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Ethylene glycol and methanol poisonings: case series and review.


Ethylene glycol (EG) and methanol (MTH) poisonings are important health problems because of their severe morbidity and mortality. (1) Since many of the clinical signs and symptoms associated with EG and MTH poisonings are nonspecific, it is important for the clinician to consider these toxicities since early treatment offers the best prognosis and prevents death. (2) Many hospitals are unable to perform EG and MTH measurements in a timely fashion; which in this case, a combination of a metabolic acidosis associated with a high anion gap and osmolar gap is considered the hallmark of toxic alcohol intoxication. (3,4)

We undertook a retrospective chart review of all adult patients admitted with a diagnosis of EG or MTH intoxication in order to identify laboratory abnormalities associated with ingestion as well as to determine outcomes. A review of the clinical features, pharmacokinetics, laboratory analysis, and management of EG and MTH poisonings is included in the discussion.

Materials and Methods

A retrospective chart review of all adult patients admitted to our institution with a diagnosis of EG or MTH intoxication during a 15-year period was done. Age, sex, type of poisoning, EG and MTH levels, degree of acidosis, initial anion gap (AG) and osmolar gap (OG), need for mechanical ventilation, antidote use, renal dysfunction, need for dialysis, and length of hospital stay were recorded. Hospital outcomes included renal function, need for dialysis at hospital discharge, and mortality. The equation used to calculate the OG:

OG = Measured serum osmolarity (mOsm/L) - Calculated serum osmolarity (mOsm/L),

where the measured serum osmolarity was obtained via the freezing point depression method. The calculated serum osmolarity was determined by the following equation:

2*Na + Glu/18 + BUN/2.8.

When an alcohol drip was used as an antidote, standard guidelines of the American Academy of Clinical Toxicology Practice Guidelines, were used which included a loading dose of 7 ml/kg of a 10% ethanol solution given over thirty minutes, followed by a continuous infusion of 1-2 ml/ kg/hr of a 10% ethanol solution in order to maintain the serum ethanol levels between 100 to 150 mg/dl. (5)


Eleven of the 14 patients were men, ages 19 to 59 (mean 43). Ethylene glycol accounted for ten of the toxic alcohol levels. The mean serum EG and MTH levels were 111mg/dl (range 9 to 290) and 142mg/dl (range 52 to 230) respectively. The mean pH was 7.02 (range 6.54 to 7.43). All patients had an increased anion gap metabolic acidosis and osmolar gap, (excluding one patient for whom data were unavailable) with a mean anion gap of 21 meq/l (range 15 to 31) and mean osmolar gap of 48 mOsm/l (range 29 to 81) correspondingly. Eleven required mechanical ventilation. Twelve were treated with an ethanol drip while two received fomepizole. All underwent hemodialysis. At hospital discharge, three had persistent renal insufficiency not requiring dialysis; one remained on dialysis, while seven had regained normal renal function. The average hospital stay was 8 days (range 1 to 23 days). Three patients died despite use of antidote and dialysis; all had severe metabolic encephalopathy from MTH poisoning, and death occurred after withdrawing support. Table 1 shows patient characteristics and outcomes.


EG and MTH are common industrial solvents present in a wide range of solutions. These alcohols are responsible for accidental, suicidal, and epidemic poisonings. (1) In the 2004 annual report of the Toxic Exposure Surveillance System (TESS), there were 5,562 exposures with 23 deaths and 979 exposures with 4 deaths related to EG and MTH toxicity respectively in the United States (US). (1) A review of the clinical presentation, diagnosis and treatment of EG and MTH intoxication will be discussed.

Ethylene glycol: Clinical Features

EG is a sweet-tasting substance that is often a component of antifreeze, but can also be found in engine coolants and hydraulic brake fluids. (3) Because of its sweet taste, ability to intoxicate, and relatively low cost, it is often used as a substitute for ethanol. (3)

Many authors describe three phases of EG poisoning: neurological phase, cardiopulmonary phase, and renal phase. (5) Although these stages may be concurrent, the classification offers a temporal theoretical description of EG poisoning. (5)

Stage 1: Neurological (30 minutes to 12 hours after ingestion)

