Cardiac Surgery In Infants Research Articles

Detection of Cerebral High-Intensity Transient Signals by NeoDoppler during Cardiac Catheterization and Cardiac Surgery in Infants.

There is a risk of gaseous and solid micro-embolus formation during transcatheter cardiac interventions and surgery in children with congenital heart disease (CHD). Our aim was to study the burden of high-intensity transient signals (HITS) during these procedures in infants. We used a novel color M-mode Doppler (CMD) technique by NeoDoppler, a non-invasive ultrasound system based on plane wave transmissions for transfontanellar continuous monitoring of cerebral blood flow in infants. The system displays CMD with 24 sample volumes and a Doppler spectrogram. Infants with CHD undergoing transcatheter interventions (n=15) and surgery (n=13) were included. HITS were manually detected based on an "embolic signature" in the CMD with corresponding intensity increase in the Doppler spectrogram. Embolus-to-blood ratio (EBR) defined HITS size. A total of 1169 HITS with a median EBR of 9.74 dB (interquartile range [IQR]: 5.10-15.80 dB) were detected. The median number of HITS in the surgery group was 45 (IQR: 11-150), while in the transcatheter group the median number was 12 (IQR: 7-24). During cardiac surgery, the highest number of HITS per hour was seen from initiation of cardiopulmonary bypass to aortic X-clamp. In this study we detected frequent HITS and determined the feasibility of using NeoDoppler monitoring for HITS detection.

Association between cuffed tracheal tube use and reduced ventilator-associated pneumonia and conditions after elective cardiac surgery in infants and young children.

Ventilator-associated pneumonia (VAP) is a serious complication in children after cardiac surgery that may result from micro-aspiration. However, the current recommendation to use cuffed tracheal tubes (TTs) versus uncuffed TTs in children is still uncertain. Our main aim was to evaluate the incidence of VAP, ventilator-associated tracheobronchitis (VAT) and ventilator-associated conditions (VAC) in children up to five years old who underwent elective cardiac surgery. Single-center, prospective before-and-after study at a tertiary pediatric intensive care unit (PICU) in Italy. 242 patients (121 in each group) through the following periods: phase I (from Jan 2017 to 20th Feb 2018), during which children were intubated with uncuffed TTs; phase II (from 21th Feb 2018 to Feb 2019), during which children were intubated with cuffed TTs. Data were collected using an electronic dedicated database. Median age was five months. The use of cuffed tubes reduced the risk of VAC and VAP respectively 15.8 times (95% CI 3.4-73.1, P=0.0008) and 14.8 times (95% CI 3.1-71.5, P=0.002). No major related airway complications were observed in the cuffed TTs group. Average treatment effect, calculated after propensity score matching, confirmed the significant effect of cuffed TTs on VAC and VAP. Our study suggests a marked reduction of VAP and VAC associated with use of a cuffed versus uncuffed TT in infants and children ≤5 years of age after elective cardiac surgery. A randomized clinical trial is needed to confirm these results and define the impact of use of a cuffed versus uncuffed TT across other relevant ICU outcomes and non-cardiac PICU patients.

