Status Asthmaticus
PICU RESIDENT LECTURE SERIES
LUCILE PACKARD CHILDREN’S HOSPITAL
(UPDATED: JUNE 2014)
Objectives
 General principals
 Pathophysiology
 Pharmacologic Therapies
 Respiratory Management
Relevance
 Asthma affects 6 million children in the United
States, making it the most common chronic disease
of childhood.1,2

Up to 10 % have severe disease unresponsive to typical
therapeutic interventions.
 Annually, childhood asthma accounts for 4 million
outpatient visits, 600,000 emergency department
visits, 150,000 hospitalizations, and 75 deaths.3
Pathophysiology
 Primary pathophysiology
 Airway inflammation & hyper-reactivity
 Smooth muscle spasm
 Mucosal edema & plugging
 Status asthmaticus
 Reversible
 Recurrent
 Diffuse
 Obstructive
Pathophysiology
 Pathologic changes in the airway  airflow
obstruction  premature airway closure on
expiration  dynamic hyperinflation  hypercarbia
 Dynamic hyperinflation or “air-trapping” also leads
to ventilation / perfusion (V/Q) mismatching
causing hypoxemia
 PaO2 = FiO2(Patm – PH2o) – paCO2/0.8
Pathophysiology
Interstium
Epithelium
Hypersecretion
Epithelial damage
with exposed nerve
endings
Hypertrophy of goblet
cells and mucus glands
Equals airway
obstruction and
resultant air trapping
Pharmacologic Targets
 Relaxation of bronchial smooth muscles
 B2 receptors
 M1 receptors
 Improving oxygen delivery
 Attenuating underlying inflammation
 Instituting vigorous pulmonary toilet
Pharmacologic Therapies
 Albuterol
 Atrovent
 Methylprednisone/Decadron
 Magnesium Sulfate
 Terbutaline
 Aminophylline
 Heliox
 Ketamine
 Oxygen
 Epineprhine
Albuterol
 MOA:
 Inhaled B2 agonist
 B2 receptor  activates adenylate cyclase  increases cAMP  activates protein
kinase A  inhibits of myosin-light chain phosphorylation and decreases
intracellular Ca2+
 Dosing: Continuous nebulization – 10–20 mg/hr with an O2 flow
rate of 10–12 L/min

Superior to intermittent nebulization  Rapid improvement, cost effective,
patient friendly 4,5
 Advantages: rapid acting, rapidly administered, easily titrated
 Disadvantages: tachycardia (B2 effects on heart), hyperglycemia
(glycogenolysis & gluconeogenesis), hypokalemia (intracellular
shunting).
Ipratroprium Bromide
 MOA:
 Muscarinic agonist (anticholinergic)
 M1 receptor  decrease cGMP  decreases intracellular Ca2+
 Dosing: 0.25–0.5 mg nebulized q 4h
 Advantages: no systemic anticholinergic action
 Disadvantages: unilateral pupillary dilation can
occur with local medication entry
Corticosteroids
 MOA:


Systemically reduce inflammation, decrease mucus production, and
enhance the effects of B2-agonists.2
Prevents the sustained inflammatory phase which occurs 6-8 hours
after allergen exposure
 Dosing:


Methylprednisone: 0.5–1 mg/kg IV q 6h (2-4 mg/kg/day), duration
5-7 days
Decadron6: 0.3–0.6 mg/kg IM x 1
 Steroids should be administered IV to assure adequate
drug delivery in a timely manner
Magnesium Sulfate
 MOA:
 Inhibits Ca2+ influx into cytosol  smooth muscle relaxant
 Increases B2 agonist affinity for its receptor, thereby potentiating its effect
 Inhibits histamine release from mast cells
 Dosing: 50 mg/kg IV over 20 min with max of 2 gm
 Advantages: has been shown to be effective in “severe” (FEV1<25%
predicted) asthma
 Disadvantages: rarely noted: hypotension, respiratory depression &
muscle weakness can be treated with IV Calcium Gluconate

