1. Susman, Ed

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MIAMI BEACH, Fla.-For the vast majority of advanced cancer patients admitted to the hospital with delirium, use of the anti-psychotic agent haloperidol may be sufficient to control the problem without any additional treatment, researchers reported here at the International Symposium on Supportive Care in Cancer.

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In a poster presentation, the research team from the University of Texas MD Anderson Cancer Center said that the need to switch patients with delirium from haloperidol is required only infrequently-but when haloperidol is not sufficient to defeat delirium, the prognosis is poor.


"Neuroleptic rotation from haloperidol was required in only 23 percent of patients," said Seong Hoon Shin, MD, a visiting researcher at MD Anderson and an internal medicine faculty member at Kosin University College of Medicine in Busan, Korea. "This means that haloperidol was effective to control delirium in the palliative care setting.


"The main reason patients needed to rotate neuroleptics was treatment failure-which occurred in 34 of the 39 patients who received second-line therapy, mainly with chlorpromazine. There were five patients who required rotation due to adverse events," he stated.


A total of 91 of the patients treated only with haloperidol-71 percent- were discharged from the unit. The initial median daily dose of haloperidol in these patients was 5 mg, and the median time of treatment was five days. The ending median dose of haloperidol was 6 mg.


In-patient mortality among those patients requiring treatment in addition to haloperidol was 59 percent compared with 29 percent for those treated only with haloperidol. The mortality rate in this series of patients with advanced cancer and delirium was 36 percent.


Overall, 57 percent of patients treated with first-line haloperidol had observed improvement in their delirium symptoms; 33 percent of those patients requiring second-line therapy showed improvement, Shin reported.


"Delirium is one of the most distressing syndromes in terminal cancer patients," the researchers noted. "It is characterized by acute confusion, an altered level of consciousness, restlessness, decreased cognition and abnormal perception, all of which tend to fluctuate over the course of the day. Delirium is associated with a higher rate of morbidity and mortality, longer hospital stay, higher health care costs, and significant distress to patients, family members, and professional caregivers."


The current management of delirium, however, Shin explained, involves identifying and removing any potentially reversible causes and prescribing pharmacologic and non-pharmacologic interventions. Non-pharmacologic measures such as "environmental control" and aids for orientation are recommended. However, if these fail to alleviate symptoms, pharmacologic neuroleptic treatment and/or benzodiazepines are typically recommended.


"The optimal order and dose of neuroleptics for delirium has not been well defined. In our acute palliative care unit, haloperidol is mainly used as a first-line neuroleptic followed by rotation to chlorpromazine if patients continue to experience agitated delirium. A better understanding of the effectiveness of first-line haloperidol would help optimize the management of delirium in palliative care."

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Study Details

The research team conducted a retrospective review of the charts of 167 consecutive patients with advanced cancer who were admitted to the acute palliative care unit between January 1, 2012 and March 31, 2013. Patients were included in the study if they were given a diagnosis of delirium based on clinical diagnosis by a palliative care specialist or received a score of 7 or greater on the 30-point Memorial Delirium Assessment Scale. They were included if they were treated with haloperidol as a first-line therapy.


More than 70 percent of the patients eligible for the study were in ECOG performance status class 4. About 23 percent of the patients had been diagnosed with gastrointestinal cancers; 17 percent had hematologic cancers; 16 percent had lung cancer; 11 percent had breast cancer; 10 percent had gynecologic cancers; five percent had genitourinary cancers; five percent had sarcomas; four percent had head and neck cancers; and 17 percent had various other cancers, the researchers reported.


Of the patients who did not need to have their anti-psychotic medication rotated, 52 percent were diagnosed with hyperactive and mixed delirium; the others had hypoactive delirium. The percentages were similar for those who required rotation to a second-line treatment-59 percent were diagnosed with hyperactive or mixed delirium and 41 percent were diagnosed with hypoactive delirium.


The researchers reported that 92 of the patients were transferred to the acute palliative care unit from an oncology department and 58 patients were transferred from an emergency department. Of the patients discharged from the palliative care unit who survived, 49 percent were sent home; 46 percent were transferred to in-hospital hospice, and the rest were transferred to another hospital. All the patients were diagnosed with Stage 4 cancer.


Of the patients in the study, 128 required therapy with only haloperidol; 39 patients needed a second neuroleptic. The doctors in the retrospective study discontinued haloperidol in 33 or those cases, and in six cases a second neuroleptic was added to the regimen.


None of various other factors (cancer diagnosis and stage, duration of stay in the acute palliative care unit, delirium subtype, do-not-resuscitate status at admission, admission source, and symptom burden) were found to be associated with need for neuroleptic rotation. About 70 percent of the patients in the study were treated with benzodiazepines in addition to anti-psychotic medication, Shin reported.


'Very Effective Anti-Nausea Drug'

Asked for his opinion for this article, the meeting's Program Chair, Declan Walsh, MD, Professor and Director of the Harry R. Horvitz Center for Palliative Medicine at the Cleveland Clinic, said, "Haloperidol is really a great drug. I would agree with the researchers' finding that this is a very well-tolerated drug. We use it as an anti-nausea drug as well as an anti-psychotic drug. It is a very effective anti-nausea drug."


The symposium, which had the theme "Supportive Care Makes Excellent Cancer Care Possible," is sponsored by the Multinational Association of Supportive Care in Cancer and the International Society of Oral Oncology. About 900 people from approximately 50 different countries attended this year.