Practical ToxicologyEthanol Toxicosis: A Review - Today's Veterinary Practice

Practical Toxicology
Ethanol Toxicosis: A Review

July/August 2017   •   (Volume 7, Number 4)

Tina Wismer, DVM, DABVT, DABT, ASPCA Animal Poison Control Center, Urbana, Illinois

Welcome to Practical Toxicology, brought to you in partnership between Today’s Veterinary Practice and the ASPCA Animal Poison Control Center (APCC) (aspcapro.org/poison). This column provides practical clinical information about diagnosing and treating pets that have been exposed to potentially harmful substances.

The APCC:

  • Provides 24-hour diagnostic and treatment recommendations by specially trained veterinary toxicologists
  • Protects and improves animal lives through toxicology education, consulting services, and case data review
  • Developed and maintains AnTox, an animal toxicology database system that identifies and characterizes toxic effects of substances in animals
  • Works closely with human poison control centers to provide animal poisoning information
  • Offers extensive veterinary toxicology consulting to organizations in industry, government, and agriculture.

If treating a patient that requires emergency care for poisoning, call the APCC at 888-426-4435.

Although we mostly think of ethanol (ethyl alcohol) as the alcohol used in beverages, it is also found in other substances: liquid medications, cosmetics, hand sanitizers, perfumes, colognes, mouthwashes, food flavorings (eg, vanilla extract), alcohol-filled chocolates, and fermenting yeast bread dough. Ethanol is produced from fermentation of sugar, cellulose, or starch, which is why ingestion of raw yeast dough causes intoxication.1 Although ethanol is used to treat ethylene glycol toxicosis, ingestion of ethanol can be dangerous. Most animal exposures to ethanol result from beverages being left unattended. Alcoholic drinks made with milk or cream are especially attractive to pets.

ETHANOL ABSORPTION

Ethanol is a central nervous system (CNS) depressant. It enhances the inhibitory effects of gamma-aminobutyric acid (GABA) at the GABA-A receptor and competitively inhibits the binding of glycine at the N-methyl-d-aspartate receptor (it disrupts excitatory glutaminergic neurotransmission).2 Ethanol also stimulates release of other inhibitory neurotransmitters, such as dopamine and serotonin.

Ethanol is absorbed rapidly and completely from the stomach, small intestine, and colon. In humans, 80% to 90% is absorbed within 30 to 60 minutes.3 Ethanol can also be absorbed dermally, especially if the skin is not intact.2 Peak plasma levels occur 30 minutes to 2 hours after ingestion but can be delayed after larger doses or in the presence of food.3 Although the time to reach peak plasma levels in these situations is increased, there is little difference in the amount absorbed.4 Most ingested ethanol (95%) is metabolized in the liver by alcohol dehydrogenase to acetaldehyde and then to acetic acid.3 About 5% to 10% is excreted unchanged in the breath, urine, sweat, and feces.3,5,6

The elimination half-life is not meaningful because it is affected by saturation of the metabolizing enzymes.5 At lower concentrations, the elimination rate may be nonlinear (first-order reaction), but it becomes linear (zero-order reaction) at high concentrations when all the available alcohol dehydrogenase is occupied.5 In the average human adult, the blood level of ethanol decreases by 15 to 20 mg/dL per hour.6 In animals, the onset of action is typically within 1 hour of exposure; most animals recover within 12 to 24 hours.7–9

The amount of ethanol needed to cause intoxication varies depending on its concentration in the substance ingested (Table 1). The published oral lethal dose in dogs is 5.5 to 7.9 g/kg of 100% ethanol.11 One milliliter of ethanol is equal to 0.789 g. Kammerer et al reported a case of lethal ethanol toxicosis in a dog caused by the massive ingestion of rotten apples.12

Table 1 Ethanol Concentrations in Alcoholic Beverages and Other Household Products 5,10

SUBSTANCEPROOFa% ETHANOL BY VOLUME
Light beer5–72.5–3.5
Beer8–124–6
Ale10–165–8
Wine20–4010–20
Mouthwash14–27
Amaretto34–5617–28
Aftershave19–90
Schnapps40–10020–50
Coffee liqueurs42–5321–26.5
Brandy70–8035–40
Bourbon80–9040–45
Rum80–8240–41
Cognac80–8240–41
Vodka80–8240–41
Whiskey80–9040–45
Tequila80–9240–46
Gin80–9440–47
Cologne/perfume50
Hand sanitizers60–95
aFor alcoholic beverages, the proof is double the percentage of alcohol present.

