Diagnostic Agreement Between TEG5000 and TEG6S in the Assessment of Hemostasis in Pediatric Cardiac Surgery: A Prospective Non-inferiority Study.

Thromboelastography (TEG) is a point-of-care test (POCT) used to analyze the hemostatic properties of whole blood. TEG® 5000and TEG® 6s (Haemonetics Corp, USA) measure the same parameters describing clot viscoelasticity using different methodologies. The purpose of this study was to evaluate agreement between TEG5000 and TEG6s measurements. We analyzed prospectively collected tests resulting from paired blood samples in cardiac surgery pediatric patients at one hour (T0) and 24 h (T1) postoperatively. Each citrated sample was utilized for TEG® 5000 and TEG ®6s. Six specific TEG parameters were analyzed and compared: R kaolin time (RK), R kaolin heparinase (RKH) time, K kaolin time (KK), K kaolin heparinase time KH (KKH), Maximum Amplitude kaolin (MAK), Maximal Amplitude Kaolin Heparinase (MAKH). We enrolled 30 patients. Median (interquartile range) patients' age was 206 (20-597) days. All surgical patients underwent correction except 5 who were palliated. At T0, RK and RKH showed an average (standard deviation) % bias of 15.8 (31) and 16.1 (28), respectively, with similar results at T1. A % bias of -6 (23) and - 6 [15] in MAK was found at T0 and T1, respectively. Similarly, MAKH % bias was 1.5 (22) and 7.6 (29) at T0 and T1, respectively. At both timepoints, low % biases (< ± 6%) were demonstrated in KK and KKH. All parameters showed improved coagulation from T0 to T1, but without significant interaction between type of device and time. Analysis of the entire pool of 60 paired samples showed no agreement in diagnostic performance (within the range vs. outside the range) in 12 (20%), 5 (9.8%), 1 (1.7%), 4 (7.8%), 9 (15%), and 5 (9.8%) cases for RK, RKH, MAK, MAKH, KK and KKH, respectively. We observed substantial agreement in MAK and KK in a cohort of pediatric patients undergoing uncomplicated cardiac surgery. Our findings suggest that TEG®5000 and TEG®6s are interchangeable for assessing these parameters.

Ventricular-Arterial Coupling in Children and Infants With Congenital Heart Disease After Cardiopulmonary Bypass Surgery: Observational Study.

OBJECTIVES: Ventricular-arterial coupling represents the interaction between the left ventricle and the arterial system. Ventricular-arterial coupling is measured as the ratio between arterial elastance and ventricular end-systolic elastance. Scant information is available in critically ill children about these variables. The aim of this study was to prospectively assess ventricular-arterial coupling after pediatric cardiac surgery and evaluate its association with other commonly recorded hemodynamic parameters. DESIGN: Single-center retrospective observational study. SETTING: Pediatric cardiac surgery operating room. PATIENTS: Children undergoing corrective cardiac surgery. INTERVENTIONS: Hemodynamic monitoring with transesophageal echocardiography. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients with biventricular congenital heart disease, who underwent elective cardiac surgery with cardiopulmonary bypass, were enrolled before operating room discharge. Chen single-beat modified method was applied to calculate ventricular-arterial coupling. The median arterial elastance and end-systolic elastance values were 5.9 mm Hg/mL (2.2-9.3 mm Hg/mL) and 4.3 mm Hg/mL (1.9-8.3 mm Hg/mL), respectively. The median ventricular- arterial coupling was 1.2 (1.1-1.6). End-systolic elastance differences between patients with a ventricular-arterial coupling below (low ventricular-arterial coupling) and above (high ventricular-arterial coupling) the median value were -5.2 (95% CI, -6.28 to -0.7; p = 0.008). Differently, arterial elastance differences were -2.1 (95% CI, -5.7 to 1.6; p = 0.19). Ventricular-arterial coupling showed a significant association with pre-ejection time (r, 0.44; p = 0.02), total ejection time (r, -0.41; p = 0.003), cardiac cycle efficiency (r, -0.46; p = 0.02), maximal delta pressure over delta time (r, -0.44; p = 0.02), ejection fraction (r, -0.57; p = 0.01), and systemic vascular resistances indexed (0.56; p = 0.003). After adjustment, total ejection time (p = 0.001), pre-ejection time (p = 0.02), and ejection fraction (p = 0.001) remained independently associated with ventricular-arterial coupling. CONCLUSIONS: Median ventricular-arterial coupling values in children after cardiac surgery appear high (above 1). Uncoupling was particularly evident in high ventricular-arterial coupling patients who showed the lowest end-systolic elastance values (but not significantly different arterial elastance values) compared with low ventricular-arterial coupling. Ventricular-arterial coupling appears to be inversely proportional to pre-ejection time, total ejection time, and ejection fraction.

