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Background: Safety data on recombinant activated factor VII (rFVIIa, NovoSeven; Novo Nordisk A/S, Bagsværd, Denmark) in actively hemorrhaging trauma patients are limited. We present detailed safety data from a large multicenter, randomized, placebo-controlled phase III study (the CONTROL trial)., Methods: Data from 560 patients were analyzed. Subjects were monitored for adverse events (AEs) after rFVIIa or placebo administration. Incidences, timing, and presence of risk factors were reported by site investigators, supported by external study monitors and overseen by an independent Data Monitoring Committee., Results: There were no differences in overall mortality, organ system failure, or AEs, serious AEs, or medical events of special interest. Arterial and venous thromboembolic (TE) events and their risk factors were similar in both groups. The greatest risk factor for TE events was a chest injury requiring mechanical ventilation >3 days (86%). There were four site investigator-reported myocardial infarctions in the rFVIIa group of which only one met diagnostic criteria preestablished by the Data Monitoring Committee. There were no reported myocardial infarctions in the placebo group. Troponins were increased in 30% of all patients. The rate of acute respiratory distress syndrome was lower in the rFVIIa (3.0%) than in the placebo (7.2%) group (p = 0.022)., Conclusions: This represents the largest placebo-controlled dataset of rFVIIa use in trauma patients to date. In this prospective study of critically bleeding trauma patients, rFVIIa use was associated with an imbalance of investigator-reported Acute myocardial infarction/non-ST segment elevation myocardial infarction (AMI/NSTEMI), but was not associated with an increased risk for other AEs, including TE complications.

Objectives: The objectives of this study were 1) to assess potential changes in the incidence and outcome of sepsis after multiple trauma in Germany between 1993 and 2008 and 2) to evaluate independent risk factors for posttraumatic sepsis., Design: Retrospective analysis of a nationwide, population-based prospective database, the Trauma Registry of the German Society for Trauma Surgery., Setting: A total of 166 voluntarily participating trauma centers (levels I-III)., Patients: Patients registered in the Trauma Registry of the German Society for Trauma Surgery between 1993 and 2008 with complete data sets who presented with a relevant trauma load (Injury Severity Score of ≥ 9) and were admitted to an intensive care unit (n = 29,829)., Interventions: None., Measurements and Main Results: Over the 16-yr study period, 10.2% (3,042 of 29,829) of multiply injured patients developed sepsis during their hospital course. Annual data were summarized into four subperiods: 1993-1996, 1997-2000, 2001-2004, and 2005-2008. The incidences of sepsis for the four subperiods were 14.8%, 12.5%, 9.4%, and 9.7% (p < .0001), respectively. In-hospital mortality for all trauma patients decreased for the respective subperiods (16.9%, 16.0%, 13.7%, and 11.9%; p < .0001). For the subgroup of patients with sepsis, the mortality rates were 16.2%, 21.5%, 22.0%, and 18.2% (p = .054), respectively. The following independent risk factors for posttraumatic sepsis were calculated from a multivariate logistic regression analysis: male gender, age, preexisting medical condition, Glasgow Coma Scale score of ≤ 8 at scene, Injury Severity Score, Abbreviated Injury ScaleTHORAX score of ≥ 3, number of injuries, number of red blood cell units transfused, number of operative procedures, and laparotomy., Conclusions: The incidence of sepsis decreased significantly over the study period; however, in this decade the incidence remained unchanged. Although overall mortality from multiple trauma has declined significantly since 1993, there has been no significant decrease of mortality in the subgroup of septic trauma patients. Thus, sepsis has remained a challenging complication after trauma during the past 2 decades. Recognition of the identified risk factors may guide early diagnostic workup and help to reduce septic complications after multiple trauma.

