ASTHMA & PREGNANCY

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Pregnancy & Asthma : 

Pregnancy & Asthma ANISH JOSHI

Definition : 

1-Dec-08 2 Definition Chronic inflammatory disorder with airway hyper- responsiveness and var. airflow obstruction Reversible Status asthmaticus Severe obstruction persisting for days or weeks or not responding after 30 to 60 minutes of intensive therapy

Epidemiology : 

1-Dec-08 3 Epidemiology 7% (William’s) 10-12% of adults 15% of children (Harrison)

Clinical manifestations : 

1-Dec-08 4 Clinical manifestations Classic triad : Wheezing, cough, dyspnea Chest tightness, sputum Chronic with episodic exacerbation

Triggers : 

1-Dec-08 5 Triggers Respiratory irritants ( Perfumes, smoke, detergents, strong odors ) Allergens ( pets, carpets, dust mites Dermatophagoides pteronyssinus, pollen ) Infections ( URI-RSV, bronchitis, sinusitis ) Drugs (Morphine, Beta-blockers, Aspirin) Stress Exercise Cold air Air pollution, Occupation Toluene, Fungal amylase in bakers Diet low in antioxidants –Vit C, A, Mg, Se, Omega 3 PUFA. High in Na or Omega 6PUFA GERD Hormonal (Menses, Hyperthyroidism)

Slide 6: 

1-Dec-08 6 Pathophysiology

Slide 7: 

1-Dec-08 7

Physical examination : 

1-Dec-08 8 Physical examination Wheezing and prolonged expiratory phase Presence of nasal polyps, rhinitis, rash  allergic component Exacerbationpulsus paradoxus, accessory muscle use

Diagnostic studies : 

1-Dec-08 9 Diagnostic studies PFTs PEFR ↓ FEV1 (Reversible), FEV1/FVC ↓ RV and TLC↑ Flow volume loops Allergy suspected serum IgE, eosinophils, skin testing Sputum Curschmann’s spirals ( mucus casts of distal airways) Charcot-Leyden crystals eosinophils

Differential diagnosis : 

1-Dec-08 10 Differential diagnosis All that wheezes is not asthma CHF COPD Upper airway obstruction Tumor Laryngeal edema ...etc

Slide 11: 

1-Dec-08 11 Classification of Severity CLASSIFY SEVERITY Clinical Features Before Treatment Symptoms Nocturnal Symptoms FEV1 or PEF STEP 4 Severe Persistent STEP 3 Moderate Persistent STEP 2 Mild Persistent STEP 1 Intermittent Continuous Limited physical activity Daily Attacks affect activity > 1 time a week but < 1 time a day < 1 time a week Asymptomatic and normal PEF between attacks Frequent > 1 time week > 2 times a month  2 times a month  60% predicted Variability > 30% 60 - 80% predicted Variability > 30%  80% predicted Variability 20 - 30%  80% predicted Variability < 20% The presence of one feature of severity is sufficient to place patient in that category.

Treatment : 

1-Dec-08 12 Treatment Quick relief medications Long-term control medications

Quick relief ‘RELIEVER’ medications : 

1-Dec-08 13 Quick relief ‘RELIEVER’ medications β2-agonists Salbutamol (Albuterol), terbutaline Methylxanthines Aminophylline, Theophylline Anticholinergics Ipratropium & Tiatropium bromide MOA: Bronchodilators

Long term ‘CONTROLLER ’ medications : 

1-Dec-08 14 Long term ‘CONTROLLER ’ medications Corticosteroids Leukotriene modifiers Zafirlukast, Montelukast,Zileuton Mast cell stabilisers Nedocromil/Cromolyn Long acting β2-agonists Salmeterol, Formoterol, Bambuterol Methylxanthines Theophylline Anticholinergics Ipratropium bromide Bronchodilators MOA: Prevent or reverse inflammation

Quick Relief  agonists : 

1-Dec-08 15 Quick Relief  agonists MOA: 1.  receptors  G protein  cAMP  Bronchodilatation 2.  mucociliary transport 3.  release of mediators Short acting (30-90 min.) (epinephrine, isoproterenol, isoetharine) Adv: Immediate action Disadv: Only by inhalation or parenteral

Slide 16: 

1-Dec-08 16 Long acting(4-6 h): Selective 2-agonists terbutaline, fenoterol, Salbutamol(albuterol) Adv: Highly specific, No cardiac side effect except high doses Can be given by all routes Disadv: Tremors Salbutamol: 2-4 mg oral, 0.5 mg im/s.c, 100-200 g/puff Preferred route inhalation, equivalent to iv in severe asthma Terbutaline: 0.25 mg sc or inhalation, 5 mg oral

Slide 17: 

