Researchers Need to Study ARDS Survivors After They Leave the ICU
By Michael Gibbons

Survivors of acute respiratory distress syndrome are like the old soldiers in Gen. Douglas MacArthur's famous quote: They just fade away. After ARDS patients win the battle for their lives in ICUs, stabilize and exit hospitals' doors, they're no longer subject to the same intense clinical scrutiny.

Too few of these veterans of critical illness are asked how they feel and what they think two, four, 10 or more years after their ordeals. But their self-assessments, insights and observations could help physicians take the full measure of ARDS. Such knowledge could help new ARDS patients cope emotionally with the lingering deficits that will alter their lives forever.

When ARDS survivors were asked recently what bothered them during the late phases of recovery, they cited severe sleep disruptions, hallucinations, depression, disturbing dreams and memories about the ICU, persistent memory lapses, cognitive difficulties, anger and guilt over what they put their families through, and dismay over personality differences and changes to their voices. Many survivors were surprised at how long it took them to recover and complained of not having enough information about what they had gone through. ₁

QUALITY OF LIFE

For instance, studies of bronchoalveolar lavage fluid in ARDS survivors suggest that intervening in the inflammatory process during the acute phase not only improves patients' immediate survival but also their long-term physiologic measures, such as forced vital capacity (FVC).

Positive changes in FVC and other measures can affect patients' quality of life, the metric that matters most to patients. "People, to some extent, are willing to trade quantity of life for quality if their quality of life is very poor," said Dr. Curtis of Seattle's Harborview Medical Center.

As with other measures, quality of life in the years following the acute phase of ARDS and acute lung injury (ALI), a secondary complication of ARDS, remains largely unexplored. "We don't have much knowledge of the causal pathways toward decreased health-related quality of life and decreased mental health status after acute lung injury," observed Craig Weinert, MD, another ATS speaker. "Until we firm up these causal pathways, we'll have a hard time answering the question: How long do the effects of ALI persist?"

A number of tools exist that can take objective measurements of health-related quality of life (HRQL) in ARDS survivors, explained Kenneth Steinberg, MD, an associate professor of medicine, also at Harborview.

Most are generic, such as the sickness impact profile, the Short Form-36, the perceived quality of life scale, the Center for Epidemiologic Studies depression score and the post-traumatic stress syndrome score. A few are respiratory specific, such as the St. George Respiratory Quotient (SGRQ) and the Chronic Respiratory Questionnaire (CRQ).

According to data from ARDS patients who have taken these questionnaires, HRQL is impaired initially after the acute phase but improves over time, with the most dramatic improvements occurring three to six months after extubation, Dr. Steinberg said. Patients under age 40 continued to improve after six months in self-reported health status reports, unlike those on the other side of 40.

"HRQL and functional status are severely affected by ARDS but improve over time, and the improvement after a year is variable," Dr. Steinberg observed. "We must identify risk factors that lead to abnormal HRQL, then develop interventions to minimize these long-term adverse outcomes ARDS patients are reporting. Clinical trials now need to include HRQL and other outcomes, and we need to have information to provide to patients."

DISPARITY

Dr. Steinberg also noted a curious phenomenon: Patients' perceptions of their HRQL "don't always correlate with objective measures of health outcome." Apparently, a spirometer can measure the capacity of a lung but not the capacity of a patient to endure suffering.

In a study published in 1988, Donald Patrick, PhD, MSPH, et al. examined 69 ICU survivors over age 65 who all had relatively short ICU stays. He administered to each patient the perceived quality of life test scale as well as the sickness impact profile. "Some patients with severe dysfunction on the sickness impact profiles nevertheless had very high satisfaction levels with their lives and vice versa," Dr. Steinberg reported.²

Patrick et al. speculated that such patients either rationalize about their decreased functional status or else adjust to lower levels of health. "These results suggest that failure to return to pre-admission functional status may not diminish patient satisfaction with their lives or their willingness to undergo the ICU experience again," Dr. Steinberg said. "Most seem to adapt to their lower level of functionality."

Consider, for instance, the remarkable emotional resilience displayed by someone near and dear to Dr. Steinberg — his aunt. Some years after undergoing a splenectomy, she developed pneumococcal sepsis, ARDS, renal failure and wound up as a quad amputee due to disseminated intravascular coagulation.

