231012019 Ethanol intoxication in adults - UpToDate U plot Date’ Mfficial reprint from UpToDate® www.uptodate.com ©2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved. o. Wolters Kluwer Ethanol intoxication in adults Authors: Ethan Cowan, MD, MS, Mark Su, MD, MPH Section Editor: Stephen J Traub, MD. Deputy Editor: Jonathan Grayzel, MD, FAAEM All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Sep 2019, | This topic last updated: May 08, 2018. INTRODUCTION ‘Two-thirds of American adults consume beverages containing ethanol (ethyl alcohol), and moderate ethanol intake appears to reduce the risk of myocardial infarction and other heart diseases. However, up to 10 percent of adults in the United States abuse ethanol, and worldwide acute ethanol intoxication is associated with numerous complications, including traffic accidents, domestic violence, homicide, and suicide. Death from alcohol poisoning remains a major concer [1]. Uncomplicated ethanol intoxication is estimated to be responsible for over 600,000 emergency department visits each year in the United States alone [2]. (See "Cardiovascular benefits and risks of moderate alcohol consumption" and “Risky drinking and alcohol use disorder: Epidemiology, pathogenesis, clinical An overview of the pathophysiology, clinical features and management of acute ethanol intoxication in adults will be presented here. The health effects of chronic alcohol abuse, the recognition and management of alcohol withdrawal, and ethanol intoxication in children are discussed separately. (See "Management of m af in vere ho! 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 [3]. 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 aleohol was approved by the Alcohol and Tobacco Tax and Trade hips: www uplodate.com/contanslethanoLinloxicalion n-adulsiprin7search=inloxicacion aleohol&source: ss08usa... 10 arch_resull&selectedT2aro2019 Ethanol noscation in adults - UpToDate Bureau in 2015 under the brand name Palcohol. These products are typically 50 percent alcohol by weight and are intended to be mixed to form a product that is 10 percent alcohol by volume [4]. Ethanol is also found in a variety of common household products, including mouthwash, perfume, cologne, cooking extracts, and over-the-counter medications. Ethanol (CH3CH,OH) is a water-soluble alcohol that rapidly crosses cell membranes [5]. 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) [6]. 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 [7]. 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 alcohol intoxication [8]. (See "Pathogenesis of alcoholic 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 [9]. Binge drinking, which is generally defined as consuming 25 alcoholic drinks on a single occasion, generally results in acute intoxication [10]. 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 as a result of ethanol-induced peripheral vasodilation, or secondary to volume loss [11,12]. Signs associated with particular serum ethanol concentrations in nonalcoholics are described below, (See ‘Serum alcohol concentration an: jated signs' below.) Acute alcohol intoxication can also induce multiple metabolic derangements including hypoglycemia, hyperlactatemia, hypokalemia, hypomagnesemia, hypocalcemia, and hypophosphatemia [5]. (See “Easting ketosis and alcoholic ketoacidosis" and "Clinical manifestations and treatment of tps: uplodate.com/contenslethanoLinloxicalion n-adulsiprin7search=inloxicacion aleohol&source:231072019 Ethanol intoxication in adults - UpToDate DIFFERENTIAL DIAGNOSIS: A CRITICAL CONSIDERATION Alcohol 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 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 alcohol poisonin: p" and "General approach to tial management of the critically ill adult ind "Serum osmolal ith an unknown LABORATORY EVALUATION Serum alcohol concentration and associated signs — Measurements from serum provide the most accurate determination of a patient's alcohol level. Alternative methods, such as breath analysis, provide more rapid results, but often give slightly lower ethanol concentrations than those obtained from venous blood [13,14]. In most of the United States, the legal blood alcohol concentration (BAC) limit is 80 mg/dL. (17 mmollL). The signs and symptoms of alcohol intoxication vary widely depending upon: the patient's genetics; the type, amount, and rate of alcohol intake; and the frequency and pattem of alcohol use [15]. In individuals who do not abuse alcohol, the clinical effects of ethanol intoxication are relatively more predictable. Conversely, the effects of inebriation on individuals with a history of chronic alcohol abuse are unpredictable and such patients may demonstrate little clinical evidence of intoxication even with BACs over 400 mg/dL (88 mmol/L). ‘Among patients who do not abuse alcohol chronically, clinical signs often associated with particular ranges of the BAC are as follows (table 2): tps: uplodate.com/contenslethanoLinloxicalion n-adulsiprin7search=inloxicacion aleohol&source:zari2019 Ethanol noscation in adults - UpToDate * 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 alcohol 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 alcohol 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). Itis 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 alcohol, making the BAC an unreliable predictor of clinical symptoms. As one important example, the use of alcohol mixed with energy drinks (AmEDs), particularly among young adults and adolescents, has been increasing [16], and the combined effects of caffeine and ethanol can present a complex clinical picture. While caffeine may antagonize some effects of alcohol, other potentially harmful effects can persist [17,18]. Overall, it remains unclear to what extent AMEDs affect alcohol-induced psychomotor impairment and sedation [19]. (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), we initially obtain a serum ethanol concentration and basic chemistry studies (serum glucose, basic electrolytes). 