Status

Status Asthmaticus
Asthmaticus in
in Children
Children

Heinrich Werner
Pediatric Critical Care
University of Kentucky Children’s
Hospital
©hwerner
Status asthmaticus

Objectives
Objectives
The participant will increase his/her

 Awareness of rising morbidity/mortality of severe asthma in

children
 Ability to define who is at risk for dying
 Understanding of the pathologic, metabolic and
biomechanical events
 Ability to predict respiratory failure and to determine the
need for early transfer
 Ability to tailor the therapeutic regimen according to
severity and progression of status asthmaticus
Status asthmaticus

Status
Status Asthmaticus
Asthmaticus in
in Children
Children
Epidemiology
Pathophysiology
Presentation and Assessment
Treatment
Status asthmaticus

Status
Status Asthmaticus
Asthmaticus in
in Children
Children
Epidemiology
Prevalence
Morbidity
Mortality
Risk factors
Pathophysiology
Presentation and assessment
Treatment
Status asthmaticus : Epidemiology

Prevalence
Prevalence
The prevalence of pediatric asthma in the
US is increasing
60

50
1975
40 1980-81
1985
30 1989
1990-92
20
1993-95
10

0
0-4 yrs 5-14 yrs 15-34 yrs

Rate of self-reported asthma/1,000 population

Mannino DM. MMWR 1998;47(1):1-27
Status asthmaticus : Epidemiology

Morbidity
Morbidity
The morbidity of pediatric asthma in the
US is increasing
70

60
Rate per 10,000 population

50
< 1 year
40 1-4 years
30 5-14 years
15-24 years
20

10

0
1980

1982

1984

1986

1988

1990

1992
Hospital discharge rates for asthma
MMWR 1996;45(17):350-3
Status asthmaticus : Epidemiology

Mortality
Mortality
The mortality of pediatric asthma in the US
is increasing
7

6
Rate per 1,000,000 population

4 0-4 years
5-14 years
3
15-34 years
2

0
1979-80 1981-83 1984-86 1987-89 1990-92 1993-95
Rates of death in children from asthma
Mannino. MMWR 1998;47(1):1-27
Status asthmaticus : Epidemiology

Risk
Risk factors
factors for
for fatal
fatal asthma
asthma
Medical
Previous attack with rapid/severe deterioration or respiratory
failure or seizure/loss of consciousness
Psychosocial
Denial, non-compliance
Depression or other psychiatric disorder
Dysfunctional family
Inner city resident
Ethnic
Non-white child
Status asthmaticus

Status
Status Asthmaticus
Asthmaticus in
in Children
Children
Epidemiology
Pathophysiology
Cytokines
Airway pathology
Autonomic nervous system
Pulmonary mechanics
Cardiopulmonary interactions
Metabolism
Presentation and assessment
Treatment
Status asthmaticus : Pathophysiology

Pathophysiology
Pathophysiology
Asthma is primarily an inflammatory disease

Smooth muscle
spasm Airway edema

Mucous plugging
Status asthmaticus : Pathophysiology

Inflammatory
Inflammatory cytokines
cytokines
Activated mast cells and lymphocytes
produce pro-inflammatory cytokines
(histamine, leukotrienes, PAF), which are
increased in asthmatics’ airways and
bloodstream
Status asthmaticus : Pathophysiology

Irritable
Irritable and
and damaged
damaged airway
airway
Hypersecretion

Epithelial damage with

exposed nerve endings

Hypertrophy of goblet cells

and mucus glands
Status asthmaticus : Pathophysiology

Airway
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
 Status asthmaticus : Pathophysiology

Autonomic
Autonomic nervous
nervous system
system

Bronchodilation Bronchoconstriction
Circulating catecholamines -
Sympathetic stimulate ß-receptors

Vagal signals stimulate Vagal signals stimulate

Parasympathetic bronchodilating M2 - bronchoconstricting M3-
receptors receptors

Nonadrenergic- Release of bronchodilating Release of tachykinins (substance

noncholinergic neurotransmitters (VIP, NO) P, neurokinin A)

