REVIEW ARTICLE

An update on Management of Life-threatening

Asthma in Children
Eric YT Chan, Daniel K. Ng

Division of Respirology and Critical Care, Department of Paediatrics, Kwong Wah Hospital, Hong Kong SAR, China

Abstract

Asthma is a common in children and a small percentage required paediatric intensive care unit
(PICU) admission. The severity of attack can be estimated by history, physical examination, lung
function, oximetry, transcutaneous carbon dioxide and assessing response to initial therapy. Beta2
agonists, anticholinergics and corticosteroids are the initial treatments. In this article, the common
initial treatment will be updated followed by discussion on additional treatment after admission to
PICU. (J Pediatr Resp Dis 2011;7:77-85)
Key words: asthma, child, intensive care

INTRODUCTION
Asthma is common in children. Only a small
percentage of asthmatic children require paediatric
intensive care unit (PICU) admission. Hon et al showed
3% of total PICU admission was due to life threatening
asthma and 20% of them required intubation.1 In this
article, we present a brief review of management of
life-threatening asthma requiring admission to PICU.

Life-threatening asthma
Asthma is a chronic airway inflammatory disease
characterized by hyper-responsiveness of the airways
to various stimuli and reversible expiratory airflow
obstruction. Life-threatening asthma refers to acute
severe asthma requiring admission to PICU. Some lifethreatening asthma becomes fatal asthma. Fortunately
fatal asthma is rare and the risk factors include previous
mechanical ventilation, previous intensive care unit
admission and history of recurrent hospitalizations.2
Identifying the cases for PICU admission is
important as most fatal asthma cases are due to delayed
recognition of life-threatening asthma and subsequent
delayed admission to PICU. In the authors centre,
no fatal cases occurred after admission to PICU in
Correspondence: Dr. Daniel K. Ng,
Room 303, Nursing Quarter, Kwong Wah Hospital,
Waterloo Road, Kowloon, Hong Kong. E-mail:
dkkng@ha.org.hk. Received: August 8, 2011.
Accepted: August 19, 2011.

the last 10 years. The degree of wheeze may not

correlate well with the asthma severity.3 A distant or
absent breath sound is much worse than a loud wheezy
chest. The National Institute of Health Guidelines for
the Diagnosis and Management of Asthma (NAEPP
guidelines) suggest a forced expiratory volume at 1
second (FEV1) or peak expiratory flow rate (PEFR)
of 50 to 80% of predicted/personal best and a FEV1
or PEFR of <50% predicted/personal best as moderate
attack and severe attack respectively.4 However, doing
FEV1 or PEFR is difficult in children, particularly
during an asthma attack. For life-threatening asthma
cases, close observation of respiratory effort, pulse
oximetry, level of consciousness and response to
bronchodilator are equally if not more important. The
authors found pulse oximetry to be especially helpful
and asthma children with SpO2 <90% is suffering
from severe asthma. Altered consciousness, physically
exhausted or impaired circulation are late signs and
those cases often required intubation. For those patients
who present with severe asthma, active consideration
should be given to transfer the case to PICU for further
management. Criteria for PICU admission was listed
in Table 1.

Investigations
History and physical examination are the most
important aspects to confirm the diagnosis. Chest
radiograph (CXR) may help identify pneumonia and/or
pneumothorax but it is not routinely indicated as CXR

Journal compilation 2011 Taiwan Society of Pediatric Pulmonology

Chan EY, et al.

Table 1. Criteria for admission to PICU
1) severe asthma not responsive to initial short acting bronchodilator
2) Persistent SpO2 less than 95% despite oxygen therapy of 2-4 L/min via nasal cannula
3) Confusion, drowsiness, silent chest
4) Marked parental anxiety about response to treatment

Figure 1. Pulsus paradoxus (lower tracing) with variation of baseline SpO2 tracing. (upper tracing)

abnormalities in unintubated asthmatic children are

rare.5 Taking blood from an irritated child is difficult
and sometimes may worsen the clinical condition.
Pulse oximetry and transcutaneous carbon dioxide
monitoring are helpful. The pulse wave form of pulse
oximetry also provide a clue as the baseline tracing
variation of pulse oximetry may help to identify pulsus
paradoxus (Figure 1) in asthmatic patient.6 In sedated
and ventilated case, arterial and venous lines are
required.

