Rationale: Fibrinolysis resistance in sepsis associates with thrombotic burden, multi-organ failure and death. The degrees and dynamics of resistance that associate with mortality in acute sepsis are unknown, and a simple tool to aid clinician interpretation of fibrinolysis measurements is lacking. Objectives: To establish a point of care grading tool of fibrinolysis resistance that aligns with scoring systems for disease acuity, is substantiated by plasma fibrinolysis markers and enables rapid investigation of the fibrinolysis state at the point of care. Methods: Prospective observational study of 116 adult sepsis/septic shock patients with sequential measurements of fibrinolysis resistance during Intensive Care Unit (ICU) admission using tissue plasminogen activator (tPA) enhanced viscoelastic testing (VET). The clot lysis time (TPA-LT) adjusted for fibrin clot amplitude (TPA-LT/FIBA10, sec/mm) underwent cluster analysis and was evaluated against disease severity scores, standard pathology, clinical outcomes and fibrinolysis markers. Measurements and Main Results: Three clusters of progressively increasing fibrinolysis resistance were identified (Grades 1-3). At admission, Grade 3 associated with the highest disease severity, organ failure, haematological and biochemical perturbations, fibrinolysis marker inhibitory profile and mortality (42% versus 24% and 15% in Grade 2 and Grade 1, respectively) with a 3.9-fold [95% CI 1.4-11] increased hazard ratio for death at 28 days compared to Grade 1. Transitions between grades were frequent over 7 days with a reduced Grade associated with decreased risk of death. Conclusions: Grading of fibrinolysis resistance in sepsis enables rapid identification of patients at greatest mortality risk with any dynamic improvement corresponding to favourable clinical outcomes. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study received departmental funding only ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: South Western Sydney Local Health District Human Research Ethics Committee (2022/ETH02122). Consent was waived as permitted under the National Statement on Ethical Conduct in Human Research 2023 for low risk research in critically ill patients. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data interaction app links provided in manuscript For original data, please contact corresponding authors. [https://fortitude.shinyapps.io/TPA\_FIB\_CORREL][1] [1]: https://fortitude.shinyapps.io/TPA_FIB_CORREL

Haemorrhage and blood product usage are common in venoarterial extracorporeal membrane oxygenation (VA ECMO) and associated with increased mortality. A prospective, investigator-initiated, longitudinal observational cohort study on major haemorrhagic events in 12 ECMO centres from 3 continents for three predefined subgroups (VA ECMO initiated during cardio-pulmonary resuscitation (ECPR), after cardiothoracic surgery (CTS), for cardiogenic shock (CS)). The aim was to describe haemorrhagic complications as well as transfusion practice and anticoagulation for the whole population as well as the subgroups. In addition, independent baseline predictors for red blood cell (RBC) transfusions were evaluated. 545 prospective patients were included between 2019 and 2022 (ECPR 149, CTS 169, CS 227). Hospital mortality was 46

Background: Successfully resuscitated out-of-hospital cardiac arrest (OHCA) patients often experience cerebral malperfusion, possibly due to impaired autoregulation. Understanding the link between arterial pressure and cerebral blood flow (CBF) is essential for optimising cerebral oxygenation. This study examined early post-resuscitation CBF autoregulation and assessed the feasibility of identifying patient-specific optimal mean arterial pressure (MAPopt) from data obtained during prehospital care. Methods: We performed a post hoc analysis of 12 OHCA patients treated by a physician-staffed helicopter emergency services unit. Frontal lobe regional oxygen saturation (rSO(2)) and invasive arterial pressure were recorded during prehospital post-resuscitation care. The cerebral oximetry index (COx), defined as the correlation coefficient between rSO(2) and MAP, was calculated as a time series for each patient. COx values were plotted in 5 mmHg MAP increments and reviewed by two independent experts to determine patient specific MAPopt. Results: The mean duration of near-infrared spectroscopy monitoring was 47 min. MAPopt was identifiable in eight of 12 patients (66%). Seven patients (58%) showed impaired autoregulation, as mean COx > 0.3. Map and rSO(2) demonstrated a nonlinear relationship, with lower MAP associated with reduced cerebral oxygenation. MAPopt for the cohort was approximately 80 mmHg. Conclusions: Cerebral autoregulation assessment after OHCA is feasible with physiological data recorded in prehospital setting. Low blood pressure was associated with reduced cerebral oxygenation. Impaired autoregulation was found in most patients. Large inter-individual variation in optimal blood pressure precluded the determination of a common target pressure and emphasises the need for personalised haemodynamic management in the ultra-acute post-resuscitation phase.

