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Acute Lung Injury and ARDSAcute Lung Injury and ARDS
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DefinitionsDefinitions
e or mer can- uropean onsensus on erence
(NAECC) criteria: Onset - Acute and persistent -
presence of edema
Oxygenation criteria - Impaired oxygenation regardless of the PEEP
concentration, with a Pao2/Fio2 ratio 300 torr (40 kPa) for ALI and 200
Exclusion criteria - Clinical evidence of left atrial hypertension or apulmonary-artery catheter occlusion pressure of 18 mm Hg.
Bernard GR et al., Am J Respir Crit Care Med 1994
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The 1994 NAECC Definition LimitationsThe 1994 NAECC Definition Limitations
Descriptive definition - Permits inclusion of a multiplicity of clinicalentities ranging from autoimmune disorders to direct and indirectpu monary n ury
Does not address the cause of lung injury
The radiological criteria are not sufficiently specific
Does not account for the level of PEEP used, which affects the
Pao2/Fio2 ratio
Does not specify the presence of nonpulmonary organ system
Does not include the different specific mechanistic pathwaysinvolved in producing lung injury
Atabai K and Matthay MA, Thorax 2000Abraham E et al., Crit Care Med 2000
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The 1998 NAECC UpdatedThe 1998 NAECC Updated
1. The collection of epidemiologic data should be based on the.
2. The severity of ALI/ARDS should be assessed by the Lung InjuryScore (LIS) or by the APACHE III or SAPS II scoring systems.
3. The factors that affect prognosis should be taken into account.
The most important of these are incorporated into the GOCAstratification s stem.
4. It will be also useful to record: Information relating to etiology (at a minimum, direct or indirect cause)
, ,of care
Presence of failure of other organs and other time-dependent covariates
Follow-up information, including recovery of lung function and quality of life
Artigas A et al., Am J Respir Crit Care Med 1998
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Stratification System of Acute Lung InjuryStratification System of Acute Lung Injury
LetterLetter MeaningMeaning ScaleScale DefinitionDefinition
G
as exc ange
Gas exchange
1
23A
2 2
Pao2/Fio2 200 -300
Pao2/Fio2 101 200Pao2/Fio2 100Spontaneous breathing, no PEEP
(to be combinedwith the numeric
descriptor)CD
, - 2Assisted breathing, PEEP 6-10 cmH2OAssisted breathing, PEEP 10 cmH2O
AB
Lung onlyLung + 1 organ
CD
Lung + 2 organsLung + 3 organs
C Cause
12
UnknownDirect lung injury
A Associateddiseases
01
2
No coexisting disease that will cause death within 5 yrCoexisting disease that will cause death within 5 yr but not within 6moCoexisting disease that will cause death within 6 mo
Artigas A, et al. Am J Respir Crit Care Med. 1998.
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EpidemiologyEpidemiology
NIH, 1972 - Incidence of ARDS in the United States:5 .
(approximately 150,000 cases per year)International multi-center ALI/ARDS cohort studies1989 - 2002
Incidence estimates of ALI/ARDS = 1.3 to 22 cases per 105.
ARDS Network Study (NAECC definitions), 2003 -
Incidence of ALI/ARDS in the United States: 32 casesper 105 person.years (range 16 - 64)
Goss CH et al., ARDS Network, Crit Care Med 2003
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Clinical Disorders Associated with theClinical Disorders Associated with the
Direct insult Indirect insult
ommon
Aspiration pneumoniaPneumonia
ommon
SepsisSevere trauma
Less commonInhalation injury
Pulmonary contusions
Less common
Acute pancreatitis
Near drowning
Reperfusion injury
Transfusion-related TRALI
Disseminated intravascular
coagulationBurns
Head injury
Drug overdose
Atabai K, Matthay MA. Thorax. 2000.Frutos-Vivar F, et al. Curr Opin Crit Care. 2004.
