Case 1: Alcoholic inpatient with pneumonia
A 45-year-old man is hospitalized for fever and cough and started on appropriate antibiotic treatment for community-acquired pneumonia. While in the hospital, he develops a headache and begins to feel restless and agitated. He drinks four beers nightly on weekdays and eight beers daily on weekends. He has chronic liver disease and has had alcohol withdrawal seizures in the past. His last drink was 12 hours ago. Outpatient medications are lactulose and propranolol, but he has not been adherent with this regimen. He is given thiamine, glucose, intravenous fluids, and multivitamins.
On physical examination, the patient is diaphoretic. He is alert and oriented but tremulous. Temperature is 38.4 °C (101.1 °F), blood pressure is 182/94 mm Hg, pulse rate is 118/min, and respiration rate is 20/min. Jaundice is present. Numerous spider angiomas and palmar erythema are present. Other than tachycardia, the cardiac examination is normal. Crackles are heard in the left lower lung field. There is a small amount of ascites. The liver is not palpable, but the spleen tip is easily palpable. The deep tendon reflexes are brisk. There is no clonus.
Which of the following is the most appropriate treatment of this patient's current symptoms?
Case 2: Vomiting and diarrhea, then intubation
A 37-year-old man is evaluated in the emergency department for nausea and vomiting of 12 hours' duration. The patient states that he has been drinking large amounts of alcohol for several weeks and has eaten very little for the past week. His last alcoholic drink was more than 24 hours ago. He also reports intermittent diarrhea for the past 2 months. History is notable for chronic alcoholism. He takes no medications.
On physical examination, the patient is cachectic. Blood pressure is 100/65 mm Hg, and pulse rate is 105/min. BMI is 17. Proximal muscle wasting is noted. There is no evidence of jaundice or ascites. The liver is enlarged and mildly tender. There is no asterixis. Neurologic examination is unremarkable.
While awaiting the results of laboratory studies, the patient is given intravenous saline with dextrose and vitamins. His respiration rate becomes markedly diminished, and he requires intubation.
His laboratory studies show albumin 3.0 g/dL (30 g/L) and calcium 8.0 mg/dL (2.0 mmol/L). Electrolytes are sodium 132 mEq/L (132 mmol/L), potassium 3.4 mEq/L (3.4 mmol/L), chloride 90 mEq/L (90 mmol/L), bicarbonate 32 mEq/L (32 mmol/L), magnesium 1.7 mg/dL (0.7 mmol/L), and phosphorus 1.5 mg/dL (0.48 mmol/L).
Which of the following is the most likely cause of this patient's respiratory failure?
Case 3: Found somnolent in the woods
An 18-year-old man is evaluated in the emergency department after being found somnolent in a wooded area close to his home. His shirt is covered with emesis. He was last seen in his normal state of health 3 hours ago. His medical history is notable for anxiety, and his only medication is sertraline.
On physical examination, temperature is 38.5 °C (101.3 °F), blood pressure is 98/58 mm Hg, pulse rate is 108/min, and respiration rate is 12/min; BMI is 26. Oxygen saturation is 85% breathing ambient air. The skin is warm. Neurologic examination reveals obtundation and semipurposeful movement of all extremities with painful stimulation. Normal muscle tone is noted, but reflexes are difficult to elicit. Pulmonary examination reveals shallow inspiration with rhonchi in the right lower lung field. Cardiac examination reveals a regular rhythm. The abdomen is soft and nondistended with no overt tenderness.
Laboratory studies show blood urea nitrogen 14 mg/dL (5.0 mmol/L), glucose 180 mg/dL (10 mmol/L), lactate 2.8 mEq/L (2.8 mmol/L), plasma osmolality 325 mOsm/kg H2O and blood ethanol is absent. Electrolytes are sodium 140 mEq/L (140 mmol/L), potassium 3.2 mEq/L (3.2 mmol/L), chloride 104 mEq/L (104 mmol/L), and bicarbonate 6 mEq/L (6 mmol/L). Arterial blood gases, when breathing 50% oxygen by mask, are pH 7.17, Pco2 17 mm Hg (2.3 kPa), and Po2 120 mm Hg (16.0 kPa).
Which of the following is the most likely diagnosis?
A. Isopropyl alcohol poisoning
B. Methanol poisoning
C. Salicylate poisoning
D. Serotonin syndrome
Case 4: Abdominal pain
A 43-year-old man is evaluated in the emergency department for abdominal pain. He has a history of alcohol abuse, with repeated episodes of acute intoxication requiring medical therapy. He also has a history of several episodes of acute pancreatitis, but no history of seizure disorder. He takes no medications.
