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TREATMENT OF EXTREMELY PREMATURE NEWBORN INFANT WITH INO. CLINICAL CASE

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Research Paper

Medical Science

E-ISSN No : 2454-9916 | Volume : 5 | Issue : 11 | Nov 2019

TREATMENT OF EXTREMELY PREMATURE NEWBORN INFANT WITH INO. CLINICAL CASE 1

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Radulova P. | Slancheva B. | Marinov R. 1 2

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University Hospital of Obstetrics and Gynecology “ Maichin dom”, Sofia. National Heart Hospital, Sofia.

ABSTRACT Prolonged inhaled nitric oxide (iNO) from birth in preterm neonates with BPD improves endogenous surfactant function as well as lung growth, angiogenesis, and alveologenesis. As a result there is a reduction in the frequency of the “new” form of BPD in neonates under 28 weeks of gestation and birth weight under 1000 gr. Delivery of inhaled nitric oxide is a new method of prevention of chronic lung disease. According to a large number of randomized trials iNO in premature neonates reduces pulmonary morbidity and leads to a reduction of the mortality in this population of patients. This new therapy does not have serious side effects. We represent a clinical case of extremely premature newborn infant with BPD treated with iNO. KEYWORDS: bronchopulmonary dysplasia, pulmonary hypertension, extremely premature infant, inhaled nitric oxide. INTRODUCTION: Inhaled nitric oxide is a pulmonary vasodilator. The drug has been used since 1992 and from 1999 is the drug of choice for treatment of Persistent pulmonary hypertension in newborns /PPHN/[9,10,11,12]. At this moment its usage in premature infants is quite uncertain. In 2006 Ballard et al. published in New England Journal of Medicine that prolonged inhaled nitric oxide (iNO) from birth in preterm neonates with BPD improves endogenous surfactant function as well as lung growth, angiogenesis, and alveologenesis. As a result there is a reduction in the frequency of the “new” form of BPD in neonates under 28 weeks of gestation and birth weight under 1000 gr. Delivery of inhaled nitric oxide is a new method of prevention of chronic lung disease. According to a large number of randomized trials iNO in premature neonates reduces pulmonary morbidity and leads to a reduction of the mortality in this population of patients. This new therapy does not have serious side effects [2,19, 23]. MATERIALS AND METHODS: We represent a clinical case of extremely premature newborn infant with BPD treated with iNO. The patient was born from abnormal twin pregnancy, complicated with preeclampsia and preterm, premature rupture of membranes/PPROM/. The mother received corticosteroid prophylaxis before birth. The newborn infant was 25 weeks of gestation, male gender, with birth weight of 500gr. In the delivery room he received full CPR including endotracheal intubation and mechanical ventilation. After stabilization of the condition the baby was admitted to the NICU. In the NICU the general condition of the baby was poor with hypotension, inconstant systolic murmur. He was on mechanical ventilation/MV/ - SIPPV with high oxygen support, reaching 100%. The infant had clinical and X-ray data for neonatal respiratory distress syndrome /RDS/. /Fig.1/ Surfactant was given twice during the first day but the baby remained with unstable hemodynamics, metabolic acidosis and hypotension. The hypoxic pulmonary failure required MV with high inspiratory pressures and oxygen support. The infant was also treated with high frequency ventilation /HFOV/ for 48 hours. Two months after birth the baby was still on MV despite two unsuccessful attempts for extubation and giving him nCPAP. The patient had a lot of hypoxic spells, bronchospasms and X-ray data typical for Broncho-pulmonary dysplasia /BPD/. /Fig.2/ We consulted the infant with cardiologist and we did echocardiography, which showed: ASD second type with left to right shunt, no PDA; right ventricular dilatation 10 mm.; persistent high pulmonary pressure in diastole 28-32 mmHg. These results questioned the possible treatment with iNO. The brain ultrasound of the baby showed second grade intraventricular hemorrhage /IVH/. We started treatment with iNO for 12 days following the scheme: 3 days – 20 ppm, 5 days – 10 ppm, 3 days – 5 ppm, 1 day – 2 ppm. During the whole treatment coagulation status and methemoglobin levels were followed and they stayed at the normal range. During this period we noticed no side effects and no deterioration of the general condition of the child.

