By Kathryn Radigan, MD
Attending Physician, Division of Pulmonary and Critical Care, Stroger Hospital of Cook County, Chicago; Assistant Professor of Medicine, Rush University Medical Center
Dr. Radigan reports no financial relationships relevant to this field of study.
SYNOPSIS: Although increased strength at hospital discharge is associated with improved five-year survival in acute respiratory distress syndrome survivors, weakness at discharge, whether resolving or persistent, is associated with worse subsequent survival.
SOURCE: Dinglas VD, Aronson Friedman L, Colantuoni E, et al. Muscle weakness and 5-year survival in acute respiratory distress syndrome survivors. Crit Care Med 2017;45:446-453.
Although associations between inpatient measures of muscle weakness and increased hospital mortality and worse survival up to a year later have been reported, the relationship between muscle weakness and long-term survival remains unclear.
To investigate the relationship between post-ICU muscle weakness and five-year survival trajectories, Dinglas et al conducted a longitudinal, prospective cohort study in 13 medical, surgical, and trauma ICUs within four hospitals in Baltimore.
All patients who were mechanically ventilated and met the American-European Consensus Conference criteria for acute lung injury (ALI) were screened. Patients were excluded from enrollment if they had a high short-term mortality unrelated to acute respiratory distress syndrome (ARDS), an important barrier to outcome assessment, or substantial exposure to critical care services prior to enrollment.
The consenting patients then were evaluated prospectively at three, six, 12, 24, 36, 48, and 60 months after ARDS onset. In addition to vital status, the date and cause of death was determined from family members and then verified through a commercial version of the Social Security Death Master File. If the vital status could not be ascertained, the patient was censored according to his or her last day known to be alive.
Muscle strength was examined with standardized manual muscle testing using the Medical Research Council (MRC) sum score (range, 0-60; higher is better) at hospital discharge and at three, six, 12, 24, 36, and 48 months after ARDS. Post-ICU weakness was defined as a sum score < 48.
Out of 274 ARDS survivors who were eligible for consent, 156 patients consented to enroll in the study. For those who did not consent, 71 were unable to consent at hospital discharge, 22 were unable to complete strength assessment at discharge, 16 withdrew consent during follow-up, and nine were unable to complete strength assessment at follow-up.
At discharge, 38% of patients experienced muscle weakness. For every one point increase in MRC sum score at discharge, there was an association with improved survival (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.98). The outcomes were similar when followed longitudinally (HR, 0.95; 95% CI, 0.93-0.98).
Even though the presence of weakness at discharge was associated with worse five-year survival (HR, 1.75; 95% CI, 1.01-3.03), the association was diminished and no longer significant when evaluated longitudinally over five-year follow-up (HR, 1.54; 95% CI, 0.82-2.89).
Compared to patients with the trajectory of no muscle weakness, patients with persistent or resolving trajectories of muscle weakness also were associated with worse survival (HR, 3.01; 95% CI, 1.12-8.04 and HR, 3.14; 95% CI, 1.40-7.03, respectively).
More than one-third of ARDS survivors experienced muscle weakness. Patients with more strength at discharge and during follow-up experienced improved five-year survival. ARDS survivors who experienced both persistent and resolving trajectories of muscle weakness experienced worse survival.
COMMENTARY
Although it is well described that ARDS survivors who experience muscle weakness as inpatients experience increased hospital mortality and worse one-year survival,1,2 the relationship between muscle weakness and late mortality in ARDS survivors is unknown.
To further investigate the association of post-ICU muscle weakness with long-term survival, Dinglas et al conducted a five-year prospective, multisite, longitudinal follow-up study of 156 ARDS survivors. Thirty-eight percent of survivors experienced muscle weakness at discharge, and ARDS survivors with greater strength at discharge and during follow-up were noted to demonstrate improved survival. Experiencing trajectories of persistent and resolving muscle weakness was associated with three times greater risk of death.
Although this study revealed that ARDS survivors who are weak at discharge experienced a poorer long-term prognosis, there remain many unanswered questions. The main concern regarding the study is that there appears to be an underestimate of patients who experienced muscle weakness at discharge.
The study authors estimated approximately 38% of patients were weak at discharge, but 22 patients were excluded from the study because they were not able to complete strength assessment at discharge, and nine patients were unable to complete strength assessment at follow-up. These populations clearly represent weak patients. Furthermore, 71 patients were unable to consent. A population without the ability to consent also may have represented a significant number of weak patients.
It also remains unclear whether there is a direct relationship between muscle weakness and long-term mortality, or whether weakness in ARDS survivors is a marker of a larger overarching theme of new-onset frailty or pre-existing frailty worsened by critical illness.
Although the question of new-onset frailty is more difficult to address, researchers did their best to address pre-existing frailty. Patients who would be viewed at the extreme spectrum of pre-existing frailty were excluded. This included patients with life expectancies less than six months due to pre-existing illness, patients who had an order that limited the use of life support therapies, patients with cognitive impairment, and patients with substantial exposure to critical care.
The concern for frailty was addressed further after adjusting for age, Charlson comorbidity index, and mean daily Sequential Organ Failure Assessment (SOFA) score. After adjusting for these factors, increased muscle strength at hospital discharge still was associated with long-term survival. For every one-point increase in MRC sum score, there was an association with improved survival (HR for death, 0.96; 95% CI, 0.94-0.98; P < 0.001). Although often thought to be a subjective measure, researchers did their best, as MRC was under rigorous quality control and evaluated as a continuous and binary (MRC sum score < 48) exposure variable.
This study highlighted that five-year outcomes for ARDS survivors were very similar to one-year outcomes. Once a patient developed weakness, adverse outcomes followed, even if the patient was on a trajectory to recovery. Further research that aims to determine the mechanisms linking muscle weakness, mortality, and treatments to potentially mitigate this relationship is critical.
For now, clinicians must stress the importance of starting rehabilitation as soon as possible after the initiation of mechanical ventilation. Schweikert et al highlighted this concern, as they were able to show that interruption of sedation along with physical and occupational rehabilitation is most important during mechanical ventilation, specifically within a median of 1.5 days after intubation.3
Additional studies also have shown that early ICU rehabilitation is associated with decreased one-year rehospitalization and mortality.4
For now, timely physical and occupational rehabilitation, a sedation protocol, and aggressive appropriate extubation are critical. It also is prudent that physicians caring for ICU survivors after hospitalization are apprised of these data as knowledge of these outcomes should help in the planning of care decisions. ICU follow-up clinics, which provide comprehensive care to ICU survivors, hopefully will become a norm in the future.
In conclusion, more than one-third of ARDS survivors experience muscle weakness, and this is a key determinant of functional disability and late mortality. Even ARDS survivors who experienced resolving trajectories of muscle weakness over time experienced increased rates of five-year mortality.
REFERENCES
- Ali NA, O’Brien JM, Jr., Hoffmann SP, et al. Acquired weakness, handgrip strength, and mortality in critically ill patients. Am J Respir Crit Care Med 2008;178:261-268.
- Hermans G, Van Mechelen H, Clerckx B, et al. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med 2014;190:410-420.
- Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: A randomised controlled trial. Lancet 2009;373:1874-1882.
- Morris PE, Griffin L, Berry M, et al. Receiving early mobility during an intensive care unit admission is a predictor of improved outcomes in acute respiratory failure. Am J Med Sci 2011;341:373-377.
Although increased strength at hospital discharge is associated with improved five-year survival in acute respiratory distress syndrome survivors, weakness at discharge, whether resolving or persistent, is associated with worse subsequent survival.
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