Postoperative EEG abnormalities in relation to neurodevelopmental outcomes after pediatric cardiac surgery.

BACKGROUND: We had reported that postoperative EEG background including sleep-wake cycle (SWC) and discharge (seizures, spikes/sharp waves) abnormalities were significantly correlated with adverse early outcomes in children after cardiac surgery. We aimed to analyze the relations between these EEG abnormalities and neurodevelopmental outcomes at about 2 years after cardiac surgery. METHODS: We enrolled 121 patients undergoing cardiac surgery at 3.3 months (0.03 ~ 28 months). EEG abnormalities described above during the first postoperative 48 h were evaluated. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination and performance skills at 16 ~ 31 months of age. RESULTS: EEG background abnormalities occurred in 59/121 (48.8%) patients and 33 (55.9%) unrecovered to normal by 48 h. Abnormal SWC occurred in 15 (12.4%) patients and 7 (5.8%) unrecovered to normal by 48 h. EEG seizures occurred in 11 (9.1%) patients with frontal lobe seizures in 4. Spikes/sharp waves occurred in 100 (82.6%). EEG background abnormalities, number of spikes/sharp waves and frontal lobe seizures were significantly associated with neurodevelopmental impairment at about 1 ~ 2 year after surgery (Ps ≤ 0.05). CONCLUSIONS: Most parameters of EEG abnormalities were significantly associated with neurodevelopmental impairment after cardiac surgery. IMPACT: Neurodevelopmental impairment in children with congenital heart disease remain poorly understood. Previous studies had reported that either EEG seizures or background abnormalities were associated with worse neurodevelopmental outcomes. Our present study showed that all the EEG background and discharge abnormalities including EEG background, seizures and spikes/sharp waves in the early postoperative period were significantly associated with neurodevelopmental impairment at about 1 ~ 2 years after cardiac surgery. Comprehensive evaluation of early postoperative EEG may provide further insights about postoperative brain injury, its relation with neurodevelopmental impairment, and guide to improve clinical management.

Perioperative EEG background and discharge abnormalities in children undergoing cardiac surgery: a prospective single-centre observational study.

BACKGROUND: We analysed the characteristics of abnormal electroencephalogram (EEG) patterns before, during, and 48 h after cardiac surgery in patients with heterogeneous congenital heart disease to assess their relationship to demographic and perioperative variables and to early patient outcomes. METHODS: In 437 patients enrolled in a single centre, EEG was evaluated for background (including sleep-wake cycle) and discharge (seizures, spikes/sharp waves, pathological delta brushes) abnormalities. Clinical data (arterial blood pressure, doses of inotropic drugs, and serum lactate concentrations) were recorded every 3 h. Postoperative brain MRI was performed before discharge. RESULTS: Preoperative, intraoperative, and postoperative EEG was monitored in 139, 215, and 437 patients, respectively. Patients with a degree of preoperative background abnormalities (n=40) had more severe intraoperative and postoperative EEG abnormalities (P<0.0001). Intraoperatively, 106/215 (49.3%) patients progressed into an isoelectric EEG. Longer durations of isoelectric EEG were associated with more severe postoperative EEG abnormalities and brain injury on MRI (Ps≤0.003). Postoperative background abnormalities occurred in 218/437 (49.9%) patients, and 119 (54.6%) of them had not recovered after surgery. Seizures occurred in 36/437 (8.2%) patients, spikes/sharp waves in 359/437 (82.2%), and pathological delta brushes in 9/437 (2.0%). Postoperative EEG abnormalities correlated with degree of brain injury on MRI (Ps≤0.02). Demographic and perioperative variables were significantly correlated with postoperative EEG abnormalities, which in turn correlated with adverse clinical outcomes. CONCLUSIONS: Perioperative EEG abnormalities occurred frequently and correlated with numerous demographic and perioperative variables and adversely correlated with postoperative EEG abnormalities and early outcomes. The relation of EEG background and discharge abnormalities with long-term neurodevelopmental outcomes remains to be explored.

Cerebral Autoregulation Status in Relation to Brain Injury on Electroencephalogram and Magnetic Resonance Imaging in Children Following Cardiac Surgery.

