Unexpected NADPH Hydratase Activity in the Nitrile Reductase QueF from Escherichia coli.

The nitrile reductase QueF catalyzes NADPH-dependent reduction of the nitrile group of preQ0 (7-cyano-7-deazaguanine) into the primary amine of preQ1 (7-aminomethyl-7-deazaguanine), a biologically unique reaction important in bacterial nucleoside biosynthesis. Here we have discovered that the QueF from Escherichia coli-its D197A and E89L variants in particular (apparent kcat ≈10-2  min-1 )-also catalyze the slow hydration of the C5=C6 double bond of the dihydronicotinamide moiety of NADPH. The enzymatically C6-hydrated NADPH is a 3.5:1 mixture of R and S forms and rearranges spontaneously through anomeric epimerization (ß→α) and cyclization at the tetrahydronicotinamide C6 and the ribosyl O2. NADH and 1-methyl- or 1-benzyl-1,4-dihydronicotinamide are not substrates of the enzymatic hydration. Mutagenesis results support a QueF hydratase mechanism, in which Cys190-the essential catalytic nucleophile for nitrile reduction-acts as the general acid for protonation at the dihydronicotinamide C5 of NADPH. Thus, the NADPH hydration in the presence of QueF bears mechanistic resemblance to the C=C double bond hydration in natural hydratases.

End-of-life decisions in surgical intensive care medicine - the relevance of blood transfusions.

BACKGROUND: End-of-life decisions (EOLDs) are common in the intensive care unit (ICU). EOLDs underlie a dynamic process and limitation of ICU-therapies is often done sequentially. Questionnaire-based and observational studies on medical ICUs and in palliative care reveal blood transfusions as the first therapy physicians withhold as an EOLD. METHODS: To test whether this practice also applies to surgical ICU-patients, in an observational study, all deceased patients (n = 303) admitted to an academic surgical ICU in a three-year period were analyzed for the process of limiting ICU-therapies. RESULTS: Restriction of further surgery (85.4%) and limiting doses of vasopressors (75.8%) were the most frequent forms of limitations in surgical ICU therapies. Surgical patients, who had blood transfusions withheld (44.6%), had more ICU-therapies withheld or withdrawn simultaneously than patients who had transfusions maintained (5 ± 2 vs. 2 ± 1, p < 0.001). Secondary EOLDs and subsequent limitations occurred less frequently in patients who had transfusions withheld with their first EOLD (17.1% vs. 35.6%, p < 0.05). CONCLUSION: Limitation orders for blood transfusions are not a prioritized decision in EOLDs of surgical ICU patients. Withholding blood transfusions correlates with discontinuation of further significant life-support therapies. This suggests that EOLDs to withhold blood transfusions are part of the most advanced limitations of therapy on the surgical ICU.

End-of-life decisions in intensive care medicine-shared decision-making and intensive care unit length of stay.

BACKGROUND: Most deaths on the intensive care unit (ICU) occur after end-of-life decisions (EOLD) have been made. During the decision-making process, responsibility is often shared within the caregiver team and with the patients' surrogates. The intensive care unit length of stay (ICU-LOS) of surgical ICU-patients depends on the primary illness as well as on the past medical history. Whether an increasing ICU-LOS affects the process of EOLD making is unknown. METHODS: A retrospective analysis was conducted on all deceased patients (n = 303) in a 22-bed surgical ICU of a German university medical center. Patient characteristics were compared between surgical patients with an ICU-LOS up to 1 week and those with an ICU-LOS of more than 7 days. RESULTS: Deceased patients with a long ICU-LOS received more often an EOLD (83.2% vs. 63.6%, p = 0.001). Groups did not differ in urgency of admission. Attending intensivists participated in every EOLD. Participation of surgeons was significantly higher in patients with a short ICU-LOS (24.1%, p = 0.003), whereas nurses and the patients' surrogates were involved more frequently in patients with a long ICU-LOS (18.8%, p = 0.021 and 18.9%, p = 0.018, respectively). CONCLUSION: EOLDs of surgical ICU-patients are associated with the ICU-LOS. Reversal of the primary illness leads the early ICU course, while in prolonged ICU-LOS, the patients' predicted will and the expected post-ICU-quality of life gain interest. Nurses and the patients' surrogates participate more frequently in EOLDs with prolonged ICU-LOS. To improve EOLD making on surgical ICUs, the ICU-LOS associated participation of the different decision makers needs further prospective analysis.

