August 22, 2016

Article Review

ARDS is a common pathology and is still associated today with significant mortality and morbidity. Over the last two decades, the understanding of the pathophysiology of ARDS drastically has changed the ventilator strategy adopted in these patients. Lung protective ventilation has been more readily utilised in order to reduce the mechanical stresses on the lungs and has been associated with survival benefits in randomised clinical trials and is now the standard of care in ARDS (1).

The open lung ventilation approach involves increasing the level of PEEP in combination with protective ventilation (2). However, the best level of PEEP remains elusive and controversial. 

The EPvent trial (3) demonstrated that a ventilator strategy using oesophageal pressure (as an estimate of the pleural pressure) to titrate the level of PEEP in order to maintain a positive transpulmonary pressure, improves oxygenation and compliance in patients with ARDS compared to a control group titrating PEEP according to ARDS network standard of care recommendations.
Amato and al. recently reported that driving pressure of the respiratory system is a good marker for the severity of lung injury (4). High levels of driving pressure of the respiratory system were correlated with increased mortality despite the implementation of lung protective ventilation. Nonetheless, respiratory system driving pressure does not account for variable chest wall compliance in patients with ARDS. 

The authors of this study retrospectively analysed the data of 56 patients included in the EPvent trial and examined the relationships between respiratory system driving pressure, transpulmonary driving pressure, pulmonary mechanics and 28-day mortality (5). They postulate that chest wall compliance and pleural pressure vary widely between patients and therefore by eliminating the effect of the chest wall, the transpulmonary driving pressure should be a better marker for monitoring and prognostication of ARDS.

56 patients had an oesophageal balloon-catheter inserted in order to estimate transpulmonary pressure (airway pressure minus total PEEP). In the intervention group, PEEP was adjusted to achieve a positive transpulmonary pressure of 0-10 cmH2O at end-expiration. The control group had PEEP titrated as per standard low PEEP ARDSnet tables. The driving pressure of the respiratory system (plateau pressure minus PEEP), the transpulmonary driving pressure (end-inspiratory transpulmonary pressure minus end expiratory transpulmonary pressure) and pulmonary mechanics were examined at baseline, 5 minutes and 24 hours after a recruitment maneuver in these 2 groups. The 28-day survivors were compared to the non-survivors and the intervention group was compared to the control group.


  • The baseline characteristics were very well balanced between the 29 patients in the control group and the 27 patients in the intervention group.
  • PEEP was similar in the 2 groups at baseline (13 cm H2O in the control group vs 12,7 cm H2O in the intervention group) but was significantly higher at 5 min (12,9cm vs 20 cmH2O) and 24h (11 vs 19,3 cm H2O) in the intervention group.
  • There was no difference at baseline and 5 minutes in respiratory system or transpulmonary pressure between the 28-day survivors and non-survivors. At 24 hours, survivors showed a significant decrease in both respiratory system and transpulmonary driving pressure.
  • There is a strong correlation between the variation of the driving pressures and the elastance between baseline to 24 hours that does not appear to be related to difference in Vt between the intervention group and the control group.
  • Transpulmonary and respiratory driving pressure and their variations (baseline to 5 min and baseline to 24 h) seem to be correlated by a strong linear relationship.

Strategies titrating PEEP to target positive transpulmonary pressure in ARDS result in lower respiratory system and transpulmonary driving pressure secondary to improved elastance. Decreased respiratory system and transpulmonary driving pressures at 24 h were associated with improved 28-day mortality.

The results of this study correlate with previously reported trials and suggest that low tidal volumes and high levels of PEEP are a key component of a safer ventilation strategy only if this strategy results in a lower pulmonary driving pressure. However, this study is underpowered to determine a difference in the prognostic value for mortality of respiratory system and the transpulmonary driving pressure. It appears unclear if driving pressure is a parameter to target at the bedside (as for tidal volume or plateau pressure) or simply a marker of poorly compliant lungs.

This study performed by Baedorf Kassis contributes to the literature advocating for a more individualised bedside approach to target the best PEEP using oesophageal pressure to account for chest wall dynamics in patients with ARDS. 

In spite of that, some limitations should be noted. The study is single-centred and is a retrospective analysis of a previously published study. The small size of the sample limits the impact of the statistical analysis and prevents any attempt to generalise the results.  
Further large-scale prospective studies should evaluate the role of respiratory system and transpulmonary driving pressures as a tool to optimise ventilation settings and their prognostic values in patients with ARDS.

Article review prepared by Stéphane Ledot and Antonella Tosinas on behalf of the ESICM Journal Review Club.


1. The Acute respiratory distress syndrome network (2000). 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 342: 1301-1308

2. Matthias Briel, Maureen Meade, Alain Mercat et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome. JAMA 2010; 303 (9): 865-873

3. Talmor D, Sarge T, Malhotra A et al (2008). Mechanical ventilation guided by esophageal pressure acute lung injury. N Engl J Med 359:2095-2104

4. Marcelo B.P Amato, Maureen O.Meade, Arthur S. Slutsky et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 372; 8: 747-755

5. Elias Baedorf Kassis, Stephen H.Loring and Daniel Talmor. Mortality and pulmonary mechanics in relation to respiratory system and transpulmonary driving pressures in ARDS. Intensive Care Med 2016 Aug;42(8):1206-13. doi: 10.1007/s00134-016-4403-7. Epub 2016 Jun 18.



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