Reducing Hyperoxia Exposure in Infants Requiring Veno-Arterial Extracorporeal Membrane Oxygenation after Cardiac Surgery.

Recent studies have suggested worse outcomes in patients exposed to hyperoxia while supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). However, there are no data regarding the effect of reducing hyperoxia exposure in this population by adjusting the fraction of inspired oxygen (FiO2) of the sweep gas of the ECMO circuit. A retrospective review of 143 patients less than 1 year of age requiring VA-ECMO following cardiac surgery from 2007 to 2018 was completed. 64 patients had a FiO2 of the sweep gas < 100% with an average PaO2 of 210 mm Hg in the first 48 h of support [vs 405 mm Hg in the group with a FiO2 = 100% (p < 0.0001)]. There was no difference in mortality at 30 days after surgery or other markers of end-organ injury with respect to whether the FiO2 was adjusted. At least one PaO2 value < 200 mm Hg in the first 24 h on ECMO in patients with a FiO2 < 100% trended toward a significant association (OR = 0.45, 95% CI = 0.21-1.01) with decreased risk of 30-day mortality when compared to those patients with a FiO2 = 100% and all PaO2 values > 200 mm Hg. Only 47% of patients with a FiO2 < 100% had an average PaO2 less than 200 mm Hg which indicates that the intervention of reducing the FiO2 of the sweep gas was not entirely effective at reducing hyperoxia exposure. Future research is needed for developing clinical protocols to avoid hyperoxia and to identify mechanisms for hyperoxia-induced injury on VA-ECMO.

Prediction of extubation failure in the paediatric cardiac ICU using machine learning and high-frequency physiologic data.

BACKGROUND: Cardiac intensivists frequently assess patient readiness to wean off mechanical ventilation with an extubation readiness trial despite it being no more effective than clinician judgement alone. We evaluated the utility of high-frequency physiologic data and machine learning for improving the prediction of extubation failure in children with cardiovascular disease. METHODS: This was a retrospective analysis of clinical registry data and streamed physiologic extubation readiness trial data from one paediatric cardiac ICU (12/2016-3/2018). We analysed patients' final extubation readiness trial. Machine learning methods (classification and regression tree, Boosting, Random Forest) were performed using clinical/demographic data, physiologic data, and both datasets. Extubation failure was defined as reintubation within 48 hrs. Classifier performance was assessed on prediction accuracy and area under the receiver operating characteristic curve. RESULTS: Of 178 episodes, 11.2% (N = 20) failed extubation. Using clinical/demographic data, our machine learning methods identified variables such as age, weight, height, and ventilation duration as being important in predicting extubation failure. Best classifier performance with this data was Boosting (prediction accuracy: 0.88; area under the receiver operating characteristic curve: 0.74). Using physiologic data, our machine learning methods found oxygen saturation extremes and descriptors of dynamic compliance, central venous pressure, and heart/respiratory rate to be of importance. The best classifier in this setting was Random Forest (prediction accuracy: 0.89; area under the receiver operating characteristic curve: 0.75). Combining both datasets produced classifiers highlighting the importance of physiologic variables in determining extubation failure, though predictive performance was not improved. CONCLUSION: Physiologic variables not routinely scrutinised during extubation readiness trials were identified as potential extubation failure predictors. Larger analyses are necessary to investigate whether these markers can improve clinical decision-making.

Cardiac Networks United: an integrated paediatric and congenital cardiovascular research and improvement network.

Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network - Cardiac Networks United - that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups - heart centre executives, research leaders, learning health system experts, and parent advocates - offer their perspectives on the need for this new collaborative effort.

Severe Acute Kidney Injury Following Stage 1 Norwood Palliation: Effect on Outcomes and Risk of Severe Acute Kidney Injury at Subsequent Surgical Stages.

