ASTHMA - Medication & Treatment

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22 Current Allergy & Clinical Immunology, March 2011 Vol 24, No. 1
THE TREATMENT OF ACUTE ASTHMA IN
CHILDREN
Correspondence: Dr Sharon Kling, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, PO Box
19063, Tygerberg 7505. Tel +27-21-938-9506, fax +27-21-938-9138, e-mail [email protected]
ABSTRACT
Despite advances in the understanding and man-
agement of asthma, children continue to present to
health care institutions with acute asthma exacer-
bations. An accurate assessment of the severity of
the acute attack is essential to ensure optimal treat-
ment. The cornerstones of acute asthma treatment
remain inhaled short-acting β
2
-agonists (SABA), oral
corticosteroids, and oxygen. The inhaled therapy
may be administered by means of an oxygen- or
air-driven nebuliser, but the pressurised metered-
dose inhaler-spacer combination is preferable under
certain circumstances. Inhaled ipratropium bromide
should be added to the nebulised SABA in the event
of a poor response to treatment. Other therapeutic
options for non-responders are intravenous magne-
sium sulphate and intravenous salbutamol.
Sharon Kling, MB ChB, DCH (SA), FCPaed (SA),
MMed(Paed), M Phil (Applied Ethics)
Pierre Goussard, MB ChB, MMed(Paed)
Robert P Gie, MB ChB, MMed(Paed), FCPaed (SA)
Department of Paediatrics and Child Health, Tygerberg
Children’s Hospital and Stellenbosch University, Tyger-
berg, South Africa
INTRODUCTION
Great advances in our understanding and management
of asthma have been made during the past two de-
cades. Despite this and the improved use of controller
medication, asthma exacerbations continue to pose a
dilemma for paediatricians. Martinez
1
points out that
asthma exacerbations are a major component of asth-
ma morbidity in both preschool and school-aged chil-
dren, and that exacerbations occur despite adherence
to adequate doses of controller therapy.
Asthma is defined as a disease with variable airway
inflammation and airflow obstruction. Asthma exacer-
bations are defined as ‘acute or subacute episodes of
progressively worsening shortness of breath, cough,
wheezing, and chest tightness – or some combina-
tion of these symptoms.’
2
The pathophysiology of an
asthma exacerbation includes airway oedema, mucus
secretion and smooth-muscle spasm (bronchospasm).
ASSESSMENT OF SEVERITY OF AN ACUTE
ATTACK OF ASTHMA
It is essential to assess the severity of an acute attack
of asthma so that appropriate management can be insti-
tuted. The signs that should be assessed are pulse rate,
respiratory rate, amount of breathlessness (ability to
talk and feed), use of accessory muscles of respiration,
extent and loudness of wheezing (which becomes less
audible with increasingly severe airways obstruction),
level of consciousness and presence of agitation (sug-
gesting hypoxaemia). Table I details the features used
in the assessment of severity of an acute attack.
3,4
INITIAL MANAGEMENT OF ACUTE ASTHMA
IN CHILDREN
The foundations of the treatment of acute asthma are
bronchodilators, corticosteroids and oxygen.
Inhaled β
2
-agonists constitute first-line therapy in
acute asthma. Treatment with an inhaled short-acting
β
2
-agonist (SABA) bronchodilator should be started as
early as possible.
4
The bronchodilator may be given by
means of an oxygen- or air-driven nebuliser or with a
metered-dose inhaler (MDI) and spacer combination.
5

The SABA should be given as 3 doses 20 minutes apart,
and the patient assessed for a response. Systemic cor-
ticosteroids (CS) should be administered early in the
acute exacerbation. The oral route is the preferred route
of administration of CS. The doses of SABA and CS are
given in Table II.
Poor response to initial therapy for acute
asthma
If there is an inadequate response to the above ther-
apy after an hour, add nebulised ipratropium bromide
(IB) every 20 minutes for the first 2 hours and 4-hourly
thereafter.
6
ISSUES RELATED TO INITIAL MANAGEMENT
OF ACUTE ASTHMA
Oxygen
All children who have life-threatening asthma (Table I)
or those with oxygen saturations <94% should receive
high-flow oxygen via a mask or nasal-prong oxygen to
obtain saturations ≥95%.
4
Inhaled β
2
-agonists
As previously stated, inhaled SABA may be given either
by means of a nebuliser or with an MDI-spacer combina-
tion. Studies suggest that the MDI-spacer combination
is more efficacious as well as more cost-effective than
the nebuliser,
5
provided that the patient is not acutely
dyspnoeic.
7
There is also evidence that children who
receive the SABA via the MDI-spacer combination have
fewer side-effects such as tachycardia and are less
prone to hypoxia than when being nebulised.
8
Home-
made spacers such as the 500 ml cooldrink bottle are
as efficacious as the commercially designed spacers.
