Prospective randomized double-blind study to evaluate the superiority of Vasopressin versus Norepinephrine in the management of the patient at renal risk undergoing cardiac surgery with cardiopulmonary bypass (NOVACC trial).

BACKGROUND: Cardiac surgery-associated acute kidney injury (CS-AKI) affects up to 30% of patients, increasing morbidity and healthcare costs. This condition results from complex factors like ischemia-reperfusion injury and renal hemodynamic changes, often exacerbated by surgical procedures. Norepinephrine, commonly used in cardiac surgeries, may heighten the risk of CS-AKI. In contrast, vasopressin, a noncatecholaminergic agent, shows potential in preserving renal function by favorably affecting renal hemodynamic. Preliminary findings, suggest vasopressin could reduce the incidence of CS-AKI compared to norepinephrine. Additionally, vasopressin is linked to a lower incidence of postoperative atrial fibrillation, another factor contributing to longer hospital stays and higher costs. This study hypothesizes that vasopressin could effectively reduce CS-AKI occurrence and severity by optimizing renal perfusion during cardiac surgeries. STUDY DESIGN: The NOVACC trial (NCT05568160) is a multicenter, randomized, double blinded superiority-controlled trial testing the superiority of vasopressin over norepinephrine in patients scheduled for cardiac surgery with cardiopulmonary bypass (CPB). The primary composite end point is the occurrence of acute kidney injury and death. The secondary end points are neurological, cardiologic, digestive, and vasopressor related complications at day 7, day 30, day 90, hospital and intensive care unit lengths of stay, medico-economic costs at day 90. CONCLUSION: The NOVACC trial will assess the effectiveness of vasopressin in cardiac surgery with CPB in reducing acute kidney injury, mortality, and medical costs. CLINICAL TRIAL REGISTRATION: NCT05568160.

Right ventriculoarterial coupling surrogates and long-term survival in LVAD recipients: Results of the ASSIST-ICD multicentric registry.

BACKGROUND: Prediction of outcomes remains an unmet need in LVAD candidates. Development of right heart failure portends an excess in mortality but imaging parameters of right ventricular systolic function have failed to demonstrate a prognostic role. By integrating pulmonary pressure, right ventriculoarterial coupling could fill this gap. METHODS: The ASSIST-ICD registry was used to test right ventriculoarterial coupling surrogate parameters at implantation for the prediction of all-cause mortality. RESULTS: The ratio of the tricuspid annular plane systolic excursion over the estimated systolic pulmonary pressure (TAPSE/sPAP) was not associated with long-term survival in univariate analysis (p = 0.89), neither was the pulmonary artery pulsatility index (PAPi) (p = 0.13). Conversely, the ratio of the right atrial pressure over the pulmonary capillary wedge pressure (RAP/PCWP) was associated with all-cause mortality (p <0.01). After taking tricuspid regurgitation severity, LVAD indication, LVAD model, age, blood urea nitrogen, and pulmonary vascular resistance into account, RAP/PCWP remained associated with survival (HR 1.35 [1.10 - 1.65], p <0.01). CONCLUSION: Among pre-implant RVAC surrogates, only RAP/PCWP was associated with long-term all-cause mortality in LVAD recipients. This association was independent of established risk factors.

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.

Involvement of Vasopressin in Tissue Hypoperfusion during Cardiogenic Shock Complicating Acute Myocardial Infarction in Rats.

