David S. Cooper

Interstage mortality after the Norwood procedure: Results of the multicenter Single Ventricle Reconstruction trial

OBJECTIVEnFor infants with single ventricle malformations undergoing staged repair, interstage mortality is reported at 2% to 20%. The Single Ventricle Reconstruction trial randomized subjects with a single morphologic right ventricle undergoing a Norwood procedure to a modified Blalock-Taussig shunt (MBTS) or a right ventricle-to-pulmonary artery shunt (RVPAS). The aim of this analysis was to explore the associations of interstage mortality and shunt type, and demographic, anatomic, and perioperative factors.nnnMETHODSnParticipants in the Single Ventricle Reconstruction trial who survived to discharge after the Norwood procedure were included (nxa0=xa0426). Interstage mortality was defined as death postdischarge after the Norwood procedure and before the stage II procedure. Univariate analysis and multivariable logistic regression were performed adjusting for site.nnnRESULTSnOverall interstage mortality was 50 of 426 (12%)-13 of 225 (6%) for RVPAS and 37 of 201 (18%) for MBTS (odds ratio [OR] for MBTS, 3.4; Pxa0<xa0.001). When moderate to severe postoperative atrioventricular valve regurgitation (AVVR) was present, interstage mortality was similar between shunt types. Interstage mortality was independently associated with gestational age less than 37 weeks (OR, 3.9; Pxa0=xa0.008), Hispanic ethnicity (OR, 2.6; Pxa0=xa0.04), aortic atresia/mitral atresia (OR, 2.3; Pxa0=xa0.03), greater number of post-Norwood complications (OR, 1.2; Pxa0=xa0.006), census block poverty level (Pxa0=xa0.003), and MBTS in subjects with no or mild postoperative AVVR (OR, 9.7; Pxa0<xa0.001).nnnCONCLUSIONSnInterstage mortality remains high at 12% and is increased with the MBTS compared with the RVPAS if postoperative AVVR is absent or mild. Preterm delivery, anatomic, and socioeconomic factors are also important. Avoiding preterm delivery when possible and close surveillance after Norwood hospitalization for infants with identified risk factors may reduce interstage mortality.

Risk factors for hospital morbidity and mortality after the Norwood procedure: A report from the Pediatric Heart Network Single Ventricle Reconstruction trial

OBJECTIVESnWe sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in newborn infants with hypoplastic left heart syndrome and other single right ventricle anomalies enrolled in the Single Ventricle Reconstruction trial.nnnMETHODSnPotential predictors for outcome included patient- and procedure-related variables and center volume and surgeon volume. Outcome variables occurring during the Norwood procedure and before hospital discharge or stage II procedure included mortality, end-organ complications, length of ventilation, and hospital length of stay. Univariate and multivariable Cox regression analyses were performed with bootstrapping to estimate reliability for mortality.nnnRESULTSnAnalysis included 549 subjects prospectively enrolled from 15 centers; 30-day and hospital mortality were 11.5% (63/549) and 16.0% (88/549), respectively. Independent risk factors for both 30-day and hospital mortality included lower birth weight, genetic abnormality, extracorporeal membrane oxygenation (ECMO) and open sternum on the day of the Norwood procedure. In addition, longer duration of deep hypothermic circulatory arrest was a risk factor for 30-day mortality. Shunt type at the end of the Norwood procedure was not a significant risk factor for 30-day or hospital mortality. Independent risk factors for postoperative renal failure (nxa0=xa046), sepsis (nxa0=xa093), increased length of ventilation, and hospital length of stay among survivors included genetic abnormality, lower center/surgeon volume, open sternum, and post-Norwood operations.nnnCONCLUSIONSnInnate patient factors, ECMO, open sternum, and lower center/surgeon volume are important risk factors for postoperative mortality and/or morbidity during the Norwood hospitalization.

Early Developmental Outcome in Children With Hypoplastic Left Heart Syndrome and Related Anomalies The Single Ventricle Reconstruction Trial

