Comprehensive linear and nonlinear heart rate variability normative data in children.

BACKGROUND: The autonomic nervous system (ANS) is critical in regulating involuntary bodily functions, including heart rate. Heart rate variability (HRV) reflects the complex interplay between the ANS and humoral factors, making it a valuable noninvasive tool for assessing autonomic function. While HRV has been extensively studied in adults, normative data for HRV in children, primarily based on long-term rhythm recordings, are limited. OBJECTIVE: This study aimed to establish comprehensive normative data for HRV in children. METHODS: In this retrospective study, we examined 24-h Holter monitors of children aged 1 day to 18 years, divided into six age groups, at Nemours Children's Health in Orlando, Florida, spanning the years 2013-2023. HRV analysis encompassed time-domain, frequency-domain, and nonlinear indices. RESULTS: Holter data for a total of 247 patients in six age groups were included. An age-related uptrend was observed in all time- and frequency-domain variables except the normalized unit of low-frequency power. Entropy analysis revealed contradictory results among different entropy techniques. Sample and approximate entropy analyses were consistent and showed less complexity and more predictability of HRV with decreasing heart rate, while Shannon entropy analysis showed the opposite. Fractal detrended fluctuation analysis exhibited significant decreases across the age groups, suggestive of diminishing self-similarity of HRV patterns. CONCLUSION: Control of heart rate and HRV is a highly complex process and requires further study for a better understanding. It seems that no single parameter can fully elucidate the entire process. A combination of time-domain, frequency-domain, and nonlinear indices may be necessary to explain HRV behavior in the growing body.

Single-Center Experience Using the Cardiohelp System for Neonatal and Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) systems have continued to evolve and improve with the development of smaller and portable systems. The Cardiohelp (Maquet Getinge Cardiopulmonary AG, Rastatt, Germany) portable life support device is a compact ECMO system used widely in adults and for ECMO transport. Reports of its use in neonatal and pediatric centers remain limited. In this single-center retrospective review, we describe our institutional experience with the Cardiohelp. DESIGN: Single-center retrospective review. SETTING: Neonatal ICUs and PICUs in a tertiary-care children's hospital. PATIENTS: Seventeen pediatric patients on ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Median (interquartile range, IQR) of patient age was 0.5 years (0-7 yr). Eleven of 17 patients were on veno-arterial ECMO, five on veno-venous ECMO, and one on veno-venoarterial ECMO. All veno-venous and veno-venoarterial runs ( n = 6) were accomplished with bicaval, dual-lumen cannulae. Median duration on Cardiohelp was 113 hours (IQR 50-140 hr). Median anti-Xa level for patients was 0.43 IU/mL (IQR 0.35-0.47 IU/mL), with median heparin dose of 23.6 U/kg/hr (IQR 17.6-28.1 U/kg/hr). Median plasma-free hemoglobin was 41.4 mg/dL (IQR 30-60 mg/dL). Circuit change was required in three cases. Fourteen patients survived ECMO, with 13 patients surviving to discharge. CONCLUSIONS: We have used the Cardiohelp system to support 17 neonatal and pediatric ECMO patients, without complications. Further studies are warranted to compare complications, outcomes, and overall cost with other institutions and other existing ECMO systems.

Pediatric extracorporeal life support for refractory status asthmaticus: ELSO Registry trends from the past decade.

BACKGROUND: Extracorporeal life support (ECLS) for status asthmaticus (SA) is rare. Increased safety and experience may increase utilization of ECLS for SA. METHODS: We reviewed pediatric (<18 years old) patients requiring ECLS for SA between 1998 and 2019 within the Extracorporeal Life Support Organization (ELSO) Registry and Nemours Children's Health (NCH) system. We compared patient characteristics, pre-ECLS medications, clinical data, complications, and survival to discharge between Early (1988-2008) and Late (2009-2019) eras. RESULTS: From the ELSO Registry, we identified 173 children, 53 in Early and 120 in Late eras, with primary diagnosis of SA. Pre-ECLS hypercarbic respiratory failure was similar between eras (median pH 7.0 and pCO2 111 mm Hg). Venovenous mode (79% vs. 82%), median ECLS time (116 vs. 99 h), time to extubation (53 vs. 62 h), and hospital survival (89% vs. 88%) also remained similar. Intubation to cannulation time significantly decreased (20 vs. 10 h, p = 0.01). ECLS without complication occurred more in the Late era (19% vs. 39%, p < 0.01), with decreased hemorrhagic (24% vs. 12%, p = 0.05) and noncannula-related mechanical (19% vs. 6%, p = 0.008) complications. Within NCH, we identified six Late era patients. Pre-ECLS medication favored intravenous beta agonists, bronchodilators, magnesium sulfate, and steroids. One patient died from neurological complications following pre-ECLS cardiac arrest. CONCLUSIONS: Collective experience supports ECLS as a rescue therapy for pediatric SA. Survival to discharge remains good, and complication rates have improved. Pre-ECLS cardiac arrest may potentiate neurologic injury and impact survival. Further study is needed to evaluate causal relationships between complications and outcomes.