Background Disturbed cerebral autoregulation has been reported in children with congenital heart disease before and during cardiopulmonary bypass surgery, but not after. We sought to characterize the cerebral autoregulation status in the early postoperative period in relation to perioperative variables and brain injuries. Methods and Results A prospective and observational study was conducted in 80 patients in the first 48 hours following cardiac surgery. Cerebral oximetry/pressure index (COPI) was retrospectively calculated as a moving linear correlation coefficient between mean arterial blood pressure and cerebral oxygen saturation. Disturbed autoregulation was defined as COPI >0.3. Correlations of COPI with demographic and perioperative variables as well as brain injuries on electroencephalogram and magnetic resonance imaging and early outcomes were analyzed. Thirty-six (45%) patients had periods of abnormal COPI for 7.81 hours (3.38 hours) either at hypotension (median <45 mm Hg) or hypertension (median >90 mm Hg) or both. Overall, COPI became significantly lower over time, suggesting improved autoregulatory status during the 48 postoperative hours. All of the demographic and perioperative variables were significantly associated with COPI, which in turn was associated with the degree of brain injuries and early outcomes. Conclusions Children with congenital heart disease following cardiac surgery often have disturbed autoregulation. Cerebral autoregulation is at least partly the underlying mechanism of brain injury in those children. Careful clinical management to manipulate the related and modifiable factors, particularly arterial blood pressure, may help to maintain adequate cerebral perfusion and reduce brain injury early after cardiopulmonary bypass surgery. Further studies are warranted to determine the significance of impaired cerebral autoregulation in relation to long-term neurodevelopment outcomes.

Postoperative hypernatremia is associated with worse brain injuries on EEG and MRI following pediatric cardiac surgery.

Objectives: Dysnatremia is a common electrolyte disturbance after cardiopulmonary bypass (CPB) surgery for congenital heart disease (CHD) and a known risk factor for adverse neurological events and clinical outcomes. The objective of this study was to evaluate the association of dysnatremia with worse abnormal EEG patterns, brain injuries detected by magnetic resonance imaging (MRI) and early adverse outcomes. Methods: We monitored continuous EEG in 340 children during the initial 48 h following cardiac surgery. Demographics and clinical characteristics were recorded. Sodium concentrations were measured in the arterial blood gas analysis every 6 h. Hyponatremia and hypernatremia were classified by the average of sodium concentrations over 48 h. Postoperative cerebral MRI was performed before hospital discharge. Results: In our patient cohort, dysnatremia was present in 46 (13.5%) patients. Among them, hyponatremia occurred in 21 (6.2%) and hypernatremia in 25 (7.4%). When compared to patients with normonatremia, hyponatremia was not associated with EEG abnormalities and early adverse outcomes (Ps ≥ .14). In hypernatremia group, the CPB time was significantly longer and more frequent use of DHCA (Ps ≤ .049). After adjusting for time, CPB time and the use of DHCA, hypernatremia was significantly associated with worse EEG abnormalities (including background, seizures and pathological delta brushes), more severe brain injuries on MRI (Ps ≤ .04) and trended to be associated with longer postoperative mechanical ventilation time (P = .06). Conclusion: Hypernatremia and hyponatremia were common in children after cardiac surgery. Hypernatremia, but not hyponatremia, was significantly associated with worse EEG abnormalities and more severe brain injuries on MRI and extended postoperative mechanical ventilation time.

Reliability and validity of the FFQ and feeding index for 7-to 24-month-old children after congenital heart disease surgery.

BACKGROUND: Congenital heart disease (CHD) is the most common congenital defect in neonates. Infants with CHD often have more nutritional difficulties, but currently, there is no unified Food Frequency Questionnaire (FFQ) for infants and young children aged 7-24 months in China. Therefore, we designed this study to assess the reliability and validity of the FFQ and feeding index for 7-to 24-month-old children after congenital heart disease surgery. METHODS: From July to October 2018, infants and young children aged 7-24 months after congenital heart disease surgery in Guangzhou were selected. Participants were categorized into two groups, in the first group (n = 95), the FFQ was completed twice at intervals of 7-10 days to assess reproducibility. In the second group (n = 98), participants accomplished both the FFQ and the 24-h diet records from 3 consecutive days to assess validity. The score of the Infant and Child Feeding Index (ICFI) and its qualified rate were caculated. Intraclass correlation coefficients (ICC) and Spearman correlation coefficient (SCC) were calculated for reliability and validity, respectively. RESULTS: The average intraclass correlation coefficients and spearman correlation coefficient of the FFQ were 0.536 and 0.318, all with statistical significance except the frequency of meat added. The ICFI of the first group was 8.61 (± 3.20), the qualified rate was 0.06% (6/95). The intraclass correlation coefficients of the ICFI ranged from 0.374 to 0.958; and the spearman correlation of the ICFI was -0.066 to -0.834. CONCLUSIONS: The FFQ possesses satisfactory reliability and moderate validity. The reliability of the ICFI is acceptable, but the validity results are quite different, indicating that the questionnaire is limited in the evaluation of the ICFI.

