Más contenido relacionado


Management of Severe BPD

  1. Management of Severe BPD PPHN Medications
  2.  Airways are free of epithelial metaplasia, smooth muscle hypertrophy and fibrosis  Fewer, larger more simplified alveoli  Decreased septation (less alveolar complexity)  Dysregulated pulmonary vascular development New BPD: arrest of development of the small and large airways * Image: public domain Hussain A, Human Pathology 1998;29:710-717 Coalson JJ, Seminars in Perinatology 2006;30:179-184 Coalson JJ, Path Chronic Lung dis, New York, Marcel Decker, 2000. Jobe AJ, Pediatric Research 1999; 46(6):641
  3. The phenotype depends largely on the stage of lung development at the time of delivery. Reprinted from Pharmacology and Therapeutics, Vol 114 (Kajekar R, Pharmacol Therap 2007;114:129–145)  Vasculogenesis parallels alveolar/saccule development  Interstitial extracellular matrix (scaffolding) also develops during this period  Thus, injury alters normal lung development and architecture
  4. Established BPD Established BPD :A different disease needing a different approach to treatment Evolving BPD
  5. Maldistribution of ventilation in Severe BPD Fast compartment: low R, normal or high C Slow compartment - high R, normal or low C
  6. With advances in care, a more “severe” BPD phenotype has emerged… Despite use of antenatal steroids and postnatal surfactant…  More survivors  More tracheostomies  More home ventilation and complex care  Outcomes occur across treatment modalities  No obvious modality that prevents BPD Baraldi E and Filippone M, NEJM, 2007 Jobe A, Bancalari E Bronchopulmonary Dysplasia 2001 Coalson JJ, Pathology of BPD 2006
  7. 4 Phases of BPD Management Clinical Trajectory of severe phenotype BPD
  8. Principles of chronic care 1. Minimal impact respiratory support 2. Optimal nutrition for growth and repair 3. Prevention of infection 4. Prevention of cor pulmonale 5. Optimal nutrition for growth and repair 6. Intensive neurodevelopmental assistance lead by a team of nursing, OT, PT, massage and speech therapists
  9. Pro-growth state Inadequate respiratory support Inflammation Unbalanced fluid/nutrient supply Stress Infection/Illness Improved nutritional status Respiratory progress Developmental progress Improved state regulation Linear growth Parent involvement/ Environment Interdisciplinary care Barriers to achieving a pro-growth state Outcomes of a pro-growth state Logan JW, Curtiss J, et al. Ped Resp Reviews 2018 (in press)
  10. Transdisciplinary Model of Care • Develop communication loops for mapping progress with cares and developmental activities • Is the baby able to do age- matched activities? What are the barriers? • Does child have enough reserve? Incorporate feedback on stability into PACE of medical care plans/weaning Abman SH, J. of Pediatrics 2017;181:12-28 Shepherd EG, J Perinatology 2012;32:33–38
  11. An adequately supported infant with severe BPD:  Quiet and alert  Good eye contact  No evidence of resp distress  Stable O2 saturations  Good growth (linear) Clinical exam is important!
  12. BPD with PPHN: Emerging entity
  13. PPHN: Components in BPD • Dynamic ( reactive/ vascular) component: Depends of the number of alveoli recruited, mechanics of ventilatory support, age of the baby, exacerbating factors such as viral infections, atelectasis etc • Fixed( interstitial) Component: Right ventricular pressure overload: concentric hypertrophy of RV septal flattening Increased pulmonary artery pressures
  14. Risk factors for association of PPHN with BPD • History of IUGR • History of SGA status. • Increased risk from 36 weeks - 52 weeks, when the developmental demands of the infant require tolerance to more handling and PO feeding, and therefore increased metabolic needs.
