Relationship of admission plasma gelsolin levels to clinical outcomes in patients after major trauma

Actin-scavenging proteins, e.g., plasma gelsolin, counteract the pathophysi ological consequences of actin leaked into the circulation from dying cells , but the capacity of this defense system can be overwhelmed by massive tis sue injury. We examined the prognostic implications of plasma gelsolin leve ls obtained near the time of admission to our revel I Trauma Unit on the su bsequent clinical course in a group of patients with severe traumatic injur ies. Blood samples were obtained from 13 patients shortly after major traum a and 11 healthy volunteers who served as the control group. Plasma gelsoli n levels were assayed by quantitative Western blotting. Duration of mechani cal ventilation, stay in the Trauma Intensive Care Unit, and development of acute respiratory distress syndrome (ARDS) were measured as clinical outco mes reflecting the complexity of the hospital course. Subsequently, we eval uated an additional 52 patients after major and minor trauma to extend our earlier observations. Plasma gelsolin concentrations were significantly low er in our 13 original patients compared with healthy controls. Levels below 250 mg/L (> 2 standard deviations below the mean of the control group) wer e associated with prolonged mechanical ventilation and a stay in the intens ive care unit greater than or equal to 13 days. Both patients whose gelsoli n level was < 100 mg/L in this first series developed ARDS. Including all 6 5 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 patien ts with and without ARDS, respectively (p < 0.0001) and 398 mg/L in survivo rs versus 259 mg/L for patients who expired (p < 0.0001). Ten of the 13 pat ients (77%) with gelsolin levels at the time of admission more than 2 SD be low the control mean had "bad outcomes," defined as mechanical ventilation for greater than or equal to 13 days in the Trauma Intensive Unit, ARDS, an d/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 ca nnot be determined from our study. The potential therapeutic benefits of in fusions of recombinant human plasma gelsolin for patients in whom multiorga n dysfunction commonly follows a serious but self-limited insult have not y et been investigated.