Toxic Alcohol Ingestions: Clinical Features, Diagnosis, and Management : Clinical Journal of the American Society of Nephrology

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Toxic Alcohol Ingestions

Clinical Features, Diagnosis, and Management

Kraut, Jeffrey A.; Kurtz, Ira

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Clinical Journal of the American Society of Nephrology 3(1):p 208-225, January 2008. | DOI: 10.2215/CJN.03220807
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Lactic acidosis and diabetic ketoacidosis (DKA) are the most common causes of acute metabolic acidosis (1,2). Much less frequent but of great importance clinically are the alcohol intoxications shown in Table 1. Methanol, ethylene glycol, diethylene glycol, and propylene glycol intoxication and alcoholic ketoacidosis can produce hyperosmolality and metabolic acidosis (39). Isopropanol intoxication is usually associated with hyperosmolality alone (4,5). Importantly, several of these disorders can be fatal or produce irreversible tissue damage if they are not quickly recognized and treated appropriately (415).

Effect of Alcohols on Serum Osmolality and the Osmolal Gap

The normal serum osmolality of 285 to 290 mOsm/L is due to sodium and its counterbalancing ions, bicarbonate and chloride, and glucose and urea. It can be calculated using the following equation:

The serum osmolality measured by freezing point depression is usually within 10 mOsm/L of the calculated serum osmolality (16). Accumulation of low molecular weight substances in the serum (such as each of the alcohols) will raise the measured serum osmolality above that of the calculated serum osmolality, producing an osmolal gap (4,5,1618). The effect of each of the alcohols on serum osmolality is shown in Table 2. Methanol gives rise to the greatest increment in serum osmolality, followed by ethanol, isopropanol, ethylene glycol, propylene glycol, and diethylene glycol in that order (4,5,12,13,16,1826).

An osmolal gap can also be found in some other disorders that might be considered in the differential diagnosis of alcohol-related intoxications, such as ketoacidosis, lactic acidosis, and renal failure and in critically ill patients with hyponatremia, but this osmolal gap is ≤15 to 20 mOsm/L (21,22,27). Thus, an osmolal gap >20 mOsm/L indicates accumulation in the blood of one of the alcohols; however, the absence of an osmolal gap does not exclude an alcohol-related intoxication, because alcohol concentrations that are sufficient to produce clinical and laboratory abnormalities might not raise serum osmolality appreciably (12,13,2325). A marked discrepancy between the serum osmolal gap and the severity of the clinical effects of these alcohols is not uncommon (68,2325,28).

Absorption, Distribution, Metabolism, and Elimination from the Body

Methanol, isopropanol, and propylene glycol are absorbed through normal skin (12,13,2932), whereas ethylene glycol and diethylene glycol are absorbed in significant amounts only after the integrity of the skin is breached (33). Inhalation of methanol or topical absorption of ethylene glycol, propylene glycol, isopropanol, and diethylene glycol can produce in-toxications (12,13,3034), but most intoxications occur after their oral ingestion or, in the case of propylene glycol (4,5,12,13,35,36), after intravenous administration.

The volume of distribution, half-life, and route of elimination of the alcohols after oral ingestion are summarized in Table 3. Methanol, ethylene glycol, diethylene glycol, propylene glycol, ethanol, and isopropanol are rapidly absorbed from the gastrointestinal tract (4,5,12,13,37). Once absorbed, they have a volume of distribution similar to that of body water with peak blood concentrations occurring within 30 to 60 min (12,13,37). Subsequently, they are metabolized in the liver or excreted primarily by the kidney. Figures 1 and 2 summarize the metabolic pathway of each of the alcohols.

Oxidation of the alcohols is first catalyzed by the liver enzyme alcohol dehydrogenase (ADH), this process being a critical step in their biotransformation (12,13,17,3740): Methanol is metabolized to formaldehyde (6,12), ethylene glycol to glycoaldehyde (6,13), propylene glycol (present as DL isomers) to lactaldehyde (41), isopropanol to acetone (4), and ethanol to acetaldehyde (39). Formaldehyde is then metabolized via the enzyme formaldehyde dehydrogenase to formic acid, formate then being metabolized to CO2 and H2O, a process that depends on liver tetrahydrofolate concentrations (12,15). This pathway is easily saturable, contributing to accumulation of formic acid in the blood.

Glycoaldehyde is converted to glycolic acid via aldehyde dehydrogenase (ALDH) and then to glyoxylic acid and oxalic acid (13,42,43). Glycolic acid can also be metabolized to α-hydroxy-β-ketoadipate or glycine (13). Lactaldehyde is metabolized to l-lactic acid by ALDH or, alternatively, to methylglyoxal (41), but d-lactate can also be formed. l-Lactate enters the gluconeogenic pathways; d-Lactate is metabolized to pyruvate and CO2. Acetone is usually eliminated via the kidneys unchanged. Acetaldehyde is metabolized by ALDH to acetic acid, and the acetic acid is converted to acetyl CoA, which can enter the citric acid cycle. Diethylene glycol was postulated to be metabolized to glycolic acid and oxalate acid, but subsequent studies have shown that it is oxidized by ADH to 2-hydroxyethoxyacetaldehyde and then via ALDH to 2-hydroxyethoxyacetic acid (HEAA) (11,4448); HEAA then is excreted by the kidneys. A certain proportion of each of the alcohols is excreted by the kidney: 50 to 70% of diethylene glycol, 25 to 45% of propylene glycol, 20% of ethylene glycol, 20% of isopropanol, 2 to 5% of ethanol, and 1 to 2% of methanol (12,13,37,47,4951). Two to 3% of methanol is excreted by the lungs (12,50).

General Principles of Treatment

Basic principles underlying treatment of methanol, ethylene glycol, and diethylene glycol intoxications are summarized in Table 4. Absorption from the gastrointestinal tract is rapid; therefore, gastric lavage, induced emesis, or use of activated charcoal must be initiated within 30 to 60 min of ingestion to be beneficial.

Administration of ethanol or fomepizole to attenuate the metabolism of the alcohols is an integral part of therapy. Although ethanol has never been approved by the Food and Drug Administration for this purpose, it has been used in the treatment of methanol and ethylene glycol intoxication for many years (6,12,13,52,53). Ethanol has 10 to 20 times greater affinity for ADH than the other alcohols; at a serum concentration of 100 mg/dl, it completely inhibits ADH (54). It is cleared by dialysis; therefore, the dosage has to be increased when patients undergo dialysis.

Fomepizole (4-methylpyrazole) Antizol (Jazz Pharmaceuticals, Palo Alto, CA) has approximately 500 to 1000 times greater affinity for ADH than ethanol and can completely inhibit ADH at a much lower serum concentration (12,55). Although it is effective when given orally, it is available only as an intravenous preparation in the United States (12,56). It has a volume of distribution of 0.6 to 1.0 L/kg and low protein binding. It is eliminated by hepatic metabolism and renal excretion. Studies in humans have confirmed its effectiveness in preventing metabolism of methanol and ethylene glycol to their toxic byproducts (12,13,5658); as a result, it is approved for the treatment of both intoxications. Fomepizole has also been used off-label to treat diethylene glycol intoxication (17,44). It is cleared by dialysis; therefore, the dosage has to be increased in patients who undergo hemodialysis.

Table 5 summarizes advantages and disadvantages of fomepizole and ethanol in the treatment of the alcohol intoxications. Fomepizole does not cause the slowing of mentation noted with alcohol. The rate of its elimination from the body is more predictable, making monitoring of blood levels less necessary; therefore, patients do not have to be treated in the intensive care unit (13,40,50,53,55,5860). Hypoglycemia that occasionally is found with ethanol is absent (12,53). Alcohol predisposes to lactic acid production and can also damage the liver; however, ethanol is easily obtained and is inexpensive, whereas fomepizole can cost as much as $5000 for 48 h of therapy per patient and may not be available in all hospitals (12,54,58).

All of the alcohols have a low molecular weight, little or absent protein binding, and a low volume of distribution and thus can be effectively removed by dialysis. Dialysis can also remove the organic acid anions such as formate, glycolate, and glyoxalate (15,28,43,61). Intermittent hemodialysis is the most efficient method of rapidly lowering serum alcohol levels or removing the organic acid anions (6,18,28,40,43), although continuous renal replacement therapy can also be used (40). Peritoneal dialysis is rarely used because of the low clearance of the alcohol or organic acid anion.

The response to dialysis can be evaluated by serial measurements of the alcohol. In the absence of these measurements, changes in serum osmolality can be used if it has been elevated (18,19,23,25,31). Serum formate and glycolate levels have been determined to assess the response to therapy in some clinical studies of methanol and ethylene glycol intoxications (14,28,43,61,62). However, serum formate and or glycolate levels cannot be obtainable routinely in most clinical laboratories; therefore, in selected cases, examination of the serum anion gap can be used instead to determine the impact of treatment on the levels of these toxic metabolites (1,2,12,23).

Treatment of the metabolic acidosis with base has been recommended by most experts (12,13,28,52). Base administration has also been postulated to increase renal excretion of formate and glycolate (28,58,61,62). Base can be given intravenously or via dialysis. The delivery of base with dialysis might be preferred to lessen complications of base therapy (63). Folic acid to enhance the metabolism of formate (12) and pyridoxine or thiamine to promote the conversion of glyoxylate to glycine, and glycolic acid to α[Combining Acute Accent]-hydroxy-β-ketoadipate, respectively has also been recommended (13).

Methanol Intoxication


Methanol is used in industrial production and is also present in windshield wiper fluid, antifreeze, and model airplane fuel. It is also used in lieu of ethanol. It is colorless and has only a faint odor.

