Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome (ARDS) 

ARDS (Acute Respiratory Distress Syndrome) is a diffuse inflammatory lung injury characterized by:

• Increased alveolar-capillary permeability
• Non-cardiogenic pulmonary edema
• Severe hypoxemia
• Reduced lung compliance

Leading to acute respiratory failure requiring oxygen or ventilatory support.

Berlin Definition (2012) — Diagnostic Criteria

Severity Classification

New Global Definition of ARDS (2023)

Developed by international critical care experts led by Luciano Gattinoni and the European Society of Intensive Care Medicine task force.

Why Was a New Definition Needed?

Limitations of the Berlin Definition:

1. Excluded patients on HFNC/NIV
2. Required PEEP ≥5 cmH₂O
3. Required arterial blood gas (PaO₂)
4. Required bilateral infiltrates on chest imaging
5. Poor applicability in low-resource settings
6. Did not recognize “early ARDS” on noninvasive support

If arterial blood gas unavailable:

SpO₂/FiO₂ (S/F ratio) may be used(when patient is on HFNC or or NIV/CPAP with at least 5 cm H 2 O PEEP and if Sp O 2 ≤ 97%)

• Only PaO₂/FiO₂ 201–300 mmHg with PEEP/CPAP ≥5 cm H₂O(Mild ARDS) Can be diagnosed on NIV/CPAP.
• For moderate -severe ARDS intubation Required.

Epidemiology

• Incidence: ~10% of ICU admissions
• ~23% of mechanically ventilated patients

Etiology

Pathophysiology

ARDS progresses through three overlapping phases.

Exudative Phase (Day 1–7)

Histological Hallmark-Diffuse Alveolar Damage (DAD)

• Hyaline membranes
• Alveolar edema
• Neutrophilic infiltration

Proliferative Phase (Day 7–21)

Repair phase involving:

• Type II pneumocyte proliferation
• Fibroblast activation
• Partial resolution of edema

Fibrotic Phase (Late ARDS)

Occurs in ~30–40% of patients.

Features:

• Interstitial fibrosis
• Pulmonary hypertension
• Severe reduction in lung compliance

Clinical Features

Symptoms

• Dyspnea
• Tachypnea
• Hypoxemia

Signs

Investigations

Do All possible investigations relevant to history  to find out cause of ARDS,Finding out cause has paramount importance!!

• CBC
• Blood cultures.
• Nasopharyngeal PCR for influenza, COVID-19 etc
• Sputum culture & staining 
• Urine Culture, Urine Antigen
• Procalcitonin, C-reactive protein.
• If suspected Fungal Assessment 

Arterial Blood Gas

Early:Respiratory alkalosis

Late:Severe hypoxemia—Possible respiratory acidosis

 Chest X-ray

• Bilateral diffuse infiltrates
• “White lung”

 CT Scan(Gold standard imaging)

Lung Ultrasound

• Cardiogenic pulmonary edema: B-lines distributed throughout the lung, pleural effusions, pleural line is normal (thin).
• ARDS: patchy areas with B-lines intermixed with areas with A-lines (normal lung),pleural line may appear thick/ragged.

 Hemodynamic Assessment

To exclude cardiogenic edema.Methods:

• Echocardiography
• Pulmonary artery catheter (rarely used)

Differential Diagnosis

Management

• Lung Protective Ventilation 
• Established by the ARDSNet ARMA Trial.
• No ventilator mode has been proven superior.The priority is lung-protective ventilation, not the specific mode.
• Volume Assist-Control (VC-CMV / VC-AC)—Most commonly used mode in ARDS trials

Predicted Body Weight Formula

• Male:PBW = 50 + 0.91(height cm − 152.4)
• Female:PBW = 45.5 + 0.91(height − 152.4)

What about Peak Pressure?-Although not guideline-mandated:

• Ppeak <35–40 cmH₂O is commonly accepted.
• If Ppeak >40–45 cmH₂O, investigate:Secretions—Bronchospasm—ETT obstruction—Pneumothorax—Excessive tidal volume—Excessive PEEP

The key question is always:What is the plateau pressure?

Peak airway pressure has no specific guideline limit because it is heavily influenced by airway resistance and does not reliably reflect alveolar overdistension.

PEEP Strategy

Purpose:Prevent alveolar collapse —Reduce atelectrauma—Reduce FiO₂ requirement—Achieve lung recruitment safely—Improve oxygenation—Reduce shunt fraction

Evidence for High vs Low PEEP

Major trials:ALVEOLI,LOVS,EXPRESS

Findings:

• No major mortality benefit overall
• Moderate-severe ARDS may benefit from higher PEEP
• Better oxygenation and fewer rescue therapies

Methods to Set Optimal PEEP

 Optimal PEEP -The PEEP at which Driving pressure is lowest or Changes minimally despite increasing PEEP.Best physiologic marker of optimal PEEP = Highest compliance (lowest elastance)

1. ARDSNet PEEP-FiO₂ Table

Disadvantages:Can not be applicable to focal ARDS(this can be check by chest X-ray pathology is focal or not)

2. Compliance Method

• Increase PEEP gradually and identify best compliance.
• Compliance improves with recruitment but worsens with overdistension.
• Optimal PEEP:Highest static compliance
• Static compliance formula: Cstat =(Pplat −PEEP)/VT
• Higher compliance suggests better recruitment without excessive overdistension.

3. Driving Pressure Guided PEEP

• Driving pressure:ΔP=Pplat −PEEP
• Goal:Keep driving pressure < 15 cm H₂O
• Lower driving pressure associated with improved survival.
• If increasing PEEP:

• Decreases driving pressure → beneficial recruitment
• Increases driving pressure → overdistension likely

Example:Before recruitment

• PEEP = 8 and Pplat = 24 and Driving pressure = 16

After increasing PEEP:PEEP = 12,Pplat = 25 but Driving pressure = 13(Driving pressure falls → recruitment occurred → beneficial.)

4. Pressure-Volume Curve Method

• Identify:Lower inflection point (LIP) and Upper inflection point
• Set PEEP: Slightly above LIP
• Limitations: In ARDS, lung recruitment (opening of collapsed alveoli) does not occur only at the lower inflection point of the pressure-volume curve. Instead, alveoli may continue to open throughout the entire curve, even at pressures above the upper inflection point.At the same time, some already-open alveoli may become overdistended (overstretched), leading to hyperinflation, which is commonly seen on CT scans.

5. Esophageal Pressure Guided PEEP

• Uses esophageal balloon to estimate pleural pressure.
• Transpulmonary pressure:PL =Paw −Ppl

Useful in:

• Obesity
• Elevated abdominal pressure
• Severe ARDS

Goal:End-expiratory transpulmonary pressure around 0–5 cm H₂O

Disadvantage-Unfortunately, a larger follow-up multicenter

randomized trial of esophageal pressure–directed PEEP for patients with moderate-to-severe ARDS failed to demonstrate a difference of mortality or ventilator free days compared with conventional PEEP titration strategies.

Other Ventilation Modes

High-Frequency Oscillatory Ventilation(HFOV)

Trials:OSCILLATE,OSCAR Results:No benefit,Possible harm

Airway Pressure Release Ventilation (APRV)

it is an alternative invasive mechanical-ventilation strategy for ARDS. Its theoretical advantage is maintaining a relatively high continuous airway pressure for most of the respiratory cycle, with brief pressure releases to allow CO₂ removal, while permitting spontaneous breathing.—No proven mortality benefit but improvements in ventilator-free days, extubation, and hemodynamics

Best candidates for APRV

• ARDS with substantial dependent/posterior atelectasis or recruitable lung
  • APRV’s prolonged high-pressure phase may help maintain recruitment.
• Patients who cannot undergo prone positioning
  • APRV may be considered when proning is contraindicated or not feasible.
• Morbidly obese patients with significant atelectasis
  • Higher mean airway pressure may be useful because obesity increases pleural pressure and promotes dependent lung collapse.
  • However, obesity alone is not an indication for APRV.
• Patients with difficult-to-control respiratory drive
  • APRV may be useful when maintaining spontaneous breathing is desirable and deep sedation/neuromuscular blockade is problematic.
  • However, excessive spontaneous effort can increase transpulmonary pressure and potentially contribute to P-SILI.

Permissive Hypercapnia

• Allowed in ARDS ventilation.
• Reason:Low tidal volume leads to CO₂ retention.
• Acceptable:pH ≥ 7.20
• IV bicarbonate can be used to treat low pH
• Contraindications of Permissive Hypercapnia :

• Raised ICP
• Severe pulmonary hypertension
• Pregnancy(relative contraindication)

Prone Positioning

• Supported by the PROSEVA Trial
• Consider after >12 hours of ventilator optimization to rule out patients with pseudoARDS(Atelactasis)
• Indication:PaO₂/FiO₂ <150
• Protocol:≥16 hours/day

Proning can be stopped if the patient is able to maintain a PaO2/FiO2 ratio >150 mm  with an FiO2 ≤0.6, at least four hours after supination.

Neuromuscular Blockade

Used early in severe ARDS.during the first 48 hours 

Evidence:ACURASYS Trial

Drug:Cisatracurium infusion (48 hrs)

Benefits:

• Reduced ventilator asynchrony
• Improved oxygenation

For ventilator Asynchrony Use Propofol/ketamine/fentanyl.

Corticosteroids

• Consider if PaO2/FiO2 <200 mm hg & no contraindication(active fungal or mycobacterial infection).
• Benefit when <7 days after admission
• DEXA-ARDS trial utilized 20 mg dexamethasone for 5 days, followed by 10 mg dexamethasone for 5 days (or discontinuation before 10 days, if the patient was extubated). 
• SCCM/ESICM guidelines recommend methylprednisolone 1 mg/kg/day, with a gradual taper over 14 days.
• Benefits:Reduced ventilation duration,Possible mortality reduction

Fluid Strategy

• Trial: FACTT Trial
• Approach:Restrict fluid strategy after initial stabilization,can Use diuretics
• Benefits:Shorter ventilation duration

Assess Fluid Responsiveness Before Giving Fluids

Static measures such as CVP are poor predictors.

Prefer dynamic indices:

Only give fluid if responsive.

Type of Fluids

Preferred Balanced Crystalloids

• Ringer Lactate
• Plasma-Lyte

Advantages:

• Less hyperchloremia
• Less renal vasoconstriction

ECMO

Used in refractory hypoxemia.

Evidence: EOLIA Trial

Indications:

Type:VV ECMO

Recruitment Maneuvers

Transient increase in airway pressure.

Examples:

• Sustained inflation(PEEP 35–45 cmH₂O and Sustained inflation 30–60 sec)
• Staircase recruitment

Evidence: uncertain benefit(RMs can neither be recommended nor discouraged for all patients, but can be considered on an individualized basis for patients with life-threatening hypoxemia.)

Stress Index

Used during volume-controlled ventilation.

Evaluates the shape of the inspiratory pressure-time curve.

Interpretation

Mechanical Power

Definition-Total energy transferred from ventilator to lung per minute.Represents cumulative risk of VILI.

Components

Mechanical power integrates:

• Tidal volume
• Respiratory rate
• Driving pressure
• PEEP
• Flow
• Airway pressure

into a single variable.

Simplified Formula (Volume Control)

MP=0.098×RR×VT×(Ppeak −0.5×ΔP)

Where:

• MP = Mechanical Power (J/min)
• RR = Respiratory Rate
• VT = Tidal Volume (L)
• ΔP = Driving Pressure

Interpretation

Why Important?

A patient may have: Safe VT or Safe Pplat but High RRo r High PEEP leading to excessive energy delivery.

Mechanical power captures the combined effect of all ventilator settings.

HFNC and BiPAP in ARDS

Mild–moderate hypoxemic ARDS

→ HFNC 40–60 L/min(FLORALI trial)
→ Adjust FiO₂ to maintain appropriate SpO₂
→ Check ROX index
→ Consider awake prone positioning in appropriate patients

If respiratory distress remains significant despite HFNC

→ Consider NIV/BiPAP(RECOVERY-RS trial)in a closely monitored ICU setting in a cooperative patient without contraindications.check HACOR score.

• Awake proning can be used with high flow nasal cannula (HFNC), CPAP, or BiPAP.

Severe ARDS / rapidly worsening patient

→ Do not persist with HFNC/BiPAP simply to avoid intubation.
→ Proceed to endotracheal intubation and lung-protective mechanical ventilation when there is failure of noninvasive support.

Adjunctive Therapies

Complications

• Secondary infections
• ICU myopathy
• Delirium
• Fibrosis

ARDS Mortality Causes

Most deaths due to:Sepsis,Multi-organ failure NOT hypoxemia alone.

Emerging Concepts

ARDS Phenotypes

Two biological phenotypes identified:

Precision Medicine

Future therapy may involve:

• Biomarker-guided treatment
• Personalized ventilation

Trials in ARDS 

Reference

1. Irwin & Rippe’s Intensive Care Medicine (9th Edition)

Lilly CM, Kelly WF, Irwin RS, Boyle WA III, editors. Irwin and Rippe’s Intensive Care Medicine. 9th ed. Philadelphia: Wolters Kluwer; 2023. 

2. The Washington Manual of Critical Care (4th Edition)

Kollef MH, Despotovic V, Kraft BD, McDonald RK, Nguyen N, editors. The Washington Manual of Critical Care. 4th ed. Philadelphia: Wolters Kluwer; 2024. 

3.Ohs manual of critical Care