Effect of a Low vs. Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS:
A Randomized Clinical Trial.
Writing Group for the PReVENT Investigators .  Simonis. JAMA. 2018; 320(18):1872-1880

All right pop quiz, hotshot. Altered patient gets intubated in the ED.  He’s almost to the ICU. The RT asks you for vent settings.  What do you do Jack. What do you do …


In this somewhat blinded RCT of low (4-6 ml/kg) versus intermediate (10 ml/kg) in patients WITHOUT ARDS for the composite primary outcome of number of ventilator-free days AND alive at day 28, there was not difference between the 2 groups. Setting your tidal volume anywhere less than or equal to 10 is probably fine in the patients without ARDS/Lung issues.


This study was a randomized clinical trial conducted at ICUs of 6 hospitals in the Netherlands. The trial did utilize concealed allocation and intention to treat analysis. The trial enrolled patients who received invasive ventilation just before or after admission to the ICU and who were expected to be intubated for more than 24 hours. Patients were to be randomized within 1 hour of initiation of ventilation in the ICU. Exclusion criteria were the presence of ARDS, strictly following the criteria of the Berlin Definition for ARDS. Patients were randomized in a 1:1 ratio to a low or intermediate tidal volume ventilation strategy group.  Patients assigned to the low tidal volume group started at a tidal volume of 6 mL/kg predicted body weight (PBW) and received either volume-controlled or pressure support ventilation. Tidal volume was then decreased by 1 mL/kg PBW every hour to a minimum of 4 mL/kg PBW. With pressure support ventilation, the lowest level of pressure support was used to reach the target tidal volume with a minimum of 5 cm H2O. If tidal volume increased more than 8 mL/kg PBW with the minimum pressure support, this was to be accepted.

Patients assigned to the intermediate tidal volume group started at a tidal volume of 10 mL/kg PBW using a volume-controlled ventilation mode. If the plateau pressure exceeded 25 cm H2O, tidal volume was decreased in increments of 1 mL/kg PBW per hour. Additional use of analgesia, sedation or muscle relaxants, with the purpose of allowing the assigned ventilation strategy, was not permitted.

The primary (composite) outcome(s) was the number of ventilator-free days AND alive at day 28, defined as the number of days that a patient was alive and free from invasive ventilation. Secondary outcomes included ICU and hospital length of stay; ICU, hospital, and 28- and 90-day mortality; and the occurrence of pulmonary complications, including the development of new ARDS, ventilator-associated pneumonia, severe atelectasis, and pneumothorax. Mortality at day 28 was not included as a secondary outcome in the original protocol but was subsequently added in the updated protocol. A sample size of 952 patients (476 per group) was estimated to have 80% statistical power to show a difference of 1 ventilator-free day at day 28 allowing for a 20% dropout rate.  In a pre-specified exploratory analysis, the effects of the intervention on the primary outcome were investigated in subgroups: with vs. without pneumonia; with vs. without sepsis; PaO2/FiO2 less than or equal to 200 vs. greater than 200, etc.


Between September 1, 2014, and August 20, 2017, 3695 patients were screened. More than 80% of the patients were admitted to the ICU for a medical reason. The most frequent reason for invasive ventilation was cardiac arrest.

The median time between the start of ventilation and randomization was 0.88 hours (IQR, 0.36-2.01).  During the first 3 days of ventilation, tidal volumes and airway pressures were significantly different among the groups. Plateau and driving pressure were lower and respiratory rate was higher in the low tidal volume group than in the intermediate tidal volume group, while minute ventilation and PEEP did not differ significantly between groups.

For the primary outcome there was no difference between the two groups. Patients in both groups had a median of 21 ventilator-free days  (mean difference, –0.27 [95% CI −1.74 to 1.19]; P = .71). There was no significant difference in ANY of the secondary outcomes nor in any of the subgroups. The differences on day 3 were only in the respiratory variables. In the low tidal volume the groups had a higher paCO2 (42 vs. 38), more patients with a pH <7.25 (7 vs. 1), and more respiratory acidosis (17 vs. 8). The driving pressure (Plateau minus the PEEP, which some argue as the value most consistent with barotrauma) was lower in the Low TV group vs. Intermediate (11 vs. 14).


Thus it would seem on its face that there may be no differences between low TV and intermediate TV for patients without ARDS. This may be due to the fact that we aren’t talking low vs. high TV but intermediate TV. There were some respiratory parameters such as more acidosis and lower driving pressures in the low TV group but for both groups the driving pressure was under 15 which some would say is the “safe” range.  Of note respiratory rate was not elevated and the minute ventilation was not different suggesting that the VT may not have been that different. Overall there is a range of TV’s that are probably fine for the patient














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