VENTILATOR-INDUCED LUNG INJURY file• Jv = Kfc [(Pcap - Pint) - s (Ppl -Pint)] Pression Pression de...
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Didier Dreyfuss
Assistance Publique – Hôpitaux de Paris, Hôpital Louis Mourier,
Service de Réanimation Médico-chirurgicale, Colombes, France
Université Paris Diderot, Sorbonne Paris Cité, INSERM U1137
Paris, France
VENTILATOR-INDUCED LUNG INJURY
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Conflit d’intérêt
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• Aucun
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• « Recognition that mechanical ventilation,
although life-saving, can contribute to
patient morbidity and mortality has been the
most important advance in the management
of patients with ALI and ARDS » 3
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Mechanical ventilators, by applying high
transpulmonary pressure to the nonuniformly
expanded lungs of some patients who would
otherwise die of respiratory insufficiency, may
cause the hemorrhage and hyaline membranes
found in such patients’ lungs at death.
Mead, JAP 1970
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Lésions induites par la ventilation
(VILI)
• = création ou aggravation de lésions pulmonaires
- notion issue de données expérimentales
Webb et Tierney, 1974 ; Parker 1984
Dreyfuss et Saumon, 1985
- pertinence clinique récemment démontrée
ARDS Network, 2000
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Buts de la ventilation mécanique
• Assurer oxygénation et décarboxylation
• ET éviter d’aggraver les lésions pulmonaires déjà existantes,
• Dont on sait (expérimentalement) qu’elles rendent le poumon plus sensible aux effets délétères de la ventilation mécanique: des volumes courants habituellement « inoffensifs » deviennent délétères
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Recommandations d’experts – SRLF 2005
• L’un des objectifs de la VM est de limiter ces risques de complications- en assurant un support ventilatoire le moins traumatique possible- dans l'attente de l'efficacité des thérapeutiques spécifiques de l'affection sous-jacente ayant conduit au SDRA.
• 9 [7-9]
• Accord Fort
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Recommandations d’experts – SRLF 2005
• La prévention et la reconnaissance de ces complications
liées à la VM doivent représenter une priorité des
services prenant en charge des SDRA.
• 9 [8-9]
• Accord fort
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L’ŒDÈME PULMONAIRE
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2 types d’œdèmes
pulmonaires
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• Œdème hydrostatique
• Œdème de perméabilité
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Equation de Starling
• Jv = Kfc [(Pcap - Pint) - s (Ppl - Pint)]Pression Pression
de filtration d’absorption
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2 types de micro-vaisseaux
pulmonaires
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• Alvéolaires
• Extra-alvéolaires
• Réagissent différemment à la
distension pulmonaire
• Sont le site d’échanges
liquididiens
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Evolution des resistances vasculaires
pulmonaires en fonction de l’expansion
pulmonaire
Permutt S., J Appl Physiol 1961
Ventilation
Mécanique
Au
gm
enta
tion
des
RV
P
Augmentation Ptm
Œdème Hydrostatique
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At a transpulmonary pressure of 30 cmH2O, the pressure tending
to expand an atelectatic region surrounded by fully expanded lung would
be approximately 140 cmH2O.
Mead
JAP 1970
Interdépendance pulmonaire
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17Webb and Tierney, ARRD 1974
Ventilator-induced lung injury
Ventilation avec pression inspiratoire à 45cmH2O
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Mécanisme hydrostatique
• Inactivation surfactant par élongation-
compression au cours de la VM
– Augmentation pression transmurale vaisseaux
alvéolaires
• Phénomène d’interdépendence
– Augmentation pression transmurale vaisseaux
extra-alvéolaires
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Equation de Starling
• Jv = Kfc [(Pcap - Pint) - s (Ppl - Pint)]Pression Pression
de filtration d’absorption
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20Albert JCI 1979
Inactivation du surfactant et pression microvasculaire
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Albert, JAP 1980
Relationship between alveolar pressure and rate of hydrostatic
edema formation in in situ lobes of open-chest dogs.
Pulmonary arterial and venous pressures were kept at 1 cm H2O.
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Eléments en faveur de l’ Œdème de perméabilité
Altération de la perméabilité alvéolo-capillaire
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23Egan, J. Physiol 1976
Effect of static inflation on alveolar epithelial permeability
(equivalent pore radius) of fluid-filled sheep lobes in situ.
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24Parker, JAP 1984
Augmentation de la perméabilité épithéliale avec l’augmentation
du volume pulmonaire
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Trois mécanismes possibles de
VILI
• Volotrauma (surdistension)
• Atélectrauma (ouverture-fermeture
alvéoles)
• Biotrauma (activation cytokines)
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Dreyfuss and Saumon AJRCCM 1998
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29Dreyfuss et al, ARRD, 1985
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Dreyfuss et Saumon, AJRCCM 1998
A thin part of an
endothelial cell
(En) is detached
from the basement
membrane
(arrowhead)
forming a bleb
filled with
electron-dense
material of the
same density as the
plasma,
Interstitial edema
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thin part of the endothelial cell is disrupted and floats in the capillary
lumen (arrows) after becoming detached from the basement membrane
Dreyfuss et Saumon, AJRCCM 1998
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There are many gaps in an alveolar type I cell. The endothelial cell is
detached from the basement membrane. Interstitial edema
Dreyfuss et Saumon, AJRCCM 1998
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Widespread destruction of epithelial cells leads to denudation of
basement membranes (arrowheads). Many gaps in the capillary
endothelium allow close contact between cytoplasmic processes of
an intracapillary polymorphonuclear neutrophil (PN) and the
basement membraneDreyfuss et Saumon, AJRCCM 1998
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Dreyfuss et Saumon, AJRCCM 1998
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Déterminisme des lésions: pression ou volume ?
Dreyfuss et al, Am Rev Respir Dis, 1988
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Déterminisme des lésions: pression ou volume ?
Dreyfuss et al, Am Rev Respir Dis, 1988
Notion de
« Volotrauma »
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Création d’un œdème pulmonaire intertitiel:
administration d’ANTU
Dreyfuss et al, AJRCCM, 1995
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38Dreyfuss et al, AJRCCM, 1995
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DONC pour résumer
Les lésions induites par la VM sont
essentiellement le fait d’un œdème pulmonaire de
perméabilité (ou lésionnel)
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EFFET DE LA PEEP SUR CES LESIONS DE VILI
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Effet Peep
Dreyfuss et al, Am Rev Respir Dis, 1988
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Dreyfuss et al.
ARRD 1988
Peep may reduce
VILI
zeep
10 cmH2O
peep
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Lésions pulmonaires à bas volume:
Concept d’atélectrauma
Argiras, Brit J Anaesth 1987
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Argiras 1987
Sandhar 1988
Muscedere 1994
Sohma 1992
Effect of high Peep
Reduction of injury
Reduction of injury
Reduction of injury
Type of injury
saline lavage
saline lavage
saline lavage
HCl instillation No effect
Effect of peep set above the LIP
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45Dreyfuss ARRD 1993
Peep may favor VILI
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46Toung, SGO 1978
Lobe de poumon de chien, isolé, perfusé, agressé à l’HCl:
sur un poumon lésé, l’application d’une PEP diminue le shunt par
réouverture d’alvéoles initialement collabées.
En contre partie, augmentation de la fuite capillaire des vaisseaux
extraalvéolaires et aggravation de l’œdème pulmonaire.
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Effet du décubitus ventral
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Prone positioning attenuates and redistributes ventilator-induced lung injury in dogs. Broccard et al. Critical Care Medicine. 28(2):295-303, 2000.
Prone
Supine
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Et le « biotrauma »?????
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50Tremblay, JCI 1997§ P <0.05 vs C; * P <0.05 vs C, MVHP, MVZP; † P <0.05 vs C, MVHP
1,400
1,200
200
100
0
1,400
1,200
200
100
0
2,000
1,600
100
50
0
1,200
1,400
1,200
400
200
0
1,000
800
600
400
200
0
600
400
20
10
0
500
TNF IL-1 IL-6
MIP-2 IFN- IL-10
*
†
§
§
* *
*
**
Co
nc
en
tra
tio
n (
pg
/ml)
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51Ricard et al, AJRCCM, 2001.
Cytokines in BAL ex vivo
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52
Cytokines in BAL in vivo
Ricard et al, AJRCCM, 2001.