Background: Inpatient psychotherapeutic support has been shown to reduce mental health problems in severely injured patients. However, this effect mostly disappears after discharge. The aim of this study was to compare short-term inpatient versus continued long-term outpatient psychotherapeutic support., Methods: Patients with at least two injuries of a combined Abbreviated Injury Scale Severity Score Index≥5 were included in the study. Of 862 screened patients, 113 met all inclusion criteria. They were randomly assigned to a short-term group (n=59), where only inpatient support was given, and a long-term group (n=54), with additional outpatient sessions. The cognitive behavioral treatment was standardized by a manual. Psychological assessment for depression, anxiety, and posttraumatic stress disorder (PTSD) was performed in written form at the time of inclusion, discharge, and 6 months, 12 months, and 18 months after trauma., Results: Forty-one percent (n=46) of all patients completed follow-up visits. The results show that symptoms of depression, anxiety, and PTSD disappeared more often in the long-term group than in the short-term group 1 year after trauma. Differences nearly reach significance for anxiety (p=0.051) and PTSD (p=0.059). Twenty-one percent of the short-term group patients showed at least one mental health disorder compared with no patients in the long-term group 1 year after trauma (p=0.035)., Conclusion: Psychotherapeutic support of severely injured patients seems to be more effective in reducing depression, anxiety, and PTSD if extended further into outpatient care. This conclusion should be considered preliminary because of the small number of study patients.

Background: Benefits of high ratios of fresh frozen plasma (FFP) to packed red blood cells (pRBC) in massively transfused trauma patients have been reported previously. This study aimed to assess the effect of higher FFP:pRBC ratios on outcome in patients receiving less than massive transfusion during acute trauma care., Methods: The multicenter trauma registry of the German Trauma Society (2005-2008) was retrospectively analyzed for patients aged≥16 years with an Injury Severity Score≥16 who had received multiple but not massive transfusion between emergency room arrival and intensive care unit (ICU) admission, i.e., at least 4 but less than 10 pRBC units (4≤pRBC units<10). Patients who died within 1 hour after hospital admission were excluded. Three groups were analyzed according to FFP:pRBC ratio: low (<1:1, LR), balanced (1:1, BR), and high ratio (>1:1, HR). BR was defined as pRBC units=FFP units±1 FFP unit., Results: A total of 1,362 patients met study criteria (LR=760, BR=392, and HR=210). Patient characteristics were similar among groups. For the three groups (LR, BR, and HR) sepsis was reported in 17.1%, 18.2%, and 17.6% (p=0.9), incidence of multiple organ failure was 49.1%, 47.9%, and 52.4% (p=0.6), whereas mortality was 26.8%, 21.7%, and 15.2% (p=0.001), respectively. Ongoing pRBC-transfusion after ICU admission occurred in 68.1%, 66.7%, and 53.9% (p<0.001), respectively. ICU/hospital lengths of stay were comparable between groups. Multivariate logistic regression identified a high FFP:pRBC ratio as independent predictor for survival (odds ratio, 0.52, p=0.013)., Conclusions: Trauma patients receiving less than massive transfusion might also benefit from higher FFP:pRBC ratios, as these were associated with significantly lower mortality rates and decreased blood product utilization during subsequent ICU treatment, whereas morbidity was comparable among groups. Additional prospective trials are necessary.

Background: Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes., Methods: We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma "bundles" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases., Results: Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts., Conclusions: rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.

The Educational Initiative on Critical Bleeding in Trauma was formed to assess current data and to guide future research and practice in the management of coagulopathy after severe trauma. The Educational Initiative on Critical Bleeding in Trauma recently published structured literature reviews on animal models and mechanisms of trauma-associated coagulopathy and the results of a survey of international clinical practice. The authors convened a symposium in July 2008 and invited researchers and opinion leaders in trauma care, transfusion medicine, and coagulation research to discuss current understanding and management and to identify future areas of exploration. This document reviews the content and conclusions of the meeting. The association between trauma and bleeding from patient registries, basic science, and clinical studies was confirmed, as was the association between the coagulopathy that presents early after major injury and excess mortality. Meeting participants identified the need for consensus definitions and common terminology to describe coagulopathy after trauma, including the term acute coagulopathy of trauma shock to describe the early coagulopathy induced by tissue injury/shock and the global term trauma-induced coagulopathy to describe coagulopathy after injury and its sequelae (loss, consumption, acidemia, acute coagulopathy, and dilution). Other conclusions included the need for increased clinical awareness, new methods and tools for early diagnosis, consistent early preventative strategies, and evidence-based therapies for these conditions.

