MANAGEMENT OF ACUTE SEVERE ASTHMA

Dr DHANNURAM MANDAVI

INTRODUCTION
Asthma is a chronic lung disease with airway obstruction, airway inflammation and airway hyper-reactivity to various stimuli, often reversible with bronchodilators and antiinflammatory drugs.

PATHOPHYSIOLOGY
1)Extrinsic cause(IgE mediated/allergens) 2)intrinsic cause (non IgE mediated/Infection) Allergens leads to a) Early Reaction within 10 min

Due to histamine; leukotriene- C;D;E ;PAF & bradykinin

Mucosal edema; bronchoconstriction ;mucus secretions

Inhibited by B2 agonist

b) Late Reaction

Develop 3-4 hr & peak at 6-12hr

Mast cell Mediator & ILs ;TNF-Alfa;PGs

Inflammatory reaction & Mucosal Edema Clinical Asthma Inhibited by Premedication with Steroids

Triggering Factors
immunologic & non immunologic
bronchospasm & inflammation Airway obstruction & hyper- reactivity Ventilation perfusion abnormality VaQ-mismatch

Hypoxemia
Hyperventilation PaCO2, pH Hypoventilation PaCO2 pH

Environment Biological - Allergens and genetic risk - Infections Age - Immune - Microbes - Lung - Pollutants - Repair -Stress

Innate and adaptive immune development (Atopy) - Respiratory viral infections Lower airway injury - Aeroallergens - ETS - Pollutants/ toxicants - Persistent inflammation - AHR - Remodeling - Airways growth and differentiation

Aberrant Repair

ASTHMA

CLINICAL SIGNS IN ABNORMAL PHYSIOLOGY

Pathology Clinical presentation

Increased airway resistance

Retraction with increasing severity -Use of accessory muscles Head bobbing anterior flexion of head during inspiration in infants
-prolonged expiration ; silent chest -wheeze -rhonchi -Elevated shoulder -Increased AP diameter of chest

Airway obstruction -Muscle spasm -Mucosal edema Excess trapping of air

Excess mucus secretion

Wet sounds (crackles) more often predominant in infants Irritability,confusion,refusal to feed, semi coma,
Bounding pulses, warm hands, dilated retinal vessels

Hypoxia
Hypercarbia

DIAGNOSIS OF ACUTE SEVERE ASTHMA

History and patterns of symptoms

Physical examination
Measurements of lung function

SUSPECT ASTHMA WITH:

Intermittent wheezing, cough, dyspnea. Increased rate of breathing. Symptoms worse at night and in early morning. Associated with triggers.

ASSESSMENT OF SEVERITY OF AN ACUTE EPISODE

Assess for presence of .Red flag. signs which suggest threat to life: Altered sensorium (drowsy or very agitated) Bradycardia;Poor pulse volume; cyanosis Excessive diaphoresis ABG: rate of rise of pCO2>5mm Hg/hr, pCO2>40 mm Hg, pO2<60 mm Hg, metabolic acidosis (-BE>710) SaO2 on room air < 92%

IF RED FLAG SIGNS ARE ABSENT, GRADE SEVERITY OF EXACERBATION BY PULMONARY SCORE :
Score Respiratory rate <6yrs >6yrs Wheezing present Accessory muscle use

<30

<20

None

No apparent activity

31-45 35 46-60 50 >60 >50 0-3 Mild 4-6 Moderate >6 Severe

21-

Terminal expiration with stethoscope

Questionable increase Increase apparent

36- Entire expiration with stethoscope During inspiration and expiration without stethoscope

Maximum activity

Add score

ASCERTAIN THE FOLLOWING INFORMATION:

Duration of episode Medications the child is already using as preventers Reliever medications taken before reporting to doctor Precipitating factors

IDENTIFY RISK FACTORS FOR ACUTE SEVERE ASTHMA:

Previous exacerbations: Chronic steroid-dependent asthma Prior intensive care admission / mechanical ventilation / life threatening episode Poor compliance with preventer therapy Current exacerbation: Rapid onset and progress of symptoms Frequent visits to doctor in preceding few days Visit to emergency room in past 48 hours Economic and logistic constraints to healthcare access

