Asthme Aigu Grave Prise en charge initiale

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1 Asthme Aigu Grave Prise en charge initiale
Sergio Salmeron Service de Pneumologie - Allergologie Fondation Hôpital Saint Joseph, Paris

2 Asthme aigu aux urgences - les questions -
Ampleur du problème, mortalité ? Évaluation - critères de gravité ? Traitement prioritaire ? Critères de réponse ? Mesures de prévention ? « Plan d’action écrit »

3 AAG – Mortalité surtout extra-hospitalière
2000 décès par an en France McFadden, AJRCCM 2003

4 ASUR - Gravité à l’arrivée n = 3772 1997-1998
Asthme aigu grave n = % DEP ≤ 30 % pred ± s. d’alarme Exacerbation sévère n = % DEP % pred Légère / modérée n = % DEP > 50 % pred 3 décès à l’hôpital 75% Lancet 2001; 358:

5 Signes de gravité - AAG Attention discordance Clinique – DEP (jeunes)
Signes d’alarme Troubles de vigilance Pauses respiratoires Silence auscultatoire Cyanose Signes de gravité Orthopnée Contraction SC Sueurs Parole impossible Agitation FC ≥ 110 / min FR ≥ 30 / min DEP < 30 % th PaCO2 > 40 mm Hg Attention discordance Clinique – DEP (jeunes) 150 l/min

6 AAG – Ventilation Point d’inflexion de la ventilation en cas d’obstruction sévère 16 16 14 14 12 12 10 10 VA L/min VA L/min VE 8 8 6 6 VA 4 4 2 2 10 20 30 40 50 60 70 80 90 100 Pred-FEV1 % Mc Fadden, NEJM 1968

7 AAG : Relation obstruction bronchique et PaO2
Relation assez lâche entre PaO2 et obstruction Bronchique Mac Fadden, N Engl J Med, 1968

8 AAG : Relation obstruction bronchique et PaCO2
Une PaCO2 > 40 mmHg Témoigne d’une obstruction Majeure VEMS < 30% pred Mac Fadden, N Engl J Med, 1968

9 Traitement de l’AA aux Urgences
Traitement conventionnel Première ligne : BD inhalés β2+, Antichol, corticoïdes, Deuxième ligne : idem + β2+ IV, adré, amino… Traitement non conventionnel Sulfate de Magnésium Heliox Ketamine Halogénés

10 AAG – β2 agonistes nébulisés vs IV
Supériorité de la voie inhalée dans l’AAG hypercapnique PEF Pa CO2 Clinical Index 200 ** 15 150 50 10 * L/min 100 mm Hg * 5 40 50 ** ** 1 hr 1 hr 1 hr salbutamol *p  0.05 N = 47 NEB : 5mg x 2 **p  0.001 NEB Group IV Group IV : 0.5mg en 1h Salmeron, AJRCCM 1994

11 2 Agonistes - Visualisation scanner
Tamura G, NEJM 2005 VEMS = 1.27 L (50%) L

12 7 methodologically strong studies
Travers, Chest 2002 7 methodologically strong studies Evidence is lacking to support the use of IV β2 -agonists in ED patients with severe acute asthma. Clinical benefit appears questionable, Potential clinical risks are obvious. The only recommendations for IV β2+ use : when inhaled therapy is not feasible, controlled clinical trial Guidelines : ASA or Life-threatening with poor response to Tt Although statistically nonsignificant, 7 methodologically strong studies demonstrated that peak expiratory flows and heart rates were unchanged following β2 -agonist use compared to all other treatments at 60 min (8.3 L/min [95%CI, 17.6 to 34.2] and 3.65 beats/min [95% CI, 2.9 to 10.2], respectively), with an increased risk of adverse effects (OR, 1.98; 95% CI, 0.5 to 8.2). Conclusions:Evidence is lacking to support the use of IV β2 -agonists in ED patients with severe acute asthma. Moreover, the clinical benefit appears questionable, while the potential clinical risks are obvious. The only recommendations for IV β2 -agonist use should be in those patients in whom inhaled therapy is not feasible, or in the context of a controlled clinical trial comparing IV β2 -agonists with standard care vs standard care alone. Indeed the latest British Thoracic Society this year do not recommend IV beta mimetics in adults, contrary to the GINA guidelines of 1998 that mention to consider the IV route in case nebulisation fails.