On physical examination, temperature is 37.4 °C (99.3 °F), blood pressure is 112/66 mm Hg, and pulse rate is 76/min. BMI is 20. There is no evidence of trauma or head injury. There is no evidence of ascites. The abdomen is tender to palpation. Neurologic examination reveals normal pupillary and corneal reflexes, normal muscle tone, and a downgoing plantar reflex.
Laboratory studies show blood urea nitrogen 28 mg/dL (10 mmol/L), calcium 8.6 mg/dL (2.2 mmol/L), creatinine 1.2 mg/dL (106.1 µmol/L) (baseline, 0.8 mg/dL [70.7 µmol/L]), ethanol 62 mg/dL (0.062 g/dL), glucose 72 mg/dL (4 mmol/L), lactate 0.8 mEq/L (0.8 mmol/L), plasma osmolality 293 mOsm/kg H2O, and phosphorus 3.7 mg/dL (1.2 mmol/L).
Electrolytes are sodium 135 mEq/L (135 mmol/L), potassium 4.9 mEq/L (4.9 mmol/L), chloride 96 mEq/L (96 mmol/L), and bicarbonate 12 mEq/L (12 mmol/L). Urinalysis shows pH 5.5, specific gravity 1.020, and no blood, ketones, or cells.
Which of the following is the most likely cause of this patient's acidosis?
A. Acute kidney injury
B. Alcoholic ketoacidosis
C. D-Lactic acidosis
Case 5: GI upset and low calcium
A 47-year-old man presents to the emergency department with weakness and shakiness. He has a long history of alcohol abuse but significantly decreased his usual daily alcohol intake over the past week because of gastrointestinal upset, nausea, and diarrhea. Medical history is otherwise unremarkable, and he takes no medications.
On physical examination, the patient is awake and oriented but tremulous. Mucous membranes are dry. Temperature is 37.3 °C (99.1 °F), blood pressure is 139/76 mm Hg, pulse rate is 101/min, and respiration rate is 15/min. BMI is 19. Cardiopulmonary examination is unremarkable. The abdomen is diffusely tender to palpation. Periodic spontaneous twitching is noted in the major muscle groups.
Laboratory studies are significant for a serum calcium level of 6.5 mg/dL (1.6 mmol/L), serum albumin level of 2.6 g/dL (26 g/L), serum potassium of 3.4 mEq/L (3.4 mmol/L), and normal kidney function studies. Serum parathyroid hormone and 25-hydroxyvitamin D levels are pending.
An electrocardiogram shows prolongation of the QT interval.
Which of the following is the most appropriate next diagnostic test to evaluate this patient's hypocalcemia?
A. 1,25-Dihydroxyvitamin D level
B. 24-Hour urine calcium excretion
C. Ionized calcium level
D. Magnesium level
Answers and commentary
Correct answer: C. Lorazepam.
Lorazepam is the most appropriate treatment for this patient with alcohol withdrawal and chronic liver disease. Alcohol withdrawal symptoms can start within 4 hours to several days after the last drink. Alcohol activates the same receptor as γ-aminobutyric acid, which is the major inhibitory neurotransmitter in the brain, causing central nervous system depression. If ethanol has been present frequently enough in a heavy drinker to develop tolerance and dependence, sudden withdrawal creates a state of central nervous system hyperactivity, which can be life threatening.
Early symptoms include agitation, tremulousness, headache, and symptoms of autonomic hyperactivity (fever, diaphoresis, tachycardia, and hypertension). As withdrawal becomes more severe, patients may experience seizures and/or hallucinations, usually within 12 to 24 hours of abstinence. Delirium tremens is a systemic syndrome characterized by hypertension, tachycardia, diaphoresis, fever, disorientation, and hallucinations. Onset is usually 48 to 96 hours after the last drink and sometimes persists for many days. Benzodiazepines are the treatment of choice for alcohol withdrawal. Thiamine, glucose, and folate are supplemented routinely, and nutrition should be instituted early.