MANAGING ACUTE ASTHMA EPISODE

RULE OF 6 MS IN MANAGEMENT OF ACUTE SEVERE ASTHMA

Pathology to be corrected Metabolic correction Measures Humidified warm oxygen,Sodium bicarbonate as per base excess Inhalational beta 2 agonists Iv methyl xanthenes Steroids to be used at the earliest

Muscle spasm to be relieved

Mucosal edema

Mucus secretions in excess

Maintain Hydration

Monitor for infections

Antibiotics if mucus is yellow or green or evidence of pneumonia

Mechanical breathing

Ventilators

Acute Asthma initial Assessment Impending Respi.Failure Moderate to severe attack -oxygen -beta 2 agonist or - inj epinephrine/terbutaline -corticosteroids i/v or oral

Reassess after 1hr

Good response -increase interval B/w neb. Observe for 2-4 hrs Discharge on bronchodilators

Poor / partial response -Contd above therapy add aminophylline give iv fluids,correct acidosis

no response after 2-4hrs continue above therapy trial of MgSo4/terbutaline no response/impending respiratory failure transfer to ICU continue same as above trial of iv ketamine

features of respiratory failure

intubate & ventilate

TREATMENT OF AN ACUTE EPISODE

MILD(0-3)
Home plan
SA 2 agonist via MDI + Spacer +/- mask q 20 mins * 3 Sustained 4-6 hrs

Not sustained for 4-6 hrs or risk factors

Start first dose rescue steroid and schedule early doctor visit

Failed Home Plan

Visit hospital

MODERATE(4-6)

Start first dose rescue steroid on the way to hospital

If seen first at this stage
SA 2 agonist via neb or MDI + Spacer +/- mask q 20 mins * 3 or Adrenaline/Terbutaline sc q 20min*3

Commence/Continue rescue steroid

-observe hourly for 3-4 hrs -Contd with hrly neb and oxygen

Sustained 4-6 hrs

Reduce SA 2 agonist q 4-6 hrs and plan discharge If no improvement shift to next

SEVERE(>6)
Seen at initial stage
-O2,iv fluids,iv steroids if needed -SA2 agonist neb q 1hr or contd -Ipratropium neb q30 min * 3 then q 6hrs with monitoring

Reassess Intensify
-contd with neb -Aminophylline cont infusion -monitor sr potassium,counts,SaO2,CXRay -Terbutaline cont iv infusion -MgSO4 iv infusion over 30 min

Sustained for 4-6 hrs : Follow the principle Last in First out - Discharge criteria

not Improving: -Proceed to ICU

RED FLAG SIGNS : ICU MANAGEMENT

Seen first at this stage

Continue intensified ward plan -Blood gas studies -Possible intubation and mechanical ventilation with ketamine and midazolam/fentanyl iv infusion,vecuronium paralysis if req

Step down to ward plan Assess discharge criteria

DO NOT ROUTINELY USE

Antibiotics Mucolytic Cough suppressants Sedatives Chest physiotherapy

SELECTION OF DEVICES
Device Nebulizer Age Suitable for all ages

MDI (Metered dose inhaler)

Children over 10 yrs Spacer still recommended

MDI with Spacer

Suitable for all ages

MDI with Spacer and mask

Dry powder inhaler DPI

< 3 yrs

> 6 yrs

INSTRUCTIONS FOR USAGE OF DEVICES

MDI +Spacer + Mask
-Attach mask to the mouth end of spacer -Shake MDI & insert in MDI end of spacer device

-Cover baby's mouth & nose with mask

-Press canister & encourage the baby to take tidal breathing with mouth open 5-10 times -Remove baby mask & wait for 30-60 sec before repeating

MDI + Spacer -Remove cap of MDI & shake it & insert into spacer -place mouthpiece of spacer -Start breathing in& out & observe movement of valve -once breathing pattern established press canister & contd to breathe 5-10 times -Remove the device & wait for 30 sec before repeating

METERED DOSE INHALER

-Remove cap & shake inhaler in vertical direction
-Breath out gently -Put mouthpiece in mouth & start inspiration which should be slow & deep press canister down & contd to inhale deeply -Hold breath for 10 sec or as long as possible then breath out slowly -Wait for few sec before repeating

