Delirium is an exceedingly prevalent syndrome among patients with cancer, but is underrecognized and undertreated, according to Alan Valentine, MD, Chair, Department of Psychiatry, The University of Texas M.D. Anderson Cancer Center, Houston, and Darryl Etter, PsyD, Clinical Psychologist, VA Eastern Colorado Health Care System, Denver, at a webinar hosted by the American Psychosocial Oncology Society in July 2016. Providers often do not recognize the symptoms of delirium and, therefore, do not take the necessary steps to reduce its emotional, physical, and financial effects. Implementation of behavioral and environmental strategies coupled with patient and provider education on the clinical presentations of delirium can reduce its risk and impact, they said.
Delirium has been defined as “a transient organic mental syndrome of acute onset characterized by global impairment of cognitive functions, a reduced level of consciousness, attentional abnormalities, increased or decreased psychomotor activity and a disordered sleep-wake cycle.”
“It’s pretty hard to improve on this clinical definition of delirium,” said Dr Valentine. “Although I would suggest the level of consciousness might be heightened,” he added.
The hyperactive variant is characterized by psychomotor agitation (eg, pacing, wringing hands), excitability, increased response to stimuli, and visual hallucinations, according to Dr Valentine. “The hyperactive version is the diagnosis that’s not going to be missed. These patients are possibly combative and may need to be in restraints,” he said.
Hypoactive delirium, conversely, is often overlooked by clinicians. It is characterized by decreased psychomotor activity and listlessness, and is often mistaken for depression. But the mixed variant, in which psychomotor activity and arousal vary irregularly and changes are unexpected and sudden, is the variant of delirium seen most often.
“This is the form of delirium where staff and caretakers might be more at risk, because the change is so unpredictable. So it’s important to educate staff on these various presentations,” Dr Valentine added.
Up to 40% of patients with cancer and up to 50% of stem-cell transplant recipients have delirium. “At MD Anderson, we have the largest transplant program in the United States, and a good percentage of the delirium patients we service are coming off of stem-cell programs,” Dr Valentine said.
In advanced cancer, the prevalence can reach 80%, and delirium on the whole costs up to $152 billion annually in the United States, “which means great financial implications for an already overburdened system,” he emphasized.
Common causes of the syndrome include infection, hypoxia, metabolic disturbance, intoxication, and drug withdrawal. “All drugs have some chance of causing delirium, but there are some heavy hitters. And for particularly impaired patients, or patients with baseline-impaired cognition who are going to be vulnerable to everything, the drugs that might not otherwise be frequent offenders for delirium may put the patient into a delirious state,” Dr Valentine suggested.
He warned that providers should be aware when using prokinetic drugs, such as metoclopramide, and sedatives, such as benzodiazepine. Certain chemotherapy drugs, such as ifosfamide and methotrexate (especially intravenous, high-dose, or intrathecal), are also associated with delirium, and when interferon is given with interleukin, “you can almost predict delirium or a cognitive disorder,” he said. “But these patients are often quite critically ill when they’re receiving these agents, so it may be hard to pin the delirium on the agent itself.”
In the stem-cell transplant setting, conditioning drugs, such as busulfan, can contribute to delirium. Dr Etter warned that in the transplant population, delirium is most likely to occur approximately 2 weeks posttransplant, when mucositis is getting worse and more opioids are used for pain management.
“Sometimes these patients have been stabilized, but now it’s the delirium that’s keeping them in the hospital,” said Dr Valentine. Few reports of delirium have been associated with immunotherapy agents, but with the increasing use of these drugs, this could change, he added.
Reducing Risk and Managing Symptoms
“We want to start by trying to resolve the fact that delirium is underrecognized and undertreated,” said Dr Etter. “It’s so common in oncology patients that it’s almost seen as normal and part of the process—they get disoriented and confused. It’s not seen as something that has significant consequences for functioning and morbidity.”
He stressed the importance of screening; awareness; management of nonmodifiable risk factors (ie, age, baseline cognitive impairment, preexisting mental disorders) and potentially modifiable risk factors (ie, metabolic disturbances, >3 medications added, use of bladder catheters); and timely and accurate diagnosis and monitoring of delirium symptoms.
