Diffuse inflammatory lung injury causing refractory hypoxemia. The cornerstone of management is lung-protective ventilation -low tidal volumes, prone positioning, and avoiding further barotrauma.
๐ Overview
Definition
ARDS is acute, diffuse inflammatory lung injury causing increased alveolar-capillary permeability, pulmonary edema, and severe hypoxemia not explained by cardiac failure. Definition uses the Berlin Definition of ARDS (2012).
Bilateral opacities on CXR/CT (not explained by effusion/collapse)
Origin of edema
Not fully explained by heart failure or fluid overload
Oxygenation (P/F)
Used to grade severity (see below), with PEEP โฅ 5 cmHโO
ARDS Severity Classification
Severity
PaOโ/FiOโ (P/F Ratio)
Mortality
Mild
200โ300 mmHg
~27%
Moderate
100โ200 mmHg
~32%
Severe
< 100 mmHg
~45%
All measured with PEEP โฅ 5 cmHโO. Most common patient profile: critically ill adult with sepsis or pneumonia, often requiring mechanical ventilation.
Most Common Causes of ARDS
Cause
Approx %
Sepsis
~40โ50%
Pneumonia
~30โ40%
Aspiration
~10โ15%
Trauma / contusion
~5โ10%
Pancreatitis
~3โ5%
Massive transfusion (TRALI)
~2โ5%
Inhalational injury
< 2%
Direct (Pulmonary) Causes
Pneumonia (bacterial, viral, fungal)
Aspiration of gastric contents
Pulmonary contusion, inhalation injury
Near-drowning
Indirect (Extrapulmonary) Causes
Sepsis (most common overall cause)
Pancreatitis
Massive transfusion / TRALI
Burns, trauma, DIC
Drug overdose (heroin, aspirin, cocaine)
Stepwise Pathophysiology
ARDS occurs through three overlapping phases. The key physiologic problem is shunt hypoxemia -blood passes through non-ventilated alveoli, so oxygen therapy alone often fails.
1. Exudative Phase (First 7 Days)
Initial inflammatory injury.
Step
Pathology
Lung insult
Infection, aspiration, trauma
Macrophage activation
Cytokine release (TNF-ฮฑ, IL-1, IL-6)
Neutrophil recruitment
Endothelial damage
โ Capillary permeability
Protein-rich edema floods alveoli
Alveolar flooding
Impaired gas exchange, โ compliance, shunt physiology
Results: โ compliance, severe hypoxemia, shunt physiology. Lungs become stiff, small (baby lung concept -only ~30% of lung is recruitable).
2. Proliferative Phase (7โ21 Days)
Repair begins.
Process
Effect
Type II pneumocyte proliferation
Surfactant restoration
Fibroblast activation
Collagen deposition
Alveolar repair
Partial recovery
3. Fibrotic Phase (โฅ 21 Days)
Occurs in severe/prolonged cases. Pulmonary fibrosis โ stiff lungs โ reduced compliance โ prolonged ventilation. Not all patients progress to this phase.
Preventing ventilator-induced lung injury is critical
๐งช Workup & Diagnosis
Diagnostic Workup
Test
Purpose
ABG
Calculate P/F ratio (PaOโ รท FiOโ). P/F < 300 = ARDS by Berlin criteria. Most important diagnostic step.
CXR
Bilateral opacities not explained by effusion or collapse (Berlin criterion)
Echo (bedside)
Rule out cardiogenic pulmonary edema (PCWP > 18 argues against ARDS). Fastest way to exclude cardiac cause.
BNP / NT-proBNP
Further differentiates cardiogenic vs non-cardiogenic edema
CBC, CMP, coags, lactate, procalcitonin
Assess severity, organ dysfunction, identify sepsis
Blood cultures
Identify infectious cause (sepsis = most common etiology)
CT chest
Dependent consolidation, ground glass opacities. Rules out PE/effusion. Not required for diagnosis.