Objective: To perform a systematic review and meta-analysis of intra-cardiac arrest and post-cardiac arrest intravascular volume therapy in adults and children. Methods: Searches were performed in Ovid Medline, Ovid Embase, and the Cochrane Library on October 30, 2025. Randomized trials and nonrandomized studies evaluating volume therapy during cardiac arrest and after return of spontaneous circulation were included. Two reviewers independently screened articles, extracted data, and assessed risk of bias. Meta-analyses were performed when appropriate. Certainty of evidence was assessed using GRADE methodology. Results: Fifty-eight articles were included representing 14 trials enrolling 4815 patients and 44 observational studies including 710,118 patients. All randomized trials enrolled adult patients. Of the observational studies, two included paediatric patients and eight included mixed populations. For nontraumatic intra-cardiac arrest, trials of specific interventions, including hypertonic saline with hydroxyethyl starch (which is no longer used in clinical practice) and cold crystalloid infusion, showed no difference in outcomes. For traumatic intra-cardiac arrest, direct evidence was limited to a single trial subgroup analysis showing no difference between blood products and crystalloids. For post-cardiac arrest, trials of cold crystalloid infusion and balanced versus unbalanced crystalloids showed no differences in outcomes. Randomized trials were assessed to have some concern to high risk of bias. Observational studies were at serious or critical risk of bias with inconsistent results. The certainty of evidence was low to very low. Conclusion: This systematic review found no trials directly comparing volume therapy to no volume therapy during cardiopulmonary resuscitation. The available trials, which compared different types of volume therapy strategies in adult patients, showed no significant difference in clinical outcomes across non-traumatic, traumatic, and post-cardiac arrest settings. Additional randomized trials are needed to establish the role of intra-and post-cardiac arrest volume therapy.

Frailty is an independent predictor of worse outcomes after critical illness, yet intensive care trials almost invariably omit reporting frailty distribution in the investigated cohort. This study investigated the magnitude and prevalence of imbalanced baseline distribution in frailty using the ordinal Clinical Frailty Scale that could contribute to clinically significant differences in apparent mortality. A database of 6968 patients admitted to intensive care unit was used to simulate enrolment of between 100 and up to 1000 patients into each of the control and interventional arms of a hypothetical two-arm trial. Both 1:1 randomisation and block randomisation using permuted blocks of variable sizes were simulated 100 times and referred to as ‘trials’. The observed relationship between the Clinical Frailty Scale and observed in-hospital mortality was used to determine thresholds for frailty imbalance sufficient to generate ≥2

BACKGROUND:Increased plasma renin concentrations have been reported in patients following cardiac surgery while correlations to clinical outcomes have varied. More evidence is needed to support the potential clinical utility of plasma renin as a biomarker guiding postoperative management, including the need for alternative pharmacotherapy when standard catecholaminergic cardiovascular support is insufficient. METHODS:Plasma concentrations were determined by direct renin immunoassay (milli-International Units per litre, mIU L-1) on admission to ICU and then six and 24 h later. Postoperative complications were assessed by the composite and separate incidence of acute kidney injury, acute myocardial infarction, shock, acute respiratory failure, new onset atrial flutter/fibrillation and cerebrovascular accident. Pharmacological support required to treat postoperative haemodynamic instability was quantified using the vasoactive-inotropic score. RESULTS:One hundred and four patients were studied and 54 (52%) met at least one diagnostic criterion for postoperative complications. Renin concentrations on admission (130 [34-445] mIU L-1) and six (119 [35-447] mIU L-1) and 24 h later (184 [54-513] mIU L-1) were not significantly different with substantial inter-individual variation. Cumulative renin concentrations over 24 h were higher in haemodynamically unstable patients (median difference 1296 [54-2943] mIU L-1, p = 0.04) and in patients with any postoperative complication (median difference 1887 [908-6177] mIU L-1, p = 0.04). Plasma renin increased by 11 mIU L-1 for each unit increase in the vasoactive-inotropic score. A statistical model using all renin measurements predicted haemodynamic instability (AUC 0.77 [0.55-0.95], p = 0.04) and shock (AUC 0.95 [0.83-1.0], p = < 0.001), but not the composite or separate incidence of the other complications. CONCLUSIONS:Haemodynamic compromise, but not postoperative complications overall, were associated with serial plasma renin concentrations during the first 24 h of ICU admission following cardiac surgery. Additional prospective studies are warranted to elucidate the relationship between renin dynamics, postoperative complications and criteria for escalating vasopressor therapy. EDITORIAL COMMENT:This prospective observational study tested whether postoperative increase in plasma renin in patients undergoing cardiac surgery was associated with postoperative complications. No such association was found, but an association between increase in plasma renin and haemodynamic compromise and need for pharmacological support was found. Larger studies are warranted to elucidate the role of plasma renin as a biomarker for postoperative complications. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT043303455.