Background— Survivors of the Norwood procedure may experience neurodevelopmental impairment. Clinical trials to improve outcomes have focused primarily on methods of vital organ support during cardiopulmonary bypass. Methods and Results— In the Single Ventricle Reconstruction trial of the Norwood procedure with modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery shunt, 14-month neurodevelopmental outcome was assessed by use of the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. We used multivariable regression to identify risk factors for adverse outcome. Among 373 transplant-free survivors, 321 (86%) returned at age 14.3±1.1 (mean±SD) months. Mean PDI (74±19) and MDI (89±18) scores were lower than normative means (each P<0.001). Neither PDI nor MDI score was associated with type of Norwood shunt. Independent predictors of lower PDI score (R2=26%) were clinical center (P=0.003), birth weight <2.5 kg (P=0.023), longer Norwood hospitalization (P<0.001), and more complications between Norwood procedure discharge and age 12 months (P<0.001). Independent risk factors for lower MDI score (R2=34%) included center (P<0.001), birth weight <2.5 kg (P=0.04), genetic syndrome/anomalies (P=0.04), lower maternal education (P=0.04), longer mechanical ventilation after the Norwood procedure (P<0.001), and more complications after Norwood discharge to age 12 months (P<0.001). We found no significant relationship of PDI or MDI score to perfusion type, other aspects of vital organ support (eg, hematocrit, pH strategy), or cardiac anatomy. Conclusions— Neurodevelopmental impairment in Norwood survivors is more highly associated with innate patient factors and overall morbidity in the first year than with intraoperative management strategies. Improved outcomes are likely to require interventions that occur outside the operating room. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Cardiac extracorporeal life support: state of the art in 2007.

Mechanical circulatory support is an invaluable tool in the care of children with severe refractory cardiac and or pulmonary failure. Two forms of mechanical circulatory support are currently available to neonates, infants, and smaller children, namely extracorporeal membrane oxygenation and use of a ventricular assist device, with each technique having unique advantages and disadvantages. The intra-aortic balloon pump is a third form of mechanical support that has been successfully used in larger children, adolescents, and adults, but has limited applicability in smaller children. In this review, we discuss the current experiences with extracorporeal membrane oxygenation and ventricular assist devices in children with cardiac disease.A variety of forms of mechanical circulatory support are available for children with cardiopulmonary dysfunction refractory to conventional management. These devices require extensive resources, both human and economic. Extracorporeal membrane oxygenation can be effectively used in a variety of settings to provide support to critically-ill patients with cardiac disease. Careful selection of patients and timing of intervention remains challenging. Special consideration should be given to children with cardiac disease with regard to anatomy, physiology, cannulation, and circuit management. Even though exciting progress is being made in the development of ventricular assist devices for long-term mechanical support in children, extracorporeal membrane oxygenation remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation.As the familiarity and experience with extracorporeal membrane oxygenation has grown, new indications have evolved, including emergent resuscitation. This utilization has been termed extracorporeal cardiopulmonary resuscitation. The literature supporting emergent cardiopulmonary support is mounting. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Due to the limitations of conventional circuits for extracorporeal membrane oxygenation, some centres have developed novel systems for rapid cardiopulmonary support. Many centres previously considered a functionally univentricular circulation to be a contraindication to extracorporeal membrane oxygenation, but improved results have been achieved recently with this complex subset of patients. The registry of the Extracorporeal Life Support Organization recently reported the outcome of extracorporeal life support used in neonates for cardiac indications from 1996 to 2000. Of the 740 neonates who were placed on extracorporeal life support for cardiac indications, 118 had hypoplastic left heart syndrome. There was no significant difference in survival between these patients and those with other defects. It is now common to use extracorporeal membrane oxygenation to support patients with a functionally univentricular circulation, and reasonable survival rates are to be expected. Although extracorporeal membrane oxygenation has become a standard of care for many paediatric centres, its use is limited to those patients who require only short-term cardiopulmonary support. Mechanical ventricular assist devices have become standard therapy for adults with cardiac failure refractory to maximal medical management. Several devices are readily available in the United States of America for adults, but there are fewer options available to children. Over the last few years, substantial progress has been made in paediatric mechanical support. Ventricular assist devices are being used with increasing frequency in children with cardiac failure refractory to medical therapy for primary treatment as a long-term bridge to recovery or transplantation. The paracorporeal, pneumatic, pulsatile Berlin Heart ventricular assist device is being used with increasing frequency in Europe and North America to provide univentricular and biventricular support. With this device, a patient can be maintained on mechanical circulatory support while extubated, being mobilized, and feeding by mouth. Mechanical circulatory support should be anticipated, and every attempt must be made to initiate support urgently rather than emergently, before the presence of dysfunction of end organs or circulatory collapse. In an emergency, these patients can be resuscitated with extracorporeal membrane oxygenation and subsequently transitioned to a long-term ventricular assist device after a period of stability.