MANAGEMENT
Oxygen and hydration

Patients with acute asthmatic attack have ventilation

perfusion mismatch. Hypoxaemia need to be treated
with oxygen preferably through a heated humidifier.
Recently, high flow oxygen through a humidified nasal
system (Figure 3), of up to 8 liter per minute in children
and more than 20 litres per minute in adults, e.g.
78

OptiflowTM (Fisher & Paykel, NZ) could be given to

patients. Theoretically, high flow of gas minimizes air
dilution of oxygen and continuous nasal flow reduces
anatomical dead space. Although the evidence of using
optiflow in asthma is lacking, the authors find this a
useful adjunct in giving oxygen supplement as well
as providing a small positive end-expiratory pressure
(PEEP) of a few cmH2O. The turbulence created by the
high flow at the laryngeal inlet also help wash out CO2.
There should be no respiratory drive suppression with
oxygen therapy if the patient does not have chronic
pulmonary disease.7 Nevertheless, a blended oxygen
source is preferred so as to allow the fraction inspired
oxygen to be titrated accordingly to SpO2.
Asthma patients may be dehydrated due to poor
intake and increased insensible water loss. On the other
hand, they are also prone to fluid retention because
of syndrome of inappropriate anti-diuretic hormone
(SIADH). History, physical examination, fluid balance,
serum and urine electrolytes and osmolarities help

Life-threatening Asthma
Initial treatment for moderate-severe asthmatic attack
Oxygen and hydration
Beta2 agonist inhaler
Ipratropium bromide inhaler
Systemic corticosteroid + inhaled corticosteroid
Macrolide if suspected co-morbid atypical pneumonia

Fair to poor response

Continuous beta2 agonist nebulization/ consider IV infusion if poor response to continuous nebulization
Corticosteroid if not yet started
IV MgSO4 infusion
Non-invasive ventilation
Inidividual consideration
IV leukotriene modifier
IV methylxanthine

Fair to poor response

Intubation and mechanical ventilation

Individual consideration
ventilation with heliox or isoflurane
bronchoscopy to rule out plastic bronchitis

Deterioration

Consider extracorporeal life support

Figure 2. Asthma management algorithm

differentiate the conditions. It is the authors practice to

give 80% maintenance fluid at the beginning. In infant
with poor oral intake, tube feeding offer better nutrition
than intravenous fluid. Previous study showed that
there was no change in lung compliance, resistance,
and the work of breathing after tube feeding in infant.8

Medications

Beta2 agonist bronchodilator is the corner stone

in managing acute asthma attack. Terbutaline and
albuterol are commonly used. Beta2 agonists can be
administered by inhalation, intravenous or oral routes.
The standard albuterol is a racemic mixture of equal
parts of R-albuterol and S-albuterol. Concern was raised
about S-albuterol that may trigger airway broncho-

constriction.9 However, there is no evidence that pure

R-albuterol, a much more expensive medication, is
superior to racemic albuterol.10 For inhaled route,
metered dose inhalers (MDI) with a spacer device
have similar effectiveness to nebulized therapy. 11,12
The dose required should be based on the severity and
response.13 In adult, four to eight puffs of MDI, every
15-20minutes, can be used.14 Our experience found that
similar doses are effective and do not cause significant
side effect in children. However, in an uncooperative
and lethargic child, frequent intermittent use of MDI
via spacer may further irritate the child and interrupt
oxygen therapy. Continuous nebulization is more cost
effective than intermittent nebulization and it allows
lesser disturbance of children.15,16 After admission to
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Chan EY, et al.

