Philippe Pouard

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 patients 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.

BackgroundThis 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. MethodsThirty-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, antithrom-bin-III, complement fragments C3a and C5a, interleukin-lβ, interleukln-6, interleukin-8, and tumor necrosis factor-a were measured before and after hemofiltration. Systemic mean arterial pressure, left atrial pressure, time to extubation, and postoperative blood loss were monitored. ResultsIn 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-α 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, lnterleukin-8, and duration of stay in the Intensive care unit. ConclusionsHemofiltration during cardiopulmonary bypass in children Improves hemodynamics and early postoperative oxygenatlon 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.

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.

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.

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.

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.

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.