Rotahaler -Hold Rotahaler vertically & insert capsule (clear end first) into square hole; make sure that top of the capsule is level with top of hole -Hold rotahaler horizontally; twist barrel in clockwise & anticlockwise direction this will split the capsule -Breathe out gently & put mouth end & take deep inspiration -Remove rotahaler from mouth & hold breath for 10 sec

NEBULIZER
Prerequisites: Optimal volume of solution in nebulizer chamber is 2 to 4 ml Particle size is 2-5 microns Driven by O2 or air Flow is 4 to 8 L/ min Electric (220V AC) or battery powered

DRUGS USED
Relievers

Short acting 2 agonists Salbutamol Levosalbutamol Anti-cholinergics Ipratropium bromide Xanthines Theophylline Adrenaline injections

PREVENTERS

Corticosteroids Anti-leukotrienes Xanthine Mast cell stabilizers Long acting 2 agonists COMBINATIONS

RELIEVERS
Drugs
Formulations Dose available

Comments

Short acting b2 agonists:

Salbutamol

MDI 100 mcg/dose

2-4 puffs as needed. May be repeated thrice at 20 min interval and then 1-4 hourly as Needed 1-2 Rotacaps as needed. May be repeated thrice at 20 min intervals and then 1-4hourly if needed 0.15 mg/kg, minimum 0.25 ml < 6 months age , 0.5 ml > 6 months age, 0.5-1 ml older children. For continuous nebulization

DPI Rotacap 200 mcg/dose

Nebulizer solution of salbutamol is compatible with nebulizer solution of sodium cromoglycate and ipratropium (can be mixed).

respirator solution 5 mg/ml

Neb repulse 2.5 mg/2.5 ml 2.5 mg/3 ml Syp 2 mg/5 ml Tab 2 mg, 4 mg, 8 mg

Use equivalent doses as respirator solution 0.15 mg/kg/dose 3-4 times a day

Discontinue nebulisation b2 agonist if using high infusion rates of iv terbutaline. Since dry powder devices require an optimal inspiratory flow rate they may not be suited to manage acute episodes. May be used for mild episodes.

Laevalbuterol

Neb repulse 0.63 mg/2.5 ml 1.25 mg/2.5 ml

3 times a day

Terbutaline

MDI 250 mcg/dose

Same as for salbutamol

respirator solution 2-5 mg diluted and 10 mg/ml nebulised Syp 1.5 mg/5ml Tab 2.5 mg, 5 mg 0.075 mg/kg/dose may be repeated thrice at 20 min intervals

Subcutaneous terbutaline is not recommended below the age of two years. IV terbutaline drip required continuous heart rate and ECG monitoring. If heart rate > 180/min or if ECG changes develop, halve the drip rate. Dose of iv terbutaline is to be halved if concurrently used with theophylline drip.

Inj 0.5 mg/ml

0.01 mg/kg sc Bolus 5-10 mcg/kg over 10 minutes followed by 2-10 mcg/kg/hour iv (1ml terbutaline + 50 ml 5% dextrose, thus, 1ml = 10 mcg terbutaline) Drug Formulations

Non-selective b2 agonists Adrenaline Inj 1 mg/ml (1:1000 solution) 0.01 mg/kg sc Non-selective b2 agents such as isoproterenol and adrenaline are used infrequently because of cardiac stimulation.

Anticholinergics Ipratropium Bromide MDI 20 mcg/dose, 40 mcg/dose DPI Rotacap 40 mcg/dose

May be used when inhaled therapy is not feasible or as an adjunct to inhaled therapy in very severe attacks 2-4 puffs as needed, may be repeated thrice at 20 mins interval and then 6-8hourly as needed 1-2 Rotacaps as needed Slower onset of action than 2 agonists but may provide additive effect in severe exacerbations.

respirator solution 0.25 mg/ml Neb respule 0.5 mg/2 ml

0.5 ml < 1 year, 1 ml Alternative in children >1 year every 20mins intolerant to for 3 doses, then every 2 agonist. 6-8 hours Use equivalent doses as respirator solution Treatment of choice in bronchospasm due to blocker medication.

Corticosteroids Prednisolone Tab 5 mg, 10 mg Syp 5 mg/5 ml, 15 mg/5 ml Inj 100 mg/vial 1-2 mg/kg/day max. 60 mg/day Rescue therapy or burst therapy

Hydrocortisone

10 mg/kg stat followed by 5 mg/kg every 6 hourly iv

Short-term therapy should continue till symptoms resolve. May be required for 3 to 7days Tapering is not necessary .

