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Updates in Treatment Options for Asthma and C.O.P.D. Patients

Updates in Treatment Options for Asthma and C.O.P.D. Patients. Jim Holliman, M.D., F.A.C.E.P. Program Manager, Afghanistan Healthcare Sector Reconstruction Project Center for Disaster and Humanitarian Assistance Medicine, Uniformed Services University Bethesda, Maryland, U.S.A.

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Updates in Treatment Options for Asthma and C.O.P.D. Patients

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  1. Updates in Treatment Options for Asthma and C.O.P.D. Patients Jim Holliman, M.D., F.A.C.E.P. Program Manager, Afghanistan Healthcare Sector Reconstruction Project Center for Disaster and Humanitarian Assistance Medicine, Uniformed Services University Bethesda, Maryland, U.S.A.

  2. Asthma and C.O.P.D. Lecture Objectives • Know presenting signs & symptoms • Be able to assess case severity • Know medication and other treatment options • Be able to formulate appropriate plans of care • Know indications for admission

  3. Asthma : Definition & General Demographics • Is a chronic inflammatory disorder of the airways, with airflow obstruction & airway inflammation, & recurring wheezing, dyspnea, & cough • Prevalence, morbidity, & mortality has increased since 1980's • Age - adjusted death rate for ages 5 to 34 increased 40 % from 1982 to 1992 • About 5000 deaths per year in U.S. • However Rowe and Camargo’s editorial in 2006 notes improved control and decreasing mortality in some countries • About 2 million E.D. visits in U.S. per year

  4. This prevalence trend is still true

  5. Morbidity and mortality aspects of asthma

  6. Triggers of asthma

  7. Additional triggers of asthma

  8. Markers of a Potentially Fatal Asthma Attack • Historical factors : • Hyperacute exacerbation • Lack of steroid use • Non-compliance • Psychiatric illness • > 3 hospital admissions • Prior intubation or barotrauma • Physical findings : • Altered mental status • Diaphoresis • Inability to speak • PEFR < 100 L / min.

  9. Diagnostic Assessments to Consider for Asthma • Peak Expiratory Flow Rate (PEFR) • Pulse oximetry • Arterial blood gas (ABG) • Hematology & chemistry studies • Chest X-ray (CXR)

  10. PEFR Considerations for Asthma • Probably the single most useful assessment test • Can stratify patients into severity groups : • < 25 % : Severe (impending resp. failure) • 25 to 50 % : moderate to severe • 50 to 70 % : mild to moderate • > 70 % : mild (can be discharged if at this value) • Initial value not highly correlated with admission rate but higher risk if < 100 or improves < 60 with Rx • Should usually not discharge if < 250 L / min.

  11. Pulse Oximetry Considerations for Asthma • Trend toward lower initial values correlating with higher chance of admission, but not very sensitive • Especially helpful in patients unable to perform PEFR and in kids • Can be at normal levels in some with severe bronchospasm

  12. ABG Considerations for Asthma • Initial ABG is poor predictor of outcome and rarely influences therapy • NOT recommended routinely • Indications : • Suspected respiratory failure • Altered mental status (need to know pCO2) • Pulse oximeter unable to track, & hypoxia is suspected • Worsening despite therapy

  13. Hematology and Chemistry Studies for Asthma • Generally are NOT needed for most cases • WBC count NOT reflective of severity or associated infection • Most patients are not dehydrated, and do not have electrolyte abnormalities (except pseudohypokalemia from beta agonists) • Only useful test might be theophylline level if the patient is taking a methylxanthine

  14. CXR Considerations for Asthma • NOT routinely needed for "typical" exacerbations • May be needed for : • New onset asthma (especially in kids) • Unclear Dx (e.g., R / O CHF, foreign body, etc.) • Asthma refractory to treatment • Respiratory failure • ETT placement • Strong clinical suspicion for infection • Chest pain (R / O pneumo - thorax or - mediastinum)

  15. 26 year old male with asthma and chest pain

  16. Same patient with arrows denoting pneumomediastinum

  17. General E.D. Management Scheme for Asthma • Triage • Primary treatments : • Beta agonists • Corticosteroids • Secondary (or "refractory") treatments : • Anticholinergics • Magnesium, leukotriene inhibitors, Heliox, antibiotics, ketamine, mucolytics • Disposition