All benzodiazepines appear similarly efficacious in reducing signs and symptoms of alcohol withdrawal. Longer-acting agents, such as chlordiazepoxide, may be more effective in preventing seizures but can pose a risk for excess sedation in older adults and patients with marked liver disease, such as this patient. Short-acting benzodiazepines, such as lorazepam, are preferred to long-acting benzodiazepines in patients with liver disease because short-acting benzodiazepines cause less metabolite buildup in the liver. In this patient, benzodiazepines will not only help to control his current symptoms but will also help to prevent him from progressing to severe alcohol withdrawal.
Clonidine and beta-blockers such as propranolol have been used as an adjunctive therapy in alcohol withdrawal because they reduce withdrawal symptoms related to autonomic hyperactivity. However, there is little evidence that either of these medications reduce or prevent seizures and delirium.
- Benzodiazepines are the treatment of choice for alcohol withdrawal.
Correct answer: E. Hypophosphatemia.
The most likely cause of this patient's respiratory failure is hypophosphatemia, which occurs in patients with chronic alcohol use, malnutrition, or critical illness. Symptoms rarely occur unless the serum phosphate concentration is <2.0 mg/dL (0.65 mmol/L); severe symptoms occur with a serum phosphate concentration <1.0 mg/dL (0.32 mmol/L). Symptoms include weakness, myalgia, rhabdomyolysis, arrhythmias, heart failure, respiratory failure, seizures, coma, and hemolysis. This patient has chronic alcoholism with moderate hypophosphatemia on presentation. Factors that contribute to hypophosphatemia in the patient with chronic alcohol use include decreased dietary intake of phosphate and vitamin D, chronic diarrhea, and a direct toxic effect of alcohol on the proximal tubule. Intravenous dextrose-containing fluids can exacerbate the hypophosphatemia by causing a refeeding syndrome. Glucose stimulates insulin release, which promotes phosphate uptake by the cells and worsening hypophosphatemia. Severe hypophosphatemia can cause respiratory failure from impaired diaphragmatic contractility.
In general, total calcium declines by 0.8 mg/dL (0.2 mmol/L) for each 1.0 g/dL (10 g/L) decrement in serum albumin concentration. This patient's calcium correction for hypoalbuminemia is 8.8 mg/dL (2.2 mmol/L), which is not low and does not explain the respiratory failure.
This patient has mild hypokalemia. Although severe hypokalemia can cause profound muscle weakness, it is unlikely that his serum potassium would decrease to such critically low levels to cause paralysis based on his current treatment.
The patient's magnesium level is within the lower limits of normal range and unlikely to be the cause of his respiratory failure.
Although the patient does have hyponatremia, it is not severe and would not result in respiratory failure. Symptoms of acute hyponatremia are caused by cerebral edema and usually do not manifest until the sodium concentration is lower than 125 mEq/L (125 mmol/L).
- Intravenous dextrose-containing fluids can exacerbate hypophosphatemia by stimulating insulin release, which promotes phosphate uptake by the cells and worsening hypophosphatemia.
Correct answer: B: Methanol poisoning.
This patient's encephalopathy, high anion gap, and elevated osmolal gap are most consistent with methanol (wood alcohol) or ethylene glycol (antifreeze) ingestion. This patient's anion gap is 30 mEq/L (30 mmol/L), and the upper limit of normal is typically 10 mEq/L (10 mmol/L). The osmolal gap is the difference between calculated and measured plasma osmolality. Plasma osmolality (mOsm/kg H2O) is calculated as follows: 2 × serum sodium (mEq/L) + plasma glucose (mg/dL)/18 + blood urea nitrogen (mg/dL)/2.8.
The measured osmolality is 325 mOsm/kg H2O. The calculated osmolality is 295 mOsm/kg H2O. The osmolal gap is 30 mOsm/kg, and the normal range is less than 10 mOsm/kg. Methanol is converted to formic acid, which is toxic to the retina of the eye. Ethylene glycol is converted by alcohol dehydrogenase to oxalic acid, which crystalizes in renal tubules and causes kidney injury. Conversion to toxic metabolites and clearance of these alcohols is greatly diminished by ethanol or intravenous fomepizole. All alcohols can be removed rapidly with dialysis.
Patients with isopropyl alcohol poisoning present with intoxication and an elevated osmolal gap, but they do not have an increased anion gap acidosis as is seen in this patient.
Salicylate toxicity is another cause of increased anion gap acidosis, encephalopathy, and vomiting. However, it does not cause elevation of the osmolal gap, as is seen in this patient.
Serotonin syndrome is a cause of fever and encephalopathy, but it typically manifests with agitation, muscle rigidity, and hyperreflexia, none of which are present in this patient. Serotonin syndrome also would not explain this patient's increased anion gap acidosis and osmolal gap. This patient's fever is most likely related to an aspiration event.
