Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial

Abstract

Importance: It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS).

Objective: To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy.

Design, setting, and participants: A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands.

Interventions: Invasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484).

Main outcomes and measures: The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax.

Results: In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, -0.27 [95% CI, -1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [-1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; -0.60 [-3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55).

Conclusions and relevance: In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy.

Trial registration: ClinicalTrials.gov Identifier: NCT02153294.

Figure 1.. Flow of Patients in the PReVENT Trial

^aIncludes chronic obstructive pulmonary disease (COPD) stage III and IV in the GOLD classification, pneumectomy or lobectomy, and restrictive pulmonary disease. COPD GOLD III is defined as severe obstruction of the airways, with FEV₁/FVC<70%, FEV₁ between 30% and 50% of predicted values. COPD GOLD IV is defined as very severe obstruction of the airways with FEV₁/FVC<70%, FEV₁ below 30% of predicted values.

Figure 2.. Kaplan-Meier Estimates for Patients in the Low Tidal Volume and Intermediate Tidal Volume Ventilation Groups

A, Median (IQR) observation period for the duration free from invasive ventilation was 4.4 days (3.7 to 5.1) for the low tidal volumes group and 4.3 days (3.4 to 5.2) for the intermediate tidal volumes group; P value for the Schoenfeld residuals was .68. B, Median observation time for survival was not computed for 90-day mortality because the minimum value observed is 0.60; P value for the Schoenfeld residuals was .13. C, Median (IQR) observation period for intensive care unit length of stay was 8.0 days (7.0 to 8.0) for the low tidal volumes group and 8.0 days (6.0 to 9.0) for the intermediate tidal volumes group; P value for the Schoenfeld residuals was 0.21. D, Median (IQR) observation period for hospital length of stay was 21.0 days (19.0 to 23.0) for the low tidal volumes group and 21.0 days (20.0 to 24.0) for the intermediate tidal volumes group; P value for the Schoenfeld residuals was .82.