Explainable machine learning model for predicting the occurrence of postoperative malnutrition in children with congenital heart disease.

BACKGROUND & AIMS: Malnutrition is persistent in 50%-75% of children with congenital heart disease (CHD) after surgery, and early prediction is crucial for nutritional intervention. The aim of this study was to develop and validate machine learning (ML) models to predict the malnutrition status of children with CHD. We used explainable ML methods to provide insight into the model's predictions and outcomes. METHODS: This prospective cohort study included consecutive children with CHD admitted to the hospital from December 2017 to May 2020. The cohort data were divided into the training and test data sets based on the follow-up time. The outcome of the study was CHD child malnutrition 1 year after surgery, the primary outcome was an underweight status, and the secondary outcomes were stunted and wasting status. We used five ML algorithms with multiple features to construct prediction models, and the performance of these ML models was measured by an area under the receiver operating characteristic curve (AUC) analysis. We also used the permutation importance and SHapley Additive exPlanations (SHAP) to determine the importance of the selected features and interpret the ML models. RESULTS: We enrolled 536 children with CHD who underwent complete repair. The proportions of children with an underweight, stunted, or wasting status 1 year after surgery were 18.1% (97/536), 12.1% (65/536), and 17.5% (94/536), respectively. All patients contributed to the generation of 115 useable features, which allowed us to build models to predict malnutrition. Five prediction algorithms were used, and the XGBoost model achieved the greatest AUC in all outcomes. The results obtained from the permutation importance and SHAP analyses showed that the 1-month postoperative WAZ-score, discharge WAZ score and preoperative WAZ score were the top 3 important features in predicting an underweight status in the XGBoost algorithm. Regarding the stunted status, the top 3 important features were the 1-month postoperative HAZ score, discharge HAZ score, and aortic clamping time. Regarding the wasting status, the top 3 important features were the hospital length of stay, formula intake, and discharge WHZ-score. We also used a narrative case report as an example to describe the clinical manifestations and predicted the primary outcomes of two children. CONCLUSIONS: We developed an ML model (XGBoost) that provides accurate early predictions of malnutrition 1-year postoperatively in children with CHD. Because the ML model is explainable, it may better enable clinicians to better understand the reasoning underlying the outcome. Our study could aid in determining individual treatment and nutritional follow-up strategies for children with CHD.

Optimal Frequency for Changing Single-Use Enteral Delivery Sets in Infants after Congenital Heart Surgery: A Randomized Controlled Trial.

Objective We aimed to assess the optimal frequency for changing single-use enteral delivery sets during postoperative enteral feeding in infants with congenital heart disease (CHD).Methods We enrolled 120 CHD infants who were fed using an enteral nutrition pump directly connected to a milk bottle with a single-use enteral delivery set in a four-arm randomized controlled trial (ChiCTR2000039544). Patients were randomized into four groups based on the replacement frequency of the enteral delivery set (6 h, 12 h, 18 h, and 24 h groups). The primary outcome was the percentage of contaminated enteral delivery sets (overgrowth of microbiota and colonization of pathogenic bacteria). Secondary outcomes included evidence of infection, gastrointestinal tolerance, intestinal microflora dysbiosis, and healthcare costs.Results The percentages of microbial overgrowth detected in the 6 h, 12 h, 18 h, and 24 h groups were 6.7%, 30.0%, 46.7%, and 80%, respectively (P < 0.001). Significant differences were observed between the 6 h and 18 h groups (P < 0.001), the 6 h and 24 h groups (P < 0.001), and the 18 h and 24 h groups (P = 0.007). Meanwhile, pathogenic bacterial colonization was detected in 0, 4, 6, and 11 delivery sets in the 6 h, 12 h, 18 h, and 24 h groups, respectively (P = 0.002). No difference in clinical symptoms was found among the four groups. The total cost per patient in the 12 h group and the 18 h group was 340.2 RMB and 226.8 RMB, respectively.Conclusion Taking into consideration both microbial overgrowth and cost-effectiveness, the results of this study indicate that for children receiving continuous enteral feeding following CHD surgery, the optimal frequency for changing the single-use enteral delivery set when formula reconstituted from powder is used is 18 hours.

