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Alcohol Toxicity • Ethanol is a 2-carbon–chain alcohol; the chemical formula is CH2 CH3 OH. It is ubiquitous throughout the world and is a leading cause of morbidity across cultures. Ethanol is the most common psychoactive drug used by children and adolescents in the United States and is one of the most commonly abused drugs in the world.
Pathophysiology • Ethanol has a volume of distribution (0.6 L/kg) and is readily distributed throughout the body. The primary route of absorption is oral, although it can be absorbed by inhalation and even percutaneously. • Ethanol exerts its actions through several mechanisms. For instance, it binds directly to the gamma-aminobutyric acid (GABA) receptor in the CNS and causes sedative effects similar to those of benzodiazepines, which bind to the same GABA receptor. Furthermore, ethanol is also an N -methyl-D-aspartate (NMDA) glutamate antagonist in the CNS. Ethanol also has direct effects on cardiac muscle, thyroid tissue, and hepatic tissue. However, the exact molecular targets of ethanol and the mechanism of action are still the subjects of ongoing research
Pathophysiology • Ethanol is rapidly absorbed, and peak serum concentrations typically occur 30-60 minutes after ingestion. Its absorption into the body starts in the oral mucosa and continues in the stomach and intestine. Both high and low concentrations of ethanol are slowly absorbed; the co-ingestion of food also slows absorption. • In young children, ethanol causes hypoglycemia and hypoglycemic seizures; these complications are not as common in older patients. Hypoglycemia occurs secondary to ethanol's inhibition of gluconeogenesis and secondary to the relatively smaller glycogen stores in the livers of young children. In toddlers who have not eaten for several hours, even small quantities of ethanol can cause hypoglycemia.
Pathophysiology • Ethanol is primarily metabolized in the liver. Approximately 90% of an ethanol load is broken down in the liver; the remainder is eliminated by the kidneys and lungs. In children, ethanol is cleared by the liver at the rate of approximately 30 mg/dL/h, which is more rapid than the clearance rate in adults. • In the liver, ethanol is broken down into acetaldehyde by alcohol dehydrogenase (ADH). Then, it is further broken down to acetic acid by acetaldehyde dehydrogenase. Acetic acid is fed into the Krebs cycle and is ultimately broken down into carbon dioxide and water. Also, a gastric isozyme of ADH breaks down a significant amount of ethanol before it can be absorbed; sex differences in ADH may, in part, account for differences in ethanol effects per given quantity consumed between men and women.
The pathway of ethanol metabolism. Disulfiram reduces the rate of oxidation of acetaldehyde by competing with the cofactor nicotinamide adenine dinucleotide (NAD) for binding sites on aldehyde dehydrogenase (ALDH).
Epidemiology • United States • Ethanol use and intoxication in adolescents is widespread in the United States. In the 2011 Youth Risk Behavior Survey, 21% of high school students admitted to drinking alcohol before age 13 years. The survey also found that 71% ever drank alcohol and 39% had at least one drink in the 30 days prior to the survey. More alarmingly, 24% rode in a vehicle with a driver who drank alcohol and 8% drove a vehicle after drinking alcohol. The actual incidence of ethanol poisoning in young children is unknown. • International • Ethanol use in countries other than the United States is common; however, literature about the incidence of ethanol intoxication in populations in other countries is scant.
Mortality/Morbidity • Trauma is the leading cause of mortality in children, and ethanol use is linked to a 3-fold to 7-fold increased risk of trauma. Ethanol use is also strongly linked to other risk-taking behaviors that can lead to minor trauma, assault, illicit drug use, and teenage pregnancy. Approximately 40% of the 10,000 annual nonautomotive pediatric deaths (usually drownings and falls) are associated with ethanol. • The concomitant use of ethanol and other drugs is common, and combinations of ethanol with other sedative-hypnotics or opioids may potentiate the sedative effects.
Mortality/Morbidity • Ethanol greatly increases the risk of trauma, especially trauma due to motor vehicle collisions or violent crimes. In a study of 295 pediatrics patients aged 10-21 years presenting to the emergency department (ED) for treatment of any type of injury, Meropol et al found that 15 patients tested positive for alcohol; however, only 4 of these patients were tested upon initial ED evaluation. Additionally, alcohol is frequently linked with injuries secondary to assault and motor vehicle crashes. • The intoxicated individual often engages in high-risk activities, despite the fact that his or her reflexes are substantially slowed. Adolescent binge drinking has been linked with high-risk behaviors such as riding in cars with intoxicated drivers, sexual activity, smoking cigarettes/cigars, suicide attempts, and illicit drug use and may be the victim of dating violence.Early alcohol use has been linked to dating violence victimization, suicidal ideation, and suicide attempts
Race • Data supporting a racial predilection in populations are limited. Studies of adult patients suggest a lower tolerance in patients of Asian descent. This is most likely due to differences in expression or enzyme activity of ADH.
