ICU · respiratory
Ventilator-Induced Lung Injury (VILI) — Mechanisms and Prevention
Also known as VILI · Ventilator-induced lung injury · Volutrauma · Atelectrauma · Barotrauma · Biotrauma · Lung-protective ventilation · Driving pressure · Transpulmonary pressure · Pendelluft
Ventilator-induced lung injury (VILI) — the lung damage caused by mechanical ventilation itself, distinct from the underlying disease process. Four mechanisms: (1) Volutrauma (alveolar overdistension from excessive tidal volume or transpulmonary pressure → epithelial/endothelial disruption → inflammation), (2) Atelectrauma (repeated cyclic opening and closing of recruitable alveoli at low end-expiratory pressure → shear stress → injury), (3) Barotrauma (alveolar rupture from excessive airway pressure → pneumothorax, pneumomediastinum, subcutaneous emphysema), (4) Biotrauma (release of inflammatory mediators [cytokines, chemokines] from mechanically stressed lung → systemic spillover → MODS). Prevention: lung-protective ventilation — Vt 4-6 mL/kg predicted body weight, plateau pressure <30 cmH2O, driving pressure (delta P = Pplat - PEEP) <15 cmH2O, PEEP optimised to avoid atelectrauma, permissive hypercapnia. Additional targets: transpulmonary pressure (PL = Pairway - P_esophageal) — oesophageal balloon manometry guides PEEP titration in obese/ARDS patients. The ARDSNet trial (2000) established Vt 6 mL/kg as standard — 22% relative mortality reduction vs 12 mL/kg. VILI is NOT limited to ARDS — it occurs in ANY mechanically ventilated patient — apply lung-protective ventilation universally.
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Overview
VILI is one of the most important concepts in modern critical care. The realisation that the ventilator — the very tool used to save lives — can itself cause lethal lung injury revolutionised mechanical ventilation practice. The ARDSNet trial (2000) is one of the most impactful ICU trials ever conducted: it proved that simply reducing tidal volume from 12 to 6 mL/kg reduced mortality by 22% (from 40% to 31%) in ARDS patients. Every mechanically ventilated patient in every ICU in the world should receive lung-protective ventilation.[1][3]
The four mechanisms of VILI
VILI mechanisms — pathophysiology and prevention
| Mechanism | What happens | Cellular injury | Prevention |
|---|---|---|---|
| Volutrauma (primary) | Excessive alveolar stretch from high tidal volume → alveolar overdistension. The VOLUME (not pressure) is the primary determinant — Dreyfuss 1988 showed that high-volume ventilation (without high pressure — using negative-pressure ventilation) caused the same injury as high-pressure ventilation | Epithelial cell disruption (type I pneumocyte tearing), capillary stress failure (endothelial gap formation → alveolar haemorrhage), basement membrane disruption. Overdistension triggers mechanotransduction → NF-kB activation → inflammatory gene expression | Low tidal volume (4-6 mL/kg PBW) — the single most important intervention |
| Atelectrauma | Repeated cyclic opening and closing of recruitable alveoli at the interface between open and collapsed lung. The shear stress at this "stress riser" zone is 4-5x the nominal airway pressure — meaning a PEEP of 5 with Vt of 400 creates shear stress of 20-25 cmH2O at the interface zone | Epithelial sloughing at the interface zone, surfactant dysfunction (surfactant is squeezed out during collapse and doesn't redistribute during reopening), hyaline membrane formation | Adequate PEEP (keep alveoli OPEN throughout the respiratory cycle — PEEP prevents end-expiratory collapse). Optimise PEEP (best PEEP = best oxygenation + best compliance + lowest delta P) |
| Barotrauma | Alveolar rupture from excessive transalveolar pressure → air escapes into interstitium → tracks along bronchovascular bundles to mediastinum → pneumomediastinum, pneumothorax, subcutaneous emphysema, pneumoperitoneum | Physical disruption of alveolar wall — air dissection along tissue planes | Limit plateau pressure (<30 cmH2O) and transpulmonary pressure (P_L <25 cmH2O). Avoid high inspiratory pressures in obstructive disease (asthma/COPD — auto-PEEP check) |
