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http://dx.doi.org/10.5385/jksn.2011.18.1.124

Oral Sildenafil in Persistent Pulmonary Hypertension of the Newborn  

Son, Su-Bin (Department of Pediatrics, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine)
Kim, Kyung-Ah (Department of Pediatrics, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine)
Yun, So-Young (Department of Pediatrics, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine)
Ko, Sun-Young (Department of Pediatrics, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine)
Lee, Yeon-Kyung (Department of Pediatrics, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine)
Shin, Son-Moon (Department of Pediatrics, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine)
Publication Information
Neonatal Medicine / v.18, no.1, 2011 , pp. 124-129 More about this Journal
Abstract
Purpose: To evaluate the effect of oral sildenafil therapy in neonates with persistent pulmonary hypertension of the newborn (PPHN) Methods: We conducted a retrospective review of 32 neonates ${\geq}$35 weeks' gestation and fraction of inspired oxygen ($FiO_2$) 1.0 with PPHN. The first dose (0.5 mg/kg) of oral sildenafil was started and 1 mg/kg was given every 6 hour thereafter. Mean airway pressure (MAP), $FiO_2$, oxygenation index (OI), mean arterial blood pressure (MBP) were documented before and 6, 12, 24, and 48 hours after sildenafil. For adverse effects, gastrointestinal symptoms, brain ultrasound, funduscopy and auditory brainstem response results were evaluated. Results: The underlying diseases of PPHN (n=32) were meconium aspiration syndrome (n=9), respiratory distress syndrome (n=8), pneumonia (n=3), and idiopathic (n=12). Thirty-one neonates survived; 3 neonates were transferred for inhaled nitric oxide (iNO) and all of them survived. In 28 infants, $FiO_2$ and OI improved significantly by 6 hours and MAP improved significantly by 48 hours after initiation of sildenafil. There were no clinically significant adverse effects of sildenafil. Conclusion: Sildenafil may be an effective and safe agent for near-term and term neonates with PPHN, providing significant improvement in oxygenation, and thus may be especially useful in the treatment of PPHN in hospitals without iNO.
Keywords
Sildenafil; Persistent pulmonary hypertension of the newborn;
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1 Shekerdemian LS, Ravn HB, Penny DJ. Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension. Am J Respir Crit Care Med 2002;165:1098-102.   DOI   ScienceOn
2 Erickson S, Reyes J, Bohn D, Adatia I. Sildenafil (Viagra) in childhood and neonatal pulmonary hypertension [abstract]. J Am Coll Cardiol 2002;39 Suppl:402a.
3 Kumar S. Indian doctor in protest after using Viagra to save "blue babies". BMJ 2002;325:181.   DOI
4 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;117:1077-83.   DOI   ScienceOn
5 Herrera TR, Concha GP, Holberto CJ, Loera GR, Rodríguez BI. Oral sildenafil as an alternative treatment in the persistent pulmonary hypertension in newborns. Rev Mex Pediatr 2006;73:107-11.
6 Namachivayam P, Theilen U, Butt WW, Cooper SM, Penny DJ, Shekerdemian LS. Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. Am J Respir Crit Care Med 2006;174:1042-7.   DOI   ScienceOn
7 Vargas-Origel A, Gomez-Rodriguez G, Aldana-Valenzuela C, Vela- Huerta MM, Alarcon-Santos SB, Amador-Licona N. The use of sildenafil in persistent pulmonary hypertension of the newborn. Am J Perinatol 2010;27:225-30.   DOI
8 Sola A, Baquero H. Oral sildenafil in neonatal medicine: "tested in adults also used in neonates". An Pediatr (Barc) 2007;66:167-76.   DOI   ScienceOn
9 Nahata MC, Morosco RS, Brady MT. Extemporaneous sildenafil citrate oral suspensions for the treatment of pulmonary hypertension in children. Am J Health Syst Pharm 2006;63:254-7.   DOI   ScienceOn
10 Leibovitch L, Matok I, Paret G. Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension. Drugs 2007;67:57-73.   DOI   ScienceOn
