ARDS 2012 Summer Lecture Series Urvashi Vaid MD, MS.
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ARDS
2012
Summer Lecture Series
Urvashi Vaid MD, MS
OUTLINE
Overview Ventilation Strategies
Tidal volume Plateau pressures PEEP VC vs PCV (APRV) Recruitment maneuvers Prone positioning ECMO
Pharmacologic interventions Fluid Management
DEFINITION1967-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
BERLIN DEFINITION
Mild Moderate Severe
Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the ROC of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553;P<.001)
Gordon D. Rubenfeld, MD,JAMA. 2012;307(23):doi:10.1001/jama.2012.5669
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 clinicalresearch 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 ARDSBrun-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 Active and passive cigarette smoking ↑BMI- ↑incidence but decrease/unchanged mortality African Americans (higher risk of death)
Treatment variables VILI- TV>6ml/kg Sepsis + fluid balance Plasma transfusion
RISK FACTORS
Genetics (Fas pathway modulation of apoptosis)
PATHOPHYSIOLOGY
The acute phase of acute lung injury and 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 acuterespiratory 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 residualcapacity; LIP, lower inflection point; UIP, upper inflection point. (Adapted from Whitehead T,Slutsky AS. The pulmonary physician in critical care: ventilator induced lung injury. Thorax2002;57:636
TIDAL VOLUMEARDSNET: NEJM May 2000
6cc/kg PBW N= 432 Death before discharge=
31% Breathing w/o assistance
day 28 = 65.7% Plateau Pressure (cm of
H2O) 25±7 Lower IL-6 levels
12cc/kg PBW N= 429 39.8%
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 lyingsupine (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 patientswith acute hypoxemic respiratory failure: a systematic review and meta-analysis. CMAJ2008;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 clinicaloutcomes in patients with acute hypoxemic respiratory failure: a systematic review andmeta-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) (ExtracorporealMembrane Oxygenation to Rescue Lung Injury in ARDS) has opened and will enrollpatients 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 methyl-
prednisolone (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
63 in MP and 28 in placebo
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
SteroidsN=63
PlaceboN=28
P value
Extubated or 1 pt reduction in LIS
44(70%) 10(35%) 0.002
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
CONSENSUS ON STEROIDS
Recent consensus statement from the American College of Critical Care Medicine quotes the results of one randomized trial in patients with early severe ARDS and recommend 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
NEUROMUSCULAR BLOCKADE 340 patients with an onset of severe ARDS within
previous 48 hours randomly assigned to receive, for 48 hours, either
cisatracurium besylate (178 patients) or placebo (162 patients)
Severe ARDS was defined as a P/F ratio of less than 150, with a PEEP of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of PBW
HR 0.68 (95% CI 0.48 to 0.98; P=0.04)
Beta-agonist infusions were found to be harmful to ARDS patients in the BALTI trials (2011)
EDEN trial- trophic feeds equivalent to full feeds in first 7 days
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!
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