Richard P. Dutton

The coagulopathy of trauma: a review of mechanisms.

BACKGROUND Bleeding is the most frequent cause of preventable death after severe injury. Coagulopathy associated with severe injury complicates the control of bleeding and is associated with increased morbidity and mortality in trauma patients. The causes and mechanisms are multiple and yet to be clearly defined. METHODS Articles addressing the causes and consequences of trauma-associated coagulopathy were identified and reviewed. Clinical situations in which the various mechanistic causes are important were sought along with quantitative estimates of their importance. RESULTS Coagulopathy associated with traumatic injury is the result of multiple independent but interacting mechanisms. Early coagulopathy is driven by shock and requires thrombin generation from tissue injury as an initiator. Initiation of coagulation occurs with activation of anticoagulant and fibrinolytic pathways. This Acute Coagulopathy of Trauma-Shock is altered by subsequent events and medical therapies, in particular acidemia, hypothermia, and dilution. There is significant interplay between all mechanisms. CONCLUSIONS There is limited understanding of the mechanisms by which tissue trauma, shock, and inflammation initiate trauma coagulopathy. Acute Coagulopathy of Trauma-Shock should be considered distinct from disseminated intravascular coagulation as described in other conditions. Rapid diagnosis and directed interventions are important areas for future research.

Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality.

BACKGROUND Traditional fluid resuscitation strategy in the actively hemorrhaging trauma patient emphasizes maintenance of a normal systolic blood pressure (SBP). One human trial has demonstrated improved survival when fluid resuscitation is restricted, whereas numerous laboratory studies have reported improved survival when resuscitation is directed to a lower than normal pressure. We hypothesized that fluid resuscitation titrated to a lower than normal SBP during the period of active hemorrhage would improve survival in trauma patients presenting to the hospital in hemorrhagic shock. METHODS Patients presenting in hemorrhagic shock were randomized to one of two fluid resuscitation protocols: target SBP > 100 mm Hg (conventional) or target SBP of 70 mm Hg (low). Fluid therapy was titrated to this endpoint until definitive hemostasis was achieved. In-hospital mortality, injury severity, and probability of survival were determined for each patient. RESULTS One hundred ten patients were enrolled over 20 months, 55 in each group. The study cohort had a mean age of 31 years, and consisted of 79% male patients and 51% penetrating trauma victims. There was a significant difference in SBP observed during the study period (114 mm Hg vs. 100 mm Hg, p < 0.001). Injury Severity Score (19.65 +/- 11.8 vs. 23.64 +/- 13.8, p = 0.11) and the duration of active hemorrhage (2.97 +/- 1.75 hours vs. 2.57 +/- 1.46 hours, p = 0.20) were not different between groups. Overall survival was 92.7%, with four deaths in each group. CONCLUSION Titration of initial fluid therapy to a lower than normal SBP during active hemorrhage did not affect mortality in this study. Reasons for the decreased overall mortality and the lack of differentiation between groups likely include improvements in diagnostic and therapeutic technology, the heterogeneous nature of human traumatic injuries, and the imprecision of SBP as a marker for tissue oxygen delivery.

Blood transfusion rates in the care of acute trauma

BACKGROUND:  Ten to 15 percent of all RBCs are used in the care of injury. Understanding patterns of RBC use is important. Routine resource allocation, planning for mass casualty situations, designing research, and optimizing triage all can be usefully informed.

Trauma mortality in mature trauma systems: are we doing better? An analysis of trauma mortality patterns, 1997-2008.

BACKGROUND Advances in care such as damage control surgery, hemostatic resuscitation, protocol-driven cerebral perfusion management, and lung-protective ventilation have promised to improve survival after major trauma. We examined injury severity, mortality, and preventability in a mature trauma system during a 12-year period to assess the overall benefits of these and other improvements. METHODS Using the institutional trauma registry and the quality management database, we analyzed the outcome and the cause of death for all primary trauma admissions from July 1, 1996, to June 30, 2008, and linked these data with patient demographics, hospital length of stay, time to death, predicted probability of survival, and peer review of in-hospital deaths. RESULTS Through fiscal year (FY) 2007, primary trauma admissions increased in number, injury severity, and age. Performance benchmarked against predicted probability of survival improved. Mortality through this era ranged from 3% to 3.7% and worsened slightly overall (p = 0.04). However, among those patients admitted with Injury Severity Score 17-25, survival improved significantly (p = 0.0003). Traumatic brain injury (TBI) accounted for 51.6% of deaths; acute hemorrhage, 30%; and multiple organ failure, 10.5%. Median time to death for uncontrollable hemorrhage, TBI, multiple organ failure was 2 hours, 24 hours, and 15 days, respectively. These patterns did not change significantly over time. CONCLUSION Survival after severe trauma and survival benchmarked against predicted risk improved significantly at our center during the past 12 years despite generally increasing age and worsening injuries. Advances in trauma care have kept pace with an aging population and greater severity of injury, but overall survival has not improved.

