Asymmetric dimethylarginine predicts perioperative cardiovascular complications in patients undergoing medium-to-high risk non-cardiac surgery.

OBJECTIVES: Perioperative cardiovascular events remain an important factor that affects surgery outcome. We assessed if asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, predicts perioperative risk, and if pre-operative supplementation with L-arginine/L-citrulline improves the plasma L-arginine/ADMA ratio. METHODS: In this prospective study, planned thoracic and/or abdominal surgery patients were randomized to receive L-arginine/L-citrulline (5 g/day) or placebo 1 to 5 days before surgery. We measured perioperative plasma ADMA and L-arginine levels. The primary outcome was a 30-day combined cardiovascular endpoint. RESULTS: Among 269 patients, 23 (8.6%) experienced a major adverse cardiovascular event. ADMA and C-reactive protein were significantly associated with the incidence of cardiovascular complications in the multivariable-adjusted analysis. The L-arginine plasma concentration was significantly higher on the day of surgery with L-arginine/L-citrulline supplementation compared with placebo. In patients with high pre-operative ADMA, there was a non-significant trend towards reduced incidence of the primary endpoint with L-arginine/L-citrulline supplementation (six vs. nine events). CONCLUSIONS: ADMA is a predictor of major adverse cardiovascular complications in the perioperative period for patients who are undergoing major abdominal and/or thoracic surgery. Supplementation with L-arginine/L-citrulline increased the L-arginine plasma concentration, enhanced the L-arginine/ADMA ratio, and induced a trend towards fewer perioperative events.

Analysis of purine receptor expression and functionality in alveolar epithelial cells.

Despite its fundamental role in providing an extensive surface for gas exchange, the alveolar epithelium (AE) serves as an immunological barrier through, e.g., the release of proinflammatory cytokines and secretion of surfactant to prevent alveolar collapse. Thus, AE is important for sustaining lung homeostasis. Extracellular ATP secreted by alveolar epithelial cells (AECs) is involved in physiological and pathological conditions and acts mainly through the activation of purine receptors (P2Rs). When studying P2R-mediated processes, primary isolated type II AECs (piAECs) still represent the gold standard in in vitro research, although their preparation is time-consuming and requires the sacrifice of many animals. Hence, cultivated immortalized and tumor-derived AEC lines may constitute a valuable alternative. In this work, we examined P2R expression and functionality in piAECs, in immortalized and tumor-derived AEC lines with the purpose of gaining a better understanding of purinergic signaling in different cell systems and assisting researchers in the choice of a suitable cell line with a certain P2R in demand. We combined mRNA and protein analysis to evaluate the expression of P2R. For pharmacological testing, we conducted calcium ([Ca2+]) measurements and siRNA receptor knockdown. Interestingly, the mRNA and protein levels of P2Y2, P2Y6, and P2X4 were detected on all cell lines. Concerning functionality, P2XR could be narrowed to L2 and piAECs while P2YR were active in all cell lines.

Improvement of perioperative care of the elderly patient (PeriAge): protocol of a controlled interventional feasibility study.

INTRODUCTION: Geriatric patients have a pronounced risk to suffer from postoperative complications. While effective risk-specific perioperative measures have been studied in controlled experimental settings, they are rarely found in routine healthcare. This study aims (1) to implement a multicomponent preoperative and intraoperative intervention, and investigate its feasibility, and (2) exploratorily assess the effectiveness of the intervention in routine healthcare. METHODS AND ANALYSIS: Feasibility and exploratory effectiveness of the intervention will be investigated in a monocentric, prospective, non-randomised, controlled trial. The intervention includes systematic information for patients and family about measures to prevent postoperative complications; preoperative screening for frailty, malnutrition, strength and mobility with nutrient supplementation and physical exercise (prehabilitation) as needed. Further components focus on potentially inadequate medication, patient blood-management and carbohydrate loading prior to surgery, retainment of orientation aids in the operating room and a geriatric anaesthesia concept. Data will successively be collected from control, implementation and intervention groups. Patients aged 65+ with impending surgery will be included. A sample size of 240, n=80 per group, is planned. Assessments will take place at inclusion and 2, 30 and 180 days after surgery. Mixed-methods analyses will be performed. Exploratory effectiveness will be assessed using mixed segmented regressions. The primary endpoint is functional status. Secondary endpoints include cognitive performance, health-related quality of life, length of inpatient stay and occurrence of postoperative complications. Feasibility will be assessed through semi-structured interviews with staff and patients and quantitative analyses of the data quality, focussing on practicability, acceptance, adoption and fidelity to protocol. ETHICS AND DISSEMINATION: The study will be carried out in accordance with the Helsinki Declaration and to principles of good scientific practice. The Ethics Committee of the Medical Association Hamburg, Germany, approved the protocol (study ID: PV5596). Results will be disseminated in scientific journals and healthcare conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03325413.

