Propylene Glycol as a Cause of an Elevated Serum Osmolality

Bekeris, Leonas; Baker, Catherine; Fenton, John; Kimball, Douglas; Bermes, Edward W.

doi:10.1093/ajcp/72.4.633

Cited by 48 publications

(12 citation statements)

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“…Drugs in which it is present include etomidate, phenytoin, diazepam, lorazepam, phenobarbital, nitroglycerin, digoxin, hydralazine, and trimethoprim-sulfamethoxazole. Cases of intoxication have been reported after topical administration for treatment for burns (31) and with oral ingestion (49), but the majority of reported cases have resulted from intravenous administration (36,100,101,104,105). In this regard, propylene glycol is used as a diluent in benzodiazepines (lorazepam concentration, vol/ vol 0.8), which commonly are administered to patients who have seizures, are undergoing alcoholic withdrawal, or are intubated (36).…”

Section: Epidemiologymentioning

confidence: 99%

“…Serum osmolality can be normal or high (26,36,105,107,109,111), and an increased serum osmolality may be the only evidence of abnormal blood concentrations. Because its half-life in blood is short, once the intravenous infusion is discontinued, serum osmolality will return rapidly to baseline.…”

Section: Laboratory Findingsmentioning

confidence: 99%

“…Because its half-life in blood is short, once the intravenous infusion is discontinued, serum osmolality will return rapidly to baseline. As a result, several clinicians have recommended using the serum osmolal gap as a surrogate for propylene glycol concentrations to evaluate the response to treatment (19,105,106,111).…”

Section: Laboratory Findingsmentioning

confidence: 99%

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Toxic Alcohol Ingestions

Kraut¹,

Kurtz²

2008

Clinical Journal of the American Society of Nephrology

370

326

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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. Table 1. Methanol, ethylene glycol, diethylene glycol, and propylene glycol intoxication and alcoholic ketoacidosis can produce hyperosmolality and metabolic acidosis (3-9). Isopropanol intoxication is usually associated with hyperosmolality alone (4,5). Importantly, several of these disorders can be fatal or produce irreversible tissue damage if they are not quickly recognized and treated appropriately (4 -15). Effect of Alcohols on Serum Osmolality and the Osmolal GapThe normal serum osmolality of 285 to 290 mOsm/L is due to sodium and its counterbalancing ions, bicarbonate and chloride, and glucose and urea. It can be calculated using the following equation:Serum osmolality (mOsm/L) ϭ 2 ϫ Na ϩ ϩ blood urea nitrogen (mg/dl)/2.8 ϩ glucose (mg/dl)/18. The serum osmolality measured by freezing point depression is usually within 10 mOsm/L of the calculated serum osmolality (16). Accumulation of low molecular weight substances in the serum (such as each of the alcohols) will raise the measured serum osmolality above that of the calculated serum osmolality, producing an osmolal gap (4,5,16 -18). The effect of each of the alcohols on serum osmolality is shown in Table 2. Methanol gives rise to the greatest increment in serum osmolality, followed by ethanol, isopropanol, ethylene glycol, propylene glycol, and diethylene glycol in that...

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Section: Epidemiologymentioning

confidence: 99%

Section: Laboratory Findingsmentioning

confidence: 99%

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Toxic Alcohol Ingestions

Kraut¹,

Kurtz²

2008

Clinical Journal of the American Society of Nephrology

370

326

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“…Absorption of the agent from creams applied to burns 157,158 and injection of multivitamin products or enoximone (a phosphodiesterase inhibitor) in infants has resulted in serum hyperosmolality, 159,160 which was associated with cardiorespiratory arrest in one case. 160 Neonates have a longer propylene glycol half-life (16.9 hours) compared with adults (5 hours).…”

Section: Propylene Glycolmentioning

confidence: 99%

“Inactive” Ingredients in Pharmaceutical Products: Update (Subject Review)

