[Emergency intervention rate in the emergency room depending on the alerting criteria : Prospective data analysis of a supraregional trauma center]. / Notfallinterventionsrate bei Schockraumpatienten in Abhängigkeit von den Alarmierungskriterien : Prospektive Datenanalyse eines überregionalen Traumazentrums.

Trauma team alert (TTA) to the emergency room (ER) takes place in the event of disturbed vital signs or serious injuries (A criteria) or after a dangerous accident (B criteria). Due to low specificity and limited personnel resources, TTA is questioned for B criteria. The consequences would be an increase in undertriage and thus endangering patients. Due to the lack of data it is unclear whether adapted ER teams would be a solution to the problem.The aim of the study was to describe ER patients according to the TTA criteria and to collect the corresponding emergency intervention rates in ER.Over 1 year, all TTAs of a supraregional trauma center were prospectively recorded, categorized according to TTA criteria (A, B and NULL criteria) and compared descriptively. NULL criteria were TTAs for which neither A nor B criteria were met. Treatment data were documented according to the TraumaRegister DGU® standard form. Emergency interventions were intubation, chest tube, cardiopulmonary resuscitation, transfusion, coagulation substitution, external pelvic stabilization and surgical hemostasis.The TTA due to A, B and NULL criteria were performed in 19.5%, 51.2% and 29.3%, respectively. The mean injury severity (ISS ± standard deviation) was 20.6 ± 21.3 for A criteria, significantly higher than for B criteria (8.0 ± 7.1) and NULL criteria (5.6 ± 8.2). The emergency intervention rate for A , B and NULL criteria was 75%, 6% and 2.1%, respectively.Differentiation according to the TTA criteria results in patient collectives with different injury severity and emergency intervention rates. This result justifies considerations to adjust team composition based on TTA criteria, as long as it is ensured that critical conditions can be identified and remedied by adapted teams.

[Optimization of criteria for activation of trauma teams : Avoidance of overtriage and undertriage]. / Optimierung der Kriterien zur Schockraumalarmierung : Vermeidung von Über- und Untertriage.

INTRODUCTION: Severely injured patients are supposed to be admitted to hospital via the trauma room. Appropriate criteria are contained in the S3 guidelines on the treatment of patients with severe/multiple injuries (S3-GL); however, some of these criteria require scarce hospital resources while the patients then often clinically present as uninjured. There are tendencies to streamline the trauma team activation criteria (TTAC); however, additional undertriage must be avoided. A study group of the emergency, intensive care medicine and treatment of the severely injured section (NIS) is in the process of optimizing the TTAC for the German trauma system. MATERIAL AND METHODS: In order to solve the objective the following multi-step approach is necessary: a) definition of patients who potentially benefit from TTA, b) verification of the definition in the TraumaRegister DGU® (TR-DGU), c) carrying out a prospective, multicenter study in order to determine overtriage and undertriage, thereby validating the activation criteria and d) revision of the current TTAC. RESULTS: This article summarizes the consensus criteria of the group assumed to be capable of identifying patients who potentially benefit from TTA. These criteria are used to test if TTA was justified in a specific case; however, as the TTCA of the S3-GL are not fully incorporated into the TR-DGU dataset and because cases must also be considered which were not subject to trauma room treatment and therefore were not included in the TR-DGU, it is necessary to perform a prospective full survey of all individuals in order to be able to measure overtriage and undertriage. CONCLUSION: Currently, the TR-DGU can only provide limited evidence on the quality of the TTAC recommended in Germany. This problem has been recognized and will be solved by conducting a prospective DGU-supported study, the results of which can be used to improve the TR-DGU dataset in order to enable further considerations on the quality of care (e. g. composition and size of the trauma team).

No effect of the cyclooxygenase-2 inhibitor etoricoxib on pre-emptive and post-operative analgesia in visceral surgery: results of a randomized controlled trial.