BAL / sputum cultures
Identify infectious precipitant; obtain after securing airway
ARDS vs Cardiogenic Pulmonary Edema
Feature
ARDS
Cardiogenic
PCWP
Normal (โค 18 mmHg)
High (> 18 mmHg)
BNP
Normal or mildly elevated
High
Cause
Lung injury (sepsis, pneumonia, aspiration)
Heart failure
Edema fluid
Protein-rich exudate
Transudate
CXR pattern
Diffuse bilateral, peripheral
Perihilar "bat wing", Kerley B lines
Response to diuresis
Minimal improvement
Significant improvement
Heart size
Normal
Often enlarged
Key differentiator: ARDS = normal filling pressures, no response to diuretics, diffuse bilateral disease. Cardiogenic = elevated filling pressures, responds to diuresis, often perihilar pattern. Echo is the fastest way to differentiate at the bedside.
๐จ Management
Lung-Protective Ventilation ARDSNet, 2000
This is the only intervention proven to reduce mortality in ARDS.ARDSNet, 2000 showed a 9% absolute mortality reduction with 6 mL/kg vs 12 mL/kg IBW. Low tidal volumes save lives. Do not let anyone override this for "patient comfort" without a very good reason.
Tidal Volume
6 mL/kg of Ideal Body Weight (IBW) -NOT actual body weight. Start at 6โ8 mL/kg, titrate down to 6 mL/kg. SSC, 2021: strong recommendation, high quality evidence. IBW male = 50 + 2.3 ร (height in inches โ 60) IBW female = 45.5 + 2.3 ร (height in inches โ 60)
If Pplat remains > 30 after reducing to 6 mL/kg, reduce further to as low as 4 mL/kg IBW. Increase RR to max 35 to maintain minute ventilation.
Plateau Pressure
Keep Pplat โค 30 cmHโOSSC, 2021 -strong recommendation, moderate quality evidence. If above, reduce TV further (down to 4 mL/kg).
Driving pressure (Pplat โ PEEP) < 12โ15 cmHโO may be advantageous in patients without spontaneous breathing LUNG SAFE, 2016. Higher plateau pressures correlated with mortality; the relationship was strongest above 29 cmHโO.
PEEP Strategy
SSC, 2021: suggests higher PEEP over lower PEEP in moderate-severe ARDS (weak recommendation, moderate evidence). Patient-level meta-analysis PEEP Meta-Analysis, 2010 found mortality benefit with higher PEEP only in P/F โค 200.
ARDSNet Lower PEEP / FiOโ Table:
FiOโ
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
PEEP
5
5โ8
8โ10
10
10โ14
14
14โ18
18โ24
ARDSNet Higher PEEP / FiOโ Table (moderate-severe):
FiOโ
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
PEEP
12
14
16
18
18
20
22
22โ24
Target: SpOโ 88โ95% or PaOโ 55โ80 mmHg.
Permissive Hypercapnia
Acceptable to allow PaCOโ to rise (up to 50โ60 mmHg) to achieve lung-protective goals. pH > 7.20 is generally tolerated. Contraindicated in raised ICP, sickle cell crisis. No single mode (VC vs PC) has demonstrated superiority as long as lung-protective principles are respected.
Prone Positioning (P/F < 150)
Prone โฅ 16 hours/dayPROSEVA, 2013 -reduced 28-day mortality from 32.8% to 16% in severe ARDS. SSC, 2021: strong recommendation, moderate quality evidence for > 12 hours daily.
Improves V/Q matching, recruits dependent lung, reduces compression by mediastinum. Meta-analysis confirmed benefit when applied within 36 hours of intubation for > 12 hrs/day in P/F < 200 Munshi, 2017. Associated with increased pressure sores (RR 1.22) but no increase in accidental extubation.
๐ Updated Practice: Old teaching: prone positioning is a rescue maneuver for refractory hypoxemia. Current practice: prone positioning is now standard of care for moderate-severe ARDS (P/F <150). PROSEVA (2013) showed 16 hours/day of proning reduced 28-day mortality from 33% to 16%, one of the largest mortality benefits ever seen in ARDS. Initiate proning early (within 12-24h), not as a last resort.
Conservative Fluid Strategy
After initial resuscitation, target even to negative fluid balance. FACTT, 2006: conservative fluid strategy reduced vent days by ~2.5 days without worsening renal function or shock. Use CVP or PAOP-guided diuresis. Avoid fluid overload -it worsens pulmonary edema and prolongs mechanical ventilation.
Neuromuscular Blockade
ACURASYS, 2010: 48h cisatracurium infusion in P/F < 150 showed 90-day mortality benefit vs deep sedation alone (RR 0.71). ROSE, 2019: no benefit vs light sedation with PRN boluses (RR 0.99).
