2 Meera Bajwa, MD, INDEX WORDS: Methanol intoxication; nitromethane; metabolic acidosis; creatinine; fomepizole. ClinicalHistory

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1 ACID-BASE AND ELECTROLYTE TEACHING CASE Spurious Elevation in Serum Creatinine Caused by Ingestion of Nitromethane: Implication for the Diagnosis and Treatment of Methanol Intoxication Anjay Rastogi, MD, 1 Brandon Itagaki, MD, 2 Meera Bajwa, MD, 1 and Jeffrey A. Kraut, MD 3,4,5 INDEX WORDS: Methanol intoxication; nitromethane; metabolic acidosis; creatinine; fomepizole. ethanol is a clear colorless liquid that is M used as a solvent in industrial production, serves as a substitute for ethanol in illegally 1 produced spirits, and is an additive to fuel. Methanol toxicity can occur with inhalation or dermal absorption, particularly in burn patients, 2 but is most common after ingestion. In 1999, approximately 2,000 cases of methanol intoxication were reported to the American Association 2 of Poison Control Centers, representing 1% of poisonings reported that year. The majority of these were caused by ingestion of ethanol to which methanol was added. The effects of methanol intoxication include metabolic acidosis, retinal damage producing visual difficulties, and neurological complications. 3 If the disorder is not recognized quickly and treatment is not instituted promptly, death or blindness may ensue. 4,5 The diagnosis of methanol intoxication is suggested by the presence of high-anion-gap metabolic acidosis associated 6 with an increased serum osmolal gap. However, either of these laboratory abnormalities may be absent depending on several factors, including time after ingestion and the presence of substances in the blood that can affect its metabolism. In this regard, if methanol is ingested with ethanol or other substances with high affinity for alcohol dehydrogenase, an enzyme critical to the generation of the toxic metabolites, clinical and biochemical abnormalities may not develop for 96 hours, making the diagnosis of this disorder more difficult. 3 We describe an individual who ingested model containing both methanol and nitromethane on 2 separate occasions separated by many months. Ingestion of the fuel led to mild metabolic acidosis associated with increased serum osmolality and a striking increase in serum creatinine concentration, measured by using a colorimetric method. However, serum creatinine measurement using an enzymatic method showed it to be normal. The patient was treated with fomepizole (Antazol; Jazz Pharmaceuticals, Palo Alto, CA) and hemodialysis and had an uncomplicated hospital course. She was discharged with normal renal function, normal electrolyte levels and acid-base balance, and no visual or neurological abnormalities. An explanation for the increased serum creatinine concentration, salient characteristics of methanol intoxication, and recommendations for treatment are reviewed. ClinicalHistory CASEREPORT A 22-year-old woman was seen in the emergency department 30 hours after reporting she ingested 16 ounces of model. The patient ingested this substance after an argument with her father and subsequently fell asleep. Two years previously, she had also ingested model airplane fuel. She was admitted to the hospital at that time and treated with hemodialysis. She recovered from the incident without sequelae and had been in good health subsequently. The patient denied abdominal pain, nausea, vomiting, visual disturbances, or headache. She denied using any other medication, chemicals, or alcohol in the period before being seen. She had no history of renal, cardiac, neurological, or hepatic disease. Renal function and blood chemistry test results were normal 6 months earlier. From the 1 Division of Nephrology and 2 Department of Medicine, UCLA Center for Health Sciences and David Geffen School of Medicine; 3 Medical and Research Services, 4 UCLA Membrane Biology Laboratory, VHAGLA Healthcare System, and 5 Division of Nephrology, VHAGLA Healthcare System and David Geffen School of Medicine, Los Angeles, CA. Received October 2, Accepted in revised form December 12, Originally published online as doi: /j.ajkd on February 15, Address correspondence to Jeffrey A. Kraut, MD, Division of Nephrology, VHAGLA Healthcare System, Wilshire Blvd, Los Angeles, CA jkraut@ ucla.edu 2008 by the National Kidney Foundation, Inc /08/ $34.00/0 doi: /j.ajkd American Journal of Kidney Diseases, Vol 52, No 1 (July), 2008: pp

