Johnson, Jeremy M. MS, CEN, CCRN
ETHANOL is the most frequently used and abused substance in the United States, where its ubiquitous use is confounded by its legal and culturally acceptable status (Berk & Henderson, 2004). Beer remains one of the top five beverages consumed by those who consume alcohol, and 75% of adult Americans will consume at least one alcoholic beverage per year, thus decreasing the taboo surrounding general alcohol consumption and solidifying it as socially acceptable behavior by all age-groups (Berk & Henderson, 2004).
Reaction time, fine motor control, and judgment are all affected when ethanol is consumed and derangements in each of these faculties can be evident when serum ethanol levels exceed 20–30 mg/dl (0.02%–0.03%; Blumenthal, Buxton, Brunton, & Parker, 2008). In most areas, serum ethanol levels exceeding 100 mg/dl (0.1%) is defined as legally intoxicated, and many states enforce a level of 80 mg/dl (0.08%) as the lower limit of intoxication (Greenberg, 2006). It is estimated that more than 50% of people who consume ethanol to exceed serum levels above 150 mg/dl (0.15%) will become grossly intoxicated (Blumenthal et al., 2008; Marini & Wheeler, 2006). Furthermore, the probability of coma and death increase significantly when serum ethanol levels exceed 300 and 600 mg/dl (0.3% and 0.6%), respectively (Marini & Wheeler, 2006). Ethanol consumption contributes to 100,000 deaths per year with most mortality results from trauma predicated by ethanol consumption and attributed solely to ethanol itself (Berk & Henderson, 2004). Moreover, 40% of motor vehicle accidents and 25% of “interpersonal trauma” are alcohol related (Berk & Henderson, 2004).
Berk and Henderson (2004) suggest that there is a gender difference noted in alcohol tolerance. Women generally have a smaller volume of distribution for alcohol as well as a decreased first pass metabolism of alcohol due to the attenuated amounts of the enzyme alcohol dehydrogenase found in their gastric mucosa when compared with that in men (Berk & Henderson, 2004; Blumenthal et al., 2008). This may contribute to a greater susceptibility of intoxication in women when compared with men (Blumenthal et al., 2008). However, Woods and Perina (2004) note that there are no gender differences among patients who develop complications, such as alcoholic ketoacidosis (AKA), from ethanol ingestion. Ingestion of food during drinking increases the risk of aspiration during episodes of vomiting but may decrease the maximal blood concentration of ethanol by almost 50% (Blumenthal et al., 2008).
Alcohol intoxication can come in many forms as the chemical form of an alcohol is nothing more than a hydroxyl (-OH) group attached to a carbon chain. The two carbon chain, ethane, provides the backbone for the hydroxyl group moiety and what is frequently referred to as “ethanol.” Frequently the alcohol ingested is ethanol; however, alcohol ingestion may also include a variety of isomers including methanol, isopropyl alcohol, and ethylene glycol. The difference between these isomers is the number of carbons found in the alcohol's chemical backbone. Each of the above mentioned isomers induce specific physiologic effects, and the management of their toxic sequelae is varied. This article will discuss clinical findings associated with ethanol ingestion and the management of these patients in the emergency department (ED). Throughout this article the terms “ethanol” and “alcohol” will be used interchangeably.
Ethanol is a central nervous system depressant. Ethanol depresses or inhibits excitatory neurotransmitters, such as glutamate, and increases the activity of inhibitory neurotransmitters, such as gamma-amino butyric acid (GABA) and glycine (Berk & Henderson, 2004).
Ethanol is absorbed throughout the entire gastrointestinal (GI) tract; however, it is chiefly absorbed in the proximal small intestine. Ethanol can be excreted in the urine, by lungs, or in sweat, depending on serum concentrations (Berk & Henderson, 2004). Approximately 90%–98% of ethanol is metabolized via hepatic mechanisms (Blumenthal et al., 2008). Under normal conditions, metabolism of ethanol occurs via two chief pathways; however, the clinically relevant points of only one pathway will be discussed. Cytosolic alcohol dehydrogenase uses the cofactor nicotinamide adenine dinucleotide (NAD+) to produce acetaldehyde and the hydrated by-product NADH (Fig 1). This acetaldehyde is further degraded by another enzyme, called acetaldehyde dehydrogenase, into the product acetate. Again, also this latter enzyme uses the NAD+ cofactor to accomplish the reaction, producing the by-product NADH. Acetaldehyde dehyrogenase is more active in the presence of high ethanol concentrations and often has increased activity with repeated exposures to alcohol (Berk, & Henderson, 2004).