First Author Spotlight

AnnouncementFirst Author SpotlightPublished Online:13 Jul 2022https://doi.org/10.1152/ajprenal.2022.323.1.AUMoreSectionsPDF (465 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat BOHAN CHENDivision of Nephrology, University of Toledo Medical Center, Toledo, OhioFigure 1.Bohan ChenDownload figureDownload PowerPointBohan Chen is a research fellow in Dr. Rujun Gong’s laboratory at the University of Toledo College of Medicine, where she studies the pathogenesis of chronic kidney diseases. She earned her MD degree at Zhengzhou University in China. In her spare time, she enjoys reading and outdoor activities [Photo: Fig. 1].https://doi.org/10.1152/ajprenal.00130.2022DOUGLASS B. CLAYTONDivision of Pediatric Urology, Department of Urology, Vanderbilt University Medical Center, Nashville, TennesseeFigure 2.Douglass ClaytonDownload figureDownload PowerPointDouglass Clayton, MD, is an Associate Professor of Urology at Vanderbilt University Medical Center and was mentored by Volker Haase, MD. His clinical work focuses on the care of children with urological problems. His research interest is centered on the role of the hypoxia-inducible factor pathway in bladder inflammation. In his spare time, he enjoys weightlifting, reading, and traveling [Photo: Fig. 2].https://doi.org/10.1152/ajprenal.00344.2021RYAN J. CORNELIUSDivision of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, OregonFigure 3.Ryan CorneliusDownload figureDownload PowerPointRyan Cornelius completed his PhD at the University of Nebraska Medical Center in Omaha, NE, mentored by Dr. Steve Sansom. In 2015, he came to Oregon Health and Science University as a postdoctoral fellow in David Ellison’s laboratory, where he studies electrolyte balance and kidney injury with a focus on the role of cullin-RING ligase regulation in the kidney. He spends his free time hiking and skiing with his wife, Sarah [Photo: Fig. 3].https://doi.org/10.1152/ajprenal.00436.2021JESSE A. DAVIDSONDepartment of Pediatrics, University of Colorado, Aurora, ColoradoFigure 4.Jesse DavidsonDownload figureDownload PowerPointJesse Davidson, MD, MPH, MSc, is an Associate Professor of Pediatrics at Children’s Hospital Colorado with dual board certification in pediatric cardiology/critical care. His research focuses on the systems biology and therapy of multiorgan injury after infant cardiac surgery, with a particular interest in leveraging metabolomic and proteomic techniques to explore the complex molecular pathways activated during postoperative injury and recovery [Photo: Fig. 4].https://doi.org/10.1152/ajprenal.00039.2022JULIAN D. C. SERNADepartment of Biochemistry, Chemistry Institute, Universidade de São Paulo, São Paulo, BrazilFigure 5.Julian SernaDownload figureDownload PowerPointJulian Serna is a PhD candidate at the Department of Biochemistry of Universidade de São Paulo, in Brazil. He completed his BS at Universidad del Valle in Chemistry. He is mentored by Dr. Alicia Juliana Kowaltowski. His research interest focuses on calcium signaling, metabolism, and mitochondrial biology. In his spare time, he enjoys learning about life on earth and doing pole sport [Photo: Fig. 5].https://doi.org/10.1152/ajprenal.00461.2021This article has no references to display. Download PDF Back to Top Next FiguresReferencesRelatedInformationRelated ArticlesThe Janus view: dual roles for hypoxia-inducible factor in renal repair after acute kidney injury 21 Jun 2022American Journal of Physiology-Renal PhysiologyInhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction 21 Jun 2022American Journal of Physiology-Renal PhysiologyCOP9 signalosome deletion promotes renal injury and distal convoluted tubule remodeling 21 Jun 2022American Journal of Physiology-Renal PhysiologyMetabolomic profiling demonstrates evidence for kidney and urine metabolic dysregulation in a piglet model of cardiac surgery-induced acute kidney injury 21 Jun 2022American Journal of Physiology-Renal PhysiologyRegulation of kidney mitochondrial function by caloric restriction 21 Jun 2022American Journal of Physiology-Renal Physiology More from this issue > Volume 323Issue 1July 2022Pages i-ii Crossmark Copyright & PermissionsCopyright © 2022 the American Physiological Society.https://doi.org/10.1152/ajprenal.2022.323.1.AUHistory Published online 13 July 2022 Published in print 1 July 2022 Metrics

Study protocol and statistical analysis plan for the Early Peritoneal Dialysis in Infants after Cardiac Surgery (EPICS) trial

Background: Peritoneal dialysis (PD) is a commonly used therapy after infant cardiac surgery. It is unclear whether early PD commenced soon after admission to an intensive care unit (ICU) after cardiac surgery results in better outcomes. Objective: To describe the study protocol and statistical analysis plan for the Early Peritoneal Dialysis in Infants after Cardiac Surgery (EPICS) trial. Design, setting, participants and intervention: The EPICS trial is an open, randomised, two-group, single-centre clinical study of infants ≤ 180 days of age who had cardiac surgery (in Risk-Adjusted Classification for Congenital Heart Surgery version 1 categories 3-6) with cardiopulmonary bypass. Participants will be randomly assigned 1:1 to early PD (treatment group) or no early PD (control group). Those assigned to the treatment group will begin receiving PD soon after ICU admission and continue receiving it for 24 hours. Those in the control group will not receive PD during the first 24 hours. Main outcome measures: The primary outcome is a composite measure consisting of one or more of death, cardiac arrest, emergency chest reopening, and requirement for extracorporeal membrane oxygenation (ECMO) within 90 days. The main secondary outcomes are duration of mechanical ventilation, ICU length of stay, hospital length of stay, vasoactive-inotropic score at 24 hours, and cumulative per cent fluid balance by end of Day 2. At Day 90, events such as mortality, requirement for ECMO, cardiac arrest, chest reopening, volume of packed red blood cell transfusion, postoperative infection, readmission to ICU, renal injury and brain injury will be assessed. Conclusions: The EPICS trial aims to evaluate the role of early PD after infant cardiac surgery in lowering the rate of a composite major outcome. In addition, it will test the effect of early PD on duration of mechanical ventilation, and on ICU and hospital length of stay. Trial registration: ACTRN12617001614381.

Impact of delayed sternal closure on wound infections following neonatal and infant cardiac surgery.

