Treating Life Threatening Asthma
Toni Petrillo-Albarano, MD
Division of Pediatric Critical Care
Children’s Healthcare of Atlanta
Asthma: Increased Severity
Hospitalization Increased 28%
-MMWR, CDC
Asthma: Increased Severity
Death Rate Increased 118% (1980 1993)
-MMWR, CDC
The Cost of Asthma
Asthma related costs
 $6.2 billion
 Direct 3.6 billion
 Indirect $2.6 billion
 Pediatric $465 million
Children Who Die from Asthma
Risk Factors:
 Severe disease - history of intubation,
seizures, rapid progress
 Lack of adequate support systems
 Psychologic disease
Children Who Die from Asthma
Risk Factors:
 Lack of perception of severity; selfweaning
 Males
 Exclusive reliance on b agonists
50% of deaths prior to hospital
Mechanisms of Status
Asthmaticus
Mucous
Hypersecretion
Bronchospasm
Mucosal
edema
Increased resistance to air
flow
Atelectasis
pCO2
pO2
Uneven
ventilation
Abnormal
V/Q
Hyperinflation
deadspace compliance
alveolar
hypoventilation
WOB
Status Asthmaticus
Oxygen
Relative hypoxemia:
 V/Q mismatch
 hypoventilation
Hypoxemia
bronchoconstriction
  agonists impair hypoxic pulmonary
vasoconstriction
shunt
Oxygen to keep pulse ox > 92%
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
Intravenous  Agonists
Most studies:
 inhaled therapy > 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
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)
Status Asthmaticus
Isoproterenol (Isuprel)
Tachycardia
Dysrhythmias
Peripheral vasodilation
Increased myocardial O2 consumption
Decreased coronary O2 delivery
“Splanchnic steal” by skeletal muscle
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
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
Status Asthmaticus
Anticholinergics
 agonist
Sympathetic
Airway
Parasympatheti
Xc
Vagolytics
Status Asthmaticus
Inhaled Ipratropium + Albuterol
120 children - severe acute asthma:
 FEV1 < 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
Status Asthmaticus
Effect of Inhaled Ipratropium
*
-Schuh, J Peds, 1995
*
*
*
*
*
*
* p < .05
Ipratropium:
Effect with FEV1 < 30%
*
*
-Schuh, J Peds,
*
*
*
*
*
* p < .05
Status Asthmaticus
IV or oral Corticosteroids
Mechanism of Effect:
interferes with leukotriene,
prostaglandins synthesis
prevent cell migration
up-regulate airway  receptors
Status Asthmaticus
IV or oral Corticosteroids
Proven effective in 3 level I trials, metaanalysis
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
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
Status Asthmaticus
Inhaled Corticosteroids
SI asthma has several characteristic features




severe asthma with persistent respiratory symptoms
frequent nighttime symptoms
chronic airflow obstruction (FEV1 <70% 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.
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
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
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
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 O‘Byrne 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
Status Asthmaticus
IV Theophylline
Phosphodiesterase inhibitor
Randomized trials (x2) - no benefit
over standard 2 agonists and/or
corticosteroids
Uncertain benefit in episodes
unresponsive to all other therapy
Status Asthmaticus
IV Theophylline
21 hospitalized children
Standard nebulized albuterol, steroids
Randomized:
IV Aminophylline load/infusion
OR
Saline placebo
-Carter, J Peds,
1993
Status Asthmaticus
IV Theophylline
•No difference in hospital days
•Confirmed by another study
- Carter, J Peds,
1993
IV Theophylline in Severe Pediatric
Asthma
-Carter, J Peds,
1993
“Methylxanthines are NOT generally
recommended.”