RESULTS AND DISCUSSIONS: His pulmonary function improved, the hypoxic spells disappeared and after 12 days of treatment the infant was extubated with no clinical signs of pulmonary failure and low oxygen needs not exceeding 30%. The control echocardiography showed reduction of the right ventricular diameter – 9 мм; TI 0-1 degree; pulmonary pressure 11 mmHg / before treatment 28-32 mmHg/. The X-ray showed data for milder degree of BPD. /Fig.3/. One month after the therapy the infant was discharged with weight 2300gr., the brain ultrasound showed no difference. The whole hospital stay of the patient was 120 days, on MV 87 days and 20 days with oxygen support. The follow up of the baby at four months corrected age showed no delay in neurological development, no retinopathy of prematurity, mild degree of BPD without oxygen needs, no cardiac problems. CONCLUSION: Two months after birth the patient was diagnosed to have late pulmonary hypertension /PH/, which is known to be more common with severe BPD (found in 29%). PH is still found in 10% of infants with none, mild or moderate BPD. Late PH is associated with prolong mechanical ventilation and oxygen support, as well as with worse respiratory outcome during infancy. These are the reasons why, it is probably appropriate to screen for PH all infants with BPD near term corrected age, even if they are clinically stable. Concerning treatment with nitric oxide in premature infants, we can emphasize that it is not recommended in the most critically ill extremely premature babies, because such treatment may be associated with brain injury or even increased mortality. Some trials show reduction of the frequency and severity of BPD, others do not prove such results [18, 22, 24, 25]. The most effective dose, start and duration of treatment, and the selection of infants most likely to benefit remain uncertain [1, 6, 14, 34]. That is why we need more clinical trials for the usage of nitric oxide in premature infants. REFERENCES: 1.

Ann R. Stark, M.D. Inhaled NO for preterm infants – Getting to Yes?, N Engl J Med 2006; 355:404-406

2.

Clark PL, Ekekezie II, Kaftan HA, Castor CA, Truog WE. Safety and efficacy of nitric oxide in chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2002;86:F41-F45

3.

Kang JL, Park W, Pack IS, et al. Inhaled nitric oxide attenuates acute lung injury via inhibition of nuclear factor-kappa B and inflammation. J Appl Physiol 2002;92:795801

4.

Haynes RL, Baud O, Kinney HC, Volpe JJ, Folkerth DR. Oxidative and nitrative injury in periventricular leukomalacia: a review. Brain Pathol 2005;15:225-233

5.

Laptook AR, O'Shea TM, Shankaran SS, Bhaskar B. Adverse neurodevelopmental outcomes among extremely low birth weight infants with a normal head ultrasound: prevalence and antecedents. Pediatrics 2005;115:673-680

6.

William ETruog. (2007) Inhaled nitric oxide for the prevention of bronchopulmonary dysplasia. Expert Opinion on Pharmacotherapy 8:10.1517/eop.2007.8.issue-10, 15051513

7.

Frances Lilian LanhellasGonçalves, Rebeca LopesFigueira, Ana Leda BertonciniSimões, Rodrigo MeloGallindo, AllanColeman, José LuisPeiró, LourençoSbragia. (2014) Effect of corticosteroids and lung ventilation in the VEGF

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and NO pathways in congenital diaphragmatic hernia in rats. Pediatric Surgery International 30, 1207-1215 8.

Pierre R.Provost, EricBoucher, YvesTremblay. (2013) Glucocorticoid metabolism in the developing lung: Adrenal-like synthesis pathway. The Journal of Steroid Biochemistry and Molecular Biology

9.

A Peliowski; Canadian Paediatric Society, Fetus and Newborn Committee Paediatr Child Health 2012;17(2):95-7 Inhaled nitric oxide use in newborns

(3): 315-330. 38. Jones C. Inhaled nitric oxide: are the safety issues being addressed? Intensive and Critical Care Nursing 1998; 14: 271-275.

10. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term.,Cochrane Database Syst, Rev 2006;(4):CD000399 11. Konduri GG, Solimano A, Sokol GM, et al; Neonatal Inhaled Nitric Oxide Study Group. 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. 12. Konduri GG, Vohr B, Robertson C, et al; Neonatal Inhaled Nitric Oxide Study Group. Early inhaled nitric oxide therapy for term and near-term newborn infants with hypoxic respiratory failure: Neurodevelopmental follow-up. J Pediatr 2007;150:235-40. 13. Van Meurs KP, Wright LL, Ehrenkranz RA, et al; Preemie Inhaled Nitric Oxide Study. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med 2005;353:13-22. 14.

Barrington KJ, Finer N. Inhaled nitric oxide for respiratory failure in preterm infants Cochrane Database Syst Rev 2010;(12):CD000509.