The Effect of Cardiac Mass and Venous Return in Children with Postural Orthostatic Tachycardia Syndrome: A Prospective, Observational Study.

Low left ventricular mass index (LVMI) is thought to limit exercise tolerance in adult patients with postural orthostatic tachycardia syndrome (POTS). This finding has not been studied in children. We evaluated the effect of LVMI and hemodynamics at baseline and during exercise in POTS versus controls. POTS and control subjects aged 12-18 years were prospectively enrolled. POTS patients underwent autonomic studies. An echocardiogram was performed on all patients at baseline and during exercise. LVMI, venous return from inferior vena cava (IVC-VTI), left ventricular dimension, and cardiac output were assessed at baseline and during exercise. Generalized linear modeling with mixed effects was used to perform repeated measures testing between POTS and controls. Eighteen POTS patients (14 female, aged 15.4 ± 1.4 years) and nine control subjects (six female, aged 15.0 ± 1.3 years; p = 0.44) were enrolled. At baseline, LVMI was similar in both groups. During exercise, IVC-VTI, left ventricular end-diastolic dimension and volume, and stroke volume were lower in POTS patients. Peak heart rate was higher in POTS patients, but cardiac output was similar in both groups. Exercise time was higher in the control group (11.4 ± 2.7 min vs 9.2 ± 2.1, p = 0.024). Lower venous return resulted in smaller cardiac dimension and stroke volume during exercise. Higher heart rate in POTS may compensate to achieve similar cardiac output compared with control subjects. Lower ventricular filling and earlier time to peak heart rate may explain lower exercise capacity in pediatric POTS.

Idiopathic Pericardial Effusions in Children: Workup and Final Diagnoses.

Pediatric idiopathic pericardial effusions are common and often have a prolonged clinical course. We hypothesized that these effusions have no standardized diagnostic workup, and ultimately have a final etiology not initially appreciated. To test these hypotheses, a hospital system-wide retrospective (1/1/1990-10/1/2019) cohort study of pericardial effusions in children (< 18 years) was conducted. Effusions were grouped by etiology and patients receiving an initial idiopathic diagnosis were further analyzed. Effusion size, diagnostic workup, final diagnosis, and time to resolution were abstracted. In total, 42/366 effusions were initially diagnosed as idiopathic. Workup was not standardized and included up to six laboratory tests including pericardial fluid analysis and infectious, metabolic, rheumatologic and thyroid workups. Treatment course involved 1 readmission in 24%, and > 1 readmission in 12%. Resolution of effusion occurred in 83% of patients within a median of 1 admission (range 1-4). Of those effusions initially deemed idiopathic, 12/42 (29%) were later found to have an underlying etiologic diagnosis including: autoimmune (7, 58%), neoplastic (2, 16%), infectious (2, 16%), and renal (1, 8%). Children initially diagnosed with idiopathic pericardial effusions have an underlying etiologic diagnosis 29% of the time, and a standardized workup may prevent delays in definitive diagnosis and treatment.

Comparison Between Physicians' and Nurse Practitioners' Resource Utilization in the Diagnosis and Management of Bronchiolitis in the Pediatric Emergency Department.

