-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
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)

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 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
ARDS
Definitions

 Acute Lung Injury

 150 – 200 mmHg < PaO2/FIO2 < 250 – 300 mmHg

 ARDS
 PaO2/FIO2 < 150 – 200 mmHg
ARDS
Epidemiology
 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
ARDS
Pathophysiology

 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

Alveolar Filling

Expansion of
interstitium with
macrophages and
inflammation
Hyaline
Membranes
ARDS
Acute Exudative Phase
ARDS
Proliferative Phase
 Type II pneumocyte
 proliferate
 differentiate into Type I cells
 reline alveolar walls

 Fibroblast proliferation
 interstitial/alveolar fibrosis
ARDS
Proliferative Phase
ARDS
Fibrotic Phase
 Characterized by:
 local fibrosis
 vascular obliteration

 Repair process:
 resolution vs fibrosis
Fibrosing alveolitis
ARDS
Pathophysiology
 Interstitial/alveolar edema

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

 Increased airway resistance

ARDS
Pathophysiology
 High ventilatory demands
 high metabolic state
 increased VD/VT
 decreased lung compliance

 Pulmonary HTN
 neurohumoral factors, hypoxia, edema
 ARDS
Clinical 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)
 ARDS
Diagnosis
 Resistant hypoxemia
 PaO2/FIO2 < 150 – 200 mmHg

 CXR
 diffuse, bilateral infiltrates

 No evidence of LV failure
 (PAWP < 18 mmHg)
ARDS
Clinical Features: CXR
ARDS
Clinical Features: CXR
Objective #6:
Describe conditions resulting
from pulmonary alterations.
 ARDS
Differential 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 26-5
Page 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
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.

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