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Background: L1CAM was originally identified as an adhesion molecule involved in neural development. In many human carcinomas L1CAM is over-expressed and is associated with a bad prognosis. We previously reported that L1CAM was absent in the vast majority of endometrioid endometrial carcinomas (ECs) (type 1) but was strongly expressed in the more aggressive serous and clear-cell ECs (termed type 2). The differential regulation of L1CAM in ECs is not well understood. Recent evidence suggests that it can be regulated by epigenetic mechanisms. Here we investigated the role of DNA-methylation of the L1CAM promoter for expression. We also studied the relationship to cancer testis (CT-X) antigens that co-localize with L1CAM on chromosome Xq28, a region that is often activated in human tumors., Methods: We used EC cell lines and primary tumor tissues for our analysis. For expression analysis we employed RT-PCR and Western blotting. DNA-Methylation of the L1CAM promoter was determined after bisulfite conversation and DNA sequencing. Tumor tissues were examined by immunohistochemical (IHC) staining., Results: We demonstrate that the treatment of L1CAM low/negative expressing EC cell lines with 5'-Azacytidine (5-AzaC) or knock-down of DNMT1 (DNA methyltransferase 1) as well as the HDAC (histone deacetylase) inhibitor Trichostatin A (TSA) up-regulated L1CAM at the mRNA and protein level. The L1CAM gene has two promoter regions with two distinct CpG islands. We observed that the expression of L1CAM correlated with hypermethylation in promoter 1 and 5-AzaC treatment affected the DNA-methylation pattern in this region. The CT-X antigens NY-ESO-1, MAGE-A3 and MAGE-A4 were also strongly up-regulated by 5-AzaC or knock-down of DNMT1 but did not respond to treatment with TSA. Primary EC tumor tissues showed a variable methylation pattern of the L1CAM promoter. No striking differences in promoter methylation were observed between tumor areas with L1CAM expression and those without expression., Conclusions: L1CAM expression correlated with methylation of the L1CAM promoter in EC cell lines. In negative cell lines L1CAM expression is up-regulated by epigenetic mechanism. Although genes localized on Xq28 are often re-expressed by human tumors, L1CAM and CT-X antigens show distinct regulation in response to HADC inhibitors and 5-AzaC.

After on-pump coronary artery bypass graft surgery, a patient had acute heparin-induced thrombocytopenia with thoracic arterial and venous thrombus formations. Complex emergency surgery with cardiopulmonary bypass and deep hypothermic circulatory arrest using bivalirudin anticoagulation was performed., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Expression of L1 cell adhesion molecule (L1CAM) is associated with poor prognosis in a variety of human carcinomas including breast, ovarian and pancreatic ductal adenocarcinoma (PDAC). Recently we reported that L1CAM induces sustained nuclear factor kappa B (NF-κB) activation by augmenting the autocrine production of interleukin 1 beta (IL-1β), a process dependent on interaction of L1CAM with integrins. In the present study, we demonstrate that transforming growth factor β1 (TGF-β1) treatment of breast carcinoma (MDA-MB231) and PDAC (BxPc3) cell lines induces an EMT (epithelial to mesenchymal transition)-like phenotype and leads to the expression of L1CAM. In MDA-MB231 cells, up-regulation of L1CAM augmented expression of IL-1β and NF-κB activation, which was reversed by depletion of L1CAM, L1CAM-binding membrane cytoskeleton linker protein ezrin, β1-integrin or focal adhesion kinase (FAK). Over-expression of L1CAM not only induced NF-κB activation but also mediated the phosphorylation of FAK and Src. Phosphorylation was not induced in cells expressing a mutant form of L1CAM (L1-RGE) devoid of the integrin-binding site. FAK- and Src-phosphorylation were inhibited by knock-down of various components of the integrin signalling pathway such as β1- and α5-integrins, integrin-linked kinase (ILK), FAK and the phosphoinositide 3-kinase (PI3K) subunit p110β. In summary, these results reveal that during EMT, L1CAM promotes IL-1β expression through a process dependent on integrin signalling and supports a motile and invasive tumour cell phenotype. We also identify important novel downstream effector molecules of the L1CAM-integrin signalling crosstalk that help to understand the molecular mechanisms underlying L1CAM-promoted tumour progression.

The L1 cell adhesion molecule (L1CAM) plays a major role in the development of the nervous system and in the malignancy of human tumors. In terms of biological function, L1CAM comes along in two different flavors: (1) a static function as a cell adhesion molecule that acts as a glue between cells; (2) a motility promoting function that drives cell migration during neural development and supports metastasis of human cancers. Important factors that contribute to the switch in the functional mode of L1CAM are: (1) the cleavage from the cell surface by membrane proximal proteolysis and (2) the ability to change binding partners and engage in L1CAM-integrin binding. Recent studies have shown that the cleavage of L1CAM by metalloproteinases and the binding of L1CAM to integrins via its RGD-motif in the sixth Ig-domain activate signaling pathways distinct from the ones elicited by homophilic binding. Here we highlight important features of L1CAM proteolysis and the signaling of L1CAM via integrin engagement. The novel insights into L1CAM downstream signaling and its regulation during tumor progression and epithelial-mesenchymal transition (EMT) will lead to a better understanding of the dualistic role of L1CAM as a cell adhesion and/or motility promoting cell surface molecule.

Background: The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition., Results: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown., Conclusions: A subset of NSCLCs with vessel tropism and increased metastasis aberrantly expresses L1CAM. L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.

Purpose of Review: Hemorrhage, transfusions and the need for re-exploration can have a detrimental effect on patient outcome in cardiac surgery. With the suspension of aprotinin from the market, only the antifibrinolytics tranexamic acid and epsilon-aminocaproic acid (EACA) are left as pharmacological options to reduce hemostatic activation and associated bleeding complications. In light of the aprotinin story, the need for large independent safety studies has become evident. The current review will focus on the question of how far the quality of available data allows for judging these agents with regard to safety and efficacy, as well as whether or not new trails are warranted., Recent Findings: Both, tranexamic acid and EACA are effective in reducing blood loss and transfusion requirements in cardiac surgery. Analysis of data is complicated as the dosing scheme, especially for tranexamic acid, varies extremely and the agents are highly overdosed in most relevant trials. Newer data indicates that in a dose-dependent fashion, tranexamic acid is associated with an increase of adverse events, particularly the observation of seizures. In these studies, however, tranexamic acid has also been highly overdosed., Summary: The lysine analogs are unspecific enzyme inhibitors. Therefore, it is conceivable that an overdosing might reveal severe clinical side-effects beyond the inhibition of plasmin. Further studies re-evaluating the drug safety of tranexamic acid and EACA using the recommended and approved doses are necessary.

