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1.  A Decline in intraoperative Renal Near Infrared Spectroscopy is associated with Adverse Outcomes in Children following Cardiac Surgery 
Renal near infrared spectroscopy (NIRS) is known to be predictive of acute kidney injury (AKI) in children following cardiac surgery using a series of complex equations and area under the curve. This study was performed to determine if a ≥ 20% reduction in renal NIRS for 20 consecutive minutes intra-operatively or within the first 24 post-operative hours is associated with 1) AKI, 2) increased AKI biomarkers, or 3) other adverse clinical outcomes in children following cardiac surgery.
Prospective single center observational study
Pediatric cardiac intensive care unit
Children less than or equal to age 4 years who underwent cardiac surgery with the use of cardiopulmonary bypass during the study period (June 2011 to July 2012).
Measurements and Main Results
A reduction in NIRS was not associated with AKI. 9/12 (75%) of patients with a reduction in renal NIRS did not develop AKI. The remaining 3 patients had mild AKI (pRIFLE-R). A reduction in renal NIRS was associated with the following adverse clinical outcomes: 1) a longer duration of mechanical ventilation (p = 0.05), 2) longer intensive care length of stay (p = 0.05), and 3) longer hospital length of stay (p < 0.01). A decline in renal NIRS in combination with an increase in serum IL-6 and serum IL-8 was associated with a longer intensive care length of stay, and the addition of urine IL-18 to this was associated with a longer hospital length of stay.
In this cohort, the rate of AKI was much lower than anticipated thereby limiting the evaluation of a reduction in renal NIRS as a predictor of AKI. A ≥ 20% reduction in renal NIRS was significantly associated with adverse outcomes in children following cardiac surgery. The addition of specific biomarkers to the model was predictive of worse outcomes in these patients. Thus, real time evaluation of renal NIRS using the specific levels of change of a 20% reduction for 20 minutes may be useful in predicting prolonged mechanical ventilation and other adverse outcomes in children undergoing cardiac surgery.
PMCID: PMC5123446  PMID: 26914625
Intensive care medicine  2012;38(7):1184-1190.
Prospective validation of vasoactive-inotropic score (VIS) and inotrope score (IS) in infants after cardiovascular surgery
Prospective observational study of 70 infants (≤90 days of age) undergoing cardiothoracic surgery. VIS and IS were assessed at 24 (VIS24, IS24), 48 (VIS48, IS48), and 72 (VIS72, IS72) hours after surgery. Maximum VIS and IS scores in the first 48 hours were also calculated (VIS48max and IS48max). The primary outcome was length of intubation. Additional outcomes included length of intensive care (ICU) stay and hospitalization, cardiac arrest, mortality, time to negative fluid balance, peak lactate, and change in creatinine.
Based on Receiver Operating Characteristic (ROC) analysis, area under the curve (AUC) was highest for VIS48 to identify prolonged intubation time. AUC for the primary outcome was higher for VIS than IS at all time points assessed. On multivariate analysis VIS48 was independently associated with prolonged intubation (OR 22.3, p=0.002), prolonged ICU stay (OR 8.1, p=0.017), and prolonged hospitalization (OR 11.3, p=0.011). VIS48max, IS48max, and IS48 were also associated with prolonged intubation, but not prolonged ICU or hospital stay. None of the scores were associated with time to negative fluid balance, peak lactate, or change in creatinine.
In neonates and infants, a higher VIS at 48 hours after cardiothoracic surgery is strongly associated with increased length of ventilation, and prolonged ICU and total hospital stay. At all time points assessed, VIS is more predictive of poor short term outcome than IS. VIS may be useful as an independent predictor of outcomes.
PMCID: PMC4984395  PMID: 22527067
Congenital; cardiovascular; VIS; children; outcomes; inotrope score
3.  Kinetics of procalcitonin and C-reactive protein and the relationship to postoperative infection in young infants undergoing cardiovascular surgery 
Pediatric research  2013;74(4):413-419.
The utility of procalcitonin and C-reactive protein (CRP) as infectious biomarkers following infant cardiothoracic surgery is not well defined.