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Clinical Risk Factors Predictive of a PoorClinical Risk Factors Predictive of a Poor
Other independent predictorsLate ARDS ( 48 hours after MV
Independent predictorsIndependent predictorsre eatedl associated withre eatedl associated with
initiation) or length of MV prior to ARDS
Organ transplantation
HIV infection
Immunosuppression
higher mortality rateshigher mortality ratesSeverity of the illness (SAPS II andAPACHE)
-Active malignancy
Oxygenation index (mean airway
pressure x Fio2 x 100/Pao2)Mechanisms of lung injury
Comorbid diseases
Sepsis
Liver dysfunction/cirrhosis
Barotrauma
Right ventricular dysfunction
Fio2 (High Fio2)
Pao2/Fio2
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Plasma Biologic MarkersPlasma Biologic Markers
Acute inflammation Interleukin(IL)-6, IL-8
Endothelial injury von Willebrand factor antigen
Epithelial type II cell molecules Surfactant protein-D
Adhesion molecule Intercellular adhesion molecule-1
(ICAM-1)
Neutrophil-endothelial interaction Soluble tumor necrosis factor
receptors I and II (sTNFRI/II)
rocoagu an ac v y ro e n
Fibrinolytic activity Plasminogen activator inhibitor-1
Ware LB. Crit Care Med. 2005.
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Mortality from ARDSMortality from ARDS
ARDS mortality rates - 31% to 74%
The variability in the rates quoted is related to differences in the.
The main causes of death are nonrespiratory causes (i.e., diewith, rather than of, ARDS).
Respiratory failure has been reported as the cause of death in 9%to 16% of patients with ARDS.
or injury, whereas late deaths are caused by sepsis or multiorgandysfunction.
prognostic factor in adults. Nevertheless, in some studies, bothPao2/Fio2 ratio and Fio2 were variables independently associatedto mortalit .
Frutos-Vivar F, et al. Curr Opin Crit Care. 2004.Vincent JL, et al. Crit Care Med. 2003.
Ware LB. Crit Care Med. 2005.
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OneOne--year Outcomes in Survivors of theyear Outcomes in Survivors of the
Persistent functional limitation Extrapulmonary diseases (primarily): Muscle wasting and weakness
(corticosteroid-induced and critical-illness-associated myopathy)Entrapment neuropathy
Heterotopic ossification
Intrinsic pulmonary morbidity (5%): Bronchiolitis obliterans organizingneumonia
Bronchiolitis obliterans
Herridge MS, et al. N Engl J Med. 2003.
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VentilatoryVentilatory--based Strategies inbased Strategies in
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PositivePositive--pressure Mechanicalpressure Mechanical
Currently, the only therapy that has been proven to be effectiveat reducin mortalit in ALI/ARDS in a lar e randomizedmulti-center, controlled trial is a protective ventilatory strategy.
Tidal volume and lateau ressure
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VentilatorVentilator--induced Lung Injuryinduced Lung Injury
ung n ury rom:
Overdistension/shear - > physical injury
Mechanotransduction - > biotraumavolutrauma
Repetitive opening/closing
Shear at open/collapsed lung interface
atelectrauma
ys em c n amma on an ea rom:
Systemic release of cytokines, endotoxin,bacteria, proteases
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VentilatorVentilator--induced Lung Injuryinduced Lung Injury
Three different pathologic entities: High-permeability type pulmonary edema
ec an ca over- n a on s or on o ung s ruc ures
Lung inflammation Biotrauma
Rouby JJ, et al. Anesthesiology. 2004.
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VentilatorVentilator--induced Lung Injuryinduced Lung Injury
g -permea ty type pu monary e ema
Mechanisms altering the alveolar-capillary barrier permeability during
- Increased transmural vascular pressure
- Surfactant inactivation
- Mechanical distortion and disruption of endothelialcells
-
Rouby JJ, et al. Anesthesiology. 2004.Ricard JD, et al. Eur Respir J. 2003.
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VentilatorVentilator--induced Lung Injuryinduced Lung Injury
Mechanical overinflation/distortion of lung structures
Emphysema-like lesions, lung cysts, and bronchiectasis
The degree of overinflation is dependent on:
- Tidal volume- Peak airwa ressure
- Duration of mechanical ventilation
- Time exposed to an Fio2 > 0.6
Rouby JJ, et al. Anesthesiology. 2004.
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VentilatorVentilator--induced Lung Injuryinduced Lung Injury
ung n amma on o rauma
Lung overinflation or overstretching produces regional and systemicinflammatoryresponse that may generate or amplify multiple-system organ
Factors converting the shear stress applied to an injured lung into regionaland systemic inflammation are still incompletely elucidated but could include:
- Repetitive opening and collapse of atelectatic lung units- ur ac an a era ons
- Loss of alveolo-capillary barrier function
- Bacterial translocation
- Overinflation of health lun re ions
Rouby JJ, et al. Anesthesiology. 2004.Dreyfuss D, et al. Am J Respir Crit Care Med. 2003.