Objectives: Early estimation of the mortality risk of severely injured patients is mandatory. To estimate the seriousness of the condition of patients with trauma, we developed the emergency trauma score (EMTRAS) for ease of use, with simple parameters that are available within 30 minutes., Design: Prospective analysis of the German Trauma Registry of multitrauma patients., Setting: EMTRAS was derived from data from 1993 through 2003. Potential parameters that were prognostic for mortality in univariate analysis were evaluated by multivariate binary logistic regression. Selected parameters were then assigned a subscore that varied from 0 to 3. The EMTRAS score was a simple addition of these subscores. EMTRAS was compared with other scores' receiver operating characteristic curves. After completion, EMTRAS was validated in patients from 2004 and 2005., Patients: A total of 11,533 patients were to be used for developing the score and 3314 patients for validating it., Main Results: The strongest predictors of mortality were age, prehospital Glasgow Coma Scale, base excess (mmol/L), and prothrombin time (% of reference). These parameters were categorized in subscores of 0 through 3. Age: <40, 40 through 60, 61 through 75, and >75 scored 0, 1, 2, and 3, respectively. Glasgow Coma Scale: 13 through 15, 10 through 12, 6 through 9, and 3 through 5 scored 0, 1, 2, and 3, respectively. Base excess: >-1, -5 through -1, -10 through -5.1, and <-10 scored 0, 1, 2, and 3, respectively. Prothrombin time: <80%, 80% through 50%, 49% through 20%, and >20% received a score of 0, 1, 2, and 3, respectively. In the validation dataset, the area under the receiver operating characteristic curve for EMTRAS was 0.828., Conclusions: EMTRAS combines four early parameters from the emergency room and accurately predicts mortality. Knowledge of the anatomical injuries is not necessary. The determination of the EMTRAS will inform caregivers of the seriousness of patients with trauma at an early stage.

Background: Severe head injury (HI) is known to be a major determinant of mortality in patients with multiple injuries but additional injuries also contribute to the clinical outcome. The Trauma Registry of the German Society for Trauma Surgery offers sufficient data for comparative outcome analysis in relation to the injury pattern., Methods: A total of 21,356 cases from Trauma Registry of the German Society for Trauma Surgery with complete data for pattern of injury (Abbreviated Injury Scale [AIS], Injury Severity Score), the incidence of hospital mortality, organ failure, sepsis, duration of hospital stay, and intubation-free days. Maximum AIS severity of HI, including brain, skull, face, and cervical spine, and injuries to the torso and/or extremities (TEI) were used for comparative subgroup analysis., Results: Overall mortality rate was 13.7% (mean age, 41.3 years; 72.6% men; mean Injury Severity Score, 24.4). Patients with relevant HI (AISHI >/=3) were found to have a higher mortality rate (22.1%) than patients with relevant TEI (12.9%). In all HI severity subgroups mortality increased consistently by about 5% with TEI of grade 4, and by 15% with TEI of grade 5, but no increase is observed for lower severity grades. The incidence of organ failure (overall 31.4%), multiple organ failure (15.0%), and sepsis (9.9%) are mainly influenced by the severity of TEI. Intubation-free days are equally influenced by both types of injuries of grade 3 or higher., Conclusions: Mortality in patients with severe trauma is mainly determined by the severity of HI, while TEI contribute consistently only from AIS grade 4 or higher.

Background: The development of coagulopathy associated with trauma is a complex process that involves a combination of many factors. It is important to be able to model experimental trauma-related coagulopathy to explore preventative and therapeutic strategies, and numerous models of traumatic coagulopathy have been explored. This systematic review assessed the primary question "What are relevant experimental models with which to study early traumatic coagulopathy?" and secondary questions on mechanisms., Methods: The author group reviewed 695 abstracts that resulted in 36 articles being fully reviewed by the group. The group identified 12 key studies (grade A) addressing the primary question. A further 10 articles were thought to be relevant but less important (grade B). Eight articles were considered worthwhile publications but not as relevant to the query (grade C), and six articles were considered not relevant after detailed review (grade D)., Results: This structured literature review demonstrated a lack of relevant models for human traumatic coagulopathy. We identify challenges in modeling traumatic coagulopathy and limitations to current experimental models and include a proposal for features of an "ideal" model of traumatic coagulopathy, but recognize that this involves major challenges., Conclusions: Models of traumatic coagulopathy need to more closely resemble human physiology and real-life conditions if they are to influence 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.

