Kidney Outcomes 5 Years After Pediatric Cardiac Surgery: The TRIBE-AKI Study. JAMA pediatrics 2016; 170 (11): 1071-1078
Acute kidney injury (AKI) after pediatric cardiac surgery is associated with high short-term morbidity and mortality; however, the long-term kidney outcomes are unclear.To assess long-term kidney outcomes after pediatric cardiac surgery and to determine if perioperative AKI is associated with worse long-term kidney outcomes.This prospective multicenter cohort study recruited children between ages 1 month to 18 years who underwent cardiopulmonary bypass for cardiac surgery and survived hospitalization from 3 North American pediatric centers between July 2007 and December 2009. Children were followed up with telephone calls and an in-person visit at 5 years after their surgery.Acute kidney injury defined as a postoperative serum creatinine rise from preoperative baseline by 50% or 0.3 mg/dL or more during hospitalization for cardiac surgery.Hypertension (blood pressure 95th percentile for height, age, sex, or self-reported hypertension), microalbuminuria (urine albumin to creatinine ratio >30 mg/g), and chronic kidney disease (serum creatinine estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2 or microalbuminuria).Overall, 131 children (median [interquartile range] age, 7.7 [5.9-9.9] years) participated in the 5-year in-person follow-up visit; 68 children (52%) were male. Fifty-seven of 131 children (44%) had postoperative AKI. At follow-up, 22 children (17%) had hypertension (10 times higher than the published general pediatric population prevalence), while 9 (8%), 13 (13%), and 1 (1%) had microalbuminuria, an eGFR less than 90 mL/min/1.73 m2, and an eGFR less than 60 mL/min/1.73 m2, respectively. Twenty-one children (18%) had chronic kidney disease. Only 5 children (4%) had been seen by a nephrologist during follow-up. There was no significant difference in renal outcomes between children with and without postoperative AKI.Chronic kidney disease and hypertension are common 5 years after pediatric cardiac surgery. Perioperative AKI is not associated with these complications. Longer follow-up is needed to ascertain resolution or worsening of chronic kidney disease and hypertension.
View details for DOI 10.1001/jamapediatrics.2016.1532
View details for PubMedID 27618162
Acute Kidney Injury in Patients Undergoing the Extracardiac Fontan Operation With and Without the Use of Cardiopulmonary Bypass. Pediatric critical care medicine 2016: -?
To describe the prevalence and risk factors for acute kidney injury in patients undergoing the extracardiac Fontan operation with and without cardiopulmonary bypass, and to determine whether acute kidney injury is associated with duration of mechanical ventilation, cardiovascular ICU and hospital postoperative length of stay, and early mortality.Single-center retrospective cohort study.Pediatric cardiovascular ICU, university-affiliated children's hospital.Patients with a preoperative creatinine before undergoing first-time extracardiac Fontan between January 1, 2004, and April 30, 2012.None.Acute kidney injury occurred in 55 of 138 patients (39.9%), including 41 (29.7%) with stage 1, six (4.4%) with stage 2, and eight (5.8%) with stage 3 acute kidney injury. Cardiopulmonary bypass was strongly associated with a higher risk of any acute kidney injury (adjusted odds ratio, 4.8 [95% CI, 1.4-16.0]; p = 0.01) but not stage 2/3 acute kidney injury. Lower renal perfusion pressure on the day of surgery (postoperative day, 0) was associated with a higher risk of stage 2/3 acute kidney injury (adjusted odds ratio, 1.2 [95% CI, 1.0-1.5]; p = 0.03). Higher vasoactive-inotropic score on postoperative day 0 was associated with a higher risk for stage 2/3 acute kidney injury (adjusted odds ratio, 1.9 [95% CI, 1.0-3.4]; p = 0.04). Stage 2/3 acute kidney injury was associated with longer cardiovascular ICU length of stay (mean, 7.3 greater d [95% CI, 3.4-11.3]; p < 0.001) and hospital postoperative length of stay (mean, 6.4 greater d [95% CI, 0.06-12.5]; p = 0.04).Postoperative acute kidney injury in patients undergoing the extracardiac Fontan operation is common and is associated with lower postoperative renal perfusion pressure and higher vasoactive-inotropic score. Cardiopulmonary bypass was strongly associated with any acute kidney injury, although not stage 2/3 acute kidney injury. Stage 2/3 acute kidney injury is a compelling risk factor for longer cardiovascular ICU and hospital postoperative length of stay. Increased attention to and management of renal perfusion pressure may reduce postoperative acute kidney injury and improve outcomes.
View details for PubMedID 27792123
Right Ventricular Outflow Tract Obstruction: Pulmonary Atresia With Intact Ventricular Septum, Pulmonary Stenosis, and Ebstein's Malformation. Pediatric critical care medicine 2016; 17 (8): S323-9
The objectives of this review are to discuss the anatomy, pathophysiology, clinical course, and current treatment strategies for pulmonary atresia with intact ventricular septum, pulmonary stenosis, and Ebstein's anomaly.MEDLINE and PubMed.Considerable advances have been made in management strategies for these complex congenital heart lesions, which have led to improved outcomes.
View details for DOI 10.1097/PCC.0000000000000818
View details for PubMedID 27490618
Acute Kidney Injury and Cardiorenal Syndromes in Pediatric Cardiac Intensive Care. Pediatric critical care medicine 2016; 17 (8): S250-6
The objectives of this review are to discuss the definition, diagnosis, and pathophysiology of acute kidney injury and its impact on immediate, short-, and long-term outcomes. In addition, the spectrum of cardiorenal syndromes will be reviewed including the pathophysiology on this interaction and its impact on outcomes.MEDLINE and PubMed.The field of cardiac intensive care continues to advance in tandem with congenital heart surgery. As mortality has become a rare occurrence, the focus of cardiac intensive care has shifted to that of morbidity reduction. Acute kidney injury adversely impact outcomes of patients following surgery for congenital heart disease as well as in those with heart failure (cardiorenal syndrome). Patients who become fluid overloaded and/or require dialysis are at a higher risk of mortality, but even minor degrees of acute kidney injury portend a significant increase in mortality and morbidity. Clinicians continue to seek methods of early diagnosis and risk stratification of acute kidney injury to prevent its adverse sequelae.
View details for DOI 10.1097/PCC.0000000000000820
View details for PubMedID 27490607
Recovery From Acute Kidney Injury and CKD Following Heart Transplantation in Children, Adolescents, and Young Adults: A Retrospective Cohort Study. American journal of kidney diseases 2016; 68 (2): 212-218
Acute kidney injury (AKI) is common in children following surgery for congenital heart disease and has been associated with poor long-term kidney outcomes. Children undergoing heart transplantation may be at increased risk for the development of both AKI and chronic kidney disease (CKD). This study examines AKI rates in children, adolescents, and young adults after heart transplantation and analyzes the relationship between AKI and CKD in this population.Retrospective cohort study.88 young patients who underwent heart transplantation at Lucile Packard Children'sHospital, Stanford, CA, September 1, 2007, to November 30,2013.The primary independent variable was AKI within the first 7 postoperative days, ascertained according to the KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria (increase in serum creatinine 1.5 times baseline within 7 days).Recovery from AKI at 3 months, ascertained as serum creatinine level< 1.5 times baseline; and development of CKD at 6 and 12 months, ascertained as estimated glomerular filtration rate< 60mL/min/1.73m(2) for more than 3 months.63 (72%) patients developed AKI; 57% had moderate (stage 2 or severe stage 3) disease. Recoveryoccurred in 39 of 63 (62%), 50% for stage 2 or 3 versus 78% for stage 1 (P=0.04). At 6 and 12 months, 3 of 82 (4%) and 4 of 76 (5%) developed CKD, respectively. At both time points, CKD was more common in those without recovery (3/22 [14%] vs 0/38 (0%); P=0.04, and 3/17 (18%) vs (0/34) 0%; P=0.03, respectively).Retrospective design, small sample size, and single-center nature of the study.AKI is common after heart transplantation in children, adolescents, and young adults. Nonrecovery from AKI is more common in patients with more severe AKI and is associated with the development of CKD during the first year.
View details for DOI 10.1053/j.ajkd.2016.01.024
View details for PubMedID 26970941
Pediatric Cardiology Boot Camp: Description and Evaluation of a Novel Intensive Training Program for Pediatric Cardiology Trainees PEDIATRIC CARDIOLOGY 2016; 37 (5): 834-844
The transition from residency to subspecialty fellowship in a procedurally driven field such as pediatric cardiology is challenging for trainees. We describe and assess the educational value of a pediatric cardiology "boot camp" educational tool designed to help prepare trainees for cardiology fellowship. A two-day intensive training program was provided for pediatric cardiology fellows in July 2015 at a large fellowship training program. Hands-on experiences and simulations were provided in: anatomy, auscultation, echocardiography, catheterization, cardiovascular intensive care (CVICU), electrophysiology (EP), heart failure, and cardiac surgery. Knowledge-based exams as well as surveys were completed by each participant pre-training and post-training. Pre- and post-exam results were compared via paired t tests, and survey results were compared via Wilcoxon rank sum. A total of eight participants were included. After boot camp, there was a significant improvement between pre- and post-exam scores (PRE 549% vs. POST 858%; p0.001). On pre-training survey, the most common concerns about starting fellowship included: CVICU emergencies, technical aspects of the catheterization/EP labs, using temporary and permanent pacemakers/implantable cardiac defibrillators (ICDs), and ECG interpretation. Comparing pre- and post-surveys, there was a statistically significant improvement in the participants comfort level in 33 of 36 (92%) areas of assessment. All participants (8/8, 100%) strongly agreed that the boot camp was a valuable learning experience and helped to alleviate anxieties about the start of fellowship. A pediatric cardiology boot camp experience at the start of cardiology fellowship can provide a strong foundation and serve as an educational springboard for pediatric cardiology fellows.
View details for DOI 10.1007/s00246-016-1357-z
View details for Web of Science ID 000377722400005
View details for PubMedID 26961569
Initial Observations of the Effects of Calcium Chloride Infusions in Pediatric Patients with Low Cardiac Output PEDIATRIC CARDIOLOGY 2016; 37 (3): 610-617
The Kidney in Critical Cardiac Disease: Proceedings From the 10th International Conference of the Pediatric Cardiac Intensive Care Society. World journal for pediatric & congenital heart surgery 2016; 7 (2): 152-163
The field of cardiac intensive care continues to advance in tandem with congenital heart surgery. The focus of intensive care unit care has now shifted to that of morbidity reduction and eventual elimination. Acute kidney injury (AKI) after cardiac surgery is associated with adverse outcomes, including prolonged intensive care and hospital stays, diminished quality of life, and increased long-term mortality. Acute kidney injury occurs frequently, complicating the care of both postoperative patients and those with heart failure. Patients who become fluid overloaded and/or require dialysis are at high risk of mortality, but even minor degrees of AKI portend a significant increase in mortality and morbidity. Clinicians continue to seek methods of early diagnosis and risk stratification of AKI to prevent its adverse sequelae. Previous conventional wisdom that survivors of AKI fully recover renal function without subsequent consequences may be flawed.
