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      A rapid analysis of plasma/serum ethylene and propylene glycol by headspace gas chromatography

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          Abstract

          A rapid headspace-gas chromatography (HS-GC) method was developed for the analysis of ethylene glycol and propylene glycol in plasma and serum specimens using 1,3-propanediol as the internal standard. The method employed a single-step derivitization using phenylboronic acid, was linear to 200 mg/dL and had a lower limit of quantitation of 1 mg/dL suitable for clinical analyses. The analytical method described allows for laboratories with HS-GC instrumentation to analyze ethanol, methanol, isopropanol, ethylene glycol, and propylene glycol on a single instrument with rapid switch-over from alcohols to glycols analysis. In addition to the novel HS-GC method, a retrospective analysis of patient specimens containing ethylene glycol and propylene glycol was also described. A total of 36 patients ingested ethylene glycol, including 3 patients who presented with two separate admissions for ethylene glycol toxicity. Laboratory studies on presentation to hospital for these patients showed both osmolal and anion gap in 13 patients, osmolal but not anion gap in 13 patients, anion but not osmolal gap in 8 patients, and 1 patient with neither an osmolal nor anion gap. Acidosis on arterial blood gas was present in 13 cases. Only one fatality was seen; this was a patient with initial serum ethylene glycol concentration of 1282 mg/dL who died on third day of hospitalization. Propylene glycol was common in patients being managed for toxic ingestions, and was often attributed to iatrogenic administration of propylene glycol-containing medications such as activated charcoal and intravenous lorazepam. In six patients, propylene glycol contributed to an abnormally high osmolal gap. The common presence of propylene glycol in hospitalized patients emphasizes the importance of being able to identify both ethylene glycol and propylene glycol by chromatographic methods.

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          The online version of this article (doi:10.1186/2193-1801-2-203) contains supplementary material, which is available to authorized users.

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          Most cited references35

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          Toxic alcohol ingestions: clinical features, diagnosis, and management.

          Alcohol-related intoxications, including methanol, ethylene glycol, diethylene glycol, and propylene glycol, and alcoholic ketoacidosis can present with a high anion gap metabolic acidosis and increased serum osmolal gap, whereas isopropanol intoxication presents with hyperosmolality alone. The effects of these substances, except for isopropanol and possibly alcoholic ketoacidosis, are due to their metabolites, which can cause metabolic acidosis and cellular dysfunction. Accumulation of the alcohols in the blood can cause an increment in the osmolality, and accumulation of their metabolites can cause an increase in the anion gap and a decrease in serum bicarbonate concentration. The presence of both laboratory abnormalities concurrently is an important diagnostic clue, although either can be absent, depending on the time after exposure when blood is sampled. In addition to metabolic acidosis, acute renal failure and neurologic disease can occur in some of the intoxications. Dialysis to remove the unmetabolized alcohol and possibly the organic acid anion can be helpful in treatment of several of the alcohol-related intoxications. Administration of fomepizole or ethanol to inhibit alcohol dehydrogenase, a critical enzyme in metabolism of the alcohols, is beneficial in treatment of ethylene glycol and methanol intoxication and possibly diethylene glycol and propylene glycol intoxication. Given the potentially high morbidity and mortality of these intoxications, it is important for the clinician to have a high degree of suspicion for these disorders in cases of high anion gap metabolic acidosis, acute renal failure, or unexplained neurologic disease so that treatment can be initiated early.
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            Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving IV benzodiazepines: a case series and prospective, observational pilot study.

            Benzodiazepines are commonly administered to medical ICU (MICU) patients. Propylene glycol (1,2-propanediol) is the solvent used to deliver lorazepam and diazepam IV. Although propylene glycol toxicity is increasingly recognized and reported, its incidence is unknown. Herein, we describe five MICU patients who acquired severe propylene glycol toxicity due to IV lorazepam or diazepam administration. Additionally, we evaluate the incidence of propylene glycol toxicity in MICU patients receiving IV lorazepam or diazepam. Case series and prospective, observational study. Eighteen-bed MICU in a 550-bed urban academic hospital. MICU patients administered IV benzodiazepines during a 3-month period were enrolled. Patients were categorized according to the IV benzodiazepine that they received. Laboratory data and highlights of their clinical course were recorded daily. The incidence of propylene glycol toxicity was determined and the groups compared. Forty-four patients were enrolled. Twenty-one patients received a benzodiazepine delivered in propylene glycol (lorazepam or diazepam), and 23 patients received a benzodiazepine delivered in an alternative solvent (midazolam). We found that four patients (19%) who received IV lorazepam or diazepam had metabolic evidence of propylene glycol toxicity. None of the patients had clinical deterioration. Neither metabolic abnormality nor clinical deterioration suggestive of propylene glycol toxicity were identified in subjects receiving IV midazolam. Propylene glycol toxicity is a potentially life-threatening iatrogenic complication that is common and preventable. It should be considered whenever a patient has an unexplained anion gap, unexplained metabolic acidosis, hyperosmolality, and/or clinical deterioration. Close monitoring of all patients receiving IV lorazepam or diazepam for early evidence of propylene glycol toxicity is warranted.
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              Recognition, treatment, and prevention of propylene glycol toxicity.

              Propylene glycol is a commonly used solvent for oral, intravenous, and topical pharmaceutical preparations. Although it is considered safe, large intravenous doses given over a short period of time can be toxic. Underlying renal insufficiency and hepatic dysfunction raise risk for toxicity. Toxic effects include hyperosmolality, increased anion gap metabolic acidosis (due to lactic acidosis), acute kidney injury, and sepsis-like syndrome. Treatment of toxicity includes hemodialysis to effectively remove propylene glycol. Prevention is best achieved by limiting the dose of propylene glycol infused.
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                Author and article information

                Contributors
                alexandra-ehlers@uiowa.edu
                cory-morris@uiowa.edu
                mkrasows@healthcare.uiowa.edu
                Journal
                Springerplus
                Springerplus
                SpringerPlus
                Springer International Publishing AG (Cham )
                2193-1801
                1 May 2013
                1 May 2013
                2013
                : 2
                : 203
                Affiliations
                Clinical Chemistry Laboratory, Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242 USA
                Article
                288
                10.1186/2193-1801-2-203
                3667371
                23741644
                4eb50224-c606-48bd-9ab9-ddfd7cc5f763
                © Ehlers et al.; licensee Springer. 2013

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 January 2013
                : 25 April 2013
                Categories
                Research
                Custom metadata
                © The Author(s) 2013

                Uncategorized
                ethylene glycol,glycols,gas chromatography,propylene glycol,toxicology
                Uncategorized
                ethylene glycol, glycols, gas chromatography, propylene glycol, toxicology

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