Delayed sternal closure is a routine procedure to reduce hemodynamic and respiratory instability in pediatric patients following cardiac surgery, particularly in neonates and infants. In this setting, the possible links between sternal wound infection and delayed sternal closure are still a matter of debate. As a part of our routine, there was a low threshold for delayed sternal closure, so we reviewed our experience with sternal wound infections with a focus on potentially related perioperative risk factors, particularly delayed sternal closure. We retrospectively identified 358 operated neonates (37%) and infants (mean age 3.6 months) in our local congenital heart disease database between January 2013 and June 2017. Potential risk factors for sternal wound infections, such as age, gender, complexity (based on Aristotle- and STS-EACTS mortality category), reoperation, use of cardiopulmonary bypass, extracorporeal membrane oxygenation, mortality and delayed sternal closure (163/358, 46%), were subjected to uni- and multivariate analysis. A total of 26/358 patients (7.3%) developed a superficial sternal wound infection. There were no deep sternal wound infections, no mediastinitis or sepsis. Applying univariate analysis, the prevalence of sternal wound infections was related to younger age, more complex surgery and delayed sternal closure. However, in multivariate analysis, sternal wound infection was only associated with delayed sternal closure (p = 0.013, odds ratio 8.6). Logistic regression revealed the prevalence of delayed sternal closure to be related to younger age, complexity, and the use of extracorporeal membrane oxygenation. In patients younger than one year, sternal wound infections are clearly related to delayed sternal closure. However, in our cohort, all sternal wound infections were superficial and acceptable, considering the improved postoperative hemodynamic stability.

Pectoralis major muscle turnover flap reconstruction for treatment of deep sternal wound infection in infants and children.

The aim of the study is to assess the therapeutic effect and applicability of pectoralis major muscle turnover flap (PMMTF) reconstruction for treatment of deep sternal wound infection (DSWI) after cardiac surgery in infants and children. From March 2013 to October 2021, 23 patients with DSWI after cardiac surgery underwent PMMTF reconstruction. The data and outcomes of the patients were retrospectively analyzed. Twenty patients were treated with unilateral PMMTF reconstruction, and three patients were treated by bilateral PMMTF. All of the sternal wounds healed successfully. All patients survived and were discharged without evidence of infection. In a follow-up period, ranging from 15 to 83 months (mean 32.6 months), all patients demonstrated normal development with no limitations to limb movements. There were no signs of chronic sternal infection in all of them. PMMTF reconstruction is a simple, feasible,and effective treatment of DSWI after cardiac surgery in infants and children, with minimal developmental problems.

Endotracheal Tube Displacement during Cardiac Surgery in Infants: A Retrospective Cohort Study of Its Incidence and Predictors

Introduction: With the traction on the trachea and intrathoracic manipulation during cardiac surgery, the position of the endotracheal tube (ETT) might be changed as compared to before surgery. Migration of the ETT during pediatric cardiac surgery is particularly problematic in infants. Methods: In this retrospective cohort study, chest X-rays were taken in the operating room just before and after surgery. The position of the ETT among all infants under 1 year of age who underwent cardiac surgery between December 2017 to December 2019 was evaluated. The displacement of the ETT position was examined by measuring the position of the tube tip from the tracheal bifurcation on a chest X-ray, and the relationship between surgery-related factors (age, height, weight, sex, surgery time, cardiopulmonary bypass, tube size, use of tube cuff) was analyzed. Results: Eighty-eight of the 141 patients were enrolled. There was a significant proximal displacement of the ETT tip during cardiac surgery. The distance from the carina to the tube tip after surgery was long, on average 2.5 mm, compared to that before surgery (P = 0.013). Cephalad displacement of the ETT either ≥5 mm or ≥2.5 mm was found in 28 and in 38 out of 88 infants after surgery, respectively. After performing multivariate analysis, the use of un-cuffed ETT was the sole exploratory variable predictive of tube tip displacement (OR 0.34, 95% CI 0.10 - 0.93 if ≥5 mm; and OR 0.24, 95% CI 0.08 - 0.75 if ≥2.5 mm displacement; P = 0.04 and 0.01, respectively). Conclusion: Proximal displacement of the ETT during cardiac surgery occurs more frequently in infants with un-cuffed ETT.

Elevated nuclear and mitochondrial cell-free deoxyribonucleic acid measurements are associated with death after infant cardiac surgery

ObjectivesMortality rates following pediatric cardiac surgery with cardiopulmonary bypass have declined over decades, but have plateaued in recent years. This is in part attributable to persistent issues with postoperative global inflammation and myocardial dysfunction, commonly manifested by systemic inflammatory response syndrome and low cardiac output syndrome, respectively. Quantified cell-free DNA (cfDNA), of nuclear or mitochondrial origin, has emerged as a biomarker for both inflammation and myocardial injury. Recent data suggest that nuclear cfDNA (ncfDNA) may quantify inflammation, whereas mitochondrial cfDNA (mcfDNA) may correlate with the degree of myocardial injury. We hypothesize that threshold levels of ncfDNA and mcfDNA can be established that are sensitive and specific for postoperative mortality mediated through independent pathways, and that association will be enhanced with combined analysis. MethodsProspective observational study of infants younger than age 1 year undergoing planned surgery with cardiopulmonary bypass. The study received institutional review board approval. Samples were drawn before skin incision, immediately after completion of cardiopulmonary bypass, and subsequently at predetermined intervals postoperatively. Association of early postoperative ncfDNA and mcfDNA levels with mortality were assessed by logistic regression with cut-points chosen by receiving operating characteristic curve exploration. ResultsData were available in 59 patients. Median age and weight were 122 days (interquartile range, 63-154 days) and 4.9 kg (interquartile range, 3.9-6.2 kg). Median STAT category was 3 (interquartile range, 1-4). The primary outcome of death was met in 3 out of 59 (5%). Combined analysis of ncfDNA and mcfDNA levels at 12 hours after the initiation of cardiopulmonary bypass with death at a threshold of 50 ng/mL ncfDNA and 17 copies/μL mcfDNA yielded 100% sensitivity and negative predictive value. The specificity (91%) and positive predictive value (38%) increased through combined analysis compared with univariate analysis. Combined analysis exhibited high specificity (93%) and negative predictive value (78%) for prolonged (>30 postoperative days) hospitalization. ConclusionsCombined analysis of early postoperative ncfDNA and mcfDNA can stratify risk of mortality and prolonged hospitalization following infant cardiac surgery. Evaluation of both ncfDNA and mcfDNA to identify states of generalized inflammation and myocardial injury may allow for targeted interventions and improved outcomes.

Abstract 12488: Serum Cystatin C is an Early Predictor of Acute Renal Injury in Infants After Cardiac Surgery With Cardiopulmonary Bypass

Introduction: Acute kidney injury (AKI) following infant cardiac surgery is common, with increased morbidity and mortality. Changes in urine output and/or serum creatinine (SCr) are unreliable in the detection of AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, and lag behind onset of renal injury. Serum Cystatin C (SCC) has been used as a biomarker of AKI in adults and older children. If SCC predicts AKI in infants following cardiopulmonary bypass (CPB) is unknown. Hypothesis: SCC is an early biomarker of AKI following infant cardiac surgery requiring CPB. Methods: 42 infants (< 1 year of age) were prospectively enrolled when presenting for cardiac surgery requiring CPB. SCC and SCr were measured at baseline (pre-operatively), and at 12, 24, and 48 hours following CPB initiation, and changes in SCC and SCr compared to baseline (ΔSCC and ΔSCr, respectively) were calculated. AKI was defined using KDIGO guidelines, as an increase in SCr ≥ 50% and/or a urine output < 0.5mL/kg/hr for ≥ 6-12 consecutive hours in the first 3 post-operative days. Subjects were divided in 2 groups: AKI and non-AKI. Receiver Operating Characteristic (ROC) curves were utilized to predict AKI based on ΔSCC and ΔSCr, and the area under the curve (AUC) was quantified. Results: AKI occurred in 17 (40.4%) subjects. Baseline SCC and SCr measurements were similar between groups, as were age, gender, weight, and CPB time. Post-operative SCC values decreased from baseline, suggesting volume overload. While SCC concentrations did not differ significantly between the 2 groups, ΔSCC measurements were significantly different in those with AKI at 12 hours (0.2 ± 0.3 vs 0.4 ± 0.2; p < 0.01) and remained different at 24 hours (0.1 ± 0.3 vs 0.3 ± 0.2; p = 0.02). ΔSCr measurements were significantly greater in the AKI group at 24 hours (0.1 ± 0.1 vs 0.0 ± 0.1; p < 0.01) and 48 hours (0.1 ± 0.1 vs. 0.0 ± 0.1; p < 0.01) but not at 12 hours. ROC curves demonstrated that both the ΔSCC at 12 hours (AUC = 0.72; p = 0.02) and the ΔSCr at 24 hours (AUC= 0.78; p < 0.01) predicted AKI. Conclusions: The 12 hour ΔSCC predicts AKI in infants after cardiac surgery, and correlated with a rise in ΔSCr the following day. Earlier detection of AKI would allow earlier post-operative intervention to mitigate renal injury in infants.

