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American Journal of Kidney Diseases

Early and Late Presentations of Ethylene Glycol Poisoning

Published:March 09, 2009DOI:https://doi.org/10.1053/j.ajkd.2008.12.019

      Index Words

      Ethylene glycol intoxication is uncommon, but can result in life-threatening metabolic acidosis, kidney failure, and death. Diagnosing such poisoning can be problematic in the absence of a clear history of ingestion, especially in patients who present with altered mental status or those who deny such consumption. Increased osmolal gap with a detectable serum ethylene glycol level is characteristic in patients presenting soon after ingestion, but increased anion gap metabolic acidosis without osmolal gap is seen in those who present late. Prompt institution of appropriate treatment can reduce the mortality and morbidity of poisoned patients, but requires clinicians to recognize these characteristic biochemical features according to whether presentation to the hospital is early or late after ethylene glycol ingestion. In cases of unexplained kidney failure, kidney biopsy may prompt the diagnosis by showing intratubular and intracellular calcium oxalate crystal deposition. We report 2 cases of ethylene glycol–induced acute kidney injury (AKI) with the diagnosis made after kidney biopsy. We discuss differences in laboratory results observed in these 2 patients because of timing of ingestion and coingestion of ethanol. We also review the toxic kinetics and clinical manifestations of ethylene glycol poisoning.

