Epidemiology and estimated economic impact of musculoskeletal injuries in polytrauma patients in a level one trauma centre in Singapore

INTRODUCTION@#Musculoskeletal injuries are the most common reason for surgical intervention in polytrauma patients.@*METHODS@#This is a retrospective cohort study of 560 polytrauma patients (injury severity score [ISS] >17) who suffered musculoskeletal injuries (ISS >2) from 2011 to 2015 in National University Hospital, Singapore.@*RESULTS@#560 patients (444 [79.3%] male and 116 [20.7%] female) were identified. The mean age was 44 (range 3-90) years, with 45.4% aged 21-40 years. 39.3% of the patients were foreign migrant workers. Motorcyclists were involved in 63% of road traffic accidents. The mean length of hospital stay was 18.8 (range 0-273) days and the mean duration of intensive care unit (ICU) stay was 5.7 (range 0-253) days. Patient mortality rate was 19.8%. A Glasgow Coma Scale (GCS) score <12 and need for blood transfusion were predictive of patient mortality (p < 0.05); lower limb injuries, road traffic accidents, GCS score <8 and need for transfusion were predictive of extended hospital stay (p < 0.05); and reduced GCS score, need for blood transfusion and upper limb musculoskeletal injuries were predictive of extended ICU stay. Inpatient costs were significantly higher for foreign workers and greatly exceeded the minimum insurance coverage currently required.@*CONCLUSION@#Musculoskeletal injuries in polytrauma remain a significant cause of morbidity and mortality, and occur predominantly in economically productive male patients injured in road traffic accidents and falls from height. Increasing insurance coverage for foreign workers in high-risk jobs should be evaluated.

The treatment of bleeding is to stop the bleeding! Treatment of trauma-related hemorrhage.

BACKGROUND: The secret with any alternative to transfusion is to minimize the need for transfusion in the first place. This can be done by reducing the volume of blood loss. The volume of blood being lost can be reduced by direct methods where possible (i.e., hemostasis at the point of bleeding), or by improving the coagulation profile of the patient, thereby improving the extrinsic coagulation. Recombinant activated factor VII (rFVIIa) offers theoretical possibilities of improving the coagulation profile. STUDY DESIGN AND METHODS: The efficacy and safety of rFVIIa for the treatment of bleeding in patients with severe blunt and penetrating trauma has been investigated in two double-blind, placebo-controlled studies within a single trial-one on patients with blunt injury and the other in similar patients with penetrating injury. RESULTS: In patients with blunt trauma alive at 48 hours, treatment with rFVIIa effected a significant reduction in the primary endpoint of 48-hour red blood cell (RBC) transfusion requirement (p = 0.02), and the safety of the dosing regimen was established. Similar trends were observed in patients with penetrating injuries. Across both studies and treatment arms, the 48-hour mortality rate ranged from 16 to 19 percent. In the blunt trauma study, this equated to 13 patients from each arm who died before the benefits of treatment could be adequately assessed. Analysis of data for the 117 blunt trauma patients who survived at least 48 hours after receiving study treatment shows that, in addition to reducing RBC requirement, rFVIIa significantly reduced the need for massive transfusion over 48 hours (>20 RBC units) (relative risk reduction of 56% [95% confidence interval: 9%-79%]; p = 0.03), and the fresh-frozen plasma (p = 0.036), platelet (p = 0.023), and cryoprecipitate (p = 0.053) requirements within 48 hours, and was associated with a significant reduction in the 30-day risk of acute respiratory distress syndrome (ARDS) (p = 0.05) and multiple organ failure and/or ARDS (p = 0.05). CONCLUSION: Treatment with adjunctive rFVIIa significantly reduces transfusion requirements in the 48 hours after severe injury and these procoagulant effects may improve clinical outcome at 30 days.

