Inhalation therapy

Recommendations for Recommendations for Inhalation TherapyInhalation Therapy

(Focusing on bronchodilator)(Focusing on bronchodilator)

4A Intern

蔡宇承

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

What are the Inhalant drugs? Antiallergic agents

Budesonide

Cromolyn sodium Bronchodilators

Ventolin nebules (βagonist)

Bricanyl solution (βagonist)

Atrovert nebulizer solution (anti- cholinergic)

Inhalant drugs

Mucolytic agents

Acetein (Acetylcysteine)

Mistabron (Mesna) Antimicrobials

Tobramycin

Pentamidine

Ribavirin

Amphotericin

Inhalant drugs

Immune modulators

Cyclosporine

Interferon α

Interferon γ Vaso-active

Prostacyclin

Nitric oxide

Inhalant drugs

Anesthetics

Opioids Other

Granulocyte-Macrophage Colony-Stimulating Factor

Surfactant

Interleukin II

Gene therapy vectors

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)

Particle Size

MMAD: mass median aerodynamic diameter

MMAD <1μm: exhaledMMAD 1~5μm: targetMMAD >5μm: oropharynx

Strict control of MMAD of the particles ensures the reproducibility of aerosol deposition and retention.

Particle Size

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 )

Metered-dose inhalers

A liquid propellant A metering valve that dispenses a constant volum

e 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

Metered-dose inhalers

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

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

Nebulizers

Nebulizers

Drugs Available for Nebulization

Inhaled beta-2 agonist bronchodilators– Short-acting (3~6hr)– Long-acting (>12hr)

Inhaled anti-cholinergics Inhaled corticosteroids

Inhaled Beta-2 Agonist Bronchodilators

Short-acting (3~6hr)– Salbutamol / Albuterol (Ventolin)– Terbutaline (Bricanyl)– Fenoterol (Berotec)

Long-acting (>12hr)– Salmeterol– Formoterol

Inhaled Anti-cholinergics

Ipratropium bromide (Atrovent)

Inhaled Corticosteroids

Beclomethasone Triamcinolone Flunisolide Budesonide (Pulmicort) Fluticasone

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

Criteria

Presence of one or more of the following criteria: Previous demonstrated response of bronchodilator Presence of auto-PEEP not eliminated by reduced rat

e, increased inspiratory flow, or decreased inspiratory to expiratory time ratio

Increased airway resistance evidenced by:• Increased peak inspiratory pressure and plateau pressure di

fference• Wheezing or decreased breathing sound• Intercostal or sternal retraction• Patient – ventilator dyssynchrony

Some Evidence Based Factsfrom American Journal of

Respiratory Critical Care Medicine

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

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 PatientsAm J Respir Crit Care Med Vol. 156. pp. 3-10, 1997

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

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

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

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.

Indication for Bronchodilator (1)

Short-acting inhaled Beta-2 Agonist Bronchodilators– Acute asthma for quickly relieving symptoms– AECOPD, maybe can combine inhaled Anti-cholin

ergics– Stable COPD combine inhaled Anti-cholinergics f

or short term use seems more effective than either alone

– In mechanically ventilated patients which present auto-PEEP or evidently increased airway resistance

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

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

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

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

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

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

Thank you for your attention!