Kaolin-activated thromboelastography and standard coagulation assays in cyanotic and acyanotic infants undergoing complex cardiac surgery: a prospective cohort study.

BACKGROUND AND AIMS: Several studies report the use of thromboelatography (TEG) to monitor coagulation in pediatric cardiac surgery. The aim of this study was to compare baseline and intraoperative TEG, TEG-functional fibrinogen, and standard coagulation assays in children with cyanotic and acyanotic congenital heart disease (CHD) undergoing cardiac surgery. METHODS: This is a prospective observational study of 63 children aged <24 months undergoing cardiac surgery with cardiopulmonary bypass (CPB). Exclusion criteria included preoperative anticoagulant therapy and hepatic failure. We collected blood at anesthesia induction (T1), at lowest temperature after CPB start (T2), and after heparin neutralization (T3). Coagulation was evaluated by TEG (reaction time [R]), k, alpha-angle, maximum amplitude (MA), MA-fibrinogen (MA-fib), and by standard coagulation assays (prothrombin time, activated partial thromboplastin time, fibrinogen level, platelet [PLT] count). RESULTS: Sixty-three patients were enrolled (38 cyanotic and 25 acyanotic). Median age was 4 [IQR 2-6] months and median weight was 5 [IQR 3.7-6.5] kg. Most common surgeries were: ventricular septal defect repair (n = 13), Fallot correction (n = 11), and arterial switch operation (n = 10). Cyanotic and acyanotic children were well matched: R, k, MA, and MA-fib at T1, T2, and T3 were not significantly different between cyanotic and acyanotic children. At T2, significant correlations were showed between MA and PLT count (r = 0.4; P = 0.0008) and k and plasma fibrinogen level (r = -0.54; P < 0.0001). At T3, significant correlations were showed between MA and PLT count (r = 0.5; P < 0.0001), G and PLT count (r = 0.6; P < 0.0001), and MA-fib and plasma fibrinogen level (r = 0.5; P = 0.002). CONCLUSIONS: According to our findings, cyanosis does not affect TEG parameters in children with CHD. PLT count and plasma fibrinogen significantly correlated (are significantly associated) with MA and MA-fib respectively, suggesting that use of TEG after protamine administration may be prompted for improved hemostatic monitoring in the perioperative phase.

Predicting Fluid Responsiveness in Children Undergoing Cardiac Surgery After Cardiopulmonary Bypass.

Dynamic parameters of fluid responsiveness (FR), namely aortic blood flow velocity variation (delta V peak), left ventricular velocity-time integral variation (delta VTI), stroke volume variation, and pulse pressure variation (PPV) have demonstrated good diagnostic performance for the prediction of response to fluid loading in mechanically ventilated critically ill adult patients. We aimed to evaluate these parameters in children undergoing cardiac surgery. A retrospective observational study of mechanically ventilated patients weighing less than 20 kg who received a volume expansion (VE) of 10 ml/kg after sternal closure was conducted. A 10% cardiac index (CI) increase divided patients into 7 responders (R) and 9 non-responders (NR). Transesophageal echocardiography and Pressure Recording Analytical Method data were retrieved. The percentage CI increase was 18.6 (12)% in R and 2.9 (5.7)% in NR (p = 0.037). Prior to VE, delta V peak, delta VTI, PPV, and SPV differed between R and NR (p = 0.045, 0.043, 0.048, 0,037 and 0.044, respectively). Systolic (p = 0.004), diastolic (p = 0.002), mean blood pressure (p = 0.003), delta V peak (p = 0.03), delta VTI (p = 0.04), CI (p = 0.01), PPV (p = 0.04), SPV (p = 0.04), and dP/dt max (maximal pressure-to-time ratio) (p = 0.02) changed the following VE in R patients. Delta V peak decreased after VE in NR patients (p = 0.004). Delta VTI and PPV showed the highest predictive values, with area under receiver operator characteristic curves of 0.76 (p = 0.049) and 0.76 (p = 0.045), respectively. Delta VTI and PPV were revealed to be potential predictors of FR in ventilated children after cardiac surgery. Their combined evaluation could be useful for fluid management after sternal closure.

Evaluation of Endotoxemia After Pediatric Cardiac Surgery With the Endotoxin Activity Assay: An Exploratory Prospective Cohort Study.

