Thomas Brockamp

Predicting on-going hemorrhage and transfusion requirement after severe trauma: a validation of six scoring systems and algorithms on the TraumaRegister DGU®

IntroductionThe early aggressive management of the acute coagulopathy of trauma may improve survival in the trauma population. However, the timely identification of lethal exsanguination remains challenging. This study validated six scoring systems and algorithms to stratify patients for the risk of massive transfusion (MT) at a very early stage after trauma on one single dataset of severely injured patients derived from the TR-DGU (TraumaRegister DGU® of the German Trauma Society (DGU)) database.MethodsRetrospective internal and external validation of six scoring systems and algorithms (four civilian and two military systems) to predict the risk of massive transfusion at a very early stage after trauma on one single dataset of severely injured patients derived from the TraumaRegister DGU® database (2002-2010). Scoring systems and algorithms assessed were: TASH (Trauma-Associated Severe Hemorrhage) score, PWH (Prince of Wales Hospital/Rainer) score, Vandromme score, ABC (Assessment of Blood Consumption/Nunez) score, Schreiber score and Larsen score. Data from 56,573 patients were screened to extract one complete dataset matching all variables needed to calculate all systems assessed in this study. Scores were applied and area-under-the-receiver-operating-characteristic curves (AUCs) were calculated. From the AUC curves the cut-off with the best relation of sensitivity-to-specificity was used to recalculate sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV).ResultsA total of 5,147 patients with blunt trauma (95%) was extracted from the TR-DGU. The mean age of patients was 45.7 ± 19.3 years with a mean ISS of 24.3 ± 13.2. The overall MT rate was 5.6% (n = 289). 95% (n = 4,889) patients had sustained a blunt trauma. The TASH score had the highest overall accuracy as reflected by an AUC of 0.889 followed by the PWH-Score (0.860). At the defined cut-off values for each score the highest sensitivity was observed for the Schreiber score (85.8%) but also the lowest specificity (61.7%). The TASH score at a cut-off ≥ 8.5 showed a sensitivity of 84.4% and also a high specificity (78.4%). The PWH score had a lower sensitivity (80.6%) with comparable specificity. The Larson score showed the lowest sensitivity (70.9%) at a specificity of 80.4%.ConclusionsWeighted and more sophisticated systems such as TASH and PWH scores including higher numbers of variables perform superior over simple non-weighted models. Prospective validations are needed to improve the development process and use of scoring systems in the future.

Renaissance of base deficit for the initial assessment of trauma patients: a base deficit-based classification for hypovolemic shock developed on data from 16,305 patients derived from the TraumaRegister DGU®

IntroductionThe recognition and management of hypovolemic shock still remain an important task during initial trauma assessment. Recently, we have questioned the validity of the Advanced Trauma Life Support (ATLS) classification of hypovolemic shock by demonstrating that the suggested combination of heart rate, systolic blood pressure and Glasgow Coma Scale displays substantial deficits in reflecting clinical reality. The aim of this study was to introduce and validate a new classification of hypovolemic shock based upon base deficit (BD) at emergency department (ED) arrival.MethodsBetween 2002 and 2010, 16,305 patients were retrieved from the TraumaRegister DGU® database, classified into four strata of worsening BD [class I (BD ≤ 2 mmol/l), class II (BD > 2.0 to 6.0 mmol/l), class III (BD > 6.0 to 10 mmol/l) and class IV (BD > 10 mmol/l)] and assessed for demographics, injury characteristics, transfusion requirements and fluid resuscitation. This new BD-based classification was validated to the current ATLS classification of hypovolemic shock.ResultsWith worsening of BD, injury severity score (ISS) increased in a step-wise pattern from 19.1 (± 11.9) in class I to 36.7 (± 17.6) in class IV, while mortality increased in parallel from 7.4% to 51.5%. Decreasing hemoglobin and prothrombin ratios as well as the amount of transfusions and fluid resuscitation paralleled the increasing frequency of hypovolemic shock within the four classes. The number of blood units transfused increased from 1.5 (± 5.9) in class I patients to 20.3 (± 27.3) in class IV patients. Massive transfusion rates increased from 5% in class I to 52% in class IV. The new introduced BD-based classification of hypovolemic shock discriminated transfusion requirements, massive transfusion and mortality rates significantly better compared to the conventional ATLS classification of hypovolemic shock (p < 0.001).ConclusionsBD may be superior to the current ATLS classification of hypovolemic shock in identifying the presence of hypovolemic shock and in risk stratifying patients in need of early blood product transfusion.

Administration of fibrinogen concentrate in exsanguinating trauma patients is associated with improved survival at 6 hours but not at discharge.

