Ethanol intoxication in adults

INTRODUCTION — In the United States, two-thirds of adults consume beverages containing ethanol (ethyl alcohol) and nearly 15 percent of people over the age of 12 have an alcohol use disorder [1]. Worldwide, acute ethanol intoxication is associated with numerous complications, including traffic accidents, domestic violence, homicide, and suicide. Death from alcohol poisoning remains a major concern with substantial increases over the past two decades [2,3]. Emergency department visits involving alcohol have increased by as much as 60 percent during the same period [4]. (See "Risky drinking and alcohol use disorder: Epidemiology, clinical features, adverse consequences, screening, and assessment".)

An overview of the pathophysiology, clinical features, and management of acute ethanol intoxication in adults is presented here. The health effects of chronic alcohol use, the recognition and management of alcohol withdrawal, and ethanol intoxication in children are discussed separately. (See "Management of moderate and severe alcohol withdrawal syndromes" and "Ethanol intoxication in children: Epidemiology, estimation of toxicity, and toxic effects".)

PATHOPHYSIOLOGY — According to the Department of Health and Human Services and the United States Department of Agriculture, one standard drink contains approximately 0.5 ounces of ethanol [5]. This corresponds to 12 fluid ounces of regular beer, 5 fluid ounces of wine, or 1.5 fluid ounces of 80-proof distilled spirit. In the United States, powdered alcohol was approved by the Alcohol and Tobacco Tax and Trade Bureau in 2015 under the brand name Palcohol. These products are typically 50 percent ethanol by weight and are intended to be mixed to form a product that is 10 percent ethanol by volume [6]. Ethanol is also found in a variety of common household products, including mouthwash, perfume, cologne, cooking extracts, and over-the-counter medications.

Ethanol (CH₃CH₂OH) is a water-soluble alcohol that rapidly crosses cell membranes [7]. Absorption of ethanol occurs via the gastrointestinal system, primarily in the duodenum and remainder of the small intestine (approximately 80 percent) and stomach (approximately 20 percent) [8]. When the stomach is empty, peak blood ethanol levels are reached between 30 and 90 minutes after ingestion. There are no data on how the absorption of powdered alcohol may differ from its liquid form, but presumably the absorption is similar.

The primary pathway of ethanol metabolism occurs in the liver via alcohol dehydrogenase [9]. Although the majority of ethanol metabolism is hepatic, other tissues do contribute. Alcohol dehydrogenase is also located in the gastric mucosa. The enzyme is found in decreased quantities in women. Less "first-pass metabolism", combined with a smaller volume of distribution, may explain the enhanced vulnerability of women to acute complications of ethanol intoxication [10]. (See "Pathogenesis of alcohol-associated liver disease", section on 'Alcohol metabolism'.)

CLINICAL FEATURES — Ethanol intoxication is common among patients requiring emergency care, although it is rarely the primary reason for acute presentation. In one study, ethanol was detected in 15 to 40 percent of unselected emergency department patients, depending on geographical location [11]. Binge drinking, which is defined as consuming five or more alcoholic drinks for males and four or more drinks for females on a single occasion, generally results in acute intoxication [12].

Signs and symptoms of acute ethanol intoxication vary and can include slurred speech, nystagmus, disinhibited behavior, incoordination, unsteady gait, memory impairment, stupor, or coma. Hypotension and tachycardia may occur as a result of ethanol-induced peripheral vasodilation, or secondary to volume loss [13,14]. Signs associated with particular serum ethanol concentrations in those who do not drink ethanol regularly are described below. (See 'Serum alcohol concentration and associated signs' below.)

Acute ethanol intoxication can also induce multiple metabolic derangements including hypoglycemia, hyperlactatemia, hypokalemia, hypomagnesemia, hypocalcemia, and hypophosphatemia [7]. (See "Fasting ketosis and alcoholic ketoacidosis" and "Clinical manifestations and treatment of hypokalemia in adults".)

DIFFERENTIAL DIAGNOSIS: A CRITICAL CONSIDERATION — Acute ethanol intoxication as a cause of altered mental status is a diagnosis of exclusion and should be considered only after ruling out more serious conditions such as head trauma, hypoxia, hypoglycemia, hypothermia, hepatic encephalopathy, and other metabolic and physiologic derangements. For head trauma in particular, existing clinical decision rules such as the Canadian CT Head Rule and NEXUS criteria may not have adequate sensitivity in intoxicated patients with minor head injury. (See "Acute mild traumatic brain injury (concussion) in adults".)

In addition, intoxication with other alcohols (methanol or ethylene glycol) should be suspected in patients with severe metabolic acidosis and an increased anion gap. Similarly, isopropyl alcohol ingestion should be suspected in a patient with unexpectedly increased levels of serum ketones or acetone without metabolic acidosis in the setting of apparent clinical alcohol intoxication. All alcohol poisonings are associated with an increased osmolal gap, if the patient presents relatively soon after the ingestion (table 1). Of note, other drugs are often ingested or otherwise taken along with alcohol, and appropriate evaluation should be performed as indicated. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis" and "Isopropyl alcohol poisoning" and "Serum osmolal gap" and "General approach to drug poisoning in adults" and "Initial management of the critically ill adult with an unknown overdose".)

LABORATORY EVALUATION

Serum alcohol concentration and associated signs — Measurements from serum provide the most accurate determination of a patient's ethanol concentration. Alternative methods, such as breath analysis, provide more rapid results, but often give slightly lower ethanol concentrations than those obtained from venous blood [15,16]. In most of the United States, the legal blood alcohol concentration (BAC) limit is 80 mg/dL (17 mmol/L).

The signs and symptoms of ethanol intoxication vary widely depending upon: the patient’s genetics; the type, amount, and rate of ethanol intake; and the frequency and pattern of alcohol use [17]. In individuals who infrequently use alcohol, the clinical effects of ethanol intoxication are more predictable. Conversely, the effects of inebriation on individuals with a history of chronic alcohol use are more unpredictable and such patients may demonstrate little clinical evidence of intoxication even with BACs over 400 mg/dL (88 mmol/L).

Among patients who infrequently use alcohol, clinical signs often associated with particular ranges of the BAC are as follows (table 2):

●With a BAC between 0.01 and 0.10 percent (<100 mg/dL or 22 mmol/L), euphoria and mild deficits in coordination, attention, and cognition may be observed.

●With a BAC between 0.10 and 0.20 percent, an individual experiences greater deficits in coordination and psychomotor skills, decreased attention, ataxia, impaired judgment, slurred speech, and mood variability.

●With a BAC between 0.20 to 0.30 percent, severe intoxication results in a lack of coordination, incoherent thoughts, confusion, and nausea and vomiting.

●When the BAC exceeds 0.30 percent, stupor and loss of consciousness can occur. Some patients experience coma and respiratory depression, and death is possible.

It should be noted that the clinical signs and symptoms of acute ethanol intoxication may not correlate with the BAC depending upon the factors described above and whether the concentration is increasing or decreasing; effects may be more prominent when levels are rising (so-called Mellanby effect).

It is also important to recognize that co-ingestion of other substances such as sympathomimetic drugs, opioids, benzodiazepines, barbiturates, and ‘designer drugs’ may either antagonize or augment the effects of ethanol, making the BAC an unreliable predictor of clinical symptoms. As one important example, the use of ethanol mixed with energy drinks (AmEDs), particularly among young adults and adolescents, has been increasing [18], and the combined effects of caffeine and ethanol can present a complex clinical picture. While caffeine may antagonize some effects of ethanol, other potentially harmful effects can persist [19,20]. Overall, it remains unclear to what extent AmEDs affect ethanol-induced psychomotor impairment and sedation [21,22]. (See "Benefits and risks of caffeine and caffeinated beverages".)

Additional studies — Laboratory studies are usually unnecessary in patients with an isolated mild ethanol intoxication. For patients with moderate to severe but uncomplicated ethanol intoxication (ie, not requiring intubation, not initially hypoglycemic, no history or clinical signs of trauma), routine laboratory studies including serum ethanol concentration and basic chemistry studies (serum glucose, basic electrolytes) may be obtained. Thereafter, assuming no initial laboratory abnormalities, a serum glucose concentration can be monitored every eight hours, while serum electrolytes do not need to be remeasured unless initially abnormal. This approach assumes that the patient is purely "intoxicated" and does not develop any acute changes in clinical status (eg, seizures). Patients with significant comorbidities may require more intensive monitoring based upon their conditions and injuries.

