Epinephrine Dosing Use During Extracorporeal Cardiopulmonary Resuscitation: Single-Center Retrospective Cohort.

OBJECTIVES: During pediatric cardiac arrest, contemporary guidelines recommend dosing epinephrine at regular intervals, including in patients requiring extracorporeal membrane oxygenation (ECMO). The impact of epinephrine-induced vasoconstriction on systemic afterload and venoarterial ECMO support is not well-defined. DESIGN: Nested retrospective observational study within a single center. The primary exposure was time from last dose of epinephrine to initiation of ECMO flow; secondary exposures included cumulative epinephrine dose and arrest time. Systemic afterload was assessed by mean arterial pressure and use of systemic vasodilator therapy; ECMO pump flow and Vasoactive-Inotrope Score (VIS) were used as measures of ECMO support. Clearance of lactate was followed post-cannulation as a marker of systemic perfusion. SETTING: PICU and cardiac ICU in a quaternary-care center. PATIENTS: Patients 0-18 years old who required ECMO cannulation during resuscitation over the 6 years, 2014-2020. Patients were excluded if ECMO was initiated before cardiac arrest or if the resuscitation record was incomplete. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 92 events in 87 patients, with 69 events having complete data for analysis. The median (interquartile range) of total epinephrine dosing was 65 mcg/kg (37-101 mcg/kg), with the last dose given 6 minutes (2-16 min) before the initiation of ECMO flows. Shorter interval between last epinephrine dose and ECMO initiation was associated with increased use of vasodilators within 6 hours of ECMO ( p = 0.05), but not with mean arterial pressure after 1 hour of support (estimate, -0.34; p = 0.06). No other associations were identified between epinephrine delivery and mean arterial blood pressure, vasodilator use, pump speed, VIS, or lactate clearance. CONCLUSIONS: There is limited evidence to support the idea that regular dosing of epinephrine during cardiac arrest is associated with increased in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.

Have you ACED it? How to successfully implement performance-oriented, Acute Critical Event Debriefing.

Acute Critical Event Debriefing (ACED) after cardiopulmonary arrests should be the standard of care. However, little literature exists on how to implement performance-focused ACED in healthcare. Based on a series of successful ACED implementations in a variety of our settings, we describe key learnings and propose best practices to aid clinicians and organizations in establishing a successful ACED program. Within this practical guide, we also present a novel, standardized debriefing tool (Hotwash) that has been adapted for a variety of clinical settings.

Predicting and Surviving Prolonged Critical Illness After Congenital Heart Surgery.

OBJECTIVES: Prolonged critical illness after congenital heart surgery disproportionately harms patients and the healthcare system, yet much remains unknown. We aimed to define prolonged critical illness, delineate between nonmodifiable and potentially preventable predictors of prolonged critical illness and prolonged critical illness mortality, and understand the interhospital variation in prolonged critical illness. DESIGN: Observational analysis. SETTING: Pediatric Cardiac Critical Care Consortium clinical registry. PATIENTS: All patients, stratified into neonates (≤28 d) and nonneonates (29 d to 18 yr), admitted to the pediatric cardiac ICU after congenital heart surgery at Pediatric Cardiac Critical Care Consortium hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 2,419 neonates and 10,687 nonneonates from 22 hospitals. The prolonged critical illness cutoff (90th percentile length of stay) was greater than or equal to 35 and greater than or equal to 10 days for neonates and nonneonates, respectively. Cardiac ICU prolonged critical illness mortality was 24% in neonates and 8% in nonneonates (vs 5% and 0.4%, respectively, in nonprolonged critical illness patients). Multivariable logistic regression identified 10 neonatal and 19 nonneonatal prolonged critical illness predictors within strata and eight predictors of mortality. Only mechanical ventilation days and acute renal failure requiring renal replacement therapy predicted prolonged critical illness and prolonged critical illness mortality in both strata. Approximately 40% of the prolonged critical illness predictors were nonmodifiable (preoperative/patient and operative factors), whereas only one of eight prolonged critical illness mortality predictors was nonmodifiable. The remainders were potentially preventable (postoperative critical care delivery variables and complications). Case-mix-adjusted prolonged critical illness rates were compared across hospitals; six hospitals each had lower- and higher-than-expected prolonged critical illness frequency. CONCLUSIONS: Although many prolonged critical illness predictors are nonmodifiable, we identified several predictors to target for improvement. Furthermore, we observed that complications and prolonged critical care therapy drive prolonged critical illness mortality. Wide variation of prolonged critical illness frequency suggests that identifying practices at hospitals with lower-than-expected prolonged critical illness could lead to broader quality improvement initiatives.

