Hospitalized, elderly, and delirious: What should you do for these patients?

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Hospitalized, elderly, and delirious: What should you do for these patients?

Delirium is a common condition in hospitalized older patients. Often, a report of a “change in mental status” is the reason geriatric patients are sent to the emergency room for evaluation, although delirium also can develop after admission.

Delirium is a marker of underlying medical illness that needs careful workup and treatment. The condition can be iatrogenic, resulting from prescribed medication or a surgical procedure; most often, it is the consequence of multiple factors. Delirium can be expensive, because it increases hospital length of stay and overall costs—particularly if the patient is discharged to a nursing facility, not to home. Patients with delirium are at higher risk of death.

Delirium often goes unrecognized by physicians and nursing staff, and is not documented in medical records. Educating the medical staff on the identification and management of delirium is a key role for consulting psychiatrists.

CASE: Confused and agitated

Ms. T, a 93-year-old resident of an assisted living facility with a history of three
cerebral vascular accidents, atrial fibrillation, hypertension, multiple deep venous thromboses, blindness in her right eye, and deafness in her right ear without a hearing aid, is brought to the hospital after a syncopal episode lasting 10 minutes that was followed by slurred speech, confusion, and transient hypotension. Her dentist recently started her on azithromycin.

In the emergency room, Ms. T’s elevated blood pressure is managed with hydralazine and diltiazem. A CT scan of the head rules out hemorrhagic stroke. Complete blood count and tests of electrolytes, vitamin B12, and thyroid-stimulating hormone are within normal limits; urinalysis is negative for urinary tract infection.

Ms. T is noted to be in and out of sleep, with some confusion. She is maintained without oral food or fluids because of concerns about her ability to swallow. After 5 or 6 hours in the ER, Ms. T is transferred to a medical unit, where she becomes agitated and paranoid, with the delusion that her daughter is an impostor. She yells, is combative, and refuses medication.

Her confusion and behaviors become worse at night: She pulls out her IV line and telemetry leads. Blood pressure remains elevated, for which she receives additional doses of hydralazine.

For behavioral management, the medical team orders a one-time IM dose of haloperidol and starts her on risperidone, 0.5 mg every 4 hours as needed, which Ms. T refuses to take. She is incontinent and has foul-smelling urine.

Ms. T’s family is shocked at her condition; nursing staff is frustrated. With her worsening paranoia, delusions, and combative behaviors towards the nursing staff, psychiatry is consulted.

How to recognize and diagnose

The Box lists DSM-5 criteria for delirium.1 The key feature is a disturbance in attention—what was referred to in DSM-IV-TR as “disturbance in consciousness.” That finding contrasts with what is seen in dementia, with its hallmark memory impairment and chronic deterioration.

In a hospital setting, the question is often asked: Does this patient have dementia or delirium? In many cases, the answer is both, because preexisting cognitive impairment is an important risk factor for delirium.

In addition to the standard clinical interview, several screening instruments or delirium rating scales have been developed. The most commonly used (Table 1) is the Confusion Assessment Method developed by Inouye and colleagues.2

Subtypes of delirium have been described, largely based on motor activity. Patients can present as hyperactive, hypoactive, mixed, or neither.3 Psychiatrists are more likely to be consulted regarding patients with hyperactive delirium, because they are the ones who scream, pull out their IV line, hallucinate, and are delusional, insisting they “have to go home”—such as the patient described in the case above.

Patients with hypoactive delirium often, on the other hand, are difficult to recognize; they present with lethargy, drowsiness, apathy, and confusion. They become withdrawn and answer slowly4; often, psychiatry is consulted to assess them for depression.

Delirium can be difficult to diagnose in patients with underlying dementia, who are not able to provide information. In such cases, obtaining collateral information from a family member or primary caretaker is crucial. Knowing the patient’s baseline helps to determine whether there has been an acute change in mental status.

CASE CONTINUED: Acute mental status changes

Ms. T’s daughter reports that her mother has not been in this condition before. At baseline, Ms. T has had memory problems but no paranoia, delusions, or agitated behaviors. Her daughter also reports that Ms. T has visual and hearing impairments and is not wearing her hearing aid.

The acute change in mental status and the perceptual disturbances indicate that Ms. T has delirium, not dementia.

 

 

Who is likely to develop delirium?

Risk factors for delirium (Table 2) include preexisting cognitive impairment, older age, vision and hearing impairment, use of psychoactive drugs, severe illness, azotemia and dehydration, a metabolic abnormality, and infection. Male sex also seems to be a risk factor, perhaps because men are more likely to abuse alcohol before admission.

Many patients become delirious after starting a new medication. An experienced geriatrician teaches that the main causes of delirium are “drugs, drugs, drugs, infections, and everything else” (Kenneth Rockwood, MD, personal communication, 2012). At admission, urinary tract infection and pneumonia are common causes of delirium, especially in geriatric patients.

What is the clinical course?

The clinical course varies widely. Delirium often is the reason that a patient is brought to the hospital, presenting with the condition at admission or early in hospitalization. The highest incidence among surgical patients appears to be on the third postoperative day—in some cases because of alcohol or drug withdrawal.

As noted in the DSM-5 criteria, delirium often comes on acutely, over hours or days. Symptoms can persist for weeks after initial onset of episodes of delirium.5 Symptoms fluctuate over the course of the day; at times, they can be missed if a provider sees the patient only while she (he) is clearer and doesn’t review nursing notes from other shifts.

How does delirium affect outcome?

Delirium has been shown to be associated with prolonged hospital stay (21 days, compared with 11 days in the absence of delirium), functional decline during hospitalization, and increased admission to long-term care (36% compared with 13%).6 In a study by O’Keefe and Lavan,6 delirious patients were more likely to sustain falls and to develop urinary incontinence, pressure sores, and other complications during hospitalization.