Methanol intoxication in the United States is uncommon with approximately 1000 to 2000 cases reported each year (approximately 1% of all poisonings) (10,12). It usually results from accidental ingestion of products containing methanol or ingestion as a method of attempting suicide or is taken in lieu of ethanol when the latter is in short supply (7,64,65).

The quantity of methanol that produces toxicity ranges from 15 to 500 ml of a 40% solution to 60 to 600 ml of pure methanol (6,12,52). The risk for methanol intoxication might be increased in the presence of low hepatic tetrahydrofolate concentrations, which affects the rate of formate metabolism (6,12).

If left untreated or if treatment is begun after the full-blown syndrome has developed, then mortality of methanol intoxication can be high. Overall mortality in three studies totaling more than 400 patients varied between 8 and 36% but increased to 50 to 80% when serum bicarbonate concentration was <10 mEq/L and/or blood pH was <7.1 when treatment was begun (7,52,66).


Metabolic acidosis and visual problems, hallmarks of this disorder, are due to metabolites of methanol. One, formaldehyde, impairs retinal oxidative phosphorylation in vitro (67), but in vivo, it is rapidly metabolized to formate with a half-life in the blood of only 1 to 2 min. Formic acid (or formate) seems to be the major cause of clinical and laboratory abnormalities: Infusion of formate causes damage to the optic disk in the absence of changes in pH (12,55,60), and the metabolic acidosis is directly correlated with blood formate concentrations (15,28,67).

Clinical Findings

The onset and severity of clinical and laboratory abnormalities depends largely on the generation of formic acid (6,12,23,28). Visual disturbances, including decreased visual acuity, photophobia, and blurred vision, and abdominal pain are the most common symptoms of methanol intoxication (7,64), one or both being found in 37 to 72% of patients (7,64). Hyperemia of the optic disks and a reduced papillary response to light may be present. The severity of the visual abnormalities is directly correlated with the severity of the metabolic acidosis (6,7,12). Although most patients will recover normal visual function, permanent impairment of vision has been observed in from 11 to 18% of patients (7,64).

Abdominal pain can be present in both the presence and the absence of pancreatitis (7,12). Neurologic abnormalities including confusion, stupor, and coma are often present (52). The most severe neurologic dysfunctions are found in patients with the most severe metabolic acidosis (6,7,28,64).

A rare complication of methanol intoxication is putaminal necrosis, which presents with rigidity, tremor, masked faces, and monotonous speech (12). It has been attributed to reduced cerebral blow flow and/or accumulation of formic acid in the putamen (12). Although the syndrome often resolves, some neurologic abnormalities can persist. Kusmaul's breathing, impaired cardiac function, and hypotension as a result of acidemia can be present and are most profound when blood pH is ≤7.2 (63).

The clinical findings in methanol intoxication often develop in a characteristic manner. Changes in mentation as a result of methanol are present within the first 6 to 24 h but can be the only abnormality for as long as 72 to 96 h if patients have also ingested ethanol (6,7,12,23,52). The absence of more prominent signs or symptoms at this stage can delay recognition of this disorder. As methanol is metabolized to formic acid, visual and more severe neurologic abnormalities become prominent (6,7,12,55,67,68).

Laboratory Findings

The serum osmolality can be increased or normal and is usually the greatest soon after ingestion of methanol. However, it can be only slightly perturbed even at this point (12,18,23,24), because an increment in serum osmolality of slightly more than 3 mOsm/L will be observed for every 10-mg/dl increase in its concentration. Thus, a methanol concentration of 50 mg/dl will increase serum osmolality by approximately 15 mOsm/L.

High anion gap metabolic acidosis (blood pH 6.8 to 7.3) primarily as a result of formic acid accumulation is often present (7,12,15,23,55,64,67,69). Lactic acidosis as a result of impairment of cellular respiration by formate or increased generation of NADH during the metabolism of methanol can also be present (6,12,23). In patients who also ingest ethanol, ketoacidosis can occur (52). Hyperchloremic metabolic acidosis noted with DKA has not been reported (70). However, the ΔAG/ΔHCO3 may be >1 in some patients, reflecting either a concomitant metabolic alkalosis or a difference in the space of distribution of formate and HCO3 (2,7,15).

The serum anion gap may be minimally increased and serum HCO3 minimally reduced early in the course of the disorder, a time when the increment in serum osmolality is the greatest. Subsequently, as methanol metabolism proceeds, the serum HCO3 falls concomitant with a rise in the anion gap and fall in the serum osmolality. After the bulk of the methanol has been metabolized, little or no increase in serum osmolality will be present, whereas the serum anion gap can be strikingly increased and the serum HCO3 markedly depressed (7,12,18,23,24). In rare instances, patients may have ocular toxicity in the presence of normal serum osmolal and anion gaps (24). The different patterns of serum osmolality and serum anion gap that can be observed with methanol and other intoxications are depicted in Figure 3.

When nitromethane (found in model airplane fuel) is ingested with methanol, the serum creatinine concentration determined using the Jaffe colorimetric method may be spuriously elevated (71). Correct determination of serum creatinine can be obtained using an enzymatic-based assay (71).

Measurement of methanol in blood is important to confirm the diagnosis of methanol intoxication and can be valuable in assessing the response to treatment. However, blood methanol is measured using gas chromatography in specialty laboratories, and the measurement can take many hours to a few days to complete. As noted previously, in the absence of measurements of methanol, assessment in changes of the serum osmolal gap can be useful in some cases, both in the diagnosis of methanol intoxication and for assessing the indication for and duration of treatment of this disorder.


The American Academy of Clinical Toxicology recommends ethanol or fomepizole be given to treat methanol intoxication based on the following criteria: Plasma methanol concentration >20 mg/dl or recent history of ingestion of methanol with serum osmolal gap >10 mOsm/L or strong clinical suspicion of methanol poisoning with at least two of the following: arterial pH <7.3, serum HCO3 <20 mEq/L, and osmolal gap >20 mOsm/L (12,54).

One prescription for the quantity of ethanol to be given is shown in Table 6. If ethanol is present in the blood, then the quantity given will have to be reduced. Alternative prescriptions are designed to provide sufficient ethanol to maintain its concentration at approximately 100 mg/dl or a molar concentration of ethanol 25% of the methanol concentration (6,12). These latter methods require continual measurement of methanol and ethanol levels, which can be difficult to obtain in most hospital settings. If ethanol is given to patients who receive hemodialysis, then the quantity of ethanol will have to be increased.

Uncontrolled observational studies and individual case reports have demonstrated that fomepizole is safe and effective in the treatment of methanol intoxication (12,55,56,58). In a study of 11 patients who were treated with intravenous fomepizole (seven of whom also underwent hemodialysis), serum formic acid concentration fell markedly and both blood pH and visual acuity returned to normal (56). Nine of the 11 patients survived. Adverse effects included headache, nausea, dizziness, and dyspepsia. Hypotension, skin rash, and transient elevation in liver enzymes have been reported in other studies (12,56). Although randomized, controlled studies to compare ethanol and fomepizole have not been done, fomepizole is preferred by most experts (12,54,56,58). If fomepizole is not available, then ethanol is a reasonable alternative. Fomepizole should be given in sufficient concentrations to maintain serum concentrations in excess of 0.8 mg/L (10 μmol/L), a level that provides constant inhibition of ADH (55). As discussed next, patients may be treated with fomepizole and hemodialysis. Table 7 lists the recommended dosage of fomepizole with and without hemodialysis (12).

Hemodialysis has been used to remove methanol and formate and to correct the metabolic acidosis (12,15,28,58,67,72,73). A recent study (74) established a formula to determine the duration of dialysis necessary to achieve a serum methanol concentration (or that of other alcohols) of <5 mmol/L (approximately 16 mg/dl with methanol), based on the predialysis serum alcohol concentration, blood flow, gender, age, height, weight, and urea clearance of the dialyzer:

where V, the Watson estimate of total body water, is in liters; A is the initial alcohol concentration in mmol/L; and k is 80% of the manufacturer's specified urea clearance in ml/min.

The role of hemodialysis in formate removal is controversial. Kerns et al. (15) found that dialysis did not appreciably decrease the half-life for formate and concluded that dialysis might provide little benefit in the treatment of methanol intoxication if serum methanol were low. By contrast, Hovda et al. (75) found that it substantially accelerated the removal of formate and suggested that hemodialysis might be used to remove formate even if methanol levels were not elevated. In addition, they described a patient who had severe methanol intoxication and metabolic acidosis and whose formate half-life (usually 2.5 to 12.5 h) was prolonged to 77 h (28). Initiation of hemodialysis reduced it more than 20-fold to 2.9 h.

The American Academy of Clinical Toxicology recommends that hemodialysis be considered in the presence of metabolic acidosis (blood pH 7.25 to 7.30), visual abnormalities, renal failure, or electrolyte imbalance unresponsive to conventional therapy and/or serum methanol concentration of >50 mg/dl (12). However, fomepizole treatment of patients with methanol intoxication even with serum concentrations >50 mg/dl either eliminated completely the need for dialysis or allowed it to be done electively many hours after hospitalization (56,75,76).

Carefully controlled randomized studies would be useful to provide evidence-based guidelines for treatment at different stages of methanol intoxication. However, in their absence, hemodialysis in association preferably with fomepizole seems reasonable for the treatment of the majority of patients with methanol intoxication. Hemodialysis will result in rapid removal of methanol, probably will enhance formate removal, and will deliver base to correct the acidosis. Also, it is a relatively safe therapeutic procedure. This combination should reduce morbidity and mortality and decrease the duration of hospitalization. Other investigators, based on their clinical experience, have come to a similar conclusion (28,72). These treatment measures should be continued until methanol concentration is <16 mg/dl or undetectable, if possible, and blood pH is >7.3 (12,54,74).

