Acute Respiratory Distress Syndrome ACNP Boot Camp 2014Stephanie Davidson, ACNP-BC

ObjectivesReview the causes and differentials for ARDSBriefly discuss the pathophysiology Discuss the clinical manifestations of ARDSUnderstand evidence based treatment options

StatisticsEpidemiologyAnnual incidence: 60/100,00020% ICU patients meet criteria for ARDSMorbidity / Mortality26-44%, most (80%) deaths attributed to non-pulmonary organ failure or sepsisRisk FactorsAdvanced age, pre-existing organ dysfunction or chronic medical illnessPatient with ARDS from direct lung injury has higher incidence of death than those from non-pulmonary injuryLevy BD, & Choi AM, Harrisons Principles of Internal Medicine, 2012

Bernard et al. AJRCCM 1994; 149:818Rice et al. Chest 2007: 132: 410

June 20, 2012, Vol 307, No. 23et al. JAMA 2012; 307:2530

-European Society of Intensive Care Medicine with endorsement from American Thoracic Society and Society of Critical Care Medicine-Devised three mutually exclusive severity categories: Mild, Moderate and Severe-Took into account: timing, chest imaging, origin of edema, oxygenation

et al. JAMA 2012; 307:2530

ARDS network N Engl J Med 2000; 342:1301Pneumonia 35%

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Other: drowning, pancreatitis, reperfusion, salicylate and narcotic OD, fat/amniotic embolism, smoke/chemical inhalation.

Causes of ARDS/ALI

Causes of ARDS

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Causes of ARDS/ALI

Severe Sepsis26%

Pneumonia35%

Aspiration15%

Trauma11%

Other13%

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Severe Sepsis 26%

Aspiration 15%

Trauma 11%

Other 13%

Causes of ARDS

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Causes of ARDS

Aspiration15%

Trauma11%

Other13%

Severe Sepsis26%

Pneumonia35%

DifferentialsLeft ventricular failure/volume overloadMitral stenosisPulmonary veno-occlusive diseaseLymphangitic spread of malignancyInterstitial and/or airway diseaseHypersensitivity pneumoniaAcute eosinophilic pneumoniaAcute interstitial pneumonitis

Pathophysiology1. Direct or indirect injury to the alveolus causes alveolar macrophages to release pro-inflammatory cytokinesWare et al. NEJM 2000; 342:1334

Pathophysiology2. Cytokines attract neutrophils into the alveolus and interstitum, where they damage the alveolar-capillary membrane (ACM). Ware et al. NEJM 2000; 342:1334

Pathophysiology3. ACM integrity is lost, interstitial and alveolus fills with proteinaceous fluid, surfactant can no longer support alveolus Ware et al. NEJM 2000; 342:1334

PathophysiologyConsequences of lung injury include:Impaired gas exchangeDecreased complianceIncreased pulmonary arterial pressure

Impaired Gas ExchangeV/Q mismatchRelated to filling of alveoliShunting causes hypoxemiaIncreased dead spaceRelated to capillary dead space and V/Q mismatchImpairs carbon dioxide eliminationResults in high minute ventilation

Decreased ComplianceHallmark of ARDSConsequence of the stiffness of poorly or nonaerated lungFluid filled lung becomes stiff/boggyRequires increased pressure to deliver Vt

Increased Pulmonary Arterial PressureOccurs in up to 25% of ARDS patientsResults from hypoxic vasoconstrictionPositive airway pressure causing vascular compressionCan result in right ventricular failureNot a practice we routinely measure

Treat the underlying causeLow tidal volume ventilationUse PEEPMonitor Airway pressuresConservative fluid managementReduce potential complicationsEvidence based management of ARDS

Hypothesis:In patients with ALI, ventilation with smaller tidal volumes (6 mL/kg) will result in better clinical outcomes than traditional tidal volumes (12 mL/kg) ventilation.ARDS Network N Engl J Med 2000; 342:1301

Low Tidal Volume VentilationWhen compared to larger tidal volumes, Vt of 6ml/kg of ideal body weight:Decreased mortalityIncreased number of ventilator free daysDecreased extrapulmonary organ failureMortality is decreased in the low tidal volume group despite these patients having:Worse oxygenationIncreased pCO2 (permissive hypercapnia)Lower pHARDSnet. NEJM 2000; 342: 1301

Low Tidal Volume VentilationARDS affects the lung in a heterogeneous fashionNormal alveoliInjured alveoli can potentially participate in gas exchange, susceptible to damage from opening and closingDamaged alveoli filled with fluid, do not participate in gas exchange

