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Acute kidney injury (AKI) is associated with impaired outcomes in critically ill COVID-19 patients. However, the prognostic significance of early AKI is poorly described. We aimed to determine whether AKI on admission to the intensive care unit (ICU) and its development within the first 48 h predict the need for renal replacement therapy (RRT) and increased mortality. An analysis of 372 patients with COVID-19 pneumonia requiring mechanical ventilation without advanced chronic kidney disease from 2020 to 2021 was performed. The AKI stages on ICU admission and Day 2 were determined using adapted KDIGO criteria. The early development of renal function was assessed by the change in AKI score and the Day-2/Day-0 creatinine ratio. Data were compared between three consecutive COVID-19 waves and with data before the pandemic. Both ICU and 90-day mortality (79% and 93% vs. 35% and 44%) and the need for RRT increased markedly with advanced AKI stage on ICU admission. Similarly, an early increase in AKI stage and creatinine implied highly increased mortality. RRT was associated with very high ICU and 90-day mortality (72% and 85%), even surpassing that of patients on ECMO. No difference was found between consecutive COVID-19 waves, except for a lower mortality in the patients on RRT in the last omicron wave. Mortality and need for RRT were comparable in the COVID-19 and pre-COVID-19 patients, except that RRT did not increase ICU mortality in the pre-COVID-19 era. In conclusion, we confirmed the prognostic significance of both AKI on ICU admission and its early development in patients with severe COVID-19 pneumonia.

Introduction: Post-operative oxygen therapy is used to prevent hypoxemia and surgical site infection. However, with improvements of anesthesia techniques, post-operative hypoxemia incidence is declining and the benefits of oxygen on surgical site infection have been questioned. Moreover, hyperoxemia might have adverse effects on the pulmonary and cardiovascular systems. We hypothesized hyperoxemia post thoracic surgery is associated with post-operative pulmonary and cardiovascular complications., Methods: Consecutive lung resection patients were included in this post-hoc analysis. Post-operative pulmonary and cardiovascular complications were prospectively assessed during the first 30 post-operative days, or hospital stay. Arterial blood gases were analyzed at 1, 6 and 12 h after surgery. Hyperoxemia was defined as arterial partial pressure of oxygen (PaO 2 )>100 mmHg. Patients with hyperoxemia duration in at least two adjacent time points were considered as hyperoxemic. Student t-test, Mann-Whitney U test and two-tailed Fisher exact test were used for group comparison. P values < 0.05 were considered statistically significant., Results: Three hundred sixty-three consecutive patients were included in this post-hoc analysis. Two hundred five patients (57%), were considered hyperoxemic and included in the hyperoxemia group. Patients in the hyperoxemia group had significantly higher PaO 2 at 1, 6 and 12 h after surgery (p < 0.05). Otherwise, there was no significant difference in age, sex, comorbidities, pulmonary function tests parameters, lung surgery procedure, incidence of post-operative pulmonary and cardiovascular complications, intensive care unit and hospital length of stay and 30-day mortality., Conclusion: Hyperoxemia after lung resection surgery is common and not associated with post-operative complications or 30-day mortality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Cardiopulmonary exercise testing parameters including ventilatory efficiency (V E /VCO 2 slope) are used for risk assessment of lung resection candidates. However, many patients are unable or unwilling to undergo exercise. V E /VCO 2 slope is closely related to the partial pressure of end-tidal carbon dioxide (P ET CO 2 ). We hypothesized P ET CO 2 at rest predicts postoperative pulmonary complications., Methods: Consecutive lung resection candidates were included in this prospective multicenter study. Postoperative respiratory complications were assessed from the first 30 postoperative days or from the hospital stay. Student t test or Mann-Whitney U test was used for comparison. Multivariate stepwise logistic regression analysis was used to analyze association with the development of postoperative pulmonary complications. The De Long test was used to compare area under the curve (AUC). Data are summarized as median (interquartile range)., Results: Three hundred fifty-three patients were analyzed, of which 59 (17%) developed postoperative pulmonary complications. P ET CO 2 at rest was significantly lower (27 [24-30] vs 29 [26-32] mm Hg; P < .01) and V E /VCO 2 slope during exercise significantly higher (35 [30-40] vs 29 [25-33]; P < .01) in patients who developed postoperative pulmonary complications. Both rest P ET CO 2 with odds ratio 0.90 (95% confidence interval [CI] 0.83-0.97); P = .01 and V E /VCO 2 slope with odds ratio 1.10 (95% CI 1.05-1.16); P < .01 were independently associated with postoperative pulmonary complications by multivariate stepwise logistic regression analysis. There was no significant difference between AUC of both models (rest P ET CO 2 : AUC = 0.79 (95% CI 0.74-0.85); V E /VCO 2 slope: AUC = 0.81 (95% CI 0.75-0.86); P = .48)., Conclusions: P ET CO 2 at rest has similar prognostic utility as V E /VCO 2 slope, suggesting rest P ET CO 2 may be used for postoperative pulmonary complications prediction in lung resection candidates., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Euglycemic diabetic ketoacidosis associated with SGLT2 inhibitors is a rare, relatively new and potentially fatal clinical entity, characterized by metabolic acidosis with normal or only moderately elevated glycemia. The mechanisms are not fully understood but involve increased ketogenesis and complex renal metabolic dysfunction, resulting in both ketoacidosis and hyperchloremic acidosis. We report a rare case of fatal empagliflozin-associated acidosis with profound hyperchloremia and review its pathogenesis., Case Presentation: A patient with type 2 diabetes mellitus treated with empagliflozin underwent an elective hip replacement surgery. Since day 4 after surgery, he felt generally unwell, leading to cardiac arrest on the day 5. Empagliflozin-associated euglycemic diabetic ketoacidosis with severe hyperchloremic acidosis was identified as the cause of the cardiac arrest., Conclusions: This unique case documents the possibility of severe SGLT2 inhibitor-associated mixed metabolic acidosis with a predominant hyperchloremic component. Awareness of this possibility and a high index of suspicion are crucial for correct and early diagnosis., (© 2023. The Author(s).)

