The Timing of

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The Timing of Inhaled Ventolin

• 91-8-26

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Aerosol therapy

• Efficacy with a smaller dose
• Rapid onset of action
• Systemic side effects are minimized

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????(Aerosol Therapy)

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• 1.???????????????
• 2.????????????
• 3.?????????

4
????(Aerosol Therapy)

• ?????????? ??
• 1.??? (nebulizer)
• 2.????? (metered dose inhaler, MDI)
• 3.?????? (dry powder inhaler, DPI)

5
Drugs Available for Nebulization

• Inhaled beta-2 agonist bronchodilators
• Short-acting (36hr)
• Long-acting (gt12hr)
• Inhaled anti-cholinergics
• Inhaled corticosteroids

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Inhaled Beta-2 Agonist Bronchodilators

• Short-acting (36hr)
• Salbutamol (Ventolin)
• Terbutaline (Bricanyl)
• Fenoterol (Berotec)
• Long-acting (gt12hr)
• Salmeterol
• Formoterol

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Inhaled Anti-cholinergics

• Ipratropium bromide (Atrovent)

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Inhaled Corticosteroids

• Beclomethasone
• Triamcinolone
• Flunisolide
• Budesonide (Pulmicort)
• Fluticasone

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Classification of Asthma
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Therapy of Asthma
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Acute Exacerbation of COPD

• 5 Guidelines
• European Respiratory Society (1995)
• British Thoracic Society (1997)
• American Thoracic Society (1995)
• American College of Chest Physicians and American
  College of PhysiciansAmerican Society of
  Internal Medicine (2001)
• GOLD (2001)
• Acute exacerbations of chronic obstructive
  pulmonary disease.
• New England Journal of Medicine. 346(13)988-94,
  2002 Mar 28.

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Acute Exacerbation of COPD

• Beta-adrenergic agonists have not been shown to
  be superior to anticholinergic agents
• Data from randomized clinical trials have not
  shown a benefit of the combined use of
  beta-adrenergic agonists and anticholinergic
  agents over therapy with either class alone
• Beta-adrenergic agonists as first-line
  bronchodilator therapy, recommend adding an
  anticholinergic agent if there is no response to
  the beta-adrenergic agonist

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Acute Exacerbation of COPD

• A short course of systemic corticosteroids (iv or
  oral) is suggested
• The optimal duration of systemic corticosteroid
  therapy for an acute exacerbation of COPD remains
  uncertain, but recent data support a course of 5
  to 10 days
• Acute exacerbations of chronic obstructive
  pulmonary disease.
• New England Journal of Medicine. 346(13)988-94,
  2002 Mar 28.

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Stable COPD (1)

• Inhaled Beta-2 Agonist Bronchodilators
• Short term benefit
• 3 RCTs of salmeterol have found significant
  improvements in symptoms and quality of life
  compared with placebo, even in the presence of
  only modest or no change in lung function
• RCTrandomized controlled trial
• Stable chronic obstructive pulmonary disease. BMJ
  1999319495-500

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Stable COPD (2)

• Inhaled Anti-cholinergics
• Short term benefit
• No major RCTs comparing ipratropium bromide
  versus placebo in chronic COPD
• Many small, placebo controlled trials used
  different end points. Most included at least some
  measure of airways obstruction and found a
  significant effect of ipratropium bromide
• Stable chronic obstructive pulmonary disease. BMJ
  1999319495-500

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Stable COPD (3)

• Combine Inhaled Beta-2 Agonist Bronchodilators
  and Inhaled Anti-cholinergics
• More effective than either alone
• 3 large RCTs (n534, 195, and 652) comparing the
  addition of ipratropium to standard dose inhaled
  beta-2 agonists for about 90 days in people with
  stable chronic COPD
• All three found significant improvements in FEV1
  of about 25 with the combination compared with
  either drug alone
• Stable chronic obstructive pulmonary disease. BMJ
  1999319495-500

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Stable COPD (4)

• Inhaled Beta-2 Agonist Bronchodilators
• Unknown effectiveness
• Oral Corticosteroids
• Short term benefit
• Stable chronic obstructive pulmonary disease. BMJ
  1999319495-500

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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

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Mechanically Ventilated Patients (2)

• In addition, 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

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Indication in Mechanically Ventilated Patients (3)

• Presence of auto-PEEP
• Which is not eliminated with reduced rate,
  increased inspiratory flow, or decreased
  inspiratory to expiratory time ratio
• Increased airway resistance as evidenced by
• increased peak inspiratory pressure and plateau
  pressure
• wheezing or decreased breath sounds
• intercostal and/or sternal retractions
• patient-ventilator dysynchrony
• AARC Clinical Practice Guideline Selection of
  Device, Administration of Bronchodilator, and
  Evaluation of Response to Therapy in Mechanically
  Ventilated Patients
• Respir Care 199944(1)105-113

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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

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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)
• MDI metered dose inhaler
• Inhaled Bronchodilator Therapy in Mechanically
  Ventilated Patients
• Am J Respir Crit Care Med Vol. 156. pp. 3-10,
  1997

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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

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Prevention of Postoperative Chest Infection

• A randomized double-blind trial
• 53 patients received upper abdominal surgery
• 21 nebulized salbutamol (5 mg) 6 hourly for a
  total of 48 hours vs. 22 saline placebo
• There was no difference in rates of postoperative
  chest infection in the two groups
• The effect of nebulized salbutamol therapy on the
  incidence of postoperative chest infection in
  high risk patients.
• Respiratory Medicine. 88(9)665-8, 1994 Oct.

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Improve Efficiency of Oxygenation after CABG

• A prospective, randomized, open controlled study
• 22 consecutive pts undergoing elective CABG
• Exclusion criteria asthma, current use of
  bronchodilators, DM, ventilation in excess of 36
  hours
• 11 receive terbutaline 0.5 mg sc 6 hourly for 48
  hours after extubation, 11 didnt
• Terbutaline improves efficiency of oxygenation
  after coronary artery bypass surgery. Journal of
  Cardiovascular Surgery. 37(1)59-62, 1996 Feb.

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Improve Efficiency of Oxygenation after CABG

• A-aDO2 increased significantly after extubation
  in both groups
• Treatment with terbutaline eliminated this change
  at 6 hrs after extubation
• Conclusion improve the efficiency of oxygenation
  in the early postoperative period
• A-aDO2 alveolar-arterial oxygen difference
• PAO2 (760-48) FiO2 PaCO2/0.8
• PaO2
• Terbutaline improves efficiency of oxygenation
  after coronary artery bypass surgery. Journal of
  Cardiovascular Surgery. 37(1)59-62, 1996 Feb.

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Conclusion (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

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Conclusion (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

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Conclusion (3)

• Inhaled corticosteroids
• Previous asthma Hx of severe persistent, moderate
  persistent, and mild persistent asthma, adjust
  therapeutic dosage to adequacy