Published online January 2, 2007
PEDIATRICS Vol. 119 No. 1 January 2007, pp. 215-216 (doi:10.1542/10.1542/peds.2006-2567)

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LETTER TO THE EDITOR

Intratracheal Sildenafil in the Newborn With Pulmonary Hypertension

Miguel Martell, MD
Fernanda Blasina, MD
Fernando Silvera, MD
Salvador Tellechea, MD
Carolina Godoy, RN
Lucía Vaamonde
Luana Benenatti, MD
Walter Olivera, MD
Department of Neonatology
University Hospital
Montevideo 11600, Uruguay

To the Editor.—

The interesting work of Baquero et al¹ showed for the first time the beneficial effects of sildenafil in a series of newborn patients affected with severe persistent pulmonary hypertension (PPHN), improving survival and the oxygenation index after oral administration of 2 mg/kg per dose. Regarding this pathology, different therapeutic strategies have been used with the aim of improving blood oxygenation in the newborn severely affected by PPHN. The gold-standard therapy for this pathology is inhaled nitric oxide (iNO), although its high cost limits its widespread use in ICUs, especially in the developing world. Moreover, in countries where iNO is available, the need to send the patient to the iNO-equipped area and the fact that there are up to 60% of patients who do not improve their oxygenation index with iNO, depending of the series and the pathology involved,² make it necessary to search for cheaper therapies, assuring quick effectiveness and stabilization of the patient going through a very high-risk situation. One of the latest explored drugs is the phosphodiesterase inhibitor type 5, sildenafil. From different works it can be concluded that the time of maximum action and duration of the effect varies depending on the dose, the route of administration, and the model or clinical situation in which sildenafil has been used.^3–7 The most used route of administration has been oral, and the duration of the effect goes from 20 minutes to 6 hours afterward.^6,7 Many other vasodilators such as prostacyclin (PGI₂) or fentanyl have also been given in both intravenous and intratracheal forms to neonates with PPHN. Unfortunately, none of these agents are selective pulmonary vasodilators.

The selectivity of sildenafil in lung tissue makes it attractive as an anti-PPHN drug. In these sense, to obtain a quick response in pulmonary circulation and as an alternative procedure, our group has explored its effects in a model of PPHN induced by meconium aspiration in newborn piglets. Sildenafil (0.75 or 1.5 mg/kg per dose administered intratracheally) induced a rapid decrease in mean pulmonary arterial pressure (PAP), which occurred as soon as 2 minutes and lasted for 120 minutes. Both doses significantly decreased PAP compared with the pressure acquired at the point of more marked changes induced by meconium aspiration, and there was no significative difference between both doses. Moreover, the PAP after sildenafil administration was not significantly different compared with basal data, before the beginning of meconium instillation in the airway. However, in this model without inotropic support, there was also a significant decrease in mean systemic arterial pressure, a fact to take into account at the moment of managing a child with this therapeutic option. These data are summarized in Fig 1 (P < .01).

View larger version (12K): [in this window] [in a new window]   FIGURE 1 Systemic arterial pressure (SAP) and PAP after treatment with sildenafil (0.75 mg/kg per dose intratracheally) after meconium aspiration in 2-day-old piglets. a P < .01.

 
These results show that sildenafil offers the possibility of quick action applied intratracheally, similar to the utility of prostacyclin, representing a cheaper solution, of particular value in any place where there is no other effective therapy available until the oral administration could provide effect or another therapy is administered.

FOOTNOTES

Statements appearing here are those of the writers and do not represent the offcial position of the American Academy of Pediatrics or its Committees. Comments on any topic, including the contents of PEDIATRICS, are invited from all members of the profession; those accepted for publication will not be subject to major editorial revision but generally must be no more than 400 words in length. The editors reserve the right to publish replies and may solicit responses from authors and others.

Please see www.pediatrics.org for instructions on submitting letters.

REFERENCES

1. 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 :1077 –1083[Abstract/Free Full Text]
2. Kinsella JP, Abman SH. Clinical approach to inhaled nitric oxide therapy in the newborn with hypoxemia. J Pediatr. 2000;136 :717 –726[CrossRef][Web of Science][Medline]
3. Weimann J, Yllrich R, Hromi H, et al. Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension. Anesthesiology. 2000;92 :1702 –1712[CrossRef][Web of Science][Medline]
4. Shekerdemian L, Ravn HB, Penny KJ. Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension. Am J Respir Crit Care Med. 2002;165 :1098 –1102[Abstract/Free Full Text]
5. Ichinose F, Erana-Garcia J, Hromi H, et al. Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension. Crit Care Med. 2001;29 :1000 –1005[CrossRef][Web of Science][Medline]
6. Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension. Circulation. 2002;105 :2398 –2403[Abstract/Free Full Text]
7. Fernández González N, Rodríguez Fernández A, Jerez Rojas J, Parrondo Garrido SM, Martínez Mengual L. Oral sildenafil as a treatment of a newborn with persistent pulmonary hypertension [in Spanish]. An Pediatr (Barc). 2004;61 :562 –568[CrossRef][Medline]

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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics

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