Injecteble steroids do not give quicker benefit but may be used in acute severe episodes or when the child is likely to vomit

Methylxanthines Aminophylline Inj 250 mg /10 ml 0.5-1 mg/kg/hr continuous infusion in 5 % dextrose Aminophylline used for t/t of acute exacerbations in patients receiving b2 agonists and steroids. . Improvement of mucociliary clearance and diaphragm contractility.

Other drugs Magnesium sulphate Inj 25 % (250 mg/ml), 50 % (500 mg/ml) 1 ml ampoule 25-50 mg/kg in normal saline infused over 30 minutes Calcium channel modulation by this drug results in decreased histamine and acetyl-choline release.

PREVENTERS
Mast cell stabilizers Sodium cromoglycate MDI 5 mg/dose DPI Rotacap 20 mg/dose Leukotriene receptor antagonists Montelukast 4 mg, 5 mg dispersib le/mouth dissolvin g tablets 10 mg tablets 1-5yrs : 4 mg once daily 6-14 yrs : 5 mg once daily > 14 yrs : 10 mg once daily Bioavailability not affected by food intake. 1-2 puffs 3-4 times a day 1 Rotacap 3-4 times a day 4 times daily regime is difficult to implement. A dose half hour prior to exercise provides protection from Exercise induced asthma for about 4-6 hours.

Effect starts soon after initiation of therapy (1st dose)

Inhaled corticosteroids
Beclomethasone dipropionate MDI 50, 100, 200, 250 mcg/dose DPI Rotacap 100,200, 400 mcg/dose
MDI 100, 200, mcg/dose DPI Rotacap 100, 200, 400 mcg/dose respirator solution 0.5 mg/2ml 1 mg/2 ml

50-400 mcg twice a day 50-400 mcg twice a day

50-400 mcg twice a day 50-400 mcg twice a day Initiating dose : 0.5-1 mg twice a day Maintenance dose : 0.25-0.5 mg twice a day 25-200 mcg twice a day 25-200 mcg twice a day 1 mg twice a day

Budesonide

-Growth monitoring is important if high doses are used. - dexamethasone is not recommended for inhalation since systemic absorption is considerable.

Fluticasone propionate

MDI 25, 50, 125 mcg/dose DPI Rotacap 50, 100, 250 mcg/dose Neb respule

Inhaled corticosteroids + Long-acting b2 agonists Fluticasone (FP) + Salmeterol (Sml) MDI a) FP 50 mcg + Sml 25 mcg/dose b) FP 125 mcg + Sml25mcg/dose c) FP 250 mcg + Sml25mcg/dose DPI Accuhaler a) FP 100 mcg + Sml50mcg/dose b) FP 250 mcg + Sml50mcg/dose c) FP 500 mcg + Sml50mcg/dose DPI Rotacaps a) FP 100 mcg + Sml50mcg/dose b) FP 250 mcg + Sml50mcg/dose c) FP 500 mcg + Sml50mcg/dose 1-2 puffs twice a day -To be used with 1-2 puffs twice a day inhaled steroid 1-2 puffs twice a day therapy and not alone. recommends usage only for children above the age of four years. 1 puff twice a day 1 puff twice a day 1 puff twice a day

1-2 Rotacaps twice a day 1 Rotacap twice a day 1 Rotacap twice a day

Methyl xanthenes

Theophylline

Sustainedrelease anhydrous theophylline tab/cap 100 mg, 200 mg, 300 mg, 450 mg Syp 50 mg/5 ml

Getting started >1 year: (rule of 3.s) Starting dose 10 mg/kg Increments 3 mg/ kg Space the increments 3 days apart Monitor levels 3 days after any increment and then only periodically if poor control/ suspicion of adverse effects <1 year: 0.2 x age in weeks + 5 (gives the dose in mg/kg)

Doses less than 12 mg/kg used -

monitoring is not necessary.

Doses more than 28 mg/kg used -

consider change of drug

Oral corticosteroids Tab 5 mg, 10 mg Syp 5 mg/5 1-2 mg/kg/day max. 60 mg/day

Prednisolone

Use minimum dose to control symptoms. Single morning dose is convenient.