      Case Report

      Clinical History

      Case 1

      A 53-year-old white man was referred by his general practitioner with suspicion of a transient ischemic attack. The patient reported acute onset of severe dizziness lasting 2 days. His wife described increased sleepiness and drowsiness for the previous 2 days associated with slurred and confused speech and recurrent falls because of an apparently weak left leg. During this time, he also was nauseated, with several episodes of vomiting. The patient had a history of chronic alcohol consumption of about 5 units daily for the past 10 years, but no history of cigarette smoking. He was investigated for weight loss 2 years previously, but upper gastrointestinal endoscopy and computed tomography (CT) of the chest and abdomen were normal.
      On examination, the patient appeared underweight with a body mass index of 18 kg/m2. He was fully conscious, but appeared mildly confused, with disorientation to time and place. Neurological examination of the cranial nerves and limbs was normal. Blood pressure was 136/78 mm Hg, and skin turgor was decreased. He was afebrile, but tachycardic, with a heart rate of 110 beats/min. Urinalysis found microscopic hematuria (2+) and proteinuria (1+). Laboratory results (Table 1) indicated AKI, with a serum creatinine level of 3.46 mg/dL (306 μmol/L). Four months before presentation, serum creatinine level was 0.71 mg/dL (63 μmol/L; estimated glomerular filtration rate > 90 mL/min/1.73 m2 [>1.50 mL/s/1.73 m2]). He had normal anion gap metabolic acidosis with a serum bicarbonate level of 13 mEq/L (13 mmol/L). No abnormalities were found on head CT, chest X-ray, and renal tract ultrasound scan. Serum complement, antinuclear antibody, antineutrophil cytoplasmic antibody, anti–glomerular basement membrane antibody, and immunoglobulin levels were normal. No paraprotein was detected on serum electrophoresis. Liver enzyme levels were within normal limits. He was given intravenous fluids, predominantly 0.9% sodium chloride of approximately 4 L/d for 3 days, in addition to about 2 L of 1.26% sodium bicarbonate during the first 12 hours, followed by oral sodium bicarbonate, 1 g thrice daily, for 1 week. His confusion resolved by the second day of hospital admission. Urine output improved from 600 mL in the first 24 hours of admission to about 1,200 and 1,800 mL/d after 48 and 72 hours, respectively. This was accompanied by normalization of acid-base disturbances. Initially, he was believed to have acute tubular necrosis secondary to volume depletion. However, only modest improvement in serum creatinine levels was observed during 6 days (Fig 1), so a kidney biopsy was performed. He was discharged home after the kidney biopsy on day 7. Renal histological examination (Fig 2) showed a large number of oxalate crystals in tubules throughout the cortex, highlighted by their birefringence under polarized light. This was associated with focal acute tubular damage, whereas glomeruli were normal. No deposition of immunoglobulins or complement was seen on immunofluorescence.
      Table 1Results of Laboratory Investigations
      InvestigationsCase 1Case 2
      First AdmissionReadmission
      Sodium (mEq/L)133147130
      Potassium (mEq/L)4.856.4
      Urea (mg/dL)55.715.1291.3
      Creatinine (mg/dL)3.462.3136.82
      Glucose (mg/dL)99.1138.7108.1
      Measured osmolality (mOsm/kg)Not available339374
      Osmolal gap (mOsm/kg)Not available324
      pH7.267.127.13
      Pco2 (kPa)3.162.13.13
      Po2 (kPa); Fio213.5 (0.2)20 (0.6)30 (0.8)
      Bicarbonate (mEq/L)13910
      Base excess (mEq/L)−15−21−20
      Lactate (mg/dL)37.84234.236.31
      Chloride (mEq/L)10911388
      Anion gap (mEq/L)112532
      Ethylene glycol (mg/L)Not available144Undetectable
      Note: Conversion factors for units: urea nitrogen in mg/dL to mmol/L, ×0.357; serum creatinine in mg/dL to μmol/L, ×8.4; glucose in mg/dL to mmol/L, ×0.05551; lactate in mg/dL to mmol/L, ×0.111; ethylene glycol in mg/L to μmol/L, ×16.11. Serum sodium, potassium, bicarbonate, chloride, and anion gap expressed in mEq/L and mmol/L are equivalent. Osmolality expressed in mOsm/kg and mmol/kg is equivalent.
      Abbreviation: Fio2, fraction of inspired oxygen.
      Figure thumbnail gr1
      Figure 1Course of kidney function, timing of kidney biopsy, and duration of continuous venovenous hemofiltration (CVVH) in patient 1.
      Figure thumbnail gr2
      Figure 2(A) Crystalline material is present in the tubules, (B) which is accentuated by the use of polarized light (hematoxylin and eosin stain; original magnification ×200).
      The patient was brought back by his wife to the casualty department 1 week after his hospital discharge with a 24-hour history of drowsiness, confusion, and slurred speech. On readmission, blood pressure was 160/90 mm Hg, with sinus tachycardia of 120 beats/min, and he was tachypneic with a respiratory rate of 40 breaths/min. Four hours after arrival, he became obtunded with a Glasgow coma scale of 4 (of 15). He was intubated and transferred to the intensive care unit. Biochemistry tests showed impaired kidney function (serum creatinine, 2.31 mg/dL [204 μmol/L]) with increased anion gap metabolic acidosis and lactate level of 234 mg/dL (26 mmol/L; normal, <19.8 mg/dL [2.2 mmol/L]); (Table 1). Serum amylase level and CT of the abdomen were normal. Toxicology screen for salicylates and paracetamol was negative.

      Case 2

      A 49-year-old Asian man presented to the casualty department with a 2-day history of a macular-papular erythematous rash on his trunk and neck stiffness. His family described an acute onset of slurred confused speech about 10 days before admission lasting 48 hours, with subsequent increased lethargy and sleepiness for the rest of the week. The patient reported severe dizziness that persisted for 5 days. He had a history of multiple sclerosis diagnosed 10 years earlier, manifested by intermittent diplopia, but otherwise, he was not debilitated. There was a history of self-harm with paracetamol overdose 5 years previously, but he denied a recent overdose. He was not using any regular medications and did not consume alcohol or use tobacco. Clinically, he had a Glasgow coma score of 15. He was afebrile and blood pressure was 138/78 mm Hg, with a heart rate of 100 beats/min. There was left-sided torticollis. He had a longstanding bilateral internuclear ophthalmoplegia, but no other neurological deficit was found. Laboratory investigations showed severe AKI (serum creatinine, 36.82 mg/dL [3,255 μmol/L]), with increased anion gap of 32 mEq/L (32 mmol/L) and normal lactate level. Osmolal gap was normal at 4 mOsm/kg (4 mmol/kg) (Table 1). Urinalysis was not performed because of anuria. C-Reactive protein level was increased at 59 mg/L (reference value, <10 mg/L), and there was mild leukocytosis of 12.4 × 109/L (normal, 4 to 11 × 109/L). Creatine kinase level was 483 U/L (normal, <200 U/L), and liver enzyme levels were normal. Toxicology screen for salicylate, paracetamol, and ethylene glycol were negative. Head CT, chest X-ray, and renal tract ultrasound scan were normal. Cerebrospinal fluid analysis for virology and microbiology were also negative. He was started on intermittent hemodialysis therapy. Four days after admission, he developed a right-sided lower motor neuron seventh cranial nerve palsy. Immunology screen (serum complement, antinuclear antibody, antineutrophil cytoplasmic antibodies, anti–glomerular basement membrane antibody, and immunoglobulins) did not show abnormalities.