| Biotrauma | Mechanically stressed alveolar cells release inflammatory mediators (IL-6, IL-8, TNF-alpha, MIP-2) into the alveolar space → these spill over into the systemic circulation → contribute to MODS (the lung as the "engine of multi-organ failure") | Mechanotransduction: mechanical stretch → stretch-activated ion channels → calcium influx → NF-kB/MAPK pathway activation → cytokine gene transcription → release of IL-6/IL-8 → neutrophil recruitment → further injury (positive feedback loop) | All of the above (low Vt + adequate PEEP + low delta P) — biotrauma is the downstream consequence of all three mechanical injuries |
Key ventilatory parameters — what to target and why
VILI prevention targets — the four key parameters
| Parameter | Target | Rationale | How to measure |
|---|---|---|---|
| Tidal volume (Vt) | 4-6 mL/kg PBW (predicted body weight) | The primary determinant of volutrauma. ARDSNet: 6 mL/kg = 22% mortality reduction vs 12 mL/kg. IMPORTANT: use PREDICTED body weight (calculated from height and sex), NOT actual body weight — obese patients need LOWER Vt than their weight suggests | PBW formula: Male = 50 + 0.91 × (height in cm - 152.4). Female = 45.5 + 0.91 × (height in cm - 152.4). Example: 170 cm male → 50 + 0.91 × 17.6 = 66 kg PBW → Vt 396 mL at 6 mL/kg |
| Plateau pressure (Pplat) | <30 cmH2O | Surrogate for alveolar overdistension. Pplat >30 = increased risk of VILI. BUT: Pplat is influenced by CHEST WALL compliance — a high Pplat in a patient with a stiff chest wall (obesity, abdominal compartment syndrome, kyphoscoliosis) may be safe because the TRANSPULMONARY pressure is not elevated | Inspiratory hold manoeuvre (0.5 sec inspiratory pause) on the ventilator — read the pressure |
| Driving pressure (delta P) | <15 cmH2O | Delta P = Pplat - PEEP = the pressure that actually VENTILATES the lung (the tidal "swings" in pressure). Amato 2015 (NEJM): delta P is the STRONGEST predictor of survival in ARDS — stronger than Vt or Pplat alone. Delta P >15 = each 1 cmH2O increase = 5% increase in mortality. Delta P reflects the CHANGE in lung volume relative to compliance (delta P = Vt / compliance) — it is the "strain" on the lung | Calculate: delta P = Pplat - PEEP. If delta P >15 despite Vt 6 mL/kg: REDUCE Vt further (to 4 mL/kg) or increase PEEP (if recruitable lung) |
| PEEP | Optimised (5-15 cmH2O typically; up to 20+ in severe ARDS) | PEEP prevents atelectrauma by keeping alveoli open at end-expiration. Too LOW → atelectrauma. Too HIGH → volutrauma (overdistension) + haemodynamic compromise (reduced venous return + reduced cardiac output). There is NO universal optimal PEEP — titrate per patient | PEEP/FiO2 table (ARDSNet). Best PEEP method: incrementally increase PEEP by 2 cmH2O, measure compliance (best compliance = best PEEP). Oesophageal balloon manometry (transpulmonary pressure-guided PEEP). Electrical impedance tomography (EIT — regional lung aeration) |
Driving pressure — the most important single parameter
Amato et al. (2015, NEJM) performed a secondary analysis of 3,562 patients from 9 RCTs and found that driving pressure (delta P = Pplat - PEEP) was the ventilatory variable that best stratified risk. Patients with delta P >15 cmH2O had significantly higher mortality, regardless of their tidal volume or PEEP setting.[2]
Why delta P is better than Vt or Pplat alone:
- Vt tells you the VOLUME delivered — but does not account for the SIZE of the aerated lung (a 400 mL Vt may be safe in a healthy lung but dangerous in a small, injured ARDS lung — the "baby lung" concept)
- Pplat tells you the PRESSURE at end-inspiration — but includes chest wall pressure (a high Pplat from stiff chest wall is not lung-injuring)
- Delta P = the pressure SWING during tidal ventilation = Vt / respiratory system compliance = directly reflects the STRAIN on the lung tissue. A high delta P means the lung is being stretched too much per breath — regardless of the absolute Vt or Pplat [1]
Clinical approach to delta P:
- If delta P <15: current settings are safe — continue
