Overview of the current use of levosimendan in France: a prospective observational cohort study.

BACKGROUND: Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale. METHOD: The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year. RESULTS: The patients included (n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock (n = 250, 41.5%), decompensated heart failure (n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment (n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation (n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up. CONCLUSIONS: We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied.

Renal replacement therapy in extra-corporeal membrane oxygenation patients: A survey of practices and new insights for future studies.

BACKGROUND: Patients under extra-corporeal membrane oxygenation (ECMO) are at high risk of developing acute kidney injury and renal replacement therapy (RRT) is frequently needed. The aim of this study was to explore RRT use in ECMO patients, as no recommendations exist in this setting. METHODS: An online questionnaire about RRT management in ECMO patients was sent to the members of the ARCOTHOVA (Anesthésie-Réanimation Coeur-Thorax-Vaisseaux) association and to the GFRUP (Groupe Francophone de Réanimation et Urgences Pédiatriques). RESULTS: Ninety intensivists from adult ICU and twenty from paediatric ICU responded to the questionnaire. RRT use was common as 67% respondents reported that more than 25% of their ECMO patients needed RRT. RRT indications were similar between centres, with persistent anuria (83%), metabolic acidosis (80%), fluid overload (78%) and hyperkalaemia (80%) being the more prevalent. Continuous renal replacement therapy was the preferred technique (97%). Continuous veno-venous haemofiltration was predominant (64%) over continuous veno-venous haemodiafiltration (21%). Unfractionated heparin was employed as first line choice anticoagulation in 61% and regional citrate anticoagulation in 16%. Integration of RRT device directly into the ECMO circuit was the preferred configuration (40%) while parallel systems with separate catheter were used in 30%. When the integrated approach was chosen, RRT device was most frequently connected with inlet and outlet lines after the ECMO pump (58%) and pressure alarms were encountered for 60% of participants. CONCLUSIONS: Our results highlight the high variability of practice between centres. They suggest the need to compare the integrated and parallel configurations of combining RRT and ECMO.

Berlin Heart EXCOR Paediatric Ventricular Assist Device: Does Weight Matter?

BACKGROUND: Berlin Heart EXCOR (BH) ventricular assist devices provide mechanical long-term circulatory support in children with end-stage heart failure, as a bridge to transplantation or to recovery. Most studies are from large-volume paediatric cardiac centres. AIM: The aim of this study was to analyse the experiences of three French centres and to compare these with available published data. METHOD: We performed a retrospective observational study of three paediatric cardiac intensive care units. All children supported with BH devices were included. Morbidity and mortality data were collected and risk factors analysed. RESULTS: Fifty-four (54) patients (54% male) were included. Survival rate was 73% while on a BH device. Median age at BH device implantation was 17 months (range 2-180 months). The predominant indication was dilated cardiomyopathy (61%). Bi-ventricular assist device was used in 25 (46%) cases. The total length of long-term circulatory support was 3,373 days, with a mean length per patient of 62.5 days (range 5-267 days). Thirty-two (32) patients were transplanted (59%) and seven (13%) were successfully weaned. Type and length of support did not influence morbidity. Main complications were renal dysfunction (57%), bleeding (41%), and infection (39%). In multivariate analysis, a weight <5 kg was significantly associated with higher mortality. CONCLUSIONS: The weight seems to be the most important risk factor of mortality in this precarious condition.

Impact of the perioperative inotropic support in grown-up congenital heart patients undergoing cardiac surgery: a propensity score adjusted analysis.

BACKGROUND: Grown-up congenital heart (GUCH) patients represent a growing population with a high morbidity risk when undergoing reparative surgery. A main preoperative feature is right ventricular failure, which represents a risk factor for postoperative low cardiac output syndrome. Levosimendan has a potentially beneficial effect. This retrospective study included consecutive GUCH patients with surgeries in a tertiary cardiothoracic centre between 01-01-2013 and 01-10-2017, to test the hypothesis that the postoperative use of levosimendan might be associated with shorter time of mechanical ventilation, when compared with the use of milrinone. To adjust for bias related to the probability of treatment assignment, it uses the inverse propensity score weighting methodology. RESULTS: Overall 363 patients had GUCH surgeries during the study period, their mean age was 31.39 ± 15.31 years, 87 patients were eligible for analysis in the Levosimendan group and 117 in the Milrinone group. The propensity score used pre- and intraoperative variables and resulted in a good balance between covariates. The Levosimendan group included patients with higher preoperative risk scores, a higher prevalence of left and right ventricular failure, who required more often the addition of epinephrine, renal replacement therapy, prolonged mechanical ventilation and intensive care stay. However, after propensity score weighting, patients in the Levosimendan group had shorter durations of mechanical ventilation (average treatment effect - 37.59 h IQR [- 138.85 to - 19.13], p = 0.01) and intensive care stay (average treatment effect - 3.11 days IQR [- 10.03 to - 1.48], p = 0.009). The number of days of additional epinephrine support was shorter and the vasoactive inotropic scores lower. CONCLUSION: We report a beneficial effect in terms of duration of mechanical ventilation and intensive care stay, and on inotropic requirements of the use of levosimendan following GUCH surgeries. The use of levosimendan in this setting requires validation at a larger scale.

Neurally adjusted ventilatory assist for children on veno-venous ECMO.

NAVA may improve veno-venous ECMO weaning in children. This is a retrospective small series, describing for the first time proof-of-principle for the use of NAVA in children on VV ECMO. Six patients (age 1-48 months) needed veno-venous ECMO. Controlled conventional ventilation was replaced with assisted ventilation as soon as lung compliance improved, and could trigger initiation and termination of ventilation. NAVA was then initiated when diaphragmatic electrical activity (EAdi) allowed for triggering. NAVA was possible in all patients. Proportionate to EAdi (1.8-26 µV), initial peak inspiratory pressures ranged from 21 to 34 cm H2O, and the tidal volume (Vt) from 3 to 7 ml/kg. During weaning, peak pressures increased proportionally to EAdi increase (5.2-41 µV), with tidal volumes ranging from 6.6 to 8.6 ml/kg. ECMO was weaned after a median time of 1.75 days on NAVA. Following ECMO weaning, the median duration of mechanical ventilation, and intensive care unit stay were 4.5 days, and 13.5 days, respectively. Survival to hospital discharge was 100%. In conclusion, combining NAVA to ECMO in paediatric respiratory failure is safe and feasible, and may help in a smoother ECMO weaning, since NAVA allows the patient to drive the ventilator and regulate Vt according to needs.

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.

Transposition of the great arteries: Rationale for tailored preoperative management.

As preoperative morbi-mortality remains significant, care of newborns with transposition of the great arteries is still challenging. In this review of the literature, we discuss the different treatments that could improve the patient's condition into the preoperative period. Instead of a standardized management, we advocate personalized care of these neonates. Considering the deleterious effects of hypoxia, special attention is given to the use of non-invasive technologies to assess oxygenation of the tissues. As a prolonged preoperative time with low cerebral oxygenation is associated with cerebral injuries, distinguishing neonates who should undergo early surgery from those who could wait longer is crucial and requires full expertise in the management of neonatal congenital heart disease. Finally, to treat these newborns as soon as possible, we support a planned delivery policy for foetuses with transposition of the great arteries.

Postoperative assessment of left ventricular function by two-dimensional strain (speckle tracking) after paediatric cardiac surgery.

BACKGROUND: Left ventricular (LV) dysfunction may complicate paediatric cardiac surgery with cardiopulmonary bypass, notably after long aortic cross-clamping (ACC). Assessment of occult myocardial injury by conventional echocardiographic variables may be difficult in the postoperative period. AIMS: To evaluate the feasibility of two-dimensional (2D) strain in the postoperative period, and to assess the effect of ACC duration on this variable. METHODS: Thirty-three paediatric patients (age<18years) with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass were included in this prospective single-centre study. Daily echocardiography was performed from the day before surgery to the fifth postoperative day. LV ejection fraction and LV 2D strain were measured. The cohort was divided into three groups according to ACC duration (group 1:<30minutes; group 2: 30-80minutes; group 3:>80minutes). RESULTS: Mean age and weight were 4.2±2.5years and 15.1±5.2kg, respectively. Feasibilities of longitudinal, circumferential and radial strains were good, and quite similar to conventional variables. Compared with conventional variables, intra- and interobserver agreements regarding 2D strain were better (r=0.916, P<0.001 and r=0.855, P<0.001 for longitudinal strain versus r=0.156, P=0.54 and r=0.064, P=0.80 for LV ejection fraction by Simpson's method). Postoperative evolution of longitudinal and circumferential strains was significantly different between the three groups (P<0.001), whereas there was no difference using conventional variables. CONCLUSION: Postoperative LV 2D strain is a feasible and reproducible method. Strain measurements seem to indicate correlation with ACC duration.

Experts' recommendations for the management of cardiogenic shock in children.