BACKGROUND:Venous return (VR) physiology may be elucidated using a calculated mean systemic filling pressure analogue (Pmsa) that reflects the stressed intravascular volume. The aim of this study was to explore differences in VR physiological variables with the hypothesis that vasopressor therapy targeting a higher mean arterial pressure (MAP) would associate with an increased volume state. This would be important to appreciate the intravascular volume effect of an intervention that traditionally is judged by the pressure response alone. METHODS:This exploratory study used data from the BOX trial that investigated a higher (MAP of 77 mmHg, MAP77) versus a lower (63 mmHg, MAP63) blood pressure target during intensive care of survivors from out-of-hospital cardiac arrest. Data from 730 patients (MAP63, n = 362 and MAP77, n = 368) were used to calculate Pmsa, the driving pressure for VR (VRdP, the difference between Pmsa and central venous pressure [CVP]), the resistance to venous return (RVR, the VRdP divided by the cardiac output [CO]) and heart efficiency (Eh, the VRdP divided by Pmsa). Linear mixed models were used to evaluate longitudinal haemodynamic data captured from admission to the intensive care unit and over 36 h. RESULTS:The Pmsa was consistently higher in the MAP77 group (p < .03) while the CVP was not statistically different. The greater Pmsa translated into a progressively increasing VRdP (p < .0001) and thus an increased CO (p < .001). Similar stroke volumes in both groups meant that CO was maintained by an increased heart rate in MAP77 (p < .001). The RVR was higher in MAP77 (p < .04) but gradually decreased in both groups, while the Eh was similar overall. CONCLUSION:In conclusion, a higher MAP target effectively increased the stressed intravascular volume to sustain a higher CO. EDITORIAL COMMENT:This post-hoc analysis of the BOX trial explores VR physiology and how it is influenced by the use of various doses of noradrenaline and dopamine. A higher blood pressure target appears to increase VR by increasing the stressed intravascular volume. This results in an increase in the CO. These findings are important given the worry about the effect of a higher afterload on cardiac function.