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. This approach assumes that the patient is purely “intoxicated” and does not develop any acute changes in clinical status (eg, seizures). Patients with significant concomitant problems require more intensive monitoring based upon their comorbidities and injuries. TREATMENT The general approach to any poisoned patient must include the following elements: hitpssiwwucuplodate.com/contenslethanal-inloxicalion n-adulslprin\?searchinloxicacion aleahol&sour s608usa... 4/10 ch_sesullfselectedTzaron01e Ethanol noscation in adults - UpToDate + 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, the use of chemical sedation may be needed to prevent the patient from harming themselves or others. Benzodiazepines and first generation (typical) antipsychotics are frequently used in these patients, but caution must be taken as these drugs can worsen the respiratory depression caused by alcohol [20,21]. Ketamine, as a single agent or adjunct to other medications, may be useful in the treatment of alcohol induced agitation [22,23]. This is discussed section on 'Management’.) Ina retrospective observational study of over 30,000 patients with acute alcohol intoxication, only one percent required critical care resources [24]. 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 [24]. Intoxicated patients presenting with these abnormalities may have occult illness or injury. ‘Once the acute intoxication is managed, appropriate evaluation or referral for possible substance abuse 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, pathogenesis, clinical manifestations, course, assessment, and diagnosis”.) Mild ethanol intoxication and ethanol cl ‘ance — Most patients with mild ethanol intoxication will require only observation and serial examination until clinical sobriety has been achieved. In patients tps: uplodate.com/contenslethanoLinloxicalion n-adulsiprin7search=inloxicacion aleohol&source: ss08usa... 5i10 arch_resull&selectedTzari2019 Ethanol noscation in adults - UpToDate with a clear history of alcohol intake and mild ethanol intoxication, and without signs of volume depletion, intravenous (IV) catheter insertion and fluid hydration are not usually necessary. There is wide variation 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 mmolL) per hour. Patients with chronic ethanol abuse 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 [25,26]. However, the disposition of these patients should not be based solely on the measured (or calculated) serum alcohol concentration. 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 alcohol 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 respiration, 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 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. hitpssiwwucuplodate.com/contenslethanal-inloxicalion n-adulslprin\?searchinloxicacion aleahol&sour ss08usa... 6/10 ch_sesullfselectedT231072019 Ethanol intoxication in adults - UpToDate FUTURE DIRECTIONS The acute and chronic effects of alcohol abuse result in significant morbidity and mortality worldwide. Efforts have been made to create novel therapies that accelerate the clearance of alcohol. As an example, metadoxine, a pyrrolidone carboxylate of pyridoxine, appears to be safe and effective in lowering blood alcohol concentrations and improving symptoms following acute intoxication [27,28]. In a double-blind, randomized controlled trial in humans with acute alcohol intoxication, metadoxine decreased the half-life of ethanol in the blood, resulting in more rapid ethanol clearance and faster recovery times compared to placebo [27]. 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 in the United States are available at all times for consultation on patients who are critically ill, require admission, or have clinical pictures that are unclear (1-800-222- 1222). In addition, some hospitals have clinical and/or medical toxicologists available for bedside consultation and/or inpatient care. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. The World Health Organization provides a listing of international poison centers at its website: www.who.intigho/phe/chemical_safe! isons_centres/en/index.html 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".) 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" to 6" 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 hitpssiwwucuplodate.com/contenslethanal-inloxicalion n-adulslprin\?searchinloxicacion aleahol&sour ss08usa... 7/10 ch_sesullfselectedT2aro2019 Ethanol ietoxction in adults - UpToDate detailed. These articles are written at the 10" to 12'" 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 "Patien! ion: Aleoho! poisoning (The Basics)" and "Patient 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 * Acute alcohol intoxication is common among patients presenting for emergency care, although it is rarely the chief reason for medical evaluation. + 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.) + Serum ethanol concentrations may be helpful in confirming the diagnosis, and for legal and forensic investigations. Ethanol concentrations may NOT correlate closely with the symptoms of acute intoxication, especially among patients who use alcohol on a chronic basis. (See ‘Serum alcohol concentration and associated signs’ above.) * Once the diagnosis of alcohol 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.) Use of UpToDate is subject to the Subscription and License Agreement. Topic 333 Version 19.0 tps: uplodate.com/contenslethanoLinloxicalion n-adulsiprin7search=inloxicacion aleohol&source:231012019 Ethanol intoxication in adults - UpToDate GRAPHICS Estimated osmolal concentration of common organic intoxicants Concentration (mg/dL) per 1 mosmol/kg elevation in osmolal sap Ethanol, 4gltl ethan 32 | Ethylene sy! 62 | 1eopropano 60 | reerence 41. Garrard A, Sollee DR, Butterfield RC, et al. Validation of a pre-existing formula to calculate the contribution of ethanol to the esmolar gap. Clin Toxicol (Phila) 2012; 50:562. Adapted from: Kulig K, Duffy JP, Linden CH, et al. Toxie effects of methanol, ethylene glycol, and isopropyl alcohol. Top Emerg Med 1984; 6:16. Graphic 52568 Version 3.0, \oxicacionaleahol&soure ss08usa... 9110 hitpsiwouuplodate.com/contanslethanal-inloxicaion n-adulsfprin sear ch_sosulselectedTit231012019 Ethanol intoxication in adults - UpToDate Clinical effects of blood alcohol concentration Blood alcohol concentration 20-50 mg/dl (4.4-11 mmol/L) 50-100 mg/dl. (11-22 mmol/L 100-150 mg/al. (22-33 mmol/L) 150-250 mg/dl. (33-55 mmol/L) 300 mg/dl. (66 mmol/L) 400 mg/dl. (88 mmol/L) Diminished fine mator coordination Impaired judgment; impaired coordination Difficulty with gait and balance | | Lethargy: duty sting upright wihow assistance | oma inthe non-habituated drinker | | Respiratory depression ‘Adapted from: Marx JA. Rosen's emergency medicine: concepts and clinical practice, Sth ed, Mosby, Inc., St. Louls 2002. p. 2513. Copyright © 2002 Elsevier. Grephic 64642 Version 5.0, hitps:wwyuplodate.com/contenslethanolnloxicalion n-adulsiprin7searchinloxicacion alechol&source=search_resullaslectodTil ~1608us.. 10/10