ASTHMA

Pediatric Critical Care Medicine

Emory University
Childrens 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 1980s due to
inhaled steroids

Asthma Prevalence

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-
IL-3
IL-4
IL-5
GM-CSF
Eosinophilic cationic proteins
Major basic proteins
Platelet activating factor
LTC4, LTD4, LTE4

Pathophysiology
Lactic acidosis:

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

Oxygen
-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
-agonists: albuterol, terbutaline; levalbuterol,
epinephrine, terbutaline

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 m are deposited in the small airway,
smaller particles tend to be exhaled)
Continuous: more consistent delivery and allow deeper tissue
penetration

Treatment
-agonists :
1- Salbutamol (albuterol): racemic mixture equal R
& S isomers
S-form has longer half life and pulm retention; proinflammatory 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 2-adrenergic receptors: may

respond favourably to neb. epinephrine

 -agonists :

Treatment

3- Epinephrine:
Alpha 1 adrenergic receptor: microvascular constriction
decrease edema
Decreases parasympathetic tone bronchodilator
Improves PaO2
SQ epinephrine
SQ terbutaline: loose 2 effect, can cause decrease uterine
blood flow and congenital malformations in pregnant patients

Side effects

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 6080mg/day

SE: hyperglycemia, hypokalemia, mood alteration, hypertension,

metabolic alkalosis, peripheral edema

Treatment
Magnesium sulfate: direct smooth ms
relaxation and anti-inflammation
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
5-lipoxygenase 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

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)