Members of the Slug/Snail family of transcription factors are thought to drive epithelial-mesenchymal-transition (EMT) in preneoplastic epithelial cells, thereby contributing to malignant transformation. One mediator in the EMT of pancreatic ductal adenocarcinoma (PDAC) cells and a potential target gene of Slug is the cellular adhesion molecule L1CAM. Using the human pancreatic ductal epithelial cell line H6c7 and the PDAC cell line Panc1, we could show that along with TGF-β1-induced EMT, L1CAM expression is increased in a Slug- but not Snail-dependent fashion. Two E-box recognition motifs in the L1CAM promoter upstream of the most distal transcriptional start site could be verified by gel shift and supershift assay to interact with Slug. ChIP assays detected an increased interaction of Slug with both recognition motifs of the human L1CAM promoter in TGF-β1-treated H6c7 cells, whereas binding of Snail was downregulated. Moreover, ChIP assays with Panc1 cells confirmed this interaction of Slug with the human L1CAM promoter and further detected an interaction of both recognition sites with RNA-polymerase II in a Slug-dependent fashion. Luciferase reporter gene assays using wild-type or single- and double-mutated variants of the L1CAM promoter confirmed transcriptional activation by Slug involving both recognition motifs. By demonstrating the direct transcriptional control of L1CAM expression through Slug during TGF-β1-induced EMT of PDAC cells, our findings point to a novel mechanism by which Slug contributes quite early to tumorigenesis. Moreover, our study is the first one describing the control of the human L1CAM promoter in tumor cells.

Background: The L1 cell adhesion molecule (L1CAM) was originally identified as a neural adhesion molecule involved in axon guidance. In many human epithelial carcinomas L1CAM is overexpressed and thereby augments cell motility, invasion and metastasis formation. L1CAM positive carcinomas are associated with bad prognosis. Recent data point out that L1CAM is regulated in a fashion similar to epithelial-mesenchymal transition (EMT). Previous studies have implied the transcription factors Slug and/or β-catenin in L1CAM transcriptional regulation. However, the regulation of human L1CAM expression at the transcriptional level is not well understood., Results: To better understand the molecular basis of L1CAM transcriptional regulation, we carried out a detailed characterization of the human L1CAM promoter. We identified two transcription start sites, the first in front of a non-translated exon 0 (promoter 1) and the other next to the first protein-coding exon 1 (promoter 2). Both sites could be verified in endometrial carcinoma (EC) cell lines and appear to be used in a cell-type specific manner. The two identified promoter regions showed activity in luciferase reporter assays. Chromatin-IP analyses confirmed the in silico predicted E-boxes, binding sites for transcription factors Snail and Slug, as well as Lef-1 sites, which are related to β-catenin-mediated transcriptional regulation, in both promoters. Overexpression of β-catenin exclusively augmented activity of promoter 1 whereas Slug enhanced promoter 1 and 2 activity suggesting that both promoters can be active. Overexpression of β-catenin or Slug could upregulate L1CAM expression in a cell-type specific manner., Conclusions: Our results, for the first time, provide evidence that the L1CAM gene has two functionally active promoter sites that are used in a cell-type specific manner. Slug and β-catenin are involved L1CAM transcriptional regulation. Nevertheless, Slug rather than β-catenin levels are correlated with L1CAM expression in EC cell lines. Our findings suggest that the L1CAM transcriptional regulation is more complex than anticipated and this study provides the basis for a better understanding of L1CAM regulation in non-neuronal/tumor cells.

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 (Deutsche Gesellschaft für Thorax-, Herz- und Gefässchirurgie, DGTHG) and the German Society for Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und lntensivmedizin, DGAI) 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 the available monitoring methods with regard to indication, procedures, predication, limits, contraindications and risks for use. The differentiated therapy of volume-replacement, positive inotropic support and vasoactive drugs, the therapy with vasodilatators, inodilatators and calcium sensitizers and the use of intra-aortic balloon pumps will also be addressed. The guideline has been developed following 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).

Endometrial carcinomas (ECs) are classified into type 1 (less aggressive) and type 2 (aggressive) tumours that differ in genetic alterations. So far, reliable immunohistochemical markers that can identify patients with high risk for recurrence are rare. We have defined the expression of L1 cell adhesion molecule (L1CAM), a biomarker previously identified for EC, and compared its expression to oestrogen receptor (ER)/progesterone receptor (PR) and E-cadherin. We found that L1CAM was absent in normal endometrium and the vast majority of endometrioid ECs (type 1) but was strongly expressed in serous and clear-cell ECs, considered as type 2. 78/272 cases were identified as L1CAM-positive endometrioid ECs that were correlated with a poor prognosis. Strikingly, we observed an inverse relationship between L1CAM and ER/PR/E-cadherin expression in all ECs. In mixed ECs, composed of endometrioid (L1CAM(-) ER/PR(+) E-cadherin(+)) and clear-cell/serous (L1CAM(+) ER/PR(-) E-cadherin(-)), both phenotypes were co-expressed. In some of these cases L1CAM was up-regulated at the leading edge of the tumour, where ER/PR and E-cadherin expression were selectively lost. In EC cell lines treated with the epithelial-mesenchymal transition (EMT) inducer TGFbeta1, L1CAM and vimentin were strongly up-regulated, while E-cadherin expression was reduced. The treatment also resulted in an increased expression of the EMT transcription factor Slug and an enhanced cell invasion. Depletion of Slug by siRNA knockdown prevented both L1CAM up-regulation and enhanced cell invasion. According to our analysis, we suggest that L1CAM is a novel marker for EMT in ECs and that L1CAM-typing could identify endometrioid ECs that have type 2-like features and are at high risk for recurrence.

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.

In Anesthesia, especially in Cardiac Anesthesia in germany exist a lots of standards, that define good quality. For external quality assurance and analysis there is a core data set defined with an extension for cardiac anesthesia for a survey of patient risk factors und complications. Because there is no obligation only a minority of hospitals take an active part and only few data exists. No external structures exist to initiate quality improvements in the participating hospitals. Furthermore there is no external quality assurance to address patient satisfaction. The German Association for Anaesthesiology and Intensive Care has established the requirements for external quality analysis. The hospitals should use these possibilities to prevent external specifications. Structures to fulfil the last step of the Demming Cycle (ACT) should be added., (Georg Thieme Verlag KG Stuttgart, New York.)

Objective: The primary objective of this nationwide survey carried out in department of cardiac anesthesia in Germany was to identify current practice with regard to neuromonitoring und neuroprotection., Methodology: The data are based on a questionnaire sent out to all departments of cardiac anesthesia in Germany between October 2007 und January 2008. The anonymized questionnaire contained 26 questions about the practice of preoperative evaluation of cerebral vessels, intra-operative use of neuromonitoring, the nature und application of cerebral protective measures, perfusion management during cardiopulmonary bypass, postoperative evaluation of neurological status, and training in the field of cerebral monitoring., Results: Of the 80 mailed questionnaires 55% were returned and 90% of department evaluated cerebral vessels preoperatively with duplex ultrasound. The methods used for intra-operative neuromonitoring are electroencephalography (EEG, 60%) for type A dissections (38.1%), for elective surgery on the thoracic and thoraco-abdominal aorta (34.1% and 31.6%, respectively) and in carotid surgery (43.2%) near infrared spectroscopy (40%), evoked potentials (30%) and transcranial Doppler sonography (17.5%), with some centers using combined methods. In most departments the central nervous system is not subjected to monitoring during bypass surgery, heart valve surgery, or minimally invasive surgery. Cerebral protective measures used comprise patient cooling on cardio-pulmonary bypass (CPB 100%), extracorporeal cooling of the head (65%) and the administration of corticosteroids (58%), barbiturates (50%) and antiepileptic drugs (10%). Neuroprotective anesthesia consists of administering inhalation anesthetics (32.5%; sevoflurane 76.5%) and intravenous anesthesia (20%; propofol and barbiturates each accounting for 46.2%). Of the departments 72.5% cool patients as a standard procedure for surgery involving cardiovascular arrest and 37.5% during all surgery using CPB. In 84.6% of department CPB flow equals calculated cardiac output (CO) under normothermia, while the desired mean arterial pressure (MAP) varies between 60 and 70 mmHg (43.9%) and between 50 and 60 mmHg (41.5%), respectively. At body temperatures less than 18 degrees C CPB flow is reduced below the calculated CO (70%) while 27% of departments use normothermic flow rates. The preferred MAP under hypothermia is between 50 and 60 mmHg (59%). The results of intra-operative neuromonitoring are documented on the anesthesia record (77%). In 42.5% of the departments postoperative neurological function is estimated by the anesthesiologist. Continuing education sessions pertaining to neuromonitoring are organized on a regular basis in 32.5% of the departments and in 37.5% individual physicians are responsible for their own neuromonitoring education., Conclusion: The present survey data indicate that neuromonitoring and neuroprotective therapy during CPB is not standardized in cardiac anesthesiology departments in Germany. The systemic use of available methods to implement multimodal neuromonitoring would be desirable.