Introduction: According to the guidelines for preoperative assessment of lung resection candidates, patients with normal forced expiratory volume in 1 s (FEV 1 ) and diffusing capacity of the lung for carbon monoxide ( D LCO ) are at low risk for post-operative pulmonary complications (PPC). However, PPC affect hospital length of stay and related healthcare costs. We aimed to assess risk of PPC for lung resection candidates with normal FEV 1 and D LCO (>80% predicted) and identify factors associated with PPC., Methods: 398 patients were prospectively studied at two centres between 2017 and 2021. PPC were recorded from the first 30 post-operative days. Subgroups of patients with and without PPC were compared and factors with significant difference were analysed by uni- and multivariate logistic regression., Results: 188 subjects had normal FEV 1 and D LCO . Of these, 17 patients (9%) developed PPC. Patients with PPC had significantly lower pressure of end-tidal carbon dioxide ( P ETCO 2 ) at rest (27.7 versus 29.9; p=0.033) and higher ventilatory efficiency ( V ' E / V ' CO 2 ) slope (31.1 versus 28; p=0.016) compared to those without PPC. Multivariate models showed association between resting P ETCO 2 (OR 0.872; p=0.035) and V ' E / V ' CO 2 slope (OR 1.116; p=0.03) and PPC. In both models, thoracotomy was strongly associated with PPC (OR 6.419; p=0.005 and OR 5.884; p=0.007, respectively). Peak oxygen consumption failed to predict PPC (p=0.917)., Conclusions: Resting P ETCO 2 adds incremental information for risk prediction of PPC in patients with normal FEV 1 and D LCO . We propose resting P ETCO 2 be an additional parameter to FEV 1 and D LCO for preoperative risk stratification., Competing Interests: Conflict of interests: M. Bratova received lecture and fees from Roche CZ, Bristol-Myers Squibb CZ and MSD CZ outside the submitted work. K. Brat received lecture and consulting fees from Chiesi CZ, Boehringer Ingelheim CZ, Novartis CZ, AstraZeneca CZ and Angelini CZ outside the submitted work. The other authors (I. Cundrle Jr, P. Homolka, M. Chobola, V. Sramek, Z. Merta, L. Mitas, M. Svoboda, Z. Chovanec and L.J. Olson) have nothing to disclose., (Copyright ©The authors 2023.)

Introduction: Ventilatory efficiency (VE/VCO2 slope) has been shown superior to peak oxygen consumption (VO2) for prediction of post-operative pulmonary complications in patients undergoing thoracotomy. VE/VCO2 slope is determined by ventilatory drive and ventilation/perfusion mismatch whereas VO2 is related to cardiac output and arteriovenous oxygen difference. We hypothesized pre-operative VO2 predicts post-operative cardiovascular complications in patients undergoing lung resection., Methods: Lung resection candidates from a published study were evaluated by post-hoc analysis. All of the patients underwent preoperative cardiopulmonary exercise testing. Post-operative cardiovascular complications were assessed during the first 30 post-operative days or hospital stay. One-way analysis of variance or the Kruskal-Wallis test, and multivariate logistic regression were used for statistical analysis and data summarized as median (IQR)., Results: Of 353 subjects, 30 (9%) developed pulmonary complications only (excluded from further analysis), while 78 subjects (22%) developed cardiovascular complications and were divided into two groups for analysis: cardiovascular only (n = 49) and cardiovascular with pulmonary complications (n = 29). Compared to patients without complications (n = 245), peak VO2 was significantly lower in the cardiovascular with pulmonary complications group [19.9 ml/kg/min (16.5-25) vs. 16.3 ml/kg/min (15-20.3); P<0.01] but not in the cardiovascular only complications group [19.9 ml/kg/min (16.5-25) vs 19.0 ml/kg/min (16-23.1); P = 0.18]. In contrast, VE/VCO2 slope was significantly higher in both cardiovascular only [29 (25-33) vs. 31 (27-37); P = 0.05] and cardiovascular with pulmonary complication groups [29 (25-33) vs. 37 (34-42); P<0.01)]. Logistic regression analysis showed VE/VCO2 slope [OR = 1.06; 95%CI (1.01-1.11); P = 0.01; AUC = 0.74], but not peak VO2 to be independently associated with post-operative cardiovascular complications., Conclusion: VE/VCO2 slope is superior to peak VO2 for prediction of post-operative cardiovascular complications in lung resection candidates., Competing Interests: The authors have declared that no competing interests exist.

Background: High endothelial venules (HEVs) are vessels specialized in the transport of lymphocytes shown to be implicated in various forms of cancer. They express peripheral node addressin (specifically recognized by the MECA-79 antibody). MECA-79 is also implicated in pregnancy through its expression by epithelial cells of the endometrium. However, the expression of MECA-79 by endothelial or epithelial (cancer) cells has never been studied in endometrial cancer., Material and Methods: In this retrospective study, we investigated the immunohistochemical expression of MECA-79 in 40 endometrioid adenocarcinoma hysterectomy specimens and compared it with its expression in 30 non-cancer hysterectomies., Results: HEVs were found in 22% of tumor specimens and in none of the non-cancer hysterectomies (p = 0.005) and were positively associated with higher grade tumors (p = 0.04). MECA-70 was expressed in tumor cells of 70% of carcinomas and in epithelial cells of 46.6% of normal endometria (p = 0.04). It was inversely associated with parametrial invasion (p = 0.03) and larger tumors (statistical trend of p = 0.07). MECA-79 expression was not associated with overall or progression-free survival., Conclusion: MECA-79 is found in HEVs and tumor cells in endometrial endometrioid adenocarcinoma., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: Cardiac myxomas are rare, predominantly sporadic tumors that can cause heart failure and systematic inflammatory symptoms, and increase the risk of emboli. Their pathophysiology remains poorly understood, but intra-tumoral inflammation and senescence seem to be implicated in it. One of the principal cellular mechanisms implicated in tumor progression is autophagy, largely unknown in myxomas. Thus, our study aimed to investigate the presence of autophagic markers in myxomas and to correlate it with their immune microenvironment., Methods: Twenty-five cardiac myxomas were studied for the autophagic markers LC3B and p62/sequestosome 1 and were compared with markers of the immune microenvironment., Results: Most myxomas showed expression of both autophagic markers. We found a positive correlation between LC3B and PD-L1, as well as CD163, and a negative correlation between LC3B and CD8, CD20, CD138, and CD117 infiltration., Conclusion: Our data not only confirm the presence of autophagic markers within cardiac myxomas but also suggest a possible association with their immune microenvironment., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Purpose: Trifluridine/tipiracil (FTD/TPI) is approved for advanced colorectal and gastric/gastroesophageal cancer; however, data in patients with renal impairment (RI) are limited. This phase I study evaluated FTD/TPI in patients with advanced solid tumors and varying degrees of RI to develop dosing guidance., Methods: Patients were enrolled into normal renal function (CrCl ≥ 90 mL/min), mild RI (CrCl 60-89 mL/min), or moderate RI (CrCl 30-59 mL/min) cohorts and administered the recommended FTD/TPI dose (35 mg/m 2 twice daily, days 1-5 and 8-12; 28-day cycle). Based on interim pharmacokinetics/safety data, patients with severe RI (CrCl 15-29 mL/min) were enrolled and received FTD/TPI 20 mg/m 2 twice daily., Results: Forty-three patients (normal renal function [n = 12]; mild RI [n = 12]; moderate RI [n = 11]; severe RI [n = 8]) were enrolled and treated. At steady state, compared to values in patients with normal renal function, FTD area under the curve (AUC) was not significantly different in patients with RI, but TPI AUC was significantly higher and increased with RI severity. FTD/TPI safety profile was consistent with prior experience, but grade ≥ 3 adverse events (AEs) were more frequent in the RI cohorts (83.3% [mild], 90.9% [moderate], 75.0% [severe], and normal [50.0%]). Hematologic AEs (anemia and neutropenia) were more frequent with RI. Overall, seven patients discontinued because of unrelated, nonhematologic AEs., Conclusion: FTD/TPI is safe and tolerable at the recommended 35 mg/m 2 dose in patients with mild/moderate RI and at the reduced 20 mg/m 2 dose in patients with severe RI., Trial Registration: NCT02301117, registration date: November 21, 2014., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Cardiac myxomas are rare tumors of incompletely elucidated pathogenesis. The aim of this study is to explore the possible presence of a senescence phenotype in cardiac myxomas, associated with an inflammatory and vasculogenic tumor microenvironment., Methods and Results: This is a retrospective study of 29 cardiac myxomas with immunohistochemical detection of various inflammatory, vascular, and senescence markers. We show that all myxomas contain tumor cells in senescence overexpressing p16, and a fraction of senescent endothelial cells. Macrophages are the principal inflammatory cell population, followed by cytotoxic T cells, with fewer plasma cells, mastocytes, and B lymphocytes. These populations are found in different intratumoral localizations. Larger tumor volume is associated with a lower percentage of myxoid matrix, higher cellularity, higher macrophage, and lower number of mast cells as well as higher PD-L1 expression by inflammatory cells. Higher vascular density is associated with higher percentage of B cells, a lower number of macrophages and higher number of mastocytes, and lower PD-L1 expression by inflammatory cells. Tumors with higher vascular density and higher cellularity show higher amounts of p16 senescent endothelial cells., Conclusions: Myxoma tumor cells are in senescence and reside inside a tumor microenvironment with a distinct inflammatory profile rich in macrophages and cytotoxic T cells, and a rich vasculature, probably attributed to a senescence-associated secretory phenotype., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier Inc.)

