Delirium, treating drug resistance, fall prevention


The following cases and commentary, which address delirium, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP14).

Delirium

Case 1: Managing delirium in ICU

A 75-year-old woman with a long history of chronic obstructive pulmonary disease is evaluated in the intensive care unit for delirium. She had a median sternotomy and repair of 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 and pulling at her lines and asking to leave the hospital despite being reassured that she needs to stay for recovery. Her arterial blood gases were normal. Notes by multiple personnel confirmed delirium and difficulty protecting her airway.

Which of the following is the most appropriate next step in managing this patient's delirium?

A. Lorazepam B. Haloperidol C. Diphenhydramine D. Propofol

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Case 2: Post-operative evaluation

A 75-year-old man undergoes postoperative evaluation after right hip fracture surgical repair. His history includes mild dementia, coronary artery disease treated with intracoronary stenting to the left anterior descending artery 2 years ago, hypertension, hyperlipidemia, and type 2 diabetes mellitus. Preoperative medications included atenolol, fosinopril, hydrochlorothiazide, simvastatin, glipizide, lorazepam as needed for sleep, and daily aspirin. Preoperatively, the physical examination was notable for normal vital signs, distress due to pain, full orientation, nonfocal neurologic findings, and normal cardiopulmonary and abdominal examinations. Laboratory studies were remarkable for a hematocrit of 38%. A chest radiograph was normal, and an electrocardiogram showed an old inferior infarction.

On postoperative day 1, he is acutely confused, agitated, rambling, illogical in speech, and unable to focus attention on conversation. The temperature is normal, pulse rate is 80 to 100/min depending on state of agitation, and blood pressure is 130/76 mm Hg. The remainder of the examination, including neurologic examination, is unremarkable.

Which of the following is the optimal postoperative management strategy for this patient?

A. Haloperidol, patient restraints, and CT of the head B. Olanzapine and MRI of the head C. Risperidone, empiric antibiotics, and lumbar puncture D. Chest radiography, electrocardiography, metabolic profile, and haloperidol

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Treating drug resistance

Case 3: Ventilator-associated pneumonia

A 36-year-old woman admitted to the intensive care unit with Guillain-Barré syndrome develops ventilator-associated pneumonia on day 11 of her hospitalization. An endobronchial aspirate is obtained, and therapy with vancomycin, piperacillin, and amikacin is started. The culture results of her endobronchial aspirate reveal methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Both pathogens are susceptible to the antibiotics that were started. On the eighth day of antibiotic therapy, she is afebrile, the chest radiograph shows a diminishing infiltrate, her tracheobronchial secretions are scanty, and her oxygenation status on 40% oxygen is adequate.

Which of the following decisions concerning her antibiotic therapy is appropriate at this time?

A. Stop all three antibiotics B. Stop vancomycin only C. Stop piperacillin and amikacin D. Continue all antibiotics until 2 weeks of therapy are completed E. Obtain additional cultures and base decision on culture results

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Case 4: Respiratory failure

A 76-year-old woman is transferred to the intensive care unit after developing respiratory failure 48 hours after being admitted to the hospital for community-acquired pneumonia. She lives alone and had been hospitalized 2 months ago for an episode of urosepsis treated with ciprofloxacin for 10 days.

On her current admission, she had right lower and right middle lobar consolidations but appeared clinically stable. Ceftriaxone therapy was started without heparin prophylaxis, and her condition subsequently deteriorated, with worsening dyspnea, progressive hypoxemia, and persistent fever, with oxygen saturation ranging from 80% to 85% on a 100% nonrebreather mask. On transfer to the intensive care unit, she is in severe respiratory distress, her heart rate is 124/min, and her respiration rate is 40/min, using accessory muscles and without sinus tenderness. She has rhonchi in all lung fields, and cardiac examination reveals no murmurs or gallops; she has symmetrical leg edema without calf tenderness. Chest radiograph shows diffuse bilateral infiltrates. A nasotracheal tube is inserted. Unfractionated subcutaneous heparin is given as prophylaxis for deep venous thrombosis. Blood, urine, and endotracheal tube aspirate cultures are sent to the laboratory.

Which one of the following is the appropriate next step in managing this patient?

A. Bronchoscopy with protected specimen brushing B. Doppler ultrasonography of the lower extremities C. Change of antibiotic therapy to vancomycin, cefepime and ciprofloxacin pending culture results D. CT scan of the sinuses, and puncture and aspiration of identified maxillary sinus fluid

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Case 5: Urosepsis

A 72-year-old female nursing-home resident is hospitalized because of urosepsis following development of a fever 2 days ago that did not respond to empiric ceftriaxone, 1 g intramuscularly daily. The patient has a chronic indwelling urinary catheter. She had a urinary tract infection 1 month ago that was treated with a short course of ciprofloxacin. Urine cultures were not obtained.