(NANC)
Status asthmaticus : Pathophysiology

Lung
Lung mechanics
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, mostly shunt
Status asthmaticus : Pathophysiology

Severe airflow Incomplete Increased lung

obstruction exhalation volume

Increased elastic Expanded small

recoil pressure airways

Increased Decreased expiratory

expiratory flow resistance

Compensated:
Hyperinflation, normocapnia
Worsening
airflow From text in :
obstruction Decompensated: Tuxen. Am Rev
Respir Dis
Severe hyperinflation, hypercapnia 1992;146:1136
Status asthmaticus : Pathophysiology

Cardiopulmonary
Cardiopulmonary interactions
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
Stalcup S. N Engl J Med 1977;297:592-6

Negative intrapleural pressure causes

increased left ventricular afterload, resulting
in risk for pulmonary edema
Buda AJ. N Engl J Med 1979;301(9):453-9
Status asthmaticus : Pathophysiology

Cardiopulmonary
Cardiopulmonary interactions
interactions
Right ventricular load
Hypoxic pulmonary vasoconstriction and lung
hyperinflation lead to increased right
ventricular afterload
Dawson CA. J Appl Physiol 1979;47(3):532-6
Status asthmaticus : Pathophysiology

Cardiopulmonary
Cardiopulmonary interactions
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.

Nl

P. paradoxus

Expir Inspir Expir Inspir

Status asthmaticus : Pathophysiology

Pulsus paradoxus correlates with

severity

All patients who presented with FEV1 of < 20%

(of their best FEV1 while well) had pulsus
paradoxus

Pierson RN. J Appl Physiol 1972;32(3):391-6

Status asthmaticus : Pathophysiology

Cardiopulmonary
Cardiopulmonary interactions
interactions
Negative intrapleural Hyperinflation
pressure

Altered hemodynamics

Pulmonary edema Pulsus paradoxus

Hypotension
 Status asthmaticus : Pathophysiology

Metabolism
Metabolism
V/Q mismatch Increased work Dehydration
of breathing
Hypoxia

Lactate Ketones

Metabolic acidosis
Status asthmaticus : Presentation

Presentation
Presentation
Audible wheezes : reasonable airflow
 Cough
“Silent chest” : ominous!
 Wheezing
 Increased work of breathing
 Anxiety
 Restlessness
 Oxygen desaturation
Status asthmaticus : Assessment

Assessment
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
Status asthmaticus : Assessment
5 = impending resp failure

Clinical Asthma Score

0 1 2
Cyanosis or None In air In 40%
PaO2 >70 in air < 70 in air < 70 in 40%

Inspiratory B/S Nl Unequal or Absent

decreased

Expir wheezing None Moderate Marked

Cerebral function Nl Depressed Coma

Agitated
Wood DW. Am J Dis Child 1972;123(3):227-8
Status asthmaticus : Assessment

Chest
Chest X-Ray
X-Ray

 Not routinely indicated

 Exceptions:
 Patient is intubated/ventilated
 Suspected barotrauma
 Suspected pneumonia
 Other causes for wheezing are being suspected
Status asthmaticus : Assessment

ABG
ABG
 Early status asthmaticus: hypoxemia,
hypocarbia
Late: hypercarbia
 Decision to intubate should not depend on
ABG, but on clinical assessment
 Frequent ABGs are crucial in the ventilated
asthmatic
Status asthmaticus

Status
Status Asthmaticus
Asthmaticus in
in Children
Children
Epidemiology
Pathophysiology
Presentation and assessment
Treatment
Conventional
General, ß-agonists, steroids, anticholinergics
Advanced
Mechanical ventilation, ketamine, inhalational anesthetics
Unusual/Unproven
Theophylline, magnesium, LTRAs, heliox, bronchoscopy
Status asthmaticus : Treatment

Oxygen
Oxygen
Deliver high flow oxygen, as
severe asthma causes V/Q
mismatch (shunt)

Oxygen will not suppress respiratory drive in

children with asthma
Schiff M. Clin Chest Med 1980;1(1):85-9
Status asthmaticus : Treatment

Fluid
Fluid
Judicious use of IV fluid necessary
 Most asthmatics are dehydrated on
presentations - rehydrate to euvolemia
 Overhydration may lead to pulmonary
edema
 SIADH may be common in severe asthma
Baker JW. Mayo Clin Proc 1976;51(1):31-4
Status asthmaticus : Treatment

Antibiotics
Antibiotics
Most infections precipitating asthma
are viral

?
Antibiotics are not routinely
indicated

Johnston SL. Pediatr Pulmonol Suppl 1999;18:141-3

Status asthmaticus : Treatment

ß-Agonists
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
Status asthmaticus : Treatment

ß-Agonists
ß-Agonists
Less than 10% of nebulized drug reach the
lung under ideal conditions
Bisgaard H. J Asthma 1997;34(6):443-67

Drug delivery depends on

 Breathing pattern
 Tidal volume
 Nebulizer type and gas flow
Status asthmaticus : Treatment

ßß -Agonists
-Agonists
Delivery of nebulized drug
 Only particles
betweenmare
deposited in alveoli
 Correct gas flow rate is
crucial
 Most devices require 10-12
L/min gas flow to generate
correct particle size
Status asthmaticus : Treatment

•ßß -Agonists
-Agonists
 Continuous nebulization is superior to
intermittent nebulization
More rapid improvement
More cost effective
More patient friendly

Papo MC. Crit Care Med 1993;21:1479-86

Ackerman AD. Crit Care Med 1993;21:1422-4
 Status asthmaticus : Treatment

ßß -Agonists
-Agonists
Dosage
 Intermittent nebulization
 2.5 - 5 mg (0.5 - 1 ml of 0.5% solution), dilute with NS
to 3 ml
 Prediluted: 2.5 mg as 3ml of 0.083% solution
 High dose: use up to undiluted 5% solution
 Continuous nebulization
 4-40 mg/hr
 High dose: up to undiluted 5% solution (≈ 150 mg/hr)
Status asthmaticus : Treatment

ßß -Agonists
-Agonists
Intravenous ß - Agonist
Consider for patients with severe air flow
limitation who remain unresponsive to
nebulized albuterol
Terbutaline is i.v. ß-agonist of choice in US
Dosage: 0.1 - 10 g/kg/min
Stephanopoulos DE. Crit Care Med 1998;26(10):1744-8
Status asthmaticus : Treatment

ßß -Agonists
-Agonists
Side effects
Tachycardia
Agitation, tremor
Hypokalemia
Status asthmaticus : Treatment

ßß -Agonists
-Agonists
Cardiac side effects
 Myocardial ischemia known to occur with i.v.
isoproterenol
No significant cardiovascular toxicity with i.v.
terbutaline (prospective study in children with
severe asthma)
Chiang VW. J Pediatr 2000;137(1):73-7
 Tachycardia (and tremor) show tachyphylaxis,
bronchodilation does not
Lipworth BJ. Am Rev Respir Dis 1989;140(3):586-92
Status asthmaticus : Treatment

Steroids
Steroids
 Asthma is an inflammatory disease
 Steroids are a mandatory element of first
line therapy regimen (few exceptions only)
140
120
100
FEV1%

80
60
Steroids Effect of i.v.
Placebo
40 hydrocortisone
20 vs. placebo
0
-5 0 6 12 18 24
-20
Hours
Fanta CH: Am J Med 1983;74:845
Status asthmaticus : Treatment

Steroids

Hydrocortisone 4-8 mg/kg x 1, then 2-4

mg/kg q 6°
Methylprednisolone 2 mg/kg x1, then 0.5-1
mg/kg q 4-6°
Status asthmaticus : Treatment