Older patients with delirium superimposed on dementia had a more than twofold increased risk of mortality compared with patients with dementia alone or with neither dementia nor delirium.7 Rockwood found that an episode of delirium was associated with a much higher rate of subsequent dementia.8

Think of an acute medical illness as a “stress test” for the brain, such that, if the patient develops delirium, it suggests an underlying brain disease that was not evident before the acute episode. After hip fracture, for example, delirium was independently associated with poor functional recovery at 1 month9 and at 2 years.10

Older patients admitted to a skilled nursing facility with delirium are more likely to experience one or more complications (73% compared with 41%).11 In the study by Marcantonio and colleagues, patients with delirium were more than twice as likely to be hospitalized again within 30 days (30% and 13%), and less than half as likely to be discharged to the community (30% and 73%). Table 3 summarizes the impact of delirium on outcomes.

Appropriate management steps

Identifying and treating underlying medical illness is the definitive treatment for delirium; in a geriatric patient with multiple medical comorbidities the pathogenesis often is multifactorial or a definitive precipitant cannot always be identified.12

Managing a patient with delirium includes both non-pharmacotherapeutic interventions, which should be considered first-line, and pharmacotherapeutic interventions. Non-pharmacotherapeutic interventions include, but are not limited to:

•  support and close observation by nursing staff

•  placing a clock or calendar in the room

•  frequent reorientation and reminders

•  placing familiar possessions in the room

•  putting the patient in an isolated room with a window

•  regulating the sleep-wake cycle.4

Pharmacotherapeutic intervention in delirium should be used for behavioral symptoms, but only for the minimum duration necessary4 and preferably oral or IV. No drugs are FDA-approved for delirium, which means that use of any agent is off-label.13

Antipsychotics are the mainstay of pharmacotherapy for delirium in most settings. The use of antipsychotics relates to the dopamine excess-acetylcholine deficiency hypothesis of delirium pathophysiology.12 Haloperidol remains the first-line agent because it is available in multiple dosages and can be given by various routes. IV haloperidol appears to carry less risk of extrapyramidal symptoms than oral haloperidol does but, as with all antipsychotics, its use warrants monitoring for QTc prolongation.12

Studies have not shown that atypical antipsychotics are superior to typical antipsychotics for delirium. Multiple studies have shown that atypicals are as efficacious as haloperidol.

Benzodiazepines are the treatment of choice for delirium caused by alcohol withdrawal. A Cochrane review found no evidence that benzodiazepines were helpful in treating delirium unrelated to alcohol withdrawal.14 In some studies, benzodiazepines were associated with an increased risk of delirium, especially in patients in the intensive care unit.15

 

 

More recently, cholinesterase inhibitors have been used to treat delirium. The reasoning behind their use is the hypothesis of a central cholinergic deficiency in delirium.12 Regrettably, there have been few well-conducted studies of these agents in delirium, and a Cochrane review found no significant benefit for cholinesterase inhibitors.16 With the same hypothesis in mind, anticholinergic medications in patients with delirium should be avoided because these agents could exacerbate delirium by further decreasing the acetylcholine level.

Because delirium is common in the hospitalized population (especially older patients), a number of studies have examined strategies to prevent or reduce its development. Inouye and colleagues conducted a controlled clinical trial, in which they intervened to reduce six risk factors for delirium: cognitive impairment, sleep deprivation, immobility, visual and hearing impairment, and dehydration in hospitalized geriatric patients. The number and duration of events of delirium were significantly lower in the intervention group.17

Brummel et al reported that reducing modifiable risk factors in intensive care unit patients—including sedation management, minimizing deliriogenic medications (anticholinergics, antihistamines), minimizing sleep disruption, and encouraging early mobility—could prevent or reduce the incidence of delirium.15

CASE CONCLUDED: Return to baseline

Ms. T’s medications are minimized or discontinued, including azithromycin, based on case reports in the literature. She is stabilized hemodynamically.

Clinicians educate Ms. T’s family about delirium. To address Ms. T’s aggressive and paranoid behaviors, clinicians request that a family member is present to reassure Ms. T. She is continued on low-dose haloperidol. The family also is asked to bring Ms. T’s hearing aid and eyeglasses.

MRI is performed after Ms. T’s behavior is under control. The scan is negative for a new stroke.

Repeat blood tests the following day show an elevated white blood cell count; urinalysis is positive for a urinary tract infection. Ms. T is started on antibiotics. Subsequent urine culture shows no bacterial growth; the antibiotics are stopped after 3 days.

Ms. T slowly improves. According to her family, she is back at baseline in 3 or 4 days.

This case illustrates the complexity of trying to identify the precise cause of delirium among the many that could be involved. Often, no single cause can be found.18

Bottom Line
Delirium is a common and potentially life-threatening condition in hospitalized geriatric patients. General hospital psychiatrists should know how to recognize and treat the condition in collaboration with their medical colleagues.

Related Resources

  • Treating delirium: a quick reference guide. Arlington, VA: American Psychiatric Association. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1662986.
  • Cook IA. Guideline watch: practice guidelines for the treatment of patients with delirium. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1681952.
  • Fearing MA, Inouye SK. Delirium. In: Blazer DG, Steffens D, eds. The American Psychiatric Publishing textbook of geriatric psychiatry. 4th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2009:229-241.
  • Ghandour A, Saab R, Mehr D. Detecting and treating delirium—key interventions you may be missing. J Fam Pract. 2011;60(12):726-734.
  • Leentjens AF, Rundell J, Rummans T, et al. Delirium: an evidence-based medicine (EBM) monograph for psychosomatic medicine practice. J Psychosom Res. 2012;73:149-152.
  • Liptzin B, Jacobson SA. Delirium. In: Sadock BJ, Sadock VA, Ruiz P, eds. Comprehensive textbook of psychiatry. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:4066-4073.

