Contemporary Care and Outcomes of Critically-ill Children With Clinically Diagnosed Myocarditis.

PURPOSE: To describe contemporary management and outcomes in children with myocarditis who are admitted to a cardiac intensive care unit (CICU) and to identify the characteristics associated with mortality. METHODS: All patients in the Pediatric Cardiac Critical Care Consortium (PC4) registry between August 2014 and June 2021 who were diagnosed with myocarditis were included. Univariable analyses and multivariable logistic regression evaluated the factors associated with in-hospital mortality. RESULTS: There were 847 CICU admissions for myocarditis in 51 centers. The median age was 12 years (IQR 2.7-16). In-hospital mortality occurred in 53 patients (6.3%), and 60 (7.1%) had cardiac arrest during admission. Mechanical ventilation was required in 339 patients (40%), and mechanical circulatory support (MCS) in 177 (21%); extracorporeal membrane oxygenation (ECMO)-only in 142 (16.7%), ECMO-to-ventricular assist device (VAD) in 20 (2.4%), extracorporeal cardiac resuscitation in 43 (5%), and VAD-only in 15 (1.8%) patients. MCS was associated with in-hospital mortality; 20.3% receiving MCS died compared to 2.5% without MCS (P < 0.001). Mortality rates were similar in ECMO-only, ECMO-to-VAD and VAD-only groups. The median time from CICU admission to ECMO was 2.0 hours (IQR 0-9.4) and to VAD, it was 9.9 days (IQR 6.3-16.8). Time to MCS was not associated with mortality. In multivariable modeling of patients' characteristics, smaller body surface area (BSA) and low eGFR were independently associated with mortality, and after including critical therapies, mechanical ventilation and ECMO were independent predictors of mortality. CONCLUSION: This contemporary cohort of children admitted to CICUs with myocarditis commonly received high-resource therapies; however, most patients survived to hospital discharge and rarely received VAD. Smaller patient size, acute kidney injury and receipt of mechanical ventilation or ECMO were independently associated with mortality.

Diuretic response after neonatal cardiac surgery: a report from the NEPHRON collaborative.

BACKGROUND: Multicenter early diuretic response (DR) analysis of single furosemide dosing following neonatal cardiac surgery is lacking to inform whether early DR predicts adverse clinical outcomes. METHODS: We performed a retrospective cohort study utilizing data from the NEPHRON registry. Random forest machine learning generated receiver operating characteristic-area under the curve (ROC-AUC) and odds ratios for mechanical ventilation (MV) and respiratory support (RS). Prolonged MV and RS were defined using ≥ 90th percentile of observed/expected ratios. Secondary outcomes were prolonged CICU and hospital length of stay (LOS) and kidney failure (stage III acute kidney injury (AKI), peritoneal dialysis, and/or continuous kidney replacement therapy on postoperative day three) assessed using covariate-adjusted ROC-AUC curves. RESULTS: A total of 782 children were included. Cumulative urine output (UOP) metrics were lower in prolonged MV and RS patients, but DR poorly predicted prolonged MV (highest AUC 0.611, OR 0.98, sensitivity 0.67, specificity 0.53, p = 0.006, 95% OR CI 0.96-0.99 for cumulative 6-h UOP) and RS (highest AUC 0.674, OR 0.94, sensitivity 0.75, specificity 0.54, p < 0.001, 95% CI 0.91-0.97 UOP between 3 and 6 h). Secondary outcome results were similar. DR had fair discrimination for kidney failure (AUC 0.703, OR 0.94, sensitivity 0.63, specificity 0.71, 95% OR CI 0.91-0.98, p < 0.001, cumulative 6-h UOP). CONCLUSIONS: Early DR poorly discriminated patients with prolonged MV, RS, and LOS in this cohort, though it may identify severe postoperative AKI phenotype. Future work is warranted to determine if early DR or late postoperative DR later, in combination with other AKI metrics, may identify a higher-risk phenotype.

Clinical Outcomes After Tracheostomy in Children With Single Ventricle Physiology: Collaborative Research From the Pediatric Cardiac Intensive Care Society Multicenter Cohort, 2010-2021.