View details for DOI 10.1177/2150135115623289
View details for PubMedID 26957397
Initial Observations of the Effects of Calcium Chloride Infusions in Pediatric Patients with Low Cardiac Output. Pediatric cardiology 2016; 37 (3): 610-617
Myocardial contractility and relaxation are highly dependent on calcium homeostasis. Immature myocardium, as in pediatric patients, is thought to be more dependent on extracellular calcium for optimal function. For this reason, intravenous calcium chloride infusions may improve myocardial function in the pediatric patient. The objectives of this study were to report the hemodynamic changes seen after administration of continuous calcium chloride to critically ill children. We retrospectively identified pediatric patients (newborn to 17years old) with hemodynamic instability admitted to the cardiac ICU between May 2011 and May 2012 who received a continuous infusion of calcium chloride. The primary outcome was improvement in cardiac output, assessed by arterial-mixed venous oxygen saturation (A-V) difference. Sixty-eight patients, mean age 0.872.67years, received a total of 116 calcium infusions. Calcium chloride infusions resulted in significant improvements in primary and secondary measures of cardiac output at 2 and 6h. Six hours after calcium initiation, A-V oxygen saturation difference decreased by 7.4% (32.62.1 to 25.22.0%, p<0.001), rSO2 increased by 5.5% (63.1 vs 68.6%, p<0.001), and serum lactate decreased by 0.9mmol/l (3.3 vs 2.4mmol/l, p<0.001) with no change in HR (149.1 vs 145.6bpm p=0.07). Urine output increased 0.66ml/kg/h in the 8-h period after calcium initiation when compared to pre-initiation (p=0.003). Neonates had the strongest evidence of effectiveness with other age groups trending toward significance. Calcium chloride infusions improve markers of cardiac output in a heterogenous group of pediatric patients in a cardiac ICU. Neonates appear to derive the most benefit from utilization of these infusions.
View details for DOI 10.1007/s00246-015-1322-2
View details for PubMedID 26687150
Dexmedetomidine Is Associated With Lower Incidence of Acute Kidney Injury After Congenital Heart Surgery PEDIATRIC CRITICAL CARE MEDICINE 2016; 17 (2): 128-134
Recent data have suggested an association between the use of dexmedetomidine and a decreased incidence of acute kidney injury in adult patients after cardiopulmonary bypass. However, no study has focused on this association among pediatric populations where the incidence of acute kidney injury is particularly high and of critical significance. The primary objective of this study was to assess the relationship between the use of postoperative dexmedetomidine and the incidence of acute kidney injury in pediatric patients undergoing cardiopulmonary bypass. The secondary objective was to determine whether there was an association between dexmedetomidine use and duration of mechanical ventilation or cardiovascular ICU stay.Single-center retrospective matched cohort study.A 20-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California.Children less than 18 years old admitted after cardiac surgery with cardiopulmonary bypass between January 1, 2012, and May 31, 2014.None.Data from a cohort of 102 patients receiving dexmedetomidine during the first postoperative day after cardiac surgery were compared to an age- and procedure-matched cohort not receiving dexmedetomidine. Cohorts had similar baseline and demographic characteristics. Patients receiving dexmedetomidine were less likely to develop acute kidney injury (24% vs 36%; odds ratio, 0.54; 95% CI, 0.29-0.99; p = 0.046). After adjusting for age, bypass time, nephrotoxin use, and vasoactive inotropic score, the use of dexmedetomidine was associated with a lower incidence of acute kidney injury with adjusted odds ratio of 0.43 (95% CI, 0.27-0.98; p = 0.048). There was no difference between the cohorts with respect to the duration of mechanical duration (1 d each; p = 0.98) or cardiovascular ICU stays (5 vs 6 d; p = 0.91).The use of a dexmedetomidine infusion in pediatric patients after congenital heart surgery was associated with a decreased incidence of acute kidney injury; however, it was not associated with changes in clinical outcomes. Further prospective study is necessary to validate these findings.
View details for DOI 10.1097/PCC.0000000000000611
View details for Web of Science ID 000369672900004
View details for PubMedID 26673841
Long-term Stability of Urinary Biomarkers of Acute Kidney Injury in Children AMERICAN JOURNAL OF KIDNEY DISEASES 2016; 67 (1): 56-61
Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI) CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 2016; 11 (1): 21-29
Novel 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.We 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 Children's 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.At long-term follow-up (mean durationSD, 70.98 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.Novel 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.
View details for DOI 10.2215/CJN.04240415
View details for Web of Science ID 000367766200007
View details for PubMedID 26576618
Association of Definition of Acute Kidney Injury by Cystatin C Rise With Biomarkers and Clinical Outcomes in Children Undergoing Cardiac Surgery JAMA PEDIATRICS 2015; 169 (6): 583-591
Research has identified improved biomarkers of acute kidney injury (AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum creatinine (SCr) and may improve AKI definition.To determine if defining clinical AKI by increases in CysC vs SCr alters associations with biomarkers and clinical outcomes.Three-center prospective cohort study of intensive care units in New Haven, Connecticut, Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18 years or younger without preoperative AKI or end-stage renal disease who were undergoing cardiac surgery. The study dates were July 1, 2007, through December 31, 2009.For biomarker vs clinical AKI associations, the exposures were first postoperative (0-6 hours after surgery) urine interleukin 18, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and liver fatty acid-binding protein. For clinical AKI outcome associations, the exposure was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or CysC).Clinical AKI, length of stay, and length of mechanical ventilation. We determined areas under the receiver operating characteristic curve and odds ratios for first postoperative biomarkers to predict AKI.The SCr-defined vs CysC-defined AKI incidence differed substantially (43.6% vs 20.6%). Percentage agreement was 71% ( = 0.38); stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined AKI. For interleukin 18 and kidney injury molecule 1, the areas under the receiver operating characteristic curve were 0.74 and 0.65, respectively, for CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs first) quintile concentrations of both biomarkers were more strongly associated with CysC-defined AKI. For interleukin 18 and kidney injury molecule 1, the odds ratios were 16.19 (95% CI, 3.55-73.93) and 6.93 (95% CI, 1.88-25.59), respectively, for CysC-defined AKI vs 6.60 (95% CI, 2.76-15.76) and 2.04 (95% CI, 0.94-4.38), respectively, for SCr-defined AKI. Neutrophil gelatinase-associated lipocalin and liver fatty acid-binding protein associations with both definitions were similar. The CysC definitions and SCr definitions were similarly associated with clinical outcomes of resource use.Compared with the SCr-based definition, the CysC-based definition is more strongly associated with urine interleukin 18 and kidney injury molecule 1 in children undergoing cardiac surgery. Consideration should be made for defining AKI based on CysC in clinical care and future studies.
View details for DOI 10.1001/jamapediatrics.2015.54
View details for Web of Science ID 000355735500015
Cardiac biomarkers and acute kidney injury after cardiac surgery. Pediatrics 2015; 135 (4): e945-56
To examine the relationship of cardiac biomarkers with postoperative acute kidney injury (AKI) among pediatric patients undergoing cardiac surgery.Data from TRIBE-AKI, a prospective study of children undergoing cardiac surgery, were used to examine the association of cardiac biomarkers (N-type pro-B-type natriuretic peptide, creatine kinase-MB [CK-MB], heart-type fatty acid binding protein [h-FABP], and troponins I and T) with the development of postoperative AKI. Cardiac biomarkers were collected before and 0 to 6 hours after surgery. AKI was defined as a 50% or 0.3 mg/dL increase in serum creatinine, within 7 days of surgery.Of the 106 patients included in this study, 55 (52%) developed AKI after cardiac surgery. Patients who developed AKI had higher median levels of pre- and postoperative cardiac biomarkers compared with patients without AKI (all P < .01). Preoperatively, higher levels of CK-MB and h-FABP were associated with increased odds of developing AKI (CK-MB: adjusted odds ratio 4.58, 95% confidence interval [CI] 1.56-13.41; h-FABP: adjusted odds ratio 2.76, 95% CI 1.27-6.03). When combined with clinical models, both preoperative CK-MB and h-FABP provided good discrimination (area under the curve 0.77, 95% CI 0.68-0.87, and 0.78, 95% CI 0.68-0.87, respectively) and improved reclassification indices. Cardiac biomarkers collected postoperatively did not significantly improve the prediction of AKI beyond clinical models.Preoperative CK-MB and h-FABP are associated with increased risk of postoperative AKI and provide good discrimination of patients who develop AKI. These biomarkers may be useful for risk stratifying patients undergoing cardiac surgery.
View details for DOI 10.1542/peds.2014-2949
View details for PubMedID 25755241
Cardiac Biomarkers and Acute Kidney Injury After Cardiac Surgery PEDIATRICS 2015; 135 (4): E945-E956
Improved outcomes with peritoneal dialysis catheter placement after cardiopulmonary bypass in infants JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2015; 149 (1): 230-236
Acute 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.Forty-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.Baseline 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%, P=.04; 85% vs 61%, P=.01). The PDC+ group had shorter time to negative fluid balance (16 vs 32 hours, P<.0001), earlier extubation (80 vs 104 hours, P=.02), improved inotrope scores (P=.04), and fewer electrolyte imbalances requiring correction (P=.03). PDC-related complications were rare.PDC 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.
View details for DOI 10.1016/j.jtcvs.2013.11.040
View details for Web of Science ID 000350550100066
View details for PubMedID 24503323
Combining Functional and Tubular Damage Biomarkers Improves Diagnostic Precision for Acute Kidney Injury After Cardiac Surgery JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2014; 64 (25): 2753-2762
Increases in serum creatinine (SCr) from baseline signify acute kidney injury (AKI) but offer little granular information regarding its characteristics. The 10th Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) suggested that combining AKI biomarkers would provide better precision for AKI course prognostication.This study investigated the value of combining a functional damage biomarker (plasma cystatin C[pCysC]) with a tubular damage biomarker (urine neutrophil gelatinase-associated lipocalin [uNGAL]), forming a composite biomarker for prediction of discrete characteristics of AKI.Data from 345 children after cardiopulmonary bypass (CPB) were analyzed. Severe AKI was defined as Kidney Disease Global Outcomes Initiative stages 2 to 3 (>100% SCr) within 7 days of CPB. Persistent AKI lasted >2 days. SCr in reversible AKI returned to baseline48 h after CPB. The composite of uNGAL (>200 ng/mg urine Cr= positive [+]) and pCysC (>0.8 mg/l= positive [+]), uNGAL+/pCysC+, measured 2 h after CPB initiation, was compared to SCr increases of50% for correlation with AKI characteristics by using predictive probabilities, likelihood ratios (LR), and area under the curve receiver operating curve (AUC-ROC) values.Severe AKI occurred in 18% of patients. The composite uNGAL+/pCysC+ demonstrated a greater likelihood than SCr for severe AKI (+LR: 34.2 [13.0:94.0] vs. 3.8 [1.9:7.2]) and persistent AKI (+LR: 15.6 [8.8:27.5] versus 4.5 [2.3:8.8]). In AKI patients, the uNGAL-/pCysC+ composite was superior to SCr for prediction of transient AKI. Biomarker composites carried greater probability for specific outcomes than SCr strata.Composites of functional and tubular damage biomarkers are superior to SCr for predicting discrete characteristics of AKI.
View details for DOI 10.1016/j.jacc.2014.09.066
View details for Web of Science ID 000346734900007
View details for PubMedID 25541128
Factors Associated with Neurodevelopment for Children with Single Ventricle Lesions JOURNAL OF PEDIATRICS 2014; 165 (3): 490-?
To measure neurodevelopment at 3 years of age in children with single right-ventricle anomalies and to assess its relationship to Norwood shunt type, neurodevelopment at 14 months of age, and patient and medical factors.All subjects in the Single Ventricle Reconstruction Trial who were alive without cardiac transplant were eligible for inclusion. The Ages and Stages Questionnaire (ASQ, n = 203) and other measures of behavior and quality of life were completed at age 3 years. Medical history, including measures of growth, feeding, and complications, was assessed through annual review of the records and phone interviews. The Bayley Scales of Infant Development, Second Edition (BSID-II) scores from age 14 months were also evaluated as predictors.Scores on each ASQ domain were significantly lower than normal (P < .001). ASQ domain scores at 3 years of age varied nonlinearly with 14-month BSID-II. More complications, abnormal growth, and evidence of feeding, vision, or hearing problems were independently associated with lower ASQ scores, although models explained <30% of variation. Type of shunt was not associated with any ASQ domain score or with behavior or quality-of-life measures.Children with single right-ventricle anomalies have impaired neurodevelopment at 3 years of age. Lower ASQ scores are associated with medical morbidity, and lower BSID-II scores but not with shunt type. Because only a modest percentage of variation in 3-year neurodevelopmental outcome could be predicted from early measures, however, all children with single right-ventricle anomalies should be followed longitudinally to improve recognition of delays.
