Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial.

Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. Design, Setting, and Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Intervention: Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. Main Outcomes and Measures: The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. Results: The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). Conclusions and Relevance: In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. Trial Registration: ClinicalTrials.gov Identifier: NCT02133573.

Anesthetic challenges in patients with multicompartmental lymphatic failure after Fontan palliation undergoing transcatheter thoracic duct decompression.

Lymphatic flow abnormalities are central to the development of protein losing enteropathy, plastic bronchitis, ascites and pleural effusions in patients palliated to the Fontan circulation. These complications can occur in isolation or multicompartmental (two or more). The treatment of multicompartmental lymphatic failure aims at improving thoracic duct drainage. Re-routing the innominate vein to the pulmonary venous atrium decompresses the thoracic duct, as atrial pressure is lower than systemic venous pressure in Fontan circulation. Transcatheter thoracic duct decompression is a new minimally invasive procedure that involves placing covered stents from the innominate vein to the atrium. Patients undergoing this procedure require multiple general anesthetics, presenting challenges in managing the sequelae of disordered lymphatic flow superimposed on Fontan physiology. We reviewed the first 20 patients at the Center for Lymphatic Imaging and Intervention at a tertiary care children's hospital presenting for transcatheter thoracic duct decompression between March 2018 and February 2023. The patients ranged in age from 3 to 26 years. The majority had failed prior catheter-based lymphatic intervention, including selective embolization of abnormal lympho-intestinal and lympho-bronchial connections to treat lymphatic failure in a single compartment. Fourteen had failure in three lymphatic compartments. Patients were functionally impaired (ASA 3-5) with significant comorbidities. Concurrent with thoracic duct decompression, three patients required fenestration closure for the resultant decrease in oxygen saturation. Ten patients had improvement in symptoms, seven had no changes and three have limited follow up. Five (25%) of these patients were deceased as of January 2024 due to non-lymphatic complications from Fontan failure.

Introduction of transcatheter edge-to-edge repair in patients with congenital heart disease at a children's hospital.

BACKGROUND: Atrioventricular valve regurgitation (AVVR) is a devastating complication in children and young adults with congenital heart disease (CHD), particularly in patients with single ventricle physiology. Transcatheter edge-to-edge repair (TEER) is a rapidly expanding, minimally invasive option for the treatment of AVVR in adults that avoids the morbidity and mortality associated with open heart surgery. However, application of TEER in in CHD and in children is quite novel. We describe the development of a peri-procedural protocol including image-derived pre-intervention simulation, with successful application to four patients. AIMS: To describe the initial experience using the MitraClip system for TEER of dysfunctional systemic atrioventricular valves in patients with congential heart disease within a pediatric hospital. METHODS: A standardized screening and planning process was developed using cardiac magnetic resonance imaging, three dimensional echocardiography and both virtual and physical simulation. Procedures were performed using the MitraClip G4 system and patients were clinically followed post-intervention. RESULTS: A series of four CHD patients with at least severe AVVR were screened for suitability for TEER with the MitraClip system: three patients had single ventricle physiology and Fontan palliation, and one had repair of a common atrioventricular canal defect. Each patient had at least severe systemic AVVR and was considered at prohibitively high risk for surgical repair. Each patient underwent a standardized preprocedural screening protocol and image-derived modeling followed by the TEER procedure with successful clip placement at the intended location in all cases. CONCLUSIONS: The early results of our protocolized efforts to introduce TEER repair of severe AV valve regurgitation with MitraClip into the CHD population within our institution are encouraging. Further investigations of the use of TEER in this challenging population are warranted.

The use of novel diffuse optical spectroscopies for improved neuromonitoring during neonatal cardiac surgery requiring antegrade cerebral perfusion.