13 2 Agonistes - Autres modalités d’administration
AD + Chambre d’inhalation 2.500 2.300 2.100 1.900 1.700 FEV1 1.500 1.300 1.100 Dry powder 0.900 MDI 0.700 Nebulizer 0.500 0.300 30 60 90 120 180 240 300 360 Raimondi, Chest 1997 TIME (minutes)

14 Nébulisation : adrénaline vs salbutamol
Pas de preuve de la supériorité de l’adrénaline 225 N = 22 Salbutamol 5 mg 175 *** Adrenaline 2mg *** *** Peak expiratory flow ( l/min) 125 *** 75 25 Base 20 min 40 min Abroug Intens Care Med 1995

15 Adrenaline vs β2 agonistes
BTS 2003 GINA 2004 Although adrenaline is sometimes considered if a severe exacerbation is unresponsive to inhaled β2 +, amore logical approach would be to add an IV β Evidence B

16 AAG – Corticoïdes systémiques
Délai d’action similaire de 3 à 4 heures pour les voies orale et IV 180 8 patients mean  SEM Prednisolone orale 160 Placebo oral Hydrocortisone I.V. Placebo I.V. saline % of pretreatment PEFR 140 120 100 2 4 6 8 10 12 Hours Ellul Micaleff 1975

17 Anticholinergiques - AAG
100 C n = 92 90 IB n = 88 80 70 IB Ipratropium FEV1 (% pred) 60 ** ** C Controle ** 50 ** ** ** 40 Salbu : 400 μg/10 min ± IB : 50 μg/10 min Pendant 3 heures 30 20 10 TIME ( min) Rodrigo, AJRCCM 2000 Pre 30 60 90 120 150 180

18 Anticholinergiques - AAG
Bénéfice de l’association aux 2 agonistes dans les formes les plus graves 100 100 FEV1  30% FEV1 > 30% 90 90 80 80 70 70 60 60 FEV1 (% PREDICTED) FEV1 (% PREDICTED) 50 50 40 40 30 30 C n = 70 IB n = 58 20 20 10 10 Pre 30 60 90 120 150 180 Pre 30 60 90 120 150 180 TIME ( min) TIME ( min) IB bromure d’ipratropium C contrôle Rodrigo, AJRCCM 2000

19 Ipratropium Bromide - Guidelines
GINA 2004 A combination of β2 agonist and IB may produce better bronchodilation than either drug alone Evidence B Combination therapy associated with lower admission rates (Evidence A) and greater improvement in PEF and FEV1 Evidence B BTS Nebulised IB (0.5 mg 4-6 hourly) should be added to β2 agonist treatment for patients with Acute severe asthma or life-threatening asthma or those with poor initial response to β2 agonist therapy. Grade A recommendation based on strong RCT and meta-analyses I ++

20 Absence de bénéfice aminophylline I.V.
Nébulisation 2 agonistes - AAG Absence de bénéfice aminophylline I.V. 300 200 Peak expiratory flow ( l/min) 100 Neb salbu + amino I.V. Neb salbu 6 12 18 24 30 36 42 48 Time (hours) n = 25 Zainudin, Thorax 1994

21 Methylxanthines in Severe Acute Asthma - Guidelines -
GINA/NIH 2002 Methylxanthynes have equivalent bronchodialtor effect to inhaled β2 agonists (..!), but because of increased side effects, methylxanthines should only be considered as an alternate therapy. BTS 2003 The use of IV aminophylline is not likely to result in any additional bronchodilation compared to standard care with inhaled bronchodilators and steroid tablets. Evidence I++ Side effects such as palpitations, arrhythmias and vomiting are increased if IV amino is used. Use IV amino only after consultation with senior medical staff.