View details for DOI 10.1016/j.jpeds.2014.05.019
View details for Web of Science ID 000341437100017
View details for PubMedID 24952712
Serum Brain Natriuretic Peptide and Risk of Acute Kidney Injury After Cardiac Operations in Children ANNALS OF THORACIC SURGERY 2014; 97 (6): 2142-2147
Acute kidney injury (AKI) after pediatric cardiac operations is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among children undergoing cardiac operations.This was a three-center, prospective study (2007-2009) of 277 children undergoing cardiac operations (n= 121, aged <2 years) with available preoperative BNP values. Preoperative BNP was measured and categorized into tertiles. The performance of BNP was evaluated alone and in combination with clinical factors. AKI was defined as doubling of serum creatinine or need for acute dialysis.Postoperative AKI occurred in 165 children (60%), with 118 cases (43%) being mild and 47 cases (17%) severe. Preoperative BNP was not associated with increased risk of mild or severe postoperative AKI and did not significantly improve AKI risk prediction when added to clinical models. Preoperative BNP was, however, associated with several clinical outcomes, including length of stay and mechanical ventilation. The results were similar when the analysis was repeated in the subset of children younger than 2 years of age or when the association of postoperative BNP and AKI was evaluated.Preoperative BNP levels did not predict postoperative AKI in this cohort of children undergoing cardiac operations. Both preoperative and postoperative BNP levels are associated with postoperative outcomes. Clinical Trial Registration at Clinicaltrials.gov as NCT00774137.
View details for DOI 10.1016/j.athoracsur.2014.02.035
View details for Web of Science ID 000337252200041
View details for PubMedID 24725832
Transplantation-Free Survival and Interventions at 3 Years in the Single Ventricle Reconstruction Trial CIRCULATION 2014; 129 (20): 2013-?
In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups.Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%; P=0.15) or with all available follow-up of 4.81.1 years (log-rank P=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.75.1% versus 44.76.0%; P=0.007), and right ventricular ejection fraction deteriorated in RVPAS (P=0.004) but not MBTS (P=0.40) subjects (pre-Fontan minus 14-month mean, -3.258.24% versus 0.998.80%; P=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (P=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45-0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07-4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (P<0.001) with an increasing HR over time (P=0.005): <5 months, 1.14 (95% confidence interval, 0.81-1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02-3.69); and >1 year, 2.48 (95% confidence interval, 1.28-4.80).By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time.http://www.clinicaltrials.gov. Unique identifier: NCT00115934.
View details for DOI 10.1161/CIRCULATIONAHA.113.006191
View details for Web of Science ID 000336981400009
View details for PubMedID 24705119
Performance of Kidney Injury Molecule-1 and Liver Fatty Acid-Binding Protein and Combined Biomarkers of AKI after Cardiac Surgery CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 2013; 8 (7): 1079-1088
AKI is common and novel biomarkers may help provide earlier diagnosis and prognosis of AKI in the postoperative period.This was a prospective, multicenter cohort study involving 1219 adults and 311 children consecutively enrolled at eight academic medical centers. Performance of two urine biomarkers, kidney injury molecule-1 (KIM-1) and liver fatty acid-binding protein (L-FABP), alone or in combination with other injury biomarkers during the perioperative period was evaluated. AKI was defined as doubling of serum creatinine or need for acute dialysis.KIM-1 peaked 2 days after surgery in adults and 1 day after surgery in children, whereas L-FABP peaked within 6 hours after surgery in both age groups. In multivariable analyses, the highest quintile of the first postoperative KIM-1 level was associated with AKI compared with the lowest quintile in adults, whereas the first postoperative L-FABP was not associated with AKI. Both KIM-1 and L-FABP were not significantly associated with AKI in adults or children after adjusting for other kidney injury biomarkers (neutrophil gelatinase-associated lipocalin and IL-18). The highest area under the curves achievable for discrimination for AKI were 0.78 in adults using urine KIM-1 from 6 to 12 hours, urine IL-18 from day 2, and plasma neutrophil gelatinase-associated lipocalin from day 2 and 0.78 in children using urine IL-18 from 0 to 6 hours and urine L-FABP from day 2.Postoperative elevations of KIM-1 associate with AKI and adverse outcmes in adults but were not independent of other AKI biomarkers. A panel of multiple biomarkers provided moderate discrimination for AKI.
View details for DOI 10.2215/CJN.10971012
View details for Web of Science ID 000321423100006
View details for PubMedID 23599408
Acute Kidney Injury Based on Corrected Serum Creatinine Is Associated With Increased Morbidity in Children Following the Arterial Switch Operation PEDIATRIC CRITICAL CARE MEDICINE 2013; 14 (5): E218-E224
Evaluate risk factors for and impact of acute kidney injury on children following the arterial switch operation.Single-center retrospective chart review.A tertiary children's hospital.A total of 92 patients receiving the arterial switch operation from 1997 to 2008 at severe acute kidney injury was defined as a 100% serum creatinine rise over baseline.Of 92 patients, 18 (20%) developed severe acute kidney injury. Neither patient age or weight nor cardiopulmonary bypass time correlated with the development of acute kidney injury. Acute kidney injury was associated with the following: higher postoperative day 1 (POD1) fluid balance, higher inotrope scores (POD1 and POD2), and longer: postoperative ICU length of stay (p = 0.005), overall ICU length of stay (p = 0.05), and postoperative hospital length of stay (p = 0.006). The time to peak creatinine for acute kidney injury patients was between POD1 and POD2. Correction of serum creatinine for fluid balance increased the population defined as severe acute kidney injury and strengthened the association of acute kidney injury with postoperative morbidity.Acute kidney injury following the arterial switch operation is associated with increased morbidity. In this single center, single population, and homogenous cohort of patients, the development of acute kidney injury was not correlated with age, size, or cardiopulmonary bypass time, but was still associated with prolonged duration of ventilation and hospitalization. Notably, the failure to correct serum creatinine for fluid balance underestimates the prevalence and impact of acute kidney injury.
View details for DOI 10.1097/PCC.0b013e3182772f61
View details for Web of Science ID 000319920300002
View details for PubMedID 23439467
Developing a heart institute: the execution of a strategic plan. The Journal of medical practice management : MPM 2013; 28 (6): 351-358
The Heart Institute at Cincinnati Children's Hospital Medical Center was chartered in July 2008 with the purpose of integrating clinical cardiovascular medicine with basic science research to foster innovations in care of patients with congenital heart problems. The initial administrative steering committee included representation from a basic scientist, a cardiologist, and a cardiothoracic surgeon and was charged with the development of a strategic plan for the evolution of the Institute over a five-year horizon. Using structured focus groups and staff interviews, the vision, mission, and goals were identified and refined. An integrated implementation plan addressing recruitment, capitalization, infrastructure, and market opportunities was created and executed. The preliminary results demonstrated clinical outcome improvements, increased scientific and academic productivity, and financial sustainability. All of the goals identified in the initial planning sequence were achieved within the five-year time frame, prompting an early evaluation and revision of the strategic plan.
View details for PubMedID 23866651
Semaphorin 3A Is a New Early Diagnostic Biomarker of Experimental and Pediatric Acute Kidney Injury PLOS ONE 2013; 8 (3)
Semaphorin 3A is a secreted protein that regulates cell motility and attachment in axon guidance, vascular growth, immune cell regulation and tumor progression. However, nothing is known about its role in kidney pathophysiology. Here, we determined whether semaphorin3A is induced after acute kidney injury (AKI) and whether urinary semaphorin 3A can predict AKI in humans undergoing cardiopulmonary bypass (CPB).In animals, semaphorin 3A is localized in distal tubules of the kidney and excretion increased within 3 hr after reperfusion of the kidney whereas serum creatinine was significantly raised at 24 hr. In humans, using serum creatinine, AKI was detected on average only 48 hours after CPB. In contrast, urine semaphorin increased at 2 hours after CPB, peaked at 6 hours (2596591 pg/mg creatinine), and was no longer significantly elevated 12 hours after CPB. The predictive power of semaphorin 3A as demonstrated by area under the receiver-operating characteristic curve for diagnosis of AKI at 2, 6, and 12 hours after CPB was 0.88, 0.81, and 0.74, respectively. The 2-hour urine semaphorin measurement strongly correlated with duration and severity of AKI, as well as length of hospital stay. Adjusting for CPB time and gender, the 2-hour semaphorin remained an independent predictor of AKI, with an odds ratio of 2.19.Our results suggest that semaphorin 3A is an early, predictive biomarker in experimental and pediatric AKI, and may allow for the reliable early diagnosis and prognosis of AKI after CPB, much before the rise in serum creatinine.
View details for DOI 10.1371/journal.pone.0058446
View details for Web of Science ID 000315634900088
View details for PubMedID 23469280
A Predictive Model for Neurodevelopmental Outcome After the Norwood Procedure PEDIATRIC CARDIOLOGY 2013; 34 (2): 327-333
Neurodevelopmental outcomes after the Norwood procedure for single right ventricular lesions are worse than those in the normal population. It would be valuable to identify which patients at the time of Norwood discharge are at greatest risk for neurodevelopmental impairment later in childhood. As such, this study sought to construct and validate a model to predict poor neurodevelopmental outcome using variables readily available to the clinician. Using data from the 14 month neurodevelopmental outcome of the Single-Ventricle Reconstruction (SVR) trial, a classification and regression tree (CART) analysis model was developed to predict severe neurodevelopmental impairment, defined as a Psychomotor Development Index (PDI) score lower than 70 on the Bayley Scales of Infant Development-II. The model then was validated using data from subjects enrolled in the Infant Single Ventricle (ISV) trial. The PDI scores were lower than 70 for 138 (44 %) of 313 subjects. Predictors of a PDI lower than 70 were post-Norwood intensive care unit (ICU) stay longer than 46 days, genetic syndrome or other anomalies, birth weight less than 2.7 kg, additional cardiac surgical procedures, and use of five or more medications at hospital discharge. Using these risk factors, the CART model correctly identified 75 % of SVR subjects with a PDI lower than 70. When the CART model was applied to 70 subjects from the ISV trial, the correct classification rate was 67 %. This model of variables from the Norwood hospitalization can help to identify infants at risk for neurodevelopmental impairment. However, given the overall high prevalence of neurodevelopmental impairment and the fact that nearly one third of severely affected children would not have been identified by these risk factors, close surveillance and assessment for early intervention services are warranted for all infants after the Norwood procedure.
View details for DOI 10.1007/s00246-012-0450-1
View details for Web of Science ID 000315036500020
View details for PubMedID 22864647
Association of Impaired Linear Growth and Worse Neurodevelopmental Outcome in Infants with Single Ventricle Physiology: A Report from the Pediatric Heart Network Infant Single Ventricle Trial JOURNAL OF PEDIATRICS 2013; 162 (2): 250-?
To describe neurodevelopmental outcomes in infants with single ventricle (SV) physiology and determine factors associated with worse outcomes.Neurodevelopmental outcomes for infants with SV enrolled in a multicenter drug trial were assessed at 14 months of age using the Bayley Scales of Infant Development-II. Multivariable regression analysis was used to identify factors associated with worse outcomes.Neurodevelopmental testing was performed at 14 1 months in 170/185 subjects in the trial. Hypoplastic left heart syndrome was present in 59% and 75% had undergone the Norwood operation. Mean Psychomotor Developmental Index (PDI) and mental developmental index (MDI) were 80 18 and 96 14, respectively, (normal 100 15, P < .001 for each). Group-based trajectory analysis provided a 2-group model ("high" and "low") for height z-score trajectory and brain type natriuretic peptide (BNP) trajectory. The predicted PDI scores were 15 points higher in the "high" height z-score trajectory compared with the "low" cluster (P < .001). A higher number of serious adverse events during the trial was associated with lower PDI scores (P = .02). The predicted MDI scores were 13-17 points lower in "low height trajectory-high BNP trajectory" group compared with the other 3 groups (P < .001). MDI scores were also lower in subjects who required extracorporeal membrane oxygenation during the neonatal hospitalization (P = .01) or supplemental oxygen at discharge (P = .01).Neurodevelopmental outcome at 14 months of age is impaired in infants with SV physiology. Low height trajectory and high BNP trajectory were associated with worse neurodevelopmental outcomes. Efforts to improve nutritional status alone may not improve neurodevelopmental outcomes.
