Part 3: Adjunctive and Rescue Therapies
Recruitment maneuvers and evidence from the ART trial, conservative fluid management from the FACTT trial, inhaled pulmonary vasodilators, ECMO indications and referral criteria from the EOLIA trial, high-frequency oscillatory ventilation, and corticosteroids in ARDS.
7. Recruitment Maneuvers
7.1 Concept and Rationale
Recruitment maneuvers (RMs) are transient increases in airway pressure intended to open collapsed alveoli, thereby increasing the volume of aerated lung available for tidal ventilation. The theoretical benefit is to reduce atelectrauma (cyclic opening and closing of collapsed units) and to improve oxygenation by converting shunt to functional gas-exchanging units. Once recruited, these units are held open by adequate PEEP (the “open lung” approach).1
7.2 Techniques
| Technique | Description | Duration |
|---|---|---|
| Sustained inflation | Apply continuous positive airway pressure of 30–40 cmH2O for 30–40 seconds | Single maneuver; may repeat once |
| Stepwise (staircase) recruitment | Incrementally increase PEEP in 5 cmH2O steps every 2 minutes (e.g., PEEP 10 → 15 → 20 → 25) with a fixed driving pressure (typically 15 cmH2O), then perform a decremental PEEP trial to identify the best compliance PEEP level | 15–30 minutes for full staircase |
| Extended sigh | Apply 3 breaths per minute at 45 cmH2O for 1 minute | Brief |
| Pressure-control recruitment | Set pressure-control mode with PEEP 15–20 cmH2O and inspiratory pressure achieving Paw 40–50 cmH2O for 1–2 minutes | 1–2 minutes |
7.3 Evidence: The ART Trial
The most definitive evidence regarding recruitment maneuvers comes from the Alveolar Recruitment for ARDS Trial (ART), published in 2017.2
ART Trial Design:
- 1,010 patients with moderate-to-severe ARDS (PaO2/FiO2 ≤200 with PEEP ≥10)
- Randomized to a lung recruitment strategy (stepwise recruitment maneuver with PEEP titrated by best respiratory system compliance) vs. the standard ARDSNet low PEEP/FiO2 table
- The recruitment maneuver used incremental PEEP steps up to 45 cmH2O with a driving pressure of 15 cmH2O, followed by decremental PEEP titration
Results:
| Outcome | Recruitment Strategy | Control (ARDSNet PEEP table) | Significance |
|---|---|---|---|
| 28-day mortality | 55.3% | 49.3% | p = 0.041 (HARM) |
| 6-month mortality | 65.3% | 59.9% | p = 0.04 (HARM) |
| Barotrauma | 5.6% | 1.6% | p = 0.001 |
| Cardiac arrest during RM | 2.2% | 0% | — |
| Hemodynamic compromise during RM | Common | — | — |
The ART trial demonstrated that a strategy of aggressive lung recruitment with high PEEP titrated by compliance increased mortality compared to the standard low PEEP table approach. The recruitment maneuver strategy was associated with significantly more barotrauma and hemodynamic compromise, including cardiac arrests during the recruitment maneuver itself.2
7.4 Current Recommendations
| Recommendation | Strength | Basis |
|---|---|---|
| Routine recruitment maneuvers are NOT recommended in moderate-to-severe ARDS | Strong against | ART trial demonstrated harm; European guidelines recommend against routine use23 |
| Aggressive stepwise recruitment maneuvers (to pressures >40 cmH2O) should be avoided | Strong against | ART trial; risk of barotrauma and cardiovascular collapse |
| Brief, gentle recruitment maneuvers (sustained inflation 30 cmH2O for 30 seconds) may be considered in specific situations: | Conditional | Earlier meta-analyses suggested possible benefit of gentle maneuvers1 |
| — Acute derecruitment after a circuit disconnection | — | Re-establishing lost PEEP and recruitment |
| — After suctioning that results in significant desaturation | — | Restoring baseline oxygenation |
| — As part of a PEEP titration protocol (brief maneuver followed by decremental PEEP trial) | — | Physiological assessment only; not a therapeutic strategy |
If a recruitment maneuver is performed, safety requirements include:
- Arterial line in place for continuous blood pressure monitoring
- Vasopressor support immediately available
