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.

[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.

Results of the arterial switch operation in neonates with transposed great arteries.

BACKGROUND: The arterial switch operation is judged the best palliative operation for neonates with transposed great arteries. We aimed to assess the value of analysing a large series of unselected cases by this technically demanding operation and formulate a realistic prognosis. METHODS: We reviewed all 432 neonates (mean age at operation 7 days, mean weight 3.25 kg) who underwent an arterial switch operation between 1987 and 1999. Follow-up (mean time: 4.9 years) was complete in 412 patients. FINDINGS: Survival probability and freedom from reoperation was 94% and 78% at 10 years, respectively. 26 patients died, 16 because of myocardial ischaemia. Risk factors for death included early experience, low weight, associated cardiovascular malformations (especially hypoplasia of the right ventricle or aortic arch), and difficult patterns of coronary arteries. The risk of the coronary artery pattern was greatly reduced in those who had recent operations. At last follow-up, 90% of patients had normal life without treatment, and 94% a normal heart function on echocardiography. INTERPRETATION: The arterial switch operation in neonates achieves excellent results mid-term. Obstruction of the translocated coronary arteries is responsible for most deaths and a substantial number of reoperations. Although confirmation is needed, these results allow anticipation of a favourable long-term prognosis.

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.

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.

High-volume, zero-balanced hemofiltration to reduce delayed inflammatory response to cardiopulmonary bypass in children.

BACKGROUND: In previous studies, researchers suggested a beneficial role of hemofiltration performed during cardiopulmonary bypass in children. This study was performed to assess both clinical effects and inflammatory mediator removal by high-volume, zero-fluid balance ultrafiltration during rewarming (Z-BUF). METHODS: Twenty children undergoing cardiac surgery were assigned randomly to Z-BUF or a control group. Plasma C3a, interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor, myeloperoxidase, and leukocyte count were measured before (T1) and after (T2) hemofiltration and 24 h later (T3). The intensive care unit staff was blinded to the patient's group. Postoperative alveolar-arterial oxygen gradient, time to extubation, body temperature, and postoperative blood loss were monitored. RESULTS: Ultrafiltration rate was 4,972 (3,183-6,218) mL/m2 (median [minimum-maximum]) in the Z-BUF group, where significant reductions were observed in postoperative blood loss, time to extubation (10.8[9-18] vs. 28.2 [15-58] h) and postoperative alveolar-arterial oxygen gradient (320 [180-418] vs. 551 [485-611] mmHg at T3). In the Z-BUF group, significant removal of tumor necrosis factor, IL-10, myeloperoxidase, and C3a were observed at T2. Interleukin 1, IL-6, IL-8, and myeloperoxidase were decreased at T3, suggesting earlier removal of factor(s) that may trigger their release. CONCLUSIONS: These results suggest that hemofiltration exerts some beneficial clinical effects that are not due to water removal. The role of the early removal of factors triggering the inflammatory response, rather than a direct removal of cytokines, deserves further investigation.

Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Effects on hemostasis, cytokines, and complement components.

BACKGROUND: This prospective study was intended to determine in a homogeneous population of children whether hemofiltration, performed during cardiopulmonary bypass rewarming, is able to improve hemodynamics and biologic hemostasis variables, to reduce postoperative blood loss, time to extubation, and plasma cytokines, and complement fragments. METHODS: Thirty-two children undergoing surgical correction of tetralogy of Fallot were randomly assigned to a hemofiltration or control group. Hemofiltration was performed with a polysulphone hemofilter during rewarming of cardiopulmonary bypass. Plasma clotting factors, D-dimers, antithrombin-III, complement fragments C3a and C5a, interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha were measured before and after hemofiltration. Systemic mean arterial pressure, left atrial pressure, time to extubation, and postoperative blood loss were monitored. RESULTS: In the hemofiltration group, significant reductions in 24-h blood loss (250 (176-356) vs. 319 (182-500) ml/m2, median (minimum-maximum), time to extubation (15 (9-22) vs. 19 (11-24) h), plasma concentrations of C3a, C5a, interleukin-6, and tumor necrosis factor-alpha were observed compared to control. Arterial oxygen tension on admission to the intensive care unit was significantly greater in the hemofiltration group (136 +/- 20 vs. 103 +/- 25 mmHg, mean +/- SD). Significant increases in mean arterial pressure, clotting factors, and antithrombin-III were noted for the hemofiltration group. No intergroup difference was observed in left atrial pressure, platelets count, D-dimers, interleukin-8, and duration of stay in the intensive care unit. CONCLUSIONS: Hemofiltration during cardiopulmonary bypass in children improves hemodynamics and early postoperative oxygenation and reduces postoperative blood loss and duration of mechanical ventilation. Hemofiltration is able to remove some major mediators of the inflammatory response.

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.

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.

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.

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)

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.