Volatile versus propofol sedation after cardiac valve surgery: a single-center prospective randomized controlled trial.

BACKGROUND: Optimal intensive care of patients undergoing valve surgery is a complex balancing act between sedation for monitoring and timely postoperative awakening. It remains unclear, if these requirements can be fulfilled by volatile sedations in intensive care medicine in an efficient manner. Therefore, this study aimed to assess the time to extubation and secondary the workload required. METHODS: We conducted a prospective randomized single-center trial at a tertiary university hospital to evaluate the postoperative management of open valve surgery patients. The study was randomized with regard to the use of volatile sedation compared to propofol sedation. Sedation was discontinued 60 min after admission for critical postoperative monitoring. RESULTS: We observed a significantly earlier extubation (91 ± 39 min vs. 167 ± 77 min; p < 0.001), eye-opening (86 ± 28 min vs. 151 ± 71 min; p < 0.001) and command compliance (93 ± 38 min vs. 164 ± 75 min; p < 0.001) using volatile sedation, which in turn was associated with a significantly increased workload of a median of 9:56 min (± 4:16 min) set-up time. We did not observe any differences in complications. Cardiopulmonary bypass time did not differ between the groups 101 (IQR 81; 113) versus 112 (IQR 79; 136) minutes p = 0.36. CONCLUSIONS: Using volatile sedation is associated with few minutes additional workload in assembling and enables a significantly accelerated evaluation of vulnerable patient groups. Volatile sedation has considerable advantages and emerges as a safe sedation technique in our vulnerable study population. TRIAL REGISTRATION: Clinical trials registration (NCT04958668) was completed on 1 July 2021.

Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3.

ABSTRACT: Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) levels, soluble HJV (sHJV), splenic iron content (SIC), as well as phosphorylated small mothers against decapentaplegic protein (pSMAD1/5/8) levels. In contrast, in Alk2fl/fl;Alb-Cre and Alk3fl/fl;Alb-Cre mice, which present with moderate and severe iron overload, respectively, the administration of AAV-HJV induced HJV and sHJV. However, it did not rescue the iron overload phenotypes of those mice. Serum iron levels were induced in Alk2fl/fl;Alb-Cre mice after HJV overexpression. In phosphate-buffered saline-injected Alk3fl/fl;Alb-Cre mice, serum iron levels and the expression of duodenal ferroportin remained high, whereas Hamp mRNA levels were decreased to 1% to 5% of the levels detected in controls. This was reduced even further by AAV-HJV overexpression. SIC remained low in mice with hepatocyte-specific Alk2 or Alk3 deficiency, reflecting disturbed iron homeostasis with high serum iron levels and transferrin saturation and an inability to induce hepcidin by HJV overexpression. The data indicate that ALK2 and ALK3 are both required in vivo for the HJV-mediated induction of hepcidin.

Adjusting Current Hemoglobin Thresholds: A Way to Improve Outcome in Women Undergoing Major Surgery.

Background/Objective: In the perioperative setting, a suboptimal total hemoglobin (Hb) mass puts women and men at an unreasonable disadvantage. Anemia is an independent risk factor for transfusion, postoperative complications, and mortality. The Hb cut-off value for women was set at <12.0 g/dL by the World Health Organization (WHO) and has been rigorously debated for decades. The aim of this study was to elucidate the risk for postoperative complications in female patients with Hb levels < 12.0, 12.0-12.9, and ≥13.0 g/dL. Material and Methods: Single-center retrospective analysis of female patients undergoing major surgery. Results: In total, 6,516 patients ≥18 years of age had major surgery between 2018 and 2019 and 2,446 female patients were included in analysis. Mean age was 67.4 ± 16.6, 66.4 ± 15.6, and 64.5 ± 15.5 years in female patients with preoperative Hb levels <12.0, 12.0-12.9 and ≥13.0 g/dL, respectively. The transfusion rate of red blood cells (RBCs) was significantly higher in female patients with Hb <12.0 g/dL (53%) and with Hb 12.0-12.9 g/dL (31%) compared to female patients ≥13.0 g/dL (22%). Rates of pneumonia, acute kidney injury, and sepsis were significantly higher in patients with Hb <12.0 and 12.0-12.9 g/dL compared to patients with Hb ≥13.0 g/dL. Total length of hospital stay was significantly longer in female patients with Hb <12.0 g/dL than patients with Hb 12.0-12.9 g/dL and Hb ≥13.0 g/dL (10 days vs. 8 days). Conclusion: Taken together, our data show that Hb values below 12.9 g/dL are associated with increased probability of RBC transfusions and increased risk of postoperative complications. In addition, our results indicate that postoperative outcomes for women might be optimized by increasing cut-off values for anemia. The call to revise the anemia threshold for women by the WHO can no longer be disregarded.

