Version May 2024
INTRODUCTION — The epidemiology, pharmacokinetics, and estimation of toxicity of ethanol intoxication in children are reviewed here. Evaluation and management of pediatric ethanol exposure are discussed separately (table 1). (See "Ethanol intoxication in children: Clinical features, evaluation, and management".)
EPIDEMIOLOGY — Despite its abuse potential, ethanol is broadly tolerated in a social context and is therefore ubiquitous in society. It is available in a multitude of alcoholic beverages but also concentrated in household products (eg, vanilla extract, mouthwash, hand sanitizer, perfume/cologne) (table 2).
Young children — Children under six years of age, particularly toddlers, often ingest ethanol when their exploratory behaviors lead them to unattended alcoholic beverages or to unsecured household products with high ethanol concentrations (table 2).
Thousands of ethanol exposures in children under six years of age are reported to poison control centers annually in the United States [1]. Ethanol-containing products other than alcoholic beverages (eg, perfumes, colognes, mouthwash, medicinals, or ethanol-based hand sanitizers) account for 85 to 90 percent of these exposures [2-7]. In many instances, these exposures result in little to no toxicity [8]. Furthermore, hand sanitizers may be safely used in young children with proper adult supervision. (See "COVID-19: Management in children", section on 'Safe use of hand sanitizer'.)
However, infants and young children are prone to profound hypoglycemia, coma, and hypothermia despite ingesting relatively small amounts of ethanol [2,9-12]. Deaths have been reported [9,13].
Rarely, a caretaker may intentionally give ethanol to quiet an infant or young child or as part of a pattern of physical abuse [2,14]. In addition, improper storage of ethanol and inadvertent mixing during formula preparation have been identified as mechanisms of exposure in young infants [13].
Preteens and teenagers — The World Health Organization reported that in many countries, more than half of 15- to 19-year-olds are considered drinkers [15]. According to the 2021 Youth Risk Behavior survey of United States high school students by the Centers for Disease Control and Prevention (CDC), during the previous 30 days, 23 percent drank alcohol, 11 percent binge drank, and 5 percent drove after drinking [16]. However, frequent binge drinking among United States adolescents has declined since 1991 [17-19].
In the United States, underage drinking is associated with significant negative societal outcomes, including:
●Fatal motor vehicle crashes – In the United States, approximately one in five teen drivers in fatal crashes had detectable blood alcohol, and approximately 2000 people are killed annually in crashes involving a teen driver [20].
●Emergency department visits – Approximately 100,000 alcohol-only emergency department visits occurred annually among teens and young adults 15 to 20 years of age [21].
A systematic review of youth binge drinkers reveals that abnormal or delayed development of the frontal regions of the brain may predispose to binge drinking, but also that binge drinking may further exacerbate these abnormalities [22].
Alcohol has inhibitory characteristics and therefore may be a facilitator of bullying and violence, particularly sexual violence at a time when adolescents may be initiating alcohol use and sexual activity [23]. A study of global school-based health surveys of 12- to 15-year-olds from 50 countries revealed that a number of factors, including alcohol consumption, fighting, being bullied, and suicidal ideation, increased the odds of early sexual initiation [24]. Furthermore, high school students exposed to sexual assault are at risk for negative outcomes like depressed mood and high-risk drinking, possibly perpetuating the cycle of mental illness, violence, and abuse [25].
Prevention of underage drinking in the United States requires collaborative efforts that are implemented at the local, state, and federal levels. Potential strategies advocated by the Surgeon General and Institute of Medicine are as follows [26,27]:
●Enforcement of minimum drinking age laws
●Increased taxes on alcoholic beverages
●National media campaigns targeting youth and young adults
●Decreased exposure of youth and young adults to advertising of alcoholic beverages
●Multidisciplinary, community-based alcohol abuse prevention programs
PHARMACOKINETICS
Absorption and distribution — Ethanol is typically absorbed rapidly; with peak serum levels achieved within 60 minutes of ingestion on an empty stomach [28]. High concentrations of ethanol may cause pylorospasm and delayed gastric emptying [29]. In addition, a full stomach also slows absorption. Delayed gastrointestinal transport or absorption of ethanol may translate into rapid onset of action, but delayed peak (up to three hours) and prolonged duration of effect [30].