Central Venous Catheter Utilization and Complications in the Pediatric Cardiac ICU: A Report From the Pediatric Cardiac Critical Care Consortium (PC4).

OBJECTIVES: Current central venous catheter utilization in patients within pediatric cardiac ICUs is not well elucidated. We aim to describe current use of central venous catheters in a multi-institutional cohort and to explore the prevalence and risk factors for central line-associated thrombosis and central line-associated bloodstream infections. DESIGN: Observational analysis. SETTING: Pediatric Cardiac Critical Care Consortium hospitals. PATIENTS: Hospitalizations with at least one cardiac ICU admission from October 2013 to July 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 17,846 hospitalizations and 69% included greater than or equal to one central venous catheter. Central venous catheter use was higher in younger patients (86% neonates). Surgical hospitalizations included at least one central venous catheter 88% of the time compared with 35% of medical hospitalizations. The most common location for central venous catheters was internal jugular (46%). Central venous catheters were in situ a median of 4 days (interquartile range, 2-10). There were 248 hospitalizations (2% overall, 1.8% medical, and 2.1% surgical) with at least one central line-associated thrombosis (271 total thromboses). Thrombosis was diagnosed at a median of 7 days (interquartile range, 4-14) after catheter insertion. There were 127 hospitalizations (1% overall, 1.4% medical, and 1% surgical) with at least one central line-associated bloodstream infection (136 total infections) with no association with catheter type or location. Central line-associated bloodstream infection was diagnosed at a median of 19 days (interquartile range, 8-36) after catheter insertion. Significant risk factors for central line-associated thrombosis and central line-associated bloodstream infection were younger age, greater surgical complexity, and total catheter days. CONCLUSIONS: Utilization of central venous catheters in pediatric cardiac ICUs differs according to indication for hospitalization. Although thrombosis and central line-associated bloodstream infection are infrequent complications of central venous catheter use in cardiac ICU patients, these events can have important short- and long-term consequences for patients. Total central venous catheter line days were the only modifiable risk factor identified. Future study must focus on understanding central venous catheter practices in high-risk patient subgroups that reduce the prevalence of thrombosis and central line-associated bloodstream infection.

Effect of a Pediatric Early Warning System on All-Cause Mortality in Hospitalized Pediatric Patients: The EPOCH Randomized Clinical Trial.

Importance: There is limited evidence that the use of severity of illness scores in pediatric patients can facilitate timely admission to the intensive care unit or improve patient outcomes. Objective: To determine the effect of the Bedside Paediatric Early Warning System (BedsidePEWS) on all-cause hospital mortality and late admission to the intensive care unit (ICU), cardiac arrest, and ICU resource use. Design, Setting, and Participants: A multicenter cluster randomized trial of 21 hospitals located in 7 countries (Belgium, Canada, England, Ireland, Italy, New Zealand, and the Netherlands) that provided inpatient pediatric care for infants (gestational age ≥37 weeks) to teenagers (aged ≤18 years). Participating hospitals had continuous physician staffing and subspecialized pediatric services. Patient enrollment began on February 28, 2011, and ended on June 21, 2015. Follow-up ended on July 19, 2015. Interventions: The BedsidePEWS intervention (10 hospitals) was compared with usual care (no severity of illness score; 11 hospitals). Main Outcomes and Measures: The primary outcome was all-cause hospital mortality. The secondary outcome was a significant clinical deterioration event, which was defined as a composite outcome reflecting late ICU admission. Regression analyses accounted for hospital-level clustering and baseline rates. Results: Among 144 539 patient discharges at 21 randomized hospitals, there were 559 443 patient-days and 144 539 patients (100%) completed the trial. All-cause hospital mortality was 1.93 per 1000 patient discharges at hospitals with BedsidePEWS and 1.56 per 1000 patient discharges at hospitals with usual care (adjusted between-group rate difference, 0.01 [95% CI, -0.80 to 0.81 per 1000 patient discharges]; adjusted odds ratio, 1.01 [95% CI, 0.61 to 1.69]; P = .96). Significant clinical deterioration events occurred during 0.50 per 1000 patient-days at hospitals with BedsidePEWS vs 0.84 per 1000 patient-days at hospitals with usual care (adjusted between-group rate difference, -0.34 [95% CI, -0.73 to 0.05 per 1000 patient-days]; adjusted rate ratio, 0.77 [95% CI, 0.61 to 0.97]; P = .03). Conclusions and Relevance: Implementation of the Bedside Paediatric Early Warning System compared with usual care did not significantly decrease all-cause mortality among hospitalized pediatric patients. These findings do not support the use of this system to reduce mortality. Trial Registration: clinicaltrials.gov Identifier: NCT01260831.