Preoperative hemoglobin thresholds for survival equity in women and men.

Anemia affects humans throughout life, and is linked to higher morbidity and mortality. Unclear is whether hemoglobin values are equivalent between women and men. This study evaluates the association of preoperative hemoglobin levels with in-hospital mortality and estimates thresholds for survival equity between men and women. All adult patients undergoing surgery between 2010 and 2019 from 14 German hospitals were included in the study. Thresholds for survival equity were determined with generalized additive models. In total, 842,130 patients with a median in-hospital follow-up time of 7 days were analyzed. During follow-up 20,370 deaths occurred. Preoperative hemoglobin stratified in-hospital mortality (log-rank test p < 0.001) and was associated with mortality independently of demographic risk, surgical risk and health status. For each 1 g/dL reduction in preoperative hemoglobin, the odds of mortality increased by a factor of 1.22 (95% CI 1.21-1.23, p < 0.001). A preoperative hemoglobin threshold of 10.5 g/dL reflected equivalent risk for both male and female patients. Hemoglobin levels below 10.5 g/dL had higher risk of mortality for women than for men. The findings from this study aid evidence-based thresholds, inform anemia management and promote equitable care, thus enhancing patient outcomes.

Red blood cell transfusion in patients undergoing elective primary glioblastoma resection.

BACKGROUND: Red blood cell (RBC) transfusion in patients undergoing major elective cranial surgery is associated with increased postoperative morbidity and mortality. This study aims to identify the clinical outcome of transfused glioblastoma patients undergoing primary surgical tumor resection and identify risk factors for RBC transfusion. MATERIAL AND METHODS: Between 2009 and 2019, 406 patients underwent elective primary glioblastoma resection. For multivariate analysis to assess risk factors for RBC transfusion, logistic regression was conducted. The impact of RBC transfusion on overall survival was assessed using Kaplan-Meier analysis. RESULTS: In total, 36 (8.9%) patients received RBC transfusion. Preoperative anemia rate was significantly higher in transfused patients compared to patients without RBC transfusion (33.3 vs 6.5%; p<0.0001). Postoperative complications as well as hospital length of stay (LOS) (p<0.0001) were significantly increased in transfused patients compared to non-transfused patients. After multivariate analysis, risk factors for RBC transfusion were preoperative anemia (p<0.0001), intraoperative blood loss (p<0.0001), female gender (p=0.0056) and radiation (p=0.0064). Kaplan-Meier curves revealed that RBC transfusion and being elderly (age ≥75 years) were relevant for overall survival. DISCUSSION: RBC transfusion is associated with increased postoperative morbidity and mortality in patients undergoing elective primary glioblastoma resection. Preoperative anemia and intraoperative blood loss are major risk factors for RBC transfusion. Preoperative anemia management and blood conservation strategies are crucial in patients undergoing elective primary glioblastoma resection.

Extract from the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery - Patient Blood Management.

The 2022 Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery of the European Society of Cardiology are an update on the previous guidelines reported in 2014. The revised guidelines provide standardized perioperative cardiovascular management of surgical patients and emphasis on risk assessment of the patient combined with the inherent risk of the surgical procedure. One of the novelties in these guidelines is the Patient Blood Management programme, which is based on a three pillar concept: preoperative hemoglobin optimization, minimize iatrogenic blood loss and bleeding, and harness tolerance to anemia in an effort to improve patient outcome. In this review, we highlight the three pillars of Patient Blood Management and recommendations made by the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.

User Perceptions of Visual Blood: An International Mixed Methods Study on Novel Blood Gas Analysis Visualization.