On physical examination on admission, the patient is more confused than usual. Temperature is 40°C (104°F), pulse rate is 152/min and regular, respiration rate is 38/min, and blood pressure is 80/50 mm Hg. Left flank pain is present. There are no focal neurologic findings.

The leukocyte count is 20,000/μL (20 x 109/L) with 80% segmented neutrophils and 5% band forms. Urinalysis shows 4+ leukocytes and bacteria. A urine leukocyte esterase assay is positive. Urine cultures obtained in the nursing home are growing 100,000 colonies/mL of Klebsiella species; results of susceptibility testing are pending.

Which of the following is the most appropriate empiric intravenous antibiotic agent for this patient?

A. Imipenem B. Ceftazidime C. Ampicillin–sulbactam D. Trimethoprim–sulfamethoxazole E. Moxifloxacin

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Fall prevention

Case 6: Frequent slipping

An 82-year-old woman is evaluated in a nursing facility because of recurrent falls. The staff reports that she has frequent “slips/trips” that have resulted in falls, but no history of dizziness or syncope. The patient has mild-moderate cognitive impairment, osteoarthritis involving her knees and low back (managed with acetaminophen and ibuprofen), decreased hearing (she has declined a hearing aid), and osteoporosis (treated with calcium and vitamin D supplements). Her son is concerned that she may fall and fracture her hip and asks you to do what you can to prevent this occurrence.

Which of the following will best reduce the risk of hip fracture in this patient?

A. Refer her for physical therapy B. Add alendronate to her osteoporosis treatment C. Use restraints to keep her from rising unattended D. Have her wear hip protectors E. Refer her for otologic evaluation

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Case 7: ED evaluation after fall

A 78-year-old woman is evaluated in an emergency department after falling and sustaining soft tissue injuries. She fell after getting up to urinate in the middle of the night, stating she felt dizzy upon standing and fell enroute to the bathroom. She has had two other falls in the past year, once when she tripped over a curb, and another time when she lost her balance when she turned quickly. Her medical history includes hypertension well controlled on hydrochlorothiazide, 25 mg/d; depression and anxiety managed with sertraline, 100 mg at bedtime, and lorazepam, 1 mg up to twice a day as needed; and gastroesophageal reflux disease treated with omeprazole. She lives alone and does not smoke or drink.

On physical examination her heart rate is 64/min and blood pressure 128/72 mm Hg supine, and 72/min and 118/68 mm Hg upon standing Her vision is mildly impaired (20/40), lower extremity strength is 5/5 except hip flexors are 5-?symmetrically, and her gait is fairly stable. She successfully performed a Get Up and Go test in 10 seconds.

Which of the following is the most appropriate next step in managing this patient's recurrent falls?

A. Refer her to ophthalmology B. Discontinue lorazepam C. Discontinue hydrochlorothiazide D. Refer her for physical therapy E. Substitute buspirone for sertraline

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Answers and commentary

Case 1

Correct answer: B. Haloperidol

Treat delirium in the intensive care unit. The appropriate treatment for this patient is haloperidol. The recommended drugs of choice for delirium are antipsychotic agents, although no drugs are FDA-approved for this indication. Ongoing randomized, placebo controlled trials are investigating different management strategies for ICU delirium. In one study by Skrobik and colleagues, olanzapine and haloperidol were similar in terms of delirium resolution, and the study did not include a placebo group. 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 antipsychotics, and especially “typical” agents such as haloperidol, pose a risk of torsades de pointes and extrapyramidal side effects as well as the more rare neuroleptic malignant syndrome.

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. Diphenhydramine and other antihistamines are a major risk factor causing delirium, especially in older patients. There is no evidence that propofol has any role in improving delirium resolution. Lastly, the best study of delirium prevention to date was by Inouye and colleagues, in which nonpharmacologic means of preventing delirium were successful in reducing the relative risk of delirium by about one-third. Although this was not an ICU study, it emphasizes the importance of considering nonpharmacologic issues as a way of either preventing or treating delirium.

Key points

  • No drug is FDA-approved for the treatment of delirium, but clinical practice guidelines recommend antipsychotic agents, such as haloperidol.
  • All antipsychotics, and especially “typical” agents, pose a risk of torsades de pointes and extrapyramidal side-effects as well as the more rare neuroleptic malignant syndrome.

