Status Asthmaticus

1. Status Asthmaticus

2. Pathophysiology • Asthma is primarily an inflammatory disease Smooth muscle spasm Airway edema Mucous plugging

3. Inflammatory cytokines • Activated mast cells and lymphocytes produce pro-inflammatory cytokines (histamine, leukotrienes, PAF), which are increased in asthmatics’ airways and responsible for inflammatory response

4. Irritable and damaged airway

5. Airway • The irritable and inflamed airway is susceptible to obstruction triggered by • Allergens • Infections • Irritants including smoke • Exercise • Emotional stress • GE reflux • Drugs • Other factors

6. Lung mechanics • Hyperinflation • Obstructed small airways cause premature airway closure, leading to air trapping and hyperinflation • Hypoxemia • Inhomogeneous distribution of affected areas results in V/Q mismatch, and even shunt

7. Autonomic nervous system Bronchodilation Bronchoconstriction Sympathetic Circulating catecholamines stimulate ß-receptors - • Vagal signals stimulate bronchodilating M2 - receptors • Vagal signals stimulate bronchoconstricting M3-receptors Parasympathetic Nonadrenergic-noncholinergic (NANC) Release of bronchodilating neurotransmitters (VIP, NO) • Release of tachykinins (substance P, neurokinin A)

8. Severe airflow obstruction Incomplete exhalation Increased lung volume Increased elastic recoil pressure Expanded small airways Increased expiratory flow Decreased expiratory resistance Decreased expiratory resistance Compensated: Hyperinflation, normocapnia Worsening airflow obstruction Decompensated: Severe hyperinflation, hypercapnia

9. Presentation Audible wheezes : reasonable airflow • Cough • Wheezing • Increased work of breathing • Anxiety • Restlessness • Oxygen desaturation “Silent chest” : ominous!

10. Cardiopulmonary interactions • Left ventricular load • Spontaneously breathing children with severe asthma have negative intrapleural pressure (as low as -35 cmH2O) during almost the entire respiratory cycle • Negative intrapleural pressure causes increased left ventricular afterload, resulting in risk for pulmonary edema

11. Cardiopulmonary interactions • Right ventricular load • Hypoxic pulmonary vasoconstriction and lung hyperinflation lead to increased right ventricular afterload

12. Cardiopulmonary interactions • Pulsus paradoxus • P. paradoxus is the clinical correlate of cardiopulmonary interaction during asthma. It is defined as exaggeration of the normal inspiratory drop in systolic BP : normally < 5 mmHg, but > 10 mmHg in pulsus paradoxus. Normal P. paradoxus Inspir Inspir Expir Expir

13. Pulsus paradoxus correlates with severity • All patients who presented with FEV1 of < 20% (of their best FEV1 while well) had pulsus paradoxus

14. Cardiopulmonary interactions Negative intrapleural pressure Hyperinflation Altered hemodynamics Pulmonary edema Pulsus paradoxus Hypotension

15. Metabolism Increased work of breathing V/Q mismatch Dehydration Hypoxia Lactate Ketones Metabolic acidosis

16. Assessment • Findings consistent with impending respiratory failure: • Altered level of consciousness • Inability to speak • Absent breath sounds • Central cyanosis • Diaphoresis • Inability to lie down • Marked pulsus paradoxus

17. Chest X-Ray • Indications: • Patient is intubated/ventilated • Suspected barotrauma • Suspected pneumonia • Other causes for wheezing are being suspected

18. ABG? • Early status asthmaticus: hypoxemia, hypocarbia • Late: hypercarbia • Decision to intubate should not depend on ABG, but on clinical assessment • End tidal CO2 should be measured in intubated patients

19. Oxygen • Deliver high flow oxygen, as severe asthma causes V/Q mismatch • Oxygen will not suppress respiratory drive in children with asthma

20. Fluid Goals • Judicious use of IV fluid necessary • Most asthmatics are dehydrated on presentations - rehydrate to euvolemia • Overhydration may lead to pulmonary edema • SIADH may be seen in severe asthma