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.

The American College of Surgeons Committee on Trauma's Advanced Trauma Life Support Course is currently taught in 50 countries. The 8th edition has been revised following broad input by the International ATLS subcommittee. Graded levels of evidence were used to evaluate and approve changes to the course content. New materials related to principles of disaster management have been added. ATLS is a common language teaching one safe way of initial trauma assessment and management.

Study Design: A technical report of fluoroscopy guided placement of augmented iliosacral screws in osteoporotic insufficiency fractures of the sacrum., Objective: To describe a combined approach of navigated iliosacral screw placement and screw augmentation as an option for osteosynthesis of sacral insufficiency fractures in the elderly., Summary of Background Data: The incidence of sacral insufficiency fractures is increasing. Outcome of conservative treatment is inconsistent. Recently sacroplasty is propagated as an interventional therapy but the long-term outcome is still unknown. Evidence from finite element models suggests that stabilization of the sacrum achieved by sacroplasty is insufficient to restore the weight bearing capacity of the sacrum permanently., Methods: We suggest a minimally invasive fluoroscopically navigated iliosacral screw osteosynthesis with cement augmentation of the screws for treatment of insufficiency fractures of the sacrum., Results: The procedure, especially fluoroscopic visualization and navigation of the osteoporotic sacrum is technically feasible. A total radiograph time of 7,4 minutes, including image acquisition for navigation and fluoroscopic control of cement injection, is acceptable and can be expected to be significantly reduced with repeated applications of the procedure. The patient presented in the report was discharged to rehabilitation soon after the operation. An assistive device (delta wheel) is only needed for longer walking distances. Pain was reduced drastically immediately after surgery., Conclusion: In general, fractures are treated by reduction and fixation to restore the biomechanical function of the injured bone. These principles should be applied to elderly patients with osteoporotic fractures as well. The technique reported here is adapted to the special demands of the elderly patient, i.e., minimally invasive, support of the weakened bone by cement augmentation, bone protective screw positioning and safety due to navigation support.

Background: To develop a simple scoring system that allows an early and reliable estimation for the probability of mass transfusion (MT) as a surrogate for life threatening hemorrhage following multiple trauma., Methods: Potential clinical and laboratory variables documented in the Trauma Registry of the German Trauma Society (DGU) (1993-2003; n=17,200) were subjected to univariate and multivariate logistic regression analysis to predict the probability for MT., Results: Clinical and laboratory variables available from data sets were screened for their association with mass transfusion. MT was defined by transfusion requirement of >or=10 units of packed red blood cells from emergency room (ER) to intensive care unit admission. Seven independent variables were identified to be significantly correlated with an increased probability for MT: systolic blood pressure (<100 mm Hg=4 pts, <120 mm Hg=1 pt), hemoglobin (<7 g/dL=8 pts, <9 g/dL=6 pts, <10 g/dL=4 pts, <11 g/dL=3 pts, and <12 g/dL=2 pts), intra-abdominal fluid (3 pts), complex long bone and/or pelvic fractures (AIS 3/4=3 pts and AIS 5=6 pts), heart rate (>120=2 pts), base excess (<-10 mmol/L=4 pts, <-6 mmol/L=3 pts, and <-2 mmol/L=1 pt), and gender (male=1 pt). These variables were incorporated into a risk score, the Trauma Associated Severe Hemorrhage Score (TASH-Score, 0-28 points). Performance of the score was tested with respect to discrimination, precision, and calibration. Increasing TASH-Score points were associated with an increasing probability for MT., Conclusion: The TASH-Score is an easy-to-use scoring system that reliably predicts the probability for MT after multiple trauma. Taken as a surrogate for life threatening bleeding calculation may focus attention on relevant variables indicative for risk and impact strategies to stop bleeding and stabilize coagulation in acute trauma care.

