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Trauma may cause a relevant reduction in antithrombin (AT) III activity, which is associated with adverse events. The very early changes in AT III activity after accident trauma are still unclear and possible relations with Interleukin (IL)-6, which is known to interact with AT III, have not been investigated so far. Upon approval of the IRB/IEC, 30 patients were enrolled with multiple injuries (ISS 9-75). Groups were performed according to injury severity, IL-6 concentration, and survivors versus non-survivors. Blood samples were collected at the scene of accident then at 2, 4, 6, 12, and 24 h and at day 3, 5, 10 and 15. No patient received AT III concentrates. In all groups a reduction in AT III activity occurred, which was most pronounced in very severe injuries. The activity re-increased spontaneously and steadily in all groups regardless of the IL-6 concentration. There was no clear impact of the AT III activity on survival.

Objective: The long-term outcome of trauma patients basically depends on the relation between the clearance capacity of the organism, e.g., the lungs, and the antigenic (inflammatory) load in relation to the amount of damaged and perfused tissue. It is necessary to determine quality and quantity of fracture and soft-tissue damage by clinical means as early as possible. It is unknown whether biochemical markers and the impact of soft-tissue trauma correlate and whether there is a predictive value on clinical outcome., Methods: A total of 107 trauma patients were prospectively enrolled in the study. Blood samples were collected immediately at the site of accident, at hospital admission, and every 2 hours for an interval of 24 hours, then daily. In addition to the biochemical analysis of 20 different substances, the following data were collected and correlated to the laboratory results: Injury Severity Score, polytrauma score of Hannover, modified fracture index, and soft-tissue index. These primary clinical findings as well as the laboratory data were correlated to criteria of clinical outcome such as length of stay in the intensive care unit, length of hospital stay, infections, systemic inflammatory response syndrome, sepsis, multiple organ failure score according to Goris, and finally to primary (< 72 hours), secondary (> 72 hours), and overall lethality. The determination of individual extent and severity of soft-tissue trauma is based on standard partial body volumes derived from healthy volunteers. In addition, clinical estimation of the degree of soft-tissue damage according to the usual classifications was performed., Results: Significant (p > 0.05) correlations were found between fracture as well as soft-tissue trauma and intensive care unit stay, hospital stay, infections, systemic inflammatory response syndrome, multiple organ failure score, serum concentrations/activities of serum interleukin-6 and -8 and creatine kinase during the first 24 hours after trauma. Severe soft-tissue trauma was related to secondary lethality, however, without statistical significance., Conclusion: The amount of fracture and soft-tissue damage can be estimated early by analysis of serum interleukin-6 and creatine kinase and is of great importance with regard to long-term outcome after trauma.

Unlabelled: There is compelling data from several clinical studies on the impact of various anti- and proinflammatory mediators on traumatized patients. Immediate trauma-related results, however, are only available from animal experiments so far. Therefore, in this prospective clinical study the following questions were addressed: (I) Is there any marker in the preclinical phase that give information independent of and better than conventional studies conducted so far, (II) does this possible factor prove to be a (significant) predictor of late complications and/or poor overall outcome, and (III) does this mediator provide information that can alter treatment decisions?, Methods: Upon approval of the local IRB/IEC, 85 patients (pts) were enrolled who suffered from multiple injuries. The pts were rescued by the helicopter-based service of the German Army Hospital in Ulm. The first blood samples were drawn at the site of accident and at admission, then in hourly to daily intervals. The plasma concentrations of following mediators were analyzed: Prostanoids, products of O2-radicals, soluble adhesion molecules, various cytokines, C-reactive protein, creatinine kinase, and neopterin. All values were calculated in relation to the actual plasma protein content to eliminate fluid-induced dilution effects. Subsets of patients were performed according to the severity of trauma (ISS < 9; 9-17; 18-31; > 32), based on the different injury pattern, and survivors versus nonsurvivors as well., Results: As early as at the scene of accident, all patients revealed a severity-dependent increase in most mediators' plasma levels. There was, however, also a pattern-related inflammatory response that was most pronounced in pts who had suffered from thoracic trauma irrespective of whether it was associated with multiple trauma. In a total, 15 pts died within 72 h after the accident. In those casualties, the plasma concentrations of prostaglandin E2 (P < 0.03), glutathione (P < 0.01) as well as creatinine kinase (P < 0.05) were more markedly elevated when compared with survivors., Conclusion: Although there were severity-dependent as well as pattern-related releases of various mediators, which in part were more apparent in nonsurviving patients, we failed in proving any predictive marker to specifically discriminate outcome.

Since nitric oxide (NO) contributes to both circulatory disorders and host defense, we analyzed the NO production in (poly)trauma patients (pts) in a prospective (pre)clinical study starting as early as at the scene of accident. Upon approval of the local IRB/EC, 85 multiple injured pts were enrolled. Subsets were performed according to trauma severity (ISS) and injury pattern, and between survivors versus nonsurvivors. The first blood sample was collected at the scene of accident, then in hourly to daily intervals. NO production was assessed by measuring nitrate+nitrite plasma levels. To estimate dilution effects, all values were calculated according to the actual plasma protein content. The extent of trauma was appraised by C-reactive protein (CRP) levels. Immediately after trauma, NO2-+NO3- plasma levels were always elevated. This was most pronounced in thoracic injury, irrespective of whether it was combined with multiple trauma. Nitrate+nitrite levels returned to normal within 24 h. CRP generation increased during 12 h following trauma and was most marked in severest trauma (ISS >50). For the first time, we show very early data following major trauma that demonstrate that NO overproduction starts immediately after trauma. However, systemic NO2-+NO3- levels actually reflect the severity of injury only during the first 2 h. Thereafter, NO generation is rather related to the individual trauma pattern, e.g., chest trauma. Nonetheless, the role of NO after severe trauma and especially in thoracic injury remains unclear and should further be elucidated in a specific study.

