1. Guidelines to Asthma Management in the Emergency Department Sujit Iyer, M.D.

2. Goals To understand the burden of pediatric asthma in the emergency department setting To understand how time sensitive management of asthma can improve symptoms faster, and at times change disposition To understand the basics of the asthma management pathway in our emergency department NOTE: Dosing and recommendations are based on current pediatric literature – regimens may vary by institution and clinical expertise

3. Asthma – Burden of Disease 8.9% of all children have asthma (6.5 million) 3.8 million children had an asthma attack in the last year 12.8 million school days missed in one year (2002-03 data) 755,000 ED visits ANNUALLY (#3 of all causes) – 198,000 Hospitalizations (#1 of all causes) Estimated cost to treat annually: $3.2 billion

4. Risk factors – severe asthma ICU admissions, history of mechanical ventilation or rapid deterioration Seizures or syncope with exacerbations Use of more than 2 MDI canisters a month Poor adherence to controller therapy Failure to perceive disease as severe

5. How do you assess severity in asthma? Combination of physical exam and historical findings You should be able to “report” your physical and historical findings to the attending and label your patient as : – Mild, Moderate, Severe Following is an example of ways to categorize. Please see asthma pathway sheet in ED also

6. Critical Asthmatic Severe wheezing (inspiratory and expiratory) OR Absent breath sounds Agonal respirations Severe tachypnea (>50% of normal RR) OR bradypnea/apnea (poor sign) Severe retractions / Paradoxical breathings (seesaw) Lethargy, decreased muscle tone Pulse OX < 92% on Room Air

7. Quick guide to normal RR and HR An easy way to remember grossly normal RR and HR: AgeRespiratory Rate < 2 months< 60 breaths/minute 2 – 12 months< 50 breaths/minute 1 -5 years< 40 breaths/minute 6 – 8 years< 30 breaths/minute AgeHeart Rate 2 – 12 months< 160 beats/minute 1 -2 years< 120 beats/minute 2 – 8 years< 110 beats/minute

8. What do I do? Inhaled beta agonists – Small Volume Nebulizers (SVN) vs. Continuous therapy SVN: 90% of drug lost in machine, more RT labor intensive Continuous therapy: less RT labor intensive, child needs to tolerate mask – preferred method for those needing repeat treatments for an extended period – Nebulized vs. MDIs MDIs at least AS effective if not superior Not feasible in severe asthmatic with depressed mental status or “too tired to breathe” Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma, Cochrane Review, 2006

9. What do I do? How much albuterol (general guide, will vary by institution) See pathway –moderate/severe exacerbation, start with continuous WeightUnit dose (0.5%)Continuous < 5 kg1.25 mg (0.25 ml)5 mg/hr (1ml/hr) 5-10 kg2.5 mg (0.5 ml)_10 mg/hr (2ml/hr) 10-20 kg3.75 mg (0.75 ml)15 mg/hr (3 ml/hr) >20 kg5 mg (1ml)20 mg/hr (4 ml/hr)

10. Bad signs Respiratory arrest imminent: – Drowsy, confused, altered mental status – Paradoxical breathing – Absence of wheeze

11. The sick asthmatic – impending respiratory arrest 1 st : ABCS – we ALWAYS try to avoid intubation, see later difficult to manage, higher complications – May need to consider in those with apnea, asystole Consider subcutaneous beta-2 agonists – Terbutaline SC: 0.01 mg/kg per dose (0.01 mL/kg of a 1 mg/mL solution) with a maximum dose of 0.4 mg (0.4 mL) – Epinephrine SC: 0.01 mg/kg (0.01 mL/kg of 1:1000 solution [1 mg/mL]), with a maximum dose of 0.4 mL (0.4 mg) Solumedrol 2mg/kg IV (max 125 mg) Albuterol x 3 doses (vs. continuous) plus Ipatropium IV Magnesium Sulfate (50mg/kg, max 2 grams) IV Terbutaline – Bolus: 2-10 mcg/kg – Infusion: 0.08 - 0.4 mcg/kg/min (maximum 6 mcg/kg/min)

