Dynamic parameters of fluid responsiveness in the operating room : An analysis of intraoperative ventilation framework conditions.

BACKGROUND: Reliable assessment of fluid responsiveness with pulse pressure variation (PPV) depends on certain ventilation-related preconditions; however, some of these requirements are in contrast with recommendations for protective ventilation. OBJECTIVE: The aim of this study was to evaluate the applicability of PPV in patients undergoing non-cardiac surgery by retrospectively analyzing intraoperative ventilation data. MATERIAL AND METHODS: Intraoperative ventilation data from three large medical centers in Germany and Switzerland from January to December 2018 were extracted from electronic patient records and pseudonymized; 10,334 complete data sets were analyzed with respect to the ventilation parameters set as well as demographic and medical data. RESULTS: In 6.3% of the 3398 included anesthesia records, patients were ventilated with mean tidal volumes (mTV) > 8 ml/kg predicted body weight (PBW). These would qualify for PPV-based hemodynamic assessment, but the majority were ventilated with lower mTVs. In patients who underwent abdominal surgery (75.5% of analyzed cases), mTVs > 8 ml/kg PBW were used in 5.5% of cases, which did not differ between laparoscopic (44.9%) and open (55.1%) approaches. Other obstacles to the use of PPV, such as elevated positive end-expiratory pressure (PEEP) or increased respiratory rate, were also identified. Of all the cases 6.0% were ventilated with a mTV of > 8 ml/kg PBW and a PEEP of 5-10 cmH2O and 0.3% were ventilated with a mTV > 8 ml/kg PBW and a PEEP of > 10 cmH2O. CONCLUSION: The data suggest that only few patients meet the currently defined TV (of > 8 ml/kg PBW) for assessment of fluid responsiveness using PPV during surgery.

International survey of neurosurgical anesthesia (iSonata) : An international survey of current practices in neurosurgical anesthesia.

BACKGROUND: No standardized recommendations have been currently defined for anesthesia management of patients undergoing elective intracranial surgery. It can therefore be assumed that international clinical institutions have diverging approaches or standard operating procedures (SOP) which determine the type of general anesthesia, hemodynamic management, neuromuscular blockade, implementation of hypothermia and postoperative patient care. OBJECTIVE: This international survey aimed to assess perioperative patient management during elective intracranial procedures. This survey was performed from February to October 2018 and 311 neurosurgical, maximum care centers across 19 European countries were contacted. The aim was to evaluate the anesthesia management to provide relevant data of neuroanesthesia practices across European centers. The survey differentiated between vascular and non-vascular as well as supratentorial and infratentorial procedures. RESULTS: A total of 109 (35.0%) completed questionnaires from 15 European countries were analyzed. The results illustrated that total intravenous anesthesia was most commonly implemented during elective intracranial procedures (83.8%). All centers performed endotracheal intubation prior to major intracranial surgery (100%). Central venous lines were placed in 63.3% of cases. Moderate intraoperative hypothermia was carried out in 12.8% of the procedures, especially during vascular supratentorial and infratentorial surgery. A neuromuscular blockade during surgery was implemented in 74.1% of patients. Assessment of the neuromuscular junction was performed in 59.2% of cases, 76.7% of patients were immediately extubated in the operating room. 84.7% of these patients were directly transferred to a monitoring ward or an intensive care unit (ICU) and 55.1% of ventilated patients were transferred directly to an ICU. CONCLUSION: The data demonstrate that many aspects of anesthesia management during elective intracranial surgery vary between European institutions. The data also suggest that a broad consensus exists regarding the implementation of total intravenous anesthesia, airway management (endotracheal intubation), the implementation of urinary catheters, large bore peripheral venous lines and the broad availability of cross-matched red blood cell concentrates. Nevertheless, anesthesia management (e.g. central venous catheterization, moderate hypothermia, neuromuscular monitoring) is still handled differently across many European institutions. A lack of standardized guidelines defining anesthetic management in patients undergoing intracranial procedures could explain this variability. Further studies could help establish optimal anesthesia management for these patients. This in turn could help in the development of national and international guidelines and SOPs which could define optimal management strategies for intracranial procedures.

Comparison of blood pressure monitoring by applanation tonometry and invasively assessed blood pressure in cardiological patients.