OBJECTIVE: This study aimed to describe the resource utilization of nurse practitioners (NPs) in the pediatric emergency department (ED) and compare among physicians. METHODS: A retrospective cross-sectional study of secondary data analysis in a level 1 academic pediatric trauma center was conducted. Patients were aged 1 to 24 months, evaluated in the ED between January 1, 2014, and November 30, 2018, with a diagnosis of bronchiolitis or wheezing. Data included age group, length of stay, disposition, diagnostic tests (chest radiography [CXR], viral testing, respiratory syncytial virus test), treatment (bronchodilator, corticosteroid, antibiotic), and medical provider (physician, NP, combination of both). Resources were evaluated before (early era) and after (late era) the implementation of an institutional clinical practice guideline.Comparisons between groups were done through χ2, Fisher exact, or Kruskal-Wallis test, as appropriate. RESULTS: A total of 5311 cases were treated by a physician (65.3%), an NP (30.3%), or a combination of both (4.3%). The was a difference in the use of CXR, respiratory syncytial virus testing, bronchodilators, and corticosteroids among providers (P = 0.001). In the late era, NPs were less likely to order a bronchodilator (odds ratio [OR], 0.390 [95% confidence interval, 0.318-0.478; P < 0.001]), whereas physicians were less likely to order a CXR (OR, 0.772 [0.667-0.894, P = 0.001]), bronchodilator (OR, 0.518 [0.449-0.596, P < 0.001]), or a corticosteroid (OR, 0.630 [0.531-0.749, P < 0.001]). CONCLUSIONS: Nurse practitioners made fewer diagnostic and therapeutic orders. A clinical practice guideline on the diagnosis and management of children with bronchiolitis successfully decreased the use of nonrecommended tests and therapies among NP and physicians.

A shifting landscape: Practice patterns and outcomes of cystic fibrosis and non-cystic fibrosis pediatric lung transplantation.

BACKGROUND: New drugs may further decrease the need for lung transplant (LTx) in pediatric patients with cystic fibrosis (CF), but few studies highlight pediatric non-CF LTx characteristics and outcomes. METHODS: The ISHLT registry was used to report morbidity, graft failure, and survival for primary pediatric (<18 years) LTx performed 1990-2017. Recipient/donor characteristics and long-term outcomes were analyzed for CF and non-CF recipients. Survival was assessed using Kaplan-Meier curves. RESULTS: Of 2232 primary LTx, (43% in males), 918 (41%) were performed for non-CF indications; most commonly pulmonary hypertension (43%). Non-CF patients were younger (median age 11 vs. 15, p < .001), and more frequently on inotropes and/or extracorporeal membrane oxygenation (15% vs. 2.4%, p < .001) at transplant, compared to CF recipients. In-hospital major complications more commonly affected CF LTx recipients (57% vs. 48%, p = .003), but 30-day mortality was higher in the non-CF group (9% non-CF vs. 5% CF, p < .001). One-, five-, and ten-year mortality was 18%, 50%, and 65% for CF recipients, respectively, and 21%, 45%, and 58% for non-CF recipients (p = .01 at 10 years). Five-year survival was significantly better for non-CF females versus CF females (56% vs. 48%, p = .013), but was similar between groups for males (55% vs. 54%, p = .305). While age was a late outcomes risk factor, pulmonary hypertension and later transplants eras were protective. CONCLUSIONS: Early mortality is higher and late mortality is lower in non-CF LTx. Current non-CF LTx outcomes leave room for improvement. Further study is needed to evaluate the effects of center volume and pediatric-specific experience on outcomes.

Cell-Free Plasma Hemoglobin and Male Gender Are Risk Factors for Acute Kidney Injury in Low Risk Children Undergoing Cardiopulmonary Bypass.