2 182 Physical examination in the emergency department showed temperature of 37.2 C, regular pulse of 100 beats/min, blood pressure of 132/50 mm Hg in the sitting position, and respiratory rate of 16 breaths/min. Lungs were clear to auscultation and percussion. Cardiac examination showed no murmurs or gallops, and abdominal examination showed no tenderness. There was no peripheral edema. She was alert and responsive without focal neurological signs. Additional Investigations Results of blood work performed during her hospitalization are listed in Table 1. On urinalysis, there was trace protein and 1 ketones. Urinalysis showed no cells or crystals. Urine myoglobin level was less than 1 mg/l. Serum acetaminophen, ethyl alcohol, acetone, and isopropyl alcohol were undetectable. A renal ultrasound showed normalsized kidney without abnormalities. Diagnosis On the basis of a history of ingestion of the ; serum osmolal gap of approximately 70 mosm/kg H 2 O (70 mmol/kg H 2 O); undetectable blood acetaminophen, ethyl alcohol, and isopropyl alcohol; and normal blood glucose concentration, a presumptive diagnosis of methanol intoxication was made. Clinical Follow-up The patient was treated initially with fomepizole therapy and 4 hours of hemodialysis. She subsequently was dialyzed on 2 other occasions. Fomepizole therapy was continued throughout this period with the following regimen: 1,200 mg every 12 hours for 3 doses and 700 mg every 12 hours for 3 doses. On the second day after admission, repeated laboratory studies (Table 1) showed a serum creatinine level that decreased to 8.4 mg/dl (743 mol/l) with the Jaffé reaction and serum osmolality of 303 mosm/kg H 2 O (303 mmol/kg H 2 O). Serum methanol concentration obtained on admission Rastogi et al was 71 mg/dl (22.15 mmol/l; value reported 48 hours after admission). Serum methanol concentration from the second day of admission, after hemodialysis and fomepizole treatment, was 26 mg/dl (8.11 mmol/l). Because of recognition that 1 of the components of model interferes with measurement of serum creatinine when performed using the Jaffé reaction, blood obtained on admission was retested using an enzymatic assay and showed a serum creatinine concentration of 0.5 mg/dl (44 mol/l). The patient remained alert without evidence of neurological, visual, or abdominal abnormalities throughout her hospital course. Serum electrolyte levels and renal function were normal at the time of discharge. DISCUSSION The patient reported the ingestion of model airplane fuel in a suicide attempt approximately 30 hours before admission. A previous attempt using this same method was unsuccessful a few years before admission. Chemical examination of serum on admission showed an increased osmolal gap, findings consistent with accumulation in the blood of a low-molecular-weight substance. Toxicological analysis 48 hours after admission confirmed this substance as methanol. Serum bicarbonate concentration and serum anion gap at the time of admission were only mildly abnormal, consistent with a low rate of production of formic acid, the major metabolite of methanol. The patient was treated with intermittent hemodialysis concomitantly with administration of fomepizole, a specific inhibitor of alcohol dehydrogenase, which has an affinity for the enzyme at least 1,000 times greater than methanol. 7 Treatment re- Table 1. Laboratory Studies During Hospitalization Test Admission 17 Hours After Admission Day 2 Day 3 Sodium (meq/l) Potassium (meq/l) Chloride (meq/l) Total carbon dioxide (meq/l) Blood urea nitrogen (mg/dl) Serum creatinine (mg/dl)* Creatinine kinase (U/L) 150 Anion gap (meq/l) Serum osmolality (mosm/kg H 2 O) Osmolal gap (mosm/kg H 2 O) 70 Methanol (mg/dl) Note: Dialysis was performed on admission and on days 2 and 3. To convert serum creatinine in mg/dl to mol/l, multiply by 88.4; urea nitrogen in mg/dl to mmol/l, multiply by Sodium, potassium, chloride, and total carbon dioxide levels in meq/l are equivalent to levels expressed in mmol/l. Anion gap, serum osmolality, and osmolal gap amounts in mosm/kg are equivalent to levels expressed in mmol/kg. *Values obtained using the Jaffé reaction. Normal range is 12 to 180 U/L.