The aim of this study was to evaluate the accuracy and precision of non-invasive continuous blood pressure measurement by applanation tonometry (AT) in awake or anaesthetised cardiological intensive care patients. Patients suffering from highly impaired left ventricular function atrial fibrillation or severe aortic valve stenosis were included into the study. Arterial blood pressure was recorded by applanation tonometry (T-Line 400, Tensys Medical®, USA) and an arterial line in awake or anaesthetised patients. Discrepancies in mean (MAP), systolic (SAP), and diastolic (DAP) arterial pressure between the two methods were assessed as bias, limits of agreement and percentage error respectively. In 31 patients a total of 27,900 measurements were analyzed. The concordance correlation coefficient was 0.23, 0.45 and 0.06 for MAP, SAP and DAP, respectively. For all patients bias for MAPAT compared to MAPAL was 14.96 mmHg (SAPAT 4.51 mmHg; DAPAT 19.12 mmHg) with limits of agreement for MAPAT of 46.25 and - 16.33 mm Hg (SAPAT 48.00 and - 38.98 mmHg; DAPAT 50.12 and - 11.89 mmHg). Percentage error for MAPAT was 56.8% (42.7% for SAPAT; 75.2% for DAPAT). We conclude that the AT method is not reliable in ICU patients with severe cardiac comorbidities.

Is applanation tonometry a reliable method for monitoring blood pressure in morbidly obese patients undergoing bariatric surgery?

BACKGROUND: The aim of this study was to evaluate the validity of non-invasive continuous BP measurement by applanation tonometry in morbidly obese patients undergoing bariatric surgery. METHODS: Arterial blood pressure (AP) was recorded intraoperatively both by applanation tonometry (AT) (T-Line 200pro, Tensys Medical(®), USA) and an arterial line (AL) after radial cannulation in obese patients undergoing bariatric surgery. Discrepancies between the two methods were assessed as bias, limits of agreement and percentage error. Mean, systolic, and diastolic arterial pressures were assessed (MAP, SAP, DAP respectively). Trending ability was assessed by concordance based on four-quadrant plotting. RESULTS: Mean (sd) BMI of the 28 patients was 49.4 (9.7 kg m(-2)). A total of 201 907 time points were available for analysis. Bias for MAPAT compared with MAPAL was +3.97 mm Hg (SAPAT +3.45 mm Hg; DAPAT +3.66 mm Hg) with limits of agreement for MAPAT of -14.47 and +22.41 mm Hg (SAPAT -22.0 and +28.9 mm Hg; DAPAT -15.7 and +23.1 mm Hg). Percentage error for MAPAT was 23.5% (23.4% for SAPAT; 30.5% for DAPAT). Trending ability for MAP, SAP, and DAP revealed a concordance of 0.74, 0.72, and 0.71, respectively. CONCLUSIONS: Continuous BP assessment by applanation tonometry is feasible in morbidly obese patients undergoing bariatric surgery. However, despite a low mean difference, 95% limits of agreement and trending ability indicate that the technology needs to be improved further, before being recommended for routine use in this group of patients.

New insights into Brunner syndrome and potential for targeted therapy.

We report two families with Brunner syndrome living in one state of Australia. The first family had a predicted protein-truncating variant of monoamine oxidase A (MAOA) (p.S251KfsX2). Affected males had mild intellectual disability (ID), obsessive behaviour, limited friendships and were introverted and placid during clinical interview. The family disclosed episodic explosive aggression after a diagnosis was made. The second family had a missense variant in MAOA (p.R45W). Affected males had borderline-mild ID, attention deficit disorder and limited friendships. One had a history of explosive aggression in childhood and episodic symptoms of flushing, headaches and diarrhoea. Their carrier mother had normal intelligence but similar episodic symptoms. Characteristic biochemical abnormalities included high serum serotonin and urinary metanephrines and low urinary 5-hydroxyindoleacetic acid (5-HIAA) and vanillylmandelic acid (VMA). Symptomatic individuals in the second family had particularly high serotonin levels, and treatment with a serotonin reuptake inhibitor and dietary modification resulted in reversal of biochemical abnormalities, reduction of 'serotonergic' symptoms and behavioural improvement. Brunner syndrome should be considered as a cause of mild ID with paroxysmal behavioural symptoms. It can be screened for with serum/urine metanephrine and serotonin measurement. Cautious treatment with a serotonin reuptake inhibitor, dietary modifications and avoidance of medications contraindicated in patients on monoamine oxidase inhibitors can improve symptoms.

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.

[Goal-directed hemodynamic therapy: Concepts, indications and risks]. / Zielorientierte Volumen- und Kreislauftherapie : Konzepte, Indikationen und Risiken.

Goal-directed hemodynamic therapy is becoming increasingly more interesting for anesthesiologists and intensive care physicians. Meta-analyses of studies evaluating perioperative therapy algorithms demonstrated a reduction of postoperative morbidity compared to the previous clinical practices. In this review article the basic concepts of goal-directed hemodynamic therapy and the principles of previously employed therapy algorithms are described and discussed. Furthermore, the questions of how these therapy strategies can be transferred into daily clinical practice and whether these therapeutic approaches might even bear risks for patients are elucidated.