View details for DOI 10.1016/j.jpeds.2012.07.048
View details for Web of Science ID 000313579900008
View details for PubMedID 22939929
The association of albumin/creatinine ratio with postoperative AKI in children undergoing cardiac surgery. Clinical journal of the American Society of Nephrology 2012; 7 (11): 1761-1769
This study determined if preoperative and postoperative urine albumin/creatinine ratios (ACRs) predict postoperative AKI in children undergoing cardiac surgery (CS).This was a three-center, prospective study (2007-2009) of 294 children undergoing CS (n=145 aged <2 years). Urine ACR was measured preoperatively and 0-6 hours after intensive care unit arrival. AKI outcomes were based on the Acute Kidney Injury Network serum creatinine (SCr) criteria (stage 1 AKI, 50% or 0.3 mg/dl SCr rise from baseline; and stage 2 or worse AKI, SCr doubling or dialysis). AKI was predicted using preoperative and postoperative ACRs and postoperative ACR performance was compared with other AKI biomarkers.Preoperative ACR did not predict AKI in younger or older children. In children aged <2 years, first postoperative ACR 908 mg/g (103 mg/mmol) predicted stage 2 AKI development (adjusted relative risk, 3.4; 95% confidence interval, 1.2-9.4). In children aged 2 years, postoperative ACR 169 mg/g (19.1 mg/mmol) predicted stage 1 AKI (adjusted relative risk, 2.1; 95% confidence interval, 1.1-4.1). In children aged 2 years, first postoperative ACR improved AKI prediction from other biomarker and clinical prediction models, estimated by net reclassification improvement (P0.03), but only when serum cystatin C was also included in the model.Postoperative ACR is a readily available early diagnostic test for AKI after pediatric CS that performs similarly to other AKI biomarkers; however, its use is enhanced in children aged 2 years and in combination with serum cystatin C.
View details for DOI 10.2215/CJN.12751211
View details for PubMedID 22917706
The Association of Albumin/Creatinine Ratio with Postoperative AKI in Children Undergoing Cardiac Surgery CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 2012; 7 (11): 1761-1769
Risk factors for hospital morbidity and mortality after the Norwood procedure: A report from the Pediatric Heart Network Single Ventricle Reconstruction trial JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2012; 144 (4): 882-895
We 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.Potential 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.Analysis 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 (n=46), sepsis (n=93), increased length of ventilation, and hospital length of stay among survivors included genetic abnormality, lower center/surgeon volume, open sternum, and post-Norwood operations.Innate patient factors, ECMO, open sternum, and lower center/surgeon volume are important risk factors for postoperative mortality and/or morbidity during the Norwood hospitalization.
View details for DOI 10.1016/j.jtcvs.2012.05.019
View details for Web of Science ID 000309111600024
View details for PubMedID 22704284
Biomarkers of acute kidney injury in pediatric cardiac patients BIOMARKERS IN MEDICINE 2012; 6 (3): 273-282
Acute kidney injury is a common and significant complication among pediatric patients with congenital heart disease, occurring most commonly after cardiopulmonary bypass. Current laboratory methods of diagnosis are not timely enough to guide management decisions, thus spurring interest in discovering new biomarkers of acute injury. Several promising candidates, including NGAL, IL-18 and KIM-1, have been the subject of recent investigation and may facilitate earlier and more accurate diagnosis of renal injury within this cohort. There is little evidence demonstrating that it will be possible to rely upon one particular biomarker as a single agent, and evidence supports that the use of biomarker panels will be most effective. Further clinical validation and broader commercial availability of these novel biomarkers will probably revolutionize the care of pediatric cardiac patients with renal injury.
View details for DOI 10.2217/BMM.12.27
View details for Web of Science ID 000306455100004
View details for PubMedID 22731900
Early Developmental Outcome in Children With Hypoplastic Left Heart Syndrome and Related Anomalies The Single Ventricle Reconstruction Trial CIRCULATION 2012; 125 (17): 2081-?
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.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.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.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.
View details for DOI 10.1161/CIRCULATIONAHA.111.064113
View details for Web of Science ID 000306959200017
View details for PubMedID 22456475
Temporal Relationship and Predictive Value of Urinary Acute Kidney Injury Biomarkers After Pediatric Cardiopulmonary Bypass JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2011; 58 (22): 2301-2309
We investigated the temporal pattern and predictive value (alone and in combination) of 4 urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin [IL]-18, liver fatty acid-binding protein [L-FABP], and kidney injury molecule [KIM]-1) for cardiac surgery-associated acute kidney injury (AKI).Serum creatinine (S(Cr)) is a delayed marker for AKI after cardiopulmonary bypass (CPB). Rapidly detectable AKI biomarkers could allow early intervention and improve outcomes.Data from 220 pediatric patients were analyzed. Urine samples were obtained before and at intervals after CPB initiation. AKI was defined as a 50% increase in S(Cr) from baseline within 48 h after CPB. The temporal pattern of biomarker elevation was established, and biomarker elevations were correlated with AKI severity and clinical outcomes. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement, and integrated discrimination improvement.AKI occurred in 27% of patients. Urine NGAL significantly increased in AKI patients at 2 h after CPB initiation. IL-18 and L-FABP increased at 6 h, and KIM-1 increased at 12 h. Biomarker elevations were correlated with AKI severity and clinical outcomes and improved AKI prediction above a clinical model. At 2 h, addition of NGAL increased the AUC from 0.74 to 0.85 (p < 0.0001). At 6 h, NGAL, IL-18, and L-FABP each improved the AUC from 0.72 to 0.91, 0.84, and 0.77, respectively (all p < 0.05). The added predictive ability of the biomarkers was supported by net reclassification improvement and integrated discrimination improvement. Biomarker combinations further improved AKI prediction.Urine NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and are correlated with disease severity and clinical outcomes after pediatric CPB. These biomarkers, particularly in combination, may help establish the timing of injury and allow earlier intervention in AKI.
View details for DOI 10.1016/j.jacc.2011.08.017
View details for Web of Science ID 000297149900008
View details for PubMedID 22093507
Perioperative care of a child with transposition of the great arteries. Current treatment options in cardiovascular medicine 2011; 13 (5): 456-463
Because a minority of patients with D-transposition of the great arteries are diagnosed in utero by ultrasound, most present after delivery with cyanosis. In the absence of apparent lung disease, cyanotic neonates suspected of having a cardiac lesion should be immediately transferred to an intensive care unit at a pediatric tertiary care center for monitoring, resuscitation, and to define the cardiac anatomy and physiology. A prostaglandin E-1 infusion is usually initiated to maintain ductal patency and promote intra-cardiac mixing. In the past, balloon atrial septostomy (BAS) was routinely performed to enlarge the atrial septal defect and improve intra-cardiac mixing while the infants awaited surgery. Recent literature has reported an increase risk of stroke in neonates who undergo BAS, although more recent studies refute this. Our current practice is to perform BAS in neonates who have both echocardiographic evidence of a restrictive atrial septum and hypoxia or instability that is unresponsive to other interventions. The occasional patient who does not respond to initial management may have elevated pulmonary vascular resistance and may stabilize with pulmonary vasodilators, such as inhaled nitric oxide. Rarely, a child does not respond to interventional and pharmacologic resuscitation and requires mechanical support pre-operatively with extracorporeal membrane oxygenation (ECMO). In our experience, ECMO has been a successful bridge to corrective surgery with excellent outcomes. After pre-operative stabilization, arterial switch procedure is typically performed in the first week of life with very favorable early results.
View details for DOI 10.1007/s11936-011-0138-5
View details for PubMedID 21706195
Early postoperative serum cystatin C predicts severe acute kidney injury following pediatric cardiac surgery KIDNEY INTERNATIONAL 2011; 80 (6): 655-662
In this multicenter, prospective study of 288 children (half under 2 years of age) undergoing cardiac surgery, we evaluated whether the measurement of pre- and postoperative serum cystatin C (CysC) improves the prediction of acute kidney injury (AKI) over that obtained by serum creatinine (SCr). Higher preoperative SCr-based estimated glomerular filtration rates predicted higher risk of the postoperative primary outcomes of stage 1 and 2 AKI (adjusted odds ratios (ORs) 1.5 and 1.9, respectively). Preoperative CysC was not associated with AKI. The highest quintile of postoperative (within 6h) CysC predicted stage 1 and 2 AKI (adjusted ORs of 6 and 17.2, respectively). The highest tertile of percent change in CysC independently predicted AKI, whereas the highest tertile of SCr predicted stage 1 but not stage 2 AKI. Postoperative CysC levels independently predicted longer duration of ventilation and intensive care unit length of stay, whereas the postoperative SCr change only predicted longer intensive care unit stay. Thus, postoperative serum CysC is useful to risk-stratify patients for AKI treatment trials. More research, however, is needed to understand the relation between preoperative renal function and the risk of AKI.
View details for DOI 10.1038/ki.2011.123
View details for Web of Science ID 000294458900013
View details for PubMedID 21525851
Postoperative Biomarkers Predict Acute Kidney Injury and Poor Outcomes after Pediatric Cardiac Surgery JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 2011; 22 (9): 1737-1747
Acute kidney injury (AKI) occurs commonly after pediatric cardiac surgery and associates with poor outcomes. Biomarkers may help the prediction or early identification of AKI, potentially increasing opportunities for therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions 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 outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. Severe AKI, defined by dialysis or doubling in serum creatinine during hospital stay, occurred in 53 participants at a median of 2 days after surgery. The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI. After multivariable adjustment, the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay, longer intensive care unit stay, and duration of mechanical ventilation. The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with areas under the curve of 0.72 and 0.71, respectively. The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, urine IL-18 and urine NGAL, but not plasma NGAL, associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery.
View details for DOI 10.1681/ASN.2010111163
View details for Web of Science ID 000295705800021
View details for PubMedID 21836147
Postoperative Biomarkers Predict Acute Kidney Injury and Poor Outcomes after Adult Cardiac Surgery JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 2011; 22 (9): 1748-1757
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.
View details for DOI 10.1681/ASN.2010121302
View details for Web of Science ID 000295705800022
View details for PubMedID 21836143
Acute kidney injury and critical cardiac disease. World journal for pediatric & congenital heart surgery 2011; 2 (3): 411-423
The field of cardiac intensive care continues to advance in tandem with congenital heart surgery. The survival of patients with critical congenital heart disease is seldom in question. Consequently, the focus has now shifted to that of morbidity reduction and eventual elimination. Acute kidney injury (AKI) after cardiac surgery is associated with adverse outcomes, including prolonged intensive care and hospital stays, diminished quality of life, and increased long-term mortality. Acute kidney injury occurs frequently, complicating 30% to 40% of adult and pediatric cardiac surgeries. Patients who require dialysis are at high risk of mortality, but even minor degrees of postoperative AKI portend a significant increase in mortality and morbidity.