Background: Surgical procedures involving the aortic arch present unique challenges to maintaining cerebral perfusion, and optimal neuroprotective strategies to prevent neurological injury during such high-risk procedures are not completely understood. The use of antegrade cerebral perfusion (ACP) has gained favor as a neuroprotective strategy over deep hypothermic circulatory arrest (DHCA) due to the ability to selectively perfuse the brain. Despite this theoretical advantage over DHCA, there has not been conclusive evidence that ACP is superior to DHCA. One potential reason for this is the incomplete understanding of ideal ACP flow rates to prevent both ischemia from underflowing and hyperemia and cerebral edema from overflowing. Critically, there are no continuous, noninvasive measurements of cerebral blood flow (CBF) and cerebral oxygenation (StO2) to guide ACP flow rates and help develop standard clinical practices. The purpose of this study is to demonstrate the feasibility of using noninvasive, diffuse optical spectroscopy measurements of CBF and cerebral oxygenation during the conduct of ACP in human neonates undergoing the Norwood procedure. Methods: Four neonates prenatally diagnosed with hypoplastic left heart syndrome (HLHS) or a similar variant underwent the Norwood procedure with continuous intraoperative monitoring of CBF and cerebral oxygen saturation (StO2) using two non-invasive optical techniques, namely diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy (FD-DOS). Changes in CBF and StO2 due to ACP were calculated by comparing these parameters during a stable 5 min period of ACP to the last 5 min of full-body CPB immediately prior to ACP initiation. Flow rates for ACP were left to the discretion of the surgeon and ranged from 30 to 50 ml/kg/min, and all subjects were cooled to 18°C prior to initiation of ACP. Results: During ACP, the continuous optical monitoring demonstrated a median (IQR) percent change in CBF of -43.4% (38.6) and a median (IQR) absolute change in StO2 of -3.6% (12.3) compared to a baseline period during full-body cardiopulmonary bypass (CPB). The four subjects demonstrated varying responses in StO2 due to ACP. ACP flow rates of 30 and 40 ml/kg/min (n = 3) were associated with decreased CBF during ACP compared to full-body CPB. Conversely, one subject with a higher flow6Di rate of 50 ml/kg/min demonstrated increased CBF and StO2 during ACP. Conclusions: This feasibility study demonstrates that novel diffuse optical technologies can be utilized for improved neuromonitoring in neonates undergoing cardiac surgery where ACP is utilized. Future studies are needed to correlate these findings with neurological outcomes to inform best practices during ACP in these high-risk neonates.

Impaired Maternal-Fetal Environment and Risk for Preoperative Focal White Matter Injury in Neonates With Complex Congenital Heart Disease.

Background Infants with congenital heart disease (CHD) are at risk for white matter injury (WMI) before neonatal heart surgery. Better knowledge of the causes of preoperative WMI may provide insights into interventions that improve neurodevelopmental outcomes in these patients. Methods and Results A prospective single-center study of preoperative WMI in neonates with CHD recorded data on primary cardiac diagnosis, maternal-fetal environment (MFE), delivery type, subject anthropometrics, and preoperative care. Total maturation score and WMI were assessed, and stepwise logistic regression modeling selected risk factors for WMI. Among subjects with severe CHD (n=183) who received a preoperative brain magnetic resonance imaging, WMI occurred in 40 (21.9%) patients. WMI prevalence (21.4%-22.1%) and mean volumes (119.7-160.4 mm3) were similar across CHD diagnoses. Stepwise logistic regression selected impaired MFE (odds ratio [OR], 2.85 [95% CI, 1.29-6.30]), male sex (OR, 2.27 [95% CI, 1.03-5.36]), and older age at surgery/magnetic resonance imaging (OR, 1.20 per day [95% CI, 1.03-1.41]) as risk factors for preoperative WMI and higher total maturation score values (OR, 0.65 per unit increase [95% CI, 0.43-0.95]) as protective. A quarter (24.6%; n=45) of subjects had ≥1 components of impaired MFE (gestational diabetes [n=12; 6.6%], gestational hypertension [n=11; 6.0%], preeclampsia [n=2; 1.1%], tobacco use [n=9; 4.9%], hypothyroidism [n=6; 3.3%], and other [n=16; 8.7%]). In a subset of 138 subjects, an exploratory analysis of additional MFE-related factors disclosed other potential risk factors for WMI. Conclusions This study is the first to identify impaired MFE as an important risk factor for preoperative WMI. Vulnerability to preoperative WMI was shared across CHD diagnoses.

Dose Escalation Pharmacokinetic Study of Intranasal Atomized Dexmedetomidine in Pediatric Patients With Congenital Heart Disease.

