S2e guideline: positioning and early mobilisation in prophylaxis or therapy of pulmonary disorders : Revision 2015: S2e guideline of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI).

The German Society of Anesthesiology and Intensive Care Medicine (DGAI) commissioneda revision of the S2 guidelines on "positioning therapy for prophylaxis or therapy of pulmonary function disorders" from 2008. Because of the increasing clinical and scientificrelevance the guidelines were extended to include the issue of "early mobilization"and the following main topics are therefore included: use of positioning therapy and earlymobilization for prophylaxis and therapy of pulmonary function disorders, undesired effects and complications of positioning therapy and early mobilization as well as practical aspects of the use of positioning therapy and early mobilization. These guidelines are the result of a systematic literature search and the subsequent critical evaluation of the evidence with scientific methods. The methodological approach for the process of development of the guidelines followed the requirements of evidence-based medicine, as defined as the standard by the Association of the Scientific Medical Societies in Germany. Recently published articles after 2005 were examined with respect to positioning therapy and the recently accepted aspect of early mobilization incorporates all literature published up to June 2014.

[Short version S2e guidelines: "Positioning therapy and early mobilization for prophylaxis or therapy of pulmonary function disorders"]. / Kurzversion S2e-Leitlinie - "Lagerungstherapie und Frühmobilisation zur Prophylaxe oder Therapie von pulmonalen Funktionsstörungen".

The German Society of Anesthesiology and Intensive Care Medicine (DGAI) commissioned a revision of the S2 guidelines on "positioning therapy for prophylaxis or therapy of pulmonary function disorders" from 2008. Because of the increasing clinical and scientific relevance the guidelines were extended to include the issue of "early mobilization" and the following main topics are therefore included: use of positioning therapy and early mobilization for prophylaxis and therapy of pulmonary function disorders, undesired effects and complications of positioning therapy and early mobilization as well as practical aspects of the use of positioning therapy and early mobilization. These guidelines are the result of a systematic literature search and the subsequent critical evaluation of the evidence with scientific methods. The methodological approach for the process of development of the guidelines followed the requirements of evidence-based medicine, as defined as the standard by the Association of the Scientific Medical Societies in Germany. Recently published articles after 2005 were examined with respect to positioning therapy and the recently accepted aspect of early mobilization incorporates all literature published up to June 2014.

[Scientific monitoring of the visitation procedure in inpatient rehabilitation centres of the German statutory pension insurance fund--the "Visit II" Project]. / Wissenschaftliche Begleitung der Weiterentwicklung des Visitationsverfahrens für Reha-Kliniken der Deutschen Rentenversicherung Bund--Das Projekt "Visit II".

Visitation procedures are an established method of external quality assurance. They have been conducted for many years in the German statutory pension insurance's medical rehabilitation centres and have continuously been refined and standardized. The overall goal of the visitation procedure implemented by the German statutory pension fund is to ensure compliance with defined quality standards as well as information exchange and counselling of rehabilitation centres. In the context of advancing the visitation procedure in the German statutory pension funds' medical rehabilitation centres, the "Visit II" Project was initiated to evaluate the perspectives and expectations of the various professional groups involved in the visitations and to modify the materials used during visitations (documentation form and manual). Evaluation data from the rehabilitation centres visited in 2008 were gathered using both written surveys (utilization analysis) and telephone-based interviews with administration managers and chief physicians. The utilization analysis procedure was evaluated with regard to its methodological quality. In addition, the pension insurance physicians in charge of patient allocation during socio-medical assessment were surveyed with regard to potential needs for revision of the visitation procedure. Data collection was complemented by expert panels with auditors. Interviews with users as part of the formative evaluation of the visitation procedure showed positive results regarding acceptance and applicability of the visitations as well as of the utilization analysis procedures. Various suggestions were made with regard to modification and revision of the visitation materials, that could be implemented in many cases. Documentation forms were supplemented by current scientifically-based topics in rehabilitation (e. g., vocationally oriented measures), whereas items with minor relevance were skipped. The manual (for somatic indications) was thoroughly revised. The transparent presentation of visitation processes and visitation criteria has proven to be a useful basis for strengthening the cooperation between the statutory pension insurance funds and the rehabilitation centres. Moreover, it is a helpful tool for the systematic and continuous advancement of this complex method by including all parties involved.

