Impact of Red Blood Cell Transfusion on In-hospital Mortality of Isolated Coronary Artery Bypass Graft Surgery: A Retrospective Observational Study of French Nationwide 3-year Cohort.

OBJECTIVE: To assess the relationship between red blood cell (RBC) transfusion exposure and in-hospital mortality after isolated coronary artery bypass graft (CABG) surgery. BACKGROUND: RBC transfusion was commonly used to treat anemia in isolated CABG surgery, but transfusion was found an independent risk factor of postoperative mortality; recent guidelines on patient blood management strategy issued in the last decade may have changed transfusion incidence and related mortality. METHODS: A retrospective cohort study was conducted from the National database on patients' hospital discharge reports. Consecutive adult patients who underwent isolated CABG surgery in France from January 1, 2016, to December 31, 2018, were included. The primary outcome was the in-hospital mortality rate. RBC transfusion during the hospital stay was identified by specific codes and ordered as categorical variables (no, moderate, or massive transfusion). RESULTS: A total of 37,498 participants were studied [mean (SD) age, 66.5 (9.6) years, 31,587 (84.2%) were men]. In-hospital mortality rate was 1.45% (n=541) and RBC transfusion rate was 9.4% (n=3521). In-hospital deaths were more frequent among transfused patients [1.06% (361) if no transfusion up to 10.2% (n=113) if massive transfusion]. After adjustment for confounding variables, RBC transfusion remained a significant independent factor of in-hospital mortality: odds ratio=1.66 (95% confidence interval: 1.27-2.19, P <0.001) for moderate transfusion, 6.40 (95% confidence interval: 5.07-8.09, P <0.001) if massive. CONCLUSIONS AND RELEVANCE: Despite a modest patients' exposure to transfusion, this study suggests that RBC administration is an independent factor of in-hospital mortality in isolated CABG surgery.

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.

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.

Terlipressin, a vasoactive prodrug recommended in hepatorenal syndrome, is an agonist of human V1, V2 and V1B receptors: Implications for its safety profile.

Terlipressin is recommended as a gold standard to treat hepatorenal syndrome complicating liver cirrhosis. It is presented as a specific V1A receptor agonist, beyond its enzymatic conversion into lysine8-Vasopressin (LVP), able to counteract the splanchnic vasodilation. However, the complete pharmacological characterization of this drug with respect to the different vasopressin receptor subtypes is missing. We studied terlipressin intrinsic properties, focusing not only on V1A, but also on other vasopressin receptor subtypes. The experimental studies were conducted on rat and human cellular models. Binding experiments were performed on rat liver membranes and CHO cells transfected with the different human vasopressin receptor subtypes. Agonist status was assessed from inositol phosphate or cyclic AMP assays, and measurement of intracellular calcium variations, performed on cultured vascular smooth muscle cells from rat aorta and human uterine artery and CHO cells. Terlipressin binds to the rat and human V1A receptors with an affinity in the micromolar range, a value 120 fold lower than that of LVP. It induces a rapid and transient intracellular calcium increase, a robust stimulation of phospholipase C but with reduced maximal efficiencies as compared to LVP, indicating a partial V1A agonist property. In addition, terlipressin is also a full agonist of human V2 and V1B receptors, with also a micromomolar affinity. CONCLUSIONS: Terlipressin is a non-selective vasopressin analogue, exhibiting intrinsic agonist properties. Its full V2 receptor agonism may result in renal effects potentially aggravating water retention and hyponatremia of cirrhosis.

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.

Post cardiac surgery vasoplegia is associated with high preoperative copeptin plasma concentration.

INTRODUCTION: Post cardiac surgery vasodilatation (PCSV) is possibly related to a vasopressin deficiency that could relate to chronic stimulation of adeno-hypophysis. To assess vasopressin system activation, a perioperative course of copeptin and vasopressin plasma concentrations were studied in consecutive patients operated on for cardiac surgery. METHODS: Sixty-four consecutive patients scheduled for elective cardiac surgery with cardiopulmonary bypass were studied. Hemodynamic, laboratory and clinical data were recorded before and during cardiopulmonary bypass, and at the eighth postoperative hour (H8). At the same time, blood was withdrawn to determine plasma concentrations of arginine vasopressin (AVP, radioimmunoassay) and copeptin (immunoluminometric assay). PCSV was defined as mean arterial blood pressure < 60 mmHg with cardiac index ≥ 2.2 l/min/m², and was treated with norepinephrine to restore mean blood pressure > 60 mmHg. Patients with PCSV were compared with the other patients (controls). Student's t test, Fisher's exact test, or nonparametric tests (Mann-Whitney, Wilcoxon) were used when appropriate. Correlation between AVP and copeptin was evaluated and receiver-operator characteristic analysis assessed the utility of preoperative copeptin to distinguish between controls and PCSV patients. RESULTS: Patients who experienced PCSV had significantly higher copeptin plasma concentration before cardiopulmonary bypass (P < 0.001) but lower AVP concentrations at H8 (P < 0.01) than controls. PCSV patients had preoperative hyponatremia and decreased left ventricle ejection fraction, and experienced more complex surgery (redo). The area under the receiver-operator characteristic curve of preoperative copeptin concentration was 0.86 ± 0.04 (95% confidence interval = 0.78 to 0.94; P < 0.001). The best predictive value for preoperative copeptin plasma concentration was 9.43 pmol/l with a sensitivity of 90% and a specificity of 77%. CONCLUSIONS: High preoperative copeptin plasma concentration is predictive of PSCV and suggests an activation of the AVP system before surgery that may facilitate depletion of endogenous AVP stores and a relative AVP deficit after surgery.