View details for DOI 10.1177/2150135111407214
View details for PubMedID 23803993
Neutrophil Gelatinase-Associated Lipocalin Concentrations Predict Development of Acute Kidney Injury in Neonates and Children after Cardiopulmonary Bypass JOURNAL OF PEDIATRICS 2011; 158 (6): 1009-U195
To investigate neutrophil gelatinase-associated lipocalin (NGAL) as an early acute kidney injury (AKI) biomarker after neonatal and pediatric cardiopulmonary bypass (CPB).Serum and urine samples were obtained before and at intervals after CPB from 374 patients. AKI was defined as a serum creatinine (S(Cr)) concentration increase from baseline 0.3 mg/dL in neonates and 50% in children within 48 hours of CPB. Logistic regression was used to assess predictors and clinical outcomes associated with AKI.AKI developed in 30% of patients. Plasma and urine NGAL thresholds significantly increased in patients with AKI at 2 hours after CPB and remained elevated at all points, with 2-hour NGAL the earliest, strongest predictor of AKI. In non-neonates, 2-hour plasma and urine NGAL thresholds strongly correlated with length of hospital stay and severity and duration of AKI.Plasma and urine NGAL thresholds are early predictive biomarkers for AKI and its clinical outcomes after CPB. In neonates, we recommend a 2-hour plasma NGAL threshold of 100 ng/mL and 2-hour urine NGAL threshold of 185 ng/mL for diagnosis of AKI. In non-neonates, recommended AKI thresholds are 50 ng/mL for both 2-hour plasma and urine NGAL.
View details for DOI 10.1016/j.jpeds.2010.12.057
View details for Web of Science ID 000290558600029
View details for PubMedID 21300375
Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: A prospective multicenter study CRITICAL CARE MEDICINE 2011; 39 (6): 1493-1499
To determine the incidence, severity, and risk factors of acute kidney injury in children undergoing cardiac surgery for congenital heart defects.Prospective observational multicenter cohort study.Three pediatric intensive care units at academic centers.Three hundred eleven children between the ages of 1 month and 18 yrs undergoing pediatric cardiac surgery.None.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.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.
View details for DOI 10.1097/CCM.0b013e31821201d3
View details for Web of Science ID 000290715000037
View details for PubMedID 21336114
The Outcome of Neutrophil Gelatinase-Associated Lipocalin-Positive Subclinical Acute Kidney Injury A Multicenter Pooled Analysis of Prospective Studies JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2011; 57 (17): 1752-1761
The aim of this study was to test the hypothesis that, without diagnostic changes in serum creatinine, increased neutrophil gelatinase-associated lipocalin (NGAL) levels identify patients with subclinical acute kidney injury (AKI) and therefore worse prognosis.Neutrophil gelatinase-associated lipocalin detects subclinical AKI hours to days before increases in serum creatinine indicate manifest loss of renal function.We analyzed pooled data from 2,322 critically ill patients with predominantly cardiorenal syndrome from 10 prospective observational studies of NGAL. We used the terms NGAL(-) or NGAL(+) according to study-specific NGAL cutoff for optimal AKI prediction and the terms sCREA(-) or sCREA(+) according to consensus diagnostic increases in serum creatinine defining AKI. A priori-defined outcomes included need for renal replacement therapy (primary endpoint), hospital mortality, their combination, and duration of stay in intensive care and in-hospital.Of study patients, 1,296 (55.8%) were NGAL(-)/sCREA(-), 445 (19.2%) were NGAL(+)/sCREA(-), 107 (4.6%) were NGAL(-)/sCREA(+), and 474 (20.4%) were NGAL(+)/sCREA(+). According to the 4 study groups, there was a stepwise increase in subsequent renal replacement therapy initiation-NGAL(-)/sCREA(-): 0.0015% versus NGAL(+)/sCREA(-): 2.5% (odds ratio: 16.4, 95% confidence interval: 3.6 to 76.9, p < 0.001), NGAL(-)/sCREA(+): 7.5%, and NGAL(+)/sCREA(+): 8.0%, respectively, hospital mortality (4.8%, 12.4%, 8.4%, 14.7%, respectively) and their combination (4-group comparisons: all p < 0.001). There was a similar and consistent progressive increase in median number of intensive care and in-hospital days with increasing biomarker positivity: NGAL(-)/sCREA(-): 4.2 and 8.8 days; NGAL(+)/sCREA(-): 7.1 and 17.0 days; NGAL(-)/sCREA(+): 6.5 and 17.8 days; NGAL(+)/sCREA(+): 9.0 and 21.9 days; 4-group comparisons: p = 0.003 and p = 0.040, respectively. Urine and plasma NGAL indicated a similar outcome pattern.In the absence of diagnostic increases in serum creatinine, NGAL detects patients with likely subclinical AKI who have an increased risk of adverse outcomes. The concept and definition of AKI might need re-assessment.
View details for DOI 10.1016/j.jacc.2010.11.051
View details for Web of Science ID 000289715600005
View details for PubMedID 21511111
Prenatal diagnosis and risk factors for preoperative death in neonates with single right ventricle and systemic outflow obstruction: Screening data from the Pediatric Heart Network Single Ventricle Reconstruction Trial JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2010; 140 (6): 1245-1250
The purpose of this analysis was to assess preoperative risk factors before the first-stage Norwood procedure in infants with hypoplastic left heart syndrome and related single-ventricle lesions and to evaluate practice patterns in prenatal diagnosis, as well as the role of prenatal diagnosis in outcome.Data from all live births with morphologic single right ventricle and systemic outflow obstruction screened for the Pediatric Heart Network's Single Ventricle Reconstruction Trial were used to investigate prenatal diagnosis and preoperative risk factors. Demographics, gestational age, prenatal diagnosis status, presence of major extracardiac congenital abnormalities, and preoperative mortality rates were recorded.Of 906 infants, 677 (75%) had prenatal diagnosis, 15% were preterm (<37 weeks' gestation), and 16% were low birth weight (<2500 g). Rates of prenatal diagnosis varied by study site (59% to 85%, P < .0001). Major extracardiac congenital abnormalities were less prevalent in those born after prenatal diagnosis (6% vs 10%, P = .03). There were 26 (3%) deaths before Norwood palliation; preoperative mortality did not differ by prenatal diagnosis status (P = .49). In multiple logistic regression models, preterm birth (P = .02), major extracardiac congenital abnormalities (P < .0001), and obstructed pulmonary venous return (P = .02) were independently associated with preoperative mortality.Prenatal diagnosis occurred in 75%. Preoperative death was independently associated with preterm birth, obstructed pulmonary venous return, and major extracardiac congenital abnormalities. Adjusted for gestational age and the presence of obstructed pulmonary venous return, the estimated odds of preoperative mortality were 10 times greater for subjects with a major extracardiac congenital abnormality.
View details for DOI 10.1016/j.jtcvs.2010.05.022
View details for Web of Science ID 000284149200007
View details for PubMedID 20561642
Proteomic Identification of Early Biomarkers of Acute Kidney Injury After Cardiac Surgery in Children AMERICAN JOURNAL OF KIDNEY DISEASES 2010; 56 (4): 632-642
Serum creatinine is a delayed marker of acute kidney injury (AKI). Our purpose is to discover and validate novel early urinary biomarkers of AKI after cardiac surgery.Diagnostic test study.Children undergoing cardiopulmonary bypass surgery. The test set included 15 participants with AKI and 15 matched controls (median age, 1.5 year) of 45 participants without AKI. The validation set included 365 children (median age, 1.9 year).Biomarkers identified using proteomic profiling: (1)-microglobulin, (1)-acid glycoprotein, and albumin.AKI, defined as 50% increase in serum creatinine level from baseline within 3 days of surgery.Proteomic profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) showed 3 protein peaks that appeared consistently within 2 hours in children who developed AKI after cardiopulmonary bypass surgery. The proteins were identified as (1)-microglobulin, (1)-acid glycoprotein, and albumin. Using clinical assays, results were confirmed in a test set and validated in an independent prospective cohort. In the validation set, 135 (37%) developed AKI, in whom there was a progressive increase in urinary biomarker concentrations with severity of AKI. Areas under the curve for urinary (1)-microglobulin, (1)-acid glycoprotein, and albumin at 6 hours after cardiac surgery were 0.84 (95% CI, 0.79-0.89), 0.87 (95% CI, 0.83-0.91), and 0.76 (95% CI, 0.71-0.81), respectively. Participants with increasing quartiles of biomarkers showed increasing lengths of hospital stays and durations of AKI (P < 0.001).Single-center study of children with normal kidney function at recruitment. The SELDI-TOF MS technique has limited sensitivity for the detection of proteins greater than the 20-kDa range.Urinary (1)-microglobulin, (1)-acid glycoprotein, and albumin represent early, accurate, inexpensive, and widely available biomarkers of AKI after cardiac surgery. They also offer prognostic information about the duration of AKI and length of hospitalization after cardiac surgery.
View details for DOI 10.1053/j.ajkd.2010.04.014
View details for Web of Science ID 000281962500007
View details for PubMedID 20599305
Serum Cystatin C Is an Early Predictive Biomarker of Acute Kidney Injury after Pediatric Cardiopulmonary Bypass CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 2010; 5 (9): 1552-1557
Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). Serum creatinine (SCr), the current standard, is an inadequate marker for AKI since a delay occurs before SCr rises. Biomarkers that are sensitive and rapidly measurable could allow early intervention and improve patient outcomes. We investigated the value of serum cystatin C as an early biomarker for AKI after pediatric CPB.We analyzed data from 374 prospectively enrolled children undergoing CPB. Serum samples were obtained before and at 2, 12, and 24 hours after CPB. Cystatin C was quantified by nephelometry. The primary outcome was AKI, defined as a > or =50% increase in SCr. Secondary outcomes included severity and duration of AKI, hospital length of stay, and mortality. A multivariable stepwise logistic regression analysis was used to assess predictors of AKI.One hundred nineteen patients (32%) developed AKI using SCr criteria. Serum cystatin C concentrations were significantly increased in AKI patients at 12 hours after CPB (P < 0.0001) and remained elevated at 24 hours (P < 0.0001). Maximal sensitivity and specificity for prediction of AKI occurred at a 12-hour cystatin C cut-off of 1.16 mg/L. The 12-hour cystatin C strongly correlated with severity and duration of AKI as well as length of hospital stay. In multivariable analysis, 12-hour cystatin C remained a powerful independent predictor of AKI.Serum cystatin C is an early predictive biomarker for AKI and its clinical outcomes after pediatric CPB.
View details for DOI 10.2215/CJN.02040310
View details for Web of Science ID 000281685600004
View details for PubMedID 20538834
Comparison of Shunt Types in the Norwood Procedure for Single-Ventricle Lesions. NEW ENGLAND JOURNAL OF MEDICINE 2010; 362 (21): 1980-1992
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.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.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).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.)
View details for Web of Science ID 000278054000006
View details for PubMedID 20505177
Urinary Netrin-1 Is an Early Predictive Biomarker of Acute Kidney Injury after Cardiac Surgery CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 2010; 5 (3): 395-401
Netrin-1, a laminin-related axon guidance molecule, is highly induced and excreted in the urine after acute kidney injury (AKI) in animals. Here, we determined the utility of urinary netrin-1 levels to predict AKI in humans undergoing cardiopulmonary bypass (CPB).Serial urine samples were analyzed by enzyme-linked immunosorbent assay for netrin-1 in 26 patients who developed AKI (defined as a 50% or greater increase in serum creatinine after CPB) and 34 controls (patients who did not develop AKI after CPB).Using serum creatinine, AKI was detected on average only 48 hours after CPB. In contrast, urine netrin-1 increased at 2 hours after CPB, peaked at 6 hours (2462 +/- 370 pg/mg creatinine), and remained elevated up to 48 hours after CPB. The predictive power of netrin-1 as demonstrated by area under the receiver-operating characteristics curve for diagnosis of AKI at 2, 6, and 12 hours after CPB was 0.74, 0.86, and 0.89, respectively. The 6-hour urine netrin-1 measurement strongly correlated with duration and severity of AKI, as well as length of hospital stay (all P < 0.05). Adjusting for CPB time, the 6-hour netrin-1 remained a powerful independent predictor of AKI, with an odds ratio of 1.20 (95% confidence interval: 1.08 to 1.41; P = 0.006).Our results suggest that netrin-1 is an early, predictive biomarker of AKI after CPB and may allow for the reliable early diagnosis and prognosis of AKI after CPB, before the rise in serum creatinine.