It has been postulated that metabolism of formate is enhanced by folic acid, and given the lack of adverse effects, administration of folate as adjunctive therapy seems reasonable (12,15). Administration of base is recommended to treat the metabolic acidosis and promote the renal removal of formate (15,61). Criteria proposed for initiation of base therapy are not well established with recommendations to initiate it in the presence of any metabolic acidosis (pH <7.3) or only in the presence of severe acidemia (blood pH <7.1 to 7.2) (12,75).

Ethylene Glycol Intoxication


Ethylene glycol is used in industrial production and is present in automobile coolants, heat transfer fluids, and runway deicers. It is colorless and odorless and has a sweet taste. Intoxication has resulted from topical applications of ethylene glycol–containing solutions to burns (77), but most intoxications result from oral ingestion of ethylene glycol–containing products (most frequently antifreeze), ethanol-based products containing ethylene glycol, or rarely contaminated drinking water (13). Ethylene glycol may be ingested as a cheap substitute for alcohol, taken in an attempt to commit suicide, or ingested accidentally. Ethylene glycol intoxication is more frequent than methanol intoxication. In 1999, the American Association of Poison Control Centers reported more than 5800 cases reflecting approximately 2% of the poisoning reported in that year in the United States (10). More than 600 of these cases (approximately 11%) occurred in children younger than 6 yr, and more than 800 (approximately 14%) occurred in children aged 6 to 19 yr (10).

The mortality of ethylene glycol intoxication is variable, ranging from 1 to 22% (8,10,78). The highest mortality is found in patients with the most severe metabolic acidosis and the longest duration between exposure and initiation of treatment: Either blood pH <7.1 or initiation of treatment >10 h after exposure (8,78). Although the lethal dosage of ethylene glycol has been reported to be 1.4 to 1.5 ml/kg body wt, death has been reported with lower amounts, and survival has been reported with much greater amounts (37). These observations could indicate some differences in susceptibility to the adverse effects of this alcohol.


Metabolic acidosis and organ dysfunction primarily result from generation of glycolic and oxalic acid from metabolism of ethylene glycol (13,37,43,79). The accumulation of glycolic acid is the primary cause of metabolic acidosis, but glycolate also impairs cellular respiration, and this effect can contribute to the development of lactic acidosis in some patients (6,37,43). Acute renal failure (ARF), myocardial dysfunction, neurologic function, and possibly pulmonary dysfunction result from deposition of oxalate with calcium in the kidney, heart, brain, and lung (8,13,37). Deposition of calcium oxalate in tissues also produces hypocalcemia, which depresses cardiac function and BP (13,37,80).

Because clinical and laboratory abnormalities are due to metabolites of ethylene glycol, co-ingestion of ethanol can delay their appearance by several hours (13,37,57). In the multicenter study examining the use of fomepizole in ethylene glycol intoxication (57), 12 (60%) of 19 had measurable blood ethanol levels, and four of the 12 had blood levels >100 mg/dl.

Clinical Findings

The signs and symptoms of ethylene glycol have been reported to develop in three distinct stages: First there are neurologic abnormalities, followed by cardiopulmonary dysfunction, and finally renal dysfunction (13,37,57). However, it is not uncommon for neurologic, cardiopulmonary, and renal failure to be present together (37).

Initially, only mild confusion or stupor is present as a result of the effects of ethylene glycol. Within 12 to 24 h after ingestion (in the absence of ethanol), neurologic signs and symptoms can become more profound and focal signs may appear. Autopsy studies have revealed cerebral edema with calcium oxalate crystals in brain tissue at this point. Many of the deaths with ethylene intoxication have been reported to occur at this stage or shortly thereafter (37,80).

Cardiopulmonary signs and symptoms appear next and include shortness of breath associated with physical evidence of congestive heart failure. Myocarditis and pulmonary infiltrates with calcium oxalate crystal deposits in the myocardium or lungs have been found on autopsy examination (37). After 24 to 72 h, ARF, which can be oliguric or nonoliguric, develops (37,81). Rarely, ARF can be seen in the absence of other stigmata of ethylene glycol intoxication; therefore, this entity should be considered in the differential diagnosis of unexplained ARF (37). The appearance of cranial neuropathies, which are usually transient in nature, 8 to 15 d after ethylene glycol ingestion has been described (82). Signs and symptoms related to the presence of metabolic acidosis, such as Kusmaul breathing, and a predisposition to congestive heart failure or hypotension can be found at all stages and are most prominent in patients with blood pH <7.1 to 7.2.

Laboratory Findings

The serum osmolality can be normal or elevated and is usually the highest within the first several hours after ingestion (13,24,37,38,43). As with methanol, even at this time it may be only slightly elevated. A serum concentration of 50 mg/dl will raise serum osmolality only approximately 9 mOsm/L. As ethylene glycol is metabolized to glycolic acid, a high anion gap metabolic acidosis will ensue. In this regard, approximately 86% of patients will be acidotic at the time of presentation (13,37,83). Hyperchloremic acidosis at presentation or with treatment has not been reported.

It is postulated that glycolic and not oxalic acid is primarily responsible for the metabolic acidosis (14,38,43,78) based on a strong correlation between the measured glycolate concentration in the blood and the serum anion gap (13,43,78). However, the urinary excretion of oxalate and/or its deposition in tissues could result in an underestimation of its contribution to the metabolic acidosis.

The severity of the metabolic acidosis and level of glycolate in the blood are important prognostic signs: Patients with a serum HCO3 ≤5 mEq/L, blood pH <7.1, or serum glycolate level ≥8 to 10 mmol/L are more likely to die and/or develop ARF (14,78). In this regard, an important predictor of ARF and mortality is the time elapsed between ingestion of ethylene glycol and recognition of this intoxication, both being more frequent the longer it takes before a diagnosis is made and treatment is begun (13). Lactic acidosis can also be present and is more prominent in patients with the highest serum glycolate levels (37,43). However, serum lactate can be spuriously elevated if it is measured using a lactate oxidase–based method, because ethylene glycol is recognized by this enzyme (84).

An increase in the serum osmolal gap and high anion gap metabolic acidosis can be present simultaneously, but as more of ethylene glycol is metabolized, serum osmolality will fall, whereas the serum anion gap will stay elevated or rise further. In some cases, both serum osmolality and the serum bicarbonate and anion gap can be normal, the only remnant of the disorder being the finding of calcium oxalate crystals on pathologic examination of the tissues (37).

Four to 8 h after ingestion of ethylene glycol, calcium oxalate crystals will be present in the urine (38). Crystalluria can persist for as long as 40 h in the absence of renal failure and up to 4 d in its presence (37,38,81). The nature of the crystals can change with time: Within the first 4 to 5 h, envelope-shaped calcium oxalate dihydrate crystals are present; between 5 and 7 h, a mixture of monohydrate and dihydrate crystals are present; and after 7 h, only the needle-shaped monohydrate is present (37,38). Hypocalcemia, which is most profound many hours after ethylene glycol ingestion, is frequent at a time when oxalate crystalluria is prominent (13,37).

The diagnosis of ethylene glycol intoxication is confirmed by detection of elevated ethylene glycol levels as determined by gas chromatography (13,37,40,85). Falsely positive levels of ethylene glycol have been reported in the presence of both an elevated serum lactate dehydrogenase and lactate concentrations and with ketoacidosis (37,85). However, marked elevations in blood concentrations of ethylene glycol are unlikely to be caused by these abnormalities.

Sodium fluorescein is added to some brands of antifreeze at a final concentration of 20 μg/ml (86,87). Examination of urine (collected in containers without intrinsic fluorescence) for visible fluorescence after exposure to ultraviolet light at a wavelength of approximately 360 nm with a Wood's lamp has been used as an additional diagnostic tool (8689). There are several pitfalls with this test. A number of drugs, food products, toxins, and endogenous compounds can contribute to urine fluorescence, producing false-positive results (86,87,89,90). The urine fluorescence is often short lived because the half-life of sodium fluorescein is 4.25 h (8689). Not every brand of antifreeze contains fluorescein. Also, the optimal excitation wavelength of fluorescein is approximately 494 nm (86,87). Thus, urine initially considered negative with a Wood's lamp demonstrated fluorescence when studied using a fluorimeter at this wavelength (8689). Finally, fluorescence is pH dependent and will be minimal or absent at a urine pH ≤4.5 (86,87). Physicians, therefore, should be cautious about either excluding or confirming the diagnosis on the basis of this test, and decision about initiating treatment should never be made on its basis alone.


Volume expansion with or without mannitol and bicarbonate may increase the urinary excretion of ethylene glycol and its metabolites and theoretically help to forestall oxalate-induced ARF (37). Indications and prescription for the use of ethanol in treatment of ethylene glycol is similar to that for methanol.

The effectiveness of fomepizole in the treatment of ethylene glycol intoxication was first demonstrated in a small number of case reports (13,53,79). In 1999, Brent et al. (57) reported a multicenter, prospective, observational study of 19 patients who had ethylene glycol intoxication and metabolic acidosis (serum HCO3 4 to 28 mEq/L) and were treated with fomepizole (17 of whom also underwent hemodialysis). Within a few hours of fomepizole therapy, serum glycolate levels fell and acid-base parameters improved. With addition of dialysis, serum glycolate levels fell from a mean of 89.7 mg/dl to undetectable values, and acid-base parameters normalized within 24 h (57). Eighteen of the 19 survived. All patients without renal failure before treatment maintained normal renal function, and renal function retuned to normal in six of nine patients with renal failure. Other studies confirmed the effectiveness of fomepizole in contributing to improvement of metabolic acidosis and avoidance or resolution of renal failure (58,59).