Steroids
Steroids
Significant side effects
 Hyperglycemia
 Hypertension
 Acute psychosis
 Unusual or unusually severe infections
Steroids contraindicated with active or
recent exposure to chickenpox
 Allergic reaction
Reported with methylprednisolone,
hydrocortisone and prednisone*

* Vanpee D. Ann Emerg Med 1998;32(6):754. Kamm GL. Ann Pharmacother 1999;33(4):451-60.
Schonwald S. Am J Emerg Med 1999;17(6):583-5. Judson MA. Chest 1995;107(2):563-5.
Status asthmaticus : Treatment

Anticholinergics - Ipratropium

Quaternary atropine derivative

Not absorbed systemically
Thus minimal cardiac effects
(But you will find a fixed/dilated pupil if the nebulizer mask slips over
an eye!)
Status asthmaticus : Treatment

Anticholinergics

Change in FEV1 is significantly greater when

ipratropium was added to ß-agonists (199 adults)
Rebuck AS: Am J Med 1987;82:59

Highly significant improvement in pulmonary

function when ipratropium was added to
albuterol (128 children). Sickest asthmatics
experienced greatest improvement
Schuh S. J Pediatr 1995;126(4):639-45
Status asthmaticus : Treatment

Ipratropium
Dose-Response
Dose-Response Curve
Curve in
in Children
Children (n=19,
(n=19, age
age 11-
11-
17
17 yrs)
yrs)
Average increase in FEV1 (over 4 hrs)
0.4
0.3
0.2
0.1
0
7.5 25 75 250
Dose (micrograms)
Davis A: J Pediatr 1984;105:1002
Status asthmaticus : Treatment

Ipratropium
Ipratropium
Nebulize 250 - 500 g every 4-6 hours

Schuh S. J Pediatr 1995;126(4):639-45

Goodman and Gilman's. 9th ed. New York: McGraw-Hill; 1996
Status asthmaticus : Treatment

Intubation,
Intubation, Ventilation
Ventilation
Absolute indications:
Cardiac or respiratory arrest
Severe hypoxia
Rapid deterioration in mental state

Respiratory acidosis does not dictate

intubation
Status asthmaticus : Treatment

Why
Why hesitate
hesitate to
to intubate
intubate the
the
asthmatic
asthmatic child?
child?
 Tracheal foreign body
aggravates bronchospasm
 Positive pressure ventilation
increases risk of barotrauma
and hypotension
Tuxen DV. Am Rev Respir Dis 1987;136(4):872-9

 > 50% of morbidity/mortality during severe asthma

occurs during or immediately after intubation
Zimmerman JL. Crit Care Med 1993;21(11):1727-30
Status asthmaticus : Treatment

Intubation
Intubation
 Preoxygenate, decompress stomach
 Sedate (consider ketamine)
 Neuromuscular blockade (may avoid
large swings in airway/pleural pressure)
 Rapid orotracheal intubation (consider
cuffed tube)
Status asthmaticus : Treatment

Immediately
Immediately after
after intubation
intubation
 Expect hypotension, circulatory depression
 Allow long expiratory time
 Avoid overzealous manual breaths
 Consider volume administration
 Consider pneumothorax
 Consider endotracheal tube obstruction (++
secretions)
Status asthmaticus : Treatment

Mechanical
Mechanical ventilation
ventilation
 Positive pressure ventilation worsens
hyperinflation/risk of barotrauma
 Thoughtful strategies include:
Pressure-limited ventilation, TV 8-12 ml/kg, short Ti,
rate 8-12/min (permissive hypercapnia)
Cox RG. Pediatr Pulmonol 1991;11(2):120-6
Pressure support ventilation using PS=20-30 cmH2O
(may decrease hyperinflation by allowing active
exhalation)
Wetzel RC. Crit Care Med 1996;24(9):1603-5
Status asthmaticus : Treatment

