Care of the newborn with persistent pulmonary hypertension

Atención al recién nacido con hipertensión pulmonar persistente

Persistent pulmonary hypertension syndrome of the newborn is a clinical condition that occurs in the presence of some risk factors, conditioned by persistent high pressure in the pulmonary artery that alters the transition from foetal to neonatal circulation.
Objective: To create a clinical practice guideline for managing these patients.
Methodology: The principles defined by the Colombian Ministry of Social Protection in its instructions to develop evidence-based clinical practice guidelines were followed.
Materials and methods: A search was made in the literature using Lilacs, Embase, PubMed, Mdconsult, Cochrane, Scopus, Clinicaltrials.gov databases and internet browsers, in English and Spanish.
Discussion: This syndrome occurs in 1.9 per 1000 of live births, and its incidence is estimated at 0.2% of all live-born infants. It is considered an important problem in our neonatal intensive care unit (NICU) as it contributes to morbidity and mortality in preterm or term infants. It is not a singular disease, and may be primary or secondary. An analysis is also presented of the conditions that account for the main reasons for admission to the NICU such as in-utero and perinatal asphyxia, infection, meconium aspiration syndrome, respiratory distress syndrome, and hypoplastic lungs.
Conclusions: Early diagnosis of the underlying cause is critical in order to initiate adequate treatment.

1. Steinhorn RH, Farrow KN. Pulmonary hypertension in the neonate. NeoReviews. 2007;8:e14–21.

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

3. Yoder BA, Kirsch EA, Barth WH Jr, Gordon MC. Changing obstetric practices associated with decreasing incidence of meconium aspiration syndrome. Obstet Gynecol. 2002;99(5, Part 1):7–9.

4. Ramachandrappa A, Jain L. Elective cesarean section: Its impact on neonatal respiratory outcome. Clin Perinatol. 2008;35:373–93.

5. Ministerio de la Protección Social. Guía metodológica para la elaboración de guías de práctica clínica basadas en la evidencia, de evaluaciones económicas y de evaluación del impacto de la implementación de las guías en el POS y en la unidad de pago por capitación del sistema general de seguridad social en salud colombiano. Bogotá: Ministerio de la Protección Social; 2009. p. 344.

6. Oñate-Ocaña L, Ochoa-Carrillo F. Sistema GRADE para clasificar nivel de evidencia y grado de las recomendaciones para la elaboración de guías de buena práctica clínica. Cir Ciruj. 2009;77:417–9.

7. Sociedad Colombiana de Neumología Pediátrica. Guías de práctica clínica. Hipertensión arterial pulmonar en niños [consultado 22 Ago 2014]. Disponible en: http://issuu.com/acnp/docs/hipertension-arterial 20120203 005511?e=3790791/2664823

8. Puthiyachirakkal M, Mhanna MJ. Pathophysiology, management, and outcome of persistent pulmonary hypertension of the newborn: A clinical review. Front Pediatr. 2013;1:23.

9. Cabral JE, Belik J. Persistent pulmonary hypertension of the newborn: Recent advances in pathophysiology and treatment. J Pediatr (Rio J). 2013;89:226–42.

10. Klinger JR. The nitric oxide/cGMP signaling pathway in pulmonary hypertension. Clin Chest Med. 2007;28:143–67.

11. Walsh-Sukys MC, Tyson JE, Wright LL, Bauer CR, Korones SB, Stevenson DK, et al. Persistent pulmonary hypertension of the newborn in the era before nitric oxide: Practice variation and outcomes. Pediatrics. 2000;105 1 Pt 1:14–20.

12. Niccolls C. Persistent pulmonary hypertension of the newborn. J Neonatal Nurs. 2012;18:63–71.

13. Abdel AH, Amin AS. Risk factors and outcomes of persistent pulmonary hypertension of the newborn in neonatal intensive care unit of al-Minya University Hospital in Egypt. J Clin Neonatol. 2013;2:78–82.