OBJECTIVE: Children with congenital heart diseases undergoing surgery with cardiopulmonary bypass are exposed to a high risk of perioperative endotoxemia. The aim of our study was to prospectively evaluate endotoxin assay activity reference levels during the postoperative phase of infants undergoing cardiac surgery for congenital heart disease and to assess their association with perioperative variables and postoperative infections. DESIGN: Prospective exploratory single-center cohort study. SETTING: Tertiary pediatric cardiac ICU. PATIENTS: Infants undergoing cardiac surgery with cardiopulmonary bypass were enrolled. Exclusion criteria were preoperative suspected or confirmed infection, the need for extracorporeal membrane oxygenation or a ventricular assist device in any perioperative phase, surgery for heart transplantation, and/or urgent surgery. INTERVENTIONS: Serial measurements of endotoxin assay activity were performed at baseline, pediatric cardiac ICU arrival, postoperative day 1 and 2. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients were enrolled. Overall, 14 of 25 patients (58%) presented at least one endotoxin assay activity level greater than 0.4 during the study period (normal level is < 0.4). Endotoxin assay activity levels tended to significantly increase from baseline to postoperative day 1 and 2 and from pediatric cardiac ICU arrival to postoperative day 2 (p < 0.0001). Endotoxin assay activity greater than 0.6 predicted Gram-negative infections with a sensitivity of 0.40, a specificity of 0.95, a positive predictive value of 0.66, and a negative predictive value of 0.86. At multivariable regression, endotoxin assay activity on postoperative day 1 resulted independently associated with cardiopulmonary bypass duration, lactate, temperature peak, and vasoactive inotropic score at pediatric cardiac ICU arrival. Children with endotoxin assay activity levels greater than 0.6 (vs all the others) showed a significantly higher median (interquartile) number of ventilation days: 8 (2-39) versus 1.5 (1-3 (p = 0.02). CONCLUSIONS: This exploratory study showed that endotoxin assay activity levels in infants undergoing cardiopulmonary bypass are frequently above 0.4 and peak 24-48 hours after surgery and appear to be associated with perioperative impaired organ perfusion. Endotoxin assay activity is not useful to predict Gram-negative infections.

Clinical Factors Associated with Dose of Loop Diuretics After Pediatric Cardiac Surgery: Post Hoc Analysis.

A post hoc analysis of a randomized controlled trial comparing the clinical effects of furosemide and ethacrynic acid was conducted. Infants undergoing cardiac surgery with cardiopulmonary bypass were included in order to explore which clinical factors are associated with diuretic dose in infants with congenital heart disease. Overall, 67 patients with median (interquartile range) age of 48 (13-139) days were enrolled. Median diuretic dose was 0.34 (0.25-0.4) mg/kg/h at the end of postoperative day (POD) 0 and it significantly decreased (p = 0.04) over the following PODs; during this period, the ratio between urine output and diuretic dose increased significantly (p = 0.04). Age (r -0.26, p = 0.02), weight (r -0.28, p = 0.01), cross-clamp time (r 0.27, p = 0.03), administration of ethacrynic acid (OR 0.01, p = 0.03), and, at the end of POD0, creatinine levels (r 0.3, p = 0.009), renal near-infrared spectroscopy saturation (-0.44, p = 0.008), whole-blood neutrophil gelatinase-associated lipocalin levels (r 0.30, p = 0.01), pH (r -0.26, p = 0.02), urinary volume (r -0.2755, p = 0.03), and fluid balance (r 0.2577, p = 0.0266) showed a significant association with diuretic dose. At multivariable logistic regression cross-clamp time (OR 1.007, p = 0.04), use of ethacrynic acid (OR 0.2, p = 0.01) and blood pH at the end of POD0 (OR 0.0001, p = 0.03) was independently associated with diuretic dose. Early resistance to loop diuretics continuous infusion is evident in post-cardiac surgery infants: Higher doses are administered to patients with lower urinary output. Independently associated variables with diuretic dose in our population appeared to be cross-clamping time, the administration of ethacrynic acid, and blood pH.

Furosemide versus ethacrynic acid in pediatric patients undergoing cardiac surgery: a randomized controlled trial.

