Literature DB >> 29392569

Assessing Propylene Glycol Toxicity in Alcohol Withdrawal Patients Receiving Intravenous Benzodiazepines: A One-Compartment Pharmacokinetic Model.

Ashley Jahn1, Charlie Bodreau2, Kate Farthing3, Fawzy Elbarbry4,5.   

Abstract

BACKGROUND AND OBJECTIVES: While some case reports indicate that high doses of propylene glycol (PG) may result in metabolic acidosis, there has been no large-scale study that evaluated the risk of metabolic acidosis in patients receiving PG-containing benzodiazepines for acute alcohol withdrawal. This study was undertaken to evaluate the potential toxicity of PG in patients with acute alcohol withdrawal treated with intermittent intravenous bolus doses of diazepam and/or lorazepam.
METHODS: This is a retrospective case study using data collected from 18 randomly selected patients receiving one or both of these medications per a modified Clinical Institute Withdrawal Assessment for Alcohol (CIWA) Class 3 protocol. Plasma levels of PG were estimated using a one-compartment pharmacokinetic model.
RESULTS: Only two patients had an elevated anion gap compared to their baseline value with one also experiencing a significant increase in serum creatinine. No increases in serum osmolarity were noted. Analysis showed that the benzodiazepine dose received was a good predictor of the estimated PG concentration (r = 0.6), but was poorly correlated with the anion gap. No significant correlation was found with the creatinine clearance or serum creatinine. Patients receiving several daily doses were at higher risk of developing an anion gap (r = 0.33), but the estimated maximum PG concentration did not correlate with the anion gap or serum concentration.
CONCLUSION: It does not appear that intermittent bolus administration of intravenous benzodiazepines for alcohol withdrawal influenced renal function or anion gap regardless of number of administered doses, amount of PG received, or the estimated PG concentration.

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Year:  2018        PMID: 29392569     DOI: 10.1007/s13318-018-0462-1

Source DB:  PubMed          Journal:  Eur J Drug Metab Pharmacokinet        ISSN: 0378-7966            Impact factor:   2.441


  14 in total

1.  Osmolar gap metabolic acidosis in a 60-year-old man treated for hypoxemic respiratory failure.

Authors:  R Arbour; B Esparis
Journal:  Chest       Date:  2000-08       Impact factor: 9.410

2.  Propylene glycol-induced lactic acidosis in a patient with normal renal function: a proposed mechanism and monitoring recommendations.

Authors:  Bruce W Neale; Eleanor L Mesler; Michael Young; Jill A Rebuck; Wolfgang J Weise
Journal:  Ann Pharmacother       Date:  2005-09-13       Impact factor: 3.154

Review 3.  Efficacy and safety of pharmacological interventions for the treatment of the Alcohol Withdrawal Syndrome.

Authors:  Laura Amato; Silvia Minozzi; Marina Davoli
Journal:  Cochrane Database Syst Rev       Date:  2011-06-15

4.  Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving IV benzodiazepines: a case series and prospective, observational pilot study.

Authors:  Kevin C Wilson; Christine Reardon; Arthur C Theodore; Harrison W Farber
Journal:  Chest       Date:  2005-09       Impact factor: 9.410

5.  Propylene glycol-induced lactic acidosis in a patient receiving continuous infusion pentobarbital.

Authors:  Melissa A Miller; Allison Forni; Dinesh Yogaratnam
Journal:  Ann Pharmacother       Date:  2008-08-12       Impact factor: 3.154

6.  Propylene glycol pharmacokinetics and effects after intravenous infusion in humans.

Authors:  P A Speth; T B Vree; N F Neilen; P H de Mulder; D R Newell; M E Gore; B E de Pauw
Journal:  Ther Drug Monit       Date:  1987-09       Impact factor: 3.681

7.  Propylene glycol accumulation in critically ill patients receiving continuous intravenous lorazepam infusions.

Authors:  Erica L Horinek; Tyree H Kiser; Douglas N Fish; Robert MacLaren
Journal:  Ann Pharmacother       Date:  2009-11-17       Impact factor: 3.154

8.  Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults.

Authors:  Alejandro C Arroliga; Nadine Shehab; Kevin McCarthy; Jeffrey P Gonzales
Journal:  Crit Care Med       Date:  2004-08       Impact factor: 7.598

Review 9.  The role of GABAA receptors in mediating the effects of alcohol in the central nervous system.

Authors:  Martin Davies
Journal:  J Psychiatry Neurosci       Date:  2003-07       Impact factor: 6.186

10.  Propylene glycol-associated renal toxicity from lorazepam infusion.

Authors:  Ndidi E Yaucher; Jeffrey T Fish; Heidi W Smith; Jeffrey A Wells
Journal:  Pharmacotherapy       Date:  2003-09       Impact factor: 4.705

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