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Acute Asthma Exacerbation: Management in the ED. Patrick PLAISANCE, M.D., PhD. Associate Professor Department of Anesthesia, MGH, MUHC. NIH Definition. Chronic inflammatory changes in the bronchial submucosa Increased responsiveness of the airways Reversible expiratory airway obstruction.
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Acute Asthma Exacerbation: Management in the ED Patrick PLAISANCE, M.D., PhD. Associate Professor Department of Anesthesia, MGH, MUHC.
NIH Definition • Chronic inflammatory changes in the bronchial submucosa • Increased responsiveness of the airways • Reversible expiratory airway obstruction
Ventilatory and Hemodynamic Consequences • Ventilatory : • dynamic resistances • residualvolume • Atelectases • V/P mismatching • Airways dynamic collapse • Hemodynamic : • Paradoxical pulse > 18 mmHg
Triggering Factors • Infection: • Bacterial sinusitis • Tracheo-bronchial infection • Viral infection of the airways • Medications: • Beta blockers (collyrium), aspirine, NSAI, antibiotics • Others: • Gastro-oesophageal reflux • Psycho-sociological factors • Stress • Exercise • Stop of chronic treatment
Bad Prognosis Factors • Previous severe exacerbations • Hospitalization within the last year • Psycho-sociological factors • Previous intubations • Stop of corticosteroid treatment • Low patient’s compliance
Importance of an Early Treatment
Inhalation versus IV Infusion in Mild Exacerbations
Inhalation versus IV Infusion in Severe Exacerbations
Efficacy of the Inhaled Route - nebulizer - gas flow - driving gas
Advantages of the Inhaled Route • Direct respiratory tropism • Short onset of action • Low doses • Less side-effects • Simultaneous O2 delivery • Humidification of the airways
Intermittent versus Continuous Nebulization • Small benefit from continuous nebulization • Gibbs et al. Acad Emerg Med, 2000 • Beneficial effect on severe exacerbations • No increased side-effects • Moler et al. Am J Respir Crit Care Med, 1995 • Reduction of staff time • Fink et al. Respir Care 2000
Guidelines on Nebulizer Therapy(British Thoracic Society, Thorax 1997) • Driving gas (SpO2 > 90%): • Air + simultaneous O2 (nasal prong) • O2 • Fill volume of 4 mL (if residual volume > 1 mL) • Flow rate 6-8 L/min • Nebulization time < 10 min
Meter-Dose Inhalerswith Holding Chambers • As effective as nebulizers (Cates et al. Cochrane Database Syst Rev, 2000) • Similar hospital admission rate • Similar improvement in PEFR and FEV1 • Children: • HR more important • duration of the treatment in the ED • Progressive administration of the medication • Interesting for children < 3 years
2+ Mechanism of Action • muco-ciliary clearence • vascular permeability • Inhibition of transmitter release from mast cells
2 Agonists • Selective (Terbutaline, Salbutamol) • First line therapy • Short onset of action (2-5 min) • Long duration of action (3-6 h) • Different routes of administration • Non selective (epinephrine) • Vasoconstricting agent • Short duration of action • Side effects
AnticholinergicsMechanism of Action • Ach competitive inhibitors • muscarinic receptors antagonists • Bronchodilators • Inhibitors of the bronchoconstriction induced by irritant agents
Anticholinergics + 2 AgonistsChildren • Schuh S et al. Pediatr 1995: • N = 120 • 5-17 y.o. • FEV1, PEFR, hospitalization stay: • Salbutamol < salbutamol + 1 ipratropium < Salbutamol + 3 ipratropium • More interesting in severe exacerbations
Anticholinergics + 2 +Meta-analyses Children • Plotnick LH et al. Cochrane Database Syst Rev 2000 • N = 836 children • Spirometric improvement • Hospital admission rates
Anticholinergics + 2 AgonistsMeta-analyses Adults • Rodrigo et al. Am J Med 1999 • n = 1483 • Randomized studies, double-blind, controlled • Results: • Pulmonary function improvement • Hospital admission • Stoodley et al. Ann Emerg Med 1999 • N = 1377 • Slight clinical improvement • No side-effects
Anticholinergics and 2+ in Adults Groups PEFR (L/min) PEFR (L/min) PEFR (L/min) Hospital T12h T36h T60h stay (d) _______________________________________________________ S + IB 12h 68 62 56 5,4* S + IB 36h 81 73 47 4,1 S + IB 60h 100 69 42 4 * p < 0,01 Brophy C et al. Thorax 1998
Corticosteroids • hospital admission if administered within the 1st hour • Equal benefit of orally and IV administration • Rowe et al. Cochrane Database Syst Rev, 2000 • Dose ranging from 30-400 mg methylprednisolone : • Manser et al. Cochrane Database Syst Rev, 2000 • Inhaled vs systemic corticosteroids: (Edmonds et al. Cochrane Database Syst Rev. 2003) • PEFR and FEV1 as compared with placebo • as effective as systemic corticosteroids ? • Combination better than systemic route alone ?