      Additional Investigations

      Case 1

      The renal histological state of oxalate deposition in tubules (Fig 2) combined with the acute acid-base disturbance suggested acute ethylene glycol intoxication. Serum ethylene glycol level (measured by means of gas chromatography with flame ionization detection) 6 hours after presentation was 144 mg/L (2,320 μmol/L), with osmolal gap of 32 mOsm/kg (32 mmol/kg). Baseline serum ethanol was not measured by our laboratory.

      Case 2

      No ethylene glycol was detected in a blood sample obtained from the patient 1 hour after presentation. One week after hospital admission, a kidney biopsy was performed (Fig 3). This showed acute tubular necrosis with both degenerative and regenerative changes, accompanied by moderate deposition of oxalate crystals within the tubular lumina. Immunofluorescence and electron microscopy did not show immunostaining and electron-dense deposits within glomeruli, respectively.
      Figure thumbnail gr3
      Figure 3(A) A crystal within a tubule associated with flattening and necrosis of the tubular epithelium (B) shows birefringence under polarized light (hematoxylin and eosin stain; original magnification ×400).

      Diagnosis

      AKI caused by ethylene glycol poisoning was suspected in both patients. In patient 1, the diagnosis of acute ethylene glycol poisoning was confirmed by means of detectable ethylene glycol in serum. He subsequently admitted to ingesting automobile antifreeze in attempts to self-harm. About 100 mL of antifreeze mixed in a glass of cider apparently was consumed 3 days before the first admission, and about 150 mL of antifreeze (with an unspecified amount of cider) was consumed 24 hours before his second presentation.
      Although no serum ethylene glycol was detectable in patient 2, he eventually admitted to drinking about 500 mL of antifreeze 10 days before presentation in an attempt to take his life because of depression.

      Clinical Follow-up

      Patient 1 was started on continuous venovenous hemofiltration for 5 days until the acidosis was corrected. He received an intravenous ethanol infusion for 48 hours, maintaining a serum ethanol level of 100 mg/dL. Serum ethylene glycol became undetectable 48 hours after the simultaneous initiation of ethanol infusion and continuous venovenous hemofiltration. He subsequently made a complete renal recovery (Fig 1). However, patient 2, a late presenter, remains on hemodialysis therapy 7 months after the AKI.

