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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%).

There are no consensus guidelines for the management of postoperative nausea and vomiting (PONV) in German speaking countries. This meeting was intended to develop such guidelines on which individual health care facilities can derive their specific standard operating procedures (SOPs). Anesthesiologists reviewed published literature on key topics which were subsequently discussed during two meetings. It was emphasized that recommendations were based on the best available evidence. The clinical relevance of individual risk factors should be viewed with caution since even well proven risk factors, such as the history of PONV, do not allow the identification of patients at risk for PONV with a satisfactory sensitivity or specificity. A more useful approach is the use of simplified risk scores which consider the presence of several risk factors simultaneously. Most individual antiemetic interventions for the prevention of PONV have comparable efficacy with a relative risk reduction of about 30%. This appears to be true for total intravenous anesthesia (TIVA) as well as for dexamethasone and other antiemetics; assuming a sufficiently high, adequate and equipotent dosage which should be weight-adjusted in children. As the relative risk reduction is context independent and similar between the interventions, the absolute risk reduction of prophylactic interventions is mainly dependent on the patient's individual baseline risk. Prophylaxis is thus rarely warranted in patients at low risk, generally needed in patients with a moderate risk and should include a multimodal approach in patients at high risk for PONV. Therapeutic interventions of PONV should be administered promptly using an antiemetic which has not been used before. The group suggests algorithms where prophylactic interventions are mainly dependent on the patient's risk for PONV. These algorithms should provide evidence-based guidelines allowing the development of SOPs/policies which take local circumstances into account.

The optimum intrathecal dose of hyperbaric levobupivacaine for spinal anaesthesia during elective caesarean section has not yet been investigated.A total of 30 parturients undergoing elective caesarean section were included in this prospective, randomised, double-blind study. Parturients received either 7.5, 10 or 12.5 mg hyperbaric 0.5% levobupivacaine intrathecally. Analgesic, sensory and motor block characteristics as well as maternal and fetal levobupivacaine plasma concentrations were determined.Of the parturients receiving 7.5 mg levobupivacaine 40% required supplementary intravenous opioid analgesics intraoperatively and none achieved complete motor block. Compared to 7.5 mg levobupivacaine, 10 and 12.5 mg significantly prolonged duration of effective analgesia postoperatively (median: 45 vs. 81 and 96 min, respectively). Both maternal and fetal levobupivacaine plasma concentrations were low, with dose-dependent, statistically significant differences in maternal plasma concentrations.Levobupivacaine 7.5 mg did not provide satisfactory intraoperative analgesia in all parturients. There were no statistically significant differences between 10 and 12.5 mg levobupivacaine with respect to analgesic, sensory and motor block characteristics. Therefore, based on these data, 10 mg levobupivacaine is recommended for parturients undergoing elective caesarean section with spinal anaesthesia.

Hemodynamic monitoring and adequate volume-therapy, as well as the treatment with positive inotropic drugs and vasopressors, are the basic principles of the postoperative intensive care treatment of patient after cardiothoracic surgery. The goal of these S3 guidelines is to evaluate the recommendations in regard to evidence based medicine and to define therapy goals for monitoring and therapy. In context with the clinical situation the evaluation of the different hemodynamic parameters allows the development of a therapeutic concept and the definition of goal criteria to evaluate the effect of treatment. Up to now there are only guidelines for subareas of postoperative treatment of cardiothoracic surgical patients, like the use of a pulmonary artery catheter or the transesophageal echocardiography. The German Society for Thoracic and Cardiovascular Surgery and the German Society for Anaesthesiology and Intensive Care Medicine made an approach to ensure and improve the quality of the postoperative intensive care medicine after cardiothoracic surgery by the development of S3 consensus-based treatment guidelines. Goal of this guideline is to assess available monitoring methods and their risks as well as the differentiated therapy of volume-replacement, positive inotropic support and vasoactive drugs, the therapy with vasodilators, inodilators and calcium-sensitizers and the use of intra-aortic balloon pumps. The guideline has been developed according to the recommendations for the development of guidelines by the Association of the Scientific Medical Societies in Germany (AWMF). The presented key messages of the guidelines were approved after two consensus meetings under the moderation of the Association of the Scientific Medical Societies in Germany (AWMF).

The perioperative administration of beta blockers is a controversial issue. Numerous trials failed to show any significant benefit or disadvantage because of low event rates and insufficient statistical power.In July 2005 McGory et al. and Devereaux et al. separately published 2 meta-analyses, raising the question of the perioperative administration of beta blockers for patients undergoing non-cardiac surgery. In February 2006, Schouten et al. published an additional meta-analysis concerning the same question. This evidence is supplemented by the publication of Lindenauer et al. in 2005. These trials will be critically appraised in this review.McGory et al. concluded from their data that the perioperative administration of beta blockers significantly reduced cardiovascular mortality. However, this conclusion is clearly not valid because of methodological deficits of the meta-analysis. In addition, the publications by Devereaux et al. and Schouten et al. did not support the results of the analysis by McGory et al.There is still no clear evidence to prove a significant benefit for the unselected perioperative use of beta blockers in patients undergoing non-cardiac surgery. While high-risk patients and those undergoing major surgical procedures seem to profit, low-risk patients may be more harmed than helped by this intervention. The fact that 3 meta-analyses raising the same question produced substantially different results, underlines the importance of critically appraising each meta-analysis.