SSC, 2021: suggests intermittent NMBA boluses over continuous infusion (weak recommendation, moderate evidence). Overall, NMBAs reduce barotrauma (RR 0.55). ATS, 2024: conditional recommendation for NMBAs in early (<48h) severe ARDS (P/F โค 100). Cisatracurium preferred, may have anti-inflammatory pleiotropic effects. Typical dosing: 15 mg bolus then 37.5 mg/hr ร 48h.
If NMBAs used, ensure adequate sedation and analgesia.
๐ Updated Practice: Old teaching: set PEEP as high as possible to recruit alveoli in ARDS. Current practice: driving pressure (plateau pressure minus PEEP) is the ventilatory variable most strongly associated with survival (Amato, NEJM 2015). Target driving pressure <15 cmH2O. Higher PEEP is beneficial in moderate-severe ARDS (P/F <200) but not in mild ARDS (PEEP Meta-Analysis, 2010). The ART trial (2017) showed aggressive recruitment maneuvers increased mortality.
ECMO Referral
Consider VV-ECMO if P/F < 80 despite optimal settings, pH < 7.15, or plateau pressure > 35 cmHโO. EOLIA, 2018: supports VV-ECMO as rescue in severe ARDS at experienced centers. SSC, 2021: weak recommendation, low quality evidence. ATS, 2024: conditional recommendation for VV-ECMO in selected severe ARDS (pooled RR 0.76; 95% CI 0.60โ0.95; moderate certainty). Refer early -do not wait until irreversible organ failure.
Oxygenation Strategy Before Intubation
High-Flow Nasal Cannula (HFNC)
SSC, 2021: suggests HFNC over NIV for sepsis-induced hypoxemic respiratory failure (weak recommendation, low quality evidence). FLORALI, 2015: HFNC improved 90-day survival vs NIV (OR 0.42) and reduced intubation in severe hypoxemia (P/F โค 200): 35% vs 58%. HFNC provides flows up to 60 L/min, FiOโ up to 100%, with washout of nasopharyngeal dead space and modest PEEP effect (~3โ5 cmHโO).
NIV in ARDS:SSC, 2021 issued no recommendation for NIV vs invasive ventilation in sepsis-induced hypoxemic respiratory failure. LUNG SAFE, 2016: NIV used in 15% of ARDS with higher failure rates in severe disease. NIV failure is an independent mortality risk factor. If trialing NIV: monitor closely for Vt, work of breathing, and need for intubation.
Corticosteroids in ARDS
Steroids have an evolving role in ARDS -evidence now supports early dexamethasone in moderate-to-severe ARDS.
Early dexamethasone in moderate-to-severe ARDS (P/F โค 200):DEXA-ARDS, 2020: dexamethasone 20 mg IV daily ร 5 days โ 10 mg daily ร 5 days. Reduced 60-day mortality (21% vs 36%, p=0.0047) and increased ventilator-free days. Start within 30h of ARDS diagnosis. This applies to non-COVID ARDS. Supported by CoDEX, 2020, which also showed dexamethasone increased ventilator-free days in moderate-severe ARDS.
Unresolving/fibroproliferative ARDS (after day 7):ARDS Steroid Trial, 2007: methylprednisolone 1 mg/kg/day with slow taper improved LIS score and reduced mechanical ventilation days. Do NOT start after day 14 -ARDSNet LaSRS, 2006: late initiation associated with increased 60- and 180-day mortality.
COVID-19 ARDS:RECOVERY, 2020: dexamethasone 6 mg/day ร 10 days reduced 28-day mortality in patients on mechanical ventilation (29.3% vs 41.4%). CAPE COVID, 2020 found that low-dose hydrocortisone did not significantly reduce treatment failure in COVID pneumonia. REMAP-CAP, 2021 showed IL-6 inhibitors (tocilizumab, sarilumab) improved organ support-free days and survival in severe COVID when combined with corticosteroids.
