Serum activin a levels associated with mortality but not physical function in critically ill patients: a prospective observational study.

Introduction: The molecular mechanisms responsible for ICU Acquired Weakness (ICUAW) are poorly understood. Novel biomarkers may provide potential therapeutic targets, and assist in the identification of patients at risk of ICUAW. Activin A is a strong negative regulator of muscle mass, is elevated in sepsis and predicts mortality in acute respiratory failure. It is unclear whether muscle wasting in critically ill humans is related to elevated activin A levels. Objective(s): To investigate the relationship between serum activin A levels and physical function at ICU and hospital discharge. Method(s): This study was a prospective longitudinal observational cohort study. To date, 16 participants have been recruited from 2 tertiary ICUs from metropolitan hospitals in Melbourne, Australia. Participants were included if they were mechanically ventilated > 48 hours and were expected to have a total ICU stay of > 5 days. Total serum activin A levels were measured daily in ICU by specific assays. Grip strength and Medical Research Council Sum Score (MRC-SS) were completed daily in ICU. Physical Function in ICU Test Scored, Six-Minute Walk Test and Timed Up and Go Test were completed on ICU discharge and hospital discharge. Result(s): Nine of the sixteen participants survived to complete at least one physical outcome measure. Median serum activin A levels were lower in the participants who survived to ICU discharge (pseudo-R2 0.0822, p=0.021) but were not related to in hospital mortality (pseudo-R2 0.0422, p=0.078). Initial activin A levels were lower in participants who survived to hospital discharge (pseudo-R2 0.0614, p=0.048). Serum activin A levels were not related to any of the physical outcome measures at any time point. Conclusion(s): High serum activin A levels were associated with increased mortality but not worse physical function in critically ill patients.