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En résumé
• Comportement différent des vaisseaux
alvéolaires et extra-alvéolaires
• Hyperinflation répétée: œdème pulmonaire
– mécanismes hydrostatiques:
• inactivation du surfactant: fuite par Vx alvéolaires
• augmentation Ptm Vx extra-alvéolaires
– troubles de perméabilité microvasculaire et
épithéliale alvéolaire: diffuse alveolar damage
• Déterminant essentiel du VILI: volume télé-
inspiratoire et surdistensions régionales
• Rôle de la Peep: compliqué….
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ET LA CLINIQUE ????
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• Le concept de petit poumon.
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Copyright 1995 by the American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use. American Medical Association, 515 N. State St, Chicago, IL 60610. ??diteur American Medical Association.
2
Figure 1
Improved Survival of Patients With Acute Respiratory Distress Syndrome (ARDS): 1983-1993.Milberg, John; Davis, Donna; Steinberg, Kenneth; Hudson, Leonard
JAMA. 273(4):306-309, Jan 25, 1995.
Figure 1 . Crude (solid line) and adjusted (dashed line) acute respiratory distress syndrome (ARDS) fatality rates, total population, Harborview Medical Center, 1983 through 1993. Rates are adjusted for ARDS risk group, age, and gender
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ARDS and MECHANICAL VENTILATION
TIDAL VOLUME
Tidal volume : ml/kg
1965 Sykes (BJA) 10-15
1969 McIntyre (Can Anesth S. J.) 8-14
1970 Kumar (NEJM) 11 and 13
1972 Pontoppidan (NEJM) 10-15
Falke (JCI) 9-24
Lutch, Murray (Ann.Int. Med) 10-16
1973 Kumar (Crit.Care Med) BT: 50% 12-18
1974 Steir (JTCVS) PNTX 18 (14-21)
1975 Suter (NEJM) 15
1979 Hemmer (Anesthiol) 15
1981 Jardin (NEJM) 12-20
1983 Mathru (Crit.Care Med) 12-15
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• 5183 mechanically ventilated patients
• 231 ARDS
– VT: 8,7 ml/kg
– Pplat: 28 cmH2O
– PEEP = 8 cmH2O
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AR DSnetAR DSnet
Mortality Prior to Hospital DischargeMortality Prior to Hospital Discharge
0
10
20
30
40
50
M ortality
(Percent)
6 m l/kg 12 m l/kg
P=0.0054
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6262
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• Rôle excessif attribué à la prévention de
« l’atélectrauma »
• Au détriment de la prévention du
« volotrauma »
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Scaling VT acording to respiratory mechanics
and not to PBW
• Driving pressure (DP) = VT/Crs
• Pplat = Peep + VT/Crs
• VT/Crs = Pplat - Peep = DP
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Prévention de « l’atélectrauma »
par une PEP « plus » haute???
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696969
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7070
Mercat et al.
7070
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7171
Meade et al.
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7272
Briel et al
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+++++ Regardez la « driving pressure » et la Pplat !!!74
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Et la ventilation par oscillations à
haute fréquence (HFOV) ??
Même motif, même punition….
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Can DeltaP explain these
findings?
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Réduire le volotrauma avec
des moyens simples
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En résumé
• Volotrauma: certain
• Atelectrauma: incertain dès qu’un niveau
minimum de PEP est appliqué
• Biotrauma: discutable
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Les erreurs fondamentales
• Méconnaissance du rôle majeur de la
distension télé-inspiratoire (ou « statique »
en HFO): « volotrauma »
• Surestimation du rôle de
« l’atélectrauma » (ouverture-refermeture)
• Errements à propos du « biotrauma »
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Une certitude, une proposition, une inconnue
et un corollaire, une prospective
• La certitude: le volotrauma est un déterminant essentiel de
la mortalité associée à la ventilation mécanique et la PEP
peut y contribuer si elle est excessive
• La proposition: ne régler la PEP qu’en fonction de la PO2
souhaitée et non pour éviter « l’atélectrauma » est
bénéfique
• L’inconnue: la toxicité réelle de la FiO2 élevée
• Le corollaire: si on admet que la FiO2 élevée n’est pas
problématique, l’utilisation de PEP systématiquement
élevée est inutile
• La prospective: place de l’ECMO et de l’ECCOR? 83
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Paul Simon and
Didier Dreyfuss (after…or before several beers)84