acute lung injuryjhghjnb

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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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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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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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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



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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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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)



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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



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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

.



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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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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).



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22

20

24

8

12PEEP

0

4

. . . . . . . .

FIO2


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8%Sepsis

22%

sp ra on

15%

Transfusion

5%Other

Pneumonia

10%



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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



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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

.



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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



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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-



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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



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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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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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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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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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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.



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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

acute lung injuryjhghjnb

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