Plasma specimens from coronavirus disease 2019 patients were double-tested for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies by two different batches of MAGLUMI 2019-nCov immunoglobulin M/immunoglobulin G (IgM/IgG) assays to evaluate IgM/IgG levels, qualitative interpretation, antibody kinetics, and linearity of diluted specimen. Here we show that (i) high-level IgM specimens need to be diluted with negative human plasma but not kit diluents and (ii) measured anti-SARS-CoV-2 IgM/IgG concentrations are substantially higher with later marketed immunoassay batch leading to (iii) the change of qualitative interpretation (positive vs. negative) in 12.3% of specimens measured for IgM, (iv) the informative time-course pattern of antibody production only when data from different immunoassay batches are not combined., (© 2020 Wiley Periodicals LLC.)

Introduction: Critically ill patients are exposed to a high risk of developing thromboembolism. Moreover, standard prophylaxis with subcutaneous (SC) heparin is less efficient in patients requiring vasopressors. The aim is a comparison of pharmacokinetics between SC and intravenous (IV) applied nadroparin., Methods: Thirty-eight ventilated ICU patients requiring vasopressor support were randomized into a single dose of nadroparin 3,800 IU (0.4 mL) subcutaneously (SC group) or 1,900 IU (0.2 mL) intravenously (IV group). Anti-factor Xa activity (anti-Xa) was observed over 24 h; data are stated as median (IQR)., Results: Peak anti-Xa was significantly higher in the IV group 0.42 (0.39-0.43) IU/mL than in the SC group 0.16 (0.09-0.18) IU/mL (p < 0.001). There was a trend towards higher area under the curve (AUC) of anti-Xa in the SC group 1.41 (0.41-1.80) IU/mL × h than in the IV group 1.04 (0.93-1.13) IU/mL × h (p = 0.08). In the SC group, there was a negative correlation between anti-Xa AUC and both capillary refill time Xa (r = -0.86) and norepinephrine dose (r = -0.68). In the IV group, anti-Xa decrease half-life was 1.6 (1.4-2.0) h., Conclusions: IV administration of 1,900 IU of nadroparin led to a predictable effective peak anti-Xa. After SC administration, anti-Xa was heterogeneous and significantly influenced by peripheral perfusion., (© 2019 S. Karger AG, Basel.)

Sympathetic activation of β-adrenoreceptors (β-AR) represents a hallmark in the development of heart failure (HF). However, little is known about the underlying mechanisms of gene regulation. In human ventricular myocardium from patients with end-stage HF, we found high levels of phosphorylated histone 3 at serine-28 (H3S28p). H3S28p was increased by inhibition of the catecholamine-sensitive protein phosphatase 1 and decreased by β-blocker pretreatment. By a series of in vitro and in vivo experiments, we show that the β-AR downstream protein kinase CaM kinase II (CaMKII) directly binds and phosphorylates H3S28. Whereas, in CaMKII-deficient myocytes, acute catecholaminergic stimulation resulted in some degree of H3S28p, sustained catecholaminergic stimulation almost entirely failed to induce H3S28p. Genome-wide analysis of CaMKII-mediated H3S28p in response to chronic β-AR stress by chromatin immunoprecipitation followed by massive genomic sequencing led to the identification of CaMKII-dependent H3S28p target genes. Forty percent of differentially H3S28p-enriched genomic regions were associated with differential, mostly increased expression of the nearest genes, pointing to CaMKII-dependent H3S28p as an activating histone mark. Remarkably, the adult hemoglobin genes showed an H3S28p enrichment close to their transcriptional start or end sites, which was associated with increased messenger RNA and protein expression. In summary, we demonstrate that chronic β-AR activation leads to CaMKII-mediated H3S28p in cardiomyocytes. Thus, H3S28p-dependent changes may play an unexpected role for cardiac hemoglobin regulation in the context of sympathetic activation. These data also imply that CaMKII may be a yet unrecognized stress-responsive regulator of hematopoesis., Competing Interests: The authors declare no competing interest.