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VentilatorVentilator--induced Lung Injuryinduced Lung Injury
Two primary mechanistic factors:
Overdistension of the alveoli by high transpulmonary pressures:volutrauma
Shear-stress forces produced by repetitive alveolar recruitment andderecruitment (collapse)
Animal data so com ellin that in earl 1990s the SCCM andACCP recommended reduction in tidal volume and limiting end-expiratory plateau pressure to < 35 cm H20
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Tidal Volume Strategies in ARDSTidal Volume Strategies in ARDS
Traditional Approach
High priority to traditional
Low Stretch Approach
High priority to lunggoa s o ac - ase a anceand patient comfort
Lower priority to lung
protection
Lower priority to traditional-
protection
and comfort
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ARDS Net Study 01: HypothesisARDS Net Study 01: Hypothesis
In patients with ALI/ARDS, ventilation with reduced tidal
v u w v u u p v su v v .
ung-pro ec ve s ra eg es
ARDS Network. N Engl J Med. 2000.
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ARDS Network Low VARDS Network Low VTT TrialTrial
Patients with ALI/ARDS (NAECC definitions) of < 36 hours
Ventilator procedures Volume-assist-control mode
RCT of 6 vs. 12 ml/kg of predicted body weight PBW Tidal Volume(PBW/Measured body weight = 0.83)
Plateau ressure 30 vs. 50 cmH O
Ventilator rate setting 6-35 (breaths/min) to achieve a pH goal
of 7.3 to 7.45
I/E ratio:1.1 to 1.3 2 - 2 -
Allowable combination of FiO2 and PEEP:
FiO2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0 1.0 1.0 1.0
PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 18 20 22 24The trial was stopped early after the fourth interim analysis (n = 861
for efficacy; p = 0.005 for the difference in mortality between groups)
ARDS Network. N Engl J Med. 2000.
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ARDS Network:ARDS Network:Im roved Survival with Low VIm roved Survival with Low V
1.0
.
0.8
0.7atients
.
0.5
0.4rtion
of
Lower tidal volumesLower tidal volumes
SurvivalSurvival
0.3
0.2
0.1
Prop DischargeDischarge
Traditional tidal valuesTraditional tidal values
SurvivalSurvival
0.0180160140120100806040200
ARDS Network. N Engl J Med. 2000.
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ARDS Network:ARDS Network:
Death before discharge home andbreathing without assistance (%)
31.0 39.8 0.007
reat ng w t out ass stance yday 28 (%)
65.7 55.0 < 0.001
No. of ventilator-free days, days 1 12 11 10 11 0.007
Barotrauma, days 1 to 28 (%) 10 11 0.43
.nonpulmonary organs or systems,days 1 to 28
.
ARDS Network. N Engl J Med. 2000.
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Median Organ Failure Free DaysMedian Organ Failure Free Days
Pulmonary = 6 ml/kg= 12 ml/k
CNS**
Cardiovascular **Coagulation **
**
0 7 14 21 28
Days
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ARDS Network: Additional FindingsARDS Network: Additional Findings
In ALI and ARDS patients, 6 ml/kg PBW tidal volume ventilationstrategy was associated with:
PaO2/FiO2 lower in 6 ml/kg low VT group High RR prevented hypercapnia with minimal auto-PEEP (difference of
No difference in their supportive care requirements (vasopressors-IV fluids-fluid balance-diuretics-sedation)
~10% mortality reduction ess organ a ures
Lower blood IL-6 and IL-8 levels
ARDS Network. N Engl J Med. 2000. Parsons PE, et al. Crit Care Med. 2005.Hough CL, et al. Crit Care Med. 2005. Cheng IW, et al. Crit Care Med. 2005.
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VentilatorVentilator--induced Lung Injuryinduced Lung Injury
Two primary mechanistic factors:
Overdistension of the alveoli by high transpulmonary pressures
Shear-stress forces produced by repetitive alveolar recruitment andderecruitment (collapse) - Atelectrauma
In animal models, the repetitive cycle of alveolar collapse and re-recruitment has been associated with worsening lung injury. Theextent of this in ur has been reduced in animals throu h the useof PEEP levels that prevent derecruitment at end-expiration.
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VT
~ 6 ml/kg
PEEP ~13-16
VT~12 ml/kg
PEEP ~9
Significant prognostic factors responsible of the ventilatory treatment
APACHE II score
Mean PEEP during the first 36 hours (with a protective effect)
Driving pressures (PPLAT - PEEP) during the first 36 hours
Amato M, et al. N Engl J Med. 1998.