BACKGROUND: Atomized intranasal dexmedetomidine is an attractive option when sedation is required for pediatric patients as either premedication or the sole agent for noninvasive, nonpainful procedures. While intranasal dexmedetomidine is used frequently in this population, it is still unclear what dose and time of administration relative to the procedure will result in the optimal effect. Knowledge regarding the maximum concentration (C max ) and time to reach maximum concentration (T max ) of intranasally administered dexmedetomidine is the first step toward this. The risk of hemodynamic instability caused by increasing doses of dexmedetomidine necessitates a greater understanding of the pharmacokinetics in children. METHODS: Sixteen pediatric patients 2 to 6 years of age undergoing elective cardiac catheterization received 2 or 4 µg/kg dexmedetomidine intranasally. Plasma concentrations were determined by liquid chromatography-tandem mass spectrometry with a validated assay. Descriptive noncompartmental analysis provided estimates of peak concentrations and time to reach peak concentrations. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling. Simulations were performed using the final model to assess dose concentrations with an alternative dosing regimen of 3 µg/kg. RESULTS: A median peak plasma concentration of 413 pg/mL was achieved 91 minutes after 2 µg/kg dosing, and a median peak plasma concentration of 1000 pg/mL was achieved 54 minutes after 4 µg/kg dosing. A 1-compartment pharmacokinetic model adequately described the data. Three subjects in the 4 µg/kg dosing cohort achieved a dose-limiting toxicity (DLT), defined as a plasma dexmedetomidine concentration >1000 pg/mL. None of these subjects had any significant hemodynamic consequences. Simulations showed that no subjects would experience a level >1000 pg/mL when using a dose of 3 µg/kg. CONCLUSIONS: Concentrations associated with adequate sedation can be achieved with intranasal dexmedetomidine doses of 2 to 4 µg/kg in children 2 to 6 years of age. However, 50% of our evaluable subjects in this cohort reached a plasma concentration >1000 pg/mL. Doses of 3 µg/kg may be optimal in this population, with simulated concentrations remaining below this previously established toxicity threshold. Further studies correlating concentrations with efficacy and adverse effects are needed.

Electroencephalography as a tool to predict cerebral oxygen metabolism during deep-hypothermic circulatory arrest in neonates with critical congenital heart disease.

Objectives: Recent research suggests that increased cerebral oxygen use during surgical intervention for neonates with congenital heart disease may play a role in the development of postoperative white matter injury. The objective of this study is to determine whether increased cerebral electrical activity correlates with greater decrease of cerebral oxygen saturation during deep hypothermic circulatory arrest. Methods: Neonates with critical congenital heart disease requiring surgical intervention during the first week of life were studied. All subjects had continuous neuromonitoring with electroencephalography and an optical probe (to quantify cerebral oxygen saturation) during cardiac surgical repair that involved the use of cardiopulmonary bypass and deep hypothermic circulatory arrest. A simple linear regression was used to investigate the association between electroencephalography metrics before the deep hypothermic circulatory arrest period and the change in cerebral oxygen saturation during the deep hypothermic circulatory arrest period. Results: Sixteen neonates had both neuromonitoring modalities attached during surgical repair. Cerebral oxygen saturation data from 5 subjects were excluded due to poor data quality, yielding a total sample of 11 neonates. A simple linear regression model found that the presence of electroencephalography activity at the end of cooling is positively associated with the decrease in cerebral oxygen saturation that occurs during deep hypothermic circulatory arrest (P < .05). Conclusions: Electroencephalography characteristics within 5 minutes before the initiation of deep hypothermic circulatory arrest may be useful in predicting the decrease in cerebral oxygen saturation that occurs during deep hypothermic circulatory arrest. Electroencephalography may be an important tool for guiding cooling and the initiation of circulatory arrest to potentially decrease the prevalence of new white matter injury in neonates with critical congenital heart disease.

Sequestration of Dexmedetomidine in Ex Vivo Cardiopulmonary Bypass Circuits.