COMPLICATIONS
Pneumothorax Pneumomediastinum Subcutaneous emphysema Atelectasis Bacterial/Viral pneumonia

DISCHARGE PLAN
Continue treatment with inhaled SA2 agonist MDI + spacer +/- mask q 4-6 hrs for 3-7 days Continue course of rescue steroid for 3-7 days (tapering not necessary) Review compliance, trigger elimination, preventer drug use. Review & initiate long term strategy Plan follow up visit within 7-14 days

PROGNOSIS
Although potentially fatal, long term prognosis is good in children. Most children with viral infection triggered asthma will be symptom free by 5 yrs of age By 8 yrs airway caliber reaches adult size and may be responsible for improvement in some more By adolescent age almost 90% become symptom free

REFERENCES
- Asthma by consensus;IAP Respiratory Chapter Dec 2001 - Nelson textbook of paediatrics - IAP textbook of paediatrics 4th edition (2009) - Medical emergencies in children;Meharban Singh - Textbook of paediatrics -O.P. Ghai

THANKYOU

Classification of Asthma Severity FOR ADULTS AND CHILDREN AGE DAYS WITH NIGHTS > 5 YEARS WHO CAN USE A SYMPTOM WITH SPIROMETER OR PEAK FLOW S SYMPTOMS METER PEF FEV1 or PEF[*] % Variability Predicted Normal (%) Continual Frequent 60 >30 Daily >1/wk >60<80 80 >30 2030

CLASSIFICATIO N STEP

Severe persistent Moderate persistent Mild persistent

4 3 2

>2/wk, but >2/mo <1 time/day 2/wk <2/mo

Mild intermittent

80

<20

STEPWISE T/T OF ASTHMA

Step 4 severe persistent inhaled high dose corticosteroids +long acting inhaled B2-agonist {oral corticosteroids if needed}

Step3 moderate persistent

Medium-dose inhaled corticosteroids + long acting inhaled B2 agonists OR leukotriene receptor antagonist / theophylline may be used

Step2 Low dose inhaled corticosteroid OR cromolyn / leukotriene mild persistent asthma receptor antagonist Step1 mild intermittent Short acting inhaled B2 agonists OR oral B2-agonist

Step Down Step Up --

Review t/t every 1 to 6 month & stepwise reduction of t/t may be possible If control is not maintained consider step up first review patient medication technique/adherence & environmental

Asthma Predictive Index for Children

MAJOR CRITERIA Parent asthma

MINOR CRITERIA Allergic rhinitis

Eczema Inhalant allergen sensitization

Wheezing apart from colds Eosinophils 4%

Food allergen sensitization

DIAGNOSIS
LAB TESTS PULMONARY FUNCTION TESTING Spirometry -objective measure of airflow obstruction -Feasable in children > 6 yrs of age -Reproducible efforts indicate test validity;if on 3 attempts FEV1 is within 5%,highest of the three is used INTERPRETATION

Airflow limitation

-low FEV1 (relative to percentage of predicted norms) -FEV1/FVC ratio < 0.80
Improvement in FEV1 >= 12% or >= 200ml

Bronchodilator response to inhaled beta agonist

Exercise challenge

Worsening in FEV1 >= 15%

Exhaled nitric oxide FEno -a marker of airway inflammation in asthma -helps titrate medications and confirm the diagnosis

LAB TESTS

INTERPRETATION

Peak expiratory flow (PEF) monitoring -simple,inexpensive,home use tool -suitable for age > 4 yrs -Poor perceivers of airflow obstruction can have daily objective documentation -morning and evening PEFs(best of three attempts) to be measured for several weeks to determine the personal best -variation > 20% is consistent with asthma Radiology -PA and lateral views CXRays often appear normal -subtle and nonspecific findings of hyperinflation and peribronchial thickening -can be helpful in identifying abnormalities that are hallmarks of asthma masqueraders(aspiration pneumonitis,bronchiolitis obliterans) -also helpful in detecting complications during exacerbations like atelectasis,pneumomediastinum,pneumothorax -CT chest again for asthma masqueraders like bronchiectasis,cystic fibrosis,aspergillosis etc.