[Thromboelastography/-metry and external quality control. Results of a pilot study]. / Evaluation von Ringversuchsproben zur externen Qualitätssicherung viskoelastischer Messungen - Eine Pilotstudie.

Thromboelastography/thromboelastometry (TEG/ROTEM) is widely used in near-patient setting, especially in perioperative and intensive care medicine for the management of acute bleeding. Until now a comprehensive quality management especially an external quality control of TEG/ROTEM results is not established. Here we report about our results of a pilot survey performed in 2008 and 2009 integrated in the External Quality Assessment Schemes (EQAS) performed by INSTAND. According to this first EQAS data ROTEM results can be controlled in external quality schemes using lyophilized plasma samples. The clot firmness (A20) and clot formation kinetics characterized by the alpha-angle showed very good reproducibility both between the participants and between different surveys. Variations for CT and CFT were considerably higher especially in the plasma sample with reduced fibrinogen level. Regular participation in an external quality assurance will help to confirm this beneficial technology in emergency settings.

[Artificial blood - coming soon or never reaching clinical maturity?]. / Gibt es eine Zukunft für künstliche Blutersatzstoffe?

Formerly developed resuscitation fluids solely imitated the main function of the blood -oxygen transport. A research driven by the army requested an oxygen carrier that does not need cross typing and cooled storage. Artificial oxygen carriers (AOC) use either the molecular oxygen bondage to hemoglobin: HBOC- "hemoglobin based oxygen carriers" or the physical dissolution of oxygen in the blood plasma compartment by hyperbaric pressure in perfluorocarbon emulsions (PFC). Decades of preclinical and clinical research did pass but the results were disappointing- in Russia, a not well designed PFC is available locally and the only approved HBOC in South Africa is not being used much. Other products, just prior to filing for FDA approval, did not achieve convincing study results and research and production was stopped. Some trials have been stopped by the FDA for safety reasons, half of trials with the primary endpoint reduction of allogeneic transfusion requirement were unsuccessful or offset by an increased blood requirement later. However, some ventures currently are trying to use the knowledge gained so far and are investigating third and fourth generation products of artificial blood components. These imitate the cellular structure of red cells as micells, nanocapsules, (ABC- artificial blood cells) or gas bubbles (microbubbles), admixture of volume substitutes such as starches, gelatin or albumin or use hyperbaric oxygenation [38]. Artificial platelets are in clinical phase IIa, recombinant albumin in phase III. In this article, a short overview about the current situation on artificial blood products is given. The critical point for the break through for artificial blood products did not come yet but could be ahead-

[Perioperative management of patients with coronary stents in non-cardiac surgery]. / Perioperatives Management von Patienten mit Koronarstents bei nichtherzchirurgischen Eingriffen.

In patients with coronary stents scheduled for surgery the question arises whether and how antiplatelet therapy should be continued. Risks of perioperative bleeding and of acute stent thrombosis have to be considered simultaneously. The bleeding risk depends primarily on the kind of surgery and on patient comorbidity. The risk of stent thrombosis is increased in these patients due to the thrombogenic surface of the stents. The main determinants are hereby the time duration after stent implantation, the kind of the stent [uncoated (bare-metal stent, BMS) or coated (drug-eluting stent, DES)], as well as angiographic and clinical patient factors. Therefore, perioperative antiplatelet therapy has to be individually adapted for each patient. Bridging with heparin is ineffective. Bridging with intravenous antiplatelet drugs during the perioperative interruption of oral antiplatelet therapy might be a potential procedure in high-risk patients. Whether bedside monitoring of antiplatelet therapy improves the perioperative management of these patients and reduces adverse outcome is object of current studies.

[Thrombelastometric detection of factor XIII deficiency]. / Erfassung eines Faktor-XIII-Mangels mit der Thrombelastometrie.

