Acute Respiratory Distress

Syndrome
Dr Renu Sinha
Additional Professor
Dept. Of Anaesthesiology, Critical Care & pain Medicine
AIIMS
 ARDS, or Acute Respiratory Distress Syndrome
• Inflammatory lung condition involving both lungs
• Inflammation leads to injury of lung tissue and
leakage of blood and plasma into the airspaces
resulting in low oxygen levels in the blood.
• Mechanical ventilation is required both to deliver
higher concentrations of oxygen and to provide
ventilation to remove carbon dioxide from the body.
• Inflammation in the lung may lead to inflammation
elsewhere causing shock and injury or dysfunction in
the kidneys, heart, and muscles.
 First described 1967 by Ashbaugh and colleagues
 Synonyms
– Shock lung
– Traumatic wet lung
• Incidence:
– Acute lung injury (ALI): 17.9-78.9 cases per 100,000 person-years
– Acute respiratory distress syndrome (ARDS): 13.5-58.7 cases per 100,000
person-years
Bernard et al. AJRCCM 1994; 149:818
Rice et al. Chest 2007: 132: 410
 June 20, 2012, Vol 307, No. 23

-Three categories depending on severity:

I. Mild,
II. Moderate
III. Severe

-according to timing, chest imaging, origin of edema,

oxygenation
et al. JAMA 2012; 307:2530
et al. JAMA 2012; 307:2530
Pneumonia
35%

ARDS network N Engl J Med 2000; 342:1301

Other causes
 Differential Diagnosis
• Left ventricular failure/volume overload
• Mitral stenosis
• Pulmonary veno-occlusive disease
• Lymphangitic spread of malignancy
• Interstitial and/or airway disease
– Hypersensitivity pneumonia
– Acute eosinophilic pneumonia
– Acute interstitial pneumonitis
 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
Pathophysiology

1. Direct or indirect
injury to the alveolus
causes alveolar
macrophages to
release pro-
inflammatory cytokines

Ware et al. NEJM 2000; 342:1334

Pathophysiology

2. Cytokines attract
neutrophils into the
alveolus and
interstitium, where
they damage the
alveolar-capillary
membrane (ACM).

Ware et al. NEJM 2000; 342:1334

Pathophysiology

3. ACM integrity is
lost, interstitial and
alveolus fills with
proteinaceous fluid,
surfactant can no
longer support
alveolus

Ware et al. NEJM 2000; 342:1334

 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
 Pathological findings
• Diffuse alveolar damage
• Neutrophils, macrophages, erythrocytes
• Hyaline membranes
• Protein-rich edema in alveolar spaces
 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: 10-13%
• CT: diffuse interstitial opacities & 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
 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
 Pathophysiology

• Consequences of lung injury include:

– Impaired gas exchange
– Decreased compliance
– Increased pulmonary arterial pressure
 Impaired Gas Exchange
• V/Q mismatch
– Related to filling of alveoli
– Shunting causes hypoxemia
• Increased dead space
– Related to capillary dead space and V/Q mismatch
– Impairs carbon dioxide elimination
– Results in high minute ventilation
 Decreased Compliance
• Hallmark of ARDS
• Consequence of the stiffness of poorly or nonaerated
lung
• Fluid filled lung becomes stiff/boggy
• Requires increased pressure to deliver Vt
Increased Pulmonary Arterial Pressure
• Occurs in up to 25% of ARDS patients
• Results from hypoxic vasoconstriction
• Positive airway pressure causing vascular
compression
• Can result in right ventricular failure
Evidence based management of ARDS
• Goal:
– Treat the underlying cause: antibiotics
– a protective strategy of lung ventilation
• Low tidal volume ventilation
• Use PEEP
• Monitor Airway pressures
• Conservative fluid management
• Reduce potential complications
• Mortality:
– Respiratory failure
– Secondary infections, other organ failures, or the
complications of prolonged hospitalisation.
 Oxygenation
• SpO2: 88%
 Low Tidal Volume Ventilation
• Larger tidal volumes (12ml/kg) vs Vt of 6ml/kg of ideal body
weight:
• Decreased mortality
• Increased number of ventilator free days
• Decreased extrapulmonary organ failure

• ↓Mortality in the low TV gr despite these patients having:

• Worse oxygenation
• Increased pCO2 (permissive hypercapnia)
• Lower pH
ARDSnet. NEJM 2000; 342: 1301
 Low Tidal Volume Ventilation
ARDS affects the lung in a
heterogeneous fashion
• Normal alveoli
• Injured alveoli can potentially
participate in gas exchange,
susceptible to damage from
opening and closing
• Damaged alveoli filled with fluid,
do not participate in gas
exchange
 Low Tidal Volume Ventilation
• Protective measure to avoid over distention of
normal alveoli
• Uses low (normal) tidal volumes
• Minimizes airway pressures
• Uses Positive end-expiratory pressure (PEEP)
 PEEP: high vs low

• Higher levels of PEEP/FiO2 does not improve

outcomes
– may negatively impact outcomes:
• Causing increased airway pressure
• Increase dead space
• Decreased venous return
• Barotrauma
 PEEP
• Positive End Expiratory Pressure
• Every ARDS patient needs it
• Goal is to maximize alveolar recruitment and
prevent cycles of recruitment/derecruitment
 Recruitment
- 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