BACKGROUND:An acute episode of delirium among adults following cardiac surgery is associated with increased length of stay in intensive care, prolonged mechanical ventilation, and increased risk of mortality. This robust systematic review with Bayesian meta-analysis, including trial sequential analysis, has been undertaken to explore the use of dexmedetomidine to reduce the occurrence of delirium. METHODS:A systematic search for relevant published clinical trial reports was registered on PROSPERO (CRD42023460126) and guided by the PRISMA statement guidelines. Databases included Cochrane, CINAHL, PubMed, Embase, Medline and PsychInfo. Studies included were randomised controlled trials reporting on the adult population (> 18 years) undergoing cardiac surgery, comparing dexmedetomidine to another drug or placebo. Trials of paediatric populations, protocols and reviews were excluded. The primary outcome examined was the effect of dexmedetomidine on the incidence of delirium in postoperative cardiac surgery in the Intensive Care Unit (ICU). Secondary outcomes of interest were the occurrence of hypotension, bradycardia, length of ICU stay and sedation utilised in the control and comparator groups. Trial sequential analysis and meta-regression were used to explore heterogeneity. Risk ratios (RRs) and Bayesian posterior probabilities are presented. The prior for this was empirical, being based on distributions for emergency and critical care systematic reviews from the Cochrane Database. The Cochrane ROB-2 tool was utilised to assess risk of bias, and the GRADE approach for certainty of evidence is presented. RESULTS:A total of 699 randomised control trials were identified. After the removal of duplicates and screening for eligibility, 27 studies were included in the meta-analysis. The Robust Bayesian Model Averaging summary effect for delirium prevention was estimated to be 0.76 (95% credible interval [CrI] 0.56-1.00) for using dexmedetomidine, with a posterior probability of 97% of any treatment effect. Meta-regression suggested that the baseline risk of delirium is a strong indicator of increased effectiveness, and trial sequential analysis indicates potential effectiveness. A low risk of bias was evident in 19 of the 27 studies, 6 studies had some risk of bias, and 2 studies were judged to be high risk. The certainty of evidence used across the 27 studies was determined to be low overall. CONCLUSIONS:Dexmedetomidine may reduce the risk of delirium among adults following cardiac surgery; however, uncertainty remains due to heterogeneity. Therefore, adequately powered and well-designed multi-centre trials are needed to address this current uncertainty. EDITORIAL COMMENT:The effects of dexmedetomidine on postoperative delirium in adult cardiac surgical patients: a Bayesian meta-analysis and trial sequential analysis. This systematic review with meta-analysis concerning evidence for possible effects of dexmedetomidine on post-cardiac surgery delirium presents detailed analysis showing a possible treatment drug effect on reducing post-operative delirium in this type of cohort, though still with some uncertainty.

BACKGROUND:The international multi-center randomized controlled STEPCARE-trial will investigate optimal management of sedation, temperature, and mean arterial pressure (MAP) during intensive care in out-of-hospital cardiac arrest (OHCA) patients due to various etiologies. The primary outcome is mortality at 6 months. This protocol describes an extended follow-up sub-study of the STEPCARE-trial with the main objective to provide detailed long-term outcomes for survivors and caregivers. It will focus on potential neuroprotection and improved recovery for different targets of sedation, temperature, and MAP management at 6 and 12 months post-OHCA. METHODS:All survivors and one caregiver per survivor at selected STEPCARE sites will be invited to participate. Randomization is stratified by site. This sub-study extends the main STEPCARE follow-up at 6 months by undertaking detailed assessments, face-to-face meetings, inclusion of a caregiver, and repeating the assessments at 12 months. Our main outcome for survivors is cognitive function measured by the Montreal Cognitive Assessment, and for caregivers, the caregiver burden measured by the Zarit Burden Interview. Additional outcomes include symptoms of anxiety, depression, post-traumatic stress disorder, fatigue, physical function, life satisfaction, and life impact (disability), assessed by psychometrically robust measures. The estimated sample size is 600. Efforts to improve interrater reliability and decrease missing data are integral to the study design. CONCLUSION:These detailed long-term outcomes will explore the possible benefits or risks of fever, sedation, and blood pressure management in post-OHCA survivors. Additionally, this study will explore survivorship after cardiac arrest from various perspectives, including different causes of arrest. CLINICALTRIALS:gov: NCT0207942.

