1. health and fitness
2. disease
3. asthma

Indian J Pediatr (2010) 77:1417–1423
DOI 10.1007/s12098-010-0189-8
REVIEW
Management of Status Asthmaticus in Children
Sunil Saharan & Rakesh Lodha & Sushil K. Kabra
Received: 21 July 2010 / Accepted: 18 August 2010 / Published online: 8 September 2010
# Dr. K C Chaudhuri Foundation 2010
Abstract Asthma is a common chronic inflammatory disorder of the airways characterized by recurrent wheezing,
breathlessness, and coughing. Acute exacerbations of asthma
can be life-threatening; annual worldwide estimated mortality
is 250,000 and most of these deaths are preventable. While
most of the acute exacerbations can be managed successfully
in the emergency room, few children have severe exacerbations requiring intensive care. Mainstay of treatment for status
asthmaticus are inhaled β2 agonist and anticholinergic agents,
oxygen along with corticosteroids. Children who do not
respond well to initial treatment require parenteral β2 agonist
and magnesium. Rarely, sick children need parenteral
aminophylline infusion and mechanical ventilation. Guidelines for diagnosis, treatment, ventilator management and
supportive care for status asthmaticus in children are
discussed in the protocol.
Keywords Children . Status asthmaticus . Respiratory
distress
Introduction
Asthma is a chronic inflammatory disorder of the airways
characterized by recurrent episodes of wheezing, breathlessness, and coughing, particularly at night or in the early
morning. Episodes of bronchoconstriction are associated
with airflow obstruction within the lung that is often
reversible either spontaneously or with treatment. Asthma
S. Saharan : R. Lodha (*) : S. K. Kabra
Department of Pediatrics, All India Institute of Medical Sciences,
Ansari Nagar,
New Delhi 10029, India
e-mail: [email protected]
is a common problem worldwide, with an estimated 300
million affected individuals [1]. Global prevalence of
asthma ranges from 1% to 18% of the population in
different countries [1]. Annual worldwide deaths from
asthma have been estimated at 250,000 with no correlation
of mortality with prevalence [1]. In India, as per ISSAC
phase three study, there was increase in asthma prevalence
in 6–7 year age group from 6.2 to 6.8% and in 13–14 year
age group there was decrease in asthma prevalence from
6.7 to 6.4% [2]. There are no data regarding incidence of
acute asthma exacerbation in children in India. In the
United States, as per 2005 National Center for Health
Statistics estimates, asthma prevalence was 22.5 million
(7.7% of population) and exacerbations included approximately 15 million outpatient visits, 2 million emergency
room visits and 500,000 hospitalizations over 1 year [3]. In
our pediatric emergency service, approximately 4% of all
visits are for acute asthma (unpublished data). Of these
children, only 5–10 children (<1% of children with acute
asthma) need PICU admission for management.
Status asthmaticus is defined as severe asthma that fails
to respond to inhaled β2 agonists, oral or IV steroids, and
O2, and that requires admission to the hospital for treatment
[4].
Clinical Presentation
Transient worsening of asthma may occur as a result of
exposure to risk factors for asthma symptoms, or “triggers,”
such as exercise, air pollutants [5], certain weather
conditions, e.g., thunderstorms [6], viral infections of the
upper respiratory tract (particularly rhinovirus and respiratory syncytial virus) [7] or allergen exposure which increase
inflammation in the lower airways.
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The presentation of status asthmaticus varies by severity,
asthmatic trigger, and patient age. Most children present
with cough, wheezing, and increased work of breathing.
The degree of wheezing does not correlate well with
severity of the disease. The noisy chest is a reassuring sign
while distant or absent breath sounds (‘silent chest’) along
with increased respiratory effort usually precede respiratory
failure. Agitation or dyspnea along with altered level of
consciousness, inability to speak, central cyanosis, diaphoresis, and inability to lie down, especially in older
children, should be recognized as severe respiratory
compromise [8]. The presence of pulsus paradoxus correlates with the severity of the asthma attack and may be
useful in monitoring the severity of illness [9, 10]. Highrisk factors for asthma severity and fatality include previous
severe sudden deterioration, past PICU admissions and
previous respiratory failure with the need for mechanical
ventilation.
The history should include: severity and duration of
symptoms, including exercise limitation and sleep disturbance; all current medications, including dose (and device)
prescribed, dose usually taken, dose taken in response to
the deterioration, and response to this therapy; time of onset
and cause of the present exacerbation; and risk factors for
asthma-related death.