A brain machine interface framework for exploring proactive control of smart environments.

Brain machine interfaces (BMIs) can substantially improve the quality of life of elderly or disabled people. However, performing complex action sequences with a BMI system is onerous because it requires issuing commands sequentially. Fundamentally different from this, we have designed a BMI system that reads out mental planning activity and issues commands in a proactive manner. To demonstrate this, we recorded brain activity from freely-moving monkeys performing an instructed task and decoded it with an energy-efficient, small and mobile field-programmable gate array hardware decoder triggering real-time action execution on smart devices. Core of this is an adaptive decoding algorithm that can compensate for the day-by-day neuronal signal fluctuations with minimal re-calibration effort. We show that open-loop planning-ahead control is possible using signals from primary and pre-motor areas leading to significant time-gain in the execution of action sequences. This novel approach provides, thus, a stepping stone towards improved and more humane control of different smart environments with mobile brain machine interfaces.

Catecholamine dosing and survival in adult intensive care unit patients.

BACKGROUND: Volume management and vasopressor support remain the gold standard of critical care for patients with shock. However, prolonged therapy with catecholamines in high doses is associated with a negative patient outcome. The aim of the present study was to analyze the administered levels of catecholamines over time with respect to survival, and to identify a cut-off to allow a prediction of survival. METHODS: Consecutively, 9,108 adult patients during 22 months were evaluated. This group included 1,543 patients treated with epinephrine and/or norepinephrine with any dose at any time. Time and dosages of the applied drugs, the sequential organ failure assessment and acute and chronic health evaluation II scores on admission and daily, the length of intensive care unit stay, and the outcomes were recorded. RESULTS: The non-survivors received higher doses of norepinephrine and epinephrine than the survivors (p < 0.001). The receiver operator characteristic curve for the area under the curve with non-survival as the classifier revealed a cut-off level of 294.33 µg/kg for norepinephrine with a sensitivity of 74.73 % and a specificity of 70.48 % and a cut-off for epinephrine of 70.36 µg/kg with a sensitivity of 83.87 % and a specificity of 72.79 %. Dose-dependent time curves using these cut-off values were calculated. CONCLUSIONS: Survival of patients with prolonged therapy with norepinephrine and epinephrine above the evaluated thresholds is poor, whereas short-term application of high-dose catecholamines is not associated with poor outcome. Therefore, it remains for the individual clinician, patients, and their surrogates to decide whether the use of high doses of vasopressors is appropriate in view of the low probability of survival.

Quality indicators in intensive care medicine for Germany - fourth edition 2022.

The measurement of quality indicators supports quality improvement initiatives. The German Interdisciplinary Society of Intensive Care Medicine (DIVI) has published quality indicators for intensive care medicine for the fourth time now. After a scheduled evaluation after three years, changes in several indicators were made. Other indicators were not changed or only minimally. The focus remained strongly on relevant treatment processes like management of analgesia and sedation, mechanical ventilation and weaning, and infections in the ICU. Another focus was communication inside the ICU. The number of 10 indicators remained the same. The development method was more structured and transparency was increased by adding new features like evidence levels or author contribution and potential conflicts of interest. These quality indicators should be used in the peer review in intensive care, a method endorsed by the DIVI. Other forms of measurement and evaluation are also reasonable, for example in quality management. This fourth edition of the quality indicators will be updated in the future to reflect the recently published recommendations on the structure of intensive care units by the DIVI.

Effects of intensivist coverage in a post-anaesthesia care unit on surgical patients' case mix and characteristics of the intensive care unit.

INTRODUCTION: There is an increasing demand for intensive care in hospitals, which can lead to capacity limitations in the intensive care unit (ICU). Due to postponement of elective surgery or delayed admission of emergency patients, outcome may be negatively influenced. To optimize the admission process to intensive care, the post-anaesthesia care unit (PACU) was staffed with intensivist coverage around the clock. The aim of this study is to demonstrate the impact of the PACU on the structure of ICU-patients and the contribution to overall hospital profit in terms of changes in the case mix index for all surgical patients. METHODS: The administrative data of all surgical patients (n = 51,040) 20 months prior and 20 months after the introduction of a round-the-clock intensivist staffing of the PACU were evaluated and compared. RESULTS: The relative number of patients with longer length of stay (LOS) (more than seven days) in the ICU increased after the introduction of the PACU. The average monthly number of treatment days of patients staying less than 24 hours in the ICU decreased by about 50% (138.95 vs. 68.19 treatment days, P <0.005). The mean LOS in the PACU was 0.45 (± 0.41) days, compared to 0.27 (± 0.2) days prior to the implementation. The preoperative times in the hospital decreased significantly for all patients. The case mix index (CMI) per hospital day for all surgical patients was significantly higher after the introduction of a PACU: 0.286 (± 0.234) vs. 0.309 (± 0.272) P <0.001 CMI/hospital day. CONCLUSIONS: The introduction of a PACU and the staffing with intensive care staff might shorten the hospital LOS for surgical patients. The revenues for the hospital, as determined by the case mix index of the patients per hospital day, increased after the implementation of a PACU and more patients can be treated in the same time, due to a better use of resources.