BACKGROUND Despite poor evidence and high costs, fibrinogen concentrate (FC) represents one of the most frequently used hemostatic agents in exsanguinating trauma. The aim was to assess whether the administration of FC in severely injured patients was associated with improved outcomes. METHODS Patients documented in the Trauma Registry of the German Society for Trauma Surgery (primary admissions, Injury Severity Score [ISS] ≥16) who had received FC during initial care between emergency department (ED) arrival and intensive care unit admission (FC+) were matched with patients who had not received FC (FC−). RESULTS The matched-pairs analysis yielded two comparable cohorts (n = 294 in each group) with a mean ISS of 37.6 ± 13.7 (FC+) and 37.1 ± 13.3 (FC−) (p = 0.73); the mean age was 40 ± 17 versus 40 ± 16 (p = 0.72), respectively. Patients were predominantly male (71.1% in both groups, p = 1.0). On emergency department arrival, hypotension (systolic blood pressure, ⩽90 mm Hg) occurred in 51.4% (FC+) and 48.0% (FC−) (p = 0.41), and base excess was −7.4 ± 5.3 mmol/L for FC+ and was −7.5 ± 6.2 mmol/L for FC− (p = 0.96). Patients were administered 12.8 ± 14.3 (FC+) versus 11.3 ± 10.0 (FC−) packed red blood cell units (p = 0.20). Thromboembolism occurred in 6.8% (FC+) versus 3.4% (FC−) (p = 0.06), and multiple organ failure occurred in 61.2% versus 49.0% (p = 0.003), respectively. Whereas 6-hour mortality was 10.5% for FC+ versus 16.7% for FC− (p = 0.03), the mean time to death was 7.5 ± 14.6 days versus 4.7 ± 8.6 days (p = 0.006). The overall hospital mortality rate was 28.6% versus 25.5% (p = 0.40), respectively. CONCLUSION This is the first study to investigate the effect of FC administration in bleeding trauma. In our large population of severely injured patients, the early use of FC was associated with a significantly lower 6-hour mortality and an increased time to death, but also an increased rate of multiple organ failure. A reduction of overall hospital mortality was not observed in patients receiving FC. LEVEL OF EVIDENCE Therapeutic study, level IV.

Predictive Models and Algorithms for the Need of Transfusion Including Massive Transfusion in Severely Injured Patients

Background: Despite improvements on how to resuscitate exsanguinating patients, one remaining key to improve outcome is to expeditiously and reproducibly identify patients most likely to require transfusion including including massive transfusion (MT). This work summarizes yet developed algorithms/scoring systems for transfusion including MT in civilian and military trauma populations. Methods: A systematic search of evidence was conducted utilizing OVID/MEDLINE (1966 to present) and the ‘Medical Algorithms Project’. Results and Conclusions: The models developed suggest combinations of physiologic, hemodynamic, laboratory, injury severity and demographic triggers identified on the initial evaluation of the bleeding trauma patient. Many approaches use a combination of dichotomous variables readily accessible after arrival but others rely on time-consuming calculations or complex algorithms and may have limited real-time aplication. Weighted and more sophisticated systems including higher numbers of variables perform superior. A common limitation to all models is their retrospective nature, and prospective validations are urgently needed. Point-of-care viscoelastic testing may be an alternative to these systems.

The golden hour of shock - how time is running out: prehospital time intervals in Germany--a multivariate analysis of 15, 103 patients from the TraumaRegister DGU(R).

Objectives Although prehospital treatment algorithms have changed over the past years, the prehospital time of multiple trauma patients of some 70 min and the on-scene-treatment time (OST) of some 30 min have not changed since 1993. The aim of this study was to critically assess specific interventions and conditions at the scene in relation to their impact on prehospital rescue intervals. Methods We performed a retrospective data analysis of all multiple injured patients from the TraumaRegister DGU (English: German Trauma Society) from January 1993 to December 2010. Exclusion criteria were missing or implausible data regarding prehospital timelines. With OST as an independent variable, different models of multivariate regression were performed to identify parameters with relevant impact on the OST. Results 15 103 datasets were included in this study. Based on the mean OST of 32.7 (±18.6) min and a constant absolute term of 16.2 (±1.5) min, we identified seven procedures and nine environmental parameters with significant impact on OST. Intubation (9.3±0.8 min) and being a car occupant (8.0±0.8 min) were associated with the most prolonged OSTs. A Glasgow Coma Scale ≤8 (−4.5±0.7 min) and cardiopulmonary resuscitation (−2.8±1.7 min) resulted in its most relevant reduction. Admission to a Level III facility led to a reduced overall prehospital time (60.0±24.6 min) compared with Level I (70.0±28.5 min) and II (66.8±27.4 min) trauma centres. Conclusions This study identified characteristic interventions and conditions with significant impact on prehospital treatment times. Current treatment concepts should be re-evaluated with respect to these results.

