Impact of a bundle of care (intravenous iron, erythropoietin and transfusion metabolic adjustment) on post-operative transfusion incidence in cardiac surgery: a single-centre, randomised, open-label, parallel-group controlled pilot trial.

Background: Red blood cell (RBC) transfusions are frequent in patients after cardiac surgery. This study assessed whether a bundle of care including pre-operative and post-operative administration of erythropoietin (EPO) with intravenous iron supplementation, and restrictive transfusion adjusted for ScvO2 could result in reduced postoperative transfusions. Methods: In this single-centre, randomised, open-label, parallel-group controlled pilot study, patients undergoing elective cardiac surgery with high risk of transfusion in a University Hospital were enrolled by the investigator and the randomisation procedure using a central internet-based system was made by the clinical research assistant. Since the trial was open-label, no masking was used. Patients were assigned (1:1) to either the STOP group (40,000 IU subcutaneous EPO combined with 20 mg/kg intravenous ferric carboxymaltose if Hb < 13 g/dL the day before surgery or at ICU admission, and RBC transfusion if Hb ≤ 8 g/dL and ScvO2 ≤ 65%, or additional EPO dose if 8 < Hb < 13 g/dL) or to the control group (RBC transfusion if Hb ≤ 8 g/dL, or, if 8 < Hb < 13 g/dL, intravenous iron sucrose 200 mg or 300 mg according to weight). Primary outcome was the incidence of postoperative RBC transfusion up to hospital discharge or postoperative day 28. The trial is registered with ClinicalTrials.gov, NCT04141631. Findings: Between Jan 20, 2020, and Sept 6, 2022, among 128 patients enrolled, 123 (male, 54.4%, 67/123) were included in the full analysis set: 62 in the STOP group and 61 in the control group. Nine patients (14.5%, 9/62) in the STOP group required RBC transfusion vs 19 (31.2%, 19/61) in the control group (odds ratio 0.37 [95% CI: 0.15-0.91], p = 0.03). The median length of follow up to transfusion was 2.6 days (1.5; 4.6) and 3.3 (1.6; 4.2) in control and STOP groups respectively (p = 0.61). Interpretation: The bundle of care may reduce postoperative RBC transfusion. The findings should be taken with caution due to the unblinded and exploratory nature of the study. Funding: University of Montpellier Hospital and Vifor Pharma.

Early temporary mechanical circulatory support for cardiogenic shock: Real-life data from a regional cardiac assistance network.

BACKGROUND: Temporary mechanical circulatory support as well as multidisciplinary team approach in a regional care organization might improve survival of cardiogenic shock. No study has evaluated the relative effect of each temporary mechanical circulatory support on mortality in the context of a regional network. METHODS: Prospective observational data were retrieved from patients consecutively admitted with cardiogenic shock to the intensive care units in 3 centers organized into a regional cardiac assistance network. Temporary mechanical circulatory support indication was decided by a heart team, based on the initial shock severity or if shock was refractory to medical treatment within 24 hours of admission. A propensity score for circulatory support use was used as an adjustment co-variable to emulate a target trial. The primary endpoint was in-hospital mortality. RESULTS: Two hundred and forty-six patients were included in the study (median age: 59.5 years, 71.9% male): 121 received early mechanical assistance. The main etiologies were acute myocardial infraction (46.8%) and decompensated heart failure (27.2%). Patients who received early mechanical assistance had more severe conditions than other patients. Their crude in-hospital mortality was 38% and 22.4% in other patients but adjusted in-hospital mortality was not different (hazard ratio 0.91, 95% CI:0.65-1.26). Patients with mechanical assistance had a higher rate of complications than others with longer Intensive Care Unit and hospital stays. CONCLUSIONS: In the conditions of a cardiac assistance regional network, in-hospital mortality was not improved by early mechanical assistance implantation. A high incidence of complications of temporary mechanical circulatory support may have jeopardized its potential benefit.

Restrictive Transfusion Strategy after Cardiac Surgery.

