ards the fundamentals. objectives know the epidemiologic risk factors for ards understand the...
TRANSCRIPT
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ARDS
The Fundamentals
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Objectives
• Know the epidemiologic risk factors for ARDS • Understand the pathogenesis of lung
dysfunction in ARDS• Know how to diagnose ARDS• Understand the pathophysiology of ARDS• Know the principles of management in ARDS• Plan mechanical ventilation in ARDS
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Features of ARDS
• Definition: clinically defined hypoxemic
respiratory failure• Causes: multiple• Pathophysiology: heterogeneous process
mediated by inflammatory pathways• Treatment: identify and treat underlying cause
and provide supportive care
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DefinitionAmerican-European Consensus Conference
(1994)• Require:
– 1)Acute onset and persistence of respiratory symptoms
– 2) Frontal chest radiograph w/bilateral infiltrates– 3) No clinical evidence of left atrial hypertension
(pulmonary capillary wedge <18 mm Hg)• Define:
– ALI: P/F ratio <300 mm Hg– ARDS: P/F ratio <200 mm Hg
Bernard GR et al., Am J Respir Crit Care Med 1994
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Problems with the Definition
• Broad definition that does not address cause• What is acute??• Radiology criteria unspecific• P/F ratio does not account for PEEP or MAP• P/F ratio has not been shown to correlate
with the severity of the lung injury, the
clinical course, or mortality
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Epidemiology
• Mortality decreasing– > 50% in mid 80’s– 36% in mid 90’s
UpToDate
Mortality is still significant
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CausesMultifactorial• Direct Lung Injury
– Aspiration / chemical pneumonitis– Infectious PNA– Trauma – contusions, penetrating injury, inhalation injury– Near drowning– Fat embolism
• Indirect Injury– Inflammation, sepsis– Multiple trauma, burns– Shock, hypoperfusion– Acute pancreatitis– Bypass– Transfusion related
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Causes: Children
• Shock, sepsis, drowning seem to be top three• In single institution:
– Highest incidence (12%) for ARDS was for those with sepsis/viral pneumonia/smoke inhalation/drowning
– 2.7% of all admissions developed ARDS.
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Risk Factors of Poor Outcome• Clinical
– Severity of illness (APACHE)– Other organ involvement, comorbid conditions
• Specifically liver dysfunction– Sepsis
• Plasma Markers– Acute inflammation (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 TNF receptors I and II)– Procoagulant activity (Protein C)– Fibrinolytic activity (Plasminogen activator inhibitor-1)
Ware LB. Crit Care Med. 2005
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Early deaths (within 72 hours) are caused by the underlying illness or injury, whereas late
deaths are caused by sepsis or multiorgan dysfunction
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Pathophysiology of ARDSInsult
↓
Activation of inflammatory mediators and cellular components
↓
cytokines (TNF, IL-1, IL-6, IL-8)
neutrophil infiltration
↓
damage to capillary endothelial and
alveolar epithelial cells
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Pathophysiology of ARDS
• Starling forces fall out of balance– Increased in capillary hydrostatic pressure– Diminished oncotic pressure gradient
• Exudative fluid in both the interstitium and alveoli– impaired gas exchange– decreased compliance– increased pulmonary arterial pressure– Type II pneumocyte damage decreased surfactant– Loss of aeration (mainly in caudal and dependent lung
regions in patients lying supine)
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A Picture is Worth a Thousand Words?
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The 3 Pathologic Phases of ARDS
• Exudative Phase – diffuse alveolar damage
• Proliferative Phase – pulm edema resolves– myofibroblasts infiltrate the – interstitium– collagen begins to deposit
• Fibrotic Phase– obliteration of normal lung architecture– diffuse fibrosis and cyst formation
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Principles of Management• Identify and treat underlying process• Offer supportive care• Improve gas exchange• Trial unproven last ditch therapies
No effective modalities to intervene
the only therapy that has been proven to be effective at reducing mortality in ARDS in a large,
randomized, multi-center, controlled trial is a protective ventilatory strategy
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Supportive Care
• Sedatives and neuromuscular blockade• Hemodynamic management• Nutritional support• Control of blood glucose levels• VAP and other nosocomial infection
prevention• Prophylaxis against DVT and GI bleeding
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Sedatives and NMBs
• improve tolerance of mechanical ventilation• decrease oxygen consumption
BUT• routinely wake patients each day• use intermittent doses when possible• follow a sedation and analgesia protocol
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Paralysis: improved oxygenation vs. prolonged neuromuscular
weakness• multicenter RCT of ARDS patients - N=340• cisatracurium vs. placebo drip x 48 hrs • statistically significant decrease in 90-day
mortality for subset of patients with P/F < 120 • there was no difference in the frequency of
ICU-acquired neuromuscular weaknessPapazian L , et al. Neuromuscular blockers in early acute respiratory distress syndrome. NEJM. 2010 Sep;363(12):1107-16
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Hemodynamic Management
• Decrease oxygen consumption– Because of pulmonary shunting, increasing SvO2 may increase
SaO2– Avoid fever – Avoid anxiety and pain – Avoid excessive use of respiratory muscles
• Improve oxygen delivery– CO x (SaO2 x Hgb x 1.34)
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Nutrition
• ARDS is a catabolic state• Use gut when able• Avoid overfeeding• Keep HOB 30 degrees upright for reflux precautions in
intubated patients • Arginine: inhibit platelet aggregation, improve wound
healing, changes into NO• Glutamine: fuel for mucosa, lymphocytes, macrophages• PolyUnsaturated Fatty Acids: affect immune balance
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VAP
• Pulmonary edema is an excellent growth medium for bacteria
• Pneumonia is difficult to diagnose• Proven strategies
– keep HOB elevated– avoid unnecessary antibiotics– good mouth care– wean vent timely– avoid excessive sedation– vent circuit change per protocol – routine vent tubing care
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Improve Gas Exchange
• Mechanical ventilator strategies• Use of high fractions of inspired oxygen • Prone positioning
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There’s no free lunch!