The American Academy of Clinical Toxicology recommends that ethanol or fomepizole be given in the presence of ethylene glycol level >20 mg/dl or a documented history of ingestion of potentially toxic amounts of ethylene glycol and serum osmolal gap >10 mOsm/L or history or strong clinical suspicion of ethylene glycol poisoning and two of the following abnormalities: Arterial pH <7.3, serum bicarbonate concentration <20 mEq/L, osmolal gap >10 mOsm/L, and the presence of oxalate crystals (13).

Hemodialysis is effective in rapidly lowering ethylene glycol levels and removing glycolate (43,62,78). The mean clearance rate of ethylene glycol is approximately 145 to 230 ml/min. The duration of hemodialysis necessary to reduce ethylene glycol concentrations can be estimated using the formula described by Hirsch et al. (74). Glycolate clearance is approximately 60% of urea clearance (43), and hemodialysis was shown to reduce its elimination half-life by more than four-fold (62).

Hemodialysis has been recommended for the treatment of ethylene glycol intoxication in the presence of severe metabolic acidosis that is unresponsive to therapy (blood pH <7.25), the presence of renal failure particularly if severe, and ethylene glycol levels >50 mg/dl (13). Because the serum concentration of glycolic acid has been shown by some to be an important prognostic sign, hemodialysis is also recommended if concentrations are >8 to 10 mmol/L (78).

Some investigators have found that hemodialysis is not necessary even in the face of very high ethylene glycol levels (79,91). In a retrospective study, eight of 11 patients with ethylene glycol intoxication were treated only with fomepizole without dialysis (79). Twenty-one percent of the patients were comatose, 34% had severe metabolic acidosis, and 11% had significant renal failure. Patients without renal failure recovered without developing renal failure or other complications, and only one of the 11 died.

Similar to methanol intoxication, given the relative safety of hemodialysis, its effectiveness in removing the alcohols and potentially toxic metabolites and the difficulty of obtaining rapid measurements of ethylene glycol or glycolate levels, consideration should be given to initiation of hemodialysis in concert with fomepizole in the majority of suspected or documented cases of ethylene glycol intoxication to prevent calcium oxalate deposition and renal failure and to reduce the cost of hospitalization. However, controlled, prospective studies would be useful in developing evidence-based guidelines, and a comparison of fomepizole alone versus dialysis with fomepizole is indicated.

Administration of thiamine may promote metabolism of glycolic acid to α-hydroxyl-β-ketoadipate, whereas administration of pyridoxine will promote metabolism of glyoxylate to glycine (13,40). Treatment with these compounds could be of value therefore in promoting the breakdown of the organic acids to less injurious products, although this has not been proved. Conversely, their administration is associated with little morbidity. Base administration to treat metabolic acidosis and perhaps augment urinary excretion or organic acid anions has been recommended by most experts (13).

Diethylene Glycol Intoxication


Diethylene glycol is used in industrial production, is present in brake fluid, and is used as an illegal adulterant in ethanol spirits or in medication (17,46). Sporadic cases of accidental poisoning or its use as a means of attempting suicide have been described (17,44,92). However, this intoxication has primarily been reported in outbreaks in which the diethylene glycol was used as a solvent for medications (46,9396).

The first reported cases of diethylene glycol intoxication in the United States in 1937 were directly responsible for the passage of the Federal Food Drug and Cosmetic Act in 1938 (46). Since then, outbreaks have occurred in China, Haiti, India, Bangladesh, and Latin America (9,46,95). In four of the outbreaks, only children were affected (9,46,93,96). This has been attributed to the smaller size of children. Importantly, the mortality approached 90% in some instances (9,93,96). The high mortality could be the result of late recognition of the disorder. All of these cases described resulted from oral ingestion of diethylene glycol. A single case of diethylene glycol from topical application has been reported (33). The toxic dose of diethylene glycol has been estimated at 0.14 mg/kg body wt and the lethal dose at 1 to 1.63 g/kg body wt (11,17). However, there is great variability in susceptibility to diethylene glycol, suggesting that individual risk factors are important (11,93).


Metabolic acidosis and organ dysfunction initially attributed to generation of glycolic acid and oxalic acid is presently postulated to result from the generation of HEAA from the metabolism of diethylene glycol (11,46,47,92,93,9799). The mechanism by which HEAA produces cellular dysfunction remains unclear.

Clinical Findings

The time from ingestion of diethylene glycol until the onset of clinical findings has not been well established because, in most cases, several days had elapsed until the diagnosis of diethylene glycol intoxication was made (9,11,46,96). However, in one study of five patients who presented within 24 h after the ingestion (92), clinical findings were similar to those noted in patients who were seen several days after ingestion.

Acute oliguric and nonoliguric renal failure is frequent (9,92,93,96). In patients who survived, irreversible renal failure has been reported; however, the factors that contribute to irreversibility of the renal failure are not clear (92,93). Hepatitis, pancreatitis, and neurologic abnormalities are seen, and patients commonly present with abdominal pain, diarrhea, headache, and altered mental status (9,17,46,92,93,96). Physical examination at the time can demonstrate hepatomegaly and jaundice. Although rare, cranial neuropathies and bulbar palsy appearing 10 to 14 d after the ingestion have been reported, even though patients had been treated with ethanol infusion and hemodialysis (92). Signs and symptoms related to the presence of metabolic acidosis described previously are often prominent.

Laboratory Findings

Serum osmolality can be high or normal (17,92). The molecular weight of diethylene glycol is relatively high (106); therefore, hyperosmolality is less frequent than with the other alcohols. Metabolic acidosis ranging from mild to severe is usually present if patients are seen ≥24 h after ingestion (11,17,92,96). Elevations in blood amylase and liver enzymes reflect the presence of both pancreatic and hepatic injury. Blood urea nitrogen, serum creatinine, and potassium concentration are elevated as a result of renal failure.

Serum diethylene glycol concentration is measured using gas chromatography in a specialized laboratory (17). Documentation of high levels in contaminated medication has been reported, and this may be a valuable method of confirming exposure in large outbreaks.


Administration of inhibitors of ADH and ALDH to rats given diethylene glycol completely prevented production of HEAA (47), and a young girl with known ingestion of diethylene glycol intoxication but without metabolic acidosis or renal failure was treated successfully with fomepizole without dialysis (44). Dialysis with or without fomepizole or ethanol has been used in the treatment of most patients (9,17,92,93). In part, the use of dialysis resulted from the high prevalence of renal failure in these patients (9,93,94,96); however, because diethylene glycol and possibly HEAA are theoretically dialyzable, use of dialysis even in the absence of renal failure seems logical. Two case reports of children who did not have renal failure and were treated with ADH inhibitors and/or dialysis have been reported, both of whom recovered (17,44). Similarly, five patients with diethylene glycol intoxication were treated with ethanol and dialysis with complete recovery in two (92); one of the patients died, and two others developed irreversible renal failure.

The clearance of diethylene glycol is not known. In one case in which diethylene glycol levels in blood were measured before and after dialysis, the predialysis levels were extremely low and those obtained after dialysis were undetectable (17). However, given its relatively small molecular weight, its clearance should be not too dissimilar from that of the other alcohols. No studies examining the dialysis of its major metabolite HEAA have been published.

Given the high mortality and the risk for irreversible renal failure, treatment of suspected patients with fomepizole and hemodialysis is warranted. Clearly, documentation of a cohort of patients, particularly children, presenting with ARF and metabolic acidosis should arouse the suspicion of the clinician (9,11,46,93,94,96). Because other diagnostic clues such as an increment in serum osmolality are inconsistent, the clinician may be forced to initiate treatment before confirmation of the diagnosis.

Propylene Glycol


Propylene glycol is used as a solvent for intravenous, oral, and topical pharmaceutical products (29,100105) and as a major ingredient of some antifreeze and hydraulic fluids (49). Drugs in which it is present include etomidate, phenytoin, diazepam, lorazepam, phenobarbital, nitroglycerin, digoxin, hydralazine, and trimethoprim-sulfamethoxazole. Cases of intoxication have been reported after topical administration for treatment for burns (31) and with oral ingestion (49), but the majority of reported cases have resulted from intravenous administration (36,100,101,104,105). In this regard, propylene glycol is used as a diluent in benzodiazepines (lorazepam concentration, vol/vol 0.8), which commonly are administered to patients who have seizures, are undergoing alcoholic withdrawal, or are intubated (36). The exact prevalence is not known, but a study of 21 patients receiving benzodiazepines in the intensive care unit revealed that four (19%) had either an increased serum anion gap or a fall in serum bicarbonate concentration consistent with propylene glycol toxicity (36).

The serum propylene glycol concentration associated with toxicity has ranged from 12 to 520 mg/dl, but toxicity is most likely to occur at blood concentration in excess of 100 mg/dl (19,106,107). Patients with impaired liver or kidney function are said to be at increased risk for developing toxicity (107). In contrast to methanol, ethylene glycol, and diethylene glycol, the mortality of propylene glycol is low, despite its administration to patients with multiple organ dysfunction (19,36,49,100,104107).


Metabolic acidosis associated with propylene glycol has been attributed to generation of lactic acid during its metabolism (49,108111). Both l- and d-lactic acidosis have been described (109111). Renal failure has been described in some patients, and proximal tubular cell injury has been reported in cultured renal cells exposed to propylene glycol, but the pathogenic mechanisms of renal toxicity are unclear (110,111).

Clinical Findings

Clinical findings attributable to propylene glycol intoxication other than those associated with renal failure or metabolic acidosis are limited. After intravenous administration with benzodiazepines, central nervous system depression may occur, but this is an expected result of the medication rather than due to propylene glycol (29,104,107,109).

Laboratory Findings

Laboratory abnormalities are the most common evidence of propylene glycol intoxication. Serum osmolality can be normal or high (26,36,105,107,109,111), and an increased serum osmolality may be the only evidence of abnormal blood concentrations. Because its half-life in blood is short, once the intravenous infusion is discontinued, serum osmolality will return rapidly to baseline. As a result, several clinicians have recommended using the serum osmolal gap as a surrogate for propylene glycol concentrations to evaluate the response to treatment (19,105,106,111).

Mild l-lactic acidosis with serum lactate concentration in the range of 2 to 6 mEq/L can be found, but more severe lactic acidosis is infrequent (36,104,109). Rare cases of d-lactic acidosis have been reported (110).

Renal dysfunction has been described in a small percentage of patients, some of whom had pathologic evidence of tubular necrosis (36,106,107,109111). However, this is not common. In one carefully controlled observational study, renal function, as assessed by measurement of serum creatinine concentration, was not reduced, although serum propylene glycol concentrations were at levels at which other evidence of propylene glycol toxicity has been described (36).


Because this disorder is iatrogenic, prevention by limiting the dosage of propylene glycol that is given to patients in the intensive care unit may be the best treatment. Zar et al. (111) recommended that propylene glycol be given in doses not to exceed 2.9 g/h (<69 mg/d). Based on the concentration of propylene glycol in lorazepam for example, this could be achieved by limiting lorazepam to <166 mg/d. This dosage might have to be reduced further in patients with significant risk factors.

The metabolic acidosis is usually mild to moderate in degree, and discontinuation of medication containing propylene glycol can lead to correction of the acidosis in ≤24 h in most patients (36). In the face of extremely high blood concentrations, hemodialysis is extremely effective in rapidly reducing serum propylene glycol levels (107). Therefore, in the face of renal failure, extremely high serum propylene glycol levels, or severe metabolic acidosis, early institution of dialysis is warranted (35,107,111). Although theoretically fomepizole should be beneficial, its use has not been reported. However, a patient with a serum propylene glycol concentration of 470 mg/dl, the highest reported blood level, was treated with ethanol infusion alone. He was discharged after 48 h having had only minimal lactic acidosis and no sequelae (49). Thus, in cases of propylene glycol intoxication with very high blood concentrations and lactic acidosis, administration of fomepizole along with dialysis is warranted. If severe lactic acidosis is present and dialysis is not done, then base might be given, although this remains controversial (63).

Alcoholic Ketoacidosis


The syndrome of alcoholic ketoacidosis (AKA) is uncommon in patients with acute ethanol intoxication, being found in <10% of patients (112114). It is most frequent in patients who have long-term ethanol intake and liver disease and develop the syndrome after a period of binge drinking (39,112) and is associated with reduced food intake and episodes of vomiting; the latter might explain the concurrence of metabolic alkalosis noted in some patients (39,112,115,116).

A large number of patients with methanol or ethylene glycol intoxication have developed these intoxications after ingesting contaminated ethanol-based products, and, in these cases, serum ethanol levels are high (55,57). In this regard, increased levels of ketones in the blood or urine have been found in from 2 to 20% of patients with methanol intoxication (52,56), consistent with AKA. Although AKA often occurs in patients with significant comorbid conditions, the mortality is often low: In a study of 74 patients with AKA, only 1% died (39).


Although oxidation of ethanol in the liver generates acetaldehyde, which is converted to acetate and acetyl CoA, a precursor of ketone bodies, the ketogenesis has been primarily attributed to stimulation of lipolysis and free fatty acids generation from the low insulin levels and development of increased levels of counterregulatory hormones such as epinephrine, cortisol, and glucagon in these patients (115). Excess production of acetoacetic acid and β-hydroxybutyric acid underlies the metabolic acidosis, with increased NADH favoring production of β-hydroxybutyrate compared with acetoacetate (115), the ratio of these ketones rising from the normal value of 3:1 to more than 9:1 (112115). The increased NADH also favors increased lactic acid production; therefore, concomitant lactic acidosis even in the absence of impaired tissue perfusion is not uncommon (39,112,115). However, the increase in lactic acid production is small, and severe lactic acidosis in the absence of sepsis or hypotension is rare (39,112,114,115).

Clinical Findings

Because this disorder is most frequent in chronic alcoholic patients with acute and chronic liver and pancreatic disorders, it may be difficult to distinguish clinical findings that are due to AKA from those that are due to liver or pancreatic disease (39,112,117). Abdominal pain, nausea and vomiting, and altered mental status are the most prominent symptoms, being found in approximately 25 to 37% of patients (39). Changes in mental status without focal neurologic signs are frequent. Abdominal tenderness on palpation and enlargement of the liver and occasionally the spleen may reflect the presence of acute or chronic liver disease. Nonspecific symptoms and signs related to the presence of metabolic acidosis can be observed.

Laboratory Findings

Metabolic acidosis alone is common, but more frequently there are mixed acid-base disorders, including respiratory alkalosis and metabolic acidosis, metabolic acidosis associated with metabolic alkalosis, or triple disturbances including respiratory and metabolic derangements (3,39,112,116,117). The metabolic acidosis is usually of the high anion gap variety. Hyperchloremic acidosis, described in patients with DKA is uncommon, even after treatment with saline (115). Hyponatremia, hypokalemia and/or hyperkalemia, and hypophosphatemia are also commonly found (39,112,117).

The serum osmolality is often normal, because AKA is often found after most of the ethanol has been metabolized (39,112,115). However, serum osmolality can be elevated as a result of an elevated serum concentration of either ethanol or ketones (21,22,39,112,118120). In some patients, the increased serum osmolality is due to substances other than ketones or ethanol. Braden et al. (118) reported an increase in the serum osmolal gap in a patient with alcohol intoxication but undetectable ethanol levels. Serum concentrations of glycerol, acetone, and the acetone metabolites acetol and 1,2-propanediol were increased, accounting for 92% of the osmolal gap.

Theoretically, the diagnosis of alcohol ketoacidosis is confirmed by detection of elevated ethanol levels. However, serum ethanol concentrations are often undetectable (39,112,117,119,120). Therefore, the clinician will often have to rely on a history of alcohol ingestion and the absence of stigmata of diabetes in making the diagnosis of AKA. Ketones in body fluids are detected by the nitroprusside reaction. This test detects acetoacetate but not β-hydroxybutyrate. Therefore, the nitroprusside test of urine of blood may revealed a trace positive reading (112,114,115,119,120). Negative readings, although they can occur, are uncommon: Only 10 of 74 patients with AKA had a negative test for ketones. (39).

Blood glucose can be low normal or high (39,112,114,115,119121). Hypoglycemia has been attributed to the presence of depleted glycogen stores and reduced gluconeogenesis. If hyperglycemia is present, then it can make the distinction from DKA difficult.


Resolution of AKA occurs after administration of dextrose and/or saline; however, the metabolic acidosis resolves more quickly and β-hydroxybutyrate levels fall more rapidly when both are administered together (121,122). Saline administration alone, although effective in restoring volume deficits, could also theoretically convert the metabolic acidosis to a hyperchloremic form, as described for DKA (70). However, none of the patients who had AKA and were given saline developed hyperchloremic acidosis, whereas >50% of the patients with DKA did (115). Resolution of AKA after fluid administration is often more rapid than DKA (mean time 6 versus 16 h) (115).

At present, it is recommended that both dextrose and saline be administered in a patient with AKA to restore volume deficits and provide glucose to prevent hypoglycemia. Insulin is not routinely recommended. However, if significant hyperglycemia or life-threatening acidemia is present, then insulin may be indicated (122). Base administration is not usually required given the rapid resolution of acid-base abnormalities once appropriate therapy is initiated.



Isopropanol is used in various industrial products, as a cleaning agent, deicer, and in rubbing alcohol. Isopropanol intoxication results from its accidental ingestion or its use in suicide attempts or when used in lieu of ethanol (4,5). In 1997, 1999, and 2004, a total of almost 27,000 exposures (most of them minor) were reported to poison control centers; one third were in children who were younger than 6 y (10,123,124). Mortality is often less than with methanol or ethylene glycol intoxication (0.1% in 2004) (124).

Some investigators had suggested that isopropanol concentrations >150 mg/dl produce coma and hypotension and levels >200 mg/dl are said to be incompatible with life (4,125). By contrast, Lacouture et al. (126) found that severe hypotension with coma was found only with serum isopropanol levels >400 mg/dl.


Although isopropanol is metabolized to acetone, which itself might be toxic, the cause of the clinical and laboratory abnormalities seem to be due to the effects of isopropanol on organ function (4,5,125128).

Clinical Findings

Clinical findings usually appear within 30 to 60 min after ingestion, although they can take as long as 3 to 4 h to develop (4,5,126,128). Abdominal pain, nausea, vomiting, diarrhea, and changes in mentation are the most common findings. Hypotension can be present in the face of very high isopropanol levels.

Laboratory Findings

The most common laboratory abnormality is an increase in the serum osmolality (4,5,126,127). Metabolic acidosis is usually absent, unless hypotension is sufficient to produce lactic acidosis (126128). Because one of the major metabolites of isopropanol is acetone, the nitroprusside reaction will be positive (4,126). The triad of normal acid-base parameters, hyperosmolality, and a positive nitroprusside reaction of urine and/or blood should suggest this diagnosis.

