ASTHMA

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ASTHMA
Pediatric Critical Care Medicine Emory
University Childrens Healthcare of Atlanta
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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

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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 gt11.5 billion per year
• 35/100.000 fatality, mostly pre-hospital older
  pop
• Seasonal exacerbation pattern but ICU admission
  remains constant
• lt10 life threatening exacerbation 2-20 with
  ICU admission 4 intubation
• Reduction in mortality (63) in the 1980s due to
  inhaled steroids

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Asthma Prevalence
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Pathophysiology

• Airway inflammation, smooth muscle constriction,
  and airway obstruction
• VQ mismatch (lt0.1)- 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

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Asthma
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Histamine Tryptase PGD2 LTC4 IL-4 IL-5 IL-6 TNF-a
IL-3 IL-4 IL-5 GM-CSF
Eosinophilic cationic proteins Major basic
proteins Platelet activating factor LTC4, LTD4,
LTE4
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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

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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.

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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

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Pathophysiology

• CV effects pulsus paradoxus decrease
  arterial systolic pressure in inspiration)
  gt12mmHg
• 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

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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

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Clinical Presentation

• Baseline PEF and FEV1 are important
• PEF 35-50 of predicted value acute asthmatic
  exacerbation
• Pre-treatment FEV1 or PEF lt25 or post treatment
  lt40 predicted indication for hospitalization

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Treatment

• Oxygen
• ß-agonists
• Corticosteroids
• Magnesium sulfate
• Anticholinergics
• Methylxanthines
• Leukotriene modulators
• Heliox
• Mechanical ventilatory support

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Treatment

• Oxygen supplement to keep satgt90
• Severe hypoxemia is uncommon
• Careful with 100 oxygen supplementation may
  result in respiratory depression followed by
  carbon dioxide retention

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Treatment

• ß-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 µm are
  deposited in the small airway, smaller particles
  tend to be exhaled)
• Continuous more consistent delivery and allow
  deeper tissue penetration

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Treatment

• ß-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 ß2-adrenergic receptors
  may respond favourably to neb. epinephrine

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Treatment

• ß-agonists
• 3- Epinephrine
• Alpha 1 adrenergic receptor microvascular
  constriction ? decrease edema
• Decreases parasympathetic tone ? bronchodilator
• Improves PaO2
• SQ epinephrine
• SQ terbutaline loose ß2 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

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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

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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

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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

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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

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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))

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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 1231018-25)

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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)

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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)

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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
  5547-52)