11 Young TE, Mangum OB. Neofax: a manual of drugs used in neonatal care. 23rd ed. Montvale: Thomson Reuters, 2010:198-9.
12 Filan PM, McDougall PN, Shekerdemian LS. Combination pharmacotherapy for severe neonatal pulmonary hypertension. J Paediatr Child Health 2006;42:219-20.   DOI   ScienceOn
13 Steinhorn RH, Kinsella JP, Pierce C, Butrous G, Dilleen M, Oakes M, et al. Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension. J Pediatr 2009;155:841-7.e1.   DOI   ScienceOn
14 Atz AM, Adatia I, Wessel DL. Rebound pulmonary hypertension after inhalation of nitric oxide. Ann Thorac Surg 1996;62:1759-64.   DOI   ScienceOn
15 Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology 1999;91:307-10.   DOI   ScienceOn
16 Yu HJ, Sung SI, Kim JK, Seo HJ, Choi SH, Yoo HS, et al. Two cases of neonatal persistent pulmonary hypertension treated by venovenous extracorporeal membrane oxygenation (V-V ECMO). J Korean Soc Neonatol 2010;17:109-15.
17 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: comparison with inhaled nitric oxide. Circulation 2002;105:2398- 403.   DOI   ScienceOn
18 Lepore JJ, Maroo A, Pereira NL, Ginns LC, Dec GW, Zapol WM, et al. Effect of sildenafil on the acute pulmonary vasodilator response to inhaled nitric oxide in adults with primary pulmonary hypertension. Am J Cardiol 2002;90:677-80.   DOI   ScienceOn
19 Saygili A, Canter B, Iriz E, Kula S, Tunaoglu FS, Olguntürk R, et al. Use of sildenafil with inhaled nitric oxide in the management of severe pulmonary hypertension. J Cardiothorac Vasc Anesth 2004;18:775-6.   DOI
20 Preston IR, Klinger JR, Houtches J, Nelson D, Farber HW, Hill NS. Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension. Respir Med 2005;99:1501-10.   DOI   ScienceOn
21 Shekerdemian LS, Ravn HB, Penny DJ. Interaction between inhaled nitric oxide and intravenous sildenafil in a porcine model of meconium aspiration syndrome. Pediatr Res 2004;55:413-8.   DOI   ScienceOn
22 Wang YW, Lin HC, Yang YY, Hou MC, Lee SD. Sildenafil decreased pulmonary arterial pressure but may have exacerbated portal hypertension in a patient with cirrhosis and portopulmonary hypertension. J Gastroenterol 2006;41:593-7.   DOI   ScienceOn
23 Lemus-Varela ML, Sola A, Gomez-Meda BC, Zamora-Perez AL, Ramos-Ibarra ML, Batista-Gonzalez CM, et al. Oral sildenafil citrate lacks genotoxicity and cytotoxicity in a primate model: Callithrix jacchus. J Perinatol 2006;26:423-7.   DOI   ScienceOn
24 de Rosalmeida MC, Saraiva LD, da Graca JR, Ivo BB, da Nobrega MV, Gondim FA, et al. Sildenafil, a phosphodiesterase-5 inhibitor, delays gastric emptying and gastrointestinal transit of liquid in awake rats. Dig Dis Sci 2003;48:2064-8.   DOI   ScienceOn
25 Marsh CS, Marden B, Newsom R. Severe retinopathy of prematurity (ROP) in a premature baby treated with sildenafil acetate (Viagra) for pulmonary hypertension. Br J Ophthalmol 2004; 88:306-7.   DOI   ScienceOn
26 Gamboa D, Robbins D, Saba Z. Bleeding after circumcision in a newborn receiving sildenafil. Clin Pediatr (Phila) 2007;46:842-3.   DOI   ScienceOn
27 Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, et al. ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. J Am Coll Cardiol 1999;33:273-82.   DOI   ScienceOn
28 Mukherjee B, Shivakumar T. A case of sensorineural deafness following ingestion of sildenafil. J Laryngol Otol 2007;121:395-7.
29 Boden G, Bennett C. The management of persistent pulmonary hypertension of the newborn. Curr Paediatr 2004;14:290-7.   DOI   ScienceOn
30 Walsh MC, Stork EK. Persistent pulmonary hypertension of the newborn. Rational therapy based on pathophysiology. Clin Perinatol 2001;28:609-27.   DOI   ScienceOn
31 Kinsella JP, Abman SH. Clinical approach to inhaled nitric oxide therapy in the newborn with hypoxemia. J Pediatr 2000;136:717-26.
32 Lorch SA, Cnaan A, Barnhart K. Cost-effectiveness of inhaled nitric oxide for the management of persistent pulmonary hypertension of the newborn. Pediatrics 2004;114:417-26.   DOI   ScienceOn