BACKGROUND: Recent guidelines on transfusion in cardiac surgery suggest that hemoglobin might not be the only criterion to trigger transfusion. Central venous oxygen saturation (Svo2), which is related to the balance between tissue oxygen delivery and consumption, may help the decision process of transfusion. We designed a randomized study to test whether central Svo2-guided transfusion could reduce transfusion incidence after cardiac surgery. METHODS: This single center, single-blinded, randomized controlled trial was conducted on adult patients after cardiac surgery in the intensive care unit (ICU) of a tertiary university hospital. Patients were screened preoperatively and were assigned randomly to two study groups (control or Svo2) if they developed anemia (hemoglobin less than 9 g/dl), without active bleeding, during their ICU stay. Patients were transfused at each anemia episode during their ICU stay except the Svo2 patients who were transfused only if the pretransfusion central Svo2 was less than or equal to 65%. The primary outcome was the proportion of patients transfused in the ICU. The main secondary endpoints were (1) number of erythrocyte units transfused in the ICU and at study discharge, and (2) the proportion of patients transfused at study discharge. RESULTS: Among 484 screened patients, 100 were randomized, with 50 in each group. All control patients were transfused in the ICU with a total of 94 transfused erythrocyte units. In the Svo2 group, 34 (68%) patients were transfused (odds ratio, 0.031 [95% CI, 0 to 0.153]; P < 0.001 vs. controls), with a total of 65 erythrocyte units. At study discharge, eight patients of the Svo2 group remained nontransfused and the cumulative count of erythrocyte units was 96 in the Svo2 group and 126 in the control group. CONCLUSIONS: A restrictive transfusion strategy adjusted with central Svo2 may allow a significant reduction in the incidence of transfusion.

Blood Loss Kinetics During the First 12 Hours After On-Pump Cardiac Surgical Procedures.

BACKGROUND: Anemia and coagulation management and a restrictive transfusion strategy are key points of blood management in patients undergoing cardiac surgical procedures. However, little consideration has been given to the kinetics of postoperative bleeding. This prospective observational study investigated bleeding kinetics from chest tubes to assess whether it was possible to predict, within the early postoperative hours, major bleeding at 12 postoperative hours. METHODS: Adult cardiac surgical patients who were admitted consecutively to the postoperative intensive care unit in a tertiary academic hospital from January to June 2016 were included. Blood volume was collected from the chest drains, and major bleeding was defined as bleeding exceeding the 90th percentile of the volume distribution at 12 postoperative hours. Receiver operating characteristics curve analysis was performed with hourly bleeding thresholds to determine the best predictor of major bleeding. RESULTS: In 292 patients, bleeding at 12 postoperative hours ranged from 60 to 2190 mL (median, 350 mL), and 30 patients had major bleeding, with a threshold of 675 mL. Bleeding volume declined logarithmically, 54% [IQR, 45% to 63%] within the first 4 hours. Patients with major bleeding had a higher bleeding volume every hour (P < .004). A good predictive value was observed within the first 2 hours (2.73 mL/kg; receiver operating characteristics area under the curve, 0.87 ± 0.04 [IQR, 0.79 to 0.94]; P< .001). CONCLUSIONS: The hourly rate of chest tube blood loss seems to be relevant to predict, within the first postoperative hours after cardiac surgical procedures, major bleeding at 12 postoperative hours. Early detection of blood loss may help to improve a patient's blood conservation strategy because it may prompt preemptive treatments.

Pulse pressure and end-tidal carbon dioxide for monitoring low native cardiac output during veno-arterial ECLS: a prospective observational study.

BACKGROUND: Veno-arterial extracorporeal life support (VA-ECLS) results in cardiopulmonary shunting with reduced native cardiac output (NCO). Low NCO occurrence is common and associated with risk of thromboembolic and pulmonary complications. Practical tools for monitoring NCO during VA-ECLS would therefore be valuable. Pulse pressure (PP) and end-tidal carbon dioxide (EtCO2) are known to be related to cardiac output. We have designed a study to test whether PP and EtCO2 were efficient for the monitoring of NCO during VA-ECLS. METHODS: In this prospective single-center observational study, patients who underwent a VA-ECLS for cardiogenic shock from January 2016 to October 2017 were included, provided low NCO was suspected by a PP < 20 mmHg. NCO was measured with pulmonary artery catheter or echocardiography and compared to PP and EtCO2. The ability of PP and EtCO2 to predict NCO < 1 L/min was evaluated with receiver operating characteristics (ROC) curves. RESULTS: Among the 106 patients treated with VA-ECLS for cardiogenic shock during the study period, 26 were studied, allowing the collection of 196 study points. PP and EtCO2 relationships with NCO were nonlinear and showed strong correlations for NCO < 2 L/min (r = 0.69 and r = 0.78 respectively). A PP < 15 mmHg and EtCO2 < 14 mmHg had good predictive values for detecting NCO < 1 L/min (area under ROC curve 0.93 [95% CI 0.89-0.96] and 0.97 [95% CI 0.94-0.99] respectively, p = 0.058). CONCLUSIONS: PP and EtCO2 may offer an accurate real-time monitoring of low NCO events during VA-ECLS support. Further studies are needed to show if their utilization may help to implement therapeutic strategies in order to prevent thromboembolic and respiratory complications associated with VA-ECLS, and to improve patients' prognosis. TRIAL REGISTRATION: NCT03323268 , July 12, 2016.