The effect of non-invasive ventilation on intra-abdominal pressure.

BACKGROUND: Non-invasive ventilation is a well-established treatment modality in patients with respiratory failure of different aetiologies. A previous case report described how non-invasive ventilation caused gastric distension and intra-abdominal hypertension with subsequent cardio-respiratory arrest and clinical recovery following resuscitative efforts including gastric decompression with a nasogastric tube. METHODS: The aim of this prospective multicentre observational study was to assess the effect of non-invasive ventilation on intra-abdominal pressure. Following informed consent, intra-abdominal pressure and PaCO2 were measured before and after the application of non-invasive ventilation for up to three days in critically ill patients requiring non-invasive ventilation. RESULTS: Thirty-five patients were enrolled; mean (±SD) age of 67.8 (±12.5) years, median (interquartile range) body mass index of 27.9 (24.5-30.0) kg m-2, Acute Physiology and Chronic Health Evaluation II score of 15.8 (±6.4). On admission and after 24 hours of non-invasive ventilation, intra-abdominal pressure was 11.0 (7.5-15.0) mm Hg and 11.0 (8.5-14.5) mm Hg (P = 0.82) and PaCO2 was 44.4 (±11.4) mm Hg and 51.3 (±14.3) mm Hg (P = 0.19), respectively. CONCLUSIONS: The application of non-invasive ventilation was not associated with an increase in intra-abdominal pressure over 72 hours in this small observational study. Thus, it appears that intra-abdominal pressure does not frequently increase when applying non-invasive ventilation in critically ill patients with respiratory failure.

The effect of hospital size and surgical service on case cancellation in elective surgery: results from a prospective multicenter study.

BACKGROUND: Short-term case cancellation causes frustration for anesthesiologists, surgeons, and patients and leads to suboptimal use of operating room (OR) resources. In many facilities, >10% of all cases are cancelled on the day of surgery, thereby causing major problems for OR management and anesthesia departments. The effect of hospital type and service type on case cancellation rate is unclear. METHODS: In 25 hospitals of different types (university hospitals, large community hospitals, and mid- to small-size community hospitals) we studied all elective surgical cases of the following subspecialties over a period of 2 weeks: general surgery, trauma/orthopedics, urology, and gynecology. Case cancellation was defined as any patient who had been scheduled to be operated on the next day, but cancelled after the finalization of the OR plan on the day before surgery. A list of possible cancellation reasons was provided for standardized documentation. RESULTS: A total of 6009 anesthesia cases of 82 different anesthesia services were recorded during the study period. Services in university hospitals had cancellation rates 2.23 (95% confidence interval [CI] = 1.49 to 3.34) times higher than mid- to small-size community hospitals 12.4% (95% CI = 11.0% to 13.8%) versus 5.0% (95% CI = 4.0% to 6.2%). Of the surgical services, general surgical services had a significantly (1.78, 95% CI = 1.25 to 2.53) higher cancellation rate than did gynecology services-11.0% (95% CI = 9.7% to 12.5%) versus 6.6% (95% CI = 5.1% to 8.4%). CONCLUSIONS: When benchmarking cancellation rates among hospitals, comparisons should control for academic institutions having higher incidences of case cancellation than nonacademic hospitals and general surgery services having higher incidences than other services.

Rabbit neurospheres as a novel in vitro tool for studying neurodevelopmental effects induced by intrauterine growth restriction.