OBJECTIVES: To identify associations of severe acute kidney injury early after stage 1 (Norwood) operation with risk of severe acute kidney injury and comorbidities at subsequent palliative stages in patients with hypoplastic left heart syndrome and other single ventricle lesions with left-sided obstruction. DESIGN: Retrospective cohort study. Severe acute kidney injury defined as Kidney Disease Improving Global Outcomes stage 3. SETTING: Single pediatric cardiac center. PATIENTS: Infants less than or equal to 28 days old with single ventricle physiology and left-sided obstruction undergoing stage 1 operation between September 2007 and November 2012 (n = 136). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of severe acute kidney injury was 21% (28/136) following stage 1, 12% (12/98) following stage 2 palliation (superior cavo-pulmonary anastomosis), and 10% (7/73) following stage 3 palliation (total cavo-pulmonary anastomosis). Severe acute kidney injury early after stage 1 operation was significantly associated with continuous intravenous loop diuretic infusion, need for extracorporeal membrane oxygenation, and in-hospital death (all p < 0.05). Gestational age at birth was associated with severe acute kidney injury at stage 2 (p = 0.04) and stage 3 (p = 0.01). Severe acute kidney injury at stage 1 was an independent risk factor for severe acute kidney injury at stage 2 (adjusted odds ratio, 4.3; 95% CI, 1.1-16.9; p = 0.04). Development of severe acute kidney injury after stage 1 was associated with longer mechanical ventilation time after stage 3 (p = 0.047). CONCLUSIONS: Severe acute kidney injury after stage 1 palliation was an independent risk factor for developing severe acute kidney injury at stage 2, and was associated with prolonged duration of mechanical ventilation following stage 3. Information on the incidence and associated risk factors for postoperative acute kidney injury in hypoplastic left heart syndrome patients from multiple congenital heart centers is a necessary next step to further understand the long-term burden of severe acute kidney injury after staged palliation.

Design and initial results of a programme for routine standardised longitudinal follow-up after congenital heart surgery.

BACKGROUND: With improvements in early survival following congenital heart surgery, it has become increasingly important to understand longer-term outcomes; however, routine collection of these data is challenging and remains very limited. We describe the development and initial results of a collaborative programme incorporating standardised longitudinal follow-up into usual care at the Children's Hospital of Philadelphia (CHOP) and University of Michigan (UM). METHODS: We included children undergoing benchmark operations of the Society of Thoracic Surgeons. Considerations regarding personnel, patient/parent engagement, funding, regulatory issues, and annual data collection are described, and initial follow-up rates are reported. RESULTS: The present analysis included 1737 eligible patients undergoing surgery at CHOP from January 2007 to December 2014 and 887 UM patients from January 2010 to December 2014. Overall, follow-up data, of any type, were obtained from 90.8% of patients at CHOP (median follow-up 4.3 years, 92.2% survival) and 98.3% at UM (median follow-up 2.8 years, 92.7% survival), with similar rates across operations and institutions. Most patients lost to follow-up at CHOP had undergone surgery before 2010. Standardised questionnaires assessing burden of disease/quality of life were completed by 80.2% (CHOP) and 78.4% (UM) via phone follow-up. In subsequent pilot testing of an automated e-mail system, 53.4% of eligible patients completed the follow-up questionnaire through this system. CONCLUSIONS: Standardised follow-up data can be obtained on the majority of children undergoing benchmark operations. Ongoing efforts to support automated electronic systems and integration with registry data may reduce resource needs, facilitate expansion across centres, and support multi-centre efforts to understand and improve long-term outcomes in this population.

Tight glycemic control versus standard care after pediatric cardiac surgery.