Renal Replacement Therapy in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is a lifesaving procedure used in neonates, children, and adults with severe, reversible, cardiopulmonary failure. On the basis of single-center studies, the incidence of AKI occurs in 70%-85% of ECMO patients. Those with AKI and those who require renal replacement therapy (RRT) are at high risk for mortality, independent of potentially confounding variables. Fluid overload is common in ECMO patients, and is one of the main indications for RRT. RRT to maintain fluid balance and metabolic control is common in some but not all centers. RRT on ECMO can be performed via an in-line hemofilter or by incorporating a standard continuous renal replacement machine into the ECMO circuit. Both of these methods require specific technical considerations to provide safe and effective RRT. This review summarizes available epidemiologic data and how they apply to our understanding of AKI pathophysiology during ECMO, identifies indications for RRT while on ECMO, reviews technical elements for RRT application in the setting of ECMO, and finally identifies specific research-focused questions that need to be addressed to improve outcomes in this at-risk population.

A multicenter international survey of renal supportive therapy during ECMO: The Kidney Intervention during Extracorporeal Membrane Oxygenation (KIDMO) group

Acute kidney injury and fluid overload (FO) are associated with increased mortality in critically ill patients, including the subset supported with extracorporeal membrane oxygenation (ECMO). The indication for and method of application of renal support therapy (RST) during ECMO is largely unknown beyond single-center experiences. The current study uses a survey design to document practice variation regarding RST, including indication, method of interface with the ECMO circuit, and prescribing practices. Sixty-five international ECMO centers (31%) responded to an online electronic survey regarding RST during ECMO. Nearly a quarter of centers (23%) reported using no RST during ECMO. Among those using the therapy, the predominant mode of therapy applied was convection and included slow continuous ultrafiltration and continuous venovenous hemofiltration. The predominant indication for RST was the treatment (43%) or prevention (16%) of FO. Nephrology rather than critical care medicine is reported as the prescribing service in a majority of centers with a significant difference between US centers and non-US centers. The results of this study identify a wide variation in practice regarding RST during ECMO that will offer multiple important avenues for further research by this group and others regarding the interface of RST and ECMO.

Gestational Age at Birth and Outcomes After Neonatal Cardiac Surgery An Analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database

Background— Gestational age at birth is a potentially important modifiable risk factor in neonates with congenital heart disease. We evaluated the relationship between gestational age and outcomes in a multicenter cohort of neonates undergoing cardiac surgery, focusing on those born at early term (ie, 37–38 weeks’ gestation).nnMethods and Results— Neonates in the Society of Thoracic Surgeons Congenital Heart Surgery Database who underwent cardiac surgery between 2010 and 2011 were included. Multivariable logistic regression was used to evaluate the association of gestational age at birth with in-hospital mortality, postoperative length of stay, and complications, adjusting for other important patient characteristics. Of 4784 included neonates (92 hospitals), 48% were born before 39 weeks’ gestation, including 31% at 37 to 38 weeks. Compared with a 39.5-week gestational age reference level, birth at 37 weeks’ gestational age was associated with higher in-hospital mortality, with an adjusted odds ratio (95% confidence interval) of 1.34 (1.05–1.71; P =0.02). Complication rates were higher and postoperative length of stay was significantly prolonged for those born at 37 and 38 weeks’ gestation (adjusted P <0.01 for all). Late-preterm births (34–36 weeks’ gestation) also had greater mortality and postoperative length of stay (adjusted P ≤0.003 for all).nnConclusions— Birth during the early term period of 37 to 38 weeks’ gestation is associated with worse outcomes after neonatal cardiac surgery. These data challenge the commonly held perception that delivery at any time during term gestation is equally safe and appropriate and question the related practice of elective delivery of fetuses with complex congenital heart disease at early term.nn# CLINICAL PERSPECTIVE {#article-title-35}Background— Gestational age at birth is a potentially important modifiable risk factor in neonates with congenital heart disease. We evaluated the relationship between gestational age and outcomes in a multicenter cohort of neonates undergoing cardiac surgery, focusing on those born at early term (ie, 37–38 weeks’ gestation). Methods and Results— Neonates in the Society of Thoracic Surgeons Congenital Heart Surgery Database who underwent cardiac surgery between 2010 and 2011 were included. Multivariable logistic regression was used to evaluate the association of gestational age at birth with in-hospital mortality, postoperative length of stay, and complications, adjusting for other important patient characteristics. Of 4784 included neonates (92 hospitals), 48% were born before 39 weeks’ gestation, including 31% at 37 to 38 weeks. Compared with a 39.5-week gestational age reference level, birth at 37 weeks’ gestational age was associated with higher in-hospital mortality, with an adjusted odds ratio (95% confidence interval) of 1.34 (1.05–1.71; P=0.02). Complication rates were higher and postoperative length of stay was significantly prolonged for those born at 37 and 38 weeks’ gestation (adjusted P<0.01 for all). Late-preterm births (34–36 weeks’ gestation) also had greater mortality and postoperative length of stay (adjusted P⩽0.003 for all). Conclusions— Birth during the early term period of 37 to 38 weeks’ gestation is associated with worse outcomes after neonatal cardiac surgery. These data challenge the commonly held perception that delivery at any time during term gestation is equally safe and appropriate and question the related practice of elective delivery of fetuses with complex congenital heart disease at early term.

