Association Between Dead Space to Tidal Volume Ratio and Duration of Respiratory Support After Extubation in Children With Congenital Heart Disease.

Children with cardiac disease liberated from mechanical ventilation often receive noninvasive respiratory support (NRS) postextubation via high-flow nasal cannula, CPAP, or noninvasive ventilation. Predicting the type and duration of postextubation NRS can be challenging due to a lack of objective tools to guide decision-making. The dead space to tidal volume ratio (V/V) is a potential tool to guide this decision.

Association Between 25% Albumin and Fluid Balance in Mechanically Ventilated Children.

Albumin is often used to augment diuresis in fluid overloaded patients. The purpose of this study was to determine the association between albumin administration and fluid balance and respiratory outcomes in mechanically ventilated children. This was a single-center retrospective cohort study of patients 1 month to <18 years old admitted to the pediatric or cardiac ICU between July 1, 2013, and July 1, 2019 who received 25% albumin while mechanically ventilated.

Pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.

Background: New drugs to target different pathways in pulmonary hypertension has resulted in increased combination therapy, but details of this use in infants are not well described. In this large multicenter database study, we describe the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.

Methods: We identified inborn infants discharged home from a Pediatrix neonatal ICU from 1997 to 2020 exposed to inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for greater than two consecutive days.

Noninvasive Ventilation or CPAP in the Initial Treatment Phase of Small Infants With Respiratory Failure.

Respiratory failure in infants is a common reason for admission to the pediatric ICU (PICU). Although high-flow nasal cannula (HFNC) is the preferred first-line treatment at our institution, some infants require CPAP or noninvasive ventilation (NIV). Here we report our experience using CPAP/NIV in infants <10 kg.

Characterizing Enoxaparin's Population Pharmacokinetics to Guide Dose Individualization in the Pediatric Population.

Background And Objective: Pediatric dosing of enoxaparin was derived based on extrapolation of the adult therapeutic range to children. However, a large fraction of children do not achieve therapeutic anticoagulation with initial dosing. We aim to use real-world anti-Xa data obtained from children receiving enoxaparin per standard of care to characterize the population pharmacokinetics (PopPK).

Factors Associated With Successful Extubation Readiness Testing in Children With Congenital Heart Disease.

Background: In children with congenital heart disease, extubation readiness testing (ERT) is performed to evaluate the potential for liberation from mechanical ventilation. There is a paucity of data that suggests what mechanical ventilation parameters are associated with successful ERT. We hypothesized that ERT success would be associated with certain mechanical ventilator parameters.

Association Between Hypoglycemia and the Occurrence of Early Onset Sepsis in Premature Infants.

Background: We examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU).

Methods: We included infants discharged from 358 NICUs between 1997 and 2020 with gestational age <34 weeks, ≥1 culture collected in the first 3 days of life, and ≥1 serum glucose value recorded on the day of or day prior to culture collection. We used multivariable logistic regression and inverse probability weighting (IPW) and constructed models for three definitions of hypoglycemia: American Academy of Pediatrics (AAP), Pediatric Endocrine Society, and a definition based on neurodevelopmental studies.

Diagnostic Utility of Cerebrospinal Fluid White Blood Cell Components for the Identification of Bacterial Meningitis in Infants.

Background: To evaluate the diagnostic and predictive utility of cerebrospinal fluid (CSF) white blood cell (WBC) components in the diagnosis of bacterial meningitis in infants discharged from the neonatal intensive care unit (NICU).

Methods: We identified a cohort of infants discharged from a Pediatrix NICU between 1997 and 2020 who did not have an immunodeficiency, had at least 1 CSF culture collected within the first 120 days of life, and at least 1 CSF laboratory specimen obtained on the day of culture collection. We only included an infant's first CSF culture and excluded cultures from CSF reservoirs and those growing contaminants or nonbacterial organisms.

Aphasia Associated With Acute on Chronic Kidney Failure in an Adolescent.

Acute and chronic kidney disease (CKD) have known neurological associations resulting from uremia, electrolyte disturbances, comorbidities such as hypertension, or other toxin accumulation. Reversible focal neurological deficits are relatively uncommon and poorly understood sequelae of kidney disease. Herein, we describe an unusual case of an adolescent male who developed acute aphasia during his initial presentation for acute kidney injury (AKI) superimposed on progressive CKD stage 5 associated with uremia and multiple electrolyte derangements.

Development and Temporal Validation of a Machine Learning Model to Predict Clinical Deterioration.

Objectives: Early warning scores detecting clinical deterioration in pediatric inpatients have wide-ranging performance and use a limited number of clinical features. This study developed a machine learning model leveraging multiple static and dynamic clinical features from the electronic health record to predict the composite outcome of unplanned transfer to the ICU within 24 hours and inpatient mortality within 48 hours in hospitalized children.

Methods: Using a retrospective development cohort of 17 630 encounters across 10 388 patients, 2 machine learning models (light gradient boosting machine [LGBM] and random forest) were trained on 542 features and compared with our institutional Pediatric Early Warning Score (I-PEWS).

Noninvasive Ventilation or CPAP for Postextubation Support in Small Infants.

Background: Infants with a high risk of extubation failure are often treated with noninvasive ventilation (NIV) or CPAP, but data on the role of these support modalities following extubation are sparse. This report describes our experience using NIV or CPAP to support infants following extubation in our pediatric ICUs (PICUs).

Methods: We performed a retrospective study of children < 10 kg receiving postextubation NIV or CPAP in our PICUs.

Using Pharmacokinetic Modeling and Electronic Health Record Data to Predict Clinical and Safety Outcomes after Methylprednisolone Exposure during Cardiopulmonary Bypass in Neonates.