Isopropanol levels will usually be elevated. Serum creatinine, if measured with the colorimetric method, can be elevated in the absence of renal failure as a result of the interference of acetone with the creatinine determination (4).


Supportive measures are often sufficient if the patient is not comatose and/or hypotensive. If hypotension is present along with coma, then initiation of hemodialysis has been recommended (4,126128). The blood level of isopropanol at which dialysis should be initiated is not clear. Correlations between the severity of the clinical outcome and the blood levels of isopropanol have revealed conflicting results (126128). Some studies have suggested blood levels of 150 to 200 mg/dl can be associated with increased mortality (125,128), whereas, in others, only blood concentrations of approximately 400 mg/dl were associated with a poor outcome (126). Given the effectiveness of dialysis in removing isopropanol and the safety of this procedure, it seems reasonable to initiate hemodialysis in the presence of severe coma, hypotension, or serum isopropanol levels >200 mg/dl.

Conclusions and Future Considerations

Several of the alcohol intoxications can produce severe cellular dysfunction, which can be irreversible, and if they are untreated or treatment is initiated late in their course, then they can be associated with a very high mortality. Therefore, a high index of suspicion for these disorders should be maintained in the presence of unexplained metabolic acidosis or hyperosmolality, unexplained ARF, or neurologic dysfunction. Recent reports of contamination of medication with diethylene glycol further emphasize the importance of these disorders (94,95).

Given the absence of inexpensive and rapid diagnostic tools in common use to detect these intoxications, early treatment including fomepizole and/or dialysis might have to be initiated before a definitive diagnosis is made, particularly in the cases of methanol, ethylene glycol, and diethylene glycol intoxications. In this regard, a high priority should be given for developing methods to diagnose these disorders rapidly and thereby facilitate the initiation of appropriate therapy (129).

Table 8 summarizes salient epidemiologic aspects, key clinical and laboratory findings listed in the order of their usefulness for diagnosis, and important indicators of a poor prognosis. Table 9 summarizes the authors’ recommendations for indications and timing of initiation and duration of specific therapy for each of the disorders. In regard to treatment, as has been emphasized before, controlled studies are not available to evaluate the usefulness of many of the various therapies. Therefore these recommendations represent conclusions gleaned from the authors’ analysis of the literature and may differ from those of the American Academy of Clinical Toxicology, particularly with recommendations for the early initiation of hemodialysis for several of the disorders. Randomized, controlled studies of all modalities of treatment would be valuable to facilitate the development of evidence-based guidelines for therapy, particularly of methanol, ethylene glycol, diethylene glycol, and isopropanol, the disorders with potentially the highest mortality.



Figure 1:
Metabolic pathways for ethanol, methanol, and ethylene glycol. Although, the metabolites for each alcohol differ, the initial metabolic step facilitated by the enzyme alcohol dehydrogenase (ADH) is an important determinant of generation of these products and serves as an important therapeutic target. Enzymes for only the first two steps of each pathway are shown. The conversion of formate to CO2 and H2O depends on adequate folate concentrations. Pyridoxine promotes the metabolism of glyoxylate to glycine, and thiamine promotes metabolism of glycolic acid to α-hydroxy-β-ketoadipate. ALDH, aldehyde dehydrogenase; FMD, formaldehyde dehydrogenase.
Figure 2:
Metabolic pathways for isopropanol, diethylene glycol, and propylene glycol. Although the metabolites for each alcohol differ, the initial metabolic step facilitated by the enzyme ADH is an important determinant of generation of these products and serves as an important therapeutic target. Enzymes for only the first two steps of each pathway are shown.
Figure 3:
Evolution of changes in the serum osmolal and anion gaps during the course of methanol intoxication. Data from studies of methanol intoxication have revealed that early in the course of the disorder, the serum osmolal gap is the greatest and the serum anion gap the least. As metabolism of the parent alcohol proceeds, the serum osmolal gap and serum anion gap approximate each other. At later stages, the serum osmolal gap may return to baseline, whereas the serum anion gap continues to rise. Although it is presumed that a similar pattern would hold for many of the alcohol intoxications, sufficient data to confirm this are not available. Adapted from reference (23), with permission.
Table 1:
Major alcohol intoxicationsa
Table 2:
Effect of alcohols on serum osmolality
Table 3:
Volume of distribution, route of elimination, and elimination kinetics of major alcohols
Table 4:
General principles in the treatment of alcohol intoxicationsa
Table 5:
Comparison of fomepizole and ethanol in treatment of toxic alcohol ingestionsa
Table 6:
Recommended dosage of ethanol for treatment of methanol or ethylene glycol intoxicationa
Table 7:
Recommended dosage of fomepizole for patients with methanol and ethylene glycol intoxicationa
Table 8:
Epidemiology, diagnostic clues, poor prognostic factors, and recommendations for treatment of toxic alcohol ingestionsa
Table 9:
Recommendations for treatment of toxic alcohol ingestionsa

This work was supported by funds from the Veterans Administration (J.A.K.) and the Max Factor Family Foundation, the Richard and Hinda Rosenthal Foundation, and the Fredrika Taubitz Fund (I.K.).

We acknowledge the superb assistance of the information specialist Susan Efteland in reviewing the database and the secretarial assistance of Leslie Edelstein. We acknowledge the preparation of the figures by Gene Gushansky.

