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Competing Interests: BG is currently CEO and majority shareholder of Healthplus.ai B.V. and subsidiaries. BG has also consulted for and received research grants from Philips NV and Edwards Lifesciences LLC. SvdM works as a data scientist and PhD at Healthplus.ai and LUMC. SvdM owns share options in Healthplus.ai.

Introduction: Hypotension in the ICU is common, yet management is challenging and variable. Insight in management by ICU physicians and nurses may improve patient care and guide future hypotension treatment trials and guidelines., Methods: We conducted an international survey among ICU personnel to provide insight in monitoring, management, and perceived consequences of hypotension., Results: Out of 1464 respondents, 1197 (81.7%) were included (928 physicians (77.5%) and 269 nurses (22.5%)). The majority indicated that hypotension is underdiagnosed (55.4%) and largely preventable (58.8%). Nurses are primarily in charge of monitoring changes in blood pressure, physicians are in charge of hypotension treatment. Balanced crystalloids, dobutamine, norepinephrine, and Trendelenburg position were the most frequently reported fluid, inotrope, vasopressor, and positional maneuver used to treat hypotension. Reported complications believed to be related to hypotension were AKI and myocardial injury. Most ICUs do not have a specific hypotension treatment guideline or protocol (70.6%), but the majority would like to have one in the future (58.1%)., Conclusions: Both physicians and nurses report that hypotension in ICU patients is underdiagnosed, preventable, and believe that hypotension influences morbidity. Hypotension management is generally not protocolized, but the majority of respondents would like to have a specific hypotension management protocol., Competing Interests: Declaration of Competing Interest TWLS received research grants and honoraria from Edwards Lifesciences (Irvine, CA, USA) and Masimo Inc. (Irvine, CA, USA) for consulting and lecturing and from Pulsion Medical Systems SE (Feldkirchen, Germany) for lecturing (all payments made to institution). DPV reported receipt of personal fees and other from Edwards Lifesciences (Irvine, CA, USA) as well as consultancy fees and research grants from Philips (Eindhoven, the Netherlands) and Hemologic (Amersfoort, the Netherlands). APJV reported receipt of grants from Edwards Lifesciences (Irvine, CA, USA) and Philips (Eindhoven, the Netherlands). WHV, JS, JS, SR, TGVC, WKL, PT, PWGE, PRT, JB, BFG, and FP declare that they have no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Although hypotension in ICU patients is associated with adverse outcome, currently used definitions are unknown and no universally accepted definition exists., Methods: We conducted an international, peer-reviewed survey among ICU physicians and nurses to provide insight in currently used definitions, estimations of incidence, and duration of hypotension., Results: Out of 1394 respondents (1055 physicians (76%) and 339 nurses (24%)), 1207 (82%) completed the questionnaire. In all patient categories, hypotension definitions were predominantly based on an absolute MAP of 65 mmHg, except for the neuro(trauma) category (75 mmHg, p < 0.001), without differences between answers from physicians and nurses. Hypotension incidence was estimated at 55%, and time per day spent in hypotension at 15%, both with nurses reporting higher percentages than physicians (estimated mean difference 5%, p = 0.01; and 4%, p < 0.001)., Conclusions: An absolute MAP threshold of 65 mmHg is most frequently used to define hypotension in ICU patients. In neuro(trauma) patients a higher threshold was reported. The majority of ICU patients are estimated to endure hypotension during their ICU admission for a considerable amount of time, with nurses reporting a higher estimated incidence and time spent in hypotension than physicians., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Intraoperative hypotension, with varying definitions in literature, may be associated with postoperative complications. The aim of this meta-analysis was to assess the association of intraoperative hypotension with postoperative morbidity and mortality., Methods: MEDLINE, Embase and Cochrane databases were searched for studies published between January 1990 and August 2018. The primary endpoints were postoperative overall morbidity and mortality. Secondary endpoints were postoperative cardiac outcomes, acute kidney injury, stroke, delirium, surgical outcomes and combined outcomes. Subgroup analyses, sensitivity analyses and a meta-regression were performed to test the robustness of the results and to explore heterogeneity., Results: The search identified 2931 studies, of which 29 were included in the meta-analysis, consisting of 130 862 patients. Intraoperative hypotension was associated with an increased risk of morbidity (odds ratio (OR) 2.08, 95 per cent confidence interval 1.56 to 2.77) and mortality (OR 1.94, 1.32 to 2.84). In the secondary analyses, intraoperative hypotension was associated with cardiac complications (OR 2.44, 1.52 to 3.93) and acute kidney injury (OR 2.69, 1.31 to 5.55). Overall heterogeneity was high, with an I2 value of 88 per cent. When hypotension severity, outcome severity and study population variables were added to the meta-regression, heterogeneity was reduced to 50 per cent., Conclusion: Intraoperative hypotension during non-cardiac surgery is associated with postoperative cardiac and renal morbidity, and mortality. A universally accepted standard definition of hypotension would facilitate further research into this topic., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Intraoperative hypotension is associated with increased morbidity and mortality. Current treatment is mostly reactive. The Hypotension Prediction Index (HPI) algorithm is able to predict hypotension minutes before the blood pressure actually decreases. Internal and external validation of this algorithm has shown good sensitivity and specificity. We hypothesize that the use of this algorithm in combination with a personalized treatment protocol will reduce the time weighted average (TWA) in hypotension during surgery spent in hypotension intraoperatively., Methods/design: We aim to include 100 adult patients undergoing non-cardiac surgery with an anticipated duration of more than 2 h, necessitating the use of an arterial line, and an intraoperatively targeted mean arterial pressure (MAP) of > 65 mmHg. This study is divided into two parts; in phase A baseline TWA data from 40 patients will be collected prospectively. A device (HemoSphere) with HPI software will be connected but fully covered. Phase B is designed as a single-center, randomized controlled trial were 60 patients will be randomized with computer-generated blocks of four, six or eight, with an allocation ratio of 1:1. In the intervention arm the HemoSphere with HPI will be used to guide treatment; in the control arm the HemoSphere with HPI software will be connected but fully covered. The primary outcome is the TWA in hypotension during surgery., Discussion: The aim of this trial is to explore whether the use of a machine-learning algorithm intraoperatively can result in less hypotension. To test this, the treating anesthesiologist will need to change treatment behavior from reactive to proactive., Trial Registration: This trial has been registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov, ID: NCT03376347 . The trial was submitted on 4 November 2017 and accepted for registration on 18 December 2017.