Meade, M et al, JAMA. 2008; 299(6):637-645

-PEEP: to increase alveolar recruitment while limiting
hyperinflation
-Two groups: moderate PEEP (5-9cm H2O) vs. level of
PEEP to reach a plateau pressure of 28-30cm H2O
-It didn’t significantly reduce mortality;
however, it did improve lung function
decreased days on vent and organ failure duration
Mercatt, M, et al. JAMA. 2008; 299(6):646-655.
 PEEP
• As FiO2 increases, PEEP should also increase

ARDSnet. NEJM 2004; 351, 327

 Airway Pressures in ARDS
• Plateau pressure is most predictive of lung injury
• Goal plateau pressure < 30, the lower the better
• Decreases alveolar over-distention & 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
• Ascites
Terragni et al. Am J Resp Crit Care Med. 2007; 175(2):160
 Permissible Plateau Pressures
• Assess cause of high Plateau Pressures
• Always represents some pathology:
– Stiff, non-compliant lung: ARDS, heart failure
– Pneumothorax
– Auto-peeping
– Mucus Plug
– Right main stem intubation
– Compartment syndrome
– Chest wall fat / Obesity
 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
• ECMO
– RCT of 40 adults showed no benefit

JAMA 1979;242:2193-6. Am J Respir Crit Care Med. 2002;166:801-8

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

-Randomized control trial, stopped with 548 of 1200
patients
-Found early initiation of HFOV does not reduce and
may increase hospital mortality

Ferguson, N, et al, NEJM 2013; 368: 795-805.

-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

Young, D, et al,NEJM. 2013; 368:806-813

 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

JAMA 1998;280:159-65, N Engl J Med 2006;354:1671-84

~No benefit of corticosteroids on survival

~When initiated 2 weeks after onset of ARDS,

associated with significant increase in mortality rate
compared to placebo group

N Engl J Med. 2006; 354:1671

 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

N Engl J Med. 1996;334:1417-21. Crit Care Med. 1998;26:15-23.

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

N Engl J Med 2006; 354: 2213

 Results
• Using 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

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

N Engl J Med. 2006;354:2564

Fluid Management
• Increased 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
diuresis
• CVP used as guide, goal <4
• Shortens time on vent and ICU
length of stay (13 days vs 11
days)

ARDSnet. NEJM 2006; 354: 2564

 Weaning
• Daily CPAP breathing trial
– FiO2 <.40 and PEEP <8
– Patient has acceptable spontaneous breathing efforts
– No vasopressor requirements, use judgement

• Pressure support weaning

– PEEP 5, PS at 5cm H2O if RR <25
– If not tolerated, ↑RR, ↓Vt – return to A/C

• Unassisted breathing
– T-piece, trach collar
– Assess for 30minutes-2 hours
 Weaning
• Tolerating Breathing Trial?
– SpO2 ≥90
– Spontaneous Vt ≥4ml/kg PBW
– RR ≤35
– pH ≥7.3
– Pass Spontaneous Awakening Trial (SAT)
– No Respiratory Distress ( 2 or more)
• HR > 120% baseline
• Accessory muscle use
• Abdominal Paradox
• Diaphoresis
• Marked Dyspnea
– If tolerated, consider extubation
 Putting it all together
1) Calculate patient’s predicted body weight:
• Men (kg) = 50 + 2.3(height in inches – 60)
• Females (kg) = 45.5 + 2.3(height in inches – 60)
2) Set Vt = predicted body weight x 6cc
3) Set initial rate to approximate baseline minute ventilation
(RR x Vt)
4) Set FiO2 and PEEP to obtain SaO2 goal of >=88%
5) Diuresis after resolution of shock
6) Refer to ARDSnet guidelines
Common Problems
 Refractory Hypoxia
• Mechanical Trouble (tubing, ventilator, ptx, plugging)
• Neuromuscular blockade
• Recruitment maneuvers – positioning, “good lung down”
optimizes V/Q mismatch
• Increase PEEP
• Inhaled 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
-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 ventilator without increase
in muscle weakness
Papazian, L, et al. NEJM 2010; 363: 1107-1116.
 Supportive Therapies
• Treat underlying infection
• DVT prophylaxis / stress ulcer prevention
• HOB 30°
• Hand washing
• Use full barriers with chlorhexidine
• Sedation / analgesia
• Feeding protocol
• Avoid contrast nephropathy
• Pressure ulcer prevention, turning Q2h
• Avoid steroid use
 Treatment
• Tt underlying disease that caused ARDS: early and effective
antibiotics for pneumonia or sepsis.
• Small breaths and low pressures from the ventilator (so called
low tidal volume and pressure ventialtion).
• conservative use of intravenous fluids combined with
removal of excess fluids with diuetics lessens the need for
mechanical ventilation.
• Death: 40 percent% cases of severe form (multiple organ
failure).
 Conclusion
• Recovery dependent on health prior to onset

• Within 6 months, will have reached max recovery

• At 1 year post-extubation, >1/3 have normal spirometry

• Significant burden of emotional and depressive symptoms

with increased depression and PTSD in ARDS survivors
• Survivor clinic catches symptoms early by screening patients

• New treatment modalities, lung protective ventilation

Levy BD, & Choi AM, Harrison’s Principles of Internal Medicine, 2012
 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