Figure 4. Small particle aerosol generator (SPAG)

Figure 3. Blender and high flow nasal system

PICU, the authors prefer use of large volume nebulizer,

e.g. small particle aerosol generator (SPAG) (Figure
4), that can maintain output for five to eight hours.
17,18
Common dosage is 4-10mg/hour, higher dose, 4080mg/hour could be used for life-threatening asthma.19
It is important to bear in mind that less than 10% of
nebulized medication reached the lung.20 Moreover, the
percentage of inhaled medications via nebulizer is likely
to be highly variable and changes with the patients
conditions. In our experience, continuous nebulization
of albuterol, 5mg/hour for young children, 10mg/
hour for bigger children is safe and effective. Regular
frequent reassessment is required to assess response
and side effect of continuous therapy. Nebulizers are
usually driven by oxygen, flow of around 10L/min.
Using heliox as the driving gas in aerosol system was
studied, most studies did not demonstrate beneficial
effect by heliox as the driving gas, 21-23 unless a semiclosed delivery system is used.22 A paediatric study
showed better pulmonary index score in heliox driven
albuterol nebulization patients.24 Intravenous beta 2
agonist should be considered when inhaled route is not
found to be effective. Intravenous albuterol, 0.5 g,
80

can be given. Albuterol should be diluted to 200 g/

ml. Undiluted albuterol can be given via central venous
catheter in fluid restricted case. With selective beta 2
agonist, there is no significant cardiac toxicity except
tachycardia.25 Other side effects include hypokalaemia
and tremor. Close monitoring is important for
continuous nebulization or infusion of albuterol.

Anticholinergics

Most paediatric studies used ipratropium bromide.

It is given by inhalation and dosage varied from 0.25
mg nebulization for once to 0.5 mg every 20 minutes, 3
times. Previous report suggested a significant reduction
in the clinical score after combined treatment than
salbutamol alone, without increase in side effects.26
Calvo et al reported that ipratropium bromide 20 g
inhaler combined with salbutamol nebulizer given
every 15 minutes improves asthma attack at a faster
rate.27 Davis et al showed that ipatropium bromide has
a dose dependent bronchodilator effect, at a dose >75
g and plateau off at 250 g.28 In our experience, 80 g
ipratropium bromide MDI with spacer and salbutamol
MDI with spacer is the preferred initial treatment.

Life-threatening Asthma

Corticosteroids

Corticosteroid is an anti-inflammatory medication

and it is an important medication in treatment of
asthma. Increasing dose of inhaled steroid seems
to be effective during acute attack 29 but the role in
severe asthma attack is not clear. Systemic steroid is
the preferred route. However, Rodrigo et al found that
corticosteroid did not influence the early course of acute
asthma 30 which suggested corticosteroid may take up
to 24 hours to be effective. On the other hand, Rodrigo
et al also showed that high dose inhaled corticosteroid
improved lung function as early as 3 hours after
administration.31 Theoretically, prescribing inhaled and
systemic corticosteroid together as initial treatment
may provide an early effect and adequate immunosuppression afterwards. It is the authors practice to
give systemic steroid as well as inhaled corticosteroid
(ICS) for those admitted for severe or life-threatening
asthma for the reasons listed before and to emphasize
the role of ICS in asthma management. For systemic
corticosteroid, methylprednisolone is preferred because
of its lower mineralocorticoid effect. Study suggested
that intravenous methylprednisolone followed by oral
methylprednisolone is more efficacious in terms of
better pulmonary function, and safer treatment in terms
of less impact on blood glucose level than intravenous
hydrocortisone followed by oral prednisolone.32
Methylprednisolone, 0.5 to 1.0 mg/kg every 6 hours,
stepping down to 1mg per kg per day the following day
is used in our department. Duration of therapy depends
on the severity of asthma and it is usually given for
5 to 7 days. Side effects including hyperglycemia,
hypertension, and acute psychosis had been reported,
33
although it has never been observed in the authors
practice.

Magnesium sulfate

Magnesium induces smooth-muscle relaxation

secondary to inhibition of calcium uptake 34 which
should be beneficial in asthma when bronchoconstriction
accounts partially for the lower airway obstruction
in asthma. Intravenous magnesium sulfate (MgSO4),
25 mg/kg, was found to improve in lung function in
asthmatic children.35 Dosage of magnesium sulfate
ranges from 25-75 mg/kg in children.35 In general,
single dose of MgSO4 can be infused over 20 minutes.

