Pascal Vouhé

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.

Circulating Endothelial Cells A New Candidate Biomarker of Irreversible Pulmonary Hypertension Secondary to Congenital Heart Disease

Background— Congenital heart disease can be complicated by pulmonary arterial hypertension (PAH), the reversibility of which is often difficult to predict. We recently reported a lung biopsy study showing impaired apoptotic regulation of endothelial cells in irreversible PAH. The objective of the present study was to identify noninvasive biomarkers of endothelial turnover that could be used to identify congenital heart disease patients at risk of irreversible PAH. Methods and Results— Circulating endothelial cells (CECs) isolated with CD146-coated beads and circulating CD34+CD133+ progenitor cells (CPCs) were quantified in peripheral vein, pulmonary artery, and pulmonary vein blood samples from 26 patients with congenital heart disease (16 with reversible PAH [median age 2 years] and 10 with irreversible PAH [median age 9 years]) and 5 control patients. Surgical lung biopsy was performed in 19 cases. As expected, endothelial remodeling was observed in irreversible PAH but not in reversible PAH. CEC and CPC numbers were each similar in the 3 types of blood samples. CEC numbers were significantly higher in patients with irreversible PAH (median 57 CEC/mL) than in patients with reversible PAH and control subjects (median 3 CEC/mL in the 2 groups). In contrast, CPC numbers did not differ among patients with irreversible or reversible PAH and control subjects (median 84, 64, and 44 CPC/105 lymphocytes, respectively, in the 3 groups). Conclusions— Irreversible PAH in congenital heart disease is associated with endothelial damage and with increased circulating endothelial cell counts. The present study suggests that CECs could be a valuable tool to define therapeutic strategies in congenital heart disease patients with PAH.

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.

Pulmonary Embolectomy: A 20-Year Experience at One Center

Between 1968 and 1988, 96 consecutive patients with acute massive pulmonary embolism underwent pulmonary embolectomy under cardiopulmonary bypass. The operative mortality rate was 37.5%. We analyzed 12 clinical and hemodynamic variables by univariate and multivariate analyses to assess the predictive factors of postoperative outcome. Multivariate analysis disclosed that cardiac arrest and associated cardiopulmonary disease were independent predictors of operative death. Long-term follow-up (range, 2 to 144 months; mean, 56 months) information was available for 55 of the 60 discharged patients: 6 had died, and 5 complained of persistent mild or severe exertional dyspnea (New York Heart Association class II). These results help assess the preoperative risk in patients undergoing pulmonary embolectomy. They also show that, in the few patients who do not benefit from optimal medical therapy, pulmonary embolectomy remains an acceptable procedure in view of the long-term results.

Sensitivity and Specificity of Prenatal Features of Physiological Shunts to Predict Neonatal Clinical Status in Transposition of the Great Arteries

Background—Although prenatal diagnosis of transposition of the great arteries (TGA) reduces neonatal mortality, the preoperative course can be complicated in infants with a restrictive foramen ovale (FO) or a ductus arteriosus (DA) constriction. We sought to determine the specificity and sensitivity of prenatal features of physiological shunts in predicting postnatal clinical status in prenatally diagnosed TGA in babies delivered in a tertiary care center providing all facilities for neonatal urgent care. Methods and Results—The outcomes of 130 fetuses with TGA were reviewed over a period of 5.5 years. Restriction of the FO and/or constriction of the DA could be analyzed in 119/130 fetuses at 36±2.7 weeks of gestation. Twenty-four out of 119 had at least 1 abnormal shunt (23 FO, 5 DA, and 4 both). Thirteen of 130 neonates had profound hypoxemia (PaO2<25 mm Hg) and metabolic acidosis (pH <7.15) in the first 30 minutes and required immediate balloon atrioseptostomy. Two who had abnormal FO and DA died despite aggressive resuscitation. The specificity and sensitivity of the fetal echo in predicting neonatal emergency were 84% and 54%, respectively. The specificity and sensitivity of a combination of restrictive FO and DA constriction were 100% and 31%, respectively. Conclusions—Restriction of the FO and/or of the DA has a high specificity to predict the need for emergency neonatal care in fetuses with TGA, but the sensitivity is too low to detect all high-risk fetuses. Exceptional procedures should be considered for fetuses that have a combination of restrictive FO and DA constriction.

Modified Blalock-Taussig shunts: results in infants less than 3 months of age.