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.

Pulmonary hypertension after pneumonectomy: a preclinical model in rats and human pulmonary endothelial cells.

OBJECTIVES: Pulmonary hypertension and heart disease contribute to the high morbidity rate following pneumonectomy (PN). The pathophysiology is still poorly understood. The objective was to investigate the consequences of PN on cardiopulmonary function in rats and to explore in vitro the involved mechanisms. METHODS: Sixty Sprague-Dawley male rats randomly underwent either a right PN (PN group) or sham surgery. Ten rats per group were sacrificed on postoperative days 3, 7 and 28. Cardiopulmonary alterations were investigated by echocardiographic, haemodynamic and histological analyses. In vitro, the shear stress was reproduced using a Flexcell Tension™ cyclic stretch on cultured human pulmonary endothelial cells (P-ECs) to investigate the impact on pulmonary artery smooth muscle cell (PA-SMC) growth. Data are expressed as mean ± SD. RESULTS: Mean pulmonary arterial pressure gradually increased in the PN group to reach 35 ± 7 mmHg on postoperative day 28 vs 18 ± 4 in sham (P = 0.001), likewise the proportion of muscularized distal pulmonary arteries, 83 ± 1% vs 5 ± 1%, respectively (P < 0.001), related to in situ PA-SMC proliferation. The right ventricle area and lateral wall thickness were doubled in the PN group on postoperative day 28. The left ventricle ejection fraction decreased on postoperative days 7 and 28 while the right ventricle function was maintained. In vitro, the human PA-SMC growth was significantly greater when seeded with stretched vs non-stretched P-EC media, highlighting the role of shear stress on the P-EC paracrine function. CONCLUSIONS: Right PN led to pulmonary hypertension and proportional right heart remodelling in rats. The shear stress related to high blood flow alters the pulmonary endothelial paracrine control of SMC growth.

Terlipressin, a provasopressin drug exhibits direct vasoconstrictor properties: consequences on heart perfusion and performance.

OBJECTIVE: Terlipressin has been proposed as an alternative treatment to catecholamines to restore blood pressure in septic shock. Terlipressin is considered as a vasopressin prodrug capable of releasing small but sustained amounts of [Lysine] vasopressin (LVP) and to provide prolonged biological effect. However, terlipressin may act as a direct vasopressor beyond its conversion into LVP. We investigated terlipressin direct vasoconstrictive properties and consequences on myocardial perfusion and performance. DESIGN: Experimental studies. SETTINGS: National Research Institute Laboratories. SUBJECTS: Rat aorta and heart, human uterine artery. INTERVENTIONS: Studies of vasoconstriction on isolated vascular rings obtained either from rat aorta or human uterine artery, and of coronary flow, ventricular performance, and heart rhythm on rat hearts using a modified Langendorff heart apparatus. MEASUREMENTS AND MAIN RESULTS: Terlipressin induced a rapid, saturable, and dose-dependent contraction of rat aortas and human uterine arteries. Although the maximal terlipressin-induced vasoconstriction observed on rat arteries was weaker than LVP, or arginine-vasopressin, pharmacologic properties on human arteries, such as full agonism and strong maximal effect (900% of the maximal response obtained with phenylephrine), suggest a high potential of terlipressin to directly vasoconstrict human vessels. Similarly, terlipressin induced a saturable and dose-dependent vasoconstriction of coronary arteries that was reversible and antagonized by selective V1a antagonists. Maximum rates of left ventricle pressure rise (dP/dtmax) and fall (dP/dtmin) decreased both only in proportion to the decrease in coronary flow. CONCLUSIONS: Besides long lasting effect through slow conversion into LVP, terlipressin is a fast acting vasopressor peptide per se that has an impact on coronary circulation and myocardial function.

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.

Active Bleeding after Cardiac Surgery: A Prospective Observational Multicenter Study.

