Aprotinin, transfusions, and kidney injury in neonates and infants undergoing cardiac surgery.

BACKGROUND: A significantly increased risk of acute kidney injury (AKI) with the prophylactic use of aprotinin has been reported in adults undergoing cardiac surgery, but not in children. Blood product transfusions have also been shown to carry an independent risk of AKI. The present study assessed associations between AKI, aprotinin, and transfusions in neonates and infants undergoing cardiac surgery. METHODS: All neonates and infants undergoing surgery with cardiopulmonary bypass over a 42 month period, before and after the withdrawal of aprotinin, were included retrospectively. AKI was assessed by the Acute-Kidney-Injury-Network classifications. A propensity score was used to balance treated and untreated groups. RESULTS: Three hundred and ninety patients received aprotinin and 568 patients did not. Inverse probability of treatment weighting resulted in good balance between groups for baseline and surgical characteristics. Controls underwent surgery with smaller bypass circuits and fewer transfusions. After adjustment for the use of miniaturized circuits and for the year of surgery, no significant association between the incidence of AKI, dialysis, and aprotinin was noted. Red blood cell transfusions were associated with an increased risk of AKI and dialysis: odds ratios (ORs) 1.64 (1.12-2.41) and 2.07 (1.13-3.73), respectively; as were fresh frozen plasma transfusions, ORs 2.28 (1.68-3.09) and 3.11 (1.95-4.97), respectively. Platelet transfusions were associated with an increased risk of dialysis: OR 2.20 (1.21-4.01). CONCLUSIONS: Blood product transfusions, but not the prophylactic use of aprotinin, are significantly associated with AKI after cardiac surgery in neonates and infants.

Pediatric perfusion in Japan: 2010 practice survey.

We report here Japan's first pediatric perfusion survey. It covers practices from January 2007 through December 2009. Of the 70 congenital heart centers contacted, 53 (76%) completed the survey. They reported performing 3,379 pediatric cardiopulmonary bypass (CPB) procedures in 2009, 3,408 in 2008, and 3,358 in 2007.Twenty-eight percent of all centers used CPB circuits with a priming volume between 151-200 ml. All centers used pre-bypass ultrafiltration and only 6% used retrograde autologous priming. A biomaterial-coated circuit was used by 78% of the centers, a roller pump as the arterial pump by 91%, vacuum-assisted venous drainage by 39%, dilutional ultrafiltration by 48%, and modified ultrafiltration at the end of the procedure by 30%. A regional oxygen saturation monitor was used by 69% of the centers and high flow (150-200 ml/kg/min) management with alpha-stat blood gas control was standard during moderate to normothermic CPBs. Crystalloid cardioplegia solution was used as myocardial protection by 56% of the centers, electronic recording of monitoring data by 51%. The centers performed 98 pediatric extracorporeal membrane oxygenation procedures in 2007, 109 in 2008, and 119 in 2009; 58% of the centers used a centrifugal pump. This survey provides a description of the current practice in Japan. Future surveys will identify trends and rate of change in practice.

Inhaled nitric oxide as a therapy for pulmonary hypertension after operations for congenital heart defects.

Seventeen infants were treated with inhaled nitric oxide for critical pulmonary artery hypertension after operations for congenital heart defects. In all 17 patients conventional medical therapy consisting of hyperventilation, deep sedation/analgesia, and correction of metabolic acidosis had failed. All children were monitored with a transthoracic pulmonary artery catheter inserted at operation. Pulmonary artery hypertension was defined as an acute rise in pulmonary pressure associated with a decrease in oxygen arterial or venous saturation. After failure of conventional medical therapy, 20 ppm of inhaled nitric oxide was administered to the patient. In all patients the pulmonary pressures decreased (mean pulmonary arterial pressure decreased by -34% +/- 21%) without significant change in systemic arterial pressure, whereas the oxygen arterial saturation and oxygen venous saturation increased by 9.7% +/- 12% and 37% +/- 28%, respectively. Fifteen children were discharged from the intensive care unit at 10 +/- 6 days (range 3 to 26 days) and two died. This study demonstrates that inhaled nitric oxide exerts a selective pulmonary vasodilation without decreasing systemic arterial pressure in children with congenital heart disease. The increased values of mixed venous oxygen saturation and urinary output suggest that this selective lowering of pulmonary vascular resistance improved the overall hemodynamics. The potential toxic effects of nitric oxide and nitrogen dioxide necessitate careful consideration of the risks and benefits of inhaled nitric oxide therapy.

