Physiologic responses to exercise in survivors of critical illness: an exploratory pilot study

BACKGROUND: ICU survivors suffer from impaired physical function and reduced exercise capacity, yet the underlying mechanisms are poorly understood. The goal of this exploratory pilot study was to investigate potential mechanisms of exercise limitation using cardiopulmonary exercise testing (CPET) and 6-min walk testing (6MWT). METHODS: We enrolled adults aged 18 years or older who were treated for respiratory failure or shock in medical, surgical, or trauma ICUs at Vanderbilt University Medical Center (Nashville, TN, United States). We excluded patients with pre-existing cardiac dysfunction, a contraindication to CPET, or the need for supplemental oxygen at rest. We performed CPET and 6MWT 6 months after ICU discharge. We measured standard CPET parameters in addition to two measures of oxygen utilization during exercise (VO(2)-work rate slope and VO(2) recovery half-time). RESULTS: We recruited 14 participants. Low exercise capacity (i.e., VO(2Peak) < 80% predicted) was present in 11 out of 14 (79%) with a median VO(2Peak) of 12.6 ml/kg/min [9.6–15.1] and 6MWT distance of 294 m [240–433]. In addition to low VO(2Peak), CPET findings in survivors included low oxygen uptake efficiency slope, low oxygen pulse, elevated chronotropic index, low VO(2)-work rate slope, and prolonged VO(2) recovery half-time, indicating impaired oxygen utilization with a hyperdynamic heart rate and ventilatory response, a pattern seen in non-critically ill patients with mitochondrial myopathies. Worse VO(2)-work rate slope and VO(2) recovery half-time were strongly correlated with worse VO(2Peak) and 6MWT distance, suggesting that exercise capacity was potentially limited by impaired muscle oxygen utilization. CONCLUSIONS: These exploratory data suggest ICU survivors may suffer from impaired muscular oxygen metabolism due to mitochondrial dysfunction that impairs exercise capacity long-term. These findings should be further characterized in future studies that include direct assessments of muscle mitochondrial function in ICU survivors.