Patient safety in undergraduate medical education: Implementation of the topic in the anaesthesiology core curriculum at the University Medical Center Hamburg-Eppendorf.

Introduction: The focus of public attention and health policy is increasingly being drawn to patient safety. According to studies, more than 30,000 patients die each year as a result of medical errors. To date, learning objectives such as patient safety have not played a role in the core curriculum for medical education in Germany. The National Competence-Based Catalogue of Learning Objectives for Undergraduate Medical Education contains a total of 13 learning objectives relating to this subject. Methods: In a descriptive study, learning content was implemented within the "Operative Medicine" study block offered by the Faculty of Medicine at Universität Hamburg. The definition and occurrence of errors as well as strategies for dealing with and avoiding errors were set as the learning objectives for an interactive lecture, problem-based learning (PBL) case as well as the bedside teaching on anaesthesiology. Students were able to evaluate the lecture directly. During the simulator session on anaesthesia, the safety-relevant information that students requested from patients was compared with the questions asked by a control group in the previous trimester. Results: The topic of patient safety could be integrated into the "Operative Medicine" curriculum through a number of minor changes to classes. The accounts of personal experiences and importance assigned to the subject were considered positive, while content perceived as redundant was criticised. In the simulator, the students appeared to request more comprehensive preoperative safety-relevant information than the control group. Conclusion: The subject's relevance, positive feedback and trend towards a change in behaviour in the simulator lead the authors to deem introduction of the topic of patient safety a success.

Determinants of Perioperative Outcome in Frail Older Patients.

BACKGROUND: Older patients are undergoing surgery in increasing numbers. Frailty is a key risk factor associated with higher rates of complications and mortality, longer hospital stays, and functional impairment. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, including guidelines from Germany and abroad. RESULTS: Many studies have been published on the assessment of frailty and its consequences, but the scientific investigation of this topic and the clinical utility of the findings are made more difficult by the lack of a uniform definition and of uniform instruments for assessment. Some definitions of frailty include only physical aspects, while others encompass cognitive, emotional, and social factors as well. Despite this variability, the assessment of frailty enables better estimation of the perioperative risk so that the patient can be optimally prepared for the operation. Especially for frail elderly patients, an interdisciplinary approach is called for over the entire perioperative treatment period. CONCLUSION: In the future, the definition of frailty will need to be standardized so that this parameter can be properly assessed and investigated in comparative studies.

Dead space ventilation promotes alveolar hypocapnia reducing surfactant secretion by altering mitochondrial function.