View details for DOI 10.2215/CJN.05140709
View details for Web of Science ID 000275325000003
View details for PubMedID 20007677
Ventilator-Associated Pneumonia in the Pediatric Intensive Care Unit: Characterizing the Problem and Implementing a Sustainable Solution JOURNAL OF PEDIATRICS 2009; 154 (4): 582-587
To characterize ventilator-associated pneumonia (VAP) in our pediatric intensive care unit (PICU), implement an evidence-based pediatric VAP prevention bundle, and reduce VAP rates.The setting is a 25-bed PICU in a 475-bed free-standing pediatric academic medical center. VAP was diagnosed according to Centers for Disease Control and National Nosocomial Infections Surveillance System definitions. A pediatric VAP prevention bundle was established and implemented. Baseline VAP rates were compared with implementation and post-bundle-implementation periods.VAP is significantly associated with increased PICU length of stay, mechanical ventilator days, and mortality rates (length of stay VAP 19.5+/-15.0 vs non-VAP 7.5+/-9.2, P< .001; ventilator days VAP 16.3+/-14.7 vs non-VAP 5.3+/-8.4, P< .001; mortality VAP 19.1% vs non-VAP 7.2%, P= .01). The VAP rate was reduced from 5.6 (baseline) to 0.3 infections per 1000 ventilator days after bundle implementation; P< .0001. Subglottic/tracheal stenosis, trauma, and tracheostomy are significantly associated with VAP.PICU VAP is associated with increased morbidity and mortality rates. A multidisciplinary improvement team can implement a sustainable pediatric-specific VAP prevention bundle, resulting in VAP rate reduction.
View details for DOI 10.1016/j.jpeds.2008.10.019
View details for Web of Science ID 000264808000028
View details for PubMedID 19054530
Safety of intravenous use of ketorolac in infants following cardiothoracic surgery CARDIOLOGY IN THE YOUNG 2009; 19 (1): 105-108
To evaluate the impact of intravenous ketorolac on renal function and haematologic values in patients less than six months old following cardiothoracic surgery.Ketorolac is a potent nonsteroidal anti-inflammatory drug indicated for short term management of moderate to severe post-operative pain. Little data is available related to its safety in infants less than six months of age.This was a retrospective, case-control chart review of 19 patients aged less than six months of age with biventricular circulations who received intravenous ketorolac following cardiothoracic surgery. They were compared with 19 age-matched control patients. Those with functionally univentricular anatomy were excluded due to their higher risk for renal impairment following surgery. Student's t-test was used to compare the incidence of renal impairment and haematologic complications between the groups, as well as the number of analgesic doses administered. Charts were reviewed for number of blood transfusions.Patients receiving intravenous ketorolac had no statistically significant changes in pre-operative versus post-treatment renal function or haematologic effects compared to the control group. No statistically significant differences were detected for number of post-operative blood transfusions or additional analgesic administration between groups.Intravenous ketorolac appears to be safe when used in infants less than six months of age with biventricular circulations following cardiothoracic surgery. Ketorolac as used in these patients does not decrease the use of standard analgesic therapy.
View details for DOI 10.1017/S1047951109003527
View details for Web of Science ID 000264075200016
View details for PubMedID 19134246
Serum Interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study CRITICAL CARE 2009; 13 (4)
Acute kidney injury (AKI) is associated with high mortality rates. New biomarkers that can identify subjects with early AKI (before the increase in serum creatinine) are needed to facilitate appropriate treatment. The purpose of this study was to test the role of serum cytokines as biomarkers for AKI and prolonged mechanical ventilation.This was a case-control study of children undergoing cardiac surgery. AKI was defined as a 50% increase in serum creatinine from baseline within 3 days. Levels of serum interleukin (IL)-1beta, IL-5, IL-6, IL-8, IL-10, IL-17, interferon (IFN)-gamma, tumor necrosis factor-alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using a bead-based multiplex cytokine kit in conjunction with flow-based protein detection and the Luminex LabMAP multiplex system in 18 cases and 21 controls. Levels of IL-6 and IL-8 were confirmed with single-analyte ELISA; IL-18 was also measured with single-analyte ELISA.IL-6 levels at 2 and 12 hours after cardiopulmonary bypass (CPB) and IL-8 levels at 2, 12 and 24 hours were associated with the development of AKI using the Wilcoxon rank-sum test and after adjustment for age, gender, race, and prior cardiac surgery in multivariate logistic regression analysis. In patients with AKI, IL-6 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation (defined as mechanical ventilation for more than 24 hours postoperatively) by receiver operator curve (ROC) analysis, with an area under the ROC curve of 0.95. IL-8 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation in all patients. Serum IL-18 levels were not different between those with and without AKI.Serum IL-6 and IL-8 values identify AKI early in patients undergoing CPB surgery. Furthermore, among patients with AKI, high IL-6 levels are associated with prolonged mechanical ventilation, suggesting that circulating cytokines in patients with AKI may have deleterious effects on other organs, including the lungs.
View details for DOI 10.1186/cc7940
View details for Web of Science ID 000272225600001
View details for PubMedID 19570208
Urinary aprotinin as a predictor of acute kidney injury after cardiac surgery in children receiving aprotinin therapy PEDIATRIC NEPHROLOGY 2008; 23 (8): 1317-1326
Proteomic analysis has revealed potential early biomarkers of acute kidney injury (AKI) in children undergoing cardiopulmonary bypass (CPB), the most prominent one with a mass-to-charge ratio of 6.4 kDa. The objective of this study was to identify this protein and test its utility as a biomarker of AKI. Trypsin-digested protein bands were analyzed by tandem mass spectrometry (MS/MS) to identify the protein in urine samples. Surface-enhanced laser desorption/ionization time-of-flight analysis and a functional activity assay were performed to quantify urinary levels in a pilot study of 106 pediatric patients undergoing CPB. The protein was identified as aprotinin. Urinary aprotinin levels 2 h after initiation of CPB were predictive of AKI (for functional assay: 92% sensitivity, 96% specificity, area under the curve of 0.98). By multivariate analysis, the urinary aprotinin level 2 h after CPB was an independent predictor of AKI (beta = 0.001, P < 0.0001). The 2 h urinary aprotinin level correlated with serum creatinine, duration of AKI, and length of hospital stay. We concluded that urinary aprotinin levels 2 h after initiation of CPB predict the development of AKI and adverse clinical outcomes.
View details for DOI 10.1007/s00467-008-0827-9
View details for Web of Science ID 000257811700018
View details for PubMedID 18506488
Metabonomics of acute kidney injury in children after cardiac surgery PEDIATRIC NEPHROLOGY 2008; 23 (6): 977-984
Acute kidney injury (AKI) is a major complication in children who undergo cardiopulmonary bypass surgery. We performed metabonomic analyses of urine samples obtained from 40 children that underwent cardiac surgery for correction of congenital cardiac defects. Serial urine samples were obtained from each patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50% or greater rise in baseline level of serum creatinine, was noted in 21 children at 48-72 h after cardiac surgery. The principal component analysis of liquid chromatography/mass spectrometry (LC/MS) negative ionization data of the urine samples obtained 4 h and 12 h after surgery from patients who develop AKI clustered away from patients who did not develop AKI. The LC/MS peak with mass-to-charge ratio (m/z) 261.01 and retention time (tR) 4.92 min was further analyzed by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate (HVA-SO4), a dopamine metabolite. By MS single-reaction monitoring, the sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/microl for HVA-SO4 at 12 h after surgery. We concluded that urinary HVA-SO4 represents a novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac surgery.
View details for DOI 10.1007/s00467-008-0756-7
View details for Web of Science ID 000255413700017
View details for PubMedID 18320237
Urine NGAL predicts severity of acute kidney injury after cardiac surgery: A prospective study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 2008; 3 (3): 665-673
The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). In this study, whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT analyzer, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL) can predict AKI after CPB was tested.In a pilot study with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the ARCHITECT assay were highly correlated (r = 0.99). In a subsequent study, 196 children undergoing CPB were prospectively enrolled and serial urine NGAL measurements obtained by ARCHITECT assay. The primary outcome was AKI, defined as a > or = 50% increase in serum creatinine.AKI developed in 99 patients (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels correlated with severity and duration of AKI, length of stay, dialysis requirement, and death.Accurate measurements of urine NGAL are obtained using the ARCHITECT platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.
View details for DOI 10.2215/CJN.04010907
View details for Web of Science ID 000255382300005
View details for PubMedID 18337554
Urinary biomarkers in the early diagnosis of acute kidney injury KIDNEY INTERNATIONAL 2008; 73 (7): 863-869
A change in the serum creatinine is not sensitive for an early diagnosis of acute kidney injury. We evaluated urinary levels of matrix metalloproteinase-9 (MMP-9), N-acetyl-beta-D-glucosaminidase (NAG), and kidney injury molecule-1 (KIM-1) as biomarkers for the detection of acute kidney injury. Urine samples were collected from 44 patients with various acute and chronic kidney diseases, and from 30 normal subjects in a cross-sectional study. A case-control study of children undergoing cardio-pulmonary bypass surgery included urine specimens from each of 20 patients without and with acute kidney injury. Injury was defined as a greater than 50% increase in the serum creatinine within the first 48 h after surgery. The biomarkers were normalized to the urinary creatinine concentration at 12, 24, and 36 h after surgery with the areas under the receiver-operating characteristic curve compared for performance. In the cross-sectional study, the area under the curve for MMP-9 was least sensitive followed by KIM-1 and NAG. Combining all three biomarkers achieved a perfect score diagnosing acute kidney injury. In the case-control study, KIM-1 was better than NAG at all time points, but combining both was no better than KIM-1 alone. Urinary MMP-9 was not a sensitive marker in the case-control study. Our results suggest that urinary biomarkers allow diagnosis of acute kidney injury earlier than a rise in serum creatinine.
View details for DOI 10.1038/sj.ki.5002715
View details for Web of Science ID 000254085100013
View details for PubMedID 18059454
Unilateral pulmonary edema and acute rheumatic fever EUROPEAN JOURNAL OF PEDIATRICS 2008; 167 (4): 465-467
Although the diagnostic criteria for acute rheumatic fever (ARF) are well known, a high index of suspicion is necessary in order to assure timely diagnosis and appropriate treatment. We present a case of an 8-year-old child who presented with unilateral pulmonary edema secondary to acute mitral insufficiency due to ARF. ARF should be considered in the differential diagnosis of unilateral pulmonary edema in children.
View details for DOI 10.1007/s00431-007-0491-2
View details for Web of Science ID 000253573400018
View details for PubMedID 17450381
Factors prolonging length of stay in the cardiac intensive care unit following the arterial switch operation CARDIOLOGY IN THE YOUNG 2008; 18 (1): 41-50
The arterial switch operation has become the preferred procedure for surgical management of transposition, defined on the basis of concordant atrioventricular and discordant ventriculo-arterial connections. We conducted a retrospective evaluation of our experience in 61 infants with this segmental combination, seen from January, 1997, to July, 2003, in order to determine the factors that are associated with a prolonged postoperative course. Factors independently associated with a prolonged postoperative stay in the cardiac intensive care unit included prematurity, difficulty in feeding, capillary leak, need for preoperative inotropic support, and postoperative infectious complications. Future research is warranted designed to minimize the impact of capillary leak and postoperative infectious complications. In addition, based on these results, our practice has evolved to initiate enteral feedings in the preoperative period if feasible, with such enteral feedings resumed as soon as possible following surgery.