Drug Brand Names

Azithromycin • Zithromax                 Hydralazine • Apresoline

Diltiazem • Cardizem                        Risperidone • Risperdal

Haloperidol • Haldo

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.


Featured Audio

Benjamin Liptzin, MD, describes the distinction between dementia and delirium. Dr. Liptzin is Chair of Psychiatry, Baystate Medical Center, Springfield, Massachusetts, and Professor and Deputy Chair, Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.

References

1. Diagnostic and statistical manual of mental disorders, 5th ed. Arlington, VA: American Psychiatric Association; 2013. 

2. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: The Confusion Assessment Method. A new method for detection of delirium. Ann Intern Med. 1990;113:941-948.

3. Liptzin B, Levkoff SE. An empirical study of delirium subtypes. Br J Psychiatry. 1992;161:843-845.

4. Martins S, Fernandes L. Delirium in elderly people: a review. Front Neurol. 2012;3:101.

5. Levkoff SE, Liptzin B, Evans D, et al. Progression and resolution of delirium in elderly patients hospitalized for acute care. Am J Geriatr Psychiatry. 1994;2:230-238.

6. O’Keefe S, Lavan J. The prognostic significance of delirium in older hospitalized patients. J Am Geriatr Soc. 1997;45:247-248.

7. Tsai MC, Weng HH, Chou SY, et al. One-year mortality of elderly inpatients with delirium, dementia or depression seen by a consultation-liaison service. Psychosomatics. 2012;53:433-438.

8. Rockwood K, Cosway S, Carver D, et al. The risk of dementia and death after delirium. Age Ageing. 1999;28:551-556.

9. Marcantonio E, Flacker JM, Michaels M, et al. Delirium is independently associated with poor functional recovery after hip fracture. J Am Geriatr Soc. 2000;48:618-624.

10. Dolan MM, Hawkes WG, Zimmerman SI, et al. Delirium on hospital admission in aged hip fracture patients: prediction of mortality and 2-year functional outcomes. J Gerontol A Biol Sci Med Sci. 2000;55:M27-M34.

11. Marcantonio ER, Kiely DK, Simon SE, et al. Outcomes of elders admitted to post-acute facilities with delirium. J Am Geriatr Soc. 2005;53:963-969.

12. Bledowski J, Trutia A. A review of pharmacologic management and prevention strategies of delirium in the intensive care unit. Psychosomatics. 2012;53:203-211.

13. Breitbart W, Alici-Evcimen Y. Why off-label antipsychotics remain first-choice drugs for delirium. Current Psychiatry. 2007;6(9):49-63.

14. Lonergan E, Luxenberg J, Areosa Sastre A. Benzodiazepines for delirium. Cochrane Database Syst Rev. 2009;(4):CD006379. doi: 10.1002/14651858.CD006379.pub3.

15. Brummel NE, Girard TD. Preventing delirium in the ICU. Crit Care Clin. 2013;(29):51-65.

16. Overshott R, Karim S, Burns A. Cholinesterase inhibitors for delirium. Cochrane Database Syst Rev. 2008(1):CD005317. doi: 10.1002/14651858.CD005317.

17. Inouye SK, Bogardus ST, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340:669-676.

18. Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA. 1990;263:1097-1101.

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Author and Disclosure Information

Ramanpreet Toor, MD
Fellow, Psychosomatic Medicine
Department of Psychiatry
Cambridge Hospital
Cambridge, Massachusetts


Benjamin Liptzin, MD 
Chair of Psychiatry
Baystate Medical Center
Springfield, Massachusetts
Professor and Deputy Chair
Department of Psychiatry
Tufts University School of Medicine
Boston, Massachusetts

Steven V. Fischel, MD, PhD
Program Director
Psychiatry Residency Program
Medical Director
Psychiatry Consultation Service
Baystate Medical Center
Springfield, Massachusetts
Assistant Professor
Department of Psychiatry
Tufts University School of Medicine
Boston, Massachusetts

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Author and Disclosure Information

Ramanpreet Toor, MD
Fellow, Psychosomatic Medicine
Department of Psychiatry
Cambridge Hospital
Cambridge, Massachusetts


Benjamin Liptzin, MD 
Chair of Psychiatry
Baystate Medical Center
Springfield, Massachusetts
Professor and Deputy Chair
Department of Psychiatry
Tufts University School of Medicine
Boston, Massachusetts

Steven V. Fischel, MD, PhD
Program Director
Psychiatry Residency Program
Medical Director
Psychiatry Consultation Service
Baystate Medical Center
Springfield, Massachusetts
Assistant Professor
Department of Psychiatry
Tufts University School of Medicine
Boston, Massachusetts

Author and Disclosure Information

Ramanpreet Toor, MD
Fellow, Psychosomatic Medicine
Department of Psychiatry
Cambridge Hospital
Cambridge, Massachusetts


Benjamin Liptzin, MD 
Chair of Psychiatry
Baystate Medical Center
Springfield, Massachusetts
Professor and Deputy Chair
Department of Psychiatry
Tufts University School of Medicine
Boston, Massachusetts

Steven V. Fischel, MD, PhD
Program Director
Psychiatry Residency Program
Medical Director
Psychiatry Consultation Service
Baystate Medical Center
Springfield, Massachusetts
Assistant Professor
Department of Psychiatry
Tufts University School of Medicine
Boston, Massachusetts

Article PDF
Article PDF

Delirium is a common condition in hospitalized older patients. Often, a report of a “change in mental status” is the reason geriatric patients are sent to the emergency room for evaluation, although delirium also can develop after admission.

Delirium is a marker of underlying medical illness that needs careful workup and treatment. The condition can be iatrogenic, resulting from prescribed medication or a surgical procedure; most often, it is the consequence of multiple factors. Delirium can be expensive, because it increases hospital length of stay and overall costs—particularly if the patient is discharged to a nursing facility, not to home. Patients with delirium are at higher risk of death.