Safety of rFVIIa in hemodynamically unstable polytrauma patients with traumatic brain injury: post hoc analysis of 30 patients from a prospective, randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Trauma is a leading cause of mortality and morbidity, with traumatic brain injury (TBI) and uncontrolled hemorrhage responsible for the majority of these deaths. Recombinant activated factor VIIa (rFVIIa) is being investigated as an adjunctive hemostatic treatment for bleeding refractory to conventional replacement therapy in trauma patients. TBI is a common component of polytrauma injuries. However, the combination of TBI with polytrauma injuries is associated with specific risk factors and treatment modalities somewhat different from those of polytrauma without TBI. Although rFVIIa treatment may offer added potential benefit for patients with combined TBI and polytrauma, its safety in this population has not yet been assessed. We conducted a post hoc sub analysis of patients with TBI and severe blunt polytrauma enrolled into a prospective, international, double-blind, randomized, placebo-controlled study. METHODS: A post hoc analysis of study data was performed for 143 patients with severe blunt trauma enrolled in a prospective, randomized, placebo-controlled study, evaluating the safety and efficacy of intravenous rFVIIa (200 + 100 + 100 microg/kg) or placebo, to identify patients with a computed tomography (CT) diagnosis of TBI. The incidences of ventilator-free days, intensive care unit-free days, and thromboembolic, serious, and adverse events within the 30-day study period were assessed in this cohort. RESULTS: Thirty polytrauma patients (placebo, n = 13; rFVIIa, n = 17) were identified as having TBI on CT. No significant differences in rates of mortality (placebo, n = 6, 46%, 90% confidence interval (CI): 22% to 71%; rFVIIa, n = 5, 29%, 90% CI: 12% to 56%; P = 0.19), in median numbers of intensive care unit-free days (placebo = 0, rFVIIa = 3; P = 0.26) or ventilator-free days (placebo = 0, rFVIIa = 10; P = 0.19), or in rates of thromboembolic adverse events (placebo, 15%, 90% CI: 3% to 51%; rFVIIa, 0%, 90% CI: 0% to 53%; P = 0.18) or serious adverse events (placebo, 92%, 90% CI: 68% to 98%; rFVIIa, 82%, 90% CI: 60% to 92%; P = 0.61) were observed between treatment groups. CONCLUSION: The use of a total dose of 400 (200 + 100 + 100) microg/kg rFVIIa in this group of hemodynamically unstable polytrauma patients with TBI was not associated with an increased risk of mortality or with thromboembolic or adverse events.

Cost-Effectiveness of Recombinant Activated Factor VII as Adjunctive Therapy for Bleeding Control in Severely Injured Trauma Patients in Germany.

PURPOSE: The purpose of this study was to assess the cost-effectiveness of recombinant activated factor VII (rFVIIa) as adjunctive therapy for the control of bleeding in patients with severe blunt trauma injuries in Germany. The primary outcome measure was incremental cost per quality-adjusted life-year (QALY) gained. MATERIALS AND METHODS: We developed a cost-effectiveness model based on patient-level data from a 30 day international, randomized, placebo-controlled phase II trial. The data were supplemented with secondary data from the German Trauma Register and German life tables to estimate lifetime costs and benefits. We assumed that the non-significant difference in mortality observed in the phase II trial of 5% in favor of rFVIIa could be verified in the ongoing, much larger follow-up trauma study. We adopted the perspective of third-party payers in Germany, and included all trauma-related healthcare costs. RESULTS: The incremental cost per QALY gained with rFVIIa relative to placebo was e29,451. The probability that this was below e30,000 and e40,000 was 51 and 58%, respectively. The estimates were sensitive to the differences observed in mortality and the applied discount rate. CONCLUSIONS: Based on preliminary evidence from a phase II trial, we conclude that, relative to placebo, rFVIIa may be a cost-effective therapy from the thirdparty payer perspective in Germany.

Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials.

BACKGROUND: Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma. METHODS: Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 microg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose. RESULTS: Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups. CONCLUSION: Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.