Since the beginning of the era of cardiac surgery hypothermia remains a mainstay in perioperative management. This role is increasingly being questioned because of many disadvantages and the lack of evidence of advantages. Using modern techniques of perfusion and myocardial protection as well as improved surgical techniques the results with normothermia seem to be comparable. The importance of hypothermia in present day cardiac surgery is discussed with respect to myocardial and cerebral protection.

Standards of quality assurance according to DIN EN ISO 9001:2000 have been implemented in many university hospital departments, but often teaching activities are not included. This work presents a method that allows, after having defined the various teaching activities as sub-processes of one single core process, to include the manifold teaching activities of university hospital departments into the certification process. The stepwise description of the prerequisites for including teaching activities into ISO 9001 certification is illustrated by a concrete implementation example.

Introduction: The discussion about perioperative withdrawal or continuation of angiotensin-converting enzyme inhibitors (ACEI) remains controversial. Should it be continued to avoid peaks in blood pressure and heart rate during anesthesia? Or should it be discontinued the day before to avoid clinically relevant hypotonia? What is the greater risk? Since there are only a few studies dealing with this question, we compared the cardio-circulatory reaction during anesthesia after withdrawal and with continuation of ACEI therapy., Methods: A total of 100 hypertonic patients chronically treated with ACEIs were included in this prospective, randomized, double blind study. The last ACEI medication was given with the premedication in the morning (premed) or on the day before (withdrawal). Blood pressure and heart rate during induction and termination of anesthesia were compared between both groups. A threshold value for vasopressor therapy was determined to be a mean arterial pressure of 60 mmHg., Results: In the premed group Akrinor was necessary significantly more often and in higher dosages. Nevertheless, following induction the blood pressure and heart rates were significantly lower compared to the withdrawal group. The highest blood pressure and heart rate during induction and termination of anesthesia did not differ between the groups., Conclusions: The continuation of ACEI therapy in the morning is not associated with a better control of blood pressure and heart rate but causes a more pronounced hypotension which forced a therapy more often. Patients chronically treated with ACEI should receive the ACEI the last time on the day before the operation and not with the premedication in the morning.

Background: In Germany, more than 100,000 patients are monitored and treated in 80 intensive care units (ICUs) following cardiac surgery each year. The controversies concerning the different methods of hemodynamic monitoring and the appropriate agents for volume therapy and inotropic support are well known. However, little is known about how monitoring and treatment are currently performed., Methods: A questionnaire with 39 questions was sent to the leading physicians of 80 ICUs in Germany, treating patients after cardiac surgery. The questions to be answered covered the current practice of hemodynamic monitoring, volume replacement, inotropic/vasopressor support and transfusions in patients after cardiac surgery., Results: Sixty-nine per cent of the questionnaires were completed and returned. All ICUs used basic monitoring as recommended by the societies. The use of advanced hemodynamic monitoring included the pulmonary artery catheter (58.2%), transesophageal echocardiography (38.1%) and transpulmonary dilution techniques (13%). Crystalloids (21.2%) and colloids (73%) were used for volume replacement. Epinephrine (41.8%) and dobutamine (30.9%) were the first-choice inotropic drugs for the treatment of low cardiac output syndrome, followed by phosphodiesterase inhibitors (14.5%). Second-choice drugs for the treatment of low cardiac output syndrome were enoximone (29%), milrinone (25%) and dobutamine (25%). A written transfusion protocol and a transfusion threshold for red blood cells existed in 59% and 79% of ICUs, respectively., Conclusion: Hemodynamic monitoring and the variability in clinical practice with regard to volume replacement, transfusion triggers and the use of vasopressors/inotropes in cardiac surgery patients tend to follow the results of traditional experience rather than current scientific knowledge. Guidelines are therefore necessary to help to improve the standards of intensive care after cardiac surgery and thus the outcome of patients.

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).

Aim: The aim of this study was to determine the incidence of renal dysfunction according to the Acute-Dialysis-Quality Initiative-(ADQI)-RIFLE grading system in cardiac surgery in Germany in 2003 and to determine if variations in the incidence of renal dysfunction are related to clinical practice patterns., Design: prospective cohort analysis and practice pattern survey., Measurements: 81 hospitals were requested to report prospectively sampled quality-management-data on patient load, case mix, aortic-cross-clamp-time, baseline and maximal plasma creatinine (CreaP), new-onset-renal-replacement-therapy, and clinical practice concerning the use of fluids, inotropic and vasopressor drugs, and diuretics. Fifty-one (63%) centers answered the survey. Twenty-six centers (32%)(representative for 29 623 patients(reported creatinine data., Results: The incidence of a 50%, 100%, or 150% increase in plasma creatinine (graded as risk, injury, and failure according to the ADQI-RIFLE-system) were 9% (2-40%), 5% (0.8-30%), and 2% (0.6-33%), respectively, overall 15.4% (3.1-75%). The incidence of new-onset renal-replacement-therapy was 4.5% (0.6-24%). Centers with a low incidence of renal dysfunction 8.7% (3.1-15.4%)differed from those with a high incidence 51% (15.7-75%)by being more liberal with fluids, not preferring dopamine in ''renal'' or inotropic doses, and preferring noradrenaline as a vasopressor (all: P<0.05), but not by case mix, frequency of urgent or emergency cases, and the use of loop diuretics., Conclusions: Renal dysfunction is a frequent complication following cardiac surgery in many German heart centers. The variance between centers may not be explained by patient heterogeneity and may be related to different strategies regarding fluid therapy and the use of inotropes and vasopressors.

Objective: The Anaesthesiological Questionnaire (ANP) is a self-rating method for the assessment of postoperative complaints and patient satisfaction. The questionnaire was adapted for use in cardiac anaesthesia (ANP-KA). The study was conducted to show the value of ANP-KA as a practicable means of assessing the patient's state after cardiac anaesthesia and for its use in quality assurance., Methods: A total of 1,688 patients from 19 clinics were included who had exclusively received heart valve surgery, CABG surgery or both operations. They completed the ANP-KA between days 1 and 8 postoperatively., Results: The ANP-KA was completed by 79.1% of the patients without any assistance. The highest incidence rates were reported for a dry mouth/thirst (85.1%) and for pain in the area of surgery (60.2%). Plausible and significant differences in patients' symptoms between the grading for the immediate postoperative period and the current state at filling in the questionnaire were found. Women reported more postoperative complaints than men but no differences were found between male and female patients with regard to satisfaction with anaesthesiological care and convalescence. More complaints were reported after heart valve surgery than after CABG and satisfaction with convalescence was significantly lower after heart valve surgery. The clinics differed with respect to the reported somatic complaints and satisfaction scales., Conclusion: The results demonstrate the practicability and validity of the ANP-KA for the assessment of postoperative complaints and patient satisfaction after cardiac surgery.