RETRACTED ARTICLE: The association between neutrophil–lymphocyte ratio and poor outcomes following infant cardiac surgery

BackgroundNeutrophil–lymphocyte ratio (NLR) is a valuable indicator for evaluating inflammation and adverse outcomes after cardiac surgery. The objective of this study was to evaluate the association of perioperative NLR with clinical outcomes in infants undergoing congenital heart surgery with cardiopulmonary bypass.MethodsWe performed a retrospective review of 424 consecutive infants (≤ 1 year) undergoing cardiac surgery between January 2019 and September 2019. Neonates (≤ 28 days) and patients with incomplete NLR data were excluded. The study endpoint was a composite of poor outcomes after surgery. We assess the correlation between perioperative NLR and clinical outcomes. A receiver operating characteristic curve and multivariable logistic regression were applied to identify the prognosis performance of postoperative NLR for poor outcomes.ResultsA total of 68 (16%) infants experienced at least one of the poor outcomes. Postoperative NLR on the third day after the surgery showed the best prognostic significance (AUC = 0.763, 95%CI 0.700–0.826) among perioperative period, with a cut-off value of 2.05. Postoperative NLR was also strongly correlated with mechanical ventilation time, length of ICU and hospital stay (p < 0.001). Multivariable logistic regression revealed that elevated postoperative NLR (OR 3.722, 95%CI 1.895–7.309, p < 0.001) was an independent risk factor for poor outcomes in infants after cardiac surgery.ConclusionsPostoperative NLR was correlated with increased mechanical ventilation time, length of ICU and hospital stay. Elevated postoperative NLR was an independent predictor for poor outcomes after cardiac surgery in infants.

Neurodevelopmental Outcomes after Congenital Heart Disease Surgery in Infancy: A 2-Year Serial Follow-Up.

Background: The aim of this study is to assess the neurodevelopmental status of infant patients who underwent cardiac surgery in infancy and to investigate the factors affecting the neurodevelopmental status. Methods: This retrospective study included 108 patients who underwent cardiac surgery before the age of one. We used the Bayley Scales of Infant Development II to evaluate the neurodevelopmental status. All patients were analyzed according to the presence of the syndrome. Patients without the syndrome were analyzed according to the presence of brain lesions. Results: The mean mental developmental index (MDI) and the mean psychomotor developmental index (PDI) were 76.11 ± 20.17 and 65.95 ± 18.34, respectively, in the first evaluation, and 73.98 ± 22.53 and 69.48 ± 20.86, respectively, in the second evaluation. In the subgroup analysis, no significant difference was observed between the first evaluation and the second evaluation. Conclusions: No significant difference was observed in the degree of development of the patients in the two evaluation periods. Although the presence of syndrome, brain lesion, or gestational age affected the degree of developmental delay, more than half of the patients had developmental delay in the two evaluation periods in any of the subgroup. Therefore, the necessity of early screening and early rehabilitation intervention is emphasized.

Renal tissue desaturation and acute kidney injury in infant cardiac surgery: a prospective propensity score-matched cohort study

BackgroundPrevious studies on the association between renal tissue desaturation and acute kidney injury (AKI) in infant cardiac surgery are limited by small sample sizes and inconsistent results. This prospective study aimed to determine the association between renal desaturation and AKI in infants undergoing surgical repair of an isolated ventricular septal defect (VSD). MethodsInfants undergoing VSD repair involving cardiopulmonary bypass participated in this prospective cohort study. The exposure of interest was renal tissue desaturation, defined as at least 20% decrease in saturation from baseline for at least 60 consecutive seconds. Intraoperative care was not guided by renal oxygenation, as the anaesthesiologists were blinded to the monitor. The outcome was AKI arising within postoperative Days 1–3. The primary analysis was based on propensity score-matched infants with and without intraoperative renal desaturation. ResultsIntraoperative renal desaturation was detected in 38 of 242 infants using near-infrared spectroscopy. This group of infants was matched with 114 infants without intraoperative renal saturation after propensity score matching. Acute kidney injury occurred in 47% (18/38) and 27% (31/114) of infants with or without renal desaturation, respectively. Infants with renal desaturation had higher odds of developing AKI than infants without renal desaturation based on conditional logistic regression (odds ratio 2.79; 95% confidence interval: 1.21–6.44; P=0.016). The cumulative time of renal desaturation correlated moderately with the ratio of postoperative peak creatinine to preoperative baseline creatinine (r=0.51; P<0.001). ConclusionsIntraoperative renal desaturation is associated with increased odds of developing AKI after surgical repair of an isolated VSD involving cardiopulmonary bypass in infants. Clinical trial registrationNCT03941015.