BACKGROUND:Acutely infected critically ill patients develop coagulopathies and perturbations to the fibrinolysis system that manifest as immunothrombosis. Whole blood viscoelastic testing, using an exogenous fibrinolytic agent to enhance fibrinolysis (FE-VET) can assess both processes of coagulation and fibrinolysis at the bedside. This scoping review aimed to illustrate clinical applicability, knowledge gaps and unmet needs for this emerging technology. METHODS:A systematic search of bibliographic databases and the grey literature was performed between the 10th October 2024 and the 14th January 2025 using a pre-published protocol and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline for scoping reviews (PRISMA-ScR). Studies reporting FE-VET to investigate fibrinolysis in acutely infected patients admitted to the intensive care unit were assessed, including associations with disease severity and clinical outcomes. RESULTS:The search identified 297 studies with 24 included in this review. Fifteen studies were observational (12 prospective, 3 retrospective), 4 case reports and series, 2 validation studies, 2 letters, and 1 poster abstract. No randomised controlled trials were identified. Most studies used varying concentrations of tissue plasminogen activator (tPA) to enhance fibrinolysis, with FE-VET performed at a single time point and the lysis time to achieve 50% reduction of maximum clot firmness being the most frequently reported variable. Fibrinolysis resistance was the prevailing state reported in acute sepsis or COVID-19 infections and associated with increased disease severity and worse clinical outcomes. CONCLUSION:Viscoelastic testing using a fibrinolysis enhancing agent demonstrated a spectrum of fibrinolysis resistance in acutely infected critically ill patients, associated with increased disease severity and mortality. Standardisation of the concentrations of fibrinolysis enhancing agents and the reporting of clot lysis parameters across testing devices are needed to establish reference values. This would improve future clinical studies of fibrinolysis, including trials of fibrinolytic therapies using a personalised medicine approach.

This study assessed the accuracy of three International Classification of Diseases (ICD) codes methods derived from Global Burden of Disease (GBD) sepsis study (modified GBD method) in identifying sepsis, compared to the Angus method. Sources of errors in these methods were also reported. Prospective multicentre, observational, study. Emergency Department patients aged ≥ 16 years with high sepsis risk from nine hospitals in NSW, Australia were screened for clinical sepsis using Sepsis 3 criteria and coded as having sepsis or not using the modified GBD and Angus methods. The three modified GBD methods were: Explicit—sepsis-specific ICD code recorded; Implicit—sepsis-specific code or infection as primary ICD code plus organ dysfunction code; Implicit plus—as for Implicit but infection as primary or secondary ICD code. Agreement between clinical sepsis and ICD coding methods was assessed using Cronbach alpha (α). For false positive cases (ICD-coded sepsis but not clinically diagnosed), the ICD codes leading to those errors were documented. For false negatives (clinically diagnosed sepsis but ICD-coded), uncoded sources of infection and organ dysfunction were documented. Of 6869 screened patients, 450 (median age 72.4 years, 48.9

INTRODUCTION:Viscoelastic testing (VET) has been implemented in clinical care to diagnose and manage coagulation in patients with manifest or high risk of major bleeding. However, the breakdown of formed blood clots, that is, fibrinolysis, has been comparatively less studied. There is an increasing recognition that acute infections trigger a dysregulated immunothrombotic response, which has focused attention on viscoelastic testing to identify in particular fibrinolysis resistant states. METHODS:This scoping review on fibrinolysis assessment using viscoelastic testing will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Publications will be included in the review if they evaluate the fibrinolytic capacity of adult patients admitted to an intensive care unit (ICU) for acute infection (including SARS-CoV2) using VET assays that included a fibrinolytic agent. No date or language restrictions will be applied, and all study designs will be considered. A peer-reviewed search strategy will be employed in multiple electronic bibliographic databases and will also include the grey literature. RESULTS:The included studies will be reported by descriptive analyses and tabulated results. CONCLUSION:This scoping review aims to map the research describing viscoelastic testing (VET) to assess fibrinolysis in acutely infected critically ill patients, with the goal of identifying diagnostic capabilities, any associations with patient outcomes, and the potential to guide clinical management.

Cardiac output and mixed venous oxygen saturation are key variables in monitoring adequate oxygen delivery and have typically been measured using pulmonary artery catheterisation. The capnodynamic method measures effective pulmonary blood flow utilising carbon dioxide kinetics in ventilated patients. Combined with breath-by-breath measurements of carbon dioxide elimination, a non-invasive approximation of mixed venous oxygen saturation can be calculated. This study primarily investigated the agreement between mixed venous oxygen saturation calculated using the capnodynamic method and blood gas analysis of mixed venous blood sampled via a pulmonary artery catheter in 47 haemodynamically stable postoperative cardiac patients. Both measurements were synchronised and performed during alveolar recruitment by stepwise changes to the level of positive end-expiratory pressure. Simultaneously, we studied the agreement between effective pulmonary blood flow and thermodilution cardiac output. The Bland–Altman method for repeated measurements and calculation of percentage error were used to examine agreement. Measurements before and after alveolar recruitment were analysed by a paired t test. The study hypothesis for agreement was a limit of difference of ten percentage points between mixed venous oxygen saturation using the capnodynamic algorithm vs. catheter blood gas analysis. Capnodynamic calculation of mixed venous saturation compared to blood gas analysis showed a bias of -0.02 [95