Primary repair of tetralogy of Fallot in infancy.

From June 1983 to April 1988, 100 consecutive infants with symptomatic tetralogy of Fallot (without pulmonary atresia) were operated on. Ages ranged from 0.5 to 12 months (mean 7.3 +/- 3.7). Twenty patients were 0.5 to 3 months, 21 were 3 to 6 months, and 59 were 6 to 12 months of age. Mean weight was 6.5 kg +/- 1.7. Seventy patients received a transannular patch. The hospital mortality rate was 3% and there were no late deaths. Cumulative follow-up was 180 patient-years. Causes of death included hypoplastic pulmonary arteries (4 and 5 months old) and right ventricular failure (4 months old). The most important factors influencing right ventricular outflow tract reconstruction were neither weight (p = 0.90) nor age (p = 0.05) but rather were the ratio between weight and pulmonary arterial outflow tract diameter (p = 0.0005) and the ratio between body surface area and pulmonary arterial outflow tract diameter (p less than 0.0001). The last 48 patients were operated on with no deaths. During this period, operative management differed essentially in myocardial protection with blood cardioplegia. The predicted 30-day survivorship after repair was 90% to 99% (95% confidence limits). No ventricular arrhythmias have been detected after repair (mean follow-up 22.2 months). Mean right ventricular/left ventricular end-diastolic dimension ratio was (0.53 +/- 0.10 with M-mode echocardiography. These early results encourage us to proceed with primary repair of infants with symptomatic tetralogy of Fallot thanks to improved surgical management and enhanced myocardial protection.

Review of efficacy parameters.

BACKGROUND: The deleterious effects of cardiopulmonary bypass are greater in pediatric patients than in adults. The use of aprotinin to manipulate hemostasis has become an important factor in attempts to reduce adverse consequences of these effects. METHODS: This article reviews the literature on the use of aprotinin in pediatric cardiac surgery. RESULTS: Available studies have many deficiencies, often including lack of placebo control, nonhomogeneous populations and procedures, and absence of information on aprotinin plasma concentrations. Comparison of trial results is further complicated by differences in dose regimens, heparin-protamine protocols, and priming. CONCLUSIONS: Further trials are required to adequately assess aprotinin effect on platelet preservation, particularly in neonates, to evaluate aprotinin's antiinflammatory action, and to determine optimum dosages to achieve specific objectives. Aprotinin in pediatric cardiac surgery has been found to be associated with no adverse effects, to decrease fibrinolytic and probably platelet activation, and to offer important clinical benefits in specific groups of patients.

Anomalous left coronary artery from the pulmonary artery: results of isolated aortic reimplantation.

Thirty-one consecutive children with anomalous left coronary artery underwent direct aortic reimplantation of the anomalous artery without an associated procedure. There were five deaths (16%; 70% confidence limits, 9% to 26%), three in the hospital and two early (within 3 months). The severity of preoperative left ventricular dysfunction was the only incremental risk factor for mortality: 31% mortality rate among patients with left ventricular shortening fraction of less than 0.20 versus 0% among patients with a left ventricular shortening fraction of 0.20 or more (p = 0.03). There were no late deaths up to 6 years, a survival rate of 84% +/- 7%. Late results were studied in 23 survivors having a follow-up of longer than 12 months. Ninety-six percent were free of symptoms; left ventricular function recovered to normal in all patients; moderate to severe mitral regurgitation decreased to minimal or no regurgitation in most patients (5/7); and the reimplanted anomalous left coronary artery was patent in each patient. Based on this study, we reached five conclusions. (1) Direct aortic reimplantation is technically feasible in most patients with anomalous left coronary artery and yields a high rate of late patency. (2) Left ventricular resection is unnecessary. (3) The mitral valve should not be interfered with at the initial operation, but mitral regurgitation may persist in a few patients and necessitate later operation. (4) In patients with moderate left ventricular dysfunction, the operative risk is low and early operation indicated. (5) In patients with severe left ventricular dysfunction, the operative risk is high; heart transplantation may be suggested, but our current approach favors an immediate corrective procedure.

