Transcript Therapies for Acute Asthma

Therapies for Acute Asthma
Dr K Sathiamoorthy
Consultant Paediatrician
Shree Sakthi Hospital
Asthma is More Prevalent
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Asthma is the most common disease of
childhood
Affects 9% of kids (groups 15-20%)
10 million missed days of school
570,000 ED visits (1995, < 15 year olds)
Is Asthma More Severe?
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Hospitalization rates  till mid 90’s
Death- rates for all ages
– 2.1/1,000,000 kids < 5 years
– 3.7/1,000,000 kids 5-14 years
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Intubation rates
–  in mid 80’s - 90’s (0.25 - 0.6 of hospital
admits for children with asthma
Asthma Death
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Half at home
Some unpredictable
Risk factors
– poor compliance, hx severe disease,
poverty
– Late presentation
Established Therapies for Asthma
Exacerbation
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Oxygen
Steroids
Beta agonists
Anticholinergics
Steroids for an “Inflammatory”
Disease
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Systemic steroids for all hospitalized pts
Equally effective IV vs PO
Some effect in several hrs, peak 9-12
hrs
Recommended dose is 1 mg/kg per
dose q 4-6 hours of prednisone or IV
Hydrocortisone
Mechanism of Action
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Multiple effects: Am J Resp Crit Care 1996; 154:
S21-27, Barnes
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 production of: interleukins, TNF alpha,
GMCSF
 breakdown of IL-2
 iNO synthase, cyclo-oxygenase,
phospholipase A2
 protease inhibitors, β-2 receptors
 cellular immune function & mucus
formation
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Steroid Therapy
 t1/2
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of prednisone 2-4 hours
Regimens 3- 5 days - stop w/o taper
Inhaled budesonide (1600 μgm/day) for
21 days after admit relapse (JAMA
1999; 281: 2119-2126, by Rowe et al)
Beta agonists
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Most used and effective bronchodilators
actives adenyl cyclase  cAMP
cAMP activates protein kinase leading
to smooth muscle relaxation
Available PO, inhaled, SC and IV
Inhaled β agonists
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Greater bronchial dilatation  systemic
effects
All dosed to effect
When to give continuous not crystal
clear
Continuous cheaper, associated with
faster improvement &  LOS
Delivery of Inhaled Medication
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Affected by particle size & shape, pt
breathing factors and airway caliber
particle size (1-5 μm ideal)
Jet nebulizers - (average particle 1.5-6
μm) (1-5% inhaled)
MDI’s - powder and a liquid propellant
(15 m/sec) (7-14 % inhaled)
MDI vs Nebs
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ED & hospital asthma- MDI’s- cost
and same to slightly  LOS (Arch Dis Child
1999; 80: 421-423, Dewar et al)
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MDI’s hard to give continuously
If intubated MDI’s have better drug
delivery (3-4% with 6.5 ETT vs < 1%
neb)
Continuous Salbutamol
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Recommended doses 1-5 mg/kg/hr
Toxicity- hypokalemia, agitation,
tremulousness, tachycardia, ventricular
dysrhythmias, hypoxia
dosed to effect
IV Terbutaline alternative
Anticholinergics
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Ipatropium- quarternary amino acid
blocks cholinergic bronchoconstriction
About 10% improvement in PEF over
B2 agonist alone
Three repeat doses in ED-  admission
and  PEF. Schuh et al (250
μgm/dose,J Pediatr 1995; 126: 639-45)
dosed q 6 hours after admission
Other Therapies
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Theophylline
Magnesium sulfate
Heliox
Theophylline
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Still recommended as a second line
agent for asthma
Mechanism of action: nonselective III
and IV PDE inhibitor- cAMP & cGMP
immunomodulatory, anti-inflammatory
and bronchoprotective effects
toxicity can be unpredictable
Theophylline for Status
Asthmaticus
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Yung and South (Arch Dis Child 1998; 79: 405410) studies 163 kids
0/81 Aminophylline patients intubated
compared to 5/82
2/3’s had nausea and vomiting
Magnesium Sulfate
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Decreases free Ca++- smooth muscle
relaxation, may stabilize Mast cells and
 histamine release
No definitive studies
Bloch et al (Chest 1995; 107: 1576-81)
– 67 adults 2 gm MgSO4
– subset of severe FEV1 (< 25%) had
admission rates
Magnesium Sulfate
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Paediatric dose 25-100 mg/kg over 20
minutes
Target serum level 3.5- 4.5 mg/dL
?dose response relationship is present
May or may not work- but nontoxic
Heliox
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?Established therapies
Post extubation stridor RCT Kemper et
al (Crit Care Med 1991; 19: 356-9)
Heliox improves delivery of nebulized
meds. Anderson et al (Am Rev Respir Dis
1993; 147: 524-528)
Mechanical Ventilation
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Indications - profound hypoxemia, lifethreatening respiratory muscle fatigue
or altered mental status
Mechanical Ventilation
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Historically associated with increased
risk of death.