Critically ill patients with shock receiving vasopressor or inotrope therapy in ICU are often exposed to relative hypotension, which is quantified as percentage blood pressure deficit relative to usual pre-illness blood pressure. Whether minimising such blood pressure deficit, by adjusting blood pressure targets according to patients’ pre-illness blood pressure (individualised blood pressure target strategy), can improve clinical outcomes remains unclear. Therefore, we are conducting a multicenter randomised controlled trial, the REACT SHOCK RCT, comparing individualised blood pressure targets to standard care among critically ill patients with shock. The REACT SHOCK RCT is an international, multicenter, parallel-group, randomised, standard-care controlled, clinical superiority trial that will be conducted in up to 35 ICUs in Australia, Ireland, Singapore, UK and USA. In total, 1260 patients, receiving vasopressor therapy for non-haemorrhagic shock in ICU, will be randomly assigned to individualised mean arterial blood pressure (MAP) targets (determined as an average of 2–5 recent pre-illness blood pressure readings within last 3 years, with a MAP target range of 55 to 95 mmHg) or standard care (default MAP target of 65 mmHg) in a 1:1 ratio. The REACT SHOCK RCT is anticipated to complete recruitment by 2028. The primary endpoint is all-cause 14-day mortality. Secondary endpoints are major adverse kidney events by day 14, all-cause 90-day mortality, survival time to 14 days and 90 days, and renal replacement therapy free days by day 28. The REACT SHOCK RCT is the first international multicenter randomised clinical trial designed to ascertain whether an individualised blood pressure target strategy is superior to standard care for critically ill patients with shock. This trial will generate evidence that may influence current recommendations for MAP targets during management of shock in ICU. The pre-specified protocol summary and statistical analysis plan are presented here. Prospectively registered on Australian and New Zealand Clinical Trials Registry (ANZCTRN 12623000044628); ClinicalTrials.gov ID NCT05850962 dated 29th April 2023.

Background. Increased plasma renin concentrations have been reported in patients following cardiac surgery while correlations to clinical outcomes have varied. More evidence is needed to support the potential clinical utility of plasma renin as a biomarker guiding postoperative management, including the need for alternative pharmacotherapy when standard catecholaminergic cardiovascular support is insufficient Methods. Plasma concentrations were determined by direct renin immunoassay (milli-International Units per litre, mIU.l − 1 ) on admission to ICU and then six and 24 hours later. Postoperative complications were assessed by the composite and separate incidence of acute kidney injury, acute myocardial infarction, shock, acute respiratory failure, new onset atrial flutter/fibrillation and cerebrovascular accident. Pharmacological support required to treat postoperative haemodynamic instability was quantified using the vasoactive-inotropic score. Results. 104 patients were studied and 54 (52%) met at least one diagnostic criterion for postoperative complications. Renin concentrations on admission (130 [34–445] mIU.l − 1 ) and six (119 [35–447] mIU.l − 1 ) and 24 hours later (184 [54–513] mIU.l − 1 ) were not significantly different with substantial inter-individual variation. Cumulative renin concentrations over 24 hours were higher in haemodynamically unstable patients (median difference 1296 [54-2943] mIU.l − 1 , p = 0.04) and in patients with any postoperative complication (median difference 1887 [908–6177] mIU.l − 1 , p = 0.04). Plasma renin increased by 11 mIU.l − 1 for each unit increase in the vasoactive-inotropic score. A statistical model using all renin measurements predicted haemodynamic instability (AUC 0.77 [0.55–0.95], p = 0.04) and shock (AUC 0.95 [0.83-1.0], p = < 0.001), but not the composite or separate incidence of the other complications. Conclusions. Haemodynamic compromise in postoperative cardiac patients could be predicted using serial plasma renin concentrations measured during the first 24 hours of ICU admission, supporting the potential role of renin as a biomarker for targeted haemodynamic management. Additional prospective studies are warranted to elucidate the relationship between renin dynamics, postoperative complications, and to establish evidence-based criteria for escalating vasopressor therapy. Trial registration: ClinicalTrials.gov NCT043303455 (registered 8 March 2020)