Pediatric cardiac transplantation for congenital heart defects: surgical considerations and results.

Among 54 children who underwent 55 heart transplantations, 24 (44%) (mean age, 4.9 +/- 4.8 years; range, 9 days to 18 years) had congenital defects with the following diagnoses: single-ventricle variants (6), hypoplastic left heart syndrome variants (5), transposition complex (6), and miscellaneous defects (7). Twenty patients (83%) had undergone 43 prior operations. Additional surgical procedures included repositioning of transposed great arteries (11), reconstruction of the aortic pathway (4), reconstruction of the pulmonary pathway (8), correction of situs inversus (1), and correction of anomalous pulmonary (1) or systemic (1) venous drainage. Reconstructive procedures were performed using donor or recipient tissue or both. There were six early deaths (hyperacute rejection, 1 patient; pulmonary hypertension, 1; graft failure, 2 patients; infection, 2) and six late deaths (sudden death, 2; chronic rejection, 2; nonspecific graft dysfunction, 1; lymphoproliferative disease, 1). The survival rate was 43% +/- 12% at 3 years. No deaths were related to surgical technique. Survival was not significantly different in pediatric recipients with cardiomyopathy (67% +/- 9%; p = 0.22). Accelerated coronary artery disease was noted in 4 operative survivors (22%; 70% confidence limits, 12% to 36%). All late survivors were free from cardiac symptoms after a mean follow-up of 34 +/- 24 months (range, 6 to 71 months). Based on this study, we reached three conclusions. (1) Careful planning of both harvesting and transplantation procedures allows heart transplantation in recipients with congenital heart diseases. (2) The surgical technique may be demanding, but the early risk is not increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal arterial switch operation: coronary artery patterns and coronary events.

OBJECTIVE: To determine the incidence of coronary events following neonatal arterial switch and to identify potential risk factors for death and coronary events. METHODS: The total experience (236 consecutive arterial switch operations) of one surgeon was studied. Associated procedures included ventricular septal defect closure in 37 patients (16%) and aortic arch repair in 14 patients (6%)). The influence of various patient, procedural, support technique and experience variables was analyzed. RESULTS: There were 19 deaths (8-70% confidence limits = 6-10%). Survival at 1 month, 1 year and 5 years was 93, 92 and 92%, respectively. Risk factors for death included small birth weight (P = 0.0015), hypoplasia of right ventricle (P < 0.0001), aortic arch obstruction (P < 0.0001) and coronary patterns with coronary arteries coursing between the great arteries (P = 0.0066). Coronary events occurred in 26 patients (11-70% confidence limits = 9-13%) and involved coronary deaths (11 patients), non fatal myocardial infarctions (8 patients) and coronary stenoses or occlusions (7 patients). Freedom from coronary events at 1 month, 1 year and 5 years was 94, 91 and 88%, respectively. Risk factors for coronary events included coronary patterns with retropulmonary course of the left main or left circumflex coronary artery (P = 0.0122), coronary patterns with coronary arteries coursing between the great arteries (P < 0.0001), all variations of intramural coronary arteries (P = 0.0010) and commissural origin of coronary ostia (P = 0.0171). CONCLUSIONS: (1) In most neonates, arterial switch operation carries a low operative risk and provides excellent mid-term results; (2) The operative risk remains increased in some subsets; and (3) Some coronary patterns increase the risk of coronary events. Further surgical experience may improve the results.

Heart- and heart-lung transplantation in children.

