A 70-year-old female is brought into the clinic by her daughter due to concerns about her mother's sleeplessness, isolation, weight loss, falls, and anxiety over the past year. In addition, since the patient has been staying at her daughter's home the past 3 days, she began vomiting, hallucinating, perspiring profusely, and wanting to return to her own home. The patient has no history of medical problems. She is disheveled, confused, diaphoretic, and tremulous. Her blood pressure is 162/110 mm Hg, pulse is 120 bpm, and temperature is 38.5°C. She blames her symptoms on being unable to have a cigarette. She also blames her daughter's nagging. When asked about alcohol use, the patient says she has had a cocktail every evening since she retired from her job last year, and that this helps her to sleep.
Question 25.2.1 Which of the following best describes the patient's current clinical condition?
Answer 25.2.1 The correct answer is "A." The patient presents tachycardic, hypertensive, and febrile, with diaphoresis, tremors, vomiting, and hallucinations. All of these findings are included in the diagnostic criteria for alcohol withdrawal. "B" is incorrect. Acute intoxication is characterized by slurred speech, unsteady gait, nystagmus, and impaired memory and judgment. "C," "D," and "E" are incorrect and are discussed later in this case.
The criteria for alcohol withdrawal include: (1) The patient has stopped or reduced a previously heavy alcohol intake and (2) at least two of the following within hours or days: autonomic hyperactivity (hypertension, sweating, tachycardia, etc.), hand tremor, insomnia, nausea or vomiting, hallucinations, agitation, anxiety, or grand mal seizures. In addition, one must have significant distress or impairment in functioning with the withdrawal and no other illness causing the symptoms.
Question 25.2.2 Which class of drugs would you choose to treat the symptoms of alcohol withdrawal?
A) Benzodiazepines.
B) Antipsychotics.
C) Antibiotics.
Answer 25.2.2 The correct answer is "A." The treatment of choice is metabolic support and the use of benzodiazepines to decrease physical distress and to prevent major withdrawal (delirium tremens, DT) from occurring. "B" is incorrect. Antispychotics may control behavior but they do not prevent withdrawal seizures and vasomotor instability. "D" is incorrect. Although alcohol will work to prevent withdrawal, it has a fairly short half-life, and you generally do not want to endorse the use of alcohol in a patient with an alcohol use problem. "E" is singularly incorrect. Phenytoin does nothing to prevent alcohol withdrawal seizures.
The traditional "banana bag" with multivitamins is unnecessary. Oral vitamin supplements are just as effective and less expensive. The only exception is thiamine, which you may want to give IV or IM if the patient has a true thiamine deficiency.
Question 25.2.3 What would be the best approach to evaluating this patient for alcoholism?
A) Ask her the average amount she drinks.
B) Ask her how often she drinks.
C) Ask her how frequently she gets drunk.
D) Ask what her family and friends say about her drinking.
E) Pour a bourbon in front of her and see what happens.
Answer 25.2.3 The correct answer is "D." The defense mechanism of denial is so strongly evident in alcoholism that the best approach is to explore how alcohol affects her life, rather than direct questions about drinking behavior. Information from family and friends may provide a more accurate account of the problem. The CAGE questionnaire is a very brief and useful screening tool, employed effectively in the primary care setting. A positive answer to two or more questions is very sensitive and specific for an alcohol use disorder. It consists of asking the patient the following four questions:
Have you ever
C: felt that you should Cut Down on your drinking?
A: been Annoyed that people criticized your drinking?
G: felt bad or Guilty about your drinking?
E: taken a drink first thing in the morning (Eye Opener) to get rid of a hangover or steady your nerves?
Asking the question "How many times in the past year have you had five or more drinks in a day (for men) or four or more drinks (for women) in a day?" is a useful screen for frequency of heavy drinking. A positive screen is one or more incidents of heavy drinking. If you have a positive screen, ask about usual frequency and quantity of alcohol consumed to help determine the presence or absence of alcohol abuse or dependence. This question alone has about a 82% sensitivity for detecting an alcohol use disorder. Specificity is comparable at about 79%. Sensitivity for the CAGE ranges from about 75% to 95%, but the CAGE may miss nondependent alcohol use disorders (e.g., binge drinking). Yet another possible screen for alcohol use disorders, and one commonly found in primary care clinics, is the Alcohol Use Disorders Identification Test (AUDIT). This is a 10 question survey that has a sensitivity of 92% and a specificity at 94%.