OBJECTIVES: To determine the relationship between the production of cell-free plasma hemoglobin and acute kidney injury in infants and children undergoing cardiopulmonary bypass for cardiac surgery. DESIGN: Prospective observational study. SETTING: Twelve-bed cardiac ICU in a university-affiliated children's hospital. PATIENTS: Children were prospectively enrolled during their preoperative outpatient appointment with the following criteria: greater than 1 month to less than 18 years old, procedures requiring cardiopulmonary bypass, no preexisting renal dysfunction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma and urine were collected at baseline (in a subset), the beginning and end of cardiopulmonary bypass, and 2 hours and 24 hours after cardiopulmonary bypass in 60 subjects. Levels of plasma hemoglobin increased during cardiopulmonary bypass and were associated (p < 0.01) with cardiopulmonary bypass duration (R = 0.22), depletion of haptoglobin at end and 24 hours after cardiopulmonary bypass (R = 0.12 and 0.15, respectively), lactate dehydrogenase levels at end cardiopulmonary bypass (R = 0.27), and change in creatinine (R = 0.12). Forty-three percent of patients developed acute kidney injury. There was an association between plasma hemoglobin level and change in creatinine that varied by age (overall [R = 0.12; p < 0.01]; in age > 2 yr [R = 0.22; p < 0.01]; and in < 2 yr [R = 0.03; p = 0.42]). Change in plasma hemoglobin and male gender were found to be risk factors for acute kidney injury (odds ratio, 1.02 and 3.78, respectively; p < 0.05). CONCLUSIONS: Generation of plasma hemoglobin during cardiopulmonary bypass and male gender are associated with subsequent renal dysfunction in low-risk pediatric patients, especially in those older than 2 years. Further studies are needed to determine whether specific subgroups of pediatric patients undergoing cardiopulmonary bypass would benefit from potential treatments for hemolysis and plasma hemoglobin-associated renal dysfunction.

American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock.

OBJECTIVES: The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine "Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock." DESIGN: Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006-2014). The PubMed/Medline/Embase literature (2006-14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. MEASUREMENTS AND MAIN RESULTS: The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. CONCLUSIONS: The major new recommendation in the 2014 update is consideration of institution-specific use of 1) a "recognition bundle" containing a trigger tool for rapid identification of patients with septic shock, 2) a "resuscitation and stabilization bundle" to help adherence to best practice principles, and 3) a "performance bundle" to identify and overcome perceived barriers to the pursuit of best practice principles.

Changes in Bronchiolitis Characteristics During the COVID-19 Pandemic: A Description of Pediatric Emergency Department Visits in a Community Hospital, 2019-2021.

A retrospective, cross-sectional study of children with bronchiolitis aged 1 to 24 months during an ED visit between 2019 and 2021 was performed. Chi-square or Kruskal-Wallis was used to compare groups. The gamma coefficient was used to measure the association of variables through time. Bronchiolitis cases decreased by 75% from 2019 to 2020 and rose back to prepandemic levels by 2021. Radiographs (gamma -0.443), steroids (gamma -0.298), and bronchodilators (gamma -0.414) decreased during the study period (P < .001). Laboratory studies (gamma 0.032), viral testing (gamma 0.097), antibiotic use (gamma -0.069), and respiratory support (gamma 0.166) were unchanged. The decrease in steroids and bronchodilators was related to a clinical pathway that discouraged their use. Respiratory support remained unchanged. The COVID-19 pandemic (2019-2021) seems to have had little effect on the severity or resource utilization associated with bronchiolitis but may have unraveled a potential bronchiolitis phenotype that may have been more prominent during the pandemic.

The Accuracy of Transcutaneous Bilirubin as a Screening Test in Preterm Infants.

OBJECTIVE: To determine the accuracy of transcutaneous bilirubin (TcB) to predict total serum bilirubin (TSB) in preterm infants across gestational age (GA) ranges and to calculate the cost-effectiveness of TcB as the primary screening test of choice for neonatal jaundice in neonatal intensive care unit (NICU) settings. METHODS: Single-center retrospective study of infants aged ≤ seven days admitted to the NICU over a six-month period with a paired TSB and TcB, with or without phototherapy as part of their routine clinical care. Infants were divided into GA-specific groups as term, late preterm, moderate preterm, and very preterm. Measurement bias (bias=TSB-TcB) was calculated on the paired TSB and TcB values, and a Bland-Altman analysis was carried out. The impacts of additional infant-specific variables on the bias were assessed with univariate and multivariate linear regression techniques. The potential direct cost savings associated with the use of TcB as the primary screening test were calculated. RESULTS: A total of 263 paired TSB and TcB samples from 95 patients were included (130 paired samples from term (n=60), 75 from late preterm (n=21), 27 from moderate preterm (n=7), and 31 from very preterm (n=7)). The mean paired measurement bias across all the GA groups was -0.9 ± 2.9 mg/dL. The sensitivity and specificity of TcB in GA < 35 weeks were 92% and 62%, respectively. A conservative estimate of a one-third reduction in TSB measurement by using TcB as the primary screening test will have a direct cost saving of $3,148 over a six-month period. CONCLUSION: Our data suggest that TcB is a safe and potentially cost-effective screening test for jaundice across GA groups.

