Severe trauma leads to sustained muscle loss, induced frailty, and distinct temporal changes in myokine and chemokine profiles of older patients

Abstract

Introduction: Sarcopenia is a known risk factor for adverse outcomes across multiple disease states, including severe trauma. Factors such as age, hyperinflammation, prolonged immobilization, and critical illness may not only exacerbate progression of this disease but may also contribute to the development of induced sarcopenia, or sarcopenia secondary to hospitalization. This study seeks to (1) determine the effects of severe traumatic injury on changes in skeletal muscle mass in older adults; (2) test whether changes in skeletal muscle mass are associated with clinical frailty, physical performance, and health-related quality of life; and (3) examine trauma-induced frailty and temporal changes in myokine and chemokine profiles.

Methods: A prospective, longitudinal cohort study of 47 critically ill, older (≥45 years) adults presenting after severe blunt trauma was conducted. Repeated measures of computed tomography-based skeletal muscle index, frailty, and quality of life were obtained in addition to selected plasma biomarkers over 6 months.

Results: Severe trauma was associated with significant losses in skeletal muscle mass and increased incidence of sarcopenia from 36% at baseline to 60% at 6 months. Severe trauma also was associated with a transient worsening of induced frailty and reduced quality of life irrespective of sarcopenia status, which returned to baseline by 6 months after injury. Admission biomarker levels were not associated with skeletal muscle index at the time points studied but demonstrated distinct temporal changes across our entire cohort.

Conclusions: Severe blunt trauma in older adults is associated with increased incidence of induced sarcopenia and reversible induced frailty. Despite muscle wasting, functional decline is transient, with a return to baseline by 6 months, suggesting a need for holistic definitions of sarcopenia and further investigation into long-term functional outcomes in this population.

Figure 1.. Flowchart depicting patient record identification, screening and enrollment numbers with inclusion and exclusion criteria.

Figure 2.. Mean SMI, PMI and mHU at baseline (T1), three (T3) and six (T4) months post-discharge.

Significant differences over time are noted for the entire cohort. Severely injured elderly patients had significant loss of skeletal muscle mass that persisted at six months. Pre-existing sarcopenia was not associated with an increased rate of muscle loss at measured time points. SMI, skeletal muscle index; PMI, psoas muscle index; mHU, muscle density.

Figure 3.. Trends in mean Rockwood CFS, EQ-5D-3L Utility Index, grip strength, and SPPB over time.

Clinical frailty was significantly increased by mean Rockwood CFS at two weeks and three months post-injury across the entire cohort (A), with lower reported HRQOL across these time points as well (B), with a recovery to baseline by six months. Dominant hand grip strength was found to steadily improve in the months post-injury (C), as did SPPB scores at three and six months (D). These trends were conserved regardless of age, baseline sarcopenia, or development of acute sarcopenia (all p>0.05). CFS, clinical frailty scale; HRQOL, health-related quality of life; SPPB, short performance physical battery.

Figure 4.. Mean biomarker and myokine concentrations at baseline (T1), two weeks/or hospital discharge (T2), and at three (T3) or six (T4) months post-discharge.

Distinct temporal trends in inflammatory marker and myokine concentrations were noted for the entire cohort and were largely conserved, with the exception of IL-10, which was significantly lower in patients with pre-existing sarcopenia compared to non-sarcopenic trauma patients at hospital admission (p=0.0497).