CLINICAL SIGNS

The most common clinical signs of ethanol toxicosis are ataxia, lethargy, vomiting, and recumbency. In more severe cases, hypothermia, disorientation, vocalization, hypotension, tremors, tachycardia, acidosis, diarrhea, respiratory depression, coma, seizures, and death may occur.4

Alcohol is directly irritating to the stomach and causes vomiting. High ethanol blood levels also stimulate emesis. The concern with vomiting during intoxication is that at high blood ethanol concentrations, the muscles that control the epiglottis become slow to react or even paralyzed. This increases the risk for aspiration.13 Ethanol intoxication reduces peripheral oxygen delivery and metabolism and causes mitochondrial oxidative dysfunction, potentially resulting in shock or hypoxia in an acutely intoxicated patient.14

Hypothermia may result from multiple mechanisms. Peripheral vasodilation, CNS depression, ethanol interference with the thermoregulator mechanism, and/or impaired behavioral responses to a cold environment all lead to a lowered body temperature.3

MANAGEMENT

  • Induce emesis only in asymptomatic animals. Activated charcoal is not indicated because it binds poorly to ethanol.15 In addition, because ethanol toxicosis is characterized by vomiting, the risk for charcoal aspiration is high.
  • In cases of dermal exposure, bathe the animal to reduce both dermal absorption and ingestion resulting from grooming behaviors.
  • Monitor heart rate and rhythm, blood pressure, and body temperature. Monitor for acidosis and calculate anion gap if possible. The normal anion gap for dogs and cats is 10 to 15 mEq/L. Values greater than 25 mEq/L are considered acidotic.16 Although there are no data on how often acidosis occurs in pets, about 45% of intoxicated humans become acidotic.17
  • Monitor for hypoglycemia. If dietary and hepatic (glycogenolysis) sources of glucose are exhausted, hypoglycemia may result. During the oxidation of ethanol, the ratio between oxidized and reduced forms of nicotinamide adenine dinucleotide increases, which increases the conversion of pyruvate to lactate. This leads to a lack of the key intermediate in gluconeogenesis, pyruvate, and hypoglycemia ensues.18 Hypoglycemia, which can result in seizures and coma, is a serious complication of acute alcoholic intoxication.10 Dextrose may need to be added to IV fluids.
  • IV fluids do not accelerate ethanol clearance in intoxicated patients but should be started for supportive purposes.19 Use isotonic solutions. Sodium bicarbonate (0.5 × kg body weight × base deficit = deficit in mEq) can be added to combat metabolic acidosis. Give half the sodium bicarbonate dose over 3 to 4 hours.20
  • Treat any arrhythmias symptomatically (atropine for bradycardia, lidocaine for ventricular premature contractions). Control seizures not related to hypoglycemia with diazepam. If the animal is comatose, pass an endotracheal tube and position the patient to prevent aspiration. In cases of severe intoxication, monitor oxygen saturation and be prepared to mechanically support the animal’s breathing. Yohimbine (0.11 mg/kg IV), atipamezole (100 mcg/kg IV), or naloxone (0.1 mg/kg IV) can be tried to reverse severe CNS depression or coma.20 This reversal effect does not appear to be predictable or consistent in animals.21

Animals that are mildly affected may be monitored at home. Patients with significant CNS depression, those requiring airway protection or ventilatory support, and those with seizures, acid-base disturbances, or hypoglycemia should be admitted for monitoring and supportive care. In severe cases, hemodialysis may be considered. Keno and Langston reported using hemodialysis in a dog with rapid clinical recovery.22 Hemodialysis can eliminate ethanol approximately 3 to 4 times more rapidly than liver metabolism alone.

Although ethanol levels may be determined from blood, serum, plasma, and urine, they are seldom measured in pets.23 In most cases, such measurements need to be performed at a human hospital. In humans, blood ethanol concentrations between 150 and 300 mg/dL (32.6 to 65.2 mmol/L) generally cause obvious signs and symptoms. Death is usually associated with blood ethanol levels >400 mg/dL (86.8 mmol/L).3 In the case report by Kammerer et al, the dog that ingested rotten apples exhibited vomiting, ataxia, tremors, and dehydration and died 48 hours later with an alcoholemia of 300 mg/dL.12 If the blood ethanol level cannot be measured, serum or plasma osmolality may be used to estimate it, using the following formula24:

Blood ethanol level [g/L] = Osmolal gap/27

DIFFERENTIAL DIAGNOSIS

Most ethanol intoxications are unmistakable because of the odor of alcohol on the pet’s breath. However, other toxic differentials for intoxicated patients include salicylates, marijuana, toluene, ethylene glycol, methanol, isopropanol, benzodiazepines, barbiturates, opiates, and gamma-hydroxybutyric acid.7–9 Nontoxic differentials include lactic acidosis, uremia, diabetic ketoacidosis, cardiovascular accident, hypoglycemia, and hypoxia.7–9

PROGNOSIS

In most cases of ethanol ingestion, the prognosis is good. Cases complicated by aspiration of gastric contents, presence of other ingested material, or preexisting disease have a more guarded prognosis. Intoxicated animals are also predisposed to traumatic injuries.

References

  1. Bingham E, Cohrssen B, Powell CH. Patty’s Toxicology. Vol. 6. 5th ed. New York: John Wiley & Sons; 2001.
  2. Fleming M, Mihic SJ, Harris RA. Ethanol. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill; 2006:591-606.
  3. Yip L. Ethanol. In: Nelson LS, Lewis NA, Howland M, et al, eds. Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011:1115-1128.
  4. Valentine WM. Short-chain alcohols. Vet Clin North Am 1990;20(2):515-523.
  5. Baselt RC. Disposition of Toxic Drugs and Chemicals in Man. 5th ed. Foster City, CA: Chemical Toxicology Institute; 2000.
  6. Brennan DF, Betzelos S, Reed R. Ethanol elimination rates in an ED population. Am J Emerg Med 1995;13(3):276-280.
  7. Heard K. Ethanol. In: Dart RC et al, eds. The 5 Minute Toxicology Consult. Philadelphia: Lippincott Williams & Wilkins; 2000:112-113.
  8. Yip L. Methanol. In: Dart RC et al, eds. The 5 Minute Toxicology Consult. Philadelphia: Lippincott Williams & Wilkins; 2000:498-499.
  9. Hurlbut KM. Isopropyl alcohol. In: Dart RC et al, eds. The 5 Minute Toxicology Consult. Philadelphia: Lippincott Williams & Wilkins; 2000:452-453.
  10. Hornfeldt CS. A report of acute ethanol poisoning in a child: mouthwash versus cologne, perfume and after-shave. Clin Toxicol 1992;30(1):115-121.
  11. Wimer WW, Russel JA, Kaplan HL. Alcohols Toxicology. Park Ridge, NJ: Noyes Data Corp; 1983:8-76.
  12. Kammerer M, Sachot E, Blanchot D. Ethanol toxicosis from the ingestion of rotten apples by a dog. Vet Hum Toxicol 2001;43(6):349-350.
  13. Johnson HRM. At what blood levels does alcohol kill? Med Sci Law 1985;25:127-130.
  14. Gutierrez CA, Lambert C, Harrah J. Moderate alcohol intoxication directly reduces peripheral oxygen delivery and utilization (abstract). Acad Emerg Med 1999;6:391-392.
  15. Cooney DO. Effects of Activated Charcoal on Major classes of drugs and chemicals. In: Cooney DO, ed. Activated Charcoal in Medical Applications, 2nd New York: Marcel Dekker; 1995:197-244.
  16. Braden GL, Strayhorn CH, Germain MJ. Increased osmolol gap in alcoholic acidosis. Arch Intern Med 1993;153(20):2377-2380.
  17. Zehtabchi S, Sinert R, Baron BJ, et al. Does ethanol explain the acidosis commonly seen in ethanol-intoxicated patients? Clin Toxicol 2005;43(3):161-166.
  18. Hoffman RS, Goldfrank LR. Ethanol-associated metabolic disorders. Emerg Med Clin North Am 1989;7(4):943-961.
  19. Li J, Mills T, Erato R. Intravenous saline has no effect on blood ethanol clearance. J Emerg Med 1999;17(1):1-5.
  20. Plumb DC. Plumb’s Veterinary Drug Handbook. 8th ed. Ames, IA: Wiley-Blackwell, 2015.
  21. Lister RG, Durcan MJ, Nutt DJ, Linnoila M. Attenuation of ethanol intoxication by alpha-2 adrenoceptor antagonists. Life Sci 1989;44(2):111-119.
  22. Keno LA, Langston CE. Treatment of accidental ethanol intoxication with hemodialysis in a dog. J Vet Emerg Crit Care 2011;21(4):363-368.
  23. Olson KR. Comprehensive evaluation and treatment of poisoning and overdose. In: Olson KR, ed. Poisoning & Drug Overdose. Norwalk, CT: Appleton & Lange; 1994.
  24. Weiss M, Thurnheer U. Die osmotische Lucke zur Diagnose der Alkoholintoxikation. Schweiz Med Wochenschr 1988;118:845-848.

Tina Wismer, DVM, DABVT, DABT, is responsible for overseeing medical recommendations made by the veterinary staff at ASPCA Animal Poison Control Center (APCC). She is also highly involved in lecturing, making media appearances, and writing, and she coordinates the APCC’s extern program. Dr. Wismer earned her undergraduate degree from Ohio’s University of Findlay and received her DVM from Purdue University. Her first job was in a small animal practice in Michigan. She then worked for an emergency practice in South Bend, Indiana, before joining the APCC. Dr. Wismer has written several peer-reviewed toxicology articles and book chapters. She is an adjunct instructor at the University of Illinois, previously a visiting professor at St. Matthews University (Cayman), a consultant for VIN (Veterinary Information Network), and a Master Gardener.

 

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