Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator testing

AbstractOBJECTIVESWe compared the ability of inhaled nitric oxide (NO), oxygen (O2) and nitric oxide in oxygen (NO+O2) to identify reactive pulmonary vasculature in pulmonary hypertensive patients during acute vasodilator testing at cardiac catheterization.BACKGROUNDIn patients with pulmonary hypertension, decisions regarding suitability for corrective surgery, transplantation and assessment of long-term prognosis are based on results obtained during acute pulmonary vasodilator testing.METHODSIn group 1, 46 patients had hemodynamic measurements in room air (RA), 100% O2, return to RA and NO (80 parts per million [ppm] in RA). In group 2, 25 additional patients were studied in RA, 100% O2and 80 ppm NO in oxygen (NO+O2).RESULTSIn group 1, O2decreased pulmonary vascular resistance (PVR) (mean ± SEM) from 17.2 ± 2.1 U·m2to 11.1 ± 1.5 U·m2(p < 0.05). Nitric oxide caused a comparable decrease from 17.8 ± 2.2 U·m2to 11.7 ± 1.7 U·m2(p < 0.05). In group 2, PVR decreased from 20.1 ± 2.6 U·m2to 14.3 ± 1.9 U·m2in O2(p < 0.05) and further to 10.5 ± 1.7 U·m2in NO+O2(p < 0.05). A response of 20% or more reduction in PVR was seen in 22/25 patients with NO+O2compared with 16/25 in O2alone (p = 0.01).CONCLUSIONSInhaled NO and O2produced a similar degree of selective pulmonary vasodilation. Our data suggest that combination testing with NO+O2provides additional pulmonary vasodilation in patients with a reactive pulmonary vascular bed in a selective, safe and expeditious fashion during cardiac catheterization. The combination of NO+O2identifies patients with significant pulmonary vasoreactivity who might not be recognized if O2or NO were used separately

Survival after bidirectional cavopulmonary anastomosis: Analysis of preoperative risk factors

ObjectivePrognostic factors for survival after bidirectional cavopulmonary anastomosis for functionally single ventricle are not well defined. We analyzed preoperative hemodynamic and echocardiographic data to determine risk factors for death or transplantation at least 1 year after bidirectional cavopulmonary anastomosis.MethodsData for all patients who underwent bidirectional cavopulmonary anastomosis before 5 years of age at our institution from September 1995 through June 2005 were analyzed. Available preoperative echocardiograms and catheterizations were reviewed. Survivors were compared with those who died or underwent transplantation. Bivariable associations between demographic and clinical risk factors and survival status (alive without transplantation vs dead or transplanted) were assessed with Wilcoxon rank sum test and χ2 or Fisher exact tests. Survival functions were constructed with Kaplan–Meier estimates, and event times compared between subgroups with log–rank tests. Cox proportional hazard modeling was used for multivariable modeling of risk of death or transplantation.ResultsOne hundred sixty-seven patients underwent bidirectional cavopulmonary anastomosis with hemi-Fontan (n = 62) or bidirectional Glenn (n = 105) operations. Three patients died before discharge, 11 died later, and 1 has undergone transplantation. Freedom from death or transplantation after bidirectional cavopulmonary anastomosis was 96% at 1 year and 89% at 5 years. Multivariable analysis of preoperative variables showed atrioventricular valve regurgitation to be an independent risk factor for death or transplantation (hazard ratio 2.8, 95% confidence interval 1.1–7.1, P = .02).ConclusionAlthough survival after bidirectional cavopulmonary anastomosis is high, preoperative atrioventricular valve regurgitation is an important risk factor for death or transplantation