Comparison of an automated respiratory systolic variation test with dynamic preload indicators to predict fluid responsiveness after major surgery.

BACKGROUND: Predicting the response of cardiac output to volume administration remains an ongoing clinical challenge. The objective of our study was to compare the ability to predict volume responsiveness of various functional measures of cardiac preload. These included pulse pressure variation (PPV), stroke volume variation (SVV), and the recently launched automated respiratory systolic variation test (RSVT) in patients after major surgery. METHODS: In this prospective study, 24 mechanically ventilated patients after major surgery were enrolled. Three consecutive volume loading steps consisting of 300 ml 6% hydroxyethylstarch 130/0.4 were performed and cardiac index (CI) was assessed by transpulmonary thermodilution. Volume responsiveness was considered as positive if CI increased by >10%. RESULTS: In total 72 volume loading steps were analysed, of which 41 showed a positive volume response. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.70 for PPV, 0.72 for SVV and 0.77 for RSVT. Areas under the curves of all variables did not differ significantly from each other (P>0.05). Suggested cut-off values were 9.9% for SVV, 10.1% for PPV, and 19.7° for RSVT as calculated by the Youden Index. CONCLUSION: In predicting fluid responsiveness the new automated RSVT appears to be as accurate as established dynamic indicators of preload PPV and SVV in patients after major surgery. The automated RSVT is clinically easy to use and may be useful in guiding fluid therapy in ventilated patients.

Changes in sevoflurane plasma concentration with delivery through the oxygenator during on-pump cardiac surgery.

BACKGROUND: It is unclear what factors affect the uptake of sevoflurane administered through the membrane oxygenator during cardiopulmonary bypass (CPB) and whether this can be monitored via the oxygenator exhaust gas. METHODS: Stable delivery of sevoflurane was administered to 30 elective cardiac surgery patients at 1.8 vol% (inspiratory) via the anaesthetic circuit and ventilator. During CPB, sevoflurane was administered in the oxygenator fresh gas supply (Compactflo Evolution™; Sorin Group, Milano, Italy). Sevoflurane plasma concentration (SPC) was measured using gas chromatography. Changes were correlated with bispectral index (BIS), patient temperature, haematocrit, plasma albumin concentration, oxygenator fresh gas flow, and the sevoflurane concentration in the oxygenator exhaust at predefined time points. RESULTS: The mean SPC pre-bypass was 54.9 µg ml(-1) [95% confidence interval (CI): 50.6-59.1]. SPC decreased to 43.2 µg ml(-1) (95% CI: 40.3-46.1; P<0.001) after initiation of CPB, and was lower still during rewarming and weaning from bypass, 39.4 µg ml(-1) (95% CI: 36.6-42.3; P<0.001). BIS did not exceed a value of 55. SPCs were higher during hypothermia (P<0.001) and with an increase in oxygenator fresh gas flow (P=0.015), and lower with haemodilution (P=0.027). No correlation was found between SPC and the concentration of sevoflurane in the oxygenator exhaust gas (r=-0.04; 95% CI: -0.18 to 0.09; P=0.53). CONCLUSIONS: The uptake of sevoflurane delivered via the membrane oxygenator during CPB seems to be affected by hypothermia, haemodilution, and changes in the oxygenator fresh gas supply flow. Measuring the concentration of sevoflurane in the exhaust from the oxygenator is not useful for monitoring sevoflurane administration during bypass.

Genome wide identification and classification of alternative splicing based on EST data.

MOTIVATION: Alternative splicing is currently seen to explain the vast disparity between the number of predicted genes in the human genome and the highly diverse proteome. The mapping of expressed sequences tag (EST) consensus sequences derived from the GeneNest database onto the genome provides an efficient way of predicting exon-intron boundaries, gene structure and alternative splicing events. However, the alternative splicing events are obscured by a large number of putatively artificial exon boundaries arising due to genomic contamination or alignment errors. The current work describes a methodology to associate quality values to the predicted exon-intron boundaries. High quality exon-intron boundaries are used to predict constitutive and alternative splicing ranked by confidence values, aiming to facilitate large-scale analysis of alternative splicing and splicing in general. RESULTS: Applying the current methodology, constitutive splicing is observed in 33,270 EST clusters, out of which 45% are alternatively spliced. The classification derived from the computed confidence values for 17 of these splice events frequently correlate (15/17) with RT-PCR experiments performed for 40 different tissue samples. As an application of the confidence measure, an evaluation of distribution of alternative splicing revealed that majority of variants correspond to the coding regions of the genes. However, still a significant fraction maps to non-coding regions, thereby indicating a functional relevance of alternative splicing in untranslated regions. AVAILABILITY: The predicted alternative splice variants are visualized in the SpliceNest database at http://splicenest.molgen.mpg.de

An integrated gene annotation and transcriptional profiling approach towards the full gene content of the Drosophila genome.