INTRODUCTION: Clinical effects of furosemide (F) and ethacrynic acid (EA) continuous infusion on urine output (UO), fluid balance, and renal, cardiac, respiratory, and metabolic function were compared in infants undergoing surgery for congenital heart diseases. METHODS: A prospective randomized double-blinded study was conducted. Patients received 0.2 mg/kg/h (up to 0.8 mg/kg/h) of either F or EA. RESULTS: In total, 38 patients were enrolled in the F group, and 36, in the EA group. No adverse reactions were recorded. UO at postoperative day (POD) 0 was significantly higher in the EA group, 6.9 (3.3) ml/kg/h, compared with the F group, 4.6 (2.3) ml/kg/h (P = 0.002) but tended to be similar in the two groups thereafter. Mean administered F dose was 0.33 (0.19) mg/kg/h compared with 0.22 (0.13) mg/kg/h of EA (P < 0.0001). Fluid balance was significantly more negative in the EA group at postoperative day 0: -43 (54) ml/kg/h versus -17 (32) ml/kg/h in the F group (P = 0.01). Serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels and incidence of acute kidney injury did not show significant differences between groups. Metabolic alkalosis occurred frequently (about 70% of cases) in both groups, but mean bicarbonate level was higher in the EA group: 27.8 (1.5) M in the F group versus 29.1 (2) mM in the EA group (P = 0.006). Mean cardiac index (CI) values were 2.6 (0.1) L/min/m(2) in the F group compared with 2.98 (0.09) L/min/m(2) in the EA group (P = 0.0081). Length of mechanical ventilation was shorter in the EA group, 5.5 (8.8) days compared with the F group, 6.7 (5.9) (P = 0.06). Length of Pediatric Cardiac Intensive Care Unit (PCICU) admission was shorter in the EA group: 14 (19) days compared with 16 (15) in the F group (P = 0.046). CONCLUSIONS: In cardiac surgery infants, EA produced more UO compared with F on POD0. Generally, a smaller EA dose is required to achieve similar UO than F. EA and F were safe in terms of renal function, but EA caused a more-intense metabolic alkalosis. EA patients achieved better CI, and shorter mechanical ventilation and PCICU admission time. TRIAL REGISTRATION: Clinicaltrials.gov NCT01628731. Registered 24 June 2012.

Multisite Near Infrared Spectroscopy During Cardiopulmonary Bypass in Pediatric Patients.

Multisite near infrared spectroscopy (NIRS) monitoring during pediatric cardiopulmonary bypass (CPB) has not been extensively validated. Although it might be rational to explore regional tissue saturation at different body sites (namely brain, kidney, upper body, lower body), conflicting results are currently provided by experience in children. The aim of our study was to evaluate absolute values of multisite NIRS saturation during CPB in a cohort of infants undergoing pediatric cardiac surgery to describe average differences between cerebral, renal, upper body (arm), and lower body (thigh) regional saturation. Furthermore, the correlation between cerebral NIRS and cardiac index (CI) at CPB weaning was evaluated. Twenty-five infants were enrolled: their median weight, age, and body surface area were 3.9 (3.3-6) kg, 111 (47-203) days, and 0.24 (0.22-0.33) m(2) , respectively. Median Aristotle score was 8 (6-10), and vasoactive inotropic score at CPB weaning was 16 (14-25). A total of 17 430 data points were recorded by each sensor: two-way ANOVA showed that time (P < 0.0001) and site (P = 0.0001) significantly affected variations of NIRS values: however, if cerebral NIRS values are excluded, sensor site is no more significant (P = 0.184 in the no circulatory arrest [noCA] group and P = 0.42 in the circulatory arrest [CA] group). Analysis of NIRS saturation changes over time showed that, at all sites, average NIRS values increased after CPB start, even if the increase of cerebral saturation was less intense than other sites (P < 0.0001). Detailed analysis of interaction between site of NIRS measurement and time point showed that cerebral NIRS (ranging from 65 to 75%) was always significantly lower than that of other channels (P < 0.0001) that tended to be in the range of oversaturation (80-90%), especially during the CPB phase. Average cerebral NIRS values of patients who did not undergo circulatory arrest (CA) during CPB, 10 min after CPB weaning, were associated with average CI values with a significant correlation (r = 0.7, P = 0.003). In conclusion, during CPB, cerebral NIRS values are expected to remain constantly lower than somatic sensors, which instead tend to show similar elevated saturations, regardless of their position. Based on these results, positioning of noncerebral NIRS sensors during CPB without CA may be questioned.

Pressure recording analytical method and bioreactance for stroke volume index monitoring during pediatric cardiac surgery.

