Effects of escalating doses of sildenafil on hemodynamics and gas exchange in children with pulmonary hypertension and congenital cardiac defects.

OBJECTIVE: Sildenafil (Viagra, Pfizer) is being increasingly used to treat pulmonary hypertension in children. However, there are limited data available to suggest dosage regimens. The purpose of this study was to determine the effects of escalating doses of sildenafil on hemodynamics and gas exchange in children with pulmonary hypertension because of congenital cardiac defects. DESIGN: Prospective, observational study. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PARTICIPANTS: Ten children with pulmonary hypertension because of congenital cardiac defects who were in the intensive care unit and on nitric oxide after cardiac surgery. INTERVENTION: Patients received sildenafil every 4 hours via a gastric tube in incremental doses of 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, and 2.0 mg/kg along with nitric oxide during their stay in the intensive care unit until they were extubated. Hemodynamic and arterial blood gas measurements were taken before (baseline) and 60 minutes after the administration of sildenafil. MEASUREMENTS AND MAIN RESULTS: All doses of sildenafil caused significant reduction in pulmonary artery pressure with no significant effect on systemic arterial and central venous pressures. Arterial partial pressure of oxygen was decreased after a 2.0 mg/kg dose of sildenafil but not significantly. No significant differences were found among the 4 doses. CONCLUSION: For the treatment of pulmonary hypertension in children with congenital cardiac defects, a 0.5 mg/kg dose of sildenafil every 4 hours is therapeutically as effective as a 2.0 mg/kg dose every 4 hours. However, a large dose-ranging and pharmacokinetic study of sildenafil in children with pulmonary hypertension because of congenital cardiac defects is needed to validate the safety and efficacy of the dose-range and dosing interval suggested by this study.

Impact of stentless aortic valves on left ventricular function and hypertrophy: current best available evidence.

Past four decades have seen a gradual evolution in aortic valve replacement surgery. The ideal valve substitute should combine central flow, low transvalvular gradient, low thrombogenicity, durability, easy availability, resistance to infection, freedom from anticoagulation, and easy implantability. Although there are several types of valves available to replace the diseased aortic valve-autograft, allograft, xenograft, mechanical, and bioprosthetic valves-none is ideal. On one end of the spectrum is the pulmonary autograft, which comes closest to achieving these goals, but creates a double valve procedure for single valve disease, while on the other end are the mechanical valves and stented tissue valves, which allow easy "off the shelf" availability as well as easy implantability but are limited by the potential drawback of causing intrinsic obstruction to some extent because of the space occupied by the stent and sewing ring. Stentless xenograft aortic valves have been developed as a compromise between these ends of the valve spectrum. Stentless aortic valves have been reported to provide more physiologic hemodynamic behavior and cause more timely and thorough regression of ventricular hypertrophy. This review article attempts to evaluate current best available evidence from randomized controlled trials to assess the impact of stentless aortic valves on left ventricular function and hypertrophy.

Is sildenafil effective for treating pulmonary hypertension after pediatric heart surgery?

A best evidence topic in pediatric cardiac surgery was written according to a structured protocol. The question addressed was whether sildenafil was effective in treating postoperative pulmonary hypertension after pediatric heart surgery. Altogether 28 papers were found using the reported search, of which three represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that oral sildenafil may be useful in reducing pulmonary vascular resistance and can be considered for treatment of postoperative pulmonary hypertension after pediatric heart surgery. However, evidence from a large, multicenter, randomized controlled trial is needed to validate the safety and efficacy of sildenafil for use in postoperative pediatric cardiac surgical patients.

Current status of the Contegra conduit for pediatric right ventricular outflow tract reconstruction.

Reconstruction of the right ventricular outflow tract (RVOT) is needed in a wide variety of congenital heart diseases at the time of primary repair, or later for replacement of existing valves or conduits. Ideally, the conduit or valve needed for such reconstruction should be formed of autologous tissue that grows, resists infection, lasts for the life span of the patient, and is readily available in all sizes. Such a conduit is not available, though several alternatives have been used, none of which is without potential drawbacks. One alternative--the Contegra bovine jugular vein conduit (Medtronic, Inc., Minneapolis, MN, USA)--was introduced in 1999 and has gained widespread application, with increasing enthusiasm for its use. The Contegra conduit consists of a bovine jugular vein with an incorporated trileaflet valve. The conduit tissue is extremely pliable and offers optimal conditions for surgical handling. Moreover, the proximal tubular segment allows construction of the proximal anastomosis to the right ventricle, without the use of additional material. Increasingly, experience with the Contegra conduit is being published; hence, a literature search was conducted to evaluate available evidence on current use of the device in pediatric RVOT reconstruction.