Problematic- patients have severe
airway obstruction and develop air
trapping, pneumothorax &
bronchopleural fistula.
Limits delivery of inhaled meds.
Severity of Asthma Exacerbation
Mild
Mod
Severe
Breathless
w/ walking
w/talking
at rest
talks
sentences
phrases
words
Accessory
muscles use
Pulsus
paradox
PEF
usually not
commonly
usually
< 10 mm Hg
10-20 mm Hg > 20 mm Hg
80%
50-80%
< 50%
Sat on RA
> 95%
91-95%
< 91%
PaCO2
< 42 torr
< 42 torr
> 42 torr
Management Mild-Moderate
Asthma Exacerbation
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PEF > 50%
Oxygen sats > 90%, repeated inhaled
b-2 agonist, systemic steroids
Reassess PEF 50-80%, treat 1-3 hrs
If PEF > 70% 1 hr after tx- Discharge
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with written plan
course of steroids
close medical follow
education
Management Moderate Asthma
Exacerbation
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PEF < 50%
Oxygen sats > 90%, repeated inhaled β2 agonist & anti-cholinergics,
systemic steroids
Reassess PEF 50-70%, Admit ward
Oxygen sats > 90%, repeated inhaled β2 agonist q 1-3 hours &
inhaled anti-cholinergics,
systemic steroids
Management of Severe Asthma
Exacerbation
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PEF < 50%
Oxygen sats > 90%, repeated inhaled
bBbß-2 agonist & anti-cholinergics,
systemic steroids
Reassess PEF < 50% admit PICU
Oxygen sats > 90%, continuous inhaled
bBbß-2 agonist & inhaled anticholinergics, systemic steroids
Near or Impending Respiratory
Failure
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Oxygen > 90% (goal)
IV steroids
Continuous ß-2 agonist inhaled
Repeated anti-cholinergics inhaled
Move to ICU for intubation
My Treatment for Severe Asthma
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IV Hydrocortisone(4mg/kg/dose q6)
Salbutamol (5-10mg) X three +
ipatroprium 500mcg
Move to PICU if life threatening
Continuous salbutamol nebs.
If not improving, consider IV
salbutamol/Aminiphyline
My Treatment for Severe Asthma
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If still clinically in marked distress
Blood gases worsening
Try MgSO4
If intubating expect problems
My Treatment for Severe Asthma
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Intubate with Sedation +paralysis
Sedative infusion
Handbag pt to determine initial rate and
pressure limits
Allow spontaneous ventilation
Volume support or pressure support
mode
Thank you
2008 Guidelines
2.4 DIAGNOSIS IN ADULTS (1)
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based on the recognition of a characteristic pattern of
symptoms and signs and the absence of an alternative
explanation for them
the key is to take a careful clinical history
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if asthma is a likely diagnosis, the history should
explore possible causes, particularly occupational
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even in relatively clear-cut cases, to try to obtain
objective support for the diagnosis
2008 Guidelines
2.4 DIAGNOSIS IN ADULTS (2)
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whether or not this should happen before starting
treatment depends on the certainty of the initial
diagnosis and the severity of presenting symptoms
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repeated assessment and measurement may be
necessary before confirmatory evidence is acquired.
2008 Guidelines
2.4 DIAGNOSIS IN ADULTS (3)
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Confirmation hinges on demonstration of airflow
obstruction varying over short periods of time
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Spirometry is preferable to measurement of peak
expiratory flow because it allows clearer identification of
airflow obstruction, and the results are less dependent
on effort
2008 Guidelines
2.4 DIAGNOSIS IN ADULTS (4)
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Spirometry should be the preferred test where available
(training is required to obtain reliable recordings and to
interpret the results)
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A normal spirogram (or PEF) obtained when the patient
is not symptomatic does not exclude the diagnosis of
asthma.