Objective: Postoperative care for ankle fractures is generally 1 of 2 regimens: 1) functional treatment combined with early weightbearing (EWB), or 2) immobilization in a cast/orthosis for 6 weeks without weightbearing (6WC). The objective of this study was 2-fold: 1) to follow a prospective group treated with EWB as to long-term subjective and objective outcomes, and 2) to compare a subset of this group with a matched group of historic controls treated with 6WC., Design: Prospective, clinical, cohort observation, and retrospective matched pair analysis., Setting: University hospital, level 1 trauma center., Patients: Forty-three patients (20 males; mean age, 49 +/- 14 years) with operated Weber B/C fractures underwent EWB. For comparison, 23 patients of this group were matched to a same number of historic controls with respect to age, gender, body mass index, and fracture type., Intervention: Open reduction and internal fixation (ORIF) using a 1/3-tubular-fibula-plate for the fibula, and malleolar screws for the medial malleolus fracture (in cases with a bimalleolar ankle fracture) followed by EWB or 6WC., Main Outcome Measurements: Olerud and Tegner scores at follow-up (at least 12 months after surgery), time to full weightbearing, return to work, pain intensity (numerical rating scale (NRS)), and hospital stay. Statistical comparisons were performed by using the Mann-Whitney U test or Fisher exact test (P < 0.05)., Results: Patients with EWB were full weightbearing at 7 +/- 3 weeks and returned to work at 8 +/- 5 weeks after surgery. At follow-up (mean, 20 +/- 11 months after surgery), all EWB patients showed good results in the Olerud score (90 +/- 13 points). Matched-pair analysis in 23 patients in each group revealed differences between EWB and 6WC groups for hospital stay (mean, 10.8 +/- 4.7 vs. 13.6 +/- 6 days; P = 0.12), time to full weightbearing (mean, 7.7 +/- 3.1 vs. 13.5 +/- 9.4 weeks; P = 0.01), and time until return to work (mean 9.2 +/- 5.5 vs. 10.8 +/- 7 weeks; P = 0.63). No differences concerning pain intensities were observed (EWB vs. 6WC: NRS = 1.9 vs. 1.7; P = 0.12). At follow-up, Olerud scores were generally considered good for both groups; however, mean values in EWB patients were slightly higher (87 +/- 14 vs. 79 +/- 19 points; P = 0.25). In both groups, the majority of patients reached their preinjury level of activity as demonstrated by Tegner scores., Conclusions: EWB patients tolerated earlier full weightbearing compared with 6WC patients, and there were no disadvantages with EWB compared with 6WC concerning hospital stay, pain intensities, time until return to work, and Olerud/Tegner Scores. Potential candidates for EWB are patients with a stable osteosynthesis of their fractured ankles as judged by the responsible surgeon, compliance, and high motivation.

Background: Femur-shaft fracture treatment (FSFT) follows controversial management concepts after multiple trauma: primary-definitive osteosynthesis, secondary-definitive osteosynthesis after temporary external fixation (EF) in all patients, or individualized primary- or secondary-definitive osteosynthesis ("risk-adapted damage control orthopedics"). This study compares the concepts by analyzing literature evidence and a prospective multicenter database., Methods: A systematic literature analysis was performed. The German Trauma Society trauma registry was used to assess variables predictive of treatment concept., Results: Contradictory results in 63 controlled trials failed to support a "generalized management strategy." In all, 1,465 FSFTs in 8,057 trauma registry patients (age 39 +/- 19.5 years; Injury Severity Score [ISS] 23.5 +/- 14.9; 17.3% mortality) were treated initially (<24 hour) by EF, nail, or plate in 47.0%, 41.1%, and 11.9%, respectively. Despite large interhospital variability, EF was more likely with increasing severity of ISS, Glasgow Coma Score, thorax trauma, base excess, coagulation abnormalities, and initial probability of death., Conclusions: Clinical "reality" reflects the controversies of "scientific evidence" for FSFT after multiple trauma in Germany. Although decision making is currently based on unvalidated criteria, anatomic and physiologic injury severity appears to influence the choice of management concept.