      Discussion

      Intoxication with ethylene glycol can be life-threatening. The cases presented illustrate the difficulty diagnosing ethylene glycol poisoning in the absence of a history of ingestion on presentation. Although both patients had symptoms characteristic of ethylene glycol intoxication, initial laboratory results differed (Table 1), primarily because of the pharmacokinetics of ethylene glycol and the periods between ingestion and presentation (Table 2). Kidney biopsy is rarely performed in these circumstances, but can lead to the diagnosis when intratubular oxalate crystals with positive birefringence under polarized light are seen on light microscopy (Figure 2, Figure 3). However, kidney failure associated with oxalate nephropathy can be caused by a number of conditions. In addition to ethylene glycol poisoning, ingestion of a large amount of ascorbic acid may increase the risk of calcium oxalate crystallization.
      • Baxmann A.C.
      • De O.G.
      • Mendonça C.
      • Heilberg I.P.
      Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients.
      Autosomal recessive primary hyperoxaluria, seen commonly in the pediatric population, results in defective oxalate metabolism, often associated with systemic oxalosis.
      • Danpure C.J.
      Advances in the enzymology and molecular genetics of primary hyperoxaluria type 1 Prospects for gene therapy.
      • Seargeant L.E.
      • deGroot G.W.
      • Dilling L.A.
      • Mallory C.J.
      • Haworth J.C.
      Primary oxaluria type 2 (l-glyceric aciduria): A rare cause of nephrolithiasis in children.
      Malabsorption syndromes caused by ileal resection, Crohn ileitis, or jejunoileal bypass for morbid obesity also predispose patients to form calcium oxalate renal calculi.
      • Nightingale J.M.
      The short bowel syndrome.
      • McLeod R.S.
      • Churchill D.N.
      Urolithiasis complicating inflammatory bowel disease.
      • Mole D.
      • Tomson C.
      • Mortensen N.
      • Winearls C.
      Renal complications of jejuno-ileal bypass for obesity.
      None of these conditions was present in our patients.
      Table 2Comparison of Laboratory Features Seen in Patients Presenting Early and Later in the Course of Ethylene Glycol Poisoning
      LaboratoryEarlyLate
      Anion gapNormal or mildly increasedIncreased
      Osmolal gapIncreasedNormal
      Serum ethylene glycolDetectableNot detectable
      Oxalate crystalluriaMay be present
      May be seen 4 to 8 hours after ethylene glycol ingestion, up to 40 hours in the absence of acute kidney injury (AKI).
      May be present
      Present up to 4 days with AKI.
      Kidney functionNormal or mild AKISevere AKI
      low asterisk May be seen 4 to 8 hours after ethylene glycol ingestion, up to 40 hours in the absence of acute kidney injury (AKI).
      Present up to 4 days with AKI.
      Ethylene glycol is the active ingredient in antifreeze for vehicle engines, but it also is found in various domestic or industrial cleaning products. The sweet taste of ethylene glycol, which is odorless and colorless, makes it palatable even in toxic quantities to both humans and animals; hence, its nickname “sweet killer.”
      • Barceloux D.G.
      • Krenzelok E.P.
      • Olson K.
      • Watson W.
      American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning.
      • Eder A.F.
      • McGrath C.M.
      • Dowdy Y.G.
      • et al.
      Ethylene glycol poisoning: Toxicokinetic and analytical factors affecting laboratory diagnosis.
      • Sivilotti M.L.
      • Burns M.J.
      • McMartin K.E.
      • Brent J.
      Toxicokinetics of ethylene glycol during fomepizole therapy: Implications for management For the Methylpyrazole for Toxic Alcohols Study Group.
      • Moreau C.L.
      • Kerns II, W.
      • Tomaszewski C.A.
      • et al.
      Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning META Study Group.
      Ethylene glycol (CH2OH-CH2OH) is rapidly and completely absorbed from the gastrointestinal tract and achieves peak concentration within 30 to 60 minutes after oral ingestion. The majority of absorbed ethylene glycol, which has a low molecular weight of about 62 Da, is metabolized by the liver (80%) with a short half-life of 3 to 8 hours. The remaining 20% is eliminated by the kidneys, but the rate of excretion through this route is slow, with a half-life of 18 to 20 hours.
      • Barceloux D.G.
      • Krenzelok E.P.
      • Olson K.
      • Watson W.
      American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning.
      • Eder A.F.
      • McGrath C.M.
      • Dowdy Y.G.
      • et al.
