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

Publication ,  Journal Article
Hill, KD; Tunks, RD; Barker, PCA; Benjamin, DK; Cohen-Wolkowiez, M; Fleming, GA; Laughon, M; Li, JS
Published in: Pediatr Crit Care Med
July 2013

OBJECTIVES: To determine sildenafil exposure and hemodynamic effect in children after stage II single-ventricle surgery. DESIGN: Prospective, dose escalation trial. SETTING: Single-center, pediatric catheterization laboratory. PATIENTS: 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. INTERVENTIONS: 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). MEASUREMENTS: Peak sildenafil and desmethyl sildenafil concentration, change in hemodynamic parameters measured by cardiac catheterization and echocardiography including indexed pulmonary vascular resistance, and myocardial performance. MAIN RESULTS: 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. CONCLUSIONS: 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.

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Published In

Pediatr Crit Care Med

DOI

ISSN

1529-7535

Publication Date

July 2013

Volume

14

Issue

6

Start / End Page

593 / 600

Location

United States

Related Subject Headings

  • Vascular Resistance
  • Ultrasonography
  • Treatment Outcome
  • Sulfones
  • Sildenafil Citrate
  • Purines
  • Prospective Studies
  • Piperazines
  • Phosphodiesterase 5 Inhibitors
  • Pediatrics
 

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Hill, K. D., Tunks, R. D., Barker, P. C. A., Benjamin, D. K., Cohen-Wolkowiez, M., Fleming, G. A., … Li, J. S. (2013). Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery. Pediatr Crit Care Med, 14(6), 593–600. https://doi.org/10.1097/PCC.0b013e31828aa5ee
Hill, Kevin D., Robert D. Tunks, Piers C. A. Barker, Daniel K. Benjamin, Michael Cohen-Wolkowiez, Gregory A. Fleming, Matthew Laughon, and Jennifer S. Li. “Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery.Pediatr Crit Care Med 14, no. 6 (July 2013): 593–600. https://doi.org/10.1097/PCC.0b013e31828aa5ee.
Hill KD, Tunks RD, Barker PCA, Benjamin DK, Cohen-Wolkowiez M, Fleming GA, et al. Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery. Pediatr Crit Care Med. 2013 Jul;14(6):593–600.
Hill, Kevin D., et al. “Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery.Pediatr Crit Care Med, vol. 14, no. 6, July 2013, pp. 593–600. Pubmed, doi:10.1097/PCC.0b013e31828aa5ee.
Hill KD, Tunks RD, Barker PCA, Benjamin DK, Cohen-Wolkowiez M, Fleming GA, Laughon M, Li JS. Sildenafil exposure and hemodynamic effect after stage II single-ventricle surgery. Pediatr Crit Care Med. 2013 Jul;14(6):593–600.

Published In

Pediatr Crit Care Med

DOI

ISSN

1529-7535

Publication Date

July 2013

Volume

14

Issue

6

Start / End Page

593 / 600

Location

United States

Related Subject Headings

  • Vascular Resistance
  • Ultrasonography
  • Treatment Outcome
  • Sulfones
  • Sildenafil Citrate
  • Purines
  • Prospective Studies
  • Piperazines
  • Phosphodiesterase 5 Inhibitors
  • Pediatrics