-Dr. K. V. Raman,Dean, MTPGRIHS

Objectives

Define ARDS and describe the pathological process

Know causes of ARDS, and differential diagnosis

Understand specific challenges in mechanical ventilation of patients with ARDS

Understand treatment strategies and evidence behind them

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Respiratory Failure

Respiratory failure is an alteration in the function of the respiratory system that causes the partial pressure of arterial oxygen (PaO2) to fall below 50 mm Hg (hypoxemia) and/or the partial pressure of arterial carbon dioxide (Paco2) to rise above 50 mmHg (hypercapnia), as determined by arterial blood gas (ABG) analysis.

Respiratory failure is classified as acute/ chronic.

Etiology: 1. Cardiogenic pulmonary edema.

2. Acute respiratory distress syndrome (ARDS)

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Pulmonary edema

Acute pulmonary edema refers to excess fluid in the lung, either in the interstitial spaces or in the alveoli.

Most often occurs as result of cardiac disorders (Left CHF, MI…etc)

Signs/Symptoms: 1. Crackles. 2. Dyspnea and cough. 3. Tachycardia. 4. Cyanosis, cold diaphoretic skin. 5. Restlessness. 6. Jugular venous distention. (JVD)

ARDS

First described 1967 by Ashbaugh and colleagues

Severe lung injury characterized by non-cardiogenic pulmonary edema, decreased lung compliance, refractory hypoxemia

1994 Consensus Definition Acute onset (<2 weeks) Bilateral infiltrates on chest xray PCWP ≤18mmHg or lack of evidence of left

atrial hypertension Acute lung injury if PaO2/FiO2 ≤300 ARDS if PaO2/FiO2 ≤200

ARDSDefinitions

Acute Lung Injury 150 – 200 mmHg < PaO2/FIO2 < 250 –

300 mmHg

ARDS PaO2/FIO2 < 150 – 200 mmHg

ARDSEpidemiology Incidence:

5 – 71 per 100,000

Financial cost: $5,000,000,000 per annum

Risk factors for ARDS

Most common causes ARDS

Pneumonia (34%) Sepsis (27%) Aspiration (15%) Trauma (11%)

Pulmonary contusion Multiple fractures

Causes of ARDS

ARDSPathophysiology

Profound inflammatory response

Diffuse alveolar damage acute exudative phase (1-7days) proliferative phase (3-10 days) chronic/fibrotic phase (> 1-2 weeks)

ARDS Acute Exudative Phase

Basement membrane disruption Type I pneumocytes destroyed Type II pneumocytes preserved

Surfactant deficiency inhibited by fibrin decreased type II production

Microatelectasis/alveolar collapse

ARDS Acute Exudative Phase

ARDS Acute Exudative Phase

Acute (Exudative) Phase

Expansion of interstitium with macrophages and inflammation Hyaline

Membranes

Alveolar Filling

ARDS Acute Exudative Phase

ARDSProliferative Phase Type II pneumocyte

proliferate differentiate into Type I cells reline alveolar walls

Fibroblast proliferation interstitial/alveolar fibrosis

ARDSProliferative Phase

ARDSFibrotic Phase Characterized by:

local fibrosis vascular obliteration

Repair process: resolution vs fibrosis

Fibrosing alveolitis

ARDSPathophysiology Interstitial/alveolar edema

Severe hypoxemia due to intra-pulmonary shunt (V/Q = 0) shunt ~ 25% - 50%

Increased airway resistance

ARDSPathophysiology High ventilatory demands

high metabolic state increased VD/VT

decreased lung compliance

Pulmonary HTN neurohumoral factors, hypoxia, edema

ARDSClinical Features

Acute dyspnea/tachypnea rales/rhonchi/wheezing

Resistant hypoxemia PaO2/FIO2 < 150 – 200 mmHg

CXR diffuse, bilateral infiltrates

No evidence of LV failure (PAWP < 18 mmHg)

ARDSDiagnosis

Resistant hypoxemia PaO2/FIO2 < 150 – 200 mmHg

CXR diffuse, bilateral infiltrates

No evidence of LV failure (PAWP < 18 mmHg)

ARDSClinical Features: CXR

ARDSClinical Features: CXR

Objective #6:Describe conditions resulting from pulmonary alterations.