Ketamine
Ketamine
Dissociative anesthetic with strong
analgesic effect
Direct bronchodilating action
Useful for induction (2 mg/kg i.v.) as well as
continuous infusion (0.5 - 2 mg/kg/hr)
Induces bronchorrhea, emergence reaction
Status asthmaticus : Treatment

Inhalational
Inhalational anesthetics
anesthetics
Halothane, isoflurane have bronchodilating
effect
Halothane may cause hypotension,
dysrhythmia
Requires scavenging system, continuous
gas analysis
Status asthmaticus : Treatment

Theophylline
Theophylline
 Role in children with severe asthma
remains controversial
 Narrow therapeutic range
 High risk of serious adverse effects
 Mechanism of effect in asthma remains
unclear
Status asthmaticus : Treatment

Theophylline
Theophylline
May have a role in selected, critically ill children
with asthma unresponsive to conventional
therapy:
 Randomized, placebo-controlled, blinded trial (n=163) in children with
severe status asthmaticus
 Theophylline group had greater improvement in PFTs and O 2 saturation
 No difference in length
FEV 1 (%)
of PICU stay
60
 Theophylline group had signifi- 50

cantly more N/V 40

30 Placebo
Theophylline
20
Yung M. Arch Dis Child 1998;79(5):405-10.
10
0
Prior 6 hr 12 hr 24 hr
Status asthmaticus : Treatment

Magnesium
Magnesium

Smooth-muscle relaxation by inhibition of

calcium uptake (=bronchodilator)
Dosage recommendation: 25 - 75 mg/kg i.v.
over 20 minutes
Status asthmaticus : Treatment

Magnesium
Magnesium
Several anecdotal reports
Only one randomized pediatric trial
 Randomized, placebo-controlled, blinded trial (n=31) in children
with acute asthma in ER (MgSO4 25 mg/kg i.v. for 20 min)
 Magnesium group had significantly greater improvement in
FEV1/PEFR/FVC 60

 Magnesium group more likely 50

to be discharged home 40

30 Placebo
 No adverse effects Magnesium
20

10
Ciarallo L. J Pediatr 1996;129(6):809-14.
0
50 min 80 min 110 min
Status asthmaticus

Leukotriene
Leukotriene receptor
receptor antagonists
antagonists
(LTRAs)
(LTRAs)
Asthmatic children have increased
leukotriene levels (blood, urine) during
an attack. Level falls as attack resolves
Sampson AP. Ann N Y Acad Sci 1991;629:437-9.

LTRA administration is associated with

improvement in lung function in
asthmatics
Gaddy JN. Am Rev Respir Dis 1992;146(2):358-63.
Status asthmaticus

LTRAs
LTRAs
Steroid administration to asthmatics has
little effect on leukotriene levels
O'Shaughnessy KM. Am Rev Respir Dis 1993;147(6 Pt 1):1472-6.

Thus, LTRAs may offer additional benefits

to asthmatics on steroids
Reiss TF. Arch Intern Med 1998;158(11):1213-20.
Status asthmaticus

Intravenous
Intravenous LTRAs
LTRAs in
in moderate
moderate
to
to severe
severe asthma
asthma
A single dose of i.v.
montelukast
(Singulair®) was
associated with
significant
improvement in lung
function compared to
standard therapy

Camargo CA, Jr. Am J Respir Crit Care Med 2003;167(4):528-33.

Status asthmaticus

LTRAs
LTRAs –– Remaining
Remaining questions
questions
 Will they offer added benefit in the acute, severe
asthmatic child already on ß-agonists, steroids,
anticholinergics ?
 More rapid improvement in lung function/clinical score?
 Reduced/shortened hospitalization?
 Fewer PICU admissions?
 Cost ?
 Adverse effects ?
Status asthmaticus : Treatment

Helium
Helium -- Oxygen
Oxygen (Heliox)
(Heliox)
 Helium lowers gas density (if at least
60% helium fraction)
 Reduces resistance during turbulent flow
 Renders turbulent flow less likely to
occur
Status asthmaticus : Treatment

