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SDRA persistant: que faire ????
Laurent PAPAZIAN Réanimation des Détresses
Respiratoires et des Infection Sévères Unité de Recherche en Maladies
Infectieuses et Tropicales Émergentes - UMR-CNRS 6236
Aix-Marseille Université Marseille
Evolution des lésions
oedème
prolifération
organisation fibreuse
Régression de la fibrose
• Quelques cas cliniques documentés par histologie
• EFR
• amélioration jusqu ’à 6 mois après sevrage VM
Suchyta et al. Chest 91
Hassenstein et al. Anasth. Intensiv. Notfallmed. 80
Suchyta et al. Chest 91
Peters et al. ARRD 89
Alberts et al. Chest 83
McHugh et al. AJRCCM 94
McHugh et al. AJRCCM 94
LBA et diagnostic de fibrose
• Marqueurs: PIIINP – 3-7 j après début du SDRA
– 1er j de VM Clark et al. Ann Intern Med 95
Pugin et al. Crit Care Med 99
Pas de biomarqueur fiable et validé !
Corticoïdes et SDRA
auteur étude n doses durée délai histo infections mortalité
Ashbaugh AS 85 ouverte 10 8 - 10 >7J 8J oui 20% 20%
Bernard NEJM 87 double 50 120 1J 12 h non 16% 60%
Bone Chest 87 double 152 120 1J avant non ? 61%
Hooper Chest 90 ouverte 10 > 4 > 3 s 11J non 20% 20%
Meduri Chest 91 ouverte 8 2 - 3 6 s 15J oui 50% 25%
Meduri Chest 94 ouverte 25 2 - 3 6 s ? 9/25 44% 24%
Meduri Chest 95 ouverte 9 2 - 3 6 s 9J non ? 44%
Corticoïdes et SDRA
• Multicentrique en double-aveugle • 24 patients • Solumédrol: 2 mg/kg/j dès J7 • Mortalité hospitalière
– 62% vs 12% (p = 0,03)
Meduri et al. JAMA 98
NIH ARDSnet 2006 1997 - 2003
• P/F < 200 • J7-J28 • MePrednisolone
– 2 mg/kg/J/14J – 1 mg/kg/J/7J – /4J
NIH ARDSnet 2006
Neuromyopathies
NS
* *
NIH ARDSnet 2006
%
Corticoïdes précoces, à faible dose et en IV continue
• 1997 – 2002 • Multicentrique, double-aveugle, 2:1 • Inclusion: persistance SDRA après 72h • MePrednisolone
– 1mg/kg – puis IV continu
• 1 mg/kg de J1 à J14 • 0,5 mg/kg de J15 à J21 • 0,25 mg/kg de J22 à J25 • 0,125 mg/kg de J26 à J28
• En l’absence de baisse du LIS vers J7-9, MePred 2 mg/kg en ouvert
Meduri et al. Chest 2007
Meduri et al. Chest 2007
http://www.globalrph.com/corticocalc.htm
70 mg MePrednisolone = 350 mg hydrocortisone
200 mg hydrocortisone = 40 mg MePrednisolone
• Unanswered questions • Is the patient really free of infection? • Is the cause of ARDS correctly identified? • Is fibrosis present?
OLB in ARDS patients • Why ?
– Fibrosis potentially reversible – Corticosteroids at the fibroproliferative phase
Meduri et al. JAMA 98
Steinberg KP et al. NEJM 2006
PSB BAL TA DPC CPIS
cut-off = 103 104 104 105 106 103 6
Torrès AJRCCM 94 36/50 50/45 - - - - -
Marquette AJRCCM 95 58/89 47/100 67/75 67/75 53/87 - -
Chastre AJRCCM 95 82/89 91/78 - - - - -
Papazian AJRCCM 95 33/95 50/95 72/80 56/95 44/100 67/80 72/85
Lack of sensitivity and specificity of respiratory sampling techniques
sensitivity/specificity
64 autopsies in ARDS patients (AECC criteria)
De Hemptinne et al. Chest 2009
n PEEP PaO2/FiO2 morbidity
Hill JTCVS 76 42 bed 6.5 (0 - 15) 84 (30 - 350) 1 air leak 1HR 1inf
Ashbaugh AS 85 10 ? 10 - 20 42 - 74 0
Costa Auler EJRD 86 5 OR 5 - 12 123 (50 - 255) ?
Warner ARRD 88 20 OR ? ? ?
Meduri Chest 91 7 OR ? ? ?
Canver JCVS 94 27 OR 9 ± 1 ? 6 air leaks 2 PNO
Meduri Chest 94 12 OR ? ? 1 air leak
OLB and ARDS
Decision to perform an OLB
Agreement of ≥ 3 intensivists and a thoracic surgeon
After at least 5 days of evolution of ARDS
No decrease of the Lung Injury Score
Negative microbiological investigations
Potential indication for corticosteroid treatment
Decision to perform an OLB
Agreement of ≥ 3 intensivists and a thoracic surgeon
After at least 5 days of evolution of ARDS
No decrease of the Lung Injury Score
Negative microbiological investigations
Potential indication for corticosteroid treatment
Microbiological exams performed prior to OLB • Cytomegalovirus: BAL, blood and urine cultures (+ antigenemia pp65)
• Serologies, conventional cultures, PCR • all herpesviruses • respiratory syncytial virus • rhinovirus, adenovirus • influenza and parainfluenza viruses
• BAL cultures • Bacteria • Herpes virus • Legionella (in addition to antigenuria) • Mycoplasma pneumoniae • Mycobacteria (direct examination and culture) • Aspergillosis
• Cytology on BAL
Open-lung biopsy procedure
• Anticoagulant therapy stopped for at least 12h prior
to the procedure
• In the ICU (at bedside) or in the OR – PaO2/FiO2 < 120 mmHg = OLB in the ICU
– Risk of bleeding and/or pleural symphyses = OLB in the OR
Ventilator management
• Sedation, muscle paralysis • Tidal volume: 6-8 ml/kg • FiO2 = 1
ARDS n = 790
age, 57±17 years SAPS II on admission, 48±22 ICU mortality, 54%
OLB n = 100
age, 58±16 years SAPS II on admission, 68±21
Papazian et al. CCM 2007
Complications • Hemodynamic = 0 • Infection = 0 • Hemorrhage = 1 (250 ml) • Mechanical = 10
8 2
PaO2/FiO2
Persistent air leak: risk factors • 53 ARDS patients (1989-2000) • 16/53 (30.2%) developed an air leak lasting
more than 7 days Cho et al. Ann Thorac Surg 2006
Histological results n
Fibrosis 16
Fibrosis and infection 29
Infection 28
Diffuse alveolar damage 13
Miscellaneous Systemic lupus erythematosus 2
Bronchioloalveolar carcinoma 1
Amiodarone toxicity 2
Intraalveolar hemorrhage 1
Allograft rejection 1
Drug toxicity 2
Rheumatoid lung and Mycobacterial infection 1
Acute eosinophilic pneumonia 1
Carcinomatous lymphangitis 2
Microangiitis 1 Papazian et al. CCM 2007
Fibrosis 53% !!!!!
CMV and fibrosis
• Mice
• Peritonitis
• After 3 weeks – CMV –
– CMV reactivation
– CMV reactivation + Gancyclovir
Cook et al. Crit Care Med 2006
Diagnosis of CMV
Papazian et al. Anesthesiology 1998
Difficult to diagnose !
Unexpected micro-organisms
BAL⊕ 4-fold increase in antibody titer
stable increased antibody titer
VAP episodes, n=120
Berger et al. Emerg Infect Dis 2006
New treatment after OLB results 78 patients Papazian et al. CCM 2007
Corticosteroids 28% !!!!!
NIH ARDSnet 2006
1997 - 2003
• P/F < 200 • d7-Jd8 • MePrednisolone
TransBronchial Lung Biopsy • Hemoptysis
– 3 of 14 – 1 of 13 – 3 of 25 – 4 of 38
• Pneumothorax – 1 of 14 – 2 of 13 – 8 of 38
• Insufficient lung sample for histological analysis – 3 of 25
Papin et al. Chest 1986
Pincus et al. CCM 1987
Martin et al. Chest 1995
Papin et al. Chest 1986
Pincus et al. CCM 1987
Martin et al. Chest 1995
Bulpa et al. Eur Respir J 2003
Bulpa et al. Eur Respir J 2003
N infection
< 4 10%
Alveoli 4 - 19 17%
≥ 20 41%
TBLB and infection
Fraire et al. Chest 1992
≥ 103
TA monday and friday
< 103
antibiotics
BAL cytology, cultures (bacteria, virus, fungi), serologies, antigenemia
No antibiotics
clinical suspicion
≥ 103
TA monday and friday
< 103
< 104
antibiotics
BAL cytology, cultures (bacteria, virus, fungi), serologies, antigenemia
No antibiotics
Stop antibiotics ≥ 104
anti-infective agents same narrow spectrum
change
clinical suspicion
≥ 103
TA monday and friday
< 103
< 104
antibiotics
BAL cytology, cultures (bacteria, virus, fungi), serologies, antigenemia
No antibiotics
Stop antibiotics ≥ 104
anti-infective agents same narrow spectrum
change
clinical suspicion
OLB corticosteroids
no modification
ARDS
Conclusions
• Corticoïdes devraient être – Précédés d’une biopsie
• Précédés d’un LBA+sang/urines
• Plutôt OLB que BTB
• En attendant marqueur de fibrose validé ?
– Administrés tôt
– A une posologie de 1-2 mg/kg/J
