In the first study of its kind, Fred Hutchinson researchers found that half of patients undergoing conventional stem-cell transplantation exhibit signs of delirium, but the symptoms can be subtle and easily missed by care providers.
Dr. Jesse Fann, a psychiatrist in the Clinical Research Division's Biobehavioral Sciences department and director of the Seattle Cancer Care Alliance's Psychiatry and Psychology Consultation Service, led the analysis of 90 patients, ages 22 to 62 years, who agreed to participate in the study prior to undergoing stem-cell transplants at Fred Hutchinson. Results of the study were published in the Feb. 15 issue of the journal Cancer.
Delirium is a condition that develops quickly and involves changes in consciousness, attention, cognition (thinking and reasoning) and perception. The symptoms tend to fluctuate but overall, a delirious state is a sudden and significant decline from the previous level of functioning in the patient. "The brain's neurons aren't firing in their usual, coordinated way," said Fann, also part of the University of Washington's Psychiatry and Behavioral Sciences department. The symptoms are due to an underlying medical condition, a medication, substances such as alcohol or other drugs, or a combination of these factors. Delirium is usually temporary and is not a long-term psychiatric disorder.
Delirium defined
Clinicians usually identify delirium by the more classic symptoms of hallucinations, delusions, agitation and disorientation. However, Fann and colleagues found that in the transplant-patient population, delirium often presented differently. The most prominent symptoms were sleep-wake cycle disturbances, in the form of excessive sleepiness during the day and very interrupted sleep at night; hypoactive behavior, such as lethargy; and cognitive impairment, including inattention and memory difficulties. Several symptoms begin to increase prior to a delirium episode and can warn clinicians to closely monitor the patient.
For transplant patients, episodes of delirium lasted an average of 10 days, with peak severity at the end of the second week post-transplantation. "Out of a 30-day hospitalization, for example, that's a third of their stay," Fann said. "10 days of being delirious is a significant amount of time." Affected patients are less likely to participate in important activities for transplant recovery, such as eating, walking and physical therapy and are less able to communicate important symptoms to their health care providers.
"Delirium has been a relatively unrecognized and underappreciated problem, partly because it's not detected in many cases," Fann said. "Some clinicians feel that the symptoms are to be expected and, therefore, it's not necessary to treat them."
"But research shows that delirium is common and it is important to detect and manage it because it can lead to significant medical complications, self-harm and even increased mortality."
Once detected, care providers try to identify the underlying causes of delirium. The patient may need an alternative or lower dose of pain, nausea or sleep medication, treatment for infection or an electrolyte imbalance corrected.
Delirium symptoms are managed with medication. Researchers have found that it is also important to monitor the patient's safety, frequently orient and reassure the patient, provide consistent contact with medical staff and family members, maximize appropriate sensory input (ensure the patient is wearing glasses or hearing aids, if needed), getting the patient moving and minimizing overstimulation (like excess noise).
Besides pointing to an underlying medical condition, delirium can affect health in a number of ways that may lead to more complications or higher death rates. Delirious patients are more likely to contract pneumonia, especially dangerous in immune-compromised patients. They get more bed sores and have lengthened hospital stays, potentially increasing their risk for subsequent infection and slowing recovery.
Multiple risk factors
The researchers, who followed the patients from before transplant to 30 days post-transplant, found delirium was also significantly associated with distress and fatigue in the patients. "In many cases, there is some awareness of the condition in the patients themselves, and it can be an incredibly frightening experience," Fann said. "It's very distressing to family members and other caregivers, too, including nursing staff."
Multiple factors put transplant patients at high risk for delirium. "They are especially vulnerable because of their baseline level of lower physical and cognitive functioning, perhaps due to the cancer itself or prior chemotherapy," Fann said. "Also, people with poor kidney or liver function are susceptible because of a reduced ability to clear medications. Certain kinds of cancers — acute leukemia and solid tumors — seem to put patients at higher risk."
"And a number of medications can cause delirium, including corticosteroids, opioid medications (narcotics used for pain management), and nausea, sleep or anxiety medications — all commonly used in the transplant setting."
With the publication of this and earlier landmark papers on delirium, the researchers say recognition and treatment of the condition have improved. "This study has raised awareness of delirium among clinicians, and I think we're doing a better job of recognizing and treating it," Fann said. The UW Medical Center and Alliance are close to implementing standardized clinical procedures for monitoring delirium and confusion in their patients. Fann has presented his findings at scientific meetings for physicians and nurses who treat patients with cancer. He has also co-authored an updated section on delirium in the American Psychiatric Association's standard diagnostic manual.
The study patients were assessed post-transplant at 80 days, six months, and one year. Fann and colleagues are analyzing the extended data for future papers on longitudinal risk factors and short- and long-term outcomes, such as cognitive functioning, quality of life and mortality. He and other colleagues are also tracking delirium episodes in non-myeloblative or "mini-transplant" patients; since those patients only receive minimal doses of chemotherapy and radiation compared to conventional transplants, Fann believes the risk and incidence of delirium may be different in this population.
Co-authors included Drs. Catherine Alfano and Karen Syrjala, of Fred Hutchinson; Bart Burington and Dr. Wayne Katon, UW; and Sari Roth-Roemer, Arizona Medical Psychology. The study was funded by grants from the American Cancer Society and the UW.