  18. Triage Considerations for Asthma • All patients with acute asthma should be quickly taken to a monitored treatment area • Initial nursing interventions : • Pulse oximetry • Oxygen by nasal prongs (or blow-by mask for kids) • Cardiac monitor (if moderate to severe) • PEFR • IV line if severe • Notify physician

  19. Main Therapy for Acute Asthma Exacerbations : Inhaled Beta Agonists • MDI-spacer delivery may be equivalent to traditional nebulizer • The patient may think MDI Rx in E.D. will be ineffective since has already tried it at home • Continuous nebulization may be more effective in severe cases, but no difference for moderate cases (although takes less E.D. personnel time) • Albuterol doses are 10 to 30 mg / hr for adults, 5 to 7.5 mg / hr for kids

  20. Choices for Short Acting Beta Agonists (SABA’s) • Albuterol (Ventolin, Proventil) • PO 0.1 to 0.2 mg/kg/dose up to 12 mg/day • MDI one to two puffs q 20 minutes X 3 or : • 2.5 mg of 0.5 % solution via nebulizer q 20 minutes X 3 • Levalbuterol (Xopenex) • R isomer of albuterol • MDI 1 to 2 puffs q 4 h • Not shown superior to racemic albuterol (but is more expensive) • Metaproterenol (Alupent) • Same doses for MDI and nebulizer as albuterol • No big comparative studies versus albuterol

  21. Considerations for Parenteral Use of Beta Agonists • Subcutaneous may be useful for rare patient not able to receive aerosol • Terbutaline probably safest (0.01 mg/kg, max. 0.3 mg) • Epinephrine (same dose; causes more HBP) • For "crashing" patient, give IV • 0.1 mg diluted and via SLOW IV push • then 0.4 mcg/kg/min IV drip • Prior to discharge, can give Susphrine (epi tannate in oil) SQ at 0.005 mg/kg (more useful for allergic reactions) although availability of this med has decreased

  22. Long Acting Beta Agonists (LABA’s) • Salmeterol (Serevent) MDI 50 mcg bid • Onset in 10 to 20 minutes & duration 12 hours • Twice as expensive as albuterol • Useful for nocturnal asthma • May be useful prior to E.D. discharge to help prevent early relapse • Formoterol (Oxis, Foradil) MDI 12 to 25 mcg bid • Note FDA black box warning for these

  23. Clinical Use Guidelines for the LABA’s • NOT to be used as monotherapy for long term control of asthma • Recommended in combination with Inhaled Corticosteroids (ICS) for long term control in moderate and severe persistent asthma • NOT to be used frequently or chronically before exercise because this may mask poorly controlled asthma

  24. Other Medications for Acute Asthma • "Primary" Meds • Corticosteroids • Anticholinergics • Magnesium • "Secondary" Meds • Methylxanthines • Ketamine • Heliox • Halothane • Leukotriene inhibitors

  25. Use of Systemic Steroids in Asthma • Clearly shown to decrease admission & relapse rates • Oral route is fine for most • 40 to 60 mg prednisone / day for adults • 2 mg / kg per day for kids • 5 day duration best (typical length of attack) • taper usually not needed • IV only for severe dyspnea, emesis, altered mental status, or intubated (IV versus PO shows same acute effects) • Methylprednisolone, hydrocortisone, dexamethasone

  26. Use of Inhaled Steroids for Asthma • Regular use decreases need for beta agonists & relapse rates • Use during an acute attack may just increase cough • Use of spacer and post-Rx mouth rinse decrease side effects (dysphonia, oral Candidiasis)

  27. Choices of Inhaled Steroids for Asthma (via MDI’s) • Fluticasone (Flovent) 250 to 500 mcg bid • Budesonide (Pulmicort, Rhinocort) 200 to 800 mcg bid • Triamcinolone (Azmacort) 2 to 4 puffs bid to qid • Beclomethasone (Vanceril, Beclovent) 84 to 840 mcg per day • Virtually all patients should be on one of these after discharge

  28. Use of Anticholinergics for Acute Asthma • Inhaled (via MDI or nebulizer) these decrease bronchospasm by reducing vagal tone • Atropine (0.2 to 0.5 mg) • Glycopyrrolate (Robinul) 0.2 to 0.4 mg • Ipratropium (Atrovent) 250 to 500 mcg • Several studies show mild added benefit when added to first three beta agonist nebulizations in E.D. (not helpful after this) • Ipratropium has low rate of side effects • May help undefined subsets of patients

