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Sildenafil exposure and hemodynamic effect after Fontan surgery.

Publication ,  Journal Article
Tunks, RD; Barker, PCA; Benjamin, DK; Cohen-Wolkowiez, M; Fleming, GA; Laughon, M; Li, JS; Hill, KD
Published in: Pediatr Crit Care Med
January 2014

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.

Duke Scholars

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Published In

Pediatr Crit Care Med

DOI

ISSN

1529-7535

Publication Date

January 2014

Volume

15

Issue

1

Start / End Page

28 / 34

Location

United States

Related Subject Headings

  • Vascular Resistance
  • Sulfones
  • Stroke Volume
  • Sildenafil Citrate
  • Purines
  • Pulmonary Artery
  • Prospective Studies
  • Postoperative Care
  • Piperazines
  • Phosphodiesterase 5 Inhibitors
 

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Tunks, R. D., Barker, P. C. A., Benjamin, D. K., Cohen-Wolkowiez, M., Fleming, G. A., Laughon, M., … Hill, K. D. (2014). Sildenafil exposure and hemodynamic effect after Fontan surgery. Pediatr Crit Care Med, 15(1), 28–34. https://doi.org/10.1097/PCC.0000000000000007
Tunks, Robert D., Piers C. A. Barker, Daniel K. Benjamin, Michael Cohen-Wolkowiez, Gregory A. Fleming, Matthew Laughon, Jennifer S. Li, and Kevin D. Hill. “Sildenafil exposure and hemodynamic effect after Fontan surgery.Pediatr Crit Care Med 15, no. 1 (January 2014): 28–34. https://doi.org/10.1097/PCC.0000000000000007.
Tunks RD, Barker PCA, Benjamin DK, Cohen-Wolkowiez M, Fleming GA, Laughon M, et al. Sildenafil exposure and hemodynamic effect after Fontan surgery. Pediatr Crit Care Med. 2014 Jan;15(1):28–34.
Tunks, Robert D., et al. “Sildenafil exposure and hemodynamic effect after Fontan surgery.Pediatr Crit Care Med, vol. 15, no. 1, Jan. 2014, pp. 28–34. Pubmed, doi:10.1097/PCC.0000000000000007.
Tunks RD, Barker PCA, Benjamin DK, Cohen-Wolkowiez M, Fleming GA, Laughon M, Li JS, Hill KD. Sildenafil exposure and hemodynamic effect after Fontan surgery. Pediatr Crit Care Med. 2014 Jan;15(1):28–34.

Published In

Pediatr Crit Care Med

DOI

ISSN

1529-7535

Publication Date

January 2014

Volume

15

Issue

1

Start / End Page

28 / 34

Location

United States

Related Subject Headings

  • Vascular Resistance
  • Sulfones
  • Stroke Volume
  • Sildenafil Citrate
  • Purines
  • Pulmonary Artery
  • Prospective Studies
  • Postoperative Care
  • Piperazines
  • Phosphodiesterase 5 Inhibitors