14. Van Loon RL, Roofthooft MT, Hillege HL, ten Harkel AD, van Osch-Gevers M, Delhaas T, et al. Pediatric pulmonary hypertension in the Netherlands: Epidemiology and characterization during the period 1991 to 2005. Circulation. 2011;124:1755–64.

15. Razzaq A, Quddusi AI, Nizami N. Risk factors and mortality among newborns with persistent pulmonary hypertension. Pak J Med Sci. 2013;29:1099.

16. Van Marter LJ, Hernandez-Diaz S, Werler MM, Louik C, Mitchell AA. Nonsteroidal antiinflammatory drugs in late pregnancy and persistent pulmonary hypertension of the newborn. Pediatrics. 2013;131:79–87.

17. Lapointe A, Barrington KJ. Pulmonary hypertension and the asphyxiated newborn. J Pediatr. 2011;158 2 Suppl: e19–24.

18. Bhutani VK, Chima R, Sivieri EM. Innovative neonatal ventilation and meconium aspiration syndrome. Indian J Pediatr. 2003;70:421–7.

19. Roofthooft M, Elema A, Bergman K, Berger R. Patient characteristics in persistent pulmonary hypertension of the newborn. Pulm Med. 2011:2011.

20. Baker CD, Abman SH, Mourani PM. Pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. Pediatr Allergy Immunol Pulmonol. 2014;27:8–16.

21. Advances in the diagnosis and management of persistent pulmonary hypertension of the newborn (PPHN). Pediatr Clin North Am. 2009;56:579–85.

22. Walsh MC, Fanaroff JM. Meconium stained fluid: Approach to the mother and the baby. Clin Perinatol. 2007;34:653–65.

23. Razzaq A, Iqbal Quddusi A, Nizami N. Risk factors and mortality among newborns with persistent pulmonary hypertension. Pak J Med Sci. 2013;29:1099–104.

24. Datin-Dorriere V, Rouzies S, Taupin P, Walter-Nicolet E, Benachi A, Sonigo P, et al. Prenatal prognosis in isolated congenital diaphragmatic hernia. Am J Obstet Gynecol. 2008;198, 80.e1-80.e5.

25. Marzo Castillejo M, Montaño Barrientos A. El sistema GRADE para la toma de decisiones clínicas y la elaboración de recomendaciones y guías de práctica clínica. Aten Primaria. 2007;39:457–60.

26. Turan S, Turan OM, Salim M, Berg C, Gembruch U, Harman CR, et al. Cardiovascular transition to extrauterine life in growth-restricted neonates: Relationship with prenatal Doppler findings. Fetal Diagn Ther. 2012;33:103–9.

27. Kadivar M, Kiani A, Kocharian A, Shabanian R, Nasehi L, Ghajarzadeh M. Echocardiography and management of sick neonates in the intensive care unit. Congenit Heart Dis. 2008;3:325–9.

28. Lawson S. Persistent pulmonary hypertension of the newborn. 2008. Revisado Mayo de 2014 [consultado 22 Ago 2014]. Disponible en: http://www.rcecs.com/MyCE/PDFDocs/course/V7041.pdf

29. Gasque G. Hipertensión pulmonar persistente del recién nacido. Rev Mex Pediatr. 2009;76:220–30.

30. Bassler D, Kreutzer K, McNamara P, Kirpalani H. Milrinone for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev. 2010:11.

31. Ko SY, Chang YS, Park WS. Clinical response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn. J Korean Med Sci. 1998;13:500–6.

32. Edwards MO, Kotecha SJ, Kotecha S. Respiratory distress of the term newborn infant. Paediatr Respir Rev. 2013;14: 29–36.

33. Ru-Jeng T, Tzong-Jin W. Persistent pulmonary hypertension of the newborn. J Formos Med Assoc. 2013;112:177–84.

34. Sutton J, Meyer R. Left ventricular function in persistent pulmonary hypertension of the newborn. Computer analysis of the echocardiogram. Br Heart J. 1983;50:540–9.

