The following cases and commentary, which address delirium, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).
Case 1: Medicating ICU delirium
A 75-year-old woman with a history of chronic obstructive pulmonary disease is evaluated in the intensive care unit for delirium. She had a median sternotomy and repair of an aortic dissection and was extubated uneventfully on postoperative day 4. Two days later she developed fluctuations in her mental status and inattention. While still in the intensive care unit, she became agitated, pulling at her lines, attempting to climb out of bed, and asking to leave the hospital. Her arterial blood gas values are normal. The patient has no history of alcohol abuse. The use of frequent orientation cues, calm reassurance, and presence of family members has done little to reduce the patient's agitated behavior.
Which of the following is the most appropriate therapy for this patient's delirium?
Case 2: Pinpointing the cause
A 67-year-old man is evaluated in the emergency department for confusion and agitation secondary to malignant hypertension. Initial blood pressure is 230/130 mm Hg, and funduscopic examination reveals papilledema.
He is admitted to the intensive care unit, and therapy with nitroprusside by continuous infusion is begun; the therapy is titrated over the next 3 days. The encephalopathy and papilledema resolve with control of the blood pressure. However, he becomes more confused and lethargic. The physical examination is normal. He is afebrile, with a blood pressure of 100/70 mm Hg and a pulse rate of 60/min. He is oriented only to person. There are no focal findings on the neurologic examination and no evidence of nuchal rigidity.
Arterial blood gases reveal: pH 7.2; PCO2 20 mm Hg; PO2 90 mm Hg (on ambient air). Venous PO2 is 72 mm Hg. Serum electrolyte panel shows: sodium 140 mEq/L (140 mmol/L); potassium 3.8 mEq/L (3.8 mmol/L); chloride 90 mEq/L (90 mmol/L), and bicarbonate 9 mEq/L (9 mmol/L).
Which of the following is the most likely cause of the patient's findings?
A. Cyanide toxicity
B. Delirium tremens
C. Hepatic encephalopathy
D. Hypoxic-ischemic encephalopathy
E. Wernicke encephalopathy
Case 3: Evaluation tool selection
A 68-year-old man with chronic obstructive pulmonary disease, hypertension, and hyperlipidemia is being weaned from mechanical ventilation after an exacerbation. The patient's current medications are ipratropium bromide and albuterol (both by metered-dose inhaler through the ventilator), prednisone, lisinopril, and atorvastatin.
He is started on a spontaneous breathing trial, which he initially tolerates well but later shows evidence of oxygen desaturation and agitation. He is given increasing doses of lorazepam to cause sedation, and assist-control ventilation is resumed. The following day he is calm but is not focused and fails to follow commands consistently.
Which of the following is the best test to assess the patient's mental status?
A. Beck Depression Inventory
B. Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)
C. CT scan of the head
D. Metabolic profile
E. Mini-Mental State Examination
Case 4: Diagnosing disorientation
A 78-year-old woman is evaluated in the intensive care unit for disorientation. The patient recently developed the acute respiratory distress syndrome secondary to community acquired pneumonia, and mechanical ventilation was started 2 days ago. She lives alone and functions well independently.
The patient is on a ventilator; she has received small doses of lorazepam over the past 48 hours and appears comfortable. She has recently become disoriented, is not interacting as well with her family as she had before, and has had fluctuations in mental status over the past 24 hours.
On physical examination, pulse rate is 92/min, but vital signs are otherwise normal. Neurologic examination shows no focal abnormalities, and cranial nerve examination is normal. She is calm and awake but cannot follow directions to do the “random letter A test” by squeezing the examiner's hand only on hearing the letter “A”; she also cannot organize her thinking to answer simple questions. When asked whether she is seeing things or hearing things that are not there, she shakes her head “No.” Laboratory studies show hemoglobin of 9.9 g/dL (99 g/L) and a leukocyte count of 11,000/µL (11 × 109/L) with a normal differential. Metabolic panel reveals plasma glucose of 180 mg/dL (10.0 mmol/L); serum total thyroxine and thyroid-stimulating hormone levels are normal.
Which of the following is the most likely diagnosis?
Case 5: End-of-life medication management
An 85-year-old terminally ill woman is evaluated in a home hospice setting. She has metastatic breast cancer to the spine, lungs, and liver. She has had progressive anorexia and weight loss and is dependent on family for all activities of daily living. She has an advance directive stating she does not want cardiopulmonary resuscitation or artificial nutrition. Her pain has been well controlled on a fentanyl transdermal patch and immediate-release morphine as needed for pain. These medications have been stable over the past month. Last night, the patient became confused and agitated, trying to get out of bed and repeatedly stating she needed to look for her deceased husband. There is no dyspnea, fever, dysuria, chest discomfort, or abdominal discomfort. She rates her back pain as 1 on a scale of 1 to 10. She continues to require immediate-release morphine.
Vital signs are normal. The patient is alert and oriented to name and place but cannot remember the year or date. The patient is still agitated and confused, picking at her clothes during the examination.
Which of the following is the most appropriate management for this patient?
