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Treating Life Threatening Asthma

Treating Life Threatening Asthma. Toni Petrillo-Albarano, MD Division of Pediatric Critical Care Children’s Healthcare of Atlanta. Asthma: Increased Severity Hospitalization Increased 28%. - MMWR , CDC. Asthma: Increased Severity Death Rate Increased 118% (1980 - 1993). - MMWR , CDC.

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Treating Life Threatening Asthma

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  1. Treating Life Threatening Asthma Toni Petrillo-Albarano, MD Division of Pediatric Critical Care Children’s Healthcare of Atlanta

  2. Asthma: Increased SeverityHospitalization Increased 28% -MMWR, CDC

  3. Asthma: Increased SeverityDeath Rate Increased 118% (1980 - 1993) -MMWR, CDC

  4. The Cost of Asthma Asthma related costs • $6.2 billion • Direct 3.6 billion • Indirect $2.6 billion • Pediatric $465 million

  5. Children Who Die from Asthma • Risk Factors: • Severe disease - history of intubation, seizures, rapid progress • Lack of adequate support systems • Psychologic disease

  6. Children Who Die from Asthma • Risk Factors: • Lack of perception of severity; self-weaning • Males • Exclusive reliance on b agonists • 50% of deaths prior to hospital

  7. Mechanisms of Status Asthmaticus Increased resistance to air flow pCO2 pO2 Bronchospasm Mucous Hypersecretion Mucosal edema Hyperinflation Uneven ventilation Atelectasis deadspace compliance Abnormal V/Q alveolar hypoventilation WOB

  8. Status AsthmaticusOxygen • Relative hypoxemia: • V/Q mismatch • hypoventilation • Hypoxemia bronchoconstriction • agonists impair hypoxic pulmonary vasoconstriction shunt • Oxygen to keep pulse ox > 92%

  9. Status AsthmaticusBeta2 Agonist Therapy • Mainstay of therapy • Rapid onset • Selective 2: • Metaproterenol • Terbutaline • Albuterol • Mode of delivery: • Inhaled vs Systemic • Intermittent vs Continuous • Nonintubated vs Intubated

  10. Intravenous  Agonists • Most studies: • inhaled therapy > to IV  agonist • Greater side effects with IV • Potential benefit severe bronchospasm • Experience anecdotal with severe SA • IV Terbutaline: • bolus 10 mcq/kg • infusion 0.1-4.0 mcq/kg/min

  11. Status AsthmaticusIsoproterenol (Isuprel) • Almost pure  effects • Potent vasodilator • pulmonary • bronchial • Increased cardiac output • Widened pulse pressure • Increases flow to non-critical tissue beds (skeletal muscle)

  12. Status Asthmaticus Isoproterenol (Isuprel) • Tachycardia • Dysrhythmias • Peripheral vasodilation • Increased myocardial O2 consumption • Decreased coronary O2 delivery • “Splanchnic steal” by skeletal muscle

  13. Severe Asthma Intravenous Isoproterenol • Equivocal results • high incidence of dysrhythmias • report of fatal myocardial ischemia • “DO not use IV Isuprel in the treatment of asthma ...” -NHLBI statement

  14. Status Asthmaticus Subcutaneous  Agonists • Epinephrine/Terbutaline • No advantage over inhaled  agonists • Increased side effects • Indications: • inability to cooperate with inhalation therapy • rapidly decompensating patient • failure to respond to inhaled beta-agonists

  15. Status AsthmaticusAnticholinergics Airway  agonist Sympathetic Parasympathetic X Vagolytics

  16. Status AsthmaticusInhaled Ipratropium + Albuterol • 120 children - severe acute asthma: • FEV1 < 50% • Albuterol (0.15 mg/kg) x 3 within 60 minutes PLUS • Randomized: • control saline • ipratropium 250 mcq x 1 • ipratropium 250 mcg x 3 -Schuh, J Peds, 1995