Unfortunately, you cannot always trust the family's history either. They may be enabling the alcohol addiction or unaware of it. Also, laboratory workups (e.g., liver enzymes) cannot be relied upon to make the diagnosis of alcohol abuse/dependence—although elevated GGT and AST/ALT ratio of 2 are supportive but terribly nonspecific.
Upon further questioning, you begin to uncover a long history of heavy drinking—seems that there was more than just a nightcap.
Question 25.2.4 Which of the following statements about this patient's situation is TRUE?
A) Cerebellar degeneration is uncommon.
B) She is at risk for developing peripheral neuropathy.
C) Alcoholic "fatty liver" is irreversible.
D) She is at decreased or normal risk for heart disease.
E) Immune function should remain relatively intact.
Answer 25.2.4 The correct answer is "B." Peripheral neuropathy can be seen in 10% of heavy drinkers as a result of vitamin deficiencies and the direct impact alcohol has on nerve function. "A" is incorrect because cerebellar degeneration—suggested by ataxia and nystagmus—does occur as a result of alcohol overuse. "C" is incorrect because alcoholic "fatty liver" will reverse with abstinence from alcohol. "D" is incorrect. Heavy drinking raises blood pressure and levels of triglycerides, increasing risk of myocardial infarction. Finally, "E" is incorrect. Heavy drinking lowers the white blood cell count and interferes with specific aspects of the immune system; for example, it compromises T-cell function.
This patient reports to you that she has needed to drink increasing amounts of alcohol to help her fall asleep.
Question 25.2.5 The need for increasing amounts of alcohol is an example of:
A) Intoxication.
B) Dependence.
C) Tolerance.
D) Relapse.
E) Abuse.
Answer 25.2.5 The correct answer is "C." Tolerance is defined as the need for increasing amounts of a drug to achieve the same response as initial use of the drug. "A" is incorrect. Intoxication is a characteristic syndrome of maladaptive behavior or psychological changes that occurs with substance use, is drug-specific, and reverses when the drug use is discontinued. "D" is incorrect. Relapse involves re-starting use of the drug after being abstinent for a while.
DSM-IV divided substance abuse and substance dependence. DSM-5 views these two categories as different points on a spectrum of substance use disorder. The criteria for substance use disorder are at least 2 of the following 11 criteria (clustered in 4 groups):
Impaired control: 1taking more or for longer than intended, 2unsuccessful efforts to stop or cut down use, 3spending a great deal of time obtaining, using, or recovering from use, or 4craving for substance.
Social impairment: 5failure to fulfill major obligations due to use, 6continued use despite problems caused or exacerbated by use or 7important activities given up or reduced because of use.
Risky use: 8recurrent use in hazardous situations and 9continued use despite physical or psychological problems caused or exacerbated by use.
Pharmacologic dependence: 10developing tolerance or 11withdrawal
Question 25.2.6 Which of the following lab test results are you most likely to find in this patient?
A) Microcytic anemia.
B) Low ferritin.
C) Decreased serum triglycerides.
D) Hyperglycemia.
E) Increased gamma-glutamyltransferase (GGT).
Answer 25.2.6 The correct answer is "E." Elevated GGT is considered to be the most sensitive indicator of alcohol intake and is often present along with elevation of the alanine and aspartate transaminases (ALT and AST). Remember that GGT is not specific, as it is an inducible enzyme and can be induced by a number of medications. The classic AST:ALT ratio in active alcohol abusers is 2:1. Remember, however, that these laboratory findings are not specific for alcohol use and can be caused by medications and other illnesses. The other answers are incorrect. Patients with alcoholism typically have macrocytic anemia, elevated serum triglycerides, and hypoglycemia. Ferritin is often increased in active alcohol users in the absence of iron overload. In addition, the transferrin saturation may be elevated because alcohol inhibits transferrin synthesis.
You have ordered liver function tests, but the results will not be available until the next day. The laboratory technician is out getting Botox.
Question 25.2.7 Which of the following medications would be indicated to prevent DT in a patient with hepatic impairment?
E) Clonazepam (Klonopin).
