The following cases and commentary, which focus on delirium, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 16). Correct answers begin on page 26.
Case 1: Heart failure readmission
A 94-year-old woman is brought to the emergency department by her daughter for a 5-day history of progressive weakness, anorexia, dizziness, and mild confusion. She was hospitalized 2 weeks ago for an acute exacerbation of chronic heart failure that was treated with intravenous diuretics and an increase in her daily oral diuretic dose. She initially did well following discharge, and a follow-up appointment with her primary care physician is scheduled for next week. She has a history of chronic atrial fibrillation, upper gastrointestinal bleeding owing to a duodenal ulcer 18 months ago, COPD, hypertension, post-herpetic neuralgia, chronic kidney disease, depression, anxiety, and seasonal rhinitis. Medications are furosemide, potassium chloride, aspirin, omeprazole, ipratropium and albuterol inhalers, metoprolol, gabapentin, loratadine, and as-needed lorazepam.
On physical examination, she is a pleasant but frail-appearing woman who is arousable but mildly confused. Temperature is 37.3°C (99.1°F), blood pressure is 108/56 mm Hg, pulse rate is 95/min, and respiration rate is 16/min. Oxygen saturation is 94% on ambient air. The mucous membranes are dry. The pupils are symmetric and reactive. Heart examination is significant for an irregularly irregular rate and a grade 3/6 crescendo-decrescendo murmur at the right upper sternal border. The lungs are clear to auscultation. The abdomen is scaphoid without hepatosplenomegaly. There is no peripheral edema. Her neurologic examination is nonfocal except for her cognitive deficits.
Laboratory studies show normal serum electrolytes and a plasma glucose level of 110 mg/dL (6.1 mmol/L). Her serum creatinine level is 1.4 mg/dL (123.8 µmol/L), increased from 1.2 mg/dL (106.1 µmol/L) at the time of hospital discharge. Her complete blood count reveals a leukocyte count of 7500/µL (7.5 × 109/L) with a normal differential, a hematocrit of 35%, and normal platelet count. A urinalysis shows trace ketones but no cells. A chest radiograph is significant for severe kyphoscoliosis and changes consistent with emphysema, but not pneumonia or heart failure.
Which of the following is the most likely cause of the patient's clinical presentation?
A. Acute kidney injury
B. Medication effect
C. Occult infection
D. Recent stroke
Case 2: Alcoholic hepatitis
A 39-year-old man is admitted to the hospital for new-onset agitation, fluctuating level of consciousness, and tremors. He is diagnosed with acute alcoholic hepatitis.
On physical examination, temperature is 38.8°C (101.8°F), blood pressure is 95/55 mm Hg, pulse rate is 130/min, and respiration rate is 30/min. Jaundice is noted. The abdomen is protuberant with ascites but is soft, with no abdominal rigidity or guarding. There is no blood in the stool. The patient is agitated and disoriented, is unable to maintain attention, and appears to be having visual hallucinations. He believes that the nurse has stolen his wallet (which is in his bedside drawer) in order to obtain his identity. He is diaphoretic and tremulous. Asterixis is absent, and the remainder of the neurologic examination is normal.
Which of the following is the most appropriate management?
B. CT of the head
D. Lactulose enema
Case 3: Agitation in the ICU
A 66-year-old woman is admitted to the hospital after falling at home and dislocating her artificial hip. The next day she becomes acutely short of breath and is transferred to the intensive care unit. She is diagnosed with acute pulmonary embolism and a heparin infusion is started. Her pain is managed with a patient-controlled intravenous analgesia pump. She undergoes closed reduction of her dislocated hip the following day, with temporary interruption of her anticoagulation. The day after her hip reduction, she is more comfortable and her pain medication requirements are lower. On day five, however, she becomes agitated and fearful, alternating with periods of inattention and somnolence.
On physical examination, vital signs are normal. She is awake but lethargic. It is difficult to obtain a history because of her inattentiveness. The cardiopulmonary examination is normal. There are no focal deficits on the neurologic examination. Results of arterial blood gas analysis are normal.
Which of the following is the most likely diagnosis?
A. Acute hemorrhagic stroke
B. Acute respiratory failure
D. Opioid withdrawal
E. Recurrent thromboembolism
Case 4: Young man with confusion
A 25-year-old man is evaluated in the emergency department for a 2-week history of progressive jaundice and the recent onset of confusion. His medical history is unremarkable.
