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Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery.

ABSTRACT: To determine sildenafil exposure and hemodynamic effect in children after stage II single-ventricle surgery.Prospective, dose escalation trial.Single-center, pediatric catheterization laboratory.Twelve children poststage II single-ventricle surgical palliation and undergoing elective cardiac catheterization: median age 1.9 years (range, 0.8, 4.0), weight 11?kg (8, 13), nine females, and 10 with a single right ventricle.Catheterization and echocardiography performed before and immediately after single-dose IV sildenafil (0.125, 0.25, 0.35, or 0.45?mg/kg over 20?min).Peak sildenafil and desmethyl sildenafil concentration, change in hemodynamic parameters measured by cardiac catheterization and echocardiography including indexed pulmonary vascular resistance, and myocardial performance.Maximum sildenafil concentrations ranged from 92 to 775?ng/mL and were above the in vitro threshold needed for 77% phosphodiesterase type 5 (PDE-5) inhibition in 80% of subjects and 90% inhibition in 80% of subjects with doses ?0.35?mg/kg. Sildenafil lowered pulmonary vascular resistance index in all 12 subjects (median pulmonary vascular resistance index 2.2 [range, 1.6, 7.9]; decreased to 1.7 [1.2, 5.4] WU × m; p < 0.01) with no dose-response effect. Sildenafil improved pulmonary blood flow (+8% [0, 20], p = 0.04) and saturations (+2% [0, 16], p = 0.04) in those with baseline pulmonary vascular resistance index ? 2 WU × m (n = 7). Change in saturations correlated inversely with change in pulmonary vascular resistance index (r = 0.74, p < 0.01). Sildenafil also lowered mean blood pressure (-12% [-20, +10]; p = 0.04). There was no change in cardiac index and no effect on myocardial performance. There were no adverse events.Sildenafil demonstrated nonlinear exposure with high interindividual variability but was well tolerated and effectively lowered pulmonary vascular resistance index in all subjects. Sildenafil did not acutely improve myocardial performance or increase cardiac index.

SUBMITTER: Hill KD

PROVIDER: S-EPMC3782306 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery.

Hill Kevin D KD 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

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20130701 6

<h4>Objectives</h4>To determine sildenafil exposure and hemodynamic effect in children after stage II single-ventricle surgery.<h4>Design</h4>Prospective, dose escalation trial.<h4>Setting</h4>Single-center, pediatric catheterization laboratory.<h4>Patients</h4>Twelve children poststage II single-ventricle surgical palliation and undergoing elective cardiac catheterization: median age 1.9 years (range, 0.8, 4.0), weight 11 kg (8, 13), nine females, and 10 with a single right ventricle.<h4>Interv ...[more]

PMID: 23823195

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Project description:Background The impact of neighborhood socioeconomic status (SES) on outcomes following first-stage palliation of single ventricle heart disease remains incompletely characterized. Methods and Results This was a single-center, retrospective review of consecutive patients who underwent the Norwood procedure from January 1, 1997 to November 11, 2017. Outcomes of interest included in-hospital (early) mortality or transplant, postoperative hospital length-of-stay, inpatient cost, and postdischarge (late) mortality or transplant. The primary exposure was neighborhood SES, assessed using a composite score derived from 6 US census-block group measures related to wealth, income, education, and occupation. Associations between SES and outcomes were assessed using logistic regression, generalized linear, or Cox proportional hazards models, adjusting for baseline patient-related risk factors. Of 478 patients, there were 62 (13.0%) early deaths or transplants. Among 416 transplant-free survivors at hospital discharge, median postoperative hospital length-of-stay and cost were 24 (interquartile range, 15-43) days and $295 000 (interquartile range, $193 000-$563 000), respectively. There were 97 (23.3%) late deaths or transplants. On multivariable analysis, patients in the lowest SES tertile had greater risk of early mortality or transplant (odds ratio [OR], 4.3 [95% CI, 2.0-9.4; P<0.001]), had longer hospitalizations (coefficient 0.4 [95% CI, 0.2-0.5; P<0.001]), incurred higher costs (coefficient 0.5 [95% CI, 0.3-0.7; P<0.001]), and had greater risk of late mortality or transplant (hazard ratio, 2.2 [95% CI, 1.3-3.7; P=0.004]), compared with those in the highest tertile. The risk of late mortality was partially attenuated with successful completion of home monitoring programs. Conclusions Lower neighborhood SES is associated with worse transplant-free survival following the Norwood operation. This risk persists throughout the first decade of life and may be mitigated with successful completion of interstage surveillance programs.

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Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery.

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Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery.

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