Poor outcomes in ethylene glycol (EG) poisoning are mainly due to late diagnosis and/or inadequate treatment.¹ We present a case where there was no history to support EG ingestion but clinical findings together with miscalculation of lactate levels supported EG poisoning.  Our patient was successfully treated with a combination of continuous renal replacement therapy (CRRT) and fomepizole. 

Introduction

Ethylene glycol poisoning occurs either as a consequence of using ethylene glycol as a cheap substitute for alcohol or intentional ingestion in a suicide attempt.² We present the case of a man presenting with severe metabolic acidosis and subsequently reduced Glasgow Coma Scale (GCS). 

EG toxicity was suspected due to progressively worsening pH and the discrepancy between lactate measured by the ABG machine and the laboratory. Treatment was started immediately with fomepizole and CRRT, and toxicity was confirmed within 24 hours. 

This case highlights the need to suspect the clinical signs of EG toxicity and commence treatment immediately pending laboratory toxicity results, and the effectiveness of the combination of CRRT and fomepizole in resolving the toxicity (within 48 hours in this case).

Case report

A 67-year-old 70kg Caucasian male was brought to casualty by ambulance with a two-day history of slurred speech, sweating, confusion, leg weakness and vomiting. The GCS on initial presentation was 13/15 and then suddenly deteriorated to 3/15, so the patient was intubated and transferred to ICU for critical care management. His arterial blood gas (ABG) revealed a high anion gap metabolic acidosis of 32.5mmol/L and an osmolar gap of 72. 

The laboratory reported a lactate of 1.8mmol/L but on the mobile ABG machine it was immeasurably high. A blood ethanol level of <10mg/L excluded alcohol intoxication. Initial differential diagnosis included sepsis, myocardial or neurological events. However, there were no clinical signs as transthoracic echocardiography (TTE) was normal and computerised tomography (CT) was normal.

EG toxicity was then suspected, largely due to worsening pH 6.92 and the discrepancy between lactate measurements. A sample was sent for toxicology screening to Beaumont Poisons Information Unit. An MSU showed the presence of calcium oxalate, hippuric acid crystals and sodium urate crystals. Fomepizole and CVVHDF were initiated empirically. The family could not provide any information to support deliberate or inadvertent ingestion of EG.

EG poisoning was confirmed when the sample from day 1 showed ethylene glycol and glycolic acid levels of 3,496mg/L and 931mg/L, respectively. On day three both had fallen to <40mg/L so antidote treatment was discontinued. The patient had received 48 hours of fomepizole and CRRT.

Discussion

EG is metabolised by alcohol dehydrogenase to glycolaldehyde, which is then oxidised to glycolic acid. The mechanism of EG poisoning is mainly due to its metabolites and consists of three stages. The initial case history of neurological and gastrointestinal symptoms (similar to those of alcohol poisoning) was consistent with stage 1. Stage 2 was seen as high blood pressure and metabolic acidosis. 

These symptoms are a result of accumulation of organic acids formed by EG metabolism. If untreated, death occurs most commonly during this period. Stage 3 is kidney failure due to calcium crystal formation and occurs 24-72 hours after EG exposure.³

In the case of this patient, the portable ABG machine could not distinguish between lactate and glycolate, and reported the toxin as lactate resulting in an unreadable lactate level, while the laboratory returned a normal result. This finding is a hallmark of EG toxicity and such a discrepancy is a clue to the presence of poison.

Haemodialysis remains an important adjunctive therapy, especially in cases of late admission in patients with severe metabolic acidosis. Fomepizole or ethanol is the recommended antidote for EG poisoning. The efficacy of fomepizole and ethanol as antidotes is based on their preferential binding to alcohol dehydrogenase. Ethanol competes with ethylene glycol and methanol as substrates for alcohol dehydrogenase (binding 500-1,000 times stronger to the enzyme as compared to methanol), whereas fomepizole acts as a competitive antagonist of the enzyme (binding 80,000 times stronger than methanol). Both ethanol and fomepizole inhibit the metabolism of the parent ethylene glycol and methanol and prevent the accumulation of toxic metabolites. 

Ethanol presents difficulties in maintaining therapeutic concentrations, especially during dialysis, and reported fluctuations of serum ethanol concentration place patients at risk of subtherapeutic or toxic serum ethanol concentrations.¹

Fomepizole is a competitive inhibitor of alcohol dehydrogenase, which catalyses the initial steps in the metabolism of EG to its toxic metabolites. Fomepizole is preferred to ethanol due to its lack of adverse effects, minimal CNS depressant effects, and its slower and more reproducible rate of elimination.⁵

A loading dose of 15mg/kg was initially administered, although there is no dosing recommendation in the manufacturer’s literature for the form of filtration (CVVHF/HDF) used in this case. Fomepizole is significantly removed by HD, so a continuous regimen of 1mg/kg/hr was prescribed as per Toxbase recommendations.^4,6

This case highlights the high index of suspicion required to initiate EG antidote treatment. Despite the significant EG toxicity, the patient improved significantly within 48 hours of initiation of fomepizole and CVVHF/HDF. 

References

1. Application to include Fomepizole on the WHO Model List of Essential Medicines. www.who.int/selection_medicines/committees/expert/19/applications/Fomepizole_4_2_AC_Ad.pdf
2. Mangera Z et al. Successful outcome of accidental ethylene glycol poisoning despite delayed presentation. BMJ Case Reports 2010; 10.1136/bcr.01.2010.2682
3. Brent J. Current Management of Ethylene Glycol Poisoning. Drugs 2001; 61: 979-88
4. Fomepizole (antidote) www.toxbase.org/General-Info/Antidotes-doses-and-sources/Fomepizole last accessed 19/08/2014
5. Poisons Information Centre of Ireland. Antidote List. www.poisons.ie/downloads - Lab-Assay-Book.pdf last accessed 23/10/2014
6. Jobard E et al. 4-Methylpyrazole and hemodialysis in ethylene glycol poisoning. Clin. Toxicol. 1996; 34: 373-377