ASTHMA
Pediatric Critical Care Medicine
Emory University
Children’s Healthcare of Atlanta
Asthma
• Episodes of increased breathlessness, cough, wheezing, chest
tightness.
• Exacerbations may be abrupt or progressive
• Always related to decreases in expiratory (also in
inspiratory in severe cases) airflows
• Hallmarks: airway inflammation, smooth muscle
constriction and mucous plugs
Epidemiology
 Most common chronic disease in the world: varies between
regions
 More prevalent in westernized countries but more severe in
developing countries
 Yr of cost 2005 >$11.5 billion per year
 35/100.000 fatality, mostly pre-hospital & older pop
 Seasonal exacerbation pattern but ICU admission remains
constant
 <10% life threatening exacerbation: 2-20% with ICU
admission; 4% intubation
 Reduction in mortality (63%) in the 1980’s due to inhaled
steroids
Asthma Prevalence
4
Pathophysiology
• Airway inflammation, smooth muscle constriction, and
airway obstruction
• VQ mismatch (<0.1)- decrease vent with normal perfusion
• Intrapulmonary shunt is prevented due to collateral
ventilation, hypoxic pulmonary vasoconstriction, rarely
functionally complete obstruction  mild hypoxemia
• Worsening of hypercapnea is indicative of impending
respiratory failure in combination of lactic acidosis
• Worsening of hypoxemia after beta-agonist is common due
to removal of hypoxic induced pulmonary vasoconstriction
Asthma
Histamine
Tryptase
PGD2
LTC4
IL-4
IL-5
IL-6
TNF-α
IL-3
IL-4
IL-5
GM-CSF
Eosinophilic cationic proteins
Major basic proteins
Platelet activating factor
LTC4, LTD4, LTE4
Pathophysiology
• Lactic acidosis:
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Changes in glycolysis due to high dose beta agosist;
Increased wob, anaerobic metabolism
Coexisting profound tissue hypoxia
Over production of lactic acid by the lungs
Decrease lactate clearance due to hypoperfusion
Pathophysiology
• Significantly reduced: FEV1; FEV1/FVC, Peak expiratory
flow; maximal expiratory flow at 75%, 50% and 25%, and
maximal exiratory flow between 25% and 75% of the FVC
• Abnormally high airway resistance: 5-15x normal due to
shortening of airway smooth muscle, airway edema and
inflammation, excessive luminal secretions.
Pathophysiology
• Dynamic hyperinflation: Auto PEEP (intrinsic positive end
expiratory pressuse PEEPi): directly proportional to minute
ventilation and the degree of obstruction
– Shifts tidal breathing to the less compliant part of the respiratory
system pressure volume curve
– Flatten diaphragm  reduces the generation of force
– Increase dead space  increase minute ventilation for adequate
ventilation
– “Silent chest”: lower inspiratory flow due to dynamic hyperinflation
– Asthma increases all three components of respiratory system load:
resistance, elastance and minute volume
– Diaphragmatic blood flow is reduced  worsening of respiratory
distress
Pathophysiology
• CV effects: “pulsus paradoxus” – decrease arterial systolic
pressure in inspiration) >12mmHg
– Expiration: increase in venous return, rapid RV filling  shifting of
interventricular septum causing LV diastolic dysfunction
– Large negative intrathoracic pressure: increase LV afterload by
impairing systolic emptying.
– Pulmonary pressure increases due to hyperinflation  increase RV
afterload
Clinical Presentation
• Respiratory distress: sitting upright, dyspneic &
communicate using short phrases
• Severe obstruction: rapid, shallow breathing and use of
accessory muscles
• Life threatening: cyanosis, gasping, exhaustion,
hypotension and decreased consciousness
• PE: inspiratory & expiratory wheezes  silent chest
• Intensity of wheezing is not a predictor of respiratory failure
• Mild hypoxemia
• Blood gas: hypoxemia, hypocapnea & respiratory alkalosis
in mild asthma
• Normocapnea & hypercapnea: impending respiratory failure
Clinical Presentation
• Baseline PEF and FEV1 are important
• PEF 35-50% of predicted value: acute asthmatic
exacerbation
• Pre-treatment FEV1 or PEF <25% or post treatment <40%
predicted: indication for hospitalization
Treatment
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Oxygen
β-agonists
Corticosteroids
Magnesium sulfate
Anticholinergics
Methylxanthines
Leukotriene modulators
Heliox
Mechanical ventilatory support
Treatment
• Oxygen: supplement to keep sat>90%
– Severe hypoxemia is uncommon
– Careful with 100% oxygen supplementation: may result in
respiratory depression followed by carbon dioxide retention
Treatment
• β-agonists: albuterol, terbutaline; levalbuterol, epinephrine,
terbutaline
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Mediate respiratory smooth ms relaxation
Decrease vascular permeability
Increase mucocilliary clearance
Inhibit release of mast cell mediator
Onset is rapid, repetitive or continuous administration produces
incremental bronchodilation
– MDIs: with spacer device have similar effects to nebulizer
– Aerolized:
» Utilize adequate flow rate (10-12L/min): higher flow rate, smaller
particles (0.8-3 μm are deposited in the small airway, smaller particles
tend to be exhaled)
» Continuous: more consistent delivery and allow deeper tissue
penetration
Treatment
• β-agonists :
» 1- Salbutamol (albuterol): racemic mixture equal R & S isomers
• S-form has longer half life and pulm retention; pro-inflammatory
properties
• More accumulative SE
» 2- Levosalbutamol (levalbuterol): R-salbutamol
• Can be beneficial after S-form accumulate with SE
• Can evoke 4x bronchodilation effects with 2x systemic SE
» Genetic variations in β2-adrenergic receptors: may respond
favourably to neb. epinephrine
Treatment
• β-agonists :
– 3- Epinephrine:
» Alpha 1 adrenergic receptor: microvascular constriction  decrease
edema
» Decreases parasympathetic tone  bronchodilator
» Improves PaO2
» SQ epinephrine
» SQ terbutaline: loose β2 effect, can cause decrease uterine blood flow and
congenital malformations in pregnant patients
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Side effects
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CV: MI especially in IV isoprenaline (isoproterenol)
Hypokalemia
Tremor
Worsening of ventilation/perfusion mismatch
Treatment
• Corticosteroids:
– Decrease inflammation
– Increase the number and sensitivity of Beta-adrenergic receptors
– Inhibit the migration and function of inflammatory cells (esp.