BACKGROUND: While the genome sequences for a variety of organisms are now available, the precise number of the genes encoded is still a matter of debate. For the human genome several stringent annotation approaches have resulted in the same number of potential genes, but a careful comparison revealed only limited overlap. This indicates that only the combination of different computational prediction methods and experimental evaluation of such in silico data will provide more complete genome annotations. In order to get a more complete gene content of the Drosophila melanogaster genome, we based our new D. melanogaster whole-transcriptome microarray, the Heidelberg FlyArray, on the combination of the Berkeley Drosophila Genome Project (BDGP) annotation and a novel ab initio gene prediction of lower stringency using the Fgenesh software. RESULTS: Here we provide evidence for the transcription of approximately 2,600 additional genes predicted by Fgenesh. Validation of the developmental profiling data by RT-PCR and in situ hybridization indicates a lower limit of 2,000 novel annotations, thus substantially raising the number of genes that make a fly. CONCLUSIONS: The successful design and application of this novel Drosophila microarray on the basis of our integrated in silico/wet biology approach confirms our expectation that in silico approaches alone will always tend to be incomplete. The identification of at least 2,000 novel genes highlights the importance of gathering experimental evidence to discover all genes within a genome. Moreover, as such an approach is independent of homology criteria, it will allow the discovery of novel genes unrelated to known protein families or those that have not been strictly conserved between species.

The role of the nurse manager in ambulatory care: results of a national survey.

Increasing complexity in ambulatory care settings requires nurse managers who can function at higher levels. Little agreement currently exists regarding the role expectations and academic preparation needed for nurse managers in ambulatory care settings. The majority of surveyed ambulatory care nurse managers (40%) have an AD or diploma as their highest level of academic preparation, and have thus acquired the majority of their management skills in the practice setting. The authors express concern that there are pressures to employ non-nurses as managers in ambulatory health care settings and that ambulatory nurse managers are often seen as not needing advanced academic preparation. A wide variety of settings including university and community hospitals, outpatient departments, physician group practices and HMOs, currently employ nurse managers in their multidisciplinary ambulatory care sites. The majority of ambulatory care nurse managers describe their model of care as either the medical model or the functional model.

Dimensions of the staff nurse role in ambulatory care: Part IV--Developing nursing intensity measures, standards, clinical ladders, and QI programs.

Ambulatory care nurse executives must design valid mechanisms to support new models of nursing care delivery. Data from a national survey of practicing ambulatory care nurses can assist in this process. Research data can be used as a resource for developing ambulatory nursing intensity measures, standards, clinical ladders, and quality improvement programming. This is Part IV of a four-part series.

Dimensions of the staff nurse role in ambulatory care: Part III--Using research data to design new models of nursing care delivery.

A national survey of 606 practicing staff nurses provides the basis for a data set that delineates the desired future role for nurses in ambulatory care. The core dimensions of future practice can be used to develop new models of ambulatory nursing care delivery, such as primary prevention, primary health care, and primary nursing as well as a case management and paired-partners model. The final part in this series, which will be published in the September/October issue, will examine the development of nursing intensity measures, standards, clinical ladders, and quality improvement programs.

Dimensions of the staff nurse role in ambulatory care: Part II--Comparison of role dimensions in four ambulatory settings.

Ambulatory care nursing is one of the fastest growing and least studied areas of nursing practice. Information from a national survey of ambulatory nurses has been used to delineate the core dimensions of the current staff nurse role. Comparison of practice patterns of ambulatory staff nurses employed in university hospitals, community hospitals, physician group practices, and health maintenance organizations can provide insights for nurse managers interested in improving ambulatory nursing care delivery. Part III of this series, which will be published in the July/August 1995 issue, will examine how to use research data to design new models of nursing care delivery.

Dimensions of the staff nurse role in ambulatory care: Part I--Methodology and analysis of data on current staff nurse practice.

Defining the core dimensions of the current staff nurse role is a critical first step in demonstrating the worth of professional nurses in ambulatory settings. Data generated by a 1992 national survey of 606 ambulatory staff nurses provides insight into current practice. Managers may use this information to attract and retain staff nurses, remove barriers to clinical practice, and modify practice patterns to improve the quality of care in ambulatory settings. Part II of this series, which will be published in the May/June 1995 issue, will examine the scope and dimensions of the staff nurse role in different practice settings.

Supporting nursing research. A representative program.

As nurses gain more experience, they often question the basis of nursing practice and want to find answers through clinical nursing research. Completion of a research project, however, often is difficult because of staffing constraints. The authors describe the design and conception of two funded programs that support clinical nursing research in a pediatric tertiary hospital.