ARDSDifferential Diagnosis

CARDIOGENIC PULMONARY EDEMA

Bronchopneumonia

Hypersensitivity pneumonitis

Pulmonary hemorrhage

Acute interstitial pneumonia (Hamman-Rich Syndrome)

Differential diagnosis

Pulmonary edema from left heart failure

Diffuse alveolar hemorrhage

Acute eosinophilic pneumonia

Lupus pneumonitis Acute interstitial

pneumonia Pulmonary alveolar

proteinosis

BOOP or COP Hypersensitivity

pneumonitis Leukemic infiltrate Drug-induced

pulmonary edema and pneumonitis

Acute major pulmonary embolus

Sarcoidosis Interstitial pulmonary

fibrosis

Excluding other diagnoses Echo Central venous catheter Bronchoscopy with bronchoalveolar

lavage (to eval for hemorrhage, AEP, etc)

Chest CT

Management of ARDS

Treat underlying illness Sepsis, etc

Nutrition Supportive care DVT prophylaxis GI prophylaxis Medications

Acute (Exudative) Phase

Rapid onset respiratory failure in patient at risk for ARDS

Hypoxemia refractory to oxygen Chest xray resembles cardiogenic

pulmonary edema Bilateral infiltrates worse in dependent

lung zones, effusions Infiltrates may be asymmetric

Acute Phase - Radiographs

Fibroproliferative Phase

Persistent hypoxemia Fibrosing alveolitis Increased alveolar dead space Decreased pulmonary compliance Pulmonary hypertension

From obliteration of capillary bed May cause right heart failure

Fibroproliferative phase

Chest xray shows linear opacities consistent with evolving fibrosis

Pneumothorax in 10-13% of patients CT: diffuse interstitial opacities and bullae Histologically, fibrosis, mesenchymal cells,

vascular proliferation, collagen and fibronectin accumulation

Can start 5-7 days after symptom onset Not present in every patient with ARDS,

but does portend poorer prognosis

Fibroproliferative phase

Recovery phase

Gradual resolution of hypoxemia Hypoxemia improves as edema resolves via

active transport Na/Cl, aquaporins Protein removal via endocytosis Re-epithelialization of denuded alveolar space

with type II pneumocytes that differentiate into type I cells

Improved lung compliance Chest xray and CT findings resolve PFTs improve, often normalize

Complications in Managing ARDS patients

Mechanical ventilation causes: Overdistention of lungs (volutrauma)

Further damaging epithelium Increased fluid leak, indistinguishable from ARDS

damage Barotrauma

Rupture alveolar membranes Pneuomothorax, pneumomediastinum

Sheer stress Opening/closing alveoli Inflammatory reaction, cytokine release

Oxygen toxicity Free radical formation

Action of surfactant

Barotrauma

Objective #2:Describe conditions resulting from pulmonary alterations.

Pneumothorax

Figure 26-5Page 758

Objective #1:Describe conditions resulting from pulmonary alterations.

Ventilator management – ARDSnet protocol

861 patients randomized to Vt 10-12 mg/kg ideal body weight and plateau pressure ≤50cmH2O vs Vt 6-8 mg/kg IBW and plateau pressure ≤30cm H2O

KEYS Low tidal volumes – 6-8mL/kg ideal body

weight Maintain plateau (end-inspiratory) pressures

<30cm H20 Permissive hypercapnia and acidosis

Decreased mortality by 22%

Positive End-Expiratory Pressure (PEEP)

Titrate PEEP to decrease FiO2 Goal sat 88% with FiO2 <60%

Minimize oxygen toxicity PEEP can improve lung recruitment and

decrease end-expiratory alveolar collapse (and therefore right-to-left shunt)

Can also decrease venous return, cause hemodynamic compromise, worsen pulmonary edema

ARDSnet PEEP trial of 549 patients show no difference in mortality or days on ventilator with high vs low PEEP

Other Ideas in Ventilator Management

Prone positioning May be beneficial in certain subgroup, but

complications including pressure sores RCT of 304 patients showed no mortality benefit

High-frequency oscillatory ventilation In RCT, improved oxygenation initially, but

results not sustained after 24 hours, no mortality benefit

Drug therapy

Agents studied: Corticosteroids Ketoconazole Inhaled nitric oxide Surfactant

No benefit demonstrated

Steroids in ARDS

Earlier studies showed no benefit to early use steroids, but small study in 1990s showed improved oxygenation and possible mortality benefit in late stage

ARDSnet trial (Late Steroid Rescue Study “LaSRS” – “lazarus”) of steroids 7+ days out from onset of ARDS

180 patients enrolled, RCT methylprednisolone vs placebo

Overall, no mortality benefit Steroids increased mortality in those with sx >14 days

Other drugs in ARDS

Ketoconazole ARDSnet study of 234 patients, ketoconazole did

NOT decrease mortality, duration of mechanical ventilation or improve lung function