eosinophils)
– No inherent bronchodilator
– Administer within 1 hr of onset: lower hospitalization rate, improve
pulm functions
» Onset of action: 2-6 hrs
» Dose 40mg/day, limited evidence of additional efficacy of 60-80mg/day
– SE: hyperglycemia, hypokalemia, mood alteration, hypertension,
metabolic alkalosis, peripheral edema
Treatment
• Magnesium sulfate: direct smooth ms relaxation and antiinflammation
– Controversies in inhaled mag. sulfate
– 40mg/kg/dose Q6, max 2gm in adults
• Anticholinergics: ipratropium bromide
– selective for muscarinic airway (proximal airway), absence of
systemic effects
– Slow onset of action: 60-90 min, less bronchodilation
Treatment
• Methylxanthines: theophyline and aminophyline
– Mechanism of actions: phosphodiesterase inhibitor; stimulate
endogenous catecholamine release; beta adrenergic receptor agonist
and diuretic, augment diaphragmatic contractility; increase binding
of cyclic adenosine monophosphate ; prostaglandins antagonist
– No additional benefit in acute attack
Treatment
• Leukotriene modulators:
– Potent lipid mediators derived from arachidonic acid with the 5lipoxygenase pathway
– 2 main groups: LTB4 and cysteinyl leukotrienes (CysLTs): LTC4,
LTD4, LTE4
– Mediators in allergic airway disease
– CysLTs: produce: bronchoconstriction, mucous hypersecretion,
inflammatory cell recruitment, increased vascular permability,
proliferation of airway smooth ms
– Less potent in bronchodilation and anti-inflammatory than long
acting beta agonist and steroids
– Administration of single IV dose or PO doses showed improvement
in acute attacks
Treatment
• Heliox: 60-80% blend
– Laminar flow, increase ventilation, decrease wob, pulsus paradoxus
and A-a gradient, delay onset of respiratory muscle fatigue
– Controversies in benefits
– In mechanical ventilated patients, heliox helps to lower peak
inspiratory pressure, improve pH and PCO2
(Shamel et al. Helium-oxygen therapy for pediatric acute sever asthma requiring mechanical
ventilation. Pediatr Crit Care Med 2003:(4))
Treatment
• Non invasive positive pressure ventilation
– Decrease wob and auto-peep
– Improve comfort, decrease need for sedation, decrease VAP and LOS
– No benefits of positive pressure in delivering nebulized meds
(Caroll, C. Noninvasive ventilation for the treatment o facute lower respiratory tract
disease in children. Clin Ped Emerg Med)
– Risks: aspiration, gastric distension, barotrauma
– NIPPV + conventional managements associated with improved lung
function and faster alleviation of the symptoms
(Soroksy, A. et al.
A pilot prospective, randomized, placebo-controlled trial of bilevel positive airway
pressure in acute asthmatic attack. Chest 2003; 123:1018-25)
Treatment
• Mechanical ventilation
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Avoid excessive airway pressure, min hyperinflation
Permissive hypercapnea, low TV, low rate, short I-time
Continuous sedation and NMB as needed
Low PEEP vs High PEEP (overcome the critical closing pressure
facilitated exhalation)
Treatment
• Inhalational Anesthetics: Halothane, Isoflurane
– Beta adrenergic receptor stimulation, increase in cAMP – ms
relaxation; impede antigen-antibody mediated enzyme production
and the release of histamine from leukocytes
– Continuous administration:
– SE: myocardial depression and arrhythmias
(Vaschetto, R. et al. Inhalational Anesthetic in Acute Severe Asthma. Current Drug targets, 2009, 10,
826-32)
Treatment
• ECMO
– When all treatment modalities failed
– V-V ECMO: facilitates CO2 removal; CV stabilization; short run
– Complications: brain death or CNS hemorrhage and cardiac arrest
(Mikkelsen ME et al. Outcomes using extracorporeal life support for adult respiratory failure
due to status asthmaticus. ASAIO J 2009; 55:47-52)