Published online ahead of print. Publication date available at


1. Gabow PA, Kaehny WD, Fennessey PV, Goodman SI, Gross PA, Schrier RW: Diagnostic importance of an increased serum anion gap. N Engl J Med303 :854– 858,1980
2. Kraut JA, Madias NE: Serum anion gap: Its uses and limitations in clinical medicine. Clin J Am Soc Nephrol2 :162– 174,2007
3. Hojer J: Severe metabolic acidosis in the alcoholic: Differential diagnosis and management. Hum Exp Toxicol15 :482– 488,1996
4. Zaman F, Pervez A, Abreo K: Isopropyl alcohol intoxication: A diagnostic challenge. Am J Kidney Dis40 :E12 ,2002
5. Abramson S, Singh AK: Treatment of the alcohol intoxications: Ethylene glycol, methanol and isopropanol. Curr Opin Nephrol Hypertens9 :695– 701,2000
6. Jacobsen D, McMartin KE: Methanol and ethylene-glycol poisonings: Mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol Adverse Drug Exp1 :309– 334,1986
7. Hovda KE, Hunderi OH, Tafjord AB, Dunlop O, Rudberg N, Jacobsen D: Methanol outbreak in Norway 2002–2004: Epidemiology, clinical features and prognostic signs. J Intern Med258 :181– 190,2005
8. Karlsonstiber C, Persson H: Ethylene-glycol poisoning: Experiences from an epidemic in Sweden. J Toxicol Clin Toxicol30 :565– 574,1992
9. Hanif M, Mobarak MR, Ronan A, Rahman D, Donovan JJ, Bennish ML: Fatal renal failure caused by diethylene glycol in paracetamol elixir: The Bangladesh epidemic. BMJ311 :88– 91,1995
10. Litovitz TL, Klein-Schwartz W, White S, Cobaugh DJ, Youniss J, Drab A, Benson BE: 1999 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med18 :517– 574,2000
11. Ferrari LA, Giannuzzi L: Clinical parameters, postmortem analysis and estimation of lethal dose in victims of a massive intoxication with diethylene glycol. Forensic Sci Int153 :45– 51,2005
12. Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA: American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol40 :415– 446,2002
13. Barceloux DG, Krenzelok EP, Olson K, Watson W: American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning. J Toxicol Clin Toxicol37 :537– 560,1999
14. Jacobsen D, Ovrebo S, Ostborg J, Sejersted OM: Glycolate causes the acidosis in ethylene glycol poisoning and is effectively removed by hemodialysis. Acta Med Scand216 :409– 416,1984
15. Kerns W, Tomaszewski C, McMartin K, Ford M, Brent J: Formate kinetics in methanol poisoning. J Toxicol Clin Toxicol40 :137– 143,2002
16. Smithline N, Gardner KD: Gaps: Anionic and osmolal. JAMA236 :1594– 1597,1976
17. Brophy PD, Tenenbein M, Gardner J, Bunchman TE, Smoyer WE: Childhood diethylene glycol poisoning treated with alcohol dehydrogenase inhibitor fomepizole and hemodialysis. Am J Kidney Dis35 :958– 962,2000
18. Hunderi OH, Hovda KE, Jacobsen D: Use of the osmolal gap to guide the start and duration of dialysis in methanol poisoning. Scand J Urol Nephrol40 :70– 74,2006
19. Barnes BJ, Gerst C, Smith JR, Terrell AR, Mullins ME: Osmol gap as a surrogate marker for serum propylene glycol concentrations in patients receiving lorazepam for sedation. Pharmacotherapy26 :23– 33,2006
20. Chabali R: Diagnostic use of anion and osmolal gaps in pediatric emergency medicine. Pediatr Emerg Care13 :204– 210,1997
    21. Almaghamsi AM, Yeung CK: Osmolal gap in alcoholic ketoacidosis. Clin Nephrol48 :52– 53,1997
    22. Schelling JR, Howard RL, Winter SD, Linas SL: Increased osmolal gap in alcoholic ketoacidosis and lactic acidosis. Ann Intern Med113 :580– 582,1990
    23. Hovda KE, Hunderi OH, Rudberg N, Froyshov S, Jacobsen D: Anion and osmolal gaps in the diagnosis of methanol poisoning: clinical study in 28 patients. Intensive Care Med30 :1842– 1846,2004
    24. Jacobsen D, Bredesen JE, Eide I, Ostborg J: Anion and osmolal gaps in the diagnosis of methanol and ethylene glycol poisoning. Acta Med Scand212 :17– 20,1982
    25. Haviv YS, Rubinger D, Zamir E, Safadi R: Pseudo-normal osmolal and anion gaps following simultaneous ethanol and methanol ingestion. Am J Nephrol18 :436– 438,1998
    26. Robinson AG, Loeb JN: Ethanol ingestion commonest cause of elevated plasma osmolality. N Engl J Med284 :1253– 1255,1971
    27. Sklar AH, Linas SL: The osmolal gap in renal failure. Ann Intern Med98 :481– 482,1983
    28. Hovda KE, Mundal H, Urdal P, McMartin K, Jacobsen D: Slow formate elimination in severe methanol poisoning: A fatal case report. Clin Toxicol45 :516– 521,2007
    29. Peleg O, Bar-Oz B, Arad I: Coma in a premature infant associated with the transdermal absorption of propylene glycol. Acta Paediatr87 :1195– 1196,1998
    30. Frenia ML, Schauben JL: Methanol inhalation toxicity. Ann Emerg Med22 :1919– 1923,1993
    31. Fligner CL, Jack R, Raisys V, Twiggs GA: Hyperosmolality induced by propylene glycol: A complication of silver sulfadiazine therapy. JAMA253 :1606– 1609,1985
    32. Arditi M, Killner MS: Coma following use of rubbing alcohol for fever control. Am J Dis Child141 :237– 238,1987
    33. Cantarell MC, Fort J, Camps J, Sans M, Piera L, Rodamilans M: Acute intoxication due to topical application of diethylene glycol. Ann Intern Med106 :478– 479,1987
    34. Lakind JS, McKenna EA, Hubner RP, Tardiff RG: A review of the comparative mammalian toxicity of ethylene glycol and propylene glycol. Crit Rev Toxicol29 :331– 365,1999
    35. Wilson KC, Reardon C, Farber HW: Propylene glycol toxicity in a patient receiving intravenous diazepam. N Engl J Med343 :815 ,2000
    36. Wilson KC, Reardon C, Theodore AC, Farber HW: Propylene glycol toxicity: A severe iatrogenic illness in ICU patients receiving IV benzodiazepines—A case series and prospective, observational pilot study. Chest128 :1674– 1681,2005
    37. Eder AF, McGrath CM, Dowdy YG, Tomaszewski JE, Rosenberg FM, Wilson RB, Wolf BA, Shaw LM: Ethylene glycol poisoning: Toxicokinetic and analytical factors affecting laboratory diagnosis. Clin Chem44 :168– 177,1998
    38. Jacobsen D, Hewlett TP, Webb R, Brown ST, Ordinario AT, McMartin KE: Ethylene glycol intoxication: Evaluation of kinetics and crystalluria. Am J Med84 :145– 152,1988
    39. Wrenn KD, Slovis CM, Minion GE, Rutkowski R: The syndrome of alcoholic ketoacidosis. Am J Med91 :119– 128,1991
    40. Brent J: Current management of ethylene glycol poisoning. Drugs61 :979– 988,2001
    41. Christopher MM, Eckfeldt JH, Eaton JW: Propylene glycol ingestion causes D-lactic acidosis. Lab Invest62 :114– 118,1990
    42. Hess R, Bartels MJ, Pottenger LH: Ethylene glycol: An estimate of tolerable levels of exposure based on a review of animal and human data. Arch Toxicol78 :671– 680,2004
    43. Gabow PA, Clay K, Sullivan JB, Lepoff R: Organic acids in ethylene glycol intoxication. Ann Intern Med105 :16– 20,1986
    44. Borron SW, Baud FJ, Garnier R: Intravenous 4-methylpyrazole as an antidote for diethylene glycol and triethylene glycol poisoning: A case report. Vet Hum Toxicol39 :26– 28,1997
    45. Ballantyne B, Snellings WA: Developmental toxicity study with diethylene glycol dosed by gavage to CD rats and CD-1 mice. Food Chem Toxicol43 :1637– 1646,2005
      46. Woolf AD: The Haitian diethylene glycol poisoning tragedy: A dark wood revisited. JAMA279 :1215– 1216,1998
      47. Mathews JM, Parker MK, Matthews HB: Metabolism and disposition of diethylene glycol in rat and dog. Drug Metab Disp19 :1066– 1070,1991
      48. Wiener HL, Richardson KE: Metabolism of diethylene glycol in male rats. Biochem Pharmacol38 :539– 541,1989
      49. Brooks DE, Wallace KL: Acute propylene glycol ingestion. J Toxicol Clin Toxicol40 :513– 516,2002
      50. Brown MJ, Shannon MW, Woolf A, Boyer EW: Childhood methanol ingestion treated with fomepizole and hemodialysis. Pediatrics108 :E77 ,2001
      51. Mulligan CJ, Robin RW, Osier MV, Sambuughin N, Goldfarb LG, Kittles RA, Hesselbrock D, Goldman D, Long JC: Allelic variation at alcohol metabolism genes (ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population. Hum Genet113 :325– 336,2003
      52. Bennett JL, Cary FH, Mitchell GL, Cooper MN: Acute methyl alcohol poisoning: A review based on experiences in an outbreak of 323 cases. Medicine32 :431– 463,1953
      53. Jacobsen D, McMartin KE: Antidotes for methanol and ethylene glycol poisoning. J Toxicol Clin Toxicol35 :127– 143,1997
      54. Chu J, Wang RY, Hill NS: Update in clinical toxicology. Am J Respir Crit Care Med166 :9– 15,2002
      55. Brent J, McMartin K, Phillips S, Aaron C, Kulig K: Fomepizole for the treatment of methanol poisoning. N Engl J Med344 :424– 429,2001
      56. Megarbane B, Borron SW, Trout H, Hantson P, Jaeger A, Krencker E, Bismuth C, Baud FJ: Treatment of acute methanol poisoning with fomepizole. Intensive Care Med27 :1370– 1378,2001
      57. Brent J, McMartin K, Phillips S, Burkhart KK, Donovan JW, Wells M, Kulig K: Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med340 :832– 838,1999
      58. Megarbane B, Borron SW, Baud FJ: Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Med31 :189– 195,2005
      59. Sivilotti ML, Burns MJ, McMartin KE, Brent J: Toxicokinetics of ethylene glycol during fomepizole therapy: Implications for management. Ann Emerg Med36 :114– 125,2000
      60. Sivilotti ML, Burns MJ, Aaron CK, McMartin KE, Brent J: Reversal of severe methanol-induced visual impairment: No evidence of retinal toxicity due to fomepizole. J Toxicol Clin Toxicol39 :627– 631,2001
      61. Hovda KE, Andersson KS, Urdal P, Jacobsen D: Methanol and formate kinetics during treatment with fomepizole. Clin Toxicol43 :221– 227,2005
      62. Moreau CL, Kerns W, Tomaszewski CA, McMartin KE, Rose SR, Ford MD, Brent J: Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. J Toxicol Clin Toxicol36 :659– 666,1998
      63. Kraut JA, Kurtz I: Use of base in the treatment of severe acidemic states. Am J Kidney Dis38 :703– 727,2001
      64. Paasma R, Hovda KE, Tikkerberi A, Jacobsen D: Methanol mass poisoning in Estonia: Outbreak in 154 patients. Clin Toxicol45 :152– 157,2007
      65. Brent J, Lucas M, Kulig K, Rumack BH: Methanol poisoning in a 6-week-old infant. J Pediatr118 :644– 646,1991
      66. Liu JJ, Daya MR, Carrasquillo O, Kales SN: Prognostic factors in patients with methanol poisoning. J Toxicol Clin Toxicol36 :175– 180,1999
