therapies for acute asthma dr k sathiamoorthy consultant paediatrician shree sakthi hospital
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Therapies for Acute Asthma
Dr K Sathiamoorthy
Consultant Paediatrician
Shree Sakthi Hospital
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Asthma is More Prevalent
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)
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Is Asthma More Severe? 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
Intubation rates in mid 80’s - 90’s (0.25 - 0.6 of hospital
admits for children with asthma
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Asthma Death
Half at home Some unpredictable Risk factors
– poor compliance, hx severe disease, poverty
– Late presentation
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Established Therapies for Asthma Exacerbation Oxygen Steroids Beta agonists Anticholinergics
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Steroids for an “Inflammatory” Disease 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
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Mechanism of Action
Multiple effects: Am J Resp Crit Care 1996; 154: S21-27, Barnes
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 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)
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Beta agonists
Most used and effective bronchodilators actives adenyl cyclase cAMP cAMP activates protein kinase leading
to smooth muscle relaxation Available PO, inhaled, SC and IV
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Inhaled β agonists
Greater bronchial dilatation systemic effects
All dosed to effect When to give continuous not crystal
clear Continuous cheaper, associated with
faster improvement & LOS
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Delivery of Inhaled Medication
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)
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MDI vs Nebs
ED & hospital asthma- MDI’s- cost and same to slightly LOS (Arch Dis Child 1999; 80: 421-423, Dewar et al)
MDI’s hard to give continuously If intubated MDI’s have better drug
delivery (3-4% with 6.5 ETT vs < 1% neb)
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Continuous Salbutamol
Recommended doses 1-5 mg/kg/hr Toxicity- hypokalemia, agitation,
tremulousness, tachycardia, ventricular dysrhythmias, hypoxia
dosed to effect IV Terbutaline alternative
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Anticholinergics
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
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Other Therapies
Theophylline Magnesium sulfate Heliox
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Theophylline
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
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Theophylline for Status Asthmaticus Yung and South (Arch Dis Child 1998; 79: 405-
410) studies 163 kids 0/81 Aminophylline patients intubated
compared to 5/82 2/3’s had nausea and vomiting
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Magnesium Sulfate
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
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Magnesium Sulfate
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
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Heliox
?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)
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Mechanical Ventilation
Indications - profound hypoxemia, life-threatening respiratory muscle fatigue or altered mental status
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Mechanical Ventilation
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.
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Severity of Asthma Exacerbation
Mild Mod SevereBreathless w/ walking w/talking at rest
talks sentences phrases words
Accessorymuscles use
usually not commonly usually
Pulsusparadox
< 10 mm Hg 10-20 mm Hg > 20 mm Hg
PEF 80% 50-80% < 50%
Sat on RA
PaCO2
> 95%
< 42 torr
91-95%
< 42 torr
< 91%
> 42 torr
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Management Mild-Moderate Asthma Exacerbation PEF > 50% Oxygen sats > 90%, repeated inhaled -
2 agonist, systemic steroids Reassess PEF 50-80%, treat 1-3 hrs If PEF > 70% 1 hr after tx- Discharge
– with written plan
– course of steroids
– close medical follow
– education
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Management Moderate Asthma Exacerbation PEF < 50% Oxygen sats > 90%, repeated inhaled β-
2 agonist & anti-cholinergics, systemic steroids
Reassess PEF 50-70%, Admit ward Oxygen sats > 90%, repeated inhaled β-
2 agonist q 1-3 hours & inhaled anti-cholinergics, systemic steroids
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Management of Severe Asthma Exacerbation PEF < 50% Oxygen sats > 90%, repeated inhaled
ß-2 agonist & anti-cholinergics, systemic steroids
Reassess PEF < 50% admit PICU Oxygen sats > 90%, continuous inhaled
ß-2 agonist & inhaled anti- cholinergics, systemic steroids
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Near or Impending Respiratory Failure Oxygen > 90% (goal) IV steroids Continuous ß-2 agonist inhaled Repeated anti-cholinergics inhaled Move to ICU for intubation
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My Treatment for Severe Asthma
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
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My Treatment for Severe Asthma
If still clinically in marked distress Blood gases worsening Try MgSO4
If intubating expect problems
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My Treatment for Severe Asthma
Intubate with Sedation +paralysis Sedative infusion Handbag pt to determine initial rate and
pressure limits Allow spontaneous ventilation Volume support or pressure support
mode
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Thank you
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2008 Guidelines2.4 DIAGNOSIS IN ADULTS (1)
- 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
- if asthma is a likely diagnosis, the history should explore possible causes, particularly occupational
- even in relatively clear-cut cases, to try to obtain objective support for the diagnosis
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2008 Guidelines2.4 DIAGNOSIS IN ADULTS (2)
- whether or not this should happen before starting treatment depends on the certainty of the initial diagnosis and the severity of presenting symptoms
- repeated assessment and measurement may be necessary before confirmatory evidence is acquired.