Assessment of Severity
The assessment of severity of status asthmaticus is based on
clinical observation of child. The severity of exacerbation is
assessed by evaluating pulse rate, respiratory rate, use of
accessory muscles and ability to complete a sentence.
Becker asthma score is a quick assessment of severity by
using respiratory rate, wheezing, inspiratory: expiratory
ratio and accessory muscle use (Table 1). A score >4 is
considered moderate status asthmaticus while patient with
score 7 and above should be admitted to the ICU [11].
Oxygen saturation should be closely monitored, preferably
by pulse oximetry. Oxygen saturation in children should
normally be greater than 95%, and oxygen saturation less
than 92% is a good predictor of the need for hospitalization
[12]. Complicating factors such as pneumonia, atelectasis,
pneumothorax, or pneumomediastinum should be identified
early.
Chest Radiography Chest radiographs should be obtained
in children with first time wheeze, clinical evidence of
parenchymal disease or those requiring admission to PICU.
Radiographs have a limited role in the management of
status asthmaticus but may be indicated when there is
suspected air leak, pneumonia, or the underlying cause of
wheezing is in doubt [13].
Indian J Pediatr (2010) 77:1417–1423
Blood Gas Arterial blood gas measurements should be
obtained in all children at baseline and subsequently as
indicated. The patient should continue on supplemental
oxygen while the measurement is made. A PaO2 <60 mm
Hg and a normal or increased PaCO2 (especially >45 mm
Hg) indicates the presence of respiratory failure [13]. The
decision to intubate an asthmatic child should be made on
clinical grounds. Arterial blood gas measurement is useful
to assess pulmonary gas exchange and pulse oximetry is
not a reliable measure of adequate ventilation. Usually in
children with status asthmaticus, hypocarbia is present
early and normalization of CO2 with persistent respiratory
distress may indicate impending respiratory failure. Frequent blood gas measurements are required in intubated
children in order to follow clinical progress.
Treatment
The mainstays of treatment for status asthmaticus are as
discussed below (Figs. 1, 2 and 3).
General Children with status asthmaticus admitted to the
PICU require IV access, continuous pulse oximetry and
cardiorespiratory monitoring. Sedation should be strictly
avoided during exacerbations of asthma in the nonintubated children because of the respiratory depressant
effect of anxiolytic and hypnotic drugs [14, 15]. For
children who require mechanical ventilation, it is preferable to have an arterial and central venous access.
Fluid Poor fluid intake, increased loss of insensible fluids
and vomiting may cause dehydration in the asthmatic child.
Fluid replacement should be aimed towards restoration of
euvolemia; isotonic fluid like normal saline or Ringer’s
lactate should be used to correct the dehydration. Fluid
balance should be monitored carefully to avoid overhydration as this may precipitate pulmonary edema. Once
euvolemia is restored, maintenance intravenous fluids
should be started. Careful attention should be paid to serum
potassium values, which may decrease because of use of β2
receptor agonists.
Antibiotics Antibiotics are not routinely indicated in
children with status asthmaticus; these should be used in
children with evidence of bacterial infection as indicated
by high fever, purulent secretions, consolidation on X ray
film or very high leucocyte counts.
Oxygen Oxygen should be administered by nasal cannulae,
by mask, or rarely, by head box in some infants in order to
achieve arterial oxygen saturation of 95%. Oxygen therapy
Indian J Pediatr (2010) 77:1417–1423
1419
Table 1 Assessment of severity of acute asthma-Becker asthma score [11]
Score
Respiratory rate (per min)
Wheezing
I/E ratio
Accessory muscle use
0
1
2
3
<30
30–40
41–50
>50
None
Terminal expiration
Entire expiration
Inspiration and entire expiration
1:1.5
1:2
1:3
>1:3
None
1 site
2 sites
3 sites or neck strap muscle use
should be titrated using pulse oximetry to maintain
satisfactory oxygen saturation [16].
β2 agonists β2 receptor agonists remain the mainstay of
therapy in status asthmaticus. They can be administered via
the inhaled, intravenous, subcutaneous, or oral routes.
Salbutamol and terbutaline are generally preferred due to
relative β2-selectivity. In a recent study by Qureshi et al.,
there was no difference in clinical asthma score in children
with moderate to severe asthma exacerbations after
Fig. 1 Protocol on approach to
children with status asthmaticus
treatment with racemic salbutamol when compared with
lev-salbutamol [17].