9

Children younger than 3 years of age will require a spac-
er which has a mask attached to the mouthpiece.
For mild-moderate acute asthma attacks, 4-6 puffs of a
SABA actuated into the spacer may be sufficient, but up
to 10 puffs may be required for more severe asthma at-
tacks. The puffs should not be actuated all at once, but
at intervals of about 10 seconds between puffs, and 5
breaths of tidal breathing should follow each actuation.
If the acute asthma attack is severe or life-threatening,
the SABA should be administered at intervals of 20-
30 minutes by means of an oxygen-driven nebuliser.
There is no advantage to giving continuous nebulised
β
2
-agonists outside the intensive care unit (ICU); IB
should be added if there is a poor response to the initial
doses of β
2
-agonists.
Current Allergy & Clinical Immunology, March 2011 Vol 24, No. 1 23
Formoterol is a long-acting β
2
-agonist with a rapid onset
of action, and it could therefore be used in the acute
attack of asthma. A recent systematic review of nine
trials concluded that formoterol may be used in the
treatment of acute asthma in the setting of the emer-
gency department.
10
Steroid therapy
If systemic steroids are used early on in the emergency
department, the need for admission to hospital is re-
duced.
11
Steroids have an onset of action of approxi-
mately 3-4 hours. The oral and intravenous routes have
similar efficacy and onset of action, so the oral route is
the preferred route of administration of CS.
12,13
Intra-
venous therapy is only indicated in the child with very
severe acute asthma who is vomiting or is too ill to take
oral medication. The steroids should be given for ap-
proximately 3 days, but the length of the course does
depend on the child’s condition and how long it takes
for the child to recover from the acute attack of asthma.
It is unnecessary to taper the dose of steroids unless
the steroid course is longer than 2 weeks.
4
Regarding inhaled steroids (ICS), their usual role is in the
maintenance therapy of chronic asthma. ICS may im-
prove airflow in acute asthma, with a more rapid onset
than systemic steroids if administered in very high dos-
es (approximately 5 times those given for maintenance
therapy, in 2-3 divided doses, at varying intervals). The
biggest disadvantage is the cost of the ICS compared to
prednisone.
14
There is currently insufficient evidence to
recommend the use of ICS in acute asthma. It is, how-
ever, important that maintenance doses of ICS should
be continued or started as soon as possible to form the
basis of the child’s chronic asthma management plan.
4
Ipratropium bromide (IB)
The combination of the nebulised anticholinergic, IB,
with a nebulised β
2
-agonist has been shown to result in
greater bronchodilatation than a β
2
-agonist alone.
6
The
most severely affected patients benefit the most, and
IB should be considered in combination with inhaled β
2
-
agonists in the more severe forms of asthma, especial-
ly early in the acute attack, or if there is an incomplete
response to inhaled β
2
-agonists on their own. Initially IB
should be mixed in the same nebuliser as the β
2
-agonist
and administered every 20-30 minutes for the first few
hours after admission. Thereafter the β
2
-agonist should
be weaned to 1-2 hourly depending on the clinical re-
sponse, and the IB should be weaned to 4-6 hourly or
stopped.
4
OTHER THERAPIES IN THE MANAGEMENT OF
ACUTE ASTHMA
Magnesium sulphate
A single dose of IV magnesium sulphate has been
shown to be safe and effective in those patients with
acute severe asthma who have had a poor response
to initial therapy. The response to magnesium appears
to be best in patients who present with very severe
illness.
15
The dose is 25-50 mg/kg/dose (maximum 2 g)
by slow IV infusion.
Intravenous salbutamol
The use of IV salbutamol (15 µg/kg over 10 minutes as a
once-off dose) in the early management of acute severe
asthma in children presenting to the emergency depart-
ment has been shown to reduce the duration of the
exacerbation and hasten the discharge from hospital of
the children.
16,17
In the ICU IV salbutamol by continuous
infusion may be considered if inhaled therapy is ineffec-
tive or for severe refractory asthma. It must be done
with continuous ECG monitoring and regular electrolyte
measurement (low serum potassium is a side-effect of
multiple doses of inhaled and IV salbutamol). The dose
of salbutamol consists of a loading dose of 5 µg/kg/min
for 1 hour, then 1-2 µg/kg/min IV as an infusion.