Sex • Data supporting a sex predilection in populations are limited. Studies in adults have reported that gastric ADH breaks down a significant amount of ethanol before it can be absorbed, which may, in part, account for differences in tolerance between men and women. Interestingly, one study found that among children aged 12-20, more drinking without binges was reported among girls than among boys but that binge-drinking rates were still similar.
History • Ethanol intoxication is often difficult to diagnose in young children and toddlers. Important questions to ask parents include the following: • Was a source of ethanol easily available to the child? For instance, was an open alcoholic drink left out after a party? • Is the alcohol in the house locked up? Are ethanol beverages in a place that the child can easily reach? • Is the child taking any over-the-counter medications that might contain alcohol, such as cough and cold medications? • Could older siblings in the house have given the child alcohol? • Did the parents give the child an alcohol bath? • Did the child drink an ethanol-containing substance (eg, perfume, cleaning fluids) not meant to be ingested?
History • If ingestion is known or suspected, determining exactly what and how much the patient ingested is important. The name, composition, and concentration of the alcohol are helpful. o If the amount is unknown, have the parents estimate how much was in the container and subtract that amount from the total volume of the container to estimate the amount ingested or possibly ingested. o The amount of ethanol in a product is often expressed as a percentage, which is the ratio of the volume of pure ethanol to the total volume of fluid. The formula for determining the percentage of ethanol is as follows: X% = X g/100 mL The concentration of ethanol in distilled spirits may be expressed as a proof, which is equal to twice the percentage of ethanol.
History • Ethanol concentrations in some common substances are as follows: liquid cold remedies, 2-25%; mouthwashes, 7-27%; rubbing alcohol, usually 70% (although most commonly, rubbing alcohol contains isopropanol); aftershave lotions, 15-80%; and perfumes and colognes, 25-95%. Other toxic alcohols are also often found in these products, such as methanol in perfume or cologne. • o Ethanol concentrations in some common alcoholic beverages are as follows: whiskey, 40-60%; liqueurs, 22-50%; wine, 8-16%; and beer, 3-7%. • o Be aware that patients often grossly underestimate the amount of Ethanol that they ingested.
History • • Obtain a history from the emergency medical services (EMS) personnel, parents, relatives, or anyone else who accompanied the patient to the hospital. • • Because ethanol predisposes patients to other causes of altered mental status (eg, trauma), consider the other causes as well. • • Be aware of the other substances in the ingested fluid that may be toxins. • • Because of potential legal implications in the United States, pediatric patients are often evasive in stating their history of possible ingestion. Outside the United States, ethanol consumption by children is often more culturally acceptable and less stigmatized. • • Adolescents often present to the emergency department (ED) with acute illness or decreased mental status. Often, these patients do not admit to their use of alcohol. Assess for a history of possible ethanol use in all patients who present to the ED with an altered mental status. • • A positive family history of alcohol abuse is significant because children of parents with alcoholism have a 2-fold to 4-fold increased risk of alcoholism.
Physical • Infants and toddlers have a clinical course significantly different from that of adolescents and adults. Ethanol ingestion and intoxication can lead to a marked hypoglycemic state in infants and young children. Ethanol has a CNS depressant action that can also lead to respiratory depression and hypoxia. Ethanol has a sedative effect, producing general CNS depression, respiratory depression, and often hypoglycemia. Young children often present to the ED after drinking discarded alcoholic beverages left within their reach during and after parties or after ingesting a fluid that contains ethanol. In older children and adolescents, ethanol intoxication causes CNS depression, leading to respiratory depression. Hypoglycemia is less common in this group.
Physical • As with all patients, a careful physical examination is warranted. In patients in whom ethanol ingestion is suspected, carefully evaluate his or her mental status and perform a thorough neurologic examination. Evaluate for signs of trauma, neglect, and illicit drug use. Ethanol ingestion makes the patient more prone to trauma due to accidents or crime. The clinician's most crucial clues to ethanol ingestion are a change in the patient's mental status and the smell of alcohol on the patient's breath. The presence or absence of ethanol on breath cannot be used to diagnose or exclude ethanol intoxication.
Physical • Compared with nonintoxicated teenagers, intoxicated teenagers are much more likely to be affected by violence, even after drinking only one alcoholic beverage. Recent reports describe the use of sedatives with alcohol to create date-rape drug combinations. Therefore, possible sexual assault should be considered in teenaged patients. • Young children commonly ingest ethanol when they drink a liquid not meant for consumption, such as perfume or cleaning agents. Frequently, other chemicals in the ingested substance are more toxic than the ethanol. Therefore, a detailed physical examination is important to evaluate for any signs and symptoms caused by these other toxins. Also, give special attention to the examination of the oral cavity and airway because substances in cleaning agents can cause chemical burns to these areas. • In children, the classic triad of signs of ethanol intoxication includes coma, hypoglycemia, and hypothermia. These signs usually occur when the Ethanol level in the blood exceeds 50-100 mg/dL. However, hypoglycemia can be seen with serum Ethanol levels as low as 50 mg/dL. Relatively small amounts of ethanol can produce hypoglycemia, especially in patients with low glycogen stores, such as infants and small children who have not eaten for several hours.
