Transcript ARDS - Thomas Jefferson University

ARDS
June 2011
Summer Lecture Series
Urvashi Vaid M.D.
OUTLINE
 Overview
 Ventilation Strategies
 Tidal volume
 Plateau pressures
 PEEP
 VC vs PCV (APRV)
 Recruitment maneuvers
 Prone positioning
 ECMO
 Pharmacologic interventions
 Fluid Management
DEFINITION
1967-The Lancet
“severe dyspnea, tachypnea, cyanosis that is refractory to oxygen therapy,
loss of lung compliance, and diffuse alveolar infiltration seen on chest x-ray.”
AECC DEFINITION-1994
 ALI




Acute onset
Bilateral chest infiltrates
PCWP ≤ 18mm Hg or absence of clinical e/o LA
hypertension
PaO2 : FiO2 ratio ≤ 300
 ARDS


PaO2 : FiO2 ratio ≤ 200
And all the above
 Independent of PEEP

Bernard et al, Am J Respir CCM; 1994;149:818-24
MURRAY LUNG INJURY
SCORE (LIS)
 Radiography
 Oxygenation
 Compliance
 PEEP
 But doesn’t exclude left heart failure
EPIDEMIOLOGY
 8-year retrospective cohort study of ICU patients in the
Mayo Clinic, which provides all ICU-level care to the
population of Olmsted County, Minnesota
 Total of 795 episodes (787 new, 8 recurrent) of
ARDS/ALI identified
 Age- and sex-adjusted incidence rates dropped from 81
to 38 cases per 100,000 person-years
 MORTALITY: Observational studies indicate 40%, but
RCTs indicate 20-25%
OBSERVED 60-DAY MORTALITY-2944 PATIENTS
Spragg RG, Bernard GR, CheckleyW, et al. Beyond mortality: future clinical
research in acute lung injury. Am J Respir Crit Care Med 2010;181(10):1121–7
ETIOLOGY
 Direct pulmonary causes
 pneumonia (bacterial or viral)
 aspiration pneumonitis
 inhalation injury/ Near drowning
 lung contusion
 Indirect extrapulmonary causes
 extrapulmonary sepsis
 trauma with shock
 burn injury
 blood transfusion
 drug overdoses
 pancreatitis
PROGRESSION FROM ALI
TO ARDS








The Acute Lung Injury Verification of Epidemiology (ALIVE) study
COHORT STUDY performed in 78 ICUs of 10 European countries
All patients admitted for > 4 hours were screened for ALI and followed
for 2 months
ALI occurred in 463 (7.1%) of 6522 admissions and 16.1% of all
mechanically ventilated patients
65.4% of cases present on ICU admission
Among 136 patients initially presenting with ALI, 74 patients (55%)
evolved to ARDS within 3 days
The ICU and hospital mortality rates were 22.6% and 32.7% (P <.001)
and 49.4% and 57.9% (p=.0005), respectively, for ALI and ARDS
Importantly, this study confirmed that more than half of patients
admitted with ALI rapidly evolved to ARDS, and that mortality rates
associated with ALI are significantly lower than those of patients with
ARDS
Brun-Buisson C, Minelli C, Bertolini G, et al. Epidemiology and outcome of acute lung injury in
European intensive care units. Results from the ALIVE study. Intensive Care Med
2004;30(1):51–61.
RISK FACTORS
PREDICTING MORTALITY
 Patient variables
Etiology of ALI (aspiration, pulmonary-sepsis vs
trauma)
 Severity of illness and immunosuppression
 Age
 Alcohol abuse
 ↑BMI- ↑incidence but decrease/unchanged mortality
 Treatment variables
 VILI- TV>6ml/kg
 Sepsis
 + fluid balance
 Plasma transfusion