Sustainability of protocolized handover of pediatric cardiac surgery patients to the intensive care unit.

BACKGROUND: Transfer of patient care among clinicians (handovers) is a common source of medical errors. While the immediate efficacy of these initiatives is well documented, sustainability of practice changes that results in better processes of care is largely understudied. AIMS: The objective of the current investigation was to evaluate the sustainability of a protocolized handover process in pediatric patients from the operating room after cardiac surgery to the intensive care unit. METHODS: This was a prospective study with direct observation assessment of handover performance conducted in the cardiac ICU (CICU) of a free-standing, tertiary care children's hospital in the United States. Patient transitions from the operating room to the CICU, including the verbal handoff, were directly observed by a single independent observer in all phases of the study. A checklist of key elements identified errors classified as: (1) technical, (2) information omissions, and (3) realized errors. Total number of errors was compared across the different times of the study (preintervention, postintervention, and the current sustainability phase). RESULTS: A total of 119 handovers were studied: 41 preintervention, 38 postintervention, and 40 in the current sustainability phase. The median [Interquartile range (IQR)] number of technical errors was significantly reduced in the sustainability phase compared to the preintervention and postintervention phase, 2 (1-3), 6 (5-7), and 2.5 (2-4), respectively P = 0.0001. Similarly, the median (IQR) number of verbal information omissions was also significantly reduced in the sustainability phase compared to the preintervention and postintervention phases, 1 (1-1), 4 (3-5) and 2 (1-3), respectively. CONCLUSIONS: We demonstrate sustainability of an improved handover process using a checklist in children being transferred to the intensive care unit after cardiac surgery. Standardized handover processes can be a sustainable strategy to improve patient safety after pediatric cardiac surgery.

Natural history of chronic thromboembolic pulmonary disease with no or mild pulmonary hypertension.

BACKGROUND: We describe baseline characteristics, disease progression and mortality in chronic thromboembolic pulmonary disease patients as a function of mean pulmonary artery pressure (mPAP) according to new and previous definitions of pulmonary hypertension. METHODS: All patients diagnosed with chronic thromboembolic pulmonary disease between January, 2015 and December, 2019 were dichotomized according to initial mPAP: ≤ 20 mmHg ('normal') vs 21-24 mmHg ('mildly-elevated'). Baseline features were compared between the groups, and pairwise analysis performed to determine changes in clinical endpoints at 1-year, excluding those who underwent pulmonary endarterectomy or did not attend follow-up. Mortality was assessed for the whole cohort over the entire study period. RESULTS: One hundred thirteen patients were included; 57 had mPAP ≤ 20 mmHg and 56 had mPAP 21-24 mmHg. Normal mPAP patients had lower pulmonary vascular resistance (1.6 vs 2.5WU, p < 0.01) and right ventricular end-diastolic pressure (5.9 vs 7.8 mmHg, p < 0.01) at presentation. At 3 years, no major deterioration was seen in either group. No patients were treated with pulmonary artery vasodilators. Eight had undergone pulmonary endarterectomy. Over 37 months median follow-up, mortality was 7.0% in the normal mPAP group and 8.9% in the mildly-elevated mPAP group. Cause of death was malignancy in 62.5% of cases. CONCLUSIONS: Chronic thromboembolic pulmonary disease patients with mild pulmonary hypertension have statistically higher right ventricular end-diastolic pressure and pulmonary vascular resistance than those with mPAP ≤ 20 mmHg. Baseline characteristics were otherwise similar. Neither group displayed disease progression on non-invasive tests up to 3 years. Mortality over 37 months follow-up is 8%, and mainly attributable to malignancy. Further prospective study is required to validate these findings.

Racial and Ethnic Variation in ECMO Utilization and Outcomes in Pediatric Cardiac ICU Patients.

