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Background Anemia, characterized by low hemoglobin levels, is a global public health concern. Anemia is an independent factor worsening outcomes in various patient groups. Blood transfusion has been the traditional treatment for anemia; its triggers, primarily based on hemoglobin levels; however, hemoglobin level is not always an ideal trigger for blood transfusion. Additionally, blood transfusion worsens clinical outcomes in certain patient groups. This narrative review explores alternative triggers for red blood cell transfusion and their physiological basis. Main Text The review delves into the physiology of oxygen transport and highlights the limitations of using hemoglobin levels alone as transfusion trigger. The main aim of blood transfusion is to optimize oxygen delivery, necessitating an individualized approach based on clinical signs of anemia and the balance between oxygen delivery and consumption, reflected by the oxygen extraction rate. The narrative review covers different alternative triggers. It presents insights into their diagnostic value and clinical applications, emphasizing the need for personalized transfusion strategies. Conclusion Anemia and blood transfusion are significant factors affecting patient outcomes. While restrictive transfusion strategies are widely recommended, they may not account for the nuances of specific patient populations. The search for alternative transfusion triggers is essential to tailor transfusion therapy effectively, especially in patients with comorbidities or unique clinical profiles. Investigating alternative triggers not only enhances patient care by identifying more precise indicators but also minimizes transfusion-related risks, optimizes blood product utilization, and ensures availability when needed. Personalized transfusion strategies based on alternative triggers hold the potential to improve outcomes in various clinical scenarios, addressing anemia’s complex challenges in healthcare. Further research and evidence are needed to refine these alternative triggers and guide their implementation in clinical practice.

Anemia is highly prevalent among oncological patients and is often managed with red blood cell transfusions. Current guidelines predominantly rely on hemoglobin levels to guide transfusion, but hemoglobin alone may not accurately reflect oxygen delivery. Physiological triggers, particularly the oxygen extraction ratio (O 2 ER), could provide a more individualized transfusion strategy. This prospective, single-center, observational study included 107 clinically stable adult oncology patients at the Kazakh Institute of Oncology and Radiology. All patients required red blood cell transfusion based on a restrictive trigger (Hb 70 g/L). Patients were stratified into two groups according to their baseline O 2 ER (≤ 35.4% or > 35.4%). The primary outcome was the change in O 2 ER before and one hour after transfusion. We also measured changes in central venous oxygen saturation (ScvO 2 ), central venous oxygen partial pressure (PvO 2 ), arteriovenous oxygen difference (A-V O 2 diff), lactate, and veno-arterial carbon dioxide difference (ΔCO 2 ). Patients with higher baseline oxygen extraction ratio (O 2 ER > 35.4%) demonstrated more pronounced improvements in oxygenation parameters—including O 2 ER, ScvO 2 , PvO 2 , A‑V O 2 diff, and ΔCO 2 —following transfusion, compared to patients with O 2 ER ≤ 35.4%. Although baseline hemoglobin levels and post-transfusion increases in hemoglobin were similar between groups, significant differences were observed across all physiological markers of oxygen transport. Correlation analyses showed significant associations between baseline O 2 ER and changes in PvO 2 , ScvO 2 , A‑V O 2 diff, ΔCO 2 , and lactate. In contrast, baseline hemoglobin demonstrated no significant correlations with most physiological response parameters, except for a moderate but statistically significant correlation with the change in blood lactate levels. Lactate levels remained within normal limits in the majority of patients, indicating that critical oxygen delivery thresholds were not reached. In stable cancer patients with anemia, hemoglobin levels alone may not adequately capture oxygen delivery status. The oxygen extraction ratio and other physiological triggers offer valuable insights into which patients may benefit most from transfusion. Our findings support a more individualized transfusion strategy, though larger randomized controlled trials are warranted to confirm the safety and efficacy of physiological triggers in broader patient populations. Trial Registration The study protocol was retrospectively registered on ClinicalTrials.gov (NCT06952361, Initial Release 04/23/2025).