2008 Guidelines
Differential diagnosis of asthma in adults, according to the
presence or absence of airflow obstruction (FEV1/FVC <0.7)
Without airflow obstruction
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Chronic cough syndromes
Hyperventilation syndrome
Vocal cord dysfunction
Rhinitis
Gastro-oesophageal reflux
Cardiac failure
Pulmonary fibrosis
With airflow obstruction
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COPD
Bronchiectasis*
Inhaled foreign body*
Obliterative bronchiolitis
Large airway stenosis
Lung cancer*
Sarcoidosis*
*may also be associated with
non-obstructive spirometry
ADULT with symptoms that may be due to asthma
Clinical History and examination
Spirometry (or PEF if spirometry not available)
Intermediate Probability
High Probability
Obstructive
Normal
FEV/FVC <70%
FEV/FVC >70%
Trial of Treatment
Response?
Yes No
Assess compliance
and inhaler technique.
Reconsider the diagnosis
Consider further tests
or referral
Asthma diagnosis confirmed
Continue Rx
Low Probability
Investigate and treat
alternative diagnosis
Reconsider probable
diagnosis
Further investigation
Response?
No Yes
Manage according to
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alternative diagnosis
Patient with symptoms that may be due to asthma
Clinical History and examination
Spirometry (or PEF if spirometry not available)
High Probability
1)Symptoms (cough, wheeze, SOB or chest tightness):
• worse at night and in the morning
• in response to exercise, allergen exposure and cold air
• after taking aspirin or beta blockers
2) History of atopic disease
3) Family history of asthma or atopic disease
4) Widespread wheeze
5) Evidence of airway narrowing
(NB Normal spirometry when free of symptoms does not
exclu
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Patient with symptoms that may be due to asthma
Clinical History and examination
Spirometry (or PEF if spirometry not available)
High Probability
Trial of Treatment
Response?
Yes
Asthma diagnosis confirmed
Continue Rx
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Patient with symptoms that may be due to asthma
Clinical History and examination
Spirometry (or PEF if spirometry not available)
High Probability
Trial of Treatment
Response?
Yes No
Assess compliance
and inhaler technique.
Reconsider the diagnosis
Consider further tests
or referral
Asthma diagnosis confirmed
Continue Rx
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Patient with symptoms that may be due to asthma
Clinical History and examination
Spirometry (or PEF if spirometry not available)
Low Probability
Highprobability
Probabilityequals:
Low
1) Cough in the absence of wheeze or breathlessness
2) Prominent dizziness, light headedness, peripheral tingling
3) Repeatedly normal clinical examination even when
Trial of Treatment
symptomatic
4) No evidence of Assess
airwaycompliance
narrowing when symptomatic
and inhaler technique.
5)
Voice disturbance
Response?
Reconsider the diagnosis
6) Yes
Symptoms
colds only
No withConsider
further tests
or referral
7) Chronic productive cough
8)
Significant
smoking
history (>20 pack years)
Asthma
diagnosis
confirmed
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9) Cardiac
disease
Continue
Rx
Patient with symptoms that may be due to asthma
Clinical History and examination
Spirometry (or PEF if spirometry not available)
Low Probability
High Probability
Trial of Treatment
Response?
Yes No
Assess compliance
and inhaler technique.
Reconsider the diagnosis
Consider further tests
or referral
Asthma diagnosis confirmed
Continue Rx
Investigate and treat
alternative diagnosis
Response?
Yes
Manage according to
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alternative diagnosis
Patient with symptoms that may be due to asthma
Clinical History and examination
Spirometry (or PEF if spirometry not available)
Low Probability
High Probability
Trial of Treatment
Response?
Yes No
Assess compliance
and inhaler technique.
Reconsider the diagnosis
Consider further tests
or referral
Asthma diagnosis confirmed
Continue Rx
Investigate and treat
alternative diagnosis
Reconsider probable
diagnosis
Further investigation
Response?
No Yes
Manage according to
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alternative diagnosis
Patient with symptoms that may be due to asthma
Clinical History and examination
Spirometry (or PEF if spirometry not available)
Intermediate Probability
High Probability
Obstructive
Normal
FEV/FVC <70%
FEV/FVC >70%
Trial of Treatment
Response?
Yes No
Assess compliance
and inhaler technique.
Reconsider the diagnosis
Consider further tests
or referral
Asthma diagnosis confirmed
Continue Rx
Low Probability
Investigate and treat
alternative diagnosis
Reconsider probable
diagnosis
Further investigation
Response?
No Yes
Manage according to
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alternative diagnosis
Patient with symptoms that may be due to asthma
Clinical History and examination
Spirometry (or PEF if spirometry not available)
Intermediate Probability
High Probability
Obstructive
Normal
FEV/FVC <70%
FEV/FVC >70%
Trial of Treatment
Response?
