OBJECTIVE:Single-use supplies stored in bedside supply carts with paper packaging cannot be wiped with disinfectants. We aimed to determine the prevalence of pathogens on these unused supplies. DESIGN:Prospective study over 7 weeks in 2025. SETTING:Two pediatric ICUs at a university affiliated children's hospital. PATIENTS:The unit of analysis was the bedside supply cart from each discharged ICU patient. INTERVENTIONS:One swab was used to swab three supply items contained in a single drawer in a room's bedside cart. Carts had two drawers sampled, each with a swab for bacterial culture and respiratory viral nucleic acid amplification testing (NAAT). RESULTS:Paper-packaged supply items (n = 840) from 70 consecutive bedside carts were swabbed after patient discharge. All bacterial swabs had no growth of pathogen [0/140 (0%), 95% CI 0%, 2.3%)]. A non-pathogen was cultured from 8/140 (5.7%) swabs [7/70 (10.0%) carts], most with scant growth [7/8 (87.5%) only one colony]. Non-pathogens (common commensal skin and oral flora) included coagulase-negative staphylococci (n = 5), Actinomyces oris (n = 1), aerobic spore-forming Bacillus (n = 1), and viridans group streptococcus [non-anginosus] (n = 1). Of viral swabs, 3/140 (2.1%, 95% CI 0.5%, 6.4%) were NAAT positive (3/70 (4.3%) carts). Room isolation status, length of stay, and ICU were not associated with a positive bacterial or viral swab. CONCLUSIONS:Bacterial pathogen detection on supplies, a necessary step in transmission, was extremely low. Viral NAAT detection on supplies was low and likely exaggerated the risk of fomite transmission, as whether there was viable virus at sufficient concentration to transmit infection is unknown.

Achieving antibiotic pharmacodynamic targets is critical to surviving sepsis. The purpose of this study was to determine the achievement of pharmacodynamic target-free minimum plasma concentration (fCmin)-during the first 2 days of high-dose 6-h intravenous meropenem or piperacillin-tazobactam in critically ill children, and to identify its predictors. This was a prospective observational study conducted in two pediatric intensive care units of children admitted between 2022 and 2023 who were prescribed meropenem or piperacillin-tazobactam. Primary outcomes were achievement of pharmacodynamic target fCmin (defined as fCmin>MIC or fCmin>4×MIC). Secondary outcomes included predictors of target concentrations and time to resolution of signs of severe infection using univariate and multivariable regressions. Of 49 patients, 47 had an antibiotic concentration measured at 24 h, and 38 at 48 h. At 24 h, 48 h, or either time point, augmented renal clearance (ARC) occurred in 13/30 (43%), 14/22 (64%), and 17/30 (57%), respectively. For epidemiologic cutoff values, fCmin>MIC occurred in 17/47 (36%) and 13/38 (34%) at 24 and 48 h, and fCmin>4×MIC occurred in 3/47 (6%) and 4/38 (11%). Target tazobactam concentrations (fCmin>0.5 or >2mg/L) occurred in 48% or 64% of the patients and 28% or 39% of the patients at 24 and 48 h. Potentially neurotoxic concentrations occurred in 1/9 (11%) patients on meropenem at 48 h, and in none receiving piperacillin-tazobactam. Only ARC independently predicted not achieving fCmin>MIC at 48 h (odds ratio 0.04 [95% CI 0.00, 0.69] P = 0.026). Therapeutic antibiotic concentration did not predict the time to resolution of severe symptoms and signs of sepsis (n = 32). In this cohort of critically ill children, high doses of piperacillin-tazobactam or meropenem did not often achieve pharmacodynamic targets and were rarely toxic.

OBJECTIVE:To determine whether the severity of pulmonary hypertension (PH), assessed at cardiac catheterization, is associated with bronchopulmonary dysplasia (BPD) severity and mortality. STUDY DESIGN:We analyzed clinical data from subjects with BPD-PH enrolled in the PPHNet Registry between 2014 and 2024. BPD severity was based on the Neonatal Research Network grading system at 36 weeks postmenstrual age. Survival and clinical associations were estimated using Cox proportional hazards regression with delayed entry-to-risk-set and competing risk methodologies. RESULTS:The study included 320 subjects (gestational age, 25.8 ± 2.0 weeks (range 22.2 to 31.6 weeks); postnatal age 5.0 months (IQR 3.3, 8.6; range birth to 12 years) at the time of PH diagnosis. The severity of BPD was 27% (grade 1), 44% (grade 2), and 29% grade 3. Twenty-two percent (n = 69) of subjects underwent cardiac catheterization within 1 month of echocardiographic diagnosis of PH. Hemodynamic features by cardiac catheterization were similar between grades of BPD severity. Five-year survival postdiagnosis was 94%, 94%, and 87%, respectively, for Grades 1, 2, and 3 BPD. Twenty-five of 320 (8%) subjects died, including 6 with pulmonary vein stenosis. CONCLUSIONS:Among subjects with BPD-PH undergoing cardiac catheterization, more deaths occurred among children with Grade 3 BPD. However, there were no substantive differences in invasive measurements of pulmonary hemodynamics based on BPD severity.

The six-minute walk test (6MWT) is a common method to assess submaximal exercise capacity in children and adults with pulmonary arterial hypertension (PAH) and other chronic diseases. There is no guideline specifically for 6MWT in children. In this observational pilot study, we evaluated the impact of procedural variations on the outcome of the 6MWT in the real-world clinical setting at pediatric PAH programs. We collected 6MWT data from 33 children with PAH participating in a multicenter, prospective, non-interventional study. Data range/quantiles and standard deviation (SD) were used to describe distribution of the six-minute walk distance (6MWD) and data variability. Levene’s test was used to test for heterogeneity of variance with the two sites of similar altitude and their age/height/weight-matched Panama Function Class II participants. We analyzed all 33 eligible participants and their qualified first walks at five centers (A-E) with 6MWD ranges of 420–570, 357–683, 418–481, 400–700, 377–549 m, respectively. Site D performed the 6MWT in a busy hallway and allowed parental/caregiver’s cheering, while Site E performed the 6MWT in a secluded area with no parental/caregiver involvement. Mean 6MWD and SD for Sites D and E were 547 (125) and 432 (67.5) meters, respectively (p = 0.03). In conclusion, procedural variations seem to associate with 6MWD data variability. Although interpretation of our results is limited by the small sample size, our findings suggest that standardizing pediatric 6MWT procedures are needed. Graphical Abstract

OBJECTIVE:To investigate the feasibility of using actigraphy to measure physical activity (pA) and heart rate variability (HRV) as study endpoints in pediatric pulmonary arterial hypertension (PAH) and to compare their performance to 6-minute-walk distance (6MWD), a common primary endpoint used in PAH clinical trials in adults and children who can walk and understand the test process. STUDY DESIGN:We conducted a prospective, multicenter, noninterventional study in pediatric PAH patients and healthy children. Actiheart and Fitbit Charge 2 recorded pA and heart rate data. HRV was defined as SD of daily heart rate. Actigraphy pA and HRV and 6MWD from the same subjects were analyzed to compare children with PAH with controls, and Panama functional classification (FC) III vs II. Power/sample size simulations were conducted to detect hypothetical treatment effect equivalent to differences seen between FC III and FC II. RESULTS:We enrolled 116 children: 90 and 98 adhered with Actiheart and Fitbit, respectively. Actigraphy daily pA was ∼36% lower (P < .05) and daily HRV was ∼18% lower (P < .05) in children with PAH (n = 62) than healthy controls (n = 54). Daily pA and daily HRV trended ∼17% lower in FC III than FC II, whereas 6MWD showed little difference. Simulation at 80% power showed that pA required 175 subjects per group and HRV required 40 per group to detect the difference/effect, whereas 6MWD required over our maximum sample size of 200. CONCLUSIONS:Actigraphy is a feasible measure in pediatric PAH. Compared with 6MWD, pA and HRV may be more sensitive in differentiating Panama FC III from II. HRV may improve actigraphy's utility in pediatric PAH.

Pulmonary vasodilator treatment can improve hemodynamics, right ventricular function, symptoms, and survival in pediatric pulmonary hypertension (PH). However, clinical trial data are lacking due to many constraints. One major limitation is the lack of relevant trial endpoints reflective of hemodynamics or functional status in patients in whom standard exercise testing is impractical, unreliable, or not reproducible. The Kids Mod PAH trial (Mono- vs. Duo Therapy for Pediatric Pulmonary Arterial Hypertension) is an ongoing multicenter, Phase III, randomized, open-label, pragmatic trial to compare the safety and efficacy of first-line combination therapy (sildenafil and bosentan) to first-line monotherapy (sildenafil alone) in 100 pediatric patients with PH across North America. Investigators will measure participants' physical activity with a research-grade, wrist-worn actigraphy device at multiple time points as an exploratory secondary outcome. Vector magnitude counts per minute and activity intensity will be compared between the treatment arms. By directly and noninvasively measuring physical activity in the ambulatory setting, we aim to identify a novel, simple, inexpensive, and highly reproducible approach for quantitative assessment of exercise tolerance in pediatric PH. These data will increase the field's understanding of the effect of pulmonary vasodilator treatment on daily activity - a quantitative measure of functional status and wellbeing in pediatric PH and a potential primary outcome for future clinical trials in children with cardiopulmonary disorders.

Pulmonary hypertension (PH) is a significant health problem that contributes to high morbidity and mortality in diverse cardiac, pulmonary, and systemic diseases in children. Evidence-based advances in PH care have been challenged by a paucity of quality endpoints for assessing clinical course and the lack of robust clinical trial data to guide pharmacologic therapies in children. While the landmark adult AMBITION trial demonstrated the benefit of up-front combination PH therapy with ambrisentan and tadalafil, it remains unknown whether upfront combination therapy leads to more rapid and sustained clinical benefits in children with various categories of PH. In this article, we describe the inception of the Kids Mod PAH Trial, a multicenter Phase III trial, to address whether upfront combination therapy (sildenafil and bosentan vs. sildenafil alone) improves PH outcomes in children, recognizing that marked differences between the etiology and therapeutic response between adults and children exist. The primary endpoint of this study is WHO functional class (FC) 12 months after initiation of study drug therapy. In addition to the primary outcome, secondary endpoints are being assessed, including a composite measure of time to clinical worsening, WHO FC at 24 months, echocardiographic assessment of PH and quantitative assessment of right ventricular function, 6-min walk distance, and NT-proBNP levels. Exploratory endpoints include selected biomarkers, actigraphy, and assessments of quality of life. This study is designed to pave the way for additional clinical trials by establishing a robust infrastructure through the development of a PPHNet Clinical Trials Network.

IntroductionThe clinical deterioration commonly experienced by pediatric patients with pulmonary arterial hypertension (PAH) has motivated a shift in the treatment of pulmonary hypertension (PH) through innovations in surgical salvage interventions. The Occlutech fenestrated atrial septal defect (FASD) Occluder and the atrial flow regulator (AFR), which provides a protective, atrial-level shunt during hypertensive crises, have found an important role in treating pediatric patients with PAH. Other groups of pediatric patients with PH may also benefit from a similar protective physiology. The primary aim of this work is to present a single center's experience with AFR and FASD devices for managing a heterogeneous group of pediatric PH patients. A secondary goal is to identify hemodynamic changes and complications following device implantation.Materials and MethodsWe performed a retrospective review of all pediatric PH patients who, after being found suitable, either successfully or unsuccessfully received an FASD or AFR device between January 2015 and December 2021 at the Stollery Children's Hospital in Edmonton, Canada.ResultsFourteen patients (eight female) with a median age of 4.6 (range 0.3–17.9) years and a median body mass index of 15.1 (Q1 = 13.8, Q3 = 16.8) kg/m2 underwent device implantation: five received FASDs, eight received AFRs, and one was ultimately unable to receive an implant due to thrombosed iliac vessels and required surgical intervention. Of the fourteen patients, seven were in group 1 (PAH), one was in group 3 (lung disease), and six were in group 5 (primarily pulmonary hypertension vascular disease) under the World Symposium PH classification. All patients were on mono-, dual-, or triple-drug PH therapy. Device stabilization was not possible for two patients, who then required a repeat catheterization. Of the group 1 patients, three AFR and three FASD implants were successful, while one FASD implant was unsuccessful due to thrombosed vessels. At a six-month clinical assessment, all group 1 patients had patent devices and improved WHO FCs.ConclusionThis work presents a single center's experience with AFR and FASD implants in a heterogeneous group of fourteen pediatric patients with severe PH. This treatment strategy is novel in the pediatric population and so this work provides momentum for future studies of interventional cardiac catheterization procedures for pediatric patients with PH. Further collaborations are required to develop criteria to identify ideal pediatric candidates and optimally time interventions in order to maximize the benefits of this treatment.

EDITORIAL article Front. Pediatr., 25 May 2023Sec. Pediatric Cardiology Volume 11 - 2023 | https://doi.org/10.3389/fped.2023.1220070

IntroductionSelexipag, an oral nonprostanoid prostaglandin receptor agonist, has led to reduced morbidity and mortality in adults with pulmonary arterial hypertension (PAH). While the adult literature has been extrapolated to suggest selexipag as an oral treatment for severe pediatric pulmonary hypertension (PH), longitudinal, multicenter data on the benefits of selexipag in this population are lacking. The purpose of this study is to present a longitudinal, multicentre experience with selexipag in a relatively large cohort of pediatric PH patients and add to the existing selexipag literature.Materials and methodsWe performed a retrospective, multicenter review describing the clinical outcomes of pediatric PH patients receiving selexipag in addition to standard oral pulmonary vasodilator therapy across three Canadian centers between January 2005 and June 2021.ResultsTwenty-four pediatric patients (fifteen female) with a mean age of 9.7 (range 2.0–15.5) years were included. Of this cohort, eighteen (75.0%) were in group 1, one (4.2%) was in group 2, four (16.7%) were in group 3, and one (4.2%) was in group 4. Twenty-two (91.7%) patients were on dual PH therapy after six months. Dosing was targeted to achieve 20–30 mcg/kg/dose orally every twelve hours. Median dose after twelve months was 30 mcg/kg/dose. Twelve months following selexipag initiation, median decreases of 0.2 cm in tricuspid annular plane systolic excursion, 3.5 mmHg in right-ventricular systolic pressure, and 6.1 mmHg in mean pulmonary arterial pressure were observed; none of these changes were statistically significant. Three patients died, one clinically deteriorated and required admission to a pediatric intensive care unit, ten had gastrointestinal symptoms, and three had flushing.ConclusionSelexipag appears to be a safe and effective adjunctive therapy for pediatric PH patients and has a tolerable adverse effect profile aside from gastrointestinal disturbances. Additional prospective studies of changes in hemodynamics and functional classification over a longer period and with a larger sample are needed. Future research should aim to identify subgroups that stand to benefit from the addition of selexipag as well as optimal timing and dosing for the pediatric population.

Pulmonary arterial hypertension (PAH) is a disease characterized by pathological remodeling of the pulmonary vasculature causing elevated pulmonary artery pressures and ultimately, right ventricular failure from chronic pressure overload. Heterozygous pathogenic GDF2 (encoding bone morphogenetic protein 9 (BMP9)) variants account for some (>1%) adult PAH cases. Only three pediatric PAH cases, harboring homozygous or compound heterozygous variants, are reported to date. Ultra-rare pathogenic GDF2 variants are reported in hereditary hemorrhagic telangiectasia and overlapping disorders characterized by telangiectasias and arteriovenous malformations (AVMs). Here, we present two siblings with PAH homozygous for a GDF2 mutation that impairs BMP9 proprotein processing and reduces growth factor domain availability. We confirm an absence of measurable plasma BMP9 whereas BMP10 levels are detectable and serum-dependent endothelial BMP activity is evident. This contrasts with the absence of activity which we reported in two children with homozygous pathogenic GDF2 nonsense variants, one with PAH and one with pulmonary AVMs, both with telangiectasias, suggesting loss of BMP10 and endothelial BMP activity in the latter may precipitate telangiectasia development. An absence of phenotype in related heterozygous GDF2 variant carriers suggests incomplete penetrance in PAH and AVM-related diseases, indicating that additional somatic and/or genetic modifiers may be necessary for disease precipitation.

Objective To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syn-drome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry.Study design We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome.Results Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49 year (IQR, 0.21-1.77 years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syn-drome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspira-tion (31%). Pulmonary hypertension resolved in 43% after 3 years, associated with a diagnosis of pulmonary hyper-tension at age <6 months (54% vs 29%; P = .002) and a pretricuspid shunt (65% vs 38%; P = .02). Five-year transplantation-free survival was 88% (95% CI, 80%-97%). Tracheostomy (hazard ratio [HR], 3.29; 95% CI, 1.61-6.69) and reflux medication use (HR, 2.08; 95% CI, 1.11-3.90) were independently associated with a compos-ite outcome of severe pulmonary hypertension.Conclusions Despite high rates of cardiac and respiratory comorbidities that influence the severity of pulmonary hypertension, children with Down syndrome-associated pulmonary hypertension generally have a survival rate similar to that of children with non-Down syndrome-associated pulmonary hypertension. Resolution of pulmonary hyperten-sion is common but reduced in children with complicated respiratory comorbidities. (J Pediatr 2023;252:131-40).