Surfactant Multicenter trial, 725 patients with sepsis-

induced ARDS, surfactant had no effect on 30-day survival, ICU LOS, duration of mechanical ventilation or physiologic function

Inhaled Nitric oxide 177 patients RCT, improved oxygenation, but no

effect on mortality of duration of mechanical ventilation

Fluid management

“Dry lungs are happy lungs” ARDSnet RCT of 1000 patients (FACTT),

Conservative vs liberal fluid strategy using CVP or PAOP monitoring to guide, primary outcome: death. Conservative fluids Improved oxygenation More ventilator-free days More days outside ICU No increase in shock or dialysis No mortality effects

Keys to management

Treat underlying illness Supportive care

Low tidal volume ventilation Nutrition Prevent ICU complications

Stress ulcers DVT Nosocomial infections Pneumothorax No routine use of PA catheter

Diuresis/avoidance of volume overload Give lungs time to recover

Survival and Long Term Sequelae

Traditionally mortality 40-60% May be improving, as mortality in

more recent studies in range 30-40% Nonetheless survivors report

decreased functional status and perceived health

1 year after ARDS survival

Lung Function: FEV1 and FVC were normal; DLCO minimally

reduced Only 20% had mild abnormalities on CXR

Functionally: Survivors’ perception of health was <70% of

normals in: Physical Role: Extent to which health limits physical

activity Physical Functioning: Extent to which health limits work Vitality: Degree of energy patients have

6 minutes walk remained low Only 49% had returned to work

Summary

ARDS is a clinical syndrome characterized by severe, acute lung injury, inflammation and scarring

Significant cause of ICU admissions, mortality and morbidity

Caused by either direct or indirect lung injury Mechanical ventilation with low tidal volumes

and plateau pressures improves outcomes So far, no pharmacologic therapies have

demonstrated mortality benefit Ongoing large, multi-center randomized

controlled trials are helping us better understand optimal management

Thank you

References

Rubenfeld GD, et al. Incidence and outcomes of acute lung injury N Engl J Med. 2005;353:1685-93.

Luhr OR, et al. Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF study group. Am J Respir Crit Care Med. 1999;159:1849061,

Bersten AD et al. Australian and New Zealand Intensive Care Society Clinical Trials Group. Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian states. Am J Respir Crit Care Med. 2002;165:443-8.

Connors AF Jr, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT investigators. JAMA. 1996;276:889-97.

Richard C, et al. Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2003;290:2713-20.

Wheeler AP, et al. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med. 2006:354:2213-24.

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342:1301-8.

National Heart, Lung and Blood Institues Acute Respiratory Distress (ARDS) Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury. N Enlg J Med. 2006;354:2564-75.

Kollef, MH, Schuster DP. The acute respiratory distress syndrome. N Engl J Medicine 1995;332(1):27-37.

Pulmonary artery catheters

Often used to help evaluate for cardiogenic pulmonary edema

SUPPORT trial (retrospective study) first raised doubts about utility

Two multicenter RCTs confirmed lack of mortality benefit of PA catheters in ARDS (ARDSnet FACTT)

Monitoring CVP equally effective, so PAC not recommended in routine management

References

Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2000;283:1995-2002.

Anzueto A, et al. Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group. N Engl J Med. 1996;334:1417-21.

Dellinger RP et al. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med. 1998;26:15-23.

Zapol WM, et al. Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. JAMA 1979;242:2193-6.

Derdak S, et al. High-frequency oscillatory ventilation for adult respiratory distress syndrome: a randomized controlled trial. Am J Respir Crit Care Med. 2002;166:801-8.

Bernard GR, et al. High-dose steroids in patients with the adult respiratory distress syndrome. N Engl J Med. 1987;317:1565-70.

Steinberg KP, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006:354:1671-84.

Ware LB, MA Matthay. The acute respiratory distress syndrome. N Engl J Med 2000;342:1334-49.

Meduri GU et al. Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA 1998;280:159-65.

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006;354:1671-84.

ARDS Network

NIH-funded consortium of 10 centers, 24 hospitals, 75 intensive care units

Goal to design large RCTs to determine effective treatments

Key ARDSnet studies: Ventilator volumes Steroids PEEP Volume management/PA catheter

Steroids in ARDS

ARDSnet Tidal Volume Study

ARDSnet Fluid Management

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Nursing Management:

1. Administer medications as prescribed. Morphine,

diuretics, cardiac glycosides,vasodilators,aminophylline.

2. Give oxygen in high concentration.

3. Position the pt. upright to decrease venous return and

allow maximum lung expansion.

4. Monitor vital signs and electrolytes balance.