BACKGROUND: In some studies, tight glycemic control with insulin improved outcomes in adults undergoing cardiac surgery, but these benefits are unproven in critically ill children at risk for hyperinsulinemic hypoglycemia. We tested the hypothesis that tight glycemic control reduces morbidity after pediatric cardiac surgery. METHODS: In this two-center, prospective, randomized trial, we enrolled 980 children, 0 to 36 months of age, undergoing surgery with cardiopulmonary bypass. Patients were randomly assigned to either tight glycemic control (with the use of an insulin-dosing algorithm targeting a blood glucose level of 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) or standard care in the cardiac intensive care unit (ICU). Continuous glucose monitoring was used to guide the frequency of blood glucose measurement and to detect impending hypoglycemia. The primary outcome was the rate of health care-associated infections in the cardiac ICU. Secondary outcomes included mortality, length of stay, organ failure, and hypoglycemia. RESULTS: A total of 444 of the 490 children assigned to tight glycemic control (91%) received insulin versus 9 of 490 children assigned to standard care (2%). Although normoglycemia was achieved earlier with tight glycemic control than with standard care (6 hours vs. 16 hours, P<0.001) and was maintained for a greater proportion of the critical illness period (50% vs. 33%, P<0.001), tight glycemic control was not associated with a significantly decreased rate of health care-associated infections (8.6 vs. 9.9 per 1000 patient-days, P=0.67). Secondary outcomes did not differ significantly between groups, and tight glycemic control did not benefit high-risk subgroups. Only 3% of the patients assigned to tight glycemic control had severe hypoglycemia (blood glucose <40 mg per deciliter [2.2 mmol per liter]). CONCLUSIONS: Tight glycemic control can be achieved with a low hypoglycemia rate after cardiac surgery in children, but it does not significantly change the infection rate, mortality, length of stay, or measures of organ failure, as compared with standard care. (Funded by the National Heart, Lung, and Blood Institute and others; SPECS ClinicalTrials.gov number, NCT00443599.).

Collaborative quality improvement in the cardiac intensive care unit: development of the Paediatric Cardiac Critical Care Consortium (PC4).

Despite many advances in recent years for patients with critical paediatric and congenital cardiac disease, significant variation in outcomes remains across hospitals. Collaborative quality improvement has enhanced the quality and value of health care across specialties, partly by determining the reasons for variation and targeting strategies to reduce it. Developing an infrastructure for collaborative quality improvement in paediatric cardiac critical care holds promise for developing benchmarks of quality, to reduce preventable mortality and morbidity, optimise the long-term health of patients with critical congenital cardiovascular disease, and reduce unnecessary resource utilisation in the cardiac intensive care unit environment. The Pediatric Cardiac Critical Care Consortium (PC4) has been modelled after successful collaborative quality improvement initiatives, and is positioned to provide the data platform necessary to realise these objectives. We describe the development of PC4 including the philosophical, organisational, and infrastructural components that will facilitate collaborative quality improvement in paediatric cardiac critical care.

Splanchnic near-infrared spectroscopy and risk of necrotizing enterocolitis after neonatal heart surgery.

Infants with critical congenital heart disease, especially patients with a single-ventricle (SV) physiology, are at increased risk for the development of necrotizing enterocolitis (NEC). Decreased splanchnic oxygen delivery may contribute to the development of NEC and may be detected by regional oximetry (rSO2) via splanchnic near-infrared spectroscopy (NIRS). This prospective study enrolled 64 neonates undergoing biventricular (BV) repair or SV palliation for CHD and monitored postoperative splanchnic rSO2 before and during initiation of enteral feedings to determine whether changes in rSO2 are associated with risk of NEC. Suspected or proven NEC was observed in 32 % (11/34) of the SV subjects and 0 % (0/30) of the BV subjects (p = 0.001). Compared with the BV subjects, the SV palliated subjects had significantly lower splanchnic rSO2 before and during initiation of enteral feedings, but the groups showed no difference after correction for lower pulse oximetry (SpO2) in the SV group. The clinical parameters were similar among the SV subjects with and without NEC except for cardiopulmonary bypass times, which were longer for the patients who experienced NEC (126 vs 85 min; p = 0.03). No difference was observed in splanchnic rSO2 or in the SpO2-rSO2 difference between the SV subjects with and without NEC. Compared with the patients who had suspected or no NEC, the subjects with proven NEC had a lower average splanchnic rSO2 (32.6 vs 47.0 %; p = 0.05), more time with rSO2 less than 30 % (48.8 vs 6.7 %; p = 0.04) at one-fourth-volume feeds, and more time with SpO2-rSO2 exceeding 50 % (33.3 vs 0 %; p = 0.03) before feeds were initiated. These data suggest that splanchnic NIRS may be a useful tool for assessing risk of NEC, especially in patients with an SV physiology.