3 Nitromethane and Methanol Intoxication 183 sulted in a significant decrease in serum methanol concentration and osmolality without development of more severe metabolic acidosis, visual difficulty, or neurological complications. A strikingly increased serum creatinine level of 23.7 mg/dl (2,095 mol/l) was present on admission, consistent with acute renal failure. Although serum creatinine level was increased, blood urea nitrogen level was within the normal range, serum potassium concentration was not increased, daily urine output was greater than 1 L, and renal ultrasound showed no obstruction. Furthermore, creatine kinase values were not increased, excluding rhabdomyolysis. These findings suggested that serum creatinine determination might be spurious. The model ingested by the patient, commonly referred to as glow fuel, contained nitromethane ( 35%) in addition to methanol ( 43%). The former compound was shown to spuriously increase serum creatinine levels when measured by using the Jaffé method. 8 Repeated measurement of serum creatinine using an enzymatic assay confirmed that serum creatinine concentration was normal. This case exemplifies some potential problems that can be encountered in the diagnosis of simultaneous methanol and nitromethane intoxication, the importance of historical information, and the value of rapid initiation of appropriate treatment to decrease mortality and prevent the development of serious complications. Epidemiological Characteristics of Methanol Intoxication Methanol, or wood alcohol, is used to make such products as plastic, plywood, and paint. It is present in windshield wiper fluid, antifreeze, and model. It is colorless and described as either odorless or having a faint pungent odor. These physical properties make its detection difficult. Review of records from poison control centers in the United States showed that approximately 1,000 to 2,000 cases of methanol intoxication are reported each year. 2 Similar outbreaks of methanol intoxication also were reported throughout the world. 3 The majority of cases of methanol intoxication are caused by ingestion of ethanol adulterated with methanol, accidental ingestion by children, or its use in suicide attempts. Mortality rates of patients with methanol intoxication are variable: in the 1953 epidemic, it was approximately 8%, 9 and in 1 recent outbreak in Sweden, it was approximately 28%. 3 Mortality and complications are related to severity of metabolic acidosis upon presentation. In 2 studies composed of more than 370 patients, serum bicarbonate concentration less than 10 meq/l ( 10 mmol/l) or blood ph less than 7.0 was associated with a mortality rate of 50% to 89%. 9,10 Furthermore, development of irreversible blindness and neurological complications also was more frequent in patients with severe metabolic acidosis. 5,10 Thus, early recognition of the disorder is important. Review of the MEDLINE database showed only 4 case reports of coingestion of methanol and nitromethane contained in model, similar to this patient. 8,11-13 In 2 other cases, nitromethane was absorbed from race car fuel after a car accident, although methanol was not detected in the blood. 13,14 Salient characteristics of these patients are listed in Table 2. As a consequence, clinicians might not be aware of the possible impact of nitromethane on serum creatinine concentration, which could have important ramifications for the diagnosis and treatment of methanol intoxication. Metabolism of Methanol As shown in Fig 1, methanol is metabolized in the liver by the enzyme alcohol dehydrogenase to formaldehyde. Formaldehyde is then converted to formic acid, a process catalyzed by the enzyme formaldehyde dehydrogenase, and finally to carbon dioxide and water. The metabolism of methanol can be delayed substantially by the presence of ethanol or other substance with a greater affinity for the enzyme alcohol dehydrogenase. In our patient, the strikingly increased serum osmolality (explained only in part by increased serum methanol levels) predicted an increase in serum osmolality of 24 mosm/kg (24 mmol/kg) and mild metabolic acidosis found 30 hours after the ingestion is consistent with delayed metabolism of methanol. The delay in metabolism presumably is caused by substances in the that effectively compete with methanol for binding to alcohol dehydrogenase. Of the compounds present in the, polyalkaline glycol seems the most likely candidate.