The effect of Levosimendan on postoperative natriuretic peptides in noncardiac surgical patients remains unknown. Thus, this study evaluates the effect of a perioperative levosimendan administration on postoperative N-terminal brain pro natriuretic peptide (NT-proBNP) concentrations. In this prospective, double-blinded, parallel group, placebo-controlled, phase III trial 115 patients were assigned to perioperative single-dose of 12.5 mg of levosimendan and 115 to placebo between October 2020 through November 2023 (clinicaltrials.gov: NCT04329624). The primary outcome was postoperative maximum NT-proBNP concentration within the first 3 postoperative days. 228 patients completed the trial. Postoperative maximum NT-proBNP concentrations did not differ significantly between the groups (effect estimate: −64.51 ng.L -1 ; 95% CI −332.66 to 195.56; p = 0.61). Here, we show that perioperative levosimendan administration did not lead to a significantly lower release in postoperative NT-proBNP after noncardiac surgery. Here, the authors investigate the effect of perioperative levosimendan on postoperative subclinical heart failure, evaluated via NT-proBNP measurements in cardiac risk patients undergoing noncardiac surgery, and show no significant difference between levosimendan and placebo on the postoperative maximum NT-proBNP release.

Supplemental oxygen is a simple method to improve arterial oxygen saturation and might therefore improve myocardial oxygenation. Thus, we tested whether intraoperative supplemental oxygen reduces the risk of impaired cardiac function diagnosed with NT-proBNP and myocardial injury after noncardiac surgery (MINS) diagnosed with high-sensitivity Troponin T. Parallel-arm double-blinded single-centre superiority randomized trial. Operating room and postoperative recovery area. 260 patients over the age of 45 years at-risk for cardiovascular complications undergoing major abdominal surgery. Administration of 80% versus 30% oxygen throughout surgery and for the first two postoperative hours. The primary outcome was the postoperative maximum NT-proBNP concentration in both groups, which was assessed within 2 h after surgery, and on the first and third postoperative day. The secondary outcome was the incidence of MINS in both groups. 128 patients received 80% oxygen and 130 received 30% oxygen throughout surgery and for the first two postoperative hours. There was no significant difference in the median postoperative maximum NT-proBNP concentration between the 80% and the 30% oxygen group (989 pg.mL−1 [IQR 499; 2005] and 810 pg.mL−1 [IQR 409; 2386], effect estimate: 159 pg.mL−1, 95%CI -123, 431, p = 0.704). There was no difference in the incidence of MINS between both groups. (p = 0.703). There was no beneficial effect of perioperative supplemental oxygen administration on postoperative NT-proBNP concentration and MINS. It seems likely that supplemental oxygen has no effect on the release of NT-proBNP in patients at-risk for cardiovascular complications undergoing major abdominal surgery. ClinicalTrials.gov: NCT 03366857. https://clinicaltrials.gov/ct2/results?cond=NCT+03366857&term=&cntry=&state=&city=&dist= •Intraoperative inspired 80% versus 30% oxygen showed no significant effect in postoperative NT-proBNP concentration.•The incidence of MINS did not differ significantly between the 80% and 30% oxygen group.•NT-proBNP and Troponin T increased significantly in all patients after major abdominal surgery.

Background N-terminal pro brain natriuretic peptide (NT-proBNP) and troponin T are released during myocardial wall stress and/or ischemia and are strong predictors for postoperative cardiovascular complications. However, the relative effects of goal-directed, intravenous administration of crystalloid compared to colloid solutions on NT-proBNP and troponin T, especially in relatively healthy patients undergoing moderate- to high-risk noncardiac surgery, remains unclear. Thus, we evaluated in this sub-study the effect of a goal-directed crystalloid versus a goal-directed colloid fluid regimen on postoperative maximum NT-proBNP concentration. We further evaluated the incidence of myocardial injury after noncardiac surgery (MINS) between both study groups. Methods Thirty patients were randomly assigned to receive additional intravenous fluid boluses of 6% hydroxyethyl starch 130/0.4 and 30 patients to receive lactated Ringer’s solution. Intraoperative fluid management was guided by oesophageal Doppler-according to a previously published algorithm. The primary outcome were differences in postoperative maximum NT-proBNP (maxNT-proBNP) between both groups. As our secondary outcome we evaluated the incidence of MINS between both study groups. We defined maxNT-proBNP as the maximum value measured within 2 h after surgery and on the first and second postoperative day. Results In total 56 patients were analysed. There was no significant difference in postoperative maximum NT-proBNP between the colloid group (258.7 ng/L (IQR 199.4 to 782.1)) and the crystalloid group (440.3 ng/L (IQR 177.9 to 691.2)) during the first 2 postoperative days ( P  = 0.29). Five patients in the colloid group and 7 patients in the crystalloid group developed MINS ( P  = 0.75). Conclusions Based on this relatively small study goal-directed colloid administration did not decrease postoperative maxNT-proBNP concentration as compared to goal-directed crystalloid administration. Trial registration ClinicalTrials.gov ( NCT01195883 ) Registered on 6th September 2010.