Since January 1987, 16 prepubertal children have undergone heart (13) or heart-lung (3) transplantation. Immunosuppression included cyclosporine and azathioprine and excluded steroids except in case of rejection. The indications for heart transplantation were hypoplastic left heart syndrome (4 infants, mean age = 2 months), congenital heart disease (4 patients, mean age = 5.7 years) and cardiomyopathy (5 patients, mean age = 2.8 years). There were 4 early deaths (acute graft failure in 2, pulmonary hypertension in 1, infection in 1) and 1 late death (heart failure at 3 months). The 8 survivors had a mean follow-up of 12 months (range 1-19 months). Late complications were minimal. There were 4 episodes of rejection in 2 patients. There was no infection, normal somatic growth and no systemic hypertension. Renal function remained within normal limits although mild-to-moderate tubulointerstitial lesions were found in 4 renal biopsies. Three children (9-11 years old) underwent heart-lung transplantation. The early postoperative course was difficult with 6 episodes of rejection and 5 infections. One patient died at 3 months from infectious complications. One child has a complete rehabilitation 8 months posttransplantation. The last patient is clinically well at 7 months but has a residual tracheal stenosis. The long-term fate of these children, and particularly the long-term effects of cyclosporine therapy are unknown. Heart and heart-lung transplantation remain under investigation but may be reasonable approaches for infants and children with end-stage cardiac and/or pulmonary disease.

Arterial switch operation: a new technique of coronary transfer.

A successful outcome after arterial switch operation (ASO) for transposition of the great arteries (TGA) depends in large part on the adequacy of transfer of the coronary arteries to the neoaorta. The present paper describes a new technique of coronary transfer which was used in 43 patients: 28 neonates with TGA and intact septum (with coarctation in one), 10 neonates with TGA and ventricular septal defect (with coarctation in one), 2 children undergoing ASO after failed Senning operation and 3 patients with complex TGA. A standardized uniform technique of coronary transfer was used; this technique involved reimplantation of the two coronary ostia side by side after excision of a single button of neoaortic wall. Most coronary patterns were encountered: the usual pattern in 30, circumflex from right coronary artery in 7, inverted coronary arteries in 3, inverted circumflex and right coronary arteries in 3. There was no early coronary-related mortality or morbidity. One late death (3 months) was probably coronary-related. The overall coronary risk was 2.3% (70% confidence limits = 0.3%-7.5%). The proposed technique of coronary transfer can be used in most patients with TGA (all patients without coronary arteries running between the great arteries) and entails a low coronary risk.

Primary definitive repair of interrupted aortic arch with ventricular septal defect.

The optimal surgical management (primary or staged repair) of interrupted aortic arch (IAA) with ventricular septal defect (VSD) remains to be determined. A consecutive series of 14 neonates, aged 3-18 days (mean: 10 +/- 6 days) underwent primary complete repair. Mean weight was 3.3 +/- 0.4 kg. Eleven patients had IAA type B, 2 had type A and 1 had type C. Six infants had the Di George syndrome. Preoperative management (mean: 5 +/- 4 days) included prostaglandin E1 (14/14), intubation and ventilation (13/14), and inotropic support (11/14). Surgery was performed under deep hypothermia and circulatory arrest and involved resection of all ductal tissue, direct end-to-side aortic arch anastomosis and patch closure of the VSD. There were 2 early deaths (14%, 70% CL: 5%-31%): low cardiac output (1), residual VSD (1). Four patients (33%, 70% CL: 13%-52%) underwent reoperation for recurrent aortic obstruction (3 patients, 1 death) or left ventricular outflow tract obstruction (LVOTO) (1 patient). The results improved with time: no death and no recurrent aortic obstruction in the last 8 patients. At last follow-up (11 patient, mean follow-up = 24 +/- 9 months), all patients were free of cardiac symptoms; none had persistent aortic obstruction; 4 had LVOTO (gradient greater than 20 mm Hg) and 1 (with the Di George syndrome) had severe mental disorders. Primary complete repair provides satisfactory results in most infants born with IAA and VSD. An adequate direct aortic arch anastomosis should entail a low risk of recurrent obstruction. LVOTO develops in many cases and may require further surgery.

Heart transplantation in children: risk factors of early and late mortality.