- Abort the maneuver immediately if: MAP <60 mmHg, SpO2 <88%, new arrhythmia, or pneumothorax suspected
- Do not exceed 40 cmH2O airway pressure during the maneuver unless under expert guidance
- Limit duration of sustained inflation to ≤30 seconds
- Document the response (change in compliance, oxygenation, driving pressure)
8. Fluid Management in ARDS
8.1 Pathophysiology of Pulmonary Edema in ARDS
ARDS is fundamentally a disease of increased pulmonary vascular permeability. Protein-rich edema fluid floods the alveolar space, impairing gas exchange and reducing lung compliance. Unlike cardiogenic pulmonary edema, the edema in ARDS forms at normal or low hydrostatic pressures. However, elevated hydrostatic pressure (from fluid overload, left ventricular failure, or aggressive resuscitation) compounds the permeability edema and worsens the clinical picture.4
The relationship between intravascular volume and pulmonary edema in ARDS is therefore:
- Any increase in pulmonary capillary hydrostatic pressure drives more fluid across the already-damaged capillary endothelium
- Fluid restriction reduces hydrostatic pressure and may allow partial resolution of edema through lymphatic drainage
- Aggressive diuresis can reduce extravascular lung water and improve oxygenation and compliance
- However, excessive fluid restriction may compromise cardiac output, organ perfusion, and renal function
8.2 The FACTT Trial
The landmark Fluid and Catheter Treatment Trial (FACTT), published in 2006 by the ARDS network investigators, compared conservative vs. liberal fluid management strategies in ARDS.4
FACTT Trial Design:
- 1,000 patients with acute lung injury (PaO2/FiO2 <300 with bilateral infiltrates)
- Randomized to conservative fluid management (target CVP <4 mmHg or PAOP <8 mmHg) vs. liberal fluid management (target CVP 10–14 mmHg or PAOP 14–18 mmHg)
- Protocol included explicit algorithms for fluid boluses, diuretics (furosemide), and vasopressors based on hemodynamic targets
- The trial also had a 2×2 factorial design comparing pulmonary artery catheter vs. central venous catheter, which showed no difference in outcomes
Results:
| Outcome | Conservative Strategy | Liberal Strategy | Significance |
|---|---|---|---|
| 60-day mortality | 25.5% | 28.4% | p = 0.30 (NS) |
| Ventilator-free days (28-day) | 14.6 ± 10.0 | 12.1 ± 10.4 | p < 0.001 |
| ICU-free days (28-day) | 13.4 ± 10.2 | 11.2 ± 10.4 | p < 0.001 |
| Cumulative fluid balance day 7 | −136 ± 491 mL | +6,992 ± 502 mL | p < 0.001 |
| Dialysis requirement | No significant difference | — | — |
| Shock-free days | No significant difference | — | — |
The conservative strategy resulted in a net negative fluid balance (approximately 7 liters less fluid over 7 days compared to the liberal group) and significantly more ventilator-free and ICU-free days, without increasing organ failure or need for dialysis.4
8.3 Practical Fluid Management Protocol
Based on the FACTT trial and subsequent evidence, the following approach is recommended after initial resuscitation of the underlying cause (e.g., sepsis):45
Phase 1: Initial Resuscitation (First 6–12 Hours)
- Treat the underlying cause (e.g., early antibiotics and fluid resuscitation for sepsis per the surviving sepsis campaign guidelines)
- Use hemodynamic targets and dynamic assessments (pulse pressure variation, passive leg raise) to guide initial fluid resuscitation
- Avoid excessive crystalloid administration; target the minimum volume needed to achieve hemodynamic stability
Phase 2: Conservative Fluid Management (After Hemodynamic Stabilization)
| Parameter | Target | Action |
|---|---|---|
| Intravascular volume assessment | Euvolemic to mildly hypovolemic | Use clinical assessment, CVP trends, dynamic indices |
| Fluid balance target | Even to negative daily balance | Furosemide as primary tool |
| Furosemide dosing | Start 20–40 mg IV bolus; titrate to urine output | Target urine output 0.5–1 mL/kg/hr; may escalate to 80–160 mg bolus or continuous infusion (5–40 mg/hr) |