IntroductionThe effect of different anaesthetics on the incidence of postoperative delirium is still not entirely clear. Therefore, we will evaluate the effect of desflurane versus sevoflurane versus propofol for the maintenance of anaesthesia on the incidence of postoperative delirium in older adults undergoing moderate- to high-risk major non-cardiac surgery. We will further compare the incidences of delayed neurocognitive recovery, long-term postoperative neurocognitive disorder, postoperative nausea and vomiting between the groups.Methods and analysisIn this multicentre, prospective, observer-blinded, randomised controlled clinical trial, we will include 1332 patients ≥65 years of age undergoing moderate- to high-risk major non-cardiac surgery lasting at least 2 hours. Patients will be randomly 1:1:1 assigned to receive desflurane, sevoflurane or propofol for anaesthesia. Maintenance of anaesthesia will be performed in a goal-directed manner using processed electroencephalography with an intraoperative goal of bispectral index 40–60. Our primary outcome will be the incidence of postoperative delirium within the first five postoperative days. Postoperative delirium will be assessed using the three-dimensional-confusion assessment method (3D-CAM) or CAM-intensive care unit (ICU) in the morning and evening of the first five postoperative days by blinded study personnel. The primary outcome, the incidence of postoperative delirium, will be compared between the three study groups using a χ2 test. Furthermore, a logistic regression model for the incidence of postoperative delirium will be performed, accounting for randomised groups as well as other predefined confounding factors.Ethics and disseminationThis clinical trial has been approved by the ethics committee and the Federal Office for Safety in Healthcare as the competent authority for clinical trials in Austria. The results of this trial will be published in a peer-reviewed journal.Trial registration numberClinicalTrials.gov NCT05990790.

Background Ischaemia/reperfusion (I/R) injury is associated with renal tissue damage during deceased donor renal transplantation. The effect of mannitol to reduce I/R injury during graft reperfusion in renal transplant recipients is based on weak evidence. We evaluated the effect of mannitol to reduce renal graft injury represented by 16 serum biomarkers, which are indicators for different important pathophysiological pathways. Our primary outcome were differences in biomarker concentrations between the mannitol and the placebo group 24 h after graft reperfusion. Additionally, we performed a linear mixed linear model to account biomarker concentrations before renal transplantation. Methods Thirty-four patients undergoing deceased donor renal transplantation were randomly assigned to receive either 20% mannitol or 0.9% NaCl placebo solution before, during, and after graft reperfusion. Sixteen serum biomarkers (MMP1, CHI3L1, CCL2, MMP8, HGF, GH, FGF23, Tie2, VCAM1, TNFR1, IGFBP7, IL18, NGAL, Endostatin, CystC, KIM1) were measured preoperatively and 24 h after graft reperfusion using Luminex assays and ELISA. Results Sixteen patients in each group were analysed. Tie2 differed 24 h after graft reperfusion between both groups ( p  = 0.011). Change of log2 transformed concentration levels over time differed significantly in four biomarkers (VCAM1,Endostatin, KIM1, GH; p  = 0.007; p  = 0.013; p  = 0.004; p  = 0.033; respectively) out of 16 between both groups. Conclusion This study showed no effect of mannitol on I/R injury in patients undergoing deceased renal transplantation. Thus, we do not support the routinely use of mannitol to attenuate I/R injury. Trial registration NCT02705573 . Registered on 10th March 2016.

Background Elevated postoperative N -terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are predictive for cardiac adverse events in noncardiac surgery. Studies indicate that supplemental oxygen decreases sympathetic nerve activity and might, therefore, improve cardiovascular function. Thus, we will test the effect of perioperative supplemental oxygen administration on NT-proBNP release after surgery. Methods/design We will conduct a single-center, double-blinded, randomized trial at the Medical University of Vienna, including 260 patients with increased cardiac risk factors undergoing moderate- to high-risk noncardiac surgery. Patients will be randomly assigned to receive 80% versus 30% oxygen during surgery and for 2 h postoperatively. The primary outcome will be the difference in maximum NT-proBNP release after surgery. As secondary outcomes we will assess the effect of supplemental oxygen on postoperative maximum troponin T concentration, oxidation-reduction potential, von Willebrand factor concentration and perioperative fluid requirements. We will perform outcome measurements 2 h after surgery, on postoperative day 1 and on postoperative day 3. The NT-proBNP concentration and the oxidation-reduction potential will also be measured within 72 h before discharge. Discussion Our trial should determine whether perioperative supplemental oxygen administration will reduce the postoperative release of NT-proBNP in patients with preoperative increased cardiovascular risk factors undergoing noncardiac surgery. Trial registration ClinicalTrials.gov, ID: NCT03366857 . Registered on 8th December 2017.