[Oscillating physiotherapy for secretolysis]. / Oszillierende Physiotherapie zur Sekretolyse.

Assisted coughing and mechanical cough aids compensate for the weak cough flow in patients with neuromuscular diseases (NMD). In cases with preserved respiratory muscles also breathing techniques and special devices, e. g., flutter or acapella can be used for secretion mobilisation during infections of the airways. These means are summarised as oscillating physiotherapy. Their mechanisms are believed to depend on separation of the mucus from the bronchial wall by vibration, thus facilitating mucus transport from the peripheral to the central airways. In mucoviscidosis and chronic obstructive pulmonary disease their application is established, but there is a paucity of data regarding the commitment in patients with neuromuscular diseases. The effective adoption of simple oscillation physiotherapeutic interventions demands usually a sufficient force of the respiratory muscles--exceptions are the application of the percussionaire (intrapulmonary percussive ventilator, IPV) or high frequency chest wall oscillation (HFCWO). In daily practice there is evidence that patients with weak respiratory muscles are overstrained with the use of these physiotherapeutic means, or get exhausted. A general recommendation for the adoption of simple oscillating physiotherapeutic interventions cannot be made in patients with NMDs. Perhaps in the future devices such as IPV or HFCWO will prove to be more effective in NMD patients.

[Further development and validation of a clinical auditing procedure for rehabilitation facilities]. / Weiterentwicklung und Validierung eines Verfahrens zur Visitation von Rehabilitationseinrichtungen.

Visitations (audits) are considered an instrument of external quality assurance by which the structural and organizational set-up of health facilities can be assessed on site by external experts. The Deutsche Rentenversicherung Bund (including the former Bundesversicherungsanstalt für Angestellte, BfA, the statutory pension insurance agency for white collar employees) is the largest body responsible for rehabilitation in Germany, and it regularly carries out visitations in the approximately 650 rehab centres it sends its patients to. The project presented in this article aimed at developing a manual with detailed descriptions of the procedures and criteria of the assessment, as well as at checking the inter-rater-reliability of the assessment. The manual was developed in cooperation with experts of the Deutsche Rentenversicherung Bund. It contains a description of the areas to be assessed during a visitation as well as leading questions and criteria for the evaluation of single features. The manual was examined in "test visitations" in 10 centres, each of which was visited by three visitation teams (1 medical and 1 administrative expert) simultaneously. When the resulting 30 assessments were compared, the criterion "overall quality of the centre" (which was assessed on a 10-point scale) showed precise agreement in 47 %, and a deviation by 1 point in 33 % of the cases. Single features assessed on a three-point scale (no improvement needed/improvement recommended/immediate improvement obligatory) resulted in precise agreement in between 80 % ("medical and therapeutic processes") and 86 % ("structural features") of the cases. Two-point scales (condition fulfilled or not fulfilled) showed an agreement between 89 % ("internal quality management") and 97 % ("single structural features"). In order to maintain and further develop this good inter-rater-reliability, the visitors of Deutsche Rentenversicherung Bund are continually trained in applying the visitation manual. In addition to transferring knowledge, these internal training courses are aimed at exchanging views and experience in order to enhance consensus among the visitors. This approach of Deutsche Rentenversicherung Bund could be regarded as "internal quality assurance" of its visitation procedure.

Systemic inflammatory response after endoscopic (TEP) vs Shouldice groin hernia repair.