Dexmedetomidine (DEX) is a sedative used in combination with other drugs in neonates and infants undergoing cardiac surgery using cardiopulmonary bypass (CPB). This study aimed to evaluate the disposition of DEX after administration to the ex vivo CPB circuits following different bolus doses and continuous infusion of DEX, including the effect of circuit coating, temperature, and modified ultrafiltration (MUF). Cardiopulmonary bypass circuits were setup ex vivo and primed with reconstituted blood. Dexmedetomidine was administered to the circuit (as a single bolus or single bolus along with continuous infusion). The circuit was allowed to equilibrate during the first 5 minutes, blood samples were collected at multiple time points (5-240 minutes). Blood samples were processed to collect plasma and analyzed for DEX with a validated assay. The majority of DEX sequestration in ex vivo CPB circuits occurred within the first 15 minutes. The percent of DEX remained in plasma pre-MUF (16-71%) and post-MUF (22-92%) varied depending on the dose and dosing scheme. Modified ultrafiltration significantly increased the plasma concentration of DEX in 19 of 23 circuits by an average of 12.1 ± 4.25% (p < 0.05). The percent sequestration of DEX was lower in CPB circuits at lower DEX doses compared to higher doses. A combination of DEX initial loading dose and continuous infusion resulted in steady concentrations of DEX over 4 hours. At therapeutically relevant concentrations of DEX (485-1,013 pg/ml), lower sequestration was observed in ex vivo CPB circuits compared to higher doses. The sequestration of DEX to circuits should be considered to achieve the optimal concentration of DEX during CPB surgery.

Association of Ongoing Cerebral Oxygen Extraction During Deep Hypothermic Circulatory Arrest With Postoperative Brain Injury.

Cardiac surgery utilizing circulatory arrest is most commonly performed under deep hypothermia (∼18°C) to suppress tissue oxygen demand and provide neuroprotection during operative circulatory arrest. Studies investigating the effects of deep hypothermic circulatory arrest (DHCA) on neurodevelopmental outcomes of patients with congenital heart disease give conflicting results. Here, we address these issues by quantifying changes in cerebral oxygen saturation, blood flow, and oxygen metabolism in neonates during DHCA and investigating the association of these changes with postoperative brain injury. Neonates with critical congenital heart disease undergoing DHCA were recruited for continuous intraoperative monitoring of cerebral oxygen saturation (ScO2) and an index of cerebral blood flow (CBFi) using 2 noninvasive optical techniques, diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS). Pre- and postoperative brain magnetic resonance imaging (MRI) was performed to detect white matter injury (WMI). Fifteen neonates were studied, and 11/15 underwent brain MRI. During DHCA, ScO2 decreased exponentially in time with a median decay rate of -0.04 min-1. This decay rate was highly variable between subjects. Subjects who had larger decreases in ScO2 during DHCA were more likely to have postoperative WMI (P = 0.02). Cerebral oxygen extraction persists during DHCA and varies widely from patient-to-patient. Patients with a higher degree of oxygen extraction during DHCA were more likely to show new WMI in postoperative MRI. These findings suggest cerebral oxygen extraction should be monitored during DHCA to identify patients at risk for hypoxic-ischemic injury, and that current commercial cerebral oximeters may underestimate cerebral oxygen extraction.

Attrition between the superior cavopulmonary connection and the Fontan procedure in hypoplastic left heart syndrome.

OBJECTIVE: We investigated the incidence and predictors of failure to undergo the Fontan in children with hypoplastic left heart syndrome who survived superior cavopulmonary connection. METHODS: The cohort consists of all patients with hypoplastic left heart syndrome who survived to hospital discharge after superior cavopulmonary connection between 1988 and 2017. The primary outcome was attrition, which was defined as death, nonsuitability for the Fontan, or cardiac transplantation before the Fontan. Subjects were excluded if they were awaiting the Fontan, were lost to follow-up, or underwent biventricular repair. The study period was divided into 4 eras based on changes in operative or medical management. Attrition was estimated with 95% confidence intervals, and predictors were identified using adjusted, logistic regression models. RESULTS: Of the 856 hospital survivors after superior cavopulmonary connection, 52 died, 7 were deemed unsuitable for Fontan, and 12 underwent or were awaiting heart transplant. Overall attrition was 8.3% (71/856). Attrition rate did not change significantly across eras. A best-fitting multiple logistic regression model was used, adjusting for superior cavopulmonary connection year and other influential covariates: right ventricle to pulmonary artery shunt at Norwood (P < .01), total support time at superior cavopulmonary connection (P < .01), atrioventricular valve reconstruction at superior cavopulmonary connection (P = .02), performance of other procedures at superior cavopulmonary connection (P = .01), and length of stay after superior cavopulmonary connection (P < .01). CONCLUSIONS: In this study spanning more than 3 decades, 8.3% of children with hypoplastic left heart syndrome failed to undergo the Fontan after superior cavopulmonary connection. This attrition rate has not decreased over 30 years. Use of a right ventricle to pulmonary artery shunt at the Norwood procedure was associated with increased attrition.