On physical examination, he is confused. Temperature is 36.9°C (98.4°F), blood pressure is 96/60 mm Hg, pulse rate is 120/min, and respiration rate is 22/min. BMI is 21. He is deeply jaundiced and asterixis is noted. No organomegaly is present.
Laboratory studies show hematocrit 40%, leukocyte count 12,400/µL (12.4 × 109/L), platelet count 350,000/µL (350 × 109/L), INR 2.5 (normal range, 0.8-1.2), alanine aminotransferase 240 units/L, aspartate aminotransferase 140 units/L, total bilirubin 20.5 mg/dL (350.6 µmol/L) and creatinine 2.5 mg/dL (221 µmol/L).
Abdominal ultrasonography discloses a normal liver and spleen size. There is minimal ascites but no organomegaly. The portal vein has a normal diameter. There is no bile duct dilatation.
Which of the following is the most appropriate management?
A. Administer fresh frozen plasma
B. Administer intravenous mannitol
C. Perform endoscopic retrograde cholangiopancreatography
D. Refer for liver transplantation
Case 5: Confusion and dementia
A 78-year-old woman is evaluated in the emergency department for a 1-week history of progressive agitation and confusion. She has no history of fever or falling episodes. The patient lives in a nursing home, has advanced dementia, and is dependent on others for all activities of daily living. She can indicate when she needs to void and generally is not incontinent. She can ambulate with a cane but must be accompanied because of a tendency to wander. Although she enjoys being around others and can make simple conversation with family members and nursing home personnel, she does not recognize anyone by name or remember what was said. She has a history of osteoarthritis, hypertension, atrial fibrillation, anxiety, and depression. There have been no recent additions or changes to her medications, which are hydrochlorothiazide, warfarin, amitriptyline, alprazolam, and oxybutynin.
Physical examination is noncontributory.
Results of a complete blood count, comprehensive metabolic profile, and urinalysis are normal. A chest radiograph reveals no evidence of infection or heart failure.
Which of the following is most appropriate as an initial step in management?
A. Add donepezil
B. Add risperidone
C. Discontinue anticholinergic and sedative medications
D. Obtain an electroencephalogram
Case 6: Recent bariatric surgery
A 34-year-old man is evaluated in the emergency department for confusion. Three weeks ago he underwent a Roux-en-Y gastric bypass for morbid obesity. He has had poor oral intake since the surgery because of nausea. Vitamin B12 injections were prescribed, but he has not started them yet. He recently took hydrocodone for pain, but he has not needed it for several days. His only current medication is a multivitamin with iron.
On physical examination, he is afebrile. Blood pressure is 115/80 mm Hg (no orthostatic changes), and pulse rate is 85/min. The mucous membranes are moist, and there is no skin tenting. He has an ataxic gait, nystagmus, and a disconjugate gaze. The remainder of the neurologic examination is normal.
Laboratory studies, including a complete blood count, glucose, and electrolytes, are normal.
Which of the following is the most appropriate next step in management?
A. CT of the head
B. Glucose infusion
C. Intravenous naloxone
D. Intravenous thiamine
E. Subcutaneous vitamin B12
Answers and commentary
Correct answer: B. Medication effect.
The patient's clinical presentation is likely the result of overmedication in an elderly patient who has significant medical comorbidities and is taking numerous medications. She was recently hospitalized and had medication adjustments made in the setting of chronic kidney disease, including an increase in her diuretic dose, that have led to volume depletion, which, in turn, may have led to changes in her kidneys' ability to metabolize drugs that are renally cleared.
Polypharmacy is becoming more common as the population ages. Twelve percent of patients in the United States older than 65 years take 10 or more medications each week, and adverse drug reactions in the elderly account for 10% of emergency department visits and up to 17% of acute hospitalizations. Numerous medications on this patient's list could cause adverse reactions. For example, gabapentin can cause dizziness and weakness and needs to be dose-adjusted in the setting of kidney disease. A review of every patient's medications, particularly in the elderly, should be a part of routine care to avoid polypharmacy and potential medication-related adverse events.
Although this patient has an apparent decline in her kidney function as estimated by her serum creatinine level, there is no clear evidence of acute kidney injury being the primary cause of her altered mental status.
Infection should always be a primary consideration in elderly patients presenting with mental status changes and failure to thrive. However, in this patient there is no evidence of infection as a cause of her symptoms.
The patient has atrial fibrillation and is not receiving anticoagulation therapy. She does, therefore, have an increased risk for thromboembolic disease. However, her neurologic examination is nonfocal, which would be less consistent with stroke as the underlying cause of her presentation.