Endoscopic techniques are commonly used for many different types of surgery. It is claimed that videoendoscopic procedures have the advantage of being less traumatic and of offering higher postoperative patient comfort than conventional open techniques. The extent of tissue trauma can be evaluated on the basis of the inflammatory response observed in the wake of surgery. Available studies that have compared endoscopic and conventional techniques suggest that endoscopic cholecystectomy, laparoscopic colorectal resection, and thoracoscopic pulmonary resection have immunologic advantages over conventional approaches. The objective of this prospective study was to determine whether endoscopic hernia repair techniques are also preferable to conventional procedures and to what extent the anesthetic technique (local or general anesthesia) influences the postoperative inflammatory response. For this purpose, biochemical monitoring of cytokine activity [C-reactive protein (CRP), prostaglandin F1alpha (PGF1alpha), neopterin, interleukin-6 (IL-6)] was done prospectively in 101 patients [totally extraperitoneal approach (TEP) n=32, unilateral n=12, bilateral n=20; Shouldice n=69, local anesthesia (LA) n=23, general anesthesia (GA) n=46] before and until 3 days after surgery. The parameters IL-6 and PGF1alpha suggested that the immune trauma immediately after surgery was significantly higher in the group of patients with endoscopic hernia repair than in the group of patients who received a Shouldice repair. No significant differences were observed after the first postoperative day. A comparison between the TEP group and the patients who received conventional surgery under local anesthesia showed that the TEP approach was also associated with a higher postoperative neopterin level. Within the first 3 days after surgical intervention, bilateral endoscopic hernia repair induced no significantly higher inflammatory response than the surgical treatment of unilateral conditions. The anesthetic procedure that was used in the Shouldice operation had no significant effect on inflammatory response. Unlike other types of endoscopic surgery, the repair of groin hernias using an endoscopic technique cannot be regarded as a minimally invasive procedure that is less traumatic than conventional approaches. Instead, the conventional Shouldice procedure appears to cause the lowest inflammatory response and to be the least traumatic approach to hernia repair, especially when it is performed under local anesthesia.

Animal models of sepsis.

Knowledge of sepsis is growing rapidly and new pathogenetic concepts and therapeutic strategies evolve. The animal models of sepsis catalyze this development. Any model of this complex disease is inevitably a compromise between clinical realism and experimental simplification. Against the background of current pathogenetic concepts this review tries to analyze the validity and clinical relevance of each model. Endotoxemia and bacteremia represent models without an infectious focus. They reproduce many characteristics of sepsis and are highly controlled and standardized. However, they reflect a primarily systemic challenge and create neither an infectious focus nor the protracted immune reaction that characterizes sepsis. In this respect, any model with an infectious focus is decisively closer to clinical reality. In these models the peritoneal cavity is contaminated either by bacteria or inoculated feces or perforation of the bowel wall. Both the bolus injection and the implantation of carriers loaded with bacteria or feces are used. In fecal spesis and perforation models the complete spectrum of enteric pathogens is present in the septic focus and infective selection is undisturbed. Here the pathophysiologic and immunologic features of clinical sepsis are successfully reproduced. However, presumably due to inadequate control of the bacterial challenge, only poor interlaboratory standardization is possible. As to optimize models for the clinical reality the choice of an appropriate class of models is crucial. Moreover the incorporation of clinical therapy such as volume resuscitation, antibiotic therapy and surgical treatment of the septic focus is indispensable. Finally, the importance of simulation of comorbidities cannot be overemphasized.

Does a postimplantation syndrome following endovascular treatment of aortic aneurysms exist?

The postimplantation syndrome (PIS) is a weakly defined condition that has been observed following endovascular treatment of aortic aneurysms; the postulated criteria include significant leukocytosis, fever, and/or coagulation disturbances. Among the factors that are supposed to contribute to this syndrome are contact activation by the stent covering with consecutive endothelial activation. Associated clinical parameters of a PIS were perioperatively monitored in the postoperative phase in a total of 69 patients with infrarenal aortic aneurysms treated with Y-stent grafts. C-reactive protein (CRP)-levels, leukocyte concentrations, and body temperature curves were directly compared to those of 50 patients undergoing conventional transperitoneal aneurysm resection. A subgroup of 10 patients of the endovascular group was compared with 13 operated-on patients with regard to an ischemia-reperfusion syndrome of the lower extremities. The mediator determinations were performed on venous (femoral vein) as well as in systemic (arterial) blood samples. The incidence of temperature values above 38 degrees C was higher in patients following endovascular treatment (72%) compared to conventionally operated-on patients (28%). CRP levels were not significantly different within the first 8 post-operative days. During open surgery, significantly higher values for lactate and lower pH levels were observed (p<0.01), as well as higher 6 keto prostaglandin F1alpha (PGF1alpha) levels. There was a short peak of PGF1alpha during eventeration of the intestine during the operative procedure that could not be detected during endovascular manipulations. The clinical and biochemical parameters do not prove the presence of a PIS following endovascular treatment of aortic aneurysms. In contrast, during open surgery the unspecific inflammatory reaction is higher, but not long-lasting. In the future, the suggested phenomenon of a decreased antiinflammatory cytokine response during endovascular surgery needs to be further examined.

Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs.

We investigated the effect of mercaptoethylguanidine (MEG, 3 mg kg(-1)h(-1)), a combined selective inducible nitric oxide synthase (iNOS) inhibitor, a peroxynitrite and oxygen free radical scavenger with cyclooxygenase-inhibitor properties on intestinal and hepatic perfusion, O2 exchange, and metabolism during long-term hyperdynamic porcine endotoxemia. MEG was started 12 h after onset of endotoxemia. At baseline and after 12, 18, and 24 h of endotoxemia, hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal and hepatic venous lactate/pyruvate ratio, free glutathione (GSH), and 8-isoprostanes were measured. Expired NO and plasma nitrate levels were assessed as well. MEG blunted the endotoxin-induced increase in expired NO and prevented the progressive fall in blood pressure without affecting cardiac output. It attenuated both systemic and regional venous acidosis without influencing the impairment of hepatosplanchnic metabolism nor counteracting the increase in GSH levels. In our model MEG failed to beneficially affect variables of oxidative stress.

Early inflammatory mediator response following isolated traumatic brain injury and other major trauma in humans.

The inflammatory response following isolated traumatic brain injury (TBI) is characterised by the release of pro- and anti-inflammatory mediators. In order to determine the important mediators regarding survival and outcome of patients with severe traumatic isolated head injuries, we performed this prospective preclinical and clinical study starting upon arrival at the site of the accident. After approval by the local ethics board committee, 94 multiple-injury patients were enrolled. Of these, 72 patients suffered from major injuries; the other 22 patients had a severe isolated brain injury and were allotted to subsets of survival or nonsurvival. Of the pro- and anti-inflammatory mediators (cytokines, arachidonic acid metabolites and soluble adhesion molecules), interleukin-6 (IL-6), IL-12 and malone dialdehyde (MDA) appeared to be of specific importance; maximum IL-6 plasma levels were eightfold higher in cases of nonsurvival than in those of survival. Patients that did not survive TBI were the only ones to express an IL-12 increase, whereas survivors and patients with other major trauma did not show any increase within the first 24 h. An early distinct decrease of MDA showed in patients who did not survive TBI, in contrast to survivor patients who exposed almost constant levels during the first 24 h.

Reduced serum total reductive capacity in lethal severe trauma.

BACKGROUND: Risk assessment is a prerequisite for effective treatment and triage in severe injury. A novel substrate-based assay to measure total reductive capacity (TORC) in serum was used to stratify risk of lethal outcome in severe trauma in a clinical trial. METHODS: Serum of patients with severe trauma (Injury Severity Score > 19) was obtained at the accident site, at admission, and at regular intervals thereafter. TORC was determined and correlated to outcome. The TORC assay uses thiol-labeled arachidonic acid as substrate from which free thiols are released by reductive amino acids and the specific activity of phospholipase A2. Free thiols are coupled to monochrombimone, and the resulting fluorescence is proportional to TORC. RESULTS: Eighteen patients with lethal severe trauma and 16 patients who survived were studied. Injury Severity Scores (lethal, 33 (29--43); survival, 31 (25--42); p = NS) and Polytrauma Scores (lethal, 25 [18--32]; survival, 26 [23--31], p = NS) were not significantly different. At the accident site, patients with a lethal course had significantly lower TORC than nonlethal cases (59.2 +/- 5.1 ng/mL vs. 89.5 +/- 6.7 ng/mL; p < 0.001). Values at admission were similar (lethal, 51.2 +/- 7 ng/mL; survival, 73.8 +/- 9 ng/mL; p < 0.01). At the accident site and at admission, TORC < 82.3 ng/mL was prognostic of lethal outcome (sensitivity, 88%; specificity, 65%/73% and 69%, respectively, for admission). CONCLUSION: Serum reductive potential at the site of accident or at admission allows the stratification of trauma patients with respect to lethal outcome in severe trauma when severity scores fail to do so.

Hepatic oxygen exchange and energy metabolism in hyperdynamic porcine endotoxemia: effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX30.