Within minutes to several hours after EG poisoning, transient inebriation and euphoria, similar to the symptoms of ethanol intoxication, may be observed. (6) EG is a more potent CNS depressant than ethanol; the degree of obtundation for an equivalent serum level of ethylene glycol is more profound than for ethanol. (7) Nausea and vomiting can also occur due to direct irritation of the gastrointestinal tract by EG as confirmed by visualization under endoscopy as well as the appearance of focal hemorrhages in the gastric lining at autopsy. (7) As EG metabolism progresses, manifestations of central nervous system (CNS) depression, such as coma, hypotonia, hyporeflexia, seizures, and meningismus, replace earlier symptoms. (3,8) Cerebral edema, secondary to direct cytotoxic damage as well as the deposition of calcium oxalate in the CNS, as verified in autopsy studies, contributes to CNS depression. (9)

Stage 2: Cardiopulmonary (12-24 hours after ingestion)

Symptoms during this phase (3) include shortness of breath and physical findings are consistent with congestive heart failure. (8,9) In serious cases, severe metabolic acidosis with compensatory hyperventilation can develop accompanied by multiple organ failure. Most deaths occur in this stage. (5)

Stage 3: Renal (24-72 hours after ingestion)

The third stage can include oliguria and flank pain indicative of acute tubular necrosis and renal failure. (5) The renal toxicity of EG is thought to be due to a combination of hydronephrosis from calcium oxalate crystals and a direct toxic effect from EG metabolites. (8) Tubular atrophy and interstitial fibrosis are poor prognostic indicators of renal function. (7) Recovery of renal function is typically complete but may require several months of hemodialysis. (3)

Methanol: Clinical Features

MTH is a highly toxic alcohol commonly found in a variety of commercial products such as windshield wiper fluid, gas line antifreeze, paint strippers, and industrial solvent. (3) Symptoms and signs of MTH intoxication usually are limited to the CNS, eyes, and gastrointestinal tract. Initial symptoms may appear as soon as 12 hours post-ingestion, but usually develop 24 hours after ingestion. (10) Initial symptoms may resemble these of ethanol intoxication including drowsiness, confusion, nausea, and vomiting. (3) It produces less euphoria than ethanol. (10) Visual disturbances range from blurred vision, photophobia, visual field defects, and blindness. (11) Fundoscopic exam may reveal hyperemia of the optic disc or papilledema.11 There may be pupillary dilation and loss of the pupillary reflex. (10) Visual changes with MTH poisoning are due to microtubule and mitochondrial destruction in the retrolaminar optic nerve. (10) Severity of the visual abnormalities is directly correlated with the severity of the metabolic acidosis. (9) Severe poisoning is associated with cerebral edema, coma, and seizures. (11) Survivors may develop a parkinsonism-like syndrome which correlates with CT evidence of destruction in the putamen and subcortical white matter hemorrhage. (12) Survivors may have permanent blindness or neurological deficits. (2)


Pharmacokinetics of ethylene glycol and methanol

EG and MTH are rapidly absorbed after oral ingestion and both have a small volume of distribution (0.5-0.8 L/kg).9 The estimated minimum lethal adult dose of EG and MTH is 100 ml and 10 ml correspondingly. (3) Both undergo metabolism through hepatic alcohol dehydrogenase (ADH) to toxic metabolites as seen in Figure 1 and Figure 2.13 With normal renal function, the elimination half life of EG is 3-8 hours and that of MTH is 14-30 hours. (9) If ADH is competitively blocked by another agent, such as ethanol or fomepizole, then metabolism is halted and the parent compounds are eventually renally eliminated unchanged. (14)

Laboratory Abnormalities of ethylene glycol and methanol intoxications

The Anion Gap

Although determination of the anion gap is considered essential in the diagnosis of toxic alcohol ingestion, an anion gap acidosis will be observed only after the parent compound has been metabolized to its toxic by-products (approximately 3-6 hours depending on the elimination half life of the alcohol). (14) Glycolic acid and formic acid are largely responsible for the anion gap metabolic acidosis in the metabolism of EG and MTH respectively. (3) However, some of the acidosis stems from the production of lactate and is due to the reduction of nicotinamide adenine dinuleotide to nicotinamide adenine dinucliotide, reduced form. (3) Furthermore, the anion gap cannot be relied on as an accurate screening tool in cases where ethanol is a coingestant. (15) An ethanol level of greater than 100 mg/dl competitively inhibits ADH and will increase the elimination half life by fivefold or more. (14)

All patients admitted with a diagnosis of EG or MTH intoxication had an elevated anion gap (Table 1). It is of interest that patient number nine presented with a very high ethylene glycol level with only a mild elevation of the anion gap; it is presumed that patient number nine presented very early in the course of toxicity given that there was not any evidence of other sources of intoxication.

