Elevated Copeptin Levels Are Associated with Heart Failure Severity and Adverse Outcomes in Children with Cardiomyopathy.

In children with cardiomyopathy, the severity of heart failure (HF) varies. However, copeptin, which is a biomarker of neurohormonal adaptation in heart failure, has not been studied in these patients. In this study, we evaluated the correlation of copeptin level with functional HF grading, B-type natriuretic peptide (BNP), and echocardiography variables in children with cardiomyopathy. Furthermore, we determined if copeptin levels are associated with adverse outcomes, including cardiac arrest, mechanical circulatory support, heart transplant, or death. In forty-two children with cardiomyopathy with a median (IQR) age of 13.1 years (2.5-17.2) and a median follow-up of 2.5 years (2.2-2.7), seven (16.7%) children had at least one adverse outcome. Copeptin levels were highest in the patients with adverse outcomes, followed by the patients without adverse outcomes, and then the healthy children. The copeptin levels in patients showed a strong correlation with their functional HF grading, BNP level, and left ventricular ejection fraction (LVEF). Patients with copeptin levels higher than the median value of 25 pg/mL had a higher likelihood of experiencing adverse outcomes, as revealed by Kaplan-Meier survival analysis (p = 0.024). Copeptin level was an excellent predictor of outcomes, with an area under the curve of 0.861 (95% CI, 0.634-1.089), a sensitivity of 86%, and a specificity of 60% for copeptin level of 25 pg/mL. This predictive value was superior in patients with dilated and restrictive cardiomyopathies (0.97 (CI 0.927-1.036), p < 0.0001, n = 21) than in those with hypertrophic and LV non-compaction cardiomyopathies (0.60 (CI 0.04-1.16), p = 0.7, n = 21).

Incidence of Acute Neurological Events in Neonates and Infants Undergoing Cardiac Surgery Using a High-Hematocrit/ High-Flow Bypass Strategy.

Background: The incidence of new acute neurological injury occurring in neonates and infants during cardiac surgery utilizing cardiopulmonary bypass is reportedly 3% to 5%. In 2013, we adopted a high flow rate, and high hematocrit bypass strategy, and sought to assess the incidence of early neurological injuries associated with this strategy. Methods: Neonates and infants undergoing cardiopulmonary bypass between January 2013 and December 2019 (n = 714) comprise the study. Adverse neurological events (ANEs) were defined as any abnormality of pupils, delayed awakening, seizures, focal neurological deficits, concerns prompting neurological consultation, or any abnormality on neurological imaging in the postoperative period. Our bypass strategy included a high flow rate (150-200 mL/kg/min), without reduction of flow rates during cooling and maintaining a target hematocrit on bypass > 32% with a terminal hematocrit of > 42%. Results: Median weight at the time of the procedure was 4.6 kg (IQR 3.6-6.1 kg) with the smallest patient weighing 1.36 kg. There were 46 premature patients (6.4%). There were 149 patients (20.9%) patients who underwent deep hypothermic circulatory arrest with a median time of 26 min (IQR 21-41 min). Hospital mortality was 3.5% (24/714, 95% CI: 2.28-5.13). The incidence of neurological events as defined above was 0.84% (6/714, 95% CI: 0.31-1.82). Neurological imaging identified ischemic injury in 4 patients and intraventricular hemorrhage in 2. Conclusions: High flow/high hematocrit bypass strategy was associated with a low incidence of ANE in this vulnerable population.

Use of Aminophylline to Reverse Acute Kidney Injury in Pediatric Critical Care Patients.

OBJECTIVE: Acute kidney injury (AKI) is a complication encountered in 18% to 51% of pediatric critical care patients admitted for treatment of other primary diagnoses and is an independent risk factor for increased morbidity and mortality. Aminophylline has shown promise as a medication to treat AKI, but published studies have shown conflicting results. Our study seeks to assess the reversal of AKI following the administration of aminophylline in critically ill pediatric patients. METHODS: We performed a single-institution retrospective chart review of pediatric inpatients who were diagnosed with AKI and subsequently treated with non-continuous dose aminophylline between January 2016 and December 2018. Data were collected beginning 2 days prior to the initial dose of aminophylline through completion of the 5-day aminophylline course. RESULTS: Nineteen therapies among 17 patients were included in analysis. Twelve of the therapies resulted in resolution of AKI during the study period. We observed urine output increase of 19% (p = 0.0063) on the day following initiation of aminophylline therapy in the subset of patients whose AKI resolved. Trends toward decreased serum creatinine and lower inotropic support were also noted. CONCLUSIONS: Based on these findings, aminophylline could be considered a potentially effective medication for use as rescue therapy in critically ill children with AKI. Limitations include small study population and retrospective nature. Further research in this area with a larger study population and a randomized control trial would allow for better characterization of the efficacy of aminophylline in reversal of AKI.

Association of Diagnostic Stewardship for Blood Cultures in Critically Ill Children With Culture Rates, Antibiotic Use, and Patient Outcomes: Results of the Bright STAR Collaborative.

Importance: Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics. Objective: To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes. Design, Setting, and Participants: This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes. Exposures: A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative). Main Outcomes and Measures: The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock. Results: Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation. Conclusions and Relevance: Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

Fluid Accumulation After Neonatal Congenital Cardiac Operation: Clinical Implications and Outcomes.

BACKGROUND: This study was conducted to determine the association between fluid balance metrics and mortality and other postoperative outcomes after neonatal cardiac operation in a contemporary multicenter cohort. METHODS: This was an observational cohort study across 22 hospitals in neonates (≤30 days) undergoing cardiac operation. We explored overall percentage fluid overload, postoperative day 1 percentage fluid overload, peak percentage fluid overload, and time to first negative daily fluid balance. The primary outcome was in-hospital mortality. Secondary outcomes included postoperative duration of mechanical ventilation and intensive care unit (ICU) and hospital length of stay. Multivariable logistic or negative binomial regression was used to determine independent associations between fluid overload variables and each outcome. RESULTS: The cohort included 2223 patients. In-hospital mortality was 3.9% (n = 87). Overall median peak percentage fluid overload was 4.9% (interquartile range, 0.4%-10.5%). Peak percentage fluid overload and postoperative day 1 percentage fluid overload were not associated with primary or secondary outcomes. Hospital resource utilization increased on each successive day of not achieving a first negative daily fluid balance and was characterized by longer duration of mechanical ventilation (incidence rate ratio, 1.11; 95% CI, 1.08-1.14), ICU length of stay (incidence rate ratio, 1.08; 95% CI, 1.03-1.12), and hospital length of stay (incidence rate ratio, 1.09; 95% CI, 1.05-1.13). CONCLUSIONS: Time to first negative daily fluid balance, but not percentage fluid overload, is associated with improved postoperative outcomes in neonates after cardiac operation. Specific treatments to achieve an early negative fluid balance may decrease postoperative care durations.

Impact of Different Cardiopulmonary Bypass Strategies on Renal Injury After Pediatric Heart Surgery.

BACKGROUND: The purpose of this study is to compare the incidence and severity of acute kidney injury (AKI) after open heart surgery in neonates and infants for two different cardiopulmonary bypass (CPB) strategies. METHODS: In all, 151 infants undergoing cardiac surgery were prospectively enrolled between June 2017 and June 2018 at two centers, one using conventional CPB (2.4 L · min-1 · m-2, 150 mL · kg-1 · min-1) with reduction of flow rates with moderate hypothermia and with a targeted hematocrit greater than 25% (center 1, n = 91), and the other using higher bypass flow rates (175 to 200 mL · kg-1 · min-1) and higher minimum hematocrit (greater than 32%) CPB (center 2, n = 60). The primary endpoint was the incidence of postoperative AKI as defined by Acute Kidney Injury Network criteria and risk factors associated with AKI. RESULTS: Preoperative characteristics and complexity of surgery were comparable between centers. The overall incidence of early postoperative AKI was 10.6% (16 of 151), with 15.4% (14 of 91) in center 1 and 3.3% (2 of 60) in center 2 (P = .02). Mean lowest flow rates on CPB were 78 mL · kg-1 · min-1 vs 118 mL · kg-1 · min-1 and mean highest hematocrit on separation from CPB were 33% vs 43% at center 1 and 2, respectively (P < .001). Center 1 used less packed red blood cells but more fresh frozen plasma than center 2 (P = .001). By multivariate analysis, only lower flows on CPB (78 vs 96 mL · kg-1 · min-1, P = .043) and lower hematocrit at the end of CPB (33% vs 37%, P = .007) were associated with AKI. CONCLUSIONS: In this contemporary comparative study, higher flow rates and higher hematocrit during cardiopulmonary bypass were associated with better preservation of renal function.

Accessing Femoral Arteries Less than 3 mm in Diameter is Associated with Increased Incidence of Loss of Pulse Following Cardiac Catheterization in Infants.

To evaluate whether avoidance of a risk factor associated with loss of pulse (LOP) following femoral artery (FA) catheterization in infants identified from previous study, was associated with decreased incidence of LOP during a prospective evaluation. Since initiation of routine ultrasound guided femoral arterial access (UGFAA) for infants undergoing catheterization in Jan 2003-Dec 2011 (Period-1), our incidence of LOP had stayed steady. Prospective evaluation between Jan 2012-Dec 2014 (Period-2), identified FA-diameter < 3 mm as risk factor for LOP. Between Jan 2015-Dec 2018 (Period-3), an initiative to avoid UGFAA for FA-diameter < 3 mm was implemented to determine whether that led to a decreased incidence of LOP. FA-diameter was measured prior to USGFAA and ratio of outer diameter of arterial sheath to luminal diameter of cannulated artery (OD/AD ratio) was calculated during Periods-2 and 3. The incidence and risk factors for LOP were assessed during the three periods. FA-access rates dropped significantly during Period-3 (56.7% vs. 93.8% and 90.4% during Periods-1 and 2, respectively, p < 0.001). Incidence of LOP in Period-3 decreased to 2.7% compared to 12.5% (Period-1) and 17.4% (Period-2) (p < 0.001). By multivariate analysis, FA size < 3 mm and an OD/AD ratio > 40% were the only significant independent predictors for LOP (OR 6.48, 95% CI 2.3-11.42, p < 0.001 and OR 4.16, 95% CI 1.79-8.65, p < 0.01, respectively). Access of femoral artery < 3 mm and OD/AD ratio > 50% are associated with increased incidence of LOP. Avoidance of these factors may help decrease complications in infants undergoing cardiac catheterizations.

Construction of Femoral Vessel Nomograms for Planning Cardiac Interventional Procedures in Children 0-4 Years Old.

The objectives of this study were to construct femoral artery (FA) and femoral vein (FV) nomograms in children aged 0-4 years and to construct probability curves for the occurrence of arterial access complications based on the size of the FA. The FV and FA are commonly accessed during cardiac catheterizations in children with congenital heart diseases (CHD). However, nomograms for vessel dimensions based on child's age or size are not available. This knowledge may be helpful for interventional planning. A prospective study was performed on 400 children (age 0-4 years) with CHD undergoing cardiac catheterizations over a 3-year period. Ultrasound evaluation of the right and left FA and FV was performed under anesthesia prior to vascular access. Regression modeling was applied to derive nomograms based on quantile polynomial regression, which yielded good fit to the data judged by R-squared. GAMLSS transformation method was used to formulate smoothed percentiles. A separate prospective evaluation of FA to determine the size below which loss of pulse (LOP) are likely to occur was performed. Nomograms for FA and FV diameter and cross-sectional area against age and body surface area and probability curves for FA LOP were constructed. It is now possible to examine ultrasound-based normal sizes of femoral vein and artery in children 0-4 years of age. Femoral vessel nomograms and LOP probability curves may help with interventional planning. Future studies with larger sample size, including children of other ages may be useful.

Concurrent Use of Calcium Chloride and Arginine Vasopressin Infusions in Pediatric Patients with Acute Cardiocirculatory Failure.

Acute heart failure (AHF) can cause low cardiac output and poor end-organ perfusion. Inotropic agents along with vasodilators can improve organ perfusion. Arginine vasopressin (AVP) and calcium chloride (CaCl) infusions are increasingly being used in low cardiac output states in pediatric AHF. We retrospectively reviewed 77 patients (0-18 years) with AHF admitted between January 2014 and May 2017 who received concurrent AVP and CaCl infusions. Surrogates of cardiac output and organ perfusion included hemodynamic vital signs, laboratory parameters, and urine output (UO). Organ dysfunction and vasopressor inotropic scores were also calculated. Median (IQR) age was 0.88 years (0, 3.75), and median weight was 6.62 kg (3.5, 13.7). Congenital heart disease was present in 70% (46/77) patients. Univentricular physiology was present in 25% (25/77) patients. None of the patients were in the immediate postoperative period. Median durations of AVP and CaCl were 2 days (1, 3) and 3 days (2, 6), respectively. Using Wilcoxon-signed rank test and Bonferroni correction, post hoc comparison showed that at 8 h post infusion, all systolic blood pressure (SBP) and diastolic blood pressure (DBP) results, and UO were greater than those 1 h prior to infusion. Median SBP increased from 79 mm Hg (71, 92) 1 h prior to 97 mm Hg (84, 107) 8 h post. Median DBP increased from 44 mm Hg (35, 52) 1 h prior to 54 mm Hg (44, 62) 8 h post. Heart rate showed a decrease between measurements 1 h prior to infusion and 8 h post, with median scores 146 (127, 162) and 136 (114, 150) beats per minute, respectively. Within first 8 h, median UO continuously increased from 6 mL/h. (0, 25) at 1 h post infusion to 20 mL/h. (2, 62) at 8 h post infusion. Median pediatric logarithmic organ dysfunction scores on days 4 through 7 post infusion were lower compared to day 1; median vasopressor inotropic scores on day 2 through 7 post infusion were lower compared to day 1. Serum lactate level, arterial pH, and base excess all showed favorable trend. Concurrent use of AVP and CaCl infusions may improve surrogates of cardiac output, and intensive care outcomes, and prevent organ dysfunction in children with AHF.

Cavopulmonary Anastomosis During Same Hospitalization as Stage 1 Norwood/Hybrid Palliative Surgery.

BACKGROUND: Limited literature has examined characteristics of infants with hypoplastic left heart syndrome (HLHS) who remain hospitalized during the interstage period. We described their epidemiologic characteristics, in-hospital outcomes, and identified risk factors that predict the need for superior cavopulmonary anastomosis (SCPA) during the same hospitalization. METHODS: This retrospective multicenter database analysis included infants with HLHS who underwent stage 1 palliation from 2004 through 2013. RESULTS: Among 5374 infants with HLHS, 314 (5.8%) underwent SCPA during the same hospitalization as stage 1 palliation. They had a higher incidence of baseline comorbidities, complications, and interventions than infants who were discharged. Despite an overall increase in need for SCPA in the same hospitalization across different eras, there was no significant statistical difference in mortality in the two groups in the same era. Septicemia, necrotizing enterocolitis, modified Blalock-Taussig shunt, cardiac catheterization, cardiopulmonary resuscitation, extracorporeal membrane oxygenation, gastrostomy tube, and antiarrhythmic agents were independently associated with increased odds of undergoing SCPA during the same hospitalization. Patients undergoing right ventricle to pulmonary artery shunt were less likely to remain hospitalized until stage 2 palliation. Nonsurvivors in the SCPA group had greater need for interventions and worse intensive care unit outcomes. CONCLUSIONS: Infants with HLHS who remain hospitalized after stage 1 until their stage 2 palliation differ significantly from infants who were discharged. Several clinical characteristics, comorbidities, and need for interventions are associated with the likelihood for undergoing stage 2 palliation during the same hospitalization. Timely identification and intervention of adjustable causes of heart failure may improve outcomes.