      Ethylene glycol poisoning: Toxicokinetic and analytical factors affecting laboratory diagnosis.
      • Sivilotti M.L.
      • Burns M.J.
      • McMartin K.E.
      • Brent J.
      Toxicokinetics of ethylene glycol during fomepizole therapy: Implications for management For the Methylpyrazole for Toxic Alcohols Study Group.
      The ethylene glycol molecule in itself is relatively nontoxic and produces clinical features similar to ethanol intoxication and central nervous system sedation, as observed in both our patients. In the liver, ethylene glycol is metabolized primarily by alcohol dehydrogenase (ADH) to produce glycoaldehyde, which is converted to glycolate by aldehyde dehydrogenase. The increased anion gap metabolic acidosis seen in patients with ethylene glycol poisoning is predominantly caused by glycolate and occurs 12 to 48 hours after ingestion. Further metabolism to glycoxylate and oxalate is relatively slow, which allows accumulation of glycolate, leading to worsening acidosis, increasing anion gap (Table 2), and cardiopulmonary decompensation.
      • Moreau C.L.
      • Kerns II, W.
      • Tomaszewski C.A.
      • et al.
      Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning META Study Group.
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      • McMartin K.E.
      Methanol and ethylene glycol poisonings Mechanism of toxicity, clinical course, diagnosis and treatment.
      • Hess R.
      • Bartels M.J.
      • Pottenger L.H.
      Ethylene glycol: An estimate of tolerable levels of exposure based on a review of animal and human data.
      Coingestion of ethanol may delay the onset of ethylene glycol toxicity because it also is metabolized by ADH. Ethanol has an affinity about 100 times greater for ADH than ethylene glycol. The presence of ethanol therefore will inhibit and delay the formation of toxic metabolites of ethylene glycol, which may explain the absence of increased anion gap metabolic acidosis in the initial admission of patient 1.
      • Barceloux D.G.
      • Krenzelok E.P.
      • Olson K.
      • Watson W.
      American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning.
      • Eder A.F.
      • McGrath C.M.
      • Dowdy Y.G.
      • et al.
      Ethylene glycol poisoning: Toxicokinetic and analytical factors affecting laboratory diagnosis.
      • Wacker W.E.
      • Haynes H.
      • Druyan R.
      • Fisher W.
      • Coleman J.E.
      Treatment of ethylene glycol poisoning with ethyl alcohol.
      • Ammar K.A.
      • Heckerling P.S.
      Ethylene glycol poisoning with normal anion gap caused by concurrent ethanol ingestion: Importance of the osmolal gap.
      High anion gap metabolic acidosis may be a characteristic biochemical feature of ethylene glycol poisoning, but it also can be seen in patients with severe renal failure. However, measurement of glycolate was not available in our institution to determine the cause of the high anion gap in patient 2, who presented late with severe AKI. Currently, intravenous infusion of ethanol is our standard therapy to saturate ADH, but fomepizole (4-methylpyrazole), a potent inhibitor of ADH, is an effective first-line antidote.
      • Baud F.J.
      • Galliot M.
      • Astier A.
      • et al.
      Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole.
      • Borron S.W.
      • Mégarbane B.
      • Baud F.J.
      Fomepizole in treatment of uncomplicated ethylene glycol poisoning.
      Advantages over ethanol include a greater affinity for ADH of about 500 to 1,000 times, a lack of intoxicating effects, and more reliable achievement of therapeutic concentration. Fomepizole also may obviate the need for dialysis in patients who present early with increased serum ethylene glycol, but without significant acidosis.
      • Brent J.
      • McMartin K.
      • Phillips S.
      • et al.
      Fomepizole for the treatment of ethylene glycol poisoning Methylpyrazole for Toxic Alcohols Study Group.
      Marked lactic acidosis was seen in patient 1 during his readmission with shock, bowel ischemia, status epilepticus, and salicylate poisoning, all excluded as possible causes. An increased lactate level can occur as an artifact because of the structural similarity of the lactate and glycolate molecules or misreading by certain chemical analyzers.
      • Woo M.Y.
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      • Nadler S.P.
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      Artifactual elevation of lactate in ethylene glycol poisoning.
      • Lindsay S.
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      • Brooks D.
      Artifactual elevation of plasma l-lactate in the presence of glycolate—A potential for misdiagnosis.