Assessment of postoperative risk factors for EEG abnormalities in routine clinical management after paediatric cardiopulmonary bypass.

OBJECTIVES: The postoperative risk factors for electroencephalogram(EEG) abnormalities after paediatric cardiopulmonary bypass (CPB) remain to be identified. We investigated the characteristics of EEG abnormalities and risk factors in routine clinical management post-CPB. METHODS: EEG and cerebral oxygen saturation (ScO2) were monitored in 96 patients (aged 3 days, 37 months, median 5 months) for 72 h post-CPB. Clinical measurements included 4-hourly arterial and central venous pressure, arterial blood gases, doses of inotropic and vasoactive drugs, daily C-reactive protein (CRP) and NT-proB-type Natriuretic Peptide (NT-proBNP). Demographics, STAT categories and outcomes (duration of mechanical ventilation,CICU stay) were recorded. Un. RESULTS: Seizures occurred in 20 patients (20.8%) beginning at 0-48 hand lasting 10 min-31 h; background abnormalities occurred in 67 (69.8%) beginning at 0-8 h and lasting 4-48 h. Patients with EEG abnormalities had worse outcomes. In univariable regression, seizures positively correlated with STAT categories, CPB time, temperature, blood pressure, central venous pressure, NT-proBNP, CRP, lactate and epinephrine, negatively with ScO2 and PaCO2 (P < 0.001 for lactate and epinephrine, P < 0.1 for the remaining). The degree of background abnormalities positively correlated with STAT categories, CPB time, operative time, central venous pressure, milrinone, negatively with blood pressure (P = 0.0003-0.087); it negatively correlated with lower dose of epinephrine (P < 0.001) and positively with higher dose (P = 0.03l). In multivariable regression, seizures positively correlated with epinephrine, lactate and temperature; the background abnormality correlations remain significant except for milrinone and operative time (P < 0.001 for epinephrine, P < 0.05 for the remaining). CONCLUSIONS: Numerous perioperative risk factors are associated with EEG abnormalities post-CPB. The most significant and consistent risk factor is epinephrine.

Multifaceted Function of Myosin-18, an Unconventional Class of the Myosin Superfamily.

Myosin is a diverse superfamily of motor proteins responsible for actin-based motility and contractility in eukaryotic cells. Myosin-18 family, including myosin-18A and myosin-18B, belongs to an unconventional class of myosin, which lacks ATPase motor activity, and the investigations on their functions and molecular mechanisms in vertebrate development and diseases have just been initiated in recent years. Myosin-18A is ubiquitously expressed in mammalian cells, whereas myosin-18B shows strong enrichment in striated muscles. Myosin-18 family is important for cell motility, sarcomere formation, and mechanosensing, mostly by interacting with other cytoskeletal proteins and cellular apparatus. Myosin-18A participates in several intracellular transport processes, such as Golgi trafficking, and has multiple roles in focal adhesions, stress fibers, and lamellipodia formation. Myosin-18B, on the other hand, participates in actomyosin alignment and sarcomere assembly, thus relating to cell migration and muscle contractility. Mutations of either Myo18a or Myo18b cause cardiac developmental defects in mouse, emphasizing their crucial role in muscle development and cardiac diseases. In this review, we revisit the discovery history of myosin-18s and summarize the evolving understanding of the molecular functions of myosin-18A and myosin-18B, with an emphasis on their separate yet closely related functions in cell motility and contraction. Moreover, we discuss the diseases tightly associated with myosin-18s, especially cardiovascular defects and cancer, as well as highlight the unanswered questions and potential future research perspectives on myosin-18s.

Application effect of initiation of enteral nutrition at different time periods after surgery in neonates with complex congenital heart disease: A retrospective analysis.