BACKGROUND: Pre-emptive analgesia in perioperative care has potential benefits for patients. The pre-emptive and postoperative analgesic effects of the cyclooxygenase-2 inhibitor etoricoxib have been investigated using a 2 × 2 factorial trial design. METHODS: According to the 2 × 2 factorial study design, 103 patients scheduled for visceral surgery, were randomly allocated to two groups prior to surgery. Patients could receive either etoricoxib or placebo (to investigate pre-emptive analgesia). Subsequent to surgery, patients randomly received either etoricoxib or placebo, again. It follows, that four treatment modalities (continuous or replaced intervention) result, to investigate postoperative analgesia. Main Outcome Measure was the cumulative morphine use 48 h post-surgery. Other outcomes included pain intensities, pain thresholds and sensory detection. RESULTS: Eighty-six patients (female n = 42; mean age 53.82 ± 13.61 years) were evaluated on the basis of an intention to treat analysis. Pre-emptive administration of 120 mg etoricoxib did not significantly reduce the cumulative morphine dose within the first 48 h after surgery, when compared to the administration of placebo. The analysis of the post-operative treatment groups showed a non-significant 8% reduction in morphine dose during the continuous administration of etoricoxib. There were no changes in sensory perception as detected with QST before and after surgery or between groups. CONCLUSIONS: The effect of administering etoricoxib was not superior to placebo in reducing the morphine dose required for postoperative analgesia. The lack of changes in peripheral nociception suggests that central algetic mechanisms are of higher impact in the development of postoperative pain following abdominal or thoracic surgery.

Expressiveness of global coagulation parameters in dilutional coagulopathy.

BACKGROUND: Plasma-free volume replacement in haemorrhage often results in dilutional coagulopathy. Prothrombin time index (PTI) and activated partial thromboplastin time (aPTT) are used for monitoring haemostasis but have not yet been clinically evaluated. Our aim was to investigate the effects of haemodilution on the course of global coagulation tests and clotting factors (CFs). METHODS: Blood samples from each of 10 volunteers were diluted with sodium chloride 0.9% (saline) or 6% hydroxyethyl starch 130/0.4 (HAES) by 30-80%. PTI, aPTT, CF, and the thrombelastometric parameters (ROTEM(®)) coagulation time (CT) and maximum clot firmness (MCF) were determined. RESULTS: Dilution-dependent CF decreased in an almost linear manner and was not influenced by the diluent. Critically low activities for CF of ∼30% and a fibrinogen concentration <100 mg dl(-1) were measured at dilutions of between 60% and 75%. Critically low CF activities of about 30% were indicated by a PTI of 35-40%. PTI and MCF decreased continuously, demonstrating a good correlation with CF activities and fibrinogen. aPTT and CT showed a linear course up to a dilution of 65-75% corresponding to CF activities of 30-40%. Thereafter, values became pathological. PTI and aPTT were not influenced by the type of diluent, whereas the diluents had profound differences on results of thromboelastometry. CONCLUSIONS: PTI and MCF are useful for monitoring dilution and intervention points. aPTT and CT reflect intervention points when showing pathological values. The type of diluents does not seem to interfere with PTI and aPTT, but HAES impairs haemostasis in ROTEM(®) more profoundly than saline.

[Disseminated nocardiosis : Diagnostic challenge]. / Disseminierte Nocardiose : Diagnostische Herausforderung.

Nocardiosis is a rarely found bacterial infection in Europe which can particularly affect immunocompromized patients. Localized infections of the dermis and lungs, as well as disseminated infections can be observed. Suspicion of nocardiosis should be reported to the microbiological laboratory so that goal-directed molecular genetic techniques and extended cultivation can be implemented for identification of the causative agent. A multitude of antibiotics can be used for successful therapy but the duration of therapy must be extended over 6-12 months. The mortality of disseminated infections ranges between 15-85% depending on the underlying immune status of the patient. The polymorphic appearance of nocardiosis is described based on the case of an intensive care patient.

