 39:59.
  13. Barceloux DG, Krenzelok EP, Olson K, Watson W. American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee. J Toxicol Clin Toxicol 1999; 37:537.
  14. Levine M, Curry SC, Ruha AM, et al. Ethylene glycol elimination kinetics and outcomes in patients managed without hemodialysis. Ann Emerg Med 2012; 59:527.
  15. Baud FJ, Galliot M, Astier A, et al. Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. N Engl J Med 1988; 319:97.
  16. Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med 1999; 340:832.
  17. Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of methanol poisoning. N Engl J Med 2001; 344:424.
  18. Shannon M. Toxicology reviews: fomepizole--a new antidote. Pediatr Emerg Care 1998; 14:170.
  19. Battistella M. Fomepizole as an antidote for ethylene glycol poisoning. Ann Pharmacother 2002; 36:1085.
  20. Sivilotti ML. Ethanol: tastes great! Fomepizole: less filling! Ann Emerg Med 2009; 53:451.
  21. Dart RC, Borron SW, Caravati EM, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med 2009; 54:386.
  22. Lepik KJ, Levy AR, Sobolev BG, et al. Adverse drug events associated with the antidotes for methanol and ethylene glycol poisoning: a comparison of ethanol and fomepizole. Ann Emerg Med 2009; 53:439.
  23. Rasamison R, Besson H, Berleur MP, et al. Analysis of fomepizole safety based on a 16-year post-marketing experience in France. Clin Toxicol (Phila) 2020; 58:742.
  24. Sivilotti ML, Burns MJ, McMartin KE, Brent J. Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. For the Methylpyrazole for Toxic Alcohols Study Group. Ann Emerg Med 2000; 36:114.
  25. Boyer EW, Mejia M, Woolf A, Shannon M. Severe ethylene glycol ingestion treated without hemodialysis. Pediatrics 2001; 107:172.
  26. Paasma R, Hovda KE, Tikkerberi A, Jacobsen D. Methanol mass poisoning in Estonia: outbreak in 154 patients. Clin Toxicol (Phila) 2007; 45:152.
  27. Zakharov S, Pelclova D, Navratil T, et al. Fomepizole versus ethanol in the treatment of acute methanol poisoning: Comparison of clinical effectiveness in a mass poisoning outbreak. Clin Toxicol (Phila) 2015; 53:797.
  28. Paasma R, Hovda KE, Hassanian-Moghaddam H, et al. Risk factors related to poor outcome after methanol poisoning and the relation between outcome and antidotes--a multicenter study. Clin Toxicol (Phila) 2012; 50:823.
  29. Ghannoum M, Lavergne V, Gosselin S, et al. Practice Trends in the Use of Extracorporeal Treatments for Poisoning in Four Countries. Semin Dial 2016; 29:71.
  30. Chow MT, Di Silvestro VA, Yung CY, et al. Treatment of acute methanol intoxication with hemodialysis using an ethanol-enriched, bicarbonate-based dialysate. Am J Kidney Dis 1997; 30:568.
  31. Dorval M, Pichette V, Cardinal J, et al. The use of an ethanol- and phosphate-enriched dialysate to maintain stable serum ethanol levels during haemodialysis for methanol intoxication. Nephrol Dial Transplant 1999; 14:1774.
  32. Youssef GM, Hirsch DJ. Validation of a method to predict required dialysis time for cases of methanol and ethylene glycol poisoning. Am J Kidney Dis 2005; 46:509.
  33. McMurray M, Carty D, Toffelmire EB. Predicting methanol clearance during hemodialysis when direct measurement is not available. CANNT J 2002; 12:29.
  34. Burns AB, Bailie GR, Eisele G, et al. Use of pharmacokinetics to determine the duration of dialysis in management of methanol poisoning. Am J Emerg Med 1998; 16:538.
  35. Ghosh A, Boyd R. Leucovorin (calcium folinate) in "antifreeze" poisoning. Emerg Med J 2003; 20:466.
  36. McMartin KE, Martin-Amat G, Makar AB, Tephly TR. Methanol poisoning. V. Role of formate metabolism in the monkey. J Pharmacol Exp Ther 1977; 201:564.
  37. Coulter CV, Farquhar SE, McSherry CM, et al. Methanol and ethylene glycol acute poisonings - predictors of mortality. Clin Toxicol (Phila) 2011; 49:900.
  38. Hassanian-Moghaddam H, Zamani N, Roberts DM, et al. Consensus statements on the approach to patients in a methanol poisoning outbreak. Clin Toxicol (Phila) 2019; 57:1129.
  39. Hantson P, Vanormelingen P, Lecomte C, et al. Fatal methanol poisoning and organ donation: experience with seven cases in a single center. Transplant Proc 2000; 32:491.