Objective: On December 26, 2004, a giant earthquake shocked Southeast Asia, triggering deadly flood waves (tsunami) across the Indian Ocean. More than 310,000 people have been reported dead and millions left destitute. Shortly thereafter, European governments organized airborne home transfer of most severely injured tourists using MedEvac aircraft. On arrival, patients were distributed to various medical centers. One cohort of the severely injured was admitted to the Cologne-Merheim Medical Center (Germany) for further surgical and intensive care treatment. The objective of this report was to characterize typical injury patterns along with microbiological findings and psychoemotional aspects unique to the tsunami disaster., Design: Observational study., Setting: Adult intensive care unit of a university hospital., Patients: Seventeen severely injured tsunami victims were screened on arrival for characteristic injury patterns. In parallel, multifocal microbiological assessment was performed to identify pathogens responsible for high-level wound contamination., Interventions: Standard clinical management., Measurements and Main Results: The predominant pattern of injury comprised multiple large-scale soft-tissue wounds (range, 2 x 3 to 60 x 60 cm) of lower extremities (88%), upper extremities (29%), and head (18%). Additional injuries included thoracic trauma with hemopneumothorax and serial rib fractures (41%) and peripheral bone fractures (47%). A major problem associated with wound management was significant contamination. Microbiological assessment identified a variety of common (Pseudomonas 54%, Enterobacteriae 36%, Aeromonas spp. 27%) but also uncommon isolates that were often multiply resistant (multiply resistant Acinetobacter and extended-spectrum beta-lactamase-positive Escherichia coli, 18% each). Upper respiratory tract specimens contained a high rate of multiply resistant Acinetobacter species but also methicillin-resistant Staphylococcus aureus, Aeromonas hydrophilia, Pseudomonas species, and Candida albicans. Apart from these findings, all patients displayed severe signs of posttraumatic stress response., Conclusions: Individuals who survived their initial injuries and who were evacuated to Europe had traumatic injuries to head, chest, and limbs that were often contaminated with highly resistant bacteria.

Traumatic brain injury (TBI) is present in two-thirds of patients with multiple injuries and in one-third combined with injuries of the extremities. Studies on interactive effects between central and peripheral injuries are scarce due to the absence of clinically relevant models. To meet the demand for "more-hit" models, an experimental model of combined neurotrauma (CNT) incorporating a standardized TBI via lateral fluid percussion (LFP) together with a peripheral bone fracture, i.e., tibia fracture, is introduced. Sprague-Dawley rats were randomized to four experimental groups: controls (n = 10), animals with TBI (n = 30), animals with tibia fracture (n = 30), and animals with CNT (n = 30). Morphological aspects of brain and bone injury were analyzed via standard histopathological procedures and x-ray. Trauma-induced neuromotor dysfunction was assessed using a standardized neuroscore. For interactive effects between injuries, we studied the extent and temporal pattern of circulating interleukin 6 (IL-6) levels via immunoassay and callus formation at fracture sites by means of microradiography. LFP produced an ipsilateral lesion with cortical contusion, hemorrhage, mass shift, and neuronal cell loss (adjacent cortex and hippocampus CA-2/-3), along with contralateral neuromotor dysfunction. X-rays confirmed complete fractures in the middle of the bone shaft. The type of injury (P < 0.001) and time (P = 0.022) were significantly associated with increased IL-6 levels. CNT produced the highest IL-6 plasma levels with a maximum peak at 6 h after trauma (P < 0.001). Similarly, callus formation at fracture sites in CNT was significantly increased versus fracture only (P < 0,01). The CNT model mimics a variety of clinically relevant features known from human multiple injury, including TBI, and offers novel approaches for investigation of interactive mechanisms and therapeutic approaches.

