Inhalation therapy

1. Recommendations for Recommendations for
Inhalation TherapyInhalation Therapy
(Focusing on bronchodilator)(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 of
Respiratory 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!