Methods to Enhance Causal Inference for Assessing Impact of Clinical Informatics Platform Implementation.

BACKGROUND: Hospitals are increasingly likely to implement clinical informatics tools to improve quality of care, necessitating rigorous approaches to evaluate effectiveness. We leveraged a multi-institutional data repository and applied causal inference methods to assess implementation of a commercial data visualization software in our pediatric cardiac intensive care unit. METHODS: Natural experiment in the University of Michigan (UM) Cardiac Intensive Care Unit pre and postimplementation of data visualization software analyzed within the Pediatric Cardiac Critical Care Consortium clinical registry; we identified N=21 control hospitals that contributed contemporaneous registry data during the study period. We used the platform during multiple daily rounds to visualize clinical data trends. We evaluated outcomes-case-mix adjusted postoperative mortality, cardiac arrest and unplanned readmission rates, and postoperative length of stay-most likely impacted by this change. There were no quality improvement initiatives focused specifically on these outcomes nor any organizational changes at UM in either era. We performed a difference-in-differences analysis to compare changes in UM outcomes to those at control hospitals across the pre versus postimplementation eras. RESULTS: We compared 1436 pre versus 779 postimplementation admissions at UM to 19 854 (pre) versus 14 160 (post) at controls. Admission characteristics were similar between eras. Postimplementation at UM we observed relative reductions in cardiac arrests among medical admissions, unplanned readmissions, and postoperative length of stay by -14%, -41%, and -18%, respectively. The difference-in-differences estimate for each outcome was statistically significant (P<0.05), suggesting the difference in outcomes at UM pre versus postimplementation is statistically significantly different from control hospitals during the same time. CONCLUSIONS: Clinical registries provide opportunities to thoroughly evaluate implementation of new informatics tools at single institutions. Borrowing strength from multi-institutional data and drawing ideas from causal inference, our analysis solidified greater belief in the effectiveness of this software across our institution.

Personnel and unit factors impacting outcome after cardiac arrest in a dedicated pediatric cardiac intensive care unit.

OBJECTIVE: To assess the impact of personnel and unit factors on outcome from cardiac arrest in a dedicated pediatric cardiac intensive care unit. DESIGN: Retrospective medical record review. SETTING: Dedicated cardiac intensive care unit at a quaternary academic children's hospital. PATIENTS: Children and young adults who had cardiac arrest while cared for in the pediatric cardiac intensive care unit from January 1, 2006, to December 31, 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred two index cardiac arrests over a 3-yr period in our pediatric cardiac intensive care unit were reviewed. We defined successful resuscitation as either return of spontaneous circulation or successful cannulation to extracorporeal membrane oxygenation. Differences in resuscitation rates were assessed across categorical systems variables using logistic regression. The rate of successful resuscitation was 84% (return of spontaneous circulation 74%, extracorporeal membrane oxygenation 10%). Survival to hospital discharge was 48% for patients who had a cardiac arrest. 11% of arrests during the week and 31% during weekends (odds ratio 3.8; 95% confidence interval 1.2-11.5) were not successfully resuscitated. Unsuccessful resuscitation was significantly more likely when the primary nurse had <1 yr of experience in the pediatric cardiac intensive care unit (50% <1 yr vs. 13% >1 yr; odds ratio 6.8; confidence interval 1.5-31.0). Cardiac arrest on a weekend day and <1-yr pediatric cardiac intensive care unit nursing experience were also associated with unsuccessful resuscitation in a multivariable model. Resuscitation outcomes were similar when senior intensive care unit attending physicians were on-call at the time of arrest compared with other intensive care unit staff (17% unsuccessful vs. 15%; odds ratio 1.2; confidence interval 0.4-3.7). Arrests where the attending physician was present at the onset resulted in unsuccessful resuscitation 18% of the time vs. 14% for events where the attending was not present (odds ratio 1.3; confidence interval 0.5-3.9). CONCLUSIONS: Our data suggest that personnel and unit factors may impact outcome after cardiac arrest in a pediatric cardiac intensive care unit. Weekend arrests and less experience of the primary nurse were risk factors for unsuccessful resuscitation. Neither presence at arrest onset nor experience of the attending cardiac intensivist was associated with outcome.