Early aggressive use of fresh frozen plasma does not improve outcome in critically injured trauma patients.

Objectives:Recent data from Iraq supporting early aggressive use of fresh frozen plasma (FFP) in a 1:1 ratio to packed red blood cells (PRBCs) has led many civilian trauma centers to adopt this resource intensive strategy. Methods:Prospective data were collected on 806 consecutive trauma patients admitted to the intensive care unit over 2 years. Patients were stratified by PRBC:FFP transfusion ratio over the first 24 hours. Stepwise regression models were performed controlling for age, gender, mechanism of injury, injury severity, and acute physiology and chronic health evaluation (APACHE) 2 score to determine if early aggressive use of PRBC:FFP improved outcome. Results:Seventy-seven percent of patients were male (N = 617) and 85% sustained blunt injury (n = 680). Mean age, injury severity score (ISS), and APACHE score were 43 ± 20 years, 29 ± 13, and 13 ± 7, respectively. Mean number of PRBCs and FFP transfused were 7.7 ± 12 U, 6 U, and 5 ± 12 U, respectively. Three hundred sixty-five (45%) patients were transfused in the first 24 hours. Sixty-eight percent (n = 250) of them received both PRBCs and FFP. Analyzing these patients by stepwise regression controlling for all significant variables, the PRBC:FFP ratio did not predict intensive care unit days, hospital days, or mortality even in patients who received massive transfusion (≥10 U). Furthermore, there was no significant difference in outcome when comparing patients who had a 1:1 PRBC:FFP ratio with those who did not receive any FFP. Conclusion:Early and aggressive use of FFP does not improve outcome after civilian injury. This may reflect inherent differences compared with military injury; however, this practice should be reevaluated.

Recombinant factor viia for control of hemorrhage: early experience in critically ill trauma patients

STUDY OBJECTIVE To examine our institutional experience with recombinant Factor VIIa (rFVIIa) as a treatment for exsanguinating hemorrhage in critically ill trauma patients. DESIGN Retrospective case review. SETTING A specialized trauma and critical care hospital, serving as the quaternary referral center for trauma and surgical shock in the state of Maryland. PATIENTS All patients with diffuse coagulopathy and impending exsanguination, given rFVIIa in an effort to control life-threatening hemorrhage. Patients were in the intensive care unit (ICU) or operating room (OR) and included both acute admissions and late-stage patients with multiple organ system failure. INTERVENTIONS Patients of interest were those that had received rFVIIa. MEASUREMENTS Examination of medical records, including pharmacy data, laboratory results, and the institutional trauma registry. MAIN RESULTS Administration of rFVIIa contributed to successful control of hemorrhage in three of five patients. Failure in two patients was mostly likely due to overwhelming shock and acidosis. CONCLUSIONS Administration of rFVIIa shows promise in the treatment of exsanguinating hemorrhage. Prospective, controlled clinical trials of this therapy are strongly recommended.

Management of Coagulopathy in the Patients With Multiple Injuries: Results From an International Survey of Clinical Practice

BACKGROUND Bleeding is one of the leading causes of preventable death after traumatic injury. Trauma-associated coagulopathy complicates the control of bleeding. The published approaches on the management of this coagulopathy differ significantly. METHODS A qualitative international survey of clinical practice among senior physicians responsible for the treatment of patients with multiple injuries (Injury Severity Score > or = 16) was conducted to document common practices, highlight the variabilities, and profile the rationale behind existing clinical practices around the world. RESULTS Survey results are based on 80 (32%) completed returns, representing 25 countries with 93% of respondents employed by trauma centers and a mean of 20 years clinical experience. There are regional differences in the clinical specialty of physicians responsible for trauma management decisions. Blood loss, temperature, pH, platelets, prothrombin time/INR/activated partial thromboplastin time, and overall clinical assessment, were the most common criteria used to assess coagulopathy. Forty-five percent of respondents claimed to follow a massive transfusion protocol in their institution, 19% reported inconsistent protocol use and 34% do not use a protocol. The management of hypothermia, acidosis, blood products, and adjuvant therapy showed regional as well as institutional variability, and surprisingly few massive transfusion protocols specifically address these issues. CONCLUSIONS The results of this survey may serve to draw attention to the need for a common definition of coagulopathy and standardized clinical protocols to ensure optimal patient care.