Antifibrinolytic therapy with the serine protease inhibitor Aprotinin or the lysine analogues epsilon-aminocapronic acid or tranexamic acid is a therapeutic measure to reduce perioperative blood loss during cardiac surgery. In an international, prospective, non-randomised phase 4 observation study, Mangano et al. investigated the effectiveness and side-effects of Aprotinin, epsilon-aminocapronic acid and tranexamic acid in comparison to no antifibrinolytic therapy in a total of 4,374 patients who underwent cardiac surgery with extracorporeal circulation. In the opinion of Mangano et al. the results of this study question the safety and effectiveness of Aprotinin for reduction of perioperative blood loss by cardiac surgery patients. Despite a critical review of the study and results reported by Mangano et al., the authors of the present paper come to the conclusion that, in view of the availability of more reasonably priced alternatives in Germany, it appears to be sensible to give preference to tranexamic acid instead of aprotinin.

We compared the ease of viewing the glottis under direct vision during conventional laryngoscopy with the quality of indirectly viewing on a monitor during laryngoscopy with a Macintosh videolaryngoscope in a multicenter study.After ethical approval and written informed consent of 300 patients with no anticipated difficult airway, conventional laryngoscopy with a Macintosh videolaryngoscopy blade was performed and the quality of the view of the glottis was assessed and documented according to the Cormack and Lehane scoring system as modified by Yentis and Lee. Subsequently, the indirect viewing conditions on the monitor were documented without changing the position of the blade. Differences between both distributions were analyzed using the Bland-Altman Test.Videolaryngoscopy improved the laryngoscopy score by 1 grade in 72 cases, by 2 grades in 17 cases and by 3 grades in 2 cases. A relevant improvement (from grades III/IV to II) was found in 28 patients. Viewing conditions worsened in 3 cases by 1 grade, in 4 cases by 2 grades and in 3 cases by 3 grades. A statistical analysis of the data gave a bias of 0.31 and an SD bias of 0.77.The 95% confidence interval of the distribution ranged from -1.12 to 1.81.Videolaryngoscopy can lead to better viewing conditions but in rare cases it may result in worse viewing conditions.

The expected cost-explosion in transfusion medicine (increasing imbalance between donors and recipients, treatment of transfusion-associated complications) increases the socio-economic significance of the development of safe and effective synthetic oxygen carriers as an alternative to the transfusion of allogeneic red blood cells. Currently two types of artificial oxygen carriers have been tested for safety and efficacy in cases of severe anemia otherwise requiring transfusion. Solutions based on human or bovine hemoglobin (HBOC) possess vasoconstrictor properties in addition to their oxygen transport capacity. The impact of vasoconstriction on tissue perfusion and organ function is however not yet fully understood. Nevertheless, in 2001 the bovine HBOC Hemopure was approved in South Africa for treatment of acutely anemic surgical patients. The purely synthetic perfluorocarbon (PFC) emulsions increase the physically dissolved portion of arterial oxygen content. Due to their particulate nature (emulsion droplets) PFCs may only be infused in low doses to avoid overload and malfunction of phagocytic cells of the reticulo-endothelial system. As part of a multimodal blood conservation program (including normovolemic hemodilution and hyperoxia) the low-dose administration of Oxygent effectively increases intraoperative anemia tolerance. Although reduction of perioperative allogeneic blood transfusion has already been demonstrated for HBOC and PFC, the global clinical establishment of artificial oxygen carriers is not to be expected in the near future.

For decades it has been assumed, that smoking within 6 hours of anesthesia and surgery raises the incidence of perioperative cardiopulmonary complications (PPC) including aspiration. Therefore, every patient is advised to stop smoking at the day before surgery, and not to smoke at all at the day of surgery. If the patient does not follow this advice, this will result in a postponement of anesthesia and surgery. The present article aims at re-investigating the scientific basis of this dogma in anesthesia, which virtually forbids smoking at short-term prior to surgery. The influence of short-term (6 h) abstinence from smoking on the perioperative pulmonary morbidity has not been systematically investigated. Interestingly, giving up smoking less than two months prior to surgery does not significantly decrease, but rather may increase the incidence of PPC. With respect to the risk of aspiration, smoking does not increase either the volume or the acidity of gastric juices. A short-lived reduction in the tone of the lower esophageal sphincter is reversible within minutes after termination of smoking. While the emptying of liquid gastric juices is not influenced by smoking, there is a certain delay in the propulgation of solid food. This effect, however, is probably of no clinical relevance in patients, who had their last solid meal the evening before surgery. Hence, we conclude that the anesthesia dogma, which rules out smoking shortly prior to anesthesia, cannot be based on an otherwise increased incidence of pulmonary aspiration or other pulmonary morbidity. However, acute smoking (probably by an increase in COHb) may increase the incidence of myocardial ischemia during exercise and anesthesia. With reference to this possible cardiac complication it still seems reasonable to discourage smoking at least 12 to 48 hours prior to surgery in patients with elevated cardiac risk.

Introduction Studying false memories gives insights into basic memory (control) mechanisms and executive functioning. One paradigm that allows for the systematic investigation of false memories-directed forgetting (DF)-has been investigated in a multitude of design variants and populations. In its item-method variant, participants are presented an array of stimuli, each of which is followed by a remember (R) or a forget (F) instruction. On a subsequent surprise memory test, recognition rate for R stimuli is generally higher than for F stimuli. Previous studies of the authors suggest this effect to be borne not only by veridical but also by false memories. Objectives The present study aimed at modulating false alarms by transcranial direct current stimulation (TDCS). TDCS is a non-invasive, well-tolerated technique that is used to investigate healthy and impaired neuronal functions. Cortical activity is thought to be enhanced by anodal TDCS and to be reduced by cathodal TDCS. Methods Eighty-three healthy subjects participated in a double-blind sham-controlled crossover study. TDCS (20 min, 1 mA) to the left dorsolateral prefrontal cortex (dlPFC) or sham stimulation were applied during the encoding phase of a DF task. Results Whereas hits yielded the classic DF effect in all three groups, false alarm patterns differed massively. Under anodal stimulation, false alarm rates were significantly higher than under sham stimulation. Under cathodal stimulation, in turn, they were significantly lower. No between-group response bias difference was observed. Conclusion To our knowledge, this is the first study that shows a dose effect of brain stimulation on a complex cognitive task.

