The potential impact of coagulation factor XIII in trauma-induced coagulopathy - a retrospective case series analysis.

BACKGROUND: The role of factor XIII (FXIII) in trauma-induced coagulopathy (TIC) is not fully understood. METHODS: We evaluated FXIII supplementation in severely injured patients with persistent bleeding. This was a retrospective case series analysis. RESULTS: Twenty-four patients received FXIII concentrate within 24 h of admission for bleeding that continued after transfusion of > 6 U red blood cells (RBCs); control patients (n = 27) did not receive FXIII concentrate. Both study groups were similar regarding injury severity score and global coagulation tests, but FXIII activity levels were significantly higher and lactate levels significantly lower in the control group, respectively. The differences in FXIII activity between the groups could be attributed to a more severe trauma-induced coagulopathy in FXIII-deficient patients, as demonstrated by lower fibrinogen and higher lactate levels. The median dose of FXIII concentrate within 24 h of admission was 2500 IU (IQR: 1250-4375). Median 24-h transfusion of RBCs (primary study endpoint) was significantly higher in the FXIII group versus controls (10.0 U, IQR 5-14 U vs. 2, IQR 0-6 U; p < 0.01). Subsequently, while patients were in the intensive care unit, there was no statistically significant difference regarding RBC transfusion anymore and the overall clinical outcomes were similar in both patient groups. CONCLUSIONS: The substitution of FXIII in patients who were more seriously compromised due to higher lactate levels and who presented with initially more severe bleedings than patients in the control group, resulted in a comparable transfusion necessity after 24 h. Thus, we guess that the substitution of FXIII in severely injured patients with ongoing bleeding might have an impact on their clinical outcome.

The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing.

Factor XIII (FXIII) is a protein involved in blood clot stabilisation which also plays an important role in processes including trauma, wound healing, tissue repair, pregnancy, and even bone metabolism. Following surgery, low FXIII levels have been observed in patients with peri-operative blood loss and FXIII administration in those patients was associated with reduced blood transfusions. Furthermore, in patients with low FXIII levels, FXIII supplementation reduced the incidence of post-operative complications including disturbed wound healing. Increasing awareness of potentially low FXIII levels in specific patient populations could help identify patients with acquired FXIII deficiency; although opinions and protocols vary, a cut-off for FXIII activity of ~ 60-70% may be appropriate to diagnose acquired FXIII deficiency and guide supplementation. This narrative review discusses altered FXIII levels in trauma, surgery and wound healing, diagnostic approaches to detect FXIII deficiency and clinical guidance for the treatment of acquired FXIII deficiency.

Analysis of extracorporeal membrane oxygenation in trauma patients with acute respiratory distress syndrome: A case series.

BACKGROUND: Thoracic trauma is the most common injury in polytrauma patients. Often associated with the development of an acute respiratory distress syndrome (ARDS), conservative treatment options are very restricted and reach their limits quickly. OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a wellestablished therapy in cardio-thoracic surgery and internal medicine intensive care units. The purpose of this study is to analyse the potential benefit of ECMO therapy in ARDS treatment in polytrauma patients. DESIGN: Retrospective case series. SETTING: Level 1 trauma centre, Germany, 04/2011-04/2019. PATIENTS: Nineteen patients with ARDS treated with a veno-venous ECMO system. MAIN OUTCOME MEASURES: This study focused on the time leading to therapy initiation, the severity of thoracic and overall injury. The Sequential Organ Failure Assessment (SOFA) Score, the Murray Score, the Abbreviated Injury Scale (AIS) 2005 level and the Injury Severity Score (ISS) were analysed. The results were analysed regarding survival and death. RESULTS: The survival rate was 53%. The ISS was the same for survivors and deceased patients (p = 0.604). Early initiation of ECMO therapy showed a significant trend for survivors (p = 0.071). The SOFA Score level before ECMO therapy was significantly lower in the survivors than in those who died (p = 0.035). The AISThorax level for survivors showed a significantly higher score level than the one for deceased patients (p = 0.05). CONCLUSION: ECMO therapy in polytrauma patients is a safe and effective option, in particular when used early in ARDS treatment. The overall severity of organ failure determined the likelihood of survival rather than the thoracic trauma itself.

