Stefano Morelli

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.

Mechanical Assist Device as a Bridge to Heart Transplantation in Children Less Than 10 Kilograms

BACKGROUND Despite the remarkable advances with the use of ventricular assist devices (VAD) in adults, pneumatic pulsatile support in children is still limited. We report a retrospective review of our experience in very small children (<10 kg of body weight). METHODS Ten consecutive children weighing less than 10 kg were offered mechanical support with Berlin Heart (Berlin Heart AG, Berlin, Germany) as a bridge to heart transplant from March 2002 to March 2010. RESULTS The median patient age was 10.4 months (38 days to 2.2 years). The median patient weight was 6.4 kg (2.9 to 10 kg). Prior to VAD implantation, all children were managed by multiple intravenous inotropes and mechanical ventilation (8) or extracorporeal membrane oxygenation (2). The median pre-VAD pulmonary vascular resistance index was 5.7 Woods units/m(2). Three patients required biventricular mechanical support, but in all other cases a single left VAD proved sufficient. The median duration of VAD support was 61 days (2 to 168 days). Four deaths occurred; from stroke in three and sepsis in one. Five patients were successfully bridged to heart transplantation after a median duration of mechanical support of 89 days (37 to 168 days) and another is still waiting a suitable organ after 77 days of VAD support. There were no complications related to postoperative bleeding. Five patients required at least one pump change. Of 5 patients undergoing heart transplant, 3 developed an extremely elevated (>60%) panel reactive antibody by enzyme-linked immunosorbent assay, confirmed by Luminex (Luminex Corp, Austin, TX). All 3 experienced at least one acute episode of rejection in the first month after heart transplant, needing plasmapheresis. The survival rate after heart transplantation was 100% with a median follow-up of 7.5 months. CONCLUSIONS Mechanical support in very small children with end-stage heart failure is an effective strategy of bridge to heart transplantation with a reasonable mortality rate. The high rate of complications suggests to optimize indications and timing of VAD implantation.

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.

Neurological complications during pulsatile ventricular assistance with the Berlin Heart EXCOR in children: incidence and risk factors.

The aim of this study is to describe the incidence of brain injury (BI) in children with end-stage cardiac failure who were supported with the Berlin Heart EXCOR ventricular assist device (VAD) as a bridge to heart transplantation. Between January 2002 and January 2012, all patients <18 years of age who underwent the implantation of the Berlin Heart EXCOR at Bambino Gesú Childrens Hospital were included. A total of 25 patients were included in this study. Median age and weight at implantation were 22.4 months (range 3.6-154.2) and 10 kg (range 4.5-36), respectively. Diagnosis included cardiomyopathy (n = 20) and congenital heart disease (n = 5). Eleven patients received atrial cannulation. Nine patients underwent biventricular assist device support. Seven patients underwent extracorporeal membrane oxygenation before the implantation of the EXCOR VAD. Median duration of VAD support was 51 days (range 2-167). Nine patients had evidence of acute BI including intracranial hemorrhage (n = 5) and cerebral ischemia (n = 4). Freedom from BI at 30, 60, and 90 days from VAD implantation was 80.7, 69.9, and 43.3%, respectively. Weight <10 kg at implantation was significantly associated with BI. BI is a frequent complication among children supported with EXCOR VAD and is associated with lower weight at implantation. However, our data do not support the association between size and BI. Future prospective multicenter studies are warranted to further help understand the etiology and the impact of BI and to improve functional outcomes for children undergoing EXCOR VAD mechanical support.

Management of fluid balance in continuous renal replacement therapy: technical evaluation in the pediatric setting.

Fluid overload control and fluid balance management represent very important factors in critically ill children requiring renal replacement therapy A relatively high fluid volume administration in children and neonates is often necessary to deliver adequate amounts of blood derivatives, vasopressors, antibiotics, and parenteral nutrition. Fluid balance errors during pediatric continuous renal replacement therapy (CRRT) might significantly impact therapy delivery and have been described as potentially lethal. The aim of this study was to evaluate the accuracy of delivered vs. prescribed net ultrafiltration (UF) during CRRT applied to 2 neonates and 2 small children, either as dialytic treatment alone or during extracorporeal membrane oxygenation (ECMO). In accordance with an Acute Dialysis Quality Initiative workgroup statement, net UF was defined as the “overall amount of fluid extracted from the patient in a given time”. Mean prescribed net UF was 18.5 ml/h (SD=6.7) during neonatal treatments and 70.3 ml/h (SD=22.5) during CRRT in small children. Daily net UF ranged from 200 mL to about 600 mL in the 2 neonates and from 1,200 to 1800 mL in the 2 children. The percentage error of delivered net UF ranged from −1.6% to 5.8% of the prescribed level. The mean error of the ECMO/CRRT patients was 3.024 ml/h vs. 0.45 m/h for the CRRT patients (p<0.001). The same difference was not evident when the 2 neonates were compared with the 2 small children (without considering the presence of ECMO). CRRT and net UF delivery appeared to be accurate, safe, and effective in this small cohort of high-risk pediatric patients.

Pneumatic pulsatile ventricular assist device as a bridge to heart transplantation in pediatric patients.

Despite the remarkable advances with the use of ventricular assist devices (VAD) in adults, pneumatic pulsatile support in children is still limited. We report on our experience in the pediatric population. A retrospective review of 17 consecutive children offered mechanical support with Berlin Heart as a bridge to heart transplant from February 2002 to April 2010 was conducted. The median patient age was 3.9 years (75 days to 13.3 years). The median patient weight was 14.1 kg (2.9-43kg). Before VAD implantation, all children were managed by multiple intravenous inotropes and mechanical ventilation (14) or extracorporeal membrane oxygenation (3). All patients had right ventricular dysfunction. Nine patients required biventricular mechanical support (BVAD), but in all other cases a single left ventricular assist device proved sufficient (47%). The median duration of VAD support was 47 days (1-168 days). The median pre-VAD pulmonary vascular resistance index (Rpi) was 5.7 WU/m(2) (3.5 to 14.4WU/m(2) ). Eleven patients (65%) were successfully bridged to heart transplantation after a median duration of mechanical support of 68 days (6-168 days). Six deaths occurred (35%), three for neurological complications, one for sepsis, and two others for device malfunctioning. Since 2007, the survival rate of our patients has increased from 43% to 80%, and the need for BVAD has decreased from 86% to 30%. In two patients with Rpi >10WU/m(2) , unresponsive to pulmonary vasodilatator therapy, Rpi dropped to 2.2 and 2WU/m(2) after 40 and 23 days of BVAD support, respectively. Seven patients (41%) required at least one pump change. Of 11 patients undergoing heart transplant, four developed an extremely elevated (>60%) panel reactive antibody by enzyme-linked immunosorbent assay, confirmed by Luminex. All of them experienced at least one acute episode of rejection in the first month after heart transplant, needing plasmapheresis. The survival rate after heart transplantation was 100% with a median follow-up of 25.4 months (6 days to 7.7 years). Mechanical support in children with end-stage heart failure is an effective strategy as a bridge to heart transplantation with a reasonable morbidity and mortality. BVAD support may offer an additional means to reverse extremely elevated pulmonary vascular resistance.

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