Even though the microsphere method frequently is used to determinate bone blood flow, validation of this technique for bone blood flow measurement is incomplete. The method is based on the principle that injected microspheres are distributed with the arterial blood and trapped in the capillaries because of their diameter (15 microm). The number of spheres lodged in an organ is proportional to its blood flow. The number of radioactive or fluorescent microspheres in a specific organ is determined indirectly by measuring radioactivity or fluorescence intensity in the organ. In this study the reliability and precision of the microsphere method for determining bone blood flow was established using radioactive and fluorescent microspheres. Six female, anesthetized New Zealand rabbits received left ventricular injections of pairs of fluorescent and/or radioactive microspheres. The humerus, femur, and tibia were dissected in a standardized manner and blood flow was determined in each sample. Comparison of relative blood flow values showed an excellent correlation between radioactive and fluorescent microspheres. The percentage difference and variation between two simultaneously injected sets of microspheres was minimal for radioactive microspheres (0.8% +/- 9.6%) and for fluorescent microspheres (0.2% +/- 11.4%). Regional bone blood flow in different regions of the femur, tibia, or humerus ranged from 2.2-28.1 mL/minute/100 g, but there was no significant difference between right and left bone samples of the same region after repeated measurement. Radioactive and fluorescent microspheres allow precise determination of regional bone blood flow.

Levobupivacaine, the S-enantiomer of racemic bupivacaine, will be available in Germany in mid-2004. Pharmacological studies demonstrated that, compared to bupivacaine, levobupivacaine has equal local anaesthetic potency with reduced potential for cardiac and CNS toxicity. This review introduces the new long-acting amide local anaesthetic levobupivacaine to the reader and evaluates its place in obstetric analgesia and anaesthesia compared to bupivacaine and ropivacaine.

Ageing of the population increases the number of large orthopedic surgical interventions in elder people. High perioperative blood loss together with a reduced tolerance to anemia increase the transfusion probability in this patient subgroup. The expected cost explosion in the transfusion system (cost intensive quality management, imbalance between the number of donors and recipients) as well as the remaining transfusion related risk of hemolysis, infection and immunosuppression reflect the high socio-economic significance of the development of institutional transfusion programs. The present article summarizes: (1) the (patho-) physiology of anemia compensation, (2) the decision making for transfusion in healthy patients and patients with cardiovascular disease, and (3) the currently applied pre- and intraoperative techniques to reduce allogeneic transfusion in orthopedic patients.

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular (RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng.kg(-1).min(-1)) and, consecutively, ILO (60 ng.kg(-1).min(-1)) for 20 min each. We measured pulmonary artery pressure (PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E(es)). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E(es) was enhanced during all doses tested, which reached statistical significance during EPO(25 ng) and ILO, but not during EPO(50 ng). PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function.

Viele Eingriffe an der Lunge, aber auch andere thoraxchirurgische Eingriffe sowie besondere Konstellationen im Bereich der Intensivmedizin erfordern die Ein-Lungen-Ventilation (ELV). Eine Einteilung in absolute (seltene) und rela-tive (haufige) Indikationen fur ELV ist hilfreich fur die Entscheidungsfindung (Tabelle 6.5.1).

Das Spektrum der Patienten in der Mund-Kiefer-Gesichtschirurgie reicht vom Saugling mit kraniofazialen Missbildungen uber den (poly-)traumatisierten Patienten mit Verletzungen des Gesichtsschadels, dem Patienten mit Kiefersperre durch Abszess bis zum alteren Tumorpatienten mit typischen kardiovaskularen Begleiterkrankungen.

The central anticholinergic syndrome (CAS) is a rarely observed condition after general anaesthesia. There are no definitive criteria to set the diagnosis of CAS. The syndrome may manifest in clinical neurological signs, such as hyperactive states or a depressed CNS state. The diagnosis usually depends on a process of exclusion of other conditions and is confirmed after rapid recovery following administration of physostigmine. We report on a 34-year-old patient who suddenly lost consciousness and developed respiratory arrest 1 h after general anesthesia and normal postoperative recovery. CAS was considered, although apnea has not been reported as a clinical symptom of this disease up to now and no peripheral signs of CAS were observed. After the administration of 1 mg physostigmine the symptoms resolved immediately and the patient started sufficient spontaneous breathing. However, corresponding to the plasma elimination half-life of the drug, further comatose episodes with apnea occurred. Therefore, the patient was admitted to the ICU and an infusion of physostigmin at a rate of up to 5 mg/h was started. Due to this therapy the patient's state became stable and 15 h after the first manifestation of CAS the infusion of physostigmin was discontinued. The following postoperative course was uneventful. In case of reduced vigilance with apnea after general anaesthesia, central anticholinergic syndrome should be considered. For diagnostic and therapeutic purposes the administration of physostigmine should be attempted.