Case report of 2 young adults suggested that in very

severe asthmatic attack, 2 grams MgSO4 can be infused
over 2 minutes which obviated the need for intubation.36
Magnesium sulfate should be diluted to 60 mg/ml;
up to 200 mg/ml in fluid restricted case. Mild side
effects include nausea and flushing. Potential severe
side effects include muscle weakness, respiratory
depression, and cardiac arrhythmias.
Another potential use of MgSO4 is for it to be given
by nebulized route with beta 2 agonist. A study using
11.1% MgSO4 nebulization showed beneficial effect in
lung function37 while another study using 6.3% MgSO4
showed no beneficial effect.38 Dosage and concentration
of nebulized MgSO4 need to be further studied to see its
effect on acute asthma.

Leukotrienes modifiers

Montelukast is a leukotriene receptor antagonist and

daily oral dose is used in persistent asthma. For acute
asthma, intravenous montelukast in addition to standard
therapy causes rapid benefit and is well tolerated in
adults with initial FEV1 70% predicted.39 Further
study showed that intravenous montelukast added to
standard care in adults with acute asthma, initial FEV1
50% predicted, produced significant relief of airway
obstruction for 2 hours, with an onset of action as early
as 10 minutes and there was no significant difference
between 7 mg and 14 mg.40 However, in a paediatric
study involving children with FEV1 75% predicted
despite 120 minutes of standard therapy, administration
of intravenous montelukast, 5.25 mg, was not found
to be significantly better than placebo in improving
FEV1, symptoms, or overall hospital course though the
medication was well tolerated.41

Methylxanthines

Theophylline is a phosphodiesterase inhibitor

and has been used to treat bronchospasm for a long
time. Potential mechanisms include stimulating
endogenous catecholamine release, act as a diuretic,
increase binding of cAMP and act as prostaglandin
antagonist. Intravenous aminophylline, loading dose of
6 mg/kg, up to 500 mg, (for cases not on maintenance
theophylline) followed by 1 mg/kg infusion was
being used in children.42 A paediatric study showed
81

Chan EY, et al.

that life-threatening asthma unresponsive to frequent

nebulized albuterol, ipratropium, and intravenous
steroid, responded to aminophylline with improved
oxygen saturation and pulmonary function.43 However,
meta-analysis of adult studies did not show definite
advantage of aminophylline in acute asthma.44,45
Moreover, aminophylline toxicities are common with
vomiting, tachycardia, agitation, cardiac arrhythmias,
hypotension and seizure because of the narrow
therapeutic range (therapeutic range: 10-20 g/ml vs.
toxic range >15 g/ml.)

Macrolide

Macrolide has antimicrobial actions against

organisms such as Chlamydia pneumoniae and
Mycoplasma pneumoniae and it also has antiinflammatory action. The role of macrolide in asthma
management was controversial.46 Hanhan et al showed
that 42% of their severe asthmatic patient had positive
Mycoplasma pneumoniae IgM antibody and suggested
with the presence of infiltrates on chest X-ray in status
asthmaticus, tests for Mycoplasma pneumoniae should
be done.47

Ventilation support

Non-invasive positive pressure ventilation (NIV)

with expiratory positive airway pressure and inspiratory
positive airway pressure of 6 cmH2O and 8 cmH2O
respectively was shown to improve FEV1 in mild
to moderate cases without bronchodilator therapy.48
Cochrane database only include one trial for analysis in
2005 which showed benefit with NIV when compared
to usual medical care alone, there was significant
improvements in hospitalisation rate, number of
patients discharged from emergency department, lung
function and respiratory rate.49 Brandao et al showed
that jet nebulization through a non-invasive positive
pressure with inspiratory positive airway pressure 15
cmH2O and expiratory positive airway pressure 10
cmH2O is better than nebulization with spontaneous
breathing.50 Adult study suggested using a high PEEP
pressure and low delta pressure strategy 50 although
data in children is lacking. The clinician should stay
at the bedside to start the NIV with CPAP of at least 5
cmH2O and gradually titrated up or change to Bi-level
positive airway pressure as stated before with frequent
reassessment and close monitoring in PICU to ensure
82

timely intubation should it be necessary. Nebulization

of medications can be given with nebulizer via the
inspiratory limb of circuit to minimize disruption of
NIV.