Spillover of Early Extubation Practices From the Pediatric Heart Network Collaborative Learning Study.

OBJECTIVES: The Pediatric Heart Network Collaborative Learning Study used collaborative learning strategies to implement a clinical practice guideline that increased rates of early extubation after infant repair of tetralogy of Fallot and coarctation of the aorta. We assessed early extubation rates for infants undergoing cardiac surgeries not targeted by the clinical practice guideline to determine whether changes in extubation practices spilled over to care of other infants. DESIGN: Observational analyses of site's local Society of Thoracic Surgeons Congenital Heart Surgery Database and Pediatric Cardiac Critical Care Consortium Registry. SETTING: Four Pediatric Heart Network Collaborative Learning Study active-site hospitals. PATIENTS: Infants undergoing ventricular septal defect repair, atrioventricular septal defect repair, or superior cavopulmonary anastomosis (lower complexity), and arterial switch operation or isolated aortopulmonary shunt (higher complexity). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Aggregate outcomes were compared between the 12 month pre-clinical practice guideline and 12 months after study completion (Follow Up). In infants undergoing lower complexity surgeries, early extubation increased during Follow Up compared with Pre-Clinical Practice Guideline (30.2% vs 18.8%, p = 0.006), and hours to initial postoperative extubation decreased. We observed variation in these outcomes by surgery type, with only ventricular septal defect repair associated with a significant increase in early extubation during Follow Up compared with Pre-Clinical Practice Guideline (47% vs 26%, p = 0.006). Variation by study site was also seen, with only one hospital showing an increase in early extubation. In patients undergoing higher complexity surgeries, there was no difference in early extubation or hours to initial extubation between the study eras. CONCLUSIONS: We observed spillover of extubation practices promoted by the Collaborative Learning Study clinical practice guideline to lower complexity operations not included in the original study that was sustainable 1 year after study completion, though this effect differed across sites and operation subtypes. No changes in postoperative extubation outcomes following higher complexity surgeries were seen. The significant variation in outcomes by site suggests that center-specific factors may have influenced spillover of clinical practice guideline practices.

Decreasing Interstage Mortality After the Norwood Procedure: A 30-Year Experience.

Background The superior cavo-pulmonary connection was introduced at our institution in 1988 for infants undergoing surgery for hypoplastic left heart syndrome. Patients with hypoplastic left heart syndrome remain at high risk for mortality in the time period between the Norwood procedure and the superior cavo-pulmonary connection. The primary objectives of this study were to compare interstage mortality across 4 eras and analyze factors that may impact interstage mortality. Methods and Results Patients with hypoplastic left heart syndrome who underwent the Norwood procedure, were discharged from the hospital, and were eligible for superior cavo-pulmonary connection between January 1, 1988, and December 31, 2017, were included. The study period was divided into 4 eras based on changes in operative or medical management. Mortality rates were estimated with 95% CIs. Adjusted and unadjusted logistic regression models were used to identify risk factors for mortality. There were 1111 patients who met the inclusion criteria. Overall, interstage mortality was 120/1111 (10.8%). Interstage mortality was significantly lower in era 4 relative to era 1 (4.6% versus 13.4%; P=0.02) during the time that age at the superior cavo-pulmonary connection was the lowest (135 days; P<0.01) and the interstage monitoring program was introduced. In addition, use of the right ventricle to pulmonary artery shunt was associated with decreased interstage mortality (P=0.02) and was more routinely practiced in era 4. Conclusions During this 30-year experience, the risk of interstage mortality decreased significantly in the most recent era. Factors that coincide with this finding include younger age at superior cavo-pulmonary connection, introduction of an interstage monitoring program, and increased use of the right ventricle to pulmonary artery shunt.