| Albumin | Consider 25% albumin (25–50 g) as adjunct to furosemide if serum albumin <3.0 g/dL | SAFE-RELIEF pilot data suggest potential benefit; albumin draws fluid from interstitium to intravascular space, enhancing diuretic response |
| Vasopressor management | Maintain MAP ≥65 mmHg | Initiate or uptitrate vasopressors (norepinephrine first-line) if MAP falls below target during diuresis rather than giving fluid boluses |
| Monitor renal function | Serum creatinine, urine output, BUN | Accept mild creatinine elevation (0.3–0.5 mg/dL increase) if patient is making urine and hemodynamically stable; do not reflexively fluid-resuscitate |
Key principles:
- After initial resuscitation, avoid “maintenance” IV fluids — use only medications and nutrition as fluid sources
- Target even-to-negative fluid balance from day 2 onward
- The 7-liter fluid difference in the FACTT trial translated to approximately 2.5 more ventilator-free days
- Conservative fluid management and lung-protective ventilation are complementary strategies
8.4 Extravascular Lung Water Monitoring
Extravascular lung water (EVLW) can be measured using transpulmonary thermodilution (e.g., PiCCO system) and provides a direct quantification of pulmonary edema.6
| EVLW Index (mL/kg) | Interpretation |
|---|---|
| <7 | Normal |
| 7–10 | Mild pulmonary edema |
| 10–15 | Moderate pulmonary edema |
| >15 | Severe pulmonary edema |
- EVLW-guided fluid management is not standard practice but may be useful in complex cases (e.g., simultaneous ARDS and septic shock requiring aggressive resuscitation)
- Elevated EVLW is an independent predictor of mortality in ARDS
- A decreasing EVLW trend correlates with clinical improvement
9. Inhaled Pulmonary Vasodilators
9.1 Mechanism and Rationale
Inhaled pulmonary vasodilators are delivered directly to ventilated alveoli, where they cause selective vasodilation of the pulmonary vasculature supplying those aerated regions. This redirects blood flow from shunt (non-ventilated) regions to ventilated alveoli, improving V/Q matching and oxygenation without causing systemic hypotension.7
9.2 Agents
9.2.1 Inhaled Nitric Oxide (iNO)
| Parameter | Detail |
|---|---|
| Mechanism | Activates guanylate cyclase in pulmonary vascular smooth muscle → increased cGMP → vasodilation; rapidly inactivated by hemoglobin (no systemic vasodilation) |
| Starting dose | 5–20 ppm (parts per million) |
| Typical dose range | 5–40 ppm |
| Onset | Minutes |
| Monitoring | Methemoglobin levels (every 8–12 hours; hold if >5%); nitrogen dioxide levels (toxic byproduct; keep <2 ppm) |
| Delivery | Requires specialized delivery system integrated into the ventilator circuit |
| Weaning | Taper gradually (do not abruptly discontinue — risk of rebound pulmonary hypertension and hypoxemia) |
| Cost | High (can exceed $3,000–$5,000 per day in many health systems) |
9.2.2 Inhaled Epoprostenol (Prostacyclin)
| Parameter | Detail |
|---|---|
| Mechanism | Activates adenylate cyclase → increased cAMP → pulmonary vasodilation and platelet inhibition |
| Starting dose | 10,000–50,000 ng/mL solution delivered via in-line nebulizer at 8 mL/hr |
| Typical dose range | 10,000–50,000 ng/mL continuous nebulization |
| Onset | Minutes |
| Monitoring | Platelet count (antiplatelet effect); systemic blood pressure (rare systemic absorption) |
| Delivery | Via vibrating mesh nebulizer (preferred) or jet nebulizer placed in the inspiratory limb of the ventilator circuit |
| Weaning | Taper gradually over hours |
| Cost | Significantly lower than inhaled nitric oxide |
9.3 Evidence for Inhaled Pulmonary Vasodilators in ARDS
| Finding | Detail |
|---|---|
| Oxygenation | Both agents reliably improve PaO2/FiO2 by 10–30% in 60–70% of patients with ARDS78 |
| Mortality | No randomized trial has demonstrated a mortality benefit for either agent in ARDS78 |
| Meta-analysis | A Cochrane review of inhaled nitric oxide in ARDS found no mortality benefit and a possible increase in renal dysfunction8 |
| Role | Rescue/bridge therapy for refractory hypoxemia; temporizing measure while arranging ECMO or awaiting response to other interventions |