TREATMENT — The general approach to any poisoned patient must include the following elements:

●Evaluation: including recognition that poisoning has occurred, identification of the agent (or agents) involved, assessment of the severity, and prediction of toxicity. (See "General approach to drug poisoning in adults".)

●Management: consisting of supportive care, prevention of drug absorption, and when appropriate the administration of antidotes and enhancement of drug elimination. (See "Gastrointestinal decontamination of the poisoned patient" and "Enhanced elimination of poisons".)

The treatment for isolated acute ethanol intoxication is primarily supportive. As a general rule, all intoxicated patients should receive a rapid bedside glucose determination, followed by dextrose infusion if hypoglycemia is present. In addition, all patients presenting with acute ethanol intoxication should be carefully assessed for occult traumatic injuries and should be asked whether they have ingested or otherwise taken other drugs or potentially harmful substances. Patients presenting with coma secondary to ethanol intoxication should receive at least 100 mg of parenteral thiamine to prevent or treat Wernicke's encephalopathy, along with dextrose. (See "Wernicke encephalopathy", section on 'Treatment' and "Wernicke encephalopathy", section on 'Prevention'.)

Some patients with acute ethanol intoxication and altered sensorium can be agitated, violent, and uncooperative. In such cases, de-escalation techniques or sedation with medication may be needed to prevent the patient from harming themselves or others. Benzodiazepines and first generation (typical) antipsychotics are frequently used for sedation in these patients, but caution must be taken as these drugs can worsen the respiratory depression caused by ethanol [23,24]. Ketamine, as a single agent or adjunct to other medications, may be useful in the treatment of ethanol-induced agitation [25,26]. This is discussed separately. (See "Assessment and emergency management of the acutely agitated or violent adult", section on 'Management'.)

In a retrospective observational study of over 30,000 patients with acute ethanol intoxication, only one percent required critical care resources [27]. Risk factors for intensive care unit (ICU) level care included abnormal vital signs (eg, hypotension, tachycardia, fever, and hypothermia), hypoxia, hypoglycemia, and the need for parenteral sedation [27]. Intoxicated patients presenting with these abnormalities may have occult illness or injury.

Once the acute intoxication is managed, appropriate evaluation or referral for possible alcohol use disorder should be made. (See "Brief intervention for unhealthy alcohol and other drug use: Efficacy, adverse effects, and administration" and "Screening for unhealthy use of alcohol and other drugs in primary care" and "Risky drinking and alcohol use disorder: Epidemiology, clinical features, adverse consequences, screening, and assessment".)

Mild ethanol intoxication and ethanol clearance — Most patients with mild ethanol intoxication will require only observation and serial examination until clinical sobriety has been achieved. In patients with a clear history of ethanol intake and mild intoxication, and without signs of volume depletion or significant vital sign abnormalities, intravenous (IV) catheter insertion and fluid hydration are not usually necessary.

There is wide variation among individuals in the metabolism of ethanol. The unhabituated drinker clears ethanol from the blood stream at an approximate rate of 15 to 20 mg/dL (3 to 4.5 mmol/L) per hour. Patients with chronic alcohol use can clear ethanol at a rate of 25 to 35 mg/dL (5.5 to 8 mmol/L) per hour, or even faster in some cases [28,29]. However, the disposition of these patients should not be based solely on the measured (or calculated) blood alcohol concentration (BAC). Patients with mild intoxication can be safely discharged when no longer clinically intoxicated and deemed by the clinician to be no danger to themselves or others. Ideally, the patient should be discharged into the care of a competent, sober individual.

Moderate ethanol intoxication — Patients with moderate ethanol intoxication with signs of volume depletion, hypotension or malnutrition may require IV catheter insertion and fluid hydration. At a moderate to severe level of intoxication, any alteration in the level of consciousness must be further investigated.