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Case 2

Correct answer: D. Chest radiography, electrocardiography, metabolic profile, and haloperidol

The patient has risk factors for postoperative delirium (increasing age, cognitive impairment, and benzodiazepine use), which is characterized by acute, fluctuating mental status changes, with difficulty in focusing or maintaining attention, and disorganized thinking. The appropriate next step in management is to complete a full evaluation, including metabolic profile, chest radiography, electrocardiography, and review of medications, to determine the cause(s) of delirium. Potential causes of postoperative delirium include hyponatremia, severe hyperglycemia, marked decline in hemoglobin, hypoxemia, infection, unstable coronary syndrome, pneumonia, and opiate medications. Once the initial evaluation is completed, haloperidol or newer antipsychotics can be prescribed for sedation, and empiric antibiotics and CT or MRI of the head can be performed if indicated. A recent trial showed that newer antipsychotic agents were not superior to haloperidol in management of delirium, nor have they been shown to be more effective or have fewer adverse effects than haloperidol in these patients. Empiric sedation alone may obscure the signs of ongoing delirium.

Although a quiet, supportive environment with orientation cues, nutrition, and hydration is indicated in this setting, restraints should be avoided because they may increase the patient's anxiety and fear and worsen agitation. Because this patient's clinical scenario is not suggestive of infection, CNS malignancy, subarachnoid hemorrhage, demyelinating diseases, or the Guillain-Barré syndrome, performing lumbar puncture in this patient is not indicated.

Key point

  • In addition to a physical examination, most patients with postoperative delirium should be evaluated with electrocardiography, chest radiography, and metabolic panel.

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Case 3

Correct answer: A. Stop all three antibiotics

Until recently, the accepted duration of therapy for ventilator-associated pneumonia was 15 days or even up to 3 weeks. Studies have shown, however, that this prolonged duration of antibiotics may not be necessary. Duration of antibiotic therapy should be based on clinical resolution of symptoms and signs of infection, radiologic improvement, and requirement for less ventilatory support with improving oxygenation. Patients with ventilator-associated pneumonia who respond adequately to the antibiotics, whose pathogens are susceptible to the initial antibiotic regimen, and who are immunocompetent are candidates for short-term antibiotic therapy. The patient in this question meets all of these criteria for discontinuing antibiotics. Another reason to discontinue antibiotics early is when an alternative diagnosis, especially atelectasis, is found that explains the infiltrate and clinical manifestations suspicious of ventilator-associated pneumonia.

Although a sub-group analysis of a study by Chastre and colleagues showed Pseudomonas infections to be associated with more frequent relapse if treated with 8 days of antibiotics versus 15 days, there was no difference in mortality. In this young patient without comorbidities and with good clinical response, it would reasonable to discontinue the antibiotics and follow closely. Repeat endobronchial aspirate cultures should not be used to determine the discontinuation of antibiotics. In fact, it has been shown that bacterial colonization, especially with non-fermenting bacilli such as Pseudomonas, persists in spite of resolution of signs and symptoms of pneumonia.

Key point

  • For ventilator-associated pneumonia manifesting clinical resolution of symptoms and signs of infection, radiologic improvement, and requirement for less ventilatory support with improving oxygenation, courses of no more than 8 days of antibiotic therapy are associated with as good outcomes as longer courses.

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Case 4

Correct answer: C. Change of antibiotic therapy to vancomycin, cefepime and ciprofloxacin pending culture results

This patient failed to respond to initial antibiotic therapy. However, the history of a prior hospital admission within 90 days places the patient at risk for resistant organisms and antibiotic coverage should reflect this. She needs coverage for methicillin- resistant Staphylococcus aureus (MRSA) as well as for Pseudomonas spp. An endotracheal tube aspirate culture has been submitted to the laboratory. The history of prior antibiotic use increases the likelihood of false-negative results, but quantitative or semiquantitative cultures would likely reveal any resistant pathogens present. Antibiotic coverage can then be tailored depending on culture results. Thus, cultures of the lower respiratory tract can be used to reduce the duration of antibiotic therapy. Bronchoscopy with protected specimen sampling has not been shown to improve outcomes beyond that achieved by lower respiratory tract cultures alone and thus is not recommended. The nasotracheal tube increases the risk of sinusitis compared to orotracheal intubation, but not within the first few days, so a sinus CT would be premature at this point. Likewise for lower extremity Doppler ultrasonography, even though the patient did not receive prophylactic anticoagulation initially. The risk of deep venous thrombosis increases once a patient is intubated for respiratory failure but not for a few days, and the clinical picture is that of a respiratory infection with sepsis. Prophylaxis with heparin or enoxaparin should certainly be initiated unless there are contraindications. Patients should also remain semirecumbent at 30 to 45 degrees to reduce the occurrence of ventilator-associated pneumonia.