BACKGROUND: In acute respiratory distress syndrome (ARDS), pulmonary perfusion failure increases physiologic dead space ventilation (VD/VT), leading to a decline of the alveolar CO2 concentration [CO2]iA. Although it has been shown that alveolar hypocapnia contributes to formation of atelectasis and surfactant depletion, a typical complication in ARDS, the underlying mechanism has not been elucidated so far. METHODS: In isolated perfused rat lungs, cytosolic or mitochondrial Ca2+ concentrations ([Ca2+]cyt or [Ca2+]mito, respectively) of alveolar epithelial cells (AECs), surfactant secretion and the projected area of alveoli were quantified by real-time fluorescence or bright-field imaging (n=3-7 per group). In ventilated White New Zealand rabbits, the left pulmonary artery was ligated and the size of subpleural alveoli was measured by intravital microscopy (n=4 per group). Surfactant secretion was determined in the bronchoalveolar lavage (BAL) by western blot. RESULTS: Low [CO2]iA decreased [Ca2+]cyt and increased [Ca2+]mito in AECs, leading to reduction of Ca2+-dependent surfactant secretion, and alveolar ventilation in situ. Mitochondrial inhibition by ruthenium red or rotenone blocked these responses indicating that mitochondria are key players in CO2 sensing. Furthermore, ligature of the pulmonary artery of rabbits decreased alveolar ventilation, surfactant secretion and lung compliance in vivo. Addition of 5% CO2 to the inspiratory gas inhibited these responses. CONCLUSIONS: Accordingly, we provide evidence that alveolar hypocapnia leads to a Ca2+ shift from the cytosol into mitochondria. The subsequent decline of [Ca2+]cyt reduces surfactant secretion and thus regional ventilation in lung regions with high VD/VT. Additionally, the regional hypoventilation provoked by perfusion failure can be inhibited by inspiratory CO2 application.

Asymmetric and Symmetric Dimethylarginines are Markers of Delayed Cerebral Ischemia and Neurological Outcome in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is the major cause of lethality and neuronal damage in patients who survived the primary subarachnoid hemorrhage (SAH). Asymmetric and symmetric dimethylarginines (ADMA and SDMA) inhibit nitric oxide production from L-arginine via distinct mechanisms. Elevated ADMA levels are associated with vasospasm after SAH. We aimed to study the time course of ADMA and SDMA in plasma and ventricular cerebrospinal fluid (CSF) and their associations with DCI and outcome. METHODS: We measured ADMA and SDMA in 34 SAH patients with an external ventricular drain at admission and on days 3, 6, 8, 12, and 15 and followed them up for clinical status and neurological outcome until 30 days post-discharge. DCI was defined as the appearance of new infarctions on cerebral computed tomography or magnetic resonance imaging. RESULTS: ADMA and SDMA plasma concentrations did not differ significantly at baseline between patients who suffered DCI (N = 14; 41%) and not; however, plasma ADMA reached a peak on days 8 and 15 after hemorrhage in patients with DCI (0.81-0.91 µmol/l). Baseline plasma L-arginine/ADMA ratio was significantly lower in patients with DCI (57.1 [34.3; 70.8] vs. 68.7 [55.7; 96.2]; p < 0.05). ADMA and SDMA concentrations in CSF were significantly higher in patients with DCI than without. In multivariable-adjusted linear regression models, CSF ADMA was negatively associated with the incidence of DCI (OR 0.03 [0.02-0.70]; p = 0.04), whereas CSF SDMA on the day of hemorrhage predicted poor neurological outcome until 30 days after discharge (OR 22.4 [1.21-416.02]; p = 0.04). CONCLUSIONS: Our study shows that ADMA and the L-arginine/ADMA ratio are associated with the incidence of DCI after SAH. By contrast, SDMA was associated with initial neuronal damage and poor neurological outcome after SAH. These data support the hypothesis that ADMA and L-arginine affect the pathophysiology of cerebral ischemia after SAH, while SDMA is a biomarker of neurological outcome after SAH.

Syndecan-1 as a biomarker for sepsis survival after major abdominal surgery.

AIM: Sepsis is a serious complication following surgery and identification of patients at risk is of high importance. Syndecan-1 (sSDC1) levels are known to be elevated during sepsis. MATERIALS & METHODS: Fifty-five patients scheduled for major abdominal surgery were prospectively included and sSDC1 concentrations were measured during hospital stay. RESULTS: Patients with postoperative sepsis showed a continued increase of sSDC1 levels and exhibited higher median sSDC1 concentrations at day 1 compared with nonseptic patients 90.3 versus 16.5 ng/ml. A significant association of sSDC1 levels with the incidence of sepsis and death was demonstrated. CONCLUSION: This study identifies sSDC1 as potential biomarker for sepsis and survival after abdominal surgery.

