Combination reduces agitated delirium among patients with advanced cancers
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The addition of lorazepam to haloperidol reduced symptoms of agitated delirium among individuals with advanced cancers, according to study findings.
The double blind randomized trial included 75 patients with advanced cancer admitted to acute palliative care units with delirium and recalcitrant agitation. Trial participants had received nonpharmacologic treatment and low-dose haloperidol.
Researchers assigned patients to one of four regimens: scheduled haloperidol (n =16), lorazepam (n=20), combination haloperidol and lorazepam (n =19) or placebo (n=20).
Range in Richman Agitation Sedation Scale (RASS) score in the first 24 hours served as the study’s primary outcome.
All groups showed significant reductions in RASS scores at 24 hours, findings presented at ESMO Congress showed.
A prespecified intention-to-treat comparison revealed significantly lower RASS scores with lorazepam-only vs. haloperidol only (mean difference,-2.1; 95% CI, –3.4 to –0.9), as well as between the haloperidol-lorazepam combination group vs. haloperidol only (–2.0; 95% CI, –3.2 to –0.8).
Individuals assigned placebo required significantly more rescue doses within the initial 24 hours.
“We’re interested in understanding how we can take these findings and implement them in a personalized way,” researcher David Hui, MD, MSc, director of supportive and palliative care research at The University of Texas MD Anderson Cancer Center, told Healio. “We want to find the right treatment for each patient and ultimately provide goal-concordant care at the end of life.”
Hui spoke with Healio about current treatments for agitated delirium in advanced cancer, and discussed the importance of managing this distressing condition.
Healio: How prevalent is agitated delirium among people with advanced cancer, and what impact does it have?
Hui: When patients enter the last days and weeks of life, delirium or confusion becomes very common. It’s almost universal. Brain function begins to deteriorate and, in about half of those patients, the brain is not able to control this restlessness or agitation.
Agitated delirium has a huge impact on patients’ well-being, and the well-being of the people around them. When patients are confused, they might be aware of the fact that they are confused. It's a bit like when people are intoxicated — they might be aware that their behavior is altered, but they can’t necessarily control it. When patients are restless, they sometimes pull on their IVs, they pull tubes out, or they fall out of bed. They might say or do things they don’t mean. It’s upsetting to the patients themselves and to their loved ones. Providers also find it challenging to see the patient in this state. We want to help, but our treatment options are limited.
Healio: What is the current treatment for agitated delirium?
Hui: There is a wide range of options. There are nonpharmacologic measures like hearing aids, keeping patients hydrated and keeping the room dark. These options have been studied but, when a patient is agitated, these are difficult to implement.
Haloperidol is the most common medication option for reducing restlessness or agitation. Other options — such as lorazepam — are occasionally used, but the evidence is so mixed that some people are concerned about using it. Others feel it is necessary to give patients additional support. That’s why we needed a study to answer these important questions.
We conducted an NIH-funded four arm study to compare haloperidol with haloperidol plus lorazepam, lorazepam alone or placebo. The placebo arm allowed us to see whether these medications are truly useful.
Healio: What did you find?
Hui: We found lower levels of agitation in the three groups that used medication. Patients who received medication required fewer doses of rescue medications. This is important, because every dose of rescue medication indicates a failure of our treatment to prevent the agitation. This means a lot of suffering along the way, at a critical time of life. Our findings suggest that a more proactive approach to using these medicines can be useful. We also found that, consistent with a previous finding of ours, haloperidol plus lorazepam was more effective than haloperidol alone, and lorazepam alone was quite effective, as well. This opens some opportunities to consider these regimens for this unique situation.
Healio: What is the most important take-home message or clinical implication of your findings?
Hui: Our data support the use of these medications in a proactive manner because, when we give placebo, patients are more restless and need more doses of rescue.
Another important message is that there’s not just one way to give these medications. We evaluated these three regimens, and they are all possibilities to consider. We just need to know the strengths and weaknesses of each of these approaches.
Of course, more sedation will make people sleepy, and they may not be as communicative. These patients have fairly resistant delirium, so it’s not as though they are communicating well to begin with. However, sometimes a family member doesn’t want their loved one to be sleeping all of the time. The goals are very personal, and that is why we need to have options. Our study provides potential for these options. Having conversations with each family gives us an opportunity for us to personalize this approach further.
Healio: Is there anything else you’d like to mention?
Hui: We are incredibly grateful to the patients and family members who were involved in this study. Even in the last days of their lives, they were willing to help us answer some of the most challenging questions about a difficult condition.
References:
- ESMO: Combination therapy reduced agitated delirium in patients with advanced cancers (press release). Available at https://www.mdanderson.org/newsroom/esmo--combination-therapy-reduced-agitated-delirium-in-patients-with-advanced-cancers.h00-159700701.html. Posted Sept 13, 2024. Accessed Oct 14, 2024.
- Hui D, et al. Abstract # 14760. Presented at: European Society for Medical Oncology Congress; Sept. 13-17, 2024. Barcelona, Spain.
For more information:
David Hui, MD, MSc can be reached at dhui@mdanderson.org.
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