Delirium Is Often Misdiagnosed in Advanced Cancer

CLEVELAND—Delirium, although common in patients with advanced cancer, is poorly understood, Donna S. Zhukovsky, MD, said at a conference on palliative medicine held at the Cleveland Clinic Foundation. Properly identifying delirium can be difficult, and the literature shows that it frequently goes unrecognized by physicians and nurses, said Dr. Zhukovsky, of the Cleveland Clinic Foundation’s Harry R. Horvitz Center for Palliative Medicine.

Delirium is characterized by a disturbance in consciousness and a change in cognition that develop in a brief period of time, she said. It tends to fluctuate over the course of the day, so that patients with delirium may have periods of normality interspersed with delirium.

In cancer patients, treatment side effects of drugs or radiation can cause delirium. Other possible causes include metabolic encephalopathies, infection, anemias, nutritional deficiencies, and paraneoplastic syndromes.

Although impaired thinking and memory are common to both delirium and dementia, patients with dementia tend to have a more stable course, Dr. Zhukovsky said. They have a more gradual onset of cognitive impairment, and their impairment does not fluctuate throughout the day. They usually have no clouding of consciousness and deteriorate over longer periods of time.

Delirium is present in 8% to 85% of cancer patients, according to the literature, with the variation explained by different study populations and assessment tools. “Delirium is found in 20% to 40% of people with advanced cancer,” Dr. Zhukovsky said.

Delirium is extremely common preceding death, which raises implications for obtaining patient consent to medical treatment. In one study, patients developed cognitive failure, on average, 16 days prior to death. The cause of the delirium could not be identified in 56% of these patients (Bruera E et al: J Pain Symptom Manage 7:192-195, 1992).

When treating delirium, the clinician must recognize that the situation is often related to multiple factors, including the disease process, medical comorbidities, and medications, Dr. Zhukovsky said.

Three Subtypes

There are three delirium subtypes: hypoalert, hyperalert, and mixed. These different subtypes have different prognoses, with hyperalert having the best prognosis in terms of mortality, she said.

Patients with hyperalert (or hyperactive) delirium are agitated, often with hallucinations and delusions. This is the most common type of delirium, she said, and it is often quickly identified because of the patient’s behavioral problems.

With hypoalert (or lethargic) delirium, patients are sleepy and withdrawn. Hypoalert delirium is frequently undiagnosed or misdiagnosed as depression. “People with the hypoalert form are often not recognized because they are not behavioral problems and therefore are not treated,” Dr. Zhukovsky said.

People with delirium may have periods of normal cognition. This further complicates the diagnosis. In the Bruera study, cognitive failure identified by the Mini-Mental Status Exam (see box) was overlooked by the physician on the same day in 23% of cases and by the nurse in 20% of cases.

Assessment Tools for Delirium

The Mini-Mental Status Examination (MMSE) is the “gold standard” of neurophysical tests. However, for patients with speech, motor, or visual disabilities, it has limitations, Dr.

Zhukovsky said at the conference on palliative care. In addition, the 3 to 5 minutes needed to do the MMSE may be too taxing for a sick patient.

Many other tools exist for the assessment of delirium, each with its own strengths and weaknesses. Clearly, the development of more sensitive and user friendly” assessment tools is needed, Dr. Zhukovsky said.

She recommended the study of Smith et al for a look at more than 20 assessment instruments, including the MMSE (J Pain Symptom Manage 10:35-77, 1995). The tools were evaluated according to four characteristics: ease of administration, speed of administration, normative data, and reliability. Four types of validity were also evaluated: inspection, screening, diagnostic, and severity.

Treatment for delirium includes adding orienting devices to the environment, such as clocks, calendars, and nightlights, she said. However, the mainstay of treatment is dopamine-blocking agents such as haloperidol, while correcting the contributing causes whenever possible.