"She would score pretty poorly, I think, on a lot of our health-related quality of life scores," he said. "But she is thrilled to be alive and to see multiple members of her family get married, have kids and graduate."

On the other hand, many who survive ARDS perceive themselves as much sicker than warranted by the relatively mild abnormalities in vital capacity they sustain, according to Dr. Weinert. True, these patients suffer diminished exercise capacity due to neuromuscular weakness in their peripheral muscles. That's enough to torpedo their self-assessment of their physical function.

"It's quite distressing to patients when they feel as weak as a wet noodle for months and months despite the fact that their doctors say their lungs are all fine," Dr. Weinert pointed out.

Dr. Steinberg concluded: "This disparate view that patients sometimes have about their own quality of life and what we measure with tests is something we need to struggle with."

ARDS AND COGNITION

ARDS survivors must not only recoup their physical stamina, they have to clear away the mental cobwebs as well.

Ramona Hopkins, PhD, of the department of critical care medicine at LDS Hospital in Salt Lake City, Utah, studied cognition in ARDS patients from 1994 to 1999 using standardized tests and questionnaires. Every patient she followed had some cognitive impairment at discharge and most still struggled with problems of memory, attention and other thought processes a year later.³

Dr. Hopkins originally enrolled 116 ARDS patients on mechanical ventilation with PaO₂/FiO₂ < or equal to 150 mmHg. Of these, 42 died within a year while undergoing ICU treatment. Of the remaining 74 (33 men and 41 women), three died before the one-year follow-up. Four others declined to participate in cognitive testing.

The patients averaged 46 years of age with a few over age 60. They averaged 28 days in the ICU.

Dr. Hopkins' team tested depression/anxiety, IQ, memory, attention, synaptic processing speed, and the ability to think, organize and solve problems that is known, collectively, as the brain's "executive" function.

Most patients (61 percent) still had cognitive impairment a year after discharge in at least one area. Processing speed was the most commonly impaired area, followed by memory, executive function, attention span and IQ. Fifteen percent of the patients showed more pronounced anxiety and depression.

Like mountain climbers who suffer altitude sickness, ARDS survivors incur cognitive deficits from low levels of tissue oxygen, Dr. Hopkins noted. Her team took more than 170,000 pulse oximetry measurements. These data showed a mean O₂ sat. of < 90 percent for 114 hours per patient (a few as high as 700 hours); < 85 for 11 hours per patient and < 80 percent for 0.8 hours per patient.

Significant correlations emerged between decreased O₂ sat. and attention, IQ, memory, executive function and processing speed. "The amount of time a patient was hypoxemic was associated with impaired cognitive performance," Dr. Hopkins said. "Hypoxemia may explain why some patients had problems returning to work or problems performing work."

She thinks inflammation and elevated cytokine levels also may correlate to cognitive deficits. Furthermore, CT scans of the brains of 15 ARDS patients (nine males) who spent longer than the usual 28 days in the ICU showed significant enlargement of the lateral ventricles. This finding indicates brain atrophy; as brain tissue dies, cerebral spinal fluid fills in the area, resulting in ventricular enlargement.

"I think (cognitive deficits in ARDS survivors) are really multifactorial, but there might be a number of factors we can look at for intervention to improve brain outcome," she concluded.

ADVISING PATIENTS

Physicians can glean the results of existing ARDS research to advise patients of what to expect in the future, said Dr. Weinert of the University of Minnesota Medical Center in Minneapolis. First of all, if patients survive the acute phase and are off the ventilator for 30 days or so, "we can usually tell them they are unlikely to die at this point," he said.

Pulmonary function diminishes after the acute phase of ARDS, then improves and stabilizes by six to 12 months post-extubation. Most patients have only mild dysfunction. They tend to show a marked decrease in activities of daily living that improves to near normal six months out or so, according to randomized trials of carefully selected patients with minimal amounts of co-morbid conditions.

Dr. Weinert recommended giving this advice to patients suffering ALI:

ALI shouldn't shorten your life once you get off the ventilator, but what caused you to get ALI may. Your pulmonary function should improve during the next six months, but your respiratory symptoms and decreased exercise capacity may persist for years. And you may have problems thinking for a year or more that may cause job or relationship difficulties. You may have mood problems or distressful thoughts about your time in the ICU. If these are more than just mild, or if they persist, you may need to have them evaluated and seek further help.

Michael Gibbons is senior associate editor of ADVANCE.