Blood gas analysis plays a central role in modern medicine. Advances in technology have expanded the range of available parameters and increased the complexity of their interpretation. By applying user-centered design principles, it is possible to reduce the cognitive load associated with interpreting blood gas analysis. In this international, multicenter study, we explored anesthesiologists' perspectives on Visual Blood, a novel visualization technique for presenting blood gas analysis results. We conducted interviews with participants following two computer-based simulation studies, the first utilizing virtual reality (VR) (50 participants) and the second without VR (70 participants). Employing the template approach, we identified key themes in the interview responses and formulated six statements, which were rated using Likert scales from 1 (strongly disagree) to 5 (strongly agree) in an online questionnaire. The most frequently mentioned theme was the positive usability features of Visual Blood. The online survey revealed that participants found Visual Blood to be an intuitive method for interpreting blood gas analysis (median 4, interquartile range (IQR) 4-4, p < 0.001). Participants noted that minimal training was required to effectively learn how to interpret Visual Blood (median 4, IQR 4-4, p < 0.001). However, adjustments are necessary to reduce visual overload (median 4, IQR 2-4, p < 0.001). Overall, Visual Blood received a favorable response. The strengths and weaknesses derived from these data will help optimize future versions of Visual Blood to improve the presentation of blood gas analysis results.

Endogenous anti-tumorigenic nitro-fatty acids inhibit the ubiquitin-proteasome system by directly targeting the 26S proteasome.

Nitro-fatty acids (NFAs) are endogenous lipid mediators causing a spectrum of anti-inflammatory effects by covalent modification of key proteins within inflammatory signaling pathways. Recent animal models of solid tumors have helped demonstrate their potential as anti-tumorigenic therapeutics. This study evaluated the anti-tumorigenic effects of NFAs in colon carcinoma cells and other solid and leukemic tumor cell lines. NFAs inhibited the ubiquitin-proteasome system (UPS) by directly targeting the 26S proteasome, leading to polyubiquitination and inhibition of the proteasome activities. UPS suppression induced the unfolded protein response, resulting in tumor cell death. The NFA-mediated effects were substantial, specific, and enduring, representing a unique mode of action for UPS suppression. This study provides mechanistic insights into the biological actions of NFAs as possible endogenous tumor-suppressive factors, indicating that NFAs might be key structures for designing a novel class of direct proteasome inhibitors.

German Patient Blood Management Network: effectiveness and safety analysis in 1.2 million patients.

BACKGROUND: Patient Blood Management (PBM) is a patient-centred, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood whilst promoting patient safety and empowerment. The effectiveness and safety of PBM over a longer period have not yet been investigated. METHODS: We performed a prospectively designed, multicentre follow-up study with non-inferiority design. Data were retrospectively extracted case-based from electronic hospital information systems. All in-hospital patients (≥18 yr) undergoing surgery and discharged between January 1, 2010 and December 31, 2019 were included in the analysis. The PBM programme focused on three domains: preoperative optimisation of haemoglobin concentrations, blood-sparing techniques, and guideline adherence/standardisation of allogeneic blood product transfusions. The outcomes were utilisation of blood products, composite endpoint of in-hospital mortality and postoperative complications (myocardial infarction/ischaemic stroke/acute renal failure with renal replacement therapy/sepsis/pneumonia), anaemia rate at admission and discharge, and hospital length of stay. RESULTS: A total of 1 201 817 (pre-PBM: n=441 082 vs PBM: n=760 735) patients from 14 (five university/nine non-university) hospitals were analysed. Implementation of PBM resulted in a substantial reduction of red blood cell utilisation. The mean number of red blood cell units transfused per 1000 patients was 547 in the PBM cohort vs 635 in the pre-PBM cohort (relative reduction of 13.9%). The red blood cell transfusion rate was significantly lower (P<0.001) with odds ratio 0.86 (0.85-0.87). The composite endpoint was 5.8% in the PBM vs 5.6% in the pre-PBM cohort. The non-inferiority aim (safety of PBM) was achieved (P<0.001). CONCLUSIONS: Analysis of >1 million surgical patients showed that the non-inferiority condition (safety of Patient Blood Management) was fulfilled, and PBM was superior with respect to red blood cell transfusion. CLINICAL TRIAL REGISTRATION: NCT02147795.

Visual Blood, a 3D Animated Computer Model to Optimize the Interpretation of Blood Gas Analysis.