Background: Previous studies have reported racial disparities in extracorporeal membrane oxygenation (ECMO) utilization in pediatric cardiac patients. Objectives: The objective of this study was to determine if there was racial/ethnic variation in ECMO utilization and, if so, whether mortality was mediated by differences in ECMO utilization. Methods: This is a multicenter, retrospective cohort study of the Pediatric Cardiac Critical Care Consortium clinical registry. Analyses were stratified by hospitalization type (medical vs surgical). Logistic regression models were adjusted for confounders and evaluated the association between race/ethnicity with ECMO utilization and mortality. Secondary analyses explored interactions between race/ethnicity, insurance, and socioeconomic status with ECMO utilization and mortality. Results: A total of 50,552 hospitalizations from 34 hospitals were studied. Across all hospitalizations, 2.9% (N = 1,467) included ECMO. In medical and surgical hospitalizations, Black race and Hispanic ethnicity were associated with severity of illness proxies. In medical hospitalizations, race/ethnicity was not associated with the odds of ECMO utilization. Hospitalizations of other race had higher odds of mortality (adjusted odds ratio [aOR]: 1.61; 95% CI: 1.22-2.12; P = 0.001). For surgical hospitalizations, Black (aOR: 1.24; 95% CI: 1.02-1.50; P = 0.03) and other race (aOR: 1.50; 95% CI: 1.17-1.93; P = 0.001) were associated with higher odds of ECMO utilization. Hospitalizations of Hispanic patients had higher odds of mortality (aOR: 1.31; 95% CI: 1.03-1.68; P = 0.03). No significant interactions were demonstrated between race/ethnicity and socioeconomic status indicators with ECMO utilization or mortality. Conclusions: Black and other races were associated with increased ECMO utilization during surgical hospitalizations. There were racial/ethnic disparities in outcomes not explained by differences in ECMO utilization. Efforts to mitigate these important disparities should include other aspects of care.

Prospective Assessment of Coronary Artery Flows Before and After Cardiopulmonary Bypass in Children With a Spectrum of Congenital Heart Disease.

Background: Normative data for the effect of cardiopulmonary bypass (CPB) on coronary artery Doppler velocities by transesophageal echocardiography in paediatric patients with congenital heart disease (CHD) are lacking. The objective of the study was to prospectively examine the effects of CPB on coronary artery flow patterns by transesophageal echocardiography before and after CPB in children with CHD. Methods: All cases undergoing CHD surgery at the Hospital for Sick Children, Toronto, were eligible. The excluded cases included Norwood operation, heart transplantation, or weight <2.5 kg. Coronary Dopplers and coronary flow reserve (CFR) for the right coronary artery (RCA) and left anterior descending (LAD) were obtained. Multivariable analyses using linear regression models were performed, adjusted for age and cross-clamp time. Results: From May 2017 to June 2018, 69 children (median age at surgery: 0.7 years, interquartile range [IQR]: 0.4-3.7 years; median weight: 7.4 kg, IQR: 5.8-13.3 kg) were included. They were grouped into shunt lesions (N = 26), obstructive lesions (N = 26), transposition of the great arteries (N = 5), and single ventricle (N = 12). N = 39 (57%) were primary repairs, and 56 (81%) had 1 CPB run. For RCA and LAD peak velocities, there was an increase from pre- to post-CPB in RCA peak 39 cm/s (IQR: 30-54 cm/s) to 65 cm/s (IQR: 47-81 cm/s), P < 0.001, mean CFR 1.52 (IQR: 1.25-1.81), and LAD peak 49 cm/s (IQR: 39-60 cm/s) to 70 cm/s (IQR: 52-90 cm/s), P < 0.001, mean CFR 1.48 (IQR: 1.14-1.77). Conclusions: Coronary flow velocities increase from pre- to post-CPB in congenital heart lesions. CFR is consistent across all lesions but is relatively low compared with the adult population.

