Ethanol, also known as alcohol, is a colorless, flammable, and volatile liquid with a characteristic aroma. It can mix with water and most organic solvents. Acute ethanol poisoning, also referred to as acute alcohol poisoning, refers to a state of excitement followed by inhibition caused by ingesting an excessive amount of alcohol or alcoholic beverages at one time.
Etiology
Ethanol serves as an important industrial solvent. Alcoholic beverages contain ethanol, with ethanol concentrations varying depending on the production process. Beverages derived from the fermentation of grains or fruits typically have lower ethanol concentrations, measured in volume percentages (L/L): beer contains 3%–5%, yellow rice wine 12%–15%, and wine 10%–25%. Distilled spirits, such as brandy and whiskey, contain ethanol concentrations ranging from 40% to 60%. Alcohol is commonly consumed as a drink, and excessive intake of high-ethanol-content distilled spirits can lead to poisoning.
Pathophysiology
Ethanol Metabolism
Ethanol (CH3CH2OH) is a water-soluble alcohol that easily crosses cell membranes and is rapidly absorbed through the gastrointestinal system, primarily in the stomach (70%) and the duodenum (25%), with a small amount absorbed in the intestine. When the stomach is empty, blood ethanol levels peak within 30–90 minutes after ingestion. Up to 10% of the total ethanol is excreted through the kidneys and lungs, while the remaining 90% is metabolized in the liver. Initially, ethanol is oxidized by alcohol dehydrogenase to acetaldehyde, which is further oxidized by aldehyde dehydrogenase to acetic acid. Acetic acid is then converted to acetyl-CoA and enters the tricarboxylic acid cycle, ultimately breaking down into CO2 and H2O. Ethanol metabolism follows a rate-limiting mechanism, with a clearance rate of 2.2 mmol/kg·h (100 mg/kg·h). An adult can clear approximately 7g of ethanol per hour (equivalent to 9ml of 100% ethanol). The decline in blood ethanol concentration occurs at approximately 0.43 mmol/h (20 mg/dl·h). Although individual tolerance to elevated blood ethanol concentrations varies widely, the lethal blood ethanol concentration is relatively consistent among individuals. For most adults, a lethal dose corresponds to ingesting approximately 250–500 ml of pure ethanol in one sitting.
Mechanism of Toxicity
Acute Toxicity Effects
Central Nervous System Depression
Ethanol has lipophilic properties and rapidly crosses nerve cell membranes in the brain, affecting specific enzymes in the membranes and thereby disrupting cell function. Its depressant effect on the central nervous system progresses with increasing doses, starting in the cerebral cortex and descending through the limbic system, cerebellum, reticular formation, and eventually the medulla. At low doses, ethanol causes excitation due to its inhibition of GABA (gamma-aminobutyric acid) receptor-mediated suppression in brain cells. As blood ethanol levels rise, the cerebellum is affected, leading to ataxia; the reticular formation is suppressed, resulting in drowsiness and unconsciousness; and at extremely high concentrations, medullary centers are inhibited, causing respiratory or circulatory failure.
Metabolic Abnormalities
Ethanol metabolism in liver cells produces large amounts of reduced nicotinamide adenine dinucleotide (NADH), significantly increasing the NADH-to-NAD ratio (oxidized form). This ratio may rise to two to three times the normal level, resulting in lactic acid elevation, ketone body accumulation, metabolic acidosis, and disrupted gluconeogenesis, which can cause hypoglycemia.
Tolerance, Dependence, and Withdrawal Syndrome
Tolerance
After consuming alcohol, individuals may experience a sense of relaxation and excitement. As drinking continues, tolerance develops, requiring increased alcohol intake to achieve the same effects.
Dependence
Dependence may manifest as psychological reliance, characterized by a craving for alcohol to achieve a sense of euphoria. Physiological dependence occurs when the body adapts to ethanol, leading to withdrawal-induced discomfort upon cessation.
Withdrawal Syndrome
Long-term alcohol use results in physical dependence. When alcohol consumption is reduced or stopped, symptoms opposite to those of alcohol intoxication may appear. The underlying mechanism involves diminished GABA inhibition upon withdrawal, coupled with elevated plasma norepinephrine levels, leading to sympathetic nervous system overactivity, such as excessive sweating and tremors.