The prevalence of abnormal results of conventional coagulation tests on admission to a trauma center

BACKGROUND: Several groups have reported that a fraction of severely injured patients have abnormal coagulation tests at presentation to trauma centers, even in the absence of significant crystalloid resuscitation. These patients have high mortality, but their prevalence in trauma populations is not clear from the reports.

Decompressive laparotomy to treat intractable intracranial hypertension after traumatic brain injury.

INTRODUCTION Increases in intra-abdominal pressure (IAP) can cause increases in intracranial pressure (ICP). Recently, we noticed that abdominal fascial release could be useful in treating intracranial hypertension (ICH) after traumatic brain injury (TBI). We added this as an option in our treatment of TBI. METHODS In our institution, ICH is treated with an algorithm using osmolar therapy, CSF drainage and barbiturates. Patients with refractory ICH have routine measurement of IAP. If elevated, consideration is given to decompressive laparotomy. We retrospectively reviewed all patients admitted from January 2000 through July 2003 who had abdominal decompression to treat refractory ICH. RESULTS From 1/00 to 7/03, 17 patients underwent decompressive laparotomy for intractable ICH. Thirteen male and 4 females all sustained blunt injury. All had failed maximal therapy including 14 who had had decompressive craniectomy. Mean ICP was 30 +/- 8.1 mmHg (range 20-40 mmHg) before decompression. No patients had evidence of abdominal compartment syndrome (ACS). Before decompression mean IAP was 27.5 (+/- 5.2) mmHg (range 21-35 mmHg). After abdominal decompression ICP dropped precipitously by at least 10 mmHg to a mean of 17.5 (+/- 3.2) mmHg (range 10-25 mmHg). In 6 patients the decrease in ICP was transient. All died. The remaining 11 had sustained decreases in ICP. All survived, made neurologic recovery and were discharged to a rehabilitation facility. CONCLUSION Decompressive laparotomy can be a useful adjunct in the treatment of ICH failing maximal therapy following TBI. More work will need to be done to precise the exact indications for this therapy.

Multidisciplinary approach to the challenge of hemostasis.

A multidisciplinary panel consisting of experts chosen by the 2 chairs of the group representing experts in anesthesiology, blood banking, hematology, critical care medicine, and various surgical disciplines (trauma, cardiac, pediatric, neurologic, obstetrics, and vascular) convened in January 2008 to discuss hemostasis and management of the bleeding patient across different clinical settings, with a focus on perioperative considerations. Although there are many ways to define hemostasis, one clinical definition would be control of bleeding without the occurrence of pathologic thrombotic events (i.e., when balance among procoagulant, anticoagulant, fibrinolytic, and antifibrinolytic activities is achieved). There are common hemostatic challenges that include lack of scientific evidence and standardized guidelines for the use of therapeutic drugs, need for reliable and rapid laboratory tools for measuring hemostasis, and individual variability. Clinically meaningful and accurate real-time laboratory data reflecting a patients hemostatic status are needed to guide treatment decisions. Current available routine laboratory tests of hemostasis (e.g., platelet count, prothrombin time/international normalized ratio, and activated partial thromboplastin time) do not reflect the complexity of in vivo hemostasis and can mislead the clinician. Although point-of-care coagulation monitoring tests including measures of thromboelastography/elastometry provide insight into overall hemostatic status, they are time-consuming to perform, complex to interpret, and require trained personnel. There is a particular need to develop laboratory tests that can measure the effects of anticoagulant and antiplatelet agents for individual patients, predict bleeding complications, and guide therapy when and if treatment with blood products or pharmacologic drugs is required. Formation of an organization comprised of specialists who treat bleeding patients will foster multidisciplinary collaborations and promote discussions of the current state of hemostasis treatment and future priorities for hemostasis research. Controlled trials with clinically meaningful end points and suitable study populations, as well as observational studies, investigator-initiated studies, and large registry and database studies are essential to answer questions in hemostasis. Because of the complexities of maintaining hemostatic balance, advances in hemostasis research and continuing communication across specialties are required to improve patient care and outcomes.