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Goal Directed Therapies for Asthma

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Goal Directed Therapies for Asthma

  1. 1. Goal Directed Therapies for Asthma Ira M. Cheifetz, MD, FCCM, FAARC Professor of Pediatrics Chief, Pediatric Critical Care Medical Director, PICU & Peds Resp Care Duke Children’s Hospital
  2. 2. What is Asthma?  Acute and chronic inflammatory disorder of the airways and epithelium  Most common respiratory disease of children  Affects between 7-10% of the pediatric population  Asthma triad: smooth muscle spasm (bronchoconstriction), airway edema (inflammation), airway plugging (mucous formation)
  3. 3. Pathophysiology: The Asthma Triad
  4. 4. Inflammatory Mediators ♦ Cytokines are one category of mediators that play a significant role in the chronic inflammatory process in asthma ♦ The products are associated with WBCs, mast cells, & other lung airway cells ♦ Mediators induce broncho-constriction, edema and mucus secretion
  5. 5. Air Trapping Inhalation AIR
  6. 6. Air Trapping Exhalation
  7. 7. Pathophysiology ♦ Hyperinflation – obstructed small airways cause premature airway closure – air trapping and hyperinflation ♦ Hypoxemia – inhomogeneous distribution of affected areas results in V/Q mismatch
  8. 8. Initial Presentation of Wheezing 20% 30% 1-2 years <1 year 20% 2-3 years 30% >3 years
  9. 9. Why do children wheeze?  Increased airway resistance / airway narrowing  Derived from Poiseuille’s equation, resistance is proportional to 1/radius 44  In small airways, very minor changes in airway diameter significantly alter airflow  The increased ‘turbulence’ in the narrowed airways generates the high-pitched noise of wheezing
  10. 10. All that wheezes is NOT asthma! ♦ Other causes of wheezing: – bronchiolitis – cystic fibrosis – gastroesophageal reflux – chronic lung disease of infancy (BPD) – primary ciliary dyskinesia – anatomic abnormalities • tracheoesophageal fistula (TEF) • vascular ring • bronchomalacia
  11. 11. Clinical Presentation  Cough  Wheezing  Increased work of breathing  Anxiety  Restlessness  Oxygen desaturation
  12. 12. Basic Treatment Principles  Standard therapy remains focused on bronchodilators, anti-inflammatory agents, and mucus thinning agents as needed  Systemic or inhaled corticosteroids remain the most effective agents for symptomatic control of asthma  Other agents include long-acting bronchodilators, leukotriene-modifiers, theophylline, heliox, magnesium, and inhaled anesthetics
  13. 13. Basic Treatment Principles  Children present difficulties in drug delivery: – small airways and rapid respiratory rate – nose breathers – aversion to things on the face (masks) – lack of cooperation/fussiness & crying  With training and consistency, children adapt and will cooperate with nebulized meds.
  14. 14. Treatment Hierarchy: Step 1 ♦ Oxygen ♦ Inhaled short acting beta-agonists - intermittent vs. continuous - effective dosing is based on minute ventilation – not mg/kg dosing ♦ Corticosteroids - oral vs. parenteral ♦ Ipratropium?
  15. 15. Treatment Hierarchy: Step 2 ♦ Continuous beta-agonist therapy ♦ IV corticosteroids ♦ Subcutaneous beta-agonists ♦ Heliox
  16. 16. Gas Densities Relative density of He-O2 and N2-O2 2 2 2 mixtures compared with 100% O2. 2 Oppenheim-Eden, Chest, 2001.
  17. 17. Laminar Gas Flow  Laminar gas flow is more efficient than turbulent gas flow.  Poiseuille’s Law: Flow rate = P  r4 8l  Independent of gas density.  So, does heliox improve laminar gas flow and, if so, how?
  18. 18. Reynold’s Number  Re =  VD   Re > 4000 = turbulent flow   Re < 2100 = laminar flow   Densities:  O2 = 1.43, N2 = 1.25, He = 0.18  Heliox is more likely to yield a lower  Reynold’s number and improved gas
  19. 19. Turbulent Gas Flow  Occurs in constricted passages  Flow rate = k P     gas density yields  gas flow.  Heliox improves turbulent gas flow.
  20. 20. Gas Flow Forced expiratory flow rates in healthy infants Davis, J Appl Physiol, 1999.
  21. 21. Heliox P-V Loops
  22. 22. Asthma and Heliox in the ED  After 20 minutes of therapy – Heliox group: PEF  58.4% – N2-O2 group: PEF  10.1% Kass, Chest, 1999.
  23. 23. Heliox and Asthma * p < 0.001 * Kudukis, J Pediatr, 1997.
  24. 24. Heliox and Asthma * * p < 0.001 Kudukis, J Pediatr, 1997.
  25. 25. The ‘Spiral’ Effect ‘some’ improve gas heliox exchange increase decrease heliox FiO2 concentration
  26. 26. The ‘Spiral’ Effect improve gas exchange increase decrease heliox FiO2 concentration
  27. 27. Treatment Hierarchy: Step 3 ♦ Magnesium ♦ Intravenous beta-agonists ♦ IV aminophylline
  28. 28. Late-stage Asthma ♦ Impending respiratory failure – altered level of consciousness – inability to speak – inability to protect airway – absent breath sounds – central cyanosis – diaphoresis – inability to lie down – marked pulsus paradoxus
  29. 29. Avoid intubation, if possible…. ♦ An ETT cannot stent open the smaller airways, where the problem is. ♦ Positive pressure ventilation overdistends airways and making air trapping worse ♦ Asthma is a disease of exhalation – not inhalation! ♦ Intubate based on the patient’s clinical appearance and indicators of pending respiratory failure
  30. 30. Treatment Hierarchy: Step 4 ♦ Mechanical ventilation ♦ Sedation / neuromuscular blockade ♦ Inhaled anesthetics ♦ Venovenous extracorporeal membrane oxygenation (ECMO)
  31. 31. ECMO
  32. 32. Other Considerations  Oxygen – Asthma is primarily a disease of ventilation – Significant oxygen requirement occurs with severe asthma with resultant V/Q mismatch, esp. if asthma is coupled with pneumonia  Antibiotics – Generally not indicated as most infectious precipitants of asthma exacerbations are viral – Consider coverage for mycoplasma  SIADH: may be present in severe asthma
  33. 33. Natural History of Peds Asthma Transient early Non-atopic IgE-associated Wheezing Prevalence wheezers wheezers wheeze/asthma 0 3 6 11 Age (Years)

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