Acid-base homeostasis is crucial for all physiological processes in the body and is evaluated using arterial blood gas (ABG) analysis. Screens or printouts of ABG results require the interpretation of many textual elements and numbers, which may delay intuitive comprehension. To optimise the presentation of the results for the specific strengths of human perception, we developed Visual Blood, an animated virtual model of ABG results. In this study, we compared its performance with a conventional result printout. Seventy physicians from three European university hospitals participated in a computer-based simulation study. Initially, after an educational video, we tested the participants' ability to assign individual Visual Blood visualisations to their corresponding ABG parameters. As the primary outcome, we tested caregivers' ability to correctly diagnose simulated clinical ABG scenarios with Visual Blood or conventional ABG printouts. For user feedback, participants rated their agreement with statements at the end of the study. Physicians correctly assigned 90% of the individual Visual Blood visualisations. Regarding the primary outcome, the participants made the correct diagnosis 86% of the time when using Visual Blood, compared to 68% when using the conventional ABG printout. A mixed logistic regression model showed an odds ratio for correct diagnosis of 3.4 (95%CI 2.00-5.79, p < 0.001) and an odds ratio for perceived diagnostic confidence of 1.88 (95%CI 1.67-2.11, p < 0.001) in favour of Visual Blood. A linear mixed model showed a coefficient for perceived workload of -3.2 (95%CI -3.77 to -2.64) in favour of Visual Blood. Fifty-one of seventy (73%) participants agreed or strongly agreed that Visual Blood was easy to use, and fifty-five of seventy (79%) agreed that it was fun to use. In conclusion, Visual Blood improved physicians' ability to diagnose ABG results. It also increased perceived diagnostic confidence and reduced perceived workload. This study adds to the growing body of research showing that decision-support tools developed around human cognitive abilities can streamline caregivers' decision-making and may improve patient care.

Visual Blood, Visualisation of Blood Gas Analysis in Virtual Reality, Leads to More Correct Diagnoses: A Computer-Based, Multicentre, Simulation Study.

Interpreting blood gas analysis results can be challenging for the clinician, especially in stressful situations under time pressure. To foster fast and correct interpretation of blood gas results, we developed Visual Blood. This computer-based, multicentre, noninferiority study compared Visual Blood and conventional arterial blood gas (ABG) printouts. We presented six scenarios to anaesthesiologists, once with Visual Blood and once with the conventional ABG printout. The primary outcome was ABG parameter perception. The secondary outcomes included correct clinical diagnoses, perceived diagnostic confidence, and perceived workload. To analyse the results, we used mixed models and matched odds ratios. Analysing 300 within-subject cases, we showed noninferiority of Visual Blood compared to ABG printouts concerning the rate of correctly perceived ABG parameters (rate ratio, 0.96; 95% CI, 0.92-1.00; p = 0.06). Additionally, the study revealed two times higher odds of making the correct clinical diagnosis using Visual Blood (OR, 2.16; 95% CI, 1.42-3.29; p < 0.001) than using ABG printouts. There was no or, respectively, weak evidence for a difference in diagnostic confidence (OR, 0.84; 95% CI, 0.58-1.21; p = 0.34) and perceived workload (Coefficient, 2.44; 95% CI, -0.09-4.98; p = 0.06). This study showed that participants did not perceive the ABG parameters better, but using Visual Blood resulted in more correct clinical diagnoses than using conventional ABG printouts. This suggests that Visual Blood allows for a higher level of situation awareness beyond individual parameters' perception. However, the study also highlighted the limitations of today's virtual reality headsets and Visual Blood.

Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 µg/L of sodium selenite prior to cardiopulmonary bypass, 2000 µg/L immediately postoperatively, and 1000 µg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

How do I/we forecast tomorrow's transfusion? A focus on recipients' profiles.