Lung Transplantation following Emergency Pneumonectomy in a Polytraumatized 18-Year-Old.

Introduction. On rare occasions, a pneumonectomy needs to be performed after a severe polytrauma. Statistically, this procedure increases the mortality rate to 50%. One option to reduce this high rate could be an organ transplantation if a matching organ can be found. However, the current literature lacks any documentation of such a case. One reason for this stems from the fact that regulations for organ transplantation are very restricted and rarely allow exceptions. In addition, the chance for survival of polytraumatized patients in need of organs in the acute phase of the therapy is often quite unsure. Case Presentation. In this paper, we present the case of an 18-year-old patient who was involved in a serious motorcycle accident. His injury severity score was 29, but he suffered from severe bleeding in his lung which made a pneumonectomy necessary. The procedure led to a severe deterioration of his overall condition. An ECMO therapy was initiated, which effectively only slowed the aggravation. Therefore, he was transferred to our clinic where he was stabilized temporarily. A few days later, his situation turned worse. Since he had no other chance of survival, he was scheduled for a lung transplantation and was assigned an organ. After the transplantation, he stabilized quickly and recovered almost completely. Discussion. In this report, we want to show that an exception to the rules for organ transplantation might make sense on rare occasions. However, to increase the chance for any success, patients must be transferred to highly specialized clinics capable of treating patients with severe conditions. This might be the only chance for those patients to survive.

A Rare Case of Complex Pelvic Injury and Associated Intrathecal Fat Embolism due to Spinopelvic Dislocation with Sacral Burst Fracture.

INTRODUCTION: Pelvic and lumbar spine injuries are very common especially in multiple trauma patients. The usual mechanism in young patients leading to pelvic fractures is a high-energy trauma such as traffic accidents. In elderly patients, low energy traumas are causal for such injuries. Compared to the high number of patients with pelvic or lumbar spine injuries, cerebral fat embolism is a quite rare finding but it needs to be considered to not misinterpret the radiological findings. CASE: We present the case of a 41-year-old patient, who got hit and trapped in the lumbar region by a hydraulic arm in a car repair shop. The patient was primarily admitted to a level II trauma center. The radiological and clinical examinations revealed an open pelvic type C injury in terms of a spinopelvic dissociation, dislocation of the left hip joint, rupture of the mesentery of the rectum and colon sigmoideum, and a complex injury to the left ureter. Additionally, CT scan showed fluid with higher density than cerebro spinal fluid (CSF) in the lateral ventricles indicating an intracranial bleeding. After an immediate surgery to stabilize the patient, he was admitted to a level I trauma center. The reanalysis of the existing CT datasets combined with a new head CT leads to the conclusion that the high density fluid in the lateral ventricles is not a intracranial bleeding but rather fat deriving from the complex pelvic and lumbar spine fracture into the CSF system. Therefore, an immediate operation was performed to stabilize the spinopelvic dissociation and to close the injured dural sheath. Additionally, a ventricle drainage has been placed, which confirmed the diagnosis of intrathecal fat embolism. Afterwards, complex plastic surgery was necessary to restore the soft tissue damage. CONCLUSIONS: Intrathecal fat embolism in muliple trauma patients is a rare condition, which should be considered in patients with complex spine or pelvic injuries. It is important to distinguish this rare condition from intracranial bleedings, which are much more common because the consequent therapeutic strategy is quite different. In case of intrathecal fat embolism, a ventricle drainage system should be placed immediately, and the underlying spine or pelvic injuries need to be stabilized combined with closure of the dural sheath to prevent continuous fat embolism and meningeal infection.

