External validation of the PC-ECMO score in postcardiotomy veno-arterial extracorporeal membrane oxygenation.

Reliable stratification of the risk of early mortality after postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) remains elusive. In this study, we externally validated the PC-ECMO score, a specific risk scoring method for prediction of in-hospital mortality after postcardiotomy V-A-ECMO. Overall, 614 patients who required V-A-ECMO after adult cardiac surgery were gathered from an individual patient data meta-analysis of nine studies on this topic. The AUC of the logistic PC-ECMO score in predicting in-hospital mortality was 0.678 (95%CI 0.630-0.726; p < 0.0001). The AUC of the logistic PC-ECMO score in predicting on V-A-ECMO mortality was 0.652 (95%CI 0.609-0.695; p < 0.0001). The Brier score of the logistic PC-ECMO score for in-hospital mortality was 0.193, the slope 0.909, the calibration-in-the-large 0.074 and the expected/observed mortality ratio 0.979. 95%CIs of the calibration belt of fit relationship between observed and predicted in-hospital mortality were never above or below the bisector (p = 0.072). The present findings suggest that the PC-ECMO score may be a valuable tool in clinical research for stratification of the risk of patients requiring postcardiotomy V-A-ECMO.

A Descriptive Analysis of Hybrid Cannulated Extracorporeal Life Support.

BACKGROUND: Extracorporeal life support (ECLS) is pivotal for sustaining the function of failing hearts and lungs, and its utilization has risen. In cases where conventional cannulation strategies prove ineffective for providing adequate ECLS support, the implementation of an enhanced system with a third cannula may become necessary. Hybrid ECLS may be warranted in situations characterized by severe hypoxemia of the upper extremity, left ventricular congestion, and dilatation. Additionally, it may also be considered for patients requiring respiratory support or experiencing hemodynamic instability. METHOD: All hybrid ECLS cases of adults at the University Hospital Zurich, Switzerland, between January 2007 and December 2019 with initial triple cannulation were included. Data were collected via a retrospective review of patient records and direct export of the clinical information system. RESULTS: 28 out of 903 ECLS cases were initially hybrid cannulated (3.1%). The median age was 57 (48.2 to 60.8) years, and the sex was equally distributed. The in-hospital mortality of hybrid ECLS was high (67.9%). In-hospital mortality rates differ depending on the indication (ARDS: 36.4%, refractory cardiogenic shock: 88.9%, cardiopulmonary resuscitation: 100%, post-cardiotomy: 100%, others: 75%). Survivors exhibited a lower SAPS II level compared with non-survivors (20.0 (12.0 to 65.0) vs. 55.0 (45.0 to 73.0)), and the allogenic transfusion of platelet concentrate was observed to be less frequent for survivors (0.0 (0.0) vs. 1.8 (2.5) units). CONCLUSION: The in-hospital mortality rate for hybrid ECLS was high. Different indications showed varying mortality rates, with survivors having lower SAPS II scores and requiring fewer platelet concentrate transfusions. These findings highlight the complexities of hybrid ECLS outcomes in different clinical scenarios and underline the importance of rigorous patient selection.

Inter-institutional analysis of the outcome after postcardiotomy veno-arterial extracorporeal membrane oxygenation.

INTRODUCTION: Patients requiring postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) have a high risk of early mortality. In this analysis, we evaluated whether any interinstitutional difference exists in the results of postcardiotomy V-A-ECMO. METHODS: Studies on postcardiotomy V-A-ECMO were identified through a systematic review for individual patient data (IPD) meta-analysis. Analysis of interinstitutional results was performed using direct standardization, estimation of observed/expected in-hospital mortality ratio and propensity score matching. RESULTS: Systematic review of the literature yielded 31 studies. Data from 10 studies on 1269 patients treated at 25 hospitals were available for the present analysis. In-hospital mortality was 66.7%. The relative risk of in-hospital mortality was significantly higher in six hospitals. Observed versus expected in-hospital mortality ratio showed that four hospitals were outliers with significantly increased mortality rates, and one hospital had significantly lower in-hospital mortality rate. Participating hospitals were classified as underperforming and overperforming hospitals if their observed/expected in-hospital mortality was higher or lower than 1.0, respectively. Among 395 propensity score matched pairs, the overperforming hospitals had significantly lower in-hospital mortality (60.3% vs 71.4%, p = 0.001) than underperforming hospitals. Low annual volume of postcardiotomy V-A-ECMO tended to be predictive of poor outcome only when adjusted for patients' risk profile. CONCLUSIONS: In-hospital mortality after postcardiotomy V-A-ECMO differed significantly between participating hospitals. These findings suggest that in many centers there is room for improvement of the results of postcardiotomy V-A-ECMO.

