Cristiana Garisto

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

IntroductionThe 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).MethodsA 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.ResultsWe 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).ConclusionsThe 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 registrationClinical Trial.Gov NCT00982527.

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).

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

It is currently uncertain which hemodynamic monitoring device reliably measures stroke volume and tracks cardiac output changes in pediatric cardiac surgery patients.

Brain natriuretic peptide is removed by continuous veno-venous hemofiltration in pediatric patients

We wanted to evaluate if brain natriuretic peptide (BNP) is cleared during continuous veno-venous hemofiltration (CVVH) sessions in children with congenital heart disease. A prospective observational single-center study was conducted in a post-cardiac surgery intensive care unit of the city childrens hospital. Ten children requiring CVVH for acute kidney injury following cardiac surgery were enrolled. Seven of them were undergoing postoperative extracorporeal membrane oxygenation. BNP clearance was evaluated by the difference between pre-filter and post-filter BNP blood amount indexed to pre-filter BNP concentration. All CVVH treatments were performed with 0.6 m2 polyacrylonitrile filter, in predilution setting, at a dose of 80 ml/kg/h. Troponin I and myoglobin levels were also measured and CVVH clearances of these markers calculated for comparison with BNP. A significant decrease in post-filter compared with pre-filter levels of BNP was shown in all 10 cases (P<0.01). Median BNP clearance was 35.6 (29-39.3) ml/min. Troponin I and myoglobin levels did not show any significant drop between pre- and post-filter values (P>0.05) and their clearance was significantly lower than BNP (P: 0.0004). A daily analysis of BNP levels showed a significant decrease of its blood concentration. BNP levels were significantly reduced after three and four days from CVVH start (P<0.05). During 80 ml/kg/h CVVH, utilizing polyacrylonitrile membranes, BNP is efficiently cleared from blood in a small cohort of pediatric post-cardiosurgical patients. In this situation, BNP absolute blood levels may be unpredictable.

Initial experience with levosimendan infusion for preoperative management of hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) in the neonatal period is characterized by pulmonary overflow coupled with systemic hypoperfusion resulting in myocardial dysfunction, multiorgan failure, and severe metabolic derangement. This condition requires that the patient be stabilized by timely medical management before surgical palliation. The safety and efficacy of levosimendan were evaluated with six neonates affected by HLHS who had clinical signs of impending pulmonary overflow/systemic hypoperfusion, defined as tachypnea ([50 breaths/min), tachycardia (heart rate, [180 beats/min), hepatomegaly, central/toe temperature gradient exceeding 10 C, and lactate levels higher than 2 mmol/l. Levosimendan is a novel inodilator agent belonging to the family of calcium sensitizer agents with documented efficacy in treating adult congestive heart failure [2]. To date, few data exist on its use for pediatric patients [4], and no data exist on its use for HLHS neonates. The institutional review board of our hospital approved the use of levosimendan for such a cohort of patients. If all predefined signs of systemic hypoperfusion remained evident for more than 4 h after initial treatment (intravenous furosemide 1 mg/kg, packed red blood cells transfusions targeting a hematocrit level higher than 45%, children warming up to a toe temperature higher than 30 C), the patients were proactively sedated and intubated. Initial ventilator settings, with an inspired oxygen fraction (FiO2) of 30%, aimed to maintain normocapnia (partial pressure of carbon dioxide in arterial gas (PaCO2), 40– 45 mmHg). A central venous catheter was placed in the superior vena cava (SVC), and levosimendan infusion at 0.1 lg/kg/min was administered as the sole inotropic agent. All patients were receiving prostaglandin E1 infusion at 0.01 lg/kg/min since birth for ductal patency. Data are expressed as mean ± standard deviation. The Mann–Whitney test was used to compare means. A p value less than 0.05 was considered significant. The mean patient age at the time of intubation was 2.2 ± 0.5 days. All the patients received a classic Norwood procedure with a Blalock-Taussig shunt after a mean levosimendan administration time of 22 ± 8 h, from start of infusion to initiation of surgery. Lactate levels decreased from 4.22 ± 2.5 to 2.1 ± 0.4 mmol/l (p \ 0.05). Base excess increased from –1.92 ± 4 to 3.5 ± 3 mmol/l (p \ 0.05). The SVC oxygen saturation/systemic saturation (a-vO2) gradient decreased from 41.4% ± 12% to 29% ± 5% (p \ 0.05). Cerebral near infrared spectroscopy (NIRS) saturation improved from 57.8% ± 15.8% to 69.2% ± 7% (p \ 0.05). Central body temperature remained constant between 36 ± 1.5 C and 36.5 ± 0.5 C, whereas peripheral temperature increased significantly from 25.5 ± 1.4 C to 30.4 ± 0.4 C (p \ 0.05). The pulmonary-to-systemic flow ratio (Qp/Qs) was calculated according to the following formula: SatO2 – SvO2/ 99 –SatO2), where SatO2 and SvO2 are the arterial and SVC oxygen saturations, respectively. The pulmonary vein oxygen saturation was assumed to be 99%. The Qp/Qs decreased from 3.8 ± 1.2 to 2.1 ± 0.34 (p \ 0.05). Heart L. Di Chiara Z. Ricci (&) C. Garisto S. Morelli C. Giorni V. Vitale S. Picardo Division of Pediatric Cardiac Anesthesia/Intensive Care Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Pediatric Hospital, Piazza S.Onofrio, 00100 Rome, Italy e-mail: z.ricci@libero.it