Improved outcomes with peritoneal dialysis catheter placement after cardiopulmonary bypass in infants

BACKGROUNDnAcute kidney injury (AKI) is common in infants after cardiopulmonary bypass and is associated with poor outcomes. Peritoneal dialysis improves outcomes in adults with AKI after bypass, but pediatric data are limited. This retrospective case-matched study was conducted to determine if the practice of peritoneal dialysis catheter (PDC) placement during congenital heart surgery is associated with improved clinical outcomes in infants at high risk for AKI.nnnMETHODSnForty-two infants undergoing congenital heart surgery with planned PDC placement (PDC+) were age-matched to infants undergoing similar surgery without PDC placement (PDC-). Demographic, baseline and outcome data were compared. Our primary outcome was negative fluid balance on postoperative days 1 to 3. Secondary outcomes included time to negative fluid balance, time to extubation, frequency of electrolyte corrective medications, inotrope scores, and other clinical outcomes.nnnRESULTSnBaseline data did not differ between groups. The PDC+ group had a higher percentage of negative fluid balance on postoperative days 1 and 2 (57% vs 33%, Pxa0=xa0.04; 85% vs 61%, Pxa0=xa0.01). The PDC+ group had shorter time to negative fluid balance (16 vs 32 hours, Pxa0<xa0.0001), earlier extubation (80 vs 104 hours, Pxa0=xa0.02), improved inotrope scores (Pxa0=xa0.04), and fewer electrolyte imbalances requiring correction (Pxa0=xa0.03). PDC-related complications were rare.nnnCONCLUSIONSnPDC use is safe and associated with earlier negative fluid balance and improved clinical outcomes in infants at high risk for AKI. Routine PDC use should be considered for infants undergoing cardiopulmonary bypass. Further prospective studies are essential to prove causative effects of PDC placement in this population.

Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI)

BACKGROUND AND OBJECTIVESnNovel urinary kidney damage biomarkers detect AKI after cardiac surgery using cardiopulmonary bypass (CPB-AKI). Although there is growing focus on whether AKI leads to CKD, no studies have assessed whether novel urinary biomarkers remain elevated long term after CPB-AKI. We assessed whether there was clinical or biomarker evidence of long-term kidney injury in patients with CPB-AKI.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnWe performed a cross-sectional evaluation for signs of chronic kidney injury using both traditional measures and novel urinary biomarkers in a population of 372 potentially eligible children (119 AKI positive and 253 AKI negative) who underwent surgery using cardiopulmonary bypass for congenital heart disease at Cincinnati Childrens Hospital Medical Center between 2004 and 2007. A total of 51 patients (33 AKI positive and 18 AKI negative) agreed to long-term assessment. We also compared the urinary biomarker levels in these 51 patients with those in healthy controls of similar age.nnnRESULTSnAt long-term follow-up (mean duration±SD, 7±0.98 years), AKI-positive and AKI-negative patients had similarly normal assessments of kidney function by eGFR, proteinuria, and BP measurement. However, AKI-positive patients had higher urine concentrations of IL-18 (48.5 pg/ml versus 20.3 pg/ml [P=0.01] and 20.5 pg/ml [P<0.001]) and liver-type fatty acid-binding protein (L-FABP) (5.9 ng/ml versus 3.9 ng/ml [P=0.001] and 3.2 ng/ml [P<0.001]) than did AKI-negative patients and healthy controls.nnnCONCLUSIONSnNovel urinary biomarkers remain elevated 7 years after an episode of CPB-AKI in children. However, there is no conventional evidence of CKD in these children. These biomarkers may be a more sensitive marker of chronic kidney injury after CPB-AKI. Future studies are needed to understand the clinical relevance of persistent elevations in IL-18, kidney injury molecule-1, and L-FABP in assessments for potential long-term kidney consequences of CPB-AKI.

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.