Junctional ectopic tachycardia after infant heart surgery: incidence and outcomes.

Junctional ectopic tachycardia (JET) is an arrhythmia observed almost exclusively after open heart surgery in children. Current literature on JET has not focused on patients at the highest risk of both developing and being negatively impacted by JET. The purpose of this study was to determine the overall incidence of JET in an infant patient cohort undergoing open cardiac surgery, to identify patient- and procedure-related factors associated with developing JET, and to assess the clinical impact of JET on patient outcomes. We performed a nested case-control study from the complete cohort of patients at our institution younger than 1 year of age who underwent open heart surgery between 2005 and 2010. JET patients were compared with an age matched control group undergoing open heart surgery without JET regarding potential risk factors and outcomes. The overall incidence of JET in infants after open cardiac surgery was 14.3 %. From multivariate analyses, complete repair of tetralogy of Fallot [adjusted odds ratio (AOR) 2.0, 95 % CI 1.12-3.57] and longer aortic cross clamp times (AOR 1.02, 95 % CI 1.01-1.03) increased the risk of developing JET. Patients with JET had longer length of intubation, intensive care unit stays, and total length of hospitalization, and were more likely to require extracorporeal membrane oxygenation support (13 vs. 4.3 %). JET is a common postoperative arrhythmia in infants after open heart operations. Both anatomic substrate and surgical procedure contribute to the overall risk of developing JET. Developing JET is associated with worse clinical outcomes.

Nicorandil attenuates ventricular dysfunction and organ injury after cardiopulmonary bypass.

BACKGROUND: Nicorandil, an adenosine triphosphate-sensitive potassium channel agonist and nitric oxide donor, is a coronary vasodilator used to treat ischemia-induced chest pain, but it's potential cardioprotective benefits during open heart surgery have not been thoroughly investigated. The study objective was to assess the impact of nicorandil on postoperative ventricular dysfunction and end-organ injury in an established experimental model of open-heart surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest. We hypothesized that nicorandil would attenuate myocardial ischemia-reperfusion (IR) injury, preserve ventricular function, and reduce end-organ injury. METHODS: Rabbits were cannulated for CPB, followed by 60 min of aortic cross-clamp (ACC) with cold cardioplegic arrest, and 120 min of recovery after ACC removal. Nicorandil (or normal saline vehicle) was given intravenously 5 min before ACC and continued throughout the recovery period. Left ventricular developed pressure (LVDP), systolic contractility (LV + dP/dt), and diastolic relaxation (LV -dP/dt) were continuously recorded, and blood and tissue samples were collected for measurement of oxidant stress (OS), inflammation, apoptosis, and organ injury. RESULTS: Nicorandil significantly attenuated IR-induced LV dysfunction compared to saline control (R-120: LV + dP/dt: 1596 ± 397 vs. 514 ± 269 mmHg/s, p = 0.010; LV -dP/dt: -1524 ± 432 vs. -432 ± 243 mmHg/s, p < 0.001; LVDP: 55 ± 11 vs. 22 ± 5 mmHg, p = 0.046). Furthermore, nicorandil inhibited IR-induced increases in OS, inflammation, apoptosis, and organ injury. CONCLUSIONS: Nicorandil exhibits myocardial protection by attenuation of IR-induced LV dysfunction associated with OS, inflammation, apoptosis, and organ injury. Nicorandil should be explored further as a potential therapeutic strategy for limiting global IR injury during open-heart surgery in humans.

Impact of N-acetylcysteine on neonatal cardiomyocyte ischemia-reperfusion injury.