Objectives: One-lung ventilation (OLV) may be complicated by hypoxemia. Ventilatory efficiency, defined as the ratio of minute ventilation to carbon dioxide output (V E /VCO 2 ), is increased with ventilation/perfusion mismatch and pulmonary artery hypertension, both of which may be associated with hypoxemia. Hence, the authors hypothesized increased V E /VCO 2 will predict hypoxemia during OLV., Design: Prospective observational study., Setting: Single-center, university, tertiary care hospital., Participants: The study comprised 50 consecutive lung resection candidates., Interventions: All patients underwent cardiopulmonary exercise testing before surgery. Patients who required inspired oxygen fraction (F i O 2 ) ≥0.7 to maintain arterial oxygen (O 2 ) saturation >90% after 30 minutes of OLV were considered to be hypoxemic. The Student t or Mann-Whitney U test were used for comparison of patients who became hypoxemic and those who did not. Multiple regression analysis adjusted for age, sex, and body mass index was used to evaluate which parameters were associated with the V E /VCO 2 slope. Data are summarized as mean ± standard deviation., Measurements and Main Results: Twenty-four patients (48%) developed hypoxemia. There was no significant difference in age, sex, and body mass index between hypoxemic and nonhypoxemic patients. However, patients with hypoxemia had a significantly higher V E /VCO 2 slope (30 ± 5 v 27 ± 4; p = 0.04) with exercise and lower partial pressure of oxygen/F i O 2 (129 ± 92 v 168 ± 88; p = 0.01), higher mean positive end-expiratory pressure (6.6 ± 1.5 v 5.6 ± 0.9 cmH 2 O; p = 0.02), and lower mean pulse oximetry O 2 saturation/F i O 2 index (127 ± 20 v 174 ± 17; p < 0.01) during OLV. Multiple regression showed V E /VCO 2 to be independently associated with the mean pulse oximetry O 2 saturation/F i O 2 index (b = -0.28; F = 3.1; p = 0.05)., Conclusions: An increased V E /VCO 2 slope may predict hypoxemia development in patients who undergo OLV., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Physiologically, leptin concentration is controlled by circadian rhythm. However, in critically ill patients, circadian rhythm is disrupted. Thus we hypothesized that circadian leptin concentration changes are not preserved in critically ill patients. Ten consecutive critically ill heart failure patients with the clinical indication for mechanical ventilation and sedation were included into our study. Plasma leptin concentration was measured every 4 h during the first day (0-24 h) and during the third day (48-72 h) after admission. During the first day, there were significant leptin concentration changes (ANOVA, p<0.05), characterized by an increase in concentration by 44 % (16-58 %); p=0.02 around noon (10 am-2 pm) and then a decrease in concentration by 7 % (1-27 %); p=0.04 in the morning (2 am-6 am). In contrast, there was no significant change in leptin concentration during the third day after admission (ANOVA, p=0.79). Based on our preliminary results, we concluded that in critically ill heart failure patients, the circadian rhythm of plasma leptin concentration seems to be preserved during the first but not during the third day after admission.

The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely, exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific deletion of Hdac4 show reduced exercise capacity, which was characterized by cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that NR4A1 negatively regulated contractile function in a manner that depended on the HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in which epigenetic regulation of a metabolic pathway affects calcium handling. Activation of this axis during intermittent physiological stress promotes cardiac function, whereas its impairment in sustained pathological cardiac stress leads to heart failure.

Background: Respiratory induced heart rate variability (rHRV) was analysed in mechanically ventilated patients during two levels of sedation and brain death. Our aim was to determine whether rHRV can distinguish between different levels of sedation and especially between brain death and sedated patients., Methods: In this study 30 critically ill and 23 brain death patients were included and four respiratory rates of 15, 12, 8 and 6 breaths per minute, each lasting 5 min were used. Two sedation levels, basal and deep, were performed in the critically ill patients. Heart rate and blood pressure changes induced by ventilation were subsequently detected and analysed., Results: Significant differences were found in rHRV and rHRV adjusted for tidal volume (rHRV/VT) between critically ill and brain death patients during slow breathing at 6 or 8 breaths per minute. The rHRV at 6 breaths per minute was below 15 ms in all brain death subjects except one. The rHRV/VT was lower than 25 ms/l at both 6 and 8 breaths per minute in all brain death patients and simultaneously at 75% of non-brain death patients was higher (specificity 1, sensitivity 0.24). Differences in rHRV and rHRV/VTs between basal and deep sedation were not significant., Conclusions: The main clinical benefit of the study is the finding that rHRV and rHRV/VT during 6 and 8 breaths per minute can differentiate between critically ill and brain death patients. An rHRV/VT exceeding 25 ms/l reliably excludes brain death.