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VILI• Pulmonary edema
– Mechanical ventilation alters the alveolar-capillary barrier permeability• Increased transmural vascular pressure• Surfactant inactivation• Mechanical distortion and disruption of endothelial cells• Regional activation of inflammatory cells
• Lung inflammation– Repetitive opening /collapse of atelectatic lung units– Surfactant alterations– Loss of alveoli-capillary barrier function– Bacterial translocation– Overinflation of healthy lung regions
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Normal – 5 min – 20 min of 45 cmH2O
Dreyfuss, Am J Respir Crit Care Med 1998;157:294-323
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ARDS Network Study
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ARDS Network Study
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ARDS Network Study – Other Findings
• No difference in their supportive care requirements (vasopressors-IV fluids-fluid balance-diuretics-sedation)
• ~10% mortality reduction• Less organ failures• Lower IL-6 and IL-8 levels
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Physiologic Effects of Hypercapnia
• Resp– Benefits: Improves oxygenation by
• Enhancing hypoxic pulmonary vasoconstriction and decreasing intrapulmonary shunting
• right-shift of oxygen-hemoglobin dissociation curve
– Dangers: • Low PaO2. For a constant FIO2, as the PaCO2 ↑, PAO2 ↓ (alveolar gas equation). • Low pH. (Henderson Hasselbalch equation) • Decreased ventilatory reserve. Small changes in
alveolar ventilation big change in CO2 when unhealthy
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Physiologic Effects of Hypercapnia
• Renal: Worsens perfusion by– direct renal vasoconstriction from acidosis and
sympathetic-meditated release of NE– But, maintains pH with compensatory bicarb
reabsorption
• CV: Compromises hemodynamics– Sympathetic stimulation with increased CO
• Increased HR and SV, decreased SVR – Intracellular acidosis of cardiomyocytes– When combined with high PEEP strategy, can lead to
severely decreased preload and cardiovascular compromise
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Permissive HypercapniaIs it worth it?
• Early adult ARDS trial showed a reduction in expected mortality of 56% to an actual mortality of 26%
• Included in adult trauma patients protocol for mechanical ventilation
• Several pediatric studies showing benefit when used in conjunction with low TV and high PEEP
Hickling, CCM, 1994
Nathens, J Trauma, 2005
Sheridan, J Trauma, 1995
Paulson, J Pediatr, 1996
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PEEP
• Improves oxygenation by– Increasing end-expiratory lung volume– Recruiting unventilated alveoli– Decreasing perfusion to unventilated alveoli– Improving V/Q matching– Decreasing intrapulmonary shunt
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PVR Increases at Lung Volumes Below and Above FRC
Lung Volume
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What is adequate PEEP?
• Measuring P/V curve is not practical clinically.
• A single inflation P/V curve doesn’t represent whole lung.
• The P/V curve for the whole lung = sum of multiple regional P/V curves
• A lot of variation btwn dependent and nondependent lung
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Recruitment Maneuvers
• inflating to 40 cm H2O for 15 - 26 seconds• Intermittent increase of PEEP• Sigh breaths
When alveolar recruitment is optimized by increasing PEEP, recruitment maneuvers are
either poorly effective or deleterious
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Proning
Proning 7 hrs/day x 10 days
Gattinoni, et al AJRCCM 164(9), 1701-11 (2001)
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Effects from changes in position
• End expiratory views, PEEP 10• supineprone supine• Relatively quick change in alveolar
gas distribution
Gattinoni, et al AJRCCM 164(9), 1701-11 (2001)
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ProningHow does it work?