BACKGROUND: It is currently uncertain which hemodynamic monitoring device reliably measures stroke volume and tracks cardiac output changes in pediatric cardiac surgery patients. OBJECTIVE: To evaluate the difference between stroke volume index (SVI) measured by pressure recording analytical method (PRAM) and bioreactance and their ability to track changes after a therapeutic intervention. METHODS: A single-center prospective observational cohort study in children undergoing cardiac surgery with cardiopulmonary bypass (CPB) was conducted. Twenty children below 20 kg with median (interquartile range) weight of 5.3 kg (4.1-7.8) and age of 6 months (3-20) were enrolled. Data were collected after anesthesia induction, at the end of CPB, before fluid administration and after fluid administration. Overall, median-IQR PRAM SVI values (23 ml·m(-2), 19-27) were significantly higher than bioreactance SVI (15 ml·m(-2), 12-25, P = 0.0001). Correlation (r(2) ) between the two methods was 0.15 (P = 0.0003). The mean difference between the measurements (bias) was 5.7 ml·m(-2) with a standard deviation of 9.6 (95% limits of agreement ranged from -13 to 24 ml·m(-2)). Percentage error was 91.7%. Baseline SVI appeared to be similar, but PRAM SVI was systematically greater than bioreactance thereafter, with the highest gap after the fluid loading phase: 13 (12-18) ml·m(-2) vs. 23 (19-25) ml·m(-2), respectively, P = 0.0013. A multivariable regression model showed that a significant independent inverse correlation with patients' body weight predicted the CI difference between the two methods after fluid challenge (ß coefficient -0.12, P = 0.013). CONCLUSIONS: Pressure recording analytical method and bioreactance provided similar SVI estimation at stable hemodynamic conditions, while bioreactance SVI values appeared significantly lower than PRAM at the end of CPB and after fluid replacement.

Use of Confidex to control perioperative bleeding in pediatric heart surgery: prospective cohort study.

Bleeding during and after cardiac surgery is a major issue in pediatric patients. A prospective cohort study was conducted to evaluate the effect of a commercially available prothrombin complex (Confidex) administered in cardiac surgery after weaning from cardiopulmonary bypass of infants with nonsurgical bleeding. In this study, 14 patients younger than 1 year received a Confidex bolus and were matched with 11 patients of a similar age who did not receive the drug. The preoperative coagulation profile was similar in the two groups. No side effects, including anaphylaxis or thrombotic events, were observed. The numbers of units of packed red blood cells and fresh frozen plasma administered both intra- and postoperatively were similar. The postoperative coagulation examination results and thromboelastographic parameters did not differ significantly between the two groups. However, the Confidex patients bled significantly less than the control subjects during the first 24 postoperative hours. The median volume of drained blood was 0.0 ml/kg h (range 0-1.9 ml/kg h) compared with 1.9 ml/kg h (range 1-3 ml/kg h) (p = 0.009). At least one unit of packed red blood cells in the postoperative phase was required by 2 patients (14 %) in the Confidex group and six patients (54 %) in the control group (odds ratio [OR], 0.13; 95 % confidence interval [CI], 0.02-0.9; p = 0.03). The median duration of mechanical ventilation was 3 days (range 2-4 days) in the Confidex group and 4 days (range 0-8 days) in the control group (p = 0.66). The median stay in the intensive care unit was 6 days (range 5-9 days) in the Confidex group and 7 days (range 4-12 days) in the control group (p = 0.88). The use of Confidex for infants undergoing cardiac surgery was safe and effective. It reduced postoperative bleeding and allowed fewer units of packed red blood cells to be infused in the postoperative phase without major side effects.

Assessment of modified ultrafiltration hemodynamic impact by pressure recording analytical method during pediatric cardiac surgery.

OBJECTIVE: Modified ultrafiltration is commonly used in pediatric cardiac surgery. Although its clinical benefits are currently debated, modified ultrafiltration has proved to improve mean arterial pressure in the first postoperative hours. Aim of our study was to measure cardiac index, stroke volume index, and mean arterial pressure modification before and after modified ultrafiltration by means of Pressure Recording Analytical Method. DESIGN: Single-center prospective observational cohort study. SETTING: Pediatric cardiac surgery operating room. PATIENTS: Children below 20 kg that are included in the "pediatric" mode of Pressure Recording Analytical Method. MEASUREMENTS AND MAIN RESULTS: Forty patients were enrolled in this study. Median age, weight, and body surface area at surgery were 3 months (interquartile range, 10 days to 3.5 yr), 5.6 (3.1-15) kg, and 0.31 (0.21-0.56), respectively. During the modified ultrafiltration procedure, a median volume of 17 mL/kg (11-25) was ultrafiltered and a median volume of 11 mL/kg (6-17) was reinfused with a median final modified ultrafiltration balance of -0.15 mL/kg (-4.0 to 0.1). By univariate analyses, there was a 10% increase in postmodified ultrafiltration mean, systolic and diastolic pressures (p = 0.01), stroke volume index (p = 0.02), and cardiac index (p = 0.001) without significant changes in heart rate, central (left and right) venous pressures, stroke volume variation, and inotropic score. By multivariate analysis, when controlling for cardiopulmonary bypass time and age at surgery, cardiac index variation was independently associated with lower preoperative body surface area (beta coefficient -5.5, p = 0.04). CONCLUSIONS: According to Pressure Recording Analytical Method assessment, modified ultrafiltration acutely improves myocardial function, as shown by a 10% increase of systemic arterial pressure, stroke volume index, and cardiac index. This effect is more pronounced in smaller sized patients.