Key point

  • Patients with potential healthcare-acquired pneumonia (HCAP) require initial coverage for resistant organisms including methicillin-resistant Staphylococcus aureus and Pseudomonas.

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Case 5

Correct answer: A. Imipenem

Colonization with extended-spectrum β-lactamases (ESBLs) is endemic in nursing homes (about 40% of nursing-home residents are colonized with such strains). The carbapenems (imipenem, meropenem, ertapenem) are the most appropriate empiric agents for treating infections due to ESBL–producing gram-negative bacilli such as Klebsiella species.

Klebsiella isolates that are resistant to ceftriaxone are also likely to be resistant to cephalosporins because of the presence of ESBLs. Because the plasmid that carries the ESBL gene also carries other resistance determinants, most ESBL-producing strains are also resistant to aminoglycosides and sulfa compounds. About half are resistant to fluoroquinolones. Therefore, administration of ceftazidime, ampicillin–sulbactam, trimethoprim–sulfamethoxazole, or moxifloxacin will be ineffective. In addition, this patient's recent exposure to a fluoroquinolone also increases her risk of having a resistant organism. Finally, moxifloxacin does not achieve adequate therapeutic levels in the urine.

Key point

  • The carbapenems (imipenem, meropenem, ertapenem) are the most appropriate empiric agents for treating infections due to gram-negative bacilli that produce extended-spectrum β-lactamases (ESBLs).

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Case 6

Correct answer: D. Have her wear hip protectors

Although the above interventions have not been compared head-to-head, available evidence indicates that impact-absorbing external hip protectors can reduce the risk of hip fracture by 60% (and by 80% or more when worn consistently by the user)—a risk reduction that exceeds that reported for the other options. A recent editorial (Rubenstein) concluded that hip protectors offer a powerful new method to reduce the risk of hip fractures and that their use should be strongly encouraged for persons at increased risk (for example, those with osteoporosis and high fall risk).

Physical therapy is an important component of multifactorial assessments and targeted interventions to reduce the risk of recurrent falls and fall-related injuries. However, while such interventions can significantly reduce the incidence of falls (by 10% to 30%) they do not prevent the majority of falls and provide only partial protection against hip fracture. Treatment of osteoporosis is a key intervention to reduce the risk of hip fracture and also confers protection for other sites of fracture besides the hip. Although integral to reducing fall-related fractures, the relative risk reduction in hip fractures ascribed to osteoporosis treatment is less than that noted above for hip protectors (clinically both should be strongly considered). Use of restraints is generally contraindicated as there is little evidence demonstrating their efficacy in reducing falls and substantial evidence of injuries resulting from restraints. Addressing sensory deficits is an important component of multifactorial interventions to reduce fall risk, but data indicating improved hearing can reduce fall risks is lacking.

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Case 7

Correct answer: B. Discontinue lorazepam

Observational studies suggest that medications are among the most readily modifiable risk factors for falls, with psychotropic agents (benzodiazepines, tricyclic antidepressants, neuroleptics) leading the list of commonly implicated drugs. Specific single interventions that have been shown to reduce falls in randomized controlled trials include withdrawal of psychotropic medications; home hazard assessment and modification for patients with history of falling; and exercise programs. Discontinuing this patient lorazepam therapy is the most appropriate single intervention.

Falls are usually multifactorial and therefore addressing all potential contributing factors is important. However this patient's vision is not markedly impaired (20/40), and the lorazepam therapy is a more obvious and likely more important contributor to her recurrent falls. Orthostatic hypotension may have contributed to her most recent fall. However, on examination she did not have significant changes in blood pressure or heart rate upon standing, and her two other falls were not related to orthostatic positional changes. Thus the evidence to suggest that discontinuing her hydrochlorothiazide would reduce her risk of recurrent falls is less compelling than that for stopping the lorazepam. Referral for physical therapy is an important consideration for all patients with recurrent falls but this patient did not have unstable gait and she completed a timed Get Up and Go test in less than 20 seconds, again making this choice less compelling than stopping her lorazepam. Use of antidepressants has been associated with increased fall risk but much of this association may be due to confounding by indication, and there is no existing evidence to suggest that switching sertraline to buspirone would decrease her fall risk.