American Heart Association: 2005 Clinical Guidelines for CPR TSRC meeting Lufkin Texas September 14, 2007 Management of

1. American Heart Association: 2005 Clinical Guidelines for CPRTSRC meeting Lufkin Texas September 14, 2007Management of Near-Fatal Asthma By Elizabeth Kelley Buzbee AAS, RRT-NPS, RCPKingwood College Respiratory Care faculty

2. Severe asthma accounts for 2%-20% of all ICU admissions and up to 1/3rd of these patients require intubation and mechanical ventilation. [AHI pp. 139]

3. Pathophysiology per NIH 1996 clinical guidelines • Asthma… [is a ].. chronic inflammatory disorder of the airways. • Features of asthma include: — Denudation of airway epithelium — Collagen deposition beneath basement membrane — Edema — Mast cell activation — Inflammatory cell infiltration – Neutrophils (especially in sudden-onset, fatal asthma exacerbations) – Eosinophils – Lymphocytes (TH2-like cells)

4. Atopy, the genetic predisposition for the development of an IgE-mediated response to common inhaled allergens is the strongest identifiable predisposing factor for developing asthma.

5. Airway inflammation also contributes to several forms of airflow limitation, including acute bronchospasm, airway edema, mucus plug formation, and airway wall remodeling. • This last problem is thought to contribute to the difficulty in breaking some asthmatics

6. Differential diagnosis includes: • pulmonary edema, COPD, anaphylaxis, foreign body aspiration, pulmonary embolism, bronchiectasis and subglottic mass. [AHI pp. 139]

7. Clinical signs & symptoms of severe asthma per the NIH: • While the primary clinical sign of asthma is expiratory wheezing and coughing, it is important to understand that not all asthmatics wheeze and that severe airway compromise may be expressed as poor air movement.

8. History of any of the following: • Cough, worse particularly at night • Recurrent wheeze • Recurrent difficulty in breathing • Recurrent chest tightness • May have family history of atopic diseases or asthma

9. Reversible airflow limitation and diurnal variation as measured by using a peak flow meter, for example: • — Peak expiratory flow (PEF) varies 20% or more from PEF measurement on arising in the morning (before taking an inhaled short-acting beta2-agonist) to PEF measurement in the early afternoon (after taking an inhaled short-acting beta2-agonist).

10. Severity • For the purpose of treatment, asthmatics are classified as [1] mild intermittent, [2] mild persistant, [3] moderate persistant, and [4] severe persistant. • It is important to understand that near-fatal asthma exacerbation can happen to any patient at any level of severity. • Obviously, a person with severe persistant asthma is at increased risk of fatal asthma exacerbation, but the person in mild intermittent asthma is not immune to severe exacerbations. [NIH]

11. Treatment: • Initial stabilization includes aggressive treatment with supplementary 02, inhaled short-acting bronchodilators & systemic steroids. • Supplementary 02: titrate to keep Sp02 above 92%.

12. TX continued • Inhaled short-acting Beta2 bronchodilators: • studies have shown no clear advantage to SVN over MDI, but patients in severe distress have trouble operating MDI • 2.5 to 5 mg albuterol sulfate Q 15-20 minutes intermittently • 10 to 15 mg/hour by continuous nebulization • No clear benefit to levalbuterol [Xopenex TM] • Systemic steroids. • Onset of action of steroids by any route is 6-12 hours • Decreases the inflammation associated with asthmatic exacerbation • Initial adult dose of methylprednisolone is 125 mg. • Systemic steroids better than inhaled steroid for the acute exacerbation

13. Subcutaneous epinephrine/ or terbutaline • Subcutaneous epinephrine [1:1000] .01 mg/kg divided into three doses or • .25 mg subcutaneous terbutaline has prolonged onset of action • Of these two methods, subcutaneous epinephrine is preferred when the patient is in anaphylactic shock because of the alpha and Beta1 effects of the drug, • while terbutaline is a specific beta2 agonist with longer duration of action.

14. Additional treatments [after initial stabilization is started] • Cholinergic blockers such as . 5mg of Atrovent may give improvement over Albuterol alone, but it has a slow onset of action [20 minutes.] • New longer-acting cholinergic blockers such as Tiotropium [Spiriva DPI] are being studied for asthma. Remember! DPI may be difficult for persons in distress to trigger. • While not all asthmatic react favorable to the addition of cholinergic blockers, elder persons who are intolerant to Beta2 drugs and those with nocturnal symptoms might do well with these drugs. [Respiratory Care Vol 52, # 7 pp. 840]

15. Magnesium Sulfate • Mg by IV works well with Beta2 agonists & steroids. Dose is 1.2 to 2 grams over 20 minutes. • It is known that acute temporary elevation of serum magnesium can result in bronchodilation even in patients with normal magnesium levels. • Evidence also shows that magnesium acts as a competitive antagonist with calcium and reduces the neutrophilic burst associated with the inflammatory response in asthma.

16. Hazards of magnesium • When given by IV to slow down labor, women have been known to go into pulmonary edema, and one study of asthmatics found that combining magnesium sulfate and terbutaline increased terbutaline's cardiovascular side effects (Chest, 1994, Vol. 105, pp. 701-705). • Magnesium sulfate can decrease muscle strength –even to the point of respiratory failure due to paralysis.