OBJECTIVE: We compared the effects of thromboxane receptor antagonist and synthase inhibitor DTTX30 on systemic and liver blood flow, oxygen (O2) exchange and energy metabolism during 24 h of hyperdynamic endotoxemia with untreated endotoxemia. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-seven domestic pigs: 16 during endotoxemia with volume resuscitation alone; 11 with endotoxemia, volume resuscitation and treatment with DTTX30. INTERVENTIONS: Continuous infusion of Escherichia coli lipopolysaccharide (LPS) for 24 h together with volume resuscitation. After 12 h of endotoxemia, DTTX30 was administered as a bolus of 0.12 mg kg-1 followed by 12 h continuous infusion of 0.29 mg kg-1 per h. MEASUREMENTS AND RESULTS: DTTX30 effectively counteracted the endotoxin-associated increase in TXB2 levels and increased 6-keto-PGF1 alpha with a significant shift of the thromboxane/prostacyclin ratio towards predominance of prostacyclin. DTTX30 prevented the significant progressive endotoxin-induced decrease of mean arterial pressure (MAP) below baseline while maintaining cardiac output (CO), and increased the fractional contribution of liver blood flow to CO without an effect on either hepatic O2 delivery or O2 uptake. The mean capillary hemoglobin O2 saturation (HbO2) on the liver surface and HbO2 frequency distributions remained unchanged as well. CONCLUSIONS: DTTX30 significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased the endogenous glucose production (EGP) rate, EGP returned towards baseline levels in the DTTX30-treated group. Thus, in our model DTTX30 resulted in hemodynamic stabilization concomitant with improved hepatic metabolic performance.

[New methods in polytrauma surgery. Results of a Study Congress at castle Reisenburg 27/28 February 2000]. / Neue Wege in der Polytraumaforschung. Ergebnisse einer Arbeitstagung auf Schloss Reisensburg, 27./28.02.2000.

Recently, in Germany the academic environment has changed and an upheaval occurred that directly do affect academic research activities. Increasingly, the funding of scientific projects is not provided anymore by the universities themselves or the government, but has to be acquired as grants. While in the past, research was conducted by single departments, nowadays and more and more in the future scientific networks have to be established by combining 'local' and even 'distant' knowledge. With this changing background in mind representatives of different scientific institutions met at the Reisensburg castle to discuss the current state and future trends in four major research fields: "Epidemiology of Severe Trauma", "Head Injury", "Pathophysiology of Damage to the Chest", and "Posttraumatic Soft Tissue Injury".

Trauma severity-dependent changes in AT III activity.

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.

Volume replacement in trauma patients within the first 24 h and its impact on the interpretation of biochemical data.

BACKGROUND AND AIMS: Patients of the same and particularly of different trauma studies are primarily incomparable due to different volume replacements. The aim of this prospective study was to analyze the amount of initially administered fluids in trauma patients during the first 24 h and to estimate the impact of dilution on plasma protein concentrations (PPCs) of prostanoids. These substances are vascular endothelium-derived and are thus influenced by blood pressure. PATIENTS/METHODS: Sixty-nine casualties suffering from multiple injuries were enrolled in the study. The amount of any fluid administered was scrutinized during the first 24 h. Patients were divided into subsets according to trauma severity by Injury Severity Score (ISS) (group=G-I: < or = 9; G-II: 10-18; G-III: 19-32; G-IV: >32) and between survivors and non-survivors. At corresponding time points, hemoglobin, hematocrit (Hct) and PPC as well as prostaglandins (PGI, TxA, PGF2a) were evaluated at the site of accident, at hospital admission, and every hour thereafter for the first 24 h. RESULTS: During this period, the total amount of infused fluids ranged between 0.51 (G-I) and >481 (G-IV). The higher the trauma severity, the greater the volume infused (G-III/IV P=0.0003 vs G-I/II). Simultaneously, PPC dropped markedly (P<0.01). Patients who died within 36 h required higher volumes (P<0.003) than survivors. PPC was linearly related (r2=.6685, P<0.001) to Hct. During the first 24 h, the time course of prostanoid concentration was altered when dilution is not taken into account. CONCLUSION: PPC proved a suitable parameter to estimate dilution effects and to adjust plasma concentrations of prostanoids. We recommend that consideration be given to possible dilution effects during the first 24 h when interpreting biochemical data in trauma patients.

Effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX-30 on intestinal O2-exchange and energy metabolism during hyperdynamic porcine endotoxemia.

Sepsis may lead to deranged thromboxane-prostacyclin ratio with consecutive organ dysfunction. Because of the suggested role of the gut in the pathogenesis of septic shock and multiple organ failure, we investigated the effects of the novel dual thromboxane synthase inhibitor and receptor antagonist DTTX-30 (TRASI) on intestinal tissue perfusion, O2 kinetics, and energy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxemia. Before, 12, 18, and 24 h after starting continuous i.v. endotoxin (LPS), we measured portal venous (PV) blood flow, intestinal oxygen extraction (iO2ER), intracapillary hemoglobin O2 saturation (HbO2%) of the ileal wall, intramucosal ileal PCO2, PV lactate-pyruvate (L-P) ratio, and plasma levels of thromboxane and prostacyclin. Treatment with TRASI (0.12 mg/kg i.v. bolus injection followed by an infusion of 0.29 mg/kg/h) initiated after 12 h of LPS infusion markedly reduced the plasma thromboxane levels and attenuated the LPS-induced fall in systemic vascular resistance, resulting in hemodynamic stabilization. TRASI did not influence the LPS-induced increase in PV blood flow nor intracapillary HbO2%, thus reflecting unchanged microcirculatory O2 availability and decreased iO2ER, possibly because of reduced O2 requirements. Nevertheless, TRASI prevented the LPS-induced increase in the PV L-P ratio, attenuated the progression of the ileal mucosal-arterial PCO2 gap, and tended to attenuate the gradual fall of PV pH. Hence, compounds like TRASI may beneficially influence LPS-related derangements of gut energy metabolism.

Is interleukin 6 an early marker of injury severity following major trauma in humans?

HYPOTHESIS: Interleukin 6 (IL-6), a multifunctional cytokine, is expressed by various cells after many stimuli and underlies complex regulatory control mechanisms. Following major trauma, IL-6 release correlates with injury severity, complications, and mortality. The IL-6 response to injury is supposed to be uniquely consistent and related to injury severity. Therefore, we designed a prospective study starting as early as at the scene of the unintentional injury, to determine the trauma-related release of plasma IL-6 in multiple injured patients. PATIENTS AND METHODS: On approval of the local ethics committee, 94 patients were enrolled with different injuries following trauma (Injury Severity Score [ISS] median, 19; range, 3-75). The patients were rescued by a medical helicopter. Subsets were performed according to the severity of trauma--4 groups (ISS, <9, 9-17, 18-30, and >32)-and survival vs nonsurvival. The first blood sample was collected at the scene of the unintentional injury before cardiopulmonary resuscitation, when appropriate. Then, blood samples were collected in hourly to daily intervals. Interleukin 6 plasma levels were determined using a commercial enzyme-linked immunosorbent assay test. The short-term phase protein, C-reactive protein, was measured to characterize the extent of trauma and to relate these results to IL-6 release. RESULTS: As early as immediately after trauma, elevated IL-6 plasma levels occurred. This phenomenon was pronounced in patients with major trauma (ISS, >32). Patients with minor injury had elevated concentrations as well but to a far lesser extent. In surviving patients, IL-6 release correlated with the ISS values best during the first 6 hours after hospital admission. All patients revealed increased C-reactive protein levels within 12 hours following trauma, reflecting the individual injury severity. This was most pronounced in patients with the most severe (ISS, >32) trauma. CONCLUSIONS: To our knowledge, this is the first study that elucidates the changes in the IL-6 concentrations following major trauma in humans as early as at the scene of the unintentional injury. The results reveal an early increase of IL-6 immediately after trauma. Moreover, patients with the most severe injuries had the highest IL-6 plasma levels. There is strong evidence that systemic IL-6 plasma concentrations correlate with ISS values at hospital admission. Therefore, IL-6 release can be used to evaluate the impact of injury early regardless of the injury pattern.

Early biochemical characterization of soft-tissue trauma and fracture trauma.

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.

[Prognostic importance of preclinically evaluated biochemical mediators in polytrauma]. / Prognostische Bedeutung präklinisch erfasster biochemischer Mediatoren beim Polytrauma.

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.