Standardization of the Perioperative Management for Neonates Undergoing the Norwood Operation for Hypoplastic Left Heart Syndrome and Related Heart Defects.

OBJECTIVES: In-hospital complications after the Norwood operation for single ventricle heart defects account for the majority of morbidity and mortality. Inpatient care variation occurs within and across centers. This multidisciplinary quality improvement project standardized perioperative management in a large referral center. DESIGN: Quality improvement project. SETTING: High volume cardiac center, tertiary care children's hospital. PATIENTS: Neonates undergoing Norwood operation. INTERVENTIONS: The quality improvement team developed and implemented a clinical guideline (preoperative admission to 48 hr after surgery). The composite process metric, Guideline Adherence Score, contained 13 recommendations in the guideline that reflected consistent care for all patients. MEASUREMENTS AND MAIN RESULTS: One-hundred two consecutive neonates who underwent Norwood operation (January 1, 2013, to July 12, 2016) before guideline implementation were compared with 50 consecutive neonates after guideline implementation (July 13, 2016, to May 4, 2018). No preguideline operations met the goal Guideline Adherence Score. In the first 6 months after guideline implementation, 10 of 12 operations achieved goal Guideline Adherence Score and continued through implementation, reaching 100% for the last 10 operations. Statistical process control analysis demonstrated less variability and decreased hours of postoperative mechanical ventilation and cardiac ICU length of stay during implementation. There were no statistically significant differences in major hospital complications or in 30-day mortality. A higher percentage of patients were extubated by postoperative day 2 after guideline implementation (67% [30/47] vs 41% [41/99], respectively; p = 0.01). Of these patients, reintubation within 72 hours of extubation significantly decreased after guideline implementation (0% [0/30] vs 17% [7/41] patients, respectively; p = 0.02). CONCLUSIONS: This initiative successfully implemented a standardized perioperative care guideline for neonates undergoing the Norwood operation at a large center. Positive statistical process control centerline shifts in Guideline Adherence Score, length of postoperative mechanical ventilation, and cardiac ICU length of stay were demonstrated. A higher percentage were successfully extubated by postoperative day 2. Establishment of standard processes can lead to best practices to decrease major adverse events.

Outcomes for the superior cavopulmonary connection in children with hypoplastic left heart syndrome: a 30-year experience.

OBJECTIVES: The objective of this study was to estimate hospital mortality and length of stay (LOS) for children with hypoplastic left heart syndrome undergoing superior cavopulmonary connection (SCPC). METHODS: All hypoplastic left heart syndrome interstage survivors who underwent SCPC between 1 January 1988 and 31 December 2017 were included. The study period was divided into 4 eras based on changes in operative or medical management. Mortality rates were estimated using standard binomial proportions. Adjusted and unadjusted logistic regression models were used to identify risk factors for mortality and LOS. RESULTS: The most common procedures for the cohort (n = 958) were Hemi-Fontan (57.3%) or Bidrectional Glenn shunt (35.7%). The mortality was 4.1% overall and decreased in all 3 later eras compared to era 1. Factors associated with mortality in a multiple covariate model included longer total support time, earlier gestational age, longer LOS at the Norwood Procedure and need for additional procedures. Overall, the median LOS was 7.0 days with a decrease from eras 1 to 2 and plateaued in eras 3 and 4. Predictors of longer LOS included genetic anomaly, longer Norwood LOS, additional procedures, lower weight at surgery and longer total support time. The type of SCPC was not associated with mortality or LOS. CONCLUSIONS: In this large cohort of patients with hypoplastic left heart syndrome undergoing SCPC, hospital mortality has decreased significantly. LOS initially declined but plateaued in recent eras. The risk factors for mortality and longer LOS are related to patient and procedural complexity, especially the need for additional procedures at the time of SCPC.

The Congenital Cardiac Anesthesia Society-Society of Thoracic Surgeons Cardiac Anesthesia Database Collaboration.