- If delta P 15-20: consider reducing Vt (to 4-5 mL/kg) or increasing PEEP (if recruitable lung — may paradoxically REDUCE delta P by improving compliance through alveolar recruitment)
- If delta P >20: urgent optimisation needed — reduce Vt to minimum tolerated (4 mL/kg), check for pneumothorax/pleural effusion/abdominal distension (which may increase delta P), consider prone positioning (improves compliance), consider ECMO [1]
Transpulmonary pressure and oesophageal balloon manometry
Transpulmonary pressure (P_L) = airway pressure - pleural pressure = the pressure that actually DISTENDS the lung. It is the TRUE determinant of lung stress — not airway pressure alone. The problem: pleural pressure is not routinely measured. The SURROGATE is oesophageal pressure (measured via an oesophageal balloon catheter), which approximates pleural pressure.[5]
When oesophageal balloon manometry helps:
- Obese patients: high abdominal pressure → elevated pleural pressure → the ventilator's airway pressure must OVERCOME the high pleural pressure to ventilate the lung. Without knowing pleural pressure, you may set PEEP too LOW (the alveoli collapse because PEEP is insufficient to counteract the elevated pleural pressure). Transpulmonary pressure-guided PEEP (target end-expiratory P_L >0) can prevent this
- Severe ARDS: the recruitable lung may need higher PEEP than the standard ARDSNet table suggests. Transpulmonary pressure guidance allows per-patient PEEP optimisation
- Chest wall stiffness: kyphoscoliosis, ankylosing spondylitis, obesity, abdominal compartment syndrome — the stiff chest wall means a high Pplat is transmitted to the pleural space, NOT to the lung. The transpulmonary pressure (the lung-distending pressure) may be safe despite a high Pplat [1]
Lung-protective ventilation protocol — step by step
- CALCULATE PBW from height and sex. Male = 50 + 0.91 × (cm - 152.4). Female = 45.5 + 0.91 × (cm - 152.4)
- SET Vt = 6 mL/kg PBW (initial). Reduce to 4 mL/kg if plateau pressure >30 or delta P >15
- SET RESPIRATORY RATE to maintain pH >7.20 (permissive hypercapnia is acceptable — pH >7.20). Max RR 35 (avoid auto-PEEP). If COPD/asthma: lower RR to allow full expiration (avoid auto-PEEP)
- SET PEEP/FiO2 per ARDSNet table (start at PEEP 5, FiO2 0.3). Adjust based on oxygenation and delta P
- CHECK PLATEAU PRESSURE (inspiratory hold): target <30 cmH2O. If >30: reduce Vt (to 4 mL/kg minimum)
- CHECK DRIVING PRESSURE (delta P = Pplat - PEEP): target <15 cmH2O. If >15: reduce Vt or increase PEEP (if recruitable)
- CHECK FOR AUTO-PEEP (expiratory hold): especially in COPD/asthma. If auto-PEEP present: reduce RR, shorten inspiratory time, ensure adequate expiratory time
- TITRATE FiO2 to lowest setting maintaining SpO2 88-95% (PaO2 55-80 mmHg). Avoid hyperoxia (PaO2 >100 — oxidative stress)
- ACCEPT PERMISSIVE HYPERCAPNIA (pH >7.20) — do NOT increase Vt to normalise PaCO2
- MONITOR: ABG (pH, PaCO2, PaO2), plateau pressure (q4h and after any change), delta P, auto-PEEP (in obstructive disease), chest X-ray (for pneumothorax/effusion)
The ARDSNet trial — the landmark evidence
ARDSNet 2000 — Low tidal volume ventilation (PMID 10793162)
Study design
Multicentre randomised controlled trial — 861 patients
Population
Patients with ALI/ARDS (PaO2/FiO2 <300, bilateral infiltrates)
Intervention
Vt 6 mL/kg PBW + Pplat <30 vs Vt 12 mL/kg PBW + Pplat <50
Primary outcome
Mortality before hospital discharge: 31% (low Vt) vs 40% (traditional Vt) — p=0.007. NNT=11
Key finding
22% RELATIVE reduction in mortality from simply reducing tidal volume
Key finding
Permissive hypercapnia (PaCO2 rose to ~48, pH ~7.30) was tolerated — did NOT increase mortality
Key finding
Fewer ventilator days and fewer organ failures in the low-Vt group
Clinical bottom line
The MOST IMPACTFUL ICU trial ever — changed ventilation practice worldwide. Vt 6 mL/kg PBW + Pplat <30 = standard of care for ALL ventilated patients with ARDS. Mortality reduced from 40% to 31%
Amato 2015 — Driving pressure and survival (PMID 25693014)
Source
NEJM — individual patient data meta-analysis of 3,562 patients from 9 RCTs
Objective
Which ventilatory variable best predicts survival in ARDS?