Influence of intraoperative positive end-expiratory pressure level on pulmonary complications in emergency major trauma surgery.

INTRODUCTION: Pulmonary complications have a major impact on the morbidity and mortality of critically ill patients with multiple trauma. Intraoperative protective ventilation with low tidal volume may prevent lung injury and infection, whereas the role of positive end-expiratory pressure (PEEP) levels is unclear. The aim of this study was to evaluate the influence of different intraoperative PEEP levels on incidence of pulmonary complications after emergency trauma surgery. MATERIAL AND METHODS: We retrospectively analysed data of multiple trauma patients who underwent emergency surgery within 24 h after injury in our level I trauma centre (n = 86). On the basis of their intraoperative PEEP level, patients were divided into a low PEEP group with a PEEP of < 8 mbar and a high PEEP group with a PEEP of 8 mbar or higher. RESULTS: Besides differences in body mass index and preoperative oxygenation, there were no differences in patients' baseline data. There was a significant difference between incidence of pneumonia within 7 days after trauma surgery, with an incidence 26.7% in the low PEEP group and 7.3% in the high PEEP group (p = 0.02). The low PEEP group had higher pulmonary infection scores at days 3 and 5 after surgery. Oxygenation was better in the higher PEEP group postoperatively. There was no difference with respect to the incidence of acute respiratory distress syndrome, the mortality up until hospital discharge or haemodynamic parameters between groups. CONCLUSIONS: Higher PEEP levels were associated with perioperative improvement of oxygenation and a lower incidence of pneumonia, without impairment of haemodynamics. Additional studies should be initiated to confirm these observations.

Point-of-care monitoring for the management of trauma-induced bleeding.

PURPOSE OF REVIEW: Knowledge of trauma-induced coagulopathy has been grown in the past and point-of-care suitable devices for coagulation testing have been introduced. Methodology and clinical application of different systems for point-of-care coagulation monitoring are shown with a focus on thrombelastography as measured by TEG, rotational thromboelastometry as measured by ROTEM and impedance aggregometry as measured by the multiplate analyser and ROTEM platelet. RECENT FINDINGS: Two different methods for point-of-care coagulation assessment are available: viscoelastic tests (ROTEM, TEG) and impedance aggregometry. In different settings these methods have been evaluated in various publications pointing out the possibility of reducing transfusion requirements, transfusion-related side effects, and resulting costs. SUMMARY: Point-of-care assessment of coagulation in trauma patients appears to be at least promising. However, because published data mostly are of retrospective or observational nature only, there is a need for prospective, randomized and controlled studies.

First Successful Surgical Reconstruction of Bilateral Transected Main Bronchi With Extracorporeal Membrane Oxygenation Support.

Complex tracheobronchial injuries, especially if both main bronchi are involved, are life threatening and their diagnosis and successful treatment concerning short-term as well as long-term results are most challenging. This is the first report on a successful reconstruction of a complex bilateral bronchial injury under extracorporeal membrane oxygenation (ECMO) support. We present the course from prehospital treatment, establishment of ECMO in the emergency room to initial bronchoscopy, operative reconstruction, and intensive care therapy. Under these special circumstances ECMO provided a stable respiratory situation not only preoperatively but also intraoperatively without aggravating a compensated bronchial situation under aggressive ventilation.

Assessment of xylitol serum levels during the course of parenteral nutrition including xylitol in intensive care patients: a case control study.

