Acute respiratory failure due to pulmonary exacerbation in children with cystic fibrosis admitted in a pediatric intensive care unit: outcomes and factors associated with mortality.

BACKGROUND: Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission to pediatric intensive care units (PICU). The objectives of this study were to determine short and medium-term outcomes of children with CF admitted to PICU for acute respiratory failure due to pulmonary exacerbation and to identify prognosis factors. METHODS: This retrospective monocentric study included patients less than 18 years old admitted to the PICU of a French university hospital between 2000 and 2020. Cox proportional hazard regression methods were used to determine prognosis factors of mortality or lung transplant. RESULTS: Prior to PICU admission, the 29 patients included (median age 13.5 years) had a severe lung disease (median Forced Expiratory Volume in 1 s percentage predicted at 29%). Mortality rates were respectively 17%, 31%, 34%, 41% at discharge and at 3, 12 and 36 months post-discharge. Survival rates free of lung transplant were 34%, 32%, 24% and 17% respectively. Risk factors associated with mortality or lung transplant using the univariate analysis were female sex and higher pCO2 and chloride levels at PICU admission, and following pre admission characteristics: home respiratory and nutritional support, registration on lung transplant list and Stenotrophomonas Maltophilia bronchial colonization. CONCLUSION: Children with CF admitted to PICU for acute respiratory failure secondary to pulmonary exacerbations are at high risk of death, both in the short and medium terms. Lung transplant is their main chance of survival and should be considered early.

Veno-arterial extracorporeal membrane oxygenation for circulatory failure in COVID-19 patients: insights from the ECMOSARS registry.

OBJECTIVES: The clinical profile and outcomes of patients with Coronavirus Disease 2019 (COVID-19) who require veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or veno-arterial-venous extracorporeal membrane oxygenation (VAV-ECMO) are poorly understood. We aimed to describe the characteristics and outcomes of these patients and to identify predictors of both favourable and unfavourable outcomes. METHODS: ECMOSARS is a multicentre, prospective, nationwide French registry enrolling patients who require veno-venous extracorporeal membrane oxygenation (ECMO)/VA-ECMO in the context of COVID-19 infection (652 patients at 41 centres). We focused on 47 patients supported with VA- or VAV-ECMO for refractory cardiogenic shock. RESULTS: The median age was 49. Fourteen percent of patients had a prior diagnosis of heart failure. The most common aetiologies of cardiogenic shock were acute pulmonary embolism (30%), myocarditis (28%) and acute coronary syndrome (4%). Extracorporeal cardiopulmonary resuscitation (E-CPR) occurred in 38%. In-hospital survival was 28% in the whole cohort, and 43% when E-CPR patients were excluded. ECMO cannulation was associated with significant improvements in pH and FiO2 on day 1, but non-survivors showed significantly more severe acidosis and higher FiO2 than survivors at this point (P = 0.030 and P = 0.006). Other factors associated with death were greater age (P = 0.02), higher body mass index (P = 0.03), E-CPR (P = 0.001), non-myocarditis aetiology (P = 0.02), higher serum lactates (P = 0.004), epinephrine (but not noradrenaline) use before initiation of ECMO (P = 0.003), haemorrhagic complications (P = 0.001), greater transfusion requirements (P = 0.001) and more severe Survival after Veno-Arterial ECMO (SAVE) and Sonographic Assessment of Intravascular Fluid Estimate (SAFE) scores (P = 0.01 and P = 0.03). CONCLUSIONS: We report the largest focused analysis of VA- and VAV-ECMO recipients in COVID-19. Although relatively rare, the need for temporary mechanical circulatory support in these patients is associated with poor prognosis. However, VA-ECMO remains a viable solution to rescue carefully selected patients. We identified factors associated with poor prognosis and suggest that E-CPR is not a reasonable indication for VA-ECMO in this population.

Epicardial vs. transvenous implantable cardioverter defibrillators in children.

AIMS: The implantable cardioverter defibrillator (ICD) has been increasingly used in children. Both epicardial and transvenous approaches are used, with controversy regarding the best option with no specific recommendations. We aimed to compare outcomes associated with epicardial vs. transvenous ICDs in children. METHODS AND RESULTS: Data were analysed from a retrospective study including all patients <18-year-old implanted with an ICD in a tertiary centre from 2003 to 2021. Outcomes were compared between epicardial and transvenous ICDs. A total of 122 children with an ICD (mean age 11.5 ± 3.8 years, 57.4% males) were enrolled, with 84 (64.1%) epicardial ICDs and 38 (29.0%) transvenous ICDs. Early (<30 days) ICD-related complications were reported in 17 (20.2%) patients with an epicardial ICD vs. 0 (0.0%) with a transvenous ICD (P = 0.002). Over a mean follow-up of 4.8 ± 4.0 years, 25 (29.8%) patients with an epicardial ICD and 9 (23.7%) patients with a transvenous ICD experienced at least one late ICD-related complication [hazard ratio (HR) 1.8, 95% confidence interval (CI) 0.8-4.0]. Implantable cardioverter defibrillator lead dysfunction occurred in 19 (22.6%) patients with an epicardial ICD vs. 3 (7.9%) with a transvenous ICD (HR 5.7, 95% CI 1.3-24.5) and was associated with a higher incidence of ICD-related reintervention (HR 3.0, 95% CI 1.3-7.0). After considering potential confounders, especially age and weight at implantation, this association was no longer significant (P = 0.112). The freedom from ICD lead dysfunction was greater in patients with pleural coils than in those with epicardial coils (HR 0.38, 95% CI 0.15-0.96). CONCLUSION: In children, after a consideration of patient characteristics at implantation, the burden of complications and ICD lead dysfunction appears to be similar in patients with epicardial and transvenous devices. Pleural coils seem to be associated with better outcomes than epicardial coils in this population. CLINICAL TRIAL REGISTRATION: NCT05349162.

Amiodarone/N-desethylamiodarone population pharmacokinetics in paediatric patients.

The population pharmacokinetics of amiodarone and its active metabolite, N-desethylamiodarone (DEA) were investigated in paediatric patients with arrhythmias, mainly supraventricular tachycardias. A total of 55 patients from the Department of Pediatric Intensive Care and Pediatric Cardiology at Necker-Enfants malades Hospital (Paris, France) provided 72 concentrations for both amiodarone and DEA following repeated oral or intravenous administration. Blood samples drawn for biological analyses were used for drug concentrations. Plasma amiodarone concentrations were measured by a liquid chromatography method coupled with mass spectrometry and the data were modelled using the software Monolix 2019R2. Parent pharmacokinetics was described with a 2-compartment open model and the metabolite formation was connected to the central parent compartment. Parameter estimates scaled allometrically on bodyweight (normalized to 70 kg) were, respectively (% relative standard errors, RSEs), 6.32 (31%) and 7.14 L/h (26%) for elimination (CL) and intercompartmental clearances and 167 (31%) and 3930 (32%) L for V1 and V2 . Oral bioavailability was 0.362 (21.5%). The clearance between subject variability (ω, square root of the variance) was 0.462 (RSE 21%). The proportional residual variabilities were respectively 0.453 (RSE 13%) and 0.423 (RSE 12%) for amiodarone and DEA respectively. The terminal half-lives were 34 and 14.5 days for amiodarone and DEA, respectively. A dosage schedule was established for 3 weight bands in 2 time periods. The high pharmacokinetic variability suggests that therapeutic drug monitoring might be useful to improve individual efficacy and safety.

Indications and outcomes of cardiac catheterization following congenital heart surgery in children.

OBJECTIVES: Our goal was to evaluate the indications for postoperative cardiac catheterizations after paediatric cardiac surgeries and their impact on outcomes. METHODS: Non-planned cardiac catheterizations performed after congenital heart surgeries and before discharge between January 2013 and July 2019 were reviewed. Hybrid procedures were excluded. Heart defects, illness course, surgeries and catheter procedures were classified. Indications and findings were comprehensively regrouped. Outcomes were analysed. RESULTS: Cardiac catheterizations were performed on 192 patients (median age 2.3 months, weight 4.2 kg) on median postoperative day 7 (interquartile range, 2-17 days). Patients had defects of great complexity (79.9%), high disease severity index (46.4%), high Aristotle level of surgical complexity (75%) and a high Catheterization RISk Score for Pediatrics category of catheterizations (61%). Catheterizations confirmed 66% of suspected diagnoses. Confirmed diagnoses were more likely to be haemodynamic anomalies than anatomical lesions (81.3% > 53.7%, P < 0.001). Confirmed anatomical lesions were more likely to be residual than new lesions created by surgery (88.5% > 40.4%, P < 0.001). New diagnoses were identified in 36.5% of patients. Catheterization findings led to catheter-based or surgical interventions in 120 (62.5%) patients. Transcatheter interventions were successful (97.7%), immediate (89.5%) and performed across fresh suture lines (27.8%). Repeat catheterizations (76% interventional) were necessary in 25 (13%) patients. A high index of disease severity [odds ratio (OR): 16.26, 95% confidence interval (CI): 3.72-71.17], extracorporeal membrane oxygenation support (OR: 10.35, 95% CI: 2.78-38.56), delayed sternal closure (OR: 4.66, 95% CI: 1.25-17.32) and surgically acquired lesions (OR: 3.70, 95% CI: 1.22-11.16) were significant risk factors of 12-month mortality. CONCLUSIONS: Postoperative cardiac catheterizations answer both anatomical and haemodynamic questions in high-risk patients with complicated courses and guide subsequent treatment with satisfactory outcomes.

