COMPARISON OF THE EFFICACY OF SILDENAFIL ALONE VERSUS SILDENAFIL PLUS BOSENTAN IN NEWBORNS WITH PERSISTENT PULMONARY HYPERTENSION

Nazia Fatima, Sohail Arshad, Ahmad Iqbal Quddusi, Abdur Rehman, Aashee Nadeem, imran iqbal

Abstract


Background: Persistent pulmonary hypertension is a serious disease among new-borns. Inhaled nitric oxide is first line of therapy along with extracorporeal membrane oxygenation. Pulmonary vasodilators such as sildenafil, bosentan and milrinone are also used to treat persistent pulmonary hypertension especially in resource limited centres where inhaled nitric oxide is not available. The objective of this study was to compare the effect of sildenafil alone and sildenafil with bosentan on severity of tricuspid regurgitation and duration of hospitalization in new-borns with persistent pulmonary hypertension. Methods: This was single blinded clinical trial conducted at The Children’s Hospital & the Institute of Child Health, Multan, Pakistan, from July 2016 to December 2016. New-borns with pulmonary hypertension were admitted and divided into two groups. Group A was treated with sildenafil (2mg per kg per dose three times a day) and group B with both sildenafil (2 mg per kg per dose three times a day) and bosentan (1 mg per kg per dose twice a day). Results: There were 50 new-borns in each group.  The mean age, sex distribution and baseline TR measurement (mmHg) at the time of admission was similar in both the groups. Measurement of TR (mmHg) after 72 hours admission was significantly less in Group B as compared to group A (11±4.62 versus 23±4.78), p value<0.0001. The mean duration of hospital stays (days) was 10.12±5.20 in group A and 7.56±3.77 in group B (p-value <0.0001). There was no mortality in any group and no case of hypotension in both groups. Conclusion: The combined use of sildenafil and bosentan is more effective than sildenafil alone for control of pulmonary hypertension in resource limited centres.

Keywords: Persistent pulmonary hypertension; sildenafil; bosentan; echocardiography

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REFERENCES

Kinsela J, Parker TA. Respiratory failure in the newborn. In: Gleason C A, Devaskar SU, editors. Avery’s diseases of the newborn. 9th ed. Philadelphia: Elsevier; 2012. p. 647–57.

Shah PS, Ohlsson A. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev. 2007;(3) .doi: 10.1002/14651858.CD005494.pub2

MacLean MR. Endothelin-1 and serotonin: mediators of primary and secondary pulmonary hypertension? J Lab Clin Me. 1999;134:105–114.

Abman SH. New developments in the pathogenesis and treatment of neonatal pulmonary hypertension.PediatrPulmonol Suppl. 1999;18:201–04. doi: 10.1002/(SICI)1099-0496(1999)27:18+<201::AID-PPUL65>3.0.CO;2-F

Dakshinamurti S. Pathophysiologic mechanisms of persistent pulmonary hypertension of the newborn.PediatrPulmonolSuppl. 2005; 39(6):492–503doi:

1002/ppul.20201

Gersony WM, Duc GV, Sinclair JC. PFC syndrome.Circulation. 1969; 40(Suppl 3):87.

Boo NY, Rohana J, Yong SC, Bilkis AZ, Yong-Junina F. Inhaled nitric oxide and intravenous magnesium sulphate for the treatment of persistent pulmonary hypertension of the newborn. Singapore Med J. 2010;51(2):144–50. [PubMed]

Lakshminrushima S, Keszler M. Persistent pulmonary hypertension of the newborn. Neoreviews 2015;16:680-90

Konduri GG, Kim UO. Advances in the diagnosis and management of persistent pulmonary hypertension.PediatrClin North Am. 2009;56(3):579-600. doi: 10.1016/j.pcl.2009.04.004

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(4):1077–83. doi:10.1542/peds.2005-0523

Vargas-Origel A, Gomez-Rodriguez G, Aldana-Valenzuela C, Vela-Huerta MM, Alarcon-Santos SB, -Licona N. The use of sildenafil in persistent pulmonary hypertension of the newborn.Am J Perinatol.2010;27(3):225. doi:10.1055/s-0029-1239496

Mohamed WA, Ismail M. A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn.JPerinatol. 2012;32(8):608–13.doi: 10.1038/jp.2011.157

Nakwan, N., Choksuchat, D., Saksawad, R., Thammachote, P. and Nakwan, N. Successful treatment of persistent pulmonary hypertension of the newborn with bosentan. ActaPaediatr 2009;98:1683–5. doi:10.1111/j.1651-2227.2009.01386.x

Steinhorn RH, Kusic-Pajic A, Cornelisse P, Fineman JR, Gehin M, Nowbakht P, et al. Bosentan as adjunctive therapy for persistent pulmonary hypertension of the newborn: results of the FUTURE-4 study. Circulation. 2014; 130(Suppl 2):A13503. doi:10.1016/j.jpeds.2016.06.078

Hsieh TK, Su BH, Chen AC, Lin TW, Tsai CH, Lin HC.Risk factors of meconium aspiration syndrome developing into persistent pulmonary hypertension of newborn.ActaPaediatr Taiwan. 2004 45(4):203-7. PMID:156243651. Kinsela J, Parker TA. Respiratory failure in the newborn. In: Gleason CA, Devaskar SU, editors. PS Avery’s diseases of the newborn. 9th ed. Philadelphia: Elsevier, 2012; p.647–57.

Shah PS, Ohlsson A. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev 2007;(3):CD5494.

Abman SH. New developments in the pathogenesis and treatment of neonatal pulmonary hypertension. Pediatr Pulmonol Suppl 1999;18:201–4.

MacLean MR. Endothelin-1 and serotonin: mediators of primary and secondary pulmonary hypertension? J Lab Clin Med 1999;134(2):105–14.

Hsieh TK, Su BH, Chen AC, Lin TW, Tsai CH, Lin HC. Risk factors of meconium aspiration syndrome developing into persistent pulmonary hypertension of newborn. Acta Paediatr Taiwan 2004;45(4):203–7.

Dakshinamurti S. Pathophysiologic mechanisms of persistent pulmonary hypertension of the newborn. Pediatr Pulmonol Suppl 2005;39(6):492–503.

Gersony WM, Duc GV, Sinclair JC. PFC syndrome. Circulation 1969;40(Suppl 3):87.

Boo NY, Rohana J, Yong SC, Bilkis AZ, Yong-Junina F. Inhaled nitric oxide and intravenous magnesium sulphate for the treatment of persistent pulmonary hypertension of the newborn. Singapore Med J 2010;51(2):144–50.

Lakshminrushima S, Keszler M. Persistent pulmonary hypertension of the newborn. Neoreviews 2015;16(12):680–90.

Konduri GG, Kim UO. Advances in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatr Clin North Am 2009;56(3):579–600.

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(4):1077–83.

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(3):225–30.

Mohamed WA, Ismail M. A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn. J Perinatol 2012;32(8):608–13.

Prithviraj D, Reddy B, Abhijit, Deepthi, Reddy R. Oral Sildenafil in Persistent Pulmonary Hypertension of the Newborn in Invasive and Non-invasive Ventilated Babies-its Effect on Oxygenation Indices. Int J Sci Stud 2016;4(2):203-209

Uslu S, Kumtepe S, Bulbul A, Comert S, Bolat F, Nuhoglu A. A Comparison of Magnesium Sulphate and Sildenafil in the Treatment of the Newborns with Persistent Pulmonary Hypertension: A Randomized Controlled Trial. J Trop Pediatr 2011;57(4):245–50.

Engelbrecht AL. Sildenafil in the management of neonates with PPHN: A rural regional hospital experience. South Afr J Child Health 2008;2(4):166–9.

Herrera TR, Concha GP, Holberto CJ, Loera GR, Rodríguez BI. Oralsildenafil as an alternative treatment in the persistent pulmonary hypertension in newborns. Rev. MexPediatr. 2006;73:107–111.

Steinhorn RH, Kusic-Pajic A, Cornelisse P, Fineman JR, Gehin M, Nowbakht P, et al. Bosentan as adjunctive therapy for persistent pulmonary hypertension of the newborn: results of the FUTURE-4 study. Circulation 2014;130(Suppl 2):A13503.

Nakwan N, Choksuchat D, Saksawad R, Thammachote P, Nakwan, N. Successful treatment of persistent pulmonary hypertension of the newborn with bosentan. Acta Paediatr 2009;98(10):1683–5.


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