OBJECTIVES: Multicenter studies reporting outcomes following tracheostomy in children with congenital heart disease are limited, particularly in patients with single ventricle physiology. We aimed to describe clinical characteristics and outcomes in a multicenter cohort of patients with single ventricle physiology who underwent tracheostomy before Fontan operation. DESIGN: Multicenter retrospective cohort study. SETTING: Twenty-one tertiary care pediatric institutions participating in the Collaborative Research from the Pediatric Cardiac Intensive Care Society. PATIENTS: We reviewed 99 children with single ventricle physiology who underwent tracheostomy before the Fontan operation at 21 institutions participating in Collaborative Research from the Pediatric Cardiac Intensive Care Society between January 2010 and December 2020, with follow-up through December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Death occurred in 51 of 99 patients (52%). Cox proportional hazard analysis was performed to determine factors associated with death after tracheostomy. Results are presented as hazard ratio (HR) with 95% CIs. Nonrespiratory indication(s) for tracheostomy (HR, 2.21; 95% CI, 1.14-4.32) and number of weeks receiving mechanical ventilation before tracheostomy (HR, 1.06; 95% CI, 1.02-1.11) were independently associated with greater hazard of death. In contrast, diagnosis of tricuspid atresia or Ebstein's anomaly was associated with less hazard of death (HR, 0.16; 95% CI, 0.04-0.69). Favorable outcome, defined as survival to Fontan operation or decannulation while awaiting Fontan operation with viable cardiopulmonary physiology, occurred in 29 of 99 patients (29%). Median duration of mechanical ventilation before tracheostomy was shorter in patients who survived to favorable outcome (6.1 vs. 12.1 wk; p < 0.001), and only one of 16 patients with neurologic indications for tracheostomy and 0 of ten patients with cardiac indications for tracheostomy survived to favorable outcome. CONCLUSIONS: For children with single ventricle physiology who undergo tracheostomy, mortality risk is high and should be carefully considered when discussing tracheostomy as an option for these children. Favorable outcomes are possible, although thoughtful attention to patient selection and tracheostomy timing are likely necessary to achieve this goal.

Impact of Congenital Heart Disease on the Outcomes of Very Low Birth Weight Infants.

OBJECTIVE: This study aimed to investigate the association of congenital heart disease (CHD) with morbidity and mortality of very low birth weight (VLBW) infants. STUDY DESIGN: This matched case-control study included VLBW infants born at a single institution between 2001 and 2015. The primary outcome was mortality. Secondary outcomes included necrotizing enterocolitis, bronchopulmonary dysplasia (BPD), sepsis, retinopathy of prematurity, and intraventricular hemorrhage. These outcomes were assessed by comparing VLBW-CHDs with control VLBW infants matched by gestational age within a week, birth weight within 500 g, sex, and birth date within a year using conditional logistic regression. Multivariable logistic regression analyzed differences in outcomes in the VLBW-CHD group between two birth periods (2001-2008 and 2009-2015) to account for changes in practice. RESULTS: In a cohort of 44 CHD infants matched with 88 controls, the mortality rate was 27% in infants with CHD and 1% in controls (p < 0.0001). The VLBW-CHDs had increased BPD; (odds ratio [OR]: 7.70, 95% confidence interval [CI]: 1.96-30.29) and sepsis (OR: 10.59, 95% CI: 2.99-37.57) compared with the control VLBWs. When adjusted for preoperative ventilator use, the VLBW-CHDs still had significantly higher odds of BPD (OR: 6.97, 95% CI: 1.73-28.04). VLBW-CHDs also had significantly higher odds of both presumed and culture-positive sepsis as well as late-onset sepsis than their matched controls. There were no significant differences in outcomes between the two birth periods. CONCLUSION: VLBW-CHDs showed higher odds of BPD, sepsis, and mortality than VLBW infants without CHD. Future research should focus on the increased mortality and specific complications encountered by VLBW infants with CHD and implement targeted strategies to address these risks. KEY POINTS: · Incidence of CHD is higher in preterm infants than in term infants but the incidence of their morbidities is not well described.. · VLBW infants with CHD have higher odds of mortality, bronchopulmonary dysplasia, and sepsis.. · Future research is needed to implement targeted preventive responses..

Peritoneal catheters in neonates undergoing complex cardiac surgery: a multi-centre descriptive study.

BACKGROUND: The use of peritoneal catheters for prophylactic dialysis or drainage to prevent fluid overload after neonatal cardiac surgery is common in some centres; however, the multi-centre variability and details of peritoneal catheter use are not well described. METHODS: Twenty-two-centre NEonatal and Pediatric Heart Renal Outcomes Network (NEPHRON) study to describe multi-centre peritoneal catheter use after STAT category 3-5 neonatal cardiac surgery using cardiopulmonary bypass. Patient characteristics and acute kidney injury/fluid outcomes for six post-operative days are described among three cohorts: peritoneal catheter with dialysis, peritoneal catheter with passive drainage, and no peritoneal catheter. RESULTS: Of 1490 neonates, 471 (32%) had an intraoperative peritoneal catheter placed; 177 (12%) received prophylactic dialysis and 294 (20%) received passive drainage. Sixteen (73%) centres used peritoneal catheter at some frequency, including six centres in >50% of neonates. Four centres utilised prophylactic peritoneal dialysis. Time to post-operative dialysis initiation was 3 hours [1, 5] with the duration of 56 hours [37, 90]; passive drainage cohort drained for 92 hours [64, 163]. Peritoneal catheter were more common among patients receiving pre-operative mechanical ventilation, single ventricle physiology, and higher complexity surgery. There was no association with adverse events. Serum creatinine and daily fluid balance were not clinically different on any post-operative day. Mortality was similar. CONCLUSIONS: In neonates undergoing complex cardiac surgery, peritoneal catheter use is not rare, with substantial variability among centres. Peritoneal catheters are used more commonly with higher surgical complexity. Adverse event rates, including mortality, are not different with peritoneal catheter use. Fluid overload and creatinine-based acute kidney injury rates are not different in peritoneal catheter cohorts.