ABSTRACT: Early enteral nutrition (EN) promotes the recovery of critically ill patients, but the initiation time for EN in neonates after cardiac surgery remains unclear.This study aimed to investigate the effect of initiation time of EN after cardiac surgery in neonates with complex congenital heart disease (CHD).Neonates with complex CHD admitted to the CICU from January 2015 to December 2017 were retrospectively analyzed. Patients were divided into the 24-hour Group (initiated at 24 hours after surgery in 2015) (n = 32) and 6-hour Group (initiated at 6 hours after surgery in 2016 and 2017) (n = 66). Data on the postoperative feeding intolerance, nutrition-related laboratory tests (albumin, prealbumin, retinol binding protein), and clinical outcomes (including duration of mechanical ventilation, CICU stay, and postoperative hospital stay) were collected.The incidence of feeding intolerance was 56.3% in 24-hour Group and 39.4%, respectively (P = .116). As compared to 24-hour Group, prealbumin and retinol binding protein levels were higher (160.7 ±â€Š64.3 vs 135.2 ±â€Š28.9 mg/L, P = .043 for prealbumin; 30.7 ±â€Š17.7 vs 23.0 ±â€Š14.1 g/L P = .054 for retinol-binding protein). The duration of CICU stay (9.4 ±â€Š4.5 vs 13.3 ±â€Š10.4 day, P = .049) and hospital stay (11.6 ±â€Š3.0 vs 15.8 ±â€Š10.3 day, P = .028) were shorter in 6-hour Group.Early EN improves nutritional status and clinical outcomes in neonates with complex CHD undergoing cardiac surgery, without significant feeding intolerance.

Early Growth Trajectory of Infants With Simple Congenital Heart Disease and Complex Congenital Heart Disease Undergoing Cardiac Repair: A Prospective Cohort Study in China.

BACKGROUND: We aimed to evaluate the growth trajectory of infants with congenital heart disease (CHD) and to analyze the effects of disease classification on their growth trajectory. METHODS: A prospective cohort of infants with CHD was enrolled and divided into 2 groups: simple CHD (SC) and complex CHD (CC) groups. All patients were followed up for 6 months after CHD surgery. Weight for age (WAZ), length for age (LAZ), weight for length (WLZ), and head circumference for age were compared between the 2 groups using mixed-effects linear regression. RESULT: Between September 2018 and November 2019, 801 patients had data collected. The z-score trend decreased (e.g., ΔWAZ: 1.29±1.44) and then increased (e.g., ΔWAZ: 1.06±1.13), and all z-scores were below 0 from birth to 6 months postoperatively. Mixed-effects linear regression models indicated that the postoperative WAZ and WLZ scores of the CC group were lower than those of the SC group after adjustment (WAZ: ß = -0.72; 95% confidence interval [CI], -1.37 to -0.07; P = .03) (WLZ: ß = -0.93, 95% CI, -1.67 to -0.19; P = .01). The models also showed an interaction effect between disease classification and preoperative growth status on infant growth outcome (WAZ: interaction ß = -0.48; 95% CI, -0.88 to -0.07; P = .02) (WLZ: interaction ß = -0.36; 95% CI, -0.60 to -0.12; P = .004) (LAZ: interaction ß = -0.29; 95% CI, -0.56 to -0.02; P = .04). CONCLUSIONS: Compared with SC children, CC children have deficits in their early growth trajectories. The type of disease and preoperative growth status synergistically affect the early postoperative growth trajectory.

The association between the pattern of change in N-terminal pro-B-type natriuretic peptide and short-term outcomes in children undergoing surgery for congenital heart disease.

OBJECTIVES: This study aimed to determine whether changes in perioperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with short-term outcomes in children undergoing surgery for congenital heart disease (CHD). METHODS: We retrospectively included 873 consecutive children with CHD after cardiac surgery. NT-proBNP concentrations were collected from each child prior to and at 1, 12, 36 and 72 h after surgery. The patients had postsurgical follow-ups at 30, 90 and 180 days. The end point was postoperative composite adverse events. RESULTS: The patients were classified into 3 groups using joint latent class mixture time-to-event models: (i) relatively stable (86.7%), (ii) decreasing (7.2%) and (iii) increasing (6.1%). In total, 257 (29.4%) adverse events occurred. The joint latent class mixture time-to-event models showed that increasing NT-proBNP was strongly associated with adverse events, with adjusted hazard ratio of 2.33 (95% confidence interval 1.52-3.60). Multinomial logistic regression showed that the variables associated with the pattern of change were age, weight at surgery, mode of delivery and cardiopulmonary bypass time. CONCLUSIONS: The pattern of dynamic postsurgical changes in NT-proBNP may facilitate outcome stratification and identification of a high risk for adverse events.

Evaluation of Physical Fitness in Children With Congenital Heart Diseases Versus Healthy Population.