Methylxanthines • No benefit from adding methylxanthines to 2+ • More adverse effects • Parameswaran et al. Cochrane Database Syst Rev 2000
MgSO4 • Inhalation: • Improvement in clinical score (Fischl), PEFR, PP • Nannini LJJr. Am J Med 2000 • Mangat HS Eur Respir J 1998 • PEFR • IV: • Boonyavorakul C. Respiratology 2000 • Hospital admission = NS; score = NS • Rowe BH. Ann Emerg Med 2000 • admission rate in severe asthma exacerbations
Helium Properties • Inert gas, colourless, odourless • Density lower than air and O2 • No diffusion through cellular membranes • No chemical and physiological action • Action due to its physical properties No bronchodilator and anti-inflammatory action
Barach et al. Ann Int Med 1935 • The use of Helium in the Treatment of Asthma and Obstructive Lesions in the Larynx and Trachea
Studies • Small trials or case reports with poor methodology • Evaluation criteria varying from one study to another • Different treatment duration
Importance of Flow Rate . Continuous nebulization . P1 = 3,5 bars Gas flow Q = 8 L/min Q = 12.7 L/min Q = 8 L/min He/O2 He/ O2 O2 _____________________________________________________________ P2 (bars) 0.64 1.41 1.45 MMAD (mm) 5.36 3.18 3.60 Nebulized mass after 10 ’ (g) 2.25 3.35 2,.85 Nebulized mass after 15 ’ (g) 3.35 4.08 3.69 Nebulized mass after 20 ’ (g) 3.83 4.46 4.06
PEFR L/min * * * *p < 0,01
ASUR2001 Within the last 3 months 38 % 4 087 asthma exacerbations 30 % 30% 23 % 25% 20% 15% 8 % 10% 5% 0% no (n = 1237) General Practitioner (n =1555) Pneumologist (n = 962) Both (n =333) Patients having a peak flow at home : 16 % (n = 652) Salmeron et al. Asthma severity and adequacy of management in accident and emergency departments in France : a prospective study. The Lancet ; 2001 ; 358 : 629 – 35.
ASUR2001 Severity Upon Arrival Fatal asthma (PEFR < 30%) 26 % (n = 975) 49 % (n = 1834) Severe exacerbation (30 % PEFR 50 %) Mild to moderate exacerbation (PEFR > 50%) 25 % (n = 963) The severity of exacerbation is independent of : • age • gender • recent corticosteroid treatment per os • hospitalization within the last year Salmeron S, et al. Asthma severity and adequacy of management in accident and emergency departments in France : a prospective study. The Lancet ; 2001 ; 358 : 629 – 35.
ASUR2001 Treatment in the ED • inhaled 2 agonists : 92 % (n = 3492) • inhaled anticholinergics : 49 % (n = 1841) • systemic corticosteroids : 60 % (n = 2251) 95 % (n = 924) 93 % (n = 1708) 89 % (n = 860) 90 % 80 % 68 % (n = 666) 70 % 61 % (n = 1117) 51 % (n = 494) 60 % 50 % (n = 913) 49 % (n = 468) 45 % (n = 434) 50 % Fatal asthma 40 % Severe exacerbation 30 % 20 % Mild to moderate exacerbation 10 % 0 Inhaled 2 agonists Inhaled anticholinergiques Systemic corticosteroids Salmeron S, et al. Asthma severity and adequacy of management in accident and emergency departments in France : a prospective study. The Lancet ; 2001 ; 358 : 629 – 35.
Pre-Determined Management Plan • McFadden et al. Am J Med 1995 • Length of stay in the ER • Admission rates • Re-admission • Cost savings
Initial Monitoring • Pulse oxymetry • PEFR (best of three) • Pulse, BP • RR • Clinical judgement: • Cyanosis • Use of accessory muscles • Stridor • diaphoresis • Blood gasses
Initial Treatment in Children Inhaled Treatment Associated Treatment every 20’ within the 1st hour . O2 6-8 L/min (SpO2 95%) . Salbutamol or Terbutaline . Salbutamol 0.5%: 0.03 mL/kg or 7-10 g/kg SC Terbutaline 5 mg + IB 0.25 mg . HSHC 5 mg/kg or methyl- . Or 0.2-0.3 puffs/kg with MDI prednisolone 2 mg/kg IVD + HC
Initial Treatment in Adults Inhaled Treatment Associated Treatment every 20 min within the 1st hour . O2 6-8 L/min (SpO2 90%) . Salbutamol or Terbutaline . Salbutamol 2.5 mg (or 7.5 mg (0.5 mg) or epinephrine continuously) + IB 0.5 mg 0.25 mg SC . or 2-3 puffs with MDI + HC . HSHC 200-400 mg or . or epinephrine 2 mg + 3 mL NS methyl-prednisolone 1 mg/kg IV
Inhospital Treatment Initial treatment Improvement (PEFR: 50-70%) No improvement (PEFR < 50%) 2+: 1/h for 1-3 h 2+ + IB: 3/h pdt 1-3 h 2 IV Good response response>1h Examination nl PEFR > 70% Incomplete Response . Moderate signs . PEFR: 50-70% No improvement . Severe signs . PEFR < 30% . PaCO2 > 45 mmHg . PaO2 < 60 mmHg Discharge ICU PEFR > 70% Examination nl 12h with no tt Admission No improvement within 6-12h
Antibiotics • Graham et al. Cochrane Database Syst Rev. 2001 • No benefit when comparing antibiotics to placebo • Indications: GOLD-guideline (Pauwels et al. Respir Care 2001) • Worsening dyspnea and cough • Increased sputum volume and purulence • Infiltrates on the chest X-ray
NIV • VS-PEP (Shivaran U et al. Resp 1987) • residual volume • respiratory work • Risks: • Overdistension of zones with low resistance • Pulmonary hyperinflation
Conclusion • Importance of an early treatment • Importance of nebulization • Combination 2 agonists/Ipratropium Bromide • Combination of different routes • PEFR monitoring • Interest of MgSO4 and Helium ?