Key finding
Driving pressure (delta P = Pplat - PEEP) was the STRONGEST predictor of survival — stronger than Vt, Pplat, or PEEP alone
Threshold
Delta P >15 cmH2O = increased mortality. Each 1 cmH2O increase above 15 = ~5% increase in mortality
Key finding
Among patients receiving Vt 6 mL/kg (the ARDSNet standard), those with delta P <15 had significantly better survival than those with delta P >15
Clinical bottom line
Delta P is the BEST single ventilatory parameter for VILI risk stratification — target <15 cmH2O. It captures the interaction between Vt, PEEP, and lung compliance in one number
SAQ — Ventilator settings in a small, severely diseased 'baby lung'
10 minutes · 10 marks
A 65-year-old woman (height 160 cm) with severe ARDS from bacterial pneumonia (PaO2/FiO2 95 on FiO2 0.8, PEEP 12) is being ventilated. Her current settings are Vt 480 mL, RR 28, and an inspiratory hold gives a plateau pressure of 32 cmH2O. Critically appraise her ventilator settings and outline a lung-protective strategy.
SAQ — The obese ARDS patient and transpulmonary-pressure-guided PEEP
10 minutes · 10 marks
A 48-year-old man (BMI 48, height 175 cm) with severe ARDS from influenza pneumonia has refractory hypoxaemia on FiO2 0.9, PEEP 10, with a plateau pressure of 34 cmH2O. The team is reluctant to raise PEEP for fear of volutrauma. An oesophageal balloon is placed and reads 18 cmH2O at end-expiration. Discuss the role of transpulmonary pressure and how it should alter your management.
Clinical pearls
Red flags
Prognosis
VILI outcomes — the impact of lung-protective ventilation
| Strategy | Mortality in ARDS | Evidence |
|---|---|---|
| Traditional Vt (12 mL/kg) + high Pplat | 40% | ARDSNet control arm |
| Low Vt (6 mL/kg) + Pplat <30 | 31% | ARDSNet intervention arm — 22% relative reduction (NNT=11) |
| Low Vt + delta P <15 | ~25% | Amato 2015 — delta P <15 further reduces mortality |
| Low Vt + prone + ECMO | ~20-25% | For moderate-severe ARDS (PROSEVA, EOLIA) |
| VILI in non-ARDS patients | Variable | Serpa Neto 2014 — low Vt beneficial even without ARDS |
Key trials and evidence
Serpa Neto 2014 — Low Vt in non-ARDS patients (PMID 24811940)
Source
Systematic review and meta-analysis — 20 RCTs, 2,833 patients without ARDS
Population
Mechanically ventilated patients WITHOUT ARDS (surgical, medical)
Intervention
Low Vt (6-8 mL/kg) vs high Vt (10-15 mL/kg)
Primary outcome
Low Vt reduced lung injury development (ARR 2.4%), lung infection, and mortality
Key finding
Even patients without ARDS benefit from lung-protective ventilation — VILI is not exclusive to ARDS
Clinical bottom line
ALL mechanically ventilated patients should receive low Vt (6-8 mL/kg PBW), not just ARDS patients. VILI prevention is universal
Talmor 2008 — Oesophageal pressure-guided PEEP (PMID 19001507)
Source
Randomised trial — 61 patients with ALI/ARDS
Intervention
PEEP titrated by oesophageal pressure (target end-expiratory P_L >0) vs standard ARDSNet PEEP/FiO2 table
Primary outcome
Improved oxygenation (PaO2/FiO2) in the oesophageal pressure-guided group
Trend
Mortality trended towards benefit (22% vs 37%, p=0.19 — not statistically significant)
Clinical bottom line
Oesophageal balloon manometry allows per-patient PEEP optimisation — particularly useful in obese patients and severe ARDS where standard PEEP tables are inadequate
Stress and strain — the physics of VILI
VILI is fundamentally a problem of excessive mechanical stress (force per unit area, ~ pressure) and strain (change in lung volume relative to resting lung volume). Chiumello et al. measured transpulmonary pressure (stress) and the ratio Vt / end-expiratory lung volume (strain) in ARDS patients and showed that the lung behaves as a near-linear elastance: stress = specific elastance × strain, with a threshold strain >2 (i.e. tidal change larger than twice the resting lung volume) associated with overt VILI.[11] The clinical translation is that a "normal" Vt of 6 mL/kg PBW generates very high strain when the aerated ("baby") lung is small — which is exactly why ARDS patients need low Vt, and why delta P (a bedside strain surrogate) predicts injury.[11][4]