      However, the high serum lactate level in patient 1 probably was a true increase caused by inhibition of cellular metabolic enzymes by glycolate, causing lactic acidosis.
      • Eder A.F.
      • McGrath C.M.
      • Dowdy Y.G.
      • et al.
      Ethylene glycol poisoning: Toxicokinetic and analytical factors affecting laboratory diagnosis.
      • Jacobsen D.
      • McMartin K.E.
      Methanol and ethylene glycol poisonings Mechanism of toxicity, clinical course, diagnosis and treatment.
      • Bachmann E.
      • Golberg L.
      Reappraisal of the toxicology of ethylene glycol. III. Mitochondrial effects.
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      • Lepoff R.
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      This would have contributed to the significantly increased anion gap metabolic acidosis seen in patient 1 on his second presentation. The very mild lactic acidosis during the first admission could have been caused by a smaller amount of ethylene glycol consumed in the presence of ethanol, which further delayed hepatic oxidation to produce the toxic metabolite. Urine alkalinization with sodium bicarbonate, administered during the first admission, helps promote renal excretion of both ethylene glycol and glycolate.
      AKI usually takes 1 to 3 days to develop after ingestion of ethylene glycol. The mechanism of kidney failure is believed to be caused by glycolate-induced tubular cell necrosis with minimal glomerular damage. The characteristic histopathologic feature of ethylene glycol poisoning is the presence of intratubular and intracellular calcium oxalate crystals, with degeneration of tubular epithelium.
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      • Feys J.
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      Recent studies in rat models showed the accumulation of oxalate, the final metabolite product of hepatic ethylene glycol oxidation, in the form of calcium oxalate monohydrate crystals that were internalized by the proximal tubular cells, producing mitochondrial damage that resulted in cell death and tubular necrosis.
      • Cruzan G.
      • Corley R.A.
      • Hard G.C.
      • et al.
      Subchronic toxicity of ethylene glycol in Wistar and F344 rats related to metabolism and clearance of metabolites.
      • McMartin K.E.
      • Wallace K.B.
      Calcium oxalate monohydrate, a metabolite of ethylene glycol, is toxic for rat renal mitochondrial function.
      Calcium oxalate crystals may be seen in the urine of poisoned patients up to 40 hours after ingestion of ethylene glycol in the absence of kidney failure and up to 4 days in kidney failure.
      • Eder A.F.
      • McGrath C.M.
      • Dowdy Y.G.
      • et al.
      Ethylene glycol poisoning: Toxicokinetic and analytical factors affecting laboratory diagnosis.
      • Jacobsen D.
      • Hewlett T.P.
      • Webb R.
      • Brown S.T.
      • Ordinario A.T.
      • McMartin K.E.
      Ethylene glycol intoxication: Evaluation of kinetics and crystalluria.
      However, their absence would not exclude the diagnosis because oxalate crystaluria often is seen late after ethylene glycol ingestion (Table 2).
      • Jacobsen D.
      • Hewlett T.P.
      • Webb R.
      • Brown S.T.
      • Ordinario A.T.
      • McMartin K.E.
      Ethylene glycol intoxication: Evaluation of kinetics and crystalluria.
      In patient 2, no serum ethylene glycol was detected because the delay in presenting to the hospital meant that by then, all the parent alcohol had been metabolized. This explained the normal osmolal gap at presentation. Osmolal gap is derived from the difference between the laboratory measured and calculated serum osmolality and should not exceed 10 mOsm/kg (10 mmol/kg). Accumulation of any of the parent alcohols (ethanol, methanol, and ethylene glycol) will increase the measured serum osmolality to greater than that of the calculated serum osmolality, producing an osmolal gap.
      • Glasser L.
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      • Combie J.
      • Robinson A.
      Serum osmolality and its applicability to drug overdose.
      • Abramson S.
      • Singh A.K.
      Treatment of the alcohol intoxications: Ethylene glycol, methanol, isopropanol.
      • Smithline N.
      • Gardner K.D.
      Gaps: Anionic and osmolal.
      Therefore, one would expect an increased osmolal gap with high serum ethylene glycol level in acute presentation (patient 1), but a normal osmolal gap with nondetectable serum ethylene glycol level in late presention of ethylene glycol poisoning (patient 2). The significantly high osmolal gap of 32 mOsm/kg (32 mmol/kg) in patient 1 probably was caused by both the consumed ethanol and ethylene glycol. Incorporating serum ethanol measurement (if available) into the calculated serum osmolality would reflect the contribution of ethylene glycol to the increased osmolal gap.