Yes No
Assess compliance
and inhaler technique.
Reconsider the diagnosis
Consider further tests
or referral
Asthma diagnosis confirmed
Continue Rx
Low Probability
Investigate and treat
alternative diagnosis
Reconsider probable
diagnosis
Further investigation
Response?
No Yes
Manage according to
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alternative diagnosis
Patient with symptoms that may be due to asthma
Clinical History and examination
Spirometry (or PEF if spirometry not available)
Intermediate Probability
High Probability
Obstructive
Normal
FEV/FVC <70%
FEV/FVC >70%
Trial of Treatment
Response?
Yes No
Assess compliance
and inhaler technique.
Reconsider the diagnosis
Consider further tests
or referral
Asthma diagnosis confirmed
Continue Rx
Low Probability
Investigate and treat
alternative diagnosis
Reconsider probable
diagnosis
Further investigation
Response?
No Yes
Manage according to
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alternative diagnosis
Assessment: Royal College of Physicians
of London three questions
IN THE LAST WEEK / MONTH
YES
NO
“Have you had difficulty sleeping because of your asthma
symptoms (including cough)?”
“Have you had your usual asthma symptoms during the day
(cough, wheeze, chest tightness or breathlessness)?”
“Has your asthma interfered with your usual activities
(e.g. housework, work, school, etc)?”
Date
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Applies to all patients with asthma aged 16 and over.
Only use after diagnosis has been established.
© Imperial College London
Outcomes and audit. Thorax 2003; 58 (Suppl I): i1-i92
Asthma Control Test™ (ACT)
1.
In the past 4 weeks, how much of the time did your asthma keep you from getting
as much done at work, school or at home?
2.
3.
During the past 4 weeks, how often have you had shortness
of breath?
During the past 4 weeks, how often did your asthma symptoms (wheezing,
coughing, shortness of breath, chest tightness or pain) wake you up at night, or
earlier than usual in the morning?
4.
During the past 4 weeks, how often have you used your rescue
inhaler or nebulizer medication (such as salbutamol)?
5.
How would you rate your asthma control during the past
4 weeks?
Copyright 2002, QualityMetric Incorporated.
Asthma Control Test Is a Trademark of QualityMetric Incorporated.
Patient Total Score
Score
Adults
Adults
Adults
Adults
Adults
Adults
2008 Guidelines
2.1 DIAGNOSIS IN CHILDREN (1)
Asthma in children causes recurrent
respiratory symptoms of:
wheezing
cough
difficulty breathing
chest tightness
2008 Guidelines
2.1 DIAGNOSIS IN CHILDREN (2)
Clinical features that increase the probability of asthma
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More than one of the following symptoms: wheeze, cough, difficulty
breathing, chest tightness, particularly if these symptoms:
– are frequent and recurrent
– are worse at night and in the early morning
– occur in response to, or are worse after, exercise or other
triggers, such as exposure to pets, cold or damp air, or with
emotions or laughter
– occur apart from colds
Personal history of atopic disorder
Family history of atopic disorder and/or asthma
Widespread wheeze heard on auscultation
History of improvement in symptoms or lung function in response to
adequate therapy
2008 Guidelines
2.4 DIAGNOSIS IN CHILDREN (3)
Clinical features that lower the probability of asthma
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Symptoms with colds only, with no interval symptoms
Isolated cough in the absence of wheeze or difficulty
breathing
History of moist cough
Prominent dizziness, light-headedness, peripheral tingling
Repeatedly normal physical examination of chest when
symptomatic
Normal PEF or spirometry when symptomatic
No response to a trial of asthma therapy
Clinical features pointing to alternative diagnosis
CHILD with symptoms that may be due to asthma
Clinical assessment
High Probability
Intermediate Probability
Consider tests of lung
function and atopy
Trial of Treatment
Response?
Yes No
Assess compliance
and inhaler technique.
Consider further
investigation and/or
referral
Asthma diagnosis confirmed
tinue Rx and find minimum effective dose
Low Probability
Consider referral
Investigate/treat
other condition
Further
investigation
Consider
referral
Response?
No Yes
Continue Rx
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Children age 5-12 yrs
Children age 5-12 yrs
Children age 5-12 yrs
Children age 5-12 yrs
Children age 5-12 yrs
Children age 5-12 yrs
Children Less than 5 yrs
Children Less than 5 yrs
Children Less than 5 yrs
Children Less than 5 yrs
Children Less than 5 yrs