1) Mechanical ventilation may be required for severe, life-threatening asthma to prevent respiratory failure and death. Non-invasive ventilation can be tried initially but intubation may be needed. 2) Permissive hypercapnia is recommended to avoid additional lung injury from mechanical ventilation, allowing CO2 levels up to 90 mmHg if oxygenation is adequate. Sedation and sometimes paralysis are used while ventilating to reduce lung injury. 3) Weaning from mechanical ventilation begins with spontaneous breathing trials once the patient's CO2 levels normalize at a low ventilation rate and airway resistance decreases. Rescue therapies like ECMO may be required in rare cases that do not respond to usual treatments.

1. Mechanical Ventilation for
Severe Asthma
Niall D. Ferguson, MD, FRCPC, MSc
Assistant Professor
Interdepartmental Division of Critical Care
Medicine
University of Toronto

2. Asthma Death Rates
Modified from TRENDS IN ASTHMA
MORBIDITY AND MORTALITY,
ALA
• Number of Deaths in 2004 3780
• Age Adjusted Mortality in 1999 1.7 /
100,000
• Age Adjusted Mortality in 2004 1.3 /
100,000
• Reduction in Mortality
 18.8% decrease compared to 1999

3. Life Threatening Asthma
• Clinical
 inability to speak due to severe dyspnea
 altered mental status
 inter-costal retractions
 worsening fatigue
 absence of wheezing
 bradycardia
 absence of pulsus paradoxus

4. Life Threatening Asthma
• Physiologic
 PCO2 of > 42 µµΗγ
 PEF or FEV1 <20 % predicted or
personal best

5. Pathophysiology
Different patterns of fatal asthma Severe asthma Papiris 2002
Scenario of asthma death
Variable Type 1 Type 2
Time course
Subacute worsening (days).
'Slow onset – late arrival'
Acute deterioration (hours).
'Sudden asphyxic asthma'
Frequency 80–85% 15–20%
Airways Extensive mucous plugging More or less 'empty' bronchi
Inflammation Eosinophils Neutrophils
Response to
treatment
Slow Faster
Prevention Possible (?)

6. Cause of Death
• Type 1
 hypercapnic respiratory failure
 mixed acidosis
 asphyxia
 complications of mechanical ventilation,
such as barotrauma and ventilator-
associated pneumonia

7. Cause of Death
• Type 2
 rapidly severe hypercapnic respiratory
failure with combined metabolic and
respiratory acidosis
 asphyxia

8. Risk Factors for Death from Asthma
• Asthma history
 Prior severe exacerbation (intubation or ICU admission)
 Two or more hospitalizations for asthma in the past
year
 Three or more ED visits for asthma in the past year
 Hospitalization or ED visit for asthma in the past
month
 Using >2 canisters of SABA per month
 Difficulty perceiving asthma symptoms or severity of
exacerbations
 Other risk factors:
 lack of a written asthma action plan
 Sensitivity to Alternaria

9. Risk Factors: Death from Asthma
• Social history
 Low socioeconomic status or inner-city
residence
 Illicit drug use
 Major psychosocial problems
• Co-morbidities
 Cardiovascular disease
 Other chronic lung disease
 Chronic psychiatric disease

10. Differential Diagnosis
• Vocal cord dysfunction
• COPD exacerbation
• Congestive heart failure
• Pulmonary embolism
• Mechanical obstruction of the airways
(benign and malignant tumors)
• Pneumothorax
• Pneumonia

11. Asthma Severity Assessment
Symptoms Severe Respiratory
Arrest Imminent
Breathless At rest, sits
upright
Talks in Words
Alertness Usually agitated Drowsy or
confused

12. Asthma Severity Assessment
Signs Severe Respiratory
Arrest Imminent
Respiratory rate >30/minute
Accessory
muscles
Usually Paradoxical
diaphragmatic
movement
Wheeze Usually loud Absent
Pulse >120 Bradycardia

13. Asthma Severity Assessment
Signs Severe Respiratory
Arrest Imminent
Pulsus
paradoxus
>25 mmHg Absence re:
fatigue
PEF/FEV1 <40 percent <25 percent
Pa02 / PaCO2 <60 mmHg /
>42 mmHg
SaO2 <90 percent

14. Medical Management of Life
Threatening Asthma
• Oxygen
 maintain a SaO2 >90 percent
• Inhaled short acting B2 agonists
(SABA)
 4–8 puffs every 20 minutes up to 4
hours, then every 1–4 hours as needed
• Ipratropium bromide
 8 puffs every 20 minutes as needed up
to 3 hours