Late Status of Fontan Patients With Persistent Surgical Fenestration

ObjectivesThis study was undertaken to determine the effects of creating a systemic-to-pulmonary venous atrial-level communication (fenestration) at the time of the Fontan procedure on late outcomes.BackgroundFenestrations are frequently performed during Fontan procedures, but late consequences are not well described.MethodsPatient characteristics were compared between those with and without surgical fenestration among 536 subjects (mean age 11.9 years) enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study. The status of the fenestration and the association of a currently patent fenestration with health status and measures of ventricular performance were investigated.ResultsFenestration was performed in 361 patients (67%), and frequency differed by year and center (p < 0.001 for each). After adjustment for center, age at Fontan, year of Fontan, and prior superior cavopulmonary surgery, the fenestrated group had shorter length of Fontan hospital stay. At the time of cross-sectional testing 8 ± 3 years after Fontan, the fenestration remained open in 19% of subjects. Among those with confirmed fenestration closure, 59% were by catheter intervention and 1% by surgical intervention, and 40% had apparent spontaneous closure. Compared with those without evidence of a fenestration, subjects with a current fenestration were taking more medications (p = 0.02) and had lower resting oxygen saturation (median 89% vs. 95%, p < 0.001). Functional health status, exercise performance, echocardiographic variables, prevalence of post-Fontan stroke or thrombosis, and growth did not differ by current fenestration status.ConclusionsSurgical fenestration is associated with well-demonstrated early post-operative benefits. This cross-sectional study found few associations between a persistent fenestration and deleterious later outcomes

Survival Data and Predictors of Functional Outcome an Average of 15 Years after the Fontan Procedure: The Pediatric Heart Network Fontan Cohort

ObjectiveMulticenter longitudinal outcome data for Fontan patients surviving into adulthood are lacking. The aim of this study was to better understand contemporary outcomes in Fontan survivors by collecting follow‐up data in a previously well‐characterized cohort.DesignBaseline data from the Fontan Cross‐Sectional Study (Fontan 1) were previously obtained in 546 Fontan survivors aged 11.9 ± 3.4 years. We assessed current transplant‐free survival status in all subjects 6.8 ± 0.4 years after the Fontan 1 study. Anatomic, clinical, and surgical data were collected along with socioeconomic status and access to health care.ResultsThirty subjects (5%) died or underwent transplantation since Fontan 1. Subjects with both an elevated (>21 pg/mL) brain natriuretic peptide and a low Child Health Questionnaire physical summary score (<44) measured at Fontan 1 were significantly more likely to die or undergo transplant than the remainder, with a hazard ratio of 6.2 (2.9–13.5). Among 516 Fontan survivors, 427 (83%) enrolled in this follow‐up study (Fontan 2) at 18.4 ± 3.4 years of age. Although mean scores on functional health status questionnaires were lower than the general population, individual scores were within the normal range in 78% and 88% of subjects for the Child Health Questionnaire physical and psychosocial summary score, and 97% and 91% for the SF‐36 physical and mental aggregate score, respectively. Since Fontan surgery, 119 (28%) had additional cardiac surgery; 55% of these (n = 66) in the interim between Fontan 1 and Fontan 2. A catheter intervention occurred in 242 (57%); 32% of these (n = 78) after Fontan 1. Arrhythmia requiring treatment developed in 118 (28%) after Fontan surgery; 58% of these (n = 68) since Fontan 1.ConclusionsWe found 95% interim transplant‐free survival for Fontan survivors over an average of 7 years of follow‐up. Continued longitudinal investigation into adulthood is necessary to better understand the determinants of long‐term outcomes and to improve functional health status.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110738/1/chd12193.pd

A Population Pharmacokinetic Analysis of Milrinone in Pediatric Patients After Cardiac Surgery

The purpose of this study was to ascertain the optimal pharmacokinetic model for milrinone in pediatric patients after cardiac surgery when milrinone was administered as a slow loading dose followed by a constant-rate infusion. The data used for pharmacokinetic analysis were collected in a prospective, randomized, placebo-controlled multi-center trial of milrinone as prophylaxis for the development of low cardiac output syndrome after surgery for repair of complex congenital cardiac defects. Two blood samples were randomly collected from each patient for determination of plasma milrinone concentrations with subsequent population pharmacokinetic modeling. The pharmacokinetics of milrinone in pediatric patients under 6year's age were best described by a weight-normalized one compartment model after a slow loading dose followed by a constant-rate infusion. The volume of distribution was 482mlkg −1 , and was independent of age. Clearance was a linear function of age given by Cl=2.42mlkg −1 min −1 [1+0.0396*age].Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45063/1/10928_2004_Article_485925.pd