PATHOPHYSIOLOGY
 The acute phase of acute lung injury and
the ARDS is characterized by the influx
of protein-rich edema fluid into the air
spaces as a consequence of increased
permeability of the alveolar–capillary
barrier
PATHOLOGY
Apex
Hilum
Base
“BABY LUNG” to “SPONGE
LUNG”
 CT scans: amount of normally aerated tissue, measured
at end-expiration, was in the order of 200–500 g in
severe ARDS
 Respiratory compliance (ΔV/ΔP) was well correlated only
with the amount of normally aerated tissue and not with
the amount of non-aerated lung
 The ARDS lung is not “stiff” at all, but small, i.e. the
elasticity of the residual inflated lung is nearly normal
 Sponge lung: edema evenly distributed, dependant
changes are due to atelectasis from increased
hydrostatic pressures

Luciano Gattinoni Antonio Pesenti The concept of “baby lung” Intensive Care Med (2005)
31:776–784
OUTCOMES
 Pulmonary Function

Heterogeneous, but most young patients without documented
preexisting lung disease regain normal or near-normal function with
a persistent mild reduction in diffusion capacity and seem to
maintain stable pulmonary function up to 5 years after the initial
episode of severe lung injury

Herridge MS, Tansey CM, Matte´ A, et al. Canadian Critical Care Trials Group. Functional disability 5 years
after acute respiratory distress syndrome. N Engl J Med 2011;364(14):1293–304.
 Functional Disability

CINMA
Herridge MS, Tansey CM, Matte´ A, et al.
Functional disability 5 years after acute
respiratory distress syndrome.
N Engl J Med 2011;364(14):1299
ARDS and Brain injury
OUTLINE
 Overview
 Ventilation Strategies
 Tidal volume
 Plateau pressures
 PEEP
 VC vs PCV (APRV)
 Recruitment maneuvers
 Prone positioning
 ECMO
 Pharmacologic interventions
 Fluid Management
DICTUM:
LUNG PROTECTIVE VENTILATION
VILI
 Oxidant injury- keep FiO2 <60
 Barotrauma- keep alveolar inflation pressures <35 cm
H2O
 Volutrauma- Baby lung concept or stretch injury
 Atelectrauma- repeated opening and closing
 Biotrauma- release of inflammatory mediators and
bacterial translocation
VILI
 Oxidant injury- keep FiO2 <60
 Barotrauma- keep alveolar inflation pressures <35 cm
H2O
 Volutrauma- Baby lung concept or stretch injury
 Atelectrauma- repeated opening and closing
 Biotrauma- release of inflammatory mediators and
bacterial translocation
OPEN GENTLY AND KEEP THEM OPEN
Pressure-volume curve derived from a patient with ARDS. FRC, functional residual
capacity; LIP, lower inflection point; UIP, upper inflection point. (Adapted from Whitehead T,
Slutsky AS. The pulmonary physician in critical care: ventilator induced lung injury. Thorax
2002;57:636
TIDAL VOLUME
ARDSNET: NEJM May 2000
 6cc/kg PBW
 12cc/kg PBW
 N= 432
 N= 429
 Death before discharge=
 39.8%
31%
 Breathing w/o assistance
day 28 = 65.7%
 Plateau Pressure (cm of
H2O) 25±7
 Lower IL-6 levels
 55%
 33±9
PLATEAU PRESSURES
Hager DN et al. Tidal Volume Reduction in Patients with Acute Lung Injury
When Plateau Pressures Are Not High. AJRCCM 2005. Vol 172 1241-1245
787 patients from ARDS Network study
PEEP
 EXPRESS
 LOVS
 ALVEOLI
 Meta-analysis of these trials revealed no difference in
hospital mortality, although higher PEEP was associated
with reduced ICU mortality, total rescue therapies, and
death after rescue therapy

Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury
and acute respiratory distress syndrome. JAMA 2010;303(9):865–73.
VC vs PCV
PCV: variable flow so more comfortable if dyssynchrony,
prolong i time for oxygenation, control peak pressures
VC vs PCV
 RCT multicenter, 79 patients with ARDS
 PCV (n-37) versus VCV (n=42). P plat ≤ 35 cm H2O
 No difference in mortality, trend to more renal failure in
VCV group
 BUT patients in VCV group had a higher in-house
mortality related to higher number of extra-pulmonary
organ failures (78% vs 51%)
 Also TV 8cc/kg of weight
RECRUITMENT
 A recent systematic review analyzed 40 studies that
evaluated RMs; 4 were RCTs, 32 prospective studies,
and 4 retrospective cohort studies
 The sustained inflation method (ie, continuous positive
airway pressure [CPAP] of 35–50 cm H2O for 20–40
seconds) was used most often (45%), followed by high
pressure control (23%), incremental PEEP (20%), and a
high VT/sigh (10%)
 Current evidence suggests that that RMs should not be
routinely used on all ARDS patients unless severe
hypoxemia persists or as a rescue maneuver to
overcome severe hypoxemia, to open the lung when
setting PEEP, or following evidence of acute lung
derecruitment such as a ventilator circuit disconnect