Low Tidal Volume Ventilation

Protective measure to avoid over distention of normal alveoliUses low (normal) tidal volumesMinimizes airway pressuresUses Positive end-expiratory pressure (PEEP)

Hypothesis:In patients with ALI ventilated with 6 mL/kg, higher levels of PEEP will result in better clinical outcomes than lower levels of PEEP. N Engl J Med 2004; 351:327

PEEPHigher levels of PEEP/FiO2 does not improve outcomes may negatively impact outcomes:Causing increased airway pressureIncrease dead spaceDecreased venous returnBarotrauma

PEEPPositive End Expiratory PressureEvery ARDS patient needs itGoal is to maximize alveolar recruitment and prevent cycles of recruitment/derecruitment

Meade, M et al, JAMA. 2008; 299(6):637-645-983 patients, randomized into control group with ALI protocol, low Vt and PEEP vs. Open lung group with low Vt, higher PEEP and recruitment maneuvers-No statistically significant difference in mortality outcomes

Mercatt, M, et al. JAMA. 2008; 299(6):646-655.-Multicenter randomized trial, 767 patients. Set a PEEP aimed to increase alveolar recruitment while limiting hyperinflation-Randomly assigned two groups: moderate PEEP (5-9cm H2O) vs. level of PEEP to reach a plateau pressure of 28-30cm H2O-Found that it didnt significantly reduce mortality; however, it did improve lung function and decreased days on vent and organ failure duration

PEEPAs FiO2 increases, PEEP should also increase

ARDSnet. NEJM 2004; 351, 327

Auto Peep

Airway Pressures in ARDS Plateau pressure is most predictive of lung injury Goal plateau pressure < 30, the lower the betterDecreases alveolar over-distention and reduces risk of lung strain Adjust tidal volume to ensure plateau pressure at goal It may be permissible to have plateau pressure > 30 in some cases Obesity Pregnancy AscitesTerragni et al. Am J Resp Crit Care Med. 2007; 175(2):160

Permissible Plateau PressuresAssess cause of high Plateau PressuresAlways represents some pathology:Stiff, non-compliant lung: ARDS, heart failurePneumothoraxAuto-peepingMucus PlugRight main stem intubationCompartment syndromeChest wall fat / Obesity

Airway PressuresPeak Inspiratory PressurePlateau PressurePEEPAirway PressuresTime

N Engl J Med 2006; 354: 2213

Fluid and Catheter Treatment Trial--No need for routine PAC use is ALI patients--Support use of conservative strategy fluid management in patients with ALI

ResultsUsing the data from a PAC compared to that from a CVC in an explicit protocol:Did not alter survival.Did not improve organ function.Did not change outcomes for patients entering in shock compared to those without shock.PAC use resulted in more non-fatal complications, mostly arrhythmias.N Engl J Med 2006; 354: 2213

N Engl J Med. 2006;354:2564

~Hypothesis: Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary organ perfusion

~Conclusion: Conservative fluid management improved lung function and shortened mechanical ventilation times and ICU days without increasing nonpulmonary organ failures

Fluid ManagementIncreased lung water is the underlying cause of many of the clinical abnormalities in ARDS (decreased compliance, poor gas exchange, atelectasis)After resolution of shock, effort should be made to attempt diuresisCVP used as guide, goal

Hypothesis: Early application of prone positioning would improve survival in patients with severe ARDS.

Conclusion: Early application of prolonged prone positioning significantly decreased 28 day and 90 mortality in patients with severe ARDS. Guerin et al. NEJM. 2013; 368:2159

WeaningDaily CPAP breathing trialFiO2

WeaningTolerating Breathing Trial?SpO2 90Spontaneous Vt 4ml/kg PBWRR 35pH 7.3Pass Spontaneous Awakening Trial (SAT)No Respiratory Distress ( 2 or more)HR > 120% baselineAccessory muscle useAbdominal ParadoxDiaphoresisMarked DyspneaIf tolerated, consider extubation

Putting it all together1) Calculate patients predicted body weight:Men (kg) = 50 + 2.3(height in inches 60)Females (kg) = 45.5 + 2.3(height in inches 60)Set Vt = predicted body weight x 6ccSet initial rate to approximate baseline minute ventilation (RR x Vt)Set FiO2 and PEEP to obtain SaO2 goal of >=88%Diurese after resolution of shock Refer to ARDSnet guidelines

Troubleshooting Common Problems

Refractory HypoxiaMechanical Trouble (tubing, ventilator, ptx, plugging)Neuromuscular blockadeRecruitment maneuvers positioning, good lung down optimizes V/Q mismatchIncrease PEEPInhaled epoprostenol sodium (Flolan)When inhaled, the vasodilator reaches the normal lung, is concentrated in normal lung segments and recruits blood flow to functional alveoli where it is oxygenated. This decreases shunting and hypoxemia High frequency ventilation