  40. López-Navidad A, Caballero F, González-Segura C, et al. Short- and long-term success of organs transplanted from acute methanol poisoned donors. Clin Transplant 2002; 16:151.
  41. Owen EB, Calhoun AW, McDonald MJ. Reversibility of Severe Cerebral Magnetic Resonance Imaging Changes Associated with Ethylene Glycol Toxicity. J Pediatr Intensive Care 2017; 6:214.
  42. Morgan BW, Ford MD, Follmer R. Ethylene glycol ingestion resulting in brainstem and midbrain dysfunction. J Toxicol Clin Toxicol 2000; 38:445.
  43. Rostrup M, Edwards JK, Abukalish M, et al. Correction: The Methanol Poisoning Outbreaks in Libya 2013 and Kenya 2014. PLoS One 2016; 11:e0157256.
  44. Hassanian-Moghaddam H, Nikfarjam A, Mirafzal A, et al. Methanol mass poisoning in Iran: role of case finding in outbreak management. J Public Health (Oxf) 2015; 37:354.
  45. Zakharov S, Pelclova D, Urban P, et al. Use of Out-of-Hospital Ethanol Administration to Improve Outcome in Mass Methanol Outbreaks. Ann Emerg Med 2016; 68:52.
  46. Zakharov S, Rulisek J, Hlusicka J, et al. The impact of co-morbidities on a 6-year survival after methanol mass poisoning outbreak: possible role of metabolic formaldehyde. Clin Toxicol (Phila) 2020; 58:241.
  47. Naraqi S, Dethlefs RF, Slobodniuk RA, Sairere JS. An outbreak of acute methyl alcohol intoxication. Aust N Z J Med 1979; 9:65.
  48. Desai T, Sudhalkar A, Vyas U, Khamar B. Methanol poisoning: predictors of visual outcomes. JAMA Ophthalmol 2013; 131:358.
  49. Marraffa J, Forrest A, Grant W, et al. Oral administration of fomepizole produces similar blood levels as identical intravenous dose. Clin Toxicol (Phila) 2008; 46:181.
  50. Mégarbane B, Houzé P, Baud FJ. Oral fomepizole administration to treat ethylene glycol and methanol poisonings: advantages and limitations. Clin Toxicol (Phila) 2008; 46:1097; author reply 1097.
  51. Centers for Disease Control and Prevention (CDC). Fatal poisoning among young children from diethylene glycol-contaminated acetaminophen - Nigeria, 2008-2009. MMWR Morb Mortal Wkly Rep 2009; 58:1345.
  52. Schier JG, Rubin CS, Miller D, et al. Medication-associated diethylene glycol mass poisoning: a review and discussion on the origin of contamination. J Public Health Policy 2009; 30:127.
  53. Schep LJ, Slaughter RJ, Temple WA, Beasley DM. Diethylene glycol poisoning. Clin Toxicol (Phila) 2009; 47:525.
  54. Bastani P, Jammeh A, Lamar F, et al. Acute Kidney Injury Among Children Likely Associated with Diethylene Glycol-Contaminated Medications - The Gambia, June-September 2022. MMWR Morb Mortal Wkly Rep 2023; 72:217.
  55. Brent J. Lessons learned from yet another episode of diethylene glycol poisoning: it happened before and it happened again. JAMA Intern Med 2014; 174:918.
  56. Seltzer JA, Corbett B, Lasoff DR, Clark RF. Symptomatic Diethylene Glycol Ingestion Successfully Treated with Fomepizole Monotherapy. J Emerg Med 2022; 63:58.
  57. Brophy PD, Tenenbein M, Gardner J, et al. Childhood diethylene glycol poisoning treated with alcohol dehydrogenase inhibitor fomepizole and hemodialysis. Am J Kidney Dis 2000; 35:958.
  58. Besenhofer LM, McLaren MC, Latimer B, et al. Role of tissue metabolite accumulation in the renal toxicity of diethylene glycol. Toxicol Sci 2011; 123:374.
  59. Caravati EM, Erdman AR, Christianson G, et al. Ethylene glycol exposure: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 2005; 43:327.
  60. Brent J. Fomepizole for the treatment of pediatric ethylene and diethylene glycol, butoxyethanol, and methanol poisonings. Clin Toxicol (Phila) 2010; 48:401.
  61. Woolf AD, Wynshaw-Boris A, Rinaldo P, Levy HL. Intentional infantile ethylene glycol poisoning presenting as an inherited metabolic disorder. J Pediatr 1992; 120:421.
  62. Shoemaker JD, Lynch RE, Hoffmann JW, Sly WS. Misidentification of propionic acid as ethylene glycol in a patient with methylmalonic acidemia. J Pediatr 1992; 120:417.
Topic 126052 Version 13.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