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

Arroliga, Alejandro C.; Shehab, Nadine; McCarthy, Kevin; Gonzales, Jeffrey

doi:10.1097/01.ccm.0000134831.40466.39

Cited by 96 publications

(79 citation statements)

References 31 publications

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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%

Toxic Alcohol Ingestions

Kraut¹,

Kurtz²

2008

Clinical Journal of the American Society of Nephrology

354

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%

Toxic Alcohol Ingestions

Kraut¹,

Kurtz²

2008

Clinical Journal of the American Society of Nephrology

354

326

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“…The percentage of propylene glycol in these solutions varies from 35 to 80%. Although it is generally regarded as safe, potential safety concerns have been described in patients receiving these parenteral medications, especially lorazepam, which has the highest content of 80 percent of propylene glycol (PG) [2][3][4]. Long-term administration of high intravenous doses of lorazepam can result in propylene glycol accumulation with toxic effects.…”

Section: Introductionmentioning

confidence: 99%

“…Long-term administration of high intravenous doses of lorazepam can result in propylene glycol accumulation with toxic effects. These effects include hyperosmolar metabolic acidosis, hemolysis, renal dysfunction, cardiac arrhythmias, seizures and central nervous system depression [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

LC Determination of Propylene Glycol in Human Plasma After Pre-Column Derivatization with Benzoyl Chloride

Sinjewel

Swart

Lingeman

et al. 2007

Chroma

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A simple high-performance liquid chromatographic method, using photodiode array detection was developed for the determination of propylene glycol in human plasma and in the fluid retreived after continuous veno-venous hemofiltration. The method entailed alkaline derivatization with benzoyl chloride and ethylene glycol as internal standard. The separation of the compounds, after extraction with pentane, was carried out on a Pursuit C8 column with UVdetection at 230 nm. Validation samples were analyzed with an accuracy between 95 and 105%, and intra-and inter-day coefficients of variation of less than 8%. The calibration curve was linear over a concentration range of 5-100 mg L )1 with a detection limit of 1 mg L )1. Blood plasma samples of several patients were analysed by using the prescribed method with propylene glycol concentrations varying from 5 to 98 mg L )1 . Compared to previously described LC methods, this method is ten times more sensitive and thus suitable for use in pharmacokinetic studies of propylene glycol.

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“…118 LA due to propylene glycol has been reported by many authors and its incidence with high dose intravenous (IV) lorazepam has been estimated to be as high as 19%. 114,116,119,120 This disorder can frequently go unrecognized, as many other factors that induce LA often coincide in such patients. But when identified and promptly addressed, its prognosis seems to be favorable.…”

Section: Lorazepammentioning

confidence: 99%

Treatment of lactic acidosis: Appropriate confusion

Rachoin

Weisberg

McFadden

2010

Journal of Hospital Medicine

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Lactic acid is a marker of tissue ischemia but it also may accumulate without tissue hypoperfusion. In the latter circumstance, lactic acid accumulation may be an adaptive mechanism-a novel possibility quite in contrast to the traditional view of lactic acid as only a marker of tissue ischemia. Studies on the treatment of LA with sodium bicarbonate or other buffers fail to show consistent clinical benefit. Severe acidemia in the setting of LA is a particularly poorly studied area. In the settings of medication-induced LA, optimal treatment, apart from prompt cessation of the offending agent, is still unclear.

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

Cited by 96 publications

References 31 publications

Toxic Alcohol Ingestions

Toxic Alcohol Ingestions

LC Determination of Propylene Glycol in Human Plasma After Pre-Column Derivatization with Benzoyl Chloride

Treatment of lactic acidosis: Appropriate confusion

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