The aim of this study was to develop a rabbit neurosphere culture to characterize differences in basic processes of neurogenesis induced by intrauterine growth restriction (IUGR). A novel in vitro neurosphere culture has been established using fresh or frozen neural progenitor cells from newborn (PND0) rabbit brains. After surgical IUGR induction in pregnant rabbits and cesarean section 5 days later, neural progenitor cells from both control and IUGR groups were isolated and directly cultured or frozen at -80°C. These neural progenitor cells spontaneously formed neurospheres after 7 days in culture. The ability of control and IUGR neurospheres to migrate, proliferate, differentiate to neurons, astrocytes, or oligodendrocytes was compared and the possibility to modulate their responses was tested by exposure to several positive and negative controls. Neurospheres obtained from IUGR brains have a significant impairment in oligodendrocyte differentiation, whereas no significant differences are observed in other basic processes of neurogenesis. This impairment can be reverted by in vitro exposure of IUGR neurospheres to thyroid hormone, which is known to play an essential role in white matter maturation in vivo. Our new rabbit neurosphere model and the results of this study open the possibility to test several substances in vitro as neuroprotective candidates against IUGR induced neurodevelopmental damage while decreasing the number of animals and resources and allowing a more mechanistic approach at a cellular functional level.

The future development of intensive care quality indicators - a methods paper.

Introduction: Medical quality indicators (QI) are important tools in the evaluation of medical quality. Their development is subject to specific methodological requirements, which include practical applicability. This is especially true for intensive care medicine with its complex processes and their interactions. This methods paper presents the status quo and shows necessary methodological developments for intensive care QI. For this purpose, a cooperation with the Association of the Scientific Medical Societies' Institute for Medical Knowledge Management (AWMF-IMWi) was established. Methodology: Review of published German manuals for QI development from guidelines and narrative review of quality indicators with a focus on evidence and consensus-based guideline recommendations. Future methodological adaptations of indicator development for improved operationalization, measurability and pilot testing are presented, and a development process is proposed. Results: The development of intensive care quality indicators in Germany is based on an established process. In the future, additional evaluation criteria (QUALIFY criteria) will be applied to assess the evidence base. In addition, a continuous exchange between the national steering committee of the DIVI responsible for QI development and guideline development groups involved in intensive care medicine is planned. Conclusion: Intensive care quality indicators will have to meet improved methodological requirements in the future by means of an improved development process. Future QI development is intended to improve the structure of the development process, with a focus on scientific evidence and a link to guideline projects. This is intended to achieve the goal of a broad application of QI and to further evaluate its relevance for patient outcome and performance of institutions.

Multi-objective optimization with controlled model assisted evolution strategies.

Evolutionary algorithms perform robust search in complex and high dimensional search spaces, but require a large number of fitness evaluations to approximate optimal solutions. These characteristics limit their potential for hardware in the loop optimization and problems that require extensive simulations and calculations. Evolutionary algorithms do not maintain their knowledge about the fitness function as they only store solutions of the current generation. In contrast, model assisted evolutionary algorithms utilize the information contained in previously evaluated solutions in terms of a data based model. The convergence of the evolutionary algorithm is improved as some selection decisions rely on the model rather than to invoke expensive evaluations of the true fitness function. The novelty of our scheme stems from the preselection of solutions based on an instance based fitness model, in which the selection pressure is adjusted to the quality of model. This so-called lambda-control adapts the number of true fitness evaluations to the monitored model quality. Our method extends the previous approaches for model assisted scalar optimization to multi-objective problems by a proper redefinition of model quality and preselection pressure control. The analysis on multi-objective benchmark optimization problems not only confirms the superior convergence of the model assisted evolution strategy in comparison with a multi-objective evolution strategy but also the positive effect of regulated preselection in contrast to merely static preselection.

Modular Neural Mechanisms for Gait Phase Tracking, Prediction, and Selection in Personalizable Knee-Ankle-Foot-Orthoses.

Orthoses for the lower limbs support patients to perform movements that they could not perform on their own. In traditional devices, generic gait models for a limited set of supported movements restrict the patients mobility and device acceptance. To overcome such limitations, we propose a modular neural control approach with user feedback for personalizable Knee-Ankle-Foot-Orthoses (KAFO). The modular controller consists of two main neural components: neural orthosis control for gait phase tracking and neural internal models for gait prediction and selection. A user interface providing online feedback allows the user to shape the control output that adjusts the knee damping parameter of a KAFO. The accuracy and robustness of the control approach were investigated in different conditions including walking on flat ground and descending stairs as well as stair climbing. We show that the controller accurately tracks and predicts the user's movements and generates corresponding gaits. Furthermore, based on the modular control architecture, the controller can be extended to support various distinguishable gaits depending on differences in sensory feedback.

Agreement of central venous saturation and mixed venous saturation in cardiac surgery patients.

OBJECTIVE: Comparison of the bias and the limits of agreement (LOA; 2 SD) of the central venous saturation (S(cv)O(2)) before, during and after coronary artery bypass graft surgery with a simultaneous measurement of the mixed venous saturation (S(v)O(2)). DESIGN AND SETTING: Prospective controlled study in a university hospital department of anaesthesiology. PATIENTS: 60 patients with coronary artery bypass surgery, 300 paired measurements of S(v)O(2) and S(cv)O(2). MEASUREMENTS AND RESULTS: S(cv)O(2) and S(v)O(2) were analysed after induction of anaesthesia 15 min after cardiopulmonary bypass and 1, 6 and 18 h after admission to the intensive care unit. Regression analysis for the pooled measurements of S(cv)O(2) and S(v)O(2) showed a correlation R (2) = 0.52. After induction of anaesthesia 15 min after weaning from cardiopulmonary bypass and 6 h after admission to the intensive care unit the correlation coefficient was R (2) = 0.46, on admission to the intensive care unit it was R (2) = 0.42, and at 18 h it was R (2) = 0.38. Bland-Altman analysis for the measurements of S(cv)O(2) and S(v)O(2) showed a mean bias and LOA of 0.3% and -11.9 to +12.4%. In patients with a low S(cv)O(2) there was a trend to overestimate the S(v)O(2) by using the S(cv)O(2). The only factor that influenced the DeltaS(v)O(2) - S(cv)O(2) was the oxygen extraction rate (R (2) = 0.16). In patients with S(cv)O(2) below 70% this association was more pronounced (R (2) = 0.60). CONCLUSIONS: Our findings demonstrate that oxygen extraction rate is the major factor in the difference between S(v)O(2) and S(cv)O(2). Under certain circumstances S(cv)O(2) differed substantially from S(v)O(2). Therefore in selected patients both parameters should be monitored to exclude general or focal hypoperfusion.

Quality indicators in intensive care medicine for Germany - third edition 2017.

Quality improvement in medicine is depending on measurement of relevant quality indicators. The quality indicators for intensive care medicine of the German Interdisciplinary Society of Intensive Care Medicine (DIVI) from the year 2013 underwent a scheduled evaluation after three years. There were major changes in several indicators but also some indicators were changed only minimally. The focus on treatment processes like ward rounds, management of analgesia and sedation, mechanical ventilation and weaning, as well as the number of 10 indicators were not changed. Most topics remained except for early mobilization which was introduced instead of hypothermia following resuscitation. Infection prevention was added as an outcome indicator. These quality indicators are used in the peer review in intensive care, a method endorsed by the DIVI. A validity period of three years is planned for the quality indicators.

Antigenic and cellular localisation analysis of the severe acute respiratory syndrome coronavirus nucleocapsid protein using monoclonal antibodies.

A member of the family of coronaviruses has previously been identified as the cause of the severe acute respiratory syndrome (SARS). In this study, several monoclonal antibodies against the nucleocapsid protein have been generated to examine distribution of the nucleocapsid in virus-infected cells and to study antigenic regions of the protein. Confocal microscopic analysis identified nucleocapsids packaged in vesicles in the perinuclear area indicating viral synthesis at the endoplasmic reticulum and Golgi apparatus. The monoclonal antibodies bound to the central and carboxyterminal half of the nucleocapsid protein indicating prominent exposure and immunogenicity of this part of the protein. Antibodies recognised both linear and conformational epitopes. Predictions of antigenicity using mathematical modelling based on hydrophobicity analysis of SARS nucleoprotein could not be confirmed fully. Antibody binding to discontinuous peptides provides evidence that amino acids 274-283 and 373-382 assemble to a structural unit particularly rich in basic amino acids. In addition, amino acids 286-295, 316-325 and 361-367 that represent the epitope recognised by monoclonal antibody 6D11C1 converge indicating a well-structured C-terminal region of the SARS virus nucleocapsid protein and functional relationship of the peptide regions involved. Alternatively, dimerisation of the nucleocapsid protein may result in juxtaposition of the amino acid sequences 316-325 and 361-367 on one nucleoprotein molecule to amino acid 286-295 on the second peptide. The monoclonal antibodies will be available to assess antigenicity and immunological variabilities between different SARS CoV strains.

Levosimendan may improve survival in patients requiring mechanical assist devices for post-cardiotomy heart failure.