The Osmolar Gap

The parent compound contributes to the osmolar gap because it is osmotically active and has a relatively small molecular weight. (3) Toxic acids generated by EG and MTH metabolism do not contribute to the osmolar gap; thus, the longer the delay in measurement of serum osmolarity from the time of ingestion, the more likely the osmolar gap may approach normal values. (14) Although it is conventionally believed that an OG of less than 10 mOsm/L is normal, other authors have found that the range of normal osmol values within the population is large (-5 to +15 mOsm/L). (16) Also, the value of the OG depends on the equation used to determine the gap; for example, the inclusion of ethanol in its determination lowers the traditionally accepted OG. (16) Further, other conditions such as alcoholic ketoacidosis, lactic acidosis, renal failure are associated with an elevated OG. (15)


All patients admitted with EG or MTH poisoning had an elevated osmolar gap (except patient number nine where the OG data were unavailable, Table 1).


Calcium oxalate deposition in tissues is one mechanism of toxicity, which contributes to hypocalcemia. Oxalate crystalluria is considered a hallmark of EG poisoning. (9) Up to 50% of patients with EG toxicity have calcium oxalate crystals in their urine and, if present, aides in diagnosis. (5) However, the absence of calcium oxalate crystaluria does not exclude EG poisoning. (8)

Management of ethylene glycol and methanol poisoning

The first approach to a patient suspected to have toxic alcohol poisoning is appropriate airway management, resuscitation and stabilization. (2) If toxic alcohol poisoning is suspected, poison control should be contacted and specific treatment goals should be undertaken even if a history of ingestion is not obtainable.

The specific treatment goals are correction of metabolic acidosis, ADH blockade, and removal of the alcohol and its metabolites. Although there are no data to support the use of sodium bicarbonate for the treatment of toxic alcohol induced metabolic acidosis, most guidelines support this temporizing maneuver for patients with an arterial pH below 7.3 while awaiting more permanent treatment with hemodialysis. (3) Antidotes available to block the action of ADH include ethanol and fomepizole. (6) The indications for use of an antidote have been outlined by the American Academy of Clinical Toxicology as seen in Table 2.5, (10) Standard dosing regimens for ethanol and fomepizole are available in the most current guidelines. (5,10) Fomepizole is the preferred antidote because it is easier to dose, does not require frequent blood monitoring, and it does not cause CNS depression. (9) Some studies have suggested that fomepizole may be an effective and safe first line antidote for EG and MTH intoxication, possibly obviating the need for hemodialysis. (17-19) Other studies have alluded to this concept, but have called for further research to determine if fomepizole alone is adequate treatment for toxic alcohol ingestions. (20) Rapid removal of EG and MTH through hemodialysis, before they have been metabolized, remains the cornerstone of therapy. (5,10) In general, hemodialysis is indicated in patients who have metabolic acidosis, renal compromise, visual symptoms (in cases of MTH toxicity), deterioration despite intensive supportive care, or electrolyte abnormalities unresponsive to conventional therapy. (5,10) Co-factor therapy with thiamine, pyridoxine, and magnesium, to enhance the metabolism of glycolic acid, may be considered; similarly, folinic acid administration can be used in cases of MTH poisoning since it may augment the conversion of toxic to nontoxic metabolites. (5) However, there are no human studies to support these practices. (5)


The degree of metabolic acidosis at admission (serum pH less than 7.00) has been associated with a high mortality rate secondary to EG and MTH intoxication. (21-23) Coma at admission has a poor prognosis in EG and MTH overdose. (22,24-25) Most of our patients admitted for EG intoxication who survived, regained normal renal function; only one remained on hemodialysis at discharge.