Delirium often goes unrecognized by physicians and nursing staff, and is not documented in medical records. Educating the medical staff on the identification and management of delirium is a key role for consulting psychiatrists.

CASE: Confused and agitated

Ms. T, a 93-year-old resident of an assisted living facility with a history of three
cerebral vascular accidents, atrial fibrillation, hypertension, multiple deep venous thromboses, blindness in her right eye, and deafness in her right ear without a hearing aid, is brought to the hospital after a syncopal episode lasting 10 minutes that was followed by slurred speech, confusion, and transient hypotension. Her dentist recently started her on azithromycin.

In the emergency room, Ms. T’s elevated blood pressure is managed with hydralazine and diltiazem. A CT scan of the head rules out hemorrhagic stroke. Complete blood count and tests of electrolytes, vitamin B12, and thyroid-stimulating hormone are within normal limits; urinalysis is negative for urinary tract infection.

Ms. T is noted to be in and out of sleep, with some confusion. She is maintained without oral food or fluids because of concerns about her ability to swallow. After 5 or 6 hours in the ER, Ms. T is transferred to a medical unit, where she becomes agitated and paranoid, with the delusion that her daughter is an impostor. She yells, is combative, and refuses medication.

Her confusion and behaviors become worse at night: She pulls out her IV line and telemetry leads. Blood pressure remains elevated, for which she receives additional doses of hydralazine.

For behavioral management, the medical team orders a one-time IM dose of haloperidol and starts her on risperidone, 0.5 mg every 4 hours as needed, which Ms. T refuses to take. She is incontinent and has foul-smelling urine.

Ms. T’s family is shocked at her condition; nursing staff is frustrated. With her worsening paranoia, delusions, and combative behaviors towards the nursing staff, psychiatry is consulted.

How to recognize and diagnose

The Box lists DSM-5 criteria for delirium.1 The key feature is a disturbance in attention—what was referred to in DSM-IV-TR as “disturbance in consciousness.” That finding contrasts with what is seen in dementia, with its hallmark memory impairment and chronic deterioration.

In a hospital setting, the question is often asked: Does this patient have dementia or delirium? In many cases, the answer is both, because preexisting cognitive impairment is an important risk factor for delirium.

In addition to the standard clinical interview, several screening instruments or delirium rating scales have been developed. The most commonly used (Table 1) is the Confusion Assessment Method developed by Inouye and colleagues.2

Subtypes of delirium have been described, largely based on motor activity. Patients can present as hyperactive, hypoactive, mixed, or neither.3 Psychiatrists are more likely to be consulted regarding patients with hyperactive delirium, because they are the ones who scream, pull out their IV line, hallucinate, and are delusional, insisting they “have to go home”—such as the patient described in the case above.

Patients with hypoactive delirium often, on the other hand, are difficult to recognize; they present with lethargy, drowsiness, apathy, and confusion. They become withdrawn and answer slowly4; often, psychiatry is consulted to assess them for depression.

Delirium can be difficult to diagnose in patients with underlying dementia, who are not able to provide information. In such cases, obtaining collateral information from a family member or primary caretaker is crucial. Knowing the patient’s baseline helps to determine whether there has been an acute change in mental status.

CASE CONTINUED: Acute mental status changes

Ms. T’s daughter reports that her mother has not been in this condition before. At baseline, Ms. T has had memory problems but no paranoia, delusions, or agitated behaviors. Her daughter also reports that Ms. T has visual and hearing impairments and is not wearing her hearing aid.

The acute change in mental status and the perceptual disturbances indicate that Ms. T has delirium, not dementia.

 

 

Who is likely to develop delirium?

Risk factors for delirium (Table 2) include preexisting cognitive impairment, older age, vision and hearing impairment, use of psychoactive drugs, severe illness, azotemia and dehydration, a metabolic abnormality, and infection. Male sex also seems to be a risk factor, perhaps because men are more likely to abuse alcohol before admission.

Many patients become delirious after starting a new medication. An experienced geriatrician teaches that the main causes of delirium are “drugs, drugs, drugs, infections, and everything else” (Kenneth Rockwood, MD, personal communication, 2012). At admission, urinary tract infection and pneumonia are common causes of delirium, especially in geriatric patients.

What is the clinical course?

The clinical course varies widely. Delirium often is the reason that a patient is brought to the hospital, presenting with the condition at admission or early in hospitalization. The highest incidence among surgical patients appears to be on the third postoperative day—in some cases because of alcohol or drug withdrawal.

As noted in the DSM-5 criteria, delirium often comes on acutely, over hours or days. Symptoms can persist for weeks after initial onset of episodes of delirium.5 Symptoms fluctuate over the course of the day; at times, they can be missed if a provider sees the patient only while she (he) is clearer and doesn’t review nursing notes from other shifts.

How does delirium affect outcome?

Delirium has been shown to be associated with prolonged hospital stay (21 days, compared with 11 days in the absence of delirium), functional decline during hospitalization, and increased admission to long-term care (36% compared with 13%).6 In a study by O’Keefe and Lavan,6 delirious patients were more likely to sustain falls and to develop urinary incontinence, pressure sores, and other complications during hospitalization.

Older patients with delirium superimposed on dementia had a more than twofold increased risk of mortality compared with patients with dementia alone or with neither dementia nor delirium.7 Rockwood found that an episode of delirium was associated with a much higher rate of subsequent dementia.8

Think of an acute medical illness as a “stress test” for the brain, such that, if the patient develops delirium, it suggests an underlying brain disease that was not evident before the acute episode. After hip fracture, for example, delirium was independently associated with poor functional recovery at 1 month9 and at 2 years.10

Older patients admitted to a skilled nursing facility with delirium are more likely to experience one or more complications (73% compared with 41%).11 In the study by Marcantonio and colleagues, patients with delirium were more than twice as likely to be hospitalized again within 30 days (30% and 13%), and less than half as likely to be discharged to the community (30% and 73%). Table 3 summarizes the impact of delirium on outcomes.

