By Marie Rosenthal, MS

Being frail might be more important than age when estimating an ICU patient’s risk for poor outcomes, even if they have COVID-19, according to two speakers at the 2023 Critical Care Congress, in San Francisco.

Frailty affects how well a patient will tolerate an insult, so it’s important to remember that even younger patients can be frail for many reasons, noted Jeremy R. DeGrado, PharmD, BCCCP, BCPS, a clinical pharmacy practice manager at Brigham & Women’s Hospital, in Boston.

For critically ill patients who are frail, even a small insult, “whether it’s dehydration or uro-sepsis or a new medication, such as a bump in their lisinopril dose” leads to a really significant change in their ability to accommodate that, Dr. DeGrado explained.

Decreases in renal function, hepatic insults and mental status changes are other examples of insults for which “outcomes are clearly different with frailty. Age is almost a secondary issue, although I think the elderly are just more commonly frail,” he said. 

Dr. DeGrado stressed, however, that frailty not only is an issue in the ICU; specialized areas of critical care, such as the MICU, also are vulnerable spots for frail patients. “A large percentage of our MICU [medical ICU] cases, for example, are hematologic oncology patients, and so frailty is extremely common there, regardless of age.”

Quality-of-Life Issues

Older ICU patients who are frail are also at risk for poorer outcomes. The condition not only increases the risk for death, but it can lead to long-term disabilities, even if these patients survive their ICU stay, added Lauren E. Ferrante, MD, MHS, an assistant professor of medicine at Yale University School of Medicine, and the director of Operations Core, Yale Claude D. Pepper Older Americans Independence Center, both in New Haven.

Dr. Ferrante and her colleagues looked specifically at the outcomes of 341 older adults with COVID-19 who survived their hospital or ICU stay during the height of the pandemic (J Am Geriatr Soc 2022 Dec 21. doi: 10.1111/jgs.18146. Online ahead of print.).

“We identified four functional trajectories after a COVID hospitalization among older adults,” she told Infectious Disease Special Edition. “The first group was a trajectory of no disability, which included 43% of the patients. The second group had mild increased disability after discharge but fully recovered by six months (16% of patients). The third and fourth groups (23% and 18% of patients, respectively) had increased disability and did not recover over the six months after discharge,” she said.

Frailty, delirium and comorbidities were associated with worsening disability over six months post-discharge, she noted during her presentation, and age and severity of illness also were associated with the worst disability trajectory. “Pre-admission functional status—or how well a person functioned before their COVID hospitalization—was strongly associated with all of the functional trajectories over the six months after discharge,” she said.

Vigilance at Discharge Also Important

Besides considering what is happening to an older patient in the ICU, it's important to examine the outcomes if they are discharged, both speakers said. Even if they survive, they are likely to suffer long-term cognitive and other disabilities—some of which could be mitigated, they said.

“New or increased disability is present in over one-third of older survivors of a COVID hospitalization,” Dr. Ferrante said.

Many of these disabilities might seem relatively minor—such as those affecting bathing, dressing and meal preparation, for example—but they could mean the difference between living independently and not. In addition, other problems, such as cognitive dysfunction and physical disabilities, are not minor. All of them are sure to affect the older adult’s quality of life.

“It’s important that we evaluate patient-centered outcomes among older adults who survive a COVID hospitalization. We can’t just focus on mortality,” Dr. Ferrante said. Instead, one must also focus on long-term morbidity and disability among older adults after COVID-19, she noted.

Although many older adults died in the early days of the pandemic, most survived. “That really stood out for us,” Dr. Ferrante said. “Yet, at the time, nobody was actually talking about outcomes other than mortality, especially for the [older] age group, which is being disproportionately affected by COVID.&rdquo

Need for Better Medication Management

One way to help frail, older patients, regardless of the reason they are in the ICU, is to optimize their medications to account for their compromised status. Older patients have an increased likelihood of having multiple comorbidities, and about 25% to 50% of them could be considered frail, “meaning that they have a decline in various body functions and systems.”

Those declines may increase the risk for poor outcomes such as delirium, disability and death, and also may compromise the way these patients respond to drug therapy, Dr. DeGrado said. “Across the board, we’re mostly looking at decreases in absorption, metabolism and elimination, as well as changes to distribution, most likely due to increase in adipose tissue, decrease in albumin concentrations and other factors leading to alterations in drug distribution.