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2008 Guidelines2.4 DIAGNOSIS IN ADULTS (3) Confirmation hinges on demonstration of airflow
obstruction varying over short periods of time
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
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2008 Guidelines2.4 DIAGNOSIS IN ADULTS (4) Spirometry should be the preferred test where available
(training is required to obtain reliable recordings and to interpret the results)
A normal spirogram (or PEF) obtained when the patient is not symptomatic does not exclude the diagnosis of
asthma.
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2008 Guidelines
With airflow obstruction COPD Bronchiectasis* Inhaled foreign body* Obliterative bronchiolitis Large airway stenosis Lung cancer* Sarcoidosis* *may also be associated with
non-obstructive spirometry
Differential diagnosis of asthma in adults, according to the presence or absence of airflow obstruction (FEV1/FVC <0.7)
Without airflow obstruction• Chronic cough syndromes• Hyperventilation syndrome• Vocal cord dysfunction• Rhinitis• Gastro-oesophageal reflux• Cardiac failure• Pulmonary fibrosis
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ADULT with symptoms that may be due to asthma
Clinical History and examinationSpirometry (or PEF if spirometry not available)
High Probability Low ProbabilityIntermediate Probability
Yes No
ObstructiveFEV/FVC <70%
Manage according to alternative diagnosis
Response?
Investigate and treat alternative diagnosis
Yes
Trial of Treatment
Response?
Asthma diagnosis confirmedContinue Rx
No
Assess compliance and inhaler technique.
Reconsider the diagnosisConsider further tests
or referral
NormalFEV/FVC >70%
Reconsider probable diagnosis
Further investigation
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High Probability
Patient with symptoms that may be due to asthma
Clinical History and examinationSpirometry (or PEF if spirometry not available)
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 exclude asthma)
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Patient with symptoms that may be due to asthma
Clinical History and examinationSpirometry (or PEF if spirometry not available)
High Probability
Trial of Treatment
Response?
Asthma diagnosis confirmedContinue Rx
Yes
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Patient with symptoms that may be due to asthma
Clinical History and examinationSpirometry (or PEF if spirometry not available)
High Probability
Trial of Treatment
Response?
Asthma diagnosis confirmedContinue Rx
Yes No
Assess compliance and inhaler technique.
Reconsider the diagnosisConsider further tests
or referral
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Patient with symptoms that may be due to asthma
Clinical History and examinationSpirometry (or PEF if spirometry not available)
High Probability
Trial of Treatment
Response?
Asthma diagnosis confirmedContinue Rx
Yes No
Assess compliance and inhaler technique.
Reconsider the diagnosisConsider further tests
or referral
Low probability equals:1) Cough in the absence of wheeze or breathlessness2) Prominent dizziness, light headedness, peripheral tingling3) Repeatedly normal clinical examination even when
symptomatic4) No evidence of airway narrowing when symptomatic5) Voice disturbance6) Symptoms with colds only7) Chronic productive cough8) Significant smoking history (>20 pack years)9) Cardiac disease
Low Probability
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Patient with symptoms that may be due to asthma
Clinical History and examinationSpirometry (or PEF if spirometry not available)
High Probability
Trial of Treatment
Response?
Asthma diagnosis confirmedContinue Rx
Yes No
Assess compliance and inhaler technique.
Reconsider the diagnosisConsider further tests
or referral
Low Probability
Manage according to alternative diagnosis
Investigate and treat alternative diagnosis
Response?Yes
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Patient with symptoms that may be due to asthma
Clinical History and examinationSpirometry (or PEF if spirometry not available)
High Probability
Trial of Treatment
Response?
Asthma diagnosis confirmedContinue Rx
Yes No
Assess compliance and inhaler technique.
Reconsider the diagnosisConsider further tests
or referral
Low Probability
Manage according to alternative diagnosis
Response?
Investigate and treat alternative diagnosis
YesReconsider probable
diagnosisFurther investigation
No
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Patient with symptoms that may be due to asthma
Clinical History and examinationSpirometry (or PEF if spirometry not available)
High Probability
Trial of Treatment
Response?