      Cranial neuropathies previously have been reported as delayed sequelae of ethylene glycol poisoning, with onset from 8 to 18 days after significant ingestion (up to 900 mL), especially in patients who presented late to hospitals.
      • Mallya K.B.
      • Mendis T.
      • Guberman A.
      Bilateral facial paralysis following ethylene glycol ingestion.
      • Factor S.A.
      • Lava N.S.
      Ethylene glycol intoxication: A new stage in the clinical syndrome.
      • Berger J.R.
      • Ayyar R.A.
      Neurological complications of ethylene glycol intoxication Report of a case.
      • Lewis L.D.
      • Smith B.W.
      • Mamourian A.C.
      Delayed sequelae after acute overdoses or poisonings: Cranial neuropathy related to ethylene glycol ingestion.
      • Palmer B.F.
      • Eigenbrodt E.H.
      • Henrich W.L.
      Cranial nerve deficit: A clue to the diagnosis of ethylene glycol poisoning.
      • Spillane L.
      • Roberts J.R.
      • Meyer A.E.
      Multiple cranial nerve deficits after ethylene glycol poisoning.
      • Anderson B.
      • Adams M.
      Facial-auditory nerve oxalosis.
      • Fellman D.M.
      Facial diplegia following ethylene glycol.
      Patient 2 developed a right seventh cranial nerve palsy about 14 days after ingestion of ethylene glycol. Postmortem studies attribute this phenomenon to localized inflammation by oxalate microcrystals deposition, compromising the affected cranial nerve function. Partial or full recovery of the cranial nerve defects may take up to a year.
      • Lewis L.D.
      • Smith B.W.
      • Mamourian A.C.
      Delayed sequelae after acute overdoses or poisonings: Cranial neuropathy related to ethylene glycol ingestion.
      • Anderson B.
      • Adams M.
      Facial-auditory nerve oxalosis.
      The 2 patients presented illustrate distinct biochemical features related to the time lapse between ethylene glycol ingestion and presentation to the hospital. Determination of the anion and osmolal gaps is fundamental to the assessment of patients with suspected ethylene glycol poisoning. Shortly after ethylene glycol ingestion, anion gap is normal, but osmolal gap is high. As ethylene glycol is metabolized, accumulation of the toxic acids leads to an increasing anion gap metabolic acidosis accompanied by a decreasing osmolal gap. Coingestion of ethanol can ameliorate the anion gap because of delayed production of toxic metabolites by competitive inhibition of the metabolizing alcohol dehydrogenase. With late presentation to the hospital, the ethylene glycol–poisoned patient can have a normal osmolal gap, no detectable serum ethylene glycol, and more severe AKI. Therefore, clinicians must consider ethylene glycol poisoning in the differential diagnoses of unexplained AKI. Ethylene glycol poisoning must be suspected in patients with a kidney biopsy specimen showing oxalate nephropathy. Prognosis is good in early presenters provided there is timely treatment with alkali to combat acidosis, ethanol or fomepizole to prevent hepatic oxidation, and hemodialysis to effectively remove both the parent alcohol and its toxic metabolites.

      Acknowledgements

      We thank Kirsty Gordon, DipRCPath (Senior Clinical Scientist, Department of Clinical Biochemistry and Immunology, Heartlands Hospital, Birmingham, UK), who offered guidance on ethylene glycol sampling and analysis.
      Support: None.
      Financial Disclosure: None.

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      Linked Article

      • Urinalysis in Ethylene Glycol Poisoning
        American Journal of Kidney DiseasesVol. 54Issue 4
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          Ting et al1 provide an informative discussion of the early and late presentations of ethylene glycol poisoning. The authors note that calcium oxalate crystals may be seen in urine for up to 4 days after ethylene glycol ingestion in the context of kidney failure. However, patients with acute kidney injury caused by ethylene glycol poisoning may be anuric on presentation, as was the case for the second man they described. When faced with an anuric patient and reason to suspect the possibility of ethylene glycol ingestion, I have found it useful to irrigate the bladder with 50-100 mL of saline, centrifuge the drained solution, and examine the sediment under the microscope for calcium oxalate crystals.
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