In recent studies, minimum local analgesic concentrations have been defined as 0.93 mg/mL for bupivacaine and 1.56 mg/mL for ropivacaine for epidural analgesia for the first stage of labour, resulting in an analgesic potency ratio of 1 : 0.6. In the current study we compared ropivacaine and bupivacaine in a PCEA system (combined with sufentanil) taking this potency ratio into account but administering drug doses providing sufficient analgesia for all stages of labour.In a prospective, double-blinded study 114 parturients were randomised to receive either ropivacaine 2 mg/mL with sufentanil 0.75 microg/mL or bupivacaine 1.25 mg/with sufentanil 0.75 microg/mL. After epidural catheter placement, PCEA was available with boluses of 4 mL, a lock-out time of 20 min and no basal infusion rate. We evaluated pain intensity during contractions, sensory and motor function, duration of labour, mode of delivery and neonatal outcome. Consumption of local anaesthetic and opioid drugs and PCEA system variables were recorded.Mean total consumption as well as mean hourly drug consumption was significantly increased in the ropivacaine-sufentanil group. No differences in analgesic quality, sensory or motor blocking potencies or neonatal outcome variables between groups were detected. Frequency of instrumental deliveries was significantly increased in the ropivacaine-sufentanil group.The results support the findings of previously published studies postulating ropivacaine to be 40-50% less potent for labour epidural analgesia compared to bupivacaine. However, we observed an increased frequency of instrumental deliveries with ropivacaine. To evaluate the clinical relevance of these findings, further investigations are warranted.

Impaired right ventricular (RV) function may be caused by pulmonary hypertension or myocardial ischemia. It is characterized by a dilation of the RV, which is followed by an increase of wall tension and O2-consumption and a decrease of RV ejection fraction (RV 'dysfunction'). If a drop of arterial pressure occurs this my precipitate RV failure and shock (RV 'insufficiency'). Diagnosis of RV failure and monitoring of RV function is difficult. Sometimes, even a severe impairment of RV function goes undetected or is misinterpreted. Patients in the operating room or on intensive care units seem to be especially prone to RV dysfunction and failure. Since a causative therapy often is not readily available, adequate symptomatic therapy is of utmost importance. Four basic principles have to be considered: 1) Optimizing preload: The failing RV requires adequate filling for preservation of stroke volume. On the other hand, overdistension of the RV may result in RV ischemia, thereby further deteriorating RV function Hence, volume loading is important, but requires continuous monitoring. 2) Maintenance of aortic pressure: Vasopressors are indicated if there is a critical drop of coronary perfusion pressure. Norepinephrine presently is the drug of choice for this purpose. 3) Reduction of RV afterload: Whereas intravenous vasodilators are limited in their efficacy in dilating pulmonary vessels due to systemic side effects, inhaled vasodilators result in selective pulmonary vasodilation and may improve RV function. 4) Increase of RV contractility: In RV failure and shock, norepinephrine and epinephrine are the drugs of choice. Inodilators are well suited for reducing pulmonary vascular resistance due to their positive inotropic and vasodilating effects. Since systemic vasodilation may occur, these drugs must only be used in hemodynamically stable patients.

Die praoperative Diagnostik verfolgt aus Sicht des Anasthesisten drei wesentliche Ziele: Sie soll dazu beitragen, (a) das Operations- und Anasthesierisikos abzuschatzen, (b) anasthesierelevante medizinische Probleme zu identifizieren und (c) das hierdurch entstehende perioperative Risiko durch Optimierung der praoperativen Therapie zu minimieren. Wachsende okonomische Zwange haben zur Folge, das der zur Erreichung dieser Ziele erforderliche Aufwand an praoperativer Diagnostik in zunehmendem Mase einer kritischen Kosten-Nutzen-Analyse unterzogen wird. Dies hat in den vergangenen Jahren zu einer Abkehr vom System des ‘Routine-Screenings’ und hin zu einer individuell begrundbaren, rationalen Diagnostik gefuhrt. Im folgenden Beitrag werden die derzeit aktuellen Uberlegungen, Empfehlungen und Algorithmen zur praoperativen Diagnostik aus anasthesiologischer Sicht dargestellt.

Inhalation of high concentrations of nitric oxide (NO) has been shown to improve gas exchange and to reduce pulmonary vascular resistance in individuals with ischemia-reperfusion injury following orthotopic lung transplantation. We assessed the cardiopulmonary effects of low doses of NO in early allograft dysfunction following lung transplantation.Prospective clinical dose-response study.Anesthesiological intensive care unit of a university hospital.8 patients following a single or double lung transplantation who had a mean pulmonary arterial pressure (PAP) in excess of 4.7 kPa (35 mmHg) or an arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FIO2) of less than 13.3 kPa (100 mmHg).Gaseous NO was inhaled in increasing concentrations (1, 4 and 8 parts per million, each for 15 min) via a Siemens Servo 300 ventilator.Cardiorespiratory parameters were assessed at baseline, after each concentration of NO, and 15 min after withdrawal of the agent [statistics: median (25th/75th percentiles: Q1/Q3), rANOVA, Dunnett's test, p0.05]. Inhaled NO resulted in a significant, reversible, dose-dependent, selective reduction in PAP from 5.5(5.2/6.0) kPa at control to 5.1(4.7/5.6) kPa at 1 ppm, 4.9(4.3/5.3) kPa at 4 ppm, and to 4.7(4.1/5.1) kPa at 8 ppm. PaO2 increased from 12.7(10.4/17.1) to 19.2(12.4/26.0) kPa at 1 ppm NO, to 23.9(4.67/26.7) kPa at 4 ppm NO and to 24.5(11.9/28.7) kPa at 8 ppm NO. All patients responded to NO inhalation (either with PAP or PaO2), all were subject to long-term inhalation (1-19 days). All were successfully weaned from NO and were discharged from the intensive care unit.The present study demonstrates that low-dose inhaled NO may be an effective drug for symptomatic treatment of hypoxemia and/or pulmonary hypertension due to allograft dysfunction subsequent to lung transplantation.