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.

Initial Single-Center Experience With Levosimendan Infusion for Perioperative Management of Univentricular Heart With Ductal-Dependent Systemic Circulation:

The aim of this study was to evaluate the safety and the efficacy of levosimendan, a novel calcium sensitizer agent, on postoperative hemodynamic and metabolic parameters of neonates affected by single ventricle anatomy. Twenty consecutive neonates scheduled for the Norwood procedure with Blalock Taussig shunt were prospectively enrolled. All patients received an infusion of levosimendan at 0.1 μg/kg/min commencing 24 hours before surgery, and the infusion was continued for 48 hours after surgery. No side effects (intolerance to the drug, hypotension, arrhythmias) were shown. A median inotropic score (IS) of 37 was necessary to maintain a mean arterial pressure between 45 and 50 mm Hg at intensive care unit (ICU) admission: IS was significantly reduced after 72 hours (P < .05). Brain natriuretic peptide values decreased significantly from 1210 to 459 pg/mL in 72 hours (P < .05). Median SvO2 increased significantly from 38% to 59% during the evaluated period (P < .05). Cerebral near-infrared spectroscopy values were close to 40% at ICU admission with a significant stable increase to 50% after 12 hours (P < .05). Median lactate level was 13 mmol/L at ICU admission but showed a trend to a rapid and significant decrease after 12 hours (P < .05). Median urine output was surprisingly elevated, always remaining between 5.2 and 6.2 mL/kg/h throughout the postoperative period. Survival rate was 85% at 30 days (17/20 patients) and 75% (15/20) at hospital discharge. Levosimendan infusion in a cohort of neonates with univentricular anatomy was safe and potentially beneficial on postoperative hemodynamic and metabolic parameters.

Fluid Management in Pediatric Intensive Care

Fluid balance management in pediatric critically ill patients is a challenging task, since fluid overload (FO) in the pediatric ICU is considered a trigger of multiple organ dysfunction. In particular, the smallest patients with acute kidney injury are at highest risk to develop severe interstitial edema, capillary leak syndrome and FO. Several studies previously showed a statistical difference in the percentage of FO among children with severe renal dysfunction requiring renal replacement therapy. For this reason, in children priority indication is currently given to the correction of water overload. If this concept is so important in the critically ill small children, where capillary leak syndrome is a dramatic manifestation, it has probably been underestimated in critically ill adults and only recently re-evaluated. The present review will shortly describe nutrition strategies in critically ill children, it will discuss dosages, benefits and drawbacks of diuretic therapy, and alternative diuretic/nephroprotective drugs currently proposed in the pediatric setting. Finally, specific modalities of pediatric extracorporeal fluid removal will be presented. Fluid management, furthermore, is not only the discipline of removing water: it should also address the way to optimize fluid infusions and, above all, one of the most important fluids infused to all ICU patients with renal dysfunction: parenteral nutrition.

Hemodynamic monitoring by pulse contour analysis in critically ill children with congenital heart disease.

To the Editor:Proulx and colleagues (1) recently conducted a comprehensive review on the PiCCO system for cardiac output (CO) measurement, whose technology provides continuous CO calculation based on the analysis of the arterial pressure waveform calibrated after transpulmonary thermodilution. In pa