18
Intravenous aminophylline
Theophylline and its water-soluble salt aminophylline
are methylxanthine derivatives that have largely fallen
Table I. Assessment of severity of acute asthma*
Any one of the following in a child with severe asthma:
Clinical signs Measurements
Life-threatening asthma • Silent chest • SpO
2
<92%
• Cyanosis • PEFR <33% best or predicted
• Poor respiratory effort
• Hypotension, bradycardia
• Exhaustion
• Confusion or drowsiness
Acute severe asthma • Unable to complete sentences in one breath; • SpO
2
<92%
too breathless to talk or feed • PEFR 33-50%
• Agitation
• Accessory muscle use
• Pulse rate >140/min in children 2-5 years old;
>125/min in children >5 years old
• Respiration >40 breaths/min in children 2-5 years old;
>30 breaths/min in children >5 years old
Moderate asthma • Able to talk in sentences • SpO
2
≥92%
exacerbation • Pulse rate ≤140/min in children 2-5 years old; • PEFR ≥50% best or predicted
≤125/min in children >5 years old
• Respiration ≤40 breaths/min in children 2-5 years old;
≤30 breaths/min in children >5 years old
SpO2 – oxygen saturation; PEFR – peak expiratory flow rate
*Adapted from Davies et al.
3
and the British Guideline on the Management of Asthma.
4
24 Current Allergy & Clinical Immunology, March 2011 Vol 24, No. 1
out of favour because of their narrow therapeutic index
and potentially severe side-effects (cardiac arrhythmias,
convulsions). Aminophylline is not indicated in patients
with mild to moderate acute asthma, but it may be used
in cases of near-fatal or life-threatening asthma in the
ICU under continuous ECG monitoring.
4
The loading
dose is 6 mg/kg IV, then 0.5-1 mg/kg/hour by IV infu-
sion; levels should be carefully monitored.
Two studies have compared IV salbutamol and
aminophylline.
19,20
One study
19
showed equivalent re-
sults, while the other demonstrated a shorter inpatient
stay in the aminophylline group, but this group received
a bolus plus infusion while the salbutamol group only
received a bolus dose.
20
Leukotriene receptor antagonists (LTAs)
There is no clear evidence that oral LTAs have a role in
the management of moderate to severe acute asthma
exacerbations in children older than 2 years of age, al-
though they do decrease symptoms, hospitalisations
and steroid use in the primary care setting.
4,21-24
A re-
cent adult study suggested that oral montelukast as
add-on therapy at presenta-
tion improved mean peak ex-
piratory flow rates compared
to placebo,
25
and intravenous
montelukast added to stan-
dard care in adults with acute
asthma improved airway
obstruction as measured by
FEV
1
.
26
Adrenaline
Adrenaline 0.01 ml/kg of a
1:1000 solution administered
subcutaneously may be used
in patients who are moribund
on presentation to the ED, or
where inhaled therapy is not
available.
Intravenous fluids in
acute asthma
Patients with prolonged se-
vere asthma may become
dehydrated as a result of
poor intake or vomiting. It
is, however, inadvisable to
overhydrate patients with
acute asthma, and the rec-
ommended IV fluid volume
in children should not exceed
50 ml/kg/24 hours.
Unproven therapies
There is insufficient evidence to either support or refute
the use of antibiotics in acute asthma, but it is known
that the majority of acute asthma attacks are precipi-
tated by viral infections. Antibiotics should therefore
not be given routinely.
4
There is no evidence to support the use of heliox
27
or
mucolytics in children with acute asthma. Nebulised
magnesium sulphate (on its own or with nebulised
salbutamol) has shown some promise in respect of im-
proved lung function in patients with severe asthma,
28

but cannot currently be recommended for the routine
treatment of acute asthma.
4,28
ICU INDICATIONS AND MANAGEMENT
The indications for admission to ICU are detailed in Table
III. Continuous nebuliser therapy with β
2
-agonists may
be more effective than intermittent therapy in the set-
ting of severe acute asthma.
29
Some of the therapies
used in the intensive care setting are detailed above
(IV salbutamol and aminophylline). The discussion of
mechanical ventilation and adjunctive intensive care
therapies are beyond the scope of this article, and have
been discussed in detail by Prof Tex Kissoon in Current
Allergy & Clinical Immunology in August 2007.
30
Figure
1 summarises the management plan for hospital treat-
ment of children with acute asthma.
HOSPITAL DISCHARGE AND FOLLOW UP
It is difficult to define when patients can safely be
discharged after being admitted with acute asthma.
They should certainly be on treatment that they could
manage at home, and be receiving minimal inhaled β
2
-
agonists. They should receive asthma education with
emphasis placed on treatment and inhaler technique.
They should be discharged on appropriate maintenance
therapy, with a written action plan to manage exacerba-
tions. They should have a follow-up appointment with
their primary care provider within a week of discharge.
Table II. Acute asthma management: drug dosages
Inhaled short-acting β
2
-agonists Dose
Salbutamol nebuliser solution (5 mg/ml) <2 years: 2.5 mg (½ ml) + 3 ml normal saline
>2 years: 5 mg (1 ml) + 3 ml normal saline
Fenoterol nebuliser solution (1 mg/ml) <2 years: 0.5 mg (½ ml) + 3 ml normal saline
>2 years: 1 mg (1 ml) + 3 ml normal saline
MDI + spacer (mask in children <3 years) 2-10 puffs, depending on severity of
acute attack, each inhaled separately
Corticosteroids
Prednisone or prednisolone, oral 1-2 mg/kg/day, maximum dose 40 mg/day.