-Expert Panel,
NAEPP
Status Asthmaticus
Ketamine
Dissociative anesthetic
Direct bronchodilator
Potentiates catecholamines
Bronchorrhea
Other side effects:
 tachycardia

BP
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
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
Status Asthmaticus
Ketamine in Pediatrics
One small pediatric study in nonintubated patients
 10 patients
 ketamine bolus plus 1 hr infusion in addition
to standard therapy
 Improved CAS
 improved indicators of distress
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
Status Asthmaticus
Magnesium Sulfate
31 children (6-18 yrs) in ER
Asthma exacerbation:
 PEFR < 60% after albuterol
Randomized:
MgSO4 25 mg/kg
OR
Saline
-Ciarallo, J Peds, 1996
Status Asthmaticus
Magnesium Sulfate
*
*
*
*
*
* p < .05
-Ciarallo, J Peds,
1996
Status Asthmaticus
Magnesium Sulfate
*
*
*
*
*
* p < .05
-Ciarallo, J Peds,
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
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; 55:260-5)
 160 mg Po Zafirlukast improved ER
outcomes ( Ann Emerg Med 2000; 35:S10
Status Asthmaticus
Helium - Oxygen (HELIOX)
Blend of 80:20 helium:oxygen
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
Status Asthmaticus
Helium - Oxygen (HELIOX)
 Major effects to reduce resistance:
 Reduces turbulence
Used in upper airway obstruction
Improved pulsus paradoxus, PEFR in
adult asthmatics
Status Asthmaticus
Helium - Oxygen (HELIOX)
Most recent case reports and clinical studies
have found mixed results in the role of heliox
for use in asthma
Status Asthmaticus
Helium - 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
Status Asthmaticus
Helium - 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
Status Asthmaticus
Inhaled Anesthetics
Halothane, enflurane, isoflurane
Mechanisms:
 2 agonist effect
 vagolytic
 direct airway relaxation
No randomized (level I) trials
Status Asthmaticus
Inhaled 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
Response to Inhaled Anesthetics
pCO2
PIP
Status Asthmaticus
“Mechanical” Support
BiPAP
Intubation/Mechanical Ventilation
Extracorporeal Life Support
Status Asthmaticus
Non invasive Ventilation
Positive-pressure by nasal mask (BiPAP)
Potential benefits:
 airway stenting
 improve V/Q match
CPAP improved hypoxemia in 8 asthmatic
children
Status Asthmaticus
Non 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
Status Asthmaticus
Non 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.
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 ⅓ of subjects
whose FENO was greater than 47 ppb
In the absence of high FENO levels, a response to
steroid was much less likely
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 costeffectiveness of ICS therapy when used to guide
dose requirements
Status Asthmaticus
Intubation
Usually last resort
Potential M&M
Mortality rate
 in adults 0 - 40%
 in children 0 - 5%
24-33% of PICU admissions required
mechanical ventilation (very high?)
Status Asthmaticus
Intubation
Wear Depends !
Intubation by MD with experience
Have volume ready: hypotension
due to ed intrathoracic pressure
Status Asthmaticus
Intubation
Best done semi-electively
 earlier rather than later
Drugs of choice:
 Atropine
 Ketamine/Midazolam
 Succinylcholine
Status Asthmaticus
Mechanical Ventilation
GOALS:
 Rest inspiratory muscles
 Protect airway
 Provide adequate gas exchange NOT
normal exchange
 Avoid barotrauma, catastrophe
Status Asthmaticus
Mechanical Ventilation Indications
Coma
Absolute:
Respiratory or cardiac arrest
Cyanosis and hypoxemia on O2
PaCO2 greater than 50 and rising >
Relative:
5mmHg/hr
Deteriorating mental status
Minimal chest movement/air exchange
Pneumothorax
Status Asthmaticus
Mechanical Ventilation
Key approach: permissive hypercapnia
(“controlled hypoventilation”)
tolerate pCO2 to keep pH > 7.20 - 7.25
prolonged expiratory time
 rate, inspiratory time
 tidal volume
 PEEP: auto-PEEP
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
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
Therapies NOT Recommended
Antibiotics
Empiric, aggressive hydration
Chest PT
Mucolytics
Sedation??
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
Report Card: Status
Asthmaticus Therapy
Oxygen
 Agonists
Inhaled
IV
Ipratropium
Corticosteroids
Methylxanthines
C
A+
B
A
A
D
Report Card: Status Asthmaticus Therapy
Magnesium
Ketamine
HELIOX
Inhaled Anesthesia
BiPAP
B+
C
BC+
C+
Questions??