INTRODUCTION: Most case series suggest that less than half of the patients receiving a mechanical cardiac assist device as a bridge to recovery due to severe post-cardiotomy heart failure survive to hospital discharge. Levosimendan is the only inotropic substance known to improve medium term survival in patients suffering from severe heart failure. METHODS: This retrospective analysis covers our single centre experience. Between July 2000 and December 2004, 41 consecutive patients were treated for this complication. Of these, 38 patients are included in this retrospective analysis as 3 patients died in the operating room. Levosimendan was added to the treatment protocol for the last nine patients. RESULTS: Of 29 patients treated without levosimendan, 20 could be weaned off the device, 9 survived to intensive care unit discharge, 7 left hospital alive and 3 survived 180 days. All 9 patients treated with levosimendan could be weaned, 8 were discharged alive from ICU and hospital, and 7 lived 180 days after surgery (p < 0.002 for 180 day survival). Plasma lactate after explantation of the device was significantly lower (p = 0.002), as were epinephrine doses. Time spent on renal replacement therapy was significantly shorter (p = 0.023). CONCLUSION: Levosimendan seems to improve medium term survival in patients failing to wean off cardiopulmonary bypass and requiring cardiac assist devices as a bridge to recovery. This retrospective analysis justifies prospective randomised investigations of levosimendan in this group of patients.

The impact of an hematocrit of 20% during normothermic cardiopulmonary bypass for elective low risk coronary artery bypass graft surgery on oxygen delivery and clinical outcome--a randomized controlled study [ISRCTN35655335].

INTRODUCTION: Cardiopulmonary bypass (CPB) induces hemodilutional anemia, which frequently requires the transfusion of blood products. The objective of this study was to evaluate oxygen delivery and consumption and clinical outcome in low risk patients who were allocated to an hematocrit (Hct) of 20% versus 25% during normothermic CPB for elective coronary artery bypass graft (CABG) surgery. METHODS: This study was a prospective, randomized and controlled trial. Patients were subjected to normothermic CPB (35 to 36 degrees C) and were observed until discharge from the intensive care unit (ICU). Outcome measures were calculated whole body oxygen delivery, oxygen consumption and clinical outcome. A nonparametric multivariate analysis of variance for repeated measurements and small sample sizes was performed. RESULTS: In a total of 54 patients (25% Hct, n = 28; 20% Hct, n = 26), calculated oxygen delivery (p = 0.11), oxygen consumption (p = 0.06) and blood lactate (p = 0.60) were not significantly different between groups. Clinical outcomes were not different between groups. CONCLUSION: These data indicate that an Hct of 20% during normothermic CPB maintained calculated whole body oxygen delivery above a critical level after elective CABG surgery in low risk patients. The question of whether a transfusion trigger in excess of 20% Hct during normothermic CPB is still supported requires a larger prospective and randomized trial.

Small-dose epoprostenol decreases systemic oxygen consumption and splanchnic oxygen extraction during normothermic cardiopulmonary bypass.

Normothermic, nonpulsatile cardiopulmonary bypass (CPB) impairs systemic and splanchnic oxygen transport and increases gastrointestinal permeability. It is an important therapeutic goal to avoid splanchnic dysoxia during CPB. Small-dose prostacyclin therapy improves splanchnic oxygen transport and microcirculation in septic patients. In this study, we sought to determine if during cardiac surgery, the prostacyclin analog epoprostenol improves the balance of systemic and splanchnic oxygen transport. Eighteen patients undergoing cardiac valve replacement were randomized to receive either epoprostenol (3 ng x kg(-1) x min(-1)) or placebo during, and for 1 hour after, surgery. Systemic and splanchnic oxygen delivery, consumption, and extraction and arterial, mixed venous, and hepato-venous lactate concentrations were measured before, during, and after CPB. Gastrointestinal permeability was measured 1 day before and 1 day after surgery using the triple sugar permeability test. During CPB, the epoprostenol group had decreased systemic oxygen consumption and splanchnic oxygen extraction (P = 0.024). These effects were not present 1 hour after the end of epoprostenol infusion. The study was not adequately powered to determine whether epoprostenol altered the trend towards increased lactate metabolism and increased postoperative gastrointestinal permeability, nor could we demonstrate any differences between groups in clinically relevant end-points. In conclusion, these findings suggest that during normothermic CPB, small-dose epoprostenol therapy may reduce systemic oxygen consumption and splanchnic oxygen extraction.