therapies for acute asthma dr k sathiamoorthy consultant paediatrician shree sakthi hospital

Therapies for Acute Asthma

Dr K Sathiamoorthy

Consultant Paediatrician

Shree Sakthi Hospital

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)

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

Asthma Death

Half at home Some unpredictable Risk factors

– poor compliance, hx severe disease, poverty

– Late presentation

Established Therapies for Asthma Exacerbation Oxygen Steroids Beta agonists Anticholinergics

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

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

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)

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

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

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)

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)

Continuous Salbutamol

Recommended doses 1-5 mg/kg/hr Toxicity- hypokalemia, agitation,

tremulousness, tachycardia, ventricular dysrhythmias, hypoxia

dosed to effect IV Terbutaline alternative

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

Other Therapies

Theophylline Magnesium sulfate Heliox

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

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

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

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

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)

Mechanical Ventilation

Indications - profound hypoxemia, life-threatening respiratory muscle fatigue or altered mental status

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.

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

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

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

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

Near or Impending Respiratory Failure Oxygen > 90% (goal) IV steroids Continuous ß-2 agonist inhaled Repeated anti-cholinergics inhaled Move to ICU for intubation

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

My Treatment for Severe Asthma

If still clinically in marked distress Blood gases worsening Try MgSO4

If intubating expect problems

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

Thank you

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

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.

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

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.

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

39

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

40

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)

41

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

42

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

43

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

44

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

45

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

46

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%

47

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

48

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

© 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 / / /

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)

Adults

Adults

Adults

Adults

Adults

Adults

2008 Guidelines2.1 DIAGNOSIS IN CHILDREN (1)

Asthma in children causes recurrent respiratory symptoms of: wheezing cough difficulty breathing chest tightness

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

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

61

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

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