Acute heart failure (AHF) due to acute myocardial infarction (AMI) is likely to involve cardiogenic shock (CS), with neuro-hormonal activation. A relationship between AHF, CS and vasopressin response is suspected. This study aimed to investigate the implication of vasopressin on hemodynamic parameters and tissue perfusion at the early phase of CS complicating AMI. Experiments were performed on male Wistar rats submitted or not to left coronary artery ligation (AMI and Sham). Six groups were studied Sham and AMI treated or not with either a vasopressin antagonist SR-49059 (Sham-SR, AMI-SR) or agonist terlipressin (Sham-TLP, AMI-TLP). Animals were sacrificed one day after surgery (D1) and after hemodynamic parameters determination. Vascular responses to vasopressin were evaluated, ex vivo, on aorta. AHF was defined by a left ventricular ejection fraction below 40%. CS was defined by AHF plus tissue hypoperfusion evidenced by elevated serum lactate level or low mesenteric oxygen saturation (SmO2) at D1. Mortality rates were 40% in AMI, 0% in AMI-SR and 33% in AMI-TLP. Immediately after surgery, a sharp decrease in SmO2 was observed in all groups. At D1, SmO2 recovered in Sham and in SR-treated animals while it remained low in AMI and further decreased in TLP-treated groups. The incidence of CS among AHF animals was 72% in AMI or AMI-TLP while it was reduced to 25% in AMI-SR. Plasma copeptin level was increased by AMI. Maximal contractile response to vasopressin was decreased in AMI (32%) as in TLP- and SR- treated groups regardless of ligation. Increased vasopressin secretion occurring in the early phase of AMI may be responsible of mesenteric hypoperfusion resulting in tissue hypoxia. Treatment with a vasopressin antagonist enhanced mesenteric perfusion and improve survival. This could be an interesting therapeutic strategy to prevent progression to cardiogenic shock.

Outcome of Temporary Circulatory Support As a Bridge-to-Left Ventricular Assist Device Strategy in Cardiogenic Shock Patients.

OBJECTIVES: Temporary circulatory support (TCS) as a bridge-to-left ventricular assist device (BTL) in cardiogenic shock patients has been increasing, but limited data exists on this BTL strategy. We aimed at analyzing the outcome of BTL patients in a population of cardiogenic shock patients compared with those without TCS at the time of the left ventricular assist device (LVAD) surgery and identify predictors of postoperative mortality in this specific population. DESIGN: A multicenter retrospective observational study conducted in 19 centers from 2006 to 2016. SETTING: Nineteen French centers. PATIENTS: A total of 329 cardiogenic shock patients at the time of LVAD implantation were analyzed. Patients were divided in three groups: those under TCS at the time of LVAD implantation (n = 173), those with TCS removal before LVAD surgery (n = 24), and those who did not undergo a bridging strategy (n = 152). Primary endpoint was 30-day mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the BTL group, 68 (39.3%), 18 (10.4%), and 15 (8.7%) patients were under venoarterial extracorporeal membrane oxygenation, Impella, and IABP support alone, and 72 patients (20.6%) were under multiple TCS support. BTL patients presented similar 30 days survival compared with the TCS removal and non-BTL groups. However, BTL group had a significantly longer ICU duration stay, with two-fold duration of mechanical ventilation time, but the three groups experienced similar postoperative complications. Multivariate analysis identified three independent predictors of mortality in the BTL group: combined surgery with LVAD, body mass index (BMI), and heart failure (HF) duration. BTL strategy was not an independent predictor of mortality in cardiogenic shock patients who underwent LVAD. CONCLUSIONS: BTL strategy is not associated with a lower survival among cardiogenic shock patients with LVAD implantation. Predictors of mortality are combined surgery with LVAD, higher BMI, and HF duration.

Extracorporeal Membrane Oxygenation for Respiratory Failure Related to COVID-19: A Nationwide Cohort Study.