Asthma diagnosis confirmedContinue Rx
Yes No
Assess compliance and inhaler technique.
Reconsider the diagnosisConsider further tests
or referral
Low Probability
Manage according to alternative diagnosis
Response?
Investigate and treat alternative diagnosis
YesReconsider probable
diagnosisFurther investigation
No
Intermediate Probability
ObstructiveFEV/FVC <70%
NormalFEV/FVC >70%
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Patient with symptoms that may be due to asthma
Clinical History and examinationSpirometry (or PEF if spirometry not available)
High Probability Low Probability
Manage according to alternative diagnosis
Response?
Investigate and treat alternative diagnosis
YesReconsider probable
diagnosisFurther investigation
No
Intermediate Probability
ObstructiveFEV/FVC <70%
NormalFEV/FVC >70%
Trial of Treatment
Response?
Asthma diagnosis confirmedContinue Rx
Yes No
Assess compliance and inhaler technique.
Reconsider the diagnosisConsider further tests
or referral
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Trial of Treatment
Response?
Asthma diagnosis confirmedContinue Rx
Yes No
Assess compliance and inhaler technique.
Reconsider the diagnosisConsider further tests
or referral
Patient with symptoms that may be due to asthma
Clinical History and examinationSpirometry (or PEF if spirometry not available)
High Probability Low Probability
Manage according to alternative diagnosis
Response?
Investigate and treat alternative diagnosis
YesNo
Intermediate Probability
ObstructiveFEV/FVC <70%
NormalFEV/FVC >70%
Reconsider probable diagnosis
Further investigation
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© Imperial College LondonPage 49
Assessment: Royal College of Physicians Assessment: Royal College of Physicians of London three questionsof London three questions
Outcomes and audit. Thorax 2003; 58 (Suppl I): i1-i92
• Applies to all patients with asthma aged 16 and over.• Only use after diagnosis has been established.
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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1.1. In the past 4 weeks, how much of the time did your asthma keep you from getting 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?as much done at work, school or at home?
2.2. During the past 4 weeks, how often have you had shortness During the past 4 weeks, how often have you had shortness of breath?of breath?
3.3. During the past 4 weeks, how often did your asthma symptoms (wheezing, 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, coughing, shortness of breath, chest tightness or pain) wake you up at night,
or earlier than usual in the morning?or earlier than usual in the morning?
4.4. During the past 4 weeks, how often have you used your rescue During the past 4 weeks, how often have you used your rescue inhaler or nebulizer medication (such as salbutamol)?inhaler or nebulizer medication (such as salbutamol)?
5.5. How would you rate your asthma control during the past How would you rate your asthma control during the past 4 weeks?4 weeks?
ScoreScore
Patient Total ScorePatient Total ScoreCopyright 2002, QualityMetric Incorporated.Copyright 2002, QualityMetric Incorporated.Asthma Control Test Is a Trademark of QualityMetric Incorporated.Asthma Control Test Is a Trademark of QualityMetric Incorporated.
Asthma Control Test™ (ACT)
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Adults
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Adults
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Adults
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Adults
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Adults
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Adults
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2008 Guidelines2.1 DIAGNOSIS IN CHILDREN (1)
Asthma in children causes recurrent respiratory symptoms of: wheezing cough difficulty breathing chest tightness
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2008 Guidelines2.1 DIAGNOSIS IN CHILDREN (2) Clinical features that increase the probability of asthma
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
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2008 Guidelines2.4 DIAGNOSIS IN CHILDREN (3)Clinical features that lower the probability of asthma 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
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CHILD with symptoms that may be due to asthma
Clinical assessment
High Probability Low ProbabilityIntermediate Probability
Yes No
Continue Rx
Response?
Consider referral
Yes
Trial of Treatment
Response?
Asthma diagnosis confirmedContinue Rx and find minimum effective dose
No
Assess compliance and inhaler technique.
Consider further investigation and/or
referral
Consider tests of lung function and atopy
Investigate/treat other condition
Further investigation
Consider referral
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Children age 5-12 yrs
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Children age 5-12 yrs
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Children age 5-12 yrs
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Children age 5-12 yrs
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Children age 5-12 yrs
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Children age 5-12 yrs
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Children Less than 5 yrs
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Children Less than 5 yrs
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Children Less than 5 yrs
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Children Less than 5 yrs
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Children Less than 5 yrs