Intraoperative Ventilation of Morbidly Obese Patients Guided by Transpulmonary Pressure.

BACKGROUND: Bariatric surgery has proven a successful approach in the treatment of morbid obesity and its concomitant diseases such as diabetes mellitus and arterial hypertension. Aiming for optimal management of this challenging patient cohort, tailored concepts directly guided by individual patient physiology may outperform standardized care. Implying esophageal pressure measurement and electrical impedance tomography-increasingly applied monitoring approaches to individually adjust mechanical ventilation in challenging circumstances like acute respiratory distress syndrome (ARDS) and intraabdominal hypertension-we compared our institutions standard ventilator regimen with an individually adjusted positive end expiratory pressure (PEEP) level aiming for a positive transpulmonary pressure (P L) throughout the respiratory cycle. METHODS: After obtaining written informed consent, 37 patients scheduled for elective bariatric surgery were studied during mechanical ventilation in reverse Trendelenburg position. Before and after installation of capnoperitoneum, PEEP levels were gradually raised from a standard value of 10 cm H2O until a P L of 0 +/- 1 cm H2O was reached. Changes in ventilation were monitored by electrical impedance tomography (EIT) and arterial blood gases (ABGs) were obtained at the end of surgery and 5 and 60 min after extubation, respectively. RESULTS: To achieve the goal of a transpulmonary pressure (P L) of 0 cm H2O at end expiration, PEEP levels of 16.7 cm H2O (95% KI 15.6-18.1) before and 23.8 cm H2O (95% KI 19.6-40.4) during capnoperitoneum were necessary. EIT measurements confirmed an optimal PEEP level between 10 and 15 cm H2O before and 20 and 25 cm H2O during capnoperitoneum, respectively. Intra- and postoperative oxygenation did not change significantly. CONCLUSION: Patients during laparoscopic bariatric surgery require high levels of PEEP to maintain a positive transpulmonary pressure throughout the respiratory cycle. EIT monitoring allows for non-invasive monitoring of increasing PEEP demand during capnoperitoneum. Individually adjusted PEEP levels did not result in improved postoperative oxygenation.

IDH3 mediates apoptosis of alveolar epithelial cells type 2 due to mitochondrial Ca2+ uptake during hypocapnia.

In adult respiratory distress syndrome (ARDS) pulmonary perfusion failure increases physiologic dead-space (VD/VT) correlating with mortality. High VD/VT results in alveolar hypocapnia, which has been demonstrated to cause edema formation, atelectasis, and surfactant depletion, evoked, at least in part, by apoptosis of alveolar epithelial cells (AEC). However, the mechanism underlying the hypocapnia-induced AEC apoptosis is unknown. Here, using fluorescent live-cell imaging of cultured AEC type 2 we could show that in terms of CO2 sensing the tricarboxylic acid cycle enzyme isocitrate dehydrogenase (IDH) 3 seems to be an important player because hypocapnia resulted independently from pH in an elevation of IDH3 activity and subsequently in an increase of NADH, the substrate of the respiratory chain. As a consequence, the mitochondrial transmembrane potential (ΔΨ) rose causing a Ca2+ shift from cytosol into mitochondria, whereas the IDH3 knockdown inhibited these responses. Furthermore, the hypocapnia-induced mitochondrial Ca2+ uptake resulted in reactive oxygen species (ROS) production, and both the mitochondrial Ca2+ uptake and ROS production induced apoptosis. Accordingly, we provide evidence that in AEC type 2 hypocapnia induces elevation of IDH3 activity leading to apoptosis. This finding might give new insight into the pathogenesis of ARDS and may help to develop novel strategies to reduce tissue injury in ARDS.

Markers of nitric oxide are associated with sepsis severity: an observational study.