Ethanol metabolism undergoes zero order kinetics (i.e., the rate of metabolism is independent of the concentration of ethanol) owing to its approximate rate of metabolism of 8 g/hr (the equivalent of a 6 oz beer, 2.5 oz glass of wine or 0.75 oz shot of 40% [80 proof] liquor per hour) in the 70 kg adult (Blumenthal et al., 2008). Seasoned alcohol abusers clear ethanol from the blood stream at a rate of 25–35 mg/dl/hr whereas more minimal drinkers may clear ethanol more slowly, at rates between 15–20 mg/dl/hr (Berk, & Henderson, 2004). This process is severely NAD+ dependent; therefore, the availability of NAD+ is the rate-determining step, which severely limits alcohol metabolism as stated before (Blumenthal et al., 2008).
SIGNS AND SYMPTOMS OF ETHANOL INTOXICATION
While characteristic signs and symptoms of drunkenness are well known, clinicians should be warned against assuming ethanol intoxication in the absence of laboratory confirmation because many other emergent conditions can present with slurred speech, incoherentness, and unsteady gait. (Blumenthal et al., 2008). Furthermore, blood alcohol levels may poorly correlate with the degree of intoxication because of the tolerance a patient might have to ethanol (Berk & Henderson, 2004).
Alcohol-dependent patients may experience seizure activity precipitated by lower than normal blood alcohol levels, hypoglycemia, or other electrolyte abnormalities. The use of prophylactic anticonvulsants remains controversial; however, alcohol-related seizures can be treated with the administration of benzodiazepines or correction of any underlying pathology (i.e., hypoglycemia; Barnett, 2005). Clinicians should be cautioned that patients may also exhibit a mild lactic acidosis; however, significant lactic acidosis should not be attributed to alcohol intoxication or seizure activity and other causes should be considered (Berk & Henderson, 2004).
Ironically, one of the syndromes associated with ethanol occurs when the patient is undergoing acute alcohol withdrawal. Delirium tremens (DTs) is the most extreme form of ethanol withdrawal and is considered an acute medical emergency (Marini & Wheeler, 2006). It is associated with a mortality rate of 10%–15% if left untreated (Barnett, 2005). DTs usually occur after 2 or more days of withdrawal from alcohol—patients may experience hallucinations, fever, and tachycardia. Other signs may include seizures and cardiac arrhythmias. During DTs, patients are at higher risk for aspiration. Marini (2006) notes that symptoms of withdrawal (especially DTs) may mimic signs and symptoms of infection or primary neurologic processes. Treatment is aimed at curtailing symptoms by administering benzodiazepines for sedation if necessary, as well as, electrolytes and vitamins intravenously (Marini & Wheeler, 2006). Lorazepam (Ativan) is a useful sedative because it is not hepatically metabolized nor does it have any active metabolites (Marini & Wheeler, 2006).
