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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. Outline. Pathophysiology Basic Approach & Aims of Treatment Therapeutic Options

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therapeutic interventions in the management of severe asthma

Therapeutic Interventions in the Management of Severe Asthma

Mark A. Hostetler, MD, MPH

Emergency Medicine & Pediatrics

The University of Chicago

Pritzker School of Medicine

outline
Outline
  • Pathophysiology
  • Basic Approach & Aims of Treatment
  • Therapeutic Options
  • Theory, Evidence, and Limitations
  • Summary
pathophysiology
Pathophysiology
  • Adrenoceptor mediated bronchospasm
    • 2 Types: alpha & beta
    • Direct
    • Indirect
  • Airway Injury & Inflammation
    • Injury
    • Mediators
    • Immune dysregulation
adrenoceptors
Adrenoceptors
  • 2 receptors
    • cause bronchodilation
    • much more prevalent, supersede 
    • number increases the smaller the airway
  •  receptors
    • cause bronchoconstriction
    • relatively few
basic approach
2 Issues

-receptor mediated bronchoconstriction

Complex inflammatory/allergic response

2 Goals

Acute (quick) relief

Healing/reverse of inflammatory/allergic response

Basic Approach

Requires a comprehensive approach from multiple directions

therapeutic options
Therapeutic Options
  • Epinephrine
  • Inhaled -agonists, multidose ipratropium
  • Steroids (systemic vs. inhaled)
  • Mg++
  • Parenteral infusions (terb, theoph/aminoph)
  • Ketamine
  • Heliox
  • NIPPV (CPAP/BiPAP)
  • Leukotriene inhibitors
format
Format
  • Theory
  • Evidence
  • Pros/Cons
  • Dosing & Administration
evidence limitations
Evidence & Limitations
  • Well, at “the Mecca”….I was always taught….
  • I’ve reviewed the literature…
  • Where’s the data?
  • Evidence-based?
  • Problem:
    • Outcome-based, single intervention, Megatrials often lacking for severe asthma
cochrane collaboration
Systematic Reviews

Gold Standard of systematic reviews

Rigorous methodology

Weighted, pooled estimates

Updated q 2yrs

Multidisciplinary

Cochrane Collaboration
epinephrine
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)
agonist effects
-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
albuterol
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?
ipratropium multidose
Ipratropium(multidose)
  • Theory:
    • inhibits parasympathetic mediated bronchochonstriction
    • may inhibit the cholinergic effects of S-albuterol ?
  • Evidence:
  • Pros/Cons: cheap, effective…none
  • Dosing & Administration
    • 0.5mg/dose x 3 in first hour
systemic corticosteroids
Systemic Corticosteroids
  • Theory: decreased inflammation
  • Evidence:
  • Pros/Cons: cheap…immunosupression
  • Dosing & Administration
    • 2mg/kg
magnesium
Magnesium
  • Theory:
    • inhibits Ca-mediated smooth muscle constriction
    • inhibits release of acetylcholine
    • potentiates effects of -agonists
    • inhibits degranulation of mast cells
  • Evidence:
  • Pros/Cons: cheap…painful, separate IV
  • Dosing & Administration:
    • 50-75mg/kg (2g-4g max) [+15mg/kg/hr infusion ?]
inhaled budesonide
Inhaled Budesonide
  • Theory: steroid + vasoconstrictor?
  • Evidence: ?
  • Pros/Cons: easy … insuff data
  • Dosing & Administration:
    • 0.5mg/2cc (Pulmocort) ampules
    • Insufficient evidence to recommend dosage
terbutaline
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)
methylxanthines
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
ketamine
Ketamine
  • Theory: decr intracellular Ca++
    • VOCC/ROCC (Voltage vs. Receptor operated Ca++ channel)
    • Neurally-mediated (vagolytic vs. sympathomimetic)
  • Evidence: not much
  • Pros/Cons: cheap…inexperience, behavior
  • Dosing & Administration:
    • 0.5-1mg/kg load (50mg max) over 2 min
    • 1.5mg/kg/hr infusion
heliox
Heliox
  • Theory: laminar/less turbulent flow
  • Evidence: ?
  • Pros/Cons: effective ? difficult, 30-40% O2
  • Dosing & Administration:
    • Bulky set-up
    • 70:30 Helium:Oxygen mix
nippv bipap
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
bipap
BiPAP

* Opens bronchioles to

decrease alveolar air-trapping

leukotriene inhibitors
Leukotriene Inhibitors
  • Theory:
    • decreased inflammatory mediators
  • Evidence: effective, but IV use in ED ?
  • Pros/Cons: alternate … new, expensive
  • Dosing & Administration:
    • insufficient data
summary of evidence
Summary of Evidence

* Still missing: Levalbuterol, Formoterol, Inhaled Mg, Lidocaine,

Ketamine, IV LT inhibitors

summary
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”