For children who need more frequent doses of β2
agonist, continuous nebulization appears to be superior to
intermittent doses [18–20]. The usual dose of continuous
salbutamol nebulization is 0.15–0.5 mg/kg/hr, or 10–
20 mg/hr. The continuous nebulization system requires
use of an infusion pump to deliver the medication at a
constant rate to the nebulizing chamber; this rate equals the
rate of nebulization. However, in the absence of a system to
Child with acute asthma exacerbation
Clinical assessment (Pulmonary index score), pulse oximetry
Pulmonary index score
1. Respiratory rate
CXR and ABG if indicated 2. Wheezing
3. Inspiration/ expiration ratio
4. Accessory muscle use
Assessment of severity of status asthmaticus
Admit to PICU if Becker asthma score ≥7
Comfortable environment
IV access
Maintain euvolemia
Supportive care
Continuous cardio-respiratory monitoring
Avoid sedation
Monitor potassium
Antibiotics, if indicated
Management
Medications
If ventilated -arterial and central venous
access
Ventilation
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Indian J Pediatr (2010) 77:1417–1423
Fig. 2 Medications for treatment of children with status
asthmaticus
Medications
β 2 agonist
Anticholinergic agents
Salbutamol continuous nebulization0.15-0.5 mg/kg/hr, or 10-20 mg/hr
Salbutamol MDI (100 mcg) 4-8 puffs
Subcutaneous Terbutaline-0.01
mg/kg/dose (max 0.3 mg), may be
repeated q 20 -30 min for total 3
times
Ipratropium bromide
125-500 mcg (if
nebulized)
administered every 20
min for up to three
doses
then every 4-6 hrs
Corticosteroids
Hydrocortisone
10 mg/kg IV stat
Then 5 mg/kg IV q 6 hr
Switch to PO
Prednisolone 1-2 mg/kg/d
when stable
Terbutaline -loading dose 10
mcg/kg IV over 10 min followed by
0.1-10 mcg/kg/min
Other medications
Magnesium- 50 mg/kg/dose over 30 min or infusion at a rate of 10-20
mg/kg/hr, can repeat once or twice after 4-6 hrs
Theophylline- loading dose of 5-7 mg/kg infused over 20 min followed by
0.5-0.9 mg/kg/hr
Ketamine- 1 mg/kg/hr, titrated to effect
Vecuronium- 0.1 mg/kg/hr, titrated to effect
deliver continuous nebulization, back-to-back nebulization
of salbutamol in doses of 0.15 mg/kg could be used. During
weaning from continuous salbutamol inhalation, children
should be switched to intermittent salbutamol nebulization.
In some children MDI may be used; usually four to eight
puffs per dose, with each puff delivering 100 mcg. There is
Ventilation
Non-invasive ventilation
Non-invasive positive
pressure ventilation
Invasive ventilation
Volume control mode
VT <6 mL/kg
should be tried prior
to conventional
ventilation
RR approximately half of the normal for age
I:E ratio of 1:3
PEEP of 0-2 cm of H2O
In infants- pressure control ventilation with
PIP adjusted
Fig. 3 Ventilation in treatment of children with status asthmaticus
growing evidence that the use of a metered-dose inhaler
with a holding chamber is at least as effective as nebulized
salbutamol in young children with moderate to severe
asthma exacerbations [21].
Intravenous β2-agonists should be considered in patients
unresponsive to treatment with back to back or continuous
nebulization as well as those in whom nebulization is not
feasible (intubated patients, patients with prohibitively poor
air entry). There is no evidence to support the routine use of
intravenous β2 agonist in patients with severe asthma
exacerbations [22]. Terbutaline is the current intravenous
agent of choice. Terbutaline therapy is started with a
loading dose of 10 mcg/kg IV over 10 min, followed by
continuous infusion at 0.1–10 mcg/kg/min.
Subcutaneous administration of β2 agonist is primarily
used for children with no IV access and as a rapidly
available adjunct to inhaled β2 agonist. Subcutaneous
dosing for terbutaline is 0.01 mg/kg/dose, with a maximum
dose of 0.3 mg. The dose may be repeated every 15–20 min
for up to three doses.
Most adverse effects of β2-agonists in asthma relate to
cardiovascular system, including tachycardia, increased QTc
interval, dysarrhythmia, hypertension, diastolic hypotension.
Excessive central nervous system (CNS) stimulation, includ-
Indian J Pediatr (2010) 77:1417–1423
ing hyperactivity, tremors, and nausea with vomiting, are not
uncommon. Hypokalemia and hyperglycemia are the most
common metabolic derangements associated with salbutamol
use. In a prospective cohort study by Chiang et al., there was
no clinically significant cardiac toxicity in 114 pediatric
patients receiving intravenous terbutaline [23].
