Relationship of admission plasma gelsolin levels to clinical outcomes in patients after major trauma.
Actin-scavenging proteins, e.g., plasma gelsolin, counteract the pathophysiological consequences of actin leaked into the circulation from dying cells, but the capacity of this defense system can be overwhelmed by massive tissue injury. We examined the prognostic implications of plasma gelsolin levels obtained near the time of admission to our level I Trauma Unit on the subsequent clinical course in a group of patients with severe traumatic injuries. Blood samples were obtained from 13 patients shortly after major trauma and 11 healthy volunteers who served as the control group. Plasma gelsolin levels were assayed by quantitative Western blotting. Duration of mechanical ventilation, stay in the Trauma Intensive Care Unit, and development of acute respiratory distress syndrome (ARDS) were measured as clinical outcomes reflecting the complexity of the hospital course. Subsequently, we evaluated an additional 52 patients after major and minor trauma to extend our earlier observations. Plasma gelsolin concentrations were significantly lower in our 13 original patients compared with healthy controls. Levels below 250 mg/L (> 2 standard deviations below the mean of the control group) were associated with prolonged mechanical ventilation and a stay in the intensive care unit >/= 13 days. Both patients whose gelsolin level was < 100 mg/L in this first series developed ARDS. Including all 65 patients, 6 of the 10 patients who developed ARDS had admission gelsolin levels less than 250 mg/L, compared with only 7 of the 55 patients without ARDS (p = 0.0028). The mean gelsolin levels were 193 and 400 mg/L in patients with and without ARDS, respectively (p < 0.0001) and 398 mg/L in survivors versus 259 mg/L for patients who expired (p < 0.0001). Ten of the 13 patients (77%) with gelsolin levels at the time of admission more than 2 SD below the control mean had "bad outcomes," defined as mechanical ventilation for >/= 13 days in the Trauma Intensive Unit, ARDS, and/or death. Plasma gelsolin levels appear to be an early prognostic marker in patients experiencing major trauma. Whether circulating gelsolin serves a biologically vital function or is simply depleted after massive trauma cannot be determined from our study. The potential therapeutic benefits of infusions of recombinant human plasma gelsolin for patients in whom multiorgan dysfunction commonly follows a serious but self-limited insult have not yet been investigated.