• Increases FRC
• Improves ventilation of previously dependent regions
• Redistribute tidal volume to atelectatic dorsal region
• Difference in diaphragm movement: when supine, dorsal and ventral move symmetrically, when prone, dorsal > ventral
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Mechanical Ventilation Summary
• Avoid overdistension (limit tidal volume and plateau pressure)
• Avoid derecruitment (adequate PEEP)
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Unproven Therapies for Times of Desperation
• Inhaled vasodilators: iNO• Steroids• Beta Agonists• Surfactant• Liquid Ventilation• ECMO
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Role of Nitric Oxide in Lung Injury
• Optimizes V/Q matching
• Inhibits neutrophil adhesion
• Effects on long term lung disease unclear
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Role of Nitric Oxide in Lung Injury
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Steroids in ARDS
• Theoretical anti-inflammatory, anti-fibrotic benefit– Inhibit transcriptional activation of various cytokines– Inhibit synthesis of phospholipase A2 : cycloxygenase– Reduced prod. of prostanoids, PAF– fibrinogenesis
• 2 meta-analyses– High dose methylpred for < 48 hrs (30 mg/kg/d)– In early ARDS no benefit
LEFERING et al CCM 1995
CRONIN et al., CCM 1995
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Steroids in ARDS
• Randomized, double-blind, placebo-controlled trial• Adult ARDS ventilated for > 7 days without improvement• No evidence of untreated infection• Randomized:
– Placebo– Methylprednisolone 2 mg/kg/day x 14 days, tapered
over 1 month
Meduri et al, JAMA, 1998
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Steroids in ARDS
• By day 10, steroids improved:– PaO2/FiO2 ratios
– Lung injury scores– Static lung compliance
• 24 patients enrolled; study stopped due to survival difference
0102030405060708090
100
ICUsurvival
Hospitalsurvival
Steroid Placebo
Meduri et al, JAMA, 1998
P< 0.01
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Steroids in ARDSARDSNET 2006:354(16) 1671-83
• N = 180• Methylpred vs. placebo• > 14 days into course
Steroids showed no benefit
and some potential adverse
effects
NOT recommended
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Exogenous Surfactant
• Multicenter trial-uncontrolled, observational
• Calf lung surfactant (Infasurf) - intratracheal
• Immediate improvement and weaning in 24/29 children
with ARDS and 14% mortality
• In several other studies, there is no evidence for sustained
benefit from Surfactant administration
Wilson et al, CCM, 24:1996
Wilson et al, JAMA, 2005
P = 2T/r
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Liquid Ventilation• Fill the lungs with liquid – Perfluorocarbon: colorless,
odorless, inert, high vapor pressure, oxygen rich liquid
• Anti-inflammatory properties (↓ TNF, IL-1 and IL-8, inhibits neutrophil activation and chemotaxis)
• Reduces surface tension• ↑ surfactant phospholipid synthesis and secretion• 2 published adult trials of PLV in ARDS have confirmed
its safety but not efficacy over HFOVHirschl et al JAMA 1996, 275; 383-389Gauger et al, CCM 1996, 24; 16-24
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ECMO for Severe Lung Injury
• Alternative means for gas exchange
• Allows lung rest• May be beneficial in
fluid removal• High risk/ high cost
venture
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Issues with use of ECMO
• Is the disease process potentially reversible?– Is there a diagnosis?
• Are the pre-ECMO therapies harmful?– Can we prevent iatrogenic complications?– Have we created hemodynamic instability?
• Are there other complicating comorbidities?– Will these increase the risk of ECMO?
• Requires balancing the risks and benefits
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Combination Therapies
Now to look at RCTs of combination therapies ….
Just kidding
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Summary• Clinically defined• Multiple causes• Mediated by inflammatory pathways• Heterogeneous process• Identify and treat underlying cause• Do no harm• Supportive interventions
Decrease in ARDS mortality in recent years largely due to improved CCM capabilities rather than ARDS-specific
therapies
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References• ARDS Clinical Trial Network. 2006. Comparison of Two Fluid-Management Strategies in
Acute Lung Injury. N Engl J Med. 354 (24). pp 2564-75.• ARDS Clinical Trial Network. 2006. Pulmonary-Artery versus Central Venous Catheter to
Guide Treatment of Acute Lung Injury. N Engl J Med. 354 (21). pp 2213-24. • Fan, E., Needham, D.M., Stewart, T.E. Ventilatory Management of Acute Lung Injury and
Acute Respiratory Distress Syndrome. 2005. JAMA. 294 (22). pp. 2889-96. • Hansen-Flaschen, J., Siegel, M.D. Acute Respiratory Distress Syndrome: Definition;
Epidemiology; Diagnosis; and Etiology. 2006. www.utdol.com. • Heresi, G.A., Arroligo, A.C., Weidemann, H.P., Matthay, M.A. 2006. Pulmonary Artery
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