[Emergency room management of severely injured patients]. / Schockraumversorgung von schwer verletzten Patienten. Analyse vermeidbarer Abweichungen vom Behandlungsalgorithmus. Analysis of avoidable deviations from the treatment algorithm.

BACKGROUND: In cases involving major trauma life-threatening situations should be immediately diagnosed and treated. Clinical algorithms can potentially decrease the rate of complications and errors. The purpose of this study was to investigate the incidence of deviations from a multislice computed tomography based trauma room algorithm. MATERIALS AND METHODS: During a primary trauma survey an independent study monitor observed the on site treatment sequence step by step. Time intervals between admission and start of each procedure were recorded. Deviations from the algorithm and delays were analyzed. RESULTS: In 57 trauma patients a total of 49 deviations were documented. Median time between admission and transfer to the adjacent MSCT room was 9 min. Of the patients 11 were bypassed to the MSCT suite without a primary survey (19.3%). In 2 cases an absence of non-invasive blood pressure monitoring was recorded (3.5%) and 3 patients with potential cervical spine trauma were not immobilized at the scene or during primary survey (5.3%). In 8 cases focused assessment with sonography for trauma (FAST) was not performed (14%). Contrary to the algorithm 10 patients received an arterial or central venous line during initial treatment (18%) resulting in a median delay of 8 min. The deviations from the algorithm resulted in no adverse effects on complications or mortality. CONCLUSION: Self-critical analysis of trauma resuscitation can increase the quality of treatment by revealing constantly recurring faults.

[New oral anticoagulants. Consequences for perioperative coagulation diagnostics and therapy]. / Neue orale Antikoagulanzien. Konsequenzen für die perioperative Gerinnungsdiagnostik und -therapie.

Dabigatranetexilate and rivaroxaban were approved for prevention of thromboembolic events after orthopedic surgery in 2008. Dabigatran is a direct inhibitor of thrombin and rivaroxaban of factor Xa. Inhibition is reversible and the duration of action is predictable. Both drugs considerably influence the global tests of coagulation thus making postoperative coagulation monitoring more difficult. In order to keep the interaction as low as possible blood samples for assessment of the thromboplastin time (PT) and the partial thromboplastin time (PTT) should be taken immediately before the next drug administration. Blood sampling about 2-4 h after drug administration can be performed to check the efficacy of drug action. Non-urgent operations should be started earliest 24 h after the previous drug application. In cases of emergency interventions due to life-threatening bleeding, administration of prothrombin complex concentrate might be a successful treatment option. Specific antidotes are not available.

[Coagulation management of severe surgical bleeding]. / Gerinnungsmanagement bei schweren operativen Blutungen.

Severe intraoperative bleeding may endanger the patient's life, necessitate additional human resources and increase perioperative costs. The aetiology of perioperative coagulopathy is complex and consists of depletion, consumption and dilution of clotting factors and thrombocytes. Cofactors like hypothermia, acidosis and severe anaemia may aggravate coagulopathy. Previously healthy patients often show hypofibrinogenaemia as the primary trigger of coagulopathy, whereas thrombocytopenia rather is a late event during massive bleeding. Early and differentiated diagnosis is essential for initiating targeted therapy. Evaluation of the clinical bleeding situation and coagulation tests, in particular point-of-care testing like thrombelastography, should be used to guide and control the therapeutic strategy. Fresh frozen plasma, concentrates of clotting factors, platelet concentrates and antifibrinolytic drugs are available for therapy of perioperative coagulopathy. To obtain optimal benefit for the patient, these products should be applied based on a therapeutic algorithm.

Multicenter assessment of CSF-phosphorylated tau for the prediction of conversion of MCI.

BACKGROUND: The measurement of hyperphosphorylated tau (p-tau) in CSF has been proposed as a biomarker candidate for the prediction of Alzheimer disease (AD) in patients with mild cognitive impairment (MCI). However, a standard quantitative criterion of p-tau has not been evaluated. OBJECTIVE: To assess in a multicenter study the predictive accuracy of an a priori defined criterion of tau phosphorylated at threonine 231 (p-tau(231)) for the prediction of conversion from MCI to AD during a short-term observation interval. METHODS: The study included 43 MCI converters, 45 stable MCI (average follow-up interval = 1.5 years), and 57 healthy controls (at baseline only). Subjects were recruited at four international expert sites in a retrospective study design. Cox regression models stratified according to center were used to predict conversion status. Bootstrapped 95% CIs of classification accuracy were computed. RESULTS: Levels of p-tau(231) were a significant predictor of conversion (B = 0.026, p = 0.001), independent of age, gender, Mini-Mental State Examination, and ApoE genotype. For an a priori-defined cutoff point (27.32 pg/mL), sensitivity ranged between 66.7 and 100% and specificity between 66.7 and 77.8% among centers. The bootstrapped mean percentage of correctly classified cases was 79.95% (95% CI = 79.9 to 80.00%). Post hoc defined cutoff values yielded a mean bootstrapped classification accuracy of 80.45% (95% CI = 80.24 to 80.76%). CONCLUSIONS: An a priori defined cutoff value of p-tau(231) yields relatively stable results across centers, suggesting a good feasibility of a standard criterion of p-tau(231) for the prediction of Alzheimer disease.

[Hemorrhaging during pregnancy]. / Blutungen während der Schwangerschaft.

Hemorrhaging during pregnancy is often fulminant and life-threatening for mother and child. Of maternal deaths occurring during pregnancy, 25% are caused by hemorrhaging. All physicians involved in the interdisciplinary treatment of hemorrhaging during pregnancy need to be familiar with the specific pathophysiology of hemostatic changes during pregnancy, e.g. elevated hemostatic capacity, reduced anti-coagulation activity and severe alterations of the fibrinolysis system. Therapists must be able to perform a consequent, goal-directed interdisciplinary approach to prevent adverse maternal and fetal outcomes. The major issues of therapy are causal obstetric treatment of the bleeding, early detection and therapy of hyperfibrinolysis, optimization of fibrinogen and platelet levels and knowledge of the possibilities of a targeted coagulation therapy.

[Perioperative coagulation management controlled by thrombelastography. Clinical implementation illustrated by reference to a case of acquired coagulopathy following aortic stab injury]. / Durch Thrombelastographie gesteuertes perioperatives Gerinnungsmanagement. Klinische Umsetzung am Beispiel einer erworbenen Koagulopathie nach aortaler Stichverletzung.

Uncontrolled bleeding is one of the main reasons for a lethal outcome of severe trauma. Loss, consumption and dilution of clotting factors and platelets induce a complex acquired coagulopathy. Beside surgical control of bleeding, early and precise coagulation therapy is essential for successful treatment. We report on a patient whose life-threatening bleeding and perioperative coagulopathy after a knife injury to the aorta was successfully treated by surgical control of the bleeding and subsequent targeted coagulation therapy with factor concentrates and fresh-frozen plasma. The coagulopathy was diagnosed and managed by means of bed-side thrombelastography.

[Safety of plasma-derived factor concentrates: an example of pharmacovigilance with fibrinogen and factor XIII-concentrate]. / Sicherheit von Faktorenkonzentraten aus Plasma: Pharmakovigilanz am Beispiel von Fibrinogen- und Faktor-XIII-Konzentrat.

Elaborate measures for donor selection and the production of clotting factor concentrates have led to a high safety standard of these products. A multimodal approach to eliminate unwanted contents has been established by strict screening of possible donors and various inactivation procedures within the production process. The systematic registration of adverse events shows very few allergic and nonallergic reactions to plasma derived clotting factor concentrates. In none of the registered cases transmission of infections could be verified. The worldwide registration of such adverse events is not yet sufficiently established, since adequate structures are lacking in some countries. According to estimates, far less than half of occurring adverse events are registered in Germany. A European solution in the form of an official register is about to be introduced.