Anomalous left coronary artery, ventricular septal defect, and double aortic arch.

Anomalous origin of the left coronary artery from the pulmonary artery generally occurs in isolation. We report an infant diagnosed with double aortic arch and ventricular septal defect who was found to have an anomalous origin of the left coronary artery from the pulmonary artery at surgery. Successful ventricular septal defect repair, division of the arch, and aortic reimplantation of the left coronary artery was performed. This article describes a combination of lesions previously not described, highlights the altered presentation when multiple lesions coexist, discusses the propensity to miss the anomalous coronary, and reviews the literature that demonstrates the consequences of overlooking this defect.

Ascending aortic origin of a branch pulmonary artery--surgical management and long-term outcome.

OBJECTIVE: Ascending aortic origin of a branch pulmonary artery (AOPA, hemitruncus arteriosus) is a rare congenital malformation. While there have been isolated case reports, larger series, relating to long-term outcomes following surgery are few. This article analyses the surgical results of a series of nine patients, over a period of 29 years. METHODS: Between 1974 and 2003, nine patients [neonates, 6; infants, 3; male, 5; female, 4] were operated on for AOPA. Median age at presentation was 14 days (range birth to 231 days). Six [corrected] patients (group 1) had associated simple lesions like patent ductus arteriosus or right aortic arch. Three patients (group 2) had complex lesions with right ventricular outflow tract obstruction. One patient (group 2) had DiGeorge syndrome. All patients except group 2 presented with congestive cardiac failure and, in addition one had pre-operative coronary ischemia. Diagnosis was established by angiocardiography in two patients and by echocardiography in seven [corrected] The median age at operation was 28 days (range 7-365). Follow-up period ranged from 7 months to 20.5 years (median 9 years). RESULTS: All nine patients had an anomalous right pulmonary artery (RPA) arising from the proximal ascending aorta, while the left branch was of right ventricular origin. All had evidence of pulmonary hypertension or elevated right ventricular pressure pre-operatively. There was no operative mortality. Of eight patients who had direct anastomosis of the RPA to the main pulmonary artery, one required patch enlargement and another required stenting of an anastomotic stenosis. One patient had a RV-RPA conduit, which required replacement 8, 13, and 14 years later. At follow-up, all patients were alive. All patients in group 1 had normal haemodynamic function and were in NYHA class I. In group 2, all were in NYHA class II with evidence of right ventricular hypertrophy. Four patients had post-operative ventilation-perfusion scans which showed satisfactory perfusion to both lungs. CONCLUSIONS: Early surgery is indicated in this lesion and is compatible with good long-term outlook. Surgical repair should not be deferred for corrective procedures of associated cardiac anomalies.

Duroflo II heparin bonding does not attenuate cytokine release or improve pulmonary function.

BACKGROUND: Comparison of the cytokine generation and leukocyte activation properties of Duroflo II heparin bonded bypass circuit (Baxter Healthcare Corp, Compton, UK) and the conventional cardiopulmonary bypass circuit. Attempt to correlate these to pulmonary dysfunction postoperatively. METHODS: Forty patients undergoing elective, isolated coronary artery bypass grafting were randomly allocated to have either plain extracorporeal circuits (group C) or heparin bonded extracorporeal circuits (group H). Full systemic heparinization was used in all patients. The inflammatory response was assessed by measuring plasma levels of interleukin-6, interleukin-8, interleukin-10, and polymorphonuclear elastase. Gas exchange was assessed by measuring the PaO2/FIO2 ratio. RESULTS: Significant impairment of oxygenation was seen in both groups with the lowest values at the end of the operation before a gradual return to normal during the next 6 hours. There were no differences between the groups in gas exchange or times to extubation. There were significant elevations in all the cytokines, with interleukin-6 levels peaking at 4 hours in group H and 24 hours in group C, before starting to return to normal at 48 hours. The patterns of interleukin-8 and interleukin-10 rise were identical in the two groups. Polymorphonuclear elastase reached a peak at the end of the operation in group H and remained elevated up to 24 hours, whereas levels continued to rise in group C up to 4 hours. There were no significant differences in levels between groups at any time. There were no differences between the groups in blood loss or blood product usage. CONCLUSIONS: Cardiopulmonary bypass induces a systemic inflammatory response with release of cytokines and activation of leukocytes. This correlates with the severe deterioration in pulmonary gas exchange from preoperative levels up to 6 hours postoperatively (p < 0.05). In the presence of systemic heparinization, Duroflo II heparin bondingtf the circuits has minor effects on the pattern of evolution of this inflammatory response.