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PEEP in ARDS
PEEP b avoidin re etitive o enin and colla se of atelectaticlung units, could be protective against VILI
High PEEP should make the mechanical ventilation less
The recruitment is obtained essentially at end-inspiration, and the
lung is kept open by using PEEP to avoid end-expiratory collapse.PEEP, by preserving inspiratory recruitment and reestablishingend-expiratory lung volume, has been shown to prevent surfactantloss in the airways and avoid surface film collapse.
Levy MM. N Engl J Med. 2004.Rouby JJ, et al. Am J Respir Crit Care Med. 2002.
Gattinoni L, et al. Curr Opin Crit Care. 2005.
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PEEP in ARDSPEEP in ARDS
Optimal PEEP: Allowing for a given ARDS an optimization of
and VILI, while having the least detrimental effect onhemodynamics, oxygen delivery, and airway pressures.
ere as never een a consensus regar ng e op mum eveof PEEP for a given patient with ARDS.
The potential for recruitment may largely vary among theLI ARD population.
PEEP may increase PaO2 without any lung recruitment because
of a decrease in and/or a different distribution of pulmonaryperfusion.
Levy MM. N Engl J Med. 2004.Rouby JJ, et al. Am J Respir Crit Care Med. 2002.
Gattinoni L, et al. Curr Opin Crit Care. 2005.
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NIHNIH--NHLBI ARDS Network: HypothesisNHLBI ARDS Network: Hypothesis
In patients with ALI/ARDS (NAECC definitions) of < 36 hours whoreceive mechanical ventilation with a VT of 6 ml/kg of PBW, higher
PEEP may improve clinical outcomes.
NHLBI ARDS Clinical Trials Network. N Engl J Med. 2004.
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NIHNIH--NHLBI ARDS NetworkNHLBI ARDS Network
Patients with ALI/ARDS (NAECC definitions) of < 36 hours
Ventilator procedures Volume-assist-control mode
Tidal-volume goal: 6 ml/kg of predicted body weight PBW
Plateau pressure 30 cm H2O
Ventilator rate setting 6 - 35 (breaths/min) to achieve a pH goal of 7.3 if possible
I/E ratio:1.1 to 1.3 Oxygenation goal: PaO2 55 - 80 mmHg/SpO2 88 - 95%
Allowable combination of FiO2 and PEEP:
Low PEEP FiO2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0
PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 18-24
High PEEP FiO2 0.3 0.3 0.4 0.4 0.5 0.5 0.5-0.8 0.8 0.9 1.0
PEEP 12 14 14 16 16 18 20 22 22 22-24
e r a was s oppe ear y a er e secon n er m ana ys s n = on ebasis of the specified futility stopping rule).
NHLBI ARDS Clinical Trials Network. N Engl J Med. 2004.
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NIHNIH--NHLBI ARDS NetworkNHLBI ARDS Network
22
20
24
8
12PEEP
0
4
. . . . . . . .
FIO2
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NIHNIH--NHLBI ARDS NetworkNHLBI ARDS Network
8%Sepsis
22%
sp ra on
15%
Transfusion
5%Other
Pneumonia
10%
NHLBI ARDS Clinical Trials Network. N Engl J Med. 2004.
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NIHNIH--NHLBI ARDS NetworkNHLBI ARDS Network
1.0
ity
Lower PEEP, overall survival
Higher PEEP, overall survival
0.5
Pr
obabil
Higher PEEP, discharge
Lower PEEP, discharge
.0 10 20 30 40 50 60
Days after Randomization
NHLBI ARDS Clinical Trials Network. N Engl J Med. 2004.
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NIHNIH--NHLBI ARDS NetworkNHLBI ARDS Network
OutcomePEEP group
group
p value
Death before discharge home (%)
Unadjusted 24.9 27.5 0.48
Adjusted for difference in baseline covariance 27.5 25.1 0.47
Breathing without assistance by day 28 (%) 72.8 72.3 0.89
No. of ventilator-free days from day 1 to day 28 14.5 10.5 13.8 10.6 0.50
No. of days not spent in ICU from day 1 to day 28 12.2 10.4 12.3 10.3 0.83
Barotrauma (%) 10 11 0.51
. , ,hepatic, and renal organs from day 1 to day 28
.
NHLBI ARDS Clinical Trials Network. N Engl J Med. 2004.