Multi-institutional databases and registries have proliferated over the last decade in all specialties of medicine. They may be especially helpful in low-frequency/high-acuity fields such as pediatric and congenital heart diseases. The Society of Thoracic Surgeon's Congenital Heart Surgery Database (STSCHSD) is the largest single data set for the congenital heart disease population and includes contemporaneous data from over 120 programs in the United States (and several outside of the United States), capturing greater than 98% of the congenital cardiac surgical procedures in the United States. In 2010, the Congenital Cardiac Anesthesia Society partnered with the STSCHSD to incorporate anesthesia-related elements into the data set. Voluntary site participation in the anesthesia data has grown steadily. Currently, over 60 sites performing more than 60% of cardiac bypass procedures in the STSCHSD are submitting anesthesia data annually into the STSCHSD. Anesthesia data include perioperative medication usage, modalities for hemodynamic and neurologic monitoring, blood product, antifibrinolytic and procoagulant use, and anesthesia-related adverse events. This special article provides a descriptive summary of relevant findings to date, reflecting the wide variety in anesthesia practice patterns present among institutions and illustrates the functionality of a multisite registry in pediatric cardiac anesthesia which can be utilized both locally and nationally.

Clinical Update in Pediatric Sepsis: Focus on Children With Pre-Existing Heart Disease.

SEPSIS REMAINS one of the most common causes of childhood morbidity, mortality, and higher healthcare costs, with over 75,000 hospital admissions in the United States and an estimated 4 million cases worldwide per year. While standardized criteria to define sepsis are in flux, the general concept of sepsis is a severe infection that results in organ dysfunction. Although sepsis can affect previously healthy children, those with certain pre-existing comorbid conditions, including congenital and acquired heart disease, are at higher risk for both developing sepsis and having a poor outcome after sepsis. Multiple specialists including intensivists, cardiologists, surgeons, and anesthesiologists commonly contribute to the management and outcome of sepsis in children. In this article, the authors examine the evolving epidemiology of pediatric sepsis, including the subset of patients with underlying heart disease; contrast pediatric and adult sepsis; review the latest hemodynamic guidelines for management of pediatric septic shock and their application to children with heart disease; discuss the role of mechanical circulatory support; and review key aspects of anesthetic management for children with sepsis.

Results of a phase 1 multicentre investigation of dexmedetomidine bolus and infusion in corrective infant cardiac surgery.

BACKGROUND: Dexmedetomidine (DEX) is increasingly used intraoperatively in infants undergoing cardiac surgery. This phase 1 multicentre study sought to: (i) determine the safety of DEX for cardiac surgery with cardiopulmonary bypass; (ii) determine the pharmacokinetics (PK) of DEX; (iii) create a PK model and dosing for steady-state DEX plasma levels; and (iv) validate the PK model and dosing. METHODS: We included 122 neonates and infants (0-180 days) with D-transposition of the great arteries, ventricular septal defect, or tetralogy of Fallot. Dose escalation was used to generate NONMEM® PK modelling, and then validation was performed to achieve low (200-300 pg ml-1), medium (400-500 pg ml-1), and high (600-700 pg ml-1) DEX plasma concentrations. RESULTS: Five of 122 subjects had adverse safety outcomes (4.1%; 95% confidence interval [CI], 1.8-9.2%). Two had junctional rhythm, two had second-/third-degree atrioventricular block, and one had hypotension. Clearance (CL) immediately postoperative and CL on CPB were reduced by approximately 50% and 95%, respectively, compared with pre-CPB CL. DEX clearance after CPB was 1240 ml min-1 70 kg-1. Age at 50% maximum clearance was approximately 2 days, and that at 90% maximum clearance was 18 days. Overall, 96.1% of measured DEX concentrations fell within the 5th-95th percentile prediction intervals in the PK model validation. Dosing strategies are recommended for steady-state DEX plasma levels ranging from 200 to 1000 pg ml-1. CONCLUSIONS: When used with a careful dosing strategy, DEX results in low incidence and severity of adverse safety events in infants undergoing cardiac surgery with cardiopulmonary bypass. This validated PK model should assist clinicians in selecting appropriate dosing. The results of this phase 1 trial provide preliminary data for a phase 3 trial of DEX neuroprotection. CLINICAL TRIALS REGISTRATION: NCT01915277.