  17. Status AsthmaticusEffect of Inhaled Ipratropium * * * * * * * * p < .05 -Schuh, J Peds, 1995

  18. Ipratropium:Effect with FEV1 < 30% * * * * * * * -Schuh, J Peds, 1995 * p < .05

  19. Status Asthmaticus IV or oral Corticosteroids Mechanism of Effect: • interferes with leukotriene, prostaglandins synthesis • prevent cell migration • up-regulate airway  receptors

  20. Status Asthmaticus IV or oral Corticosteroids • Proven effective in 3 level I trials, meta-analysis • Decreased hospital admission if given within 30 minutes • Equally effective oral or IV • IV dose effect in 1-6 hours by reversing 2 receptor down-regulation

  21. Status Asthmaticus IV or oral Corticosteroids • Recommended dose • Prednisone or methylprednisolone • suggested initial dose 2 mg/kg • 1 mg/kg IV q 6 hours (max 60 mg) x 48 hours, • then 1mg/kg q 12 hours for 3-5 days -NHLBI Expert Panel

  22. Status Asthmaticus Inhaled Corticosteroids • SI asthma has several characteristic features • severe asthma with persistent respiratory symptoms • frequent nighttime symptoms • chronic airflow obstruction (FEV1 <70% of predicted) • tend to have required systemic GC therapy at a younger age • require higher daily maintenance doses of oral GCs • are often African American.

  23. Status AsthmaticusInhaled CorticosteroidsAcute Asthma • ICS have been considered ineffective in treatment of acute exacerbations • Nevertheless, many studies published in the last 15 years have showed therapeutic early effects (after minutes of its administration) suggesting a different mechanism of action of topical character

  24. Status AsthmaticusInhaled CorticosteroidsAcute Asthma • These rapid effects are initiated by specific interactions with membrane-bound or cytoplasmic CS receptors, or nonspecific interactions with the cell membrane • asthmatic patients present a significant increase in airway mucosal blood flow

  25. Status AsthmaticusInhaled CorticosteroidsAcute Asthma • ICS would decrease blood flow by modulating sympathetic control of vascular tone • This nongenomic action might reduce the airway obstruction, improving clinical and spirometric parameters • Furthermore, the decrease of airway blood flow is likely to enhance the action of inhaled bronchodilators by diminishing their clearance from the airway

  26. Status Asthmaticus Long term inhaled corticosteroid • Most studies done on moderate to severe persistent asthma (beneficial) • Data on mild or moderate and intermittent not well studied • Studies by O‘Byrne et al and Lange et al reinforce current practice of preventing asthma events with the regular use of ICS in patients who have symptoms on most days

  27. Status AsthmaticusIV Theophylline • Phosphodiesterase inhibitor • Randomized trials (x2) - no benefit over standard 2agonists and/or corticosteroids • Uncertain benefit in episodes unresponsive to all other therapy

  28. Status AsthmaticusIV Theophylline • 21 hospitalized children • Standard nebulized albuterol, steroids • Randomized: IV Aminophylline load/infusion OR Saline placebo -Carter, J Peds, 1993

  29. Status AsthmaticusIV Theophylline • No difference in hospital days • Confirmed by another study - Carter, J Peds, 1993

  30. IV Theophylline in Severe Pediatric Asthma -Carter, J Peds, 1993

  31. “Methylxanthines are NOT generally recommended.” -Expert Panel, NAEPP

  32. Status AsthmaticusKetamine • Dissociative anesthetic • Direct bronchodilator • Potentiates catecholamines • Bronchorrhea • Other side effects: • tachycardia • BP

  33. Status AsthmaticusKetamine • Adult studies • Case reports: • benefit in avoiding intubation • Randomized trials: • no added benefit • required lower dose due to dysphoria • Children might respond better, less dysphoria

  34. Status AsthmaticusKetamine in Pediatrics • 8 case reports: • 12 patients - not controlled • 8 months - 14 years • Positive affect in all • 9/12 intubated • Bolus/Infusion 0.2 - 2.5 mg/kg/hr