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NIHNIH--NHLBI ARDS NetworkNHLBI ARDS Network
n an pa en s, g er s ra egy was assoc a ewith: PaO2/FiO2 higher the first seven days post randomization
VT lower the first three days post randomization
No difference in RR, PaCO2, or pH
No difference in mortality rate
No difference in organ failures or barotrauma
No difference in IL-6, ICAM-1, surfactant protein-D
NHLBI ARDS Clinical Trials Network. N Engl J Med. 2004.
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Why is higher PEEP not betterWhy is higher PEEP not better
Beneficial effects of higher PEEP counteracted by adverse
effects?
Lower PEEP (or lower tidal volume) was sufficient to protect
against injury from atelectrauma (ventilation at low end-
NHLBI ARDS Clinical Trials Network. N Engl J Med. 2004.
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Lung RecruitmentLung Recruitment
First and foremost performed to provide an arterial oxygen
saturation of 90% or greater at an Fio2 of less than 60%-
risk of regional lung overinflation is a highly controversial issue
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The ARDS LungsThe ARDS Lungs
Increase in lung density from alveolar edema and inflammation
Loss of aeration (lung collapse) that predominates in caudal anddependent lung regions in patients lying supine
External compression of caudal parts of the lungs by an enlarged heart (myocardialedema, hyperdynamic profile, and pulmonary hypertension-induced right ventriculardilatation)
High pressure exerted by the abdominal content
Accumulation of fluid in the pleural space
Own increased weight (gravitation forces-weight of the edematous lung)
Consolidated alveoli - Alveolar flooding: Fluid-filled alveoli (edemafluid or inflammatory cells) that predominates in caudal anddependent lung regions in patients lying supine
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External forces applied on the lower
Vt
lobes at end inspiration and endexpiration in a patient in the supineposition and mechanically ventilated withpositive end-expiratory pressure.
Large blue arrows: Forces resulting from
tidal ventilation
Small blue arrows: Forces resultin from
aerated lung
positive end-expiratory pressure (PEEP)
Green arrows: forces exerted by the
consolidated lung
lung
PEEP
Rouby JJ, et al. Anesthesiology. 2004.
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The ARDS LungsThe ARDS Lungs
ARDS Focal Patchy Diffuse
Focal heterogeneous-Chest x-ray
(zero PEEP)
loss of aeration incaudal and dependent
lung region
ray densities
respecting lung apices
hyperdensities
White lungs
Upper lobes normallyLower lobes massivel
Massive, diffuse and
(zero PEEP)
Loss of aeration
aera e esp e aregional excess of lungtissue Lower lobes
poorly or non aerated
nonaerated The loss
of aeration involvespartially the upper lobes
a era non- or poor yaerated lung regions No normally aerated
lung region
Response to PEEP
PEEP
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The ARDS LungsThe ARDS Lungs
Early phases of ARDSDirect insult of the lung
Primary pulmonary ARDSIndirect insult of the lung
Secondary extrapulmonary ARDS
Lung tissue consolidation Microvascular congestion
Pathologic changesSevere intra-alveolar damage
(Edema, fibrin, collagen
neutrophil aggregates, red cells)
Interstitial edema
Alveolar collapse
Less severe alveolar damage
End-expiratory lung volume EELV
Static elastance of the totalrespiratory system Est,rs
wall Est,w / Static lung
elastance Est,L / / Intra-abdominal pressure
Response to PEEPEst,rs [Est,L >> Est,w]
Stretching phenomena
Est,rs [Est,L Est,w]Recruitment of previously closed
alveolar spaces
Lung recruitment ++++
Gattinoni L, et al. Am J Respir Crit Care Med. 1998.
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Respiratory Pressure/Volume (P/V) CurveRespiratory Pressure/Volume (P/V) Curve
Healthy subjectIn normal healthy volunteers, the P/V curve explore
(lung + chest wall)
ARDS
RV, Residual volume; FRC, Functional residual capacity; TLC, Total lung capacity; UIP, Upperinflection point; LIP, Lower inflection point. The critical opening pressure above which most of thecollapsed units open up and may be recruited - CLIN Compliance of the intermediate, linear segmentof the P/V curve
Maggiore SS, et al. Eur Respir J. 2003. Rouby JJ, etal. Eur Respir J. 2003.
R i i h P V lR i i h P V l
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Reinterpreting the Pressure/VolumeReinterpreting the Pressure/Volume
Measurement of the P/V curve in any given patient is not practical
clinically.
information to determine safe ventilator settings in ALI.
The P/V curve for the whole lung is a composite of multipleregional P/V curves (considerable variation from the dependent tothe nondependent lung; LIP from 50 to 30 cmH2O respectively).