In order to identify predictive risk factors of poor outcome following heart transplantation in children, we performed a retrospective analysis of our pediatric recipient population: 31 children, aged 15 days to 15 years (mean = 5.2 +/- 4.9 years). The preoperative diagnosis was cardiomyopathy in 17 (55%), congenital heart disease in 13 (42%) and end-stage valvular disease in 1 (3%). There were 5 operative deaths: hyperacute rejection (2), low cardiac output syndrome (3); 4 in-hospital deaths: infection (2), multiorgan failure (2) and 4 late deaths: acute rejection (1), chronic rejection (1), lymphoma (1), unknown (1). The actuarial probability of survival (+/- SE) was 62% +/- 10% at 1 year and 53% +/- 12% at 2 years. Univariate analysis was used to evaluate the following risk factors: age, diagnosis, hemodynamic decompensation, previous cardiac surgery, ischemic time of the graft, technique of graft preservation, preoperative pulmonary artery pressure, occurrence of postoperative low cardiac output syndrome (LCOS) with pulmonary hypertension (PHT). The occurrence of early LCOS with PHT significantly increased both early and late mortality (78% early mortality, 100% overall mortality). This syndrome occurred in 9 patients (29%) and was attributed to primary graft failure in 2, increased pulmonary vascular resistances in 6 and multiple factors in 1. Although not significant, two factors may increase early survival: young age (less than or equal to 1 year) at operation and improved technique of graft preservation.

Diffuse subaortic stenosis: modified Konno procedures with aortic valve preservation.

The Konno procedure provides adequate relief of diffuse subaortic stenosis but requires aortic valve replacement. This may be questionable in patients without aortic valve lesions. Eleven patients had diffuse subaortic stenosis and normal aortic orifice: tunnel subaortic stenosis (6 patients) or diffuse hypertrophic obstructive cardiomyopathy (5 patients). The mean age was 16 +/- 14 years (range: 3 months to 45 years). The mean subaortic gradient was 95 +/- 24 mmHg (range: 60 to 150 mmHg). Two patients had previously undergone resection of discrete subaortic stenosis. Modified Konno procedures were used: aortoseptal approach with aortic annulus division in 5 patients, conal enlargement without aortic annulus division in 6 patients. There was one early death (9%, 70% CL = 1%-27%) and no late deaths. Reoperation was required in two patients: one early for iatrogenic aortic regurgitation and one late for residual ventricular septal defect and mitral regurgitation. The mean follow-up was 3.8 +/- 4.2 years (range: 2 months to 10 years). The survivors were in functional class I (8/10), had a normal left ventricular function (9/10), were in sinus rhythm (10/10) and had left ventricular outflow tract gradients ranging up to 25 mmHg (mean = 6 +/- 10 mmHg). Residual surgery-related defects included ventricular septal defect (one) and aortic regurgitation (one). In patients with diffuse subaortic stenosis and normal aortic orifice, modified Konno procedures with aortic valve preservation are preferable, effective and can be safely performed in infants and children.

[Enoximone and pediatric heart surgery]. / Enoximone et chirurgie cardiaque pédiatrique.

The double mode of action of enoximone, inotropic and vasodilator, makes it a valuable drug in adult cardiac surgery. There have been no reports of its use in paediatric cardiac surgery. We studied its effects in 15 children with a right heart malformation, 5 with cardiac transplants and 5 with various malformations of different complexity. Enoximone was administered as an IV bolus of 1 mg/kg over 10 minutes, relayed by a continuous infusion of 7.5 gamma/kg/mn. This drug was used alone in 15 patients and in association with dobutamine or dopamine in the others. Enoximone was associated with an improved haemodynamic status after repair of right heart malformations related to better left ventricular contractility, a moderate but statistically significant elevation of mean blood pressure without tachycardia, and stable right heart filling pressures. Improved systemic perfusion was also observed in children awaiting cardiac transplantation. This treatment provided a bridge to cardiac transplantation which was attained in good condition, given the difficulties of using mechanical circulatory assistance in children and the scarcity of donors. When associated with other pulmonary vasodilators, enoximone was effective in the treatment of right heart failure with pulmonary hypertension. When used alone or in association with catecholamines, enoximone is a treatment of choice in per and postoperative paediatric intensive care, especially as the synergist effect obtained enables a reduction in the quantity of classical inotropic agents used, thereby contributing to an attenuation of the phenomenon of exhaustion observed with catecholergic drugs.