Anticholinergic Agents Anticholinergics are now a standard
of care in the treatment of acute asthma in children in
combination with β2-agonists. Anticholinergic agents are
usually administered via the inhaled route. The most
commonly used compound is ipratropium bromide which is
administered via the inhaled route. In a recent meta-analysis of
32 randomized controlled trials, it was concluded that multiple
doses of inhaled ipratropium bromide in combination with β2
agonist significantly reduced hospitalizations and improved
spirometric parameters in pediatric patients with asthma [24].
Ipratropium bromide can be delivered either by aerosol or
MDI. Initial dose range is 125–500 mcg (if nebulized) or
four to eight puffs (if via MDI) administered every 20 min
for up to three doses. The subsequent recommended dosing
interval is every 4–6 h. Ipratropium has few adverse effects
because it has poor systemic absorption. The most common
untoward effects are dry mouth, bitter taste, flushing,
tachycardia, and dizziness.
Methylxanthines Use of methylxanthines is infrequent in
acute exacerbations of asthma because they are less
effective than the β2 agonists and associated with severe
side effects. Several recent studies, however, suggest that
methylxanthines may offer some benefit in children with
status asthmaticus [25].
Methylxathine therapy may be helpful in those critically
ill children who are not responsive to steroids, inhaled and
IV β2 agonist, and O2. Aminophylline is administered by
continuous IV infusion following a loading dose of 5–7 mg/
kg infused over 20 min. In general, a loading dose of 1 mg/
kg will raise the serum theophylline level by 2 mcg/mL.
For maximum therapeutic benefit, the targetted serum
theophylline level is 10–20 mcg/mL. Serum theophylline
levels should preferably be measured 1–2 h after the
loading dose is completed. The continuous aminophylline
infusion should begin immediately after the bolus at a rate
of 0.5–0.9 mg/kg/hr. Toxicity includes nausea and vomiting, tachycardia, and agitation. Severe and life-threatening
toxicity in the form of cardiac arrhythmias, hypotension,
seizures, and death is usually associated with high
theophylline serum concentrations.
Corticosteroids Corticosteroids are included as first line of
therapy in the management of acute asthma. Oral or parenteral
corticosteroids have equal efficacy but parenteral steroids are
preferred for critically ill children. A Cochrane review
1421
demonstrated improved outcomes for children who receive
corticosteroids early during their hospital visit in the emergency department [26]. Aerosolized corticosteroids have a
limited role in the treatment of status asthmaticus [27–29].
Commonly used parenteral steroids include hydrocortisone, methylprednisolone, and dexamethasone. In view of
higher cost of methylprednisolone, hydrocortisone is used in
equivalent doses. Systemic corticosteroids begin to exert their
effect in 1–3 h and reach maximal effect in 4–8 h. Duration of
steroid therapy will depend on severity of the attack and on the
chronicity of underlying inflammation. Usually with shortterm use of high-dose steroids, significant side effects are not
seen, but it can be associated with hyperglycemia, hypertension, and acute psychosis [30]. Prolonged steroid use may
cause immunosuppression, hypothalamic-pituitary-adrenal
axis suppression, osteoporosis, myopathy, and weakness.
Magnesium Magnesium leads to smooth-muscle relaxation
secondary to inhibition of calcium uptake. A recent metaanalysis of five randomized, placebo-controlled studies
showed some benefit of adding intravenous magnesium to
nebulized β2-agonists and corticosteroids [31].
The usual dose of magnesium is 50 mg/kg/dose over
30 min or by continuous infusion at a rate of 10–20 mg/kg/
hr. It may be repeated once or twice after 4–6 h. Side effects
of magnesium administration include hypotension, CNS
depression, muscle weakness, and flushing; though, in the
studies previously mentioned, no significant untoward
effects were reported. Severe complications, such as cardiac
arrhythmia including complete heart block, respiratory
failure due to severe muscle weakness, and sudden
cardiopulmonary arrest, may occur in the setting of very
high serum magnesium levels (usually >10–12 mg/dL).
Serum magnesium levels should be regularly monitored,
when facility is available.
Refer to Fig. 2 for the use of medications.
Mechanical Ventilation (Fig. 3) Indications for intubation
in children with status asthmaticus include cardiopulmonary arrest, severe hypoxia, or rapid deterioration in mental
state. Intubation and mechanical ventlation are considered
in a child who responds poorly to initial therapy and shows
a rising PCO2.