Red blood cell (RBC) transfusion is a life-saving medical intervention and has an essential role in the management of surgical patients. However, blood donations and supply levels are decreasing, therefore there is an unmet need for the accurate prediction of the transfusion probability for surgical patients. Multiple methods have been established to predict the need for RBC transfusion. Maximum surgical blood order schedules are widely used in the clinical setting. However, these lists are not designed to accurately predict RBC utilization for an individual case as factors such as preoperative haemoglobin level, total body blood volume, comedications are not considered. Artificial intelligence and related technologies based on machine learning modelling are valuable alternatives to predict transfusion probability taking into account patient individual risk factors including among others comorbidities, laboratory parameters, use of oral anticoagulation, ASA score, surgeon's ID or applied blood saving measures. Overall, forecasting the need for a RBC transfusion can facilitate personalized medicine, quality assurance, decrease blood wastage, decrease costs, and increase patient safety. Furthermore, transfusion prediction models could facilitate blood management strategies before surgery.

European Society of Cardiology quality indicators for the cardiovascular pre-operative assessment and management of patients considered for non-cardiac surgery. Developed in collaboration with the European Society of Anaesthesiology and Intensive Care.

AIMS: To establish a set of quality indicators (QIs) for the cardiovascular (CV) assessment and management of patients undergoing non-cardiac surgery (NCS). METHODS AND RESULTS: The Quality Indicator Committee of the European Society of Cardiology (ESC) and European Society of Anaesthesiology and Intensive Care (ESAIC) in collaboration with Task Force members of the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS followed the ESC methodology for QI development. This included (1) identification, by constructing a conceptual framework of care, of domains of the CV assessment, and management of patients with risk factors or established cardiovascular disease (CVD) who are considered for or undergoing NCS, (2) development of candidate QIs following a systematic literature review, (3) selection of the final set of QIs using a modified Delphi method, and (4) evaluation of the feasibility of the developed QIs. In total, eight main and nine secondary QIs were selected across six domains: (1) structural framework (written policy), (2) patient education and quality of life (CV risk discussion), (3) peri-operative risk assessment (indication for diagnostic tests), (4) peri-operative risk mitigation (use of hospital therapies), (5) follow-up (post-discharge assessment), and (6) outcomes (major CV events). CONCLUSION: We present the 2022 ESC/ESAIC QIs for the CV assessment and management of patients with risk factors or established CVD who are considered for or are undergoing NCS y. These indicators are supported by evidence from the literature, underpinned by expert consensus, and align with the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS.

Effect of quantitative versus qualitative neuromuscular blockade monitoring on rocuronium consumption in patients undergoing abdominal and gynecological surgery: a retrospective cohort study.

The level of neuromuscular blockade can be assessed by subjective (qualitative) and objective (quantitative) methods. This study aims to compare the dosage of the neuromuscular blocking agents (NMBA) rocuronium and the need for reversion by sugammadex between those methods. A retrospective, observational analysis was conducted. In the tactile qualitative-neuromuscular monitoring-group (tactile NMM) (n = 244), muscle contractions were assessed tactilely. In the quantitative neuromuscular monitoring-group (n = 295), contractions were accessed using an acceleromyograph. Primary endpoints were dosage of rocuronium per minute operation-time (milligram per kilogram bodyweight per minute (mg/kgBW/min)), count of repeated rocuronium administrations and use of sugammadex. Secondary endpoints were: NMM use before repeated NMBA application or extubation, time to extubation, post-operative oxygen demand. A total of n = 539 patients were included. n = 244 patients were examined with tactile NMM and 295 patients by quantitative NMM. Quantitative NMM use resulted in significantly lower rocuronium dosing (tactile NMM: 0.01 (± 0.007) mg/kgBW/min vs. quantitative NMM: 0.008 (± 0.006) mg/kgBW/min (p < 0.001)). In quantitative NMM use fewer repetitions of rocuronium application were necessary (tactile NMM: 83% (n = 202) vs. quantitative NMM: 71% (n = 208) p = 0.007). Overall, 24% (n = 58) in the tactile NMM-group, and 20% (n = 60) in the quantitative NMM-group received sugammadex ((p = 0.3), OR: 1.21 (0.81-1.82)). Significantly fewer patients in the quantitative NMM-group required oxygen-supply postoperative (quantitative NMM: 43% (n = 120)) vs. tactile NMM: 57% (n = 128)) (p = 0.002). The use of quantitative assessment of NMBA results in a lower overall dosage and requires fewer repetitions of rocuronium application. Therefore, quantitative monitoring systems should be used to monitor NMBA intraoperatively to reduce NMBA dosing, while achieving continuous neuromuscular blockade.

Association of anaemia, co-morbidities and red blood cell transfusion according to age groups: multicentre sub-analysis of the German Patient Blood Management Network Registry.

BACKGROUND: Blood transfusions are common medical procedures and every age group requires detailed insights and treatment bundles. The aim of this study was to examine the association of anaemia, co-morbidities, complications, in-hospital mortality, and transfusion according to age groups to identify patient groups who are particularly at risk when undergoing surgery. METHODS: Data from 21 Hospitals of the Patient Blood Management Network Registry were analysed. Patients were divided into age subgroups. The incidence of preoperative anaemia, co-morbidities, surgical disciplines, hospital length of stay, complications, in-hospital mortality rate, and transfusions were analysed by descriptive and multivariate regression analysis. RESULTS: A total of 1 117 919 patients aged 18-108 years were included. With increasing age, the number of co-morbidities and incidence of preoperative anaemia increased. Complications, hospital length of stay, and in-hospital mortality increased with age and were higher in patients with preoperative anaemia. The mean number of transfused red blood cells (RBCs) peaked, whereas the transfusion rate increased continuously. Multivariate regression analysis showed that increasing age, co-morbidities, and preoperative anaemia were independent risk factors for complications, longer hospital length of stay, in-hospital mortality, and the need for RBC transfusion. CONCLUSION: Increasing age, co-morbidities, and preoperative anaemia are independent risk factors for complications, longer hospital length of stay, in-hospital mortality, and the need for RBC transfusion. Anaemia diagnosis and treatment should be established in all patients.

Effect of personalized perioperative blood pressure management on postoperative complications and mortality in high-risk patients having major abdominal surgery: protocol for a multicenter randomized trial (IMPROVE-multi).

BACKGROUND: Intraoperative hypotension is common in patients having non-cardiac surgery and is associated with serious complications and death. However, optimal intraoperative blood pressures for individual patients remain unknown. We therefore aim to test the hypothesis that personalized perioperative blood pressure management-based on preoperative automated blood pressure monitoring-reduces the incidence of a composite outcome of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery. METHODS: IMPROVE-multi is a multicenter randomized trial in 1272 high-risk patients having elective major abdominal surgery that we plan to conduct at 16 German university medical centers. Preoperative automated blood pressure monitoring using upper arm cuff oscillometry will be performed in all patients for one night to obtain the mean of the nighttime mean arterial pressures. Patients will then be randomized either to personalized blood pressure management or to routine blood pressure management. In patients assigned to personalized management, intraoperative mean arterial pressure will be maintained at least at the mean of the nighttime mean arterial pressures. In patients assigned to routine management, intraoperative blood pressure will be managed per routine. The primary outcome will be a composite of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery. DISCUSSION: Our trial will determine whether personalized perioperative blood pressure management reduces the incidence of major postoperative complications and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05416944. Registered on June 14, 2022.

Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19.

Objectives: To determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP). Methods: Patients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models. Results: The majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models. Conclusion: This analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors.

Patient blood management and patient safety.

PURPOSE OF REVIEW: The particular fields within patient blood management (PBM) and patient safety reviewed here include novel insights into bleeding therapy, autologous cell salvage, and perioperative anemia therapy. RECENT FINDING: World Health Organization has published that implementation of PBM is important but has not yet been performed in all hospitals. Two antibodies that mimic the function of FVIII, Emicizumab, and Mim8 have been developed. Tranexamic acid (TXA) has been investigated further in patients with hip surgery and shows reduction of bleeding. Thrombocytopenia in patients undergoing cardiac surgery is a particular concern that has been investigated in another trial. The use of autologous cell salvage was updated in form of a review and meta-analysis. And last but not least, intravenous iron in preoperative anemia therapy can reduce the number of transfusions, but especially iron carboxymaltose can cause hypophosphatemia. SUMMARY: PBM should be further implemented in more hospitals. Emicizumab and Mim8 are indicated in acquired hemophilia or hemophilia A with inhibitors. TXA was confirmed to reduce bleeding. Autologous cell salvage is state of the art to reduce transfusion requirements in major cardiac and noncardiac surgery. Serum phosphate concentrations should be monitored after administration of intravenous iron compounds.