  35. Status AsthmaticusKetamine in Pediatrics • One small pediatric study in non-intubated patients • 10 patients • ketamine bolus plus 1 hr infusion in addition to standard therapy • Improved CAS • improved indicators of distress

  36. Status AsthmaticusMagnesium Sulfate • Bronchodilator: • inhibits cellular Ca++ uptake/release • stabilizes most cell membranes • Clinical effect: • 10/13 studies showed improved PEFR in adults, children • 2 adult studies no outcome benefit

  37. Status AsthmaticusMagnesium Sulfate • 31 children (6-18 yrs) in ER • Asthma exacerbation: • PEFR < 60% after albuterol • Randomized: MgSO4 25 mg/kg OR Saline -Ciarallo, J Peds, 1996

  38. Status AsthmaticusMagnesium Sulfate * * * * * * p < .05 -Ciarallo, J Peds, 1996

  39. Status AsthmaticusMagnesium Sulfate * * * * * * p < .05 -Ciarallo, J Peds, 1996

  40. Status AsthmaticusMagnesium Sulfate Results: • ER discharge home: • 27% vs 0% control (p = .03) • No difference in hospital stay • No significant side effects -Ciarallo, J Peds, 1996

  41. Status AsthmaticusLeukotriene Antagonist • Mostly used as controller med • Some newer small studies to suggest possible benefit in acute setting • Rapid improvement in FEv1 with single IV monoleukast dose (Thorax 2000; 55:260-5) • 160 mg Po Zafirlukast improved ER outcomes ( Ann Emerg Med 2000; 35:S10

  42. Status AsthmaticusHelium - Oxygen (HELIOX) • Blend of 80:20 helium:oxygen • Biologically inert • Insoluble in human tissue • No deleterious effects • Low density gas • Air: 1.29 g/l • O2: 1.43 g/l • Helium: 0.17 g/l

  43. Status AsthmaticusHelium - Oxygen (HELIOX) • Major effects to reduce resistance: • Reduces turbulence • Used in upper airway obstruction • Improved pulsus paradoxus, PEFR in adult asthmatics

  44. Status AsthmaticusHelium - Oxygen (HELIOX) • Most recent case reports and clinical studies have found mixed results in the role of heliox for use in asthma

  45. Status AsthmaticusHelium - Oxygen (HELIOX) • Kudukis et al showed that heliox therapy resulted in a significant decrease in pulsus paradoxus, a decrease in a modified dyspnea index, and an increase in peak flow • Manthous et al reported similar findings in dyspnea index and pulsus paradoxus accompanied by an increase in peak expiratory flow. • Rivera et al the heliox group had a lower admission rate compared with the placebo group (60% vs 81%). • Other studies have shown a decrease in carbon dioxide, reversal of acidosis, and an increase in peak expiratory flow rate

  46. Status AsthmaticusHelium - Oxygen (HELIOX) • Carter et al found that short-term inhalation of heliox offered no benefit in hospitalized children with severe asthma. • Henderson et al found that 3 treatments of albuterol nebulized in heliox over 45 minutes offered no additional benefit in the ED management of mild to moderate asthma exacerbations • Rose et al found that heliox-driven continuous albuterol in the ED management no difference in peak expiratory flow rate, respiratory rate, or oxygen saturation

  47. Status AsthmaticusInhaled Anesthetics • Halothane, enflurane, isoflurane • Mechanisms: • 2 agonist effect • vagolytic • direct airway relaxation • No randomized (level I) trials

  48. Status AsthmaticusInhaled Anesthetics • 8 pediatric case reports: • effect in 7/8 • isoflurane 5/8 • Duration 1-34 hrs; • Time interval for changes: 1-2 hrs • Complications: • hypotension, • pneumothorax

  49. Response to Inhaled Anesthetics pCO2 PIP

  50. Status Asthmaticus“Mechanical” Support • BiPAP • Intubation/Mechanical Ventilation • Extracorporeal Life Support

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