  29. Use of Magnesium for Acute Asthma • Acts as smooth muscle relaxer & suppresses neutrophil burst response • Conflicting results of efficacy in different studies ( ? inadequate dosing in some) • Clearly safe & few side effects • 2.0 to 5.0 gm IV dose reasonable to try for : • Severe symptoms • Respiratory failure • Non-response to standard Rx

  30. Use of Methylxanthines for Asthma • Problems with aminophylline : • weak bronchodilator • high rate adverse side effects • narrow toxic / therapeutic window • requires monitoring of serum levels (goal 5 to 15 mcg/ml) • many medication interactions • Clearly shown to add no benefit to acute Rx with beta agonists & steroids • However, slow release forms (Slo-Bid, Theo-Dur, Uniphyl) may be useful in some patients for chronic maintenance • 5 to 8 mg/kg/day

  31. Use of Ketamine for Acute Asthma • Dissociative anesthetic • Relaxes bronchial smooth muscle • Excellent agent for RSI for critically ill asthmatic • 2 mg / kg IV or 4 mg / kg IM • Continued infusion 1 to 2.5 mg / kg / hr • May cause : • Laryngospasm • Hypertension • Hallucinations

  32. Use of Heliox for Acute Asthma • Is premixed air 20 % and helium 80 % • Gas density is lower than air so flow resistance is less • Somewhat limited usefulness for asthma because as more O2 is blended in, the gas density re-increases (max. O2 is 40 %) • Expensive if used for extended period • No major extended benefits in controlled studies

  33. Use of Leukotriene Receptor Antagonists (LTRA’s) for Asthma • Leukotrienes are released from mast cells, eosinophils, and basophils and mediate : • bronchoconstriction • mucus secretion • airway mucosal edema • The LTRA’s are useful for : • Treatment of stable, mild, persistent asthma, and prophylaxis of exercise induced asthma • decrease airway response to cold & allergens • Role in acute asthma not yet clear (IV montelukast is in phase 3 research trials)

  34. Choices of LTRA’s for Asthma • Montelukast (Singulair) • 10 mg PO hs or two hours before exercise • Systemic eosinophilia and vasculitis consistent with Churg-Strauss Syndrome rarely reported • Zafirlukast (Accolate) • 20 mg PO bid • Rarely has caused liver failure

  35. Another Category of Meds : 5-Lipoxygenase Inhibitors • Zileuton (Zyflo, Zyflo CR) • Inhibits leukotriene formation • Dose 600 mg pc and hs for Zyflo • Dose 1200 mg bid for Zyflo CR • Can cause liver failure • Not studied for acute use

  36. Still Another Category of Meds : Mast Cell Degranulation Inhibitor • Cromolyn (Intal) • Inhibits degranulation of sensitized mast cells • Attenuates bronchospasm caused by exercise, cold air, aspirin, and environmental pollutants • MDI dose 2 puffs qid or two puffs 15 to 60 minutes prior to exercise • Rarely has caused liver impairment

  37. And the Final Category of Asthma Medication : Omalizumab (Xolair) • Recombinant DNA-derived immunoglobulin G monoclonal antibody which binds selectively to human immunoglobulin E on the surface of mast cells and basophils and then reduces mediator release • Used when Sx are not controlled by inhaled steroids • Dose 150 to 375 mg SQ q 2 to 4 weeks • Annual cost $12,000 to $15,000 • Can cause anaphylaxis

  38. Combination Medications Available for Asthma • Ipratropium and albuterol (Combivent) • Nebulizer 3 ml q 20 min X 3 doses • MDI 4 to 8 puffs q 20 min X 3 • Salmeterol and Fluticasone (Advair Diskus) • 3 dosage forms ; • 100, 250, or 500 mcg fluticasone with 50 mcg salmeterol • One inhalation bid

  39. Expert Panel 3 (2007) List of Ineffective Treatments for Asthma • Methotrexate • Cyclosporin • Colchicine • Acupuncture • Chiropractic • Homeopathy • Breathing techniques • Yoga