BACKGROUND & AIMS: Xylitol has been approved for parenteral nutrition and may be beneficial in catabolic situations. The aim was to establish an easy method to monitor xylitol serum levels in patients receiving xylitol and to determine whether xylitol is safe. METHODS: A commercially available xylitol test was validated and used to measure serum levels in 55 patients admitted to our intensive care unit with an indication for parenteral nutrition with xylitol for at least 24 h. Controls consisted of the most recent 56 patients admitted to the intensive care unit who received parenteral nutrition without xylitol for at least 2 days. Xylitol serum levels were determined using the test. Adverse events, liver enzymes, lactate, bilirubin, γ-glutamyl transpeptidase, and insulin requirement were secondary endpoints. RESULTS: Patients receiving xylitol received 32.6% less insulin than controls. The amount of energy they received was comparable (xylitol: 810.1; controls: 789.8 kcal). Mean liver enzymes and lactate levels were similar in both groups. Adverse events considered attributable to xylitol did not occur. Xylitol did not accumulate in patients' blood and returned to near baseline values one day after parenteral nutrition was stopped. CONCLUSIONS: Parenteral nutrition with xylitol appears to be safe for critical care patients. There were no signs of hepatoxicity. TRIAL REGISTRATION DRKS: DRKS00004238.

Tolerability and efficacy of a low-volume enteral supplement containing key nutrients in the critically ill.

BACKGROUND & AIMS: To compare early supplementation with antioxidants and glutamine using a low-volume enteral supplement containing key nutrients to an energy adjusted standard elementary diet and to investigate its effect on clinical efficacy and tolerability in critically ill patients with sepsis/SIRS. The primary endpoints were length of stay in the ICU and sufficient enteral feed. METHODS: This was a randomized, prospective, single-blind, controlled study in 58 critically ill patients (56.9% male, mean age 46.7 years, mean APACHE II score 21.6). They received either a low-volume enteral supplement containing key nutrients or a diluted standard nutrition solution. After 10 or 14 days inflammatory parameters, catecholamine need, and maximal enteral delivery were determined. RESULTS: Patients receiving a low-volume enteral supplement containing key nutrients did not reach sufficient enteral feed more often than controls (76 vs. 62%, respectively, p = 0.17). The difference in vitamin E and selenium uptake was higher in the treatment group than controls (12.4 vs. 3.7 and 54.7 vs. 16.3, respectively, p ≤ 0.011). Parameters such as fever, antibiotic treatment, artificial ventilation, and death were comparable. This was also true for days of ICU or hospital stay (33 ± 23 and 49 ± 34 days, respectively). CONCLUSIONS: The low-volume enteral supplement containing key nutrients was well tolerated and led to a better vitamin E and selenium supply. However, it did not affect length of ICU or hospital stay. Further studies are necessary to determine which disease-specific subgroups may benefit from this supplementation or which group may be harmed.

Recipient-derived neoangiogenesis of arterioles and lymphatics in quilty lesions of cardiac allografts.

BACKGROUND: The contribution of extracardiac cells to tissue turnover in heart allografts has recently been demonstrated. Complex subendocardial infiltrates, known as Quilty lesions, are frequently observed in cardiac allografts. The origin of the different cellular components of Quilty lesions is not known. METHODS: Different constituents of these lymphonodular infiltrates were analyzed with regard to donor or recipient derivation. Laser-assisted microdissection with subsequent short tandem repeat polymerase chain reaction (PCR)-based "genetic fingerprinting" was employed. Combined immunofluorescence and fluorescence in situ hybridization for sex chromosomes was performed for confirmation in cases of gender-mismatched transplantation. Expression of angiogenic factors (FGF-2, PDGF-alpha, PDGF-alpha-receptor, and VEGF-alpha) was analyzed by quantitative real-time reverse-transcription PCR and immunohistochemistry. RESULTS: The inflammatory, nonvascular component of Quilty lesions was completely recipient-derived. Blood vessels were of mixed origin. Different compartments of blood vessels displayed different rates of recipient derivation (endothelium up to 50%, smooth muscle cells up to 15%). Lymphatic vessels were mainly recipient-derived. Of the angiogenic molecules, VEGF-alpha expression was significantly increased in the adjacent myocardium, compared to controls and the Quilty lesions themselves. CONCLUSIONS: The inflammatory compartment of Quilty lesions is of recipient origin and shows chimeric neoangiogenesis of blood and lymphatic vessels. VEGF-alpha produced in the adjacent myocardium appears to stimulate the chimeric neoangiogenesis.