Physical • Acute ethanol intoxication can cause the following: o CNS depression o Mild vasodilatation leading to a modest decrease in blood pressure o Flushed skin o Urticaria[8] o Inhibition of spermatogenesis o Hypothermia o Tachycardia o Myocardial depression o Variable pupillary response o Respiratory depression o Decreased pulmonary secretion clearance o Decreased sensitivity to airway foreign body o Diuresis o Loss of behavior inhibitions o Hypoglycemia o Loss of fine motor control
Physical • High doses of ethanol can cause the following: o Loss of gross muscle control (ataxia, slurred speech) o Acute pancreatitis o Severe myocardial depression o Hypotension o Atrial fibrillation o Lactic acidosis o Congestive heart failure o Pulmonary edema o Arrhythmias o Cardiovascular collapse o Sudden death
Physical • Chronic ethanol use can lead to the following: o Fetal alcohol syndrome o Chronic pancreatitis o Hepatic dysfunction o Hematologic disorders o Numerous electrolyte abnormalities o Hypertension o Cardiomyopathy o Malnutrition o Obesity
Differential Diagnoses • Attachment Disorders • Attention Deficit Hyperactivity Disorder (ADHD) • Cognitive Deficits • Conduct Disorder • Dehydration • Diabetic Ketoacidosis • Genetics of Hyperammonemia • Head Trauma • Hyponatremia in Emergency Medicine • Oral Hypoglycemic Agent Toxicity • Pediatric Carbon Monoxide Toxicity • Pediatric Gastroenteritis • Pediatric Hypoglycemia • Pediatric Respiratory Failure • Respiratory Distress Syndrome
Laboratory Studies • • Serum glucose level: A bedside glucose finger stick is a quick and inexpensive method of assessing hypoglycemia. Hypoglycemia in a common in young children with ethanol intoxication. • • Electrolyte levels: The anion gap measurement should be determined. Acute ethanol intoxication usually does not cause significant anion gap metabolic acidosis. The presence of a large anion gap or severe acidosis should suggest the ingestion of another substance, such as methanol or ethylene glycol. However, patients with multiple-trauma can also have marked metabolic acidosis, and ethanol intoxication predisposes patients to trauma.
Laboratory Studies • Ethanol level • The serum ethanol concentration determined to obtain a starting level. Ethanol is metabolized at a fixed rate in an individual; however, alcohol metabolism rates widely vary, and predicting an individual's metabolism rate is impossible. If ethanol levels are obtained at two different times, one can reliably predict what a patient’s ethanol level would be at a given point in the future. However, one cannot predict whether the patient would be "intoxicated" without knowing the patient's tolerance to ethanol. • A blood alcohol concentration (BAC) that could make one person apneic may be a level at which another individual would suffer withdrawal. Also, a pharmacodynamic property, called the Mellanby effect, is observed when neurological impairment is greater at a given BAC when the BAC is increasing than the impairment observed at the same BAC when the BAC is decreasing.
Laboratory Studies • Most hospitals use ethanol assays that function by enzymatic methods that utilize ADH. These assays detect ethanol only and do not have false-positive results when other toxic alcohols are present. Therefore, these assays cannot detect other toxic alcohols, and ingestion or co-ingestion of toxic alcohols or isopropanol may go unrecognized. • If ingestion of toxic alcohols is suspected, a specific assay for those alcohols or gas chromatography should be obtained.
Laboratory Studies • Clinical findings and ethanol concentrations may be categorized as follows (these are rough estimates only and have not been validated in children): • Intoxication or inebriation - 100-150 mg/dL • Loss of muscle coordination - 150-200 mg/dL • Decreased level of consciousness - 200-300 mg/dL • Death - 300-500 mg/dL • The effects widely vary based on the patient’s BAC.
Laboratory Studies • Human chorionic gonadotropin level: Urine pregnancy tests should be performed in all women of childbearing age. • Serum salicylate and acetaminophen levels: In intentional suicidal ingestions, the presence of other toxic substances must be determined, especially if the patient presents late or if he or she has ingested a substance that has a significant risk of morbidity (eg, acetaminophen, salicylate). • Urine drug levels: Older patients may have ingested recreational drugs such as cocaine, marijuana, benzodiazepines, amphetamines, and opiates.