Contexte: On ne dispose pas de données normatives sur les effets de la dérivation cardiopulmonaire (DCP) sur le débit coronarien mesuré au moyen d'une échocardiographie transœsophagienne Doppler chez des enfants présentant une cardiopathie congénitale. L'objectif de l'étude était d'examiner de manière prospective les effets de la DCP sur le débit coronarien avant et après l'intervention chez des enfants présentant une cardiopathie congénitale. Méthodologie: Tous les enfants ayant subi une intervention chirurgicale pour une cardiopathie congénitale à l'Hospital for Sick Children de Toronto étaient admissibles à l'étude, à l'exception de ceux ayant subi une intervention de Norwood ou une transplantation cardiaque, de même que les enfants pesant moins de 2,5 kg. Les résultats du test Doppler et la réserve coronarienne pour l'artère coronaire droite (ACD) et la branche antérieure de l'artère coronaire gauche (ACG) ont été obtenus. Des analyses multivariées ont été réalisées au moyen de modèles de régression linéaire, avec correction en fonction de l'âge et du temps de clampage total. Résultats: Entre mai 2017 et juin 2018, 69 enfants (âge médian au moment de la chirurgie : 0,7 an, intervalle interquartile (IIQ) : 0,4-3,7 ans; poids médian : 7,4 kg, IIQ : 5,8-13,3 kg) ont été inclus dans l'étude. Les sujets ont été répartis en quatre groupes : shunts (n = 26), lésions obstructives (n = 26), permutation des gros vaisseaux (n = 5) et ventricule unique (n = 12). Chez 39 sujets (57 %), il s'agissait d'une réparation primitive, et 56 enfants (81 %) avaient déjà subi une DCP. Les vitesses maximales dans l'ACD et dans la branche antérieure de l'ACG ont augmenté après la DCP, passant de 39 cm/s (IIQ : 30-54 cm/s) à 65 cm/s (IIQ : 47-81 cm/s), p < 0,001; réserve coronarienne moyenne : 1,52 (IIQ : 1,25-1,81) pour l'ACD, et de 49 cm/s (IIQ : 39-60 cm/s) à 70 cm/s (IIQ : 52-90 cm/s), p < 0,001; réserve coronarienne moyenne : 1,48 (IIQ : 1,14-1,77) pour la branche antérieure de l'ACG. Conclusions: Le débit coronarien augmente après une DCP dans les cas de lésions cardiaques congénitales. La réserve coronarienne est constante dans tous les types de lésions, mais elle est relativement faible comparativement à celle de la population adulte.

Hyperglycemia after pediatric cardiac surgery: impact of age and residual lesions.

OBJECTIVE: We evaluated the effect of patient age and significant residual cardiac lesions on the association between hyperglycemia and adverse outcomes in children after cardiac surgery. The incidence, severity, and duration of hyperglycemia in this patient population and perioperative factors predisposing to hyperglycemia were also delineated. DESIGN: Retrospective, observational cohort study. SETTING: Eighteen-bed pediatric cardiac critical care unit. PATIENTS: Seven hundred seventy-two children undergoing cardiac surgery with cardiopulmonary bypass during 2006 and 2007. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postoperative glucose levels were reviewed in all children who underwent cardiac surgery with cardiopulmonary bypass at our institution during 2006 and 2007 who met all inclusion criteria and none of the exclusion criteria (n = 772). The composite morbidity-mortality outcome included hospital death, cardiac arrest, renal/hepatic failure, lactic acidosis, extracorporeal membrane oxygenation use, or infection. Hyperglycemia occurred in 90% of patients and resolved within 72 hrs in most without exogenous insulin. Preoperative factors, including prostaglandins, mechanical ventilation, and cyanosis, were significantly associated with increased odds of significant hyperglycemia (>180 mg/dL for >12 hrs or any level >270 mg/dL) as were increased surgical complexity and perioperative steroid administration. Thirty-one percent of the entire cohort reached the composite outcome and the odds were significantly increased after 54 hrs of mild (elevated, but <180 mg/dL), 12 hrs of moderate (180-270 mg/dL), or any period of severe hyperglycemia (>270 mg/dL). Neonates (<1 month of age) tolerated longer periods of hyperglycemia before showing increased odds of reaching the composite morbidity-mortality end point. In the setting of important residual cardiac lesions, mild or moderate hyperglycemia was not as strongly associated with adverse outcomes. CONCLUSIONS: Age and residual cardiac lesions are important modifiers of the association between hyperglycemia and suboptimal outcomes after pediatric cardiac surgery. Use of insulin therapy for glucose control in this patient population may need to be carefully targeted toward high-risk subsets of patients.

Hemodynamic Patterns Before Inhospital Cardiac Arrest in Critically Ill Children: An Exploratory Study.

