Propylene Glycol Toxicity: A Severe Iatrogenic Illness in ICU Patients Receiving IV Benzodiazepines

Wilson, Kevin C.; Reardon, Christine Campbell; Theodore, Arthur C.; Farber, Harrison W.

doi:10.1378/chest.128.3.1674

Cited by 155 publications

(141 citation statements)

References 24 publications

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“…Inhalation of methanol or topical absorption of ethylene glycol, propylene glycol, isopropanol, and diethylene glycol can produce intoxications (12,13,30 -34), but most intoxications occur after their oral ingestion or, in the case of propylene glycol (4,5,12,13,35,36), after intravenous administration.…”

Section: Effect Of Alcohols On Serum Osmolality and The Osmolal Gapmentioning

confidence: 99%

“…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%

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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: Effect Of Alcohols On Serum Osmolality and The Osmolal Gapmentioning

confidence: 99%

Section: Epidemiologymentioning

confidence: 99%

Toxic Alcohol Ingestions

Kraut¹,

Kurtz²

2008

Clinical Journal of the American Society of Nephrology

370

326

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“…The incidence of PG toxicity is still unknown. Severity of PG toxicity ranges from common metabolic abnormalities to infrequent cases of clinical deterioration with systemic inflammatory response syndrome (SIRS) [51]. High-dose application of benzodiazepine in patients with impaired kidney function appears to be a risk factor for PG toxicity [52].…”

Section: Pathophysiologymentioning

confidence: 99%

Drug-induced acid-base disorders

et al. 2014

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The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal antiinflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g

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“…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.…”

mentioning

confidence: 99%

“…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.…”

mentioning

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 Toxicity: A Severe Iatrogenic Illness in ICU Patients Receiving IV Benzodiazepines

Cited by 155 publications

References 24 publications

Toxic Alcohol Ingestions

Toxic Alcohol Ingestions

Drug-induced acid-base disorders

Acute Renal Failure in Tetanus: Correspondence

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