“Similarly, you’ll see changes to the pharmacodynamics—things like variations in receptor sensitivity, increased permeability of the blood?brain barrier, which can increase the effects of certain medications,” he explained.

Furthermore, because these patients are more likely to be taking many medications at baseline, an ICU stay increases the potential for drug?drug interactions (OA Elderly Medicine 2013;1[1]:1). 

An awareness of these possibilities and working with the hospital pharmacist can help eliminate some of these risks for poor outcomes, he said. 

The use of sedatives and analgesics is a perfect case in point. The degree of sedation is one of the factors that healthcare workers can mitigate. Higher levels of sedation are linked to more delirium and other poor outcomes, such as  increased time on the ventilator and in the ICU, delusional memories, and post-traumatic stress disorder. A study found that patients who had delusional memories were much more likely to have worse quality-of-life scores after ICU discharge (Lancet Respir Med 2018;6[3]:213-222). The study also found that more than 70% of patients had at least one day of delirium in the ICU, and most cases were caused by the sedatives. 

“While we know that medications aren’t the only mechanism by which that can happen, we think that they play a significant role in that,” Dr. DeGrado said.

Another study found that sedation intensity increases the risk for death at 180 days (J Intensive Care Med 2022;37[8]:1060-1066). 

Deep sedation was probably the norm during the early days of COVID-19, Dr. DeGrado admitted, which could have contributed to the poor outcomes seen in so many patients. People were ventilated early, and sedated for long periods until healthcare workers figured out the best ways to treat COVID-19. This practice is particularly important for older patients because they will have reduced metabolism and elimination.

“While there’s not really a simple, real straightforward solution to [reducing deep sedation], we think application of best practices is probably our best bet: reducing infusions, more bolus therapy, patient-specific [drug] selection, less benzodiazepines,” he said.

Prescribers in the ICU also should be encouraged to adhere to best practices when it comes to pain, sedation and delirium, Dr. DeGrado stressed.

Choosing the Right Antimicrobial

Antimicrobials are another area for dose optimization to improve outcomes. “These patients are going to get a much higher level of exposure,” Dr. DeGrado said. One study looked at various antibiotics given to elderly hospitalized patients, and few had their drug concentrations remain in a therapeutic range for the time necessary to be effective (Eur J Clin Microbiol 2018;37[3]:485-493). 

“This is another reason for dose optimization and dose adjustments that are relatively frequent,” he said. “There are hepatic, renal and neurotoxicities with the use of antibiotics, not to mention increased risk for resistance and Clostridioides difficile. So making sure that we are giving the right dose, I think, is crucial, or rotating agents as needed.”

This approach “is not groundbreaking and new, but just thinking about ways that we can administer time-dependent antimicrobial agents safely by giving them as prolonged or continuous infusions, maximizing our pharmacodynamics and maximizing our MICs [minimum inhibitory concentrations] while avoiding those peaks that we know are not necessary to achieve efficacy,” he said.

Achieving vancomycin trough levels of 15-20 mcg/mL is a surrogate of an area under the curve [AUC] to MIC ratio of 400 or more, and is usually associated with improved outcomes.  However, elderly patients may not require trough levels that high to achieve their pharmacodynamic goal.

A Global Look at Medication Practices

Dr. DeGrado suggested taking a general view of overall medication practices in the ICU. “We know that there are many downsides of polypharmacy in any of our patients, but particularly in elderly patients,” he said. To properly address polypharmacy, he suggested, not only monitoring what patients are taking in the ICU, “but also making sure that drugs are discontinued when they are no longer needed.” Such efforts are worth it “because deprescribing can be as important as prescribing,” he stressed.

“We know these patients bring pharmacotherapy-related challenges,” Dr. DeGrado said.Mitigation strategies such as frequent dose minimizations or adjustments, patient-specific drug selection and deprescribing “should be done as often as possible,” he said.

Dr. Ferrante added that seminal work by geriatrician Terri R. Fried, MD, and others showed that for the older patient, “it's not mortality that matters most; it’s maintaining functional independence,” she said, noting that alleviating some of the risks for long-term disabilities will go a long way toward helping patients maintain functional independence (J Am Geriatr Soc 2020;68[3]:474-477).