Predicting Survival for Veno-Arterial ECMO Using Conditional Inference Trees-A Multicenter Study.

BACKGROUND: Despite increasing use and understanding of the process, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy is still associated with considerable mortality. Personalized and quick survival predictions using machine learning methods can assist in clinical decision making before ECMO insertion. METHODS: This is a multicenter study to develop and validate an easy-to-use prognostic model to predict in-hospital mortality of VA-ECMO therapy, using unbiased recursive partitioning with conditional inference trees. We compared two sets with different numbers of variables (small and comprehensive), all of which were available just before ECMO initiation. The area under the curve (AUC), the cross-validated Brier score, and the error rate were applied to assess model performance. Data were collected retrospectively between 2007 and 2019. RESULTS: 837 patients were eligible for this study; 679 patients in the derivation cohort (median (IQR) age 60 (49 to 69) years; 187 (28%) female patients) and a total of 158 patients in two external validation cohorts (median (IQR) age 57 (49 to 65) and 70 (63 to 76) years). For the small data set, the model showed a cross-validated error rate of 35.79% and an AUC of 0.70 (95% confidence interval from 0.66 to 0.74). In the comprehensive data set, the error rate was the same with a value of 35.35%, with an AUC of 0.71 (95% confidence interval from 0.67 to 0.75). The mean Brier scores of the two models were 0.210 (small data set) and 0.211 (comprehensive data set). External validation showed an error rate of 43% and AUC of 0.60 (95% confidence interval from 0.52 to 0.69) using the small tree and an error rate of 35% with an AUC of 0.63 (95% confidence interval from 0.54 to 0.72) using the comprehensive tree. There were large differences between the two validation sets. CONCLUSIONS: Conditional inference trees are able to augment prognostic clinical decision making for patients undergoing ECMO treatment. They may provide a degree of accuracy in mortality prediction and prognostic stratification using readily available variables.

Predictors associated with mortality of veno-venous extracorporeal membrane oxygenation therapy.

Background: The use of veno-venous extracorporeal membrane oxygenation (V-V ECMO) has rapidly increased in recent years. Today, applications of V-V ECMO include a variety of clinical conditions such as acute respiratory distress syndrome (ARDS), bridge to lung transplantation and primary graft dysfunction after lung transplantation. The purpose of the present study was to investigate in-hospital mortality of adult patients undergoing V-V ECMO therapy and to determine independent predictors associated with mortality. Methods: This retrospective study was conducted at the University Hospital Zurich, a designated ECMO center in Switzerland. Data was analyzed of all adult V-V ECMO cases from 2007 to 2019. Results: In total, 221 patients required V-V ECMO support (median age 50 years, 38.9% female). In-hospital mortality was 37.6% and did not statistically vary significantly between indications (P=0.61): 25.0% (1/4) for primary graft dysfunction after lung transplantation, 29.4% (5/17) for bridge to lung transplantation, 36.2% (50/138) for ARDS and 43.5% (27/62) for other pulmonary disease indications. Cubic spline interpolation showed no effect of time on mortality over the study period of 13 years. Multiple logistic regression modelling identified significant predictor variables associated with mortality: age [odds ratio (OR), 1.05; 95% confidence interval (CI): 1.02-1.07; P=0.001], newly detected liver failure (OR, 4.83; 95% CI: 1.27-20.3; P=0.02), red blood cell transfusion (OR, 1.91; 95% CI: 1.39-2.74; P<0.001) and platelet concentrate transfusion (OR, 1.93; 95% CI: 1.28-3.15; P=0.004). Conclusions: In-hospital mortality of patients receiving V-V ECMO therapy remains relatively high. Patients' outcomes have not improved significantly in the observed period. We identified age, newly detected liver failure, red blood cell transfusion and platelet concentrate transfusion as independent predictors associated with in-hospital mortality. Incorporating such mortality predictors into decision making with regards to V-V ECMO use may increase its effectiveness and safety and may translate into better outcomes.

Hyperlactatemia and poor outcome After postcardiotomy veno-arterial extracorporeal membrane oxygenation: An individual patient data meta-Analysis.

INTRODUCTION: Postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) is associated with significant mortality. Identification of patients at very high risk for death is elusive and the decision to initiate V-A-ECMO is based on clinical judgment. The prognostic impact of pre-V-A-ECMO arterial lactate level in these critically ill patients has been herein evaluated. METHODS: A systematic review was conducted to identify studies on postcardiotomy VA-ECMO for the present individual patient data meta-analysis. RESULTS: Overall, 1269 patients selected from 10 studies were included in this analysis. Arterial lactate level at V-A-ECMO initiation was increased in patients who died during the index hospitalization compared to those who survived (9.3 vs 6.6 mmol/L, p < 0.0001). Accordingly, in hospital mortality increased along quintiles of pre-V-A-ECMO arterial lactate level (quintiles: 1, 54.9%; 2, 54.9%; 3, 67.3%; 4, 74.2%; 5, 82.2%, p < 0.0001). The best cut-off for arterial lactate was 6.8 mmol/L (in-hospital mortality, 76.7% vs. 55.7%, p < 0.0001). Multivariable multilevel mixed-effect logistic regression model including arterial lactate level significantly increased the area under the receiver operating characteristics curve (0.731, 95% CI 0.702-0.760 vs 0.679, 95% CI 0.648-0.711, DeLong test p < 0.0001). Classification and regression tree analysis showed the in-hospital mortality was 85.2% in patients aged more than 70 years with pre-V-A-ECMO arterial lactate level ≥6.8 mmol/L. CONCLUSIONS: Among patients requiring postcardiotomy V-A-ECMO, hyperlactatemia was associated with a marked increase of in-hospital mortality. Arterial lactate may be useful in guiding the decision-making process and the timing of initiation of postcardiotomy V-A-ECMO.

Central versus Peripheral Postcardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation: Systematic Review and Individual Patient Data Meta-Analysis.

BACKGROUND: It is unclear whether peripheral arterial cannulation is superior to central arterial cannulation for postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: A systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies on postcardiotomy VA-ECMO for the present individual patient data (IPD) meta-analysis. Analysis was performed according to the intention-to-treat principle. RESULTS: The investigators of 10 studies agreed to participate in the present IPD meta-analysis. Overall, 1269 patients were included in the analysis. Crude rates of in-hospital mortality after central versus peripheral arterial cannulation for VA-ECMO were 70.7% vs. 63.7%, respectively (adjusted OR 1.38, 95% CI 1.08-1.75). Propensity score matching yielded 538 pairs of patients with balanced baseline characteristics and operative variables. Among these matched cohorts, central arterial cannulation VA-ECMO was associated with significantly higher in-hospital mortality compared to peripheral arterial cannulation VA-ECMO (64.5% vs. 70.8%, p = 0.027). These findings were confirmed by aggregate data meta-analysis, which showed that central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation (OR 1.35, 95% CI 1.04-1.76, I2 21%). CONCLUSIONS: Among patients requiring postcardiotomy VA-ECMO, central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation. This increased risk is of limited magnitude, and further studies are needed to confirm the present findings and to identify the mechanisms underlying the potential beneficial effects of peripheral VA-ECMO.

The impact of direct oral anticoagulants on viscoelastic testing - A systematic review.

Background: In case of bleeding patients and in acute care, the assessment of residual direct oral anticoagulant (DOAC) activity is essential for evaluating the potential impact on hemostasis, especially when a timely decision on urgent surgery or intervention is required. Viscoelastic tests are crucial in a modern goal-directed coagulation management to assess patients' coagulation status. However, the role of viscoelastic test to detect and quantify residual DOAC plasma levels is controversially discussed. The aim of this review was to systematically summarize the evidence of viscoelastic tests for the assessment of residual DOAC activity. Method: PubMed, Embase, Scopus, and the Cochrane Library were searched for original articles investigating the effect of rivaroxaban, apixaban, edoxaban, or dabigatran plasma levels on different viscoelastic tests of the adult population from database inception to December 31, 2021. Results: We included 53 studies from which 31 assessed rivaroxaban, 22 apixaban, six edoxaban, and 29 dabigatran. The performance of viscoelastic tests varied across DOACs and assays. DOAC specific assays are more sensitive than unspecific assays. The plasma concentration of rivaroxaban and dabigatran correlates strongly with the ROTEM EXTEM, ClotPro RVV-test or ECA-test clotting time (CT) and TEG 6s anti-factor Xa (AFXa) or direct thrombin inhibitor (DTI) channel reaction time (R). Results of clotting time (CT) and reaction time (R) within the normal range do not reliable exclude relevant residual DOAC plasma levels limiting the clinical utility of viscoelastic assays in this context. Conclusion: Viscoelastic test assays can provide fast and essential point-of-care information regarding DOAC activity, especially DOAC specific assays. The identification and quantification of residual DOAC plasma concentration with DOAC unspecific viscoelastic assays are not sensitive enough, compared to recommended anti-Xa activity laboratory measurements. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=320629], identifier [CRD42022320629].

Predictors associated with mortality of extracorporeal life support therapy for acute heart failure: single-center experience with 679 patients.

Background: Extracorporeal life support (ECLS) therapy is increasingly used for cardiac and respiratory support postcardiotomy, refractory cardiogenic shock and cardiopulmonary resuscitation. This study aims to describe in-hospital mortality of patients requiring ECLS, identify independent predictors associated with mortality and analyze changes of mortality over time. Methods: This retrospective study includes all adult ECLS cases at the University Hospital Zurich, a designated ECLS center in Switzerland, in the period 2007 to 2019. Results: ECLS therapy was required in 679 patients (median age 60 years, 27.5% female). In-hospital mortality was 55.5%. Cubic spline interpolation did not detect evidence for a change in mortality over the whole period of 13 years. In-hospital mortality significantly varied between ECLS indications: 70.7% (152/215) for postcardiotomy, 67.9% (108/159) for cardiopulmonary resuscitation, 47.0% (110/234) for refractory cardiogenic shock, and 9.9% (7/71) for lung transplantation and expansive thoracic surgery (P<0.001). Logistic regression modelling showed excellent discrimination in the receiver operating characteristic (ROC) area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87-0.92] and identified significant mortality predictors: age, simplified acute physiology score (SAPS) II, as well as new liver failure and each allogenic blood transfusion unit given per day. ECLS after cardiopulmonary resuscitation was associated with significantly higher mortality compared to ECLS for refractory cardiogenic shock. Conclusions: In-hospital mortality of patients treated with ECLS therapy is high. Outcomes have not changed significantly in the observed period. We identified age, SAPS II, new liver failure and each allogenic blood transfusion unit given per day as independent mortality predictors. Knowledge of predictors strongly associated with in-hospital mortality may affect future decisions about ECLS indications and the respective management to use this elaborate therapy more effectively.

Effect of a factor-based coagulation management on blood product use after major burn injury: A retrospective cohort study.

BACKGROUND: Transfusion of allogenic blood products was shown to be associated with more adverse events and a higher mortality in severely burned patients. This study investigated the impact of a goal-directed and factor-based coagulation algorithm on blood product use and clinical outcomes in severely burned patients. METHODS: This retrospective cohort study included adult patients admitted to the burn center of the University Hospital Zurich with major burn injuries compromising 20-80% of total body surface area. We compared two 3-year periods, one before the introduction of a goal-directed coagulation and transfusion algorithm (period 1: 2009-2011) and one after (period 2: 2016-2018). We applied linear and logistic regression models adjusted for confounders. RESULTS: We analyzed 36 patients (27.8% female) versus 42 patients (14.3% female) in period 1 and 2, respectively. Comorbidities and burn types were comparable between both collectives. Treatment according to the coagulation algorithm resulted in an overall reduction of 33 units of red blood cells (95% CI -52.8 to -12.9, p = 0.002), 9 units fresh frozen plasma (95% CI -14.7 to -2.6, p = 0.006) and 1.4g fibrinogen (95% CI -2.2 to -0.5, p = 0.001) per patient. We observed less infections (61.8% vs. 41.5%, p = 0.11) and a reduced mortality (38.9% vs. 26.8%, p = 0.33) during the algorithm treated period, although not significant. CONCLUSION: Treatment of severely burned patients with a goal-directed coagulation algorithm reduced blood product use and resulted in target-oriented administration of coagulation factors to improve outcomes.

Point-of-Care Diagnostics in Coagulation Management.

This review provides a comprehensive and up-to-date overview of point-of-care (POC) devices most commonly used for coagulation analyses in the acute settings. Fast and reliable assessment of hemostasis is essential for the management of trauma and other bleeding patients. Routine coagulation assays are not designed to visualize the process of clot formation, and their results are obtained only after 30-90 m due to the requirements of sample preparation and the analytical process. POC devices such as viscoelastic coagulation tests, platelet function tests, blood gas analysis and other coagulometers provide new options for the assessment of hemostasis, and are important tools for an individualized, goal-directed, and factor-based substitution therapy. We give a detailed overview of the related tests, their characteristics and clinical implications. This review emphasizes the evident advantages of the speed and predictive power of POC clot measurement in the context of a goal-directed and algorithm-based therapy to improve the patient's outcome. Interpretation of viscoelastic tests is facilitated by a new visualization technology.