๐ ATS 2024 Update: The ATS now formally recommends corticosteroids for ARDS (conditional recommendation, moderate certainty). Pooled analysis: RR 0.84 (95% CI 0.73โ0.96) for mortality reduction. Optimal regimen remains unknown, DEXA-ARDS protocol (above) is the most studied. ATS ARDS Guideline, 2024
What Does NOT Work in ARDS
Therapy
Outcome
Late steroids (> day 14)
โ mortality when started after day 14 ARDSNet LaSRS, 2006. Early dexamethasone (within 30h) IS beneficial -see above.
Inhaled nitric oxide (iNO)
Transient oxygenation improvement only. No mortality benefit. Increases renal dysfunction.
Surfactant
Effective in neonatal RDS. Ineffective in adult ARDS.
Increased 28-day mortality (RR 1.12). ART, 2017ATS, 2024: strong recommendation against prolonged recruitment maneuvers. Higher PEEP WITHOUT recruitment maneuvers is conditionally recommended for moderate-severe ARDS.
IV beta-agonists (salbutamol)
Increased mortality. BALTI-2, 2012
๐ Medications & Doses
Sedation & Analgesia
Analgesia-first, target light sedation (RASS 0 to โ2).PADIS, 2018 guidelines recommend protocolized sedation with daily awakening trials. PADIS Update, 2025: dexmedetomidine now suggested over propofol when light sedation and/or delirium reduction are priorities. Deep sedation (RASS โ4/โ5) only when NMBAs required.
Drug
Dose
Indication
Notes
Fentanyl (Sublimaze)
25โ200 mcg/hr IV
Analgesia (first-line)
Analgesia-first approach. Less histamine release and hypotension than morphine. Accumulates with hepatic/renal failure.
Propofol (Diprivan)
5โ50 mcg/kg/min IV
Sedation (first-line)
Rapid on/off -ideal for daily awakening trials. Monitor triglycerides q48h. Propofol infusion syndrome risk if > 80 mcg/kg/min > 48h.
Dexmedetomidine
0.2โ1.5 mcg/kg/hr IV
Light sedation (no NMBAs)
Preserves respiratory drive. Less delirium than benzos. May cause bradycardia/hypotension. Not appropriate for deep sedation.
Midazolam (Versed)
0.02โ0.1 mg/kg/hr IV
Sedation (2nd-line)
Accumulates in renal/hepatic failure โ prolonged wake-up. Associated with more delirium. Avoid long-term use.
Neuromuscular Blockade
Drug
Dose
Indication
Notes
Cisatracurium (bolus)
0.1โ0.2 mg/kg IV PRN
Intermittent use in mod-severe ARDS SSC, 2021
Preferred strategy per SSC 2021. Monitor ventilator synchrony. Does not require train-of-four for intermittent dosing.
Cisatracurium (infusion)
0.1โ0.2 mg/kg/hr IV ร 48h
Severe ARDS with refractory dyssynchrony
ACURASYS, 2010: mortality benefit vs deep sedation. ROSE, 2019: no benefit vs light sedation + boluses. Monitor with train-of-four (target 1โ2/4).
Other ARDS Medications
Drug
Dose
Indication
Notes
Methylprednisolone (Solu-Medrol)
1 mg/kg/day IV โ taper over 2 wks
Unresolving ARDS (fibroproliferative phase, day 7โ14)
ARDS Steroid Trial, 2007. Do NOT start after day 14 ARDSNet LaSRS, 2006: late steroids = โ mortality.
Dexamethasone (early)
20 mg IV daily ร 5d โ 10 mg ร 5d
Moderate-severe ARDS (P/F โค 200), start within 30h
DEXA-ARDS, 2020: reduced 60-day mortality (21% vs 36%) and โ ventilator-free days in non-COVID ARDS.
Dexamethasone (COVID)
6 mg IV/PO daily ร 10 days
COVID-19 ARDS
RECOVERY, 2020: NNT 8 in ventilated COVID patients.
Furosemide (Lasix)
Titrated to even/negative fluid balance
Conservative fluid strategy
FACTT, 2006. Start after resuscitation phase. Monitor Cr and Kโบ closely. CVP or PAOP guidance if available.
Sodium Bicarbonate
1โ2 mEq/kg IV slow push or infusion
pH < 7.15 with permissive hypercapnia
Use sparingly. Does not improve outcomes. Temporizing for severe acidemia only.
๐ On Rounds
On Rounds
Pimp Questions
What tidal volume should you use in ARDS and why?
