Margaret O. Rathier, MD

Successful prevention of delirium requires systematic evaluation of hospitalized elderly patients. In this article, we identify key risk factors to be alert for in the evaluation. We also outline a multidisciplinary approach to diagnosis and management.

Delirium is characterized by a global disorder of attention and cognition. It is present in 10% to 40% of elderly persons at the time of hospital admission; the incidence rises to 25% to 60% during the stay.

 Delirium goes unrecognized in 32% to 66% of this population.

 It affects 2.2 million hospitalized elderly persons at an estimated cost to Medicare of over $4 billion (1994 dollars) per year.

The prevalence of delirium in elderly patients differs according to the type of hospital admission; it varies from 10% to 15% in general medical and surgical wards to more than 50% in persons with hip fractures. The prevalence of delirium is even higher in the ICU; it is diagnosed in over 80% of mechanically ventilated patients.

 The risk of delirium is related to the underlying health of the patient and the magnitude and impact of the medical or surgical intervention. The risk increases with prolonged length of hospital stay.

Patients may present with the hyperactive, hypoactive, or mixed form of delirium. The hyperactive state is often recognized, but a misdiagnosis of dementia or the administration of antipsychotic or sedative drugs alone will delay the proper diagnosis and increase the complications of delirium (eg, inappropriate social behavior, increased in-hospital morbidity, and progressive decline in function that can lead to coma and death).	

The hypoactive form of delirium often goes unrecognized, which results in similar delays and complications. It is no surprise, therefore, that delirium has been associated with hospital mortality rates of 10% to 65% in addition to an increased risk of institutionalization.

 The mixed form includes the hyperactive and hypoactive states. The patient may cycle from one to another over a period of hours.

Delirium is a predictor of long-term functional decline and permanent loss of functional independence.

 A study of hospitalized elderly persons showed loss of function on average in 1 activity of daily living during hospitalization; delirium was the sole predictor of this loss of independence.

 Most studies have focused on incident delirium--that is, the onset of delirium is documented during the hospital stay--and have identified risk factors and precipitating factors.

 (For patients who present with symptoms of delirium at hospital admission, an interdisciplinary approach to improve overall function and prevent further decline in mental status is most appropriate.)

One study of incident delirium identified 4 independent baseline risk factors present on admission in elderly patients in whom delirium subsequently developed during hospitalization.

 They include vision impairment (adjusted relative risk [RR], 3.5), severe illness (RR, 3.5), cognitive impairment (eg, dementia) (RR, 2.8), and a high blood urea nitrogen­creatinine level ratio (RR, 2.0).

This predictive model can be used to identify hospitalized patients at highest risk for delirium.  Functional impairment, comorbid conditions, and related pharmacotherapy may be associated with a decline in cognitive reserve and an increased risk of delirium. Table 1 shows the rates of delirium and death or nursing home placement related to these risk factors.

Prevention strategies must address, at a minimum, the following 5 factors known to precipitate incident delirium

• Use of physical restraints (RR, 4.4).

• More than 3 medications added during the hospital stay (RR, 2.9).

The presence of 1 or 2 of these factors was associated with a 20% increase in the incidence of delirium. The presence of 3 or more was associated with a 35% increase.

Preventive strategies for nonsurgical patients

 demonstrated the value of an intervention strategy to prevent delirium in elderly hospitalized patients. This controlled clinical trial compared a group of hospitalized elderly patients who received usual inpatient care with a group who received delirium-specific preventive interventional care from a multidisciplinary team. Patients in the intervention group received standardized care to prevent cognitive impairment (orientational and cognitive-stimulating activities), sleep deprivation (relaxation and noise reduction programs), immobility (ambulation and other exercise), visual impairment (use of visual aids), hearing impairment (use of amplification devices and ear care), and dehydration (monitoring for dehydration and encouraging intake of fluids).

The approach significantly reduced the incidence of delirium (from 15% to 9.9%). A decrease in the use of sleep medications and improved cognition also were demonstrated, although there was no difference in length of hospital stay between the intervention and "usual-care" groups. The authors emphasize that primary prevention is the most effective strategy, because once delirium has occurred, intervention is less effective. Cost-effectiveness considerations may dictate that these multidisciplinary protocols be targeted to high-risk patient groups.

Subsequent studies of multifactorial educational interventions that have been designed for hospital staff to prevent delirium, increase its recognition, and improve its management have shown that the interventions help reduce hospital length of stay and are potentially cost-saving for participating hospitals.