15. Tanaka Y, Hayashi T, Kitajima H, Sumi K, Fujimura M. Inhaled nitric oxide therapy decreases the risk of cerebral palsy in preterm infants with persistent pulmonary hypertension of the newborn. Pediatrics 2007;119:1159-64. 16. Mestan KK, Marks JD, Hecox K, Huo D, Schreiber MD. Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide. N Engl J Med 2005;353:23-32. 17. Chock VY, Van Meurs KP, Hintz SR, et al; NICHD Neonatal Research Network. Inhaled nitric oxide for preterm premature rupture of membranes, oligohydramnios, and pulmonary hypoplasia. Am J Perinatol 2009;26:317-22. 18. Kinsella JP, Cutter GR, Walsh WF, et al. Early inhaled nitric oxide therapy in premature newborns with respiratory failure. N Engl J Med. 2006;355(4):354 –364 19. Ballard PL, Gonzales LW, Godinez RI, et al. Surfactant composition and function in a primate model of infant chronic lung disease: effects of inhaled nitric oxide. Pediatr Res. 2006;59(1):157–162 Jan 20. Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med. 1997;336(9):597– 604 21. Clark RH, Kueser TJ, Walker MW, et al. Low dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. N Engl J Med. 2000;342(7):469–474 22. Schreiber MD, Gin-Mestan K, Marks JD, Huo D, Lee G, Srisuparp P. Inhaled nitric oxide in premature infants with the respiratory distress syndrome. N Engl J Med. 2003;349(22): 2099 –2107 23. Ballard RA, Truog WE, Cnaan A, et al. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med. 2006; 355(4):343–353 24. Kinsella JP, Walsh WF, Bose CL, et al. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial. Lancet. 1999; 354(9184):1061–1065 25. Van Meurs KP, Wright LL, Ehrenkranz RA, et al. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med. 2005;353(1):13–22 26. Angus DC, Clermont G, Watson RS, Linde- Zwirble WT, Clark RH, Roberts MS. Costeffectiveness of inhaled nitric oxide in the treatment of neonatal respiratory failure in the United States. Pediatrics. 2003;112(6 pt 1): 1351–1360 27. Lorch SA, Cnaan A, Barnhart K. Costeffectiveness of inhaled nitric oxide for the management of persistent pulmonary hypertension of the newborn. Pediatrics. 2004;114(2):417– 426 28. Victorian Infant Collaborative Study Group. Economic outcome for intensive care of infants of birth weight 500 –999 g born in Victoria in the post surfactant era. J Paediatr Child Health. 1997;33(3):202–20 29. Hintz SR, Van Meurs KP, Perritt R, et al. Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized, controlled trial of inhaled nitric oxide. J Pediatr. 2007;151(1):16–22 30. Mestan KK, Marks JD, Hecox K, Huo D, Schreiber MD. Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide. N Engl J Med. 2005;353(1):23–32 31. Finer N, Barrington K. Nitric oxide for respiratory failure in infants born at or near term (Cochrane Review). The Cochrane Library, Oxford: Update Software 2000; (2). 32. Clark R H, Kueser T J, Walker M W, Southgate W M, Huckaby J L, Perez J A, et al. Low dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. The New England Journal of Medicine 2000; 342 (7): 469-474. 33. Subhedar N, Ryan S W, Shaw N J. Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants. Arch Dis Child Fetal Neonatal Ed 1997; 77 (3): F185-190. 34. Subhedar N, Shaw N J. Changes in oxygenation and pulmonary haemodynamics in preterm infants treated with inhaled nitric oxide. Arch Dis Child Fetal Neonatal Ed 1997; 77 (3): F191-197. 35. Mercier J C, et al. Early compared with delayed inhaled nitric oxide in moderately hypoxaemic neonates with respiratory failure: a randomised controlled trial. The Lancet 1999; 354 (9184): 1066-1071. 36. Rosenburg A. Inhaled nitric oxide in the premature infant with severe hypoxaemic respiratory failure: a time for caution. The Journal of Pediatrics 1997; 133 (6): 720-722. 37. Hess D. Adverse effects and toxicity of inhaled nitric oxide. Respiratory Care 1999; 44

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E-ISSN No : 2454-9916 | Volume : 5 | Issue : 11 | Nov 2019

Fig. 1: RDS.

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E-ISSN No : 2454-9916 | Volume : 5 | Issue : 11 | Nov 2019

Fig. 2: BPD.

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International Education & Research Journal [IERJ]


Research Paper

E-ISSN No : 2454-9916 | Volume : 5 | Issue : 11 | Nov 2019

Fig. 3: Milder BPD.

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