t he treatment

Transcription

t he treatment
The
treatment of acute asthma in
children
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, Tygerberg, South Africa
ABSTRACT
Despite advances in the understanding and management of asthma, children continue to present to
health care institutions with acute asthma exacerbations. An accurate assessment of the severity of
the acute attack is essential to ensure optimal treatment. The cornerstones of acute asthma treatment
remain inhaled short-acting β2-agonists (SABA), oral
corticosteroids, and oxygen. The inhaled therapy
may be administered by means of an oxygen- or
air-driven nebuliser, but the pressurised metereddose 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 magnesium sulphate and intravenous salbutamol.
INITIAL MANAGEMENT OF ACUTE ASTHMA
IN CHILDREN
The foundations of the treatment of acute asthma are
bronchodilators, corticosteroids and oxygen.
Inhaled β2-agonists constitute first-line therapy in
acute asthma. Treatment with an inhaled short-acting
β2-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 corticosteroids (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 therapy 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
INTRODUCTION
Great advances in our understanding and management
of asthma have been made during the past two decades. Despite this and the improved use of controller
medication, asthma exacerbations continue to pose a
dilemma for paediatricians. Martinez1 points out that
asthma exacerbations are a major component of asthma morbidity in both preschool and school-aged children, 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 exacerbations are defined as ‘acute or subacute episodes of
progressively worsening shortness of breath, cough,
wheezing, and chest tightness – or some combination 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 instituted. 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 (suggesting hypoxaemia). Table I details the features used
in the assessment of severity of an acute attack.3,4
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 β2-agonists
As previously stated, inhaled SABA may be given either
by means of a nebuliser or with an MDI-spacer combination. 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 Homemade 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 spacer 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 attacks. 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 2030 minutes by means of an oxygen-driven nebuliser.
There is no advantage to giving continuous nebulised
β2-agonists outside the intensive care unit (ICU); IB
should be added if there is a poor response to the initial
doses of β2-agonists.
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]
22
Current Allergy & Clinical Immunology, March 2011 Vol 24, No. 1
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
• SpO2 <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;
too breathless to talk or feed
• Agitation
• Accessory muscle use
• P
ulse rate >140/min in children 2-5 years old;
>125/min in children >5 years old
• R
espiration >40 breaths/min in children 2-5 years old;
>30 breaths/min in children >5 years old
Moderate asthma • Able to talk in sentences
exacerbation
• Pulse rate ≤140/min in children 2-5 years old;
≤125/min in children >5 years old
• SpO2 <92%
• PEFR 33-50%
• SpO2 ≥92%
• PEFR ≥50% best or predicted
• 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
Formoterol is a long-acting β2-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 emergency department.10
Steroid therapy
If systemic steroids are used early on in the emergency
department, the need for admission to hospital is reduced.11 Steroids have an onset of action of approximately 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 Intravenous 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 approximately 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 improve airflow in acute asthma, with a more rapid onset
than systemic steroids if administered in very high doses (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, however, 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 β2-agonist has been shown to result in
greater bronchodilatation than a β2-agonist alone.6 The
most severely affected patients benefit the most, and
IB should be considered in combination with inhaled β2-
agonists in the more severe forms of asthma, especially early in the acute attack, or if there is an incomplete
response to inhaled β2-agonists on their own. Initially IB
should be mixed in the same nebuliser as the β2-agonist
and administered every 20-30 minutes for the first few
hours after admission. Thereafter the β2-agonist should
be weaned to 1-2 hourly depending on the clinical response, 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 department 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 ineffective 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
Current Allergy & Clinical Immunology, March 2011 Vol 24, No. 1
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Table II. Acute asthma management: drug dosages
Inhaled short-acting β2-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 0.25 mg/ml; UDV 0.25 mg and 0.5 mg
Add to short-acting β2-agonist nebuliser
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 for severe asthma in emergency room
15 µg/kg as infusion over 10-15 minutes
MDI – metered-dose inhaler, UDV – unit dose vial
add-on therapy at presentation improved mean peak expiratory flow rates compared
to placebo,25 and intravenous
montelukast added to standard care in adults with acute
asthma improved airway
obstruction as measured by
FEV1.26
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 severe asthma may become
dehydrated as a result of
poor intake or vomiting. It
is, however, inadvisable to
overhydrate patients with
acute asthma, and the recommended IV fluid volume
in children should not exceed
50 ml/kg/24 hours.