In cardiac surgical patients it is a complex challenge to find the ideal balance between anticoagulation and hemostasis. Preoperative anemia and perioperative higher transfusion rates are related to increased morbidity and mortality. Patient blood management (PBM) is an evidence based patient specific individualized protocol used in the perioperative setting in order to reduce perioperative bleeding and transfusion rates and to improve patient outcomes. The three pillars of PBM in cardiac surgery consist of optimization of preoperative erythropoiesis and hemostasis, minimizing blood loss, and improving patient specific physiological reserves. This narrative review focuses on the challenges with special emphasis on PBM in the preoperative phase and intraoperative transfusion management and hemostasis in cardiac surgery patients. It is a "must" that PBM is a collaborative effort between anesthesiologists, surgeons, perfusionists, intensivists and transfusion laboratory teams. This review represents an up to date overview over "PBM in cardiac surgery patients"., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: This study aims at identifying factors that disciplines consider when diagnosing and reporting transfusion-associated circulatory overload ('TACO')., Background: TACO is a clinical diagnosis based mainly on subjective factors. Therefore, TACO could be an underreported complication of blood transfusion., Methods: A survey was conducted among critical care physicians, anaesthesiologists, haematologists, transfusion medicine physicians and haemovigilance officers using case vignettes and a questionnaire. Factors that may affect diagnosing TACO were investigated using conjoint analysis. A positive B-coefficient indicates a positive preference for diagnosing TACO. Participants rated factors influencing reporting TACO on a 0- to 100-point scale., Results: One hundred and seven surveys were returned (62%). Vignettes showed preferences in favour of diagnosing TACO with the onset of symptoms within 2 h [β 0·4(-0·1-1·0)], positive fluid balance [β 0·9(0·4-1·5)] and history of renal failure [β 0·6(0·1-1·2)]. Compared with transfusion of a single unit of red blood cells (RBC), respondents showed a preference for diagnosing TACO following a single unit of solvent/detergent (S/D) plasma or pooled platelet concentrate (PPC) [β 0·3(-0·2-0·7) resp. 0·5(-0·1-1·2)]. Multiple transfusion (6 RBC + 4 S/D plasma) was a strong preference for diagnosing TACO compared to 1 RBC and 1 S/D plasma [β 0·3(-0·8-1·3)]. Respondents did not fully take into account new hypertension and tachycardia when reporting TACO [median 70 (IQR 50-80) resp. 60 (IQR 50-80)]. No differences were observed between disciplines involved., Conclusion: When diagnosing and reporting TACO, physicians and haemovigilance officers do consider known risk factors for TACO. Reporting could be improved by increasing the awareness of haemodynamic variables in future education programmes., (© 2017 British Blood Transfusion Society.)