Background: Xenon in low concentrations has been investigated in neuroradiology to measure cerebral blood flow (CBF). Several reports have suggested that inhalation of Xenon might increase intracranial pressure (ICP) by increasing the cerebral blood flow and blood volume, raising concerns about using Xenon as an anesthetic in higher concentrations for head-injured patients. A porcine study is presented in which the effects of inhaled 75% Xenon on elevated ICP, cerebral perfusion pressure and the efficacy of hyperventilation for ICP treatment were compared with nitrous oxide anesthesia and total intravenous anesthesia (TIVA)., Methods: Twenty-one pentobarbital-anesthetized pigs (age: 12-16 weeks) were randomly assigned to three groups to receive either 4 h of Xenon-oxygen ventilation, nitrous oxide-oxygen ventilation or air-oxygen (75%/25%) ventilation, respectively. After instrumentation for parenchymal ICP measurement and ICP manipulation, an epidurally placed 6-F balloon catheter was inflated until a target ICP of 20 mmHg was achieved. After 4 h of anesthesia hyper- and hypoventilation maneuvers were performed and consecutive ICP and CBF changes were investigated., Results: Intracranial pressure and CBF increased significantly in the nitrous oxide group as compared with the controls. There was no increase of ICP or CBF in the Xenon or control group. Intracranial pressure changed in all three groups corresponding to hyper- and hypoventilation., Conclusions: During Xenon anesthesia, elevated ICP is not increased further and is partially reversible by hyperventilation. Our study suggests that inhalation of 75% Xenon seems not to be contraindicated in patients with elevated ICP.

Objective: In order to reduce losses of gases through plastic components and to reduce nitrogen accummulation during closed system anaesthesia we investigated either 10 sets of anaesthetic tubing made of silicon as used in standard clinical practice and 10 sets made of latex, which are not used anymore due to concerns about latex allergies. The results were compared to each one set made of conventional industrial rubber., Methods: Anaesthetic tubings were connected to ventilators with low fresh gas losses, suitable for closed system anaesthesia. For nitrogen measurements, a mass spectrometer was used. The fresh gas flow was set to exceed losses by leakages and the amount of gases, extracted from the system by the mass spectrometer., Results: Highest accumulation of nitrogen was found using tubings made of silicone., Conclusion: If closed anaesthetic systems in the future will be used in intensive care therapy or in case of long lasting procedures in which closed system anaesthesia is proceeded, materials other than silicone should be investigated to avoid regular purging of system and consecutive losses of gas mixtures.

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.

Background: Inhalation anesthetics decrease liver perfusion and oxygen consumption by changing the distribution pattern of perfusion between the hepatic artery and the portal vein and by direct effects on liver cells. The effects of xenon on liver perfusion and function have been not investigated until now., Methods: Fourteen pigs were randomly assigned to two groups to receive either 73-78% xenon or 75% nitrogen in oxygen with additional supplementation of pentobarbital and buprenorphine. Microspheres were used to determine the arterial perfusion of the liver and splanchnic organs. Oxygen contents were measured by catheterization of the portal and a liver vein. Lactate and glucose plasma concentrations were measured in hepatic, mixed venous and arterial blood. Alanine aminotransferase (ALT) and lactate dehydrogenase (LOH) plasma concentrations were measured in arterial blood. Urea production rates were calculated to assess hepatic metabolic function., Results: Significant higher oxygen contents were found in the liver venous blood during xenon anesthesia. No differences were found in any other investigated parameters., Conclusion: Higher oxygen content in liver venous blood observed during xenon anesthesia was not induced by changes in hepatic perfusion distribution or by an impairment of liver metabolic capacity. However, it can be explained by similar results known from inhalation anesthesia. Additionally, the effect can be caused by the reduction of plasma catecholamine concentrations during xenon anesthesia.

Background: Xenon anesthesia is known to have no adverse influence on myocardial contractility and cardiocirculatory function even in cardiac compromised patients. To make use of this advantages for cardiac surgery patients undergoing extracorporeal circulation (ECC) it must be known if oxygenators are diffusible for xenon in order to avoid losses of the very expensive noble gas., Methods: Xenon saturated blood was recirculated in an in-vitro ECC. In 8 experiments four common oxygenators were investigated using continuous mass spectrometry at the exhaust port to measure xenon concentrations in the exspired gas., Results: Xenon concentrations at the exhaust port of the oxygenator increased during filling the oxygenator with blood. Peak level was detected within one minute after onset of ECC. No xenon could be measured two minutes after onset of ECC., Conclusions: Using common oxygenators xenon is eliminated during ECC and lost into the atmosphere. To maintain anesthesia during ECC continuous xenon application would be necessary to compensate these losses. Due to its high price it would be too expensive to continue xenon anesthesia during ECC. Therefore it is not practicable to use the today's oxygenators and ECC equipment in xenon anesthesia.

Background: It is known that proinflammatory and anti-inflammatory cytokines are released during and after cardiopulmonary bypass (CPB) in infants and children. Sex steroids are known to have immunomodulatory functions, and release of the anti-inflammatory cytokine IL-10 is stimulated by progesterone in vitro. The purpose of the present study was to investigate the plasma levels of progesterone, IL-8 (proinflammatory cytokine) and IL-10, and to relate them to sex and postoperative morbidity., Method: Eighteen infants and children (eight female) undergoing CPB were prospectively studied. Plasma levels of progesterone, IL-8 and IL-10 were determined before and 10 min after the start of CPB, and immediately after CPB; and 6 h, 24 h, 3 days and 7 days postoperatively. Organ dysfunction was identified on the basis of arbitrarily defined criteria., Results: After CPB, all patients showed significant increases in plasma levels of progesterone, IL-8 and IL-10. Plasma levels of IL-10 were significantly higher in female patients, except for during the immediate postoperative period. According to the criteria used, six out of 10 male patients, but none of the female patients developed multiple organ dysfunction (MOD)., Conclusion: The present study shows that CPB induces a significant and marked increase in plasma levels of progesterone in infants and children. Studies of administration of progesterone-blocking substances to male and female animals may help to elucidate the roles of sex and progesterone in the setting of CBP.

Little is known about the haemodynamic effects of inhaled xenon on regional organ perfusion. The aim of this study was to investigate the effect of 79% xenon ventilation on organ perfusion in pigs. We investigated 10 pigs, which were randomly allocated to receive either xenon 79% or total intravenous anaesthesia (TIVA)/oxygen anaesthesia. Microspheres were used to determine organ perfusion. The following regions of interest were investigated: cerebral cortex, medulla oblongata, brainstem, cerebellum, liver, kidney, small intestine, colon, muscle, skin and heart. The results demonstrated a significant increase in regional perfusion in the brainstem (+63%), cerebral cortex (+38%), medulla oblongata (+35%) and cerebellum (+34%). All other organs showed no significant change in regional perfusion. We conclude that xenon should be used with caution in clinical situations associated with pathological increases in intracranial pressure, e.g. neurosurgical procedures, head injury, cerebral mass lesions or stroke.