We designed a prospective cohort study to evaluate procalcitonin and CRP after infant cardiothoracic surgery. Procalcitonin and CRP were drawn pre-operatively and 24/72 hours post-operation or daily in delayed sternal closure patients. Presence of infection within 10 days of surgery, vasoactive-inotropic scores at 24 and 72 hours, and length of intubation, intensive care unit stay, and hospital stay were documented.
Procalcitonin and CRP were elevated at 24 hours. Procalcitonin then decreased while CRP increased in patients undergoing delayed sternal closure or cardiopulmonary bypass. In the delayed sternal closure group, procalcitonin was significantly higher on post-operative days 2–5 in patients who ultimately developed infection. Higher procalcitonin was independently associated with increased vasoactive-inotropic score at 72 hours. CRP did not correlate with infection or post-operative support.
Procalcitonin rises after cardiothoracic surgery in infants but decreases by 72 hours while CRP remains elevated. Sternal closure may affect CRP but not procalcitonin. Procalcitonin is independently associated with circulatory support requirements at 72 hours post-operation and development of infection. Procalcitonin may have greater utility as a biomarker in this population.
PMCID: PMC3955993  PMID: 23863853
4.  Alkaline phosphatase activity after cardiothoracic surgery in infants and correlation with post-operative support and inflammation: a prospective cohort study 
Critical Care  2012;16(4):R160.
Limited evidence suggests that serum alkaline phosphatase activity may decrease after cardiac surgery in adults and children. The importance of this finding is not known. Recent studies, however, have identified a potential role for alkaline phosphatase as modulator of inflammation in multiple settings, including during adult cardiopulmonary bypass. We sought to describe the change in alkaline phosphatase activity after cardiothoracic surgery in infants and to assess for a correlation with intensity and duration of post-operative support, markers of inflammation, and short-term clinical outcomes.
Sub-analysis of a prospective observational study on the kinetics of procalcitonin in 70 infants (≤90 days old) undergoing cardiothoracic surgery. Subjects were grouped based on the use of cardiopulmonary bypass and delayed sternal closure. Alkaline phosphatase, procalcitonin, and C-reactive protein (CRP) levels were obtained pre-operation and on post-operative day 1. Mean change in alkaline phosphatase activity was determined in each surgical group. Generalized linear modeling and logistic regression were employed to assess for associations between post-operative alkaline phosphatase activity and post-operative support, inflammation, and short term outcomes. Primary endpoints were vasoactive-inotropic score at 24 hours and length of intubation. Secondary endpoints included procalcitonin/CRP levels on post-operative day 1, length of hospital stay, and cardiac arrest or death.
Mean decrease in alkaline phosphatase was 30 U/L (p = 0.01) in the non-bypass group, 114 U/L (p<0.0001) in the bypass group, and 94 U/L (p<0.0001) in the delayed sternal closure group. On multivariate analysis, each 10 U/L decrease in alkaline phosphatase activity on post-operative day 1 was independently associated with an increase in vasoactive-inotropic score by 0.7 (p<0.0001), intubation time by 6% (p<0.05), hospital stay by 5% (p<0.05), and procalcitonin by 14% (P<0.01), with a trend towards increased odds of cardiac arrest or death (OR 1.3; p = 0.06). Post-operative alkaline phosphatase activity was not associated with CRP (p = 0.7).
Alkaline phosphatase activity decreases after cardiothoracic surgery in infants. Low post-operative alkaline phosphatase activity is independently associated with increased procalcitonin, increased vasoactive/inotropic support, prolonged intubation time, and prolonged hospital stay. Alkaline phosphatase may serve as a biomarker and potential modulator of post-operative support and inflammation following cardiothoracic surgery in infants.
PMCID: PMC3580750  PMID: 22906145
5.  Morbidity of the Arterial Switch Operation 
The Annals of Thoracic Surgery  2012;93(6):1977-1983.
The arterial switch operation (ASO) has become a safe, reproducible surgical procedure with low mortality in experienced centers. We examined morbidity, which remains significant, particularly for complex ASO.