Ferguson, N, et al, NEJM 2013; 368: 795-805. -Randomized control trial, stopped with 548 of 1200 patients-Found early initiation of HFOV does not reduce and may increase hospital mortality

Young, D, et al,NEJM. 2013; 368:806-813-Multicenter randomized trial with 795 patients enrolled-found there is no significant effect of 30 day survival between patients who received HFOV and conventional mechanical ventilation

Papazian, L, et al. NEJM 2010; 363: 1107-1116.-Neuromuscular blocking agents may increase oxygenation and decrease ventilator associated lung injury in severe ARDS patients-Multicenter double blind trial with 340 patients; received 48hrs of cisatracurium (Nimbex) or placebo-Found that early administration of NBA improved 90 day survival and increased time off vent without increase in muscle weakness

Supportive TherapiesTreat underlying infectionDVT prophylaxis / stress ulcer preventionHOB 30Hand washingUse full barriers with chlorhexadineSedation / analgesiaFeeding protocolAvoid contrast nephropathyPressure ulcer prevention, turning Q2hAvoid steroid use

~No benefit of corticosteroids on survival

~When initiated 2 weeks after onset of ARDS, associated with significant increase in mortality rate compared to placebo groupN Engl J Med. 2006; 354:1671

ConclusionRecovery dependent on health prior to onsetWithin 6 months, will have reached max recoveryAt 1 year post-extubation, >1/3 have normal spirometrySignificant burden of emotional and depressive symptoms with increased depression and PTSD in ARDS survivorsSurvivor clinic catches symptoms early by screening patientsNew treatment modalities, lung protective ventilation

Levy BD, & Choi AM, Harrisons Principles of Internal Medicine, 2012

Questions ?

ReferencesAcute Respiratory Distress Syndrome Network: Ventilation with Tidal Volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New Engl J Med. 2000; 342: 1302-1308.ARDSNet: Higher versus lower Positive End-Expiratory Pressures in patients with the acute respiratory distress syndrome. New Engl J Med. 2004; 351: 327-336. ARDSNet: Efficacy and Safety of Corticosteroids for persistent acute respiratory distress syndrome. New Engl J Med. 2006; 354: 1671-1684.ARDSNet: Comparison of Two fluid management strategies in acute lung injury. New Engl J Med. 2006; 354: 2564-75.ARDSNet: Pumonary Artery versus Central Venous catheter to guide treatment of acute lung injury. New Eng J Med. 2006; 354: 2213-2224. Et al: Acute respiratory distress syndrome: The Berlin Definition. JAMA. 2012; 307(23): 2526-2533.Ferguson N, et al: High frequency oscillation in early acute respiratory distress syndrome. New Engl J Med. 2013; 368: 795-805.Guerin C et al: Prone positioning in severe acute respiratory distress syndrome. New Engl J Med. 2013; 368: 2159-2168.

ReferencesLevy B.D., Choi A.M. (2012). Chapter 268. Acute Respiratory Distress Syndrome. In A.S. Fauci, D.L. Kasper, J.L. Jameson, D.L. Longo, S.L. Hauser (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved August 17, 2013 from http://www.accesspharmacy.com.proxy.library.vanderbilt.edu/content.aspx?aID=9105737.Meade M, et al: Ventilation Strategy Using low tidal volumes, recruitment maneuvers and high post end expiratory pressure for acute lung injury and acute respiratory distress syndrome. JAMA. 2008; 299(6):637-645.Mercatt M, et al: Post end-expiratory pressure settings in adults with acute lung injury and acute respiratory distress syndrome. JAMA. 2008; 299(6): 645-655.Papazian L, et al: Neuromuscular blockers in early acute respiratory distress syndrome. New Engl J Med. 2010; 363:1107-1116.RiceTW et al: Comparison of the SpO2/FiO2 Ration and the PaO2/FiO2 Ratio in patients with acute lung injury or acute respiratory distress syndrome. Chest. 2007; 132: 410-417.

Terragan PP et al: Tidal hyperinflation during low tidal volume ventilation in Acute respiratory distress syndrome. J Resp Crit Care Med. 2007; 175: 160-166Ware LB, Matthay MA: The Acute Respiratory Distress Syndrome. New Engl J Med. 2000; 342: 1334-1349.Young D, et al: High frequency oscillation for acute respiratory distress syndrome. New Engl J Med. 2013; 368:806-813.

References

Non-cardiogenic pulmonary edemaProfound hypoxemia difference between ali and ards.

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