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 infusion; levels should be carefully monitored.
Two studies have compared IV salbutamol and
aminophylline.19,20 One study19 showed equivalent results, 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
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 precipitated by viral infections. Antibiotics should therefore
not be given routinely.4
There is no evidence to support the use of heliox27 or
mucolytics in children with acute asthma. Nebulised
magnesium sulphate (on its own or with nebulised
salbutamol) has shown some promise in respect of improved lung function in patients with severe asthma,28
but cannot currently be recommended for the routine
treatment of acute asthma.4,28
Leukotriene receptor antagonists (LTAs)
ICU INDICATIONS AND MANAGEMENT
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, although they do decrease symptoms, hospitalisations
and steroid use in the primary care setting.4,21-24 A recent adult study suggested that oral montelukast as
Table III. Indications for admission to intensive care
unit
Poor response to maximal pharmacological therapy in
ward/emergency room
Unproven therapies
The indications for admission to ICU are detailed in Table
III. Continuous nebuliser therapy with β2-agonists may
be more effective than intermittent therapy in the setting 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 treatment of children with acute asthma.
Cyanosis and hypoxaemia (PaO2 <8kPa) unrelieved by O2
HOSPITAL DISCHARGE AND FOLLOW UP
PaCO2 >4.5kPa
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 β2agonists. 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 exacerbations. They should have a follow-up appointment with
their primary care provider within a week of discharge.
PEFR <30% predicted or best
Minimal chest movement, ‘silent’ chest
Severe retraction
Deteriorating mental status, lethargy or agitation
Cardiorespiratory arrest
aO2 – oxygen partial pressure; PaCO2 – carbon dioxide partial
P
pressure, PEFR – peak expiratory flow rate.
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Current Allergy & Clinical Immunology, March 2011 Vol 24, No. 1
MANAGEMENT OF ACUTE SEVERE ASTHMA IN HOSPITAL
Initial assessment
DANGER SIGNS
History, examination, oxygen saturation (SpO2),
Cyanosis; SpO2 <92%
peak expiratory flow (PEF)
Previous ICU admission
Acute episode >12 hours
Recent oral steroids
Drowsy or confused
Silent chest on auscultation
Initial treatment
O2
Initiate therapy with O2,
Inhaled short-acting β2-agonist (SABA) (nebuliser or
MDI/spacer) 1 dose every 20 min x 1 hour
inhaled SABA, oral steroids.
Oral corticosteroid
If no response
Good response*
Incomplete/poor response**
Observe x 1 hour
Add ipratropium bromide (IB) 4 hourly
If stable, discharge
Good response*
Respiratory failure
Poor response**
Follow-up plan
Discharge
Admit to hospital
Follow-up plan
Continue O2, nebulised
SABA+IB, oral
corticosteroids
Other options
IV magnesium sulphate
IV salbutamol (once-off
dose)
Admit to ICU
IV magnesium sulphate
Continue nebulised SABA+IB
IV corticosteroids
IV salbutamol and/or aminophylline
infusions
Intubation and ventilation
*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
Fig. 1. Management of acute asthma in hospital – adapted from Kling et al.31 (with permission of the editors).
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.
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Potter PC, eds. ALLSA Handbook of Practical Allergy, 3rd ed. Paarl:
ALLSA, 2010.
First Announcement
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Joint Meeting ALLSA & PMG Congress 2011
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Provisional Programme
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New concepts in food allergy
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Primary immunodeficiency workshop and a clinical approach
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Infectious diseases in children
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