From 2003 to 2011, 101 consecutive patients underwent ASO, arbitrarily classified as “simple” (n = 52) or “complex” (n = 49). Morbidity was measured in selected complications and postoperative hospitalization. Three outcomes were analyzed: ventilation time, postextubation hospital length of stay, and a composite morbidity index, defined as ventilation time + postextubation hospital length of stay + occurrence of selected major complications. Complexity was measured with the comprehensive Aristotle score.
The operative mortality was zero. Twenty-five major complications occurred in 23 patients: 6 of 25 (12%) in simple ASO and 19 of 49 (39%) in complex ASO (p = 0.002). The most frequent complication was unplanned reoperation (15 vs 6, p = 0.03). No patients required permanent pacing. The complex group had a significantly higher morbidity index and longer ventilation time and postextubation hospital length of stay. In multivariate analysis, factors independently predicting higher morbidity were the comprehensive Aristotle score, arch repair, bypass time, and malaligned commissures. Myocardial infarction caused one sudden late death at 3 months. Late coronary failure was 2%. Overall survival was 99% at a mean follow-up of 49 ± 27 months.
In this consecutive series without operative mortality, morbidity was significantly higher in complex ASO. The only anatomic incremental risk factors for morbidity were aortic arch repair and malaligned commissures, but not primary diagnosis, weight less than 2.5 kg, or coronary patterns.
PMCID: PMC3381339  PMID: 22365263
6.  Implications of incising the ventricular septum in double outlet right ventricle and in the Ross–Konno operation☆ 
Incision into the ventricular septum in complex biventricular repair is controversial, and has been blamed for impairing left ventricular function. This retrospective study evaluates the risk of a ventricular septal incision in patients undergoing double outlet right ventricle (DORV) repair and Ross–Konno procedure.
From January 2003 to September 2007, 11 patients with DORV had a ventricular septum (VS) incision and 12 DORV patients did not. Sixteen patients had a Ross–Konno, and 16 had an isolated Ross procedure. The ventricular septal incision was made to match at least the diameter of a normal aortic annulus. In DORV, the VSD was enlarged superiorly and to the left. In the Ross–Konno, the aortic annulus was enlarged towards the septum posteriorly and to the left.
The median follow-up for the study is 19 months (1 month–4 years). For DORV, there were no significant differences in discharge mortality ( p = 0.22), late mortality ( p = 0.48), or late mortality plus heart transplant ( p = 0.093). Although patients with DORV and VSD enlargement have a more complex postoperative course, there were no differences in ECMO use ( p = 0.093), occurrence of permanent AV block ( p = 0.55), left ventricular ejection fraction (LVEF) ( p = 0.40), or shortening fraction (LVSF) ( p = 0.50). Similarly, for the Ross–Konno there were no significant differences in discharge mortality ( p = 0.30), late mortality ( p = NS), LVEF (p = 0.90) and LVSF ( p = 0.52) compared to the Ross, even though the Ross–Konno patients were significantly younger ( p < 0.0001).
Making a ventricular septal incision in DORV repair and in the Ross–Konno operation does not increase mortality and does not impair the LV function. The restriction of the VSD remains an important issue in the management of complex DORV. These encouraging results need to be confirmed by larger series.
PMCID: PMC3117298  PMID: 19269838
Double outlet right ventricle; Ventricular septal defect; Ross–Konno
7.  Enteral feeding in Prostaglandin-dependent neonates: is it a safe practice? 
The Journal of pediatrics  2008;153(6):867-869.
In many centers presurgical term neonates with prostaglandin (PGE1)-dependent cardiac lesions experience nutritional deficiency due to postponed enteral feeds. We recently adopted early enteral feeding in these infants. This retrospective study reveals feeding tolerance in 33 of 34 neonates fed enterally while receiving PGE1, suggesting the safety of this practice.
PMCID: PMC2714666  PMID: 19014824
Nutrition; prostaglandin; pediatrics; cardiovascular disease; necrotizing enterocolitis

Results 1-7 (7)