We studied 22 patients aged 53-78 years scheduled for cardiac surgery under cardiopulmonary bypass. Blood pressure, cardiac output, transcranial Doppler blood flow velocity, arterial blood gases, body temperature and protein S100B, as a marker for cerebral integrity, were evaluated in normotensive and hypertensive patients. Pre-operative mean (SD) arterial blood pressure was 93 (11) mmHg in the normotensive group compared with 116 (15) mmHg in the hypertensive group. We found an increase in protein S100B levels in both groups. Serum protein S100B concentrations in the hypertensive group were significantly higher than in the normotensive group (p < 0.001). The highest mean (SD) values were 2.04 (0.65) micromol x l(-1) in the normotensive group and 7.02 (4.55) micromol x l(-1) in the hypertensive group. These results suggest that cardiopulmonary bypass is associated with a significantly higher rate of cerebral injury in hypertensive patients than in normotensive patients. This may be due to altered autoregulation and insufficient cerebral perfusion. Modifications of cardiopulmonary bypass management for hypertensive patients might be made to decrease the risk of cerebral injury.

The high price of xenon has prevented its use in routine, clinic anaesthetic practice. Xenon therefore has to be delivered by closed-circuit anaesthesia. The accumulation of nitrogen is a significant problem within the closed circuit and necessitates flushing, which in turn increases gas expenditure and costs. In previous investigations, nitrogen concentrations between 12% and 16% have been reported in closed-circuit anaesthesia. In order to avoid such nitrogen accumulation, we denitrogenised seven pigs using a non-rebreathing system and connected the animals to a system primed with a xenon/oxygen mixture. In comparison, seven pigs were anaesthetised with xenon using a standard low-flow anaesthetic procedure. Anaesthesia time was 2 h. Nitrogen concentrations in the closed system ranged from 0.08 to 7.04% and were not significantly different from those observed during low-flow anaesthesia. Closed-circuit anaesthesia reduced the xenon expenditure 10-fold compared with low-flow anaesthesia.

Recently, computers have been used to measure key landmarks from photocopies of upper and lower study models to increase simplicity, accuracy, and informatics. This is a comparative study to evaluate the accuracy and reliability of computer-aided space analysis. Data were collected from a series of randomly selected study models. All subjects had Angle Class I molar relationships with minor malocclusions such as crowding, rotations, or diastemas. Two investigators independently measured teeth on models with a Vernier gauge that had sharpened caliper tips. Intraexaminer and interexaminer reliability was determined at 0.2 mm. All teeth, to and including the first molars, were measured. Two photocopies of each set of models were made on a photostat machine (Xerox, Japan) and were coded. A template with a ruler was used, to allow the investigator to compensate for any reduction or enlargement error during the photocopying process. The mesiodistal sizes were measured with a digitizer, and results were processed by using a dedicated computer program. Evaluations were done in a double-blind manner. The nonparametric Wilcoxon signed rank test for paired observations to compare median differences between measurements was used. Intraexaminer digitized measurements were almost identical and differed (p < 0.0001) for only one measurement. However, interexaminer manual and digitized measurements differed significantly (p < 0.001) for 20 of the 24 teeth. Nineteen of these digitized tooth measurements were smaller. The mean arch length measurements differed by 4.7 mm (p < 0.0001) in the maxilla and by 3.1 mm (p < 0.0001) in the mandible. The difference between the manual and digitized analyses may be due to the photocopying process. The inability to accurately measure a three-dimensional study cast that has been duplicated in two dimensions, convex structure of teeth, curve of Spee, tooth inclination, and tooth position may play a role. The computer-aided measuring system is reliable, but accurate mesiodistal measurements cannot be made from photocopies of dental models. Manual measurements that use a calibrated gauge produce the most accurate, reliable, and reproducible results.

Mixed dentition space analyses form an essential part of orthodontic diagnostic procedures to determine the amount of space available for the accommodation of permanent teeth. The Moyers' probability tables for computing the sizes of unerupted canines and premolars were formulated at the University of Michigan from a sample consisting of northern European white subjects and are currently used worldwide. Because tooth sizes vary significantly between different population groups, it was the purpose of this study to construct relevant probability tables that would be more applicable to black subjects. Data were collected from a series of 100 randomly selected study models of black patients. The sample was equally subdivided by gender and all subjects had Angle Class I molar relationships with only minor malocclusions such as minor crowding, rotations, or diastemas. Two investigators independently measured the teeth on the study casts with a Vernier gauge that had sharpened calliper tips. Intraexaminer and interexaminer reliability was determined at 0.2 mm. All teeth to and including the first molars were measured. These data were then utilized in regression equations for both maxillary and mandibular arches, to enable the prediction of the mesiodistal widths of the canines and two premolars. The equations and predicted values were compared with those of the Moyers' probability tables, and significant differences (p <0.05) were found (except for the prediction of maxillary canines and premolars in females at the 85 and 95 percentile probability level). New probability tables for black subjects were formulated. It is envisaged that the proposed probability tables would be more accurate for black patients of African ancestry.

Objective: Since an increased use of several blood salvaging measures has contributed to a reduction in perioperative blood loss and the requirement for banked blood in recent years, the aim of this study was to establish current postoperative drainage losses in order to evaluate whether homologous retransfusion may be a useful measure to reduce autologous transfusion in elective cardiac surgery., Design/setting: This prospective clinical investigation was performed at a University Intensive Care Unit during the first six hours following cardiac surgery., Patients: 373 men and 127 women undergoing elective cardiac surgery were investigated., Measures: The amount of shed blood was measured four and six hours postoperatively., Results: The average blood loss was higher in men than in women both in all operations as a whole (men, four hours: 223+/-73 ml, six hours 270+/-95 ml; women, four hours: 156+/-25 ml, six hours 195+/-22 ml), in valve replacement (men, four hours: 299+/-87 ml, six hours 350+/-101 ml; women, four hours: 187+/-30 ml, six hours: 219+/-31 ml) and in coronary artery bypass grafting (men, four hours: 197+/-69 ml, six hours: 242+/-83 ml; women, four hours: 128+/-15 ml, six hours: 173+/-18 ml). A blood loss of 400 ml was exceeded in 13% of men after valve replacement four and six hours postoperatively. In all other groups, less than 8% of patients had a loss of more than 400 ml both after four and after six hours., Conclusions: Postoperative drainage losses in elective cardiac surgery patients are small and a measurable advantage from retransfusion seems to be unlikely. We therefore endorse the routine use of shed mediastinal blood retransfusion in these patients.