Kunst PW et al., Crit Care Med 2000
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Recruitment Maneuvers (RMs)Recruitment Maneuvers (RMs)
Proposed for improving arterial oxygenation and enhancing
All consisting of short-lasting increases in intrathoracic pressures Vital capacity maneuver (inflation of the lungs up to 40 cm H2O, maintained
for 15 - 26 seconds) (Rothen HU. BJA. 1999; BJA 1993.)
Intermittent sighs (Pelosi P. Am J Respir Crit Care Med. 2003.)
Extended sighs (Lim CM. Crit Care Med. 2001.)
nterm ttent ncrease o (Foti G. Intensive Care Med. 2000.)
Continuous positive airway pressure (CPAP) (Lapinsky SE. Intensive Care Med. 1999.Amato MB. N Engl J Med. 1998.)
Increasin the ventilator ressures to a lateau ressure of 50 cm H O for 1-2 minutes (Marini JJ. Crit Care Med. 2004. Maggiore SM. Am J Respir Crit Care Med. 2003.)
Lapinsky SE and Mehta S, Critical Care 2005
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Recruitment Maneuvers (RMs)Recruitment Maneuvers (RMs)
Effective in improving arterial oxygenation only at low PEEP andsmall tidal volumes. When alveolar recruitment is optimized byincreasing PEEP, recruitment maneuvers are either poorly effectiveor deleterious, inducing overinflation of the most compliant regions,
hemodynamic instability, and an increase in pulmonary shuntresulting from the redistribution of pulmonary blood flow toward
nonaerate ung reg ons.
The effect of recruitment may not be sustained unless adequatePEEP is applied to prevent derecruitment.
Many questions still need to be answered: Optimal time to perform RMs (First hours after endotracheal intubation, early phase of ARDS,
after endotracheal suctioning)
How often they should be used
Their durations
The recommended ventilatory mode (CPAP, sighs, pressure controlled ventilation, shortduration high PEEP level)
The long-lasting effects of RMs on ABGs are contradictory.
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HighHigh--frequency Oscillatory Ventilationfrequency Oscillatory Ventilation
Characterized by rapid oscillations of a reciprocating diaphragm,leadin to hi h-res irator c cle fre uencies, usuall between 3and 9 Hz in adults, and very low VT. Ventilation in HFOV is
primarily achieved by oscillations of the air around the set meanairway pressure mPaw.
HFOV is conceptually very attractive, as it achieves many of the
goal of lung-protective ventilation.
Lower VT than those achieved with controlled ventilation (CV), thustheoretically avoiding alveolar distension.
Ex iration is active durin HFOV: Prevents as tra in Higher mPaws (compared to CV): Leads to higher end-expiratory lung
volumes and recruitment, then theoretically to improvements in oxygenationand, in turn, a reduction of FiO2.
Chan KPW and Stewart TE, Crit Care Med 2005
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HighHigh--frequency Oscillatory Ventilationfrequency Oscillatory Ventilation
Observational studies have demonstrated that HFOV may improveoxygenation when used as a rescue modality in adult patients with
severe a ng .
Preliminary data suggest that there may be a survival advantage.
FiO2 > 0.60 and/or SpO2 < 88% on CV with PEEP > 15 cm H2O, or
Plateau pressures (Pplat) > 30 cmH2O, or
Mean airway pressure 24 cm H2O, or
Airway pressure release ventilation Phigh 35 cm H2O
Team approach (attending physician, respiratory care team
leader, res irator care area mana er, critical care nurse, ICUrespiratory therapist)
HFOV for adults with ARDS is still in its infancy and requiresfurther evaluations.
Higgins J et al., Crit Care Med 2005
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NonNon--ventilatoryventilatory--based Strategiesbased Strategies
Fluid and hemodynamic management
Inhaled nitric oxide
Prone position ventilation
Steroids
Other drug therapy
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Fluid and Hemodynamic ManagementFluid and Hemodynamic Management
Starling Equation Qf = Kf [(Pc- PIF) s(pc pIF)]
- K ca illar filtration coefficient - P ca illar h drostatic ressure- PIF interstitial hydrostatic pressure - s oncotic reflection coefficient
- pc capillary colloid osmotic pressure - pIF interstitial colloid oncotic pressure
Increases in capillary hydrostatic pressure Increased membrane permeability
Diminished oncotic pressure gradiant
Clinical implications: Reductions in pulmonary capillary hydrostatic pressure/pulmonary artery
occlusion pressure CVP
Hemod namic monitorin to avoid tissue h o erfusion Fluid restriction/negative fluid balance Diuretics Combination therapy with colloids and furosemide?