6 mL/kg of ideal body weight. Higher tidal volumes cause volutrauma (overdistension) and worsen alveolar injury. ARDSnet 2000: 22% relative reduction in mortality with 6 vs 12 mL/kg IBW -the single most impactful ARDS trial ever done.
When do you prone a patient and what is the evidence?
P/F ratio < 150 despite optimal ventilator settings. PROSEVA 2013 prone โฅ 16 hrs/day reduced 28-day mortality from 32.8% to 16% -one of the most dramatic results in critical care medicine.
What is permissive hypercapnia and why do we accept it?
Allowing PaCOโ to rise above normal (up to ~60 mmHg) as a trade-off for achieving lung-protective tidal volumes. Increasing minute ventilation to normalize COโ would require higher tidal volumes that cause further lung injury. pH > 7.20 is generally safe. Contraindicated in raised ICP and sickle cell crisis.
What is driving pressure, and why does it matter more than plateau pressure alone?
Driving pressure = Pplat โ PEEP. It reflects the cyclic strain on functional lung tissue (the "baby lung"). A patient-level meta-analysis Driving Pressure Meta-Analysis, 2015 found driving pressure < 15 cmHโO was the strongest independent predictor of survival in ARDS -better than Vt or Pplat alone. It accounts for both the tidal volume and the functional lung size.
ACURASYS vs ROSE -how do you reconcile conflicting NMBA data?
ACURASYS, 2010 compared 48h cisatracurium infusion vs deep sedation without NMBAs โ mortality benefit. ROSE, 2019 compared infusion vs light sedation with PRN boluses โ no benefit. The difference was the control arm: it's the deep sedation that was harmful, not the NMBAs that were magical. The lesson: avoid deep sedation; use light sedation with PRN NMBA boluses as first-line SSC, 2021.
When should you start thinking about ECMO?
P/F < 80 despite optimal vent settings (PEEP optimized, Pplat โค 30, TV 6 mL/kg IBW), prone positioning, and trial of NMBAs. Also consider for pH < 7.15 from respiratory acidosis or Pplat > 35 despite TV reduction to 4 mL/kg. EOLIA, 2018 showed benefit when referred early to experienced ECMO centers. Key: refer early -don't wait for irreversible multi-organ failure.
Why should you avoid fluid overload in ARDS, and what trial supports conservative fluids?
FACTT, 2006 randomized 1,000 ARDS patients to conservative vs liberal fluid management after initial resuscitation. Conservative strategy: ~2.5 fewer ventilator days, improved oxygenation index, no increase in shock or renal failure. Mechanism: reduced hydrostatic pressure across damaged pulmonary capillaries โ less alveolar edema. Target even or negative daily fluid balance once resuscitation is complete.
What is the definition of ARDS?
Acute diffuse inflammatory lung injury โ increased alveolar-capillary permeability โ pulmonary edema โ severe hypoxemia. Diagnosed by Berlin criteria: acute onset โค 1 week, bilateral CXR opacities, not cardiogenic, P/F ratio determines severity.
What are the Berlin severity classifications?
Mild: P/F 200โ300 (~27% mortality). Moderate: P/F 100โ200 (~32% mortality). Severe: P/F < 100 (~45% mortality). All with PEEP โฅ 5 cmHโO.
What is the most common cause of ARDS?
Sepsis (~40โ50%), followed by pneumonia (~30โ40%). Sepsis is the most common indirect cause; pneumonia is the most common direct (pulmonary) cause.
Why does hypoxemia occur in ARDS?
Shunt physiology -blood passes through non-ventilated, fluid-filled alveoli without participating in gas exchange. This is why supplemental Oโ alone often fails to correct the hypoxemia, and why PEEP (to recruit collapsed alveoli) is critical.
What plateau pressure should you target?
Pplat โค 30 cmHโO. Additionally, driving pressure (Pplat โ PEEP) < 15 cmHโO is the strongest independent predictor of survival Driving Pressure Meta-Analysis, 2015.
How do you differentiate ARDS from cardiogenic pulmonary edema?
ARDS: normal PCWP (โค 18), normal BNP, protein-rich exudate, diffuse bilateral CXR, no response to diuretics. Cardiogenic: high PCWP, high BNP, transudative, perihilar "bat wing" pattern, responds to diuresis. Bedside echo is the fastest differentiator.