In the setting of chronic alcoholism, this neurologic syndrome is a result of the decreased intake and/or malabsorption of complex B vitamins, particularly thiamine. Most alcoholic beverages contain insignificant quantities of vitamins and nutrients (Blumenthal et al., 2008). Moreover, chronic alcohol use leads to changes in normal intestinal flora and mucosa owing to the malabsorption of nutrients (Blumenthal et al., 2008). Typically, there is only about an 18-day store of vitamin B1 (thiamine) within the body (Greenberg, 2006). A prolonged thiamine deficiency leads to structural degeneration in the brain (Chronister & Hardy, 2006). This degenerative damage involves areas such as the thalamus and hippocampal formation (Chronister & Hardy, 2006). These areas are important because they function in relaying sensory and motor information and short- and long-term memory storage (Chronister & Hardy, 2006). Wernicke's area is a portion of the lateral brain encompassing parts of the parietal and temporal lobes and is largely responsible for speech reception and interpretation (Haines & Mihailoff, 2006; Henkel, 2006). Thiamine deficiency results in a condition that has two large components: Wernicke's encephalopathy, which may present as gait ataxia (87% of patients), global mental confusion, nystagmus (96% of patients), and ophthalmoplegia, whereas Korsakoff's syndrome (psychosis) can manifest as confabulation and mental confusion (Barnett, 2005; Greenberg, 2006). However, it should be noted that a cumulative presentation of all of these symptoms occurs only in 10%–30% of cases (Greenberg, 2006). Confabulation results from damage to the hippocampal structures and results in the patient stringing together memory fragments and constructing a more linear “synthetic memory” of events that may never have occurred (Chronister & Hardy, 2006). Treatment begins with the administration of thiamine (as discussed below). However, not all of the signs and symptoms are reversible because of the underlying structural damage to the brain.
AKA is described as a wide anion gap acidosis that can occur when the patient with chronic alcoholism suddenly stops drinking or occur during significant acute intoxication with concomitant poor hydration and/or vomiting. Nevertheless, AKA is evident in those with a starved or dehydrated state and an abrupt decline in excessive alcohol consumption (Woods & Perina, 2004). As previously discussed, ethanol is metabolized in the liver to Acetyl Coenzyme A (Acetyl CoA) and the by-product NADH. In addition, glycogen and lipid stores are overutilized to supply the necessary energy needs of the starving cell. These biochemical reactions, as well as others, promote the degradation of Acetyl CoA into ketone bodies to provide an alternative energy source for the oxygen-requiring cells of the brain and other tissues (Woods & Perina, 2004).
Certain enzymes require NAD+ to ultimately convert beta-hydroxybuterate into acetone, which is finally excreted by the liver (Woods & Perina, 2004). Because ethanol metabolism exhausts the normal NAD+ supply, beta-hydroxybuterate cannot be broken down into its penultimate constitute and therefore cannot be excreted from the body as acetone. It should be noted that as the patient with AKA is treated and NAD+ levels return to normal, ketonuria may become evident, which reflects the natural metabolism of beta-hydroxybuterate and not a worsening of the patient's condition (Woods & Perina, 2004).
Signs and symptoms of AKA are often vague and may include tachycardia, abdominal pain, and vomiting (Woods & Perina, 2004). Ketonuria may not be evident as seen with patients in diabetic ketoacidosis due to the method of ketone detection by a given laboratory (Woods & Perina, 2004). Other laboratory values such as electrolytes, liver enzymes, and bilirubin may or may not be abnormal and must be studied closely by the treating clinician (Woods & Perina, 2004).
Ethanol is the most common cause of an osmolar gap (Berk & Henderson, 2004). Substances such as electrolytes, glucose, blood urea nitrogen, and alcohol contribute to the osmolar “content” of the blood. Much like anion gap calculations, osmolar gap is the difference between measured serum osmolality and calculated osmolality. Anion gaps are used to assess the differences between the amount of cations and anions in the blood (Fig 2). A wide anion gap in the presence of metabolic acidosis may indicate the presence of another type of alcohol and should be further investigated (Berk & Henderson, 2004). However, in the setting of AKA, Woods and Perina (2004) state that glucose levels less than 300 mg/dl (0.3%), vomiting, recent decline in ethanol intake, and unexplained wide-anion-gap metabolic acidosis should remain the diagnostic criteria for AKA.
TREATMENT AND MANAGEMENT OF ETHANOL INTOXICATION
Treatment strategies vary on the basis of the patient's history of alcohol use and current presentation. Quite often, careful observation of the patient, supportive care, and prevention of secondary insult is the primary treatment of acute ethanol intoxication while the patient naturally metabolizes the alcohol (Blumenthal et al., 2008; Marini & Wheeler, 2006). Therapy includes thiamine, glucose if necessary, and correction of electrolyte abnormalities such as hypokalemia and hypomagnesemia (Marini & Wheeler, 2006).