We aimed to evaluate and compare the physical fitness of children with different severity of the cardiac defect with their healthy peers. We included 182 children after cooperation for congenital heart disease (CHD) and 129 healthy children as controls, 6-18 years old, who performed a complete cardiopulmonary exercise test (CPET) in a cross-sectional observational study. The CHD patients were further subdivided into three subgroups according to diagnostic characteristics and surgical methods: simple CHD group (SCHD), complex CHD group (CCHD)and total cavopulmonary connection group (TCPC). Physical fitness was compared between groups using generalized linear model and multiple linear regression analysis. In comparison with age and gender adjusted healthy controls, children in SCHD, CCHD, and TCPC subgroups had accordingly graded down values of peak oxygen consumption (VO2max: 44.86 ± 5.41 vs. 39.91 ± 5.59 vs. 36.95 ± 5.92 vs. 32.04 ± 5.38 mL/kg/min, P < 0.05) and %predicted VO2max (1.01 ± 0.14 vs. 0.91 ± 0.13 vs. 0.83 ± 0.15 vs. 0.72 ± 0.13, P < 0.05) for each group. The proportion of %predicted VO2max above 80% in the CHD and the control group were 60.4% and 96.1% (P < 0.001). The VO2max decreased by 0.98 mL/kg/min per year in CHD children, and the corresponding %predicted reference diminished by 2.0%. Children with TCPC had the highest mean decrease of VO2max and %predicted VO2max per year of age (1.23 mL/kg/min, corresponding 3.0%). Although the mean overall physical fitness of children with simple and complex defect after biventricular correction were significantly different from healthy population, they were close to normal (>80%predicted VO2max). However, TCPC group had much lower exercise capacity.

Preoperative and operation-related risk factors for postoperative nosocomial infections in pediatric patients: A retrospective cohort study.

BACKGROUND: Pediatric patients undergoing invasive operations bear extra risk of developing nosocomial infections (NIs). However, epidemiological evidence of the underlying risk factors, which is needed for early prevention, remains limited. METHODS: Using data from the electronic medical records and the NI reporting system of a tertiary pediatric hospital, we conducted a retrospective analysis to identify preoperative and operation-related risk factors for postoperative NIs. Multivariable accelerated failure time models were fitted to select independent risk factors. The performance of these factors in risk stratification was examined by comparing the empirical risks between the model-defined low- and high-risk groups. RESULTS: A total of 18,314 children undergoing invasive operations were included for analysis. After a follow-up period of 154,700 patient-days, 847 postoperative NIs were diagnosed. The highest postoperative NI rate was observed for operations on hemic and lymphatic system. Surgical site infections were the NI type showing the highest overall risk; however, patients were more likely to develop urinary tract infections in the first postoperative week. Older age, higher weight-for-height z-score, longer preoperative ICU stay, preoperative enteral nutrition, same-day antibiotic prophylaxis, and higher hemoglobin level were associated with delayed occurrence of postoperative NIs, while longer preoperative hospitalization, longer operative duration, and higher American Society of Anesthesiologists score showed acceleration effects. Risk stratification based on these factors in an independent patient population was moderate, resulting in a high-risk group in which 72% of the postoperative NIs were included. CONCLUSIONS: Our findings suggest that pediatric patients undergoing invasive operations and at high risk of developing postoperative NIs are likely to be identified using basic preoperative and operation-related risk factors, which together might lead to moderately accurate risk stratification but still provide valuable information to guide early and judicious prevention.

Prognostic value of perioperative NT-proBNP after corrective surgery for pediatric congenital heart defects.

BACKGROUND: It is critically important to assess the prognostic value of NT-proBNP in the form of repeated measures among children undergoing surgery for congenital heart defects (CHD). The aim of the present study is to assess the value of repeated perioperative NT-proBNP in evaluating the time dependent and temporal trajectory in prognostics diagnosis during the perioperative period in a large series of children with CHD. METHODS: Repeated measures of NT-proBNP from 329 consecutive children with CHD were obtained before and 1, 12, and 36 h after surgery, respectively. For fully utilizing longitudinal characteristics, we employed parallel cross-sectional logistic regression, a two stage mixed effect model and trajectories over time analysis to mine the predictive value of perioperative NT-proBNP on the binary outcome of prolonged intensive care unit (ICU) stay. RESULTS: The two stage mixed effects model confirmed that both the mean NT-proBNP level (aOR = 1.46, P = 0.001) and the time trends had prognostic value on the prediction of prolonged ICU stay. In the fully adjusted logistic regression analyses based on gaussian distributions, "rapidly rising NT-proBNP" put the subjects at 5.4-times higher risk of prolonged ICU stay compared with "slowly rising" group (aOR = 5.40, P = 0.003). CONCLUSIONS: Comprehensive assessment of the time dependent and temporal trajectory in perioperative NT-proBNP, indicated by repeated measurements, can provide more accurate identification of children with higher risk of prolonged ICU stay after CHD surgery.