9.4 Practical Recommendations for Inhaled Vasodilators
| Indication | Recommendation |
|---|---|
| Refractory hypoxemia (PaO2/FiO2 <80 despite optimal ventilation, prone positioning, and adequate PEEP) | Consider inhaled epoprostenol (preferred for cost) or inhaled nitric oxide as a bridge therapy |
| Right ventricular failure complicating ARDS | Inhaled vasodilators reduce pulmonary vascular resistance selectively; may be beneficial |
| Routine use in all ARDS | NOT recommended; no mortality benefit |
| Duration | Reassess response within 30–60 minutes; if no oxygenation improvement (>10% increase in PaO2/FiO2), discontinue |
| Weaning | Taper gradually; do not abruptly stop iNO (risk of rebound pulmonary hypertension) |
10. Extracorporeal Membrane Oxygenation (ECMO)
10.1 Overview
Venovenous ECMO (VV-ECMO) provides extracorporeal gas exchange (oxygenation and CO2 removal) through an external membrane oxygenator, allowing the ventilator settings to be reduced to “ultra-protective” levels (minimal VT, low PEEP, low FiO2) while the native lungs rest and heal. Venoarterial ECMO (VA-ECMO) provides both respiratory and circulatory support and is indicated when hemodynamic failure accompanies respiratory failure.910
10.2 VV-ECMO vs. VA-ECMO
| Feature | VV-ECMO | VA-ECMO |
|---|---|---|
| Indication | Isolated respiratory failure (ARDS without hemodynamic collapse) | Combined respiratory and cardiac failure |
| Cannulation | Typically femoral vein → internal jugular vein (or dual-lumen single cannula in the right internal jugular) | Femoral vein → femoral artery (peripheral) or directly to heart (central) |
| Circulatory support | None (blood is drained and returned to the venous system) | Full circulatory support (blood returned to arterial system) |
| Differential hypoxemia | Not an issue | Risk of upper body hypoxemia if cardiac output recovers with persistent lung failure (North-South syndrome); monitor right radial SpO2 |
| Complications | Hemorrhage, hemolysis, circuit thrombosis, recirculation, infection | All VV complications plus limb ischemia (femoral cannulation), LV distension, differential hypoxemia |
10.3 Evidence: The EOLIA Trial
The most important trial of ECMO in severe ARDS is the EOLIA trial (2018).10
EOLIA Trial Design:
- 249 patients with very severe ARDS meeting at least one of:
- PaO2/FiO2 <50 mmHg for >3 hours
- PaO2/FiO2 <80 mmHg for >6 hours
- Arterial pH <7.25 with PaCO2 ≥60 mmHg for >6 hours despite optimal ventilation (VT 6 mL/kg, PEEP ≥10, prone positioning attempted)
- Randomized to immediate VV-ECMO vs. continued conventional management (with crossover to ECMO as rescue allowed)
- 28% of control patients crossed over to ECMO for refractory hypoxemia
Results:
| Outcome | ECMO Group | Control Group | Significance |
|---|---|---|---|
| 60-day mortality | 35% | 46% | p = 0.09 (NS — trial was underpowered after early termination) |
| Control crossover to ECMO | — | 28% | — |
| Mortality if control crossover excluded | 35% | 57% (non-crossover patients) | — |
| Major hemorrhage | More common | Less common | — |
Interpretation: The EOLIA trial did not reach statistical significance for its primary endpoint, but the 11% absolute mortality difference and the high crossover rate (which biased toward the null) have led most experts and guideline panels to consider ECMO beneficial in highly selected patients with the most severe ARDS when performed at experienced centers. A Bayesian reanalysis of EOLIA concluded that the posterior probability of any mortality benefit with ECMO was 88%.1011
10.4 Earlier Evidence: CESAR Trial
The CESAR trial (2009) randomized 180 patients with severe ARDS (Murray lung injury score ≥3 or pH <7.20 from hypercapnia) to referral to an ECMO center vs. continued management at the referring hospital.12
| Outcome | ECMO Referral | Control | Significance |
|---|---|---|---|
| Survival without disability at 6 months | 63% | 47% | p = 0.03 |
