Returning to a Humanistic Approach of Preventing Delirium in the ICU

The COVID-19 pandemic has wrought a lot of change on health care, and now the industry is grappling with how to move forward and recapture what was lost, said E. Wesley Ely, MD, MPH, professor of medicine and critical care, Critical Illness, Brain Dysfunction, and Survivorship Center at Vanderbilt University, during the Roger C. Bone Memorial Lecture in Critical Care at CHEST 2022.

The past 50 years of critical care medicine can be split into 2 distinct periods: 1970 to 1995 was a period of construction and adding things to the patient, such as the ventilator, and 1995 to 2020 was a period of deconstruction and finding out how to remove those things as early as possible without hurting patients.

The COVID-19 pandemic, Ely argued, took the system back to those first 25 years and reverted to sticking apparatuses to patients to get them to survive. “We lost our vision of how to remove critical illness, life support systems in a way that didn't hurt people,” he said. “That, to me, is what we have to recover from.”

Ely discussed how his mentors taught him about how he needed to go to his patient’s suffering from a place of cultural empathy regardless of age, race, religion, or politics. Throughout his lecture, Ely shared patient stories, such that of as Teresa Martin, who he remembers as a lesson learned.

Martin came into the hospital with acute respiratory distress syndrome and she was in paralysis “for days and days.” During her paralysis in a coma, she received over 125 mg per day of both benzodiazepines and morphine. He saw her months later in a post-intensive care unit (ICU) recovery clinic, where he was surprised that she only manifested single organ damage (lungs). However, he didn’t even bother to mention her brain.

“How naïve I was, and how far from the truth, as I would see a few weeks later, when Teresa returned to me with her body and brain irretrievably broken,” Ely said.

Physicians fear causing harm through a medication error or errant scalpel, but he argued more harm is done by blindly accepting usual practice as best practice, which he called “malignant normality.” And during the height of the COVID-19 pandemic, physicians re-entered a period of malignant normality fell back on the kinds of practices that were used on patients like Martin.

For years after Martin, Ely was obsessed with trying to figure out how to take patients off the ventilator faster. In one study from 1996, he and his colleagues found they could get patients off 2 days earlier.¹ In the study elderly patients, compared with younger patients, had excess death and returns to the ICU; however, he would later come to realize it was not due to the lungs, but due to delirium.

The people he worked with—geriatricians, biostatisticians, nurses, and others—helped him to understand that patients in the ICU are often depersonalized at an individual level and at a population level.

“How can I practice good medicine, if I'm stripping people [of] what makes them the individuals that they are?” Ely asked. “And yet, that's exactly what delirium was doing when we put people in deep, deep coma and sedation.”

It was then he decided he wanted to study delirium, and he was discouraged by those around him: he told it was a bad idea, he wouldn’t get funding, and the research wouldn’t get into reputable journals.

However, then he met Donna Hilley, who had been a CEO on Music Row in Nashville, Tennessee. She was in the ICU and it just so happened that her sister taught about delirium at Kaiser Permanente in California. Hilley was given the usual treatment—benzodiazepines and put on a ventilator—and at the end, she was frail and broken cognitively. According to Ely, Hilley’s life was never the same. She retired, walked with a cane, and never got back what she had before.

He began to wonder if GABAergic drugs, like benzodiazepines, were worth it.

“We had been hoodwinked,” he said. “Benzo[diazepine]s were the number one drug in the world. At one time, every patient in the ICU got tremendous amounts of these drugs.”

In 2007, he coauthored a study² the corroborated the notion that switching from benzodiazepines was a good idea, and the study also signaled that less intense sedation could save lives.

By the mid-2000s they knew ICU delirium was an independent predictor of death, more delirium led to higher mortality, and benzodiazepines as sedation were increasing delirium. There was a goal of reducing the incidence and duration of delirium by getting people off ventilators as soon as possible. “Because the box is a death box,” Ely said.

In 2008, he coauthored a paper on the results of the Awakening and Breathing Controlled trial,³ which found that waking the patient up daily from sedation led to a 32% reduction in the hazard of death after 1 year. The study also found the protocol reduced length of stay in the ICU by 4 days.

“This was the first time in critical care that [it] had ever been shown that reducing sedation could save lives,” Ely said. “And people didn't buy it at first. We got a lot of rejection of this message.”

What he also became convinced of was that delirium was creating a danger for the brain of survivors in terms of acquired dementia. After struggling to receive funding to study this, they finally received a $10 million grant from the National Institutes of Health. After enrolling 821 patients, they found that regardless of the age of the patient, 1 year after developing delirium in the ICU, one-fourth to one-third of patients had cognitive scores that were similar to patients who had traumatic brain injury (TBI) and Alzheimer disease.⁴

Ely has a daughter with TBI, which happened when she was 5 years old after falling headfirst off a diving board onto the cement. “All I can say is that I bring that with me into the ICU when I think about these patients, because it is a life-altering thing to lose these brain cells,” he said.