21. Antibiotics • Most infections precipitating asthma are viral • Antibiotics are not routinely indicated ?

22. ß-Agonists • ß-receptor agonists stimulate ß2-receptors on bronchial smooth muscle and mediate muscle relaxation • Epinephrine • Isoproterenol • Terbutaline • Albuterol Significant ß1 cardiovascular effects Relatively ß2 selective

23. ß-Agonists • Less than 10% of nebulized drug reach the lung under ideal conditions • Drug delivery depends on • Breathing pattern • Tidal volume • Nebulizer type and gas flow

24. ß -Agonists • Continuous nebulization superior to intermittent nebulization • More rapid improvement • More cost effective • More patient friendly

25. ß -Agonists • Dosage • Intermittent nebulization • 12-25 mg (0.25 - 0.5 ml of 5% solution), dilute with NS to 3 ml • High dose: use undiluted solution • Continuous nebulization • 10-60 mg/hr • High dose: use undiluted solution (≈ 60 mg/hr)

26. ß -Agonists • Intravenous ß - Agonist • Consider for all ICU patients with severe air flow limitation • Terbutaline is IV ß-agonist of choice in US • Dosage: 0.1 - 10 mg/kg/min

27. ß -Agonists • Side effects • Tachycardia • Agitation, tremor • Hypokalemia • Nausea

28. ß -Agonists • Cardiac side effects • No significant cardiovascular toxicity with IV terbutaline

29. Steroids • Asthma is an inflammatory disease • Steroids are a mandatory element of first line therapy

30. Steroids • Methylprednisolone 2 mg/kg x1, then 1-2 mg/kg q 4-6°

31. Steroids • Significant side effects • Hyperglycemia • Hypertension • Acute psychosis • Unusual or unusually severe infections

32. Intubation/Ventilation • Absolute indications: • Cardiac or respiratory arrest • Severe hypoxia • Rapid deterioration in mental state • Respiratory acidosis does not mandate intubation

33. Why hesitate to intubate the asthmatic child? • Tracheal foreign body aggravates bronchospasm • Positive pressure ventilation increases risk of barotrauma and hypotension • > 50% of morbidity/mortality during severe asthma occurs during or immediately after intubation Zimmerman JL. Crit Care Med 1993;21(11):1727-30

34. Intubation • Preoxygenate, decompress stomach • Sedate (consider ketamine) • Neuromuscular blockade (to avoid large swings in airway/pleural pressure) • Rapid orotracheal intubation (use cuffed tube)

35. Immediately after Intubation • Expect hypotension, circulatory depression • Allow long expiratory time • Avoid overzealous manual breaths • Consider volume administration • Consider pneumothorax • Consider endotracheal tube obstruction (++ secretions)

36. Mechanical ventilation • Positive pressure ventilation worsens hyperinflation/risk of barotrauma • Thoughtful strategies include: • Pressure-limited ventilation • Permissive hypercapnia • Low resp rates 8-12/min

37. Ketamine • Dissociative anesthetic with strong analgesic effect • Direct bronchodilating action • Useful for induction (2 mg/kg IV) as well as continuous infusion (0.5 - 2 mg/kg/hr) • Induces bronchorrhea, emergence reaction

38. Inhalational anesthetics • Halothane, isoflurane have bronchodilating effect • Halothane may cause hypotension, dysrhythmia • Requires scavenging system, continuous gas analysis

39. Magnesium • Smooth-muscle relaxation by inhibition of calcium uptake (=bronchodilator) • Dosage recommendation: 25 - 75 mg/kg i.v. over 20 minutes

40. Helium - Oxygen (Heliox) • Helium lowers gas density (if at least 60% helium fraction) • Reduces resistance during turbulent flow • Renders turbulent flow less likely to occur • May augment air movement in asthma

41. Bronchoscopy • Marked mucus plugging may render bronchodilating and anti-inflammatory therapy ineffective • “Plastic bronchitis” has been described in asthmatic children • Combined bronchoscopy/lavage has been used in desperately ill asthmatic children

42. Summary • Severe asthma is a major problem is children • Aggressive treatment with ß-agonist, steroids and is warranted in the sick-appearing child • Avoid intubation if possible • Mechanical ventilation may worsen bronchospasm and hyperinflation • Use low morbidity approach to mechanical ventilation