Harmful Effects of Chronic Alcohol Abuse
Nutritional Deficiencies
Alcoholic beverages provide 29.3 kJ (7 kcal) of energy per gram of ethanol but lack essential nutrients such as vitamins, minerals, and amino acids. Because alcohol is a high-calorie but nutrient-deficient beverage, prolonged heavy drinking often results in reduced food intake, leading to significant nutritional deficiencies. A deficiency in vitamin B1 may cause Wernicke-Korsakoff syndrome and peripheral neuropathy, while folate deficiency may result in megaloblastic anemia. During periods of starvation associated with chronic drinking, replenishment of glucose and multivitamins is necessary.
Toxic Effects
Ethanol irritates mucous membranes and affects glandular secretions, potentially causing esophagitis, gastritis, and pancreatitis. During ethanol metabolism in the body, free radicals are generated, leading to lipid peroxidation of cell membranes, hepatic cell death, and abnormal liver function.
Clinical Manifestations
Acute Intoxication
Acute intoxication caused by drinking excessive amounts of alcohol at one time can lead to central nervous system depression. Symptoms vary depending on the amount consumed, blood ethanol concentration, and individual tolerance. Clinically, three stages are classified:
Excitation Stage
When blood ethanol concentration reaches 11 mmol/L (50 mg/dl), symptoms such as headache, euphoria, and excitement occur. As blood ethanol concentration exceeds 16 mmol/L (75 mg/dl), individuals may exhibit talkativeness, verbosity, emotional instability, arrogance, irritability, as well as coarse or aggressive behaviors; alternatively, silence and social withdrawal may manifest. At 22 mmol/L (100 mg/dl), impaired judgment can significantly increase the risk of traffic accidents while driving.
Ataxia Stage
When blood ethanol concentration reaches 33 mmol/L (150 mg/dl), individuals may experience muscle incoordination, clumsiness, slurred speech, nystagmus, blurred vision, double vision, and an unsteady gait, all indicative of pronounced ataxia. At 43 mmol/L (200 mg/dl), symptoms such as nausea, vomiting, and drowsiness are common.
Coma Stage
When blood ethanol concentration rises to 54 mmol/L (250 mg/dl), individuals enter a coma stage, characterized by stupor, dilated pupils, and hypothermia. At concentrations exceeding 87 mmol/L (400 mg/dl), patients progress into deep coma, with symptoms such as tachycardia, hypotension, slow breathing with snoring sounds, and potential respiratory and circulatory paralysis that can be life-threatening.
In addition, severe cases may involve complications such as accidental injury, acid-base imbalance, electrolyte disturbances, hypoglycemia, pneumonia, acute myopathy, or even acute renal failure.
Withdrawal Syndrome
Chronic heavy drinkers may develop the following four types of withdrawal reactions upon sudden cessation or reduction in alcohol consumption:
Simple Withdrawal Reaction
Symptoms typically occur 6 to 24 hours after reducing alcohol intake and may include tremors, restlessness, anxiety, excitement, insomnia, tachycardia, elevated blood pressure, excessive sweating, nausea, and vomiting. These symptoms generally resolve spontaneously within 2 to 5 days.
Alcoholic Hallucinations
Patients remain conscious and retain orientation. Auditory hallucinations predominate, though visual hallucinations, illusions, and distorted perceptions may also occur. Paranoid delusions, often centered on persecution, are common and generally resolve within 3 to 4 weeks.
Withdrawal Seizures
Withdrawal seizures, often occurring alongside simple withdrawal reactions, may manifest as generalized tonic-clonic seizures. Most patients experience seizures 1 to 2 times, lasting only a few minutes, though in some cases, repeated seizures may occur over several days.
Delirium Tremens
Delirium tremens typically develops 24 to 72 hours after cessation but may appear as early as 7 to 10 hours. Symptoms include mental confusion and generalized coarse muscle tremor. The delirium is accompanied by vivid and terrifying visual hallucinations under a state of unclear consciousness. Symptoms such as tachycardia, excessive sweating, elevated blood pressure, and other signs of sympathetic nervous system overactivity may also occur.
Laboratory Tests
Serum Ethanol Concentration
During acute alcohol intoxication, the ethanol concentration in exhaled air corresponds to that in serum.
Arterial Blood Gas Analysis
Mild metabolic acidosis may be observed during acute alcohol intoxication.
Serum Electrolyte Concentrations
Both acute and chronic alcohol intoxication may involve low potassium, magnesium, and calcium levels.
