The following cases and commentary, which focus on alcohol abuse, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).
Case 1: Agitation and history of alcohol abuse
A 32-year-old man is brought to the emergency department after becoming disoriented, combative, and agitated earlier that day. He is accompanied by a friend, who states that the patient has a history of alcohol and drug abuse, including inhalants.
On physical examination, the patient is uncooperative and slightly disoriented. Temperature is normal, blood pressure is 140/88 mm Hg, and pulse rate is 98/min. The remainder of the examination is normal.
Laboratory studies show fasting glucose 110 mg/dL (6.1 mmol/L), sodium 142 meq/L (142 mmol/L), potassium 4.1 meq/L (4.1 mmol/L), chloride 109 meg/L (109 mmol/L), bicarbonate 23 meq/L (23 mmol/L), blood urea nitrogen 18 mg/dL (6.4 mmol/L), plasma osmolality 320 mosm/kg H2O (320 mmol/kg H2O), serum creatinine 1.1 mg/dL (97.2 µmol/L), serum ketones positive, and urinalysis trace glucose and 4+ ketones.
Arterial blood gas studies (with the patient breathing ambient air) show pH 7.4, PCO2 44 mm Hg, and PO2 92 mm Hg.
Which of the following is the most likely cause of this patient's clinical presentation?
A. Alcoholic ketoacidosis
B. Diabetic ketoacidosis
C. Ethylene glycol
D. Isopropyl alcohol
Case 2: Seizure after high school party
A 17-year-old male high school student is evaluated in the emergency department 1 hour after having a generalized tonic-clonic seizure while eating breakfast with his family. He says he was out late the night before with classmates and drank six cans of beer over the course of the evening. He reports having sudden, involuntary jerks of his arms this morning before the convulsion and having had similar jerks on awakening over the past 2 months when sleep deprived. He reports no history of regular alcohol or illicit substance abuse. He takes no medications.
Physical examination and neurologic examination findings are normal.
Results of laboratory studies (including a complete blood count; measurements of serum electrolyte, plasma glucose, and serum ethanol levels; and a urine toxicology screen) are normal.
A CT scan of the head shows no abnormalities.
Which of the following is the most likely diagnosis?
A. Alcohol withdrawal seizure
B. Benign rolandic epilepsy
C. Juvenile myoclonic epilepsy
D. Temporal lobe epilepsy
Case 3: Jaundice and altered mental status
A 55-year-old man is hospitalized for a 2-week history of jaundice and altered mental status. The patient has a 10-year history of alcohol dependence and has failed several attempts to stop drinking. His family reports that he had been drinking heavily every day until about 3 weeks ago.
On physical examination, the patient is confused and lethargic; the temperature is 38.0°C (100.0°F), the blood pressure is 90/60 mm Hg, the pulse rate is 120/min, and the respiration rate is 30/min. The BMI is 24. Examination reveals scleral icterus. There is no guarding on palpation of the abdomen. The liver edge is tender and easily palpable 3 cm below the right costal margin. There is no ascites, edema, or evidence of bleeding.
Laboratory studies show leukocyte count 17,000/µL (17 × 109/L), platelet count 103,000/µL (103 × 109/L), prothrombin time 26.2 s, INR 4.0, bilirubin (total) 37.0 mg/dL (632.7 µmol/L), bilirubin (direct) 17.0 mg/dL (290.7 µmol/L), aspartate aminotransferase 98 U/L, alanine aminotransferase 50 U/L, alkaline phosphatase 230 U/L, albumin 2.0 g/dL (20 g/L), and ammonia 110 µg/dL.
Chest radiograph is normal. Ultrasonography shows an enlarged, fatty liver, with no nodules, ascites, pericholecystic fluid, or bile duct dilatation. Blood and urine cultures are negative.
In addition to enteral nutrition, which of the following is the most appropriate management for this patient?