Cardiogenic shock which corresponds to an acute state of circulatory failure due to impairment of myocardial contractility is a very rare disease in children, even more than in adults. To date, no international recommendations regarding its management in critically ill children are available. An experts' recommendations in adult population have recently been made (Levy et al. Ann Intensive Care 5(1):52, 2015; Levy et al. Ann Intensive Care 5(1):26, 2015). We present herein recommendations for the management of cardiogenic shock in children, developed with the grading of recommendations' assessment, development, and evaluation system by an expert group of the Groupe Francophone de Réanimation et Urgences Pédiatriques (French Group for Pediatric Intensive Care and Emergencies). The recommendations cover four major fields of application such as: recognition of early signs of shock and the patient pathway, management principles and therapeutic goals, monitoring hemodynamic and biological variables, and circulatory support (indications, techniques, organization, and transfer criteria). Major principle care for children with cardiogenic shock is primarily based on clinical and echocardiographic assessment. There are few drugs reported as effective in childhood in the medical literature. The use of circulatory support should be facilitated in terms of organization and reflected in the centers that support these children. Children with cardiogenic shock are vulnerable and should be followed regularly by intensivist cardiologists and pediatricians. The experts emphasize the multidisciplinary nature of management of children with cardiogenic shock and the importance of effective communication between emergency medical assistance teams (SAMU), mobile pediatric emergency units (SMUR), pediatric emergency departments, pediatric cardiology and cardiac surgery departments, and pediatric intensive care units.

Severe Neonatal Pertussis Treated by Leukodepletion and Early Extra Corporeal Membrane Oxygenation.

We report the case of a 17-day-old infant with severe pertussis for whom the early initiation of veno-arterial extra corporeal membrane oxygenation and leukodepletion strategies (exchange transfusion and leukofiltration) allowed to reduce leukocytosis and pulmonary hypertension, thus leading to survival. These invasive techniques can be considered when severe pulmonary hypertension complicates hyperleukocytosis in neonates.

Single-centred experience with levosimendan in paediatric decompensated dilated cardiomyopathy.

BACKGROUND: Children with dilated cardiomyopathy in advanced heart failure may spend a long time awaiting heart transplantation. Consequently, mechanical circulatory support is sometimes required as a bridge to transplantation. Levosimendan, a positive inotropic agent, has been reported to be safe and efficient for the treatment of paediatric heart failure. AIMS: To report our experience with levosimendan in children with decompensated dilated cardiomyopathy. METHODS: Paediatric patients with dilated cardiomyopathy on the transplant waiting list and with criteria for mechanical support were included in this single-centred retrospective study. Each patient received at least one 24-hour infusion of levosimendan before mechanical circulatory support was considered. Biological and echocardiographic data were analysed. RESULTS: Six patients were included over a 24-month period. The median age was 25.5months (7.7-34.2months); 82 infusions were performed. Median B-type natriuretic peptide concentration decreased significantly between days 0 and 2 (2443ng/L [1458-3819ng/L] vs 1358ng/L [1025-2534ng/L]; P=0.003). While only a trend was noted in left ventricular ejection fraction improvement (P=0.054 by Simpson's method and P=0.068 by the Teicholz method), the subaortic velocity time integral rose significantly between days 0 and 8 (12.8cm/s [10-14.5cm/s] vs 15.3cm/s [14.3-16.9cm/s]; P=0.041). CONCLUSIONS: Levosimendan seems to improve haemodynamics in children with decompensated dilated cardiomyopathy; repeated infusions may delay the need for mechanical circulatory support while awaiting heart transplantation. This therapeutic agent should be systematically considered in this setting, in addition to conventional inotropic drugs.

Multivariable assessment of the right ventricle by echocardiography in patients with repaired tetralogy of Fallot undergoing pulmonary valve replacement: a comparative study with magnetic resonance imaging.