15. Medical Management of Life
Threatening Asthma
• Systemic corticosteroids
 40–80 mg/day in 1 or 2 divided doses
until PEF reaches 70% of predicted or
personal best
• Subcutaneous epinephrine
 0.3–0.5 mg every 20 minutes for 3 doses
sq

16. Medical Management of Life
Threatening Asthma
• Magnesium Sulphate (I.V.)
 2 grams in adults and 25–75 mg/kg up to 2
grams in children
• Heliox
 consider when using nebulizer Rx
• Methylxanthines
 increases the frequency of adverse effects
• Antibiotics
 evidence of pneumonia or sinusitis

17. Monitoring during treatment
• Serial Measurements of Lung Function
 Failure of treatment to improve predicts a more severe
course and the need for hospitalization
• Lab Studies
 Hypercapnia, metabolic acidosis, CBC, electrolytes
• Chest Radiography
 exclude complications such as lobar atelectasis,
pneumothorax, pneumomediastinum,
pneumopericardium, or alternate diagnosis such as
congestive heart failure and pneumonia
• Electrocardiogram
 signs of right heart strain

18. Severe Life Threatening
Asthma
ICU/Mechanical Ventilation

19. Criteria for ICU admission
• PaCO2 > 45 mmHg
• impaired consciousness
• respiratory arrest
• significant hypoxia (transcutaneous oxygen
saturation <92%) with severe airway
obstruction
• ICU admission may also be indicated for
respiratory arrest, altered mental status,
myocardial injury, and when there is need
for frequent nebulizer treatments.

20. Pulmonary Hyperinflation
• Increase in functional residual capacity
 Can be as much as 2x normal
• Critical limitation of the expiratory flow:
 Reduced driving forces of the expiratory flow
 Low pulmonary recoil
 High outward recoil of the chest wall generated by
the persistent activation of the inspiratory muscles
 Increased resistance to airflow
 Severely reduced airway caliber
 Expiratory narrowing of the glottic aperture

21. Pulmonary Hyperinflation
• Increase in the time constant of the
respiratory system (prolonged expiration)
• Inspiration starts before static
equilibrium is reached (PEEPi)
• PEEPi depends on:
 Vt
 Time constant of the respiratory system
 RR (shortening of the expiratory time)

24. Non-Invasive Ventilation
• Mask CPAP:
 Reduce transdiaphragmatic pressure
 Improve comfort
 Reduce hemodynamic effects (pulsus
paradoxus)
 May re-expands atelectasis
 May decreases airflow obstruction
J Crit Care 1993;8:87
Am Rev Respir Dis 1982;126:812
Chest 1996;110:767
Chest 2003;123:1018

25. Non-Invasive Ventilation
• Improve gas exchange, alleviate
respiratory distress, prevent
exhaustion and improve
hemodynamics.
• In selected patients NIV can shorten
the attack, improve lung function
and prevent ICU admission.
J Crit Care 1993;8:87
Am Rev Respir Dis 1982;126:812
Chest 1996;110:767
Chest 2003;123:1018

26. Mechanical Ventilation
• Life saving intervention needed by
a small minority of patients!
• Fewer deaths with controlled
hypoventilation compared with
ventilation in which carbon dioxide
levels were normalized
 historical cohorts and case series have
reported mortality rates of 7.5­23%

27. Mechanical Ventilation
• Mechanical ventilation is associated with
hypotension, barotrauma, infection, and
myopathy, especially when prolonged
paralysis is required with muscle
relaxants and systemic corticosteroids.
• Adverse effects reported in one
retrospective study of 88 episodes of
mechanical ventilation were hypotension
(20%), barotrauma (14%), and
arrhythmias (10%).