Notably, only 75% of patients randomized to the ECMO arm actually received ECMO; the benefit may partially reflect protocolized care at an expert center. The CESAR trial established the referral-and-transfer model for ECMO in ARDS.12
10.5 ECMO Referral Criteria
Based on the evidence and expert consensus, consider ECMO referral when:91011
Strong indications for ECMO referral:
| Criterion | Detail |
|---|---|
| PaO2/FiO2 <50 for >3 hours | Despite optimal ventilation (VT 6 mL/kg IBW, PEEP ≥10), prone positioning, and NMB |
| PaO2/FiO2 <80 for >6 hours | Despite all above measures |
| pH <7.25 with PaCO2 ≥60 for >6 hours | Despite RR 35 and VT adjusted to maximize pH |
| Inability to maintain lung-protective ventilation | Pplat >30 despite VT 4 mL/kg IBW |
Relative indications for ECMO consideration:
| Criterion | Detail |
|---|---|
| PaO2/FiO2 <100–150 with deteriorating trajectory | Despite all standard interventions |
| Murray Lung Injury Score ≥3 | Combined assessment of PaO2/FiO2, PEEP, compliance, CXR infiltrates |
| Severe air leak syndromes | Bronchopleural fistula with inability to ventilate |
| Bridge to lung transplantation | For patients with end-stage lung disease awaiting transplant |
Contraindications to ECMO:
| Contraindication | Type |
|---|---|
| Mechanical ventilation >10 days at high settings | Relative (diminishing benefit, increasing futility) |
| Major pharmacologic immunosuppression (ANC <400/mm3) | Relative |
| Active CNS hemorrhage or irreversible neurologic injury | Absolute |
| Unrecoverable underlying condition and not a transplant candidate | Absolute |
| Advanced age (>65–70 years, depending on center) | Relative (higher complication rates) |
| Severe multi-organ failure (SOFA >15) | Relative (high mortality despite ECMO) |
| BMI >40–45 (cannulation difficulty, circuit flow limitations) | Relative |
| Active uncontrolled bleeding | Absolute (ECMO requires anticoagulation) |
| Irreversible underlying pulmonary condition | Absolute |
10.6 Ventilator Management During VV-ECMO (“Ultra-Protective” Ventilation)
Once VV-ECMO is established, the ventilator strategy shifts to “lung rest”:9
| Parameter | Target |
|---|---|
| Mode | Pressure-control or pressure-support |
| Tidal volume | ≤4 mL/kg IBW (often 1–3 mL/kg) |
| Plateau pressure | ≤25 cmH2O |
| Driving pressure | ≤10 cmH2O |
| PEEP | 10–15 cmH2O (maintain recruitment) |
| FiO2 | 0.3 (minimize oxygen toxicity to the native lung) |
| Respiratory rate | 10–15 breaths/min (or lower) |
The goal is to minimize all mechanical forces applied to the injured lung while the ECMO circuit provides gas exchange. This ultra-protective strategy may facilitate more complete lung healing.
11. High-Frequency Oscillatory Ventilation (HFOV)
11.1 Concept
HFOV delivers very small tidal volumes (1–3 mL/kg) at very high frequencies (3–15 Hz, i.e., 180–900 breaths per minute) around a high mean airway pressure. The theoretical benefit is continuous recruitment with minimal tidal stretch, potentially reducing VILI.1314
11.2 Evidence: OSCAR and OSCILLATE Trials
Two large randomized trials in 2013 definitively addressed the role of HFOV in ARDS:
OSCAR Trial (2013):13
- 795 patients with moderate-to-severe ARDS
- HFOV vs. conventional ventilation
- No mortality difference (41.7% vs. 41.1%, p = 0.85)
OSCILLATE Trial (2013):14
- 548 patients with moderate-to-severe ARDS
- HFOV vs. conventional ventilation with high PEEP strategy
- Stopped early for harm: In-hospital mortality 47% vs. 35% in the HFOV vs. control groups (RR 1.33, 95% CI 1.09–1.64)
- HFOV group required more vasoactive agents and sedation
11.3 Current Recommendation
HFOV should NOT be used as a primary or routine rescue strategy in adult ARDS.315
The clinical practice guideline from the major critical care societies provides a strong recommendation against routine use of HFOV in moderate-to-severe ARDS.15 The OSCILLATE trial demonstrated harm, and the OSCAR trial showed no benefit. HFOV may impair right ventricular function through sustained high intrathoracic pressure and increased pulmonary vascular resistance.
12. Corticosteroids in ARDS
12.1 Rationale
ARDS is fundamentally an inflammatory condition. Corticosteroids may benefit through:
- Suppression of pulmonary and systemic inflammation
- Reduction of fibroproliferative response
- Improvement in lung compliance and gas exchange
- Reduction in duration of mechanical ventilation16
12.2 Key Trials
| Trial | Year | Drug/Dose | Population | Key Findings |
|---|---|---|---|---|
| ARDSNet Late Steroid Rescue Study (LaSRS) | 2006 | Methylprednisolone 2 mg/kg/day tapered over 3 weeks starting day 7–28 of ARDS | 180 patients with persistent ARDS (≥7 days) | More ventilator-free days (11.2 vs. 6.8), but no mortality benefit at 60 days; started after day 13 → increased mortality16 |
| Meduri et al. | 2007 | Methylprednisolone 1 mg/kg/day starting within 72 hours of ARDS | 91 patients with early severe ARDS | Reduced duration of MV and ICU stay; reduced mortality (24% vs. 43%, p = 0.02)17 |
| DEXA-ARDS | 2020 | Dexamethasone 20 mg IV daily × 5 days then 10 mg IV daily × 5 days started within 30 hours of ARDS onset | 277 patients with moderate-to-severe ARDS | More ventilator-free days (12.3 vs. 7.5, p < 0.0001); reduced 60-day mortality (21% vs. 36%, p = 0.0047)18 |
| COVID RECOVERY | 2021 | Dexamethasone 6 mg daily × 10 days | Hospitalized COVID-19 patients (including ARDS) | 28-day mortality reduced in those on MV (29.3% vs. 41.4%, RR 0.64)19 |
12.3 Current Recommendations for Corticosteroids in ARDS
| Recommendation | Detail |
|---|---|
| Early moderate-to-severe ARDS (<14 days onset) | Consider dexamethasone 20 mg IV daily × 5 days followed by 10 mg IV daily × 5 days, started within the first 24–48 hours of ARDS onset (DEXA-ARDS protocol)18 |
| Late/persistent ARDS (≥7 days) | Low-dose methylprednisolone (1–2 mg/kg/day with gradual taper over 2–3 weeks) may reduce duration of ventilation; avoid initiating corticosteroids after day 14 of ARDS16 |
| COVID-19 ARDS | Dexamethasone 6 mg daily for up to 10 days (established standard of care)19 |
| Infection control | Ensure adequate source control and antimicrobial therapy before initiating corticosteroids; monitor for secondary infections |
| Tapering | Always taper corticosteroids gradually; abrupt discontinuation may cause rebound inflammation |
| Hyperglycemia management | Monitor blood glucose every 4–6 hours; initiate insulin infusion protocol as needed |
13. Escalation Framework for Refractory ARDS
The following algorithm provides a structured approach to escalating therapy in ARDS that does not respond to initial management:315
13.1 Step-by-Step Escalation
| Step | Intervention | Trigger for Escalation |
|---|---|---|
| 1 | Lung-protective ventilation: VT 6 mL/kg IBW, Pplat ≤30, PEEP/FiO2 per lower table | PaO2/FiO2 <150 after 12–24 hours despite optimization |
| 2 | Higher PEEP strategy (per higher PEEP/FiO2 table); optimize driving pressure | PaO2/FiO2 <150 despite higher PEEP; or driving pressure >15 at needed PEEP |
| 3 | Prone positioning ≥16 hours/day | PaO2/FiO2 <150 with FiO2 ≥0.6 and PEEP ≥5 after stabilization |
| 4 | Consider NMB if dyssynchrony/refractory hypoxemia despite prone | Ongoing dyssynchrony compromising lung protection; PaO2/FiO2 <100 despite prone |
| 5 | Inhaled pulmonary vasodilator (epoprostenol or iNO) | PaO2/FiO2 <80 as bridge therapy; or RV failure |
| 6 | Conservative fluid management and corticosteroids | Throughout; initiate early if not already started |
| 7 | ECMO referral and transfer to ECMO center | PaO2/FiO2 <50 for >3h, <80 for >6h, or pH <7.25 with PaCO2 ≥60 for >6h despite all above; or inability to maintain lung-protective ventilation |
13.2 Interventions NOT Recommended
| Intervention | Status | Evidence |
|---|---|---|
| Routine recruitment maneuvers | Not recommended | ART trial: increased mortality2 |
| HFOV | Not recommended | OSCILLATE: increased mortality; OSCAR: no benefit1314 |
| Inhaled NO as routine therapy | Not recommended | No mortality benefit; possible renal harm8 |
| Prone positioning in mild ARDS | Not routinely recommended | Evidence supports use in severe ARDS (P/F <150)1 |
| Routine NMB for 48 hours | Not recommended | ROSE trial: no benefit vs. light sedation20 |
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