Both high energy transthoracic and direct epicardial defibrillation can result in RV and LV myocardial damage, but little is known about the damage due to defibrillation using an endocardial RV electrode. Furthermore, disturbances in postdefibrillation oxidative metabolism have been reported and may be caused by primary injury of mitochondrial integrity and function, but information about ultrastructural mitochondrial alterations is rare. We therefore studied, in 13 fox hounds, RV and LV ultrastructural alterations following multiple low energy endocardial countershocks. Using an ICD and an endocardial defibrillation system a median of 54 (43-74) countershocks with a cumulative energy of 1,558 J (844-2,141 J) was delivered. After termination of countershocks, RV and LV myocardium was examined by electron microscopy. In both ventricles, severe myocardial alterations were found, including swollen mitochondria, disruption of mitochondrial crests, and loss of integrity of the mitochondrial inner and outer membranes. At the first time a semiquantitative score, originally developed for postischemic injury, was successfully used to grade the postcountershock mitochondrial alteration, which showed a more pronounced damage in the RV (2.69 +/- 0.22 points) compared to the LV (2.18 +/- 0.22 P = 0.021). We conclude that even the use of endocardial lead systems with low energy countershocks may lead to severe mitochondrial damage, especially in the RV.

Background: Although a positive inotropic effect of hypertonic saline has been demonstrated in isolated cardiac tissue as well as in animal preparations, no information exists about a possible positive inotropic action of hypertonic saline in humans. The aim of this investigation was to determine whether a clinically relevant positive inotropic effect can be demonstrated in humans., Methods: Twenty-six patients without cardiovascular disease were randomized to receive 4 ml/kg of either 7.2% hypertonic saline/6% hetastarch or 6% hetastarch (control) at a rate of 1 ml.kg-1.min-1 while under general endotracheal anesthesia. Transesophageal echocardiography was used to evaluate left ventricular function. Arterial pressure, heart rate, and left ventricular end-systolic and end-diastolic diameter, area, and wall thickness were measured immediately before and after administration of either solution. Fractional area change, end-systolic wall stress, and the area under the end-systolic pressure-length relationship curve (ESPLRarea) were calculated. ESPLRarea was used to assess left ventricular contractility., Results: Administration of hypertonic saline/hetastarch resulted in a significant decrease of mean arterial pressure and end-systolic wall stress from 77 +/- 14 (mean +/- SD) to 64 +/- 17 mmHg (P < 0.01) and from 52 +/- 14 to 32 +/- 11 10(3) dyne/cm2 (P > 0.01), respectively. End-diastolic area and fractional area change increased from 16.5 +/- 2.9 to 21.7 +/- 3.3 cm2 (P < 0.01) and from 0.53 +/- 0.07 to 0.70 +/- 0.06 (P < 0.01), respectively, whereas there was only a minor change of ESPLRarea from 38 +/- 13 to 44 +/- 13 mmHg.cm (P < 0.05)., Conclusions: The apparent improvement of left ventricular systolic function in response to hypertonic saline/hetastarch is caused mainly by the combined effect of increased left ventricular preload and reduced left ventricular afterload. A possible positive inotropic action of hypertonic saline/hetastarch is not likely to be clinically relevant.

The pressure-time product (PTP) and work of breathing (W) were measured in 19 intubated patients during weaning from mechanical ventilation after aortocoronary bypass surgery. The patients were supported by two different ventilatory modes: biphasic continuous positive airway pressure (Biphasic CPAP; a ventilatory mode that permits spontaneous breathing at two different levels of airway pressure during inspiration and during expiration) and pressure-support ventilation (denominated as assisted spontaneous breathing, ASB). Our aim was to compare the energy cost of breathing imposed by both modes. The PTP was obtained by integrating the area enclosed by the esophageal and chest-wall static recoil pressure curves. The W performed by the patient (Wp) was calculated using Campbell's diagram method, based on the esophageal pressure curve and normalized per liter of ventilation. Two comparable support levels, corresponding to a high and a low degree of mechanical support, were studied for each ventilator mode. The levels of support were generally higher than that necessary to overcome inspiratory resistance. We found significantly higher PTP values during biphasic CPAP than during ASB (p < 0.01), whereas the Wp was the same with biphasic CPAP and ASB at both support levels. We conclude that because of the higher PTP values measured during biphasic CPAP, this mode of ventilation appears to have been more exhausting for our patients. The discrepancy between PTP and Wp is probably due to the different mechanisms of support given by the two ventilatory modes and the greater patient effort is related to those respiratory cycles that are not helped by the ventilator and which represent nearly half of the breaths during biphasic.

The effects of calcium gluconate on hemodynamics and saphenous vein graft flow in a group of patients undergoing elective coronary artery bypass grafting who developed ionized hypocalcemia at the end of the surgical procedure were examined. The patients received a central venous bolus of 15 mg/kg of calcium gluconate. Heart rate (HR), arterial pressure (AP), central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and cardiac output were measured immediately before and 30, 60, 120, 180, and 240 seconds after injection of calcium gluconate. Systemic and pulmonary vascular resistance (SVR and PVR, respectively), cardiac index (CI), stroke volume index (SVI), and right and left ventricular stroke work index (RVSWI and LVSWI, respectively), were calculated. Venous bypass flow velocity (Vbypass-flow) was assessed using a Doppler probe that was attached to the left anterior descending artery (LAD) bypass intraoperatively. Calcium gluconate significantly increased MAP, SVR, and LVSWI from 67 +/- 3 mmHg (mean +/- SEM), 1,128 +/- 128 dyne.s.cm-5 and 25 +/- 3 g.m.beat/m to a maximum of 81 +/- 5 mmHg (P < 0.01), 1,401 +/- 196 dyne.s.cm-5 (P < 0.05), and 32 +/- 4 g.m/beat/m (P < 0.01), respectively. HR, CVP, PAP, PCWP, PVR, CI, SVI, and Vbypass-flow remained unaltered. It is concluded that calcium gluconate administered to moderately hypocalcemic patients increases arterial pressure mainly by peripheral vasoconstriction. Because the increase of arterial pressure, and, thereby, coronary perfusion pressure is not associated with an increase of LAD bypass flow, vasoconstriction in the coronary vascular bed distal to the venous graft cannot be ruled out, and deterioration of the myocardial oxygen supply/demand ratio is strongly suggested.

In most ventilators used in anaesthesia tidal volume delivered during mechanical ventilation is different from the tidal volume preset at the respirator on the basis of respirator and circuit compliance and gas compression during inspiration. The error in ventilation due to the compressed volume is especially significant clinically when the tidal volume is very small or when the airway pressure is very high. In newborns and neonates in particular, decreasing lung compliance during a surgical procedure may contribute to marked hypoventilation. We therefore investigated ventilation in newborn piglets during decreasing lung compliance induced by tension pneumothorax. We used the anaesthesia ventilator CICERO (Dräger, Lübeck, Germany) and the SERVO 900 C ventilator (Siemens-Elema, Sweden). MATERIALS AND METHODS. Two anaesthesia ventilators, the CICERO (group I, n = 8) and the SERVO ventilators (group II, n = 8) were investigated following randomized selection in a group of 16 newborn piglets (Table 1). After normoventilation for 60 min a tension pneumothorax at +10 mbar was induced. After 15 min the pneumothorax was increased to +20 mbar and maintained at this level for the rest of the study. When hypercapnia (PaCO2 > 45 mmHg) resulted, the respiratory rate was increased by +10/min after 15 min with pneumothorax at +20 mbar. When hypercapnia continued, the respiratory rate was increased again 25 min and if necessary also 35 min after the induction of pneumothorax at +20 mbar. After normoventilation for 60 min (T1) (Table 2), after 15 min with pneumothorax at +10 mbar (T2) and after 15 min (T3), 25 min (T4), 35 min (T5) and 45 min (T6) with pneumothorax at +20 mbar the following parameters were obtained: central venous (CVP) and mean arterial pressure (MAP), heart rate (HR), arterial (PaCO2) and end-tidal CO2 tension (PetCO2), peak inspiratory pressure (PIP), respiratory frequency (RF) and expiratory tidal (Vtex) and minute volume (VE). RESULTS. In group I the pneumothorax resulted in a significantly smaller increase in PaCO2 (43.3 +/- 6.2 mmHg) than in group II (Fig. 1), and hypercapnia was present in only 3 piglets. Vtex (Fig. 2), VE (Fig. 3) and PIP (Fig. 5) increased significantly, with significantly higher values than in group II, while PetCO2 (Fig. 6) decreased significantly. In group II the pneumothorax was attributed to a significant increase in PaCO2 and a marked hypercapnia in all piglets (PaCO2 61.2 +/- 5.9 mmHg) (Fig. 1). Vtex (Fig. 2) and VE (Fig. 3) remained unchanged, while PIP (Fig. 5) and PetCO2 (Fig. 6) increased. Following the increase in RF (Fig. 4) in all piglets, Vtex and VE increased and PaCO2 and PetCO2 decreased. CONCLUSIONS. During ventilation of neonates with the SERVO ventilator a decrease in lung compliance will cause hypoventilation and hypercapnia. This reflected by an increase in peak inspiratory pressure and can be corrected by increasing the respiratory rate. In contrast, the CICERO is able to preserve ventilation by an internal correction for gas compression, but it does not guarantee normoventilation in all cases. In neither group does the end-tidal PCO2 reflect the true ventilation during decreasing lung compliance, so that arterial blood gas analysis seems to be mandatory for the diagnosis of hypercapnia in such situations.

Background: Left ventricular diastolic function is known to be impaired in patients with coronary artery disease and patients with valvular aortic stenosis. Phenylephrine is frequently administered as an intravenous bolus in these patients perioperatively to increase coronary perfusion pressure. Although this is common practice, there is no information about the effect of phenylephrine bolus administration on left ventricular filling dynamics., Methods: Twenty patients with coronary artery disease (group 1), 15 patients with valvular aortic stenosis (group 2), and 10 subjects without cardiovascular disease (group 3, control) entered the study. Left ventricular filling was evaluated using transesophageal pulsed Doppler echocardiography before and after phenylephrine injection given to patients whose mean blood pressure has decreased by more than 20% (and was not higher than 90 mmHg). We recorded the transmitral blood flow velocity curve and measured peak early and peak atrial flow velocity, acceleration and deceleration time of the early flow velocity peak, and mitral valve diameter. We calculated the ratio of peak early to peak atrial flow velocity (PE/PA), acceleration and deceleration rate of the early flow peak, and peak filling rate., Results: Phenylephrine effectively restored arterial pressure in all three groups. However, in group 1, phenylephrine administration resulted in a reduction of PE/PA, acceleration rate of the early flow peak, and peak filling rate from 1.25 (mean) to 0.75 (P < 0.001), 411 to 276 cm/s2 (P < 0.001), and 439 to 305 ml/s (P < 0.001), respectively. In contrast, in group 2, intravenous phenylephrine increased PE/PA, acceleration rate of the early flow peak, and peak filling rate from 0.76 to 0.97 (P < 0.001), 365 to 503 cm/s2 (P < 0.05), and 321 to 388 ml/s (P < 0.01), respectively. In the control subjects, phenylephrine caused a transient reduction of PE/PA and peak filling rate from 1.71 to 1.39 (P < 0.001) and 618 to 524 ml.s-1 (P < 0.001), respectively., Conclusions: Phenylephrine bolus administration causes an alteration of left ventricular filling in coronary artery disease patients that seems to be more marked than that seen in normal subjects. In patients with aortic stenosis no deleterious effects were observed in response to phenylephrine.

The purpose of this investigation was to determine right ventricular function during weaning from controlled ventilation comparing a biphasic positive airway pressure ventilatory support system (BiPAP [Respironics]) with pressure support ventilation (PSV). In 22 patients following coronary artery bypass grafting, both weaning techniques were used in randomized chronological order for 60 min each. Right ventricular end-systolic (RVESV) and end-diastolic volume (RVEDV) and ejection fraction (RVEF) were evaluated using the fast-response Swan-Ganz catheter. In comparison to PSV, the BiPAP system resulted in a significantly higher mean pulmonary artery pressure (20.6 +/- 5.0 vs 19.3 +/- 4.2 mm Hg, p = 0.0158), pulmonary vascular resistance index (206 +/- 55 vs 181 +/- 61 dyn.s.cm-5.m2, p = 0.0355), RVESV (92.2 +/- 36.3 vs 77.2 +/- 30.4 ml, p = 0.0017), and RVEDV (176.4 +/- 48.5 vs 161.8 +/- 43.3 ml, p = 0.0061), while the RVEF was significantly lower (46.0 +/- 11.9 vs 51.8 +/- 12.4 percent, p = 0.0012). No differences in left ventricular function or arterial blood gas analyses were measured during both study periods. In summary, the RV afterload was higher with the BiPAP system compared with PSV which suggested that this was due to differences in the respiratory support between both weaning modes. Because of the Frank-Starling mechanism, this higher afterload did cause a small but significant increase in RV volumes and a significant decrease in RV ejection fraction with the BiPAP system.

Background: Although phenylephrine bolus administration is frequently used to increase coronary perfusion pressure in patients with coronary artery disease or valvular aortic stenosis, there are no data describing its effect on left ventricular function (LVF)., Methods: Twenty patients scheduled for elective coronary artery bypass grafting (group 1) and 18 patients scheduled for elective aortic valve replacement (group 2) entered the study. The effect of phenylephrine was compared with that of norepinephrine in those patients who developed a defined degree of arterial hypotension under general anesthesia. These patients were randomized to receive an initial bolus of either phenylephrine (1 micrograms/kg) or norepinephrine (0.05 micrograms/kg) followed by a bolus of the other drug after arterial pressure and heart rate (HR) had returned to baseline. Transesophageal echocardiography was used to evaluate LVF. Arterial pressure, HR, ejection time, and LV diameter, area, and wall thickness were recorded immediately before and for 3 min after bolus administration. Fractional diameter shortening, fractional area change, mean heart rate corrected velocity of circumferential fiber shortening (mVcfc), and LV meridional end-systolic wall stress (ESWS) were calculated., Results: Both substances effectively restored arterial pressure in both groups. However, in group 1, phenylephrine administration resulted in a reduction of fractional area change from 0.51 (median) to 0.39 (P = 0.0007) and a reduction of mVcfc from 1.16 to 0.61 circ/s (P = 0.0001). End-systolic wall stress increased from 98 to 186 10(3) dyne-cm-2 (P = 0.0001). Administration of norepinephrine to group 1 and administration of either substance to the group 2 patients did not cause any significant changes of LVF., Conclusions: The results indicate that phenylephrine given as an intravenous bolus to patients with CAD anesthetized with fentanyl causes a transient impairment of LV global function and that phenylephrine bolus administration is well tolerated in patients with valvular aortic stenosis.