Both, burn trauma and sepsis induce the generation of reactive oxygen intermediates which often coincides with increased nitric oxide (NO) levels. NO takes part in both circulatory disorders and cell protection. Therefore, in a prospective (pre-)clinical study we focused on the detection of NO in polytrauma patients (pts) starting as early as at the scene of accident. Upon approval of the local ethics committee, pts with an injury severity score (ISS) ranging from 9 to 75 (mean 22) were enrolled. Subsets were performed according to the different injury pattern (long bone fractures, head injury, polytrauma with and without damage to the thorax, isolated chest trauma). The first blood sample was obtained at the scene of accident. Then, blood was collected in hourly to daily intervals. NO production was assessed by the nitrate + nitrite plasma levels. To eliminate dilution effects following volume substitution, all values were recalculated on the plasma protein content. Immediately after trauma, NO plasma levels were elevated. This was most pronounced in pts that have experienced thoracic injuries irrespective of with or without additional polytrauma. There is evidence that NO production always starts immediately after major trauma but depends on the individual trauma pattern. In addition, the results reveal that lethal outcome is associated with an increased NO generation in the early post-injury period. We conclude that NO overproduction does not necessarily prime an overall protection in patients that have suffered from mechanical trauma. The role of NO after severe trauma and especially in thoracic injury should further be elucidated in a specific study on that topic.

Background: The molecule CD14 acts as a receptor for the protein-bound endotoxin (lipopolysaccharide [LPS]) complex and mediates the cellular effects of LPS. The soluble formation, sCD14, is supposed to neutralize circulating LPS (i.e., LPS antagonist) or transfer LPS effects to endothelial cells (i.e., LPS agonist)., Objective: To elucidate the release of sCD14 per se in patients with major trauma in the early posttrauma period. Our a priori hypothesis was that sCD14 release depends on the plasma LPS concentration simultaneously measured., Patients: In a prospective study, 65 patients with multiple injuries (Injury Severity Score, 9-75) were enrolled. The patients were rescued by the medical helicopter service and directly admitted to our clinics. The plasma concentrations of sCD14 (enzyme immunoassay) and LPS (chromogenic limulus amebocyte lysate test) were analyzed. The first blood sample was collected immediately at the accident site. The following samples were drawn at intervals from 2 hours to daily for 2 weeks., Results: Sixty-one patients survived the observation time. Immediately after trauma, their mean sCD14 level was not different from that of healthy individuals. Two hours later, a pronounced increase of sCD14 was observed and sustained throughout the observation period. Even nonsurvivors showed an increased sCD14 release, but less pronounced. In all patients, plasma LPS levels were elevated during the first 12 hours., Conclusions: Major trauma caused an increased release of sCD14. This elevation, however, was not correlated to LPS levels or to the severity of trauma (estimated by trauma scores). We found no evidence that sCD14 levels are of prognostic value regarding survival. Furthermore, the release of sCD14 did not occur in an LPS-neutralizing manner, but rendered possible an LPS-independent mechanism.

24 anesthetized mongrel dogs are subjected to a standardized trauma followed by a hypotonic hemorrhagic shock. Compared with the control group (n equals 8) prophylactic treatment with heparin in the second group (n equals 8) reduces the rise of pulmonary vascular resistance only insignificantly. The correction of the metabolic acidosis with Tris does not prevent a rise of PVR in third group (n equals 8).

Twenty-six anesthesized mongrel dogs were subjected to a standardized traumatic hemorrhagic shock. Compared with the control group prophylactic treatment with high doses of methylprednisolone reduced functional and histologic alterations of the lung. Methylprednisolone in combination with heparin pretreatment prevents microthrombi but produces more alveolar bleeding.

26 mongrel dogs are subjected to a standardized bone trauma followed by a hypotonic hemorrhagic shock. Compared with a control and heparin group prophylactic treatment with Dipyridamol and Acetylsalicylic Acid decreases pulmonary vascular resistance significantly. After an initial period of hyperocagulability secondary fibrinolysis develops. The decrease of the fibrinogen level and the fall of total platelet count after trauma and hemorrhage can partly be prevented by the application of heparin, likewise the development of pulmonary microthrombosis. Histological examination shows a markedly diminished pulmonary microthrombosis.

A severe shock is produced in 18 mongrel dogs by standardized bone trauma and haemorrhagic shock. Impairment of microcirculation is demonstrated by acidosis, reduced oxygen uptake and disseminated intravascular coagulation (DIC). Further, a specific increase in pulmonary vascular resistance--independent of the reduction in blood flow--is evoked, concomitantly with the occurrence of microthrombi, oedema and haemorrhage in lung tissue. Pretreatment with heparin inhibits disseminated intravascular coagulation and reduces impairment of microcirculation and the consecutive damage of intestinal organs. However increase of pulmonary vascular resistance is unchanged and pulmonary haemorrhage is pronounced. Therefore heparin pretreatment enhances pulmonary histologic impairment after trauma and haemorrhagic shock.