The optimal procedure for shunting palliation in cyanotic infants remains to be determined. Sixty-two infants less than 3 months of age underwent 63 modified Blalock-Taussig shunts. Their age range at operation was 1 to 84 days (mean, 16 +/- 20 days). Shunts were constructed using 5-mm polytetrafluorethylene tubes in 20 patients and 4-mm polytetrafluoroethylene grafts in 43 patients. There were 13 early deaths (21%; CL, 15% to 27%) of which three deaths (5%; confidence limits, 2% to 9%) were shunt related. The survivors were followed up from 6 to 53 months (mean, 29 +/- 12.5 months). Shunt failure (occlusion, inadequate palliation) occurred in 27 patients. The overall probability rate of adequate shunt function was 58% +/- 8% at 2 years. Univariate and multivariate analyses showed that the size of the graft was a risk factor of shunt failure. Severe distortion of the pulmonary arterial branch was noted in 12 patients. The inferences are: (1) modified Blalock-Taussig shunts provide satisfactory early palliation but late shunt failure is frequent; (2) similar results should be obtained with other shunting procedures; and (3) the optimal procedure should be selected for each cyanotic infant on an individual basis.

Potts Shunt in Children With Idiopathic Pulmonary Arterial Hypertension: Long-Term Results

BACKGROUND Idiopathic pulmonary arterial hypertension (IPAH) remains a progressive fatal disease. Palliative Potts shunt has been proposed in children displaying suprasystemic IPAH. METHODS A retrospective multicenter study was performed to evaluate Potts shunt in pediatric IPAH. RESULTS Between 2003 and 2010, 8 children with suprasystemic IPAH and in World Health Organization functional class IV despite medical pulmonary arterial hypertension therapy underwent Potts shunt. Age at IPAH diagnosis ranged from 4 to 180 months (median age, 64 months). Surgical procedure was performed in a mean delay of 41.9±54.3 months (range, 4 to 167 months; median delay, 20 months) after IPAH diagnosis. Mean size of the Potts shunt was 9.25±3.30 mm. Two patients, whose medical pulmonary arterial hypertension therapy had been interrupted just after surgery, died at postoperative days 11 and 13 of acute pulmonary hypertensive crisis. After a mean follow-up of 63.7±16.1 months, the 6 children who were discharged from the hospital were alive. Functional status improved markedly in the 6 survivors, with a World Health Organization functional class I (n=4) or II (n=2) at last follow-up, consistent with significant improvement of 6-minute-walk distance (302±95 m [51%±20% of theoretical values] versus 456±91 m [68%±10% of theoretical values]; p=0.038) and decrease of brain natriuretic peptide levels (608±109 pg/mL versus 76±45 pg/mL; p=0.035). No Potts shunt was found to be restrictive at last echocardiography. CONCLUSIONS Palliative Potts shunt constitutes a new alternative to lung transplantation in severely ill children with suprasystemic IPAH, carrying a prolonged survival and persistent improvement in functional capacities.

Safety and Accuracy of 64-Slice Computed Tomography Coronary Angiography in Children After the Arterial Switch Operation for Transposition of the Great Arteries

OBJECTIVES We investigated the accuracy of 64-slice computed tomography (CT) angiography, as compared to invasive angiography, to evaluate reimplanted coronary arteries in children after arterial switch operation (ASO) for transposition of the great arteries (TGA). BACKGROUND Assessment of the integrity of reimplanted coronary arteries is crucial for long-term outcome after ASO for TGA. Noninvasive tests have limited accuracy for detecting significant coronary lesions, and invasive coronary angiography is usually required in this setting. METHODS One hundred thirty consecutive children, after ASO for TGA (age 5.6 +/- 1.1 years), underwent conventional invasive coronary angiography and coronary CT angiography using a 64-slice scanner. The ability of CT to detect significant coronary stenoses (>30% diameter reduction) of the coronary ostia and proximal segments, and other abnormalities of the coronary arteries was analyzed by blinded comparison to the invasive coronary angiogram. RESULTS The CT was fully evaluable in 126 of 130 patients (97%), allowing assessment of ostia and proximal segments of all coronary arteries. The CT correctly detected all 12 patients (9.2%) in whom invasive coronary angiography had identified significant coronary lesions, with a sensitivity, specificity, and negative predictive value of 100%. In addition, CT showed nonsignificant coronary lesions (<30% luminal narrowing) in 6 patients and allowed determination of the underlying reasons for coronary luminal narrowing, such as stretching or compression of the re-implanted coronary arteries caused by their anatomic relationship to the adjacent great vessels. CONCLUSIONS 64-slice CT coronary angiography performs as well as invasive angiography for detecting significant coronary lesions in the majority of children who have undergone the arterial switch procedure for TGA. CT also provides information on the underlying mechanism of coronary luminal narrowing.