      67. McMartin KE, Ambre JJ, Tephly TR: Methanol poisoning in human subjects. Role for formic acid accumulation in the metabolic acidosis. Am J Med68 :414– 418,1980
      68. Tephly TR: The toxicity of methanol. Life Sci48 :1031– 1041,1991
      69. Hovda KE, Urdal P, Jacobsen D: Increased serum formate in the diagnosis of methanol poisoning. J Anal Toxicol29 :586– 588,2005
      70. Adrogue HJ, Wilson H, Boyd AE, Suki WN, Eknoyan G: Plasma acid-base patterns in diabetic ketoacidosis. N Engl J Med307 :1603– 1610,1982
      71. Mullins ME, Hammett-Stabler CA: Intoxication with nitromethane-containing fuels: Don’t be “fueled” by the creatinine. J Toxicol Clin Toxicol36 :315– 320,1998
      72. Palatnick W, Redman LW, Sitar DS, Tenenbein M: Methanol half-life during ethanol administration: Implications for management of methanol poisoning. Ann Emerg Med26 :202– 207,1995
      73. Jacobsen D, Ovrebo S, Sejersted OM: Toxicokinetics of formate during hemodialysis. Acta Med Scand214 :409– 412,1983
      74. Hirsch DJ, Jindal KK, Wong P, Fraser AD: A simple method to estimate the required dialysis time for cases of alcohol poisoning. Kidney Int60 :2021– 2024,2001
      75. Hovda KE, Froyshov S, Gudmundsdottir H, Rudberg N: Fomepizole may change indication for hemodialysis in methanol poisoning: Prospective study in seven cases. Clin Nephrol64 :190– 197,2005
      76. Burns MJ, Graudins A, Aaron CK, McMartin K, Brent J: Treatment of methanol poisoning with intravenous 4-methylpyrazole. Ann Emerg Med30 :829– 832,1997
      77. Bruns DE, Herold DA, Rodeheaver GT, Edlich RF: Polyethylene glycol intoxication in burn patients. Burns Incl Therm Inj9 :49– 52,1982
      78. Porter WH, Rutter PW, Bush BA, Pappas AA, Dunnington JE: Ethylene glycol toxicity: The role of serum glycolic acid in hemodialysis. J Toxicol Clin Toxicol39 :607– 615,2001
      79. Borron SW, Megarbane B, Baud FJ: Fomepizole in treatment of uncomplicated ethylene glycol poisoning. Lancet354 :831 ,1999
      80. Leth PM, Gregersen M: Ethylene glycol poisoning. Forensic Sci Int155 :179– 184,2005
      81. Takayesu JK, Bazari H, Linshaw M, Harris NL, Walls RM, Kehoe LG: A 47-year-old man with altered mental status and acute renal failure: Ethylene glycol intoxication. N Engl J Med354 :1065– 1072,2006
      82. Lewis LD, Smith BW, Mamourian AC: Delayed sequelae after acute overdoses or poisonings: Cranial neuropathy related to ethylene glycol ingestion. Clin Pharmacol Ther61 :692– 699,1997
      83. Moriarty RW, Mcdonald RH: Spectrum of ethylene-glycol poisoning. Clin Toxicol7 :583– 596,1974
      84. Morgan TJ, Clark C, Clague A: Artifactual elevation of measured plasma L-lactate concentration in the presence of glycolate. Crit Care Med27 :2177– 2179,1999
      85. Martinez C, Lubbos H, Rose LI, Swartz C, Kayne F: False-positive ethylene glycol levels in patients with diabetic ketoacidosis. Endocr Pract4 :272– 273,1998
      86. Parsa T, Cunningham SJ, Wall SP, Almo SC, Crain EF: The usefulness of urine fluorescence for suspected antifreeze ingestion in children. Am J Emerg Med23 :787– 792,2005
      87. Winter ML, Ellis MD, Snodgrass WR: Urine fluorescence using a Wood's lamp to detect the antifreeze additive sodium fluorescein: A qualitative adjunctive test in suspected ethylene glycol ingestions. Ann Emerg Med19 :663– 667,1990
      88. Wallace KL, Suchard JR, Curry SC, Reagan C: Diagnostic use of physicians’ detection of urine fluorescence in a simulated ingestion of sodium fluorescein-containing antifreeze. Ann Emerg Med38 :49– 54,2001
        89. Casavant MJ, Shah MW, Battels R: Does fluorescent urine indicate antifreeze ingestion by children? Pediatrics107 :113– 114,2001
        90. Winter ML, Snodgrass WR: Urine fluorescence in ethylene glycol poisoning. N Engl J Med356 :611 ,2007
        91. Boyer EW, Mejia M, Woolf A, Shannon M: Severe ethylene glycol intoxication treated without hemodialysis. Pediatrics107 :172– 173,2001
        92. Alfred S, Coleman P, Harris D, Wigmore T, Stachowski E, Graudins A: Delayed neurologic sequelae resulting from epidemic diethylene glycol poisoning. Clin Toxicol43 :155– 159,2005
        93. O’Brien KL, Selanikio JD, Hecdivert C, Placide MF, Louis M, Barr DB, Barr JR, Hospedales CJ, Lewis MJ, Schwartz B, Philen RM, St. Victor S, Espindola J, Needham LL, Denerville K: Epidemic of pediatric deaths from acute renal failure caused by diethylene glycol poisoning. JAMA279 :1175– 1180,1998
        94. Lacey M, Grady D: A killer in a medicine bottle shakes faith in government. New York Times October 16,2006
        95. Bogdanich W, Hooker J: From China to Panama, a trial of poisoned medicine. New York Times May 6,2007
        96. Hari P, Jain Y, Kabra SK: Fatal encephalopathy and renal failure caused by diethylene glycol poisoning. J Trop Pediatr52 :442– 444,2006
        97. Kraul H, Jahn F, Braunlich H: Nephrotoxic effects of diethylene glycol in rats. Exp Pathol42 :27– 32,1991
        98. Auzepy P, Durand A, Hebert JL: Mechanism and treatment of acute-poisoning in male rats by diethylene-glycol. Intensive Care Med3 :196 ,1977
          99. Winek CL, Shingleton DP, Shanor SP: Ethylene and diethylene glycol toxicity. Clin Toxicol13 :297– 324,1978
          100. Glover ML, Reed MD: Propylene glycol: The safe diluent that continues to cause harm. Pharmacotherapy16 :690– 693,1996
          101. Arroliga AC, Shehab N, McCarthy K, Gonzales JP: Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults. Crit Care Med32 :1709– 1714,2004
          102. Demey HE, Bossaert LL: Propylene-glycol intoxication and nitroglycerin therapy. Crit Care Med15 :540 ,1987
            103. Melvin JJ, Hale PM, Kaye EM: Iatrogenic propylene glycol intoxication associated with the treatment of status epilepticus. Ann Neurol44 :569 ,1998
              104. Arbour R, Esparis B: Osmolar gap metabolic acidosis in a 60-year-old man treated for hypoxemic respiratory failure: Propylene glycol toxicity caused by escalating lorazepam infusion. Chest118 :545– 546,2000
              105. Bekeris L, Baker C, Fenton J, Kimball D, Bermes E: Propylene-glycol as a cause of an elevated serum osmolality. Am J Clin Pathol72 :633– 636,1979
              106. Doty JD, Sahn SA: An unusual case of poisoning. South Med J96 :923– 925,2003
              107. Parker MG, Fraser GL, Watson DM, Riker RR: Removal of propylene glycol and correction of increased osmolar gap by hemodialysis in a patient on high dose lorazepam infusion therapy. Intensive Care Med28 :81– 84,2002
              108. Bossaert LL, Demey HE: Propylene glycol Intoxication. Arch Intern Med147 :611 ,1987
              109. Reynolds HN, Teiken P, Regan ME, Habashi NM, Cottingham C, McCunn M, Scalea TM: Hyperlactatemia, increased osmolar gap, and renal dysfunction during continuous lorazepam infusion. Crit Care Med28 :1631– 1634,2000
              110. Jorens PG, Demey HE, Schepens PJ, Coucke V, Verpooten GA, Couttenye MM, Van Hoof V: Unusual D-lactic acid acidosis from propylene glycol metabolism in overdose. J Toxicol Clin Toxicol42 :163– 169,2004
              111. Zar T, Graeber C, Perazella MA: Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial20 :217– 219,2007
              112. Fulop M: Alcoholic ketoacidosis. Endocrinol Metab Clin N Am22 :209– 219,1993
              113. Fulop M, Murthy V, Michilli A, Nalamati J, Qian Q, Saitowitz A: Serum beta-hydroxybutyrate measurement in patients with uncontrolled diabetes mellitus. Arch Intern Med159 :381– 384,1999
                114. Fulop M, Bock J, Ben-Ezra J, Antony M, Danzig J, Gage JS: Plasma lactate and 3-hydroxybutyrate levels in patients with acute ethanol intoxication. Am J Med80 :191– 194,1986
                115. Umpierrez GE, DiGirolamo M, Tuvlin JA, Issacs SD, Bhoola SM, Kokko JP: Differences in metabolic and hormonal milieu in diabetic and alcohol-induced ketoacidosis. J Crit Care15 :52– 59,2000
                116. Elisaf M, Merkouropoulos M, Tsianos EV, Siamopoulos KC: Acid-base and electrolyte abnormalities in alcoholic patients. Miner Electrolyte Metab20 :274– 281,1994
                117. Bustamante EA, Levy H: Severe alkalemia, hyponatremia, and diabetic ketoacidosis in an alcoholic man. Chest110 :273– 275,1996
                118. Braden GL, Strayhorn CH, Germain MJ, Mulhern JG, Skutches CL: Increased osmolal gap in alcoholic acidosis. Arch Intern Med153 :2377– 2380,1993
                119. Duffens K, Marx JA: Alcoholic ketoacidosis: A review. J Emerg Med5 :399– 406,1987
                120. Williams HE: Alcoholic hypoglycemia and ketoacidosis. Med Clin N Am68 :33– 38,1984
                121. Miller PD, Heinig RE, Waterhouse C: Treatment of alcoholic acidosis: Role of dextrose and phosphorus. Arch Intern Med138 :67– 72,1978
                122. Halperin ML, Hammeke M, Josse RG, Jungas RL: Metabolic acidosis in the alcoholic: A pathophysiologic approach. Metabolism32 :308– 315,1983
                123. Litovitz TL, Klein-Schwartz W, Dyer KS, Shannon M, Lee S, Powers M: 1997 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med16 :443– 497,1998
                124. Watson WA, Litovitz TL, Rodgers GC, Klein-Schwartz W, Reid N, Youniss J, Flanagan A, Wruk KM: 2004 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med23 :589– 666,2004
                125. Chan KM, Wong ET, Matthews WS: Severe isopropanolemia without acetonemia or clinical manifestations of isopropanol intoxication. Clin Chem39 :1922– 1925,1993
                126. Lacouture PG, Wason S, Abrams A, Lovejoy FH: Acute isopropyl alcohol intoxication: diagnosis and management. Am J Med75 :680– 686,1983
                127. Natowicz M, Donahue J, Gorman L, Kane M, Mckissick J, Shaw L: Pharmacokinetic analysis of a case of isopropanol intoxication. Clin Chem31 :326– 328,1985
                128. Stremski E, Hennes H: Accidental isopropanol ingestion in children. Pediatr Emerg Care16 :238– 240,2000
                129. Blandford DE, Desjardins PR: A rapid method for measurement of ethylene glycol. Clin Biochem27 :25– 30,1994
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