  40. Airway Management in Asthma • Endotracheal intubation should be required in < 5% of admitted pts. • Indications for ETT : • Altered mental status due to hypercarbia or hypoxia • Progressive resp. failure or resp. acidosis despite maximal Rx • Base decision on clinical situation (not a particular value of pCO2 or pO2 or pH) • Always preoxygenate & ETT attempt should be made by most experienced operator

  41. Considerations About Nasotracheal Intubation of the Asthmatic Patient • Advantages : • Can leave pt. sitting up ( resp. distress may worsen if forced supine) • Pt.'s resp. effort often makes the procedure easy • Tube may be more comfortable for pt. • Tube less likely to be dislodged • Disadvantages : • May cause epistaxis • Requires smaller tube diameter than oral (so more airflow resistance) • May predispose pt. to sinusitis later

  42. Considerations About Orotracheal Intubation of the Asthmatic Patient • Advantages : • Method of choice if pt. apneic or markedly bradypneic • No predisposition to epistaxis or sinusitis • Larger diameter tube can be used (may permit later bronchoscopy) • Disadvantages : • Generally requires "full" Rapid Sequence Intubation (RSI) technique & supine position • May be less comfortable for pt. & more likely to dislodge

  43. Options for RSI Meds for the Asthmatic Patient • For nasal ETT may only need etomidate or benzodiazepine IV (after topical anesthesia in nose) • Usual oral ETT sequence : • Preoxygenate • Lidocaine 1.0 to 1.5 mg/kg IV • Ketamine 1.0 to 2.0 mg/kg IV • +/- benzodiazepine 1 to 5 mg IV • Succinylcholine 1.0 to 1.5 mg/kg IV • Perform intubation

  44. General Considerations for Mechanical Ventilation of the Asthmatic Patient • Mortality of ventilated pts. prior to 1984 reported as 20 to 40 % • Current mortality < 10 % using "permissive hypercapnia" • uses smaller tidal volumes • goal is to limit barotrauma • does not require normalization of pCO2 or pH

  45. Specific Guidelines for Mechanical Ventilation of the Asthmatic Patient • 1. Volume control (A/C or SIMV) preferred over pressure control to avoid overventilation • 2. Tidal volume set at 5 to 8 ml/kg • 3. Initial rate set at 6 to 10 breaths per min. • allows increased time for exhalation & avoids dynamic hyperinflation ("breath stacking")

  46. Specific Guidelines for Mechanical Ventilation of the Asthmatic Patient (cont.) • 4. Set FIO2 to keep arterial pO2 > 60 mm Hg • Should be < 50% to avoid O2 toxicity if ventilation prolonged • 5. Set PEEP adjusted to 75 to 80 % of measured auto-PEEP level • Make sure endogenous (auto) PEEP does not exceed the amount dialed on the ventilator • 6. Set Peak Insp. Flow Rate 70 to 90 L/min • Produces rapid inspiration allowing time for exhalation • End-inspiratory plateau pressures should be < 35 mm Hg

  47. Specific Guidelines for Mechanical Ventilation of the Asthmatic Patient (cont.) • 7. Sedation to prevent tachypnea & allow pt. to rest • 8. Aerosolized beta agonists should be given via ventilation circuit (continuous Rx can be done) • 9. As wheezing improves, may increase TV & rate • 10. Monitor for barotrauma (risk greater if end-insp. plateau pressure > 35 mm Hg) • 11. Monitor for clinical improvement allowing extubation

  48. Complications of Mechanical Ventilation of the Asthmatic Patient • Barotrauma due to alveolar rupture • Pneumomediastinum, pneumothorax, or SQ emphysema • Should usually treat with chest tube • May need to reset ventilation parameters to decrease end-inspiratory plateau pressure • Prolonged muscle weakness • Can be due to prolonged effect of paralytic agent used for intubation (esp. if renal insufficiency) • May be partly due to steroid Rx • Can be a myopathic syndrome with increased muscle enzymes & require ventilation for several weeks

  49. Education of the Asthmatic Patient to be Discharged from the E.D. • Consider pt. education regarding the following items prior to D/C : • MDI / spacer use training • Review of medications • Self use of short course oral steroids • Home use of PEFR • Identify PEFR #'s for which pt. should come to E.D. • Arrange F/U with primary care doctor • Asthma diary • Identify avoidable triggers (shoot any cats in the house)

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