Appropriate management steps

Identifying and treating underlying medical illness is the definitive treatment for delirium; in a geriatric patient with multiple medical comorbidities the pathogenesis often is multifactorial or a definitive precipitant cannot always be identified.12

Managing a patient with delirium includes both non-pharmacotherapeutic interventions, which should be considered first-line, and pharmacotherapeutic interventions. Non-pharmacotherapeutic interventions include, but are not limited to:

•  support and close observation by nursing staff

•  placing a clock or calendar in the room

•  frequent reorientation and reminders

•  placing familiar possessions in the room

•  putting the patient in an isolated room with a window

•  regulating the sleep-wake cycle.4

Pharmacotherapeutic intervention in delirium should be used for behavioral symptoms, but only for the minimum duration necessary4 and preferably oral or IV. No drugs are FDA-approved for delirium, which means that use of any agent is off-label.13

Antipsychotics are the mainstay of pharmacotherapy for delirium in most settings. The use of antipsychotics relates to the dopamine excess-acetylcholine deficiency hypothesis of delirium pathophysiology.12 Haloperidol remains the first-line agent because it is available in multiple dosages and can be given by various routes. IV haloperidol appears to carry less risk of extrapyramidal symptoms than oral haloperidol does but, as with all antipsychotics, its use warrants monitoring for QTc prolongation.12

Studies have not shown that atypical antipsychotics are superior to typical antipsychotics for delirium. Multiple studies have shown that atypicals are as efficacious as haloperidol.

Benzodiazepines are the treatment of choice for delirium caused by alcohol withdrawal. A Cochrane review found no evidence that benzodiazepines were helpful in treating delirium unrelated to alcohol withdrawal.14 In some studies, benzodiazepines were associated with an increased risk of delirium, especially in patients in the intensive care unit.15

 

 

More recently, cholinesterase inhibitors have been used to treat delirium. The reasoning behind their use is the hypothesis of a central cholinergic deficiency in delirium.12 Regrettably, there have been few well-conducted studies of these agents in delirium, and a Cochrane review found no significant benefit for cholinesterase inhibitors.16 With the same hypothesis in mind, anticholinergic medications in patients with delirium should be avoided because these agents could exacerbate delirium by further decreasing the acetylcholine level.

Because delirium is common in the hospitalized population (especially older patients), a number of studies have examined strategies to prevent or reduce its development. Inouye and colleagues conducted a controlled clinical trial, in which they intervened to reduce six risk factors for delirium: cognitive impairment, sleep deprivation, immobility, visual and hearing impairment, and dehydration in hospitalized geriatric patients. The number and duration of events of delirium were significantly lower in the intervention group.17

Brummel et al reported that reducing modifiable risk factors in intensive care unit patients—including sedation management, minimizing deliriogenic medications (anticholinergics, antihistamines), minimizing sleep disruption, and encouraging early mobility—could prevent or reduce the incidence of delirium.15

CASE CONCLUDED: Return to baseline

Ms. T’s medications are minimized or discontinued, including azithromycin, based on case reports in the literature. She is stabilized hemodynamically.

Clinicians educate Ms. T’s family about delirium. To address Ms. T’s aggressive and paranoid behaviors, clinicians request that a family member is present to reassure Ms. T. She is continued on low-dose haloperidol. The family also is asked to bring Ms. T’s hearing aid and eyeglasses.

MRI is performed after Ms. T’s behavior is under control. The scan is negative for a new stroke.

Repeat blood tests the following day show an elevated white blood cell count; urinalysis is positive for a urinary tract infection. Ms. T is started on antibiotics. Subsequent urine culture shows no bacterial growth; the antibiotics are stopped after 3 days.

Ms. T slowly improves. According to her family, she is back at baseline in 3 or 4 days.

This case illustrates the complexity of trying to identify the precise cause of delirium among the many that could be involved. Often, no single cause can be found.18

Bottom Line
Delirium is a common and potentially life-threatening condition in hospitalized geriatric patients. General hospital psychiatrists should know how to recognize and treat the condition in collaboration with their medical colleagues.

Related Resources

  • Treating delirium: a quick reference guide. Arlington, VA: American Psychiatric Association. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1662986.
  • Cook IA. Guideline watch: practice guidelines for the treatment of patients with delirium. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1681952.
  • Fearing MA, Inouye SK. Delirium. In: Blazer DG, Steffens D, eds. The American Psychiatric Publishing textbook of geriatric psychiatry. 4th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2009:229-241.
  • Ghandour A, Saab R, Mehr D. Detecting and treating delirium—key interventions you may be missing. J Fam Pract. 2011;60(12):726-734.
  • Leentjens AF, Rundell J, Rummans T, et al. Delirium: an evidence-based medicine (EBM) monograph for psychosomatic medicine practice. J Psychosom Res. 2012;73:149-152.
  • Liptzin B, Jacobson SA. Delirium. In: Sadock BJ, Sadock VA, Ruiz P, eds. Comprehensive textbook of psychiatry. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:4066-4073.

Drug Brand Names

Azithromycin • Zithromax                 Hydralazine • Apresoline

Diltiazem • Cardizem                        Risperidone • Risperdal

Haloperidol • Haldo

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.


Featured Audio

Benjamin Liptzin, MD, describes the distinction between dementia and delirium. Dr. Liptzin is Chair of Psychiatry, Baystate Medical Center, Springfield, Massachusetts, and Professor and Deputy Chair, Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.