Left Ventricular Strain, Arch Angulation, and Velocity-Time Integral Ratio Improve Performance of a Clinical Pathway for Fetal Diagnosis of Neonatal Coarctation of the Aorta.

INTRODUCTION: Neonatal presentation of coarctation of the aorta (CoA) is a potentially life-threatening condition that is difficult to diagnose in fetal life. We therefore sought to validate and compare novel metrics that may add diagnostic value for fetal CoA, including the diastolic to systolic aortic isthmus VTI ratio (VTId:VTIs), ascending aorta to descending aorta angle (AAo-DAo), transverse aorta to descending aorta angle (TAo-DAo), and LV longitudinal strain (LVS), then to evaluate whether these novel metrics improve specificity to identify fetuses at the highest risk for postnatal CoA without compromising sensitivity. METHODS: Retrospective cohort study of fetuses followed a prospective clinical pathway and previously classified as mild, moderate, or high-risk for CoA based on standard fetal echo metrics. Novel metrics were retrospectively measured in a blinded manner. RESULTS: Among fetuses with prenatal concern for CoA, VTId:VTIs, AAo-DAo angle, TAo-DAo angle, and LVS were significantly different between surgical and non-surgical cases (p < 0.01 for all variables). In the subgroup of moderate- and high-risk fetuses, the standard high-risk criteria (flow reversal at the foramen ovale or aortic arch) did not discriminate effectively between surgical and non-surgical cases. VTId:VTIs, AAo-Dao angle, Tao-DAo angle, and LVS all demonstrated greater discrimination than standard high-risk criteria, with specificity of 100% and PPV (positive predictive value) of 78-100%. CONCLUSIONS: The incorporation of novel metrics added diagnostic value to our clinical pathway for fetal CoA with higher specificity than the previous high-risk criteria. The incorporation of these metrics into the evaluation of fetuses at moderate- or high-risk for surgical CoA may improve prenatal counseling, allow for more consistent surgical planning, and ultimately optimize hospital resource allocation.

The development and efficacy of a paediatric cardiology fellowship online preparatory course.

BACKGROUND: The transition from residency to paediatric cardiology fellowship is challenging due to the new knowledge and technical skills required. Online learning can be an effective didactic modality that can be widely accessed by trainees. We sought to evaluate the effectiveness of a paediatric cardiology Fellowship Online Preparatory Course prior to the start of fellowship. METHODS: The Online Preparatory Course contained 18 online learning modules covering basic concepts in anatomy, auscultation, echocardiography, catheterisation, cardiovascular intensive care, electrophysiology, pulmonary hypertension, heart failure, and cardiac surgery. Each online learning module included an instructional video with pre-and post-video tests. Participants completed pre- and post-Online Preparatory Course knowledge-based exams and surveys. Pre- and post-Online Preparatory Course survey and knowledge-based examination results were compared via Wilcoxon sign and paired t-tests. RESULTS: 151 incoming paediatric cardiology fellows from programmes across the USA participated in the 3 months prior to starting fellowship training between 2017 and 2019. There was significant improvement between pre- and post-video test scores for all 18 online learning modules. There was also significant improvement between pre- and post-Online Preparatory Course exam scores (PRE 43.6 ± 11% versus POST 60.3 ± 10%, p < 0.001). Comparing pre- and post-Online Preparatory Course surveys, there was a statistically significant improvement in the participants' comfort level in 35 of 36 (97%) assessment areas. Nearly all participants (98%) agreed or strongly agreed that the Online Preparatory Course was a valuable learning experience and helped alleviate some anxieties (77% agreed or strongly agreed) related to starting fellowship. CONCLUSION: An Online Preparatory Course prior to starting fellowship can provide a foundation of knowledge, decrease anxiety, and serve as an effective educational springboard for paediatric cardiology fellows.

Impact of a clinical pathway on acute kidney injury in patients undergoing heart transplant.