BACKGROUND: Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular function and pathogen defense. Direct NO measurement in patients is unfeasible because of its short half-life. Surrogate markers for NO bioavailability are substrates of NO generating synthase (NOS): L-arginine (lArg) and homoarginine (hArg) together with the inhibitory competitive substrate asymmetric dimethylarginine (ADMA). In immune cells ADMA is cleaved by dimethylarginine-dimethylaminohydrolase-2 (DDAH2). The aim of this study was to investigate whether concentrations of surrogate markers for NO bioavailability are associated with sepsis severity. METHOD: This single-center, prospective study involved 25 controls and 100 patients with surgical trauma (n = 20), sepsis (n = 63), or septic shock (n = 17) according to the Sepsis-3 definition. Plasma lArg, hArg, and ADMA concentrations were measured by mass spectrometry and peripheral blood mononuclear cells (PBMCs) were analyzed for DDAH2 expression. RESULTS: lArg concentrations did not differ between groups. Median (IQR) hArg concentrations were significantly lower in patient groups than controls, being 1.89 (1.30-2.29) µmol/L (P < 0.01), with the greatest difference in the septic shock group, being 0.74 (0.36-1.44) µmol/L. In contrast median ADMA concentrations were significantly higher in patient groups compared to controls, being 0.57 (0.46-0.65) µmol/L (P < 0.01), with the highest levels in the septic shock group, being 0.89 (0.56-1.39) µmol/L. The ratio of hArg:ADMA was inversely correlated with disease severity as determined by the Sequential Organ Failure Assessment (SOFA) score. Receiver-operating characteristic analysis for the presence or absence of septic shock revealed equally high sensitivity and specificity for the hArg:ADMA ratio compared to the SOFA score. DDAH2 expression was lower in patients than controls and lowest in the subgroup of patients with increasing SOFA. CONCLUSIONS: In patients with sepsis, plasma hArg concentrations are decreased and ADMA concentrations are increased. Both metabolites affect NO metabolism and our findings suggest reduced NO bioavailability in sepsis. In addition, reduced expression of DDAH2 in immune cells was observed and may not only contribute to blunted NO signaling but also to subsequent impaired pathogen defense.

Reduction of clinically irrelevant alarms in patient monitoring by adaptive time delays.

The problem of high rates of false alarms in patient monitoring in anesthesiology and intensive care medicine is well known but remains unsolved. False alarms desensitize the medical staff, leading to ignored true alarms and reduced quality of patient care. A database of intra-operative monitoring data was analyzed to find characteristic alarm patterns. The original data were re-evaluated to find relevant events and to rate the severity of these events. Based on this analysis an adaptive time delay was developed that individually delays the alarms depending on the grade of threshold deviation. The conventional threshold algorithm led to 4893 alarms. 3515 (71.84 %) of these alarms were annotated as clinically irrelevant. In total 81.0 % of all clinically irrelevant alarms were caused by only mild and/or brief threshold violations. We implemented the new algorithm for selected parameters. These parameters equipped with adaptive validation delays led to 1729 alarms. 931 (53.85 %) alarms were annotated as clinically irrelevant. 632 alarms indicated the 645 clinically relevant events. The positive predictive value of occurring alarms improved from 28.16 % (conventional algorithm) to 46.15 % (new algorithm). 13 events were missed. The false positive alarm reduction rate of the algorithm ranged from 33 to 86.75 %. The overall reduction was 73.51 %. The implementation of this algorithm may be able to suppress a large percentage of false alarms. The effect of this approach has not been demonstrated but shows promise for reducing alarm fatigue. Its safety needs to be proven in a prospective study.

Dynamic device properties of pulse contour cardiac output during transcatheter aortic valve implantation.

