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Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure–Guided Strategy vs an Empirical High PEEP-FIO2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome

Author(s): Jeremy R. Beitler, Todd Sarge, Valerie M. Banner-Goodspeed, Michelle N. Gong, Deborah Cook, Victor Novack, Stephen H. Loring, Daniel Talmor, for the EPVent-2 Study Group

JAMA. 2019; doi: 10.1001/jama.2019.0555. [Epub ahead of print]

Respiratory critical care

Digest Author(s): Daniel López Padilla / 11 March, 2019

Acute Respiratory Distress Syndrome (ARDS) represents a true challenge for clinicians, giving the well demonstrated harmful effect of high tidal volumes on alveolar tissue1. On this regard, the beneficial consequences of high Positive end expiratory pressure (PEEP) for alveolar recruitment and oxygen maintenance remains unclear.

Chest and abdominal mechanics in ARDS are erratic, hence, Esophageal pressure (EP) as the surrogate gold standard for pleural pressure, might be of use to titrate PEEP in this scenario, in order to avoid ventilator induced lung injury. Until now, data showed that PEEP titration EP-guided was beneficial in terms of survival2, however, it was a single center study and lower PEEP values were used in the control group if one compares them with other trials.

In the multicenter randomized clinical trial carried out by Beitlier et al.3, 202 patients (out of 707 that were screened) admitted for ARDS, defined as a PaO2:FIO2 ≤ 200mmHg onset within the last 36 hours once that all four Berlin Definition criteria were met, were randomized to a PEEP guided by EP group (n=102) or an empirical high PEEP group (n=98). To maintain PaO2:FIO2, the combinations of ventilator FiO2 and PEEP parameters allowed values between 5 to 24 cmH2O in the control group, and transpulmonary pressures (airway pressure measured by the ventilator minus EP) between 0 to 6 cmH2O in the intervention group. The primary endpoint was a ranked composite score that incorporated death and days free from mechanical ventilation through day 28. Various parameters were assessed daily, mean (SD) PEEP the first day on protocol were 17 (6) cm H2O in the EP guided group vs 16 (4) cmH2O in the empirical PEEP-FiO2 group (P = 0.28); after seven days, there were no significant differences in PEEP, transpulmonary pressures or PaO2:FIO2 features between treatment groups. The primary endpoint did not show statistical differences also, along with a series of secondary outcomes that included 60 days or one-year mortality. Statistical power might be low giving that a difference of 10% for the primary outcome was considered for sample size, and one should extrapolate these results carefully. On the one hand it seems that high PEEP is more effective than lower values in general, and in the other hand, costly tools such as EP are not essential to achieve similar clinical outcomes, at least until new trials show differently.

Key points

  1. Ventilator induced lung injury is a true challenge in patients with ARDS, due to alveolar overdistension caused by high tidal volumes and pressures.
  2. Esophageal pressure is the goal standard measurement for pleural pressure, which leads to a correct transpulmonary pressure calculation.
  3. High PEEP seems to be more effective than lower PEEP values.
  4. No differences were found when esophageal pressure was compared to an empiric high PEEP approach.


  1. Vasques F, Duscio E, Cipulli F, Romitti F, Quintel M, Gattinoni L. Determinants and Prevention of Ventilator-Induced Lung Injury. Crit Care Clin. 2018;34:343-356.
  2. Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Toring SH. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008;359:2095-104.
  3. Beitler JR, Sarge T, Banner-Goodspeed VM, Gong MN, Cook D, Novack V, Loring SH, Talmor D; EPVent-2 Study Group. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2019 Feb 18. doi: 10.1001/jama.2019.0555. [Epub ahead of print]"