1997

Pediatrics

141

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ABSTRACT. Because of an increasing number of reports of adverse reactions associated with pharmaceutical excipients, in 1985 the Committee on Drugs issued a position statement 1 recommending that the Food and Drug Administration mandate labeling of over-thecounter and prescription formulations to include a qualitative list of inactive ingredients. However, labeling of inactive ingredients remains voluntary. Adverse reactions continue to be reported, although some are no longer considered clinically significant, and other new reactions have emerged. The original statement, therefore, has been updated and its information expanded.ABBREVIATIONS. FDA, Food and Drug Administration; MDIs, metered-dose inhalers Pharmaceutical products often contain agents that have a variety of purposes, including improvement of the appearance, bioavailability, stability, and palatability of the product. Excipients (substances added to confer a suitable consistency or form to a drug, such as the vehicle, preservatives, or stabilizers) frequently make up the majority of the mass or volume of oral and parenteral drug products. These pharmaceutical adjuvants are usually considered to be inert and do not add to or affect the intended action of the therapeutically active ingredients.Some 773 chemical agents have been approved by the Food and Drug Administration (FDA) for use as inactive ingredients in drug products.2 Inasmuch as these compounds are classified as "inactive," no regulatory statutes require listing on product labeling. Pharmacopeial guidelines, enforceable under the Food, Drug, and Cosmetic Act, do require labeling of inactive ingredients for topical, ophthalmic, and parenteral preparations; orally administered products are currently exempt. Because of pressure from professional and consumer organizations asking the FDA to require complete disclosure of all ingredients, voluntary labeling was adopted by the two major pharmaceutical industry trade associations. These voluntary guidelines contain an exemption for "trade secret" components and do not require complete disclosure of all fragrance and flavoring ingredients.Current problems encountered with "inactive" ingredients include benzalkonium chloride-induced bronchospasm from antiasthmatic drugs, aspartameinduced headache and seizures, saccharin-induced cross-sensitivity reactions in children with sulfonamide allergy, benzyl alcohol toxicity in neonates receiving high-dose continuous infusion with preserved medications, dye-related cross-reactions in children with aspirin intolerance, lactose-induced diarrhea, and propylene glycol-induced hyperosmolality and lactic acidosis. Although many other excipients have been implicated in causing adverse reactions, these are the most significant in the pediatric population. ANTIASTHMATIC MEDICATIONSIt is readily appreciated that some percentage of asthmatic children will develop a "paradoxical" bronchospasm after they inhale their medication. Because many of these reactions were attributed to sulfite, which had been highly publicized ...

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“…Propylene glycol (1, 2-propanediol) is a solvent used in intravenous preparation of lorazepam and diazepam. The toxic effects range from hyperosmolality, hemolysis, rhabdomyolysis, cardiac arrhythmia, seizure, and coma [3]. In addition, development of lactic acidosis, hypotension, and multisystem organ dysfunction in propylene glycol toxicity often mimic the features of septic shock.…”

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confidence: 99%

Acute Renal Failure in Tetanus: Correspondence

Arya

Jindal

2014

Indian J Pediatr

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To the Editor: We read the article 'Acute renal failure in tetanus' by Kaur et al. with interest [1]. The authors had reported acute kidney injury and myoglobinuria in a 10-y-old child with tetanus. We intend to highlight certain issues regarding the management of this child.The child was administered very high doses of intravenous diazepam (50 mg/kg/d) which could have predisposed to potentially life-threatening propylene glycol toxicity [2]. Propylene glycol (1, 2-propanediol) is a solvent used in intravenous preparation of lorazepam and diazepam. The toxic effects range from hyperosmolality, hemolysis, rhabdomyolysis, cardiac arrhythmia, seizure, and coma [3]. In addition, development of lactic acidosis, hypotension, and multisystem organ dysfunction in propylene glycol toxicity often mimic the features of septic shock.The normal range of serum creatinine in the 7-10 y age group is 0.22-0.6 mg/dL. The documented baseline serum creatinine level in this child was 0.9 mg/dL. This point to preexisting renal dysfunction at the onset; however, whether the underlying cause was ongoing rhabdomyolysis or autonomic dysfunction is a matter of debate.The child suffered sudden cardiac arrest on sixth day of hospitalization. The commonest cause of death in patients with severe tetanus on ventilator support is tetanusassociated autonomic dysfunction. Magnesium sulphate is useful for control of autonomic dysfunction in these patients. The muscle relaxation property of Magnesium sulphate controls spasms and cardiovascular manifestations (vasodilatation, lowering of heart rate, and reduction of systemic catecholamine release) and is responsible for ameliorating the ill effects of autonomic dysfunction. A recent randomized controlled trial also reiterated that magnesium sulphate infusion effected a reduction in the requirement of other drugs to control muscle spasms and cardiovascular instability without reducing the need for mechanical ventilation in patients with severe tetanus [4].While managing acute kidney injury due to rhabdomyolysis, infusion of large volume of intravenous fluids within the first 24 h is associated with improved outcomes [5]. Alkalinization of the urine is also practiced routinely, but evidence of significant clinical benefit is lacking. A current consensus statement suggests that sodium bicarbonate administration is neither necessary nor superior to normal saline diuresis in increasing urine pH [5].

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Propylene Glycol as a Cause of an Elevated Serum Osmolality

Cited by 48 publications

References 0 publications

Toxic Alcohol Ingestions

Toxic Alcohol Ingestions

“Inactive” Ingredients in Pharmaceutical Products: Update (Subject Review)

Acute Renal Failure in Tetanus: Correspondence

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