- Polypharmacy, particularly in elderly patients with multiple comorbid medical conditions, is a frequent cause of adverse events; ongoing review of the need and appropriate dosing of medications should be a part of routine care.
Correct answer: E. Lorazepam.
The most appropriate treatment is lorazepam for delirium tremens syndrome. The term delirium tremens is nearly universally used to refer to delirium due to alcohol withdrawal syndrome. The syndrome usually presents 48 to 96 hours after cessation of drinking, can last up to 2 weeks, and is usually exacerbated at night. The syndrome is characterized by impaired level of consciousness and disorientation (which may fluctuate significantly), reduced attention and global amnesia, impaired cognition and speech, and often hallucinations (usually tactile and/or visual) and delusions (persecutory). The condition can be rapidly fatal if not treated appropriately and aggressively. Seizure activity can occur. Benzodiazepines are the treatment of choice, with doses given as needed based on exhibited signs and symptoms consistent with alcohol withdrawal.
Empiric antibiotics would be appropriate if this patient developed sepsis, but sepsis is an unlikely cause of this patient's delirium, tremulousness, hallucinations, and paranoid ideation. His symptoms are much more suggestive of alcohol withdrawal than sepsis.
CT of the head would be the appropriate management for a suspected intracranial hemorrhage as the cause of this patient's deterioration in mental status. However, this patient does not have evidence of neurologic deficits, making alcohol withdrawal more likely than intracranial hemorrhage.
Haloperidol is used for general delirium, but it is a poor choice for delirium tremens in the setting of alcohol withdrawal because it can lower the seizure threshold and mask symptoms alerting the clinician to the severity of withdrawal.
Lactulose enema would be used in a patient with hepatic encephalopathy. Although hepatic encephalopathy is possible and can account for mental status changes, it cannot explain this patient's agitation, diaphoresis, hallucinations, and tremulousness. In addition, the patient does not manifest evidence of asterixis, typically associated with hepatic encephalopathy.
- Delirium tremens is characterized by fluctuating level of consciousness, disorientation, reduced attention, global amnesia, impaired cognition and speech, and often hallucinations and delusions.
Correct answer: C. Delirium.
The most likely diagnosis is delirium. Delirium is an acute state of confusion that may manifest as a reduced level of consciousness, cognitive abnormalities, perceptual disturbances, or emotional disturbances. It is common in the intensive care unit and should be controlled to ensure patients' safety and to allow appropriate evaluation. Delirium is classified according to psychomotor behavior as hyperactive, hypoactive, and mixed. Pure hyperactive delirium, which accounts for less than 5% of cases of intensive care unit delirium, is characterized by increased psychomotor activity with agitated behavior. Hypoactive or quiet delirium, which accounts for approximately 45% of cases, is characterized by reduced psychomotor behavior and lethargy. Mixed delirium, which accounts for approximately 50% of cases, alternates unpredictably between a hyperactive and a hypoactive manifestation.
An acute stroke is unlikely to cause fluctuating neurologic or cognitive deficits. A hemorrhagic stroke may certainly evolve, producing progressively worsening deficits, but alternating agitation and somnolence would not be typical.
There is no evidence for respiratory failure in this patient. Her arterial blood gas studies and vital signs are normal.
This patient has not been receiving opioids long enough to develop physical dependence and thus be at risk for withdrawal.
Fluctuating mental status would be an unlikely result of a recurrent pulmonary embolism. The interruption of this patient's anticoagulation for a period of a few hours for her hip reduction increases the risk of a recurrent embolism; however, this patient does not have hypoxemia or respiratory distress, which would most likely be evident if she had a recurrent embolism.
- Delirium, defined by fluctuating mental status, is common in the intensive care unit and should be controlled to ensure patients' safety and to allow appropriate evaluation.
Correct answer: D. Refer for liver transplantation.
This patient should be referred for liver transplantation. Fulminant hepatic failure (FHF) is defined as hepatic encephalopathy in the setting of jaundice without preexisting liver disease. Liver failure is classified by the number of weeks after jaundice onset that encephalopathy appears; hyperacute liver failure is within 1 week, acute liver failure is between 1 and 4 weeks, and subacute liver failure is between 4 and 12 weeks. The most common causes of FHF are medications (especially acetaminophen) and viral infections; however, many cases are of indeterminate cause. Quick recognition of FHF is essential, because the mortality rate is as high as 85%. The survival rate with transplantation for FHF is 65% to 80%. Therefore, recognition is important so that affected patients can be transferred to a liver transplantation center.