Physician experiences of workplace racial and gender microaggressions.

OBJECTIVES: To investigate racial and gender-specific microaggressions that are experienced by pediatric otolaryngologists at work. METHODS: An anonymous web-based survey consisting of 18 questions was sent to American Society of Pediatric Otolaryngology (ASPO) members via an email link. The survey included questions from the Workplace and School Microaggressions component of the Racial and Ethnic Microaggressions (REM) Scale. RESULTS: 125 out of 610 ASPO members completed the survey for a response rate of 20.5%. 28% of respondents reported experiencing a racial/ethnic microaggression in the last six months. Respondents who identified as Asian American Pacific Islander had significantly higher REM scores when compared with Caucasian respondents (p < 0.05). There was no significant difference in scores when comparing the other Race categories. Female respondents reported significantly higher gendered-microaggression scores compared to those identifying as male (p < 0.001). 66% of female respondents experienced some form of gender-based microaggression in the last six months. CONCLUSION: By providing evidence that pediatric otolaryngologists continue to report experiences of discrimination in the form of microaggressions, this study aims to increase awareness and inspire a more inclusive work environment.

Effusion Prevalence at Tympanostomy During COVID-19: Follow-Up.

OBJECTIVE: We previously reported pandemic year (2020) intraoperative middle ear effusion (MEE) rate at time of bilateral myringotomy tube (BMT) placement was 18% lower compared to pre-pandemic year (2019). After mandatory stay at home orders (MSHO) and pandemic social distancing precautions were relaxed, we aimed to assess the impact of a persistent pandemic with new COVID-19 variants on MEE presence during BMT. METHODS: This study is a retrospective chart summary exempted by Nemours institutional review board at a single tertiary children's hospital. Children < 18 years who underwent BMT during March 1, 2019-June 31, 2019 (pre-COVID), March 1, 2020-June 31, 2020 (PY1), and March 1, 2021-June 31, 2021 (PY2) were included. Statistical analysis included chi-squared and KruskalWallis. RESULTS: A total of 1069 BMTs were reviewed: 551 (52%) during pre-COVID, 227 (21%) during PY1, and 291 (27%) during PY2. There were no significant differences in age, sex, or BMI across comparison groups. Intraoperative MEE was significantly higher pre-COVID (83%) compared to PY1 (65%) and PY2 (69%) (P < .001) despite a small rebound in PY2. CONCLUSION: Intraoperative MEE remains lower in subsequent pandemic years despite relaxed public health measures and may be impacted by persistent public health measures like masking, lower return to daycare, variable social distancing, and/or change to access to health care.

Educating Surgeons to Construct Valved Conduits: What Does It Take to Achieve Reproducible Results?

BACKGROUND: Despite the demonstrated utility of surgeon-fashioned polytetrafluoroethylene (PTFE) valved conduits, methods for educating surgeons to reproducibly construct these conduits are lacking. We present a surgeon education process and early outcomes for children receiving surgeon-fashioned PTFE valved conduits during the initial learning curve. METHODS: The educational curriculum included 4 hours of proctored instruction/supervised valve construction, followed by 2 hours of individual practice. A surgeon with prior mastery of the technique provided templated designs, videos, and follow-up consultation. A retrospective medical record review (2017-2022) described early outcomes and valve function for patients receiving surgeon-fashioned PTFE right ventricle-to-pulmonary artery conduits. RESULTS: Two surgeons were educated using the method described. Fifteen valved conduits were implanted in 14 patients (median patient age, 38 months; conduit size range, 10-24 mm). At discharge, no patient had more than mild stenosis or regurgitation, and 12 of 15 valves (80%) had none or trivial regurgitation. Median follow-up was 14 months (range, 1-52 months). At the last follow-up, median peak conduit gradient of the 15 valves was low (18 mm Hg), 1 (7%) had moderate stenosis, and 1 (7%) had mild-moderate regurgitation. Two conduits were replaced concomitantly during repair of associated lesions at 14 and 38 months (sizes 10 and 12 mm, respectively). There were no deaths and no infectious complications. CONCLUSIONS: Four hours of proctored surgeon education plus deliberate practice is an effective method for teaching valved PTFE conduit construction and is associated with excellent early valve function. This study provides educational methods and initial evidence of safety for congenital surgeons wishing to learn and adopt this technique.