Video-assisted minimally invasive surgical methods with endovascular-based femoral cardiopulmonary bypass (CPB) and balloon occlusion of the aorta (Port-Access technique) were used to close an ostium-secundum atrial septal defect (ASD) in 7 patients.Minor modifications were made to the system to provide drainage of the superior vena cava. The surgery was performed through a small (3.5-5cm) right anterolateral thoracotomy with 3D video and robotic arm assistance.The operative procedures were completely uneventful and the patients were discharged four days postoperatively in good condition and with excellent cosmesis.Using the modifications described, the Port-Access surgical method can be recommended for minimally invasive closure of an ASD.

Human recombinant interleukin-10 (rhIL-10) has been found to inhibit endotoxin-induced production of several proinflammatory cytokines including tumor necrosis factor alpha (TNFalpha) from human monocytes. The exogenous therapeutic administration of rhIL-10 in acute and chronic hyperinflammatory conditions has been discussed. For none of the large animal species that have been used to study the role and effects of various mediators during septicemia, crossreactivity of rhIL-10 has been shown so far. Therefore, the aim of the present investigation was to evaluate the crossreactivity of rhIL-10 in a porcine model.To determine the effects of rhIL-10 on endotoxin-challenged porcine monocytes, we incubated porcine peripheral blood monocytes from five donors with three different concentrations of rhIL-10 (500 ng/ml, 1000 ng/ml and 2000 ng/ml, respectively) either simultaneously with, or two hours prior to lipopolysaccharide (LPS) administration.As compared to incubation with LPS (1 microg/ml) alone, coincubation with LPS and rhIL-10 (500 ng/ml, 1000 ng/ml and 2000 ng/ml) (n = 5) for four hours resulted in a marked and uniform reduction of immunoreactive TNFalpha. For preincubation (n = 5), only the addition of 500 ng/ml rhIL-10 led to a homogeneous decrease of TNFalpha levels in each sample. There was no consistent reduction in TNFalpha after preincubation with 1000 and 2000 ng/ml rhIL-10. Our results indicate crossreactivity of recombinant human interleukin-10 in porcine peripheral blood monocytes. Further investigations on the potential therapeutical role of exogenously administered rhIL-10 are thus possible in porcine models.

The aim of the present study was to investigate the pattern of ventricular dynamic contraction and its relation to changes of transseptal pressure gradient during ventilation with positive end-expiratory pressure (PEEP). For that purpose, left (LV) and right ventricular (RV) pressures as well as ventricular shortening in septal-lateral (s.l.) direction were assessed in 8 dogs (RV n = 5) exposed to experimental acute respiratory distress syndrome (eARDS) and PEEP 10 and 20 cmH2O (P10, P20). Despite maintenance of transmural central venous pressure by volume substitution, PEEP resulted in a fall of stroke index (P10 vs. eARDS: -7%, p0.05; P20 vs. P10: -28%, p0.05); this was accompanied by a fall of LV end-diastolic diameter (P10 vs. eARDS: -3.1%, p0.01; P20 vs. P10: -7.4%, p0.01). Although the transseptal LV to RV end- diastolic pressure gradient changed only minimally, there was a significant increase of paradoxic left ventricular systolic lengthening from 3.1% at eARDS to 4.5% at P10 (p0.05 vs. eARDS) and 8.4% at P20 (p0.05 vs. P10). Neither RV end-diastolic diameter nor s.l. shortening were significantly influenced by P10 or P20. It is concluded, that a rearrangement of LV dynamic contraction does occur during ventilation with PEEP, which is compatible with the concept of paradoxic systolic bulging of the interventricular septum towards the lumen of the right ventricle. Since this phenomenon occurred independent from changes of the end-diastolic pressure gradient between both ventricles, we suggest that systolic septal movement to the right is an active contractile process to support the function of a stressed RV.

Pulmonary toxicity of inhaled materials is often evaluated by (repetitive) assessment of the composition of bronchoalveolar lavage (BAL) fluid or of epithelial lining fluid (ELF) in sheep and lambs. Knowledge of the typical constituents of these fluids obtained from healthy animals is essential for identification of pathologic changes. Few studies have dealt with normal constituents of BAL fluid or ELF in sheep and lamb. The comparability of these studies, however, is limited for reasons concerning the choice of model and BAL technique. The biochemical and cellular composition of alveolar ELF obtained by a standardized BAL procedure was examined in 15 pento-barbital anesthetized 4 months old Merino lambs unexposed to inhaled substances. ELF volume was calculated by using the urea dilution method. We found 20.3 x 10(5) leucocytes per ml ELF, 87.5% of which were alveolar macrophages. Basophils and neutrophils were practically absent while 5% of the counted cells were lymphocytes. 76% of recovered cells were viable. The ELF contained 7 mg/ml total protein; enzyme activities of LDH and AP were 1692 U/l and 145 U/l, respectively.

Regional organ blood flow (RBF) is spatially heterogeneous. Relative dispersion (standard deviation S.D./mean) is often used to assess heterogeneity of RBF. Relative dispersion is a global measure of heterogeneity and is strongly influenced by the tissue sample size making comparisons between research groups inappropriate. Spatial correlation (SC) of blood flow is, on the other hand, averaged local self similarity. Both parameters change oppositely secondary to interventions. Fractal dimension ( D ) is a scale-independent measure of spatial heterogeneity and thus facilitates comparison of data. Programs for calculation of SC and D have not been published. We present two portable computer programs written in C++ for calculating SC and D . The programs were validated with six computer generated data sets of known heterogeneity. The results were in agreement with data from the literature: we conclude that the programs accurately calculate spatial correlation and fractal dimension of 1-, 2-, or 3-dimensional perfusion matrices.