Ethanol has a Vd of 0.6 L/kg with low protein binding. Thus, it is amenable to elimination enhancement by hemodialysis [30,31]. (See 'Elimination' below.)
Duration of symptoms — The elimination of ethanol in acute overdose is typically constant over time, regardless of peak levels (zero-order kinetics). In nontolerant individuals, the decline in ethanol ranges from 10 to 25 mg/dL per hour (2.2 to 5.6 mmol/L per hour). Chronic drinkers may achieve an elimination rate as high as 30 mg/dL per hour (6.7 mmol/L per hour) [32].
The estimated time to no ethanol in the blood stream in hours is calculated by dividing the peak serum ethanol concentration (mg/dL) by 10 (longest likely duration) or 25 (shortest likely duration). However, signs of intoxication may wane in a much shorter time period, especially in habituated drinkers.
Elimination — Once absorbed, ethanol should be considered as a metabolic fuel that undergoes oxidation in order to liberate energy stored in its chemical bonds. The major, but rate-limiting, metabolic pathway utilizes the enzyme alcohol dehydrogenase to convert ethanol to acetaldehyde and the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH [33]. Acetaldehyde, in turn, is metabolized via aldehyde dehydrogenase to acetate. In children under about five years of age, however, relative immaturity of hepatic dehydrogenase activity diminishes their capacity to metabolize ethanol, leading to rapid increases in blood levels and intoxication [32,34].
The microsomal ethanol oxidizing system comprises a secondary and inducible pathway for ethanol elimination [35]. In the absence of chronic ethanol consumption, little ethanol is metabolized by this pathway in children and adolescents.
The catalase system normally metabolizes a fraction of ingested ethanol but may be active in pediatric cases where very high blood ethanol levels occur. Liver catalase content in perinatal infants has been shown to be equal to or greater than that of adults [34]. Some experts have proposed that the decline in very high ethanol levels that appear to follow first order kinetics (decline in ethanol level as a percentage of total ethanol) may reflect catalase enzyme activity [34,36]. (See "Ethanol intoxication in children: Clinical features, evaluation, and management", section on 'Extracorporeal removal'.)
ESTIMATION OF TOXICITY
Formulation — The typical concentration of ethanol in alcoholic beverages varies widely (table 2). Ethanol content in alcoholic beverages is often expressed as "proof." In Australia and the United Kingdom 100-proof spirit contains 57 percent alcohol by volume, versus 50 percent alcohol by volume in the United States. For example, 151-proof rum contains 75.5 percent ethanol in the United States. In addition, many common household products and medications have high ethanol content (table 2).
Estimation of serum ethanol — A calculator provides an estimate of the peak blood ethanol level based on volume and concentration of ethanol ingested and patient weight (calculator 1). Although less accurate in children younger than 17 years of age because of age-related variations in total body water and ethanol elimination rate [37], it still can provide a reasonable estimate of blood alcohol concentration for triage purposes. However, a blood ethanol concentration should be obtained in all exposed infants and young children. (See "Ethanol intoxication in children: Clinical features, evaluation, and management", section on 'Ethanol serum concentration'.)
Ingestion of 1 g per kg of ethanol results in a peak serum ethanol concentration of approximately 100 mg/dL (22 mmol/L) [38]. This amount of ethanol corresponds to about 10 to 15 mL/kg of beer (5 percent), 4 to 6 mL/kg of wine (14 percent), and 1 to 2 mL/kg of liquor (40 percent).
A more precise estimate of expected peak serum ethanol concentration can be calculated from the patient's weight, amount of ethanol containing liquid ingested in mL, and the percent ethanol concentration by volume (calculator 1) [30]. When estimating volume ingested, a swallow of liquid in a toddler is approximately 5 mL (one teaspoon).