If there is a clear history of ethanol consumption and serial examinations demonstrate improvement in the patient's mental status, further work-up and routine laboratory tests may not be necessary. However, if there is any question of possible occult trauma or if the patient's mental status does not improve after serial examinations, a computed tomographic scan of the head should be obtained, along with other diagnostic tests as indicated.

Severe ethanol intoxication (ethanol poisoning) — All patients with severe ethanol intoxication must be provided aggressive supportive care. At high BACs, special attention must be paid to the patient’s respiratory status, including frequent reassessment of the airway and breathing. If the patient is unable to protect their airway or has inadequate oxygenation or ventilation, tracheal intubation and mechanical ventilation are required.

In patients with evidence of volume depletion or hypotension, IV hydration with isotonic crystalloid is given. All patients presenting with coma secondary to ethanol intoxication should receive parenteral thiamine to prevent or treat Wernicke's encephalopathy. (See "Wernicke encephalopathy", section on 'Treatment' and "Wernicke encephalopathy", section on 'Prevention'.)

In patients with severe intoxication, activated charcoal and gastric lavage are generally not helpful because of the rapid rate of absorption of ethanol from the gastrointestinal tract. Patients with severe intoxication requiring aggressive supportive care may be kept in the Emergency Department in an observation unit or admitted to the hospital. Most patients presenting with coma or other significant complications of ethanol intoxication require admission for close monitoring until sobriety is achieved.

FUTURE DIRECTIONS — The acute and chronic effects of ethanol use result in significant morbidity and mortality worldwide. Efforts have been made to create novel therapies that accelerate the clearance of ethanol. As an example, metadoxine, a pyrrolidone carboxylate of pyridoxine, appears to be safe and effective in lowering blood alcohol concentrations (BACs) and improving symptoms following acute intoxication [30-32]. In a double-blind, randomized controlled trial in humans with acute ethanol intoxication, metadoxine decreased the half-life of ethanol in the blood, resulting in more rapid ethanol clearance and faster recovery times compared to placebo [30]. Metadoxine is not yet approved by the United States Food and Drug Administration for the treatment of acute ethanol intoxication, and its use should be considered experimental.

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment of acute poisoning caused by recreational drug or alcohol use" and "Society guideline links: Poisoning prevention".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Alcohol poisoning (The Basics)" and "Patient education: Alcohol use — when is drinking a problem? (Beyond the Basics)" and "Patient education: Alcohol withdrawal (The Basics)")

●Beyond the basics topic (See "Patient education: Alcohol use — when is drinking a problem? (Beyond the Basics)".)

SUMMARY AND RECOMMENDATIONS

●Clinical presentation – Acute ethanol intoxication is common among patients presenting for emergency care, although it is rarely the chief reason for medical evaluation. Signs and symptoms of acute ethanol intoxication vary with severity and can include slurred speech, nystagmus, disinhibited behavior, incoordination, unsteady gait, memory impairment, stupor, or coma. Hypotension and tachycardia may occur from ethanol-induced peripheral vasodilation or secondary to volume loss. Among patients who do not use ethanol chronically, clinical signs often associated with particular ranges of the blood alcohol concentration are summarized in the following table (table 2). (See 'Clinical features' above and 'Serum alcohol concentration and associated signs' above.)

●Differential diagnosis – Management of acute intoxication requires recognition and exclusion of other potential causes of changes in mental status, such as head trauma, hypoglycemia, hypoxia, and poisoning with other agents. (See 'Differential diagnosis: A critical consideration' above.)

●Blood alcohol concentration and other laboratory testing – Obtaining blood alcohol concentrations may be helpful supporting the diagnosis of ethanol intoxication and for legal and forensic investigations. However, ethanol concentrations may not correlate closely with the symptoms of acute intoxication, especially among patients who use ethanol on a chronic basis. (See 'Laboratory evaluation' above.)

●Management – Once the diagnosis of ethanol intoxication is established, treatment is largely supportive, and consists of identification and correction of hypovolemia and hypoglycemia, close monitoring of respiratory status, and intravenous thiamine in patients at risk of Wernicke's encephalopathy. (See 'Treatment' above.)