-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)
3
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)
4
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 BOOP or COP
heart failure Hypersensitivity pneumonitis
Diffuse alveolar hemorrhage Leukemic infiltrate
Acute eosinophilic Drug-induced pulmonary
pneumonia edema and pneumonitis
Lupus pneumonitis Acute major pulmonary
Acute interstitial pneumonia embolus
Pulmonary alveolar Sarcoidosis
proteinosis 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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