While undergoing Whipple's operation (pancreaticoduodenectomy) a patient developed diffuse bleeding and an unexpectedly high blood loss. An intraoperatively performed thrombelastometry with ROTEM (Pentapharm, Munich, Germany) showed an aprotonin-resistant mild fibrinolysis and suggested the presence of an isolated deficiency of coagulation factor XIII. This was confirmed by a second thrombelastometry, where no lysis was seen after in vitro substitution of factor XIII. After administration of 1250 IU factor XIII concentrate the diffuse bleeding ceased and further substitution of coagulation factor concentrates or fresh frozen plasma was not necessary. A postoperatively performed analysis confirmed the factor XIII deficiency (52%).

[Management of hemostasis disorders after extracorporeal circulation. A clinical therapy algorithm]. / Gerinnungsmanagement bei Eingriffen mit extrakorporaler Zirkulation. Klinischer Therapiealgorithmus.

After cardiac surgery with extracorporeal circulation, approximately 20% of patients show significant bleeding tendencies and 5% require re-intervention. In 50% of patients undergoing re-operation, no surgical cause can be determined, suggesting coagulopathy after cardiopulmonary bypass (CPB). For perioperative management of transfusion of blood products and coagulation factor concentrates, a clinical algorithm for the perioperative hemostatic therapy in patients undergoing cardiac surgery with CPB has been developed. The currently available evidence and the point of care methods routinely accessible in our institution (blood gas analysis, ACT, point of care Quick value, aPTT and platelet count) were used. The intervention with plasma products, coagulation factor concentrates and hemostatic drugs after extracorporeal circulation are described. Extensive bleeding history as well as the efficacy and side effects of antifibrinolytic treatment are discussed.

[Comparison of incomplete (135 degrees ) and complete prone position (180 degrees ) in patients with acute respiratory distress syndrome. Results of a prospective, randomised trial]. / Vergleich von inkompletter (135 degrees) und kompletter Bauchlage (180 degrees) beim schweren akuten Lungenversagen. Ergebnisse einer prospektiven, randomisierten Untersuchung.

BACKGROUND: Ventilation in the prone position is carried out for improvement of pulmonary gas exchange in patients with acute respiratory distress syndrome (ARDS). We compared the effects of an incomplete prone position (IPP, 135( degrees )) with a complete prone position (CPP, 180( degrees )) in patients with ARDS. PATIENTS AND METHODS: For this trial 59 patients with ARDS were randomly assigned and were positioned in a "cross-over" design: patients of group A were placed in IPP for 6 h and then immediately positioned in CPP for another 6 h. Patients in group B were positioned in reverse order. Blood gases, hemodynamic measurements, quasistatic respiratory compliance and assessments of side effects were performed before begin, 30 min and 6 h after first positioning, then 30 min and 6 h after second positioning and 2 after repositioning. RESULTS: Turning patients in IPP and CPP resulted in a significant increase in the arterial oxygenation index (p(a)O(2)/F(I)O(2)), but this effect was more pronounced in the CPP (before: 142+/-46 mm Hg, 6 h: 253+/-107 mm Hg) than in the IPP (before: 139+/-54 mm Hg, 6 h: 206+/-75 mm Hg), and compliance was improved only in CPP. The improvement in arterial oxygenation persisted 2 h after repositioning in the supine position in both groups. The oxygenation responder rate was lower during the IPP (70.3%) in comparison with the CPP (84.0%, p<0.05). The incidence of side effects tended to be increased during the CPP. CONCLUSION: Incomplete prone position improves oxygenation in ARDS patients, but less effectively than a "classic" CPP. In these patients the use of a CPP should be preferred.

Effect of xenon on cerebral autoregulation in pigs.

There are little data on the effect of anaesthetic concentrations of xenon on cerebral pressure autoregulation. In this study, we have investigated the effect of 79% xenon inhalation on cerebral pressure autoregulation and CO2 response in pigs. Ten pigs were randomly allocated to receive xenon 79% or halothane anaesthesia, respectively, in a crossover designed study. Halothane was used to validate the experimental set-up. Transcranial Doppler was performed to determine the mean flow velocities in the middle cerebral artery (vMCA) during defined cerebral perfusion pressures and during normo-, hyper- and hypoventilation. The results showed that the inhalation of 79% xenon preserved cerebral autoregulation during conditions of normo-, hyper- and hypoventilation and at different cerebral perfusion pressures in pigs. These results suggest that with the inhalation of xenon, in the highest concentration suitable for a safe clinical use, cerebral autoregulation is preserved.