To characterize prearrest hemodynamic trajectories of children suffering inhospital cardiac arrest. DESIGN: Exploratory retrospective analysis of arterial blood pressure and electrocardiogram waveforms. SETTING: PICU and cardiac critical care unit in a tertiary-care children's hospital. PATIENTS: Twenty-seven children with invasive blood pressure monitoring who suffered a total of 31 inhospital cardiac arrest events between June 2017 and June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed changes in cardiac output, systemic vascular resistance, stroke volume, and heart rate derived from arterial blood pressure waveforms using three previously described estimation methods. We observed substantial prearrest drops in cardiac output (population median declines of 65-84% depending on estimation method) in all patients in the 10 minutes preceding inhospital cardiac arrest. Most patients' mean arterial blood pressure also decreased, but this was not universal. We identified three hemodynamic patterns preceding inhospital cardiac arrest: subacute pulseless arrest (n = 18), acute pulseless arrest (n = 7), and bradycardic arrest (n = 6). Acute pulseless arrest events decompensated within seconds, whereas bradycardic and subacute pulseless arrest events deteriorated over several minutes. In the subacute and acute pulseless arrest groups, decreases in cardiac output were primarily due to declines in stroke volume, whereas in the bradycardic group, the decreases were primarily due to declines in heart rate. CONCLUSIONS: Critically ill children exhibit distinct physiologic behaviors prior to inhospital cardiac arrest. All events showed substantial declines in cardiac output shortly before inhospital cardiac arrest. We describe three distinct prearrest patterns with varying rates of decline and varying contributions of heart rate and stroke volume changes to the fall in cardiac output. Our findings suggest that monitoring changes in arterial blood pressure waveform-derived heart rate, pulse pressure, cardiac output, and systemic vascular resistance estimates could improve early detection of inhospital cardiac arrest by up to several minutes. Further study is necessary to verify the patterns witnessed in our cohort as a step toward patient rather than provider-centered definitions of inhospital cardiac arrest.

A minimal clinically important difference measured by the Cambridge Pulmonary Hypertension Outcome Review for patients with idiopathic pulmonary arterial hypertension.

Several patient-reported outcome measures have been developed to assess health status in pulmonary arterial hypertension. The required change in instrument scores needed, to be seen as meaningful to the individual, however remain unknown. We sought to identify minimal clinically important differences in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and to validate these against objective markers of functional capacity. Minimal clinically important differences were established from a discovery cohort (n = 129) of consecutive incident cases of idiopathic pulmonary arterial hypertension with CAMPHOR scores recorded at treatment-naïve baseline and 4-12 months following pulmonary arterial hypertension therapy. An independent validation cohort (n = 87) was used to verify minimal clinically important differences. Concurrent measures of functional capacity relative to CAMPHOR scores were collected. Minimal clinically important differences were derived using anchor- and distributional-based approaches. In the discovery cohort, mean (SD) was 54.4 (16.4) years and 64% were female. Most patients (63%) were treated with sequential pulmonary arterial hypertension therapy. Baseline CAMPHOR scores were: Symptoms, 12 (7); Activity, 12 (7) and quality of life, 10 (7). Pulmonary arterial hypertension treatment resulted in significant improvements in CAMPHOR scores (p < 0.05). CAMPHOR minimal clinically important differences averaged across methods for health status improvement were: Symptoms, -4 points; Activity, -4 points and quality of life -3 points. CAMPHOR Activity score change ≥minimal clinically important difference was associated with significantly greater improvement in six-minute walk distance, in both discovery and validation populations. In conclusion, CAMPHOR scores are responsive to pulmonary arterial hypertension treatment. Minimal clinically important differences in pulmonary hypertension-specific scales may provide useful insights into treatment response in future clinical trials.

Effects of myosin heavy chain manipulation in experimental heart failure.

The myosin heavy chain (MHC) isoforms, alpha- and beta-MHC, are expressed in developmental- and chamber-specific patterns. Healthy human ventricle contains approximately 2-10% alpha-MHC and these levels are reduced even further in the failing ventricle. While down-regulation of alpha-MHC in failing myocardium is considered compensatory, we previously demonstrated that persistent transgenic (TG) alpha-MHC expression in the cardiomyocytes is cardioprotective in rabbits with tachycardia-induced cardiomyopathy (TIC). We sought to determine if this benefit extends to other types of experimental heart failure and focused on two models relevant to human heart failure: myocardial infarction (MI) and left ventricular pressure overload. TG and nontransgenic rabbits underwent either coronary artery ligation at 8 months or aortic banding at 10 days of age. The effects of alpha-MHC expression were assessed at molecular, histological and organ levels. In the MI experiments, we unexpectedly found modest functional advantages to alpha-MHC expression. In contrast, despite subtle benefits in TG rabbits subjected to aortic banding, cardiac function was minimally affected. We conclude that the benefits of persistent alpha-MHC expression depend upon the mechanism of heart failure. Importantly, in none of the scenarios studied did we find any detrimental effects associated with persistent alpha-MHC expression. Thus manipulation of MHC composition may be beneficial in certain types of heart failure and does not appear to compromise heart function in others. Future considerations of myosin isoform manipulation as a therapeutic strategy should consider the underlying etiology of cardiac dysfunction.