MAIN OBJECTIVES: To estimate the incidence of active bleeding after cardiac surgery (AB) based on a definition directly related on blood flow from chest drainage; to describe the AB characteristics and its management; to identify factors of postoperative complications. METHODS: AB was defined as a blood loss > 1.5 ml/kg/h for 6 consecutive hours within the first 24 hours or in case of reoperation for hemostasis during the first 12 postoperative hours. The definition was applied in a prospective longitudinal observational study involving 29 French centers; all adult patients undergoing cardiac surgery with cardiopulmonary bypass were included over a 3-month period. Perioperative data (including blood product administration) were collected. To study possible variation in clinical practice among centers, patients were classified into two groups according to the AB incidence of the center compared to the overall incidence: "Low incidence" if incidence is lower and "High incidence" if incidence is equal or greater than overall incidence. Logistic regression analysis was used to identify risk factors of postoperative complications. RESULTS: Among 4,904 patients, 129 experienced AB (2.6%), among them 52 reoperation. Postoperative bleeding loss was 1,000 [820;1,375] ml and 1,680 [1,280;2,300] ml at 6 and 24 hours respectively. Incidence of AB varied between centers (0 to 16%) but was independent of in-centre cardiac surgical experience. Comparisons between groups according to AB incidence showed differences in postoperative management. Body surface area, preoperative creatinine, emergency surgery, postoperative acidosis and red blood cell transfusion were risk factors of postoperative complication. CONCLUSIONS: A blood loss > 1.5 ml/kg/h for 6 consecutive hours within the first 24 hours or early reoperation for hemostasis seems a relevant definition of AB. This definition, independent of transfusion, adjusted to body weight, may assess real time bleeding occurring early after surgery.

Monitoring weaning from BIVAD Thoratec with peak oxygen consumption.

A biventricular assistance device has been implanted in a young woman for a peripartum cardiac failure. An intended weaning consisted of gradual reloading and exercise training monitored with peak oxygen consumption (VO(2)) and radionuclide-left ventricle ejection fraction. Progressive increase in peak VO(2) during partial assistance occurred more than 2 months, from 10.3 to 19 mL.kg(-1).min(-1). Successful explantation was realized when peak VO(2) exceeded 15 mL.kg(-1).min(-1) and radionuclide-left ventricle ejection fraction was more than 40% during off-pump testing.

Hypovolaemia-induced vasodilatation during angiotensin AT1 receptor blockade: role of the AT2 receptor.

AT(1) receptor antagonists may interfere with the haemodynamic determinants of arterial pressure either directly or indirectly through the stimulation of AT(2) receptor provided Ang II is available to interact with them. In order to evaluate the counteracting haemodynamic effect of AT(2) receptor, a prospective, randomized, controlled experimental study was carried out in anaesthetised juvenile pigs. Pigs were randomly assigned to receive placebo (n = 6), valsartan, an AT(1) receptor antagonist (a-AT(1) group; n = 6), or valsartan and PD 123319, an AT(2) receptor antagonist (a-AT(1-2) group; n = 6) after anaesthesia and before hypovolaemia by 20% of the total estimated blood volume. Thirty minutes after bleeding, the mean arterial pressure decreased significantly and similarly in the three groups (25-30%). The placebo group had a significant decrease in cardiac output (CO) without significant change in systemic vascular resistance (SVR). Conversely, in the a-AT(1) group, SVR decreased significantly with a moderate change in CO and addition of the AT(2) antagonist to the AT(1) antagonist (a-AT(1-2) group) did not abolish the lowering in SVR. The results suggest that AT(2) receptor has only a small if any contribution in the vasodilatation observed in the AT(1)-blockade group.

Incidence, risk factors, and prognosis of a moderate increase in plasma creatinine early after cardiac surgery.

OBJECTIVE: To evaluate the incidence and prognosis of a moderate increase in serum creatinine early after cardiac surgery. DESIGN: Retrospective clinical study. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Five hundred and ninety-one consecutive adult patients operated on for cardiac surgery during 1 year. INTERVENTIONS: Plasma creatinine was measured systematically before and during the first 3 days after surgery. Comorbid events were assessed as organ dysfunction (cardiac, pulmonary, hematologic, and neurologic), allowing us to calculate for each patient a dysfunction score (0-5). MEASUREMENTS AND MAIN RESULTS: Postoperative plasma creatinine increased by > or =20% in 15.6% of patients; eight of these required dialysis. A 20% increase in plasma creatinine was associated with other organ dysfunction in 79.3% of patients. Overall mortality rate was 2.7% and increased with the dysfunction score (17.7% for a dysfunction score > or =3). Mortality rate was 12.0% for patients who had 20% increased plasma creatinine with other organ dysfunction but was 0% for patients without other organ dysfunction. A logistic regression analysis revealed that the most important prognostic factors of death were cardiac dysfunction (odds ratio, 8.5; 95% confidence interval, 2.2-32.5) and the association of renal dysfunction and hematologic dysfunction (odds ratio = 12.0; 95% confidence interval, 3.9-37.2). Mean intensive care unit stay of patients with increased plasma creatinine was significantly longer (8.1 +/- 5.6 vs. 4.3 +/- 1.4 days, p <.01) and increased significantly with the dysfunction score (p <.01). Patients with isolated increased plasma creatinine had a significantly longer stay in the intensive care unit than patients without any organ dysfunction (4.6 +/- 1.4 vs. 3.9 +/- 0.9, p <.01). CONCLUSION: Our results suggest that a postoperative 20% increase in plasma creatinine after cardiac surgery is not rare and has a significant impact on postoperative outcome, mainly when multiple organ dysfunction occurs. Any preoperative reduced renal reserve or perioperative renal ischemia increases the renal risk.