Heliox
Heliox
Anecdotal reports of improved respiratory
mechanics in non-intubated and intubated
asthmatic children
Prospective, randomized, blinded cross-over
study of heliox in non-intubated children
with severe asthma (n=11) : no effect on
respiratory mechanics or asthma score
Carter ER. Chest 1996;109(5):1256-61.
Status asthmaticus : Treatment

Heliox

Helium-oxygen (80:20) decreased pulsus

paradoxus and increased PEFR in a
controlled trial of adult patients
Manthous CA. Am J Respir Crit Care Med 1995,151:310-314

Heliox may worsen dynamic hyperinflation

Madison JM. Chest 1995,107:597-598
Status asthmaticus : Treatment

Bronchoscopy,
Bronchoscopy, bronchial
bronchial
lavage
lavage
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
Status asthmaticus

Summary
Summary
 Severe asthma in children is increasing in prevalence
and mortality
 Aggressive treatment with ß-agonist, steroids and
anticholinergic is warranted even in the sick-appearing
child
 Avoid intubation if possible
 Mechanical ventilation will worsen bronchospasm and
hyperinflation
 Use low morbidity approach to mechanical ventilation
Status asthmaticus

Prevention

Steps toward prevention

1. Identify patients as at risk
2. Tell them about their risks
3. Organize treatment plan
4. Facilitate access to continued care
Status asthmaticus

Case
Case Scenario
Scenario (1)
(1)
A 6 y o black male with previous history of asthma is
admitted with severe respiratory distress. He is wheezing,
RR is 40/min, HR 145/min. He sits upright, leans forward,
has retractions and looks very anxious. He correctly tells
you his name and phone #, but has to take a breath after
every few words.

Discuss your initial therapeutic approach.

Status asthmaticus

Case
Case Scenario
Scenario (2)
(2)
Which of the following are mandatory in this child with severe
asthma?
(You may chose none, more than one or all)


Arterial blood gas analysis (to detect onset of respiratory
acidosis)

Continuous pulse oximetry

Chest radiograph (to rule out pneumomediastinum/ –thorax)

Frequent determination of peak expiratory flow rate

White blood cell count with differential (to assess need for
antibiotics)
Status asthmaticus

Case
Case Scenario
Scenario (3)
(3)
Given his current presentation: does this child need to be
intubated and mechanically ventilated?

Discuss indications for intubation/mechanical ventilation

in the child with severe status asthmaticus.
Status asthmaticus

Case
Case Scenario
Scenario (4)
(4)
When nebulizing drugs during status asthmaticus, the following
statement about gas flow rates is CORRECT:

A. The higher the gas flow rate through the nebulizer, the
more particles will be deposited in the patient’s alveolar
space
B. Most devices require a gas flow rate of 10-12 L/min to
generate optimal particle size
C. Gas flow rates above 5 L/min should be avoided to
maintain laminar flow in the nebulizer output
D. The nebulizer device should not be driven by 100% oxygen
Status asthmaticus

Case
Case Scenario
Scenario (5)
(5)
In addition to administration of continuously nebulized beta-
agonist and intermittent anticholinergic agonist, which of the
following is almost mandatory? Discuss pros and cons for each.

A. Intravenous bolus of aminophylline, followed by

infusion
B. Intravenous corticosteroid
C. Intravenous broad spectrum antibiotic
D. Intravenous beta-agonist infusion
E. Inhaled helium-oxygen mixture
Status asthmaticus

Case
Case Scenario
Scenario (6)
(6)
After 3 hours of therapy in the PICU, including high dose
continuous albuterol, intermittent ipratropium, I.v.
methylprednisolone as well as two infusions of magnesium
sulfate, the child becomes obtunded. His O2 saturations
begin to drop below 85%. Is this an indication for
intubation/mechanical ventilation?

If so, describe your approach to intubating this child.