C. Fresh frozen plasma
D. Liver transplantation
Case 4: Infection and chronic alcoholism
A 45-year-old woman is evaluated for fever, diminished appetite, weight loss, and cough productive of foul-smelling sputum of 2 weeks' duration. She has a history of chronic alcoholism and frequent hospital admissions for alcohol-withdrawal seizures, with the most recent episode occurring 3 weeks ago.
On physical examination, temperature is 38.3o C (101.0o F), blood pressure is 130/84 mm Hg, pulse rate is 80/min, and respiration rate is 18/min. Her breath is foul smelling and dentition is poor. Pulmonary examination reveals some crackles and rhonchi in the right anterior chest.
Laboratory studies indicate a leukocyte count of 12,500/µL (12.5 × 109/L) with 8% band forms. The chest radiograph is shown.
Sputum Gram stain results indicate gram-positive cocci in chains, gram-negative bacilli, and gram-positive bacilli.
Which of the following empiric antimicrobial regimens should be initiated?
Case 5: Unarousable young man
An 18-year-old man is evaluated in the emergency department after his mother found him unconscious in his bed at home. She reported that her son had gone to a party two nights ago, but she was not sure when he returned home. When she checked on him, he was unarousable. He has no significant medical history and takes no medications.
In the emergency department, he is afebrile, blood pressure is 110/70 mm Hg, the pulse rate is 50/min, and respiration rate is 6/min; he is intubated for airway protection.
Laboratory studies show hemoglobin 12.2 g/dL (122 g/L), leukocyte count 3400/µL (3.4 × 109/L), platelet count 110,000/µL (110 × 109/L), creatinine 3.2 mg/dL (282.9 µmol/L), aspartate aminotransferase 80 U/L, alanine aminotransferase 46 U/L, creatine kinase 18,400 U/L and INR 1.2.
Alkaline phosphatase, bilirubin, and albumin are normal. Urine dipstick is 4+ positive for occult blood. Blood alcohol level is 0.8 g/dL (174 mmol/L). Toxicology testing is positive for opiates and cocaine. Bladder catheterization reveals only 30 mL of brown urine.
Which of the following is the most likely cause of the patient's renal failure?
A. Hemolytic anemia
B. Hemolytic-uremic syndrome
C. Hepatorenal syndrome
Answers and commentary
Correct answer: D. Isopropyl alcohol.
This patient most likely has isopropyl alcohol poisoning. Manifestations of this condition resemble those in ethanol intoxication and include inebriation and a depressed mental status. Isopropyl alcohol ingestion causes acetone production, which results in ketones in the blood and urine. However, because bicarbonate is not consumed during acetone production, metabolic acidosis is absent in this setting. Isopropyl alcohol poisoning is characterized by an increased osmolal gap in the setting of positive serum and urine ketones. The osmolal gap is the difference between the measured and calculated osmolality, with the calculated osmolality obtained using the following formula:
Plasma Osmolality (mosm/kg H2O) = 2 × Serum Sodium (meq/L) + Blood Urea Nitrogen (mg/dL)/2.8 + Glucose (mg/dL)/18
This patient's calculated plasma osmolality is 296 mosm/kg H2O (296 mmol/kg H2O) and the calculated osmolal gap is 24 mosm/kg H2O (24 mmol/kg H2O), whereas the normal osmolal gap is approximately 10 mosm/kg H2O (10 mmol/kg H2O). An elevated osmolal gap suggests the presence of an unmeasured osmole and is most commonly caused by ethanol. The osmolal gap is also elevated in the presence of ethylene glycol, methanol, and isopropyl alcohol. However, isopropyl alcohol does not cause an elevated anion gap metabolic acidosis (methanol and ethylene glycol poisoning) and is not associated with retinal abnormalities (methanol poisoning) or kidney failure (ethylene glycol poisoning).
This patient's confusion and disorientation are consistent with ethylene glycol poisoning, diabetic ketoacidosis, and alcoholic ketoacidosis; however, these conditions would be associated with an anion gap metabolic acidosis. Toluene, an industrial solvent that can be abused as an inhalant, may cause confusion and disorientation in addition to metabolic acidosis, hypokalemia, hypophosphatemia, rhabdomyolysis, and elevated creatine kinase level. The absence of metabolic acidosis and hypokalemia makes toluene poisoning unlikely.