This prospective single-center study aimed to determine the responsiveness and diagnostic performance of continuous cardiac output (CCO) monitors based on pulse contour analysis compared with invasive mean arterial pressure (MAP) during predefined periods of acute circulatory deterioration in patients undergoing transcatheter aortic valve implantation (TAVI). The ability of calibrated (CCO(CAL)) and self-calibrated (CCO(AUTOCAL)) pulse contour analysis to detect the hemodynamic response to 37 episodes of balloon aortic valvuloplasty enabled by rapid ventricular pacing was quantified in 13 patients undergoing TAVI. A "low" and a "high" cut-off limit were predefined as a 15 or 25 % decrease from baseline respectively. We found no significant differences between CCO(CAL) and MAP regarding mean response time [low cut-off: 8.6 (7.1-10.5) vs. 8.9 (7.3-10.8) s, p = 0.76; high cut-off: 11.4 (9.7-13.5) vs. 12.6 (10.7-14.9) s, p = 0.32] or diagnostic performance [area under the receiver operating characteristics curve (AUC): 0.99 (0.98-1.0) vs. 1.0 (0.99-1.0), p = 0.46]. But CCOCAL had a significantly higher amplitude response [95.0 (88.7-98.8) % decrease from baseline] than MAP [41.2 (30.0-52.9) %, p < 0.001]. CCOAUTOCAL had a significantly lower AUC [0.83 (0.73-0.93), p < 0.001] than MAP. Moreover, CCO(CAL) detected hemodynamic recovery significantly earlier than MAP. In conclusion, CCO(CAL) and MAP provided equivalent responsiveness and diagnostic performance to detect acute circulatory depression, whereas CCO(AUTOCAL) appeared to be less appropriate. In contrast to CCO(CAL) the amplitude response of MAP was poor. Consequently even small response amplitudes of MAP could indicate severe decreases in CO.

Individualized early goal-directed therapy in systemic inflammation: is full utilization of preload reserve the optimal strategy?

OBJECTIVES: In severe acute pancreatitis, the administration of fluids in the presence of positive fluid responsiveness is associated with better outcome when compared to guiding therapy on central venous pressure. We compared the effects of such consequent maximization of stroke volume index with a regime using individual values of stroke volume index assessed prior to severe acute pancreatitis induction as therapeutic hemodynamic goals. DESIGN: Prospective, randomized animal study. SETTING: University animal research laboratory. SUBJECTS: Thirty domestic pigs. INTERVENTIONS: After randomization, fluid resuscitation was started 2 hours after severe acute pancreatitis induction and continued for 6 hours according to the respective treatment algorithms. In the control group, fluid therapy was directed by maximizing stroke volume index, and in the study group, stroke volume index assessed prior to severe acute pancreatitis served as primary hemodynamic goal. MEASUREMENTS AND MAIN RESULTS: Within the first 6 hours of severe acute pancreatitis, the study group received a total of 1,935.8 ± 540.7 mL of fluids compared with 3,462.8 ± 828.2 mL in the control group (p < 0.001). Pancreatic tissue oxygenation did not differ significantly between both groups. Vascular endothelial function, measured by flow-mediated vasodilation before and 6 hours after severe acute pancreatitis induction, revealed less impairment in the study group after treatment interval (-90.76% [study group] vs -130.89% [control group]; p = 0.046). Further, lower levels of heparan sulfate (3.41 ± 5.6 pg/mL [study group] vs 43.67 ± 46.61 pg/mL [control group]; p = 0.032) and interleukin 6 (32.18 ± 8.81 pg/mL [study group] vs 77.76 ± 56.86 pg/mL [control group]; p = 0.021) were found in the study group compared with control group. Histopathological examination of the pancreatic head and corpus at day 7 revealed less edema for the study group compared with the control group (1.82 ± 0.87 [study group] vs 2.89 ± 0.33 [control group, pancreatic head]; p = 0.03; 2.2 ± 0.92 [study group] vs 2.91 ± 0.3 [control group, pancreatic corpus]; p = 0.025). CONCLUSIONS: Individualized optimization of intravascular fluid status during the early course of severe acute pancreatitis, compared with a treatment strategy of maximizing stroke volume by fluid loading, leads to less vascular endothelial damage, pancreatic edema, and inflammatory response.