Reactive oxygen species (ROS) are hypothesized to play a key role in myocardial ischemia-reperfusion (IR) injury after cardiopulmonary bypass in children. Clinical studies in adults and several animal models suggest that myocardial IR injury involves cardiomyocyte apoptosis and necrosis. This study investigated a potential relationship between IR-induced ROS production and neonatal cardiomyocyte apoptosis using both in vitro and ex vivo techniques. For in vitro experiments, embryonic rat cardiomyocytes (H9c2 cells) exposed to hypoxia-reoxygenation (HR) showed a time-dependent increase in gp91 phox (a marker for ROS production by NADPH oxidases), caspase-3 (a key mediator of apoptosis) expression, and a decrease in the glutathione redox ratio. N-acetylcysteine (NAC; 0.25-2 mM), a potent antioxidant, decreased gp91 phox and caspase-3 expression, inhibited apoptosis and restored the glutathione redox ratio. For ex vivo study, IR injury significantly reduced left ventricular (LV) function and increased the expression of gp91 phox and caspase-3 in Langendorff-perfused neonatal (7-14 d) rabbit hearts. NAC (0.4 mM) treatment completely attenuated LV dysfunction after IR. In summary, neonatal myocardial IR injury is associated with an increase in cardiomyocyte oxidative stress and apoptosis. NAC attenuates apoptosis in an in vitro embryonic rat cardiomyocyte model of HR, and myocardial dysfunction in an ex vivo neonatal rabbit model of myocardial IR injury.

Low renal oximetry correlates with acute kidney injury after infant cardiac surgery.

Acute kidney injury (AKI) is a frequent complication after cardiopulmonary bypass surgery during infancy. Standard methods for evaluating renal function are not particularly sensitive nor are proximate indicators of renal dysfunction that allow intervention in real time. Near-infrared spectroscopy (NIRS) is a newer noninvasive technology that continuously evaluates regional oximetry and may correlate with renal injury and adverse outcomes after cardiac surgery in infants. This prospective observational study enrolled 40 infants (age, <12 months) undergoing biventricular repair. Continuous renal oximetry data were collected for the first 48 postoperative hours and correlated with postoperative course, standard laboratory data, and the occurrence of acute renal injury. Subjects with low renal oximetry (below 50% for >2 h) had significantly higher postoperative peak creatinine levels by 48 h (0.8 ± 0.4 vs. 0.52 ± 0.2; p = 0.003) and a higher incidence of AKI (50 vs. 3.1%; p = 0.003) than those with normal renal oximetry. These subjects also required more ventilator days and greater vasoactive support, and they had elevated lactate levels. Prolonged low renal near-infrared oximetry appears to correlate with renal dysfunction, decreased systemic oxygen delivery, and the overall postoperative course in infants with congenital heart disease undergoing biventricular repair.

Feeding complications in hypoplastic left heart syndrome after the Norwood procedure: a systematic review of the literature.

Gastrointestinal and feeding complications after the Norwood procedure in infants with hypoplastic left heart syndrome increases morbidity and mortality. These problems are the result of intraoperative challenges, shunt-dependent physiology, and the absence of best-practice guidelines. In response, a systematic review of feeding-related complications and management strategies was performed. A literature search from 1950 to March 2010 identified 21 primary research articles and 4 reviews. Dysphagia, necrotizing enterocolitis (NEC), and poor nutritional status are significant feeding-related complications. Three studies directly compared the modified Blalock-Taussig shunt with the right ventricle-to-pulmonary artery conduit (RV-PA). Patients palliated with either shunt had impaired mesenteric blood flow. Mortality did not differ between shunt types. Three studies demonstrated improved outcomes, e.g., increased survival, decreased incidence of NEC, and decreased median time to recommended daily allowance of calories, with a postoperative feeding algorithm. Two studies showed increased survival between stage I and II surgical palliation after implementation of a home-monitoring system consisting of daily weight and systemic oxygen saturation measurements. The RV-PA shunt does not significantly alter mortality or increase mesenteric blood flow. A postoperative feeding algorithm and a home-monitoring system may improve outcomes and decrease average hospital length of stay (LOS). Additional studies are needed to determine which interventions, as part of a standardized protocol, improve survival and decrease complications.

Impact of Protein-Losing Enteropathy on Inflammatory Biomarkers and Vascular Dysfunction in Fontan Circulation.