Predictors of Neurological Outcome Following Infant Cardiac Surgery Without Deep Hypothermic Circulatory Arrest

The aim of this study is to describe the clinical characteristics, perioperative course and neuroimaging abnormalities of infants with congenital heart disease (CHD) undergoing heart surgery without deep hypothermic circulatory arrest (DHCA) and identify variables associated with neurological outcome. Infants with CHD undergoing open-heart surgery without DHCA between 2009 and 2017 were identified from a cardiac surgery database. Full-term infants < 10weeks of age at the time of surgery who had both a pre- and postoperative brain magnetic resonance imaging exam (MRI) were included. Clinical characteristics and perioperative variables were collected from the electronic medical record. Brain Injury Scores (BIS) were assigned to pre- and postoperative brain MRIs. Variables were examined for association with neurological outcome at 12months of age or greater. Forty-two infants were enrolled in the study, of whom 69% (n = 29) had a neurological assessment ≥ to 12months of age. Adverse neurological outcome was associated with longer intensive care unit (ICU) stay (P = 0.003), lengthier mechanical ventilation (P = 0.031), modified Blalock-Taussig (MBT) shunt procedure (P = 0.005) and postoperative seizures (P = 0.005). Total BIS scores did not predict outcome but postoperative infarction and/or intraparenchymal hemorrhage (IPH) was associated with worse outcome by multivariable analysis (P = 0.018). Infants with CHD undergoing open-heart surgery without DHCA are at increased risk of worse neurological outcome when their ICU stay is prolonged, mechanical ventilation is extended, MBT shunt is performed or when postoperative seizures are present. Cerebral infarctions and IPH on postoperative MRI are also associated with worse outcome.

Enoxaparin Reduces Catheter-associated Venous Thrombosis After Infant Cardiac Surgery

BackgroundCentral venous catheter (CVC) related venous thrombosis (VT) after pediatric cardiac surgery increases morbidity and mortality. Although VT prevention using low-dose anticoagulation therapy has proven ineffective, anticoagulation therapy using high-dose enoxaparin to achieve a therapeutic anti-Xa level has not been studied. We hypothesized that high-dose enoxaparin would reduce VT after pediatric cardiac surgery. MethodsEnoxaparin was administered to infants aged less than 150 days when postoperative CVC duration was anticipated to extend beyond 5 days. The primary outcome was the rate of VT, reexploration for bleeding, and postoperative red blood cell transfusions per 1000 CVC days. ResultsFrom 2012 to 2019, 157 infants were treated with enoxaparin. Infants were divided into two groups: (1) subtherapeutic (n = 51), in which therapeutic anti-Xa level (0.5 to 1.0 IU/mL) was not achieved; and (2) therapeutic (n = 106), in which therapeutic anti-Xa level was achieved. Baseline demographics demonstrated a lower age at operation in the therapeutic group. The subtherapeutic group had a higher VT rate per 1000 CVC days (8.2) compared with the therapeutic group (2.6; P = .005). Reexploration for bleeding was similar between groups. The number of postoperative red blood cell transfusions per 1000 CVC days was significantly greater in the subtherapeutic group (109.4 vs 81.6; P = .008). Multivariate analysis demonstrated that higher median anti-Xa levels reduced the risk of VT (odds ratio 0.02; 95% confidence interval, 0.001 to 0.63; P = .02). ConclusionsThese data suggest that enoxaparin treatment resulting in a therapeutic anti-Xa level reduces postoperative CVC-associated VT without increasing bleeding complications.

Serum metabolic profile of postoperative acute kidney injury following infant cardiac surgery with cardiopulmonary bypass.

We sought to determine differences in the circulating metabolic profile of infants with or without acute kidney injury (AKI) following cardiothoracic surgery with cardiopulmonary bypass (CPB). We performed a secondary analysis of preoperative and 24-h postoperative serum samples from infants ≤ 120 days old undergoing CPB. Metabolic profiling of the serum samples was performed by targeted analysis of 165 serum metabolites via tandem mass spectrometry. We then compared infants who did or did not develop AKI in the first 72 h postoperatively to determine global differences in the preoperative and 24-h metabolic profiles in addition to specific differences in individual metabolites. A total of 57 infants were included in the study. Six infants (11%) developed KDIGO stage 2/3 AKI and 13 (23%) developed stage 1 AKI. The preoperative metabolic profile did not differentiate between infants with or without AKI. Infants with severe AKI could be moderately distinguished from infants without AKI by their 24-h metabolic profile, while infants with stage 1 AKI segregated into two groups, overlapping with either the no AKI or severe AKI groups. Differences in these 24-h metabolic profiles were driven by 21 metabolites significant at an adjusted false discovery rate of < 0.05. Prominently altered pathways include purine, methionine, and kynurenine/nicotinamide metabolism. Moderate-to-severe AKI after infant cardiac surgery is associated with changes in the serum metabolome, including prominent changes to purine, methionine, and kynurenine/nicotinamide metabolism. A portion of infants with mild AKI demonstrated similar metabolic changes, suggesting a potential role for metabolic analysis in the evaluation of lower stage injury.