Identification of risk factors affecting catch-up growth after infant congenital heart disease surgery: rationale and design of a multicentre prospective cohort study in China.

INTRODUCTION: Successful surgical treatment of congenital heart disease improves neonates' long-term survival and leads to catch-up growth, which however does not occur in part of the patient population for largely undetermined reasons. METHODS AND ANALYSIS: A multicentre, prospective cohort study is being conducted in four paediatric medical institutions in China to collect detailed nutritional, anthropometric and clinical data at perioperative phases and during a 1-year period of follow-up after surgery. The study is expected to recruit approximately 5000 patients by the year of 2023 when the cohort is fully established. The primary endpoint of this study is the occurrence of postoperative catch-up growth, which will be determined in both absolute and relative terms (ie, reduced anthropometric deficits from the reference measures and improved z-scores that have passed the -2 SD cut-offs). Multivariable regression analyses will be performed to identify factors that are statistically significantly associated with the absence of postoperative catch-up growth. ETHICS AND DISSEMINATION: The protocol of this study has been approved by the individual ethics committees of the participating centres (Guangzhou Women and Children's Medical Centre (2008071601), the Children's Hospital of Zhejiang University School of Medicine (2018-IRB-094), Gansu Provincial Maternity and Child-Care Hospital (2019-IRB-01) and Zhengzhou Cardiovascular Hospital (2019012001)). Written informed consent from parents will be obtained before study entry. Findings of this study will be disseminated through publications in international peer-reviewed journals and will be presented in academic conferences.

[Cannulation for extracorporeal membrane oxygenation in infants less than 5 kg].

OBJECTIVE: To summarize the experience of cannulation for extracorporeal membrane oxygenation (ECMO) in infants less than 5 kg. METHODS: Eleven infants with ECMO support who weighed less than 5 kg were admitted to critical care medicine of Guangzhou Women and Children's Medical Center from June 2016 to June 2018 were enrolled. Retrospective analysis of support type, configuration, site of cannula and complication of ECMO was performed. RESULTS: The 11 infants consisted of 9 males and 2 females. The weight on ECMO of 1.96-4.60 kg, with an average of (3.14±0.65) kg; age 0.1-30.0 days, with a median of 5.6 (1.5, 8.3) days. Four cases were given ECMO because of congenital diaphragmatic hernia with severe pulmonary hypertension and other 7 cases were cannulated due to complication of congenital cardiac surgery. All infants were received veno-arterial (V-A) ECMO. In 4 cases, the cannulas were placed in the right internal jugular vein for drainage (8-10 French catheter with 6.0-7.5 cm depth) and the right carotid artery for infusion (6-8 French catheter with 2.5-3.5 cm depth); the average time of cannulation in right carotid and jugular vessels was (73±20) minutes (range 55-100 minutes). In other 7 cases, the cannulas were inserted into the right atrium (12-14 French catheter with 2.8-3.0 cm depth) for draining blood and returning it to the ascending aorta (6-8 French catheter with 1.0-2.0 cm depth); the average time of cannulation in central vessels was (64±31) minutes (range 35-110 minutes) with exclusion of 2 cases intraoperative cannulation. There were three infants with complications. One episode was shown in vascular rupture, one in catheter site hemorrhage and one in cannula malposition with later repositioning. There was no case of insertion site infection, cannula-related bloodstream infection and accident detached cannula. CONCLUSIONS: Cannulation for ECMO can be performed in infants less than 5 kg with a high rate of success and a low rate of complication owing to appropriate catheter and skillful cannulation.

Change in N-terminal pro B-type natriuretic peptide levels and clinical outcomes in children undergoing congenital heart surgery.