Answer 25.2.7 The correct answer is "D." Benzodiazepines that are metabolized by the cytochrome P450 system will build up in the presence of liver disease, so using those with intermediate half-lives and no active metabolites is essential. Only lorazepam, oxazepam, and temazepam meet these criteria. "B" is incorrect. Although chlordiazepoxide is often used to prevent symptoms of alcohol withdrawal, it is hepatically metabolized and has an exceptionally long half-life and, therefore, should be avoided in patients with liver problems. Alprazolam is too short acting to use in this situation.
Question 25.2.8 Which of the following medications would be a good alternative to benzodiazepines to treat alcohol withdrawal in an otherwise healthy, younger individual in mild-to-moderate withdrawal?
Answer 25.2.8 The correct answer is "D." Carbamazepine has been used extensively in Europe (just like public transportation and universal health coverage … so what do they know?). Carbamazepine prevents seizures and was found superior to oxazepam in reducing global psychological distress, aggression, and anxiety. It has no abuse potential. It is superior to benzodiazepines in preventing rebound withdrawal symptoms. Relative risk of drinking again after withdrawal is three times higher for benzodiazepines compared to carbamazepine. The downside is it interacts with medicines that undergo oxidative metabolism in the liver. Alpha-adrenergic agonists ("E"), beta-blockers ("A"), and calcium channel blockers ("B") have been used to control the symptoms of alcohol withdrawal; however, they are not effective in preventing DT or seizures. "C" does not address the problem of alcohol withdrawal although there is some animal evidence that diuretics including acetazolamide may decrease brain damage from binge drinking.
You remember from a lecture that patients without serious comorbidities, either medical or psychiatric, that have mild to moderate withdrawal symptoms can safely be withdrawn in an outpatient setting. The tool that has been best validated is the revised "Clinical Institute Withdrawal Assessment for Alcohol" (CIWA-Ar) which involves assessment of the severity of 10 signs and symptoms associated with alcohol withdrawal.
Question 25.2.9 Assessment of the severity of which of the following symptoms is NOT included in that tool?
A) Headache or feelings of fullness in head.
B) Palpitations.
C) Paroxysmal sweats.
D) Tactile disturbances.
E) Tremor.
Answer 25.2.9 The correct answer is "B." Palpitations are not included in the CIWA-Ar scale. In addition to "A," "C," "D," and "E," the other signs and symptoms are nausea/vomiting, anxiety, agitation, auditory disturbance, visual disturbance, and orientation/clouding of sensorium. Each sign or symptom is given 0 to 7 points according to its severity except for orientation/clouding of sensorium which is only 0 to 4 points. Withdrawal is considered mild if the score is <15, moderate is 16 to 20, and severe is >20.
You are considering whether or not this patient has DT.
Question 25.2.10 Which of the following is true of DT?
A) The majority of patients with alcohol withdrawal develop DT if not treated.
B) Auditory hallucinations are more common than visual hallucinations in DT.
C) Symptoms of DT could easily be confused for dementia.
D) Her last drink would need to be about 1 week ago for her to have DT.
E) Autonomic instability is present in DT.
Answer 25.2.10 The correct answer is "E." Autonomic instability with elevated pulse, blood pressure, and fever are common in DT. "A" is incorrect. Minor withdrawal symptoms are quite common, but DT develops in only 3% to 5% of patients undergoing alcohol withdrawal. "B" is incorrect. Visual hallucinations are common in DT; auditory hallucinations are less likely. "C" is incorrect. Withdrawal delirium typically presents acutely over a matter of hours or days; whereas, in dementia, the cognitive decline is over a course of months to years. In addition, autonomic instability is not a feature of early dementia (OK, maybe in Shy–Drager syndrome although cognition is usually well preserved—just like our patient's liver). Finally, "D" is incorrect because the risk for DT usually peaks 72 hours after the last drink.
Question 25.2.11 Which medication would be the best choice for DT in a patient who is vomiting profusely and who has no IV access?
E) Clonazepam (Klonopin).
Answer 25.2.11 The correct answer is "D." Lorazepam is absorbed well intramuscularly. This makes it a good choice for the vomiting patient. Diazepam is erratically absorbed IM and should be administered either orally or IV. One could argue that diazepam given rectally is a reasonable alternative to lorazepam IM. However, for reasons previously stated, lorazepam is the preferred drug of those listed.
The IV form of lorazepam can also be administered sublingually to speed absorption if you want to use an oral medication. Obviously IV is even faster yet.
Question 25.2.12 DT carries a fatality rate of:
A) <1%.
B) 5%.
C) 10%.
D) 25%.
E) 50%.