The shear-stress physics of atelectrauma was established by Mead, Takishima and Leith in 1970, who calculated that the stress on a collapsing/reopening alveolus at the interface between open and closed lung can reach ~140 cmH2O for every 30 cmH2O of applied airway pressure — i.e. the local shear is roughly 4.5× the nominal transpulmonary pressure.[13] This is why an apparently "safe" airway pressure can still shred alveoli at the stress-riser interface if PEEP is too low to keep them open.[3][13]
Stress and strain — the physics of VILI at the alveolar level
| Variable | Definition | Bedside surrogate | Injurious threshold |
|---|---|---|---|
| Stress (sigma) | Transpulmonary pressure (P_L = P_aw - P_pl) — force per unit area distending the lung tissue | Plateau pressure corrected by oesophageal pressure (Pplat - P_es) | End-inspiratory P_L >25 cmH2O (Chiumello) |
| Strain (epsilon) | Change in lung volume / resting lung volume (delta V / EELV) — how much the lung is stretched | Driving pressure (delta P = Vt / C_RS) — strain maps linearly to delta P | Strain >2 (Vt >2× aerated lung volume) = VILI |
| Specific elastance | Stress / strain — near-constant (~13.7 cmH2O per unit strain in humans) | Computed from stress and strain if both measured | Used to estimate safe Vt for a given lung size |
| Stress raiser (shear) | Local stress concentration at the open/collapsed lung interface during cyclic reopening | Atelectrauma — minimised by PEEP that prevents end-expiratory collapse | ~4.5× applied pressure (Mead) — drives injury even at "safe" Pplat |
| Energising power (mechanical power) | Energy delivered to the lung per unit time = f(Vt, RR, PEEP, flow, I:E) | Mechanical power >17 J/min associated with VILI and mortality | Newer integrative metric (Gattinoni) — captures cumulative injury load |
PEEP titration strategies compared
There is no universal optimal PEEP — the right PEEP is the one that keeps recruitable alveoli open (preventing atelectrauma) without overdistending already-open units (causing volutrauma). The Briel 2010 individual-patient-data meta-analysis of three RCTs (LOVS, Express, ALVEOLI; n=2,299) found that a higher-PEEP strategy overall did not reduce mortality, but in the subgroup with PaO2/FiO2 <200 (i.e. moderate–severe ARDS) higher PEEP was associated with improved survival.[12] PEEP must therefore be individualised, not applied as a blanket high- or low-value strategy.
PEEP titration methods — pros, cons and when to use each
| Method | How it works | Pros | Cons / pitfalls |
|---|---|---|---|
| ARDSNet PEEP/FiO2 table | Paired PEEP/FiO2 steps (lower or higher PEEP arm) | Simple, validated in ARDSNet, no special equipment | Ignores individual compliance/recruitability — one-size-fits-most |
| Best compliance (decremental/incremental PEEP) | Step PEEP up/down by 2 cmH2O; pick PEEP giving best respiratory-system compliance (= lowest delta P for given Vt) | Cheap, bedside, captures patient-specific recruitability | Respiratory-system compliance includes chest wall — can mislead if chest wall stiff |
| Oesophageal pressure-guided (transpulmonary pressure) | Target end-expiratory P_L >0 and end-inspiratory P_L <25 (Talmor) | True lung-distending pressure; ideal in obesity, abdominal compartment, stiff chest wall | Invasive catheter, cardic bias of oesophageal reading, limited availability |
| Electrical impedance tomography (EIT) | Regional aeration mapping — pick PEEP that maximises dependent aeration without non-dependent overdistension (collapse/overdistension cross-point) | Regional, real-time, non-invasive | Expensive hardware, operator-dependent interpretation |
| Stress index (P-t curve shape) | Pressure-time curve during constant-flow inflation: index 0.9–1.1 = safe; <0.9 = atelectrauma (tidal recruitment); >1.1 = overdistension | Single-breath, bedside | Needs constant-flow mode; poorly validated prospectively |
Approach to a high driving pressure
When delta P remains >15 cmH2O despite Vt 6 mL/kg PBW, do NOT simply accept it — every 1 cmH2O above 15 adds ~5% to mortality.[2] Work through the contributors systematically: the commonest fix is further reducing Vt (to 4 mL/kg, accepting deeper permissive hypercapnia), then asking whether the lung is recruitable (if so, PEEP titration up — paradoxically lowering delta P by improving compliance), and finally excluding reversible extra-parenchymal causes (tension pneumothorax, large pleural effusion, abdominal compartment syndrome, auto-PEEP).