Fontan palliation has improved survival for single ventricle patients, but long-term complications persist including cardiovascular dysfunction, neurohormonal abnormalities, and protein-losing enteropathy (PLE). Although chronic inflammation contributes to morbidity, an association between inflammation and vascular dysfunction has not been studied. We assessed inflammation and vascular function in 31 Fontan-palliated patients (52% male, median age 14.3 years), including 10 PLE+. Fontan circulation was associated with altered inflammatory cytokines (TNF-α: mean 2.5 ± 1.4 vs. 0.7 ± 0.2 pg/ml, p < 0.0001; sTNFR2: 371 ± 108 vs. 2694 ± 884 pg/ml, p < 0.0001) and vascular dysfunction [log-transformed reactive hyperemia index (lnRHI) 0.28 ± 0.19 vs. 0.47 ± 0.26, p < 0.01; augmentation index (AI) -2.9 ± 13.8 vs. -16.3 ± 12.0, p = 0.001; circulating endothelial progenitor cells (cEPCs) 5.0 ± 8.1 vs. 22.8 ± 15.9, p = 0.0002)]. Furthermore, PLE+ patients showed greater inflammation (IFN-γ 6.3 ± 2.2 vs. 11.5 ± 7.9 pg/ml, p = 0.01; sTNFR1: 1181 ± 420 vs. 771 ± 350 pg/ml, p = 0.01) and decreased arterial compliance (AI: 5.4 ± 17.1 vs. -6.8 ± 10.2, p = 0.02) than PLE- patients. Circulating EPCs, but not inflammatory cytokines, were inversely associated with arterial stiffness in Fontan patients. In conclusion, chronic inflammation and vascular dysfunction are observed after Fontan operation, with greater inflammation and arterial stiffness in Fontan patients with active PLE. However, there is no clear association between inflammatory cytokines and vascular dysfunction, suggesting these pathophysiologic processes are not mechanistically linked.

Adrenocortical response in infants undergoing cardiac surgery with cardiopulmonary bypass and circulatory arrest.

OBJECTIVE: To detail changes in adrenocorticotropic hormone (ACTH), cortisol, and aldosterone levels following cardiac surgery and to test the hypothesis that postcardiotomy infants requiring excessively high-dose vasopressor support will demonstrate adrenal insufficiency which will be proportional to cardiopulmonary bypass (CPB)/circulatory arrest times and vasopressor requirements. DESIGN: Prospective observational pilot study. SETTING: A tertiary care pediatric cardiac intensive care unit. PATIENTS: Prospectively enrolled infants were divided into three subgroups: CPB, CPB with deep hypothermic circulatory arrest (DHCA), and control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A representative patient sample from each surgical group underwent preoperative synthetic ACTH testing. Postoperative serum samples for cortisol, ACTH, and inotrope score (IS) were collected at discrete intervals over 48 hrs along with patient demographics, surgical procedure, and CPB/DHCA times. Fifty-eight patients were classified by subgroup: 31 CPB, 22 DHCA, and 5 controls. Ten patients with DHCA, analyzed separately, received intraoperative steroids. Tested patients demonstrated preoperative adrenal competence. Cortisol peaked within 2 hrs of surgery without differences among groups. ACTH inversely correlated with bypass time in patients with DHCA (p = .03) but not with circulatory arrest time. Peak cortisol level did not correlate with simultaneous IS. Although not noted in any DHCA-steroid patients, nine patients had increased ACTH/cortisol ratios in association with elevated ISs suggesting inadequate adrenal responsiveness to endogenous ACTH. CONCLUSIONS: The majority of infants with congenital heart disease and intact hypothalamic-pituitary-adrenal axes demonstrated an appropriate adrenocortical stress response to cardiac surgery. Peak serum cortisol was unrelated to CPB/DHCA time and did not predict the level of inotrope support. However, a subset of patients with elevated ACTH/cortisol ratios seemed to have a clinical status consistent with adrenal insufficiency and may be a target group for early postoperative steroid therapy.

Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass.

