Intravenous sildenafil and inhaled nitric oxide: a randomised trial in infants after cardiac surgery.
OBJECTIVE
To investigate the acute effects of intravenous sildenafil on haemodynamics and oxygenation, and its interaction with inhaled nitric oxide (iNO) in infants at risk of pulmonary hypertension early after cardiac surgery.


METHODS
Prospective, randomised trial.


METHODS
Paediatric intensive care unit of a children's hospital.


METHODS
Sixteen ventilated infants early after closure of ventricular or atrioventricular septal defects, were randomly assigned to one of two groups. The study was completed in 15 infants.


METHODS
Studies were commenced within 7 h of separation from bypass. Seven infants received iNO (20 ppm) first, with the addition of intravenous sildenafil (0.35 mg/kg over 20 min) after 20 min. Eight infants received sildenafil first, iNO was added after 20 min. Vascular pressures, cardiac output and a blood gas were recorded at 0, 20 and 40 min.


RESULTS
In infants receiving iNO first, iNO lowered the pulmonary vascular resistance index (PVRI) from 3.45 to 2.95 units (p=0.01); sildenafil further reduced PVRI to 2.45 units p<0.05). In those receiving sildenafil first, PVRI was reduced from 2.84 to 2.35 units (p<0.05) with sildenafil, and fell to 2.15 units (p=0.01) with the addition of iNO. In both groups, sildenafil reduced the systemic blood pressure and systemic vascular resistance (p<0.01) and worsened arterial oxygenation and the alveolar-arterial gradient (p<0.05).


CONCLUSIONS
Intravenous sildenafil augmented the pulmonary vasodilator effects of iNO in infants early after cardiac surgery. However, sildenafil produced systemic hypotension and impaired oxygenation, which was not improved by iNO.
Stocker
Christian
C
Department of Intensive Care, Royal Children's Hospital, Flemington Road, 3052, Parkville, Victoria, Australia.
Penny
Daniel J
DJ
Brizard
Christian P
CP
Cochrane
Andrew D
AD
Soto
Rodrigo
R
Shekerdemian
Lara S
LS
D000280:Administration, Inhalation; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006344:Heart Septal Defects, Atrial / Q000601:surgery; D006345:Heart Septal Defects, Ventricular / Q000601:surgery; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control*; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects; D011687:Purines; D012307:Risk Factors; D000068677:Sildenafil Citrate; D013450:Sulfones; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D001993:Bronchodilator Agents; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate