Therapeutic Interventions in the Management of Severe Asthma

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Therapeutic Interventions in the Management of
Severe Asthma

• Mark A. Hostetler, MD, MPH
• Emergency Medicine Pediatrics
• The University of Chicago
• Pritzker School of Medicine

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Outline

• Pathophysiology
• Basic Approach Aims of Treatment
• Therapeutic Options
• Theory, Evidence, and Limitations
• Summary

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Pathophysiology

• Adrenoceptor mediated bronchospasm
• 2 Types alpha beta
• Direct
• Indirect
• Airway Injury Inflammation
• Injury
• Mediators
• Immune dysregulation

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Adrenoceptors

• ?2 receptors
• cause bronchodilation
• much more prevalent, supersede ?
• number increases the smaller the airway
• ? receptors
• cause bronchoconstriction
• relatively few

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?2 Adrenoceptor
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Inflamm marker table 1
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Basic Approach

• 2 Issues
• ?-receptor mediated bronchoconstriction
• Complex inflammatory/allergic response

• 2 Goals
• Acute (quick) relief
• Healing/reverse of inflammatory/allergic response

Requires a comprehensive approach from multiple
directions
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Therapeutic Options

• Epinephrine
• Inhaled ?-agonists, multidose ipratropium
• Steroids (systemic vs. inhaled)
• Mg
• Parenteral infusions (terb, theoph/aminoph)
• Ketamine
• Heliox
• NIPPV (CPAP/BiPAP)
• Leukotriene inhibitors

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Format

• Theory
• Evidence
• Pros/Cons
• Dosing Administration

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Evidence Limitations

• Well, at the Mecca.I was always taught.
• Ive reviewed the literature
• Wheres the data?
• Evidence-based?
• Problem
• Outcome-based, single intervention, Megatrials
  often lacking for severe asthma

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Cochrane Collaboration

• Systematic Reviews
• Gold Standard of systematic reviews
• Rigorous methodology
• Weighted, pooled estimates
• Updated q 2yrs
• Multidisciplinary

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Epinephrine

• Theory ?? agonist
• Evidence ? pending
• SQ historical
• Inhaled no better than pure beta
• Pros/Cons cheap, effective.CAD
• Dosing Administration
• 0.01mg/kg sq (max 0.3mg)

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?-agonist effects

• Sm muscle relaxation ?bronchodilation
• Additional effects
• inhibition of inflammatory mediator release
• inhibition of smooth muscle proliferation
• stimulation of mucociliary transport
• cytoprotection of respiratory mucosa
• attenuation of neutrophil activation

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Albuterol

• Theory ? agonist
• Evidence plethora of studies
• Pros/Cons cheap, effective.tachy
• Dosing Administration
• Extreme paucity of data
• Dosed per kg? vs. Autodosing by VT?
• Is more better?
• Is more worse?

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Ipratropium(multidose)

• Theory
• inhibits parasympathetic mediated
  bronchochonstriction
• may inhibit the cholinergic effects of
  S-albuterol ?
• Evidence
• Pros/Cons cheap, effectivenone
• Dosing Administration
• 0.5mg/dose x 3 in first hour

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Ipratropium, multidose(Admission)
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Systemic Corticosteroids

• Theory decreased inflammation
• Evidence
• Pros/Cons cheapimmunosupression
• Dosing Administration
• 2mg/kg

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Systemic CS(Admission)
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Magnesium

• Theory
• inhibits Ca-mediated smooth muscle constriction
• inhibits release of acetylcholine
• potentiates effects of ?-agonists
• inhibits degranulation of mast cells
• Evidence
• Pros/Cons cheappainful, separate IV
• Dosing Administration
• 50-75mg/kg (2g-4g max) 15mg/kg/hr infusion ?

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Magnesium(Admission)
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Inhaled Budesonide

• Theory steroid vasoconstrictor?
• Evidence ?
• Pros/Cons easy insuff data
• Dosing Administration
• 0.5mg/2cc (Pulmocort?) ampules
• Insufficient evidence to recommend dosage

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Inhaled CS(Admission)
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Terbutaline

• Theory ?-agonist
• Evidence ?
• Pros/Cons cheap, but...
• Dosing Administration
• 10 mcg/kg load over 5min (max 0.3mg)
• 1 mcg/kg/min infusion
• (titrated 0.4-6mcg/kg/min)

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IV Beta-agonists(PEFR)
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IV Beta-agonists(Clinical Failure)
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Methylxanthines

• Theory phosphodiesterase inhibitors
• enhances mucociliary diaphragm fxn
• inhibits release of inflamm mediators
• Evidence ?
• Pros/Cons cheap...toxicity/maintenance
• Newer agents more effective?
• Aminophylline Dosing Administration
• 6mg/kg load
• 1mg/kg/hr infusion

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IV Aminophylline(Adults-Admissions)
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IV Aminophylline(Adults-Arrythmia/Palps)
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IV Aminophylline(Children-ICU)
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IV Aminophylline(Children-Severity Scores)
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Ketamine

• Theory decr intracellular Ca
• VOCC/ROCC (Voltage vs. Receptor operated Ca
  channel)
• Neurally-mediated (vagolytic vs. sympathomimetic)
• Evidence not much
• Pros/Cons cheapinexperience, behavior
• Dosing Administration
• 0.5-1mg/kg load (50mg max) over 2 min
• 1.5mg/kg/hr infusion

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Heliox

• Theory laminar/less turbulent flow
• Evidence ?
• Pros/Cons effective ? difficult, 30-40 O2
• Dosing Administration
• Bulky set-up
• 7030 HeliumOxygen mix

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Heliox(Admissions)
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Heliox(Dyspnea scores)
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Heliox (All Studies)
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NIPPV BiPAP

• Theory Improved air exchange
• Evidence Meta-analysis
• Pros/Cons Noninvasive bulky
• Application
• Test for suitability with CPAP bag
• Labor intensive patient preparation
• Consider early

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BiPAP
Opens bronchioles to decrease alveolar
air-trapping
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BiPAP Equipment
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Leukotriene Inhibitors

• Theory
• decreased inflammatory mediators
• Evidence effective, but IV use in ED ?
• Pros/Cons alternate new, expensive
• Dosing Administration
• insufficient data

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Leukotriene inhibitors(Asthma Symptom Score)
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Summary of Evidence
Still missing Levalbuterol, Formoterol,
Inhaled Mg, Lidocaine, Ketamine, IV LT
inhibitors
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Summary

• Best Practice Standardized assessment and
  treatment continuous vs intermittent treatments
• 1) Consider Epi for very severe
• 2) Albuterol, multidose IB, Steroids
• 3) Magnesium
• 4) Consider Terbutaline, (Aminoph), Heliox,
  Ketamine
• 5) Tincture of time NIPPV
• intubate as last resort