Objectives: Transfusion-associated circulatory overload (TACO) is a severe pulmonary transfusion reaction and leading cause of transfusion-related morbidity and mortality in Europe. TACO is of particular importance in critically ill patients, since they often receive blood transfusions and have multiple risk factors for TACO. This study investigates transfusion practices in patients at risk of developing TACO, and furthermore knowledge concerning risk factors, diagnoses and treatment strategies among Dutch intensive care unit (ICU) fellows., Material and Methods: An unannounced paper-based survey was conducted among Dutch ICU fellows during an educational conference. The survey consisted of 16 multiple and open choice questions., Results: Of all 65 Dutch ICU fellows 56.8% completed the survey; of respondents 88.9% identified the correct constellation of symptoms for TACO. In total, 29.7% of the respondents are aware they are obligated to report TACO cases to the blood bank. Major risk factors for TACO that respondents identified were reduced left ventricular function, infusion volume and infusion rate. In a non-emergency setting, 45.9% of fellows start red blood cell transfusion with 2 units or more. Transfusion rates exceeded national guidelines in 15.4% of fictitious cases. TACO is treated with furosemide by 94.5% of the fellows, however goals of the therapy varied greatly., Conclusion: Dutch ICU fellows are knowledgeable of TACO symptoms, risk factors and treatment, however knowledge on reporting and transfusion practice in the setting of at risk patients for TACO should be improved., (Copyright © 2017. Published by Elsevier SAS.)

Background: Ventilator-induced dynamic hemodynamic parameters such as stroke volume variation (SVV) and pulse pressure variation (PPV) have been shown to predict fluid responsiveness in contrast to static hemodynamic parameters such as central venous pressure (CVP). We hypothesized that the ventilator-induced central venous pressure variation (CVPV) could predict fluid responsiveness., Methods: Twenty-two elective cardiac surgery patients were studied post-operatively on the intensive care unit during mechanical ventilation with tidal volumes of 6-8 ml/kg without spontaneous breathing efforts or cardiac arrhythmia. Before and after administration of 500mL hydroxyethyl starch, SVV and PPV were measured using pulse contour analysis by modified Modelflow ® , while CVP was obtained from a central venous catheter positioned in the superior vena cava. CVPV was calculated as 100 × (CVP max -CVP min )/[(CVP max + CVP min) /2]., Results: Nineteen patients (86%) were fluid responders defined as an increase in cardiac output of ≥ 15% after fluid administration. CVPV decreased upon fluid loading in responders, but not in non-responders. Baseline CVP values showed no correlation with a change in cardiac output in contrast to baseline SVV (r = 0.60, P = 0.003), PPV (r = 0.58, P = 0.005), and CVPV (r = 0.63, P = 0.002). Baseline values of SVV > 9% and PPV > 8% could predict fluid responsiveness with a sensitivity of 89% and 95%, respectively, both with a specificity of 100%. Baseline CVPV could identify all fluid responders and non-responders correctly at a cut-off value of 12%. There was no difference between the area under the receiver operating characteristic curves of SVV, PPV, and CVPV., Conclusion: The use of ventilator-induced CVPV could predict fluid responsiveness similar to SVV and PPV in post-operative cardiac surgery patients., (© 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