OBJECTIVE: Inotrope score has been proposed as a marker of illness severity after pediatric cardiac surgery despite a lack of data to support its use as such. The goal of this study was to determine the association between inotropic/vasoactive support and clinical outcome in infants after cardiac surgery. DESIGN: Retrospective chart review. SETTING: Dedicated pediatric cardiothoracic intensive care unit at an academic, tertiary care medical center. PATIENTS: One hundred seventy-four patients 0 to 6 months of age admitted to the cardiothoracic intensive care unit after cardiac surgery with cardiopulmonary bypass between August 2007 and June 2008. Forty-three percent were neonates, and 39% had functional single ventricle physiology. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hourly doses of all vasoactive medications were recorded for the first 48 hrs after admission to the cardiothoracic intensive care unit and a vasoactive-inotropic score was calculated. The maximum vasoactive-inotropic score level over the first 48 hrs was a good predictor of poor clinical outcome (death, cardiac arrest, mechanical circulatory support, renal replacement therapy, and/or neurologic injury). After controlling for diagnosis, high maximum vasoactive-inotropic score was strongly associated with a poor outcome with an adjusted odds ratio of 8.1 (95% confidence interval, 3.4-19.2; p < .001) compared with patients with a low maximum vasoactive-inotropic score. High vasoactive-inotropic score was also associated with prolonged cardiothoracic intensive care unit stay, duration of mechanical ventilation, and time to negative fluid balance. CONCLUSIONS: The amount of cardiovascular support in the first 48 hrs after congenital heart surgery with cardiopulmonary bypass predicts eventual morbidity and mortality in young infants. The degree of support is best characterized by a maximum vasoactive-inotropic score obtained during this period. The usefulness of vasoactive-inotropic score as an independent predictor of clinical outcome in infants after cardiac surgery may have important implications for future cardiothoracic intensive care unit research.

Near infrared spectroscopy (NIRS) should not be standard of care for postoperative management.

Neurologic dysfunction is a problem in patients with congenital heart disease. Near infrared spectroscopy (NIRS) may provide a real-time window into cerebral oxygenation. Enthusiasm for NIRS has increased in hopes of reducing neurologic dysfunction. However, potential gains need to be evaluated relative to cost and potential detriment of intervention before routine implementation. Responding to data in ways that seem intuitively beneficial can be risky when the long-term impact is unknown. Many centers, and even entire countries, have adopted NIRS as standard of care. Available data suggest that multimodality monitoring, including NIRS, may be a useful adjunct. However, the current literature on the use of NIRS alone does not demonstrate improvement in neurologic outcome. Data correlating NIRS findings with indirect measures of neurologic outcome or mortality are limited. Although NIRS has promise for measuring regional tissue oxygen saturation, the lack of data demonstrating improved outcomes limits the support for wide-spread implementation.

Intravenous induction of therapeutic hypothermia in the management of junctional ectopic tachycardia: a pilot study.

Therapeutic hypothermia has been used to treat children with postcardiotomy junctional ectopic tachycardia (JET). However, cooling techniques have not been systematically studied. This pilot study investigates the safety and efficacy of intravenous cold saline infusions used to augment surface cooling to achieve a core temperature of 32-34 degrees C for pediatric patients with JET. For this study, 10 patients with JET were cooled using cooling blankets and 4 degrees C normal saline infusions to a target central temperature of 32-34 degrees C. Vital signs and central temperatures were monitored continuously during the cooling period. Comprehensive metabolic panels, complete blood counts, coagulation studies, and cultures were obtained per study protocol. Therapeutic hypothermia was achieved within 65 min (interquartile range [IQR], 45-75 min). The median heart rate decreased from 187 beats per min (bpm) (IQR, 184-190 bpm) to 158 bpm (IQR, 121-162 bpm). For all the patients, atrioventricular synchrony was restored either with conversion to normal sinus rhythm or with successful atrial pacing. No clinically significant electrolyte abnormalities or bleeding events occurred. Two deaths, not directly attributable to the cooling protocol, occurred. Intravenous induction of therapeutic hypothermia can be safely and effectively performed for children with JET. Further studies, powered for clinically relevant outcomes, should evaluate this potentially valuable therapeutic method.