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Sildenafil exposure and hemodynamic effect after Fontan surgery.


ABSTRACT: OBJECTIVE:Determine sildenafil exposure and hemodynamic effect in children after Fontan single-ventricle surgery. DESIGN:Prospective dose-escalation trial. SETTING:Single-center pediatric catheterization laboratory. PATIENTS:Nine children post Fontan single-ventricle surgical palliation and undergoing elective cardiac catheterization: median (range) age and weight, 5.2 years (2.5-9.4 yr) and 16.3?kg (9.5-28.1?kg). Five children (55%) were boys, and six of nine (67%) had a systemic right ventricle. INTERVENTIONS:Catheterization and echocardiography performed before and immediately after single-dose IV sildenafil (0.25, 0.35, or 0.45?mg/kg over 20?min). MEASUREMENTS AND MAIN RESULTS:Peak sildenafil and desmethyl sildenafil concentration, change in hemodynamic variables measured by cardiac catheterization and echocardiography. Maximum sildenafil concentrations ranged from 124 to 646?ng/mL and were above the in vitro threshold needed for 77% phosphodiesterase type-5 inhibition in eight of nine children and 90% inhibition in seven of seven children with doses more than or equal to 0.35?mg/kg. Sildenafil improved stroke volume (+22%, p = 0.05) and cardiac output (+10%, p = 0.01) with no significant change in heart rate in eight of nine children. Sildenafil also lowered systemic (-16%, p = 0.01) and pulmonary vascular resistance index in all nine children (median baseline pulmonary vascular resistance index 2.4 [range, 1.3-3.7]; decreased to 1.9 [0.8-2.7] Wood Units × m; p = 0.01) with no dose-response effect. Pulmonary arterial pressures decreased (-10%, p = 0.02) and pulmonary blood flow increased (9%, p = 0.02). There was no change in myocardial performance index and no adverse events. CONCLUSIONS:After Fontan surgery, sildenafil infusion acutely improves cardiopulmonary hemodynamics, increasing cardiac index. For the range of doses studied, exposure was within the acute safety range reported in adult subjects.

SUBMITTER: Tunks RD 

PROVIDER: S-EPMC3887448 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Sildenafil exposure and hemodynamic effect after Fontan surgery.

Tunks Robert D RD   Barker Piers C A PC   Benjamin Daniel K DK   Cohen-Wolkowiez Michael M   Fleming Gregory A GA   Laughon Matthew M   Li Jennifer S JS   Hill Kevin D KD  

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20140101 1


<h4>Objective</h4>Determine sildenafil exposure and hemodynamic effect in children after Fontan single-ventricle surgery.<h4>Design</h4>Prospective dose-escalation trial.<h4>Setting</h4>Single-center pediatric catheterization laboratory.<h4>Patients</h4>Nine children post Fontan single-ventricle surgical palliation and undergoing elective cardiac catheterization: median (range) age and weight, 5.2 years (2.5-9.4 yr) and 16.3 kg (9.5-28.1 kg). Five children (55%) were boys, and six of nine (67%)  ...[more]

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