Most of our patients presented with a decreased level of consciousness and inability to give a good history. In addition, family members may be unaware of or embarrassed by the patients' extensive drinking habits and, therefore, unable or unwilling to provide much historical content. Since the signs and symptoms of EG and MTH poisoning are nonspecific, the diagnosis of EG or MTH poisoning can be missed. The clinician is limited to laboratory analyses to support the diagnosis of EG or MTH intoxication. The classic finding are an anion gap metabolic acidosis with an osmolar gap, and seen in our group of patients. If a reason for a high osmolar gap is not obvious in a patient with an anion gap metabolic acidosis, EG and MTH poisoning must be suspected. Other clinical clues to intoxication include urinary crystals indicative of EG poisoning and visual complaints supportive of MTH poisoning.

Supportive care, ADH blockade, and hemodialysis are the standard treatment for EG and MTH poisonings. Treatment must be started immediately. With prompt, aggressive treatment, most patients will recover renal function and avoid long term sequelae. (5,10)


(1.) Watson WA., Litovitz TL, Rodgers GC, et al. 2004 Annual report of the American association of poison control centers toxic exposure surveillance system. Am Journal Emergency Medicine 2005; 23(5): 589-666.

(2.) Jacobsen D, McMartin KE. Antidotes for methanol and ethylene glycol poisoning. Clinical Toxicology 1997; 35(2): 127-143.

(3.) Abramson S, Singh AK. Treatment of the alcohol intoxications: ethylene glycol, methanol, and isopropanol. Current Opinion Nephrology Hypertension 2000; 9: 695-701.

(4.) Hovda KE, Hunderi OH, Rudberg N, et al. Anion and osmolal gaps in the diagnosis of methanol poisoning: clinical study in 28 patients. Intensive Care Med 2004; 30:1842-1846.

(5.) Miller H, Barceloux DG, Krenzelok EP, et al. American academy of clinical toxicology practice guidelines on the treatment of ethylene glycol poisoning. Clinical Toxicology 1999; 37(5): 537-560.

(6.) Hall JB, Schmidt GA, Wood LD. Toxicology in adults. In principles of critical care. New York, NY. The McGraw-Hill Company 2005: 1519-1520.

(7.) Davis DP, Bramwell KJ, Hamilton RS, et al. Ethylene glycol poisoning: case report of a record-high level and a review. J Emerg Med 1997; 15(5): 653-667.

(8.) Wine H, Savitt D, Abuelo G. Ethylene glycol intoxication. Seminars in Dialysis 1994; 7(5): 338-345.

(9.) Kraut JA, Kurtz I. Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol 2008; 3(1):208-225.

(10.) Barceloux DG, Bond GR, Krenzelok EP, et al. American academy of clinical toxicology practice guidelines on the treatment of methanol poisoning. Clinical Toxicology 2002; 40(4): 415-446.

(11.) Kruse JA. Methanol poisoning. Intensive Care Med 1992; 18:391-397.

(12.) McLean DR, Jacobs H, Mielke BW. Methanol poisoning: a clinical and pathological study. Ann Neurol 1980; 8: 161-167.

(13.) Hall AH. Ethylene glycol and methanol: poisons with toxic metabolic activation. Emerg Med Rpt 1992. 13(4): 29-38.

(14.) Mycyk MB, Aks SE. A visual schematic for clarifying the temporal relationship between the anion and osmol gaps in toxic alcohol poisoning. American Journal Emergency Medicine 2003: 21(4): 333-335.

(15.) Ammar, KA, Heckerling, PS. Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: Importance of the osmolal gap. Am J Kidney Dis 1996; 27(1):130-133.

(16.) Hoffman R, Smilkstein M, Howland M, et al. Osmol gaps revisited: normal values and limitations. Clinical Toxicology. 1993;31(1): 81-93.

(17.) Megarbane B, Borron SW, Baud FJ. Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Med 2005; 31: 189-195.

(18.) Megarbane B, Borron SW, Trout H, et al. Treatment of acute methanol poisoning with fomepizole. Intensive Care Med 2001; 27:1370-1378.

(19.) Hovda KE, Froyshov S, Gudmundsdottir H, et al. Fomepizole may change indication for hemodialysis in methanol poisoning: prospective study in seven cases. Clinical Nephrology 2005; 64(3): 190-197.