The perioperative morbidity and mortality is mainly influenced by the type and duration of surgery as well as the patient's preoperative state of health. Anesthesia per se, however, may also result in severe perioperative (patho) physiological changes, which may be both desired (e.g. analgesia, vasodilation in vascular surgery) or detrimental (e.g. hypothermia, ventilatory depression) and which may differ depending on the anesthetic technique used (e.g. general anesthesia vs. regional anesthesia). Yet, all anaesthetic techniques have in common, that their effects are not limited to the duration of the surgical intervention, but may expand far into the postoperative period. Therefore, many trials have been performed in the past aiming to compare the impact of different anesthetic techniques on the incidence of postoperative techniques, no significant advantage of one or the other technique has been identified up to now with respect to postoperative mortality or severe morbidity. This finding may be due to at least three factors. 1) Many side-effects related to anesthesia--due to close postoperative monitoring--are detected and treated early in the postoperative phase (e.g. in the recovery room), thereby preventing serious complications.2) Postoperative mortality related exclusively to anesthesia probably is so low, that huge patient numbers would be required to demonstrate any significant differences between different techniques. 3) Besides the factor 'anesthesia', many other factors contribute to the anesthesia related morbidity and mortality (e.g. the factor 'anesthetist') which are hardly quantified. The fact that clear advantages for a single technique have not yet been demonstrated must not, however, result in anesthetic 'nihilism'. Rather there may be good reasons in the individual patient (e.g. lack of a recovery room), to prefer a certain anesthetic technique or drug over another, in order to lower the individual risk of anesthesia. Whether the use of a certain technique-e.g. spinal or epidural anesthesia-may contribute to a reduction of specific postoperative surgical complications (e.g. rate of reocclusion subsequent to peripheral vascular surgery) is presently under investigation.

Erkrankungen des Herz-Kreislauf-Systems weisen in der wesdichen Welt eine Pravalenz von etwa 25% auf und gehoren damit zu den haufigsten Erkrankungen uberhaupt [25]. Da die Inzidenz kardiovaskularer Erkrankungen mit zunehmendem Alter steigt, ist aufgrund der derzeitigen Struktur der Bevolkerungs- pyramide in Zukunft mit einem weiteren Anwachsen sowohl des relativen Anteils als auch der absoluten Zahlen von kardialen Risikopatienten zu rechnen. Diese mussen sich wegen der im Alter hoheren Morbiditat vermehrt operativen Eingriffen unterziehen. Schatzungen zufolge werden derzeit allein in der Bundesrepublik Deutschland pro Jahr ca. 2–3 Mio. nichtherzchirurgische Operationen - und damit auch Anasthesien - an kardialen Risikopatienten vorgenommen [26].

The classical concept for understanding the heterogeneity of regional pulmonary blood flow distribution is West’s concept of lung zones; Zones have been defined by the relationship of blood pressure in pulmonary arteries and veins to the pressure of air within the alveolar space [1]. Three such zones have been described: Areas of no flow where alveolar pressure exceeds arterial pressure; areas of ‘waterfall’ flow where alveolar pressure exceeds venous, but not arterial blood pressure; and a zone of continuous flow through arteries and veins where alveolar pressure is lower than both blood pressures. In this article, current data are reviewed that may challenge this model for the in-vivo situation. Since West’s classical description, much has been learned about the design principle nature uses to create complex trees such as the pulmonary vasculature and bronchial tree. New imaging techniques provide the clinician with overwhelming amounts of data, and progress in this field will continue to enhance resolution of pulmonary structures. We will outline a new concept of distribution of pulmonary blood flow which at the same time gives due credit to the complex structure of the pulmonary vessel tree and can reduce any amount of data on pulmonary perfusion to a single parameter describing heterogeneity.

The concept of small-volume resuscitation, the rapid infusion of a small volume (4 ml/kg BW) of hyperosmolar 7.2-7.5% saline solution for the initial therapy of severe hypovolemia and shock was advocated more than a decade ago. Numerous publications have established that hyperosmolar saline solution can restore arterial blood pressure, cardiac index and oxygen delivery as well as organ perfusion to pre-shock values. Most prehospital studies failed to yield conclusive results with respect to a reduction in overall mortality. A meta-analysis of preclinical studies from North and South America, however, has indicated an increase in survival rate by 5.1% following small-volume resuscitation when compared to standard of care. Moreover, small-volume resuscitation appears to be of specific impact in patients suffering from head injuries with increased ICP and in severest trauma requiring immediate surgical intervention. Results from clinical trials in Austria, Germany and France have demonstrated positive effects of hyperosmolar saline solutions when used for fluid loading or fluid substitution in cardiac bypass and in aortic aneurysm surgery, respectively. A less positive perioperative fluid balance, a better hemodynamic stability and improved pulmonary function were reported. In septic patients oxygen consumption could significantly be augmented. The most important mechanism of action of small-volume resuscitation is the mobilisation of endogenous fluid primarily from oedematous endothelial cells, by which the rectification of shock-narrowed capillaries and the restoration of nutritional blood, flow is efficiently promoted. Moreover, after ischemia reperfusion a reduction in sticking and rolling leukocytes have been found following hyperosmolar saline infusion. Both may be of paramount importance in the long-term preservation of organ function following hypovolemic shock. An increased myocardial contractility in addition to the fluid loading effects of hyperosmolar saline solutions has been suggested as a mechanism of action. This, however, could not be confirmed by pre-load independent measures of myocardial contractility. Some concerns have been raised regarding the use of hyperosmolar saline solutions in patients with a reduced cardiac reserve. A slower speed of infusion and adequate monitoring is recommended for high risk patients. Recently, hyperosmolar saline solutions in combination with artificial oxygen carriers have been proposed to increase tissue oxygen delivery through enhanced O2 content. This interesting perspective, however, requires further studies to confirm the potential indications for such solutions. Many hyperosmolar saline colloid solutions have been investigated in the past years, from which 7.2-7.5% sodium chloride in combination with either 6-10% dextran 60/70 or 6-10% hydroxyethyl starch 200,000 appear to yield the best benefit-risk ratio. This has led to the registration of the solutions in South America, Austria, The Czech Republic, and is soon awaited for North America.