- Isopropyl alcohol poisoning is characterized by an increased osmolal gap in the setting of positive serum and urine ketones and does not cause metabolic acidosis.
Correct answer: C. Juvenile myoclonic epilepsy.
This patient most likely has juvenile myoclonic epilepsy. Recognizing the specific epilepsy syndrome affecting a patient is crucial in selecting the appropriate therapy, making the correct prognosis, and, in some cases, providing genetic counseling. A history of myoclonic (rapid, unprovoked jerks) and generalized tonic-clonic seizures on awakening with onset in adolescence strongly suggests a diagnosis of juvenile myoclonic epilepsy. One of the most commonly encountered forms of epilepsy, juvenile myoclonic epilepsy may affect 5% to 10% of all patients with epilepsy. Seizures are often provoked by sleep deprivation, alcohol, or exposure to flickering lights.
Recognizing the specific epilepsy syndrome affecting a patient is crucial in selecting the appropriate therapy, making the correct prognosis, and, in some cases, providing genetic counseling.
Alcohol withdrawal seizures develop in chronic users of alcohol and are generally seen in combination with other signs and symptoms of alcohol withdrawal, such as delirium, tremor, tachycardia, and diaphoresis. This patient's history does not suggest alcohol withdrawal as the likely cause of his recurrent seizures.
Benign rolandic epilepsy is a syndrome seen in younger children and adolescents who have seizures, usually during sleep, that begin with focal sensory and/or motor symptoms involving the face, mouth, and throat that can then secondarily generalize. This benign syndrome is not associated with myoclonic seizures and so is not the diagnosis in this patient.
Temporal lobe epilepsy is the most common of the localization-related epilepsies, a type of epilepsy resulting from a focal brain abnormality. Temporal lobe epilepsy can often be further categorized as the result of a focal abnormality of the mesial temporal lobe. The most common seizure classification associated with mesial temporal lobe epilepsy is complex partial seizure. Characteristically, patients with complex partial seizures are awake but exhibit altered awareness, such as unresponsiveness or staring. Patients also exhibit automatisms—such as lip smacking, swallowing, picking, or manipulating objects—or automatic (purposeless, repetitive) behaviors. Patients often describe a preceding aura and, most commonly, autonomic symptoms. About one third of complex partial seizures will generalize as tonic-clonic seizures. This patient's myoclonic jerking is not compatible with temporal lobe epilepsy.
- Juvenile myoclonic epilepsy is characterized by myoclonic and generalized tonic-clonic seizures on awakening that are often provoked by sleep deprivation or alcohol.
Correct answer: B. Methylprednisolone.
This patient has severe alcoholic hepatitis. Excessive alcohol intake may cause liver disease directly or may increase the risk of an unfavorable outcome in patients with pre-existing liver disease. This patient with chronic alcohol abuse has a history of recent heavy alcohol use, elevated serum aspartate aminotransferase (AST) and alanine aminotransferase values (usually greater than 300 U/L) and a serum aspartate aminotransferase concentration that is greater than the alanine aminotransferase concentration in roughly a 2 to 1 ratio, elevated alkaline phosphatase concentration, jaundice, coagulopathy, and encephalopathy. Moreover, other causes of acute and chronic liver disease have been excluded. The severity of the presentation and poor prognosis are underscored by the presence of the very high serum bilirubin concentration, coagulopathy, and encephalopathy.
The mortality risk in this setting is calculated by the discriminant function as follows: (4.6 × [prothrombin time – control prothrombin time]) + serum bilirubin. A discriminant function score of greater than 32 identifies patients with a 50% mortality rate within 30 days and has been used to identify patients who have a survival benefit from corticosteroid therapy. In addition, nutrition therapy has been shown to improve survival in severely malnourished hospitalized alcoholic patients.