Quality Improvement Basics: A Crash Course for Pediatric Cardiac Care.

BACKGROUND: Lack of knowledge of quality improvement (QI) methodology and change management principles can explain many of the difficulties encountered when trying to develop effective QI initiatives in health care. METHODS: An interactive QI workshop at the 14th Annual Meeting of the Pediatric Cardiac Intensive Care Society provided an overview of the role of QI in health care, basic QI frameworks and tools, and leadership and organizational culture pitfalls. The top five QI projects submitted to the meeting were later presented to an expert QI panel in a separate session to illustrate examples of QI principles. RESULTS: Workshop presenters introduced two major QI methodologies used to design QI projects. Important first steps include identifying a problem, forming a multidisciplinary team, and developing an aim statement. Key driver diagrams were highlighted as an important tool to develop a project's framework. Several diagnostic tools used to understand the problem were discussed, including the "5 Why's," cause-and-effect charts, and process flowcharts. The importance of outcome, process, and balancing measures was emphasized. Identification of interventions, the value of plan-do-study-act cycles to fuel continuous QI, and use of statistical process control, including run charts or control charts, were reviewed. The importance of stakeholder engagement, transparency, and sustainability was discussed. Later, the top five QI projects presented highlighted multiple "QI done well" practices discussed during the preconference QI workshop. CONCLUSIONS: Understanding QI methodology and appropriately applying basic QI tools are pivotal steps to realizing meaningful and sustained improvement.

Hospital Costs Related to Early Extubation After Infant Cardiac Surgery.

BACKGROUND: The Pediatric Heart Network Collaborative Learning Study (PHN CLS) increased early extubation rates after infant tetralogy of Fallot (TOF) and coarctation of the aorta (CoA) repair across participating sites by implementing a clinical practice guideline (CPG). The impact of the CPG on hospital costs has not been studied. METHODS: PHN CLS clinical data were linked to cost data from Children's Hospital Association by matching on indirect identifiers. Hospital costs were evaluated across active and control sites in the pre- and post-CPG periods using generalized linear mixed-effects models. A difference-in-difference approach was used to assess whether changes in cost observed in active sites were beyond secular trends in control sites. RESULTS: Data were successfully linked on 410 of 428 eligible patients (96%) from four active and four control sites. Mean adjusted cost per case for TOF repair was significantly reduced in the post-CPG period at active sites ($42,833 vs $56,304, p < 0.01) and unchanged at control sites ($47,007 vs $46,476, p = 0.91), with an overall cost reduction of 27% in active versus control sites (p = 0.03). Specific categories of cost reduced in the TOF cohort included clinical (-66%, p < 0.01), pharmacy (-46%, p = 0.04), lab (-44%, p < 0.01), and imaging (-32%, p < 0.01). There was no change in costs for CoA repair at active or control sites. CONCLUSIONS: The early extubation CPG was associated with a reduction in hospital costs for infants undergoing repair of TOF but not CoA. This CPG represents an opportunity to both optimize clinical outcome and reduce costs for certain infant cardiac surgeries.

Genetic approaches for changing the heart and dissecting complex syndromes.

The genetic, biochemical and molecular bases of human cardiac disease have been the focus of extensive research efforts for many years. Early animal models of cardiovascular disease used pharmacologic or surgical interventions, or took advantage of naturally occurring genetic abnormalities and the data obtained were largely correlative. The inability to directly alter an organism's genetic makeup and cellular protein content and accurately measure the results of that manipulation precluded rigorous examination of true cause-effect and structure-function relationships. Directed genetic manipulation in the mouse gave researchers the ability to modify and control the mammalian heart's protein content, resulting in the rational design of models that could provide critical links between the mutated or absent protein and disease. Two techniques that have proven particularly useful are transgenesis, which involves the random insertion of ectopic genetic material of interest into a "host" genome, and gene targeting, which utilizes homologous recombination at a pre-selected locus. Initially, transgenesis and gene targeting were used to examine systemic loss-of-function and gain-of-function, respectively, but further refinements in both techniques have allowed for investigations of organ-specific, cell type-specific, developmental stage-sensitive and dose-dependent effects. Genetically engineered animal models of pediatric and adult cardiac disease have proven that, when used appropriately, these tools have the power to extend mere observation to the establishment of true causative proof. We illustrate the power of the general approach by showing how genetically engineered mouse models can define the precise signaling pathways that are affected by the gain-of-function mutation that underlies Noonan syndrome. Increasingly precise and modifiable animal models of human cardiac disease will allow researchers to determine not only pathogenesis, but also guide treatment and the development of novel therapies.