35. Bassler D, Kreutzer K, McNamara P, Kirpalani H. Milrinone for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev. 2010:11.

36. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev. 2006:CD000399.

37. Swarnam K, Soraisham AS, Sivanandan S. Advances in the management of meconium aspiration syndrome. Int J Pediatr. 2012;2012:359571.

38. Porta N, Steinhorn RH. Pulmonary vasodilator therapy in the NICU: Inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents. Clin Perinatol. 2012;39:149.

39. Konduri GG, Solimano A, Sokol GM, Singer J, Ehrenkranz RA, Singhal N, et al. A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure. Pediatrics. 2004;113:559–64. Epub 2004/03/03.

40. Turanlahti MI, Laitinen PO, Sarna SJ, Pesonen E. Nitric oxide, oxygen, and prostacyclin in children with pulmonary hypertension. Heart. 1998;79:169–74.

41. Nair J, Orie J, Lakshminrusimha S. Successful treatment of a neonate with idiopathic persistent pulmonary hypertension with inhaled nitric oxide via nasal cannula without mechanical ventilation. AJP Rep. 2012;2:29–32.

42. Hosono S, Ohno T, Kimoto H, Shimizu M, Takahashi S, Harada K. Inhaled nitric oxide therapy might reduce the need for hyperventilation therapy in infants with persistent pulmonary hypertension of the newborn. J Perinat Med. 2006;34:333–7.

43. Keszler M. High-frequency ventilation: Evidence-based practice and specific clinical indications. NeoReviews. 2006;7:e234–49.

44. Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, et al., Clinical Inhaled Nitric Oxide Research Group. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. N Engl J Med. 2000;342:469–74.

45. Recomendaciones sobre ventilación de alta frecuencia en el recién nacido.Pérez Rodríguez J, editor. Anales de Pediatría. Elsevier; 2002.

46. Ovalle O, Colmenares A. Ventilación de alta frecuencia. 2009. Revisado Mayo de 2014 [consultado 22 Ago 2014]. Disponible en: file:///C:/Users/Jossedela/Downloads/VENTILACION%20ALTA%20impreso%20junio%2009.pdf.

47. Turanlahti M, Laitinen P, Sarna S, Pesonen E. Nitric oxide, oxygen, and prostacyclin in children with pulmonary hypertension. Heart. 1998;79:169–74.

48. Bartlett RH, Gazzaniga AB, Huxtable RF, Schippers HC, O’Connor MJ, Jefferies MR. Extracorporeal circulation (ECMO) in neonatal respiratory failure. J Thorac Cardiovasc Surg. 1977;74:826–33. Epub 1977/12/01.

49. UK Collaborative ECMO Trail Group. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. Lancet. 1996;348:75–82.

50. Mugford M, Elbourne D, Field D. Extracorporeal membrane oxygenation for severe respiratory failure in newborn infants. Cochrane Database Syst Rev. 200

51. Van Berkel S, Binkhorst M, van Heijst AF, Wijnen MH, Liem KD. Adapted ECMO criteria for newborns with persistent pulmonary hypertension after inhaled nitric oxide and/or high-frequency oscillatory ventilation. Intensive Care Med. 2013;39:1113–20.

52. Shah PS, Ohlsson A. Sildenafil for pulmonary hypertension in neonates. Cochrane Database of Systematic Reviews. 2011;(Issue 8).

53. Paradisis M1, Jiang X, McLachlan AJ, Evans N, Kluckow M, Osborn D. Population pharmacokinetics and dosing regimen design of milrinone in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2007;92:F204–9.

54. Rieg AD, Suleiman S, Perez-Bouza A, Braunschweig T, Spillner JW, Schröder T, et al. Milrinone relaxes pulmonary veins in guinea pigs and humans. PLoS One. 2014;9.

55. 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.e1-847.e1.