Technically assisted assessment of volume status before surgery may be useful to direct intraoperative fluid administration. We therefore tested a recently developed whole-body bioimpedance spectroscopy device to determine pre- to postoperative fluid distribution. Using a three-compartment physiologic tissue model, the body composition monitor (BCM, Fresenius Medical Care, Germany) measures total body fluid volume, extracellular volume, intracellular volume and fluid overload as surplus or deficit of 'normal' extracellular volume. BCM-measurements were performed before and after standardized general anaesthesia for gynaecological procedures (laparotomies, laparoscopies and vaginal surgeries). BCM results were blinded to the attending anaesthesiologist and data analysed using the 2-sided, paired Student's t-test and multiple linear regression. In 71 females aged 45 ± 15 years with body weight 67 ± 13 kg and Duration of anesthesia 154 ± 69 minutes [corrected] duration of anaesthesia 154 ± 68 min, pre- to postoperative fluid overload increased from -0.7 ± 1.1 L to 0.1 ± 1.0 L, corresponding to -5.1 ± 7.5% and 0.8 ± 6.7% of normal extracellular volume, respectively (both p<0.001), after patients had received 1.9 ± 0.9 L intravenous crystalloid fluid. Perioperative urinary excretion was 0.3 ± 0.2 L [corrected]. The increase in extracellular volume was paralleled by an increase in total body fluid volume, while intracellular volume increased only slightly and without reaching statistical significance (p = 0.15). Net perioperative fluid balance (administered fluid volume minus urinary excretion) was significantly associated with change in extracellular volume (r(2) = 0.65), but was not associated with change in intracellular volume (r(2) = 0.01). Routine intraoperative fluid administration results in a significant, and clinically meaningful increase in the extracellular compartment. BCM-measurements yielded plausible results and may become useful to guide intraoperative fluid therapy in future studies.

Background Pulmonary function is impaired after major abdominal surgery and might be less impaired by restrictive fluid administration. Under the assumption of a fluid-sparing effect of colloids, we tested the hypothesis that an intraoperative colloid-based goal-directed fluid management strategy impairs postoperative pulmonary function parameters less compared to goal-directed crystalloid administration. Methods We performed a preplanned, single-center substudy within a recently published trial evaluating the effect of goal-directed crystalloids versus colloids on a composite of major complications. Sixty patients undergoing major open abdominal surgery were randomized to Doppler-guided intraoperative fluid replacement therapy with lactated Ringer’s solution ( n = 31) or unbalanced 6% hydroxyethyl starch 130/0.4 ( n = 29). A blinded investigator performed bedside spirometry (Spirobank-G, Medical International Research, Rome, Italy) preoperatively as well as 6, 24, and 48 h postoperatively. Results Median total intraoperative fluid requirements were significantly higher during crystalloid administration compared to patients receiving colloids (4567 ml vs. 3044 ml, p = 0.01). Six hours after surgery, pulmonary function parameters did not differ significantly between the crystalloid — and the colloid group: forced vital capacity (FVC): 1.6 l (1.2–2 l) vs . 1.9 l (1.5–2.4 l), p = 0.15; forced expiratory volume in 1 second (FEV1): 1.1 l (0.9–1.6 l) vs. 1.4 l (1.2–1.7 l), p = 0.18; and peak expiratory flow (PEF): 2 l.sec −1 (1.5 – 3.6 l.sec −1 ) vs. 2.3 l.sec −1 (1.8 – 3.4 l.sec −1 ), p = 0.23. Moreover, postoperative longitudinal time × group interactions of FVC, FEV1, and PEF between 6 and 48 postoperative hours did not differ significantly. Conclusion Postoperative pulmonary function parameters were similarly impaired in patients receiving goal-directed crystalloid administration as compared to goal-directed colloid administration during open abdominal surgery. Trial registration ClinicalTrials.gov ( NCT00517127 , registered on August 16, 2007) and EudraCT (2005-004602-86).