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JAMA. 2018 Nov 13;320(18):1872-1880. doi: 10.1001/jama.2018.14280.

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

Author information

Department of Intensive Care & Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, Amsterdam, the Netherlands.
Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil.
Department of Intensive Care, Gelre Hospitals, Apeldoorn, the Netherlands.
Department of Intensive Care, Westfriesgasthuis, Hoorn, the Netherlands.
Department of Intensive Care, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.
Department of Intensive Care Tergooi, Hilversum, the Netherlands.
Department of Intensive Care, Leiden University Medical Center, Leiden, the Netherlands.
Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Intensive Care & REVIVE Research VUmc Intensive Care, VU Medical Center, Amsterdam, the Netherlands.
Department of Anesthesiology and Intensive Care, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Dresden, Germany.
Department of Surgical Sciences and Integrated Diagnostics, San Martino Policlinico Hospital, IRCCS for Oncology, University of Genoa, Genoa, Italy.
Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand.



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


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.


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.


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: Identifier: NCT02153294.

[Indexed for MEDLINE]
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