Altered mental status in a nonintoxicated patient would normally provoke the clinician to conduct imaging studies to discern the cause of the patient's decreased mentation. However, it may be easy for a clinician to become dissuaded from imaging an intoxicated patient because of the incorrect presumption that the altered mental status is a result of “drunkenness.” However, Greenberg (2006) points out that patients who consume more than 3 drinks per day have a 7-fold increased risk for intracerebral hemorrhage and chronic alcohol abuse leads to brain atrophy, which includes loss of both gray and white matter (Blumenthal et al., 2008). The frontal lobe is particularly susceptible to longer course of alcohol exposure (Blumenthal et al., 2008). Chronic alcohol use also decreases global brain metabolism, which may become permanent if steps toward alcohol cessation are not taken (Blumenthal et al., 2008). Therefore, it is imperative that clinicians use appropriate imaging studies for patients whose presentation is suspect for intracranial pathology; “drunkenness” notwithstanding.
Ethanol inhibits the posterior pituitary gland from releasing vasopressin, also known as antidiuretic hormone, which leads to diuresis after alcohol consumption (Blumenthal, et al., 2008). This volume loss can cause profound dehydration and hypotension. Volume depletion and hypoglycemia may be evident in the alcohol-dependent patient. While acute hypoglcemia should be corrected with D50, the administration of D5NS may alleviate pathology related to glycogen depletion (Berk & Henderson, 2004). Fluid administration does not hasten alcohol elimination and may not be necessary in the minimally intoxicated patient (Berk & Henderson, 2004); however, fluid resuscitation in the volume-depleted patient can be accomplished with normal saline or lactated Ringer's solution.
Thiamine (vitamin B1) is a water-soluble vitamin that is critical to many metabolic processes. Under aerobic conditions, the end product of glycolysis is pyruvate, which is decarboxylated into Acetyl CoA in an irreversible reaction (Page, Curtis, Walker, & Hoffman, 2006). Among other cofactors, thiamine is needed for this decarboxylation to take place. Many authors speculate about the utility of thiamine and glucose administration because both of these substrates are needed in order to make Acetyl CoA (Page et al., 2006). As the Acetyl CoA is produced, thiamine pool is depleted and the administration of glucose to a thiamine-dependent patient (as seen in a patient with Wernicke's encephalopathy) may potentiate a variety of neurologic sequelae (Page et al., 2006). The prevailing opinion seems to be that both substances should be administered together and any particular sequence of administration is unfounded (Page et al., 2006; Hack & Hoffman, 2004). Wernicke's encephalopathy and Korsakoff's psychosis (collectively referred to as Wernicke–Korsakoff syndrome) may result when thiamine-deficient patients (30%–80% of alcohol-dependent patients) are administered glucose prior to the administration of thiamine therapy (Barnett, 2005). However, other authors believe that this claim lacks sufficient evidence (Hack & Hoffman, 2004). The administration of other vitamins is not necessary unless there is previously documented deficiency or the clinical suspicion is high for malnutrition (Berk & Henderson, 2004).
Antidotes and Resuscitation Agents
Activated charcoal is unnecessary unless there is suspicion of concomitant substance ingestion (Berk & Henderson, 2004). Similarly, only 20% of alcohol-dependent patients with concomitant opioid ingestion will awaken in response to large doses of naloxone (Narcan) (Marini & Wheeler, 2006). Marini also notes that there is no role for the administration of direct central nervous system stimulants in an otherwise obtunded patient suffering from alcohol intoxication (2006).
Chronic alcohol abusers may have decreased levels of magnesium, which contributes to their risk for stroke and other neurological conditions (Blumenthal et al., 2008). Decreases in intercellular magnesium may lead to changes in calcium flux, and it is generally agreed that most chronic alcohol abusers live in a general state of hypomagnesemia (Blumenthal et al., 2008). The efficacy of magnesium administration is a source of controversy but there seems to be no compelling evidence to suggest that administration of this nutrient is harmful to the patient (Blumenthal et al., 2008).
