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Inhalation therapy

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  • 1. Recommendations for Inhalation Therapy(Focusing on bronchodilator) 4A Intern 蔡宇承
  • 2. Why and why not? Advantages: - Less systemic toxicity - More rapid onset of medication - Delivery to target of action - Higher concentrations available in the lung Disadvantages: - Time and effort consuming - Limitation of delivery device
  • 3. What are the Inhalant drugs? Antiallergic agents Budesonide Cromolyn sodium Bronchodilators Ventolin nebules (βagonist) Bricanyl solution (βagonist) Atrovert nebulizer solution (anti- cholinergic)
  • 4. Inhalant drugs Mucolytic agents Acetein (Acetylcysteine) Mistabron (Mesna) Antimicrobials Tobramycin Pentamidine Ribavirin Amphotericin
  • 5. Inhalant drugs Immune modulators Cyclosporine Interferon α Interferon γ Vaso-active Prostacyclin Nitric oxide
  • 6. Inhalant drugs Anesthetics Opioids Other Granulocyte-Macrophage Colony-Stimulating Factor Surfactant Interleukin II Gene therapy vectors
  • 7. Respiratory tract characteristics Large surface area, good vascularization, immense capacity for solute exchange, ultra- thinness of the pulmonary epithelium Conducting region : Nasal cavity, nasopharynx, bronchi, bronchioles (first 16 generations) Respiratory region : respiratory bronchioles, alveolar ducts and sacs (17-23 generations)
  • 8. Particle Size MMAD: mass median aerodynamic diameter MMAD <1μm: exhaled MMAD 1~5μm: target MMAD >5μm: oropharynx Strict control of MMAD of the particles ensures the reproducibility of aerosol deposition and retention.
  • 9. Particle Size
  • 10. Device for Inhalation Therapy Selections of device include : – 1.Nebulizer( 霧化器 ): small volume, large volume, ultrasonic, pneumatic… – 2.Metered dose inhaler, MDI ( 定量吸入器 ) – 3.Dry powder inhaler, DPI ( 粉末型吸入器 )
  • 11. Metered-dose inhalers A liquid propellant A metering valve that dispenses a constant volume of a solution or suspension of the drug in the propellant. Inhalation technique is critical for optimal drug delivery – Actuating a MDI out of synchrony may cause negligible lower airway delivery Mainly oropharyngeal deposition Protein denaturation
  • 12. Metered-dose inhalers
  • 13. Dry powder inhalers No propellant Breath-activated, and patient coordination is not as important an issue. The drug is formulated in a filler and contained in a capsule that is placed in the device and punctured to release the powder. Proteins and macromolecules are more stable in dry powder form, this approach has been preferred for delivery of these compounds by the inhalational route
  • 14. Nebulizers Patient cooperation and coordination is not as critical Commercially available nebulizers deliver 12% to 20% of the nebulized dose into the bronchial tree. Heterogeneous drops Protein denaturation
  • 15. Nebulizers
  • 16. Nebulizers
  • 17. Drugs Available for Nebulization Inhaled beta-2 agonist bronchodilators – Short-acting (3~6hr) – Long-acting (>12hr) Inhaled anti-cholinergics Inhaled corticosteroids
  • 18. Inhaled Beta-2 Agonist Bronchodilators Short-acting (3~6hr) – Salbutamol / Albuterol (Ventolin) – Terbutaline (Bricanyl) – Fenoterol (Berotec) Long-acting (>12hr) – Salmeterol – Formoterol
  • 19. Inhaled Anti-cholinergics Ipratropium bromide (Atrovent)
  • 20. Inhaled Corticosteroids Beclomethasone Triamcinolone Flunisolide Budesonide (Pulmicort) Fluticasone
  • 21. General Indications Bronchodilator aerosol administration and evaluation of response is indicated whenever bronchoconstriction or increased airway resistance is documented or suspected in patients during mechanical ventilation - AARC Clinical Practice Guideline
  • 22. Criteria Presence of one or more of the following criteria:  Previous demonstrated response of bronchodilator  Presence of auto-PEEP not eliminated by reduced rate, increased inspiratory flow, or decreased inspiratory to expiratory time ratio  Increased airway resistance evidenced by: • Increased peak inspiratory pressure and plateau pressure difference • Wheezing or decreased breathing sound • Intercostal or sternal retraction • Patient – ventilator dyssynchrony
  • 23. Some Evidence Based Facts from American Journal ofRespiratory Critical Care Medicine
  • 24. Mechanically Ventilated Patients (1) Bronchodilator therapy is commonly used in the intensive care unit, although the indications for its use are not well defined Patients with COPD demonstrate a significant decrease in airway resistance after administration of bronchodilators Bronchodilators have been successfully used to treat acute bronchial spasm in the operating room, and they are widely used in mechanically ventilated patients with severe asthma  Inhaled Bronchodilator Therapy in Mechanically Ventilated Patients  Am J Respir Crit Care Med Vol. 156. pp. 3-10, 1997
