therapeutic interventions in the management of severe asthma mark a. hostetler, md, mph emergency...
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Therapeutic Interventions in the Management of Severe Asthma
Mark A. Hostetler, MD, MPHEmergency Medicine & Pediatrics
The University of Chicago Pritzker School of Medicine
Outline
• Pathophysiology• Basic Approach & Aims of Treatment• Therapeutic Options• Theory, Evidence, and Limitations• Summary
Pathophysiology
• Adrenoceptor mediated bronchospasm2 Types: alpha & betaDirect Indirect
• Airway Injury & Inflammation InjuryMediators Immune dysregulation
Adrenoceptors
2 receptorscause bronchodilationmuch more prevalent, supersede number increases the smaller the airway
receptorscause bronchoconstriction relatively few
2 Adrenoceptor
Inflamm marker table 1
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
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
• Theory• Evidence• Pros/Cons• Dosing & Administration
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
Epinephrine
• Theory: + agonist
• Evidence: ? pendingSQ: historical Inhaled: no better than pure beta
• Pros/Cons: cheap, effective….CAD• Dosing & Administration
0.01mg/kg sq (max 0.3mg)
-agonist effects
• Sm muscle relaxation bronchodilation• Additional effects:
inhibition of inflammatory mediator release inhibition of smooth muscle proliferationstimulation of mucociliary transportcytoprotection of respiratory mucosaattenuation of neutrophil activation
Albuterol
• Theory: agonist• Evidence: plethora of studies• Pros/Cons: cheap, effective….tachy• Dosing & Administration:
Extreme paucity of dataDosed per kg? vs. Autodosing by VT? Is more better? Is more worse?
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
Ipratropium, multidose(Admission)
Systemic Corticosteroids
• Theory: decreased inflammation• Evidence:• Pros/Cons: cheap…immunosupression• Dosing & Administration
2mg/kg
Systemic CS(Admission)
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 ?]
Magnesium(Admission)
Inhaled Budesonide
• Theory: steroid + vasoconstrictor?
• Evidence: ?• Pros/Cons: easy … insuff data• Dosing & Administration:
0.5mg/2cc (Pulmocort) ampules Insufficient evidence to recommend
dosage
Inhaled CS(Admission)
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)
IV Beta-agonists(PEFR)
IV Beta-agonists(Clinical Failure)
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 load1mg/kg/hr infusion
IV Aminophylline(Adults-Admissions)
IV Aminophylline(Adults-Arrythmia/Palps)
IV Aminophylline(Children-ICU)
IV Aminophylline(Children-Severity Scores)
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 min1.5mg/kg/hr infusion
Heliox
• Theory: laminar/less turbulent flow• Evidence: ? • Pros/Cons: effective ? difficult, 30-40% O2
• Dosing & Administration:Bulky set-up70:30 Helium:Oxygen mix
Heliox(Admissions)
Heliox(Dyspnea scores)
Heliox (All Studies)
NIPPV: BiPAP
• Theory: Improved air exchange• Evidence: Meta-analysis • Pros/Cons: Noninvasive … bulky• Application:
“Test” for suitability with CPAP bagLabor intensive patient preparationConsider early
BiPAP
* Opens bronchioles todecrease alveolar air-trapping
BiPAP Equipment
Leukotriene Inhibitors
• Theory:decreased inflammatory mediators
• Evidence: effective, but IV use in ED ?• Pros/Cons: alternate … new, expensive• Dosing & Administration:
insufficient data
Leukotriene inhibitors(Asthma Symptom Score)
Summary of Evidence OR
(Adm) % PEFR
Notes
Steroids 0.50 (0.31-0.81)
NNT 5
Multi IB 0.75 (0.62-0.89)
9.7% (5.7-13.7)
NNT 7-11
Magnesium 0.10 (0.04-0.27)
9.8% (3.8-15.8)
Inhaled CS 0.45 (0.18-1.14)
8% (3-13%)
IV Aminoph (Adults)
0.58 (0.3-1.1)
2.3% @ 12hrs 6.4% @ 24hrs
Adverse Rxns OR 2.9-4.2
IV Aminoph (Children)
8.4% FEV1 SevScore –0.7
Adverse Rxns OR 2.2-6.3
IV Terb - 24.7% (2.9- -52.3)
Clin Failure OR 1.3
* Still missing: Levalbuterol, Formoterol, Inhaled Mg, Lidocaine, Ketamine, IV LT inhibitors
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”
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