Toxic dose — The toxic dose in infants and young children is 0.4 mL/kg of 100 percent ethanol and would be expected to result in a peak serum ethanol level of 50 mg/dL (11 mmol/L) (calculator 1) [2,39]. The life-threatening dose expected to cause deep coma with respiratory depression is estimated at 4 mL/kg of 100 percent ethanol and would result in a peak ethanol level of greater than 500 mg/dL (111 mmol/L) (calculator 1) [40]. (See 'Estimation of serum ethanol' above.)
Infants and young children — Fatal hypoglycemia has occurred in young children with blood ethanol concentrations below 100 mg/dL (22 mmol/L), a serum level associated with minimal inebriation in adolescents and adults (table 3) [41]. Thus, any symptoms after exposure to ethanol in the young child warrant emergent medical evaluation regardless of estimated amount ingested. In addition, asymptomatic children who have ingested an amount of ethanol expected to result in a serum level more than 50 mg/dL (11 mmol/L) should be promptly referred for observation and measurement of blood glucose [2].
Older children and adolescents — Unhabituated older children and adolescents develop increasing intoxication with elevation of serum ethanol levels similar to adults [30,31]. Most show signs of inebriation at serum ethanol levels of 50 to 100 mg/dL (11 to 22 mmol/L). This peak blood level is typically achieved after one or two 12-ounce (360 mL) beers (5 percent ethanol content), one glass of wine, or one shot of liquor in a 50 kg child (table 3). Severe toxicity is expected with an ingestion equivalent to 6 mL/kg of 100 percent ethanol.
The clinical effect of ethanol may not precisely correlate with the degree of intoxication in a chronic drinker. Due to tolerance, individuals with alcohol use disorder may show few or no signs of intoxication at serum levels well over 100 mg/dL (22 mmol/L). (See "Ethanol intoxication in adults", section on 'Serum alcohol concentration and associated signs'.)
ACUTE TOXIC EFFECTS
Central nervous system (CNS) depression — Ethanol acts as a CNS sedative in a dose-dependent manner in overdose (table 3). In part, this action is mediated by interaction with the GABA-A receptor, resulting in increased GABA-mediated CNS inhibition [31]. Ethanol also suppresses excitatory neurotransmission controlled by activation of the N-methyl-D-aspartate (NMDA) type glutamate receptor [31]. In addition, ethanol has wide ranging effects on calcium channels, dopamine and adenosine receptors, the central adrenergic system, and the hypothalamic-pituitary-adrenal axis [30].
CNS sedation is increased when ethanol is co-ingested with other sedative-hypnotic agents (eg, benzodiazepines, barbiturates) and may lead to profound coma with respiratory depression or failure.
Ethanol-induced hypoglycemia — Decreased blood glucose below 40 mg/dL (2.22 mmol/L) is well described in children who have ingested ethanol [2,9,10,41-43]. Hypoglycemic seizures may occur and, if not promptly treated, result in death [2,9,10,41,42]. In one series, profound hypoglycemia occurred in 6 of 25 intoxicated young children [41]. While associated with fasting and poor nutrition in adults, ethanol-induced hypoglycemia in infants and young children occurs despite adequate nourishment [10].
Susceptibility to hypoglycemia in children appears to be related to metabolism of ethanol with imbalance of oxidized and reduced nicotinamide adenine dinucleotide (NAD+ and NADH). Oxidation of ethanol occurs during ethanol metabolism and requires that NAD+ be reduced, thereby decreasing the ratio of NAD+ to NADH [44]. Alteration of this ratio inhibits gluconeogenesis, and thus energy production, via the Krebs cycle [45]. As ethanol is metabolized in the child, glycogen stores are required to maintain blood glucose. Once glycogen stores are exhausted, the child becomes hypoglycemic. For this reason, hypoglycemia may occur several hours after ethanol ingestion [10].