Neutrophil gelatinase-associated lipocalin levels during extracorporeal membrane oxygenation in critically ill children with congenital heart disease: preliminary experience.

OBJECTIVE: To evaluate diagnostic and prognostic significance of neutrophil gelatinase-associated lipocalin during extracorporeal membrane oxygenation in children with congenital heart disease. DESIGN: Prospective observational study. SETTING: Pediatric cardiac intensive care unit. PATIENTS: Ten pediatric patients with congenital heart disease requiring venoarterial extracorporeal membrane oxygenation for postoperative cardiorespiratory support were prospectively enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five patients were successfully weaned from extracorporeal membrane oxygenation and survived to intensive care unit discharge; five children died during extracorporeal therapy or within 12 hrs from extracorporeal membrane oxygenation stop. Continuous renal replacement therapy after extracorporeal membrane oxygenation start was indicated for three patients. When patients on continuous venovenous hemofiltration were compared with patients not on continuous venovenous hemofiltration, diuretic administration was lower (1.5 vs. 10 mg/kg/day), extracorporeal membrane oxygenation duration was longer (7 [range, 6-14]) vs. 4 [range, 3-8] days), and survival decreased from 60% (four of seven) to 33% (one of three). Neutrophil gelatinase-associated lipocalin levels were higher at the first extracorporeal membrane oxygenation day in patients who underwent continuous venovenous hemofiltration, 285 (range, 181-513) vs. 130 (range, 81-277) ng/mL, in patients who did not undergo continuous venovenous hemofiltration (p = .045). Neutrophil gelatinase-associated lipocalin levels remained higher among patients on continuous venovenous hemofiltration than others throughout the examined extracorporeal membrane oxygenation period (p = .0007), whereas creatinine levels tended to be equivalent between the two groups (p = .38). However, a trend toward increasing neutrophil gelatinase-associated lipocalin levels was noticed also in patients not on continuous venovenous hemofiltration. CONCLUSIONS: Neutrophil gelatinase-associated lipocalin levels at the first extracorporeal membrane oxygenation day may have predictive value for continuous venovenous hemofiltration. During the course of extracorporeal membrane oxygenation support, creatinine levels were normalized in patients with acute kidney injury undergoing continuous venovenous hemofiltration; in these patients, neutrophil gelatinase-associated lipocalin levels may provide further information on kidney injury.

Whole blood assessment of neutrophil gelatinase-associated lipocalin versus pediatricRIFLE for acute kidney injury diagnosis and prognosis after pediatric cardiac surgery: cross-sectional study*.

OBJECTIVE: To assess the ability of a single whole blood neutrophil gelatinase-associated lipocalin measurement in predicting acute kidney injury occurrence, its severity, and the need for postoperative renal replacement therapy after pediatric cardiac surgery. DESIGN: Single-center prospective cross-sectional study. SETTING: Tertiary care pediatric cardiac intensive care unit. PATIENTS: Consecutive children <1 yr old with congenital heart diseases undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Neutrophil gelatinase-associated lipocalin levels were measured after pediatric cardiac intensive care unit admission. Pediatric score indicating level of renal damage by Risk, Injury, Failure, Loss of function and End-stage kidney disease (pRIFLE) was used as the reference method. Acute kidney injury was diagnosed in 90 (56%) of the 160 enrolled patients. The number of abnormal neutrophil gelatinase-associated lipocalin samples (above the cutoff level of 150 ng/mL) was 12 over 90 (13%) in acute kidney injury population and 6 over 70 in non-acute kidney injury patients (8%) (odds ratio 1.6; 95% confidence interval 0.6-4.7; p = .31). Sensitivity of neutrophil gelatinase-associated lipocalin for acute kidney injury detection was 0.13 and specificity 0.91. The number of patients with abnormal neutrophil gelatinase-associated lipocalin samples was not significantly different within pediatric score indicating level of renal damage by pRIFLE (p = .69); furthermore, we found abnormal neutrophil gelatinase-associated lipocalin levels in 4 (30%) over 13 renal replacement therapy patients and in 14 (10%) over 133 children without renal replacement therapy need (odds ratio 4.2; 95% confidence interval 1.2-10.2; p = .02). Mean cross-clamp time (p = .28), inotropic score (p = .19), surgical risk score (p = .3), mean length of mechanical ventilation (p = .48), and pediatric cardiac intensive care unit stay (p = .57) did not significantly differ between children with abnormal and normal neutrophil gelatinase-associated lipocalin values. CONCLUSIONS: Neutrophil gelatinase-associated lipocalin measured at pediatric cardiac intensive care unit arrival does not accurately predict acute kidney injury diagnosis, according to pediatric score indicating level of renal damage by pRIFLE classification. In these patients, neutrophil gelatinase-associated lipocalin might be helpful for renal replacement therapy prediction.