[Cytochrome P450 enzymes and their role in drug interactions]. / Cytochrom-P450-Enzyme und ihre Bedeutung für Medikamenteninteraktionen.

One of the factors that can alter the response to drugs is the concurrent administration of other drugs. There are several mechanisms by which drugs may interact, but most can be categorised as pharmacokinetic (absorption, distribution, metabolism, excretion), pharmacodynamic, or combined toxicity. Knowledge of the mechanism by which a given drug interaction occurs is often clinically useful and may help to avoid serious adverse events and perioperative morbidity. Although every tissue has some ability to metabolise drugs, the liver is the principal organ of drug metabolism and at the subcellular level the cytochrome P450 enzyme system is the main source of drug interaction. This article reviews the basic principles of drug metabolism and the role of cytochrome P450 in this scenario. Drugs frequently used in anaesthesia and critical care medicine such as benzodiazepines, opioid analgesics, antihypertensive and antiarrhythmic agents, antibiotics and antifungal drugs, antiemetics, histamine-receptor-antagonists, theopylline and paracetamol will be considered. The development of methods and tools which are practical and also economic, are of utmost importance since drug interaction is predictable if the metabolic pathway and the activity (genetic polymorphism) of the enzyme is known.

Palmitoylation of the Rous sarcoma virus transmembrane glycoprotein is required for protein stability and virus infectivity.

The Rous sarcoma virus (RSV) transmembrane (TM) glycoprotein is modified by the addition of palmitic acid. To identify whether conserved cysteines within the hydrophobic anchor region are the site(s) of palmitoylation, and to determine the role of acylation in glycoprotein function, cysteines at residues 164 and 167 of the TM protein were mutated to glycine (C164G, C167G, and C164G/C167G). In CV-1 cells, palmitate was added to env gene products containing single mutations but was absent in the double-mutant Env. Although mutant Pr95 Env precursors were synthesized with wild-type kinetics, the phenotypes of the mutants differed markedly. Env-C164G had properties similar to those of the wild type, while Env-C167G was degraded faster, and Env containing the double mutant C164G/C167G was very rapidly degraded. Degradation occurred after transient plasma membrane expression. The decrease in steady-state surface expression and increased rate of internalization into endosomes and lysosomes paralleled the decrease in palmitoylation observed for the mutants. The phenotypes of mutant viruses were assessed in avian cells in the context of the pATV8R proviral genome. Virus containing the C164G mutation replicated with wild-type kinetics but exhibited reduced peak reverse transcriptase levels. In contrast, viruses containing either the C167G or the C164G/C167G mutation were poorly infectious or noninfectious, respectively. These phenotypes correlated with different degrees of glycoprotein incorporation into virions. Infectious revertants of the double mutant demonstrated the importance of cysteine-167 for efficient plasma membrane expression and Env incorporation. The observation that both cysteines within the membrane-spanning domain are accessible for acylation has implications for the topology of this region, and a model is proposed.

Cytomegalovirus disease recurrence after ganciclovir treatment in kidney and kidney-pancreas transplant recipients.