BACKGROUND: To evaluate the impact of a clinical pathway on the incidence and severity of acute kidney injury in patients undergoing heart transplant. METHODS: This was a 2.5-year retrospective evaluation using 3 years of historical controls within a cardiac intensive care unit in an academic children's hospital. Patients undergoing heart transplant between May 27, 2014, and April 5, 2017 (pre-pathway) and May 1, 2017, and November 30, 2019 (pathway) were included. The clinical pathway focused on supporting renal perfusion through hemodynamic management, avoiding or delaying nephrotoxic medications, and providing pharmacoprophylaxis against AKI. RESULTS: There were 57 consecutive patients included. There was an unadjusted 20% reduction in incidence of any acute kidney injury (p = .05) and a 17% reduction in Stage 2/3 acute kidney injury (p = .09). In multivariable adjusted analysis, avoidance of Stage 2/3 acute kidney injury was independently associated with the clinical pathway era (AOR -1.3 [95% CI -2.5 to -0.2]; p = .03), achieving a central venous pressure of or less than 12 mmHg (AOR -1.3 [95% CI -2.4 to -0.2]; p = .03) and mean arterial pressure above 60 mmHg (AOR -1.6 [95% CI -3.1 to -0.01]; p = .05) in the first 48 h post-transplant, and older age at transplant (AOR - 0.2 [95% CI -0.2 to -0.06]; p = .002). CONCLUSIONS: This report describes a renal protection clinical pathway associated with a reduction in perioperative acute kidney injury in patients undergoing heart transplant and highlights the importance of normalizing perioperative central venous pressure and mean arterial blood pressure to support optimal renal perfusion.

Direct Discharge to Home From the Pediatric Cardiovascular ICU.

OBJECTIVES: To describe direct discharge to home from the cardiovascular ICU. DESIGN: Mixed-methods including retrospective Pediatric Cardiac Critical Care Consortium and Pediatric Acute Care Cardiology Collaborative data and survey. SETTING: Tertiary pediatric heart center. PATIENTS: Patients less than 25 years old, with a cardiovascular ICU stay of greater than 24 hours and direct discharge to home from January 1, 2016, to December 8, 2020, were included. Select data describing patients discharged from acute care internally and nationally from Pediatric Acute Care Cardiology Collaborative sites were compared with the direct discharge to home cohort. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Encounter- and patient-specific characteristics. Seven-day and 30-day readmission and 30-day mortality served as surrogate safety markers. A survey of cardiovascular ICU frontline providers assessed comfort and skills related to direct discharge to home.There were 364 direct discharge to home encounters that met inclusion criteria. The majority of direct discharge to home encounters were associated with a surgery or procedure (305; 84%). There were 27 encounters (7.4%) for medical technology-dependent patients requiring direct discharge to home. Unplanned 7-day readmissions among direct discharge to home patients was 1.9% compared with 4.6% (p = 0.04) of patients discharged from acute care internally. Readmission among those discharged from acute care internally did not differ from those at Pediatric Acute Care Cardiology Collaborative sites nationally. Frontline cardiovascular ICU providers had mixed levels of confidence in technical aspects and low levels of confidence in logistics of direct discharge to home. CONCLUSIONS: Cardiovascular ICU direct discharge to home was not associated with increased unplanned readmissions compared with patients discharged from acute care and may be safe in select patients. Frontline cardiovascular ICU providers feel time constraints challenge direct discharge to home. Further research is needed to identify patient characteristics associated with safe direct discharge to home and systems needed to support this practice.Summary statistics are described using proportions or medians with interquartile ranges (IQRs) and were performed using Microsoft Excel (Microsoft, Redmond, WA). Two-sample tests of proportions were used to compare readmission frequency of the DDH cohort compared with internal and national PAC3 data using STATA Version 15 (StataCorp, College Station, TX).

Postoperative Acute Kidney Injury in Williams Syndrome Compared With Matched Controls.

OBJECTIVES: Cardiovascular manifestations occur in over 80% of Williams syndrome (WS) patients and are the leading cause of morbidity and mortality. One-third of patients require cardiovascular surgery. Renal artery stenosis (RAS) is common in WS. No studies have assessed postoperative cardiac surgery-related acute kidney injury (CS-AKI) in WS. Our objectives were to assess if WS patients have higher risk of CS-AKI postoperatively than matched controls and if RAS could contribute to CS-AKI. DESIGN: This was a retrospective study of all patients with WS who underwent cardiac surgery at our center from 2010 to 2020. The WS study cohort was compared with a group of controls matched for age, sex, weight, and surgical procedure. SETTING: Patients underwent cardiac surgery and postoperative care at Lucile Packard Children's Hospital Stanford. PATIENTS: There were 27 WS patients and 43 controls (31% vs 42% female; p = 0.36). Median age was 1.8 years (interquartile range [IQR], 0.7-3.8 yr) for WS and 1.7 years (IQR, 0.8-3.1 yr) for controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postoperative hemodynamics, vasopressor, total volume input, diuretic administration, and urine output were collected in the first 72 hours. Laboratory studies were collected at 8-hour intervals. Multivariable analysis identified predictors of CS-AKI.Controlled for renal perfusion pressure (RPP) and vasoactive inotrope score (VIS), compared with controls, the odds ratio (OR) of CS-AKI in WS was 4.2 (95% CI, 1.1-16; p = 0.034). Higher RPP at postoperative hours 9-16 was associated with decreased OR of CS-AKI (0.88 [0.8-0.96]; p = 0.004). Increased VIS at hour 6 was associated with an increased OR of CS-AKI (1.47 [1.14-1.9]; p = 0.003). Younger age was associated with an increased OR of CS-AKI (1.9 [1.13-3.17]; p = 0.015). CONCLUSIONS: The OR of CS-AKI is increased in pediatric patients with WS compared with controls. CS-AKI was associated with VIS at the sixth postoperative hour. Increases in RPP and mean arterial pressure were associated with decreased odds of CS-AKI.