Background: Ventilatory efficiency (V˙e/V˙co 2 slope [minute ventilation to carbon dioxide output slope]) has been shown to predict morbidity and mortality in lung resection candidates. Patients with increased V˙e/V˙co 2 during exercise also exhibit an increased V˙e/V˙co 2 ratio and a decreased end-tidal CO 2 at rest. This study hypothesized that ventilatory values at rest predict respiratory complications and death in patients undergoing thoracic surgical procedures., Methods: Inclusion criteria for this retrospective, multicenter study were thoracotomy and cardiopulmonary exercise testing as part of routine preoperative assessment. Respiratory complications were assessed from the medical records (from the hospital stay or from the first 30 postoperative days). For comparisons, Student's t test or the Mann-Whitney U test was used. Logistic regression and receiver operating characteristic analyses were performed for evaluation of measurements associated with respiratory complications. Data are summarized as mean ± SD; p <0.05 is considered significant., Results: Seventy-six subjects were studied. Postoperatively, respiratory complications developed in 56 (74%) patients. Patients with postoperative respiratory complications had significantly lower resting tidal volume (0.8 ± 0.3 vs 0.9 ± 0.3L; p = 0.03), lower rest end-tidal CO 2 (28.1 ± 4.3vs 31.5 ± 4.2 mm Hg; p < 0.01), higher resting V˙e/V˙co 2 ratio (45.1 ± 7.1 vs 41.0 ± 6.4; p = 0.02), and higher V˙e/V˙co 2 slope (34.9 ± 6.4 vs 31.2 ± 4.3; p = 0.01). Logistic regression (age and sex adjusted) showed resting end-tidal CO 2 to be the best predictor of respiratory complications (odds ratio: 1.21; 95% confidence interval: 1.06 to 1.39; area under the curve: 0.77; p = 0.01)., Conclusions: Resting end-tidal CO 2 may identify patients at increased risk for postoperative respiratory complications of thoracic surgical procedures., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective/background: Obstructive sleep apnea (OSA) is highly prevalent and often undiagnosed in surgical patients. The aim of this study was to compare polygraphy (PG) performed on sedated patients during surgery to overnight polysomnography (PSG). It was hypothesized that perioperative PG may be used to diagnose OSA., Patients/methods: Overnight PSG was performed three days prior to surgery. For surgery, spinal anesthesia and sedation with propofol infusion were used. Sedation depth was monitored by the Bispectral index and maintained for all patients (target level 75). Echocardiography studies were available in three patients, and all were diagnosed with diastolic dysfunction. Relatively high prevalence of CSA in patients with diastolic dysfunction has been previously reported. During surgery, PG recording (Embletta) was performed. Sleep apnea was defined by the type (central/obstructive apnea ≥50%) and by the apnea-hypopnea index (AHI) (events/hour: AHI < 5 no apnea; 5 ≤ AHI < 15 mild apnea; 15 ≤ AHI < 30 moderate apnea; AHI ≥30 severe apnea). Bland-Altman plots were used for analysis, and 2 × 2 decision statistics were calculated for several cut-off values of the AHI. Data were shown as bias with limits of agreement (bias±1.96 standard deviations)., Results: Nineteen subjects were studied: nine (47%) were diagnosed with obstructive, seven (37%) with central sleep apnea, and three (16%) with no sleep apnea by overnight PSG. Perioperative PG bias was 12 (-37; 61) for AHI; 6 (-25; 37) for obstructive apnea; 0 (-4; 4) for central apnea, and 6 (-31; 43) for hypopnea. For the detection of OSA, a PG cut-off value of AHI 5 yielded 89% sensitivity and 60% specificity, AHI 15 yielded 86% sensitivity and 67% specificity, and AHI 30 yielded 100% sensitivity and 71% specificity., Conclusion: Wide limits of agreement preclude perioperative PG to be used as a diagnostic method; however, it may be useful to screen sedated surgical patients for OSA., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Severe sepsis/septic shock is associated with high mortality. In Central Europe, there is a dearth of information on the prevalence and treatment of severe sepsis. The EPOSS (Data-based Evaluation and Prediction of Outcome in Severe Sepsis) project launched in 2011 was aimed at collecting data on patients with severe sepsis/septic shock., Methods: The EPOSS study processes data from the EPOSS project database, and is a retrospective, multicentre, observational study. This included all consecutive patients aged 18 and over who were admitted to participating ICUs from 1 January 2011 to 5 November 2013 and met the inclusion criteria of severe sepsis/septic shock. The primary endpoint was to analyse the relationship between in-hospital mortality (either in ICU or after discharge from ICU) and the type and number of fulfilled diagnostic and treatment interventions during the first 6 h after the diagnosis of severe sepsis/septic shock., Results: The collected dataset involved 1082 patients meeting the criteria of severe sepsis/septic shock. Following data validation, a final dataset of 897 patients was obtained. The average age of the patient group was 64.7 years; mortality at discharge from EPOSS ICUs was 35.5% and from hospital 40.7%. Of the 10 evaluated diagnostic and treatment interventions within the initial 6 hours of identifying severe sepsis/septic shock (i.e. fulfilment of SSC bundles), four or five diagnostic and treatment interventions were administered to 58.4% patients. Combined diagnostic and treatment interventions associated with the lowest in-hospital mortality were: CVP of ≥8-12 mm Hg & MAP of ≥65 mm Hg & Urine output at ≥0.5 mL/kg/h & Lactate of ≤4.0 mmol/L & Initial lactate measured & Antibiotics in the first hour. Lactate at <4 mmol/L and MAP of ≥65 mm Hg remained statistically significant even after adjustment for patient age and APACHE II score. Statistically significantly increased in-hospital mortality was found in patients admitted from general departments (45.7%) or from other ICUs (41.6%), compared to a lower in-hospital mortality of patients transferred from outpatient clinics (26.5%) or Emergency (38.0%). Severe sepsis/septic shock patients transferred from the department of internal medicine were associated with a higher in-hospital mortality (45.1%) than surgical patients (35.5%)., Conclusions: The most effective measures associated with the lowest in-hospital mortality in septic shock patients were CVP of ≥8-12 mm Hg, MAP of ≥65 mm Hg, urine output at ≥0.5 mL/kg/h, initial lactate level of ≤4.0 mmol/L and administration of antibiotics within the first hour.

Objective: Pulse pressure variations (PPV) are mainly influenced by ventilation. The impact of sedation on PPV is not known. The aim of the study was to test the influence of sedation on pulse pressure variation in mechanically ventilated critically ill patients and to compare PPV in critically ill and brain dead patients. Beside the absolute value of PPV, the adjusted values of pulse pressure were used to eliminate influence of ventilation., Design and Intervention: Mechanically ventilated patients received four different breath frequencies. At each frequency airway pressure was adjusted to keep the end-tidal CO2 stable. In critically ill patients the frequencies were applied at basal (bispectral index - BIS median 38) and deeper sedation (BIS 29)., Main Outcome Measures: Simultaneous haemodynamic and respiratory data including oesophageal pressure were recorded, adjusted PPV were calculated as PPV/VT, PPV/dPair, PPV/dPes where VT is tidal volume, dPair and dPes are airway and oesophageal driving pressures., Setting: University Hospital, ICU., Participants: 30 critically ill and 23 patients with a diagnosis of brain death., Results: The pulse pressure variation did not change significantly during deep sedation compared to basal sedation (median 10.3 vs 10.9%) whereas PPV/dPair increased from 0.7 to 0.8%/cmH2O and PPV/dPes from 1.9%/cmH2O to 2.4%/cmH2O (p=0.04). Patients with a diagnosis of brain death had higher PPV and adjusted PPV than critically ill patients., Conclusion: Deeper sedation increases values of adjusted pulse pressure variation., (Copyright © 2015 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Sepsis continues to be a major cause of death, disability, and health-care expenditure worldwide. Despite evidence suggesting that host genetics can influence sepsis outcomes, no specific loci have yet been convincingly replicated. The aim of this study was to identify genetic variants that influence sepsis survival., Methods: We did a genome-wide association study in three independent cohorts of white adult patients admitted to intensive care units with sepsis, severe sepsis, or septic shock (as defined by the International Consensus Criteria) due to pneumonia or intra-abdominal infection (cohorts 1-3, n=2534 patients). The primary outcome was 28 day survival. Results for the cohort of patients with sepsis due to pneumonia were combined in a meta-analysis of 1553 patients from all three cohorts, of whom 359 died within 28 days of admission to the intensive-care unit. The most significantly associated single nucleotide polymorphisms (SNPs) were genotyped in a further 538 white patients with sepsis due to pneumonia (cohort 4), of whom 106 died., Findings: In the genome-wide meta-analysis of three independent pneumonia cohorts (cohorts 1-3), common variants in the FER gene were strongly associated with survival (p=9·7 × 10(-8)). Further genotyping of the top associated SNP (rs4957796) in the additional cohort (cohort 4) resulted in a combined p value of 5·6 × 10(-8) (odds ratio 0·56, 95% CI 0·45-0·69). In a time-to-event analysis, each allele reduced the mortality over 28 days by 44% (hazard ratio for death 0·56, 95% CI 0·45-0·69; likelihood ratio test p=3·4 × 10(-9), after adjustment for age and stratification by cohort). Mortality was 9·5% in patients carrying the CC genotype, 15·2% in those carrying the TC genotype, and 25·3% in those carrying the TT genotype. No significant genetic associations were identified when patients with sepsis due to pneumonia and intra-abdominal infection were combined., Interpretation: We have identified common variants in the FER gene that associate with a reduced risk of death from sepsis due to pneumonia. The FER gene and associated molecular pathways are potential novel targets for therapy or prevention and candidates for the development of biomarkers for risk stratification., Funding: European Commission and the Wellcome Trust., (Copyright © 2015 Rautanen et al. Open Access article distributed under the terms of CC-BY-NC-SA. Published by .. All rights reserved.)