Rationale: Hemodynamic assessments direct care among children with pulmonary hypertension, yet the use of cardiac catheterization is highly variable, which could impact patient care and research. Objectives: We analyzed hemodynamic findings from right heart catheterization (RHC) and left heart catheterization and acute vasodilator testing (AVT) and the safety of catheterization in children with World Symposium on Pulmonary Hypertension (WSPH) group 1 and 3 subtypes in a large multicenter North American cohort. Methods: Of 1,475 children enrolled in the Pediatric Pulmonary Hypertension Network Registry (2014-2020), there were 1,383 group 1 and 3 patients, of whom 671 (48.5%) underwent RHC at diagnosis and were included for analysis. Results: Compared with those without diagnostic RHC, these children were older, less likely to be an infant or preterm, more often female, treated with targeted pulmonary hypertension medications at diagnosis, and had advanced World Health Organization functional class. Catheterization was performed without a difference in complication rates between WSPH groups. Pulmonary capillary wedge pressure was well correlated with left ventricular end-diastolic pressure and left atrial pressures. Results of AVT using three different methods were comparable; positive AVT results were observed in 8.0-11.8% of subjects, did not differ between WSPH groups 1 and 3, and were not associated with freedom from the composite endpoint of lung transplantation or death during follow-up. Conclusions: In a large pediatric pulmonary hypertension cohort, diagnostic RHC with or without left heart catheterization in WSPH group 1 and 3 patients was performed safely at experienced pediatric pulmonary hypertension centers. Hemodynamic differences were noted between group 1 and 3 subjects. Higher mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean systemic arterial pressure ratio were associated with a higher risk of death/transplantation. Findings suggest overall safety and potential value of RHC as a standard diagnostic approach to guide pulmonary hypertension management in children.

Background There are limited data about the range of diseases, natural history, age-appropriate end-points and optimal care for children with pulmonary hypertension (PH), including the need for developing high-quality patient registries of children with diverse forms of PH to enhance care and research. Our objective was to characterise the distribution and clinical features of diseases associated with paediatric PH, including natural history, evaluation, therapeutic interventions and outcomes, as defined by the World Symposium on Pulmonary Hypertension (WSPH) classification. Methods 1475 patients were enrolled into a multisite registry across the Pediatric Pulmonary Hypertension Network (PPHNet), comprised of eight interdisciplinary PH programmes. Results WSPH Groups 1 (pulmonary arterial hypertension (PAH)) and 3 (lung or hypoxia-related PH) were the most common primary classifications (45% and 49% of subjects, respectively). The most common Group 3 conditions were bronchopulmonary dysplasia and congenital diaphragmatic hernia. Group 1 disease was predominantly associated with congenital heart disease (60% of Group 1 cases) and idiopathic PAH (23% of Group 1 cases). In comparison with Group 1, Group 3 subjects had better disease resolution (hazard ratio 3.1; p<0.001), tended to he younger at diagnosis (median (interquartile range) age 0.3 (0.0-0.6) versus 1.6 (0.1-6.9) years; p<0.001) and were more often male (57% versus 45%; p<0.001). Down syndrome, the most common genetic syndrome in the PPHNet Registry, constituted 11% of the entire PH cohort. Conclusions We find a striking proportion of paediatric PH patients with Group 3 disorders, reflecting the growing recognition of PH in diverse developmental lung diseases. Greater precision of clinical phenotyping based on disease-specific characterisation may further enhance care and research of paediatric PH.

AbstractPediatric pulmonary hypertension (PH) is a severe, life‐threatening disease associated with diverse cardiac, pulmonary, and systemic disorders, which generally requires expertise from multiple disciplines for management. Unfortunately, expert centers are limited, often due to inadequate resources or unfamiliarity with needed components for success. The Pediatric Pulmonary Hypertension Network (PPHNet) includes expert centers in North America specifically dedicated to advancing the field of pediatric PH through research and excellent clinical care. PPHNet member sites were queried for valuable program components and these findings were discussed for consensus. Here we provide a collective overview of key elements of an optimal pediatric PH program: team composition, access to services, and commitment to education. It is our intention that this document will assist newer and/or smaller programs identify avenues and resources for growth and provide avenues for collaboration.

