Treating Life Threatening Asthma

1
Treating Life Threatening Asthma

• Toni Petrillo-Albarano, MD
• Division of Pediatric Critical Care
• Childrens Healthcare of Atlanta

2
Asthma Increased Severity Hospitalization
Increased 28
-MMWR, CDC
3
Asthma Increased Severity Death 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
Bronchospasm
Mucous Hypersecretion
Mucosal edema
Hyperinflation
Uneven ventilation
Atelectasis
deadspace
compliance
Abnormal V/Q
alveolar hypoventilation
WOB
8
Status Asthmaticus Oxygen

• Relative hypoxemia
• V/Q mismatch
• hypoventilation
• Hypoxemia bronchoconstriction
• ? agonists impair hypoxic pulmonary
  vasoconstriction shunt
• Oxygen to keep pulse ox gt 92

9
Status Asthmaticus Beta2 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 gt 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 Asthmaticus Isoproterenol (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 lt 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
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Status AsthmaticusEffect of Inhaled Ipratropium







p lt .05
-Schuh, J Peds, 1995
18
Ipratropium Effect with FEV1 lt 30







-Schuh, J Peds, 1995
p lt .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
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Status Asthmaticus Inhaled Corticosteroids

• SI asthma has several characteristic features
• severe asthma with persistent respiratory
  symptoms
• frequent nighttime symptoms
• chronic airflow obstruction (FEV1 lt70 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 Asthmaticus Inhaled Corticosteroids
Acute 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

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Status Asthmaticus Inhaled Corticosteroids
Acute 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 Asthmaticus Inhaled Corticosteroids
Acute 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 OByrne 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

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Status AsthmaticusIV Theophylline

• 21 hospitalized children
• Standard nebulized albuterol, steroids
• Randomized
• IV Aminophylline load/infusion
• OR
• Saline placebo

-Carter, J Peds, 1993
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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

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Status Asthmaticus Ketamine

• Dissociative anesthetic
• Direct bronchodilator
• Potentiates catecholamines
• Bronchorrhea
• Other side effects
• tachycardia
• BP

33
Status Asthmaticus Ketamine

• 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 Asthmaticus Ketamine 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 Asthmaticus Ketamine 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 Asthmaticus Magnesium 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 Asthmaticus Magnesium Sulfate

• 31 children (6-18 yrs) in ER
• Asthma exacerbation
• PEFR lt 60 after albuterol
• Randomized
• MgSO4 25 mg/kg
• OR
• Saline

-Ciarallo, J Peds, 1996
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Status AsthmaticusMagnesium Sulfate





p lt .05
-Ciarallo, J Peds, 1996
39
Status Asthmaticus Magnesium Sulfate





p lt .05
-Ciarallo, J Peds, 1996
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Status Asthmaticus Magnesium 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 Asthmaticus Leukotriene 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 55260-5)
• 160 mg Po Zafirlukast improved ER outcomes ( Ann
  Emerg Med 2000 35S10

42
Status AsthmaticusHelium - Oxygen (HELIOX)

• Blend of 8020 heliumoxygen
• 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

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Status AsthmaticusHelium - Oxygen (HELIOX)

• Major effects to reduce resistance
• Reduces turbulence
• Used in upper airway obstruction
• Improved pulsus paradoxus, PEFR in adult
  asthmatics

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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

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Response to Inhaled Anesthetics
pCO2
PIP
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Status Asthmaticus Mechanical Support

• BiPAP
• Intubation/Mechanical Ventilation
• Extracorporeal Life Support

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Status AsthmaticusNon invasive Ventilation

• Positive-pressure by nasal mask (BiPAP)
• Potential benefits
• airway stenting
• improve V/Q match
• CPAP improved hypoxemia in 8 asthmatic children

52
Status AsthmaticusNon invasive Ventilation

• 26 children ( 7.2 years) in PICU
• 19/26 managed without intubation
• RR, HR, SaO2
• 7/26 intubated
• 11/26 BiPAP held
• Efficacy remains uncertain

-Teague, Lang, et al, ATS, 1998
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Status AsthmaticusNon invasive Ventilation

• Beers et al immediate improvement in subjects'
  clinical status upon initiation of BiPAP, with
  77 showing a decrease in respiratory rate,
  averaging 23.6 (range, 4-50), and 88 showing
  an improved oxygen saturation, averaging 6.6
  percentage points (1-28 percentage points). There
  were no adverse events due to the use of BiPAP.

