Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children.
BACKGROUND
Rebound pulmonary hypertension (PHT) can complicate the weaning of nitric oxide (NO), and is in part related to transient depletion of intrinsic cyclic guanosine monophosphate. Rebound is characterized by increased pulmonary arterial (PA) pressure, cardiopulmonary instability, and in some cases, the need to continue NO beyond the intended period of use. There is anecdotal evidence that sildenafil, a phosphodiesterase-5 inhibitor, may prevent recurrence of rebound.


OBJECTIVE
We investigated the role of sildenafil in preventing rebound (an increase in PA pressure of 20% or greater, or failure to discontinue NO) in patients in whom previous attempts had not been made to wean from NO.


METHODS
Thirty ventilated infants and children, receiving 10 ppm or greater inhaled NO, were randomized to receive 0.4 mg/kg of sildenafil, or placebo, 1 h before discontinuing NO. Twenty-nine patients completed the study.


METHODS
PA pressures and blood gases were measured before the study drug, and 1 and 4 h after stopping NO.


RESULTS
Rebound occurred in 10 of 14 placebo patients, and 0 of 15 sildenafil patients (p < 0.001). PA pressure increased by 25% (14-67) in placebo patients, and by 1%(-9-5) in sildenafil patients (p < 0.001). Four placebo patients could not be weaned from NO due to severe cardiovascular instability, whereas all sildenafil patients were weaned (p = 0.042). Duration of ventilation after study was 98.0 (47.0-223.5) h for placebo patients and 28.2 (15.7-54.6) h for sildenafil patients (p = 0.024).


CONCLUSIONS
A single dose of sildenafil prevented rebound after withdrawal of NO, and reduced the duration of mechanical ventilation. Prophylaxis with sildenafil should be considered when weaning patients from inhaled NO.
Namachivayam
Poongundran
P
Department of Intensive Care, The Royal Children's Hospital, Melbourne, Australia.
Theilen
Ulf
U
Butt
Warwick W
WW
Cooper
Sian M
SM
Penny
Daniel J
DJ
Shekerdemian
Lara S
LS
D000280:Administration, Inhalation; D001794:Blood Pressure; D004311:Double-Blind Method; D006330:Heart Defects, Congenital / Q000601:surgery; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D007223:Infant; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000503:physiopathology; D011687:Purines; D012121:Respiration, Artificial; D000068677:Sildenafil Citrate; D013450:Sulfones; D013997:Time Factors
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D000068677:Sildenafil Citrate