The initial transfusion therapy after trauma has been identified as an independent risk factor for the incidence of multiple organ failure (MOF). Late occurrence of MOF in severely injured patients may be a clinical consequence of disturbed mediator homeostasis. For this reason, levels of interleukin (IL)-6, IL-10, and soluble tumor necrosis factor receptors (sTNFR) p55 and p75 were analyzed in the plasma of patients with comparable injury severity but with a different supply of packed red blood cells (PRBC). Thirty-eight multiple trauma patients with an injury severity score range of 25-54 points were separated into two groups according to their PRBC supply within the first 24 h after trauma. Patients who received at least 15 units of PRBC were analyzed in group 2 (n = 11); the remaining patients (n = 27) were assigned to group 1. The incidence of MOF was higher (P < 0.05) in group 2 patients. Correspondingly, levels of all assayed mediators were found significantly elevated at several time points in this patient group. We conclude that increases in mediator concentrations may be causally related to the extent of blood transfusion therapy itself or to the conditions for which it was needed.

We examined whether procalcitonin (PCT) or neopterin (NT) are useful in predicting sepsis, multiple organ failure (MOF), or death after multiple trauma (MT). In a prospective clinical study, a total of 137 consecutive trauma patients (mean age 39 years, median injury severity score [ISS] 27 points) and 34 healthy volunteers were enrolled. Blood samples were collected on arrival in the emergency room until day 28 after trauma. Plasma NT was detected by enzyme-linked immunoassay and PCT plasma levels were determined using an immunoluminometric assay. The incidence of sepsis was 65%, MOF 48%, and death in hospital within 28 days 11%. After adjustment for age, gender, and ISS, PCT and NT levels during the first 2 days after injury were unable to differentiate between patients who developed sepsis or not. On the contrary, patients who developed MOF had higher PCT plasma levels on day 0 (0.60 vs. 0.15 ng/mL), and on days 1 and 2 combined (1.95 vs. 0.32 ng/mL). This difference remained significant in multivariate logistic regression (P = 0.01) and additional subgroup analyses for early and late MOF (P = 0.048 and 0.002). For NT, smaller differences were observed (4.39 vs. 3.68 nmol/L, and 7.20 vs. 5.79 nmol/L), which lost significance in multivariate analysis. On the basis of PCT, ISS, and age, a MOF prediction rule was developed and had a good predictive power (area under the curve: 0.77; P < 0.001). These findings demonstrate that high plasma concentrations of PCT in the early posttraumatic phase are an independent predictor of MOF but not of sepsis.

Background: Our knowledge about the bidirectional interactions between brain and whole organism after trauma is still limited. It was the purpose of this prospective clinical study to determine the influence of severe head trauma (SHT) as well as trauma in different anatomic injury regions on posttraumatic inflammatory mediator levels from patients with multiple injuries., Methods: Thirty-five healthy controls, 33 patients with an isolated SHT, 47 patients with multiple injuries without SHT, and 45 patients with both SHT and multiple injuries were studied. The posttraumatic plasma levels of soluble tumor necrosis factor receptors p55 and p75, interleukin (IL)-6, IL-10, and polymorphonuclear neutrophil (PMN) elastase were monitored using enzyme-linked immunosorbent assay technique. The influence of head injuries as well as thorax, abdomen, and extremity injuries on the mediator release from patients with multiple injuries was investigated by multivariate linear regression models., Results: The soluble tumor necrosis factor receptor p55/p75 ratio was significantly elevated within 3 hours of trauma in all three injury groups and returned to reference ratios after 12 hours. The lowest increase was found in patients suffering from an isolated SHT. Lowest mediator levels in this patient population were also found for IL-6, IL-10, and PMN elastase during the first 36 hours after trauma. Additional injuries to the head, thorax, abdomen, and extremity modulated mediator levels to a different degree. No specific effect was found for SHT when compared with other injury groups. Thorax injuries caused the quickest rise in mediator levels, whereas abdominal injuries significantly increased PMN elastase levels 12 to 24 hours after trauma., Conclusion: Traumatic injuries cause the liberation of various mediators, without any specific association between anatomic injury pattern and the pattern of mediator release.

This prospective, multi-center, observational study of 2069 multiple trauma patients evaluated the prognostic significance of the posttrauma base deficit (BD) on hospital and intensive care unit (ICU) admission to hemodynamic changes, volume and transfusion requirements, lactate and coagulation, as well as mortality. Furthermore, the importance of the BD development throughout a patient's course of critical illness from the time of injury to ICU admission is analyzed as a prognostic factor for fatal outcome. The data were obtained by the trauma registry of the 'Deutsche Gesellschaft für Unfallchirurgie.' The patients were subdivided into five categories of increasing BD values on hospital and ICU admission: Category I, BD < or = -2; Category II, -2 < BD < or = 2; Category III, 2 < BD < or = 6; Category IV, 6 < BD < or = 10; and Category V, BD > 10. A statistical analysis was performed by means of the ANOVA and chi-square tests. In 1264 (61.1%) of 2069 multiple trauma patients (age 39 +/- 19 years, 70.0% males, injury severity score 22 +/- 13, 18.6% mortality), the BD was documented on hospital and in 1536 (74.2%) patients on ICU admission. At both points in time, an increase in the BD category was associated with a significant decrease in systolic blood pressure and prothrombin time as well as increases in heart rate, lactate level and mortality (P < 0.0001). Also transfusion requirements (Category I: 4.5 +/- 7.7 and Category V: 13.7 +/- 13.0 packed red blood cells) increased significantly on hospital admission (P < 0.0001) with a worsening in the BD category. Mortality increased significantly (P < 0.0001) with a worsening of BD from hospital to ICU admission (from a mortality of 13% in patients with a hospital and an ICU admission BD of <6 to 45% in patients with a hospital and an ICU admission BD of >6). These data show that the base deficit is an early available important indicator to identify trauma patients with hemodynamic instability, high transfusion requirements, metabolic and coagulatory decompensation, as well as a high probability of death. The base deficit development may help to guide an early and aggressive therapy for the trauma/hemorrhage induced tissue hypoxia.

Background: Most standard trauma score systems have been developed and validated in the United States. However, trauma differs between the United States and Germany. This prospective study tested the validity of eight current trauma scoring systems (Glasgow Coma Scale, Trauma Score, Revised Trauma Score, Injury Severity Score, TRISSTS, TRISSRTS, Prehospital Index, Polytraumaschluessel) in 612 patients in Cologne., Methods: Between January 1, 1987, and December 31, 1987, 2,136 trauma related emergencies were seen by emergency physicians in the field. All trauma patients with a Trauma Score below 16 and a random sample of 10% of patients with a Trauma Score of 16 were included in the study (n = 625). Follow-up was successfully completed for 612 patients (97%). Their hospital outcome was correlated with their individual score result., Results: All trauma score systems under study showed high accuracy rates. TRISSRTS and TRISSTS performed best with values of above 0.97 for the area under the receiver operating characteristics curve., Conclusion: We conclude that the standard trauma score systems are valid tools for patient classification and support TRISSRTS as the international reference score system for the assessment of injury severity. This validation will allow comparisons between different trauma care systems.

The field strategy for trauma victims is still controversial. The first randomized study in penetrating truncal trauma by Martin et al. (1992) supported experimental findings (Gross et al., 1988, 1989; Kowalenko et al., 1992; Krausz et al., 1992b) that fluid therapy in uncontrolled haemorrhage increases mortality. No controlled data in blunt trauma are available. In this retrospective analysis of blunt trauma victims (n = 353), the parameters systolic blood pressure, capillary refilling time and Traumascore (Champion et al., 1981) were evaluated in the prehospital detection of uncontrolled bleeding. With the CART methodology (Breiman et al., 1984) systolic blood pressure (BP) was the most sensitive parameter. Uncontrolled haemorrhage was found in nearly 50% of patients whose BP was below 90 mmHg and in 66% of those whose BP was below 50 mmHg. An accompanying traumatic brain injury (TBI) impaired the ability of BP to detect uncontrolled bleeding. Future studies evaluating prehospital fluid therapy in severe blunt trauma with a mixture of injuries, should take into account that BP in our study population classified less than 50% patients with uncontrolled haemorrhage.