Fan E, Wilcox ME, Brower RG, et al. Recruitment maneuvers for acute lung injury.Am J Respir
Crit Care Med 2008;178(11):1156–63.
PRONE POSITIONING
Computed tomography scan of the lungs showing ARDS when the patient is lying
supine (left) and prone (right).
Gattinoni L, Protti A. Ventilation in the prone position:for some but not for all? CMAJ 2008;178(9):1174–6)
Evidence for Proning
 The Prone-Supine II Study is the largest clinical trial (N
5342) in adult ARDS patients, conducted in 23 centers in
Italy and 2 in Spain
 20 hours/day
 Similar 28-day mortality- 31.0% vs 32.8%; RR 0.97; (95%
CI 0.84–1.13; p=.72)
 Mortality in severe hypoxemia was decreased in the
prone group-37.8% in the prone group and 46.1% in the
supine group (RR, 0.87; 95% CI, 0.66–1.14 p=.31)

Taccone P, Pesenti A, Latini R, et al. Prone positioning in patients with moderate
and severe acute respiratory distress syndrome: a randomized controlled trial.
JAMA 2009;302:1977–84.
Evidence for Proning/Mortality
Effect of mechanical ventilation in the prone position on clinical outcomes in patients
with acute hypoxemic respiratory failure: a systematic review and meta-analysis. CMAJ
2008;178(8):1153–61
Evidence for
Proning/Oxygenation
Sud S, Sud M,Friedrich JO, et al. Effect of mechanical ventilation in the prone position on clinical
outcomes in patients with acute hypoxemic respiratory failure: a systematic review and
meta-analysis. CMAJ 2008;178(8):1153–61
PRONING-COMPLICATIONS
ECMO
ECMO
 ECMO is supportive care and is not intended as
a primary ARDS treatment
 CESAR trial



Patients were randomized to either conventional
care at 1 of 68 tertiary care centers or to a single
center using a treatment protocol that included
ECMO
The trial was stopped for efficacy after 180 patients
Survival without severe disability at 6 months was
47% vs 63% at 6 months
Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment
of conventional ventilatory support versus extracorporeal membrane
oxygenation for severe adult respiratory failure (CESAR): a multicentre
randomised controlled trial. Lancet 2009;374(9698):1351–63.
A French prospective, randomized multicenter trial (EOLIA) (Extracorporeal
Membrane Oxygenation to Rescue Lung Injury in ARDS) has opened and will enroll
patients to test the efficacy of early VV ECMO in ARDS.
BEYOND THE SCOPE…
 APRV
 HFOV
 SURFACTANT
 BIOMARKERS
 GENE THERAPY
 STEM CELLS
OUTLINE
 Overview
 Ventilation Strategies
 Tidal volume
 Plateau pressures
 PEEP
 VC vs PCV (APRV)
 Recruitment maneuvers
 Prone positioning
 ECMO
 Pharmacologic interventions
 Fluid Management
STEROIDS
 At the cellular level, patients with unresolving ARDS have
inadequate glucocorticoid-glucocorticoid receptor (GC-GR)–
mediated down-regulation of inflammatory transcription factor
nuclear factor-kB (NF-kB) despite elevated levels of circulating
cortisol, a condition recently defined as critical illness–related
corticosteroid insufficiency (CIRCI)
 Marik PE, Pastores SM, Annane D, et al. Recommendations for
the diagnosis and management of corticosteroid insufficiency in
critically ill adult patients: consensus statements from an
international task force by the American College of Critical Care
Medicine. Crit Care Med 2008;36:1937–49
STEROIDS
LATE STEROID RESCUE STUDY: LASRS
Objective
 To determine if the administration of methylprednisolone (MP), in severe persistent ARDS after 7
days, will reduce mortality and morbidity
Study Design
 Multicenter, prospective, randomized, controlled
clinical trial. MP and placebo administered in a
double-blind fashion
 MP patients came off ventilator sooner

