Kristan Staudenmayer

Systematic Review: Benefits and Harms of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications

BACKGROUND Recombinant factor VIIa (rFVIIa), a hemostatic agent approved for hemophilia, is increasingly used for off-label indications. PURPOSE To evaluate the benefits and harms of rFVIIa use for 5 off-label, in-hospital indications: intracranial hemorrhage, cardiac surgery, trauma, liver transplantation, and prostatectomy. DATA SOURCES Ten databases (including PubMed, EMBASE, and the Cochrane Library) queried from inception through December 2010. Articles published in English were analyzed. STUDY SELECTION Two reviewers independently screened titles and abstracts to identify clinical use of rFVIIa for the selected indications and identified all randomized, controlled trials (RCTs) and observational studies for full-text review. DATA EXTRACTION Two reviewers independently assessed study characteristics and rated study quality and indication-wide strength of evidence. DATA SYNTHESIS 16 RCTs, 26 comparative observational studies, and 22 noncomparative observational studies met inclusion criteria. Identified comparators were limited to placebo (RCTs) or usual care (observational studies). For intracranial hemorrhage, mortality was not improved with rFVIIa use across a range of doses. Arterial thromboembolism was increased with medium-dose rFVIIa use (risk difference [RD], 0.03 [95% CI, 0.01 to 0.06]) and high-dose rFVIIa use (RD, 0.06 [CI, 0.01 to 0.11]). For adult cardiac surgery, there was no mortality difference, but there was an increased risk for thromboembolism (RD, 0.05 [CI, 0.01 to 0.10]) with rFVIIa. For body trauma, there were no differences in mortality or thromboembolism, but there was a reduced risk for the acute respiratory distress syndrome (RD, -0.05 [CI, -0.02 to -0.08]). Mortality was higher in observational studies than in RCTs. LIMITATIONS The amount and strength of evidence were low for most outcomes and indications. Publication bias could not be excluded. CONCLUSION Limited available evidence for 5 off-label indications suggests no mortality reduction with rFVIIa use. For some indications, it increases thromboembolism.

Trauma training in simulation: translating skills from SIM time to real time.

BACKGROUND : Training surgical residents to manage critically injured patients in a timely fashion presents a significant challenge. Simulation may have a role in this educational process, but only if it can be demonstrated that skills learned in a simulated environment translate into enhanced performance in real-life trauma situations. METHODS : A five-part, scenario-based trauma curriculum was developed specifically for this study. Midlevel surgical residents were randomized to receiving this curriculum in didactic lecture (LEC) fashion or with the use of a human performance simulator (HPS). A written learning objectives test was administered at the completion of the training. The first four major trauma resuscitations performed by each participating resident were captured on videotape in the emergency department and graded by two experienced judges blinded to the method of training. The assessment tool used by the judges included an evaluation of both initial trauma evaluation or treatment skills (part I) and crisis management skills (part II) as well as an overall score (poor/fail, adequate, or excellent). RESULTS : The two groups of residents received almost identical scores on the posttraining written test. Average SIM and LEC scores for part I were also similar between the two groups. However, SIM-trained residents received higher overall scores and higher scores for part II crisis management skills compared with the LEC group, which was most evident in the scores received for the teamwork category (p = 0.04). CONCLUSIONS : A trauma curriculum incorporating simulation shows promise in developing crisis management skills that are essential for evaluation of critically injured patients.

Angiopoietin-2, Marker and Mediator of Endothelial Activation With Prognostic Significance Early After Trauma?

Objective:To measure plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) early after trauma and to determine their clinical significance. Background:Angiopoietins and VEGF play a central role in the physiology and pathophysiology of endothelial cells. Ang-2 has recently been shown to have pathogenetic significance in sepsis and acute lung injury. Little is known about the role of angiopoietins and VEGF early after trauma. Methods:Blood specimens from consecutive major trauma patients were obtained immediately upon arrival in the emergency department and plasma samples assayed for Ang-1, Ang-2, VEGF, markers of endothelial activation, protein C pathway, fibrinolytic system, and complement. Base deficit was used as a measure of tissue hypoperfusion. Data were collected prospectively. Results:Blood samples were obtained from 208 adult trauma patients within 30 minutes after injury before any significant fluid resuscitation. Plasma levels of Ang-2, but not Ang-1 and VEGF were increased and correlated independently with severity of injury and tissue hypoperfusion. Furthermore, plasma levels of Ang-2 correlated with markers of endothelial activation, coagulation abnormalities, and activation of the complement cascade and were associated with worse clinical outcome. Conclusions:Ang-2 is released early after trauma with the degree proportional to both injury severity and systemic hypoperfusion. High levels of Ang-2 were associated with an activated endothelium, coagulation abnormalities, complement activation, and worse clinical outcome. These data indicate that Ang-2 is a marker and possibly a direct mediator of endothelial activation and dysfunction after severe trauma.

The Cost Of Overtriage: More Than One-Third Of Low-Risk Injured Patients Were Taken To Major Trauma Centers

Regionalized trauma care has been widely implemented in the United States, with field triage by emergency medical services (EMS) playing an important role in identifying seriously injured patients for transport to major trauma centers. In this study we estimated hospital-level differences in the adjusted cost of acute care for injured patients transported by 94 EMS agencies to 122 hospitals in 7 regions, overall and by injury severity. Among 301,214 patients, the average adjusted per episode cost of care was

Cost-Effectiveness of Helicopter Versus Ground Emergency Medical Services for Trauma Scene Transport in the United States

5,590 higher in a level 1 trauma center than in a nontrauma hospital. We found hospital-level differences in cost among patients with minor, moderate, and serious injuries. Of the 248,342 low-risk patients-those who did not meet field triage guidelines for transport to trauma centers-85,155 (34.3 percent) were still transported to major trauma centers, accounting for up to 40 percent of acute injury costs. Adhering to field triage guidelines that minimize the overtriage of low-risk injured patients to major trauma centers could save up to

Evaluating age in the field triage of injured persons.

136.7 million annually in the seven regions we studied.

The epidemiology of trauma-related mortality in the United States from 2002 to 2010

STUDY OBJECTIVE We determine the minimum mortality reduction that helicopter emergency medical services (EMS) should provide relative to ground EMS for the scene transport of trauma victims to offset higher costs, inherent transport risks, and inevitable overtriage of patients with minor injury. METHODS We developed a decision-analytic model to compare the costs and outcomes of helicopter versus ground EMS transport to a trauma center from a societal perspective during a patients lifetime. We determined the mortality reduction needed to make helicopter transport cost less than

Triage of elderly trauma patients: A population-based perspective

100,000 and

Evaluating the Use of Existing Data Sources, Probabilistic Linkage, and Multiple Imputation to Build Population-based Injury Databases Across Phases of Trauma Care

50,000 per quality-adjusted life-year gained compared with ground EMS. Model inputs were derived from the National Study on the Costs and Outcomes of Trauma, National Trauma Data Bank, Medicare reimbursements, and literature. We assessed robustness with probabilistic sensitivity analyses. RESULTS Helicopter EMS must provide a minimum of a 15% relative risk reduction in mortality (1.3 lives saved/100 patients with the mean characteristics of the National Study on the Costs and Outcomes of Trauma cohort) to cost less than

Hypertonic saline modulates innate immunity in a model of systemic inflammation.

100,000 per quality-adjusted life-year gained and a reduction of at least 30% (3.3 lives saved/100 patients) to cost less than