Understanding and improving the long-term sequelae of ARDS

Recent research has been instrumental to understanding the long-term sequelae of acute lung injury (ALI)/ARDS. The information we present here is based on a recent review of this topic.¹ It is important to note that since patients' baseline status is not usually known, the understanding of long-term outcomes is frequently based on an imperfect comparison with population norms. These norms may not accurately represent the baseline status of patients with ALI, since these patients may be less healthy than the general population.

The major sequelae

The 6 general categories of the common sequelae of ALI are pulmonary, neuromuscular, physical function, neurocognitive, psychiatric, and quality of life (QOL).

• Pulmonary sequelae: Most ALI survivors initially have some impairment in lung function.^1,2 A reduction in carbon monoxide–diffusing capacity is the most common abnormality; it persists for at least 1 to 2 years after the patient is discharged.^1,2 Obstructive and restrictive defects in pulmonary function also are common and are typically mild.
• Neuromuscular sequelae: Neuromuscular weakness and other musculoskeletal problems are important in patients with ALI because they attribute these sequelae to impaired physical function, which is experienced during the first year of recovery.² The cause of neuromuscular sequelae is poorly understood, but it is likely multifactorial, with contributions from disuse atrophy, systemic corticosteroid use, and critical illness neuromyopathy.^2-4
• Physical function: Objective measures of impaired physical function have included patient-reported outcomes, such as delayed return to work and impairment of activities of daily living, and lower-than-predicted performance on the 6-minute walk test.^1,2
• Neurocognitive sequelae: At hospital discharge, patients with ALI have a variety of neurocognitive impairments, including deficits in attention, short-term memory, and concentration and/or global loss of cognitive function. There is improvement in these deficits at 1 and 2 years' follow-up, but 80% of patients still demonstrate some impairment in at least one measure of cognitive function.^5,6
• Psychiatric sequelae: Patients with ALI are exposed to significant physical and emotional stress in the ICU. These stressors put them at risk for long-term psychiatric morbidity. Specifically, symptoms of depression, anxiety, and posttraumatic stress disorder (PTSD) are relatively common, and PTSD may persist for many years after ALI.⁷
• QOL: As a result of these physical, cognitive, and mental health impairments, ALI survivors have reduced QOL. Studies have consistently demonstrated significantly lower QOL (compared with age-and sex-matched population norms) for years after ALI. The most rapid improvement in QOL occurs during the first 6 months after hospital discharge.⁸ These QOL impairments are generally greater in domains related to physical health than in domains related to mental health.

Improving outcomes

To develop methods for improving outcomes of ALI survivors, new research is aimed at determining the association of patients' disease characteristics and ICU management with their long-term impairments.⁹ We describe 3 examples of recent advances.

First, early mobilization in the ICU, through more intensive physical therapy and ambulation of mechanically ventilated patients, is aimed at reducing neuromuscular sequelae and improving functional status. Initial results appear promising, but significant change in ICU culture may be needed to successfully implement this advance in therapy.^10-12

Second, reducing oversedation in the ICU, via daily interruption of infusions and/or protocol-based, goal-directed sedation therapy, may improve patient's long-term outcomes, especially psychiatric sequelae.¹³ Sedative and analgesic medications routinely used in the ICU, such as lorazepam and morphine, are associated with delirium,^14,15 which is an independent predictor of death and other adverse events in ICU patients.¹⁶ Moreover, recent research is investigating the potential benefits of novel sedative agents, such as dexmedetomidine, for more effective management of sedation and reduction in delirium in the ICU, with long-term follow-up under way.¹⁷

Third, tight control of blood glucose levels in the ICU may have several important potential benefits, including reduced muscle weakness during hospitalization, which may translate into improved long-term physical function.^18,19 However, preliminary data also demonstrate that hypoglycemia in the ICU is independently associated with an increased risk of symptoms of depression during early recovery from ALI (D. M. Needham, unpublished data). Thus, tight control of blood glucose levels with careful avoidance of hypoglycemia may improve both physical and mental health outcomes.

Additional studies are under way to further evaluate the long-term outcomes of new interventions for patients with ALI. For example, we are evaluating 6- and 12-month physical, mental, and cognitive health outcomes of ALI survivors for 2 large multicenter trials, conducted by the NIH's ARDS Network. These trials will evaluate both the short- and long-term outcomes of nebulized albuterol and nutritional therapies in the ICU (see clinicaltrials.gov ID: NCT00434993 and NCT00609180).^20,21

Thus, although ALI commonly has a significant and persistent effect on many body systems, greater understanding of the cause of these sequelae and advances in improving patient outcomes are emerging.

ABDULLA AL DAMLUJI, MBChB, MPH
Division of pulmonary and critical care medicine, Johns Hopkins University School of Medicine, Baltimore.

KRISTIN A. SEPULVEDA, BA
Division of pulmonary and critical care medicine, Johns Hopkins University School of Medicine, Baltimore.

DALE M. NEEDHAM, MD, PhD
Assistant professor of medicine, division of pulmonary and critical care medicine, Johns Hopkins University School of Medicine, Baltimore.

References:

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