  • 25. Mechanically Ventilated Patients (2) A heterogeneous group of mechanically ventilated patients, including some patients without a previous diagnosis of airway obstruction, have shown improvement in their expiratory airflow after bronchodilator administration Although ARDS is primarily a disease affecting the alveoli, nebulized metaproterenol sulfate produced a decrease in airway resistance in patients with this disorder Inhaled Bronchodilator Therapy in Mechanically Ventilated Patients Am J Respir Crit Care Med Vol. 156. pp. 3-10, 1997
  • 26. Mechanically Ventilated Neonates and Infants (1) Pressure-limited, time-cycled modes of mechanical ventilation are widely used in neonates and infants Several investigators have reported that the small diameter of the endotracheal tubes and ventilator tubing and the low tidal volumes used for ventilating neonates and infants decrease aerosol delivery to the respiratory tract  Inhaled Bronchodilator Therapy in Mechanically Ventilated Patients  Am J Respir Crit Care Med Vol. 156. pp. 3-10, 1997
  • 27. Mechanically Ventilated Neonates and Infants (2) The lung deposition to be as low as 0.98 ± 0.2% and 0.22 ± 0.1% with an MDI and spacer or a jet nebulizer, respectively Even such low levels of drug deposition are adequate when considered in terms of the body weight of the patient (mg of drug deposited per kg body weight)  Inhaled Bronchodilator Therapy in Mechanically Ventilated Patients  Am J Respir Crit Care Med Vol. 156. pp. 3-10, 1997
  • 28. Mechanically Ventilated Neonates and Infants (3) Inhaled beta-adrenergic and anticholinergic drugs are effective in ventilator-supported neonates and infants with acute, subacute, and chronic lung disease The use of inhaled corticosteroids has also been advocated in infants with bronchopulmonary dysplasia  Inhaled Bronchodilator Therapy in Mechanically Ventilated Patients  Am J Respir Crit Care Med Vol. 156. pp. 3-10, 1997
  • 29. Current Guideline of Bronchodilator Usage in NTUH SICU Ventoline: first choice as Bronchodilator to reduce airway resistance in mechanically ventilated patients Atrovent: recommended to given patient with Asthma & COPD history, as a combination with Bronchodilator. Old age, long-term use, might be an indication of this combination also. Pulmicort: first line to treat pulmonary inflammatory disease. Give Ventoline before Pulmicort.
  • 30. Indication for Bronchodilator (1) Short-acting inhaled Beta-2 Agonist Bronchodilators – Acute asthma for quickly relieving symptoms – AECOPD, maybe can combine inhaled Anti- cholinergics – Stable COPD combine inhaled Anti-cholinergics for short term use seems more effective than either alone – In mechanically ventilated patients which present auto-PEEP or evidently increased airway resistance
  • 31. Indication for Bronchodilator (2) Inhaled Anti-cholinergics – AECOPD can be used or be added to short-acting inhaled beta-2 agonist bronchodilators – Stable COPD combine short-acting inhaled beta-2 agonist bronchodilators for short term use seems more effective than either alone – In mechanically ventilated patients which present auto-PEEP or evidently increased airway resistance
  • 32. AARC Recommendation I Ventilator setting: - tidal volume > 500 - Addition of inspiratory pulse (in case the inspiratory flow demands of the patient are met) - Spontaneous breath should not be suppressed
  • 33. AARC Recommendation II Humidifier use: - reduce aerosol delivery by 40% - Humidified gas should still be used for dry gas associated risk - Increase dose for compensation
  • 34. AARC Recommendation III Metered Dose Inhaler - Delivered dose significantly reduced due to failure to actuate the inhaler with the onset of inspiration - Actuate the inhaler manually for synchronizing the inspiration
  • 35. AARC Recommendation IV Nebulizer Use: - Change nebulizer every 24 hours - Leave it 30 cm proximal to endotracheal tube if possible - It may be necessary to add a filter in the expiratory limb of the circuit to maintain expiratory flow-sensor accuracy
  • 36. AARC Recommendation V Patient monitoring: - Volume ventilation: peak inspiratory pressure and the difference between peak and plateau pressure - Pressure ventilation: tidal volume - Auto-PEEP - Peak Expiratory Flow and Flow-Volume Loop - Breath Sound
  • 37. Thank you for your attention!

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