1-Dec-08 17 Ultra long(9 to 12 h): Salmeterol & formoterol For nocturnal and exercise-induced asthma Adv: Anti-inflammatory activities Disadv: Not recommended for acute episodes Salmeterol: 25 g/puff MDI, 2 puffs BD. ‘SEROFLO’ ROTACAPS (Salm + fluticasone), MDI

METHYLXANTHINES : 

1-Dec-08 18 METHYLXANTHINES Medium potency bronchodilators with ? anti-inflammatory properties. 2nd line drug Rarely used in acute condition Adv: “Controller class”, Single evening dose  nocturnal symptoms Theophylline: 100-300 mg TDS Aminophylline: Slow iv 250-500 mg

METHYLXANTHINES Contd. : 

1-Dec-08 19 METHYLXANTHINES Contd. Disadv: Metabolism  with age, erythromycin, macrolide antibiotics, quinolones , allopurinol, propranolol, phenytoin Disturbs sleep rhythm Seizures & arrythmias (>30 g/ml) Blood level monitoring (5-15 g/ml)

ANTICHOLINERGICS : 

1-Dec-08 20 ANTICHOLINERGICS Adv: Heart disease Disadv: Slow to act (60 to 90 min) Modest potency

GLUCOCORTICOIDS : 

1-Dec-08 21 GLUCOCORTICOIDS Ind: Acute illness with failure of optimal bronchodilators Chronic disease with frequent recurrence &  severity Inhaled for long term control of asthma Adv: Most potent Max. antiinflammatory

Slide 22: 

1-Dec-08 22 MP Dose: 120-180 mg iv QD 7-60 mg daily OD am as needed for control Prednisolone Dose: 60 mg QDS. Taper ½ q 5th day after 10-12 days of acute episode S/E: Long delay to peak action Interrrupted growth, HT, Gastric ulcer, Suppress PAA

Slide 23: 

1-Dec-08 23 Inhaled steroids Persistent symptoms & control inflammation Facilitate the long-term prevention  need for oral steroids Minimize acute occurrences & hospitalizations Beclomethasone: 100,200,250 g Budesonide: 200, 400 g BD- QID Fluticasone: 25,50,125 g inhalation, rotacaps 100-250 g BD  Dose needs to be individually titrated

Leukotriene receptor antagonists : 

1-Dec-08 24 Leukotriene receptor antagonists Zafirlukast, Montelukast, MOA: Inhibit or antagonise competitively against LTD4 receptor Modest bronchodilator to  asthma exercise induced & nocturnal symptoms Montelukast: 10 mg OD Zafirlukast: 20 mg BD 5 Lipooxygenase inhibitor Zileuton Not available

Slide 25: 

1-Dec-08 25 Disadv: Hep. Enz.  Interact with the drugs metabolised by liver +ve responders < 50 % No response in 1 month STOP May uncover Churg-Strauss syndrome

Mast cell stabilisers : 

1-Dec-08 26 Mast cell stabilisers Nedocromil Na, Cromolyn Na MOA: Inhibit degranulation of mast cells Reduce symptoms Lower airway reactivity Ind: Atopic patients with seasonal disease Exercise or cold induced asthma Adv: Can be given 15-20 minutes b/f contact as it can abolish late reaction Cromolyn: 1mg/puff, 2 puffs QDS Nedocromil: 4 mg or 2 puffs BD

Misc : 

1-Dec-08 27 Misc  Immunosuppressant MTX, Gold, Colchicine Effect minor & S/E considerable when used in steroid dependent patients  Opioid & sedatives Should be avoided Hypoventilation & respiratory arrest

Slide 28: 

1-Dec-08 28  Cough expectorants & mucolytics No added advantage  MgSO4 iv Not used as ? efficacy

Slide 29: 

1-Dec-08 29 Stepwise Approach to Asthma Therapy: Adults Step 1: Intermittent Asthma None required Rapid-acting inhaled 2-agonist for symptoms (but < 3-4times/day) Persistent asthma requires : Long-term-control medication Anti-inflammatory medications preferred Daily Controller Medications Reliever Medications

Slide 30: 

1-Dec-08 30 Inhaled glucocorticosteroid (< 500 μg BD or equivalent) Other options (order by cost): sustained-release theophylline, or Cromone, or leukotriene modifier Rapid-acting inhaled 2-agonist for symptoms (but < 3-4 times/day) Other options: inhaled anticholinergic, or short-acting oral 2-agonist, or short-acting theophylline Step 2: Mild Persistent Asthma Daily Controller Medications Reliever Medications Continuously review medication technique, compliance and environmental control Review treatment every three months. Step up if control is not achieved; step down if control is sustained for at least 3 months Preferred treatments are in bold print

Slide 31: 

