ACUTE RESPIRATORY
DISTRESS SYNDROME
DEFINITION
Clinical syndrome characterised by severe dyspnea (difficulty breathing) of
rapid onset, hypoxemia (low blood oxygen levels) and diffuse pulmonary
infiltrates, leading to respiratory failure.
Caused by various underlying medical and surgical disorders. The lung
injury that leads to ARDS may be direct (toxic inhalation, pneumonia) or
indirect (sepsis, trauma).
ARDS severity is categorised into three stages based on the degree of
hypoxemia:
Mild, Moderate and Severe
Prior to the COVID-19 pandemic, the annual incidence of ARDS was
estimated to be as high as 60 cases per 100,000 population.
ETIOLOGY
COMMON CAUSES:
Pneumonia and Sepsis: majority of ARDS cases (40-60%)
Aspiration of Gastric Contents
Trauma: Particularly pulmonary contusion, multiple bone fractures and
chest wall trauma/flail chest
Multiple Transfusions and Drug Overdose: less frequent
RISK FACTORS
Patients with more than one underlying medical or surgical condition – risk
for developing ARDS
Older Age, Chronic Alcohol Abuse, pancreatitis, pneumonia, sepsis,
pandemic COVID pneumonia (40-60%)
Patients with severe critical illness, APACHE II score (≥16) have a
significantly increased risk of developing ARDS
CLINICAL COURSE AND PATHOPHYSIOLOGY
The natural history of ARDS is three phases – exudative, proliferative and
fibrotic
EXUDATIVE PHASE
0 – 7 days
Alveolar capillary endothelial cells and type I pneumocytes – injured
Protein accumulates in the interstitial and alveolar spaces. Pro-inflammatory
cytokines (IL1, IL8, TNF-α) and lipid mediators (leukotriene B4) are increased
in this acute phase, leading to recruitment of leukocytes
Dysfunctional pulmonary surfactant to form hyaline membrane whorls
Pulmonary vascular injury
Neutrophils adhere to injured capillary
endothelium and transmigrating through
the interstitium into the air space, which is
filled with protein-rich edema fluid
Alveolar edema predominantly involves
dependent portions of the lung with
diminished aeration
PROLIFERATIVE PHASE
Day 7 to day 14
Many patients recover rapidly (liberated from mechanical ventilation)
Many patients still experience dyspnea, tachypnea and hypoxemia
Initiation of lung repair, the organization of alveolar exudates and a shift
from neutrophil-to-lymphocyte predominant pulmonary infiltrates
Type II pneumocytes proliferate along alveolar basement membranes and
these specialized cells synthesise new pulmonary surfactant and differentiate
into type I pneumocytes
FIBROTIC PHASE
14-21 days
Some enter a fibrotic phase that require long term support on mechanical ventilators
and supplemental oxygen
Alveolar edema and inflammatory exudates of earlier phases convert to extensive
alveolar duct and interstitial fibrosis, further leads to emphysema – like changes with
large bullae
Formation of excessive fibrous connective tissue in tunica intima (innermost layer) of
arteries in the microcirculation – progressive vascular occlusion and pulmonary
hypertension
Physiologic consequences – increased risk of pneumothorax, reductions in lung
compliance and increased pulmonary dead space
Patients experience substantial burden of excess morbidity and increased risk of
mortality
TREATMENT
Close attention required for:
(1) Recognition, treatment of underlying medical and surgical Disorders
(2) Minimization of unnecessary procedures and complications
(3) Bundled care approaches for ICU patients
(4) Recognition of nosocomial infections
(5) Adequate nutrition via enteral route when feasible
Management of mechanical ventilation:
Patients fatigued by increased work of breathing and hypoxemia
Minimizing ventilator-induced lung injury:
1. Volutrauma-repeated alveolar overdistension from excess tidal volume
2. Atelectrauma-From recurrent alveolar collapse
ARDS – heterogeneous disorder (affects dependent portions)
• Compliance differs in affected vs. Normal lung areas
• Attempt to fully inflate
Two ventilation strategies in ARDS patients:
1. Low tidal volume ventilation:
• Tidal volume = 6 ml/kg of predicted body weight
• Plateau pressure ≤ 30 cm H2O
2. Conventional tidal volume ventilation:
• Tidal volume = 12 ml/kg of predicted body weight
• Plateau pressure ≤ 50 cm H2O
Findings:
1. Mortality rate reduced from 40% to 31%
2. Use of low tidal volume and lower PEEP
Minimizing Atelectrauma by Prevention of Alveolar Collapse:
Optimal PEEP to minimize FiO2 (inspired O2 Percentage), provide adequate PaO2 (arterial
partial pressure of O2) without causing alveolar overdistention
Strategies for PEEP Adjustment:
1. Table of PEEP-FiO2 combinations
2. Static Pressure-Volume Curve
3. Esophageal Pressure Measurement
Best PEEP measurement – At bedside to determine the optimal settings that best promote
alveolar recruitment, minimize alveolar overdistention and hemodynamic instability
PRONE POSITION
Mechanical ventilation in prone position improved arterial oxygenation
without affecting mortality
2013 landmark trial demonstrated significant decrease in 28-
day mortality (32.8% to 16%) for severe ARDS (Pao2/Fio2 < 150mm Hg)
More centres are using prone positioning for severe ARDS
Requires critical care team that is experienced in “proning” as
repositioning critically ill patients can be hazardous
OTHER STRATEGIES IN MECHANICAL VENTILATION
Recruitment Maneuvers increase PEEP transiently “recruit” atelectatic lung and
improve oxygenation
No established mortality benefit from recruitment maneuvers
Mortality may increase when combined with higher baseline PEEP settings
Airway Pressure Release Ventilation (APRV) and High Frequency Oscillatory
Ventilation (HFOV) – no benefits over standard ventilation in ARDS management
Lung replacement therapy with extracorporeal membrane oxygenation (ECMO)
was shown to improve mortality for patients with ARDS
ECMO – useful as rescue therapy in select adult patients with severe ARDS
No superiority of initial ECMO use over ECMO as a rescue strategy after failure
of standard ARDS management
FLUID MANAGEMENT
➢ Increased Pulmonary Vascular Permeability in ARDS – interstitial and alveolar
edema
➢ Maintaining Low Left Atrial Filling Pressure
Minimizes Pulmonary edema and prevents further declines in arterial oxygenation and
lung compliance
Improves Pulmonary Mechanics: Enhances lung function
Shortens ICU Stay and the duration of mechanical ventilation
➢ Fluid Restriction and Diuretics
Aggressive Attempts: Reduce left atrial filling pressures.
Limitations: limited by the risk of hypotension and hypoperfusion of critical organs like
kidneys
RECOMMENDATIONS OF THE NEUROMUSCULAR BLOCKADE
Evidence based recommendation for early neuromuscular blockade is
categorized as (cisatracurum besylate), recommendation is not for routine
use
Selective use of neuromuscular blockade in severe ARDS when other
strategies (such as sedation alone) are insufficient to achieve appropriate
patient-ventilator synchrony
Clinical judgment and patient-specific factors should guide the decision to
use neuromuscular blockade
These recommendations apply to non-COVID-19-ARDS
PROGNOSIS
Mortality Rates by ARDS Severity
Mild ARDS: 34.9% ; Moderate ARDS: 40.3% ; Severe ARDS: 46.1%
Non pulmonary causes account for >80% of ARDS deaths
Non pulmonary causes with sepsis and non pulmonary organ failure
Risk Factors for Mortality:
>75 years: ~60% mortality risk
<45 years: ~20% mortality risk.
>60 years with ARDS and sepsis: threefold higher mortality risk.
Non-pulmonary Risk Factors: Preexisting organ dysfunction (chronic liver disease,
chronic alcohol abuse, chronic immunosuppression)
IMPACT OF LUNG INJURY CAUSE ON MORTALITY
Direct lung injury (pneumonia, pulmonary contusion and aspiration) are nearly twice
as likely to die as with indirect causes
Surgical and trauma patients without direct lung injury generally have higher
survival rates among ARDS patients
Predictors of Mortality:
Severity of ARDS correlates with increased mortality
Parameters like level of PEEP (≥10 cm H₂O), low respiratory system compliance (≤40
mL/cm H₂O), extensive alveolar infiltrates and high corrected expired volume per
minute (≥10 L/min)
FUNCTIONAL RECOVERY IN ARDS SURVIVORS
Prolonged Respiratory Failure and Mechanical Ventilation:
• ARDS patients often experience prolonged respiratory failure
• Dependence on mechanical ventilation for survival is common
Lung Recovery:
• Majority regain nearly normal lung function
• Maximal lung function – within 6 months
• One year post-extubation, over one-third of survivors – normal spirometry,
diffusion capacity
• Remaining patients show only mild pulmonary function abnormalities
FACTORS INFLUENCING RECOVERY
Poor recovery is associated with:
I. Low static respiratory compliance
II. High levels of required PEEP
III. Longer durations of mechanical ventilation
IV. High lung injury scores
Long-term Physical Function:
• 5 years post-ARDS – exercise limitations and decreased physical quality of life
• Occur despite normal or nearly normal pulmonary function
PSYCHOLOGICAL IMPACT
Significant psychological problems can affect ARDS survivors
and their caregivers
High rates of depression and post traumatic stress disorder
(PTSD) are common
THANK YOU
Reference :21st edition
Harrison’s principles of internal medicine