An elevated INR reflects decreased hepatic synthesis of liver-derived factors of the clotting cascade. Although this increases the risk of bleeding complications in these patients, the administration of fresh frozen plasma to correct coagulopathy is not necessary in the absence of demonstrated bleeding or the need for an invasive procedure.
Cerebral edema is the most common cause of death in patients with FHF. Management of cerebral edema includes invasive monitoring for increased intracranial pressure, typically performed at a liver transplant center. Medical treatment of cerebral edema sometimes includes the use of mannitol, but mannitol therapy is contraindicated in a patient with kidney disease.
Endoscopic retrograde cholangiopancreatography (ERCP) is indicated for assessment and management of biliary obstruction; in the setting of acute liver failure without biliary dilatation on abdominal ultrasound, ERCP is not warranted.
- The recognition of fulminant liver failure should prompt immediate referral to a liver transplantation center for intensive monitoring and consideration of liver transplantation.
Correct answer: C. Discontinue anticholinergic and sedative medications.
Older patients with cognitive impairment are especially susceptible to the effects of anticholinergic and sedative medications, such as those this patient is taking, and these drugs should be discontinued immediately, if possible. Confusion and agitation in an elderly patient with dementia are usually due to a superimposed medical condition, such as an occult infection, head trauma, stroke, metabolic derangement, or drug toxicity. Older patients may not develop a fever or systemic signs in the presence of pneumonia or a urinary tract infection, and thus infection should always be considered. Confusion also can be triggered by an environmental stress, such as a surgery, a head injury, or a medication, in older persons with dementia. Although this patient's history and physical examination revealed no signs of trauma, an acute change in mental status could indicate a fall with subsequent subdural hematoma. Therefore, a CT scan of the head also should be considered. Results of the already obtained metabolic profile should detect any metabolic derangement.
Donepezil, galantamine, and rivastigmine are acetylcholinesterase inhibitors currently approved for the treatment of mild to moderate Alzheimer disease. For the most part, treatment goals focus on delaying the worsening of Alzheimer disease symptoms, although some patients can actually show temporary partial improvement. Donepezil is not an appropriate treatment for delirium and will not be helpful in treating this patient's advanced dementia.
No FDA-approved therapies for delirium exist. However, evidence does exist demonstrating that low-dose antipsychotic agents, such as risperidone, are effective in its treatment. Both typical and atypical antipsychotic drugs carry a black box warning because of their approximately 1.6-fold increased risk of mortality and may exacerbate any coexisting signs of parkinsonism, including postural instability. A far better and safer strategy would be to discontinue unnecessary medications known to increase confusion.
Electroencephalography is not appropriate in this patient whose agitation is unlikely to represent seizure activity or postictal confusion.
- Acute confusion in a patient with dementia requires a complete medical assessment, including evaluation for occult infection.
Correct answer: D. Intravenous thiamine.
The most appropriate next step is to administer intravenous thiamine. This patient has clinical features of thiamine deficiency manifesting as Wernicke encephalopathy (nystagmus, ophthalmoplegia, ataxia, and confusion), and administration of intravenous thiamine should occur promptly. Thiamine deficiency has been reported in patients who have undergone bariatric surgery and is caused by poor postoperative oral intake. Body stores of thiamine deplete quickly. Early recognition of thiamine deficiency is crucial before the patient develops irreversible neurologic and cognitive changes.
This patient has new-onset ataxia and ocular findings on examination, but these findings can be explained by a thiamine-deficient state. Therefore, a CT of the head would be unnecessary and could delay the urgently needed administration of appropriate treatment.
Although hypoglycemia could present with neurologic features, this patient's plasma glucose level was normal on admission. Glucose administration in a patient who is thiamine deficient may worsen the clinical course because thiamine is required as a cofactor in glucose metabolism.
Although naloxone can be helpful for reversal of opiate activity, the patient has not received opioids for several days, and opioid ingestion or withdrawal would not account for his neurologic changes.
Vitamin B12 deficiency can cause neurologic manifestations, typically beginning with paresthesias and ataxia associated with loss of vibration and position sense; however, it often takes months to years after vitamin intake or absorption is impaired for a deficient state to develop. This patient will be at risk for vitamin B12 deficiency if he does not take supplemental vitamin B12, but deficiency would not have occurred within the 3 weeks since his surgery.
- Patients who have recently undergone bariatric surgery may develop thiamine deficiency, which is characterized by confusion, ataxia, nystagmus, and ophthalmoplegia.