Luca Di Chiara

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.

Fenoldopam in newborn patients undergoing cardiopulmonary bypass: controlled clinical trial

We determined if low dose fenoldopam in neonates already receiving conventional diuretics improves urine output, fluid balance, acute kidney injury incidence (AKI) and time to extubation. A prospective controlled clinical trial in a pediatric cardiac intensive care unit on 40 neonates undergoing cardiac surgery with cardiopulmonary bypass, excluding simple ventricular septal defect and atrial septal defect. Fenoldopam was infused at a low dose of 0.1 microg/kg/min soon after anesthesia induction and infusion prolonged for 72 h in 20 patients. Twenty neonates with standardized perioperative therapy except fenoldopam administration served as controls. Demographic, hemodynamic, daily urine output, creatinine, creatinine clearance, serum and urinary sodium and potassium were recorded. Inotropic score (IS) was calculated as a surrogate for the degree of hemodynamic impairment. Low dose fenoldopam infusion did not show beneficial effects in renal function. The treatment did not significantly affect IS value, AKI incidence, fluid balance control, time to sternal closure, time to extubation and time to intensive care unit discharge. Low dose fenoldopam in neonates undergoing cardiac surgery with CPB did not produce effects on urine output, fluid balance and AKI incidence. Fenoldopam was well tolerated and did not negatively affect hemodynamics and vasopressor support.

Renal replacement therapy in neonates with congenital heart disease.

BACKGROUND The acute renal failure (ARF) incidence in pediatric cardiac surgery intensive care unit (ICU) ranges from 5 to 20% of patients. In particular, clinical features of neonatal ARF are mostly represented by fluid retention, anasarca and only slight creatinine increase; this is the reason why medical strategies to prevent and manage ARF have limited efficacy and early optimization of renal replacement therapy (RRT) plays a key role in the outcome of cardiopathic patients. METHODS Data on neonates admitted to our ICU were prospectively collected over a 6-month period and analysis of patients with ARF analyzed. Indications for RRT were oligoanuria (urine output less than 0.5 ml/kg/h for more than 4 h) and/or a need for additional ultrafiltration in edematous patients despite aggressive diuretic therapy. RESULTS Incidence of ARF and need for RRT were equivalent and occurred in 10% of admitted neonates. Eleven patients of 12 were treated by peritoneal dialysis (PD) as only RRT strategy. PD allowed ultrafiltration to range between 5 and 20 ml/h with a negative balance of up to 200 ml over 24 h. Creatinine clearance achieved by PD ranged from 2 to 10 ml/min/1.73 m2. We reported a 16% mortality in RRT patients. CONCLUSION PD is a safe and adequate strategy to support ARF in neonates with congenital heart disease. Fluid balance control is easily optimized by this therapy whereas solute control reaches acceptable levels.

Cobalamin c defect presenting with isolated pulmonary hypertension

Cobalamin C (cblC) defect is the most common inborn error of vitamin B12 metabolism. Clinical features vary as does the severity of the disease. In most cases, the clinical symptoms of cblC defect tend to appear during infancy or early childhood as a multisystem disease with severe neurologic, ocular, hematologic, renal, and gastrointestinal signs. The neurologic findings are common and include hypotonia, developmental delay, microcephaly, seizures hydrocephalus, and brain MRI abnormalities. We report a case of a young boy with cblC defect, who did not undergo newborn screening, presenting at the age of 2 years with isolated pulmonary hypertension as the leading symptom. This novel way of presentation of cblC defect enlarges the spectrum of inherited diseases that must be considered in the differential diagnosis of pulmonary hypertension.

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.

Role of vasopressin in the treatment of anaphylactic shock in a child undergoing surgery for congenital heart disease: a case report

IntroductionThe incidence of anaphylactic reactions during anesthesia is between 1:5000 and 1:25000 and it is one of the few causes of mortality directly related to general anesthesia. The most important requirements in the treatment of this clinical condition are early diagnosis and maintenance of vital organ perfusion. Epinephrine administration is generally considered as the first line treatment of anaphylactic reactions. However, recently, new pharmacological approaches have been described in the treatment of different forms of vasoplegic shock.Case presentationWe describe the case of a child who was undergoing surgery for ventricular septal defect, with an anaphylactic reaction to heparin that was refractory to epinephrine infusion and was effectively treated by low dose vasopressin infusion.ConclusionIn case of anaphylactic shock, continuous infusion of low-dose vasopressin might be considered after inadequate response to epinephrine, fluid resuscitation and corticosteroid administration.

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

Neurally adjusted ventilatory assist and lung transplant in a child: A case report.

