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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: 405410) 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, lifethreatening 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 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 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 – – – – with written plan course of steroids close medical follow education Management Moderate Asthma Exacerbation 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 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 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 Guidelines 2.4 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 Guidelines 2.4 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 Guidelines 2.4 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 Guidelines 2.4 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 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 With airflow obstruction 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 39 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 40 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 41 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 42 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 43 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 44 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 45 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 46 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 47 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 48 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 • • Page 49 / / / 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 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 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 61 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