- Methanol and ethylene glycol ingestion are characterized by encephalopathy, an increased anion gap acidosis, and an elevated osmolal gap.
Correct answer: B. Alcoholic ketoacidosis.
The most likely diagnosis is alcoholic ketoacidosis. This patient has an increased anion gap metabolic acidosis of 27, and ketoacidosis due to acute ethanol intoxication is the most likely cause. Alcoholic ketoacidosis occurs in patients with chronic ethanol abuse and liver disease and develops following an episode of acute intoxication, at which time the ingested ethanol may have already been extensively metabolized, leading to low or normal serum ethanol levels. Ethanol is oxidized to acetaldehyde and then to acetic acid, during which process the electron-carrier coenzyme nicotinamide adenine dinucleotide (NAD+) is reduced to NADH in increasing amounts. Simultaneously, rising catecholamine levels cause lipolysis with subsequent generation of free fatty acids and ketone bodies, such as acetoacetate. The high ratio of NADH to NAD+ leads to increased reduction of acetoacetate to β-hydroxybutyrate. Because the nitroprusside reagent in the serum and urine ketone assays detects only acetoacetate, these tests may be falsely negative due to decreased acetoacetate levels despite the presence of increased levels of the ketone β-hydroxybutyrate, as in this case. Definitive diagnosis may require direct measurement of β-hydroxybutyrate levels in the serum, which is available in some laboratories.
Acute kidney injury can lead to an increased anion gap metabolic acidosis due to the accumulation of acidic metabolic by-products and phosphates and sulfates. However, this degree of anion gap would not be expected in this patient who is mildly prerenal with a normal serum phosphorus level.
D-Lactic acidosis is an uncommon cause of increased anion gap metabolic acidosis that is typically identified in patients with small-bowel bacterial overgrowth. Bacterial production of D-lactic acid is undetectable by the serum lactate assay, which recognizes only the L enantiomer. However, this disorder is not associated with chronic alcohol use and would not be a likely diagnostic consideration in this patient.
Rhabdomyolysis is a diagnostic consideration in a patient with a history of alcohol abuse and an anion gap metabolic acidosis, but this condition is frequently associated with hyperkalemia, hyperphosphatemia, hypocalcemia, and a urinalysis positive for blood with no erythrocytes visible on urine microscopy.
- Alcoholic ketoacidosis occurs in patients with chronic ethanol abuse, frequently with associated liver disease, and develops following an episode of acute intoxication.
Correct answer: D. Magnesium level.
This patient's magnesium level should be checked. He has a very low calcium level that is likely contributing to his clinical findings of tremulousness, muscle irritability, and electrocardiogram changes. He struggles with alcohol abuse, and his low albumin level suggests malnutrition, likely due to his chronic alcohol intake as a primary source of calories. Magnesium deficiency is common in persons who abuse alcohol. Furthermore, he has had diarrhea for several days, which will also deplete his magnesium stores. This patient's low calcium level should promote parathyroid hormone (PTH) secretion to help correct the hypocalcemia. However, decreased levels of magnesium impair release of PTH; levels in patients with significant magnesium deficiency are either low or inappropriately in the normal range. Low magnesium levels are also associated with resistance to PTH activity at the level of bone, further contributing to hypocalcemia. Therefore, in patients with hypocalcemia and hypomagnesemia, it is crucial to correct the magnesium level (to at least 2 mg/dL [0.83 mmol/L]), as it is difficult to increase calcium levels until this is done.
1,25-Dihydroxyvitamin D has a short half-life, and its measurement only reflects the active levels of vitamin D. Since active levels tend to vacillate frequently based on immediate need, this level would not be diagnostically helpful. 25-Hydroxyvitamin D levels have a longer half-life and, therefore, more accurately reflect the total body stores of vitamin D.
Measuring 24-hour urine calcium excretion in this patient would not be diagnostically helpful as significant urinary loss of calcium is uncommon, and the urine calcium level in this patient would be expected to be low due to compensatory kidney retention of calcium.
Checking the ionized calcium level is indicated in settings where abnormal serum protein binding of calcium is possible. This test is not needed in this symptomatic patient who has no suggestion of excessive protein binding of calcium. n
- Low serum magnesium levels impair parathyroid hormone secretion and require repletion before serum calcium levels may be corrected.