(20.) Green R. The management of severe toxic alcohol ingestions at a tertiary care center after the introduction of femepizole. Amer J Emer Med 2007; 25: 799-803.

(21.) Karlson-Stiber C, Persson H. Ethylene glycol poisoning: experiences from an epidemic in Sweden. Clinical Toxicology 1992; 30(4): 565-574.

(22.) Hovda KE, Hunderi H, Tafjord AB, et al. Methanol outbreak in Norway 2002-2004: epidemiology, clinical features and prognostic signs. J Int Med 2005; 258: 181-190.

(23.) Hassanian-Moghaddam H, Pajoumand A, Dadgar SM, et al. Prognostic factors in methanol poisoning. Human & Experimental Toxicology. 2007; 26: 583-586.

(24.) Liu JJ, Daya MR, Carrasquillo O, et al. Prognostic factors in patients with methanol poisoning. Clinical Toxicology 1998; 36(3): 175-181.

(25.) Hylander B, Kjellstrand CM. Prognostic factors and treatment of severe ethylene glycol intoxication. Intensive Care Med 1996; 22: 546-552.

Carol A. Montjoy, MD

Fellow, West Virginia University, Robert

C. Byrd Health Sciences Center

Aamer Rahman, MD

Pulmonary/CCM, Piedmont Pulmonary


Luis Teba, MD

Professor, West Virginia University

School of Medicine
Table 1. Patient Characteristics and Outcomes

          Age(yrs)   Sex   EG mg/dl   MTH mg/dl    PH    AG   OG

  #1         42       F      125                  7.17   18   61

  #2         42       F      134                  7.08   26   37

  #3         53       F       65                  7.12   25   29

  #4         49       M       70                  6.8    29   36

  #5         49       M        9                  7.16   26   49

  #6         59       M                   52      6.88   20   42

  #7         31       M                  102      7.31   17   98

  #8         41       M                  184      6.8    31   52

  #9         47       M      290                  7.43   15

  #10        43       M                  230      6.8    22   42

  #11        39       M       87                  7.34   21   51

  #12        48       M       49                  7.09   19   38

  #13        46       M      240                  6.54   27   81

  #14        19       M       48                  6.94   26   20

          MV    Dialysis   Fomepizole   Ethanol   Outcome

Patient                                           normal renal
  #1      Yes     yes         Yes                 function

Patient                                           Renal
  #2      Yes     yes                     yes     insufficiency

Patient                                           normal renal
  #3      No      yes                     yes     function

Patient                                           normal renal
  #4      Yes     yes                     yes     function

Patient                                           normal renal
  #5      Yes     yes                     yes     function

  #6      Yes     yes                     yes     Expired

Patient                                           normal renal
  #7      No      yes                     yes     function

  #8      Yes     yes                     yes     Expired

Patient                                           normal renal
  #9      No      yes                     yes     function

  #10     Yes     yes                     yes     Expired

Patient                                           normal renal
  #11     Yes     yes                     yes     function

  #12     Yes     yes                     yes     renal insufficiency

  #13     Yes     yes                     yes     renal insufficiency

  #14     Yes     yes         Yes                 Dialysis

EG- Ethylene glycol(mg/dl), MTH- Methanol,(mg/dl) AG-Anion gap (meq/l)

OG-Osmolar gap(mosm/l), MV (mechanical ventilation)

Table 2: Indications for the Treatment of EG and MTH Poisoning with
Ethanol or Fomepizole

Documented plasma EG or MTH concentration > 20 mg/dL


Documented recent history of ingesting toxic amounts of EG or MTH
and OG > 10 mOsm/L


History or strong clinical suspicion of EG or MTH poisoning and at
least two of the following:

(A) Arterial pH< 7.3

(B) Serum bicarbonate < 20 meq/L

(C) Osmolal gap > 10 mOsm/L

(D) Urinary oxalate crystals present (in the case of EG poisoning)

Data are from the American Academy of Clinical Toxicology Ad Hoc
Committee on the Treatment Guidelines for Ethylene Glycol and
Methanol Poisoning. (5,10)
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Title Annotation:Scientific Article
Author:Montjoy, Carol A.; Rahman, Aamer; Teba, Luis
Publication:West Virginia Medical Journal
Article Type:Report
Geographic Code:1USA
Date:Sep 1, 2010
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