Lewis CA and Martin GS, Curr Opin Crit Care 2004Klein Y, J Trauma 2004
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Inhaled Nitric OxideInhaled Nitric Oxide
Physiology of inhaled nitric oxide therapy
Selective pulmonary vasodilatation (decreases arterial and venousresistances) Selective vasodilatation of ventilated lung areas Bronchodilator action
Inhibition of neutrophil adhesion
Steudel W, et al. Anesthesiology. 1999.
Effects of Inhaled Nitric Oxide in PatientsEffects of Inhaled Nitric Oxide in Patients
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Effects of Inhaled Nitric Oxide in PatientsEffects of Inhaled Nitric Oxide in Patients
Results of a Randomized Phase II TrialResults of a Randomized Phase II Trial
, . , , , ,ppm:
Is associated with a significant improvement in oxygenation compared with.
oxygenation index was observed over the first four days.
Acutely increased the PaO2 in 60% of the patients
The percentage of patients having an acute increase in PaO2 and themagnitude of the change were similar in each of the inhaled NO dosegroups.
Appears to be well tolerated in doses between 1.25 to 40 ppm.
,more closely monitor NO2 concentrations, and methemoglobin.
There are trends in decreasing the intensity of mechanical ventilation neededto maintain adequate oxygenation and improved patient benefit at 5 ppm
inhaled NO.Dellinger RP et al., Crit Care Med 1998
LowLow dose Inhaled Nitric Oxide in Patientsdose Inhaled Nitric Oxide in Patients
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LowLow--dose Inhaled Nitric Oxide in Patientsdose Inhaled Nitric Oxide in Patients
A Randomized Controlled TrialA Randomized Controlled Trial
n pat ents w t ocumente an severe acute ung n ury
(PaO2/FiO2
250) but without sepsis or other organ systemfailure, iNO at 5 ppm:
Induces short-term improvements in oxygenation with a 20% increase inPaO2 that were maintained only during 24 - 48 hours.
Does not improve clinical outcomes or mortality
These data do not support the routine use of inhaled nitric oxide inthe treatment of acute lung injury or ARDS.
as a salvage therapy in acute lung injury or ARDS patients whocontinue to have life threatening hypoxemia despite optimization of
Taylor RW, et al. JAMA. 2004.
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Prone PositioningProne Positioning
m s e expans on o cep a c an paras erna ung reg ons
Relieves the cardia and abdominal compression exerted on thelower lobes
Makes regional ventilation/perfusion ratios and chest elastancemore uniform
Potentiates the beneficial effect of recruitment maneuvers
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Prone PositioningProne Positioning
Absolute contraindications Burns or open wounds on the face or ventral body surface
p na ns a y
Pelvic fractures
Life-threatening circulatory shock
Increased intracranial ressure
Main complications
Facial and periorbital edema
Accidental loss-displacement of the endotracheal tube, thoracic orabdominal drains, and central venous catheters
Airway obstruction
ypo ens on Arrythmias
Vomiting
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Prone PositioningProne Positioning
Improves arterial oxygenation in more than 70% of patients in earlystage of ARDS (a decrease in FiO2 20% is expected)
No baseline features that differentiate between res onders and nonresponders are known.
After the patient back to the supine position, the oxygenation mightreturn to the basal su ine value or remain elevated
Does not increase survival at the end of the 10-day study period, atthe time of discharge from the ICU, or at six months
Pao2/Fio2 88 mmHg, a, SAPS II > 49, a high tidal volume > 12 ml/kgof PBW, or all three, it may reduce mortality and limit VILI.
. ,duration ranges between six and 12 hours/day.
The optimum total duration and number of pronations depends on the
Gattinoni L et al., N Engl J Med 2001Slutsky AS. N Engl J Med 2001
Effect of Prone Positioning on the SurvivalEffect of Prone Positioning on the Survival
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Effect of Prone Positioning on the SurvivalEffect of Prone Positioning on the Survival
Oxygenation criteria
Pao2/Fio2 200 with a PEEP 5 cm H2OPao2/Fio2 300 with a PEEP 10 cm H2O
Bilateral pulmonary infiltrates
Pulmonary-capillary wedge pressure 18 mm Hg or the absence of
clinical evidence of left atrial hypertension.
Treatment protocol:After randomization, prone group patients werecontinuously kept prone for at least six hours per day fora period of 10 days.