Long-term cardiac allograft valves after heart transplant are functionally and structurally preserved, in contrast to homografts and bioprostheses.

BACKGROUND AND AIM OF THE STUDY: Homograft valves undergo degenerative changes over time, which finally lead to functional deterioration. Immunological events are believed to play a pivotal role in this process. To further evaluate this hypothesis, the valvular morphology and function, as well as comorbidities predisposing to deteriorative processes, were evaluated in patients who had undergone heart transplant more than 10 years previously. METHODS: In a consecutive cohort of 146 patients (125 males, 21 females; mean age at transplant 43.8 +/- 11.2 years), heart and valve function were assessed by color Doppler echocardiography at a mean of 5306 +/- 987 days after heart transplant. Evaluated parameters included chamber dimensions, cardiac function, valvular morphology/function, and concomitant diseases. RESULTS: Atrial and ventricular dimensions were within normal ranges for the left atrium (LA; n=7), right atrium (RA; n=7), left ventricle (LV; n=143) and right ventricle (RV; n=119). Slight enlargements occurred in the LA (n=138), RA (n=137), LV (n=1) and RV (n=11), while significant enlargements were seen in the LA (n=1), RA (n=2), LV (n=2), and RV (n=16). With regard to cardiac function, the ejection fraction (EF) was 63.9 +/- 4.9%, left ventricular isovolumic relaxation time (IVRT) 85.04 +/- 14.64 ms, fractional shortening (FS) 34 +/- 12%, and pulmonary artery systolic pressure (PASP) 29.81 +/- 6.4 mmHg. Valvular regurgitation (grade > or =2) was present in 34 patients (31 tricuspid valves, three mitral valves). No patients presented with aortic valve regurgitation. Concomitant conditions with a potential impact on calcium balance/valvular deterioration included immunologic/chronic inflammatory diseases (n=6), malignancies (n=12), kidney (n=41), cardiovascular system (n=39) and thyroid/parathyroid (n=12). CONCLUSION: During the long term after heart transplant, heart valves were characterized by normal morphology and function in the majority of cases. Although most patients presented with concomitant conditions strongly predisposing for valvular deterioration/calcification, sole immunosuppressive/anti-inflammatory therapy appears to prevent these processes in heart transplant patients.

Upregulation of endothelial adhesion molecules in hearts with congestive and ischemic cardiomyopathy: immunohistochemical evaluation of inflammatory endothelial cell activation.

OBJECTIVE: In recent years many data emphasized, that inflammatory reactions seem to be involved in the pathogenesis of ischemic (ICM) and congestive (CCM) heart disease. Since, it is well known that endothelial adhesion molecules play a pivotal role in the initiation and maintenance of inflammatory reactions we therefore, evaluated the endothelial expression of a wide variety of different adhesion molecules in hearts suffering from ICM and CCM. METHODS: Tissue samples from coronary arteries, and left and right ventricle myocardium originating form heart with ICM and CCM were evaluated. Tissue samples from healthy human donor hearts, which were not transplanted, served as controls. Evaluated adhesion molecule expression: selectin-family ELAM-1, CD62, immunoglobulin-supergene-family PECAM-1, ICAM-1, VCAM-1, integrin-family VLA-1,-2,-3,-4,-5, and -6, complementary-adhesion-molecules CD34, CD44 and the von-Willebrand-factor (vWF). RESULTS: While endocardial surfaces and coronary arteries revealed only little differences when comparing tissue samples originating from healthy donor hearts and those suffering from ICM and CCM, significant differences were found within the myocardial microvasculature. Both kinds of diseased hearts showed stronger expressions for CD62, ELAM-1, ICAM-1 and VCAM-1 (only CCM) than controls. More and above, integrin molecules showed differential expressions too. Whereas, VLA-1 showed stronger expressions in diseased hearts, VLA-3,-5, and -6 were expressed much weaker in those hearts. Complementary adhesion molecules (CD34/CD44) did not show significant differences and the vWF was not found in any sample. CONCLUSIONS: Inflammatory reactions play a pivotal role in the propagation and maintenance of both these cardiac detoriating diseases.

