Catherine D. Krawczeski

BACKGROUND: The Norwood procedure with a modified Blalock-Taussig (MBT) shunt, the first palliative stage for single-ventricle lesions with systemic outflow obstruction, is associated with high mortality. The right ventricle-pulmonary artery (RVPA) shunt may improve coronary flow but requires a ventriculotomy. We compared the two shunts in infants with hypoplastic heart syndrome or related anomalies. METHODS: Infants undergoing the Norwood procedure were randomly assigned to the MBT shunt (275 infants) or the RVPA shunt (274 infants) at 15 North American centers. The primary outcome was death or cardiac transplantation 12 months after randomization. Secondary outcomes included unintended cardiovascular interventions and right ventricular size and function at 14 months and transplantation-free survival until the last subject reached 14 months of age. RESULTS: Transplantation-free survival 12 months after randomization was higher with the RVPA shunt than with the MBT shunt (74% vs. 64%, P=0.01). However, the RVPA shunt group had more unintended interventions (P=0.003) and complications (P=0.002). Right ventricular size and function at the age of 14 months and the rate of nonfatal serious adverse events at the age of 12 months were similar in the two groups. Data collected over a mean (+/-SD) follow-up period of 32+/-11 months showed a nonsignificant difference in transplantation-free survival between the two groups (P=0.06). On nonproportional-hazards analysis, the size of the treatment effect differed before and after 12 months (P=0.02). CONCLUSIONS: In children undergoing the Norwood procedure, transplantation-free survival at 12 months was better with the RVPA shunt than with the MBT shunt. After 12 months, available data showed no significant difference in transplantation-free survival between the two groups. (ClinicalTrials.gov number, NCT00115934.)

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and increases morbidity and mortality. The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 1219 adults undergoing cardiac surgery to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse patient outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. After multivariable adjustment, the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay, longer intensive care unit stay, and higher risk for dialysis or death. The clinical prediction model for AKI had an area under the receiver-operating characteristic curve (AUC) of 0.69. Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75, respectively. Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). In conclusion, urine IL-18, urine NGAL, and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery.

OBJECTIVE: To determine the incidence, severity, and risk factors of acute kidney injury in children undergoing cardiac surgery for congenital heart defects. DESIGN: Prospective observational multicenter cohort study. SETTING: Three pediatric intensive care units at academic centers. PATIENTS: Three hundred eleven children between the ages of 1 month and 18 yrs undergoing pediatric cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute kidney injury was defined as a ≥50% increase in serum creatinine from the preoperative value. Secondary outcomes were length of mechanical ventilation, length of intensive care unit and hospital stays, acute dialysis, and in-hospital mortality. The cohort had an average age of 3.8 yrs and was 45% women and mostly white (82%). One-third had prior cardiothoracic surgery, 91% of the surgeries were elective, and almost all patients required cardiopulmonary bypass. Acute kidney injury occurred in 42% (130 patients) within 3 days after surgery. Children ≥2 yrs old and <13 yrs old had a 72% lower likelihood of acute kidney injury (adjusted odds ratio: 0.28, 95% confidence interval: 0.16, 0.48), and patients 13 yrs and older had 70% lower likelihood of acute kidney injury (adjusted odds ratio: 0.30, 95% confidence interval: 0.10, 0.88) compared to patients <2 yrs old. Longer cardiopulmonary bypass time was linearly and independently associated with acute kidney injury. The development of acute kidney injury was independently associated with prolonged ventilation and with increased length of hospital stay. CONCLUSIONS: Acute kidney injury is common after pediatric cardiac surgery and is associated with prolonged mechanical ventilation and increased hospital stay. Cardiopulmonary bypass time and age were independently associated with acute kidney injury risk. Cardiopulmonary bypass time may be a marker for case complexity.

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 (R(2)=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 (R(2)=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.