Gattinoni L, et al. N Engl J Med. 2001.
Effect of Prone Positioning on the SurvivalEffect of Prone Positioning on the Survival
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Effect of Prone Positioning on the SurvivalEffect of Prone Positioning on the Survival
Kaplan-Meier estimates of survival at six months
Gattinoni L, et al. N Engl J Med. 2001.
Effect of Prolonged MethylprednisoloneEffect of Prolonged Methylprednisolone
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Effect of Prolonged MethylprednisoloneEffect of Prolonged Methylprednisolone
Rationale: Within seven days of the onset of ARDS, many patientsexhibit a new phase of their disease marked by fibrotic lung disease or
ros ng a veo s w a veo ar co agen an ronec n accumu a on.
Patient selection: Severe ARDS/ 7 days of mechanical ventilationwith an LIS 2.5/No evidence of untreated infection
Treatment protocol: Methylprednisolone Loading dose 2 mg/kg
2 mg/kg/24 hours from day 1 to day 14 1 mg/kg/24 hours from day 15 to day 21
0.5 mg/kg/24 hours from day 22 to day 28
0.25 mg/kg/24 hours on days 29 and 30
.
In patients with unresolving ARDS, prolonged administration ofmethylprednisolone was associated with improvement in lung injury
.
Meduri GU et al.,Meduri GU et al., JAMAJAMA 19981998
Corticosteroid Therapy in ARDS:Corticosteroid Therapy in ARDS:
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Corticosteroid Therapy in ARDS:Corticosteroid Therapy in ARDS:
High-dose corticosteroids in early ARDS
Do not reverse lung injury in patients with early ARDS/worse recovery
Have no effect on mortality/even increase mortality rate Significantly increase the incidence of infectious complications
High-dose corticosteroids for unresolving ARDS of 7 daysduration who do not have uncontrolled infection
trial. A large clinical trial is needed to clearly demonstrate a survivaladvantage that outweighs the potential risks.
Patient selection: Lack of clinical improvement rather than use of only the LIS
Aggressive search for and treatment of infectious complications is necessary.
Several questions remain: Timing, dosage, and duration of late steroid therapyin ARDS/Appropriate time window for corticosteroid administration, between
.
Kopp R et al., Intensive Care Med 2002Brun-Buisson C and Brochard L, JAMA 1998
Oth D ThOth D Th
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Other Drug TherapyOther Drug Therapy
Prostaglandin E1 (PGE1) (pulmonary vasodilatation and anti-inflammatory effects on neutrophils/macrophages)
of ventilated lung areas)
Almitrine (selective pulmonary vasoconstrictor of nonventilated lung
Surfactant (prevents alveolar collapse and protects against
intrapulmonary injury and infection)Antioxidants (protect the lung from free oxygen radical production)
Partial liquid ventilation (recruitment of collapsed areas and anti-inflammatory effect)
Anti-inflammatory drugs (Ibuprofen - ketoconazole)
No recommendation can be made for their use - Rescue modality in
Combination of differentCombination of different
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Combination of differentCombination of different
Combination of iNO and prone position (Papazian L, et al. Crit Care Med. 1998.)
Combination of iNO and almitrine (Gallart L, et al. Am J Respir Crit Care Med. 1998.)
Combination of prone position, iNO, and almitrine (Jolliet P, et al. Crit CareMed. 1997. Gillart T, et al. Can J Anaesth. 1998.)
, . . .
C l iC l i
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ConclusionsConclusions
Positive pressure ventilation may injure the lung
Search for ventilatory lung protective strategiesSearch for ventilatory lung protective strategies
Alveolar distension Repeated closing and opening Oxygen toxicityVOLUTRAUMA of collapsed alveolar units
ATELECTRAUMA
Lung inflammationBIOTRAUMA
VILI
R d ti i P tiR d ti i P ti
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Recommendations in PracticeRecommendations in Practice
Principle of precaution
End-inspiratory plateau pressure < 30 - 32 cm H2O
Adequate end-expiratory lung volumes utilizing PEEP and highermean airway pressures to minimize atelectrauma and improveoxygenation
Consider recruitment maneuvers
Avoid oxygen toxicity: FiO2 < 0.7 whenever possible
Monitor hemodynamics, mechanics, and gas exchange
Address deficits of intravascular volume
Prioritize patient comfort and safety
VILI Remaining QuestionsVILI Remaining Questions
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VILI: Remaining QuestionsVILI: Remaining Questions
, ,
Role of recruitment maneuvers-
Permissive hypercapnia