Introduction Emotion recognition is a basic condition of successful social cognition and interaction. It is a prerequisite for correct attribution of mental states (‘Theory of Mind’). Schizophrenic psychoses are associated with reduction of this ability and thereby characterised with deficits in social interactions. Less activation of the left inferior prefrontal cortex (iFC), an area which includes the motoric speech area (Broca Area) as well as mirror neuron activity (BA 44), was identified as a neurophysiological signature of this deficit in patients with schizophrenia. BA 44 is considered as a basic element of emotional recognition. Transcranial direct current stimulation (tDCS) is a non-invasive technology for temporary and polarity specific modulation of cortical activity and cognitive function. Objectives This research was performed to assess the effects of tDCS on emotional recognition and possibly provide new treatment options for patients with reduction of this ability. Materials and methods In a double-blind, randomised, placebo controlled cross-over design, healthy subjects underwent either activity enhancing anodal (n = 26) or activity reducing cathodal (n = 24) tDCS (20 min, 1 mA), while performing the ’reading the mind in the eyes’ (RME) test where subjects have to infer mental states from pictures that depicted others’ eyes. The stimulating electrode was placed over the left iFC (EEG 10/20 system: F3) and the reference electrode supraorbital on the right. Results There was neither an effect on accuracy of emotion recognition under anodal (F = 0.173;p = 0.681) and cathodal (F = 0.453; p = 0.508) stimulation nor an effect on recognition speed (anodal: F = 0.029;p = 0.866; cathodal: F = 0.453;p = 0.508). We found a trend for an interaction between ’stimulation order’ and ’stimulation condition’ on reaction time (the participants were faster in the second measurement-anodal: F = 3.952; p = 0.058/ cathodal: F = 3.946; p = 0.06). This trend was not found for the number of errors (anodal: F = 0.285; p = 0.598; cathodal: F = 1.468; p = 0.239). Conclusion TDCS of the left iFC has no effect on accuracy of speed of emotional recognition in healthy subjects. However, interindividual differences in the underlying mechanisms of test performance and tDCS action may have interacted with the effect. First evidence for a reverse effect on emotional recognition in schizophrenic patients are analysed in current experiments.

Both inhaled nitric oxide (NO) and inhaled prostacyclin have been shown to selectively decrease pulmonary hypertension of various origin. The aim of the present study was to assess the potential of the NO donor sodium nitroprusside (SNP) to elicit selective pulmonary vasodilation. SNP spontaneously liberates nitric oxide in the presence of reducing substances like cysteine or glutathione, ubiquitous in many different tissues. Inhaled as an aerosol in 3 healthy lambs presenting pulmonary hypertension induced by infusion of a thromboxane analogue, low concentrations of SNP (0.02-0.6 mg/ml) revealed no effect at all. In contrast, high concentrations of SNP (1.0-20.0 mg/ml) lowered pulmonary artery pressure in conjunction with systemic arterial hypotension, suggesting systemic resorption of SNP with subsequent release of its nitroso-group. Selective pulmonary vasodilation was never observed. In conclusion, the present results do not support a selective effect of inhaled SNP in the pulmonary circulation.

For long, the right ventricle (RV) has been looked upon as a passive conduit of blood, which does not contribute to overall myocardial performance. While this is true under physiological conditions, it has been recognized only recently that an intact RV may be of crucial importance for the maintenance of cardiocirculatory stability under pathophysiological circumstances, e.g. in patients with increased pulmonary vascular resistance (PVR). Hence, several techniques have been developed to monitor RV function in these patients. With respect to the monitoring of RV preload, the validity of parameters based on pressure measurement (e.g. central venous pressure, RV end-diastolic pressure) is limited by the nonlinearity of the RV pressure-volume relationship, changes of RV compliance (e.g. ischemia, drugs), and changes of intrathoracic pressure. The measurement of RV end-diastolic volume (RVEDV) or size provides a more accurate estimation of true RV fiber preload and is currently performed using the fast-response thermodilution technique. The exact quantitation of RV afterload requires the continuous assessment of RV pressure, geometry and wall thickness, which is not possible in the clinical setting. Mean pulmonary artery pressure (PAP and PVR may roughly reflect actual RV afterload under physiological conditions. However, neither PAP nor PVR take into account changes of afterload due to changes of RV size. With respect to RV contractility, none of the techniques presently available for its measurement is both valid and suitable as a tool for clinical monitoring.