When delirium does show up, Dr Etter urges clinicians to use behavioral strategies and some level of pharmacologic management, while also working to resolve the associated underlying cause. “This can be tricky, because the average delirium has approximately 3 things causing it, and in oncology patients there’s a bit of a limited ability to affect some changes and manage some of those contributors,” Dr Etter noted.
“Since delirium in many ways is a disturbance in arousal, sleep matters,” he added. “We want to do what we can to make sleep easier to get, to make it more consolidated and restful, and to work to maintain circadian rhythms, which can be really tricky in a hospital environment.”
In the management of patients with cancer, the use of certain medications is unavoidable, but according to Dr Etter, a big part of preventing delirium is avoiding unnecessary prescriptions. “Pain itself can contribute to delirium, but pain management medications can also contribute. So it’s really important to strike a balance in terms of managing pain,” he said. When a patient with cancer is at high risk for delirium, Dr Valentine recommends regular planned medication reviews so only necessary drugs are administered.
Dr Etter also emphasizes the importance of collaborating with patients on treatment goals and enlisting the help of behavioral health providers, because the use of behavioral health strategies to manage pain and psychosocial stress is associated with decreased opioid dosing.
Clinician assessment is the gold standard in the diagnosis of delirium, but screening and assessment scales can still be helpful. “Oftentimes, nursing staff are in a better position to monitor delirium, because they’re going into patients’ rooms more often, and they’re more able to see the fluctuating course of delirium symptoms,” said Dr Etter. He explained that a doctor may only see a patient once a day, and if the patient is alert at that time, the doctor may miss the fact that the patient has episodes of disorientation, lethargy, or dysregulation.
When delirium symptoms have been identified, the subsequent differential diagnosis is of utmost importance so as to avoid misclassification of delirium as depression or dementia.
According to Dr Valentine, there are no medications approved by the FDA for delirium, but antipsychotics are the first-line treatment, and haloperidol remains the gold standard.
“But it is possible to teach an old dog new tricks,” he said. “If you look at my prescribing practices over the past 25 years, my use of these drugs, especially the antipsychotics, has gone way down. I’m now emphasizing what’s being emphasized nationally: the idea of behavioral management for these patients, especially mobilization, and 5 to 10 years ago I wasn’t doing that.”
He says that physicians have not done a sufficient job of limiting their use of benzodiazepines. “In most settings they’re deliriogenic, and they should not be used for first-line treatment of delirium,” Dr Valentine added.
Simple interventions that help create some semblance of a normal life for patients in the hospital setting can have a profound impact, according to Dr Etter. Avoiding sensory overstimulation or understimulation is crucial, because “we want to make sure people are hearing and seeing appropriately, and we want them to be able to orient themselves to what is actually happening to them rather than having their world be muddied,” he said. This means determining whether a patient has a hearing aid or wears glasses, and, if so, making sure they are worn while the patient is awake and interactive.
During the day, Dr Etter suggests encouraging cognitive engagement of patients, and keeping the lights on and windows open in their rooms. At night, rooms should be kept fairly dark, and nursing tasks should be combined so as to avoid frequent disruptions. He encourages staff to get the patient’s vital signs and administer medications in one visit, and turn down the volume on intercoms and intravenous pumps.
The use of restraints is discouraged unless absolutely necessary, because providing patients with the opportunity to be mobile and have some sort of sensory experience reduces their risk for delirium and facilitates effective engagement with their environment. “Educating staff on how to interact with patients with delirium tends to be a more successful intervention than putting someone in 4-point restraints,” he said.
Simply asking patients whether they are oriented can be effective, Dr Etter says. He encourages keeping a clock or a calendar near their bed, keeping familiar objects in their room, and limiting room changes. Asking patients the date and time, and correcting them when they are wrong can be helpful. “It doesn’t help their orientation to get the wrong answer reinforced,” he said. “And if a patient can say ‘this is my room,’ that’s helpful.”
Family education is another crucial part of managing delirium. “No matter what we do in terms of trying to prevent or manage the symptoms, there’s going to be an extent to which delirium is there, and it’s going to be distressing,” said Dr Etter. “Patients and their families have a really tough time with it, and it’s a lot easier to deal with if they know ahead of time it’s a possibility if they have a name for this unnerving syndrome, and if they know the medical team is aware of what’s going on, and they have some strategies for managing it.”