View details for DOI 10.1017/S1047951107001746
View details for Web of Science ID 000253883300007
View details for PubMedID 18093360
Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery KIDNEY INTERNATIONAL 2008; 73 (4): 465-472
Acute kidney injury (AKI) is a major complication of cardiac bypass surgery. We examined whether levels of liver fatty acid-binding protein (L-FABP) can be an early biomarker for ischemic injury by measuring this protein in the urine of 40 pediatric patients prior to and following cardiopulmonary bypass surgery. AKI was defined as a 50% increase in the serum creatinine from baseline, which was normally not seen until 24-72 h after surgery. Enzyme-linked immunosorbent assay analysis showed increased L-FABP levels (factored for creatinine excretion) of about 94- and 45-fold at 4 and 12 h, respectively, following surgery in the 21 patients who developed AKI with western blot analysis, confirming L-FABP identity. Univariate logistic regression analyses showed that both bypass time and urinary L-FABP were significant independent risk indicators for AKI. After excluding bypass time from the model and using a stepwise multivariate logistic regression analysis, urinary L-FABP levels at 4 h after surgery were an independent risk indicator with the area under the receiver-operating characteristic curve 0.810, sensitivity 0.714, and specificity 0.684 for a 24-fold increase in urinary L-FABP. Our study shows that urinary L-FABP levels represent a sensitive and predictive early biomarker of AKI after cardiac surgery.
View details for DOI 10.1038/sj.ki.5002721
View details for Web of Science ID 000252777300014
View details for PubMedID 18094680
NGAL is an early predictive biomarker of contrast-induced nephropathy in children PEDIATRIC NEPHROLOGY 2007; 22 (12): 2089-2095
We hypothesized that neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of contrast-induced nephropathy (CIN). We prospectively enrolled 91 children (age 0-18 years) with congenital heart disease undergoing elective cardiac catheterization and angiography with contrast administration (CC; Ioversol). Serial urine and plasma samples were analyzed in a double-blind fashion by NGAL enzyme-linked immunosorbent assay (ELISA). CIN, defined as a 50% increase in serum creatinine from baseline, was found in 11 subjects (12%), but detection using increase in serum creatinine was only possible 6-24 h after CC. In contrast, significant elevation of NGAL concentrations in urine (135 +/- 32 vs. 11.6 +/- 2 ng/ml without CIN, p < 0.001) and plasma (151 +/- 34 vs. 36 +/- 4 without CIN, p < 0.001) were noted within 2 h after CC in those subjects. Using a cutoff value of 100 ng/ml, sensitivity, specificity, and area under the receiver-operating characteristic (ROC) curve for prediction of CIN were excellent for the 2-h urine NGAL (73%, 100%, and 0.92, respectively) and 2-h plasma NGAL (73%, 100%, and 0.91, respectively). By multivariate analysis, the 2-h NGAL concentrations in the urine (R (2) = 0.52, p < 0.0001) and plasma (R (2) = 0.72, p < 0.0001) were found to be powerful independent predictors of CIN. Patient demographics and contrast volume were not predictive of CIN.
View details for DOI 10.1007/s00467-007-0601-4
View details for Web of Science ID 000250755700013
View details for PubMedID 17874137
Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study CRITICAL CARE 2007; 11 (6)
Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). The lack of early biomarkers has impaired our ability to intervene in a timely manner. We previously showed in a small cohort of patients that plasma neutrophil gelatinase-associated lipocalin (NGAL), measured using a research enzyme-linked immunosorbent assay, is an early predictive biomarker of AKI after CPB. In this study we tested whether a point-of-care NGAL device can predict AKI after CPB in a larger cohort.First, in a cross-sectional pilot study including 40 plasma samples (NGAL range 60 to 730 ng/ml) and 12 calibration standards (NGAL range 0 to 1,925 ng/ml), NGAL measurements by enzyme-linked immunosorbent assay and by Triage NGAL Device (Biosite Inc., San Diego, CA, USA) were highly correlated (r = 0.94). Second, in a subsequent prospective uncontrolled cohort study, 120 children undergoing CPB were enrolled. Plasma was collected at baseline and at frequent intervals for 24 hours after CPB, and analyzed for NGAL using the Triage(R) NGAL device. The primary outcome was AKI, which was defined as a 50% or greater increase in serum creatinine.AKI developed in 45 patients (37%), but the diagnosis using serum creatinine was delayed by 2 to 3 days after CPB. In contrast, mean plasma NGAL levels increased threefold within 2 hours of CPB and remained significantly elevated for the duration of the study. By multivariate analysis, plasma NGAL at 2 hours after CPB was the most powerful independent predictor of AKI (beta = 0.004, P < 0.0001). For the 2-hour plasma NGAL measurement, the area under the curve was 0.96, sensitivity was 0.84, and specificity was 0.94 for prediction of AKI using a cut-off value of 150 ng/ml. The 2 hour postoperative plasma NGAL levels strongly correlated with change in creatinine (r = 0.46, P < 0.001), duration of AKI (r = 0.57, P < 0.001), and length of hospital stay (r = 0.44, P < 0.001). The 12-hour plasma NGAL strongly correlated with mortality (r = 0.48, P = 0.004) and all measures of morbidity mentioned above.Accurate measurements of plasma NGAL are obtained using the point-of-care Triage(R) NGAL device. Plasma NGAL is an early predictive biomarker of AKI, morbidity, and mortality after pediatric CPB.
View details for DOI 10.1186/cc6192
View details for Web of Science ID 000253286500011
View details for PubMedID 18070344
Open-chest epicardial approach to transcatheter pulmonary artery stenting following heart transplantation in an infant. Congenital heart disease 2007; 2 (1): 64-69
We describe an open-chest epicardial approach to transcatheter pulmonary artery stenting in a critically ill infant following heart transplantation. Technical considerations, indications, and feasibility are discussed. This case provides another example of the value of a "hybrid" approach (combining surgery and interventional cardiology) to complex congenital heart disease.
View details for DOI 10.1111/j.1747-0803.2007.00074.x
View details for PubMedID 18377519
Surveillance for transplant coronary artery disease in infant, child and adolescent heart transplant recipients: An intravascular ultrasound study JOURNAL OF HEART AND LUNG TRANSPLANTATION 2006; 25 (8): 921-927
Transplant coronary arteriopathy (TCAD) limits graft survival after heart transplantation in adult and pediatric heart transplant recipients. Intravascular ultrasound (IVUS) provides a highly sensitive technique to detect TCAD. However, its use to determine factors associated with TCAD in pediatric recipients has been limited and its utility in surveillance for symptomatic TCAD in this population is uncertain.One hundred fifty-eight IVUS studies from 66 patients (27 <1 year and 39 >1 year at time of transplant) were performed 12 to 144 months after transplantation within the routine surveillance for TCAD. Maximal intimal thickness (MIT) and intimal index (II) were measured, and the Stanford classification was utilized to grade overall severity of disease. Mixed repeated-measures linear regression models were used to investigate the main and interaction effects of age at transplant, age at time of study, time since transplant and rejection events.Age at catheterization (p = 0.0002), transplantation at age >12 months (p = 0.014), increasing time after transplantation (p = 0.021) and the combination of late rejection and hemodynamic compromising rejection (p = 0.05) were significantly associated with increasing MIT. Age at catheterization (p = 0.0149), transplantation at age >12 months (p = 0.016), time from transplantation (p = 0.0076) and rejection with hemodynamic compromise (p = 0.01) were significantly associated with increased II. Nine patients developed evidence of severe (Stanford Class 4) TCAD by IVUS, but only 2 (22%) developed symptomatic TCAD, with a median follow-up of 44 months. Four of the 7 patients who developed symptomatic TCAD had no or minimal TCAD (Stanford Class 0 or 1) on a surveillance examination within 18 months of the onset of symptoms.Increasing time after transplantation, recipient age and age at transplantation as well as rejection history, especially rejection with hemodynamic compromise, are associated with the development of TCAD as detected by IVUS in pediatric heart transplant recipients. Severe TCAD detected by IVUS does not often rapidly progress to symptomatic TCAD. Symptomatic TCAD may develop rapidly even in patients with little or no TCAD detected by IVUS.
View details for DOI 10.1016/j.healun.2006.03.022
View details for Web of Science ID 000239795800006
View details for PubMedID 16890112
Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery KIDNEY INTERNATIONAL 2006; 70 (1): 199-203
Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). The lack of early biomarkers for AKI has impaired our ability to intervene in a timely manner. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is recently demonstrated as an early biomarker of AKI after CPB, increasing 25-fold within 2 h and declining 6 h after surgery. In the present study, we tested whether interleukin-18 (IL-18) is a predictive biomarker for AKI in the same group of patients following CPB. Exclusion criteria included pre-existing renal insufficiency and nephrotoxin use. Serial urine samples were analyzed by enzyme-linked immunosorbent assay for IL-18 in 20 patients who developed AKI (defined as a 50% or greater increase in serum creatinine after CPB) and 35 controls (age, race, and gender-matched patients who did not develop AKI after CPB). Using serum creatinine, AKI was detected only 48-72 h after CPB. In contrast, urine IL-18 increased at 4-6 h after CPB, peaked at over 25-fold at 12 h, and remained markedly elevated up to 48 h after CPB. The performance of IL-18 as demonstrated by area under the receiver operating characteristics curve for diagnosis of AKI at 4, 12, and 24 h after CPB was 61, 75, and 73% respectively. Also, on multivariate analysis, both IL-18 and NGAL were independently associated with number of days in AKI among cases. Our results indicate that IL-18 is an early, predictive biomarker of AKI after CPB, and that NGAL and IL-18 are increased in tandem after CPB. The combination of these two biomarkers may allow for the reliable early diagnosis and prognosis of AKI at all times after CPB, much before the rise in serum creatinine.
View details for DOI 10.1038/sj.ki.5001527
View details for Web of Science ID 000238969300035
View details for PubMedID 16710348
Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2005; 130 (6): 1523-1530
Neurologic deficits are common after the Norwood procedure for hypoplastic left heart syndrome. Because of the association of deep hypothermic circulatory arrest with adverse neurologic outcome, regional low-flow cerebral perfusion has been used to limit the period of intraoperative brain ischemia. To evaluate the effect of this technique on brain ischemia, we performed serial brain magnetic resonance imaging in a cohort of infants before and after the Norwood operation using regional cerebral perfusion.Twenty-two term neonates with hypoplastic left heart syndrome were studied with brain magnetic resonance imaging before and at a median of 9.5 days after the Norwood operation. Results were compared with preoperative, intraoperative, and postoperative risk factors to identify predictors of neurologic injury.Preoperative magnetic resonance imaging (n = 22) demonstrated ischemic lesions in 23% of patients. Postoperative magnetic resonance imaging (n = 15) demonstrated new or worsened ischemic lesions in 73% of patients, with periventricular leukomalacia and focal ischemic lesions occurring most commonly. Prolonged low postoperative cerebral oximetry (<45% for >180 minutes) was associated with the development of new or worsened ischemia on postoperative magnetic resonance imaging (P = .029).Ischemic lesions occur commonly in neonates with hypoplastic left heart syndrome before surgical intervention. Despite the adoption of regional cerebral perfusion, postoperative cerebral ischemic lesions are frequent, occurring in the majority of infants after the Norwood operation. Long-term follow-up is necessary to assess the functional effect of these lesions.