Disulfiram (Antabuse) is a deterrent agent that inhibits acetylaldehyde dehydrogenase, leading to the accumulation of acetaldehyde, which causes immediate and severe hangover effects (nausea, vomiting, headache, etc.) in the presence of even small amounts of alcohol. It should never be given unless the patient has abstained from ethanol ingestion for at least 12 hours and thus it is generally inappropriate for use in the ED (Blumenthal et al., 2008). Aspirin should also be avoided because it increases the bioavailability of ethanol by inhibiting alcohol dehydrogenase (Blumenthal et al., 2008).
AKA can be treated with the administration of a glucose solution (e.g., D5NS; Woods & Perina, 2004). Glucose administration aids in the cessation of ketone body formation as well as the restoration of NAD+ stores via the oxidation of NADH (Woods & Perina, 2004).
The clinician should consider the administration of magnesium and other vitamin supplements as laboratory evidence and/or clinical suspicion dictates (Woods & Perina, 2004). In cases of severe intoxication in which the patient becomes hemodynamically unstable, ethanol's miscibility with water allows it to be easily removed via hemodialysis (Blumenthal et al., 2008). This type of therapy, however, is rarely necessary (Marini & Wheeler, 2006).
Alcohol is a common ingredient in the pathology of many patients seen in the ED. Therefore, emergency clinicians need to be aware of the sequalae associated with alcohol intoxication and become familiar with general treatment strategies of such patients. It is also imperative that while experience and/or intuition may lead the clinician to falsely stereotype these patients, a certain index of suspicion must always be maintained in patients who have physical examination findings that do not match their history of present illness or injury. Clinicians should be vigilant of various subtle presentations indicating underlying pathology, especially when these conditions may be masked by the patient's intoxication with alcohol.
Barnett, G. (2005). Alcohol emergencies. In L. M. Criddle & L. Newberry (Eds.), Sheehy's manual of emergency care (6th ed., pp. 450–455). St. Louis: Elsevier-Mosby.
Berk, W. A., & Henderson, W. V. (2004) Alcohols. In J. E. Tintinalli, G. D. Kelen, & J. S. Stapczynski (Eds.), Emergency medicine: A comprehensive study guide (6th ed., pp. 1064–1065). New York: McGraw-Hill.
Blumenthal, D., Brunton, L., Buxton, I., & Parker, K. (2008). Goodman & Gilman's manual of pharmacology and therapeutics. New York: McGraw-Hill.
Chronister, R. B., & Hardy, S. G. (2006). The limbic system. In D. E. Haynes (Ed.), Fundamental neuroscience for basic and clinical applications (pp. 500–510). Philadelphia: Churchill-Livingstone-Elsevier.
Greenberg, M. (2006). Handbook of neurosurgery. New York: Thieme.
Hack, J. B., & Hoffman, R. S. (2004). General management of poisoned patients. In J. E. Tintinalli, G. D. Kelen, & J. S. Stapczynski (Eds.), Emergency medicine: A comprehensive study guide (6th ed., pp. 1015–1022). New York: McGraw-Hill.
Haines, D. E., & Mihailoff, G.A. (2006). The telencephalon. In D. E. Haynes (Ed.), Fundamental neuroscience for basic and clinical applications (pp. 244–259). Philadelphia: Churchill-Livingstone-Elsevier.
Henkel, C. K. (2006). The auditory system. In D. E. Haynes (Ed.), Fundamental neuroscience for basic and clinical applications (pp. 334–348). Philadelphia. Churchill-Livingstone-Elsevier.
Marini, J. J., & Wheeler, A. (2006). Drug overdose and poisoning. In B. Brown (Ed.), Critical care medicine (pp. 536–537). Philadelphia: Lippincott Williams & Wilkins.
Page, C., Curtis, M., Walker, M., & Hoffman, B. (2006). Drug use in disorders of nutrition. In A. Stibe (Ed.), Integrated pharmacology (pp. 596–597). Philadelphia: Elsevier-Mosby.
Woods, W. A., & Perina, D. G. (2004). Alcoholic ketoacidosis. In J. E. Tintinalli, G. D. Kelen, & J. S. Stapczynski (Eds.), Emergency medicine: A comprehensive study guide (6th ed., pp. 1304–1306). New York: McGraw-Hill.
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