Hyperoxia During Cardiopulmonary Bypass Is Associated With Mortality in Infants Undergoing Cardiac Surgery.

OBJECTIVES: Patients undergoing cardiac surgery using cardiopulmonary bypass have variable degrees of blood oxygen tension during surgery. Hyperoxia has been associated with adverse outcomes in critical illness. Data are not available regarding the association of hyperoxia and outcomes in infants undergoing cardiopulmonary bypass. We hypothesize that among infants undergoing cardiac surgery, hyperoxia during cardiopulmonary bypass is associated with greater odds of morbidity and mortality. DESIGN: Retrospective study. SETTING: Single center at an academic tertiary children's hospital. PATIENTS: All infants (< 1 yr) undergoing cardiopulmonary bypass between January 1, 2015, and December 31, 2017, excluding two patients who were initiated on extracorporeal membrane oxygenation in the operating room. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study included 469 infants with a median age of 97 days (interquartile range, 14-179 d), weight 4.9 kg (interquartile range, 3.4-6.4 kg), and cardiopulmonary bypass time 128 minutes (interquartile range, 91-185 min). A Pao2 of 313 mm Hg (hyperoxia) on cardiopulmonary bypass had highest sensitivity with specificity greater than 50% for association with operative mortality. Approximately, half of the population (237/469) had hyperoxia on cardiopulmonary bypass. Infants with hyperoxia were more likely to have acute kidney injury, prolonged postoperative length of stay, and mortality. They were younger, weighed less, had longer cardiopulmonary bypass times, and had higher Society of Thoracic Surgeons and the European Association for Cardio-Thoracic Surgery mortality scores. There was no difference in sex, race, preoperative creatinine, single ventricle physiology, or presence of genetic syndrome. On multivariable analysis, hyperoxia was associated with greater odds of mortality (odds ratio, 4.3; 95% CI, 1.4-13.2) but failed to identify an association with acute kidney injury or prolonged postoperative length of stay. Hyperoxia was associated with greater odds of mortality in subgroup analysis of neonatal patients. CONCLUSIONS: Hyperoxia occurred in a substantial portion of infants undergoing cardiopulmonary bypass for cardiac surgery. Hyperoxia during cardiopulmonary bypass was an independent risk factor for mortality and may be a modifiable risk factor. Furthermore, hyperoxia during cardiopulmonary bypass was associated with four-fold greater odds of mortality within 30 days of surgery. Hyperoxia failed to identify an association with development of acute kidney injury or prolonged postoperative length of stay when controlling for covariables. Validation of our data among other populations is necessary to better understand and elucidate potential mechanisms underlying the association between excess oxygen delivery during cardiopulmonary bypass and outcome.

Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery: A Retrospective Multicenter Study.

OBJECTIVES: We aimed to describe characteristics and operative outcomes from a multicenter cohort of infants who underwent repair of anomalous left coronary artery from the pulmonary artery. We also aimed to identify factors associated with major adverse cardiovascular events following anomalous left coronary artery from the pulmonary artery repair. DESIGN: Retrospective chart review. SETTING: Twenty-one tertiary-care referral centers. PATIENTS: Infants less than 365 days old who underwent anomalous left coronary artery from the pulmonary artery repair. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Major adverse cardiovascular events were defined as the occurrence of postoperative extracorporeal membrane oxygenation, cardiopulmonary resuscitation, left ventricular assist device, heart transplantation, or operative mortality. Factors independently associated with major adverse cardiovascular events were identified using multivariable logistic regression analysis. We reviewed 177 infants (< 365 d old) who underwent anomalous left coronary artery from the pulmonary artery repair between January 2009 and March 2018. Major adverse cardiovascular events occurred in 36 patients (20%). Twenty-nine patients (16%) received extracorporeal membrane oxygenation, 14 (8%) received cardiopulmonary resuscitation, four (2%) underwent left ventricular assist device placement, two (1%) underwent heart transplantation, and six (3.4%) suffered operative mortality. In multivariable analysis, preoperative inotropic support (odds ratio, 3.5; 95% CI, 1.4-8.5), cardiopulmonary bypass duration greater than 150 minutes (odds ratio, 6.9 min; 95% CI, 2.9-16.7 min), and preoperative creatinine greater than 0.3 mg/dL (odds ratio, 2.4 mg/dL; 95% CI, 1.1-5.6 mg/dL) were independently associated with major adverse cardiovascular events. In patients with preoperative left ventricular end-diastolic diameter measurements available (n = 116), left ventricular end-diastolic diameter z score greater than 6 was also independently associated with major adverse cardiovascular events (odds ratio, 7.6; 95% CI, 2.0-28.6). CONCLUSIONS: In this contemporary multicenter analysis, one in five children who underwent surgical repair of anomalous left coronary artery from the pulmonary artery experienced major adverse cardiovascular events. Preoperative characteristics such as inotropic support, creatinine, and left ventricular end-diastolic diameter z score should be considered when planning for potential postoperative complications.