View details for DOI 10.1016/j.jtcvs.2005.07.051
View details for Web of Science ID 000233896300008
View details for PubMedID 16307993
Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery LANCET 2005; 365 (9466): 1231-1238
The scarcity of early biomarkers for acute renal failure has hindered our ability to launch preventive and therapeutic measures for this disorder in a timely manner. We tested the hypothesis that neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for ischaemic renal injury after cardiopulmonary bypass.We studied 71 children undergoing cardiopulmonary bypass. Serial urine and blood samples were analysed by western blots and ELISA for NGAL expression. The primary outcome measure was acute renal injury, defined as a 50% increase in serum creatinine from baseline.20 children (28%) developed acute renal injury, but diagnosis with serum creatinine was only possible 1-3 days after cardiopulmonary bypass. By contrast, urine concentrations of NGAL rose from a mean of 1.6 microg/L (SE 0.3) at baseline to 147 microg/L (23) 2 h after cardiopulmonary bypass, and the amount in serum increased from a mean of 3.2 microg/L (SE 0.5) at baseline to 61 microg/L (10) 2 h after the procedure. Univariate analysis showed a significant correlation between acute renal injury and the following: urine and serum concentrations of NGAL at 2 h, and cardiopulmonary bypass time. By multivariate analysis, the amount of NGAL in urine at 2 h after cardiopulmonary bypass was the most powerful independent predictor of acute renal injury. For concentration in urine of NGAL at 2 h, the area under the receiver-operating characteristic curve was 0.998, sensitivity was 1.00, and specificity was 0.98 for a cutoff value of 50 microg/L.Concentrations in urine and serum of NGAL represent sensitive, specific, and highly predictive early biomarkers for acute renal injury after cardiac surgery.
View details for Web of Science ID 000228107600026
View details for PubMedID 15811456
Early prediction of acute renal injury using urinary proteomics AMERICAN JOURNAL OF NEPHROLOGY 2005; 25 (4): 318-326
The lack of early biomarkers for acute renal failure (ARF) has crippled our ability to launch potentially effective therapeutic measures. We tested the hypothesis that urinary proteomics could identify novel early biomarker patterns for ischemic renal injury.Sixty patients undergoing cardiopulmonary bypass (CPB) were enrolled. Urine samples obtained at 2 and 6 h post CPB were analyzed by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). The primary outcome variable was ARF, defined as a 50% or greater increase in serum creatinine.Fifteen patients (25%) developed ARF 2-3 days after CPB. SELDI-TOF-MS analysis of urine from the ARF group at baseline versus at 2 and 6 h post-CPB consistently showed a marked and statistically significant enhancement of protein biomarkers with m/z of 6.4, 28.5, 43 and 66 kDa. The same biomarkers were enhanced when comparing control versus ARF groups at 2 and 6 h post-CPB. The sensitivity and specificity of the 28.5-, 43- and 66-kDa biomarkers for the prediction of ARF at 2 h following CPB was 100%. The receiver operating characteristic curves revealed an area under the curve of 0.98.SELDI-TOF-MS is a novel, non-invasive, sensitive, highly predictive, reproducible, rapid method for the prediction of acute renal injury following CPB.
View details for DOI 10.1159/000086476
View details for Web of Science ID 000231389400002
View details for PubMedID 15961952
Rejection is reduced in thoracic organ recipients when transplanted in the first year of life JOURNAL OF HEART AND LUNG TRANSPLANTATION 2002; 21 (3): 311-318
Infant heart transplant recipients have been reported to have decreased rates of rejection when clinical criteria are used for diagnosis. This study compares the rates of acute episodes of rejection in heart and lung transplant recipients transplanted in the first year of life to those of older recipients utilizing pathologic criteria.Records of 100 consecutive lung transplant recipients (cystic fibrosis patients excluded) and 107 consecutive heart transplant recipients were reviewed with respect to: time to first rejection; total number; single versus multiple; and early (<90 days) versus late (>180 days) biopsy-proven rejection episodes. Rejection was defined as ISHLT biopsy Grade 3A or A2 for heart and lung transplant recipients, respectively. Biopsy and immunosuppression protocols were similar between groups.Kaplan-Meier analysis for freedom from rejection showed infant heart recipients were more often rejection-free (p = 0.004) as were infant lung recipients (p = 0.0001). Multivariate analysis revealed age at transplant as the most significant factor in predicting time to first rejection (age <1 year: risk ratio 0.19 [0.068-0.54] for lung transplant recipients and risk ratio 0.46 [0.27-0.78] for heart transplant recipients). Early rejection episodes occurred with less frequency in both the infant heart (19 of 63 [30%] versus 24 of 44 [50%]; p = 0.016) and lung (3 of 26 [12%] versus 63 of 74 [85%]; p = 0.001) groups. Late episodes of rejection were also less frequent in infant heart (4 of 53 [8%] versus 10 of 36 [28%], p = 0.016) and lung (0 of 23 [0%] versus 29 of 65 [45%]; p = 0.001) recipients. Multiple (> or =2) rejection episodes occurred less in infant heart (4 of 63 [6%] versus 9 of 41 [22%]; p = 0.037) and lung recipients (0 of 26 [0%] versus 17 of 74 [23%]; p = 0.003).These results demonstrate that age of <1 at time of thoracic transplantation confers significant protection from early, late and multiple episodes of acute rejection, as well as significantly greater freedom from rejection and time to first rejection.
View details for Web of Science ID 000174396600002
View details for PubMedID 11897518
Echocardiographic characterization of fundamental mechanisms of abnormal diastolic filling in diabetic rats with a parameterized diastolic filling formalism JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY 2001; 14 (12): 1166-1172
Abnormalities of diastolic function (DF) precede systolic dysfunction in diabetic cardiomyopathy. Transmitral Doppler flow analysis is the primary method for noninvasively assessing DF. We used model-based Doppler E-wave analysis to evaluate diastolic function differences between normal and diabetic rat hearts. Control rats and those with diabetes underwent echocardiography with analysis by traditional Doppler indexes and by the parameterized diastolic filling (PDF) formalism, generating 3 parameters, x0, c, and k, that uniquely characterize each E-wave. Significant intergroup differences in the E/A ratios (P <.01), isovolumic relaxation times (P <.01), and the modeling parameter c (P <.05) were found. There were no significant differences in shortening fraction, deceleration time, myocardial collagen content, or the parameters x0 and k between diabetic and control rats. These results indicate that differences in diastolic function may be noninvasively quantified and that diabetic hearts may exhibit defects in uncoupling of the contractile apparatus without concomitant increases in chamber stiffness.
View details for DOI 10.1067/mje.2001.115124
View details for Web of Science ID 000172725200005
View details for PubMedID 11734783
High-frequency ultrasound detection of the temporal evolution of protein cross linking in myocardial tissue IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL 2000; 47 (4): 1051-1058
The progressive increase in stiffening of the myocardium associated with the aging process and abetted by comorbid conditions such as diabetes may be linked to an excessive number of collagen cross links within the myocardial extra-cellular matrix. To determine whether ultrasound can delineate changes in the physical properties of heart tissue undergoing cross linking, the authors employed a model in which increased cross linking was induced by treating rat myocardial tissue with specific chemical fixatives. Rat hearts (n=5 each group) were arrested at end-diastole, insonified (30 to 50 MHz) fresh within a few minutes of excision in a phosphate buffered solution, placed in a fixative (10% formalin or 2.5% glutaraldehyde) and insonified at 30-minute intervals thereafter for 24 hours. Ultrasonic attenuation increased in tissues cross linked with formalin (maximal change: 27.2+/-3.4 dB/cm) and glutaraldehyde (maximal change: 40.2+/-5.6 dB/cm) over a 24-hour period. The frequency dependence of the attenuation coefficient increased as a function of the extent of collagen cross links in formalin (maximal change: 0.8+/-0.3 dB/cm-MHz) and glutaraldehyde (maximal change: 0.9+/-0.6 dB/cm-MHz). This study represents the first time that the precise time course of myocardial protein cross linking in situ has been characterized by using real time monitoring, and the physiologic effect has been delineated on microscopic material properties.
View details for Web of Science ID 000088175800034
View details for PubMedID 18238640
High-frequency ultrasound for quantitative characterization of myocardial edema ULTRASOUND IN MEDICINE AND BIOLOGY 2000; 26 (3): 375-384
Myocardial edema has been associated with impaired ventricular compliance and diastolic filling. To determine the sensitivity of high-frequency (40 MHz) ultrasound to myocardial edema, we employed a model in which myocardial edema was induced by immersion of tissue in isotonic saline. The effect of freezing tissue on edema formation was also evaluated. Rat hearts were arrested at end-diastole and insonified fresh within 15 min of excision (n = 5) or following being frozen for 24 h and thawed (n = 4). Measurements of attenuation, backscatter, tissue thickness and speed of sound were performed at baseline and hourly for 4 h, and compared with direct measurements of myocardial edema. Fresh tissue demonstrated a greater propensity for the development of edema than frozen tissue. Integrated backscatter increased in both tissues, whereas the magnitude and slope of attenuation decreased as edema evolved. We conclude that high-frequency ultrasound sensitively detects myocardial edema, and we propose that the extension of these methods to clinical frequencies may prove useful for monitoring and treatment of cardiac edematous disease states.
View details for Web of Science ID 000086614900003
View details for PubMedID 10773367
Transplant coronary artery disease in pediatric heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION 2000; 19 (3): 240-248
Transplant coronary artery disease (TxCAD) contributes to a large percentage of late morbidity and mortality among adult heart transplant recipients. Intracoronary ultrasound (ICUS) is a sensitive tool in the diagnosis of TxCAD in adult patients and has allowed analysis of factors contributing to disease development. Experience with ICUS in pediatrics, however, has been limited. By using ICUS we sought to determine the overall prevalence of TxCAD in pediatrics and to characterize factors associated with its development in this population.Eighty-six studies were performed in 51 pediatric patients a median of 3.4 years after heart transplantation. Evaluation included angiography and ICUS in 83 and angiography alone in 3 studies. Donor and recipient characteristics were obtained. The ICUS images were analyzed for intimal thickening and compared with coronary angiograms. The presence of any intimal thickening on ICUS was considered TxCAD. An intimal index and point of maximal intimal thickening (MIT) were measured. Vessel disease was graded 0 to 4 based on these results. Four patients had evidence of vasculopathy by angiography, whereas 32 patients (63%) had evidence of intimal proliferation by ICUS. Grade 2 or greater disease was present in 19 (37%) patients. A positive correlation was found when comparing time from transplant with intimal index and MIT (p < 0.001). No other factors were found to predict the development of disease. The overall prevalence of disease was 74% in patients studied at least 5 years after transplant. Intracoronary ultrasound can be performed safely in pediatric patients. Transplant coronary artery disease is common in infants and children after heart transplantation, although its prevalence appears to be less than in adult recipients at similar time intervals. We found no factor other than time from transplant was associated with development of disease.
View details for Web of Science ID 000086438600002
View details for PubMedID 10713248
Patterns and potential value of cardiac troponin I elevations after pediatric cardiac operations ANNALS OF THORACIC SURGERY 1998; 65 (5): 1394-1399
Perioperative myocardial injury is a major determinant of postoperative cardiac dysfunction for congenital heart disease, but its assessment during this period is difficult. The objective of this study was to determine the suitability of using postoperative serum concentrations of cardiac troponin I (cTnI) for this purpose.Cardiac troponin I levels were measured serially in the serum of patients undergoing uncomplicated repairs of atrial septal defect (n = 23), ventricular septal defect (n = 16) or tetralogy of Fallot (n = 16). The concentrations were correlated with intraoperative parameters (cardiopulmonary bypass time, aortic cross-clamp time, and cardiac bypass temperature), and postoperative parameters (magnitude of inotropic support, duration of intubation, and postoperative intensive care and hospital stay).Postoperative absolute cTnI levels were lesion specific, with a pattern of increase and decrease similar for each lesion. For the total cohort, significant correlations between postoperative cTnI levels at all times (r = 0.43 to 0.83, p < 0.05) until 72 hours were noted for all parameters, except for cardiac bypass temperature. When evaluated as individual procedure groups, no significant relationships were noted in the atrial septal defect group, whereas postoperative cTnI levels were more strongly correlated with all intraoperative and postoperative parameters in the ventricular septal defect group than in the tetralogy of Fallot group.This study suggests that cTnI values immediately after operation reflect the extent of myocardial damage from both incisional injury and intraoperative factors. Cardiac tropinin I levels in the first hours after operation for congenital heart disease are a potentially useful prognostic indicator for difficulty of recovery.
View details for Web of Science ID 000073514800039
View details for PubMedID 9594873