Death of a Simulated Pediatric Patient: Toward a More Robust Theoretical Framework.

INTRODUCTION: A theoretical framework was recently proposed that encapsulates learner responses to simulated death due to action or inaction in the pediatric context. This framework, however, was developed at an institution that allows simulated death and thus does not address the experience of those centers at which this technique is not used. To address this, we performed a parallel qualitative study with the intent of augmenting the initial framework. METHODS: We conducted focus groups, using a constructivist grounded theory approach, using physicians and nurses who have experienced a simulated cardiac arrest. The participants were recruited via e-mail. Transcripts were analyzed by coders blinded to the original framework to generate a list of provisional themes that were iteratively refined. These themes were then compared with the themes from the original article and used to derive a consensus model that incorporated the most relevant features of each. RESULTS: Focus group data yielded 7 themes. Six were similar to those developed in the original framework. One important exception was noted; however, those learners not exposed to patient death due to action or inaction often felt that the mannequin's survival was artificial. This additional theme was incorporated into a revised framework. DISCUSSION: The original framework addresses most aspects of learner reactions to simulated death. Our work suggests that adding the theme pertaining to the lack of realism that can be perceived when the mannequin is unexpectedly saved results in a more robust theoretical framework transferable to centers that do not allow mannequin death.

Current Practices in the Timing of Stage 2 Palliation.

BACKGROUND: Mortality through single-ventricle palliation remains high and the effect of the timing of stage 2 palliation (S2P) is not well understood. We investigated current practice patterns in the timing of S2P across two professional societies and compared them to actual practice patterns from two databases of patients who underwent S2P. METHODS: A ten-question survey was distributed to the members of the Congenital Heart Surgeons' Society (CHSS) and the European Congenital Heart Surgeons' Association (ECHSA). Results were summarized using descriptive statistics. Surgeon-reported preferences were compared to clinical data from the CHSS Critical Left Ventricular Outflow Tract Obstruction (LVOTO) Registry and the Pediatric Heart Network Single Ventricle Reconstruction (SVR) database. RESULTS: Overall, 38% (88 of 232) of surgeons from 74 institutions responded, of which 70% (62 of 88) were CHSS members and 30% (26 of 88) were ECHSA members. Surgeons reported performing S2P at a median of five months after stage 1 (interquartile range [IQR]: 4.5-6), with no difference between CHSS and ECHSA surgeons. Surgeons reported performing nonelective S2P at a median of 4.5 months after stage 1 (IQR: 3.5-5.5), again with no difference by society. No difference existed between the surgeon-reported preferences and patient data in the Critical LVOTO and SVR databases for the timing of elective (5 vs 5.1 vs 5.3 months, P = .19) or nonelective S2P (4.5 vs 4.6 vs 4.2 months, P = .06). CONCLUSION: There was a remarkable lack of variation in surgeon preferences regarding the timing of S2P. This may represent a natural standardization of practice across congenital heart surgery, which is notable, given the current lack of guidelines regarding the timing of S2P.

Pharmacological Manipulation of Peripheral Vascular Resistance in Special Clinical Situations after Pediatric Cardiac Surgery.

Pediatric cardiac surgery patients commonly suffer from alterations in vascular tone in the early post-operative period. Pharmacologic manipulation of systemic vascular resistance (SVR) can be complex in a variety of special patient situations including extremes of age, presence of left sided valvar lesions and the use of mechanical circulatory support. Familiarity with how these special circumstances alter SVR and the response to pharmacologic intervention will allow for tailored therapy and hopefully, optimized outcomes. This article addresses the eighth topic of the special issue entitled "Pharmacologic strategies with afterload reduction in low cardiac output syndrome after pediatric cardiac surgery".