[Fresh plasma and concentrates of clotting factors for therapy of perioperative coagulopathy: what is known?]. / Frischplasma und Faktorenkonzentrate zur Therapie der perioperativen Koagulopathie: Was ist bekannt?

Acquired, perioperative coagulopathy often develops due to acute bleeding. In the case of primarily healthy patients with normal bone marrow and liver functions, a lack of coagulation factors initiates coagulopathy before secondary thrombopenia arises. Replacement of coagulation factors can be performed by infusion of fresh plasma (single donor or pooled plasma) or concentrates of clotting factors. Fresh plasma as well as concentrates of clotting factors available in German-speaking countries are of high quality and fulfil all safety standards. Undesirable side-effects due to transmission of infections and immunological reactions are--in all probability--more uncommon for virus-inactivated plasma and clotting factors than for single donor plasma. In contrast, thromboembolic complications are unlikely when using fresh frozen plasma, because it contains a balanced ratio of pro-coagulatory and anti-coagulatory factors. For virus-inactivated pooled plasma and concentrates of clotting factors, sporadic reports of thromboembolic events have been published. Concentrates of clotting factors can be stored easily and are rapidly prepared for use. In contrast, fresh frozen plasma has to be thawed before application leading to a significant delay in the schedule. During activated hemostasis, the half-life of clotting factors is significantly reduced in comparison to a stable physiological situation. In the case of perioperative coagulopathy higher dosages of fresh plasma and clotting factors than those recommended in published guidelines are often necessary for successful treatment. When using fresh plasma for coagulation therapy the resulting volume load must be considered. In conclusion, a modern concept of perioperative coagulation management should include fresh plasma as well as concentrates of clotting factors. The anesthetist should be familiar with the available components and be able to consider and adapt them to the individual situation.

[Frequency of intervention and risk factors in monitored anesthesia care in ophthalmic surgery -- a retrospective analysis]. / Interventionshäufigkeit und Risikofaktoren bei anästhesiologischen Stand-by in der Ophthalmochirurgie -- eine retrospektive Analyse.

BACKGROUND: Patients for ophthalmic surgery have an average age of 70 - 75 years and frequently suffer from cardiopulmonary disease. Despite the fact that only local anesthesia is applied, these patients often receive monitored anesthesia care. Aims of this study were to determine the frequency of drug interventions during monitored anesthesia care and to identify risk factors for treatment. PATIENTS AND METHODS: In a retrospective study, preoperative history and anaesthetic records of 404 patients who had received monitored anesthesia care in a university hospital were analyzed for patient data, preoperative diagnoses and intraoperative anesthesiological interventions. RESULTS: Patients were 70 +/- 12 years old and had a high co-morbidity (63 % ASA-classification 3), especially an increased cardiopulmonary risk. 50 % of all patients received a drug intervention. 41 % were given an antihypertonic agent intraoperatively and 17 % received other forms of drug treatment (e. g. insulin therapy, infusion of electrolytes, antiemetics). In 2,5 % of the cases severe cardiovascular complications occurred which needed treatment (severe arrhythmias, hypertensive crisis, severe hypotension with need for catecholamine therapy). The two parameters "arterial hypertension" (54 % intervention frequency vs. 35 % without arterial hypertension) and the surgical procedure of "pars plana vitrectomy" (58 % intervention frequency vs. 41 % for cataract surgery) were associated with a significantly increased frequency for intraoperative interventions. CONCLUSIONS: The high intervention frequency for a variety of complications, especially of cardiovascular nature, advises the presence of a physician during ophthalmic operations who is trained to control such emergency situations.

[High dose fibrinogen administration for acute therapy of coagulopathy during massive perioperative transfusion]. / Hochdosierte Fibrinogengabe zur Akuttherapie von Gerinnungsstörungen bei perioperativer Massivtransfusion.