4 184 Rastogi et al Table 2. Cases of Combined Nitromethane and Methanol Exposure Serum Creatinine (mg/dl) Patient Method of Intoxication* Jaffé Enzymatic Treatment Reference 22-year-old woman 2-year 9- monthold boy 25-year-old man 39-year-old man 23-year-old woman 25-year-old man 4-year-old girl Ingestion of model Fomepizole, hemodialysis Present report Ingestion of model 6.0 Supportive care Booth et al Absorption through skin of 8.6 Normal Supportive care Gabrielli and fuel (95% nitromethane, Hammett-Stabler 14 5% methanol) after car crash Ingestion of model Ethanol, hemodialysis De Leacy et al 8 (70% methanol, 30% nitromethane) Ingestion of model 17.9 Ethanol, hemodialysis Mullins and Hammett-Stabler 13 Absorption through skin of Supportive care Mullins and fuel Hammett-Stabler 13 Ingestion of model 4.0 Normal Fomepizole Leonard and Akhtar 12 Note: To convert serum creatinine in mg/dl to mol/l, multiply by *Proportion of methanol and nitromethane present shown if available. Initial measurement. Second measurement during treatment. Actual values for creatinine with enzymatic assay not given. Clinical and Laboratory Findings With Methanol Intoxication Visual disturbances, abdominal pain, and headache are common with methanol intoxication. 3,9 In one study of 51 patients, 49% of patients manifested abdominal pain and 37% had visual disturbances. 3 Visual disturbances were attributed to the effect of formic acid. 5 The development of clinical and laboratory abnormalities with methanol intoxication can take many hours, particularly if ethanol or other substances are ingested that compete with methanol for the enzyme. 15 In a large series of more than 300 patients ingesting bootlegged whiskey, the period before overt symptoms developed averaged 24 hours, with some patients manifesting symptoms later than 72 hours. 9 Similarly, the metabolic acidosis associated with methanol intoxication, which is primarily caused by formic acid generation, may not develop for many hours. 1,3,5 In our patient, the absence of clinical findings, mildness of the metabolic acidosis (serum bicarbonate, 18 meq/l [18 mmol/l]), the minimal increase in serum anion gap (change in anion gap of 6 meq/l [6 mmol/l] compared with value obtained at discharge), and the minimal increase in serum lactate concentration (lactate generation was attributed to inhibition of cellular respiration by formate) are additional evidence that the bulk of the methanol remained unmetabolized at presentation. Diagnosis of Methanol Intoxication The diagnosis of methanol intoxication is classically considered in a patient with high-anion-gap metabolic acidosis and increased serum osmolal gap. 16 The increment in serum osmolality is related to both the concentration and molecular weight of methanol. Because the molecular weight of methanol is 32.04, serum osmolality will be increased by 3.3 mosm/kg H 2 O for every 10-mg/dL increase in serum methanol concentration. Serum methanol concentration in this patient was 71 mg/dl, which should have caused a serum osmolal gap of only 20 mosm/kg H 2 O (20 mmol/kg H 2 O). However, the serum osmolal gap was 70 mosm/kg H 2 O (70 mmol/kg H 2 O). This disparity between the predicted serum osmolal gap (based on the serum concentration of methanol) and the measured osmolal gap indicates the presence of other low-molecular-weight substances in the blood. Substances con-

5 Nitromethane and Methanol Intoxication 185 Figure 1. Metabolic pathway for methanol. Methanol is metabolized to formaldehyde under the influence of the enzyme alcohol dehydrogenase (ADH). Formaldehyde is then converted to formic acid under the influence of formaldehyde dehydrogenase (FMD) and finally to carbon dioxide (CO 2 ) and water (H 2 O). Abbreviations: NAD, nicotinamide-adenine dinucleotide; NADH, the reduced form of NAD. tained in the model that could increase serum osmolality include polyalkaline glycol (molecular weight, 102.3) and nitromethane (molecular weight, 61.01). If a history of methanol ingestion is not available, osmolal gap and high-anion-gap metabolic acidosis are important clues to the diagnosis of methanol intoxication. In our patient, the increase in serum osmolality was striking, whereas the decrease in serum bicarbonate level and increase in anion gap was modest. As noted, this constellation of laboratory findings is not unusual with methanol or other alcohol-related intoxications. Several reports of methanol intoxication showed that within the first few hours after ingestion of methanol, there was marked discordance between the increment in serum osmolality, decrease in serum bicarbonate concentration, and change in anion gap. 3,17 Subsequently, as methanol is metabolized to formic acid, serum osmolality will decrease while serum anion gap increases. Several hours after the ingestion, when most of the methanol is converted into formic acid, serum osmolality will decrease substantially, resulting in a high-anion-gap metabolic acidosis with correction of serum osmolality. Thus, hyperosmolality alone, hyperosmolality with highanion-gap metabolic acidosis, or high-anion-gap metabolic acidosis with little change in osmolality are all consistent with the diagnosis of methanol intoxication. Several other alcohol intoxications can produce clinical and laboratory abnormalities that mimic methanol intoxication, including ethylene glycol intoxication, diethylene glycol intoxication, propylene glycol intoxication, isopropanol intoxication, and alcoholic ketoacidosis. 