Maternal Hyperoxygenation Testing in Fetuses with Hypoplastic Left-Heart Syndrome: Association with Postnatal Atrial Septal Restriction.

INTRODUCTION: In fetuses with hypoplastic left-heart syndrome (HLHS), maternal hyperoxygenation (MHO) may aid risk stratification. We hypothesized that pulmonary vein (Pvein) velocity time integral (VTI) change with MHO would more reliably identify neonates who undergo emergent atrial septoplasty (EAS) than changes in pulmonary arterial pulsatility index (PA PI). METHODS: Fetuses with HLHS who underwent MHO testing at our institution between 2014 and 2019 were identified. Data were reviewed in a blinded, retrospective manner. Pvein VTI ratio (prograde:retrograde) was calculated. The primary outcome was neonatal EAS. RESULTS: Twenty-seven HLHS fetuses underwent MHO, and 5 (19%) underwent EAS. Without MHO, a Pvein VTI ratio <3 conferred 60% sensitivity and 100% specificity for EAS. With MHO, a Pvein VTI ratio <6.5 conferred 100% sensitivity and specificity. For an intermediate group of fetuses with a baseline Pvein VTI ratio 3-7, the ratio decrease with MHO conferred 100% sensitivity and specificity. Compared to the Pvein VTI ratio, PA PI was less accurate in identifying EAS neonates. DISCUSSION/CONCLUSION: Addition of MHO appears to improve the diagnostic ability of the Pvein VTI ratio to identify HLHS fetuses who undergo EAS. The Pvein VTI ratio change may more accurately identify fetuses who undergo EAS than change in PA PI and has less interobserver variability.

The Use of Clevidipine for Hypertension in Pediatric Patients Receiving Mechanical Circulatory Support.

OBJECTIVES: Limited data exist regarding the management of hypertension in pediatric patients on mechanical circulatory support. Hypertension is a known risk factor for stroke and low cardiac output in patients requiring mechanical circulatory support and a narrow therapeutic window of blood pressure is often targeted. Traditional short-acting infusions to treat hypertension, such as sodium nitroprusside, may lead to accumulation of toxic metabolites in patients with renal dysfunction. Our primary objective was to describe use of clevidipine, a continuous short-acting calcium channel blocking medication, for blood pressure control in pediatric patients on mechanical circulatory support. DESIGN: Single-center retrospective cohort study. SETTING: A 26-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California. PATIENTS: Mechanical circulatory support patients admitted to cardiovascular ICU who received clevidipine infusions between October 1, 2016, and March 31, 2019. INTERVENTIONS: Clevidipine infusion. MEASUREMENTS AND MAIN RESULTS: Data from a cohort of 38 patients who received a total of 45 clevidipine infusions were reviewed. The cohort had a median age of 2.7 years and included neonates. No patient had record of hypotensive events, code events, or received low-dose epinephrine or code-dosed epinephrine related to a clevidipine infusion. Median duration of clevidipine infusion was 4.1 days (1.5-9.2 d). Eleven patients transitioned from clevidipine to enteral antihypertensive agents, and 26 clevidipine infusions were administered as a single agent without sodium nitroprusside. Seven patients were switched from sodium nitroprusside to clevidipine to avoid cyanide toxicity, a majority of whom had elevated serum creatinine. CONCLUSIONS: In this pediatric cardiac cohort, clevidipine infusions were effective at hypertension management and were not associated with hypotensive or code events. This report details the largest cohort and longest duration of clevidipine administration within a pediatric population and did not demonstrate hypotensive events, even among neonatal populations. Clevidipine may be a reasonable cost-effective alternative antihypertensive medication compared to traditional short-acting agents.

Intraoperative Methadone Is Associated with Decreased Perioperative Opioid Use Without Adverse Events: A Case-Matched Cohort Study.

OBJECTIVE: To determine if there is an association of intraoperative methadone use and total perioperative opioid exposure in patients undergoing congenital heart surgeries. DESIGN: Retrospective, case-match cohort study. SETTING: Single center quaternary care teaching hospital. PARTICIPANTS: Seventy-four patients with congenital heart disease (CHD) undergoing surgical repair or palliative surgery. INTERVENTION: Thirty-seven patients undergoing CHD surgeries receiving intraoperative methadone were matched to 37 patients based upon age and procedure who did not receive intraoperative methadone. The primary study outcome was to evaluate total opioid use in intravenous milligrams of morphine equivalents per kilogram (mg ME/kg) within the first 36-hours postoperatively. Mann-Whitney U test was used to compare total opioid exposure. MEASUREMENTS AND MAIN RESULTS: The total opioid use was compared between groups. The methadone cohort required less opioids intraoperatively, in the first 12 hours postoperatively, and during the first 36 hours postoperatively (2.51 v 4.39 mg ME/kg, p < 0.001; 0.43 v 1.28 mg ME/kg, p = 0.001; and 0.83 v 1.91 mg ME/kg, p < 0.001) compared with the matched control cohort. There were no differences in clinical outcomes or adverse events. A dose-dependent reduction in opioid consumption in high- versus low-dose groups also was not observed. CONCLUSION: Intraoperative methadone use was associated with a decrease in perioperative opioid exposure in patients undergoing congenital heart surgery and was not associated with adverse events or prolonged durations of mechanical ventilation or ICU stay.

Rasburicase versus intravenous allopurinol for non-malignancy-associated acute hyperuricemia in paediatric cardiology patients.

OBJECTIVES: Limited data exist for management of hyperuricemia in non-oncologic patients, particularly in paediatric cardiac patients. Hyperuricemia is a risk factor for acute kidney injury and may prompt treatment in critically ill patients. The primary objective was to determine if rasburicase use was associated with greater probability normalisation of serum uric acid compared to allopurinol. Secondary outcomes included percent reduction in uric acid, changes in serum creatinine, and cost of therapy. DESIGN: A single-centre retrospective chart review. SETTING: A 20-bed quaternary cardiovascular ICU in a university-based paediatric hospital in California. PATIENTS: Patients admitted to cardiovascular ICU who received rasburicase or intravenous allopurinol between 2015 and 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from a cohort of 14 patients receiving rasburicase were compared to 7 patients receiving IV allopurinol. Patients who were administered rasburicase for hyperuricemia were more likely to have a post-treatment uric acid level less than 8 mg/dl as compared to IV allopurinol (100 versus 43%; p = 0.0058). Patients who received rasburicase had a greater absolute reduction in post-treatment day 1 uric acid (-9 mg/dl versus -1.9 mg/dl; p = 0.002). There were no differences in post-treatment day 3 or day 7 serum creatinine or time to normalisation of serum creatinine. The cost of therapy normalised to a 20 kg patient was greater in the allopurinol group ($18,720 versus $1928; p = 0.001). CONCLUSION: In a limited paediatric cardiac cohort, the use of rasburicase was associated with a greater reduction in uric acid levels and associated with a lower cost compared to IV allopurinol.

Acute kidney injury in congenital heart disease.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is associated with significant morbidity and mortality in patients with congenital heart disease undergoing cardiac surgery or in pediatric patients with congestive heart failure. RECENT FINDINGS: This review describes the definition and various manifestations of AKI, the impact of biomarkers on the diagnosis of AKI, the importance of fluid overload as a consequence of AKI and its long-term impact. SUMMARY: There are novel biomarkers for AKI detection that should facilitate early recognition and intervention to prevent or attenuate the effects of AKI and fluid overload. Previous conventional wisdom that survivors of AKI fully recover renal function without subsequent consequences is flawed.

Nephrotoxin exposure and acute kidney injury in critically ill children undergoing congenital cardiac surgery.

BACKGROUND: Though acute kidney injury (AKI) is often multifactorial, investigators are now emphasizing the specific contribution of nephrotoxins. This study examines the epidemiology of nephrotoxin exposure and nephrotoxin-associated AKI among children undergoing congenital heart surgery (CHS). METHODS: This is a retrospective cohort study of children admitted following CHS between June 1, 2014, and September 30, 2014. Nephrotoxins were defined according to the Nephrotoxic Injury Negated by Just-in-time-Action (NINJA) collaborative; high nephrotoxin exposure was defined as receipt of ≥ 3 nephrotoxins concurrently. AKI was diagnosed according to KDIGO creatinine criteria. Severe AKI was defined as KDIGO stage ≥ 2. Poisson models were used to compute adjusted relative risk (aRR) of high nephrotoxin exposure for AKI. RESULTS: One hundred fifty-four children (median age 20.4 months, IQR 2.3-59.5) were included. One hundred thirty-one (85.1%) received at least one nephrotoxin; 32 (20.8%) received ≥ 3 nephrotoxins. The most commonly administered medications were ketorolac (n = 74, 48.1%), aspirin (n = 62, 40.3%), ibuprofen (n = 51, 33.1%), vancomycin (n = 39, 25.3%), piperacillin/tazobactam (n = 35, 22.7%), and enalapril (n = 14, 9.1%). AKI occurred more commonly in those exposed to ≥ 3 nephrotoxins (62.5 vs. 50.8%); this was not statistically significant after adjusting for confounders (aRR = 1.2, 95% CI 0.9-1.7). Severe AKI was similar between those with and without high nephrotoxin exposure (21.9 vs. 19.7%, p = 0.78). CONCLUSIONS: Nephrotoxin use is common following pediatric CHS. While we found no association between high nephrotoxin exposure and AKI, this may be related to the multifactorial nature of AKI in this population. For many common nephrotoxins, less injurious agents exist and nephrotoxin exposure may represent a modifiable risk factor for AKI.