12. Steroids Systemic glucocorticoids are indicated for most children who present to the ED with acute asthma exacerbation. Exceptions: – children who respond promptly to a single albuterol treatment – children with mild exacerbations – children who have not received beta 2-agonist therapy within a few hours of presenting for medical care (who may respond to the initial dose of albuterol administered in the ED) The effects of systemic glucocorticoids may be noted within two to four hours of administration

13. Steroids Benefits of early administration of steroids (WITHIN ONE HOUR) shown in meta-analyses of 12 trials: – Early administration of systemic glucocorticoids reduced admission rates (pooled odds ratio 0.40, 95% CI 0.21-0.78) – 8 patients (95% CI 5-21) would need to be treated to prevent one admission. – Oral versus IV/IM — The NAEPP guidelines suggest that oral administration of glucocorticoids is preferred to intravenous administration because oral administration is less invasive and the effects are equivalent – Intramuscular/Intravenous administration of glucocorticoids may be warranted in patients who vomit orally administered glucocorticoids Early emergency department treatment of acute asthma with systemic corticosteroids, Cochrane Review, 2001

14. Ipatropium Bromide (Atrovent®) Inhaled anticholinergic – bronchodilation through smooth muscle relaxation Multiple reviews, studies have shown multiple doses in combo with inhaled beta 2 agonists to: – Reduce hospital admissions – Improve lung function – And DID NOT: Change length of stay when hospitalized Prevent ICU admission

15. Doctor, the pulse OX is low. I think the patient is getting sicker Why does the pulse ox in moderate asthma exacerbations PREDICTABLY go down after inhaled beta agonist treatment (transiently)? – V/Q mismatch (V = ventilation, Q = pulmonary perfusion) – In severe asthma – lung will respond by decreasing perfusion to poorly ventilated areas (shunt) – Beta agonists may initially worsen this mismatch by shunting more blood flow to areas that are poorly ventilated (improving Q to areas still with poor V)

16. V/Q mismatch V/Q ratio determines the adequacy of gas exchange In normal lung (gravity affects V/Q ratio when standing), overall V/Q of normal lung is 1 : – V/Q > 1 at apex of lung – V/Q < 1 at the base of lung When V/Q is < 1 THROUGHOUT the lung: hypoxemia Perfusion of POORLY ventilated areas leads to intrapulmonary shunting – and decreased O2 sat (hypoxemia) Perfusion will change faster than ventilation – so when start inhaled beta agonists will initially get more perfusion to areas not well ventilated  and thus INCREASE V/Q mismatch and decrease sats!

17. V/Q mismatch Diagram showing effects of decreased ventilation- perfusion ratios on arterial oxygenation in the lungs. Three alveolar-capillary units are illustrated. Unit A has normal ventilation and an alveolar PO 2 of 100 mm mL/min Hg (shown by the number in the middle of the space). The blood that circulates through this unit goes from 75% (the saturation of mixed venous blood) to 99%. Unit B has a lower ventilation-perfusion ratio and a lower alveolar PO 2 of 60 mm Hg. The blood that goes through this unit reaches a saturation of only 90%. Unit C is not ventilated at all. Its alveolar PO 2 is equivalent to that of the venous blood, which travels through the unit unaltered. The oxygen saturation of the arterial blood reflects the weighted contributions of these 3 units. If it is assumed that each unit has the same blood flow, the arterial blood would have a saturation of only 88%. Ventilation-perfusion mismatch is the most common mechanism of arterial hypoxemia in lung disease. Supplemental oxygen increases the arterial PO 2 by raising the alveolar PO 2 in lung units that, like B, have a ventilation-perfusion ratio greater than zero. When initially given inhaled beta agonists may get increased perfusion to units that look like C and transiently have a decrease in saturation, until the ventilation in these areas improves Adapted from Kliegman: Nelson’s Textbook of Pediatrics, 18 th Edition

