Published ahead of print on August 17, 2006, doi:10.1164/rccm.200605-694OC Am. J. Respir. Crit. Care Med., Volume 174, Number 9, November 2006, 1042-1047 A more recent version of this article appeared on November 1, 2006
Submitted on May 23, 2006 Sildenafil Prevents Rebound Pulmonary Hypertension After Withdrawal of Nitric Oxide in ChildrenPoongundran Namachivayam1,1 Department of Intensive Care, The Royal Children's Hospital, Melbourne, Australia, 2 Department of Intensive Care, The Royal Children's Hospital, Melbourne, Australia; The Department of Paediatrics, University of Melbourne, Melbourne, Australia, 3 The Murdoch Children's Research Institute, Melbourne, Australia; Department of Cardiology, The Royal Children's Hospital, Melbourne, Australia, 4 Department of Intensive Care, The Royal Children's Hospital, Melbourne, Australia; The Murdoch Children's Research Institute, Melbourne, Australia * To whom correspondence should be addressed. E-mail: lara.shekerdemian{at}rch.org.au.
Rationale: Rebound pulmonary hypertension (PHT) can complicate the weaning of nitric oxide (NO), and is in part related to transient depletion of intrinsic cyclic-GMP. Rebound is characterised by increased pulmonary artery (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. Objectives: 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 NO. Methods: Thirty ventilated infants and children, receiving Key words: Rebound, Pulmonary Hypertension, Sildenafil, Nitric Oxide
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10ppm inhaled NO, were randomized to receive 0.4mg/kg of sildenafil, or placebo, 1 hour before discontinuing NO. 29 patients completed the study.
Measurements: PA pressures, and blood gases were measured before the study drug, and one, and 4 hours after stopping NO. Main Results: Rebound occurred in 10/14 placebo patients, and 0/15 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) hrs for placebo patients and 28.2 (15.7,54.6) hrs for sildenafil patients (P=0.024).
Conclusion: 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.
