Correspondence

Propylene Glycol Toxicity in a Patient Receiving Intravenous Diazepam

N Engl J Med 2000; 343:815September 14, 2000

Article

To the Editor:

Alcohol withdrawal is a common problem among hospitalized patients and is frequently treated with intravenous diazepam. Propylene glycol is a solvent in which diazepam is often dissolved for intravenous infusion. We report a case of nearly fatal propylene glycol toxicity in a patient receiving intravenous diazepam for the treatment of alcohol withdrawal.

A 46-year-old man with alcoholism was admitted to the hospital with painless facial swelling attributed to angioedema. On the second hospital day, agitation, fever, flushing, tachycardia, hypertension, and tremulousness developed. Because of presumed alcohol withdrawal, he was treated with intravenous diazepam and received approximately 3000 mg over the next 24 hours. Progressively more severe tachypnea and hypotension developed; arterial blood gas studies performed while the patient was breathing room air showed that the pH was 7.16, the partial pressure of carbon dioxide was 22 mm Hg, and the partial pressure of oxygen was 90 mm Hg. Additional laboratory values were as follows: bicarbonate level, 7 mmol per liter (as compared with 23 mmol per liter 15 hours earlier); creatinine level, 2.2 mg per deciliter (as compared with 0.6); anion gap, 31 (as compared with 12); and serum osmolality, 600 mOsm per kilogram. Methanol, ethanol, ethylene glycol, and isopropyl alcohol were undetectable. The patient required treatment with two vasopressor agents and underwent emergency dialysis. After a single session of dialysis, his acid–base status normalized, his condition became hemodynamically stable, and he recovered completely. The propylene glycol level was 1300 mg per deciliter.

Propylene glycol is a clear, colorless, odorless liquid with a sweet taste. It is thought to have low toxicity and is used as a vehicle for intravenous medications, topical medications, and cosmetics.1 The Food and Drug Administration considers propylene glycol safe for use in medication and cosmetics.2 Approximately 55 percent of propylene glycol is metabolized to lactic acid by hepatic alcohol dehydrogenase. The lactic acid is then metabolized to pyruvic acid and shunted to the glycolytic pathway. The remaining 45 percent is excreted by the kidneys.1

Propylene glycol toxicity has not been well studied. The incidence of toxic effects, predisposing factors, and dose–effect relations are not known. Case reports have described hyperosmolality, with or without lactic acidosis, in patients in whom propylene glycol was used as a vehicle to deliver topical silver sulfadiazene cream,1,3 intravenous nitroglycerin,4 or etomidate.5

We believe that acidosis developed in this patient as a result of a large excess of propylene glycol that was metabolized to lactic acid. Thus, life-threatening acidosis from propylene glycol toxicity is a danger when diazepam is used intravenously in high doses to treat alcohol withdrawal and should be considered in the appropriate clinical situation.

Kevin C. Wilson, M.D.
Christine Reardon, M.D.
Harrison W. Farber, M.D.
Boston University School of Medicine, Boston, MA 02118-2394

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Citing Articles (11)

Citing Articles

1. 1

   Ajit Vigg. (2011) Principles and Practice of Sedation in Intensive Care Unit (ICU). Apollo Medicine 8:1, 13-23
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2. 2

   John W. Devlin, Stephanie Mallow-Corbett, Richard R. Riker. (2010) Adverse drug events associated with the use of analgesics, sedatives, and antipsychotics in the intensive care unit. Critical Care Medicine 38, S231-S243
   CrossRef

3. 3

   Kathleen A. Bledsoe, Andreas H. Kramer. (2008) Propylene Glycol Toxicity Complicating Use of Barbiturate Coma. Neurocritical Care 9:1, 122-124
   CrossRef

4. 4

   Brian J. Barnes, Christopher Gerst, Jennifer R. Smith, Andrea R. Terrell, Michael E. Mullins. (2006) Osmol Gap as a Surrogate Marker for Serum Propylene Glycol Concentrations in Patients Receiving Lorazepam for Sedation. Pharmacotherapy 26:1, 23-33
   CrossRef

5. 5

   Ndidi E. Yaucher, Jeffrey T. Fish, Heidi W. Smith, Jeffrey A. Wells. (2003) Propylene Glycol–Associated Renal Toxicity from Lorazepam Infusion. Pharmacotherapy 23:9, 1094-1099
   CrossRef

6. 6

   Ali H. Al-Khafaji, William E. Dewhirst, Harold L. Manning. (2002) Propylene Glycol Toxicity Associated with Lorazepam Infusion in a Patient Receiving Continuous Veno-Venous Hemofiltration with Dialysis. Anesthesia & Analgesia 94:6, 1583-1585
   CrossRef

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   V ABERNETHY, W LIEBERTHAL. (2002) Acute renal failure in the critically ill patient. Critical Care Clinics 18:2, 203-222
   CrossRef

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   S BORKAN. (2002) Extracorporeal therapies for acute intoxications. Critical Care Clinics 18:2, 393-420
   CrossRef

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      . (2001) Propyleenglycol-intoxicatie bij intraveneus toegediende diazepam. Medisch-Farmaceutische Mededelingen 39:7, 145-145
   CrossRef

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    (2001) Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 10:1, 69-84
    CrossRef

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    &NA;. (2000) Propylene glycol. Reactions Weekly &NA;:820, 10
    CrossRef