How to prepare? Drugs? ETT size, route? Anticipated problems /
complications? Initial pattern of ventilation?
Status asthmaticus

Case
Case Scenario
Scenario (7)
(7)
After you connect the child to the ventilator, he develops
marked arterial hypotension.

What is your differential diagnosis?

What should you do?
 Status asthmaticus

Suggested Reading (part 1):

1. Laitinen LA, Heino M, Laitinen A, et al. Damage of airway epithelium and bronchial reactivity in patients with
asthma. Am Rev Respir Dis 1985;131(4):599-606.
2. Beakes DE. The use of anticholinergics in asthma. J Asthma 1997;34(5):357-68.
3. Barnes PJ. Beta-adrenergic receptors and their regulation. Am J Respir Crit Care Med 1995;152(3):838-60.
4. Miro A, Pinsky M. Cardiopulmonary Interactions. In: Fuhrman B, Zimmerman J, editors. Pediatric Critical Care.
Second ed. St. Louis: Mosby; 1998. p. 250-60.
5. Stalcup SA, Mellins RB. Mechanical forces producing pulmonary edema and acute asthma. N Engl J Med
1977;297(11):592-6.
6. Rebuck AS, Pengelly LD. Development of pulsus paradoxus in the presence of airway obstruction. N Engl J Med
1973;288(2):66-9.
7. Papo MC, Frank J, Thompson AE. A prospective, randomized study of continuous versus intermittent nebulized
albuterol for severe status asthmaticus in children. Crit Care Med 1993;21:1479-86.
8. Katz RW, Kelly HW, Crowley MR, et al. Safety of continuous nebulized albuterol for bronchospasm in infants and
children [published erratum appears in Pediatrics 1994 Feb;93(2):A28]. Pediatrics 1993;92(5):666-9.
9. Schuh S, Johnson DW, Callahan S, et al. Efficacy of frequent nebulized ipratropium bromide added to frequent high-
dose albuterol therapy in severe childhood asthma. J Pediatr 1995;126(4):639-45.
10. Fanta CH, Rossing TH, McFadden ER. Glucocorticoids in acute asthma: A critical controlled trial. Am J Med
1983;74:845-51.
 Status asthmaticus

Suggested Reading (part 2):

11. Klein-Gitelman MS, Pachman LM. Intravenous corticosteroids: adverse reactions are more variable than
expected in children. J Rheumatol 1998;25(10):1995-2002.
12. Stephanopoulos DE, Monge R, Schell KH, et al. Continuous intravenous terbutaline for pediatric status
asthmaticus. Crit Care Med 1998;26(10):1744-8.
13. Chiang VW, Burns JP, Rifai N, et al. Cardiac toxicity of intravenous terbutaline for the treatment of severe
asthma in children: a prospective assessment. J Pediatr 2000;137(1):73-7.
14. Ciarallo L, Sauer AH, Shannon MW. Intravenous magnesium therapy for moderate to severe pediatric
asthma: results of a randomized, placebo-controlled trial. J Pediatr 1996;129(6):809-14.
15. Pabon H, Monem G, Kissoon N. Safety and efficacy of magnesium sulfate infusions in children with status
asthmaticus. Pediatr Emerg Care 1994;10:200-3.
16. Yung M, South M. Randomised controlled trial of aminophylline for severe acute asthma. Arch Dis Child
1998;79(5):405-10.
17. Tuxen DV, Lane S. The effects of ventilatory pattern on hyperinflation, airway pressures, and circulation in
mechanical ventilation of patients with severe airflow obstruction. Am Rev Respir Dis 1987;136(4):872-9.
18. Wetzel RC. Pressure-support ventilation in children with severe asthma. Crit Care Med 1996;24(9):1603-5.
19. Ibsen LM, Bratton SL. Current therapies for severe asthma exacerbations in children. New Horiz
1999;7(3):312-25.
20. Werner HA. Status asthmaticus in children: a review. Chest 2001;119(6):1913-29.