Capacity Building for a New Multicenter Network Within the ECHO IDeA States Pediatric Clinical Trials Network

Introduction: Research capacity building is a critical component of professional development for pediatrician scientists, yet this process has been elusive in the literature. The ECHO IDeA States Pediatric Clinical Trials Network (ISPCTN) seeks to implement pediatric trials across medically underserved and rural populations. A key component of achieving this objective is building pediatric research capacity, including enhancement of infrastructure and faculty development. This article presents findings from a site assessment inventory completed during the initial year of the ISPCTN. Methods: An assessment inventory was developed for surveying ISPCTN sites. The inventory captured site-level activities designed to increase clinical trial research capacity for pediatrician scientists and team members. The inventory findings were utilized by the ISPCTN Data Coordinating and Operations Center to construct training modules covering 3 broad domains: Faculty/coordinator development; Infrastructure; Trials/Research concept development. Results: Key lessons learned reveal substantial participation in the training modules, the importance of an inventory to guide the development of trainings, and recognizing local barriers to clinical trials research. Conclusions: Research networks that seek to implement successfully completed trials need to build capacity across and within the sites engaged. Our findings indicate that building research capacity is a multi-faceted endeavor, but likely necessary for sustainability of a unique network addressing high impact pediatric health problems. The ISPCTN emphasis on building and enhancing site capacity, including pediatrician scientists and team members, is critical to successful trial implementation/completion and the production of findings that enhance the lives of children and families

Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots

Trimethoprim-sulfamethoxazole (TMP-SMX) is an antimicrobial drug combination commonly prescribed in children and adults. The study objectives were to validate and apply an HPLC–MS/MS method to quantify TMP-SMX in dried plasma spots (DPS) and dried urine spots (DUS), and perform a comparability analysis with liquid matrices

Active vs Traditional Methods of Recruiting Children for a Clinical Trial in Rural Primary Care Clinics: A Cluster-Randomized Clinical Trial

Importance: To our knowledge, there are no published randomized clinical trials of recruitment strategies. Rigorously evaluated successful recruitment strategies for children are needed. Objective: To evaluate the feasibility of 2 recruitment methods for enrolling rural children through primary care clinics to assess whether either or both methods are sufficiently effective for enrolling participants into a clinical trial of a behavioral telehealth intervention for children with overweight or obesity. Design, setting, and participants: This cluster-randomized clinical trial of 2 recruitment methods was conducted at 4 primary care clinics in 4 separate states. Each clinic used both recruitment methods in random order. Clinic eligibility criteria included at least 40% pediatric patients with Medicaid coverage and at least 100 potential participants. Eligibility criteria for children included a rural home address, age 6 to 11 years, and body mass index at or above the 85th percentile. Recruitment began February 3, 2020, and randomization of participants occurred on August 17, 2020. Data were analyzed from October 3, 2021, to April 21, 2022. Interventions: Two recruitment methods were assessed: the active method, for which a list of potential participants seen within the past year at each clinic was generated through the electronic health record and consecutively approached by research staff based on visit date to the clinic, and the traditional method, for which recruitment included posters, flyers, social media, and press release. Clinics were randomized to the order in which the 2 methods were implemented in 4-week periods, followed by a 4-week catch-up period using the method found most effective in previous periods. Main outcomes and measures: For each recruitment method, the number and proportion of randomized children among those who were approached was calculated. Results: A total of 104 participants were randomized (58 girls [55.8%]; mean age, 9.3 [95% CI, 9.0-9.6] years). Using the active method, 535 child-parent dyads were approached and 99 (18.5% [95% CI, 15.3%-22.1%]) were randomized. Using the traditional method, 23 caregivers expressed interest, and 5 (21.7% [95% CI, 7.5%-43.7%]) were randomized. All sites reached full enrollment using the active method and no sites achieved full enrollment using the traditional method. Mean time to full enrollment was 26.3 (range, 21.0-31.0) days. Conclusions and relevance: This study supports the use of the active approach with local primary care clinics to recruit children with overweight and obesity from rural communities into clinical trials