Background: Infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) frequently receive intraoperative methylprednisolone (MP) to suppress CPB-related inflammation; however, the optimal dosing strategy and efficacy of MP remain unclear.

Methods: We retrospectively analyzed all infants under 90 days-old who received intra-operative MP for cardiac surgery with CPB from 2014-2017 at our institution. We combined real-world dosing data from the electronic health record (EHR) and two previously developed population pharmacokinetic/pharmacodynamic models to simulate peak concentration (Cmax) and area under the concentration-time curve for 24 h (AUC24) for MP and the inflammatory cytokines interleukin-6 (IL-6) and interleukin-10 (IL-10).

Association Between Dead Space to Tidal Volume Ratio and Duration of Respiratory Support After Extubation in Critically Ill Children.

Background: The dead-space-to-tidal-volume ratio (V/V) has been used to successfully predict extubation failure in children who are critically ill. However, a singular reliable measure to predict the level and duration of respiratory support after liberation from invasive mechanical ventilation has remained elusive. The objective of this study was to evaluate the association between V/V and the duration of postextubation respiratory support.

Risk of in-hospital Deterioration for Children with Single Ventricle Physiology.

Children with single ventricle physiology (SV) are at high risk of in-hospital morbidity and mortality. Identifying children at risk for deterioration may allow for earlier escalation of care and subsequently decreased mortality.We conducted a retrospective chart review of all admissions to the pediatric cardiology non-ICU service from 2014 to 2018 for children < 18 years old.

Association between simulated ketamine exposures and oxygen saturations in children.

Aim: We performed a real-world data analysis to evaluate the relationship between simulated ketamine exposures and oxygen desaturation in children.

Materials & Methods: A previously developed population pharmacokinetic model was used to simulate exposures and evaluate target attainment, as well as the association with oxygen desaturation in children ≤17 years treated with intravenous ketamine.

Results: In 2022 children, there was no significant association between simulated plasma ketamine concentrations and oxygen saturation; however, a higher cumulative area under the curve was associated with increased odds of progression to significant desaturation (<85%), though magnitude of effect was small.

Association Between Pressure Support During Extubation Readiness Testing and Time to First Extubation in Children With Congenital Heart Disease.

Background: Extubation readiness testing (ERT) is often performed in children with congenital heart disease prior to liberation from mechanical ventilation. The ideal ERT method in this population is unknown. We recently changed our ERT method from variable (10, 8, or 6 cm HO, depending on endotracheal tube size) to fixed (5 cm HO) pressure support (PS).

A systematic review of clinical study evidence for pulmonary vasodilator therapy following surgery with cardiopulmonary bypass in children with CHD.

Objectives: Complications from pulmonary hypertension are one of the leading contributors to morbidity and mortality post-cardiopulmonary bypass surgery in children with CHD. Pulmonary vasodilator therapies are commonly used post-operatively, but the optimal target patient population, therapy choice, timing of therapy initiation, and duration of therapy are not well defined.

Methods: We used PubMed and EMBASE to identify studies from 2000 to 2020 investigating the use of pulmonary vasodilator therapy post-cardiopulmonary bypass in children aged 0-18 years.

Use of Real-World Data and Physiologically-Based Pharmacokinetic Modeling to Characterize Enoxaparin Disposition in Children With Obesity.

Dosing guidance for children with obesity is often unknown despite the fact that nearly 20% of US children are classified as obese. Enoxaparin, a commonly prescribed low-molecular-weight heparin, is dosed based on body weight irrespective of obesity status to achieve maximum concentration within a narrow therapeutic or prophylactic target range. However, whether children with and without obesity experience equivalent enoxaparin exposure remains unclear.

Association Between Digoxin Use and Cardiac Function in Infants With Single-Ventricle Congenital Heart Disease During the Interstage Period.

Objectives: To examine the association between digoxin use and cardiac function assessed by echocardiographic indices in infants with single-ventricle (SV) congenital heart disease (CHD) during the interstage period.

Design: Retrospective cohort study.

Setting: Fifteen North American hospitals.

Safety and Pharmacokinetics of Exebacase in an Infant With Disseminated Staphylococcus aureus Infection.

Exebacase, an antistaphylococcal lysin produced from a bacteriophage-encoded gene, is a promising adjunctive therapy for severe methicillin-resistant Staphylococcus aureus infections. We describe the first infant to receive exebacase, dosing, and pharmacokinetics. Exebacase may be safe and efficacious in children; however, further clinical trials are needed to optimize dosing.

Development and Evaluation of a Virtual Population of Children with Obesity for Physiologically Based Pharmacokinetic Modeling.

Background And Objective: While one in five children in the USA are now obese, and more than three-quarters receive at least one drug during childhood, there is limited dosing guidance for this vulnerable patient population. Physiologically based pharmacokinetic modeling can bridge the gap in the understanding of how pharmacokinetics, including drug distribution and clearance, changes with obesity by incorporating known obesity-related physiological changes in children. The objective of this study was to develop a virtual population of children with obesity to enable physiologically based pharmacokinetic modeling, then use the novel virtual population in conjunction with previously developed models of clindamycin and trimethoprim/sulfamethoxazole to better understand dosing of these drugs in children with obesity.

The relationship between simulated milrinone exposure and hypotension in children.

Introduction: Hypotension is an adverse event that may be related to systemic exposure of milrinone; however, the true exposure-safety relationship is unknown.

Methods: Using the Pediatric Trials Network multicentre repository, we identified children ≤17 years treated with milrinone. Hypotension was defined according to age, using the Pediatric Advanced Life Support guidelines.