OBJECTIVE: To examine the association between change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and prognosis after congenital heart disease (CHD) surgery. METHODS: NT-proBNP level was measured in 873 children before and at 1, 12, 36 and 72 h after cardiac surgery. Patients were followed up at 30, 90 and 180 days after surgery. The clinical outcomes of interest included prolonged intensive care unit (ICU) stay (>3 days), prolonged mechanical ventilation (>48 h), and occurrence of adverse events (i.e. death, readmission, and infection). RESULTS: NT-proBNP increased after surgery, peaking at 12 h, and decreased progressively thereafter. Median NT-proBNP change (i.e. preoperative minus postoperative level at 72 h after surgery) was -1212.68 pg/mL (interquartile range: -3099.87 to -66.81). Adverse events occurred in 29.4% of patients. Multivariate logistic regression showed that lower body surface area (BSA), higher, the Risk Adjustment for Congenital Heart Surgery-1 score and smaller age were significantly associated with an increased risk of prolonged ICU-stay and mechanical ventilation. A decrease or a slight increase in NT-proBNP was associated with a lower risk. In multivariate cox regression, a decrease or a slight increase in NT-proBNP was associated with a lower risk of death. In addition to quartile of the NT-proBNP change, BSA was a significant predictor for adverse events. The associations for prolonged ICU-stay and mechanical ventilation were U-shaped, according to the restricted cubic spline models. The association between NT-proBNP change and death was inconclusive. CONCLUSIONS: Increase in NT-proBNP may be a useful marker for adverse outcomes in children with CHD after cardiac surgery.

Energy and Protein Requirements in Children Undergoing Cardiopulmonary Bypass Surgery: Current Problems and Future Direction.

Congenital heart disease (CHD) is 1 of the most common congenital malformations, and considerable numbers of infants and young children with CHD undergo cardiopulmonary bypass surgery. It has been increasingly realized that perioperative nutrition support plays an important role in improving clinical outcomes. The purpose of this review, by searching PubMed, was to examine the nutrition conditions in perioperative children with CHD and the main problems in nutrition management in the cardiac intensive care unit (CICU), based on which future directions were proposed. We found that preoperative poor nutrition status is common. This limited reserve of energy and protein is further compounded by the complex metabolic alterations with hypermetabolism, hypercatabolism, and hypoanabolism in the early postoperative course. Knowledge about energy and protein metabolism and requirements in children after cardiopulmonary bypass remains very limited. The current nutrition recommendations in the CICU are based on little evidence. Insufficient energy and protein supply to meet demands remains a norm in the immediate postoperative period. The commonly used predictive equations do not provide accurate estimate of energy requirement in individual patients during the highly dynamic postoperative course. Indirect calorimetry can provide the best estimate of energy requirements for children with CHD in the CICU. Measurement of nitrogen balance is the recommended method to determine the minimal protein requirement. During the early postoperative period, daily measurements of resting energy expenditure using indirect calorimetry and nitrogen balance in each individual child are essential to optimize energy and protein supply to meet requirements.

Normalization of N-Terminal Pro-B-Type Natriuretic Peptide After Cardiac Surgery Among Children With Tetralogy of Fallot.

The aim of this study was to temporally measure N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over a period of 18 months after corrective surgery among children with tetralogy of Fallot (TOF) and to explore how commonly used pharmaceuticals (i.e., spironolactone and digoxin) might affect the normalization pattern. This retrospective study included 136 children with a median age of 7 months who underwent cardiac surgery for TOF. NT-proBNP level was measured at 1, 3, 6, 12, and 18 months after the surgery. Normalization of NT-proBNP was defined as an NT-proBNP level ≤250 pg/ml. The commonly used pharmaceuticals spironolactone and digoxin after discharge were collected. The normalization pattern, normalization time, and potential influence of the pharmaceuticals were determined. The rate of normalization was 24.2% (95% confidence interval [CI] 8.58% to 68.4%) per 100 person-days. Kaplan-Meier survival analysis showed a median normalization time of 517 (95% CI 429.6 to 604.3) days. The children whose NT-proBNP level did not normalize had a significantly higher readmission rate than those whose NT-proBNP level normalized (19.0% vs 2.8%, p = 0.018). Multivariable logistic regression models confirmed that the regular users of spironolactone, alone (odds ratio = 1.45, 95% CI 1.15 to 1.83) or in combination with digoxin (odds ratio = 1.28, 95% CI 1.03 to 1.58), had markedly faster recovery trajectories for measures of NT-proBNP than the irregular users of both. In conclusion, NT-proBNP normalization after cardiac surgery for TOF is a lengthy process, and irregular use of spironolactone could lead to failure in recovery and hospital readmission.