Laboratory Studies • ABG level • A determination of the pH is important when polysubstance ingestion or ketoacidosis is suspected. The partial pressure of carbon dioxide (pCO2) can be helpful in assessing respiratory depression. • The pH also can help in ruling out the co-ingestion of methanol and ethylene glycol, because significant acidemiais associated with those ingestions. However, reports in the literature have documented that the co-ingestion of ethanol and methanol does not cause significant acidosis. • Serum calcium and magnesium levels: High concentrations of ethanol and its chronic use can deplete these cations.
Laboratory Studies • Serum osmolality: The osmolar gap can provide information about the ethanol concentration in the blood. • The osmolar gap is calculated using the following equation: gap = measured osmolality - (2 X [Na concentration]) + (glucose concentration/18) + (BUN concentration/2.8). • An osmolar gap of 22-25 mOsm/kg results for every 100 mg/dL of ethanol in the serum. A normal osmolar gap is 2 ± 6 mOsm/kg; 95% of the population have osmolar gaps between –14 and +10 mOsm/kg. • The predicted concentration of ethanol is calculated using the following equation: Ethanol concentration = (osmolar gap - 10) X 4.6. This equation may provide a gross estimate of the predicted level but varies based on the baseline osmolar gap. • Methanol levels: These results can be helpful if an ingestion of combined substances is suspected. A positive methanol level can alert the physician to a co-ingestion.
Imaging Studies • Head CT scanning is warranted in patients with a change of mental status, focal neurologic findings, or scalp bruises or lacerations and in patients in whom trauma cannot be excluded. C-spine precautions should also be used if trauma is a suspected comorbidity until the neck is thoroughly investigated. • If trauma is suspected, obtain appropriate radiography.
Medical Care • The mainstay of medical treatment of patients with ethanol toxicity is supportive care. Many modalities for treating ethanol intoxication and enhancing ethanol clearance have been attempted. In general, a conservative approach is recommended. • Hypoglycemia and respiratory depression are the 2 most immediate life-threatening complications that result from ethanol intoxication in children.
Medical Care • Initial care • Assess the airway. If necessary, secure the airway with an endotracheal (ET) tube if the patient is not maintaining good ventilation or if a significant risk of aspiration is observed. Provide respiratory support and mechanical ventilation if needed. • Obtain intravenous (IV) access and replace any fluid deficit or use a maintenance fluid infusion. Use plasma expanders and vasopressors to treat hypotension, if present. • Ensure that the patient maintains a normal body temperature. • Quickly correct hypoglycemia. In children, 2-4 mL/kg of 25% dextrose solution is usually administered. A maintenance infusion of dextrose-containing IV fluids is often required. Correct any electrolyte abnormalities found with laboratory studies. Routine empiric electrolyte replacement is not helpful; only documented electrolytic abnormalities should be corrected. • If the ingestion occurred within 1 hour of presentation, placing a nasogastric tube and evacuating the stomach contents can be helpful. • In patients with chronic ethanol abuse, administer thiamine 100 mg IV/intramuscularly (IM) to prevent neurologic injury.
Medical Care • • Additional care: • If other substances have been co-ingested, initiate specific treatment for those substances, if available. For instance, naloxone can be used to reverse respiratory depression if opiate co-ingestion is suspected.
Medical Care • Other treatments • The administration of medications to cause emesis is not recommended because of the rapid onset of CNS depression and risk of aspiration. • The administration of activated charcoal is not recommended for isolated alcohol ingestions because it does not bind hydrocarbons or alcohols. If the clinician suspects a concomitant ingestion of other toxic products, activated charcoal may be effective in absorbing these toxins. • Forced diuresis is not helpful because 90% of ethanol metabolism occurs in the liver, and only 10% of the ethanol load is secreted in the urine.
Medical Care • GABA-receptor antagonists such as naloxone and flumazenil have little effect on the CNS or respiratory depression caused by ethanol; their use is not recommended in isolated ethanol intoxication. • The effects of insulin, glucose, caffeine, and several other medications have been studied, but none consistently increases ethanol metabolism or alleviate CNS depression. • Glucose administration is important in patients who are hypoglycemic as a result of ethanol intoxication; however, this treatment does not clear ethanol from the blood.
Medical Care • Fructose infusion can increase the ethanol clearance by 25%. However, the use of fructose is not recommended because significant adverse effects may occur. For instance, fructose infusion can cause lactic acidosis, severe osmotic diuresis, and GI symptoms; therefore, it is not routinely used in the treatment of ethanol intoxication. • Hemodialysis efficiently clears ethanol from the blood but is an invasive procedure; thus, its use is not routinely recommended. Hemodialysis can be used in patients whose clinical condition is deteriorating or in patients whose CNS depression, respiratory depression, or hypotension is refractory to standard therapy. • Patients who have impaired hepatic function may require dialysis to clear an ethanol load.