The presentation of alcoholic hepatitis may resemble infection because of the fever and leukocytosis; however, this patient's chest radiograph and blood and urine cultures were negative. In the absence of active bleeding, fresh frozen plasma is not indicated. Although many patients with alcoholic hepatitis recover with appropriate therapy, it would be inappropriate to offer liver transplantation to an alcoholic patient who is not involved in rehabilitation counseling. Some transplant programs require abstinence of at least 6 months. This not only confirms a commitment to abstaining from alcohol but also allows time for improvement of the alcoholic hepatitis to the point that transplantation may not be needed. Antibiotic therapy has no role in alcoholic hepatitis. Fresh frozen plasma is not a priority in a patient with alcoholic hepatitis and a coagulopathy unless active bleeding is present.
- Patients with severe alcoholic hepatitis, as defined by a discriminant function score of 32 or more, benefit from corticosteroid therapy.
Correct answer: A. Ampicillin-sulbactam.
This patient's history of alcohol abuse and alcohol-withdrawal seizures puts her at risk for aspiration pneumonia. She now presents with a lung abscess, characterized radiologically by a cavity with an air-fluid level, which probably occurred as a complication of aspiration pneumonia. Lung abscesses are polymicrobial infections caused by anaerobic bacteria that are normally present in the mouth; micro-aerophilic streptococci, viridans streptococci, and gram-negative enteric pathogens have also been implicated. In studies using sample techniques that avoid oral contamination, anaerobes are found in about 90% of patients with lung abscess and are the only organisms isolated in about half. Possible anaerobes in patients with lung abscess as a complication of aspiration pneumonia include Peptostreptococcus species, Fusobacterium nucleatum, Prevotella melaninogenica, and Bacteroides species (including B. fragilis). Of the choices listed, only ampicillin-sulbactam would have a broad enough spectrum to cover the likely pathogens.
Of the other antimicrobial choices, levofloxacin and aztreonam would not be effective in treating oral anaerobes, and ceftriaxone would be effective in treating some oral anaerobic species but not β-lactamase-producing strains.
Although metronidazole is highly active in vitro against most anaerobes, it is not active against microaerophilic streptococci and some anaerobic cocci.
- Patients with lung abscess as a complication of aspiration pneumonia require treatment with an antimicrobial agent effective against β-lactamase-producing strains of oral anaerobes.
Correct answer: D. Rhabdomyolysis.
This patient most likely has rhabdomyolysis, which is caused by skeletal muscle damage that leads to release of intracellular components into the circulation, such as creatine kinase and lactate dehydrogenase, the heme pigment myoglobin, purines, and potassium and phosphate. The syndrome was first identified in patients with traumatic crush injuries, but there are nontraumatic causes, such as alcohol (due to hypophosphatemia), drug use, metabolic disorders, and infections. The classic triad of findings includes muscle pain, weakness, and dark urine. The diagnosis is based on clinical findings and a history of predisposing factors (such as prolonged immobilization or drug toxicity) and confirmed by the presence of myoglobinuria, an increased serum creatine kinase level, and, in some cases, hyperkalemia. The disorder usually resolves within days to weeks. Treatment consists of aggressive fluid resuscitation; fluids should be adjusted to maintain the hourly urine output at least 300 mL until the urine is negative for myoglobin. Acute kidney injury resulting from acute tubular necrosis occurs in approximately one third of patients. Dialysis is sometimes necessary.
Although fulminant hepatic failure may result in coma, dark urine, and renal failure, other tests of synthetic liver function in this patient are normal. There are no clinical features to suggest sepsis. The patient has mild anemia, but the proportionate reduction in the leukocyte and platelet counts suggests alcohol-induced bone marrow suppression. Hemolytic anemia would not explain the patient's elevated creatine kinase level and usually does not cause renal failure. Hemolytic uremic syndrome is not consistent with the clinical findings of polysubstance overdose or the laboratory finding of the elevated serum creatine kinase level.
- Nontraumatic causes of rhabdomyolysis include drug use, metabolic disorders, and infections.