We compared the accuracy and precision of the non-invasive Nexfin(®) device for determining systolic, diastolic, mean arterial pressure and pulse pressure variation, with arterial blood pressure values measured from a radial artery catheter in 19 patients following upper abdominal surgery. Measurements were taken at baseline and following fluid loading. Pooled data results of the arterial blood pressures showed no difference between the two measurement modalities. Bland-Altman analysis of pulse pressure variation showed significant differences between values obtained from the radial artery catheter and Nexfin finger cuff technology (mean (SD) 1.49 (2.09)%, p < 0.001, coefficient of variation 24%, limits of agreement -2.71% to 5.69%). The effect of volume expansion on pulse pressure variation was identical between methods (concordance correlation coefficient 0.848). We consider the Nexfin monitor system to be acceptable for use in patients after major upper abdominal surgery without major cardiovascular compromise or haemodynamic support., (© 2016 The Association of Anaesthetists of Great Britain and Ireland.)

Background: Although arterial hypotension occurs frequently with propofol use in humans, its effects on intravascular volume and vascular capacitance are uncertain. We hypothesized that propofol decreases vascular capacitance and therefore decreases stressed volume., Methods: Cardiac output (CO) was measured using Modelflow(®) in 17 adult subjects after upper abdominal surgery. Mean systemic filling pressure (MSFP) and vascular resistances were calculated using venous return curves constructed by measuring steady-state arterial and venous pressures and CO during inspiratory hold manoeuvres at increasing plateau pressures. Measurements were performed at three incremental levels of targeted blood propofol concentrations., Results: Mean blood propofol concentrations for the three targeted levels were 3.0, 4.5, and 6.5 µg ml(-1). Mean arterial pressure, central venous pressure, MSFP, venous return pressure, Rv, systemic arterial resistance, and resistance of the systemic circulation decreased, stroke volume variation increased, and CO was not significantly different as propofol concentration increased., Conclusions: An increase in propofol concentration within the therapeutic range causes a decrease in vascular stressed volume without a change in CO. The absence of an effect of propofol on CO can be explained by the balance between the decrease in effective, or stressed, volume (as determined by MSFP), the decrease in resistance for venous return, and slightly improved heart function., Clinical Trial Registration: Netherlands Trial Register: NTR2486., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The aim of this study was to characterize a glucagon challenge test as a tool in diabetes research by assessing the inter- and intra-individual variability, and investigating the activity of the autonomic nervous system (ANS) during the challenge, as this might have an indirect impact on glucose homeostasis. The study was performed in 24 healthy volunteers separated in 2 groups. The first group of 12 volunteers underwent a 5-h glucagon challenge during a pancreatic clamp procedure with infusion of [6,6-2H2]-glucose infusion in combination with heart rate variability measurements. In the second group, 12 other healthy volunteers underwent two 6-h glucagon challenges separated by 6 weeks, and fat biopsies were taken for analysis of glucagon receptor expression. Serum glucose rose rapidly after glucagon infusion, and reached a plateau at 90 min. The time profiles suggested rapid development of tolerance for glucagon-induced hyperglycemia. During the glucagon challenge intra- and inter-individual variabilities for hepatic glucose production, the rate of disappearance of glucose, and plasma glucose were approximately 10-15% for all variables. Hyperglucagonemia did not affect heart rate variability. Human adipose tissue had a low, but variable, expression of glucagon receptor mRNA. This standardized glucagon challenge test has a good reproducibility with only limited variability over 6 weeks. It is a robust tool to explore in detail the contribution of glucagon in normal and altered glucose homeostasis and can also be used to evaluate the effects of drugs antagonizing glucagon action in humans without confounding changes in ANS tone., (© Georg Thieme Verlag KG Stuttgart · New York.)