1-Dec-08 31 Inhaled glucocorticosteroid, (200 – 1000 μg BD or equivalent) plus long-acting inhaled β2agonist Other options (order by cost): Inhaled glucocorticosteroid (500 – 1000 μg BD equivalent) plus sustained-release theophylline, or Inhaled glucocorticosteroid (500 – 1000 μg BD equivalent) plus leukotriene modifier Rapid-acting inhaled 2-agonist for symptoms (but < 3 - 4 times/day) Other options: inhaled anticholinergic or short-acting oral 2-agonist or short-acting theophylline Step 3: Moderate Persistent Asthma Daily Controller Medications Reliever Medications

Slide 32: 

1-Dec-08 32 Inhaled glucocorticosteroid, (> 1000 μg BD or equivalent) plus long-acting inhaled β2agonist plus one or more of the following, if needed (order by cost): sustained-release theophylline, or leukotriene modifier or oral glucocorticosteroid Rapid-acting inhaled 2-agonist for symptoms (but < 3-4 times/day) Other options: inhaled anticholinergic or short-acting oral 2-agonist or short-acting theophylline Step 4: Severe Persistent Asthma Daily Controller Medications Reliever Medications

Slide 33: 

1-Dec-08 33 Part 4: Long-term Asthma Management Stepwise Approach to Asthma Therapy - Adults Reliever: Rapid-acting inhaled β2-agonist Controller: Daily inhaled corticosteroid Controller: Daily inhaled corticosteroid Daily long-acting inhaled β2-agonist Controller: Daily inhaled corticosteroid Daily long –acting inhaled β2-agonist plus (if needed) When asthma is controlled, reduce therapy Monitor STEP 1: Intermittent STEP 2: Mild Persistent STEP 3: Moderate Persistent STEP 4: Severe Persistent STEP Down Outcome: Asthma Control Outcome: Best Possible Results Alternative controller and reliever medications may be considered Controller: None -Theophylline-SR -Leukotriene -Oral corticosteroid

Asthma & Pregnancy : 

1-Dec-08 34 Asthma & Pregnancy Chromosome 5,6,11,12,14,16,20 15 methyl PGF2 & MethylErgometrine should be avoided if possible No evidence that pregnancy has a predictable effect on underlying asthma Progesterone has been shown to suppress the immune system and so in that sense it's protective or helpful.  inflammation. Both progesterone and estrogen: bronchodilators

Effect of asthma on pregnancyspecially if untreated well : 

1-Dec-08 35 Effect of asthma on pregnancyspecially if untreated well MATERNAL  ED visits  hospitalizations  hyperemesis  vaginal hemorrhage & accidental haemorrhage due to severe coughing  CS  respiratory failure  PIH  death FETAL  Oligohydroamnios  LBW  premature delivery  fetal demise  Meconium staining NEONATAL  neonatal hypoxemia  low newborn assessment scores  perinatal mortality

Slide 36: 

1-Dec-08 36 Cortisone PG E Easier Breathing  epinephrine GERD Stress Infection Male fetus: testosterone antiinflammatory & bronchodilator

Prevention : 

1-Dec-08 37 Prevention Decrease or control exposure to known allergens and irritants cigarette smoke, pets, foods Alcohol should be doubly avoided by the pregnant woman with asthma, because it can harm the developing fetus and because it can cause bronchial constriction as it is exhaled through the lungs Allergy desensitization

Slide 38: 

1-Dec-08 38 Asthma in the ICU

Goals : 

1-Dec-08 39 Goals Adequate Oxygenation Prevention of Barotrauma Acceptable CO2 Stabilizing Other Organ Systems

Primary management : 

1-Dec-08 40 Primary management Oxygen and Humidification Nebulized or IV Beta agonists Steroids Intravenous Theophylline Nebulized Ipratropium Subcutaneous Adrenaline Adequate Hydration Avoid Prophylactic Antibiotics

Non Invasive Ventilation : 

1-Dec-08 41 Non Invasive Ventilation May try Before Intubating Well Fitted Nasal or Face Mask Conscious enough to Protect the Airway

Indications for Mechanical Ventilation : 

1-Dec-08 42 Indications for Mechanical Ventilation If No Previous Treatment Given Respiratory Arrest Altered Mentation If on Full Treatment Respiratory Muscle Fatigue Worsening Blood Gases Drowsiness Excess Tachycardia or Tachypnoea

Ventilator settings : 

1-Dec-08 43 Ventilator settings High inspiratory flow rate A/C:TV=4-600, RR=8-10, FiO2= 60-100% PEEP=0, I:E=1:3(No Pause), Sens= -0.8 - 2

Refractory Asthma : 

1-Dec-08 44 Refractory Asthma Magnesium (10mEq/20min) Helium-Oxygen (as per FIO2) Ketamine Isoflurane Fibreoptic Bronchoscopy Broncho Alveolar Lavage ECMO Hypothermia

1-Dec-08 45 Thanks My special & sincere thanks to Dr. Kalpesh who helped me in preparation of this presentation