Stepwise approach when driving pressure (delta P) is >15 cmH2O
- RE-CHECK the measurement: inspiratory hold with no patient effort (adequately sedated, no double trigger). Re-confirm Pplat and total PEEP; delta P = Pplat - set PEEP (NOT - total PEEP if auto-PEEP present)
- REDUCE Vt to 4 mL/kg PBW (the lowest practically tolerated). Re-check delta P — if now <15, target met; accept permissive hypercapnia (pH >7.20)
- ASSESS RECRUITABILITY: perform a recruitment manoeuvre (e.g. CPAP 40 cmH2O for 40 s) — if PaO2 rises and delta P falls, the lung is recruitable → titrate PEEP upward in 2 cmH2O steps to the value with best compliance / lowest delta P
- EXCLUDE EXTRA-PARENCHYMAL CAUSES: chest X-ray/POCUS for pneumothorax or large pleural effusion (drain if present); measure bladder pressure if abdominal distension (abdominal compartment syndrome raises chest-wall pressure → delta P)
- CHECK AUTO-PEEP (expiratory hold) — if COPD/asthma: reduce RR, shorten inspiratory time, increase expiratory time; the auto-PEEP itself inflates delta P calculation
- CONSIDER PRONE POSITIONING for moderate–severe ARDS (PaO2/FiO2 <150): prone improves homogeneity of ventilation → lowers delta P and mortality (PROSEVA)[8]
- CONSIDER NEUROMUSCULAR BLOCKADE early (≤48 h) in severe ARDS to abolish dyssynchrony and P-SILI (reduces transpulmonary pressure swings)
- REFER FOR VV-ECMO if delta P remains unacceptably high with refractory hypoxaemia/hypercapnia despite the above (EOLIA criteria)[9]
Tidal hyperinflation despite "lung-protective" Vt
Terragni et al. demonstrated that even with ARDSNet-compliant Vt 6 mL/kg, a substantial subset of ARDS patients still develop tidal alveolar overdistension (volutrauma). Using CT in 30 ARDS patients ventilated at Vt 6 mL/kg + Pplat ≤30, they found that in patients with low thoracopulmonary compliance the plateau pressure was concentrated in the aerated, non-dependent lung — producing CT-evident hyperinflation in 33% of patients, with a rise in inflammatory cytokines (a biomarker of biotrauma) in exactly that subgroup.[10] Reducing Vt further (to ~4 mL/kg) abolished the hyperinflation and the cytokine rise. Lesson: Vt 6 mL/kg is a starting point, not an endpoint — drive the Vt down (or PEEP up) until delta P is acceptable.[10][3]
Terragni 2007 — Tidal hyperinflation at low Vt (PMID 17038660)
Source
Am J Respir Crit Care Med — CT + BAL cytokine study, 30 ARDS patients
Population
ARDS, all ventilated with ARDSNet protocol (Vt 6 mL/kg, Pplat ≤30)
Intervention
Reduced Vt from 6 to 4 mL/kg in the subset with CT hyperinflation
Key finding
One-third of 'properly' ventilated ARDS patients still had CT-evident tidal hyperinflation + elevated BAL cytokines (biotrauma)
Key finding
Reducing Vt to 4 mL/kg eliminated the hyperinflation and the cytokine rise
Clinical bottom line
ARDSNet Vt 6 mL/kg is a ceiling, not a target — titrate Vt (and PEEP) down/up using delta P, not the protocol number alone
PEEP strategy trials
Briel 2010 — Higher vs lower PEEP meta-analysis (PMID 20197533)
Source
JAMA — individual patient data meta-analysis of 3 RCTs (LOVS, Express, ALVEOLI), n=2,299
Population
Patients with ALI/ARDS
Intervention
Higher vs lower PEEP strategy (same low Vt)
Primary outcome
No overall mortality difference in the full cohort
Subgroup finding
In the more hypoxaemic subgroup (PaO2/FiO2 <200), higher PEEP was associated with lower mortality — supporting individualised higher PEEP in moderate-severe ARDS
Clinical bottom line
A blanket higher-PEEP strategy is not beneficial for all — titrate PEEP up in moderate-severe ARDS, avoid routine high PEEP in mild ARDS/non-ARDS
ART 2017 — Alveolar Recruitment for ARDS Trial (PMID 28973363)
Source
JAMA — multicentre RCT, 1,010 patients with moderate-severe ARDS
Population
ARDS with PaO2/FiO2 <200
Intervention
Aggressive lung recruitment (incremental PEEP to 45 cmH2O + sustained inflation) + titrated PEEP vs standard ARDSNet low-PEEP