Acute and chronic wound fluids inversely influence adipose‐derived stem cell function: molecular insights into impaired wound healing

Wound healing is a complex biological process that requires a well‐orchestrated interaction of mediators as well as resident and infiltrating cells. In this context, mesenchymal stem cells play a crucial role as they are attracted to the wound site and influence tissue regeneration by various mechanisms. In chronic wounds, these processes are disturbed. In a comparative approach, adipose‐derived stem cells (ASC) were treated with acute and chronic wound fluids (AWF and CWF, respectively). Proliferation and migration were investigated using 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) test and transwell migration assay. Gene expression changes were analysed using quantitative real time–polymerase chain reaction. AWF had a significantly stronger chemotactic impact on ASC than CWF (77·5% versus 59·8% migrated cells). While proliferation was stimulated by AWF up to 136·3%, CWF had a negative effect on proliferation over time (80·3%). Expression of b‐FGF, vascular endothelial growth factor (VEGF) and matrix metalloproteinase‐9 was strongly induced by CWF compared with a mild induction by AWF. These results give an insight into impaired ASC function in chronic wounds. The detected effect of CWF on proliferation and migration of ASC might be one reason for an insufficient healing process in chronic wounds.

Comparison of the predictive performance of the BIG, TRISS and PS09 score in an adult trauma population derived from multiple international trauma registries

BackgroundThe BIG score (Admission base deficit (B), International normalized ratio (I), andGlasgow Coma Scale (G)) has been shown to predict mortality on admission inpediatric trauma patients. The objective of this study was to assess itsperformance in predicting mortality in an adult trauma population, and to compareit with the existing Trauma and Injury Severity Score (TRISS) and probability ofsurvival (PS09) score.Materials and methodsA retrospective analysis using data collected between 2005 and 2010 from seventrauma centers and registries in Europe and the United States of America wasperformed. We compared the BIG score with TRISS and PS09 scores in a population ofblunt and penetrating trauma patients. We then assessed the discrimination abilityof all scores via receiver operating characteristic (ROC) curves and compared theexpected mortality rate (precision) of all scores with the observed mortalityrate.ResultsIn total, 12,206 datasets were retrieved to validate the BIG score. The mean ISSwas 15 ± 11, and the mean 30-day mortality rate was 4.8%. With an AUROC of0.892 (95% confidence interval (CI): 0.879 to 0.906), the BIG score performed wellin an adult population. TRISS had an area under ROC (AUROC) of 0.922 (0.913 to0.932) and the PS09 score of 0.825 (0.915 to 0.934). On a penetrating-traumapopulation, the BIG score had an AUROC result of 0.920 (0.898 to 0.942) comparedwith the PS09 score (AUROC of 0.921; 0.902 to 0.939) and TRISS (0.929; 0.912 to0.947).ConclusionsThe BIG score is a good predictor of mortality in the adult trauma population. Itperformed well compared with TRISS and the PS09 score, although it hassignificantly less discriminative ability. In a penetrating-trauma population, theBIG score performed better than in a population with blunt trauma. The BIG scorehas the advantage of being available shortly after admission and may be used topredict clinical prognosis or as a research tool to risk stratify trauma patientsinto clinical trials.

Coagulation system changes associated with susceptibility to infection in trauma patients.

BACKGROUND Infection following trauma is associated with increased morbidity and mortality and is common following severe hemorrhage. There is a strong interaction between the coagulation and immunity. The objective of this study was to establish if there was an association between changes in coagulation status after hemorrhage and the subsequent incidence of infection. METHODS Prospective cohort study of adult injured patients presenting to a major trauma center during a 2-year period. Blood was drawn at 24 hours following admission and analyzed using functional thromboelastography testing and laboratory defined tests of coagulation and blood count. Patients were followed up for infectious episodes while in the hospital using Center for Disease Control definitions. RESULTS A total of 158 patients were recruited; 71 (45%) developed infection and were older (44 years vs. 32 years, p = 0.01) and more severely injured (Injury Severity Score [ISS], 25 vs.10; p < 0.01). White blood cell counts at 24 hours were normal, and there was no difference between groups (both 9.6 × 109/L). Protein C was lower in those with infection (70.2 IU/dL vs. 83.3 IU/dL, p = 0.02), with a dose-dependent increase in infection as levels of protein C decreased. Plasmin activation at 24 hours was also strongly associated with infection plasmin-antiplasmin (infection vs. no infection, 6,156 &mgr;g/L vs. 3,324 &mgr;g/L, p = 0.03). The infection cohort had overall 12% lower procoagulant levels (varied between factor VIII 6.4% and factor II 16.2%). CONCLUSION There is a strong association between the status of the coagulation system after 24 hours and the development of infection following trauma. Improved early coagulation management may decrease infection rates in this patient group. LEVEL OF EVIDENCE Prognostic prospective study, level III.