Epidemiology and outcomes of cardiac arrest among children with Down Syndrome: a multicenter analysis.

BACKGROUND: With the increasing prevalence of Down Syndrome, it is unknown if children with Down Syndrome are associated with increased incidence of cardiac arrest and poor outcomes after cardiac arrest. The objective of this study was to evaluate the epidemiology of cardiac arrest and mortality after cardiac arrest among critically ill children with and without Down Syndrome. METHODS: Patients ≤18 years admitted at a Pediatric Health Information Systems (PHIS) participating Intensive Care Unit were included (2004-2014). Multivariable logistic regression models were fitted to evaluate association of Down Syndrome with study outcomes after adjusting for patient and center characteristics. RESULTS: A total of 849,250 patients from 44 centers were included. Of the 25,143 patients with Down Syndrome, cardiac arrest was noted among 568 (2.3%) patients with an associated mortality at hospital discharge of 248 (43.6%) patients. In contrast, of the 824,107 patients without Down Syndrome, cardiac arrest was noted among 15,822 (1.9%) patients with an associated mortality at hospital discharge of 7775 (49.1%) patients. In adjusted models, patients with Down Syndrome had a higher likelihood of having cardiac arrest as compared to patients without Down Syndrome (with vs. without Down, OR: 1.14, 95% CI: 1.03-1.25, P=0.01). Despite having a higher likelihood of cardiac arrest, patients with Down Syndrome were associated with a lower mortality after cardiac arrest (OR: 0.78, 95% CI: 0.63-0.96, P=0.02). CONCLUSIONS: Both incidence of cardiac arrest, and mortality at hospital discharge in those with cardiac arrest vary substantially in children with and without Down Syndrome.

Is Administration of Nitric Oxide During Extracorporeal Membrane Oxygenation Associated With Improved Patient Survival?

OBJECTIVE: To evaluate the outcomes associated with the use of inhaled nitric oxide during extracorporeal membrane oxygenation. DESIGN: Post hoc analysis of data from an existing administrative national database, Pediatric Health Information system (2004-2014). Multivariable logistic regression models were fitted to study the effect of inhaled nitric oxide during extracorporeal membrane oxygenation on study outcomes. SETTING: Forty-two children's hospitals across the United States. PATIENTS: Patients in the age group from 1 day through 18 years admitted to an ICU who received extracorporeal membrane oxygenation during their hospital stay were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 6,419 patients qualified for inclusion. Of these, inhaled nitric oxide was used among 3,629 patients during extracorporeal membrane oxygenation run. Approximately one half of the study patients received inhaled nitric oxide at extracorporeal membrane oxygenation initiation. The proportion of patients receiving inhaled nitric oxide during extracorporeal membrane oxygenation decreased with increasing duration of extracorporeal membrane oxygenation. After adjusting for patient characteristics and center variables, use of inhaled nitric oxide was not associated with any survival benefit. However, higher proportion of patients receiving inhaled nitric oxide were associated with prolonged hospital length of stay and prolonged duration of extracorporeal membrane oxygenation. In adjusted models, the hospital charges were higher in the inhaled nitric oxide group. The median hospital costs among patients receiving inhaled nitric oxide were higher by $39,732 (95% CI, $31,074-48,390) as compared to the patients who did not receive inhaled nitric oxide, after adjusting for patient (including hospital length of stay) and center level variables. As the duration of inhaled nitric oxide therapy increased, proportion of patients with prolonged duration of extracorporeal membrane oxygenation and prolonged hospital length of stay increased. CONCLUSIONS: This large observational analysis of use of nitric oxide during extracorporeal membrane oxygenation calls into question the benefits of inhaled nitric oxide among patients receiving extracorporeal membrane oxygenation for pulmonary or cardiac failure. Given our inability to determine type of extracorporeal membrane oxygenation and control for severity of illness, these findings should be interpreted as exploratory.