Treatment Approach for an Infant with Complex Congenitally Corrected Transposition of the Great Arteries

Objective – The aim of the paper is to present a rare and complex congenital heart defect (CHD), congenitally corrected transpo­sition of the great arteries of the heart (ccTGA) with associated anomalies, including ventricular septal defect (VSD), valvular and subvalvular pulmonary stenosis, dysplasia of the tricuspid valve, and atrial septal defect (ASD) with first-degree atrioventricular block, which was diagnosed, monitored and successfully treated with heart surgery in an infant. Case Report – A female infant was born with 3350 grams in weight, 50 cm in length, oxygen saturation of 98%, and heart rate of 170 beats per minute. The antenatal and perinatal period was normal. CHD was verified by ultrasound at the age of 3 days. Angiotensin-converting-enzyme inhibitors (ACE inhibitors) and diuretics were introduced in therapy after one month. Cardiac surgery (Senning-Rastelli proce­dure with placement of an 18-mm Contegra conduit) was performed at the age of 9 months. After the operation, the infant was stable on therapy with diuretics, antiaggregants, beta blockers, and antianemic therapy with vitamin D in prophylaxis. Conclu­sion – ccTGA with associated anomalies is a rare, life-threatening, congenital heart disease. After birth it demands correct diag­nosis, adequate follow-up, and cardiac surgery in infancy

Higher total ultrafiltration volume during cardiopulmonary bypass-assisted infant cardiac surgery is associated with acute kidney injury and fluid overload.

Ultrafiltration (UF) is used for fluid removal during and after infant cardiopulmonary bypass (CPB) surgery to reduce fluid overload. Excessive UF may have the opposite of its intended effect, resulting in acute kidney injury (AKI), oliganuria, and fluid retention. This is a single-center, retrospective review of infants treated with conventional and/or modified UF during CPB surgery. UF volume was indexed to weight. AKI was defined using serum creatinine "Kidney Disease Improving Global Outcome (KDIGO)" criteria. Fluid balance was defined according to: [Formula: see text]. Peak fluid overload was determined on postoperative day 3. Multivariable logistic regression adjusted for multiple covariates was used to explore associations with UF, AKI, and fluid overload. Five hundred thirty subjects < 1 year of age underwent CPB-assisted congenital heart surgery with UF. Sixty-four (12%) developed postoperative AKI. On multivariable regression, higher indexed total UF volume was associated with increased AKI risk (OR 1.11, 95% CI=1.04-1.19, p = 0.003). UF volume > 119.9 mL/kg did not reduce peak fluid overload. Subjects with AKI took longer to reach a negative fluid balance (2 vs. 3 days, p = 0.04). Those with more complex surgery were at highest AKI risk (STAT 3 [25-75 percentile: 3-4] in AKI group versus STAT 3 [25-75 percentile: 2-4] in non-AKI group, p = 0.05). AKI was reduced in subjects undergoing more complex surgery and treated with UF volume < 119.9 mL/kg. Judicious use of UF in more complex congenital cardiac surgery reduces the risk of AKI.

Clinical and Laboratory Predictors for the Development of Low Cardiac Output Syndrome in Infants Undergoing Cardiopulmonary Bypass: A Pilot Study.

Cardiac surgery employing cardiopulmonary bypass exposes infants to a high risk of morbidity and mortality. The objective of this study was to assess the utility of clinical and laboratory variables to predict the development of low cardiac output syndrome, a frequent complication following cardiac surgery in infants. We performed a prospective observational study in the pediatric cardiovascular ICU in an academic children’s hospital. Thirty-one patients with congenital heart disease were included. Serum levels of nucleosomes and a panel of 20 cytokines were measured at six time points in the perioperative period. Cardiopulmonary bypass patients were characterized by increased levels of interleukin-10, -6, and -1α upon admission to the ICU compared to non-bypass cardiac patients. Patients developing low cardiac output syndrome endured longer aortic cross-clamp time and required greater inotropic support at 12 h postoperatively compared to bypass patients not developing the condition. Higher preoperative interleukin-10 levels and 24 h postoperative interleukin-8 levels were associated with low cardiac output syndrome. Receiver operating characteristic curve analysis demonstrated a moderate capability of aortic cross-clamp duration to predict low cardiac output syndrome but not IL-8. In conclusion, low cardiac output syndrome was best predicted in our patient population by the surgical metric of aortic cross-clamp duration.