28. Intubation
• < 1% of asthmatics require
intubation for mechanical
ventilation.
• Rapid sequence intubation is the
method of choice
• Crucial objective is to prevent any
further increase in lung
hyperinflation

29. Intubation
• Absolute indications:
 Respiratory arrest
 Coma
• With maximum medical therapy:
 Worsening pulmonary function tests
 Decreasing PaO2
 Increasing PaCO2
 Progressive respiratory acidosis
 Declining mental status
 Increasing agitation

30. Intubation
• Post-intubation hypotension
 25% to 35% of patients after
intubation
 loss of vascular tone due to sedation,
hypovolemia, tension pneumothorax,
or hyperinflation
• Barotrauma was found to
complicate status asthmaticus in 14
to 27% of patients

31. Mechanical Ventilation
• Initial ventilator settings
 Low RR (8-12 breaths/min)
 Small Vt 6-8 cc/kg of predicted body weight
 High peak inspiratory flow (70-100 L/min)
 Prolonged expiratory time (I:E 1:2-1:3)
 PEEP to compensate for PEEPi if patient is
breathing spontaneously (80% of auto-
PEEP)
 ZEEP if patient is sedated, paralyzed and on
controlled mechanical ventilation to
maximize exhalation.

32. Permissive Hypercapnia
• PaCO2 up to 90 mm Hg
• Generally tolerated when adequate
oxygenation is achieved
• The main contraindication is
intracranial disease
• Should be avoided in patients who
have already suffered an anoxic
brain injury and cerebral edema
following cardiorespiratory arrest

33. Mechanical Ventilation
• Assessing lung inflation
 The volume at end-inspiration, termed
Vei, is determined by collecting
expired gas from total lung capacity to
functional residual capacity during 40
to 60 seconds of apnea. A Vei greater
than 20 mL/kg has been correlated
with barotrauma.
• Pplat < 30
• PEEPi Am Rev Respir Dis 1992;146:607.

34. Sedation
• Propofol for short term intubation
• Midazolam for prolonged
ventilation
• Morphine or fentanyl depending on
hemodynamics
 Morphine can cause histamine release

35. Sedation and paralysis
• Ketamine
 intravenous anesthetic with sedative,
analgesic, and bronchodilating
properties
 indirectly stimulates catecholamine
release and, in a dose of up to 2 mg/kg,
will produce bronchodilation in the
critically ill asthmatic

36. Paralysis
• Indication:
 When safe and effective mechanical
ventilation cannot be achieved by
sedation alone
• Short-term muscle paralysis

37. Medical Rx with MV
• Bronchodilators
 Higher drug dosages are required and
the dosage should be titrated to
achieve a fall in the peak-to-pause
airway pressure gradient
• General anesthetics
 Halothane and enflurane are general
anesthetic bronchodilators that can
acutely reduce peak pressure and
PaCO2 Crit Care Med 2002; 30:477–480
Intensive Care Med 1990; 16:104-107
Chest 1994;106;1401-1406
CHEST 2003; 123:891–896

38. Heliox
• Heliox, an 80:20 mixture of helium and oxygen,
can be considered in patients with respiratory
acidosis who fail conventional therapy.
• Helium is a low-density, inert gas that lowers
airway resistance and decreases respiratory work.
• Significant improvement may be noted within 10-
20 minutes of initiating therapy in the asthmatic
with severe bronchospasm.

39. Weaning from MV
• Extubation
 spontaneous breathing trial once:
 PaCO2 normalizes at a minute ventilation
that is less than 12 LPM
 airway resistance is less than 20 cm
H2O/l
 the patient follows commands, and
 neuromuscular weakness has not been
identified

40. Rescue therapies
• ECLS
 ECMO
 NovaLung
Am J Emerg Med 1997;15:566-569
Chest 1993;103:1651-54

41. Rescue therapies
• Novalung
 pumpless low resistance gas exchange
membrane reliant on arteriovenous
shunt and a sweep flow oxygen for
membrane diffusion of oxygen and
carbon dioxide.
 Arteriovenous and venovenous
 Patients: rescue therapy for patients
with refractory bronchospasm, who
failed all usual interventions, have
arterial PaCO2 >110 mmHg and have
severe acidosis.
Crit Care Med 2007; 35:945–948

42. Novalung
• Reasons
 Bronchospasm in acute severe asthma is
usually reversible, iLA should only be required
for short periods of time
 Novalung is highly effective at CO2 clearance.
Usually Oxygenation is not a major problem
 Patients with acute severe asthma have have
sufficient cardiac output and blood pressure
to maintain arteriovenous shunt across the
membrane
• Cons
 Large bore arterial and venous cannulation
 Systemic anticoagulation

43. Life Threatening Asthma
• Be on the alert in order to identify
high risk patients
• Be ready to initiate life saving
treatments, possibly even including
inhaled anaesthetics and NovaLung
• Try your best to prevent
complications

44. n.ferguson@utoronto.c
a
October 20-22, 2009
Metro Toronto Convention Centre