An unusual case of poisoning.

Abstract: The case of a 49-year-old alcoholic man with obtundation is presented. The patient was presumptively diagnosed with methanol intoxication due to the presence of metabolic acidosis with high anion and osmolar gaps. Laboratory testing revealed toxic levels of propylene glycol instead. An exercise in estimating the concentration of toxic alcohols and glycols is given, and the literature on poisoning with this unusual but commonly encountered intoxicant is briefly reviewed.

Key Words: anion gap, metabolic acidosis, osmolar gap, propylene glycol

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Establishing the diagnosis of a poisoned patient can be problematic. The patient is often obtunded and unable to provide a history or may have no knowledge or memory of exposure to toxic substances. In these situations, routine laboratory tests and calculations are often helpful in determining the etiologic agent. The finding of an anion gap metabolic acidosis with a concomitant osmolar gap is suggestive of intoxication with a toxic alcohol or glycol. We recently cared for such a patient with poisoning due to a commonly encountered but frequently overlooked intoxicant.

Case Report

Family members brought a 49-year-old alcoholic man to the emergency room after they were unable to rouse him after a night when he was reportedly out drinking, first at a local bar, and later at the home of a friend. The patient consumed alcohol daily, and family members reported that he and his friends frequently consumed a "homemade" alcoholic beverage, but the ingredients were unknown to the family. He reported no chronic medical problems and took no medications regularly.

At admission, his temperature was 98.1[degrees]F, his respiratory rate was 16 breaths/rain, his pulse was 75 beats/ rain, and his blood pressure was 127/65 mm Hg, with an oxygen saturation of 100% on room air. He was lethargic but responsive to voice. His breath had a fruity aroma. He was oriented to name and place only, and he appeared to have no gross visual problems. The remainder of the physical examination was unremarkable. Laboratory studies revealed a pH of 7.10, an anion gap of 18, and a measured serum osmolality of 333 mOsm/kg, with a calculated value of 298 mOsm/kg. The patient's ethanol level was 76 mg/dl. A serum lactate level was 5.6 mmol/L. His urinalysis was negative fur crystals.

On the basis of the clinical scenario and the history of consumption of unbonded alcohol in the past, the patient was diagnosed with methanol ingestion and admitted to the medical intensive care unit (ICU). An ethanol infusion was started, and hemodialysis was initiated. One hour into dialysis, the patient's pH had normalized, his anion gap had decreased to 7, and his osmolar gap had closed to a near-normal level of 11. The results of the patient's toxic alcohol and glycol screening panel were surprising. Ethylene glycol and methanol levels were undetectable, but the propylene glycol level was 11.8 mg/dl. Hemodialysis was stopped and the ethanol drip was tapered. The remainder of the patient's hospital course was unremarkable, and he was discharged on the third hospital day with his mental status at baseline.

Discussion

Propylene glycol (1,2-propanediol) (PG) is a colorless, nearly odorless alcohol with a variety of uses. Industrially, PG has been used as a component of automotive brake fluids and antifreeze preparations, in the production of varnishes and synthetic resins, as a preservative in the food industry, and as an emulsifier in cosmetics. (1) In pharmaceutical use, PG is used as a vehicle for the administration of unstable drugs and as a preservative. It is a major ingredient in the formulation of several commonly used parenteral drugs, including diazepam, lorazepam, nitroglycerin, and phenytoin. (2) PG can be found in many nonprescription medications, such as cough medicines and contraceptive gels, and is found in varying concentrations in personal hygiene products such as shampoos, shaving creams, and autiperspirants. (1) It is also used in topical preparations of several drugs, including burn medications (2) and keratinolytic lotions. (1) PG is readily absorbed into the body through the gastrointestinal or dermal route. The kidneys eliminate up to 50% of absorbed propylene glycol, and the remainder is metabolized in the liver by means of the alcohol dehydrogenase pathway to lactate, pyruvate, or acetone. (3,4) Patients with impaired liver or kidney function appear to be at increased risk of developing PG toxicity. (4) PG levels greater than 18 mg/dl are associated with increased serum lactate and elevated anion gap acidosis. (5) A theoretical formula for estimation of the concentration of PG (in mg/dl) is osmolar gap due to PG x 7.6. (6) Thus, our patient's PG level at the time of initial presentation was approximately 144 mg/dl.