Perioperative glycemic control with a computerized algorithm versus conventional glycemic control in cardiac surgical patients undergoing cardiopulmonary bypass with blood cardioplegia.

OBJECTIVE: In critical illness, hypoglycemia and hyperglycemia seem to influence outcome. While hypoglycemia can lead to organ dysfunction, hyperglycemia can lead to surgical site infections (SSI). In cardiac surgery, the use of blood cardioplegia is associated with high blood glucose levels. A computer-based algorithm (CBA) for guiding insulin towards normoglycemia might be beneficial. The authors' primary study end-point was the duration in a predefined blood glucose target range of 80 mg/dL to 150 mg/dL. Patients with conventional therapy served as controls. DESIGN: Prospective, randomized trial. SETTING: University hospital. PARTICIPANTS: Seventy-five patients. INTERVENTIONS: The start of therapy was the beginning of cardiopulmonary bypass. Group A: Therapy with CBA and measurement of blood glucose every 30 minutes. Group B: Measurement of blood glucose every 15 minutes using the identical CBA. Group C: Conventional therapy using a fixed insulin dosing scheme. End of therapy was defined as discharge from ICU. MEASUREMENT AND MAIN RESULTS: Glucose administration during cardioplegia did not differ between groups (A: 33 ± 12 g; B: 32 ± 12 g; C: 38 ± 20 g). Glucose levels in groups A and B stayed significantly longer in the target interval compared with group C (A: 75 ± 20%; B: 72 ± 19%; C: 50 ± 34%, p < 0.01 n = 25, respectively). There were no significant differences regarding ICU stay and SSI rates. CONCLUSIONS: Early computer-based insulin therapy allows practitioners to better achieve normoglycemia in patients undergoing major cardiac surgery with the use of blood cardioplegia.

Effects of thoracic epidural anesthesia on survival and microcirculation in severe acute pancreatitis: a randomized experimental trial.

INTRODUCTION: Severe acute pancreatitis is still a potentially life threatening disease with high mortality. The aim of this study was to evaluate the therapeutic effect of thoracic epidural anaesthesia (TEA) on survival, microcirculation, tissue oxygenation and histopathologic damage in an experimental animal model of severe acute pancreatitis in a prospective animal study. METHODS: In this study, 34 pigs were randomly assigned into 2 treatment groups. After severe acute pancreatitis was induced by intraductal injection of glycodesoxycholic acid in Group 1 (n = 17) bupivacaine (0.5%; bolus injection 2 ml, continuous infusion 4 ml/h) was applied via TEA. In Group 2 (n = 17) no TEA was applied. During a period of 6 hours after induction, tissue oxygen tension (tpO2) in the pancreas and pancreatic microcirculation was assessed. Thereafter animals were observed for 7 days followed by sacrification and histopathologic examination. RESULTS: Survival rate after 7 days was 82% in Group 1 (TEA) versus 29% in Group 2: (Control) (P <0.05). Group 1 (TEA) also showed a significantly superior microcirculation (1,608 ± 374 AU versus 1,121 ± 510 AU; P <0.05) and tissue oxygenation (215 ± 64 mmHg versus 138 ± 90 mmHG; P <0.05) as compared to Group 2 (Control). Consecutively, tissue damage in Group 1 was reduced in the histopathologic scoring (5.5 (3 to 8) versus 8 (5.5 to 10); P <0.05). CONCLUSIONS: TEA led to improved survival, enhanced microcirculatory perfusion and tissue oxygenation and resulted in less histopathologic tissue-damage in an experimental animal model of severe acute pancreatitis.

Prediction of volume-responsiveness during one-lung ventilation: a comparison of static, volumetric, and dynamic parameters of cardiac preload.