Tetralogy of Fallot and abnormal coronary artery: use of a prosthetic conduit is outdated.

OBJECTIVES: Repair of tetralogy of Fallot (ToF) can be challenging in the presence of an abnormal coronary artery (CA) in 5-12% of cases. The aim of this study was to report our experience with ToF repair without the systematic use of a right ventricle-to-pulmonary artery (RV-PA) conduit. METHODS: We conducted a monocentric retrospective study from 2000 to 2016, including 943 patients with ToF who underwent biventricular repair, of whom 8% (n = 76) presented with an abnormal CA. Mean follow-up time was 50 months (1 month-18 years). RESULTS: The most frequent CA anomaly was the left descending artery arising from the right CA (n = 47, 61.8%). The median age at repair was 7.7 months (1.8 months-16 years). Thirteen patients (17%) required prior palliation, mostly systemic pulmonary shunts for anoxic spells in the neonatal period. Surgical repair allowed us to preserve the annulus in 40 patients (53%) by combining PA trunk plasty, commissurotomy and infundibulotomy under the abnormal CA. If the annulus had to be opened (n = 35, 46%), a transannular patch was inserted after a vertical incision of the PA trunk and extended obliquely on the RV over the anomalous crossing CA (with an infundibulotomy under the abnormal CA). Three patients (4%) required the insertion of an RV-PA conduit (1 valved tube and 2 RV-PA GORE-TEX tubes with annulus conservation). The early mortality rate was 4% (n = 3); none of the deaths was coronary related. Four patients (5%) required reoperation (2 early and 2 late reoperations) for residual pulmonary stenosis, 3 of whom had annulus preservation during the initial repair. The mean RV/left ventricle (LV) pressure ratio and an RV/LV pressure ratio >2/3 were identified as risk factors for right ventricular outflow tract (RVOT) reinterventions (P = 0.0026, P = 0.0085, respectively), RVOT reoperations (P = 0.0002 for both) and reoperation for RVOT residual stenosis (P = 0.0002, P = 0.0014, respectively). Two patients underwent pulmonary valve replacement. Freedom from late reoperation was 100% at 1 year, 97% at 5 years and 84% at 10 and 15 years. CONCLUSIONS: Repair of ToF and abnormal CA can be performed without an RV-PA conduit, with an acceptable low reintervention rate. The high early mortality rate in this series remains a concern. If any doubt remains about the surgical relief of the RVOT obstruction, the RV/LV pressure ratio should always be measured in the operating room.

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.

Postoperative B-type natriuretic peptide monitoring for the assessment of the magnitude of shunting through Blalock-Taussig anastomoses.

BACKGROUND: The Modified Blalock-Taussig shunt (MBTS) is the most common palliative operation performed in patients with complex cardiac defects. Postoperative morbidity and mortality rates are high, mainly due to shunt thrombosis and over-shunting. Over-shunting may be difficult to identify postoperatively based on conventional criteria. Since plasma B-type natriuretic peptide (BNP) concentrations correlate with the magnitude of shunting in various left-to-right shunt cardiac defects, we investigated its ability to identify postoperative MBTS over-shunting. METHODS AND RESULTS: This retrospective, observational study included 42 consecutive patients (median age 9.50days, IQR: 6.00-58.25) undergoing MBTS for obstruction of the pulmonary blood flow at a tertiary referral pediatric cardiac center. The BNP threshold concentrations which accurately predicted outcome and MBTS over-shunting were derived using the ROC methodology. 443 BNP concentrations were analysed. The presence of atrio-ventricular valve regurgitation was the most important component of overall variance (72.75%). In 34 patients without regurgitation, BNP concentrations were predictive of a duration of mechanical ventilation >8days and of intensive care stay >11days, with ROC areas of 0.655 [0.597-0.719], 0.650 [0.589-0.711], a negative predictive value for the >1035pgmL-1 threshold of 0.93 and 0.96 respectively. SaO2 was less accurate for the prediction of both outcomes. In patients in whom the pulmonary flow was entirely MBTS-supplied, a BNP concentrations >1052pgmL-1 was predictive of a pulmonary-to-systemic ratio>2. CONCLUSION: In MBTS patients without atrio-ventricular valve regurgitation, maintaining BNP below 1000pgmL-1 may represent a therapeutic target to avoid over-shunting.