High-dose fenoldopam reduces postoperative neutrophil gelatinase-associated lipocaline and cystatin C levels in pediatric cardiac surgery.

INTRODUCTION: The aim of the study was to evaluate the effects of high-dose fenoldopam, a selective dopamine-1 receptor, on renal function and organ perfusion during cardiopulmonary bypass (CPB) in infants with congenital heart disease (CHD). METHODS: A prospective single-center randomized double-blind controlled trial was conducted in a pediatric cardiac surgery department. We randomized infants younger than 1 year with CHD and biventricular anatomy (with exclusion of isolated ventricular and atrial septal defect) to receive blindly a continuous infusion of fenoldopam at 1 µg/kg/min or placebo during CPB. Perioperative urinary and plasma levels of neutrophil gelatinase-associated lipocaline (NGAL), cystatin C (CysC), and creatinine were measured to assess renal injury after CPB. RESULTS: We enrolled 80 patients: 40 received fenoldopam (group F) during CPB, and 40 received placebo (group P). A significant increase of urinary NGAL and CysC levels from baseline to intensive care unit (ICU) admission followed by restoration of normal values after 12 hours was observed in both groups. However, urinary NGAL and CysC values were significantly reduced at the end of surgery and 12 hours after ICU admission (uNGAL only) in group F compared with group P (P = 0.025 and 0.039, respectively). Plasma NGAL and CysC tended to increase from baseline to ICU admission in both groups, but they were not significantly different between the two groups. No differences were observed on urinary and plasma creatinine levels and on urine output between the two groups. Acute kidney injury (AKI) incidence in the postoperative period, as indicated by pRIFLE classification (pediatric score indicating Risk, Injury, Failure, Loss of function, and End-stage kidney disease level of renal damage) was 50% in group F and 72% in group P (P = 0.08; odds ratio (OR), 0.38; 95% confidence interval (CI), 0.14 to 1.02). A significant reduction in diuretics (furosemide) and vasodilators (phentolamine) administration was observed in group F (P = 0.0085; OR, 0.22; 95% CI, 0.07 to 0.7). CONCLUSIONS: The treatment with high-dose fenoldopam during CPB in pediatric patients undergoing cardiac surgery for CHD with biventricular anatomy significantly decreased urinary levels of NGAL and CysC and reduced the use of diuretics and vasodilators during CPB. TRIAL REGISTRATION: Clinical Trial.Gov NCT00982527.

Pediatric Mechanical Circulatory Support: Pathophysiology of Pediatric Hemostasis and Available Options.

Pediatric mechanical circulatory support (MCS) is considered a strategy for heart failure management as a bridge to recovery and transplantation or as a destination therapy. The final outcome is significantly impacted by the number of complications that may occur during MCS. Children on ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are at high risk for bleeding and thrombotic complications that are managed through anticoagulation. The first detailed guideline in pediatric VADs (Edmonton Anticoagulation and Platelet Inhibition Protocol) was based on conventional antithrombotic drugs, such as unfractionated heparin (UFH) and warfarin. UFH is the first-line anticoagulant in pediatric MCS, although its profile is not considered optimal in pediatric setting. The broad variation in heparin doses among children is associated with frequent occurrence of cerebrovascular accidents, bleeding, and thrombocytopenia. Direct thrombin inhibitors (DTIs) have been utilized as alternative strategies to heparin. Since 2018, bivalirudin has become the chosen anticoagulant in the long-term therapy of patients undergoing MCS implantation, according to the most recent protocols shared in North America. This article provides a review of the non-traditional anticoagulation strategies utilized in pediatric MCS, focusing on pharmacodynamics, indications, doses, and monitoring aspects of bivalirudin. Moreover, it exposes the efforts and the collaborations among different specialized centers, which are committed to an ongoing learning in order to minimize major complications in this special pediatric population. Further prospective trials regarding DTIs in a pediatric MCS setting are necessary and in specific well-designed randomized control trials between UFH and bivalirudin. To conclude, based on the reported literature, the clinical use of the bivalirudin in pediatric MCS seems to be a value added in controlling and maybe reducing thromboembolic complications. Further research is necessary to confirm all the results provided by this literature review.

Cerebral NIRS as a marker of superior vena cava oxygen saturation in neonates with congenital heart disease.