Give for 3-5 days. No need for tapering
Hydrocortisone 4 mg/kg 4-6 hourly IV
Methylprednisolone 1-2 mg/kg 6 hourly IV
Dexamethasone 0.15 mg/kg 6 hourly IV
Anticholinergics
Ipratropium bromide nebuliser solution Add to short-acting β
2
-agonist nebuliser
0.25 mg/ml; UDV 0.25 mg and 0.5 mg solution for first 1-2 hours, then wean
to 4-6 hourly
<2 years: 0.125 mg (½ ml) + 3 ml normal
saline
>2 years: 0.25 mg (1 ml) + 3 ml normal
saline
Intravenous salbutamol as single dose 15 µg/kg as infusion over 10-15 minutes
for severe asthma in emergency room
MDI – metered-dose inhaler, UDV – unit dose vial
Table III. Indications for admission to intensive care
unit
Poor response to maximal pharmacological therapy in
ward/emergency room
Cyanosis and hypoxaemia (PaO
2
<8kPa) unrelieved by O
2
PaCO
2
>4.5kPa
PEFR <30% predicted or best
Minimal chest movement, ‘silent’ chest
Severe retraction
Deteriorating mental status, lethargy or agitation
Cardiorespiratory arrest
PaO
2
– oxygen partial pressure; PaCO
2
– carbon dioxide partial
pressure, PEFR – peak expiratory flow rate.
Current Allergy & Clinical Immunology, March 2011 Vol 24, No. 1 25
Declaration of conflict of interests
SK & PG have given talks for MSD and GSK; SK was sponsored to the
2010 ALLSA Congress by Cipla Medpro; RPG declares no conflict of
interest in respect of the contents of this article.
REFERENCES
1. Martinez FD. Managing childhood asthma: challenge of preventing
exacerbations. Pediatrics 2009; 123: S146-S150.
2. Global Strategy for Asthma Management and Prevention 2009 (Up-
date) www.ginasthma.org. Accessed 23 February 2010.
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MANAGEMENT OF ACUTE SEVERE ASTHMA IN HOSPITAL
Initial assessment
History, examination, oxygen saturation (SpO
2
),
peak expiratory flow (PEF)
Initial treatment
O
2
Inhaled short-acting β
2
-agonist (SABA) (nebuliser or
MDI/spacer) 1 dose every 20 min x 1 hour
Oral corticosteroid
DANGER SIGNS
Cyanosis; SpO
2
<92%
Previous ICU admission
Acute episode >12 hours
Recent oral steroids
Drowsy or confused
Silent chest on auscultation
Initiate therapy with O
2
,
inhaled SABA, oral steroids.
If no response
Good response*
Observe x 1 hour
Poor response**
Admit to hospital
Continue O
2
, nebulised
SABA+IB, oral
corticosteroids
Other options
IV magnesium sulphate
IV salbutamol (once-off
dose)
Discharge
Follow-up plan
If stable, discharge
Follow-up plan
Incomplete/poor response**
Add ipratropium bromide (IB) 4 hourly
Good response*
*Good response
• Not tachypnoeic
• Minimal wheezing
• No retraction
• Able to speak and feed (young child)
• PEF ≥80% predicted or personal best
**Incomplete/poor response
• Tachypnoeic
• Persistent wheezing
• Retraction present
• Impaired speech or feeding
• PEF ≤79% predicted or personal best
Respiratory failure
Admit to ICU
IV magnesium sulphate
Continue nebulised SABA+IB
IV corticosteroids
IV salbutamol and/or aminophylline
infusions
Intubation and ventilation
Fig. 1. Management of acute asthma in hospital – adapted from Kling et al.
31
(with permission of the editors).
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Potter PC, eds. ALLSA Handbook of Practical Allergy, 3rd ed. Paarl:
ALLSA, 2010.
Joint Meeting ALLSA & PMG Congress 2011
20 - 23 October • Sun City • South Africa
Provisional Programme
• New concepts in food allergy
• Understanding wheeze in young children
• Allergy management in the year 2011
• Primary immunodefciency workshop and a clinical approach
to recurrent infections in children
• Feeding newborns to prevent disease
• Infectious diseases in children
• Practice management and coding
• Financial Management for Doctors
• Ethics Session
Organising Committee
Dr Andrew Halkas
Dr Humphrey Lewis
Dr Andre van Niekerk
First Announcement
/..-..·. .
r-·.-.... s /..·.,,
Congress Ofce
Joint Meeting ALLSA & PMG Congress 2011
T+27 011 447 3876 F +27 011 442 8094
[email protected] www.allergysa.org

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