Preventive strategies for surgical patients 

These interventions are individualized according to the type of surgery--whether urgent or elective--that patients receive and their underlying health status. Not surprisingly, the highest rates of delirium occur in the subset of patients admitted for hip fracture repair. These patients are likely to be undergoing surgery on an urgent basis; they are often frail and have risk factors for incident delirium at the time of injury. In addition, they often have comorbid conditions and functional dependence. Despite the increased risk, delirium is significantly underdiagnosed in this population.

 Standard postoperative care procedures, including prevention of hypoxemia and hypotension, result in decreased incidence and severity of delirium.

Delirium rates are lower in patients undergoing elective joint replacement than in those undergoing emergent hip fracture repairs. Risk factors in the former group can be addressed preoperatively, and preventive strategies in those with cognitive, visual, or hearing impairment can be implemented to minimize sleep deprivation, immobility, and dehydration. Early detection and management of postoperative delirium helps reduce the severity of delirium in both groups.

Risk factors for delirium in patients undergoing elective noncardiac surgery include age greater than 70 years, a history of alcohol abuse, cognitive or functional impairment, metabolic disturbances, or a history of noncardiac thoracic surgery or abdominal aortic aneurysm surgery.

 Significant intraoperative blood loss and hemodynamic instability are additional risk factors.

In spite of the recognized neuropsychological consequences of coronary artery bypass graft (CABG) surgery, there are few prospective studies of delirium in elderly patients undergoing this procedure. Cognitive changes following CABG surgery have been shown to persist in 42% of patients for at least 5 years after the procedure.

 Delirium would have developed as the initial presentation of acute cognitive change in many of these patients. Postoperative delirium develops in an estimated 30% of persons 65 years and older who undergo CABG surgery.

 If this condition is not recognized and treated, it may result in long-term cognitive impairment. Protocols to prevent delirium in this very high-risk population have yet to be published.

Developing such strategies may require a better understanding of the pathophysiology of delirium and more specific targeting to the mechanism of ischemic and reperfusion injury. Interventions for early detection and management of delirium that have reduced hospital length of stay and rates of long-term institutionalization and death in other subsets of patients may protect against the long-term consequences of delirium in patients undergoing CABG surgery.

A number of studies have shown that patients in whom delirium develops have higher complication rates, longer hospital stays, and increased rates of transfer to rehabilitation or long-term­ care facilities.

 The causes of these poor outcomes--which have been observed in both medical and surgical settings--may vary according to the patient's preadmission status, illness severity, and management of the condition for which the patient was admitted. Specific protocols are being developed that intensely monitor for and prevent or aggressively manage delirium and its complications; they may improve outcomes and reduce the cost of care. One proposed model of care is the use of the Delirium Room, a 4-bed unit located in an acute care for the elderly unit.

 The Delirium Room is staffed with a certified nursing assistant 24 hours a day, utilizes a multidisciplinary-team model of care, and is restraint-free.

Table 2 lists the common causes and precipitants of delirium that require early recognition and management. Since the cause of delirium is often multifactorial, it is prudent to screen for all of these conditions. Detection of delirium and related conditions requires a careful history taking, physical examination, and patient and family interviews to establish an accurate picture of the patient's pre-illness status. Select laboratory studies as indicated from the clinical evaluation, including those shown in Table 3, should be considered in the evaluation.

Review the patient's current medications (including over-the-counter preparations) and alcohol use. Ascertain whether withdrawal from benzodiazepines or alcohol may have precipitated the delirium. Discontinue agents on the "Beers list" of medications that are best avoided by elderly persons (Table 4).

Use metoclopramide with caution, because it is associated with extrapyramidal side effects that may manifest with delirium-like features. Cimetidine and, to a lesser extent, ranitidine and other H

Delirium is a clinical diagnosis. The changing levels of confusion and consciousness associated with delirium may lead to a missed diagnosis and, hence, a lost opportunity for improving outcomes. The Confusion Assessment Method (CAM) is a useful tool that enables nonpsychiatric clinicians to quickly distinguish delirium from other causes of altered mental status in the hospital setting (Table 5).

 The CAM is sensitive and specific for the diagnosis of delirium, although the sensitivity may vary from 0.13 to 1.0,

 depending on the experience and training of the person using it. A standardized mental status examination using Folstein's Mini-Mental State Exam with additional tests of attention may also be used.