Blood Glucose Levels
Hypoglycemia may accompany acute alcohol intoxication.
Liver Function Tests
Chronic alcohol-related liver disease may result in significant liver function abnormalities.
Electrocardiogram
Alcohol-induced cardiomyopathy may manifest as arrhythmias and myocardial damage.
Diagnosis and Differential Diagnosis
Diagnosis can be established based on a history of alcohol consumption in combination with clinical manifestations, such as central nervous system depression during acute alcohol intoxication, alcohol odor in exhaled air, psychiatric symptoms and seizures associated with withdrawal syndrome, and nutritional deficits or toxic encephalopathy in chronic alcohol dependence. Measurement of ethanol concentration in serum or exhaled air also provides diagnostic confirmation.
Differential diagnosis requires distinguishing alcohol-related disorders from other diseases causing altered consciousness, such as sedative-hypnotic poisoning, carbon monoxide poisoning, cerebrovascular accidents, diabetic coma, or traumatic brain injury.
Treatment
Acute Intoxication
Mild cases generally do not require treatment, although restraint may be necessary for patients exhibiting agitation or excitement.
Patients with ataxia should rest, with proper safety precautions in place to prevent accidental injuries.
For patients in a coma, concurrent use of other substances should be considered. The primary focus is on maintaining the function of vital organs:
- Maintaining an open airway and adequate oxygen supply, with artificial respiration or endotracheal intubation administered as needed.
- Supporting circulatory function, monitoring blood pressure and pulse, and administering intravenous 5% glucose-sodium chloride solution.
- Using electrocardiographic monitoring to detect arrhythmias and myocardial damage.
- Providing warmth to maintain normal body temperature.
- Maintaining fluid, electrolyte, and acid-base balance, with magnesium supplementation in instances of hypomagnesemia. Intramuscular injection of 100 mg of vitamin B1 is recommended for the treatment of Wernicke's encephalopathy.
Enhanced diuresis is ineffective for acute ethanol intoxication. In severe cases of acute poisoning, hemodialysis may be utilized to promote ethanol elimination. Indications for dialysis include a blood ethanol concentration exceeding 108 mmol/L (500 mg/dl), accompanied by acidosis or ingestion of methanol or other suspected substances.
Hypoglycemia is one of the most severe complications of acute ethanol intoxication, necessitating close monitoring of blood glucose levels. For patients with acute altered consciousness, intravenous administration of 100 ml of 50% glucose and intramuscular injections of 100 mg each of vitamin B1` and B6 may accelerate ethanol oxidation in the body. Small doses of diazepam may help manage agitation and excessive excitement, while medications such as morphine, chlorpromazine, and barbiturate sedatives should be avoided.
Withdrawal Syndrome
Patients with withdrawal syndrome require rest and adequate sleep. Proper nutrition and supplementation with vitamins B1 and B6 should be provided. Intravenous glucose may be administered for hypoglycemia. Severe cases may warrant the use of short-acting sedatives to control symptoms without causing excessive drowsiness or ataxia. Diazepam is commonly selected, administered orally at a dose of 5–10 mg every 1–2 hours depending on the severity of symptoms. For severe cases, intravenous administration may be necessary. Once symptoms stabilize, a maintenance dose of diazepam can be given every 8–12 hours, with gradual tapering over the course of a week. Patients with a history of epilepsy may be treated with phenytoin, while those experiencing hallucinations may benefit from haloperidol.
Specialist Consultation
Alcohol-dependent individuals should seek treatment from a psychiatrist for comprehensive mental health care.
Prognosis
The prognosis for most cases of acute alcohol intoxication is favorable. Poor prognosis is associated with pre-existing heart, lung, liver, or kidney conditions, comas lasting longer than 10 hours, or blood ethanol concentrations exceeding 87 mmol/L (400 mg/dl). Alcohol-impaired driving or driving under the influence of intoxication significantly increases the risk of traffic accidents, potentially leading to death.
Chronic alcohol consumption may result in toxic damage to the brain, peripheral nerves, liver, and myocardium, as well as nutritional deficiencies. The prognosis depends on the type and severity of these conditions. Early detection and timely treatment can improve outcomes.
Prevention
Acute alcohol intoxication and other alcohol-related disorders are preventable conditions. Active efforts should align with the WHO Global Alcohol Action Plan 2022–2030 (Global Strategy to Reduce the Harmful Use of Alcohol).