[Sodium nitroprusside in hypothermic surgery under extracorporeal circulation]. / Le nitroprussiate de sodium chez l'opéré en hypothermie sous circulation extracorporelle.

Sodium nitroprusside (SNP) is a vasodilator widely used in heart surgery. Its effects before and after bypass at normal temperature have been reported. This prospective study compares 15 patients who received SNP with 5 controls. SNP's efficacy on the systemic arterial resistance index is demonstrated during cooling and rewarming. Vasoconstriction at the end of persistent hypothermia does not respond to SNP. No signs of toxicity, neither biological (metabolic acidosis) nor clinical (respiratory or cardiac problems) were observed. SNP lowers pulmonary artery resistance index during normothermia and pulsed cardiac output, but a rebound appears 45 minutes after SNP withdrawal. SNP is usefull for anaesthesia in heart surgery with hypothermia.

[Analysis of incidents, monitoring and safety devices of cardiopulmonary bypass for cardiac surgery for the year 2005 in France]. / Analyse des accidents, des moyens de monitorage et de sécurité de la circulation extracorporelle pour chirurgie cardiaque en France en 2005.

INTRODUCTION: Several surveys demonstrated that cardiopulmonary bypass (CPB) is associated with incidents that negatively affect the outcome of cardiac surgery. OBJECTIVES: In 2004, the French "Haute Autorité de santé" (an independent public scientific authority) and the French "College of Perfusion" issued recommendations concerning safety and monitoring devices for CPB. The aims of the present study were to: 1) investigate the difference between the recommendations and the clinical practice of CPB shortly after publication of the recommendations; 1) investigate the type and rate of perfusion incidents and their outcome. STUDY DESIGN: Retrospective survey. METHODS: A 62 items questionnaire was sent to all 66 centres performing cardiac surgery in France. RESULTS: Fifty-seven centres totalling 34,496 CPB procedures (response rate 86%) returned the questionnaire. There was a wide difference between the recommendations and the reported use of safety and monitoring devices. An incident was reported for every 198 CPB procedures with death occurring 1:4,864 and permanent sequelae 1:11,349 procedures respectively (permanent injury or death 1:3,220 procedures). The most frequent perfusion incidents were adverse effects to protamine (1:1,702), dissection at the arterial canulation site (1:1,792) and coagulation of the circuit (1: 4,864). CONCLUSION: This survey demonstrates that an important effort must be made in order to fill the gap between the recommendations and clinical use of monitoring and safety devices. The analysis of CPB-related incidents suggests that, with the exception of protamine adverse effects, the majority of deaths and severe permanent injuries could probably be avoided by improved use of the monitoring and safety devices.

Assessment of coagulation factor activation during cardiopulmonary bypass with a new monoclonal antibody.

Antithrombin-III (AT) is a key inhibitor of blood coagulation that neutralizes activated serine esterases by forming covalent modified complexes (ATm). A new monoclonal antibody directed against short-lived AT-activated serine protease complexes provides a means of measuring subclinical coagulation activity during cardiopulmonary bypass (CPB). Twelve patients undergoing CPB for coronary artery bypass grafting were studied and AT, ATm, D-dimers (DD), and several other coagulation and fibrinolytic markers were measured during the surgical procedure. There were decreases in AT, factors V, II, X, IX, protein S (total and free), C4b-binding protein, thrombomodulin, and platelets counts, whereas heparin, ACT, thrombospondin, plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) increased. ATm and the percentage of ATm available (ATm/AT) showed a peak during CPB. These results demonstrate that during CPB, the use of heparin produces an equilibrium involving increased coagulation activation and consumption in association with increased fibrinolysis. The equilibrated consumption of both coagulation and fibrinolytic factors leads to low levels of all factors after cardiac surgery. The ATm assay allows assessment of the differential effects of CPB and surgical trauma on coagulation activation. It is speculated that ATm levels may be useful in monitoring the consumption of coagulation factors.