Published online January 2, 2007
PEDIATRICS
Vol. 119
No. 1
January 2007, pp.
216
(doi:10.1542/peds.2006-2892)
Intratracheal Sildenafil in the Newborn With Pulmonary Hypertension: In Reply
Hernando Baquero, MD
Augusto Sola, MD
Division of Neonatology
MANA and Morristown Memorial Hospital
Morristown, NJ 07962
We thank Martell et al for their letter regarding our prospective randomized masked trial in human neonates on the effects of oral sildenafil.1 As they noted, Ichinose et al2 showed that nebulized (aerosolized) sildenafil was a selective pulmonary vasodilator with no effect on systemic arterial pressure that potentiated the effects of inhaled nitric oxide (iNO) just as when it was given orally or as an intravenous infusion.2 In that study, aerosols of 10 and 30 mg of sildenafil decreased pulmonary arterial pressure by 21% to 26%. When 10 mg of sildenafil were inhaled while simultaneously breathing 2 and 5 ppm of iNO, pulmonary arterial pressure decreased by 35% to 43%. Inhaled sildenafil did not impair systemic oxygenation, increase right-left intrapulmonary shunting, or impair the ability of iNO to reduce this shunting. Nebulized sildenafil also did not result in any apparent lung injury on microscopic examination.2 Very recently, nebulized sildenafil was proven effective in an in vitro model.3 The authors aimed to estimate pulmonary deposition of the drug from commonly used nebulizers using in vitro techniques and to create a mathematical model to predict inspired mass of aerosol. They found that the drug could be nebulized, but the expected pulmonary deposition varied depending on the nebulizer.3 This is an area of concern for incorporation of such treatment into clinical practice. In their letter, Martell et al described their findings in neonatal piglets but did not tell us how the sildenafil was prepared for intratracheal instillation or how it was instilled. We can only speculate on the pK (degree of dissociation or proton-binding affinity of this molecule), pH, dilution, solubility, particle size, and sterility of the solution prepared. All are potential inducers of severe airway and lung damage. As Martell et al mentioned, there are reports on intratracheal (nebulized) administration of prostacyclin and also of nitroprussiate and even tolazoline. The hope was to provide more selective effects and at the same time avoid systemic undesired consequences. However, these drugs were designed and approved for intravenous administration. It is worrisome to think of administering to human newborns a drug, such as sildenafil or any other, that was designed, studied, and approved for oral use only. Furthermore, the report of systemic hypotension induced by the intratracheal treatment is also intriguing and worrisome as a systemic undesired consequence. In our neonatal study and in many others in children and adults when the drug was administered orally, this known potential systemic undesired effect of sildenafil has been either nonexistent or minimal and infrequent. We agree with Martell et al about the need to find an effective and less costly option for the treatment of PPHN. Although there is still much to be learned about oral sildenafil use in neonates, at this time it seems that this alternative is much safer and efficacious than aiming for a potentially quicker action by administering sildenafil intratracheally. We believe that the research findings of this group reported in their letter should not be used at this time as support to justify instilling the oral preparation of sildenafil into the trachea of human neonates
REFERENCES
- Baquero H, Soliz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study.
Pediatrics. 2006;117
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- Ichinose F, Erana-Garcia J, Hromi H, et al. Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension.
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- Katz SL, Adatia I, Louca E, et al. Nebulized therapies for childhood pulmonary hypertension: an in vitro model.
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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
