Ethanol Toxicity

A colorless, odorless, volatile liquid. It is fully miscible in water and is lipid soluble.

Readily diffuses across lipid membranes, accounting for its ubiquitous multiorgan effects.

Heavily consumed in intoxicating beverages. Used as an additive in gasoline, as a diluent or

solvent, in many household products, and in pharmaceuticals

Its metabolism follows first-order, then after saturation, Zero-order kinetics.

Introduction

CNS depression. Malnutrition by decreasing intake or by

altering absorption, metabolism and/or utilization of nutrients.

Elevation of endotoxin in the bloodstream. Induction of microsomal enzymes. Change in the redox potential of the cell. Production of toxic metabolite

(acetaldehyde). Oxidative stress.

The unfavorable change in redox potential as a consequence of ethanol metabolism contributes to the development of metabolic disorders, increased collagen and scar tissue formation associated with alcoholism, and

a clinical syndrome of alcoholic ketoacidosis. Acetaldehyde directly affects cardiac function, interferes

with phosphorylation, causes structural and functional alterations in mitochondria and hepatocytes, and

inactivates coenzyme A. Acetaldehyde can react with intracellular proteins to

generate adducts. Ethanol metabolism through the hepatic CYP2E1 pathway

generates highly reactive oxygen radicals. The induction of hepatic enzymes by ethanol may increase

the toxicity of some substances like CCl4.

chronic ethanol consumption may promote carcinogenesis by:

Production of acetaldehyde, a weak mutagen and carcinogen.

Induction of CYP2E1 and its associated oxidative stressors and conversion of procarcinogens to carcinogens.

Depletion of S-adenosylmethionine and, consequently, induction of global DNA hypomethylation.

Increased production of inhibitory guanine nucleotide regulatory proteins and components of extracellular signal-regulated kinase-mitogen-activated protein kinase signaling.

Accumulation of iron and associated oxidative stress. Inactivation of the tumor suppressor gene BRCA1 and

increased estrogen responsiveness (primarily in the breast).

Impairment of retinoic acid metabolism.

Clinical Features

Inebriation with variable signs that differ according to the degree of intoxication.

Loss of respiratory reflexes with increased intoxication, coma and maybe death.

Flushed facies, hypothermia, diaphoresis, vomiting and hypotension.

Dysrhythmias . Diplopia, visual disturbances, and nystagmus. decreased serum ionized magnesium

concentrations. Myocardial ischemia in susceptible patients. Ethanol-induced seizures.

Immunoassay or gas chromatography is commonly used for determination of ethanol in liquid specimens in most hospitals.

The usual sample is serum, rarely plasma. Whole blood is used in forensic determination of BAL.

Breath ethanol analyzers make use of electrochemical sensors for ethanol oxidation or infrared spectral analysis for ethanol determination.

Ethanol-saliva testing is a promising alternative to breath ethanol analysis in the rapid assessment of blood ethanol levels in patients.

Blood tests that should be considered for patients with ethanol intoxication or alcoholic ketoacidosis: CBC. Electrolytes. BUN. Creatinine. Ketones. Acetone. Lipase. Liver enzymes. Prothrombin time. Ammonia. Calcium. Magnesium.

gastrointestinal decontamination may be considered in case of delayed absorption or recent ingestion.

endotracheal intubation and ventilatory support in case of severe respiratory depression.

Abnormal vital signs should be addressed and stabilized.

Patients who are combative and violent should be both physically and then chemically restrained with a benzodiazepine.

The patient's fluid and electrolyte status should be assessed and abnormalities corrected.

Hemodialysis is an effective means of enhancing the systemic elimination of ethanol .

Indications for hospital admission: persistently abnormal vital signs. persistently abnormal mental status,

with or without an obvious cause. mixed overdose with other concerning

xenobiotics. concomitant serious trauma. consequential ethanol withdrawal. associated serious disease process,

such as pancreatitis or gastrointestinal hemorrhage.

Ethanol-induced Hypoglycemia

Occurs when ethanol metabolism provides a high cellular reduction-to-oxidation (redox) ratio. This redox state favors the conversion of pyruvate to lactate, diverting pyruvate from gluconeogenesis.

Hypoglycemia associated with ethanol consumption usually occurs in malnourished chronic alcoholics and children

Clinical features include: altered consciousness, hypothermia and tachypnea, positive blood ethanol concentration, ketonuria without glucosuria, and mild acidosis.

Management of ethanol-induced hypoglycemia is similar to other causes of hypoglycemia.

Alcoholic Ketoacidosis

Ethanol metabolism generates NADH, resulting in an excess of reducing potential. This high redox state favors the conversion of pyruvate to lactate.

The body increases fatty acid metabolism as an alternative source of energy

This response is mediated by a decrease in insulin and an increased secretion of glucagon, catecholamines, growth hormone, and cortisol.

Most of the acetoacetate is reduced to β-hydroxybutyrate as a consequence of the excess reducing potential.

Volume depletion contributes to the acidosis.

Lactic acidosis caused by hypoperfusion or infection may coexist with the underlying ketoacidosis.

Patients are typically chronic ethanol users, presenting after a few days of “binge” drinking.

starved because of cessation in oral intake as a consequence of binging itself, or because of:Nausea. Vomiting. Abdominal pain from gastritis, hepatitis,

pancreatitis, or a concurrent acute illness.

Underlying medical conditions may be present.

Alcohol withdrawal may develop. Diagnosis of AKA is a diagnosis of exclusion. blood ethanol concentration is usually low or

undetectable. elevated anion gap metabolic acidosis with a

serum lactate concentration insufficient to account for the gap.

some patients will have a normal arterial pH or be alkalemic.

Reliance on the nitroprusside test alone may underestimate the severity of ketoacidosis.

Treatment should begin with adequate crystalloid fluid replacement dextrose and thiamine.

Supplemental multivitamins, potassium, and magnesium should be instituted on an individual basis.

During the recovery, β-hydroxybutyrate is converted to acetoacetate.

Mortality is rare from either ethanol-induced ketoacidosis or hypoglycemia.