Primary outcome
28-day mortality HIGHER in the recruitment group (27.8% vs 19.3%, adjusted) — trial stopped early for harm
Key finding
Aggressive maximal recruitment causes harm — increased barotrauma/volutrauma, hypotension, and death
Clinical bottom line
Do NOT perform aggressive staircase recruitment to very high pressures. Recruitment should be gentle and individualised; aggressive recruitment to 45 cmH2O is harmful
PROSEVA 2013 — Prone positioning in severe ARDS (PMID 23688302)
Source
NEJM — multicentre RCT, 466 patients with severe ARDS (PaO2/FiO2 <150)
Population
Severe ARDS, already on low-Vt ventilation
Intervention
Prone positioning for ≥16 consecutive hours/day vs continued supine
Primary outcome
28-day mortality 16.0% (prone) vs 32.8% (supine) — p<0.001; NNT≈6
Key finding
Proning nearly halved mortality in severe ARDS — by improving ventilation homogeneity (less overdistension of non-dependent, less atelectrauma of dependent lung) and reducing delta P
Clinical bottom line
Early prone positioning (≥16 h/day) is indicated for all severe ARDS (PaO2/FiO2 <150) after low-Vt ventilation is established
EOLIA 2018 — VV-ECMO for severe ARDS (PMID 29791822)
Source
NEJM — international multicentre RCT, 249 patients with very severe ARDS
Population
Severe ARDS (PaO2/FiO2 <50 for >3 h, or <80 for >6 h) despite optimised ventilation
Intervention
Early VV-ECMO vs continued conventional lung-protective ventilation (with crossover allowed)
Primary outcome
60-day mortality 35% (ECMO) vs 46% (control) — p=0.09, NOT statistically significant (but high crossover: 28% of control crossed to ECMO)
Key finding
ECMO is the ultimate VILI-avoidance strategy — it rests the lung (ultra-protective Vt) while maintaining gas exchange via the circuit
Clinical bottom line
ECMO remains a reasonable rescue for refractory severe ARDS where conventional lung-protective ventilation cannot achieve safe delta P / gas exchange; the trial's non-significance was confounded by crossover
Additional red flags
Extended clinical pearls
References
- [1]Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome N Engl J Med, 2000.PMID 10793162
- [2]Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome N Engl J Med, 2015.PMID 25693014
- [3]Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons from experimental studies Am J Respir Crit Care Med, 1998.PMID 9445314
- [4]Slutsky AS, Ranieri VM. Ventilator-induced lung injury N Engl J Med, 2013.PMID 24283226
- [5]Talmor D, Sarge T, Malhotra A, et al. Mechanical ventilation guided by esophageal pressure in acute lung injury N Engl J Med, 2008.PMID 19001507
- [6]Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between tidal volume size, duration of ventilation, and sedation needs in patients without acute respiratory distress syndrome: an individual patient data meta-analysis Intensive Care Med, 2014.PMID 24811940
- [7]Writing Group for the ART Investigators. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial JAMA, 2017.PMID 28973363
- [8]Guérin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome N Engl J Med, 2013.PMID 23688302
- [9]Combes A, Hajage D, Capellier G, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome N Engl J Med, 2018.PMID 29791822
- [10]Terragni PP, Rosboch G, Tealdi A, et al. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome Am J Respir Crit Care Med, 2007.PMID 17038660
- [11]Chiumello D, Carlesso E, Cadringher P, et al. Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome Am J Respir Crit Care Med, 2008.PMID 18451319
- [12]Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis JAMA, 2010.PMID 20197533
- [13]Mead J, Takishima T, Leith D. Stress distribution in lungs: a model of pulmonary elasticity J Appl Physiol, 1970.PMID 5442255
- [14]Dreyfuss D, Basset G, Soler P, Saumon G. Intermittent positive-pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats Am Rev Respir Dis, 1985.PMID 3901844