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; 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 2-adrenergic receptors: may respond favourably to neb. epinephrine

Treatment
-agonists :
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 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
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)