Child must be preoxygenated with 100% oxygen and
hypotension should be anticipated. A cuffed endotracheal
tube with the largest diameter appropriate for the age of the
child should be used [32]. Histamine-producing agents,
such as morphine or atracurium, must be avoided. Ketamine is a preferred induction agent in patients with severe
asthma due to its bronchodilatory action. Rapid sequence
intubation should proceed with a sedative or anesthetic,
atropine (if indicated) and followed by a rapid-acting
muscle relaxant.
1422
Goals of ventilation in status asthmaticus are to maintain
adequate oxygenation, permissive hypercarbia and adjusting minute ventilation (peak pressure, tidal volume, and
rate) in order to maintain an arterial pH of >7.2. Typically
slow ventilator rates with prolonged expiratory phase,
minimal end-expiratory pressure, and short inspiratory time
are used in order to minimize dynamic hyperinflation and
air trapping. The use of positive end-expiratory pressure in
the asthmatic patient receiving mechanical ventilation is
controversial [33]. For older children, one may begin with
volume control mode using settings of VT of 5–6 mL/kg,
RR approximately half of the normal for age, I: E ratio of
1:3 and PEEP of 2–3 cm of H2O. In infants, pressure
controlled ventilation may be used with PIP adjusted to
achieve adequate ventilation; the settings of rate, I:E ratio
and PEEP are same as above. Tracheal extubation should
be attempted as soon as possible.
Most frequent complications with ventilation in these
children are hypotension, oxygen desaturation, pneumothorax/subcutaneous emphysema, and cardiac arrest [34]. If
hypotension and/or hypoxemia do not rapidly respond to
fluid administration and alteration in ventilatory pattern, a
tension pneumothorax must be considered.
Analgesia, Muscle Relaxants, Inhalational Anesthetics Sedation in the asthmatic children is generally not indicated
except in some children who are excessively anxious (not
hypoxemic or hypercarbic) or intubated children. Sedation
should be used only in the closely monitored setting.
Mechanically ventilated children require heavy sedation
and sometimes muscle relaxants to avoid tachypnea,
ventilator asynchrony and to reduce the risk of sudden
cough-induced pulmonary barotrauma. Ketamine is a good
choice because it provides sedation and bronchodilation
with minimal respiratory depression [35]. Ketamine by
continuous infusion is the first choice for sedation, usually
combined with intermittent or continuous administration of
benzodiazepines. Usual ketamine dosing is 1 mg/kg/hr and
is adjusted to achieve sufficient sedation. However,
ketamine may lead to excessive bronchial secretions.
Among opiates, fentanyl is preferred because morphine
causes histamine release, which may exacerbate bronchospasm. Vecuronium is a commonly used meuromuscular
blocking agent with starting dose of 0.1 mg/kg/hr titrated to
achieve adequate paralysis. Inhaled general anesthetics are
indicated when other measures have failed [36].
Helium Oxygen Therapy For children who are not improving with conventional therapy or children who are receiving
high-pressure mechanical ventilatory support, heliox may
be a reasonable adjunct therapy [37]. Kim et al. demonstrated greater clinical improvement in children treated with
continuous salbutamol delivered by heliox than those
Indian J Pediatr (2010) 77:1417–1423
treated with oxygen alone delivered salbutamol [38]. In
systematic reviews of heliox for asthma [39, 40] and in
another prospective, randomized, double-blind, crossover
study of heliox in 11 nonintubated children with severe
asthma [41], heliox failed to show an effect on respiratory
mechanics or dyspnea scores.
Leukotriene Modifiers There are little data to suggest a role
for leukotriene modifiers in acute asthma [42, 43].
Noninvasive Mechanical Ventilation Noninvasive positivepressure ventilation (NIPPV) is an alternative to conventional mechanical ventilation in children with status
asthmaticus. In a crossover trial between NIPPV and
standard therapy in children with status asthmaticus,
NIPPV group had reduced work of breathing and dyspnea
as compared to the standard therapy group [44]. NIPPV
should be tried prior to the institution of conventional
mechanical ventilation in these children [45].
Chest Physiotherapy Chest physiotherapy (CPT) should
only be considered in children with clear segmental or lobar
atelectasis. In all other populations of children with status
asthmaticus, CPT has no therapeutic benefit and is not
recommended as part of routine management in the
critically ill patient with status asthmaticus.
Outcome
Mortality rates for children with severe status asthmaticus
vary in different areas with overall mortality being very
low. With improvement in ventilatory strategies, the
availability of more selective bronchodilating agents, the
prognosis has improved significantly. Nearly all asthma
deaths occur in those children who suffer a cardiopulmonary arrest prior to arrival for emergency hospital care.
Improved outpatient management strategies are necessary
to eliminate asthma related deaths in children.
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