BACKGROUND: Despite expanding use, knowledge on extracorporeal membrane oxygenation support during the COVID-19 pandemic remains limited. The objective was to report characteristics, management, and outcomes of patients receiving extracorporeal membrane oxygenation with a diagnosis of COVID-19 in France and to identify pre-extracorporeal membrane oxygenation factors associated with in-hospital mortality. A hypothesis of similar mortality rates and risk factors for COVID-19 and non-COVID-19 patients on venovenous extracorporeal membrane oxygenation was made. METHODS: The Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome-Coronavirus 2 (ECMOSARS) registry included COVID-19 patients supported by extracorporeal membrane oxygenation in France. This study analyzed patients included in this registry up to October 25, 2020, and supported by venovenous extracorporeal membrane oxygenation for respiratory failure with a minimum follow-up of 28 days after cannulation. The primary outcome was in-hospital mortality. Risk factors for in-hospital mortality were analyzed. RESULTS: Among 494 extracorporeal membrane oxygenation patients included in the registry, 429 were initially supported by venovenous extracorporeal membrane oxygenation and followed for at least 28 days. The median (interquartile range) age was 54 yr (46 to 60 yr), and 338 of 429 (79%) were men. Management before extracorporeal membrane oxygenation cannulation included prone positioning for 411 of 429 (96%), neuromuscular blockage for 419 of 427 (98%), and NO for 161 of 401 (40%). A total of 192 of 429 (45%) patients were cannulated by a mobile extracorporeal membrane oxygenation unit. In-hospital mortality was 219 of 429 (51%), with a median follow-up of 49 days (33 to 70 days). Among pre-extracorporeal membrane oxygenation modifiable exposure variables, neuromuscular blockage use (hazard ratio, 0.286; 95% CI, 0.101 to 0.81) and duration of ventilation (more than 7 days compared to less than 2 days; hazard ratio, 1.74; 95% CI, 1.07 to 2.83) were independently associated with in-hospital mortality. Both age (per 10-yr increase; hazard ratio, 1.27; 95% CI, 1.07 to 1.50) and total bilirubin at cannulation (6.0 mg/dl or more compared to less than 1.2 mg/dl; hazard ratio, 2.65; 95% CI, 1.09 to 6.5) were confounders significantly associated with in-hospital mortality. CONCLUSIONS: In-hospital mortality was higher than recently reported, but nearly half of the patients survived. A high proportion of patients were cannulated by a mobile extracorporeal membrane oxygenation unit. Several factors associated with mortality were identified. Venovenous extracorporeal membrane oxygenation support should be considered early within the first week of mechanical ventilation initiation.

European Association of Cardiothoracic Anesthesiology and Intensive Care Pediatric Cardiac Anesthesia Fellowship Curriculum: First Edition.

Pediatric cardiac anesthesia is a subspecialty of cardiac and pediatric anesthesiology dedicated to the perioperative care of patients with congenital heart disease. Members of the Congenital and Education Subcommittees of the European Association of Cardiothoracic Anaesthesiology and Intensive Care (EACTAIC) agreed on the necessity to develop an EACTAIC pediatric cardiac anesthesia fellowship curriculum. This manuscript represents a consensus on the composition and the design of the EACTAIC Pediatric Cardiac Anesthesia Fellowship program. This curriculum provides a basis for the training of future pediatric cardiac anesthesiologists by clearly defining the theoretical and practical requirements for fellows and host centers.

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.

Implantable cardiac defibrillator leads dysfunction after LVAD implantation.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) lead dysfunction has been reported after left ventricular assist device (LVAD) implantation in limited single-center studies. We aimed at describing and characterizing the incidence of ICD lead parameters dysfunction after LVAD implantation. METHODS: Among the 652 patients enrolled in the ASSIST-ICD study, only patients with an ICD prior to LVAD were included (n = 401). ICD lead parameters dysfunction following LVAD implantation is defined as follows: (a) >50% decrease in sensing threshold, (b) pacing lead impedance increase/decrease by >100Ω, and (c) >50% increase in pacing threshold. RESULTS: One hundred twenty-two patients with an ICD prior to LVAD had available ICD interrogation reports prior and after LVAD. A total of 67 (55%) patients exhibited at least one significant lead dysfunction: 17 (15%) exhibited >50% decrease in right ventricular (RV) sensing, 51 (42%) had >100 Ω increase/decrease in RV pacing impedance, and 24 (20%) experienced >50% increase in RV pacing threshold. A total of 52 patients experienced ventricular arrhythmia during follow-up and all were successfully detected and treated by the device. All lead dysfunction could be managed conservatively. CONCLUSION: More than 50% of LVAD-recipients may experience >1 significant change in lead parameters but none had severe clinical consequences.