Respiratory depression & muscle weakness are noted at levels >12 mg/dL.
(normal Mg levels are 1.5-2 mg/dL and minimal increase in level is noted with a
single dose)
Terbutaline
 MAO:
 IV B2 agonist
 B2 receptor  activates adenylate cyclase  increases cAMP  activates protein
kinase A  inhibits of myosin-light chain phosphorylation and decreases
intracellular Ca2+
 Dosing:
 Loading dose: 5–10 mcg/kg IV over 10 min
 Continuous infusion: 0.4–4 mcg/kg/min IV (incr by 0.4 mcg/kg/min q 30 mins)
 Advantages: effectively reaches areas of lung by IV infusion that
Albuterol does not due to airway obstruction
 Disadvantages / side effects: tachycardia, hyperglycemia,
hypokalemia, (rhabdomyolysis & cardiac ischemia – rarely)
Aminophylline
 MAO:
 Xanthine derivative
 competitive nonselective phosphodiesterase inhibitor  increase cAMP (by
preventing its degradation)  activates PKA  inhibits myosin-light chain
kinase and decreases intracellular Ca2+
 Inhibits TNF-alpha and leukotriene synthesis
 Dosing:
 Loading dose: 6 mg/kg over 20 min IV
 Continuous infusion: 0.6–1 mg/kg/min IV
 Advantages: may prove very effective in patients resistant to above
treatments given the different MOA
 Disadvantages / side effects: N/V, agitation, arrhythmias, seizures
 Level q8hr after drug initiation and then every morning.
 Therapeutic levels are 10 – 20 mcg/ml.
Heliox
 MOA:
 Low-density gas that increases laminar flow of oxygen and
decreases turbulent flow.
 Dosing: 60%/40% or 80%/20% helium/O2
 Advantages: has no systemic side effects
 Other: Data suggests prevents intubation. In
intubated patients, heliox has been shown to
decrease the PIP requirements.
Ketamine
 MAO:
 “Dissociative” anesthetic
 Bronchodilates by intrinsic catecholamine release
 Decreases airway resistance and maintains laryngeal tone & reflexes
 Dosing: 0.5–1 mg/kg IV, 1 time doses or continuous infusion.
 Advantages: Ketamine should be the drug of choice for
intubation induction.
 Other: it can be considered in SA patients with severe
agitation, but be prepared to intubate the patient should it
cause hypoxia. Be cautious of agitation however since it often
precedes respiratory failure.
ABG

ABG’s generally not indicated in an asthmatic

Early status asthmaticus: hypoxemia, hypocarbia
Late status asthmaticus: hypercarbia


Decision to intubate should not depend on ABG, but on clinical
assessment.

Frequent ABGs are crucial in the ventilated asthmatic.
Management
 The use of mechanical ventilation during an asthma
exacerbation is associated with significant morbidity
and increased risk of death.
 The decision to intubate a patient should not be
delayed until respiratory failure is imminent. If
progressing toward respiratory muscle fatigue, NPPV
may avoid intubation by easing WOB while awaiting
maximal therapeutic effects of pharmacotherapy. 9
Intubation
 The two primary indications to intubate an SA
patient are:


Severe hypoxia & Depressed level of consciousness
Other potential indications for mechanical ventilation include:
Obvious life-threatening respiratory distress not responding to
bronchodilator therapy
 Impending respiratory failure
 Hemodynamic compromise, including bradycardia, severe pulsus
paradoxus
 Lactic acidosis associated with increased work of breathing
 Apnea or near-apnea
 Peak flows <40% of predicted

Intubation
 General guidelines for mechanical ventilation
management:

Start with low tidal volume, permissive hypercapnia strategy.
Tidal volume 4-7 ml/kg (prevents barotrauma / volutrauma, minimize
lung distension)
 Goal pH>7.25 (may require HCO3)







Low ventilatory rate 10-14 breaths per minute
I:E ratio 1:4 to 1:6 (avoid air trapping by allowing for complete
exhalation)
PEEP match intrinsic
Peak pressures <30-35 (prevent barotrauma)
Keep well sedated – consider ketamine and versed infusions.
As the patient is on steroids, limit use of paralytics (to avoid
myopathy)
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
National Asthma Education and Prevention Program. Expert panel
report 3 (EPR-3): Guidelines for the diagnosis and management of
asthma-summary report 2007. J Allergy Clin Immunol. 2007;120(suppl
5): S94–S138
Scarfone RJ, Friedlaender E. Corticosteroids in acute asthma: past,
present, and future. Pediatr Emerg Care. 2003;19(5):355–361
Akinbami et al. Pediatrics. 2009;123(suppl 3):S131–S145.
Papo MC. Crit Care Med 1993;21:1479-86
Ackerman AD. Crit Care Med 1993;21:1422-4
Keeney et al. Pediatrics. 2014;133(3):493-499.
http://peds.stanford.edu/Rotations/picu/pdfs/14_status_asthmaticus.p
df
Howell J. Acute severe asthma exacerbations in children: Intensive care
unit management, www.uptodate.com
Mansel et al. Mechanical ventilation in patients with acute severe
asthma, Am J Med. 1990;89(1):42-8