‘Time to TASH’: how long does complete score calculation take to assess major trauma hemorrhage?

Dear Sir, Uncontrolled haemorrhage is still one of the leading causes of death within trauma patients (Evans et al., 2010) and is often exaggerated by the presence of acute traumatic coagulopathy (ATC) (Maegele et al., 2007). Despite substantial improvements in acute trauma care over the past decade, the rapid identification of patients with substantial ongoing bleeding and at risk for massive transfusion remains insufficient. Recently, our group has developed and validated the Trauma-Associated Severe Hemorrhage (TASH)-Score (Yücel et al., 2006; Maegele et al., 2011; Brockamp et al., 2012), as an easy-to-calculate and valid scoring system to predict the individual’s probability for massive transfusion, as a surrogate for life-threatening hemorrhage after multiple trauma. A major criticism of the score has been its potential lack in timely calculation during early trauma resuscitation. In this study, the time to complete TASH calculation was prospectively assessed in a cohort of trauma patients admitted to our level-1 trauma center. The setting for this prospective observational study was the emergency department (ED) of our urban level-1 trauma center, the Cologne-Merheim Medical Center (CMMC), Germany. All patients admitted during regular working hours (7 am to 7 pm) with trauma team activation were included within a 2-month period. An independent physician documented the time point of the patient arrival to the resuscitation room as well as the time point at which each variable necessary to calculate TASH was obtained. Time capture was initiated as soon as the patient arrived to the resuscitation room and prior to transfer of the patient onto the ED stretcher. Base excess (BE) and haemoglobin (Hb) were assessed by using point-of-care (POC) devices (IRMA TruePoint®, Keller Medical, Bad Soden, Germany). Potential pelvic and femoral instability were clinically assessed via manual examination by the trauma/orthopedic surgeon in charge. If in doubt, conventional X-rays were obtained. Potential free intraabdominal fluid was assessed by FAST (focused assessment with sonography for trauma) performed by the general surgeon in charge. Forty trauma patients were enrolled in the present analysis. Patients were predominantly male (78·6%), suffered from blunt trauma (95%) and presented with a mean age of 58·6 (±21·4) years. Overall, the mean time for assessment and complete

The trauma patient in hemorrhagic shock: how is the C-priority addressed between emergency and ICU admission?

BackgroundTrauma is the leading cause of death in young people with an injury related mortality rate of 47.6/100,000 in European high income countries. Early deaths often result from rapidly evolving and deteriorating secondary complications e.g. shock, hypoxia or uncontrolled hemorrhage. The present study assessed how well ABC priorities (A: Airway, B: Breathing/Ventilation and C: Circulation with hemorrhage control) with focus on the C-priority including coagulation management are addressed during early trauma care and to what extent these priorities have been controlled for prior to ICU admission among patients arriving to the ER in states of moderate or severe hemorrhagic shock.MethodsA retrospective analysis of data documented in the TraumaRegister of the ‘Deutsche Gesellschaft für Unfallchirurgie’ (TR-DGU®) was conducted. Relevant clinical and laboratory parameters reflecting status and basic physiology of severely injured patients (ISS ≥ 25) in either moderate or severe shock according to base excess levels (BE -2 to -6 or BE < -6) as surrogate for shock and hemorrhage combined with coagulopathy (Quick’s value <70%) were analyzed upon ER arrival and ICU admission.ResultsA total of 517 datasets was eligible for analysis. Upon ICU admission shock was reversed to BE > -2 in 36.4% and in 26.4% according to the subgroups. Two of three patients with initially moderate shock and three out of four patients with severe shock upon ER arrival were still in shock upon ICU admission. All patients suffered from coagulation dysfunction upon ER arrival (Quick’s value ≤ 70%). Upon ICU admission 3 out of 4 patients in both groups still had a disturbed coagulation function. The number of patients with significant thrombocytopenia had increased 5-6 fold between ER and ICU admission.ConclusionThe C-priority including coagulation management was not adequately addressed during primary survey and initial resuscitation between ER and ICU admission, in this cohort of severely injured patients.