Cardiac output is dependant of intrinsic cardiac pump function, afterload and the venous return of blood to the heart. The latest guidelines from the European Resuscitation council suggest a more individualized approach to interventions in post-resuscitation care. This individualization might be achieved by a physiological view focusing on venous return hemodynamics, incorporating both the volume state and the pressure gradient for venous return. Hypothesis We hypothesized that a mean arterial blood pressure (MAP) target of 77 mmHg would influence the volume state and venous return differently compared to a MAP target of 63 mmHg. This post-hoc study is based on the BOX-trial, which randomized comatose patients resuscitated after out of hospital cardiac arrest to either a MAP of 77 mmHg (MAP77) or 63 mmHg (MAP63). The 730 out of 789 patients included in this study were all equipped with a pulmonary artery catheter (PAC). The volume state was calculated by the analogue mean systemic filling pressure (Pmsa), a measurement for the intravascular volume: Pmsa = CVP • 0.96 + MAP • 0.04 + CO • c (anthropometric and age adjusted resting resistance). The venous return driving pressure was calculated as: Pmsa – CVP (mmHg). Parameters was compared between the MAP targets in the first 36 hours from admission. Patients in MAP77 received a significantly higher accumulated dosage of noradrenaline (NA) p<0.0001. compared to those in MAP63. A difference between groups was also found regarding administration of fluids: 6009 (IQR: 4726-7495) ml vs 5526 (IQR: 4408-6744) ml for MAP77 vs. MAP63 p<0.0001. The intravascular volume state (calculated by Pmsa) was higher in MAP77 at all timepoints compared to MAP63. While CVP was similar between both groups, the heart rate was higher in MAP77. Venous return driving pressure of blood to the heart, and therefore cardiac output, increased continuously in both groups during the initial 36h but was significantly higher in MAP77 compared to MAP63 at all timepoints p<0.0001, see figure 1. By increasing MAP with predominantly NA, the stressed vascular volume is increased providing a greater pressure gradient for venous return to the heart. Besides the increased chronotropic effect from NA, the heart adapted to the increased filling by increasing the heart rate and thus CO. By assessing hemodynamic through this holistic perspective, clinicians could be guided more effectively to improve perfusion compared to the traditional cardio centric approach. Figure 1. Venous return driving pressure in patients randomized to a high (MAP of 77 mmHg) or a low (MAP of 63 mmHg) blood pressure.Figure 1

Background: The optimal transfusion threshold for patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains uncertain. Methods: We used data from OBLEX (ClinicalTrials.gov: NCT03714048), an international, prospective, observational study conducted across 12 centres in Australia, Europe, and North America between 2019 and 2022. The study collected information on patient demographics, bleeding risk factors, transfusion practices during the first seven days of ECMO, and in-hospital mortality. Using these data, we emulated a target trial comparing the effects of liberal transfusion practice (transfusion initiated at Hb ≥ 90 g/L) and restrictive transfusion practice (transfusion initiated at Hb ≤ 70g/L) on hospital mortality within seven days of ECMO initiation. Sequential trials approach was used to estimate the causal contrast. Results: A total of 534 patients were included, with 46% dying during hospitalisation. After accounting for potential confounders, the liberal transfusion practice demonstrated a modest survival benefit within the first two days of ECMO, with differences in survival probabilities of 12% (95% CI: 3% to 21%) at day 2 and 13% (95% CI: 2% to 25%) at day 3, corresponding to the number needed to treat (NNT) of 8 and 7 respectively. These results were consistent across sensitivity and exploratory analyses. Conclusion: This target trial emulation study suggests that a liberal transfusion threshold may provide a modest survival benefit during the early course of VA-ECMO. Prospective studies are needed to confirm these findings, assess clinical adoption, and investigate underlying mechanism.