This document discusses the pathophysiology, clinical presentation, differential diagnosis, and management of acute severe asthma exacerbations requiring intensive care. Key points include: - Acute exacerbations are usually due to infectious, allergic, or irritant triggers and poor medication compliance. Presentation varies but may include accessory muscle use, tachycardia, tachypnea, and limited speech. - Management involves oxygen, nebulized beta-agonists, systemic corticosteroids, and possibly magnesium sulfate or heliox. Noninvasive positive pressure ventilation can sometimes avoid intubation. - Indications for mechanical ventilation include impending respiratory failure, mental status changes, and hypoxemia not responding to other therapies.

1. Asthma in the
Intensive Care Unit
Sean M. Caples
Assistant Professor of Medicine
College of Medicine
Mayo Clinic

2. • Definitions
• Pathophysiology
• Differential Diagnosis
• Clinical Features
• Management
Overview

3. Acute exacerbation of asthma
Pathophysiology
15% develop sudden-onset (<3 to 6 hrs)
– Allergen or irritant
– Inhaled drugs (crack cocaine)
– NSAIDS
– Stress
– Idiopathic
• Airway neutrophils; bronchoconstriction

4. Most cases are slow-onset
• Infectious, allergic, irritant triggers
• Autopsy: airway mucus plugging /
obstruction; generalized airway thickening
• Poor compliance with outpatient asthma
meds
Pathophysiology

5. Small, controlled trial of etanercept
Berry, NEJM, 2006

6. What Constitutes A Severe Case of
Asthma?
• Not based solely on organ impairment
• According to consensus guidelines, ≥ 1 of the
following:
– Accessory muscle use
– HR > 110
– Resp rate > 25-30
– Pulsus paradoxus > 25 mmHg
– Limited ability to speak
– FEV1 < 50% predicted (or peak flow)

7. The Response to β-agonists

8. Shortcomings
• Their presence or absence do NOT predict
outcomes
• About half of those considered to have “life-
threatening attacks” were discharged from the
emergency department
• Severity may best be based upon outcomes
rather than presentation

9. Differential Diagnosis
(Misdiagnosis: 8 – 25% of admissions)
• COPD
• Bronchiectasis
• Endobronchial /
tracheal pathology
• Foreign body
• Cardiogenic
pulmonary edema
• PE
• Pneumonia
• Glottic dysfunction

10. ICU Admissions
• About 20 papers over 25 years
• Criteria for admission rarely stated
• Wide range (3 to 70%) reported on need
for ventilatory assistance; estimated about
one-third

11. • 2.7% death rate
• 8.1% in those intubated
• In the USA, minorities living in large cities
are disproportionately at risk of morbidity
and mortality

12. Clinical Features
• No sign or symptom is uniformly present
• Wheezing absent 5% (a concerning
finding)
• Dyspnea absent up to 20% of the time

13. Impaired ventilatory response to hypoxia
associated with near-fatal cases
P0.1-- airway occlusion pressure 0.1 second
after the start of inspiration against an
occluded airway

14. Impaired perception of dyspnea
associated with near-fatal cases

15. Pathophysiology
Increased airway resistance (non-uniform)
Diminished flow
Air-trapping / Hyperinflation
Increased work of breathing
Changes in elastic recoil
(Muscle weakness / fatigue not common)

16. • Mild hypoxemia due to V/Q mismatch
• Slow to resolve
• Marked hypoxemia is uncommon

17. Hyperinflation
• Quantitated only in small studies
• Residual volume 400% normal
• Functional residual capacity 200% normal
• Total lung capacity slightly increased

18. Hyperinflation
Auto-PEEP
– Increases inspiratory threshold for airflow
– Decreased radius of curvature puts
diaphragm at mechanical disadvantage
– At some point, deflation no longer passive—
accessory expiratory muscles

20. Measure auto-PEEP with
end-expiratory pause

21. Cardiovascular Consequences
• Decreased preload
• Increased afterload
• Pulsus paradoxicus
Decreased cardiac output

22. Blood Gases
• Hypocapnia
• Mild hypoxemia
• Respiratory alkalosis

23. Blood Gases
• CO2 retention in about 10%
– Modest: 10-15 mmHg over normal
– Indicates FEV1 < 20%
– May recover without intubation
• Normocarbia: 15 to 20% cases
– FEV1 20 to 30%
– Impending respiratory failure

24. Blood Gases
• Metabolic Acidosis
– Compromised cardiac output—lactic acidosis
– Increased oxygen consumption of respiratory
muscles
– Aggressive sympathomimetic use

25. Management
• Pharmacologic agents
• Mechanical ventilation
– NPPV
– Invasive
• Risks
• Beside monitoring
• Adjusting the knobs

26. Oxygen
• To maintain saturations >90%
• Enhances oxygen delivery to peripheral
tissues (including respiratory muscles)
• Reverses hypoxic pulmonary
vasoconstriction

27. β-Agonists (Short-acting)
• With monotherapy, two-thirds of patients in Emerg Dept
are discharged
• 2.5mg nebulized every 20 minutes (can be given
continuously)
• Tremor and tachycardia usually mild
• Subcutaneous epinephrine or terbutaline of little added
benefit

28. Additive effects of ipratropium bromide
(anticholinergic) in more severe disease with
prolonged symptoms

29. The effects of ipratropium
are not always replicated
in other studies

30. Systemic Corticosteroids
• Conflicting results over whether these
result in physiologic changes in first 6 hrs
• May improve outcome (rates of
hospitalization) when used early

31. Cochrane Systematic Review:
Reduces Hospitalization, especially in those with more
severe disease, not already on steroids

32. 9 Trials have compared dose of drug in
severe asthma: No evidence for an Optimal
(Or higher) Dose

33. National Institutes of Health (NIH)
Expert Consensus, 2002
• 120 – 180 mg/day (prednisone, methylpred,
prednisolone) in 3 or 4 divided doses for 48 hours then
60 – 80mg/day until peak flows improve
• Oral dosing probably as good as IV if no GI upset and
intubation not planned
• Inhaled corticosteroids may have some added benefit

34. Theophylline / Methylxanthines
• No positive impact on multiple outcomes (peak flow,
hospitalization) dependent of use of steroids
• May increase adverse effects: GI, tremor, arrhythmia
• May be some benefit in children

35. Magnesium Sulfate
• Conflicting study results
• May have bronchodilatory properties via effects on
smooth muscle
• IV MgSO4 (2 to 10gm) modestly improves spirometry in
those with severe asthma but no impact found on
admission rates
• Adverse effects IV: flushing, hypotension

36. Nebulized MgSO4 may have additive bronchodilatory
properties when given with β-agonist
Hughes, Lancet, 2003

37. Leukotriene Modifiers
IV Montelukast not available in USA
Camargo, AJRCCM, 2003**Corticosteroid use not controlled for

38. Heliox
• Mixture of oxygen and helium (minimum 60% Helium)
• Reduced density promotes more efficient gas flow
characteristics
• Good for upper airway obstruction
• May increase flow rates and pulsus paradoxicus, but
available trials don’t support routine use
• In theory, may

39. Heliox may improve delivery of aerosolized
bronchodilators
Kress, AJRCCM, 2002

40. Antibiotics
2002 Expert Consensus: Not indicated in
the absence of evidence for pneumonia or
sinusitis

41. Mechanical Ventilation

42. NPPV
POSITIVE AIRWAY PRESSURE MAY:
• overcome inspiratory threshold imposed by auto-PEEP
• Improve gas exchange
• Enhance delivery of bronchodilators to peripheral airways
• Bi-level may be more comfortable than CPAP in the face of
expiratory delay

43. NPPV
• A single randomized, placebo controlled trial (used sham
NPPV mask set at IPAP 1 / EEP 1); not fully blinded
• Use of 3 hours of Bi-level in the ED in those with severe
asthma (FEV1 < 40%), in addition to standard therapy
• Improved FEV1 and rate of hospitalization
Soroksky, Chest, 2003

45. Invasive Mechanical Ventilation
Absolute indications:
mental status changes
impending respiratory arrest
Larger diameter tube preferred to minimize
resistance to airflow (≥ 8.0)
About 4% of hospital admissions

46. Post-intubation hypotension
• Common: at least one-third
• Contributors
– Effects of sedation on vascular tone
– Hypovolemia
– Worsening hyperinflation
– Tension pneumothorax (barotrauma)

47. Ventilator Settings
Key Concepts
• Peak airway pressures
– a function of flow characteristics
– likely to be elevated early
– can be aggravated by high inspiratory flow rates, dried
secretions in tube, dys-synchrony / biting
• Plateau pressure measured with end-inspiratory breath
hold
• Threshold level (i.e. < 30 to 35 cm H2O) not consistently correlated
with outcomes
• Give adequate exhalation time
– Respiratory rate / minute ventilation, flow rates

48. Plateau pressure
Peak pressure
Auto-PEEP measured here
Reasonably reliable in
the non-paralyzed patient

49. Lower inspiratory flow rates (100 L/min to 40) decrease expiratory time
causes increase in end expiratory volume (VEE)

51. • No consensus on ventilator mode
– AC vs. SIMV
– Probably best to avoid pressure control early since, with high
airway pressures, minute ventilation will be erratic
– Apply extrinsic PEEP during spontaneous modes to overcome
intrinsic PEEP (not helpful during AC)
• Risk-benefits of sedation / paralysis
– Daily interruption
• Low tidal volume ventilation (6 to 8 ml/kg)
• Permissive hypercapnia

52. Permissive Hypercapnia
• A “consequence” of low tidal volume ventilation
• May have therapeutic role (anti-inflammatory, anti-
oxidative) in research models
• Slow rise in PaCO2 well tolerated

53. Laffey et al, Lancet 1999

54. • Little data to support buffering (bicarbonate or THAM)
but it is probably not uncommon
• Theoretical risk of worsening CO2 with Bicarbonate
HCO3
- + H+ H2CO3 H2O + CO2
(THAM is a non-bicarbonate buffer)
• Might avoid hypercapnia in brain injury and myocardial
depression

55. One proposed algorithm
Corbridge and Corbridge

56. Use of Bronchodilators with Ventilator
• NO controlled trials to support recommendations
• MV patients tend to have higher dose requirements (may relate to
their disease or to technical considerations)
• MDI use
– Activate close to circuit near patient
– Use a spacer
– Temporarily turn humidifier off
– Temporarily turn down flow rate to reduce turbulence

57. Refractory cases
• Ketamine
– Sedative, analgesic, bronchodilator
• General anesthetics
– Halothane, enflurane
– High risk; very short acting
• Heliox