Plotting of Ethylene Glycol Blood Concentrations Using Linear Regression before and during Hemodialysis in a Case of Intoxication and Pharmacokinetic Review.

Youngho Kim

doi:10.1155/2015/359101

Abstract

Introduction. As blood concentration measurement of commonly abused alcohol is readily available, the equation was proposed in previous publication to predict the change of their concentration. The change of ethylene glycol (EG) concentrations was studied in a case of intoxication to estimate required time for hemodialysis (HD) using linear regression. Case Report. A 55-year-old female with past medical history of seizure disorder, bipolar disorder, and chronic pain was admitted due to severe agitation. The patient was noted to have metabolic acidosis with elevated anion gap and acute kidney injury, which prompted blood concentration measurement of commonly abused alcohol. Her initial EG concentration was 26.45 mmol/L. Fomepizole therapy was initiated, soon followed by HD to enhance clearance. Discussion. Plotting of natural logarithm of EG concentrations over time showed that EG elimination follows first-order kinetics and predicts the change of its concentration well. Pharmacokinetic review revealed minimal elimination of EG by alcohol dehydrogenase (ADH) which could be related to genetic predisposition for ADH activity and home medications as well as presence of propylene glycol. Pharmacokinetics of EG is relatively well studied with published parameters. Consideration and application of pharmacokinetics could assist in management of EG intoxication including HD planning.

Highlights

As blood concentration measurement of commonly abused alcohol is readily available, the equation was proposed in previous publication to predict the change of their concentration
Alcohols are rather benign in their original form and they become toxic by being metabolized into organic acids that consume buffering capacity with development of metabolic acidosis and cause tissue injury
Ethylene glycol is metabolized via alcohol dehydrogenase (ADH) to glycoaldehyde which is rapidly metabolized to glycolate, the metabolite mainly responsible for the metabolic acidosis in ethylene glycol intoxication

Summary

Introduction

Ethylene glycol is sweet-tasting chemical compound without odour or color found in many commercially available products such as automobile antifreeze, deicing fluids, paint, and cosmetics. Ethylene glycol is metabolized via alcohol dehydrogenase (ADH) to glycoaldehyde which is rapidly metabolized to glycolate, the metabolite mainly responsible for the metabolic acidosis in ethylene glycol intoxication. Tissue toxicity of ethylene glycol and its metabolites has been reported to show following gradient: glyoxalate > glycoaldehyde > glycolate > ethylene glycol [4]. Treatment recommendation for ethylene glycol intoxication includes alcohol dehydrogenase inhibition by fomepizole (4-methylpyrazole, Antizol) to prevent biotransformation of ethylene glycol to its toxic metabolites and enhanced clearance by hemodialysis. Case Reports in Nephrology clearance, with median fractional excretion of 25.5%, and patients with normal serum creatinine concentration at the initiation of fomepizole therapy had rapid rates of renal elimination that rationalize selective hemodialysis therapy in patients treated with fomepizole when renal elimination pathway is intact [7]. Pharmacokinetic aspect of ethylene glycol concentration during clinical course was studied and applied to predict the change of its concentration using linear regression and to estimate the required duration of hemodialysis and its efficacy

Case Report

Findings

Discussion