Answer 25.2.12 The correct answer is "B." Prior to modern treatment, the mortality reached up to almost 40% per episode. The rest are incorrect.
Question 25.2.13 Which of the following does NOT predispose to developing DT?
A) Prior episodes of DT.
B) Pneumonia.
C) Gastrointestinal (GI) bleed.
D) Female gender.
E) Hepatic failure.
Answer 25.2.13 The correct answer is "D." Female gender does not predispose an individual to DT but the other options do.
Question 25.2.14 Which of the following is NOT a complication of alcoholism?
A) Dementia.
B) Pancreatitis.
C) Hypermagnesemia.
D) Megaloblastic anemia.
E) Marchiafava–Bignami disease.
Answer 25.2.14 The correct answer is "C." All of the above, with the exception of hypermagnesemia, are associated with alcohol abuse. A few merit special comment. Alcoholic dementia may be related to direct effects of alcohol on the brain or to nutritional deficiencies. Hypomagnesemia is a complication of alcoholism. Hypomagnesemia may decrease the response to thiamine administration. Marchiafava–Bignami disease is demyelination and/or necrosis of the corpus callosum and the adjacent white matter. It presents with dementia, dysarthria, spasticity, and inability to ambulate. It can occasionally be seen in nondrinkers as well.
Elderly patients with alcohol problems often go unrecognized. Have a high index of suspicion in patients with signs and symptoms such as labile hypertension, insomnia, legal or marital problems, frequent falls and injuries, headaches or blackouts, and vague GI complaints.
Question 25.2.15 Which of the following is FALSE about alcohol use disorders?
A) Most patients who develop alcohol disorders do so by their mid-20s.
B) The lifetime prevalence of alcoholism is between 14% and 24%.
C) Alcoholism is frequently comorbid with other psychiatric illnesses.
D) Alcohol abuse is five times more frequent in males than in females.
E) About 30% of patients with alcohol abuse meet criteria for major depressive disorder.
Answer 25.2.15 The correct answer is "A." Most people who develop alcohol use disorders do so by their late 30s, not their late 20s. The rest are correct statements. Especially noteworthy is "C." Half of all people with alcohol abuse have a comorbid psychiatric diagnosis. For example, about 50% to 60% of people with bipolar illness have problems with alcohol abuse or dependence. "E" is a correct statement as well. Although over 80% of patients with alcohol use disorders complain of depressive symptoms, only 30% meet criteria for major depressive disorder. A useful way to approach patients who complain of depression along with their alcohol abuse is to obtain a longitudinal history to see which came first. If it is impossible to tease out, as is often the case, observe for 1 to 3 weeks off alcohol. If depression is still present without alcohol use, it is prudent to treat with an antidepressant. Be careful when treating alcohol abusers with antidepressants: active substance use severely reduces the efficacy of these drugs.
Substance use rates are highest between ages 18 and 25. A lot of this is experimentation that will end as the individual matures. Some, of course, will go on to chronic abuse.
Studies have shown that symptom-triggered instead of fixed-dose protocols for benzodiazepine treatment of alcohol withdrawal as an inpatient may be the best way to treat acute alcohol withdrawal. A 2002 study in the Archives of Internal Medicine demonstrated that the symptom-triggered approach to treatment resulted in less use of benzodiazepines a shorter hospital stay (20 hour vs. 62.7 hours, Arch Intern Med. 2002;162:1117–1121). Symptom-triggered approaches use the CIWA-Ar scoring system every 4 to 8 hours with benzodiazepines provided for scores >8 up to every hour. Benzodiazepine regimens utilized include: lorazepam, diazepam, and chlordiazepoxide. Rule of thumb is to use the smallest effective dose oral benzodiazepine needed to improve symptoms. IV formulations of diazepam and lorazepam may be utilized in the acute setting if needed. Of note, true DT may require absurdly large doses of benzodiazepines (our personal best is 70 mg of IV diazepam in 1 hour).
Objectives: Did you learn to…
Recognize signs and symptoms of alcohol withdrawal?
Describe diagnostic criteria for alcohol withdrawal?
Identify adverse effects of heavy alcohol use?
Differentiate between substance abuse and dependence?
Treat alcohol withdrawal?
Appreciate how denial of the illness plays a role in the assessment of substance abuse?
Identify laboratory abnormalities observed in alcohol abuse and understand the limitations of laboratory studies?