Introduction: Breast cancer treatment currently represents one of the biggest challenges in clinical oncology. The gold standard for axillary lymph node management is to perform sentinel node biopsy to avoid axillary dissection and its sequelae. The detection of radiocolloid flow outside the axillary nodes is a diagnostic and therapeutic challenge., Methods: A database search at the Department of Oncology of Palacky University, Olomouc, Czech Republic, identified 127 patients who underwent breast cancer resection with a sentinel node procedure and had radiocolloid flow into the internal mammary nodes. Sentinel node lymphoscintigraphy was performed after intraparenchymal injection. Clinical and pathological data were collected to identify possible risk factors., Results: Ten clinical and pathological parameters including age, tumor histology, axillary lymph node status, estrogen receptor expression, progesterone receptor expression, tumor grade, Ki-67 expression, Her-2 status, tumor size and tumor location were analyzed with regard to internal mammary node drainage. A cohort of 127 patients with detected drainage into the internal mammary nodes was compared with 135 patients without such drainage. Six significant risk factors, including age <50 years ( P <0.0313), tumor location in central and inner quadrants (P <0.012), larger tumor size (P <0.017), positive Her-2 status (P <0.025), progesterone receptor expression (P <10-4) and axillary lymph node involvement (P <0.01) were found to predict radiocolloid flow into the internal mammary nodes., Conclusion: Six parameters (patient age, tumor location, hormone receptor status, tumor size, Her-2 status and axillary lymph node status) should be considered in the management of breast cancer patients and help in the selection of patients for locoregional procedures encompassing the internal mammary nodes.

Objective: One of the pathologic changes that occurs during osteoarthritis (OA) is the degeneration of the pericellular matrix (PCM). Since the PCM is likely to be involved in mechanotransduction, this study was undertaken to investigate the effects of PCM-like matrix accumulation in zonal OA chondrocytes and their influence on chondrocyte response to compression., Methods: Superficial and middle/deep zone chondrocytes from macroscopically normal cartilage of OA knees were expanded and encapsulated in alginate gels. The effects of compression (short-term or long-term) and preculture on chondrocyte expression of various matrix molecules, cytokines, and matrix metalloproteinases (MMPs) were assessed. Additionally, nonexpanded chondrocytes were encapsulated in alginate and cultured in the presence or absence of transforming growth factor β1 (TGFβ1) and dexamethasone and analyzed following short-term compression experiments., Results: Expanded OA chondrocytes (superficial and middle/deep zone) that were precultured for 2 weeks under free-swelling conditions prior to dynamic compression responded more sensitively to loading and had increased matrix accumulation, increased interleukin-1β (IL-1β) and IL-4 levels, and decreased levels of MMP-2 (in the middle/deep zone) compared to the nonloaded controls. Compression also decreased MMP-3 and MMP-13 levels even without preculture. Nonexpanded chondrocytes did not respond to compression, but differences in gene expression were found depending on the zone of harvest, time in culture, and medium composition., Conclusion: Our findings demonstrate that with predeposited PCM-like matrix, compressive stimulation can enhance matrix protein accumulation in expanded OA chondrocytes. Investigations into how PCM or other matrix components differentially affect this balance under mechanical loading may provide invaluable insight into OA pathogenesis and the use of expanded cells in tissue engineering and regenerative medicine-based applications., (Copyright © 2013 by the American College of Rheumatology.)

Context: Hypothermia is known to influence thromboelastography (TEG). TEG reproducibility is generally low., Objective: The aim of this study was to evaluate the rationale of TEG temperature adjustment in patients during hypothermia. We hypothesised that temperature adjustment would not be important because of low TEG reproducibility., Design: Prospective observational study., Setting: Single-centre, secondary care study performed 01/2009 to 07/2010., Patients: Survivors of cardiopulmonary resuscitation in whom therapeutic hypothermia (32 to 34°C) was indicated for 24 h were recruited to the study which lasted 36 h. Four hundred samples from 30 patients (22 men and eight women) were obtained. No specific exclusion criteria were defined., Main Outcome Measures: Temperature adjusted and non-adjusted Kaolin-Heparinase and Rapid-TEG were done at 12-h intervals during the first 36 h., Results: Bland-Altman plots were used for analysis. During hypothermia, the bias of adjusted measurements was greater in clot formation variables for both Kaolin-Heparinase-TEG (from -15 to -19%) and Rapid-TEG (-9 to -25%) compared to normothermia (from -3 to 3% for Kaolin-Heparinase-TEG and -10 to 2% for Rapid-TEG). Bias of clot strength variables was not influenced by temperature adjustment (median -1%). The 95% limits of agreement were wide for clot formation variables and independent of temperature. In Kaolin-Heparinase-TEG (R -42 to 40% normothermia, -47 to 18% hypothermia) and in Rapid-TEG (R -117 to 97% normothermia, -114 to 95% hypothermia). Limits of agreement of clot strength variables were narrower and independent of temperature in Kaolin-Heparinase-TEG (MA -16 to 13% normothermia, -9 to 10% hypothermia) and also in Rapid-TEG (MA -27 to 24% normothermia, -18 to 20% hypothermia)., Conclusion: Although TEG analysis with temperature adjusted to the in-vivo value during hypothermia yields results with small systematic bias, the importance of temperature adjustment in clinical routine is low because of the precision limits of TEG measurement itself. Therefore, we see no need to perform TEG analysis at the in-vivo temperature.

Objectives: To validate a porcine model of ruptured abdominal aortic aneurysm (rAAA) repair., Design: Experimental study., Methods: Ten experimental and five sham-operated pigs were studied. Instrumentation for cardiac output (CO) measurement, regional blood flow (renal-REN and portal-PORT) and blood sampling (inferior vena cava (IVC), renal and portal vein) was done. Microcirculation was visualised sublingually and in ileostoma., Protocol: simulation of rAAA with bleeding (mean arterial pressure (MAP) 45 mmHg) and increased abdominal pressure (25 mmHg) for 4 h; 2 h of infrarenal clamp with shed blood retransfusion; 11 h of post-surgery care., Results: Six experimental pigs completed the protocol and are presented. Bleeding decreased CO to 95%, PORT to 80% and REN to 10% of baseline. From clamping on CO and PORT increased above baseline whereas REN (47%) with creatinine clearance remained compromised till the end. Microcirculation was affected more in ileum than sublingually. Approximately threefold increase in cytokines (tumour necrosis factor-α (TNF-alpha), interleukin (IL)-6 and IL-10) and oxidative stress markers (thiobarbituric acid-reactive substances (TBARs) and 4-hydroxy-2-trans-nonenal (HNE) was observed. Only mild increase in IL-6 and TBARs was observed in sham-operated animals. Organ histology did not reveal differences between groups., Conclusions: This near-lethal model of rAAA induced expected severe deterioration of haemodynamics and metabolism accompanied with a moderate inflammatory and oxidative stress response., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Aim: The study was carried out to evaluate the effect of several substrates on oxidative stress induced apoptosis and in K-562 cells., Methods: Glucose at 5, 11 and 30 mM concentrations was tested, as well as 5 mM glutamine and 5 mM fructose. The cells were exposed to tert-butylhydroperoxide (tBH) and apoptotic cells were evaluated by flow cytometry with FITC-Annexin V and propidium iodide. The effect of glucose concentration on DNA damage was evaluated using hydrogen peroxide and electrophoretic "DNA comets" assay at 5 mM and 30 mM glucose concentrations., Results: The exposure of cells to tBH resulted in increased number of apoptotic cells, and this effect was prevented by administration of an antioxidant - N-Acetyl cysteine. Rising concentrations of glucose added to the toxic effect of tBH; we also observed some toxic effect of fructose and no effect of glutamine. We found higher susceptibility to hydrogen peroxide induced DNA damage with 30 mM glucose concentration., Conclusion: Hyperglycemia increases the cell's susceptibility to oxidative stress and it also amplifies oxidative DNA damage. Glutamine - when used as a sole energetic substrate - showed no protective effect against oxidative stress.

Background: We investigated glucose metabolism in septic patients during hyperglycemic clamps and compared the different levels of insulinemia and glycemia., Methods: In 10 non-diabetic stable septic patients on mechanical ventilation with baseline glycemia >6 mmol/L and continuous insulin infusion, 3 steps of hyperinsulinemic clamp were performed after 8 hours without caloric intake. In step 1, the targets were insulinemia of 250 mIU/L and glycemia of 5 mmol/L; in step 2, insulinemia of 250 mIU/L and glycemia of 10 mmol/L; in step 3, insulinemia of 1250 mIU/L and glycemia of 5 mmol/L. Glucose uptake was calculated as the amount of glucose per time needed to maintain the target level of glycemia. Glucose oxidation was calculated from indirect calorimetry and urinary nitrogen losses. Values are provided as means +/- SD. A two-way analysis of variance and Scheffe's method were used for statistical analysis and p < .05 was considered significant., Results: At step 1, glucose uptake was lower than at step 2 (3.8 +/- 2.48 mg/kg/min and 7.9 +/- 3.45 mg/kg/min, respectively; p < .001). Glucose oxidation was also lower at step 1 (2.6 +/- 0.98 and 4.2 +/- 1.85 mg/kg/min, respectively; p < .01). Glucose storage was low at step 1 (0.7 +/- 1.39) and increased at step 2 (3.5 +/- 2.18; p < .05). In step 3, glucose uptake was 7.0 +/- 2.1, oxidation was 3.6 +/- 1.37, and storage was 2.9 +/- 2.79. There was no significant difference in all these parameters between steps 2 and 3. Energy expenditure between steps 1, 2 and 3 did not change (2294 + 307.42, 2334 + 341.53, and 2342 + 426.67 kcal/day, respectively). Alanine in plasma dropped significantly (p < .05): 10 mmol/L (311 +/- 55.88 mmol/L) at glycemia compared with 5 mmol/L (390 +/- 76 micromol/L) at insulinemia 250 mIU/L. It did not differ significantly from the values obtained at glycemia 5 mmol/L and insulinemia 1250 mIU/L (348 +/- 70.68 mmol/L). Even if the level of cytokines in sepsis was higher, there was no correlation between the insulin level in plasma (250 and 1250 mIU/L), glycemia (5 and 10 mmol/L) and cytokine level (IL-1beta, IL-2, IL-6, IL-8 and TNFalpha)., Conclusion: At insulinemia 250 mIU/L, a glucose level of 10 mmol/L seems to increase glucose uptake, oxidation, and storage compared with glycemia 5 mmol/L. This glucose uptake and oxidation at glycemia 10 mmol/L is comparable with the effect of extremely high insulinemia (1250 mIU/L) clamped at glycemia 5 mmol/L. A higher level of blood glucose or a high level of insulinemia significantly increases glucose uptake but not energy expenditure.

Background: The aim of our study is to assess the influence of the base solution on the availability of biologic insulin expressed in the value of total insulin using the radioimmunoassay method and to monitor the influence of the base solution on the total insulin concentration over time., Methods: Total insulin in a saline and in a total nutrient admixture was measured using the RIA method. In 15 experiments, the application of the saline by a perfusor (8 IU Actrapid HM, 100 IU/1 mL + 20 mL saline) was carried out at time intervals of baseline, 5, 10, 30, 60, 90, and 210 minutes. The application of the total nutrient admixture (8 IU Actrapid HM + 20 mL total nutrient admixture) was carried out in the same way. The MANOVA, ANOVA and paired t test with Bonferroni correction were then used for statistical evaluation., Results: The average values of insulin concentration in saline at given time intervals were 21.5 +/- 11.3 mIU/L (5.4% of the theoretically calculated concentration). The level of insulin in the total nutrient admixture did not change over time, and it reached the values of 115.2 +/- 22.3 (28.8% of the theoretically calculated concentration). Changes in insulin concentration in time were found only in the saline (ANOVA time effect p < .001 for saline; p = .26 for total nutrient admixture)., Conclusions: The availability of insulin was significantly higher in the total nutrient admixture solution than in the saline in the 3.5-hour experiment. The dependence of insulin concentration on time is present only in saline, and the main changes in insulin bioavailability are within first 60 minutes. The difference could be caused by smaller insulin absorption to the syringe walls and to the set, owing to the amino acids in the mixture. The question whether the amino acid concentration affects insulin bioavailability stays opened to other studies.