Individualized, Intraoperative Dosing of Fibrinogen Concentrate for the Prevention of Bleeding in Neonatal and Infant Cardiac Surgery Using Cardiopulmonary Bypass (FIBCON)

Background:Mediastinal bleeding is common following pediatric cardiopulmonary bypass surgery for congenital heart disease. Fibrinogen concentrate (FC) represents a potential therapy for preventing bleeding.Methods:We performed a single-center, phase 1b/2a, randomized controlled trial on infants 2.5 to 12 kg undergoing cardiopulmonary bypass surgery, aimed at (1) demonstrating the feasibility of an intraoperative point-of-care test, rotational thromboelastometry, to screen out patients at low risk of postoperative bleeding and then guide individualized FC dosing in high-risk patients and (2) determining the dose, safety, and efficacy of intraoperative FC supplementation. Screening occurred intraoperatively 1-hour before bypass separation using the rotational thromboelastometry variable fibrinogen thromboelastometry maximum clot firmness (FibTEM-MCF; fibrinogen contribution to clot firmness). If FibTEM-MCF ≥7 mm, patients entered the monitoring cohort. If FibTEM-MCF ≤6 mm, patients were randomized to receive FC/placebo (2:1 ratio). Individualized FC dose calculation included weight, bypass circuit volume, hematocrit, and intraoperative measured and desired FibTEM-MCF. The coprimary outcomes, measured 5 minutes post-FC administration were FibTEM-MCF (desired range, 8–13 mm) and fibrinogen levels (desired range, 1.5–2.5 g/L). Secondary outcomes were thrombosis and thrombosis-related major complications and postoperative 24-hour mediastinal blood loss.Results:We enrolled 111 patients (cohort, n=21; FC, n=60; placebo, n=30); mean (SD) age, 6.4 months (5.8); weight, 5.9 kg (2.0). Intraoperative rotational thromboelastometry screening effectively excluded low-risk patients, in that none in the cohort arm (FibTEM-MCF, ≥7 mm) demonstrated clinically significant early postoperative bleeding (&gt;10 mL/kg per 4 hours). Among randomized patients, the median (range) FC administered dose was 114 mg/kg (51–218). Fibrinogen levels increased from a mean (SD) of 0.91 (0.22) to 1.7 g/L (0.41). The postdose fibrinogen range was 1.2 to 3.3 g/L (72% within the desired range). The corresponding FibTEM-MCF values were as follows: pre-dose, 5.3 mm (1.9); post-dose, 13 mm (3.2). Ten patients (8 FC and 2 placebo) exhibited 12 possible thromboses; none were clearly related to FC. There was an overall difference in mean (SD) 24-hour mediastinal drain loss: cohort, 12.6 mL/kg (6.4); FC, 11.6 mL/kg (5.2); placebo, 17.1 mL/kg (14.3; ANOVAP=0.02).Conclusions:Intraoperative, individualized dosing of FC appears feasible. The need for individualized dosing is supported by the finding that a 4-fold variation in FC dose is required to achieve therapeutic fibrinogen levels.Registration:URL:https://eudract.ema.europa.eu/; Unique identifier: 2013-003532-68. URL:https://www.isrctn.com/; Unique identifier: 50553029.

Abstract 12622: Pro-inflammatory Urinary CXCL10 and VCAM Are Elevated After Infant Cardiac Surgery-associated Acute Kidney Injury (AKI)

Introduction: Acute kidney injury (AKI) occurs frequently after infant cardiac surgery and is associated with mortality. AKI mechanisms are unknown, limiting therapeutic targets. Emerging data implicates unregulated immune activation and AKI development. Hypothesis: Urinary immune biomarkers will be elevated in the urine of infants developing AKI. Methods: One hundred and twenty six infants were enrolled (median age 87 days, 74% male). Urine samples were collected pre-bypass and 6, 24, 48, and 72 hours after surgery. Urine samples underwent multiplex Luminex assays to detect six immune biomarkers: VCAM, CXCL10, MCP, IL-18, TWEAK, and C5-C9. Greater than 150% increase in serum creatinine defined AKI. The Kruskal-Wallis rank test determined the relationship between AKI and biomarker levels. Results: Thirty-five infants (27%) developed AKI. AKI subjects were younger (median 6 days (4-98) vs no AKI 107 days (7-164), p&lt;0.01). The AKI group had more complex surgery (STAT 4-5) (60% AKI vs 19% no AKI, p&lt;0.01). Bypass time was longer among the AKI group ((81 min vs 69 min (p&lt;0.01)).AKI infants had higher urinary CXCL10 levels at 24 hours (14.3 pg/ml vs 5.3 pg/ml p=0.04), 48 hours (3.4 pg/ml vs 0.75 pg/ml p=0.01), and 72 hours (1.15 pg/ml vs 0.22 pg/ml p=0.05) (Figure 1). Six-hour VCAM levels were higher among AKI infants (Median 491 pg/ml vs 0 pg/ml p=0.04). Other biomarkers showed no significant differences between groups. (Table1). Conclusions: Urinary CXCL10 and VCAM are promising pro-inflammatory biomarkers for early AKI detection and may indicate eventual AKI therapeutic targets.