PHILADELPHIA—Delirium in the ill is often unrecognized and frequently goes untreated. This metabolic brain syndrome may have multiple etiologies, resulting in differing diagnoses and treatments. Researchers have also pointed out that one of the two major subtypes of delirium—the hypoactive type in which the patient lies quietly in bed—is more apt to be overlooked than the hyperactive type in which the patient may be so agitated that oral medications to quell the delirium are impossible to administer.

NEW REPORTS ON STRESS AND TREATMENT

Two of the reports presented at the 2002 Annual Meeting of the American Psychiatric Association addressed the results of recent studies of delirium conducted at Memorial Sloan-Kettering Cancer Center in New York City. One study, presented by William Breitbart, MD, Chief of Psychiatric Services at the center, focused on stress felt not only by patients with delirium but by their spouses, caregivers, or the nursing staff.

Dr. Breitbart said that the impetus for the stress study was the research team’s belief that “one of the barriers to intervention is the lack of recognition of the distress experienced by patients with delirium, as well as by their caregivers and the nursing staff.” He added, “We also hypothesized that patients who have hypoarousal with lethargic sleeping, who are not agitated and causing nursing problems or wanting to leave the hospital, are perceived as being in less distress compared to agitated patients with delirium.”

In a prospective study of 154 delirious patients treated by the psychiatric consultation service at Memorial Sloan-Kettering from July 1 through November 1, 2000, 101 had resolution of their delirium, Dr. Breitbart said. The patients were rated on the Memorial Delirium Assessment Scale (MDAS) on the first day of consultation. Data on the etiology of the delirium, cancer diagnosis and stage, and the presence of brain metastases were reviewed. History of dementia, as well as a variety of socioeconomic variables and the Karnofsky score, was also assessed. The average Karnofsky score was about 35, he said, which indicated that the patients were “quite debilitated.”

There were multiple etiologies for the delirium: most commonly, the use of opioids or steroid drugs, hypoxia, dehydration, infection, central nervous system infection, or brain metastases. After resolution of their delirium, 94% of the participants recalled the experience and were asked to rate their distress during the episode on a 0-to-4 rating scale.

Of the 101 patients, 80% reported being extremely distressed, with a mean level of distress of 3.22. Their distress was greatest if they had delusions and if corticosteroids were the cause of their delirium. Both hyperactive and hypoactive patients reported being equally distressed. However, spouses and other caregivers were even more distressed than the patients, demonstrating a mean score of 3.75. What bothered them most was patient symptoms of brain metastases, the patient’s degree of debilitation, and patient hyperactivity in delirium.

The nurses’ mean score was 3.09; they were distressed by different issues, including the patients’ tendency to sleep all day and be awake all night, patient hallucinations, delusions, frequent paranoia—essentially, events requiring nursing intervention, such as rehydration and antibiotics. Dr. Breitbart emphasized that it is important to determine if the patient has delirium and to treat it, “because otherwise it makes the assessment of other symptoms, like pain, more difficult.”

RESPONSE RATES WITH OLANZAPINE

The second study, the results of which were also reported by Dr. Breitbart, found response—and predictors of response—with use of the atypical antipsychotic drug olanzapine to resolve the delirium. Dr. Breitbart described the results of an open-label trial of olanzapine comprising hospitalized cancer patients with delirium referred to him between July 1 and November 1, 2000, to determine its clinical utility and safety. He noted that 52 such patients were excluded because of problems with the route of administration of the drug. Also, 20 patients were excluded because they were on other neuroleptics. The remaining 82 patients were rated on the MDAS on the day they started olanzapine, on days 2 to 3, and on days 4 to 7, Dr. Breitbart said.

The dosages of olanzapine were titrated according to clinical judgment. The severity of delirium was largely in the moderate range, he reported, and half of the patients had hypoactive and half had hyperactive delirium. In about 70% of cases there were multiple etiologies for the delirium; the most common were use of steroids and opioids, hypoxia, dehydration, central nervous system problems, liver disease, and use of other medications such as the cholinergic drugs.

“The vast majority of patients improved on olanzapine treatment, and the mean improvement in MDAS scores from baseline to the end of treatment was statistically significant,” reported Dr. Breitbart. He said that by using a cutoff score of 13 on the MDAS scale, about 79% of patients improved on olanzapine, and with a more stringent cutoff score of 10, 73% had complete resolution of their delirium on olanzapine therapy.

One of the most important predictors of response, according to Dr. Breitbart, was age; 91% of those younger than 50 had resolution of their delirium and about 94% of patients up to age 70 experienced improvement, while in patients 71 and older, delirium resolution was only 42%. This may not be specific to olanzapine, he suggested—it may be that any neuroleptic would be less effective in the older patients.

The study also showed a less robust response in those with the hypoactive delirium subtype. Patients with central nervous system disease also responded less well. The primary side effect of olanzapine was sedation on initial doses ranging from 2.5 mg to 10 mg and titrating to 15 mg in some patients by study’s end. However, Dr. Breitbart added, no extrapyramidal side effects were seen in this study, in which roughly 75% of the 82 patients improved while taking this particular atypical antipsychotic.

MOST BANG FOR YOUR DIAGNOSTIC BUCK

Christopher I. Kauffman, MD, consult liaison at the Payne Whitney Clinic of New York Presbyterian Hospital, recounted the results of a retrospective chart review of 2,000 consultations during a 29-month period; 344 cases involved delirious patients, about two thirds of whom came from the general medical wards of New York Presbyterian Hospital.

It was surprising that 46% of the patients with delirium had had a premorbid psychiatric diagnosis, alcohol dependence, or dementia, he said. “We felt that approximately 40% had dementia, although in only 12% was it noted on the chart.”

Some of the test results were unexpected, Dr. Kauffman allowed, in that more than half of the patients with delirium were hypocalcemic and that renal failure and other abnormalities, like low albumen and potassium, were common. “But the most striking finding was anemia—90% of the men were anemic. The overwhelming number of patients were anemic, a facilitating factor in delirium.”

Also, there were abnormalities in 60% of the chest x-rays, revealing new findings 40% of the time. Common computed tomography findings were new CVAs, emerging hydrocephalus, and mass lesions. Hepatic failure was also common, and Dr. Kauffman observed that “there were a lot of urinary tract infections.”

In terms of tests for delirium, he believes that “a metabolic panel and the complete blood count are excellent, high-yield screening tools. You get a lot of bang for your buck. Platelet count is a little more expensive, but useful. Chest x-ray is a high-yield screening tool, and MRI seems best used when there is a need for clarification on initial computed tomography findings.

“Urinalysis is actually high yield, and one of the suggestions from this study is that if you suspect a urinary tract infection, a urinalysis isn’t even necessary; you can go straight to a urine culture, which costs about the same. Thyroid-stimulating hormone is expensive and has moderate yield. But I think its moderate yield warrants its being used in delirium.” He noted that in his chart review, 12% of patients were hypothyroid and 7% had laboratory results potentially consistent with thyroid storm.

For neurosyphilis, a trichomonas antibody test, he said, “is less expensive and more efficacious.” B12 testing is so expensive that it should be reserved “for specific scenarios,” such as when the diagnosis remains unclear after the initial screening. Dr. Kauffman also pointed out that “diagnosis of delirium is clinical; testing is to find the etiology of the disorder.”

—Jean McCann

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