22 Répartition en fonction critère de réponse prédéfini DEP > 50 %
Réponse aux 2 agonistes aux urgences Répartition en fonction critère de réponse prédéfini DEP > 50 % Non admis n = 81 80 80 Admis n = 35 70 70 60 60 50 50 PEFR (% of Predicted) 40 PEFR (% of Predicted) 40 30 30 20 20 10 10 1 heure 0.0 1.2 2.4 3.6 4.8 6.0 7.2 0.0 1.2 2.4 3.6 4.8 6.0 7.2 Salbutamol (mg) Salbutamol (mg) Rodrigo, Chest 1998

23 Magnésium IV – Réponse selon gravité
80 SEVERE 70 Mg GIVEN 60 Magnesium 50 Placebo FEV 1 (% PREDICTED) 40 30 20 10 TIME (MINUTES) 30 60 120 150 180 210 240 80 MODERATE 70 60 50 FEV 1 (% PREDICTED) Magnesium 40 Placebo 30 20 Mg GIVEN 10 TIME (MINUTES) Block, Chest 1995 30 60 120 150 180 210 240

24 IV Magnesium – AAG N = 248 Patients 18-60 yr FEV1 < 30% pred
Placebo n = 126 Magnesium n = 122 Neb Salbutamol 2.5 mg/30 min IV Cortisone 100 mg IV Magnesium 2 g / min or placebo Silverman, Chest 2002

25 Magnésium IV – AA Urgences : Méta analyse
44 Ciarello et al 45 Tiffany et al 3 Skobeloff et al 48 Devi et al 46 Skorodin et al 47 Green & Rothrock 50 Matusicwicz et al 43 Bloch et al 49 Silverman et al Combined -1 0 0.16 1 Alter,Ann Emerg Med 2000

26 Sulfate de Magnésium nébulisé
VEMS < 30% Mg Δ FEV1 = 0.83 Saline Δ FEV1 = 0.19 VEMS > 30% Mg Δ FEV1 = 0.64 Saline Δ FEV1 = 0.51 Hughes, Lancet 2003

27 IV Magnesium - GINA / NIH Guidelines 2004
IV Magnesium should not be used routinely in acute asthma exacerbations, but can help reduce hospital admission rates in selected groups of patients : - Adults with FEV1 25 – 30% pred at presentation Adults who fail to improve above 60% pred after 1 hour Evidence A IV Magnesium is usually given at a single 2-g infusion over 20 min One study isotonic Mg as an adjuvant to nebulized salbutamol, further studies… Indeed it is now recommended by the BTS 2003, based on metanalyses published in Here is the accompanying editorial in the Ann of emerg med. . These meta nallyses , with some discrepancies in their interpretation of data, reach the same concluion: which is agreed by the BTS guidelines: Idem BTS British Thoracic Society Asthma Guidelines 2003 /

28 AAG – Prise en charge initiale Conclusions
Traitement initial ß2 + nébulisés fortes doses, anticholinergiques Niveau A corticoïdes Traitement secondaire Sulfate de Mg IV Niveau A Autres traitements à évaluer

29 Bénéfice des corticoïdes inhalés
Contrôle des symptômes Optimisation Fonction resp Réduction Exacerbations Consultation urgences Hospitalisations Réduction de la mortalité Suissa, Ernst, JACI 2001

30 Probability of Remaining
Corticothérapie orale courte durée Prevention des rechutes après consultation aux urgences 100 48 47 45 46 45 43 44 90 42 40 43 42 39 38 40 37 39 38 80 35 34 Probability of Remaining Reelapse-free (%) 32 31 70 30 27 60 26 25 50 2 4 6 8 10 12 14 16 18 20 Days after Emergency Room Treatment Chapmann, NEJM 1991