Predictors of Mediastinal Exploration While on Extracorporeal Membrane Oxygenation After Pediatric Cardiac Surgery.

Cardiac surgical patients requiring extracorporeal membrane oxygenation (ECMO) are at increased risk for hemorrhage due to necessary anticoagulation, in-situ cannulas, and disturbed hemostasis. We performed a retrospective, cross-sectional study of patients 0-18 years old in our cardiac intensive care unit (CICU) cannulated to ECMO within 48 h of cardiopulmonary bypass. The 69 patients included in the study were divided into three analysis groups based on serial chest tube output per hour: no bleeding (NB) on admission to the CICU (21/69, 30%), bleeding stopped (BS) with medical management (26/69, 38%), bleeding requiring emergent mediastinal exploration (BME) (22/69, 32%). The NB group had a more favorable coagulation profile upon admission to the CICU (PTT 53 s NB, 105 s BS, 83 s BME p < 0.001, ACT 169 s NB, 225 s BS, 211 s BME, p =0.013). Only chest tube output during the first three postcannulation hours remained associated with the need for mediastinal exploration by multivariable analysis. An average chest-tube output of 11.6 mL/kg/h during the first three hours had the highest percentage of patients classified correctly (84%) for requiring mediastinal exploration during their ECMO run (sensitivity 91%, specificity 81%).

Development of a Novel Society of Thoracic Surgeons Adult Congenital Mortality Risk Model.

BACKGROUND: Operative mortality risk models for adults with congenital heart disease (ACHD) undergoing cardiac operations are essential, given the growing population of these patients, yet they are currently unavailable. Existing adult Society of Thoracic Surgeons (STS) models exclude congenital procedures, whereas existing congenital models exclude operations for acquired disease. We aimed to develop an STS mortality risk model for ACHD patients undergoing cardiac operations. METHODS: Leveraging a comprehensive list of diagnostic and procedure codes, ACHD patients who underwent cardiac operations were identified from the STS Adult Cardiac Surgery Database (versions: v2.73, v2.81, and v2.9) between 2011 and 2019. The model was developed and validated in the ACHD population using a 60/40 development/validation split. Univariate analyses and clinical expertise informed the addition of ACHD-relevant procedure and diagnosis variables to existing STS adult risk model variables. Model performance was assessed overall and in 38 subgroups based on patient demographics, procedures, and diagnoses. RESULTS: Forty-seven procedure and diagnosis variables relevant to ACHD were added to existing STS adult risk model variables. The derived ACHD model for operative mortality was well calibrated within demographic, procedural, and diagnosis subgroups and the overall ACHD population, and discrimination in the validation cohort was excellent (C statistic, 0.815) compared with the model using only existing STS adult risk model variables (C statistic, 0.79; P < .0001). CONCLUSIONS: A novel, high-performing STS ACHD mortality risk model has been developed on the basis of contemporary patient data. The ACHD risk model represents an important expansion of the STS portfolio. Implementation with an online risk calculator is planned.

In vivo PEG modification of vascular surfaces for targeted delivery.

OBJECTIVE: Thrombosis and restenosis remain problematic for many intravascular procedures. Previously, it has been demonstrated that modifying an injured vascular surface with a protein-reactive polymer could block undesirable platelet deposition. As an added benefit, it would be advantageous if one could target therapeutics to the injured site. This study investigates a site-specific delivery system to target microspheres to vascular surfaces modified with a reactive polyethylene glycol tagged with biotin. METHODS: Rabbit femoral arteries were injured with a 2F embolectomy catheter. Modification of the vascular surface was achieved using a channeled balloon catheter or small-diameter tube. Microspheres were injected intravenously through catheterization of the ear vein. Polymer modification on the injured surface and delivery of microspheres was quantified using epifluorescence microscopy at 0, 24, 48, and 72 hours. RESULTS: Polymer modification of the vascular surface could be achieved using a channeled drug delivery catheter or small-diameter tube with similar results. Maximum polymer coverage occurred at 0 hours and decreased to 85% maximal at 24 hours, 72% at 48 hours, and 67% at 72 hours. The initial number of microspheres per mm(2) binding to modified, injured arteries was 304 versus 141 for the unmodified, damaged control (P < .01). At subsequent times, the number of adherent microspheres to modified, injured arteries decreased by 50%, 70%, and 84% at 24, 48, and 72 hours, respectively; while nonspecific binding to unmodified, injured arteries quickly decreased by 93%. Initial microsphere binding to modified, healthy arteries was 153 microspheres/mm(2) as opposed to 26 microspheres/mm(2) for the unmodified, healthy controls (P < .01). CONCLUSIONS: Chemical modification of injured vessels following intravascular procedures can be readily accomplished in vivo to create a substrate for targeted delivery systems. As a proof of concept, targeted microspheres preferentially adhered to polymer-modified surfaces as opposed to injured, unmodified, or healthy vascular surfaces.