The study also found the duration of delirium was the strongest predictor of the acquisition of brain dysfunction. At this point, their research has shown delirium predicts length of stay, cost of care, death, and acquired dementia, and other research is corroborating the findings.⁵

Now that all of this is understood, they needed to find a way forward, which came in the form of the ABCDEF Bundle. The bundle is a patient safety plan:

• Analgesia: manage pain
• Both: stop drugs and stop vent
• Choice of sedation
• Delirium: assess, prevent, and manage
• Early mobility and exercise
• Family engagement and improvement

The bundle, according to Ely, is a “tool of mercy.” It allows physicians to dive into the chaos of another person’s life and provide lifting and healing, he said. The goal of the bundle is to wake people up, get them out of bed, and have them make eye contact with family members and loved ones.

In 2017, research supported the use of the bundle.⁶ In fact, as compliance with the ABCDEF Bundle went up, mortality improved, and patients had more freedom from delirium and coma. The ICU Liberation Collaborative supported the findings. As compliance with the bundle increased, so did likelihood of discharge.

He went on to show slides with almost 30 references of studies on the ABCDEF Bundle that had been published in JAMA, New England Journal of Medicine, and Lancet.

“This is incredibly robust,” Ely said. “The data are all there. Don't let anybody say to you, ‘This is warm and fuzzy.’ It may be humanistic, but it's also extremely scientifically proven.”

After all the progress made: enter COVID-19.

Early in the pandemic, research showed that 86% of patients were being treated with benzodiazepines again.⁷ Just a year prior to the pandemic, Ely had told 2 nurses to start a patient on benzodiazepine drip as a rescue drug and “they turned red.” They had never used a benzodiazepine drip. “Oh, my God, we did it. We got rid of the effing benzo[diazepine]s,” he said. “But then this [research] came out. ‘Oh, no, it's back.’”

Rates of delirium during the early months of COVID-19 had rebounded to levels seen in 2000 to 2014. A study of more than 2100 patients⁸ found that the 2 factors driving delirium in these patients were the overuse of sedations (benzodiazepines) and the underuse of family.

“What does that mean? It means we lost the [ABCEDEF] Bundle,” Ely said. Prior to COVID-19, 40 countries had compliance rates with the bundle around 70%, he said. During COVID-19, that compliance fell to 10%.

For Ely, the bundle is his tool when he needs to connect with patients and make sure they feel like a person. On his list of what to do, he recommended that providers ask the patient their favorite food, music, pets, and hobbies. “I defy you to think of a person as a set of lungs when you know these things,” he said. “You’ll have to think of them as a person.”

At the end of his lecture, Ely brought the audience back to Martin, the patient he had who set him on his learning journey. He had connected with her son, Travis, and learned he had to go to therapy and didn’t have much of a childhood because he had to care for his mother.

“I did that to her,” Ely said.

He expected the son to be angry with him, but instead, Travis recognized that the way things were done 10 or 20 years ago was different. He said that with all things, at some point, someone identifies an improvement, and Travis said that was what Ely was trying to do.

“He was exactly right,” Ely said. “It's what I've been trying to do all these years. We can look at things differently.”

References

1. Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med. 1996;335(25):1864-9. doi:10.1056/NEJM199612193352502

2. Pandharipande PP, Pub BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007;298(22):2644-2653. doi:10.1001/jama.298.22.2644

3. Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;371(9607):126-134. doi:10.1016/S0140-6736(08)60105-1

4. Pandharipande PP, Girard TD, Jackson JC, et al, BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-16. doi:10.1056/NEJMoa1301372

5. Wolters AE, van Dijk D, Pasma W, et al. Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: a prospective cohort study. Crit Care. 2014;18(3):R125. doi:10.1186/cc13929

6. Barnes-Daly MA, Phillips G, Ely EW. Improving hospital survival and reducing brain dysfunction at seven California community hospitals: implementing PAD guidelines via the ABCDEF Bundle in 6,064 patients. Crit Care Med. 2017;45(2):171-178. doi:10.1097/CCM.0000000000002149

7. Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020;382(23):2268-2270. doi:10.1056/NEJMc2008597

8. Pun BT, Badenes R, Heras La Calle G, et al, COVID-19 Intensive Care International Study Group. Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study. Lancet Respir Med. 2021;9(3):239-250. doi:10.1016/S2213-2600(20)30552-X