18 Although certain aspects of treatment of these disorders may be similar to those of methanol intoxication, differentiation between methanol intoxication and these disorders is important to be able to quickly provide appropriate therapy. Important diagnostic clues and major methods of treatment for each of these disorders are listed in Table 3. Serum creatinine level increased strikingly in this patient. Renal failure in the absence of hypotension is not common in patients with methanol intoxication, in contrast to ethylene glycol intoxication, in which crystalluria and calcium oxalate deposition can induce renal failure. 18,19 There was no evidence of rhabdomyolysis, reflected by increased creatine kinase values to explain the increased serum creatinine concentration. Therefore, had a history of ingestion of not been obtained, a diagnosis of acute renal failure could have been made. However, spurious increases in serum creatinine levels have been reported with ingestion of glow fuel or other model. Glow fuel contains nitromethane (CH 3 NO 2 ), a highly lipid-soluble moiety that interferes with the measurement of serum creatinine when determined using the Jaffé reaction. 8,13 Measurement of creatinine in blood using the Jaffé reaction is accomplished when it reacts with picrate ion formed in an alkaline medium to develop a red-orange color. The color produced from the sample is then examined in a colorimeter at a wavelength of 505 nm. The reading found is compared with standards determined by using a known amount of creatinine under the same conditions. The Jaffé reaction is known to be nonspecific. Many compounds, including protein, glucose, ascorbic acid, acetone, and keto acids, can react with picrate and cause overestimation of creatinine level in plasma. Similarly, nitromethane reacts with picrate, causing overestimation of serum creatinine concentration. 8 In the presence of nitromethane, despite normal serum creatinine concentrations, values as high as 18 to 20 times the upper limit of normal were reported. 8 In this regard, De Leacy et al 8 found a direct linear relationship between levels of nitromethane and creatinine in blood when determined using the Jaffé method. However, nitromethane does not interfere with the measurement of

6 186 Rastogi et al Table 3. Differential Diagnosis of Toxic Alcohol Intoxications Disorder Diagnostic Clues* Treatment Methanol intoxication Hyperosmolality with osmolal gap Fomepizole or alcohol High-anion-gap metabolic acidosis Dialysis Optic papillitis Folic acid Base Ethylene glycol Hyperosmolality with osmolal gap Fomepizole or alcohol intoxication High-anion-gap metabolic acidosis Dialysis Calcium oxalate crystals in urine Thiamine Acute renal failure Pyridoxine Base Diethylene glycol Hyperosmolality with osmolal gap Fomepizole or alcohol intoxication High-anion-gap metabolic acidosis Dialysis Acute renal failure Base History of cohort with similar abnormalities Propylene glycol Hyperosmolality with osmolal gap Discontinuation of medication with propylene intoxication Lactic acidosis glycol usually sufficient History of administration of medication containing propylene glycol Dialysis in selected cases with severe lactic acidosis or extremely high serum propylene glycol levels Isopropanol intoxication Hyperosmolality and osmolal gap Supportive care; consider dialysis with serum Metabolic acidosis uncommon without hypotension concentration 400 mg/dl Alcoholic ketoacidosis High-anion-gap metabolic acidosis Supportive care Positive ketones in blood or urine that become more prominent with H 2 O 2 Administration of saline and glucose Insulin with significant hyperglycemia Osmolality can be increased, but often normal Base treatment with severe metabolic acidosis History of binge drinking *Appearance of increased serum osmolality and high-anion-gap metabolic acidosis will depend on duration elapsing after ingestion and presence of other substances that affect alcohol dehydrogenase. Treatment measures depend on severity of disorder, time after ingestion, and comorbid conditions. See reference 18 for fuller details. serum creatinine when it is done using an enzymatic assay. 8 In the present case, determination of serum creatinine simultaneously using the Jaffé reaction and enzymatic assay showed a marked discrepancy. Serum creatinine level was only 0.5 mg/dl (44 mol/l) with the enzymatic assay at a time when it measured 23.7 mg/dl (2,095 mol/l) with the Jaffé reaction. Treatment of Methanol Intoxication The consensus statement of the American Academy of Clinical Toxicology published in recommends that ethanol or fomepizole, inhibitors of alcohol dehydrogenase, be administered for the treatment of patients with methanol intoxication when plasma methanol concentration is greater than 20 mg/dl, there is a recent history of ingestion of methanol in association with a serum osmolal gap greater than 10 mosm/kg H 2 O( 10 mmol/kg H 2 O), or there is strong clinical suspicion of methanol poisoning with at least 2 of the following findings: arterial ph less than 7.3, serum bicarbonate level less than 20 meq/l ( 20 mmol/l), and osmolal gap greater than 20 mosm/kg H 2 O( 20 mmol/kg H 2 O). 5,18,20 Thus, this patient met criteria for treatment with fomepizole. Hemodialysis, in addition to fomepizole, is recommended by some for presumed methanol intoxication when serum concentration is greater than 50 mg/dl (15.60 mmo/l) or in the presence of metabolic acidosis (blood ph 7.25 to 7.30), visual abnormalities, renal failure, or electrolyte imbalance unresponsive to conventional therapy. 5 However, others showed that patients with methanol concentrations greater than 50 mg/dl (15.60 mmo/l) who are not acidemic or in renal failure can be treated with fomepizole therapy alone without hemodialy-