In many anaesthesia ventilators in common use, the tidal volume delivered is different from the tidal volume preset on the respirator. Tidal volume delivered by mechanical ventilation during anaesthesia may be influenced by fresh gas flow (FGF), the respiratory rate (RR) or the inspiratory: expiratory ratio (I:E). This may cause inadequate hypo- or hyperventilation in small children, especially in newborns and neonates. Using small tidal volumes from 20 to 100 ml preset on the respirator, we investigated in a lung model the tidal volumes delivered by the anaesthesia ventilator CICERO (Dräger, FRG) with variations of FGF, RR and I:E. MATERIAL AND METHODS. The anaesthesia ventilator CICERO (software version 4.16) was equipped with the low-compliance tubes of the "Ulmer Kinder-Set" (Rüsch Co.) and the regular CO2 canister (1500 ml) of the machine. The circuit was connected to a lung model consisting of a glass clyinder filled with copper wool with a compliance of 3.3 ml/mbar. To create a pressure-volume correlation of the entire system, i.e. the lung model, the anaesthesia circuit and the ventilator, calibrated glass syringes were used and the pressure increase in the test lung was measured. This pressure-volume correlation was linear. The pressure increase in the lung model caused by the tidal volume during ventilation therefore reflected the actual tidal volume delivered. The study was performed with small tidal volumes from 20 to 100 ml that could be adjusted exactly on the ventilator. Delivered tidal volumes were studied by varying the FGF from 1 to 6 l/min and the RR from 20 to 60/min (with I:E = 1:1.5) and by varying the RR from 20 to 60/min and the I:E from 2:1 to 1:3 (with FGF = 21/min). RESULTS. By varying FGF, RR and I:E no changes in delivered tidal volumes were noted. In all settings of the ventilator studied, the delivered tidal volume was similar to the desired tidal volume preset on the ventilator. The highest deviation from the delivered tidal volume to the tidal volume preset was 17.5% with a tidal volume of 20 ml. In preset tidal volumes 30-100 ml this deviation was lower than 10%. An intermittent "auto-PEEP" up to 5 mbar was noted during high respiratory rates (50 and 60/min) combined with an I:E at 2:1 and 1:1 or with a FGF at 4 or 6 l/min. The compliance of the ventilator equipped with the circuit was 4.2 ml/mbar. CONCLUSION. The findings in this study prove that with tidal volumes ranging from 20 to 100 ml the actual tidal volume delivered by the anaesthesia ventilator CICERO is equivalent to the tidal volume set on the machine regardless of the variation of FGF, RR and I:E. These findings are mainly based on two circumstances. Firstly, fresh gas flow is fed into a reservoir and not added to the volume delivered by the bellow during inspiration as in many other respirators. Secondly, the CICERO works with a compliance correction function integrated into the machine. Computed compressible volume from the circuit and the ventilator is added to the tidal volume preset on the ventilator; therefore, the volume delivered by the bellow consists of the volume set on the ventilator plus the compressible volume. With these characteristics the anaesthesia ventilator CICERO meets important requirements for a ventilator in paediatric anaesthesia. However, for final assessment further clinical studies are required.

Noncardiac pulmonary edema can occur not only after cardiac surgery with cardiopulmonary bypass but also after noncardiac operations. This so-called transfusion-related acute lung injury (TRALI) has been attributed to the transfusion of homologous blood and plasma. In the presence of normal left ventricular function an acute increase in pulmonary capillary permeability leads to massive protein-rich pulmonary edema, reduced pulmonary function, and intravascular hypovolemia. This may be caused by leukocyte antibodies. Signs and diagnostic and therapeutic procedures are discussed with reference to a case report.

No anesthesia ventilator attached to a circle system is manufactured for use in neonates. However, a small bellows can be supplied for the following anesthesia ventilators: Spiromat NS 656 (NS), Ventilog 2 (V2) and AV1 (Draeger Co.) We investigated the minimal tidal volume delivered by each of the three ventilators. In addition, we tested the performance of the AV1 in neonatal piglets for manual and controlled ventilation, and in decreased lung compliance. MATERIALS AND METHODS. All circuits were equipped with one CO2 canister (750 ml) and the low-compliance tubes of the "Ulmer Kinder Set" (Ruesch Co.) The circuits were connected to a lung model consisting of a glass cylinder filled with copper wool with a compliance of 3.0 ml/mbar. By using calibrated glass syringes we created a pressure-volume correlation for the entire system, i.e., the lung model, the anesthesia circuit and the ventilator, which was linear for each of the three ventilators. The pressure was measured in the test lung. The pressure increase caused by the tidal volume therefore reflected the actual tidal volume delivered, which was calculated using the pressure-volume correlation. Tidal volumes were determined for varying the fresh gas flow (FGF), the respiratory rate (RR), which was varied between 20 and 60/min and the I:E ratio (IE), which was varied between 1:1 and 1:2. Six newborn piglets aged 2-12 h and with body weight 1000-1300 g were anesthetized, tracheotomized and ventilated with an oxygen-nitrous oxide mixture (FIO2 0.25). The manual ventilation lasted 30 min (period 1) and was followed by mechanical ventilation for 60 min (period 2). Thereafter, a left pneumothorax with constant pressure of 20 mbar and then 40 mbar for 15 min each was created (period 3). A fall in blood pressure was treated with 10 ml colloids in five of the six animals. During the experiment arterial blood pressure in the carotid artery, mean airway pressure at the distal end of the tracheal tube and end-tidal CO2 were continuously recorded. Arterial blood gases were analyzed at the end of each period. RESULTS. The tidal volumes delivered with an identical position of the bellows varied in ventilators NS and V2 with changes in FGF, RR and IE. Decrease in FGF, higher RR and longer expiration resulted in a decrease in the tidal volume. The "smallest" tidal volume delivered by NS varied from 50 ml (FGF 2 l/min, RR 60, IE 1:2) to 188 ml (FGF 4 l/min, RR 20, IE 1:1) and from 11 ml (FGF 2 l/min, RR 60, IE 1:2) to 110 (FGF 4 l/min, RR 20, IE 1:1) in the V2. The AV1 showed a minimal tidal volume of about 5 ml, and no changes in tidal volume attributable to alterations in FGF, RR or IE could be observed. No problems occurred during manual or mechanical ventilation in the piglets. With the experimental decrease in lung compliance no increase in airway pressure was noted, but an increase in arterial pCO2 by 8 mmHg (mean) reflects hypoventilation that was not corrected by the ventilator. DISCUSSION. We believe that the changes in tidal volume in ventilators NS and V2 are caused by adding FGF to the volume delivered by the below during inspiration. Because of the unpredictability of the tidal volumes, these ventilators are not suitable for the use in neonates. The AV1 has a very low systemic compliance which makes it suitable for use in neonatal anesthesia. However, a decrease in lung compliance is not compensated by an increase in airway pressure and leads to hypoventilation. When small tidal volumes are used in patients with low lung compliance, it does not act as expected of a volume-cycled ventilator.

We describe a transport concept ensuring unlimited continuation of cardiocirculatory monitoring, drug therapy and artificial ventilation during transfer of critically ill patients within the hospital. The basis of this concept is a mobile transport unit which can be hooked to the patient's bed, containing a power pack for the monitor, respirator or other devices dependent on power supply. The concept probably improves safety of patients not only during postoperative transfer of the ICU but enables also the safe transfer of critically ill patients from the ICU to diagnostic or therapeutic procedures.