The CAM has been adapted to the ICU setting to facilitate identification in mechanically ventilated patients. The CAM-ICU is a rapid, valid, and reliable tool for diagnosing delirium in this setting.

 Training materials can be found online at http://www.icudelirium.org.

The approach outlined in Table 3 reflects Dr McElhaney's experience in providing geriatrics consultation in tertiary care teaching hospitals in Canada and the United States. These observations have been supported by the emerging literature. We have learned that a consistent multidisciplinary approach to the detection and management of potential causes is critical to improving outcomes in patients with delirium. The use of this protocol for 5 months to manage 143 medical and surgical patients with delirium resulted in a 20% reduction in length of hospital stay and improved discharge disposition.

 When the protocol was adapted for patients undergoing CABG surgery, the length of postoperative stay in the ICU decreased by 50%.

Antipsychotic drugs and sedatives are best avoided; if required (such as when a patient's agitation may compromise treatment or lead to harm of the patient or others), they should be used for specific therapeutic indications at the lowest effective dose. To minimize the severity of delirium, avoid physical restraints and the use of drugs as chemical restraints.

It is critical to aggressively withdraw unnecessary medications and avoid medication changes that may contribute to delirium. One must be vigilant for inadvertent abrupt cessation of benzodiazepines; restarting the drug or giving an equivalent benzodiazepine is the only appropriate management of delirium to avoid benzodiazepine withdrawal.

 Similarly, benzodiazepines are used for alcohol withdrawal, although clonidine at dosages of 0.1 mg bid or tid may reduce the amount of benzodiazepine needed for this indication.

 It is often helpful to hold cognitive-enhancing drugs and antidepressants for a few days until the delirium clears. Caution is advised if the antidepressant paroxetine is to be abruptly discontinued; lowering the dose may be preferable.

It is particularly important to avoid use of complicated regimens that incorporate antipsychotics, benzodiazepines, narcotics, and/ or anticholinergics in the management of agitation. Because many of these drugs can cause delirium, combinations of them may increase agitation and create challenges to further therapeutic decisions regarding the management of agitation.

Inform families that delirium is a temporary and treatable condition and involve them in the care plan. Family members are often not aware of the transient nature of delirium and may believe a permanent change in mental status has occurred. This misunderstanding can lead them to prematurely request that the patient be placed in a long-term­care facility. When fully informed, families are more likely to adopt positive attitudes and become an important part of the treatment team.

Loxapine (Loxitane, Watson), an intermediate-acting, atypical antipsychotic agent, is our first choice for managing agitated delirium. We recommend a low oral dosage of 5 mg qhs to 10 mg bid. In our clinical experience in the management of delirium, loxapine has been associated with a lower risk of extrapyramidal side effects and is less likely to cause a paradoxical increase in agitation compared with high-potency typical antipsychotics. Because loxapine has both sedative and antipsychotic properties, other sedatives do not have to be added. Postural hypotension occurs infrequently at low doses of loxapine.

Practice guidelines for the treatment of delirium published by the American Psychiatric Association in 1999 suggested the use of haloperidol to treat delirium.

 If haloperidol is used, the recommended dosage range is 0.5 to 1 mg bid (up to 2 mg tid). It can be administered orally, intramuscularly, or intravenously, but it can cause significant extrapyramidal symptoms in frail, older adults.

Mostly open-label studies and a limited number of trials comparing different antipsychotics in the management of delirium have been published. Studies comparing haloperidol and newer antipsychotics suggest that the latter are useful in treating agitated delirium and have a better side-effect profile than the older agent.

 Risperidone can be prescribed at starting dosages of 0.5 mg bid; quetiapine (Seroquel, AstraZeneca) has been shown to be effective at starting dosages of 12.5 to 25 mg bid, as has olanzapine (Zyprexa, Eli Lilly) at dosages of 2.5 to 5 mg daily.

Finally, the identification of persistent delirium in patients who are discharged to home or another care facility is important for optimizing health outcomes,

 particularly because of the continued risk of misidentification of delirium as dementia by the caregivers. Patients in whom delirium was diagnosed on admission to rehabilitation hospitals and skilled nursing facilities had a 5-fold increase in 6-month mortality, were more likely to be rehospitalized, and were less likely to be discharged home than other admitted patients.

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Margaret O. Rathier, MD

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