Introduction: It is recognized that administration of insulin with glucose decreases catabolic response in sepsis. The aim of the present study was to compare the effects of two levels of insulinaemia on glucose metabolism and energy expenditure in septic patients and volunteers., Methods: Glucose uptake, oxidation and storage, and energy expenditure were measured, using indirect calorimetry, in 20 stable septic patients and 10 volunteers in a two-step hyperinsulinaemic (serum insulin levels 250 and 1250 mIU/l), euglycaemic (blood glucose concentration 5 mmol/l) clamp. Differences between steps of the clamp (from serum insulin 1250 to 250 mIU/l) for all parameters were calculated for each individual, and compared between septic patients and volunteers using the Wilcoxon nonpaired test., Results: Differences in glucose uptake and storage were significantly less in septic patients. The differences in glucose oxidation between the groups were not statistically significant. Baseline energy expenditure was significantly higher in septic patients, and there was no significant increase in either step of the clamp in this group; when comparing the two groups, the differences between steps were significantly greater in volunteers., Conclusion: A hyperdynamic state of sepsis leads to a decrease in glucose uptake and storage in comparison with healthy volunteers. An increase in insulinaemia leads to an increase in all parameters of glucose metabolism, but the increases in glucose uptake and storage are significantly lower in septic patients. A high level of insulinaemia in sepsis increases glucose uptake and oxidation significantly, but not energy expenditure, in comparison with volunteers.

Objective: To evaluate the effects of prone position on hepato-splanchnic hemodynamics, metabolism and gut mucosal energy balance., Design: Prospective clinical study., Setting: Medical intensive care unit in a university hospital., Patients: Eleven hemodynamically stable patients with acute lung injury (ALI) requiring mechanical ventilation., Intervention: Patients were studied in the supine position, after 90 min in the prone position and after 90 min of supine repositioning., Measurements and Results: In addition to global hemodynamics we measured intra-abdominal pressure (IAP, bladder), hepato-splanchnic blood flow (HSBF, steady state indocyanine green technique using a hepatic vein catheter) and gastric mucosal-arterial PCO(2) gap (PCO(2) gap, automated air tonometry). Systemic hemodynamics did not change during the whole study. Prone positioning did not significantly affect IAP. HSBF as well as splanchnic oxygen consumption remained unaltered, too. Similarly, neither liver lactate uptake nor indocyanine green extraction were influenced by positional changes. Finally, stable regional hemodynamics were accompanied by an unchanged PCO(2) gap., Conclusion: We conclude that if IAP and systemic hemodynamics remain unaffected, the prone position in ALI patients compromises neither hepato-splanchnic perfusion nor gastric mucosal energy balance.

The effect of exercise on gastric mucosal energy status has not been fully elucidated. The aim of this study was to evaluate the impact of submaximal cycling on gastric mucosal energy balance and its relationship to changes in systemic energy status. Ten healthy volunteers (age 20-40 years) were investigated at rest (BL), during 30 min of submaximal exercise (E) on bicycle ergometry and during the 30 min after the completion of cycling. Gastric mucosal PCO(2) ( P(gm)CO(2)) was measured by air tonometry at 10-min intervals and the gastric mucosal-arterial PCO(2) difference ( PCO(2)gap) was calculated. Hemodynamics, arterial blood gases, lactate and pyruvate were also measured. PCO(2)gap significantly increased throughout exercise [BL: 0.2 kPa (median), -0.1-0.6 kPa (25th-75th percentiles); E(10 min): 1.0 kPa, 0.8-1.7 kPa; E(20 min): 1.35 kPa, 0.8-1.8 kPa; E(30 min): 1.5 kPa, 0.9-2.0 kPa]. The early changes in PCO(2)gap ( PCO(2)gap at E(10 min) minus PCO(2)gap at BL) correlated significantly and positively with corresponding changes in arterial lactate ( r(2)=0.58, P<0.05) and lactate-to-pyruvate ratio ( r(2)=0.72, P<0.05). On recovery, all metabolic parameters normalized within 30 min. We conclude that submaximal cycling in volunteers leads to the early derangement of gastric mucosal energy balance. The time course of PCO(2)gap parallels changes in systemic energy status.

To study gas exchange in the filter during continuous venovenous hemodiafiltration (CVVHDF), an air-tight heated mixing chamber with adjustable CO2 supply was constructed and connected to a CVVHDF monitor. Bicarbonate-free crystalloid (Part 1) and packed red blood cell (Part 2) solutions were circulated at 150 ml x min(-1). Gas exchange expressed as pre-postfilter difference in CO2 and O2 contents was measured at different CVVHDF settings and temperatures of circulating and dialysis solutions. Ultrafiltration was most efficacious for CO2 removal (at 1,000 ml x h(-1) ultrafiltration CO2 losses reached 13% of prefilter CO2 content). Addition of dialysis (1,000 ml x h(-1)) increased CO2 loss to 17% and at maximal parameters (filtration 3,000 ml x h(-1), dialysis 2,500 ml x h(-1)), the loss of CO2 amounted to 35% of prefilter content. Temperature changes of circulating and/or dialysis fluids had no significant impact on CO2 losses. The O2 exchange during CVVHDF was negligible. Currently used CVVHDF is only marginally effective in CO2 removal. Higher volume ultrafiltration combined with dialysis can be expected to reach clinical significance.

Objective: To test the hypothesis that dopexamine reduces postoperative mortality and morbidity in high-risk, major abdominal surgery patients, when given to fluid-resuscitated patients starting before the operation and continued for 24 hrs after surgery., Design: Prospective, randomized, controlled, double-blind multicenter trial., Setting: Intensive care units in 13 hospitals from six European countries., Patients: A total of 412 patients with predefined high-risk criteria, undergoing major abdominal surgery with an expected duration of at least 1.5 hrs., Interventions: The patients received placebo (n = 140), dopexamine at 0.5 microg/kg/min (n = 135), or dopexamine at 2.0 microg/kg/ min (n = 137) starting after preoperative hemodynamic stabilization and continued for 24 hrs after surgery., Measurements and Main Results: The primary outcome variable was mortality at 28 days. Analysis was by intention to treat. Dopexamine had no effect on mortality (at 28 days, 13%, 7%, and 15%, for the groups receiving placebo, dopexamine at 0.5 microg/kg/ min, and dopexamine at 2.0 microg/kg/min, respectively), despite the expected dose-dependent hemodynamic responses. No effect was observed on the occurrence of organ dysfunction, duration of intensive care unit stay, or length of hospital stay., Conclusion: We conclude that dopexamine in doses that result in increased cardiac output and oxygen delivery after preoperative stabilization with fluids does not improve outcome after major abdominal surgery compared with fluids alone. Based on post hoc subgroup analysis and stratification according to the number of risk factors, we suggest that the concept should be further tested in patients at higher risk of complications or undergoing emergency surgery.