Intubation

Intubation may be inevitable if the patient present

late with respiratory arrest, cardiac arrest, severe
hypoxaemia or altered mental state. We also need to
consider intubation in an exhausted child with poor
response to maximal treatment. Pre-oxygenation and
decompression of stomach by a nasogastric tube should
be done. Rapid sequence induction with atropine, a
sedative and a rapid onset muscle relaxant should be
used. In the absence of increased intracranial pressure,
ketamine, 2 mg per kg, is the common agent used in
asthma because of the bronchodilator effect. Cuffed
endotracheal tube is preferred as high inspiratory
pressure is often required.51 Complications often occur
during or shortly after intubation.52 Hypotension occurs
due to increase in mean airway pressure and decrease
venous return which may be potentiated by sedatives
and muscle relaxants effects. In this case, hypotension
usually responses to decreasing ventilatory rate and
crystalloid bolus. Tension pneumothorax is another
cause of cardio-respiratory decompensation.
For initial ventilator setting, pressure regulated
volume control may help to ventilate with a lower peak
inspiratory pressure. We may start with tidal volume
8-12ml per kg and respiratory rate 8-12 per minute.
With peak inspiratory pressure < 45 cmH2O, Cox et al
reported that 2 out of 19 mechanical ventilated cases
had post-intubation pneumothoraces.51 Long expiratory
time is required, inspiratory to expiratory ratio is often
>1:3. To adjust the expiratory time, the ventilator
flow-time curve should be examined for the return of
expiratory flow to baseline before next inspiration.
Positive end expiratory pressure (PEEP) may cause
further air trapping in asthma but inadequate PEEP
may cause airway collapse with more air trapping
leading to increased work of breathing. End-expiratory
hold methods detect auto-PEEP and help choose an
appropriate PEEP level.
For sedation, continuous infusion of ketamine or
midazolam can achieve deep sedation. Ketamine also
has bronchodilator effect. Prolonged non-depolarizing
muscle relaxant infusion may cause an acute

Life-threatening Asthma

mypopathy.53 The muscle weakness is transient but can

be prolonged. Previous review suggested the combined
effects of corticosteroids and muscle relaxants on the
muscle cell may be responsible for the myopathy.54 As
steroid is an essential part of asthma treatment, we have
to be highly cautious in using muscle relaxant.
If ventilation is very difficult, use of helium-oxygen
therapy may lower the peak inspiratory pressure and
improving blood gas pH and partial pressure carbon
dioxide.55 Another therapy is isoflurane which was
shown to improve arterial pH and reduces partial
pressure of arterial carbon dioxide.56 For ventilator
refractory asthma, extracorporeal life support (ECLS)
can be life saving. Coleman et al supported early
use of ECLS in status asthmaticus and suggested
using a system that identifies patients at high risk
for developing refractory life-threatening asthma,
ie: those with history of multiple intubations and/or
respiratory failure requiring intubation within 6 hours
of admission; those with hemodynamic instability and/
or neurological impairment at time of admission; and
those with a duration of respiratory failure greater than
12 hours despite maximal medical therapy. Moreover,
we should consider ECLS if there is sustained PaCO2
retention above 100 mmHg and persistent serum
pH below 7.0.57 Flexible bronchoscopy should be
undertaken for those refractory cases for detection and
subsequent removal of mucus plug that was often found
to be extensive in those fatal asthma cases. Moreover,
asthma is associated with plastic bronchitis 58 which
can be diagnosed and managed by bronchoscopy.

CONCLUSION
Early identification of children with severe
asthma is important and timely treatment with
systemic steroid is often effective to prevent lifethreatening asthma. For those life-threatening
asthma cases, PICU admission for meticulous
treatment with continuous nebulized beta 2
agonist, anticholinergics and magnesium sulfate
is often life-saving. Addition of leukotrienes
modifier is to be considered individually. Early
use of NIV is often helpful to prevent respiratory
exhaustion.

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