Fluid overload independent of acute kidney injury predicts poor outcomes in neonates following congenital heart surgery.

BACKGROUND: Fluid overload (FO) is common after neonatal congenital heart surgery and may contribute to mortality and morbidity. It is unclear if the effects of FO are independent of acute kidney injury (AKI). METHODS: This was a retrospective cohort study which examined neonates (age < 30 days) who underwent cardiopulmonary bypass in a university-affiliated children's hospital between 20 October 2010 and 31 December 2012. Demographic information, risk adjustment for congenital heart surgery score, surgery type, cardiopulmonary bypass time, cross-clamp time, and vasoactive inotrope score were recorded. FO [(fluid in-out)/pre-operative weight] and AKI defined by Kidney Disease Improving Global Outcomes serum creatinine criteria were calculated. Outcomes were all-cause, in-hospital mortality and median postoperative hospital and intensive care unit lengths of stay. RESULTS: Overall, 167 neonates underwent cardiac surgery using cardiopulmonary bypass in the study period, of whom 117 met the inclusion criteria. Of the 117 neonates included in the study, 76 (65%) patients developed significant FO (>10%), and 25 (21%) developed AKI ≥ Stage 2. When analyzed as FO cohorts (< 10%,10-20%, > 20% FO), patients with greater FO were more likely to have AKI (9.8 vs. 18.2 vs. 52.4%, respectively, with AKI ≥ stage 2; p = 0.013) and a higher vasoactive-inotrope score, and be premature. In the multivariable regression analyses of patients without AKI, FO was independently associated with hospital and intensive care unit lengths of stay [0.322 extra days (p = 0.029) and 0.468 extra days (p < 0.001), respectively, per 1% FO increase). In all patients, FO was also associated with mortality [odds ratio 1.058 (5.8% greater odds of mortality per 1% FO increase); 95% confidence interval 1.008,1.125;p = 0.032]. CONCLUSIONS: Fluid overload is an important independent contributor to outcomes in neonates following congenital heart surgery. Careful fluid management after cardiac surgery in neonates with and without AKI is warranted.

First-stage palliation strategy for univentricular heart disease may impact risk for acute kidney injury.

OBJECTIVE: Norwood palliation for patients with single ventricle heart disease is associated with a significant risk for acute kidney injury, which portends a worse prognosis. We sought to investigate the impact of hybrid stage I palliation (Hybrid) on acute kidney injury risk. DESIGN: This study is a single-centre prospective case-control study of seven consecutive neonates with single ventricle undergoing Hybrid palliation. Levels of serum creatinine and four novel urinary biomarkers, namely neutrophil gelatinase-associated lipocalin, interleukin-18, liver fatty acid-binding protein, and kidney injury molecule-1, were obtained before and after palliation. Acute kidney injury was defined as a ⩾50% increase in serum creatinine within 48 hours after the procedure. Data were compared with a contemporary cohort of 12 neonates with single ventricle who underwent Norwood palliation. RESULTS: Patients who underwent Hybrid were more likely to be high-risk candidates (86 versus 25%, p=0.01) compared with those who underwent Norwood. Despite similar preoperative serum creatinine levels, there was a trend towards higher levels of postoperative peak serum creatinine (0.7 [0.63, 0.94] versus 0.56 [0.47, 0.74], p=0.06) and rate of acute kidney injury (67 versus 29%, p=0.17) in the Norwood cohort. Preoperative neutrophil gelatinase-associated lipocalin (58.4 [11, 86.3] versus 6.3 [5, 16.2], p=0.07) and interleukin-18 (30.6 [9.6, 167.2] versus 6.3 [6.3, 16.4], p=0.03) levels were higher in the Hybrid cohort. Nevertheless, longitudinal mixed-effect models demonstrated Hybrid palliation to be a protective factor against increased postoperative levels of neutrophil gelatinase-associated lipocalin (estimate -1.8 [-3.0, -9.0], p<0.001) and liver fatty acid-binding protein (-49.3 [-89.7, -8.8], p=0.018). CONCLUSIONS: In this single-centre case-control study, postoperative acute kidney injury risk did not differ significantly by single ventricle stage I treatment strategy; however, postoperative elevation in novel urinary biomarkers, consistent with subclinical kidney injury, was encountered in the Norwood cohort but not in the Hybrid cohort.