PICU RESIDENT LECTURE SERIESLUCILE PACKARD CHILDREN’S HOSPITAL

(UPDATED: JUNE 2014)

Status Asthmaticus

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

Hypersecretion

Epithelial damage with exposed nerve endings

Hypertrophy of goblet cells and mucus glands

Equals airway obstruction and resultant air trapping

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Pharmacologic Targets

Relaxation of bronchial smooth muscles B2 receptors M1 receptors

Improving oxygen delivery

Attenuating underlying inflammation

Instituting vigorous pulmonary toilet

Pharmacologic Therapies

AlbuterolAtroventMethylprednisone/DecadronMagnesium SulfateTerbutalineAminophyllineHelioxKetamineOxygenEpineprhine

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. 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

2. Scarfone RJ, Friedlaender E. Corticosteroids in acute asthma: past, present, and future. Pediatr Emerg Care. 2003;19(5):355–361

3. Akinbami et al. Pediatrics. 2009;123(suppl 3):S131–S145.4. Papo MC. Crit Care Med 1993;21:1479-865. Ackerman AD. Crit Care Med 1993;21:1422-46. Keeney et al. Pediatrics. 2014;133(3):493-499.7. http://peds.stanford.edu/Rotations/picu/pdfs/14_status_asthmaticus.p

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8. Howell J. Acute severe asthma exacerbations in children: Intensive care unit management, www.uptodate.com

9. Mansel et al. Mechanical ventilation in patients with acute severe asthma, Am J Med. 1990;89(1):42-8