BACKGROUND: With the introduction of ganciclovir, the clinical pattern of cytomegalovirus (CMV) disease has changed; CMV disease recurrence after successful treatment of the initial episode has emerged as a more common problem. We studied CMV disease recurrence in kidney transplant (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients, and identified risk factors for recurrence. METHODS: Between January 1987 and December 1995, of 1272 KTx and 287 SPK recipients, 332 developed CMV disease and were treated with a 14-day course of i.v. ganciclovir, followed by a 10-week course of oral acyclovir. Among these 332 recipients, 103 (31%) developed CMV disease recurrence more than 30 days after treatment for the initial episode; this group was compared with those recipients who did not develop recurrence (n=229). Risk factors examined were age, presence of diabetes, type of transplant (KTx vs. SPK), donor source (cadaver vs. living donor), treatment for acute rejection, pretransplant CMV serologic status, evidence of tissue-invasive CMV, and treatment of the initial episode with human immune globulin in addition to ganciclovir. RESULTS: Univariate analysis found that patients with recurrence were more likely to be diabetic (70.9% vs. 53.7%; P=0.04), to have undergone an SPK (39.8% vs. 20.5%; P=0.004), to have received a cadaver organ (78.6% vs. 61.6%; P=0.002), and to have received treatment for acute rejection (78.6% vs. 59.8%; P=0.001). Using multivariate analysis, two statistically significant risk factors were found: receiving a cadaver organ (relative risk [RR]=1.90; P=0.03) and treatment for acute rejection (RR=2.02; P=0.008). Diabetes (RR=1.44; P=0.18) and a cadaver SPK transplant (RR=1.55; P=0.12) tended toward increased risk for recurrence, but the difference did not reach statistical significance. The remaining variables were not significant. Interestingly, CMV recurrence did not significantly diminish 5-year graft survival (52.0% vs. 54.4%; P not significant) or patient survival (67.0% vs. 68.3%; P not significant) rates. CONCLUSIONS: CMV disease recurs in roughly one-third of KTx and SPK recipients after treatment of the initial episode with ganciclovir. A cadaver organ source and treatment for acute rejection were the most significant clinical risk factors for recurrence. Clinical predictors of recurrence such as these may help to identify those recipients who need more intensive therapeutic and prophylactic regimens.

Candida albicans and Escherichia coli are synergistic pathogens during experimental microbial peritonitis.

Candida albicans has been isolated with increasing frequency during intraabdominal infection; yet its role as a pathogen or copathogen remains controversial. A recent experimental study of its effect during polymicrobial peritonitis indicated that it did not enhance mortality when added to an Escherichia coli challenge, but that study used fecal or mucin-based adjuvants which are known to markedly potentiate the lethality of intraperitoneal bacteria. Therefore, we sought to examine the hypothesis that C. albicans and E. coli are synergistic copathogens that act in concert to increase mortality rates in experimental models of polymicrobial peritonitis, irrespective of the presence of growth adjuvant. To test this hypothesis, we assessed the mortality rates of previously healthy Swiss-Webster mice (20 g) that were challenged intraperitoneally (i.p.) with E. coli, C. albicans, or both, in either the presence or the absence of hemoglobin-mucin. In the absence of hemoglobin-mucin, E. coli plus C. albicans resulted in 83.3% mortality (P < 0.02) compared to either E. coli (0%) or C. albicans (0%) alone. In the presence of hemoglobin-mucin, the synergistic effect was not observed, lower numbers of E. coli alone (62.5%), C. albicans alone (75%), or both organisms together (100%, P > 0.05) provoked high lethality. These data demonstrate that in the absence of adjuvant, E. coli plus C. albicans provoked synergistic lethality. However, in the presence of hemoglobin-mucin the synergistic effect was no longer observed. Therefore, this study provides support for the contention that C. albicans is capable of acting as a copathogen during experimental peritonitis, but that this effect may be obscured by the presence of an adjuvant substance that itself markedly potentiates microbial growth.

Acute gastric dilation after trauma.

A prospective study of 100 trauma patients admitted to the resuscitation room was performed. Acute gastric dilatation was confirmed radiologically in 17 patients. The mechanism of injury was blunt trauma in 91 patients and penetrating in nine. The mean Injury Severity Score was 17. Of those patients with acute gastric dilatation, 13 (76%) had no abdominal injury. Acute gastric dilatation was suspected clinically in nine of 17 patients (53%) in whom the diagnosis was confirmed radiologically. Nasogastric tubes were placed in 31 patients. Fifteen patients had a diagnostic peritoneal lavage and nine of these had nasogastric aspiration before the procedure. Of 28 patients secondarily transferred from another hospital, three (11%) had undergone nasogastric intubation before transfer, five (18%) had acute gastric dilatation on admission and four (14%) had radiological evidence of pulmonary aspiration. Complications associated with acute gastric dilatation included gastric haemorrhage in six patients (35%), pulmonary aspiration in two (12%) and prolonged ileus in one (6%). Placement of a nasogastric tube in the absence of a clear contraindication, either before inter-hospital transfer or soon after admission to the resuscitation room is strongly recommended in the management of the multiply injured patient.