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Status Asthmaticus Nitric Oxide

• Smith et al showed that FENO measurements provide
  a useful guide about whether benefits will be
  obtained from a trial of ICS treatment.
• the response to inhaled fluticasone for 4 weeks
  was significantly greater than placebo and
  occurred predominantly in the ? of subjects whose
  FENO was greater than 47 ppb
• In the absence of high FENO levels, a response to
  steroid was much less likely

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Status Asthmaticus Nitric Oxide

• Exhaled nitric oxide (FENO) surrogate marker for
  eosinophilic airway inflammation.
• FENO may be used to guide steroid requirements
• High FENO levels may be used to predict likely
  benefits with inhaled corticosteroid (ICS)
• repeated FENO measurements improve the
  cost-effectiveness of ICS therapy when used to
  guide dose requirements

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Status AsthmaticusIntubation

• Usually last resort
• Potential MM
• Mortality rate
• in adults 0 - 40
• in children 0 - 5
• 24-33 of PICU admissions required mechanical
  ventilation (very high?)

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Status AsthmaticusIntubation

• Wear Depends ?!
• Intubation by MD with experience
• Have volume ready hypotension due to ed
  intrathoracic pressure

58
Status AsthmaticusIntubation

• Best done semi-electively
• earlier rather than later
• Drugs of choice
• Atropine
• Ketamine/Midazolam
• Succinylcholine

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Status AsthmaticusMechanical Ventilation

• GOALS
• Rest inspiratory muscles
• Protect airway
• Provide adequate gas exchange NOT normal exchange
• Avoid barotrauma, catastrophe

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Status AsthmaticusMechanical Ventilation
Indications

• Coma
• Respiratory or cardiac arrest
• Cyanosis and hypoxemia on O2
• PaCO2 greater than 50 and rising gt 5mmHg/hr
• Deteriorating mental status
• Minimal chest movement/air exchange
• Pneumothorax

Absolute
Relative
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Status AsthmaticusMechanical Ventilation

• Key approach permissive hypercapnia
• (controlled hypoventilation)
• tolerate pCO2 to keep pH gt 7.20 - 7.25
• prolonged expiratory time
• rate, inspiratory time
• tidal volume
• PEEP auto-PEEP

62
Status Asthmaticus Extracorporeal Membrane
Oxygenation

• Veno-venous bypass for life support in asthma
  unresponsive to all other therapy
• Membrane lung extremely efficient at CO2
  clearance, low-flow
• Allows for bronchoscopy

63
Status Asthmaticus Extracorporeal Membrane
Oxygenation

• 60 pediatric patients
• pCO2 at cannulation 37-284 mmHg
• Maximal therapy
• 83 survival
• 7 here who all survived without sequelae

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Therapies NOT Recommended

• Antibiotics
• Empiric, aggressive hydration
• Chest PT
• Mucolytics
• Sedation??

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Evidence-Based Guidelines Report Card

• A GOOD evidence to recommend for USE of
• treatment
• B FAIR evidence to recommend for USE
• C POOR evidence to support
• recommendation, but USE recommended
• on other grounds
• D FAIR evidence to recommend EXCLUSION
• F GOOD evidence to recommend
• EXCLUSION

-CMAJ, 1993
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Report Card Status Asthmaticus Therapy
Oxygen C ? Agonists Inhaled A
IV B Ipratropium A Corticosteroids
A Methylxanthines D
67
Report Card Status Asthmaticus Therapy
Magnesium B Ketamine C HELIOX
B- Inhaled Anesthesia C BiPAP C
68
Questions??