Delirium is a common condition in hospitalized older patients. Often, a report of a “change in mental status” is the reason geriatric patients are sent to the emergency room for evaluation, although delirium also can develop after admission.

Delirium is a marker of underlying medical illness that needs careful workup and treatment. The condition can be iatrogenic, resulting from prescribed medication or a surgical procedure; most often, it is the consequence of multiple factors. Delirium can be expensive, because it increases hospital length of stay and overall costs—particularly if the patient is discharged to a nursing facility, not to home. Patients with delirium are at higher risk of death.

Delirium often goes unrecognized by physicians and nursing staff, and is not documented in medical records. Educating the medical staff on the identification and management of delirium is a key role for consulting psychiatrists.

CASE: Confused and agitated

Ms. T, a 93-year-old resident of an assisted living facility with a history of three
cerebral vascular accidents, atrial fibrillation, hypertension, multiple deep venous thromboses, blindness in her right eye, and deafness in her right ear without a hearing aid, is brought to the hospital after a syncopal episode lasting 10 minutes that was followed by slurred speech, confusion, and transient hypotension. Her dentist recently started her on azithromycin.

In the emergency room, Ms. T’s elevated blood pressure is managed with hydralazine and diltiazem. A CT scan of the head rules out hemorrhagic stroke. Complete blood count and tests of electrolytes, vitamin B12, and thyroid-stimulating hormone are within normal limits; urinalysis is negative for urinary tract infection.

Ms. T is noted to be in and out of sleep, with some confusion. She is maintained without oral food or fluids because of concerns about her ability to swallow. After 5 or 6 hours in the ER, Ms. T is transferred to a medical unit, where she becomes agitated and paranoid, with the delusion that her daughter is an impostor. She yells, is combative, and refuses medication.

Her confusion and behaviors become worse at night: She pulls out her IV line and telemetry leads. Blood pressure remains elevated, for which she receives additional doses of hydralazine.

For behavioral management, the medical team orders a one-time IM dose of haloperidol and starts her on risperidone, 0.5 mg every 4 hours as needed, which Ms. T refuses to take. She is incontinent and has foul-smelling urine.

Ms. T’s family is shocked at her condition; nursing staff is frustrated. With her worsening paranoia, delusions, and combative behaviors towards the nursing staff, psychiatry is consulted.

How to recognize and diagnose

The Box lists DSM-5 criteria for delirium.1 The key feature is a disturbance in attention—what was referred to in DSM-IV-TR as “disturbance in consciousness.” That finding contrasts with what is seen in dementia, with its hallmark memory impairment and chronic deterioration.

In a hospital setting, the question is often asked: Does this patient have dementia or delirium? In many cases, the answer is both, because preexisting cognitive impairment is an important risk factor for delirium.

In addition to the standard clinical interview, several screening instruments or delirium rating scales have been developed. The most commonly used (Table 1) is the Confusion Assessment Method developed by Inouye and colleagues.2

Subtypes of delirium have been described, largely based on motor activity. Patients can present as hyperactive, hypoactive, mixed, or neither.3 Psychiatrists are more likely to be consulted regarding patients with hyperactive delirium, because they are the ones who scream, pull out their IV line, hallucinate, and are delusional, insisting they “have to go home”—such as the patient described in the case above.

Patients with hypoactive delirium often, on the other hand, are difficult to recognize; they present with lethargy, drowsiness, apathy, and confusion. They become withdrawn and answer slowly4; often, psychiatry is consulted to assess them for depression.

Delirium can be difficult to diagnose in patients with underlying dementia, who are not able to provide information. In such cases, obtaining collateral information from a family member or primary caretaker is crucial. Knowing the patient’s baseline helps to determine whether there has been an acute change in mental status.

CASE CONTINUED: Acute mental status changes

Ms. T’s daughter reports that her mother has not been in this condition before. At baseline, Ms. T has had memory problems but no paranoia, delusions, or agitated behaviors. Her daughter also reports that Ms. T has visual and hearing impairments and is not wearing her hearing aid.

The acute change in mental status and the perceptual disturbances indicate that Ms. T has delirium, not dementia.

 

 

Who is likely to develop delirium?

Risk factors for delirium (Table 2) include preexisting cognitive impairment, older age, vision and hearing impairment, use of psychoactive drugs, severe illness, azotemia and dehydration, a metabolic abnormality, and infection. Male sex also seems to be a risk factor, perhaps because men are more likely to abuse alcohol before admission.

Many patients become delirious after starting a new medication. An experienced geriatrician teaches that the main causes of delirium are “drugs, drugs, drugs, infections, and everything else” (Kenneth Rockwood, MD, personal communication, 2012). At admission, urinary tract infection and pneumonia are common causes of delirium, especially in geriatric patients.

What is the clinical course?

The clinical course varies widely. Delirium often is the reason that a patient is brought to the hospital, presenting with the condition at admission or early in hospitalization. The highest incidence among surgical patients appears to be on the third postoperative day—in some cases because of alcohol or drug withdrawal.

As noted in the DSM-5 criteria, delirium often comes on acutely, over hours or days. Symptoms can persist for weeks after initial onset of episodes of delirium.5 Symptoms fluctuate over the course of the day; at times, they can be missed if a provider sees the patient only while she (he) is clearer and doesn’t review nursing notes from other shifts.

How does delirium affect outcome?

Delirium has been shown to be associated with prolonged hospital stay (21 days, compared with 11 days in the absence of delirium), functional decline during hospitalization, and increased admission to long-term care (36% compared with 13%).6 In a study by O’Keefe and Lavan,6 delirious patients were more likely to sustain falls and to develop urinary incontinence, pressure sores, and other complications during hospitalization.