During acute and severe perioperative bleeding a coagulopathy due to depletion, consumption and dilution of clotting factors and thrombocytes may occur. Diagnosis and therapy of such a coagulopathy should take place immediately. We report two cases of acute coagulopathy during perioperative bleeding and massive transfusion, which were treated successfully by administration of high dose fibrinogen concentrate. Diagnosis and treatment control were performed by thrombelastography.

Sevoflurane but not isoflurane can reduce prostacyclin production of endothelial cells.

BACKGROUND AND OBJECTIVE: Little is known about the interaction of newer volatile anaesthetics with endothelial eicosanoid production. Sevoflurane may possibly reduce prostacyclin formation. Thus, we compared the influences of sevoflurane and isoflurane on endothelial prostacyclin production. METHODS: Production of prostacyclin of human umbilical vein endothelial cells was measured by the ELISA technique under basal conditions and after stimulation with calcium ionophore A 23187 10 micromol or histamine 0.1 micromol in the absence and presence of 1 and 2 minimal alveolar concentrations (MAC) of sevoflurane or isoflurane. RESULTS: The basal production of prostacyclin was unaffected by the volatile anaesthetics. Stimulation of endothelial cells increased prostacyclin formation 3-5-fold. Sevoflurane at 2 MAC, but not at 1 MAC, could reduce stimulated prostacyclin production by about half (P < 0.05). Isoflurane had no inhibitory effect. Inhibition of cyclo-oxygenase function by acetylsalicylic acid abolished the induced burst of prostacyclin formation completely. CONCLUSIONS: Sevoflurane, but not isoflurane, can reduce stimulated endothelial prostacyclin production in a concentration-dependent manner. Because at least 2 MAC of sevoflurane were required, this effect should be of minor importance under clinical conditions of balanced anaesthesia.

Aspirin, but not the more selective cyclooxygenase (COX)-2 inhibitors meloxicam and SC 58125, aggravates postischaemic cardiac dysfunction, independent of COX function.

Inhibition of cyclooxygenase (COX) might favour non-enzymatic formation of cardiodepressive isoprostanes from arachidonic acid by radicals generated during reperfusion. This could explain deleterious effects of acetylsalicylic acid (ASA) on cardiac function. We examined the influence of COX inhibition on myocardial function after low-flow ischaemia and reperfusion, employing either ASA (100 micromol/l), the partially selective COX-2 inhibitor meloxicam (0.3 micromol/l and 3.0 micromol/l), or the highly selective COX-2 inhibitor SC 58125 (1.0 micromol/l and 3.0 microgmol/l). Isolated, buffer-perfused guinea pig hearts, performing pressure-volume work before and after consecutive low-flow ischaemia and reperfusion, were used for the study. Measurement of coronary and aortic flow, ejection time and heart rate served to calculate external heart work (EHW), before and after ischaemia. Additionally, release of prostacyclin and thromboxane A2, production of lactate, consumption of pyruvate and tissue concentration of the isoprostane 8-iso-PGF2alpha were measured. ASA significantly reduced recovery of EHW (46+/-18% vs. 82+/-15% for controls), whereas meloxicam and SC 58125 did not (64+/-15% and 74+/-13% recovery, respectively). Paradoxically, ASA increased reactive hyperaemia and consumption of pyruvate in the early reperfusion phase in comparison to all other groups, while lactate production did not differ. Prostacyclin production did not increase during reperfusion and was not significantly different between groups at any time point. In contrast, thromboxane A2 release increased about fivefold in the 2nd min of reperfusion under control conditions and in the presence of SC 58125, but was inhibited by ASA and by meloxicam in both concentrations. Isoprostane content of heart tissue was not detectably influenced under the mild reperfusion conditions used here. We conclude that ASA can aggravate postischaemic cardiac dysfunction, independent of COX inhibition. The deleterious effect in the present model might be due to uncoupling of mitochondrial oxidative phosphorylation rather than to direct effects of reduced eicosanoid release or radical induced formation of isoprostanes.

Endothelial function and hemostasis.

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.