17. Xanthines • such as aminophyline/ theophylline have such dangerous side effects [cardiac arrhythmias and seizures] that they are infrequently used for asthma. • Aminophyline works by inhibiting phosphodiesterase, an enzyme that breaks down C-AMP. If C-AMP is prolonged, bronchodilation is prolonged. The therapeutic serum level of theophylline is 5-15 micrograms for asthma control.

18. Ketamine • is an anesthetic that seems to have bronchodilator properties, but it also stimulates copious secretions. Research is limited and this drug’s affect on asthma is unclear right now.

19. Heliox: • deposition of Beta2 drugs by SVN is improved with the low density helium gas mixed with 02 in 70:30 ratio, but research has not supported the use of heliox for acute asthma unless the patient is not responding to conventional care. • If the patient needs more than Fi02 30%, heliox is useless.

20. Inhaled general anesthetics • have been used to treat persons with status asthmaticus who are resistant to maximal conventional care. These drugs may enhance patient-ventilator synchrony This technique involves the ICU setting. There are no randomized studies.

21. Leukotriene blockers • have not been studied during acute attacks, but works well as maintenance drugs. • Leukotrienes created by the arachidonic acids were once called the “slow reacting substance of anaphylaxis” and is responsible for bronchospasm, vasodilation, increased capillary permeability, increased mucus production and decreased mucociliary clearance. (Colbert & Mason pp. 137 )

22. AHI 2005 guidelines regarding Mechanical ventilation in the acute asthmatic exacerbation • NIPPV with BiPap might work with the asthmatic who can still protect his airway and who has an adequate ventilatory drive. • Endotracheal intubation & mechanical ventilation is a challenge. Mechanical ventilation is complicated by air-trapping that can lead to air leaks-- even pneumothorax • RATE: 6- 10 bpm • VT: 6-8 ml/kg • I:E 1:4 or 1:5 • Flow rate 80-100 LPM to decrease the Ti

23. Permissive hypercapnea can be used to keep airway pressure down and minimize barotrauma. • If auto-PEEP is still an issue, consider decreasing the VT to 3 to 5 ml/kg and the rate by 2 bpm • Remember that removal of the circuit from the ventilator will vent off excess gases in the tube caused by air-trapping.

24. Watch for these complications: • Tube displacement. Intubate with the largest tube available and monitor it for placement with bilateral breath sounds and serial Sp02. • Tube obstruction: never forget that asthmatics do suffer from thick secretions and may require assessment of the airway and frequent suctioning. • Sudden deterioration may be seen with a pneumothorax. Remember that small pneumothorax will, in the presence of positive pressure, become a tension pneumothorax. Rapid decompression by needle aspiration or chest tube placement may be needed.

25. Recent research in asthma [Respiratory Care Vol 52 #7 July 2007] • Hazards of continuous inhaled Beta2 • During continuous short-acting Beta2 agonists doses of more than .4mg/kg/hour were associated with significant drops in serum potassium which can increase the HR. [pp.823]

26. How the Beta2 receptors are triggered

27. Hazards of long-acting inhaled Beta2 • Long-acting bronchodilators such as salmeterol are associated with increased deaths from asthma particularly if given without steroids. [pp 826-827.] Worldwide, salmeterol may be responsible for 4-5k deaths

28. In a huge study of 26k patients in 6k sites, not only was a slight, but clinically significant increase in deaths associated with LABD. The large number of African American deaths resulting during this research caused the project to be stopped. [pp. 286] • It is not known if there was a difference in these patients’ underlying asthma condition or in their compliance. More studies need to be done.

29. Racemic albuterol • There is some concern about racemic Beta2 bronchodilators such as albuterol. • The R isomer is associated with bronchodilation while the S isomer may actually cause bronchospasm. • Drugs such as levalbuterol are specific R isomer beta2 bronchodilators. • we know that the S isomer is not inert and currently the FDA will not ok any more racemic beta2 bronchodilators until the isomers are both tested for safety

30. Per RC July 2007: Recent research on the racemic Beta2 problem: • while the S isomer caused problems in vitro, this has not be duplicated in vivo [pp. 824] • when compared, the racemic albuterol and the S albuterol both showed protection against methacholine challenge • during a single dose test, there was no difference in bronchodilation nor in occurrence of adverse side effects between racemic and R albuterol [levalbuterol] • there was no problems found with racemic albuterol during adenosine challenge • there was no difference in hospital stays between racemic albuterol and levalbuterol

31. Persons who might be at increased risk for side effects of racemic beta2 bronchodilators • There are at least 9 genetic differences in Beta2 receptors. [polymorphism] • One of them [the arginine/ arginine polymorphism] found at the 16th amino-acid chain seems to be associated with impaired bronchodilation with racemic beta2 bronchodilators. • In other words, these folks may have problems with the S isomer of albuterol and more research needs to be done. [pp. 824] • 1/6th of all USA asthmatics have this genetic problem—but 25% of African Americans have this particular polymorphism. [pp. 824.]

32. Roflumilast, a phosphodiesterase 4 inhibitor is showing promising results with limiting exercised-induced drops in FEV1 with patients with asthma. Will it be as effective as xanthines without the side effects? • Homecare • A recent survey of New York City area pulmonary physicians found that 71% presented their asthmatic patients with written treatment plans. • Links: • http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm