SDRA persistant: que faire - Accueil - SRLF

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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

laurent.papazian@ap-hm.fr U R

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

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