Intravenous prostacyclin (PGI2) is a potent pulmonary vasodilator in pulmonary hypertension. However, dose-dependent systemic vasodilation, an increase in intrapulmonary shunt and hypoxemia limit its clinical application. Recently, inhaled nitric oxide (NO) has been reported to elicit selective pulmonary vasodilation, but its clinical use is restricted by its potential toxicity; furthermore, the feasibility of NO application in clinical practice seems difficult. Therefore, we investigated the effects of PGI2 aerosol on pulmonary and systemic circulation and compared the hemodynamic effects to those of inhaled NO. In 6 dogs, ventilation with a hypoxic gas mixture (FiO2 0.09-0.11) increased pulmonary vascular resistance (PVR) by 196% (HPV). Aerosolization of a PGI2 solution at a concentration of 430 ng/ml reduced hypoxia-induced increase of pulmonary artery pressure by 48% and PVR by 52% within 6-10 min without systemic vasodilation. The administered dose of PGI2 was 0.87 +/- 0.26 ng/kg/min. In 2 dogs, doubling the PGI2 concentration (860 ng/ml) did not enhance the vasodilatory effect. After termination of PGI2 inhalation, HPV was restored within 10-15 min. Inhaled NO (50 ppm) decreased the HPV-induced increase in PAP by 76% and in PVR by 73% within 5-10 min. Clinically relevant systemic vasodilation was not observed. It is concluded that inhalation of aerosolized PGI2 leads to selective pulmonary vasodilation in hypoxia-induced pulmonary hypertension. Aerosolized PGI2 at a concentration of 430 ng/ml was less potent than NO (50 ppm). However, due to the lack of known toxicity and its uncomplicated mode of application, inhaled PGI2 may be one alternative to inhaled NO in the treatment of acute pulmonary hypertension.

Regional left ventricular myocardial blood flow was studied in an experimental model of pulmonary edema and microembolization (PEM) ventilated with positive end-expiratory pressure (PEEP). The analysis was based on a 3-dimensional extension of the autocorrelation function used to assess the spatial correlation (rspat) of myocardial perfusion. Experiments were performed on 8 premedicated, anesthetized and mechanically ventilated dogs. PEM was induced with oleic acid (0.01 mg/kg) and glass beads. Successive PEEP values of 10, 15 and 20 cm H2O (P20) were applied and norepinephrine (NE, 0.2-1.0 microgram min-1 kg-1) was administered after P20. Regional perfusion was measured with radioactive microspheres. The left ventricle (LV) was dissected into 256 samples. rspat was computed as the correlation of regional perfusions of samples p units apart in the apex-to-base, endo-epicardial and angular directions. Analysis was performed after anesthesia and instrumentation (control, C), P20 and NE. Control values of rspat were around 50% in the apex-to-base and angular directions and the sign was inverted in the endo-epicardial direction. A reduction of rspat to values close to zero was observed in all directions for P20 and NE. This is the typical pattern of independent distribution. Thus, the results indicate that, under the experimental conditions used, there is some degree of neighborhood dependence of regional LV myocardial blood flow. This dependence is not observed under PEM, mechanical ventilation with PEEP and NE.

Das Herzzeitvolumen (HZV) wird durch die 4 Faktoren Vorlast, Nachlast, Kontraktilitat und Herzfrequenz beeinflust. Fur das Monitoring der myokardialen Pumpfunktion ergeben sich hieraus 2 Ansatzpunkte: 1) Man kann das HZV direkt messen. 2) Man kann versuchen, die Determinanten des HZV zu quantifizieren. Allerdings erlaubt erst die Kombination der beiden Ansatze Aussagen uber den Funktionszustand des Myokards.

Right ventricular (RV) dysfunction may occur due to increased RV afterload and, hence, might also contribute to the decrease in cardiac output following institution of PEEP in patients with adult respiratory distress syndrome (ARDS). To test this hypothesis, the authors examined the influence of PEEP on local and global RV function in 12 anesthetized dogs with experimental ARDS (eARDS) induced by pulmonary microembolization with glass beads and oleic acid. Local RV function was analyzed in the RV inflow tract (RVIT) and RV outflow tract (RVOT) by assessing both diastolic segment length, systolic segment shortening, and segment work (sonomicrometry). Global RV contractility was quantified by measuring maximum rate of pressure rise (dRVP/dtmax) and maximum velocity of contractile element shortening (Vmax). In eARDS, despite a fivefold increase in pulmonary vascular resistance, there was no change in cardiac index (CI), global RV contractility, RVIT and RVOT work, and RVIT shortening, whereas RVOT shortening decreased from 12.4 to 7.4% (P less than 0.01). Diastolic segment length increased in RVIT (P less than 0.05) but not in RVOT. PEEP of 10 cmH2O did not alter global RV contractility, RVIT and RVOT shortening, and RVIT work but reduced RVOT work (-35%; P less than 0.01) and CI (-11%; P less than 0.001). Cardiac index further decreased during PEEP of 20 cmH2O (-38%; P less than 0.001), while global RV contractility remained intact despite decreased RVIT and RVOT shortening (-32% and -69%; P less than 0.05) and work (-26% and -59%; P less than 0.01) in the presence of reduced fiber preload in both regions. From these findings, it was concluded that 1) the decreased CI during mechanical ventilation with PEEP at constant right ventricular end-diastolic pressure (RVEDP) is not caused by depressed global RV contractility in dogs with eARDS and a normal myocardium prior to insult. Decreased diastolic segment length and segment shortening during PEEP suggest that 2) PEEP reduces stroke volume by the Starling mechanism rather than by ischemia of the RV free wall. Finally, regionally incongruent changes of fiber preload indicate that 3) local differences in RV wall compliance are likely to occur subsequent to eARDS and PEEP.