Predicting fluid responsiveness, the response of stroke volume to fluid loading, is a relatively novel concept that aims to optimise circulation, and as such organ perfusion, while avoiding futile and potentially deleterious fluid administrations in critically ill patients. Dynamic parameters have shown to be superior in predicting the response to fluid loading compared with static cardiac filling pressures. However, in routine clinical practice the conditions necessary for dynamic parameters to predict fluid responsiveness are frequently not met. Passive leg raising as a means to alter biventricular preload in combination with subsequent measurement of the change in stroke volume can provide a fast and accurate way to guide fluid management in a broad population of critically ill patients.

Background: Changes in central venous pressure (CVP) rather than absolute values may be used to guide fluid therapy in critically ill patients undergoing mechanical ventilation. We conducted a study comparing the changes in the CVP produced by an increase in PEEP and stroke volume variation (SVV) as indicators of fluid responsiveness. Fluid responsiveness was assessed by the changes in cardiac output (CO) produced by passive leg raising (PLR)., Methods: In 20 fully mechanically ventilated patients after cardiac surgery, PEEP was increased +10 cm H2O for 5 min followed by PLR. CVP, SVV, and thermodilution CO were measured before, during, and directly after the PEEP challenge and 30° PLR. The CO increase >7% upon PLR was used to define responders., Results: Twenty patients were included; of whom, 10 responded to PLR. The increase in CO by PLR directly related (r=0.77, P<0.001) to the increase in CVP by PEEP. PLR responsiveness was predicted by the PEEP-induced increase in CVP [area under receiver-operating characteristic (AUROC) curve 0.99, P<0.001] and by baseline SVV (AUROC 0.90, P=0.003). The AUROC's for dCVP and SVV did not differ significantly (P=0.299)., Conclusions: Our data in mechanically ventilated, cardiac surgery patients suggest that the newly defined parameter, PEEP-induced CVP changes, like SVV, appears to be a good parameter to predict fluid responsiveness.

The aim of this study was to compare the accuracy of stroke volume variation (SVV) as measured by the LiDCOplus system (SVVli) and by the FloTrac-Vigileo system (SVVed). We measured SVVli and SVVed in 15 postoperative cardiac surgical patients following five study interventions; a 50% increase in tidal volume, an increase of PEEP by 10 cm H2O, passive leg raising, a head-up tilt procedure and fluid loading. Between each intervention, baseline measurements were performed. 136 data pairs were obtained. SVVli ranged from 1.4% to 26.8% (mean (SD) 8.7 (4.6)%); SVVed from 2.0% to 26.0% (10.2 (4.7)%). The bias was found to be significantly different from zero at 1.5 (2.5)%, p < 0.001, (95% confidence interval 1.1-1.9). The upper and lower limits of agreement were found to be 6.4 and -3.5% respectively. The coefficient of variation for the differences between SVVli and SVVed was 26%. This results in a relative large range for the percentage limits of agreement of 52%. Analysis in repeated measures showed coefficients of variation of 21% for SVVli and 22% for SVVed. The LiDCOplus and FloTrac-Vigileo system are not interchangeable. Furthermore, the determination of SVVli and SVVed are too ambiguous, as can be concluded from the high values of the coefficient of variation for repeated measures. These findings underline Pinsky's warning of caution in the clinical use of SVV by pulse contour techniques.

We evaluated cardiac output (CO) using three new methods - the auto-calibrated FloTrac-Vigileo (CO(ed)), the non-calibrated Modelflow (CO(mf) ) pulse contour method and the ultra-sound HemoSonic system (CO(hs)) - with thermodilution (CO(td)) as the reference. In 13 postoperative cardiac surgical patients, 104 paired CO values were assessed before, during and after four interventions: (i) an increase of tidal volume by 50%; (ii) a 10 cm H(2)O increase in positive end-expiratory pressure; (iii) passive leg raising and (iv) head up position. With the pooled data the difference (bias (2SD)) between CO(ed) and CO(td), CO(mf) and CO(td) and CO(hs) and CO(td) was 0.33 (0.90), 0.30 (0.69) and -0.41 (1.11) l.min(-1), respectively. Thus, Modelflow had the lowest mean squared error, suggesting that it had the best performance. CO(ed) significantly overestimates changes in cardiac output while CO(mf) and CO(hs) values are not significantly different from those of CO(td). Directional changes in cardiac output by thermodilution were detected with a high score by all three methods.