  15. Screening ECHO • At 36 weeks for all babies needing Fi02 >30% • Findings • RA enlargement • Tricuspid regurgitation • R to L shunting at PFO and/or PDA • Septal flattening, interventricular septum at end-systole • RV pressure/systemic pressure: round <50%, • Flat = 50-100%, Bowing to LV ≥100%
  16. Management: Dynamic Component • Dynamic component: Needs to be addressed promptly  Optimizing fluid management (Restrict to a goal : 130 ml/kg)  Optimizing pH ( 7.25- 7.35)  Oxygenation ( Zero tolerance to desaturations); Target sats > 95% at all times  Treat the precipitation factors: Sepsis/dehydration/Aspiration/Agitation  Sedation: Use with caution Keslar et al 2001
  17. Management: Fixed component • Primarily responds only to medications: Slow to reverse
  18. BMC Pediatrics 2019; Choi et al
  19. PPHN and Neurodevelopmental outcomes Choi et al, BMC Pediatrics 2019
  20. Al Ghanem et al, Canada; JOP 2017 PPHN and Neonatal outcomes
  21. Inhaled NO in animals with BPD Causes: Decreased airway muscle & resistance Improved compliance Decreased inflammation Improved surfactant function Protection against hyperoxic injury Improved lung growth Increased angiogenesis Enhanced alveolar formation
  22. Inhaled NO and Sildenafil
  23. • More than 3000 preterm infants in at least 11 clinical trials • Used for: • Early respiratory failure < 3 days: • rescue iNO for sick infants ------------ 7 trials • routine iNO for intubated infants ---- 2 trials • Late iNO (>3 days) • To prevent CLD ------------------------- 2 trials Clinical trials of iNO in preterm infants
  24. Mortality
  25. 2. Nutrition: Achieving a PRO-GROWTH State • Balancing factors that promote growth while avoiding exposures that interfere with it • Achieving LINEAR growth correlates with both pulmonary and neurodevelopmental outcomes. • LINEAR growth is a helpful measure of balance in the support/environment fit Sanchez-Solis M, et al. Pediatr Pulmon 2016;51(9):936-42
  26. 3. Avoid / minimize stress • Minimize lab draws, loud noise, inconsistent caregivers • Cares with containment/comfort • Encourage and support parent comfort/involvement/touch and presence (bed in room?) • “Stress” and ICU environment leads to growth suppression and limited ND gains • Encourage kangaroo care, touch, family recordings, containment w/ painful stimuli- (encourage neuro-regulation)
  27. Pharmacotherapy in Severe BPD
  28. What are the target areas for drug therapy Large airway disease Small airway disease Neural Control
  29. Bronchodilators
  30. Mechanism of Action Decreases small airway resistance Improve compliance ? Sustained benefit in sBPD
  31. Clouse et al 2016
  32. Ongoing trial….CHOP
  33. Indications: • ? Acute decrease in oxygen saturations: one time use to assess response • Active or audible wheezing appreciated, decreased breath sounds or active exhalation
  34. Diuretics
  35. Mechanism of Action
  36. • In preterm infants > 3 weeks of age with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. • Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for remaining intubated after eight weeks in infants who did not have access to corticosteroids, bronchodilators or aminophylline. • However , there is little or no evidence to support any benefit of diuretic administration on need for ventilatory support, length of hospital stay, or long-term outcome in patients receiving current therapy. Brion LP et al 2002 Use of distal diuretics for established or evolving CLD
  37. • The only loop diuretic used in the studies that met the selection criteria was furosemide • In preterm infants < 3 weeks of age developing CLD, furosemide administration has either inconsistent effects or no detectable effect. • In infants > 3 weeks of age with CLD, a single intravenous dose of 1 mg/kg of furosemide improves lung compliance and airway resistance for one hour. Chronic administration of furosemide improves both oxygenation and lung compliance • No reports on long term outcomes or survival available Brion LP et al 2002 Use of loop diuretics for established or evolving CLD
  38. Summary • Insufficient data to recommend routine use of loop diuretics but may be used in a case to case basis • Diuretics may help to reduce the need of excessive fluid restriction(<130 ml/ kg/ day) and potentially avoid nutritional deficiencies
  39. Nebulized diuretics
  40. J Pediatr Pharmacol Ther 2011
  41. Glucocorticoids • Systemic: Dexa/ Hydrocortisone • Inhaled: Budesonide
  42. Low-Dose Dexamethasone Facilitates Extubation Among Chronically Ventilator-Dependent Infants: A Multicenter, International, Randomized, Controlled Trial. DART Low-dose dexamethasone > 7 days PNA facilitated extubation; Doyle et al 2006
  43. Late steroids: Cochrane 2009 • Late >7days • 19 trials, n=1345 • Reductions in BPD (28%), extubation failure, home oxygen therapy, death (at day 28) • Trend to increase CP offset by trend to increase death before late follow up in the control group • Benefits may not outweigh
  44. Halidey L et al Pediatrics March 2018
  45. Hydrocortisone for BPD Rademaker KJ, Arch. Dis. Child. Fetal Neonatal Ed. 2008
  46. Long-TermEffectsof InhaledBudesonide forBronchopulmonary Dysplasia ( Inhaled steroids vs Placebo) NeJM 2018
  47. Long-TermEffectsof InhaledBudesonide for BronchopulmonaryDysplasia
  48. Few studies on Established BPD Haliday et al 2014
  49. Best to avoid Systemic steroids unless…
  50. Airway Edema and Planned Extubation Peri extubational Dexamethasone, for infants with history of failed extubation attempts, or known to have significant airway edema with stridor following a planned extubation. • 0.5 mg/kg/dose (max dose 10 mg flat dose) IV q 8 hours x 3 doses • First 2 doses given prior to extubation • Third dose to be given following extubation • Consider maximum dose delivery of 2 mg/kg for therapy course
  51. Exacerbation of RAD/BPD • Prednisolone when optimal medical management has failed to alleviate symptoms. • Prednisolone burst, 2 mg/kg PO/FT once 24 hours later, 0.5mg/kg/dose PO/FT, q 12 hours, for 4 days • Hydrocortisone stress dose may be used with weaning protocol over next few days • Methyl Prednisolone is optional
  52. Stress dosing: • For babies who have been on steroids for >2 weeks? And undergoing either of the following a. Elective surgery b. Emergency surgery c. Emergency interventions d. Systemic sepsis e. Exacerbations?