Clinical Examples
๐ Case 1, Pneumonia-Induced ARDS
Patient: 55M, PMH DM2. Severe CAP (Strep pneumoniae). Intubated for hypoxemic respiratory failure.
Key findings: P/F 120 (moderate ARDS). Bilateral infiltrates. BNP 45. TV 420 mL (6 mL/kg IBW), PEEP 12, FiO2 0.7. Pplat 28, driving pressure 16.
Driving pressure 16, reduce below 15 Amato et al., 2015
Conservative fluid strategy FACTT, 2006
P/F < 150, prone ≥ 16h/day PROSEVA, 2013
Light sedation (RASS -1 to -2), daily SAT/SBT assessment
Teaching point: Driving pressure (Pplat - PEEP) < 15 is the strongest predictor of survival in ARDS.
๐ Case 2, Severe ARDS Requiring Proning
Patient: 40F, previously healthy. Influenza A pneumonia. P/F 72 (severe) despite FiO2 1.0, PEEP 16.
Key findings: TV 330 mL (6 mL/kg IBW), Pplat 30, driving pressure 14. SpO2 85% supine.
Management:
Prone immediately ≥ 16h/day PROSEVA, 2013
Cisatracurium PRN boluses for dyssynchrony, not routine infusion ROSE, 2019
Light sedation (RASS -2), avoid deep sedation
If P/F remains < 80 after proning, consult ECMO center EOLIA, 2018
Oseltamivir 75 mg BID for influenza
Teaching point: PROSEVA reduced mortality from 32.8% to 16%. ACURASYS vs ROSE: deep sedation was harmful, not paralytics magical. Use light sedation + PRN NMBA boluses.
๐ Case 3, ARDS vs Cardiogenic Pulmonary Edema
Patient: 68M, PMH HFrEF (EF 25%). Bilateral infiltrates, intubated. P/F 180. Is this ARDS or decompensated HF?
Key findings: BNP 2800. Echo: EF 20%, dilated LV. Responds to IV furosemide. Cardiogenic pulmonary edema, NOT ARDS.
Management:
IV furosemide drip, target negative fluid balance
Do NOT apply low-TV strategy reflexively, volume overload, not ARDS
Teaching point: Berlin criteria require bilateral opacities NOT fully explained by cardiac failure. ARDS = normal BNP/PCWP, no diuretic response. Cardiogenic = elevated BNP/PCWP, responds to diuresis.
๐ Sample Presentation
"Mr. Torres is a 52-year-old with no significant PMH who developed ARDS in the setting of severe CAP with Streptococcus pneumoniae. He was intubated on hospital day 1. He is on lung-protective ventilation: TV 6 mL/kg IBW at 390 mL, PEEP 12, FiOโ 0.7, with a P/F ratio of 148 this morning -consistent with moderate ARDS. He was proned for 16 hours overnight with improvement in P/F to 180. His plateau pressure is 26. He is on propofol and fentanyl drips, RASS โ2. We are on day 2 of cisatracurium. Fluid balance is negative 400 mL over the last 24 hours. He remains hemodynamically stable on low-dose norepinephrine. Plan is to continue prone cycling and target daily fluid balance of at least even."
Daily Ventilator Assessment
P/F ratio -calculate every morning from ABG. Trend drives all major decisions (prone, ECMO).
Assess daily once P/F > 200 and FiOโ โค 0.4 with PEEP โค 8:
Precipitant resolving or resolved
Hemodynamically stable (off or low-dose vasopressors)
Adequate cough and gag reflex
RASS โ1 to +1 (awake, cooperative)
No planned surgery or procedures requiring deep sedation
Rapid shallow breathing index (RSBI) < 105 breaths/min/L
SBT Protocol: 30โ120 min on PS 5โ8 / PEEP 5 or T-piece. Pass = RR < 35, SpOโ > 90%, HR < 140, no accessory muscle use, no distress. โ Extubate. If fails โ resume full support, retry in 24h. WIND, 2018: daily SBTs reduce time to extubation.
Complications to Watch
Ventilator-associated pneumonia (VAP) -new fever, purulent sputum, new infiltrate on CXR after 48h of MV. Maintain HOB โฅ 30ยฐ, oral care, subglottic suctioning.