Objective: To report the successful application of neurally adjusted ventilatory assist to a child with cystic fibrosis who underwent single-lung transplantation. Design: Case report. Setting: Pediatric cardiac intensive care unit. Patient: A 15-yr-old male with cystic fibrosis was admitted to our pediatric cardiac intensive care unit after single-lung transplantation. The child had previously received two bowel resections at the age of 1 yr, right pneumonectomy at the age of 3 yrs, and endoscopic percutaneus gastrostomy at the age of 10 yrs. After transplant, the child failed several attempts of weaning off mechanical ventilation with pressure-support ventilation, due to infection, pneumothorax, and ventilator asynchrony that caused gastric distension and numerous episodes of nausea and vomiting. Intervention: Use of neurally adjusted ventilatory assist to avoid patient-ventilator dyssynchrony and consequent gastric distension. Conclusions: The utilization of neurally adjusted ventilatory assist allowed to limit the risk of overassistance and prevent patient-ventilator asynchrony and to successfully wean the child off mechanical ventilation after single-lung transplant.

Survey of the use of peripherally inserted central venous catheters in neonates with critical congenital cardiac disease.

Neonates with congenital cardiac disease are a special population. They are often critically ill, and need prolonged intravenous access. To date, no study has evaluated the efficacy and safety of peripherally inserted central venous catheters placed in this unique population. Our goal was to evaluate the use of such catheters in neonates with critical congenital cardiac disease, and to study features such as duration of use, reasons for removal of catheters, and complications. We inserted a total of 124 catheters in 115 neonates with critical congenital cardiac disease who were admitted to the Intensive Care Unit at Texas Childrens Hospital from August 2002 to August 2004. The patients had a mean age of 10 days, and a mean weight of 3.1 kilograms. The peripherally inserted catheters were in place for a mean of 22.3 days. Therapy was completed in 76.6% patients at the time of removal of the catheter. The incidence of occlusion, dislodgement, and thrombus was 4.0%, 2.4%, and 1.6%, respectively. The infection rate was 3.6 per 1000 catheter-days, with a median onset on 37 days after placement. We conclude that central venous catheters, when inserted peripherally, provide reliable and safe access for prolonged intravenous therapy in neonates with critical congenital cardiac disease.

Dose Prescription and Delivery in Neonates with Congenital Heart Diseases Treated with Continuous Veno-Venous Hemofiltration

Objectives: Renal replacement therapy may be required for acute kidney injury treatment in neonates with complex cardiac conditions. Continuous veno-venous hemofiltration is applied safely in this population but no published recommendations for dose prescription in neonates currently exist. The aim of our study was to evaluate the effects of a relatively small dialysis dose on critically ill neonates. Design: Retrospective analysis of clinical charts. Setting: Pediatric Cardiac ICU. Patients: Ten critically ill neonates with severe acute kidney injury were analyzed. The primary indication for continuous veno-venous hemofiltration initiation was severe fluid overload with oligoanuria. Interventions: None. Measurements and Main Results: The median (range) age and weight were 3 days (1–12 d) and 2.6 kg (2.1–4.2 kg), respectively, whereas the median continuous veno-venous hemofiltration duration was 17 days (3–63 d). Median prescribed blood flow rate, replacement fluid rate, and net ultrafiltration rate were 12 mL/min (9–50 mL/min), 100 mL/hr (40–200 mL/hr), and 20 mL/hr (5–45 mL/hr), respectively. The median effluent-based continuous veno-venous hemofiltration dose was 35 mL/kg/hr (11–66 mL/kg/hr), whereas the median delivered daily Kt/V per session (24 hr) was 0.5 (0.01–1.8). However, for treatment sessions lasting less than or equal to 12 versus greater than or equal to 12 hours per session, the median prescribed effluent dose was 41 (11–66) and 32 (17–60) mL/kg/hr, respectively (p = 0.06), whereas the delivered creatinine daily Kt/V values were 0.3 (0.01–0.9) and 0.9 (0.5–1.8), respectively (p < 0.0001). An inverse correlation was found between delivered daily Kt/V and the blood concentration differences of both creatinine (r = –0.3; p = 0.0093) and urea (r = –0.3; p = 0.0028) measured at the end and the beginning of a 24-hour treatment. The decrease of creatinine concentration was significantly greater during 24-hour treatment sessions with a delivered daily Kt/V greater than 0.9 than during those with daily Kt/V less than 0.9. Conclusions: Based on these findings, we propose on a provisional basis the use of daily Kt/V as a measure of continuous renal replacement therapy adequacy for critically ill neonates.