OBJECTIVES: The aim of this study was to evaluate the ability of static, volumetric, and dynamic parameters of cardiac preload to predict volume responsiveness during one-lung ventilation (OLV). DESIGN: Prospective experimental study. SETTING: Laboratory of the animal facility of the University Medical Center Hamburg-Eppendorf. PARTICIPANTS: Twenty-three German domestic pigs. INTERVENTIONS: Hypovolemia was induced by withdrawing 20 mL/kg body weight (BW) of blood. OLV was established, and the volume withdrawn was re-transfused in 3 volume-loading steps, each consisting of 7 mL/kg BW. An ultrasonic flow probe around the pulmonary artery was used to measure the stroke-volume index (SVI) and to evaluate the volume response. An increase in the SVI of ≥ 15% was considered a positive response. For each measurement time point, central venous pressure (CVP), left atrial pressure (LAP), the global end-diastolic volume index (GEDI), stroke-volume variation (SVV), and pulse-pressure variation (PPV) were recorded. The ability to predict volume responsiveness was assessed using ROC analysis. MEASUREMENTS AND MAIN RESULTS: A total of 69 volume loading steps were performed, 48 of which showed a positive volume response. ROC analysis revealed the following area under the curve (AUC) values: CVP, 0.88; LAP, 0.65; GEDI, 0.75; SVV, 0.78; and PPV, 0.83. A comparison of the areas under the ROC curves did not reveal any statistically significant differences (p>0.05), with the exception of LAP compared with CVP (p = 0.005). CONCLUSIONS: Under these OLV experimental conditions, the volumetric and dynamic parameters of preload, as well as CVP, seemed to be of similar value in predicting volume responsiveness.

Brief report: leaking esophageal probe may lead to false ventilator settings when guiding positive end-expiratory pressure by transpulmonary pressure.

Esophageal pressure (Pes) is a surrogate for intrapleural pressure. Measuring Pes during mechanical ventilation allows for positive end-expiratory pressure adjustments by transpulmonary pressure (PL), which has been shown to improve oxygenation and outcome in acute respiratory distress syndrome patients. In morbidly obese patients, we saw progressively increasing PL measurements, although airway pressure (Paw), intra-abdominal pressure, and patient position did not change. On further examination, we determined that the gradual increases of PL were artifacts caused by a leak in the pressure probes, which resulted in underestimation of Pes and overestimation of PL as derived from the equation Paw - Pes = PL.

Individually optimized hemodynamic therapy reduces complications and length of stay in the intensive care unit: a prospective, randomized controlled trial.

BACKGROUND: The authors hypothesized that goal-directed hemodynamic therapy, based on the combination of functional and volumetric hemodynamic parameters, improves outcome in patients with cardiac surgery. Therefore, a therapy guided by stroke volume variation, individually optimized global end-diastolic volume index, cardiac index, and mean arterial pressure was compared with an algorithm based on mean arterial pressure and central venous pressure. METHODS: This prospective, controlled, parallel-arm, open-label trial randomized 100 coronary artery bypass grafting and/or aortic valve replacement patients to a study group (SG; n = 50) or a control group (CG; n = 50). In the SG, hemodynamic therapy was guided by stroke volume variation, optimized global end-diastolic volume index, mean arterial pressure, and cardiac index. Optimized global end-diastolic volume index was defined before and after weaning from cardiopulmonary bypass and at intensive care unit (ICU) admission. Mean arterial pressure and central venous pressure served as hemodynamic goals in the CG. Therapy was started immediately after induction of anesthesia and continued until ICU discharge criteria, serving as primary outcome parameter, were fulfilled. RESULTS: Intraoperative need for norepinephrine was decreased in the SG with a mean (±SD) of 9.0 ± 7.6 versus 14.9 ± 11.1 µg/kg (P = 0.002). Postoperative complications (SG, 40 vs. CG, 63; P = 0.004), time to reach ICU discharge criteria (SG, 15 ± 6 h; CG, 24 ± 29 h; P < 0.001), and length of ICU stay (SG, 42 ± 19 h; CG, 62 ± 58 h; P = 0.018) were reduced in the SG. CONCLUSION: Early goal-directed hemodynamic therapy based on cardiac index, stroke volume variation, and optimized global end-diastolic volume index reduces complications and length of ICU stay after cardiac surgery.