14 days vs. 23 days, P=0.0002
 Associated with improved physiology in
MP patients

PaO2/FIO2; static compliance
 More MP patients went back on
ventilator

20 vs. 6, P = 0.008
60 day mortality
60 day mortality
Mean %
95% CI
Placebo
28.6 %
19.8-38.4
Methylprednisone
29.2 %
20.2-39.3
METHYLPREDNISOLONE INFUSION IMPROVES LUNG
FUNCTION IN PATIENTS WITH EARLY ARDS: RESULTS
OF A RCT
Steroids
N=63
Placebo
N=28
Extubated
63 in MP
and 28 in10(35%)
placebo
or 44(70%)
P value
0.002
1 pt
reduction in
LIS

Extubated
>48hrs
34(53%)
7(25%)
0.01
LIS
2.14
2.67
0.004
P/F ratio
256
178
0.006
CRP
2.9
13.1
0.001
Mortality
20.6
42.9
0.03
GU Meduri, E Golden, AX Freire, E Taylor, M Zaman, S Carson, M Gibson, R Umberger
Memphis Lung Research Program University of Tennessee HSC Memphis, TN, USA Chest
2007
CONSENSUS ON STEROIDS
 Recent consensus statement from the American College
of Critical Care Medicine, the results of one randomized
trial in patients with early severe ARDS16 indicate that 1
mg/kg/d of methylprednisolone given as an infusion and
tapered over 4 weeks
 For patients with unresolving ARDS, beneficial effects
were shown for treatment (methylprednisolone, 2
mg/kg/d) initiated before day 14 of ARDS and continued
for at least 2 weeks after extubation
 If treatment is initiated after day 14, no evidence has
shown either benefit or harm

Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management
of corticosteroid insufficiency in critically ill adult patients: consensus statements from an
international task force by the American College of Critical Care Medicine. Crit Care Med
2008;36:1937–49
VASODILATORS-iNO
 NO activates cGMP in turn activates a protein kinase that
leads to SM relaxation and vascular dilatation
 iNO flows only into well ventilated areas-improves shunt
 Shown to improve PaO2/FiO2 ratio but not mortality
 It remains a safe option for salvage therapy in ARDS
patients with refractory hypoxemia

Ashfari A, Brok J, Moller AM, et al. Inhaled nitric oxide for acute respiratory
distress syndrome [ARDS] and acute lung injury in children and adults.Cochrane
Database Syst Rev 2010;7:CD002787
VASODILATORS-PC
 PGI2 derived from arachidonic acid from vascular endothelium
 Stimulates adenylate cyclase to create cAMP leads to
increased intracellular calcium and thus smooth muscle
relaxation
 A Cochrane Database review in 2010 of IP in ARDS
determined that none of the trials of IP in adults was
appropriate for consideration for meta-analysis due to
methodologic limitations
 A randomized, double-blind placebo controlled safety and
efficacy study started in 2006 that tested IP in ARDS and
pulmonary hypertension is finished and has been
submitted for publication
OUTLINE
 Overview
 Ventilation Strategies
 Tidal volume
 Plateau pressures
 PEEP
 VC vs PCV (APRV)
 Recruitment maneuvers
 Prone positioning
 ECMO
 Pharmacologic interventions
 Fluid Management
“KEEP THEM DRY”
 FACTT
 497 in liberal and 503 in conservative
 During the study, the seven-day
cumulative fluid balance was –136±491
ml in the conservative-strategy group, as
compared with 6992±502 ml in the
liberal-strategy group (P<0.001)
SUMMARY
 TV 6 cc/kg PBW
 Plateau < 30 cm H2O
 Use PEEP
 AC- VC or PC
 Keep them dry
 iPC?
 Steroids?
THANKS!