OBJECTIVES: To investigate the correlation between cerebral near-infrared spectroscopy (NIRS) (rSO2c) and superior vena cava venous oxygen saturation (ScvO2) in newborn patients with congenital heart disease (CHD). BACKGROUND: NIRS is a noninvasive method to monitor hemoglobin oxygen saturation using nonpulsatile oximetry. METHODS: We retrospectively analyzed perioperative data from 100 newborn patients who underwent cardiac surgery for CHD. rSO2c, ScvO2 from 24 h before to 72 h after surgery were recorded. RESULTS: rSO2c had a fair correlation with ScvO2 (r 0.37; P <0.001). The relationship between rSO2c and ScvO2 did not change when analyzed between patients with cyanotic or acyanotic CHD. During the preoperative period, rSO2c levels overestimated ScvO2; in the first 18 postoperative hours, rSO2c underestimated ScvO2; after that period, they showed very close trends. Hypocapnia caused rSO2c to underestimate ScvO2; in normocapnic patients, rSO2c-ScvO2 average differences were close to zero; in hypercapnic neonates, rSO2c tended to overestimate ScvO2. The best performance of rSO2c as a surrogate of ScvO2 was found in the venous saturation ranges from 40% to 60% (r 0.3, P: 0.03). CONCLUSIONS: rSO2c in newborn patients with cyanotic and acyanotic CHD provides a continuous noninvasive information with a fair correlation with ScvO2%: some predictable variables (i.e., time from surgery, carbon dioxide, and venous saturation levels), should guide the operators to adjust rSO2c values in terms of ScvO2. Serial measures of ScvO2 seem recommended to tailor rSO2c information on actual venous saturation percentage.

Impact of Heparin- or Nonheparin-Coated Circuits on Platelet Function in Pediatric Cardiac Surgery.

BACKGROUND: Extracorporeal circuit coating has been shown to improve coagulation derangements during pediatric cardiopulmonary bypass (CPB). This study compared platelet function and hemostasis activation in pediatric cardiac surgery conducted with nonheparin coating (Balance; Medtronic, Minneapolis, MN) versus heparin-based coating (Carmeda; Medtronic) circuits. METHODS: A prospective, randomized, double-center trial was conducted in children older than 1 month undergoing congenital heart disease treatment. Blood samples were collected at baseline (T0), 15 minutes after the start of CPB (T1), and 15 minutes (T2) and 1 hour after the conclusion of CPB (T3). The primary end point of the study was to detect potential differences in ß-thromboglobulin levels between the two groups at T2. Other coagulation and platelet function indicators were analyzed as secondary end points. RESULTS: The concentration of ß-thromboglobulin increased significantly at T2 in both groups. However, there was no significant difference between the groups across all time points. There was no difference in the secondary end points between the groups. CONCLUSIONS: The two circuits showed similar biological effects on platelet function and coagulation. This observation may be useful in optimizing the conduct of CPB and in rationalizing its cost for the treatment of congenital heart disease.

Endotoxin Activity in Neonates Undergoing Cardiac Surgery: Cohort Study.

BACKGROUND: Endotoxemia in pediatric cardiac surgical patients is poorly understood. The endotoxin activity assay (EAA) levels were examined in neonates undergoing cardiac surgery in order to assess their reference levels and their association with other pre-, intra-, and postoperative risk factors for gut hypoperfusion. We finally observed if refeeding was associated with modification of endotoxin levels. METHODS: In a prospective cohort study, neonates undergoing surgery for correction or palliation were enrolled. Preterm birth, weight below 1.5 kg, the need for extracorporeal membrane oxygenation, and urgent surgery were exclusion criteria. RESULTS: Among the 26 enrolled neonates, 12 underwent on-pump and 14 off-pump surgery, 22 received a preoperative infusion of prostaglandin E2. Overall, 11 patients were surgically corrected and 15 received a palliation. Endotoxin activity assay baseline levels were inversely correlated with age at surgery ( r = -.50, P = .006) and they increased to postoperative day2 ( P = .002). On-pump versus off-pump surgery ( P =.36) and surgical palliation with a Blalock-Taussig shunt versus correction ( P = .45) did not predict increase in EAA levels. Aortic clamping for coarctation repair was associated with the lowest levels ( P = .04). Systolic, mean, and diastolic pressures were associated with EAA levels ( r = -.55, P = .01; r = -.45, P = .02; r = -.37, P = .04, respectively). Endotoxin activity assay levels after refeeding were similar to baseline levels. Patients with abdominal distension and feeding intolerance showed higher median peak EAA levels (0.7, 0.66-1.11) than asymptomatic patients (0.53, 0.35-0.64; P = .01). CONCLUSIONS: Endotoxin activity assay levels increase after elective neonatal surgery and are not modified by refeeding. High postoperative levels may predict feeding intolerance.