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.

European Association of Cardiothoracic Anesthesiology (EACTA) Cardiothoracic and Vascular Anesthesia Fellowship Curriculum: First Edition.

This special article summarizes the design and certification process of the European Association of Cardiothoracic Anesthesiology (EACTA) Cardiothoracic and Vascular Anesthesia (CTVA) Fellowship Program. The CTVA fellowship training includes a two-year curriculum at an EACTA-accredited educational facility. Before fellows are accepted into the program, they must meet a number of requirements, including evidence of a valid license to practice medicine, a specialist degree examination in anesthesiology, and appropriate language skills as required in the host centers. The CVTA Fellowship Program has 2 sequential and complementary levels of training-both with a modular structure that allows for individual planning and also takes into account the differing national healthcare needs and requirements of the 36 countries represented in EACTA. The basic training period focuses on the anesthetic management of patients undergoing cardiac, thoracic, and vascular surgery and related procedures. The advanced training period is intended to deepen and to extend the clinical and nontechnical skills that fellows have acquired during the basic training. The goal of the EACTA fellowship is to produce highly trained and competent perioperative physicians who are able to care for patients undergoing cardiac, thoracic, and vascular anesthesia.

Risk factors and prognostic impact of left ventricular assist device-associated infections.

BACKGROUND: Left ventricular assist device (LVAD)-associated infections may be life-threatening and impact patients' outcome. We aimed to identify the characteristics, risk factors, and prognosis of LVAD-associated infections. METHODS: Patients included in the ASSIST-ICD study (19 centers) were enrolled. The main outcome was the occurrence of LVAD-associated infection (driveline infection, pocket infection, or pump/cannula infection) during follow-up. RESULTS: Of the 652 patients enrolled, 201 (30.1%) presented a total of 248 LVAD infections diagnosed 6.5 months after implantation, including 171 (26.2%), 51 (7.8%), and 26 (4.0%) percutaneous driveline infection, pocket infection, or pump/cannula infection, respectively. Patients with infections were aged 58.7 years, and most received HeartMate II (82.1%) or HeartWare (13.4%). Most patients (62%) had implantable cardioverter-defibrillators (ICDs) before LVAD, and 104 (16.0%) had ICD implantation, extraction, or replacement after the LVAD surgery. Main pathogens found among the 248 infections were Staphylococcus aureus (n = 113' 45.4%), Enterobacteriaceae (n = 61; 24.6%), Pseudomonas aeruginosa (n = 34; 13.7%), coagulase-negative staphylococci (n = 13; 5.2%), and Candida species (n = 13; 5.2%). In multivariable analysis, HeartMate II (subhazard ratio, 1.56; 95% CI, 1.03 to 2.36; P = .031) and ICD-related procedures post-LVAD (subhazard ratio, 1.43; 95% CI, 1.03-1.98; P = .031) were significantly associated with LVAD infections. Infections had no detrimental impact on survival. CONCLUSIONS: Left ventricular assist device-associated infections affect one-third of LVAD recipients, mostly related to skin pathogens and gram-negative bacilli, with increased risk with HeartMate II as compared with HeartWare, and in patients who required ICD-related procedures post-LVAD. This is a plea to better select patients needing ICD implantation/replacement after LVAD implantation.

Acute kidney injury during daptomycin versus vancomycin treatment in cardiovascular critically ill patients: a propensity score matched analysis.