Role of inflammation in allogeneic and xenogeneic heart valve degeneration: immunohistochemical evaluation of inflammatory endothelial cell activation.

BACKGROUND AND AIM OF THE STUDY: Biological heart valve prostheses undergo degenerative changes which lead ultimately to dysfunction or even complete destruction. The study aim was to evaluate immunological factors and their potential role in biological heart valve destruction. METHODS: Allogeneic (n = 10) and xenogeneic (n = 3) aortic valve prostheses, as well as aortic valves retrieved from transplanted human hearts which had to be replaced due to chronic graft rejection (n = 4), were analyzed. Aortic valves from human donor hearts (n = 4) served as controls. Evaluated adhesion molecule expression included: selectin family ELAM-1, CD62; integrin family VLA-1, -2, -3, -4, -5 and -6; immuoglobulin supergene family PECAM-1, ICAM-1 and -2, and class I heavy chain proteins; complementary adhesion molecules CD34, CD44 and von Willebrand factor. RESULTS: ELAM-1, ICAM-1 and -2, CD34, CD44 and class I heavy chain proteins, which play significant roles during inflammatory processes, showed stronger expression patterns in allogeneic and xenogeneic aortic heart valve prostheses compared to native or chronically rejected valves. Furthermore, allogeneic and xenogeneic valves showed a strong thrombogenicity which stained positive for von Willebrand factor outside endothelial cells on these valves. Integrin molecules as well as CD62 showed only mild differences. CONCLUSION: Immunological reactions play a pivotal role in the degeneration of biological heart valve prostheses. As immunosuppressive therapy after heart valve replacement is not a viable option, novel approaches in 'tissue engineering' may help to avoid tissue degeneration while preserving the advantage of biological tissue origin.

Heart transplantation: echocardiographic assessment of morphology and function after more than 10 years of follow-up.

BACKGROUND: Over recent years, heart transplantation (HTX) developed into a successful option for long-term treatment of end-stage heart failure. Ten-year survival ranges between 40% and 50%. Little is known, however, about function and morphology of transplanted hearts during follow-up of more than 10 years. METHODS: In a consecutive cohort of 65 patients (55 male, 54.6 +/- 12.1 years at the time of transplantation), graft function was assessed by color Doppler echocardiography 12.5 +/- 1.4 years after heart transplantation (10 to 15 years). RESULTS: Left atrial and ventricular dimensions were found in a normal range (LA 37.7 +/- 8.9 mm, LV enddiastolic 45.6 +/- 6.4 mm, 30 to 71 mm). Ejection fraction (EF) of 71 +/- 11.7% and a fractional shortening of 35.3 +/- 10.3% presented with normal values. Left ventricular mass (male 263.8 +/- 111.4 g, female 373.0 +/- 181.1 g) was slightly increased resulting in mild hypertrophy in women. Focused on right ventricular morphology, enlargement of both the right atrium and the right ventricle (RA 40.7 +/- 11.8 mm, RV 37.4 +/- 8.3 mm) was observed in the majority of the patients. Tricuspid valve insufficiency (> grade II) was present in 46 of 65 patients; 5 patients had previously undergone tricuspid valve replacement. Atrial filling waves were detectable in only 47 of 65 patients, thus, 28% of patients showed signs of LA-dysfunction. CONCLUSIONS: More than 10 years post-HTX, cardiac grafts were characterized by normal left ventricular dimensions and ejection fraction. LA-dysfunction and RV-enlargement associated with tricuspid insufficiency were frequent findings, however, not associated with clinical signs of congestive heart failure in the majority of patients.