A. Discontinue fentanyl patch
B. Initiate haloperidol
C. Initiate lorazepam
D. Measure serum electrolytes, calcium, and renal and hepatic function
E. Schedule MRI brain scan
Case 6: Agitation after surgery
A 79-year-old woman was hospitalized 4 days ago after sustaining a right hip fracture in a fall. She underwent surgical repair with right hip replacement 3 days ago and did not awaken from general anesthesia until 12 hours after extubation. As her alertness has increased, she has become increasingly agitated, yelling at the nurses and flailing her arms; mechanical four-limb restraints were placed 2 days ago. The patient has a 4-year history of progressive cognitive decline diagnosed as Alzheimer dementia. She also has chronic atrial fibrillation treated with chronic warfarin therapy. She has no other pertinent personal or family medical history. Current medications are donepezil, memantine, atenolol, warfarin, and low-molecular-weight heparin.
On physical examination today, temperature is 37.2°C (99.0°F), blood pressure is 100/68 mm Hg, pulse rate is 100/min and irregular, respiration rate is 18/min, and BMI is 21. The patient can move all four limbs with guarding of the right lower limb. She is inattentive and disoriented to time and place and exhibits combativeness alternating with hypersomnolence. The remainder of the neurologic examination is unremarkable, without evidence of focal findings or meningismus.
Which of the following is the most likely diagnosis?
A. Acute cerebral infarction
B. Acute worsening of Alzheimer dementia
D. Postoperative delirium
Answers and commentary
Correct answer: B. Haloperidol.
When supportive care is insufficient for prevention or treatment of delirium, symptom control with medication is occasionally necessary to prevent harm or to allow evaluation and treatment in the intensive care unit. The appropriate treatment for this patient is haloperidol. The recommended therapy for delirium is antipsychotic agents, although no drugs are U.S. Food and Drug Administration–approved for this indication. Ongoing randomized, placebo-controlled trials are investigating different management strategies for intensive care unit delirium. A recent systematic evidence review found that the existing limited data indicate no superiority for second-generation antipsychotics compared with haloperidol for delirium. Haloperidol does not cause respiratory suppression, which is one reason that it is often used in patients with hypoventilatory respiratory failure who require sedation. All antipsychotic agents, and especially “typical” agents such as haloperidol, pose a risk of torsades de pointes and extrapyramidal side effects as well as the neuroleptic malignant syndrome.
Diphenhydramine and other antihistamines are a major risk factor for delirium, especially in older patients. Lorazepam is actually deliriogenic, and its use in a delirious patient should be carefully re-evaluated, other than perhaps in patients experiencing benzodiazepine withdrawal or delirium tremens. There is no evidence that propofol has any role in treating delirium.
- No drug is U.S. Food and Drug Administration–approved for the treatment of delirium, but clinical practice guidelines recommend antipsychotic agents, such as haloperidol.
Correct answer: A. Cyanide toxicity.
Cyanide may cause toxicity through parenteral administration, smoke inhalation, oral ingestion, or dermal absorption. Sodium nitroprusside, when used in high doses or over a period of days, can produce toxic blood concentrations of cyanide. In most patients, cyanide release from sodium nitroprusside is slow enough that the body's innate detoxification mechanisms can eliminate the cyanide before it interferes with cellular respiration. However, patients with low thiosulfate reserves (for example, malnourished or postoperative patients) are at increased risk for developing symptoms, even with therapeutic dosing.
A severe anion gap metabolic acidosis, combined with a reduced arterial-venous oxygen gradient (less than 10 mm Hg due to venous hyperoxia), suggests the diagnosis of cyanide toxicity. Apnea may result in a combined metabolic and respiratory acidosis. The treatment of cyanide poisoning is empiric because laboratory confirmation can take hours or days. Treatment includes administration of both sodium thiosulfate and hydroxocobalamin.
Hepatic encephalopathy can cause confusion, respiratory alkalosis, and mild hypoxemia. Hypoxic-ischemic encephalopathy typically follows an obvious anoxic event such as cardiac arrest or drowning. This patient has no history of such a precipitating event. Wernicke encephalopathy is defined by confusion, ataxia, and ophthalmoplegia, but the full triad of findings is frequently absent. The first symptoms of alcohol withdrawal occur within 6 hours of the last drink and include tremors, diaphoresis, anxiety, headache, and gastrointestinal upset. None of these conditions are associated with an anion gap metabolic acidosis and a reduced arterial-venous oxygen gradient and are therefore unlikely causes of the patient's findings.
- Sodium nitroprusside when used in high doses or over a period of days can produce toxic blood concentrations of cyanide.
Correct answer: B. Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).
The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is an instrument for nurses and physicians to use in evaluating a patient for delirium; the assessment takes less than 1 minute and is recommended for routine monitoring of all mechanically ventilated patients. The CAM-ICU, a well-validated and highly reliable method now translated into more than 10 languages, is widely used for monitoring delirium in ICU patients. The prevalence of delirium in most studies of mechanically ventilated patients is between 50% and 80%. ICU delirium has been shown to be an independent predictor of ICU and hospital length of stay, cost of care, cognitive status at hospital discharge, and 6-month mortality. The agitated, hyperactive subtype of delirium is much less common than the “quiet,” hypoactive subtype, which is generally associated with a lower likelihood of survival.
The Beck Depression Inventory II consists of 21 items to assess the intensity of depression in clinical and normal patients. The Mini-Mental State Examination (MMSE) is a 30-point questionnaire that is used to screen for cognitive impairment. It is commonly used to screen for dementia. It is also used to estimate the severity of cognitive impairment at a given time and to follow the course of cognitive changes in a patient over time.
The diagnosis of delirium is a clinical one, and there are no laboratory tests, imaging studies, or other tests that can provide greater accuracy than the CAM-ICU algorithm. Specifically, a head CT scan and metabolic profile will not establish the diagnosis of delirium as effectively as CAM-ICU.
- The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), a clinical instrument for use in evaluating a patient in the intensive care unit for delirium, takes less than 1 minute and is recommended for all mechanically ventilated patients.
Correct answer: A. Delirium.
This patient has the most common manifestation of delirium in the intensive care unit (ICU), which is hypoactive or “quiet” delirium. Delirium is a form of acute brain dysfunction that occurs in 50% to 80% of ventilated patients in the ICU. It is associated with a threefold higher rate of death by 6 months, much longer lengths of ICU and hospital stay, higher costs, and a 10-fold higher rate of chronic cognitive deficits after survival. It can be diagnosed quickly using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), which takes less than a minute in most patients. The four cardinal features of the diagnosis are (1) acute onset or fluctuations in mental status over a 24-hour period, (2) inattention, (3) disorganization of thinking, and (4) an altered level of consciousness at the time of the evaluation. Patients are defined as delirious if they are positive for features 1 and 2 and either 3 or 4. This patient has features 1, 2, and 3: she is having fluctuations in her mental status as evidenced by the Richmond Agitation Sedation Scale, is inattentive as evidenced by her inability to do the random letter A test, and cannot correctly answer simple questions that require organization of her thinking. Hallucinations may be a symptom of delirium, but they are not required for the diagnosis. She is not hyperactive or in “distress,” which is also not required for the diagnosis of delirium.
The patient has no signs of acute focal neurologic findings, which are characteristic of stroke. Dementia is an acquired chronic impairment of memory and other aspects of intellect that impedes daily functioning and is not compatible with this patient's acute fluctuating mental status. Psychosis is a disturbance in the perception of reality, evidenced by hallucinations, delusions, or thought disorganization. The patient denies hearing or seeing things that are not there, making psychosis unlikely.
- The cardinal features of delirium are (1) acute onset or fluctuations in mental status over a 24-hour period, (2) inattention, (3) disorganization of thinking, and (4) an altered level of consciousness at the time of the evaluation.
Correct answer: B. Initiate haloperidol.
The most appropriate treatment for this terminally ill patient is to initiate haloperidol. During the terminal phases of hospice care, most patients experience at least some form of altered mental status. This patient demonstrates confusion, agitation, and a deficit in attention, pointing to a likely diagnosis of delirium. There are no U.S. Food and Drug Administration–approved therapies for delirium. However, there is evidence demonstrating that low-dose antipsychotic agents are effective in the treatment of delirium.
Even though this patient is confused, she is able to articulate whether she is in pain. Confusion after a recent increase in narcotic dose is common in terminally ill patients. This patient has been on a stable fentanyl dose for 1 month, however, making this cause less likely. Discontinuation of her pain medication may subject her to inappropriate discomfort, as she still has some baseline pain.
As benzodiazepines, including lorazepam, can cause or worsen delirium, they should only be used if there is a strong component of patient anxiety or if the antipsychotic medication is ineffective after upward titration.
As this patient is in hospice care, the only reason for diagnostic testing, such as laboratory evaluation or brain MRI, would be to guide active interventions, which would result in only temporary stabilization of her condition. Such diagnostic testing is, therefore, inappropriate.
- Antipsychotic medications in small doses are effective treatment for delirium in a terminally ill patient.
Correct answer: D. Postoperative delirium.
Abrupt worsening of confusion in elderly patients with chronic dementia usually results from an acute medical problem. In addition, patients with chronic dementia from almost any cause are at greater risk for delirium after surgery with general anesthesia. This patient with a hip fracture who underwent right hip surgery with general anesthesia and did not recover from the anesthesia until 12 hours after extubation most likely has postoperative delirium. Such delirium is highly predictable and often easily managed by identification and correction of any underlying disorders and the removal or reduction of contributing factors.
In a patient with chronic atrial fibrillation who is confused postoperatively, the possibility of acute stroke must be considered. However, this patient has no clinical evidence of such an event, making this diagnosis extremely unlikely.
Surgery does not exacerbate the dementia of Alzheimer dementia (or of any other cause) but rather produces a superimposed delirium. This patient has had dementia for 4 years that has abruptly gotten worse after surgery. Although not impossible, meningitis is highly unlikely in this setting, especially given the absence of any supporting physical examination findings, including meningeal irritation.
- Patients with chronic dementia, such as Alzheimer dementia, are at greater risk for delirium after surgery with general anesthesia.