BACKGROUND: Gram-positive organisms are a leading cause of infection in cardiovascular surgery. Furthermore, these patients have a high risk of developing postoperative renal failure in intensive care unit (ICU). Some antibiotic drugs are known to impair renal function. The aim of the study was to evaluate whether patients treated for Gram-positive cardiovascular infection with daptomycin (DAP) experienced a lower incidence of acute kidney injury (AKI) when compared to patients treated with vancomycin (VAN), with comparable efficacy. METHODS: ICU patients who received either DAP or VAN, prior to or after cardiovascular surgery or mechanical circulatory support, from January 2010 to December 2012, were included in this observational retrospective cohort study. We excluded patients with end stage renal disease and antibiotic prophylaxis. The primary endpoint was the incidence of AKI within the first week of treatment. Secondary endpoints were the incidence of AKI within the first 14 days of treatment, the severity of AKI including renal replacement therapy (RRT), the rates of clinical failure (unsuccessful infection treatment) and of premature discontinuation and mortality. To minimize selection bias, we used a propensity score to compare the 2 groups. Univariate and multivariate analysis were performed to determine factors associated with AKI. RESULTS: Seventy two patients, treated for infective endocarditis, cardiovascular foreign body infection, or surgical site infection were included (DAP, n = 28 and VAN, n = 44). AKI at day 7 was observed in 28 (64%) versus 6 (21%) of the VAN and DAP patients, respectively (p = 0.001). In the multivariate analysis adjusted to the propensity score, vancomycin treatment was the only factor associated with AKI (Odds Ratio 4.42; 95% CI: 1.39-15.34; p = 0.014). RRT was required for 2 (7%) DAP patients and 13 (30%) VAN patients, p = 0.035. Premature discontinuation and clinical failure occurred more frequently in VAN group than in DAP group (25% versus 4%, p = 0.022 and 42% versus 12%, respectively, p = 0.027). CONCLUSIONS: Daptomycin appears to be safer than vancomycin in terms of AKI risk in ICU patients treated for cardiovascular procedure-related infection. Daptomycin could be considered as a first line treatment to prevent AKI in high-risk patients.

New Modalities for the Administration of Inhaled Nitric Oxide in Intensive Care Units After Cardiac Surgery or for Neonatal Indications: A Prospective Observational Study.

BACKGROUND: Nitric oxide (NO) has a well-known efficacy in pulmonary hypertension (PH), with wide use for 20 years in many countries. The objective of this study was to describe the current use of NO in real life and the gap with the guidelines. METHODS: This is a multicenter, prospective, observational study on inhaled NO administered through an integrated delivery and monitoring device and indicated for PH according to the market authorizations. The characteristics of NO therapy and ventilation modes were observed. Concomitant pulmonary vasodilator treatments, safety data, and outcome were also collected. Quantitative data are expressed as median (25th, 75th percentile). RESULTS: Over 1 year, 236 patients were included from 14 equipped and trained centers: 117 adults and 81 children with PH associated with cardiac surgery and 38 neonates with persistent PH of the newborn. Inhaled NO was initiated before intensive care unit (ICU) admission in 57%, 12.7%, and 38.9% with an initial dose of 10 (10, 15) ppm, 20 (18, 20) ppm, and 17 (11, 20) ppm, and a median duration of administration of 3.9 (1.9, 6.1) days, 3.8 (1.8, 6.8) days, and 3.1 (1.0, 5.7) days, respectively, for the adult population, pediatric cardiac group, and newborns. The treatment was performed using administration synchronized to the mechanical ventilation. The dose was gradually decreased before withdrawal in 86% of the cases according to the usual procedure of each center. Adverse events included rebound effect for 3.4% (95% confidence interval [CI], 0.9%-8.5%) of adults, 1.2% (95% CI, 0.0%-6.7%) of children, and 2.6% (95% CI, 0.1%-13.8%) of neonates and methemoglobinemia exceeded 2.5% for 5 of 62 monitored patients. Other pulmonary vasodilators were associated with NO in 23% of adults, 95% of children, and 23.7% of neonates. ICU stay was respectively 10 (6, 22) days, 7.5 (5.5, 15) days, and 9 (8, 15) days and ICU mortality was 22.2%, 6.2%, and 7.9% for adults, children, and neonates, respectively. CONCLUSIONS: This study confirms the safety of NO therapy in the 3 populations with a low rate of rebound effect. Gradual withdrawal of NO combined with pulmonary vasodilators are current practices in this population. The use of last-generation NO devices allowed good compliance with recommendations.

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.

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.