Serum Phosphate Kinetics in Acute Kidney Injury After Cardiac Surgery: An Observational Study.

OBJECTIVE: Acute kidney injury (AKI) is a common complication after cardiac surgery and may affect prognosis. Serum phosphate (SPh) elevation is well-known to occur after AKI but not well-documented. The aim of the present study was to describe SPh changes during AKI after cardiac surgery and to assess the accuracy for the diagnosis of AKI severity and recovery. DESIGN: Prospective, single center, observational study. SETTING: Intensive care unit of a tertiary university hospital. PARTICIPANTS: All patients admitted consecutively to the intensive care unit between February 2015 and March 2016. MEASUREMENTS AND MAIN RESULTS: AKI was defined according to Kidney Disease Improving Global Outcomes criteria and classified as nonsevere (stage 1) and severe (stages 2 and 3). Receiver operating characteristic curve analysis was conducted to test reliability of SPh for AKI severity and recovery. AKI occurred in 86 of the 260 patients included (33%) in the study; 58 (67%) experienced nonsevere AKI, and 28 (33%) experienced severe AKI. A significant elevation of SPh values was observed in AKI patients, which peaked at 48 hours. At this time, an SPh of 1.33 mmol/L demonstrated a good accuracy for AKI severity, with an area under the curve of 0.91 (95% confidence interval 0.82-1.00). For kidney recovery, a 25% SPh decrease 24 hours after the peak had a positive predictive value of 100%, and a 2.5% decrease allowed for the reclassification of patients when the serum creatinine had not decreased enough. CONCLUSIONS: The results showed that SPh changes closely follow AKI severity and kidney recovery after cardiac surgery. In addition to serum creatinine, this simple biological marker may help predict early favorable outcome.

Effect of Impella During Veno-Arterial Extracorporeal Membrane Oxygenation on Pulmonary Artery Flow as Assessed by End-Tidal Carbon Dioxide.

Peripheral veno-arterial extracorporeal membrane oxygenation (VA ECMO) exposes the patient to a pulmonary blood flow bypass and a left ventricle afterload increase. Impella, a catheter-mounted microaxial rotary pump, has been proposed for left ventricle (LV) unloading in combination with VA ECMO. In order to assess the effect of Impella on pulmonary flow and LV preload, we checked Doppler pulmonary artery velocity-time integral (pVTI) and LV diastolic diameter (LVED) by transesophageal echocardiography and end-tidal carbon dioxide (EtCO2) during a step-by-step increase in Impella flow (Impella ramp test). From 134 patients on VA ECMO retrieved from our database, 27 (20%) have benefited secondary Impella implantation, out of which 11 patients had available EtCO2, pVTI, and LVED measurements at various levels of Impella speeds. We observed a proportional increases in pVTI and EtCO2 and decrease in LVED (p ≤ 0.001) during Impella flow increase. There was a significant correlation between EtCO2 and pVTI (Pearson correlation coefficient 0.64; p = 0.006). The study shows that Impella improves pulmonary flow, an effect that can be easily measured by EtCO2 monitoring, and ensures LV discharge, allowing adapting Impella flow adequately to patient's individual needs.

Circulatory Support with Extracorporeal Membrane Oxygenation and/or Impella for Cardiogenic Shock During Myocardial Infarction.