Older patients with delirium superimposed on dementia had a more than twofold increased risk of mortality compared with patients with dementia alone or with neither dementia nor delirium.7 Rockwood found that an episode of delirium was associated with a much higher rate of subsequent dementia.8

Think of an acute medical illness as a “stress test” for the brain, such that, if the patient develops delirium, it suggests an underlying brain disease that was not evident before the acute episode. After hip fracture, for example, delirium was independently associated with poor functional recovery at 1 month9 and at 2 years.10

Older patients admitted to a skilled nursing facility with delirium are more likely to experience one or more complications (73% compared with 41%).11 In the study by Marcantonio and colleagues, patients with delirium were more than twice as likely to be hospitalized again within 30 days (30% and 13%), and less than half as likely to be discharged to the community (30% and 73%). Table 3 summarizes the impact of delirium on outcomes.

Appropriate management steps

Identifying and treating underlying medical illness is the definitive treatment for delirium; in a geriatric patient with multiple medical comorbidities the pathogenesis often is multifactorial or a definitive precipitant cannot always be identified.12

Managing a patient with delirium includes both non-pharmacotherapeutic interventions, which should be considered first-line, and pharmacotherapeutic interventions. Non-pharmacotherapeutic interventions include, but are not limited to:

•  support and close observation by nursing staff

•  placing a clock or calendar in the room

•  frequent reorientation and reminders

•  placing familiar possessions in the room

•  putting the patient in an isolated room with a window

•  regulating the sleep-wake cycle.4

Pharmacotherapeutic intervention in delirium should be used for behavioral symptoms, but only for the minimum duration necessary4 and preferably oral or IV. No drugs are FDA-approved for delirium, which means that use of any agent is off-label.13

Antipsychotics are the mainstay of pharmacotherapy for delirium in most settings. The use of antipsychotics relates to the dopamine excess-acetylcholine deficiency hypothesis of delirium pathophysiology.12 Haloperidol remains the first-line agent because it is available in multiple dosages and can be given by various routes. IV haloperidol appears to carry less risk of extrapyramidal symptoms than oral haloperidol does but, as with all antipsychotics, its use warrants monitoring for QTc prolongation.12

Studies have not shown that atypical antipsychotics are superior to typical antipsychotics for delirium. Multiple studies have shown that atypicals are as efficacious as haloperidol.

Benzodiazepines are the treatment of choice for delirium caused by alcohol withdrawal. A Cochrane review found no evidence that benzodiazepines were helpful in treating delirium unrelated to alcohol withdrawal.14 In some studies, benzodiazepines were associated with an increased risk of delirium, especially in patients in the intensive care unit.15

 

 

More recently, cholinesterase inhibitors have been used to treat delirium. The reasoning behind their use is the hypothesis of a central cholinergic deficiency in delirium.12 Regrettably, there have been few well-conducted studies of these agents in delirium, and a Cochrane review found no significant benefit for cholinesterase inhibitors.16 With the same hypothesis in mind, anticholinergic medications in patients with delirium should be avoided because these agents could exacerbate delirium by further decreasing the acetylcholine level.

Because delirium is common in the hospitalized population (especially older patients), a number of studies have examined strategies to prevent or reduce its development. Inouye and colleagues conducted a controlled clinical trial, in which they intervened to reduce six risk factors for delirium: cognitive impairment, sleep deprivation, immobility, visual and hearing impairment, and dehydration in hospitalized geriatric patients. The number and duration of events of delirium were significantly lower in the intervention group.17

Brummel et al reported that reducing modifiable risk factors in intensive care unit patients—including sedation management, minimizing deliriogenic medications (anticholinergics, antihistamines), minimizing sleep disruption, and encouraging early mobility—could prevent or reduce the incidence of delirium.15

CASE CONCLUDED: Return to baseline

Ms. T’s medications are minimized or discontinued, including azithromycin, based on case reports in the literature. She is stabilized hemodynamically.

Clinicians educate Ms. T’s family about delirium. To address Ms. T’s aggressive and paranoid behaviors, clinicians request that a family member is present to reassure Ms. T. She is continued on low-dose haloperidol. The family also is asked to bring Ms. T’s hearing aid and eyeglasses.

MRI is performed after Ms. T’s behavior is under control. The scan is negative for a new stroke.

Repeat blood tests the following day show an elevated white blood cell count; urinalysis is positive for a urinary tract infection. Ms. T is started on antibiotics. Subsequent urine culture shows no bacterial growth; the antibiotics are stopped after 3 days.

Ms. T slowly improves. According to her family, she is back at baseline in 3 or 4 days.

This case illustrates the complexity of trying to identify the precise cause of delirium among the many that could be involved. Often, no single cause can be found.18

Bottom Line
Delirium is a common and potentially life-threatening condition in hospitalized geriatric patients. General hospital psychiatrists should know how to recognize and treat the condition in collaboration with their medical colleagues.

Related Resources

  • Treating delirium: a quick reference guide. Arlington, VA: American Psychiatric Association. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1662986.
  • Cook IA. Guideline watch: practice guidelines for the treatment of patients with delirium. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1681952.
  • Fearing MA, Inouye SK. Delirium. In: Blazer DG, Steffens D, eds. The American Psychiatric Publishing textbook of geriatric psychiatry. 4th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2009:229-241.
  • Ghandour A, Saab R, Mehr D. Detecting and treating delirium—key interventions you may be missing. J Fam Pract. 2011;60(12):726-734.
  • Leentjens AF, Rundell J, Rummans T, et al. Delirium: an evidence-based medicine (EBM) monograph for psychosomatic medicine practice. J Psychosom Res. 2012;73:149-152.
  • Liptzin B, Jacobson SA. Delirium. In: Sadock BJ, Sadock VA, Ruiz P, eds. Comprehensive textbook of psychiatry. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:4066-4073.

Drug Brand Names

Azithromycin • Zithromax                 Hydralazine • Apresoline

Diltiazem • Cardizem                        Risperidone • Risperdal

Haloperidol • Haldo

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.


Featured Audio

Benjamin Liptzin, MD, describes the distinction between dementia and delirium. Dr. Liptzin is Chair of Psychiatry, Baystate Medical Center, Springfield, Massachusetts, and Professor and Deputy Chair, Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.

References

1. Diagnostic and statistical manual of mental disorders, 5th ed. Arlington, VA: American Psychiatric Association; 2013. 

2. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: The Confusion Assessment Method. A new method for detection of delirium. Ann Intern Med. 1990;113:941-948.

3. Liptzin B, Levkoff SE. An empirical study of delirium subtypes. Br J Psychiatry. 1992;161:843-845.

4. Martins S, Fernandes L. Delirium in elderly people: a review. Front Neurol. 2012;3:101.

5. Levkoff SE, Liptzin B, Evans D, et al. Progression and resolution of delirium in elderly patients hospitalized for acute care. Am J Geriatr Psychiatry. 1994;2:230-238.

6. O’Keefe S, Lavan J. The prognostic significance of delirium in older hospitalized patients. J Am Geriatr Soc. 1997;45:247-248.

7. Tsai MC, Weng HH, Chou SY, et al. One-year mortality of elderly inpatients with delirium, dementia or depression seen by a consultation-liaison service. Psychosomatics. 2012;53:433-438.

8. Rockwood K, Cosway S, Carver D, et al. The risk of dementia and death after delirium. Age Ageing. 1999;28:551-556.

9. Marcantonio E, Flacker JM, Michaels M, et al. Delirium is independently associated with poor functional recovery after hip fracture. J Am Geriatr Soc. 2000;48:618-624.

10. Dolan MM, Hawkes WG, Zimmerman SI, et al. Delirium on hospital admission in aged hip fracture patients: prediction of mortality and 2-year functional outcomes. J Gerontol A Biol Sci Med Sci. 2000;55:M27-M34.

11. Marcantonio ER, Kiely DK, Simon SE, et al. Outcomes of elders admitted to post-acute facilities with delirium. J Am Geriatr Soc. 2005;53:963-969.

12. Bledowski J, Trutia A. A review of pharmacologic management and prevention strategies of delirium in the intensive care unit. Psychosomatics. 2012;53:203-211.

13. Breitbart W, Alici-Evcimen Y. Why off-label antipsychotics remain first-choice drugs for delirium. Current Psychiatry. 2007;6(9):49-63.

14. Lonergan E, Luxenberg J, Areosa Sastre A. Benzodiazepines for delirium. Cochrane Database Syst Rev. 2009;(4):CD006379. doi: 10.1002/14651858.CD006379.pub3.

15. Brummel NE, Girard TD. Preventing delirium in the ICU. Crit Care Clin. 2013;(29):51-65.

16. Overshott R, Karim S, Burns A. Cholinesterase inhibitors for delirium. Cochrane Database Syst Rev. 2008(1):CD005317. doi: 10.1002/14651858.CD005317.

17. Inouye SK, Bogardus ST, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340:669-676.

18. Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA. 1990;263:1097-1101.

References

1. Diagnostic and statistical manual of mental disorders, 5th ed. Arlington, VA: American Psychiatric Association; 2013. 

2. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: The Confusion Assessment Method. A new method for detection of delirium. Ann Intern Med. 1990;113:941-948.

3. Liptzin B, Levkoff SE. An empirical study of delirium subtypes. Br J Psychiatry. 1992;161:843-845.

4. Martins S, Fernandes L. Delirium in elderly people: a review. Front Neurol. 2012;3:101.

5. Levkoff SE, Liptzin B, Evans D, et al. Progression and resolution of delirium in elderly patients hospitalized for acute care. Am J Geriatr Psychiatry. 1994;2:230-238.

6. O’Keefe S, Lavan J. The prognostic significance of delirium in older hospitalized patients. J Am Geriatr Soc. 1997;45:247-248.

7. Tsai MC, Weng HH, Chou SY, et al. One-year mortality of elderly inpatients with delirium, dementia or depression seen by a consultation-liaison service. Psychosomatics. 2012;53:433-438.

8. Rockwood K, Cosway S, Carver D, et al. The risk of dementia and death after delirium. Age Ageing. 1999;28:551-556.

9. Marcantonio E, Flacker JM, Michaels M, et al. Delirium is independently associated with poor functional recovery after hip fracture. J Am Geriatr Soc. 2000;48:618-624.

10. Dolan MM, Hawkes WG, Zimmerman SI, et al. Delirium on hospital admission in aged hip fracture patients: prediction of mortality and 2-year functional outcomes. J Gerontol A Biol Sci Med Sci. 2000;55:M27-M34.

11. Marcantonio ER, Kiely DK, Simon SE, et al. Outcomes of elders admitted to post-acute facilities with delirium. J Am Geriatr Soc. 2005;53:963-969.

12. Bledowski J, Trutia A. A review of pharmacologic management and prevention strategies of delirium in the intensive care unit. Psychosomatics. 2012;53:203-211.

13. Breitbart W, Alici-Evcimen Y. Why off-label antipsychotics remain first-choice drugs for delirium. Current Psychiatry. 2007;6(9):49-63.

14. Lonergan E, Luxenberg J, Areosa Sastre A. Benzodiazepines for delirium. Cochrane Database Syst Rev. 2009;(4):CD006379. doi: 10.1002/14651858.CD006379.pub3.

15. Brummel NE, Girard TD. Preventing delirium in the ICU. Crit Care Clin. 2013;(29):51-65.

16. Overshott R, Karim S, Burns A. Cholinesterase inhibitors for delirium. Cochrane Database Syst Rev. 2008(1):CD005317. doi: 10.1002/14651858.CD005317.

17. Inouye SK, Bogardus ST, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340:669-676.

18. Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA. 1990;263:1097-1101.

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