Michael Bressack, M.D.

1. Inpatient Management of Asthma Michael Bressack, M.D.

2. Definition • Reversible airway obstruction • Airway inflammation • Airway hyperresponsiveness • Status asthmaticus = unresponsive to initial nebulized bronchodilator

3. Pathophysiology • Airway inflammation- eosinophils, polymorphonuclear cells, lymphocytes, macrophages, mast cells • Proinflammatory mediators • Airway edema, smooth muscle hypertrophy, exudation, mucous plugging • Hypertrophy of goblet cells and mucous glands

4. Cause of Asthma Attack • Infectious, usually viral • Allergic • Irritant

5. Symptoms / Signs • Dyspnea / tachypnea / increased work of breathing / difficulty speaking • Cough • Wheeze / rhonchi / rales / decreased breath sounds • Cyanosis • Abnormal level of consciousness • Pulsus paradoxus

6. Pulsus Paradoxus • Increased pulmonary venous capacitance • Increased left ventricular afterload • Leftward shift of the interventricular septum • Alterations in pulse oximetry tracings

7. Panel A: tracing during respiratory distress- pulsus paradoxus of 16 torr (RWV respiratory waveform variation) Panel B: tracing after treatment / mild respiratory distress- pulsus paradoxus of 8 torr Hartert T., Chest, 115:477, 1999

8. Criteria for ICU Admission • Severe respiratory symptoms/exam • Worsening respiratory symptoms/exam • Abnormal neurologic status • Increasing pC02 • Barotrauma • Past history of respiratory failure

9. Therapy First-line therapy Oxygen Inhaled 2 catecholamine Corticosteroids Ipratropium inhalation

10. Inhaled 2 Catecholamine • Albuterol- 2 selective bronchodilator of small and large airways (0.15mg/kg/dose) • 2 receptor polymorphism determining responsiveness, desensitization, and downregulation • Continuous (more rapid response/cost effective) (0.4-0.8mg/kg/hr up to 10-20mg/hr), intermittent (MDI vs nebulizer) • Side effects include tachycardia, tremor/ agitation, hypoxemia, hypokalemia, arrhythmia, hypotension • Consider subcutaneous epinephrine (0.01ml/kg 1/1000) acutely with poor aerosol delivery

11. Corticosteroids • Suppresses underlying inflammation by blocking proinflammation and activating antiinflammation at the level of gene transcription • Restores 2 receptor function by reversing desensitization and downregulation • Genetic polymorphism effects response • Onset begins in 2-4 hours, peaks ~ 6-8 hrs • Dose = solumedrol 2 - 4 mg/kg/day • Risk of myopathy, especially when also receiving paralytics

12. Ipratropium • Anticholinergic quaternary derivative of atropine • Inhibits cholinergic-mediated bronchospasm • Primarily effects larger bronchi • Use in conjunction with 2 bronchodilator • Most beneficial as multiple doses (250-500g Q20 min x3) in severe asthma

13. Therapy Second-line therapy Magnesium sulfate Heliox rhDNAse Theophylline Intravenous 2 catecholamine Intravenous ketamine

14. Magnesium sulfate • Direct inhibition of Ca-mediated smooth muscle constriction • Possibly useful to prevent hospitalization and treat impending respiratory failure • 25-75 mg/kg (max 2 gm) over 20 min • Advantage is lack of cardiac stimulation (tachycardia, 02 consumption) • Side effects include nausea, vomiting, facial flushing, hypotension, muscle weakness

15. Heliox • Indication: treatment of increased airway resistance in areas of turbulent gas flow (density-dependent) • Characteristics: decreased gas density, ideally requires 60-80% helium, no adverse effects, works immediately • Goal: “therapeutic bridge”, changing the biophysical characteristics of gas flow until other treatments (e.g. steroids) take effect or until the disease improves • Mechanisms: • with turbulent flow, heliox’s low gas density causes less airflow resistance and increased flow rate (decreased work of breathing, decreased ventilatory pressures, less gas trapping) • low gas density decreases the Reynolds number, which shifts some flow from turbulent to laminar • low gas density increases the C02 diffusion coefficient, improving C02 elimination • low gas density facilitates the delivery of inhaled medications into the tracheobronchial tree • Therapeutic targets: asthma, bronchiolitis, upper airway obstruction (e.g. croup, postextubation stridor)

16. rhDNAse • Recombinant deoxyribonuclease • Decreases the sputum viscosity by degrading the extracellular DNA released by neutrophils

17. Bronchial Cast

18. Aminophylline • Phosphodiesterase inhibitor used to be first-line therapy • Relaxes airway smooth muscle, improves diaphragm function, stimulates respiratory drive, increases catecholamine release, has antiinflammatory effect • Studies show uncertain beneficial effects • Low therapeutic index- side effects include gastrointestinal (nausea, vomiting, abdominal pain), neurologic (headache, agitation, seizures), cardiovascular (arrhythmias, hypotension, cardiac metabolic rate)

19. Intravenous 2 Catecholamine (terbutaline) • Direct systemic effect with increased catecholamine side effects (load 10g/kg, max 0.4-1.0mg, followed by 0.1-4.0g/kg/min, max 1.0mg/hr) • Serious risks include hypotension, arrhythmias, tachycardia, ischemia • Risks of intravenous terbutaline are much less than isoproterenol • Maintain adequate cardiac output and blood pressure

20. Intravenous Ketamine • Dissociative anesthetic • Increases catecholamines • Direct airway smooth muscle relaxation • Inhibits vagal tone • 0.5-2.0mg/kg/hr • Can be used as treatment with or without mechanical ventilation

21. Mechanical Ventilation • Avoid intubation if at all possible. Respiratory arrest is the only absolute indication (decide clinically, not from arterial blood gas). • Consider a trial of Bipap, if tolerated, before intubation • Use ketamine (propofol also has bronchodilatory properties), paralysis, cuffed endotracheal tube • Fluid bolus prior to intubation to prevent decreased cardiac output (decreased venous return) • Basic principles are to give adequate ventilation without barotrauma and with minimal dynamic hyperinflation • low minute ventilation (tidal volume, respiratory rate) • prolonged expiratory time/shortened inspiratory time • pressure-limited ventilation, limiting PIP to 35-40cmH20, Pplateau30cmH20, PEEP 0-5cmH20 • tolerate permissive hypercapnea (pH7.20) • sedation/paralysis (minimizes dysynchrony and C02 production) • monitor for dynamic hyperinflation/intrinsic PEEP • consider extrinsic PEEP (<intrinsic PEEP)