Temporary mechanical circulatory support (TCS) is recommended for patients with profound cardiogenic shock (CS). Extracorporeal membrane oxygenation (ECMO) and Impella are possible TCS devices, but the device choice and the implantation timing are not definitely established, specifically during acute myocardial infarction. We have analyzed the respective use of ECMO or Impella (2.5, CP, or 5.0) for CS following acute myocardial infarction, from a cohort of patients who underwent TCS within 72 hours after admission for emergency percutaneous coronary intervention (PCI) from January 2009 to April 2015. Among 88 TCS-treated patients, 42 had early TCS: 23 ECMO and 19 Impella. Cardiac management, including PCI, was similar between the two groups, but ECMO patients were sicker than Impella patients (higher blood lactate level at ICU admission, higher vasoactive-inotroic and ENCOURAGE scores before TCS implantation, p ≤ 0.02). Three patients (7%) have had TCS implantation before admission, but TCS was implanted mostly in cathlab (43%, 1 during PCI, 13 just after PCI) or soon after ICU admission (50%, n = 21). Modification of the initial TCS choice was required in 10 cases (24%) for assistance upgrading in case of Impella (n = 4) or for left ventricle unloading in case of ECMO (n = 6). Extracorporeal membrane oxygenation is the technique of choice in case of profound CS, whereas Impella devices seem more appropriate for less severe hemodynamic compromise. Interestingly, the combination of both techniques may help to overcome the limits inherent to each device.

Continuous venovenous renal replacement therapy in critically ill patients: A work load analysis.

OBJECTIVES: To evaluate the nursing workload related to two techniques of continuous renal replacement therapy. RESEARCH METHODOLOGY: We analysed retrospectively the nursing work load caused directly by continuous renal replacement therapy in a cohort of patients admitted consecutively over 10 months. Two types of continuous renal replacement therapy have been compared: dialysis with regional citrate anticoagulation and haemodiafiltration with systemic heparin coagulation. SETTING: Academic Hospital Intensive Care Unit. MAIN OUTCOME MEASURES: The nursing workload was defined by the time spent in the management of continuous renal replacement therapy, including preparation of the circuit and related biological controls. RESULTS: 60 patients underwent a total of 202 sessions of continuous renal replacement therapy. The nursing workload as expressed as % time of nursing care was similar (12.3 [9.4-18.8] vs 13.4 [11.7-17.0] %, for haemodiafiltration and dialysis respectively, P=0.06). However, the distribution of the nursing workload is different: the bigger proportion of care is circuit preparation in haemodiafiltration and biology control in dialysis. CONCLUSIONS: Nursing time dedicated to continuous renal replacement therapy is similar whatever the renal replacement therapy technique. However, a longer duration of the filter and a better circuit predictability with dialysis and citrate anticoagulation are potential benefits for nursing workload.

Management and outcome of patients supported with Impella 5.0 for refractory cardiogenic shock.

INTRODUCTION: Cardiogenic shock refractory to standard therapy with inotropes and/or intra-aortic balloon pump is accompanied with an unacceptable high mortality. Percutaneous left ventricular assist devices may provide a survival benefit for these very sick patients. In this study, we describe our experience with the Impella 5.0 device used in the setting of refractory cardiogenic shock. METHODS: In this observational, retrospective, single-center study we included all the consecutive patients supported with Impella 5.0, between May 2008 and December 2013, for refractory cardiogenic shock. Patients' baseline and procedural characteristics, hemodynamics and outcome to the first 48 h of support, to ICU discharge and day-28 visit were collected. RESULTS: A total of 40 patients were included in the study. Median age was 57 years and 87.5 % were male. Cardiogenic shock resulted from acute myocardial infarction in 17 patients (43 %), dilated cardiomyopathy in 12 (30 %) and postcardiotomy cardiac failure in 7 (18 %). In 15 patients Impella 5.0 was added to an ECMO to unload the left ventricle. The median SOFA score for the entire cohort prior to circulatory support was 12 [10-14] and the duration of Impella support was 7 [5-10] days. We observed a significant decrease of the inotrope score (10 [1-17] vs. 1 [0-9]; p = 0.04) and the lactate values (3.8 [1.7-5.9] mmol/L vs. 2.5 [1.5-3.4] mmol/L; p = 0.01) after 6 h of support with Impella 5.0. Furthermore, at Impella removal the patients' left ventricular ejection fraction improved significantly (p < 0.001) when compared to baseline. Cardiac recovery, bridge to left ventricular assist device or heart transplantation was possible in 28 patients (70 %). Twenty-six patients (65 %) survived at day 28. A multivariate analysis showed a higher risk of mortality for patients with acute myocardial infarction (hazard ratio = 4.1 (1.2-14.2); p = 0.02). CONCLUSIONS: Impella 5.0 allowed fast weaning of inotropes and might facilitate myocardial recovery. Despite high severity scores at admission, day-28 mortality rate was better than predicated.