7 Nitromethane and Methanol Intoxication 187 sis. 21 Because this patient was not acidemic and measurement of serum creatinine using an enzymatic method showed she did not have acute renal failure, she might have been treated with fomepizole alone rather than being dialyzed. Although the decision to dialyze this patient was based on the presumed severity of the methanol intoxication irrespective of serum creatinine concentration, appreciation of the potential impact of nitromethane on serum creatinine concentration could be a factor in the choice of treatment modalities. In summary, methanol intoxication should be considered in individuals with high-anion-gap metabolic acidosis, hyperosmolal states, or changes in mentation without an obvious cause. To this group of findings as possible clues to the presence of methanol intoxication should be added an increased serum creatinine concentration in the absence of other stigmata of renal failure. 22 ACKNOWLEDGEMENTS We thank Lesley Edelstein for secretarial assistance. Support: The work was supported in part by research funds from the Veterans Administration, and a National Institutes of Health grant training grant, T32 DK Dr Bajwa receives grant support from the National Institutes of Health; Dr Kraut receives funding from the National Institutes of Health and the Veterans Administration Healthcare System. Financial Disclosure: None. REFERENCES 1. Tephly TR: The toxicity of methanol. Life Sci 48: , Litovitz TL, Klein-Schwartz W, White S, et al: 1999 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 18: , Hovda KE, Hunderi OH, Tafjord AB, et al: Methanol outbreak in Norway : Epidemiology, clinical features and prognostic signs. J Intern Med 258: , Abramson S, Singh AK: Treatment of the alcohol intoxications: Ethylene glycol, methanol and isopropanol. Curr Opin Nephrol Hypertens 9: , 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 Toxicol 40: , 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 Med 30: , Brent J, McMartin K, Phillips S, Aaron C, Kulig K: Fomepizole for the treatment of methanol poisoning. N Engl J Med 344: , Deleacy EA, Brown NN, Clague AE: Nitromethane interferes in assay of creatinine by the Jaffé reaction. Clin Chem 35: , Bennett JL, Cary FH, Mitchell GL, Cooper MN: Acute methyl alcohol poisoning: A review based on experiences in an outbreak of 323 cases. Medicine 32: , Liu JJ, Daya MR, Carrasquillo O, Kales SN: Prognostic factors in patients with methanol poisoning. J Toxicol Clin Toxicol 36: , Booth CJ, Naidoo D, Rosenberg AR, Kainer G: Elevated creatinine after ingestion of model aviation fuel: Interference with the Jaffé reaction by nitromethane. J Paediatr Child Health 35: , Leonard CP, Akhtar J: Co-ingestion of methanol and nitromethane: Using falsely elevated creatinine as indicator for methanol antidote use. Pediatr Crit Care Med 8: , Mullins ME, Hammett-Stabler CA: Intoxication with nitromethane-containing fuels: Don t be fueled by the creatinine. J Toxicol Clin Toxicol 36: , Gabrielli A, Hammett-Stabler C: False elevation of serum creatinine following skin absorption of nitromethane complicates the clinical diagnosis of rhabdomyolysis. Chest 113: , Jacobsen D, McMartin KE: Methanol and ethyleneglycol poisonings mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol Adverse Drug Exp 1: , Aabakken L, Johansen KS, Rydningen EB, et al: Osmolal and anion gaps in patients admitted to an emergency medical department. Hum Exp Toxicol 13: , Paasma R, Hovda KE, Tikkerberi A, Jacobsen D: Methanol mass poisoning in Estonia: Outbreak in 154 patients. Clin Toxicol 45: , Kraut J, Kurtz I. Toxic alcohol ingestions: Clinical features, diagnosis, and management. Clin J Am Soc Nephrol 3: , Eder AF, McGrath CM, Dowdy YG, et al: Ethylene glycol poisoning: Toxicokinetic and analytical factors affecting laboratory diagnosis. Clin Chem 44: , Chu J, Wang RY, Hill NS: Update in clinical toxicology. Am J Respir Crit Care Med 166:9-15, Hovda KE, Froyshov S, Gudmundsdottir H, Rudberg N: Fomepizole may change indication for hemodialysis in methanol poisoning: Prospective study in seven cases. Clin Nephrol 64: , Cook MD, Clark RF: Creatinine elevation associated with nitromethane exposure: A marker of potential methanol toxicity. J Emerg Med 33: , 2007