BACKGROUND: Evaluation of the right ventricle (RV) using transthoracic echocardiography is challenging in patients with repaired tetralogy of Fallot (rTOF). AIMS: To evaluate the accuracy of conventional echocardiographic variables and real-time three-dimensional echocardiography (RT3DE) in assessing right ventricular (RV) volumes and function compared with magnetic resonance imaging (MRI), in adult patients with rTOF and referred for pulmonary valve replacement (PVR). METHODS: Complete echocardiography was performed on 26 consecutive patients referred for PVR, before and 1 year after surgery. All variables were compared with MRI. RESULTS: Correlations between conventional variables and MRI were absent or poor when assessing RV ejection fraction (RVEF), except for fractional area of change (FAC; r=0.70, P<0.01 before PVR; r=0.68, P<0.01 after PVR) and RT3DE (r=0.96, P<0.01 before PVR; r=0.98, P<0.01 after PVR). The RV volume correlation between RT3DE and MRI was excellent before and after surgery for RV end-diastolic volume (r=0.88, P<0.01 and r=0.91, P<0.01, respectively) and RV end-systolic volume (r=0.92, P<0.01 and r=0.95, P<0.01, respectively). The accuracy of these indices, as a diagnostic test for impaired RV (<45%), was good: Youden's indexes varied from 0.47 to 0.89; areas under the receiver operating characteristic curve before and after PVR were 0.86 and 0.81 for FAC and 0.98 and 0.97 for RT3DE, respectively. CONCLUSION: Commonly used echocardiography variables, such as tricuspid annular plane systolic excursion and tricuspid annular peak systolic velocity, did not sensitively evaluate global RVEF. A global approach, that includes the whole RV and integration of its different components, was more reliable in patients with rTOF.

Lung Ultrasound in the Critically Ill Neonate.

Critical ultrasound is a new tool for first-line physicians, including neonate intensivists. The consideration of the lung as one major target allows to redefine the priorities. Simple machines work better than up-to-date ones. We use a microconvex probe. Ten standardized signs allow a majority of uses: the bat sign (pleural line), lung sliding and the A-line (normal lung surface), the quad sign and sinusoid sign indicating pleural effusion regardless its echogenicity, the tissue-like sign and fractal sign indicating lung consolidation, the B-line artifact and lung rockets (indicating interstitial syndrome), abolished lung sliding with the stratosphere sign, suggesting pneumothorax, and the lung point, indicating pneumothorax. Other signs are used for more sophisticated applications (distinguishing atelectasis from pneumonia for instance...). All these disorders were assessed in the adult using CT as gold standard with sensitivity and specificity ranging from 90 to 100%, allowing to consider ultrasound as a reasonable bedside gold standard in the critically ill. The same signs are found, with no difference in the critically ill neonate. Fast protocols such as the BLUE-protocol are available, allowing immediate diagnosis of acute respiratory failure using seven standardized profiles. Pulmonary edema e.g. yields anterior lung rockets associated with lung sliding, making the B-profile. The FALLS-protocol, inserted in a Limited Investigation including a simple model of heart and vessels, assesses acute circulatory failure using lung artifacts. Interventional ultrasound (mainly, thoracocenthesis) provides maximal safety. Referrals to CT can be postponed. CEURF proposes personnalized bedside trainings since 1990. Lung ultrasound opens physicians to a visual medicine.

High-frequency oscillatory ventilation and short-term outcome in neonates and infants undergoing cardiac surgery: a propensity score analysis.

INTRODUCTION: Experience with high-frequency oscillatory ventilation (HFOV) after congenital cardiac surgery is limited despite evidence about reduction in pulmonary vascular resistance after the Fontan procedure. HFOV is recommended in adults and children with acute respiratory distress syndrome. The aim of the present study was to assess associations between commencement of HFOV on the day of surgery and length of mechanical ventilation, length of Intensive Care Unit (ICU) stay and mortality in neonates and infants with respiratory distress following cardiac surgery. METHODS: A logistic regression model was used to develop a propensity score, which accounted for the probability of being switched from conventional mechanical ventilation (CMV) to HFOV on the day of surgery. It included baseline characteristics, type of procedure and postoperative variables, and was used to match each patient with HFOV with a control patient, in whom CMV was used exclusively. Length of mechanical ventilation, ICU stay and mortality rates were compared in the matched set. RESULTS: Overall, 3,549 neonates and infants underwent cardiac surgery from January 2001 through June 2010, 120 patients were switched to HFOV and matched with 120 controls. After adjustment for the delay to sternal closure, duration of renal replacement therapy, occurrence of pulmonary hypertension and year of surgery, the probability of successful weaning over time and the probability of ICU delivery over time were significantly higher in patients with HFOV, adjusted hazard ratios and 95% confidence intervals: 1.63, 1.17 to 2.26 (P = 0.004). and 1.65, 95% confidence intervals: 1.20 to 2.28 (P = 0.002) respectively. No association was found with mortality. CONCLUSIONS: When commenced on the day of surgery in neonates and infants with respiratory distress following cardiac surgery, HFOV was associated with shorter lengths of mechanical ventilation and ICU stay than CMV.