18. Magnesium Sulfate Consider in those who continue to deteriorate despite beta agonists, steroid, Ipatropium – May improve clinical exam and clinical asthma scores – Mechanism of action: smooth muscle relaxation – Side effects: hypotension – make sure adequately hydrated. – Dose: 50-75 mg/kg IV, max 2.0 – 2.5 grams

19. Parental beta-2 agonists See prior info on sc dosing in immediate therapy of severe asthmatic Intravenous – For those that are poorly responsive to conventional therapy (no evidence to use at beginning of therapy) – Mixed data on efficacy vs. inhaled alone – Side effects: dysrhythmias, hypertension, and myocardial ischemia – Terbutaline: 10 microgram/kg bolus over 10 minutes followed by 0.3 to 0.5 microgram/kg per minute every 30 minutes the infusion may be increased by 0.5 microgram/kg per minute to a maximum of 5 microgram/kg per minute

20. Nonstandard therapies Heliox – Mixture of helium and oxygen - ? May improve beta agonist delivery by decreasing turbulence from lower gas density – Can consider in those not responding to conventional therapy.

21. Nonconventional therapy Intubation – Associated with significant morbidity (barotrauma, hypotension) and DEATH – Asthma is a disease where you can not BREATHE OUT – intubation merely pushes AIR IN (exhalation is a passive process during mechanical ventilation) – Consider only in severe cases failing conventional therapy – Manipulation of airway can precipitate worsening bronchospasm - >50% of all complications occur during or immediately after intubation DO NOT take this decision lightly! – Relative indications after failure of conventional therapy: Hypoxemia despite high concentrations of O2 Severe/Deteriorating work of breathing Altered mental status Respiratory or cardiac arrest – Hypercarbia alone IS NOT AN INDICATION FOR INTUBATION. But rising CO2 despite max therapy may help guide management

22. Disposition Complex decision, based on clinical status and social factors Likely automatic admit: – Needs albuterol every 2-3 hours – Needing supplemental oxygen Things to consider – Time since last treatment (sustained improvement > 1 hour from last treatment good sign) – Should discharge on oral steroids and inhaled beta agonists

23. Key Points Identify key risk factors and signs of severe exam findings quickly Inhaled beta agonists, Ipatropium, and oral/iv steroids should be considered in EVERY patient with at least a moderate exacerbation RE-Evaluation and escalation of therapy in the initial hours are keys to improving disposition and preventing deterioration

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25. References 1.Mannino DM, Homa DM, Akinbami LJ, Moorman JE, Gwynn C, Redd SC. Surveillance for asthma--United States, 1980-1999. MMWR Surveill Summ. 2002;51(1):1-13. 2.Moorman JE, Rudd RA, Johnson CA, King M, Minor P, Bailey C, et al. National surveillance for asthma--United States, 1980-2004. MMWR Surveill Summ. 2007;56(8):1-54. 3.Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006(2):CD000052. 4.Castro-Rodriguez JA, Rodrigo GJ. beta-agonists through metered-dose inhaler with valved holding chamber versus nebulizer for acute exacerbation of wheezing or asthma in children under 5 years of age: a systematic review with meta-analysis. J Pediatr. 2004;145(2):172-177. 5.Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001(1):CD002178. 6.Zimmerman JL, Dellinger RP, Shah AN, Taylor RW. Endotracheal intubation and mechanical ventilation in severe asthma. Crit Care Med. 1993;21(11):1727-1730. 7.Plotnick LH, Ducharme FM. Combined inhaled anticholinergic agents and beta-2-agonists for initial treatment of acute asthma in children. Cochrane Database Syst Rev. 2000(2):CD000060. 8.Cheuk DK, Chau TC, Lee SL. A meta-analysis on intravenous magnesium sulphate for treating acute asthma. Arch Dis Child. 2005;90(1):74-77. 9.Kim IK, Phrampus E, Venkataraman S, Pitetti R, Saville A, Corcoran T, et al. Helium/oxygen- driven albuterol nebulization in the treatment of children with moderate to severe asthma exacerbations: a randomized, controlled trial. Pediatrics. 2005;116(5):1127-1133.