Background VAD support for early graft failure after HTx is a rare event in pediatrics. Methods We retrospectively describe our single-center experience with post-HTx VAD support in a cohort of patients transplanted between 01/05 and 12/20. Results Nine patients underwent VAD insertion in the early post-HTx period [median age 6.1 years (Range 0.3-20.3), median weight 17.6 kg (Range 3.5-65.0), and congenital heart disease (67%)]. Of the nine patients with early graft failure, almost half (44%) were implanted after 2015 and all of these patients had a pre-HTx plan for possible post-transplant VAD insertion. Time to VAD implant was a median of 0 day (Range 0-11). Total time on VAD support was a median of 12 days (Range 3.0-478.0). Two-thirds (n = 6; 67%) of the patients were weaned from support, retransplanted (11%) and two patients died (22%). In all of the patients where post-HTx VAD was anticipated there was 100% survival. Conclusions In this small patient series, post-HTx VAD was a useful measure in selected patients especially with pre-HTx planning. However, more shared experiences to verify these findings are needed.

Ventricular assist devices (VADs) are an increasingly common therapy for end-stage heart failure across all ages as a bridge to recovery or transplant and more recently as destination therapy. With increasing experience and difficulties with establishing therapeutic heparin levels, we have begun to explore the effectiveness of direct thrombin inhibitors in this patient population. This is a retrospective review of all long-term VAD patients, both adult and pediatric, who were anticoagulated with bivalirudin between January 2009 and January 2016. The starting dose was 0.3 mg/kg/hr, and dose was titrated for a goal partial thromboplastin time (PTT) of 70–100. There were 14 patients (13 males, 5 ≤18 years) with 17 episodes of bivalirudin therapy. The median age on initiation was 45 years (range, 15 days–67 years) with 10 episodes associated with a HeartWare HVAD, five a HeartMate II, and two with a Berlin Heart EXCOR. The predominant indication of bivalirudin therapy was suspected pump thrombosis (13/17). The median time from VAD insertion to initiation of bivalirudin was 116 days (range, 3–1,870) with the median duration of therapy being 21 days (range, 3–113). In patients with pump thrombosis, the mean baseline lactate dehydrogenase (LDH) was 229 ± 64 U/L, peak 690 ± 380 U/L, and decreased to 330 ± 243 U/L when bivalirudin was stopped. The outcomes following suspected pump thrombosis included: transitioned to warfarin (n = 7), death in two destination therapy patients who did not undergo pump exchange, transplantation (n = 2), and pump exchange (n = 2). A major bleeding complication occurred in only one patient. Our experience highlights the potential use of bivalirudin in a heterogenous VAD population. Although these initial results suggest some potential role for direct thrombin inhibitors for use in long-term VADs, larger prospective studies are required to support these preliminary observations and to determine who may benefit from direct thrombin inhibitors (DTIs) and the side effect profile in this patient population.

Introduction: Use of prostacyclins in the treatment of severe pediatric pulmonary arterial hypertension (PAH) has increased significantly over the past three decades. Chronic IV or SC administratio...

Post-operative infections in pediatric cardiac surgery are an ongoing clinical challenge, with rates between 1 and 20%. Perioperative antibiotics remain the standard for prevention of surgical-site infections, but the type of antibiotic and duration of administration remain poorly defined. Current levels of practice variation through informal surveys are very high. Rates of antibiotic-resistant organisms are increasing steadily around the world. We will identify all controlled observational studies and randomized controlled trials examining prophylactic antibiotic use in pediatric cardiac surgery. Data sources will include MEDLINE, EMBASE, CENTRAL, and proceedings from recent relevant scientific meetings. For each included study, we will conduct duplicate independent data extraction, risk of bias assessment, and evaluation of quality of evidence using the GRADE approach. We will report the results of this review in agreement with the PRISMA statement and disseminate our findings at relevant critical care and cardiology conferences and through publication in peer-reviewed journals. We will use this systematic review to inform clinical guidelines, which will be disseminated in a separate stand-alone publication. PROSPERO CRD42016052978C