Because ethanol-induced hypoglycemia results from exhausted glycogen reserves, it does not respond to glucagon administration [45] and can occur regardless of the serum ethanol concentration [36].
Other effects — The alteration of the NAD+ to NADH ratio during ethanol metabolism also favors the conversion of pyruvate to lactate [44,46]. These metabolic changes result in mild to moderate metabolic acidosis [43].
In addition to reducing energy production, ethanol suppresses shivering, thus increasing the intoxicated patient's risk for hypothermia [30,31]. Older children and adolescents may also be at risk of environmental exposure, including hypothermia and frostbite, if they drink to the point of passing out while outdoors.
Ethanol is a direct irritant of the gastric mucosa and may cause vomiting, gastritis with abdominal pain, and hematemesis [47].
Ethanol inhibits antidiuretic hormone action in the kidney [29]. This effect commonly leads to polyuria and mild to moderate dehydration, especially if accompanied by vomiting.
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".)
SUMMARY AND RECOMMENDATIONS
●Rapid overview – A rapid overview provides guidance for evaluation and management of children with ethanol intoxication (table 1). (See "Ethanol intoxication in children: Clinical features, evaluation, and management".)
●Epidemiology – Children under six years of age, particularly toddlers, often ingest ethanol when their exploratory behaviors lead them to unattended alcoholic beverages or to unsecured household products with high ethanol concentrations (table 2). (See 'Young children' above.)
Binge drinking and other forms of ethanol abuse are a common problem in preteens and adolescents. Toxicity and treatment are similar to that for adults. Comorbidities include motor vehicle crashes, physical assault, sexual assault, and mental illness. (See 'Preteens and teenagers' above.)
●Pharmacokinetics – The elimination of ethanol in acute overdose is typically constant over time, regardless of peak levels (zero-order kinetics). In nontolerant individuals, the decline in ethanol ranges from 10 to 25 mg/dL per hour. (See 'Duration of symptoms' above.)
●Estimation of toxicity - The typical concentration of ethanol in alcoholic beverages varies widely (table 2). Ingestion of 1 g per kg of ethanol results in a peak serum ethanol concentration of approximately 100 mg/dL (22 mmol/L) (calculator 1). (See 'Estimation of serum ethanol' above.)
●Toxic dose – The minimum toxic dose in infants and young children is 0.4 mL/kg of 100 percent ethanol and would be expected to result in a peak serum ethanol level of 50 mg/dL (11 mmol/L) (calculator 1). The life-threatening dose expected to cause deep coma with respiratory depression is estimated at 4 mL/kg of 100 percent ethanol with an expected peak level of 500 mg/dL (111 mmol/L ). (See 'Estimation of serum ethanol' above and 'Toxic dose' above.)
●Acute toxic effects – Common acute toxic effects include
•Central nervous system (CNS) depression – Ethanol acts as a CNS sedative in a dose-dependent manner in overdose (table 3). (See 'Central nervous system (CNS) depression' above.)
CNS depression is increased when ethanol is co-ingested with other sedative-hypnotic agents (eg, benzodiazepines, barbiturates) and may lead to profound coma with respiratory depression or failure.
•Hypoglycemia (young children) – Decreased blood glucose below 40 mg/dL (2.22 mmol/L) is well described in children who have ingested ethanol. Hypoglycemic seizures may occur and, if not promptly treated, can result in death. Fatal hypoglycemia has occurred in young children with blood ethanol concentrations below 100 mg/dL (22 mmol/L), a serum level associated with minimal inebriation in adolescents and adults. (See 'Ethanol-induced hypoglycemia' above and 'Infants and young children' above and 'Toxic dose' above.)
Because ethanol induced hypoglycemia results from exhausted glycogen reserves, even in adequately nourished children, it does not respond to glucagon administration and can occur regardless of the serum ethanol concentration. (See 'Ethanol-induced hypoglycemia' above.)
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