Activated partial thromboplastin time is a better trending tool in pediatric extracorporeal membrane oxygenation.

OBJECTIVES: To determine whether activated partial thromboplastin times are a better heparin management tool than activated clotting times in pediatric extracorporeal membrane oxygenation. DESIGN: A single-center retrospective analysis of perfusion and patient records. SETTING: Academic pediatric tertiary care center. PATIENTS: Pediatric patients (<21 yrs old) requiring extracorporeal membrane oxygenation support initiated at Children's Hospital of Pittsburgh. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Point-of-care activated clotting time and activated partial thromboplastin time values, clinical laboratory activated partial thromboplastin time values, weight-normalized heparin administration (units/kg/hr), and reported outcomes were collected for pediatric patients treated for cardiac and/or respiratory failure with extracorporeal membrane oxygenation. Spearman's ranked correlations were performed for each coagulation test compared to heparin dosage. The Bland-Altman test was used to determine the validity of the point-of-care activated partial thromboplastin time. Hazard analysis was conducted for outcomes and complications for patients whose heparin management was based on the clinical laboratory activated partial thromboplastin time or the activated clotting time. Only the clinical laboratory activated partial thromboplastin time showed a correlation (ρ = 0.40 vs. ρ = -0.04 for activated clotting time) with the heparin administration (units/kg/hr). Point-of-care activated partial thromboplastin time and activated partial thromboplastin time values correlated well (ρ = 0.76), with <5% of samples showing a difference outside 2 SDs, but differences in their absolute values (Δactivated partial thromboplastin time = 100 secs) preclude them from being interchangeable measures. Furthermore, despite no effective change in the mean activated clotting time, cardiac patients showed a significantly improved correlation to heparin dose for all coagulation tests (e.g., point-of-care activated partial thromboplastin time ρ = 0.60). Management of patients with the clinical laboratory activated partial thromboplastin time did not significantly affect patient survival rates but did significantly reduce bleeding complications and significantly increased clotting in the extracorporeal membrane oxygenation circuit. A hazard analysis demonstrated that bleeding complications were associated with an increased risk of mortality, whereas clotting complications in the extracorporeal membrane oxygenation circuit were not. CONCLUSIONS: The activated clotting time is not an accurate monitoring tool for heparin management in pediatricextracorporeal membrane oxygenation. The point-of-care activated partial thromboplastin time correlates well with the clinical laboratory activated partial thromboplastin time but cannot be substituted for the clinical laboratory activated partial thromboplastin time values. Management of pediatric extracorporeal membrane oxygenation patients with the clinical laboratory activated partial thromboplastin time reduced bleeding complications which are associated with increases in mortality.

Coagulation and hemolysis complications in neonatal ECLS: Role of devices.

Neonatal extracorporeal life support (ECLS) has enjoyed a long history of successful patient support for both cardiac and respiratory failure. The small size of this patient population has provided many technical challenges from cannulation to pumps and oxygenators. This is further complicated by the relatively meager commercial options for equipment owing to the relatively low utilization of neonatal ECLS compared to adults, which has exploded following the H1N1 epidemic and the availability of the polymethylpentene oxygenator. This paper focuses on the impact of equipment choices on thrombosis and hemolysis in neonatal ECLS and the underlying mechanisms behind them. Based upon the available evidence, it is clear neonatal ECLS requires careful attention to the selection and operation of all parts of the ECLS system. Practitioners should also be aware of the factors that increase blood cell fragility, which can impact decisions around equipment and subsequent operation.