Our differential diagnosis was constructed by noting the patient's anion gap metabolic acidosis and the presence of an osmolar gap. The differential diagnosis of an anion gap metabolic acidosis includes the presence or ingestion of methanol, uremia, diabetic ketoacidosis, phenformin, paraldehyde, ischemia, isoniazid, iron, lactate, ethylene glycol, ethanol, salicylates, starvation ketosis, or solvents (the traditional MUDPILES mnemonic). The osmolar gap further narrows the differential to methanol, ethanol, diuretics (such as mannitol or sorbitol), isopropyl alcohol, or ethylene glycol (the mnemonic here is ME DIE).

Propylene glycol, which is not normally considered in this differential, should be, because it causes the same biochemical abnormalities as the other toxic alcohols and glycols listed in the mnemonic. A series of calculations were then performed using the laboratory data and the formulae listed in Table 1. (7) The patient's osmolar gap was 35, and the measured ethanol level was 76 mg/dl. Using Formula 3, the change in serum osmolality due to the ethanol (molecular weight [MW], 46 Da) present in the serum was 16. Thus, only 16 of the 35 unmeasured osmoles could be accounted for by the existing ethanol, leaving a residual osmolar gap (Formula 4) of 19. Using Formula 5, the concentrations of other toxic substances were estimated.

Had ethylene glycol (MW, 62 Da) been present, its level would be 118 mg/dl, well above the lethal level of 21 mg/dl. Methanol (MW, 32 Da) concentration would be 61 mg/dl if present, near the lethal level of 80 mg/dl, and was the rationale for starting hemodialysis emergently. Isopropanol (MW, 60 Da) concentration was estimated at 114 mg/dl, but its presence was excluded, because isopropanol intoxication does not usually cause this degree of acidosis. (7)

Most cases of PG toxicity reported in the medical literature occur in ICU patients receiving benzodiazepine drips for sedation or in patients receiving high doses of IV medications, again, often benzodiazepines, in which PG is a dilutant. (1,2,4) In at least two other cases, patients were toxic with PG on presentation to medical attention. In one case, the source was thought to be fruit juice (8); in the other case, a source was not identified. (9) Our patient's PG source was not clearly identified; however, we suspect that it was his "homemade" beverage.

The treatment of PG intoxication is largely supportive. Measures to limit exposure to identified PG sources, such as stopping IV infusion or dermal application of the PG-containing substance, are of paramount importance. (1,2,4,5,8,10) Dialysis is generally unnecessary but achieves rapid correction of acidosis and osmolar gap. (11) Gastric lavage is not recommended for the routine management of any poisoned patient unless the patient has ingested a potentially life-threatening amount of a poison, and the procedure can be undertaken within 60 minutes of ingestion. However, clinical benefit has not been confirmed in controlled studies. (12) Likewise, charcoal binds poorly to alcohols and glycols, and its routine use is not indicated in the absence of ingestion of other adsorbable substances. (13) Death from PG intoxication is rare and appears to be due to cardiac complications of rapid IV infusion of PG-containing medications. (10) No definite toxic range of PG concentration has been established.

Conclusion

The clinical presentation and laboratory findings of a patient with PG toxicity are essentially identical to those of patients poisoned with more toxic alcohols and glycols. PG toxicity should be considered when a sedated ICU patient develops an anion gap metabolic acidosis with a high osmolar gap, as most cases of PG intoxication are related to infusion of drugs using PG as a preservative. Cases in which no source of PG was identifiable have been reported. The acidosis and serum hyperosmolality are easily reversible with removal from exposure to PG and supportive care. Death as a result of PG intoxication is rare.

Key Points

* Anion gap metabolic acidosis with concomitant osmolar gap is usually due to ingestion of a toxic alcohol or glycol.

* Propylene glycol should be considered when the differential diagnosis includes toxic alcohol or glycol intoxication.

* Although most cases of propylene glycol intoxication occur in intensive care unit patients receiving sedative infusions, cases of "community-acquired" propylene glycol intoxication have been reported.

* Propylene glycol toxicity is treated by removal of the propylene glycol source and general supportive care.

References

(1.) Catanzaro JM, Smith JG Jr. Propylene glycol dermatitis. J Am Acad Dermatol 1991;24:90-95.

(2.) Arbour R, Esparis B. Osmolar gap metabolic acidosis in a 60-year-old man treated for hypoxemic respiratory failure. Chest 2000;118:545-546.

(3.) Ruddick JA. Toxicology, metabolism, and biochemistry of 1,2-propanediol, Toxicol Appl Pharmacol 1972;21:102-111.

(4.) Cawley MJ. Short-term lorazepam infusion and concern for propylene glycol toxicity: Case report and review. Pharmacotherapy 2001;21:1140-1144.

(5.) Micromedix (database): Volume 95. Englewood, CO, Micromedix, Inc., 1998.

(6.) Ellenhorn MJ. Alcohols and glycols, in Ellenhorn MJ (ed): Ellenhorn's Medical Toxicology: Diagnosis and Treating of Human Poisoning. Baltimore, Williams & Wilkins, 1997, ed 2, pp 1156-1157.

(7.) Ismail N, Becket BN. Principles &and techniques fur dialysis, plasmapheresis, and hemoperfusion: Common poisoning and drug overdose, in Jacobson H, Striker GE, Klahr S (eds): The Principles and Practice of Nephrology. St. Louis, Mosby-Year Book, 1995, ed 2, pp 730-732.

(8.) Lolin Y, Francis DA, Flanagan RJ, et al. Cerebral depression due to propylene glycol in a patient with chronic epilepsy: The value of the plasma osmolal gap in diagnosis. Postguard Med J 1988;64:610-613.

(9.) Cate JC IV, Hedrick R. Propylene glycol intoxication and lactic acidosis. N Engl J Med 1980;303:1237 (letter).

(10.) Ford MD, Silvilotti ML. Alcohols and glycols, in Irwin RS, Cerra FB. Rippe JM (eds): Irwin and Rippe's Intensive Care Medicine. Philadelphia, Lippincott Williams & Wilkins, 1999, ed 4, pp 1478-1493.

(11.) Parker MG, Fraser GL, Watson DM, et al. Removal of propylene glycol and correction of increased osmolar gap by hemodialysis in a patient on high dose lorazepam infusion therapy. Intensive Care Med 2002;28:81-84.

(12.) Vale JA; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Position statement; Gastric lavage. J Toxicol Clin Toxicol 1997;35:711-719.

(13.) Berk WA, Henderson WV. Alcohols. in Tintinalli JE. Kelen GD, Stapczynski JS (eds): Emergency Medicine: A Comprehensive Study Guide. New York, McGraw-Hill, 1996, ed 4, pp 765-772.

From the Division of Pulmonary and Critical ('are Medicine, Allergy and Clinical Immunology, Medical University of South Carolina, Charleston, SC.

No outside financial support was provided in the preparation of this manuscript. Neither author has a commercial or proprietary interest in any drug, device, or equipment mentioned in this article.

Reprint requests to Steven A. Sahn, MIX Division of Pulmonary and Critical Care Medicine, Allergy and Clinical Immunology. Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 812 CSB, P.O. Box 250630, Charleston, SC 29425. Email: [e-mail]

Accepted December 19, 2002.