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

Abstract

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 (VO2-work rate slope and VO2 recovery half-time). Results We recruited 14 participants. Low exercise capacity (i.e., VO2Peak < 80% predicted) was present in 11 out of 14 (79%) with a median VO2Peak of 12.6 ml/kg/min [9.6–15.1] and 6MWT distance of 294 m [240–433]. In addition to low VO2Peak, CPET findings in survivors included low oxygen uptake efficiency slope, low oxygen pulse, elevated chronotropic index, low VO2-work rate slope, and prolonged VO2 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 VO2-work rate slope and VO2 recovery half-time were strongly correlated with worse VO2Peak 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.

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

“…Six months after critical illness has been overcome, mitochondrial content may restore up to normal, but structural and possibly functional impairments might persist over months, accompanied by marked muscle weakness and wasting [ 83 , 195 ]. This is supported by recent data showing that even few days of critical illness may contribute to significant alterations of mitochondrial respiratory activity up to 6 months after ICU admission [ 196 ]. Considering the dynamics of mitochondrial dysregulation during the course of critical illness, several interesting attempts can be made to restore and improve mitochondrial function and patient outcome.…”

Functional Limitations and Exercise Intolerance in Patients With Post-COVID Condition

“…Two reports found decreased VT and increased lactate levels after COVID-19, whereas other studies found no difference in VT between patients with PCC and control participants . Importantly, the former studies included patients with relevant comorbidities, hospitalizations, and occasionally intensive care or mechanical oxygen support, factors that are known to have adverse effects on peripheral muscle tissue …”

Use of portable single‐lead electrocardiogram device as an alternative for QTc monitoring in critically ill patients

“…Changes in HR between devices that led to a difference in numerical precision could be explained by a change in position from supine to sitting with an exaggerated response in relation to deconditioning, autonomic disturbances, as well as rapid changes in clinical status that can occur in ICU patients. Resting heart rate might be faster in a sitting position compared with lying, and variations in heart rate as well as QTc interval and dispersion can be produced by postural changes, especially in critically ill patients who may develop physical deconditioning and orthostatic intolerance (Aglawe et al., 2022 ; Borst et al., 1982 ; Fortrat et al., 1999 ; Jones et al., 2003 ; Levine et al., 1997 ; Mart et al., 2022 ; Nakagawa et al., 1999 ). Even though formulas try to correct QT according to heart rate, rapid changes in the R‐R interval secondary to position changes might not be adequately corrected by them (Kubo et al., 2005 ; Markendorf et al., 2018 ).…”