To support seriously ill patients with a breathing machine, doctors must choose how the ventilator delivers each breath. Three common modes are volume control, pressure control, and adaptive pressure control, but whether mode choice affects outcomes was uncertain. The MODE trial compared these modes in 566 critically ill patients in a medical ICU. The study showed similar days alive and free from the ventilator across groups, with differences in breathing patterns that may warrant further study.

The MODE trial was a pragmatic, cluster-randomized, crossover pilot trial conducted in a medical ICU evaluating whether the choice of initial ventilator mode affects outcomes for critically ill adults receiving invasive mechanical ventilation. Patients were assigned by month to receive volume control, pressure control, or adaptive pressure control during continuous mandatory ventilation, and the primary outcome was ventilator-free days through 28 days. Among 566 patients, ventilator-free days were similar across groups (median 23, 22, and 24 days, respectively; P = .60). The trial demonstrated feasibility for testing ventilator mode using a pragmatic crossover design and identified differences in intermediate ventilation metrics that support evaluation in a larger trial.

MODE Trial (Ventilator Mode and Ventilator-Free Days)

When critically ill patients need a breathing machine, clinicians must choose a mode of mechanical ventilation. The three most common modes used for mandatory ventilation are volume control, pressure control, and adaptive pressure control, but it is uncertain whether the initial choice of ventilator mode affects outcomes. The MODE trial compared these commonly used ventilator modes in routine ICU care to evaluate whether mode selection influences duration of mechanical ventilation and patient outcomes.

Importance

Mechanical ventilation is a life-sustaining therapy in critical illness, but it can also contribute to lung injury and other complications. Before the MODE Trial, it was unknown whether the choice of ventilator mode during mandatory ventilation affects clinical outcomes for critically ill adults.

Objective

To determine the effects of volume control, pressure control, and adaptive pressure control ventilation modes on ventilator-free days through 28 days among critically ill adults receiving invasive mechanical ventilation.

Interventions

In a pragmatic, cluster-randomized, crossover pilot trial conducted in a medical ICU between November 1, 2022, and July 31, 2023, patients were assigned by month to receive volume control, pressure control, or adaptive pressure control during continuous mandatory ventilation. The primary outcome was ventilator-free days through 28 days.

Results

Among 566 patients included in the primary analysis, adherence to the assigned mode during the first 72 hours was high (median proportion of assessments in the assigned mode 100% in each group). The median number of ventilator-free days was 23 days in the volume control group, 22 days in the pressure control group, and 24 days in the adaptive pressure control group (P = .60). Intermediate ventilation patterns differed across groups, including the percentage of breaths with tidal volume >8 mL/kg predicted body weight, which was higher with pressure control than with volume control or adaptive pressure control.

Conclusions and Relevance

In this pragmatic pilot trial, ventilator-free days were similar among patients assigned to volume control, pressure control, or adaptive pressure control. The trial demonstrated feasibility of a cluster-randomized crossover design for ventilator mode and identified differences in intermediate ventilation measures that support evaluation in a larger trial.

ClinicalTrials.gov Identifier: NCT05563779
Manuscript Title: Effect of Ventilator Mode on Ventilator-Free Days in Critically Ill Adults: A Randomized Clinical Trial
Journal: Chest
PMID: 40189043

Seitz KP, Lloyd BD, Wang L, Shotwell MS, Qian ET, Muhs AL, Richardson RK, Rooks JC, Hennings-Williams V, Sandoval CE, Richardson WD, Morgan TL, Thompson AN, Hastings PG, Ring TP, Stollings JL, Talbot EM, Krasinski DJ, DeCoursey BR, Marvi TK, DeMasi SC, Gibbs KW, Self WH, Mixon AS, Rice TW, Semler MW, Casey JD; Pragmatic Critical Care Research Group. Effect of Ventilator Mode on Ventilator-Free Days in Critically Ill Adults: A Randomized Clinical Trial. Chest. 2025 Oct;168(4):912-923. doi: 10.1016/j.chest.2025.03.024. Epub 2025 Apr 4. PMID: 40189043

Many patients in the intensive care unit (ICU) receive oxygen through a breathing machine. Doctors, nurses, and respiratory therapist adjust the amount of oxygen given through the breathing machine to target oxygen levels, but the ideal oxygen level to target is unknown. To understand which oxygen level is best for patients, we conducted a research study called the PILOT study. A total of 2,541 patients on breathing machines in the Vanderbilt intensive care unit participated in the study and had their clinicians target an oxygen level of 90%, 94%, or 98%. The results of the study suggested that patients did equally well when their clinicians targeted an oxygen level of 90%, 94%, or 98%.

Background: Invasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen- saturation target that will optimize clinical outcomes in this patient population remains unknown.

Methods

In a pragmatic, cluster-randomized, cluster-crossover trial conducted in the emergency department and medical intensive care unit at an academic center, we assigned adults who were receiving mechanical ventilation to a lower target for oxygen saturation as measured by pulse oximetry (Spo2) (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilator-free days) through day 28. The secondary outcome was death by day 28, with data censored at hospital discharge.

Results

A total of 2541 patients were included in the primary analysis. The median number of ventilator-free days was 20 (interquartile range, 0 to 25) in the lower-target group, 21 (interquartile range, 0 to 25) in the intermediate-target group, and 21 (interquartile range, 0 to 26) in the higher-target group (P = 0.81). In-hospital death by day 28 occurred in 281 of the 808 patients (34.8%) in the lower-target group, 292 of the 859 patients (34.0%) in the intermediate-target group, and 290 of the 874 patients (33.2%) in the higher-target group. The incidences of cardiac arrest, arrhythmia, myocardial infarction, stroke, and pneumothorax were similar in the three groups.

Conclusions

Among critically ill adults receiving invasive mechanical ventilation, the number of ventilator-free days did not differ among groups in which a lower, intermediate, or higher Spo2 target was used.

ClinicalTrials.gov Identifier:
NCT03537937.
Manuscript Title: Oxygen-Saturation Targets for Critically Ill Adults Receiving
Mechanical Ventilation
Journal: New England Journal of Medicine

PMID: 36278971

When a patient requiring a breathing machine is ready to be disconnected from that machine, providing additional oxygen support using a mask over the patient’s mouth (called “non-invasive ventilation”) or a large tube under their nose (called “high flow nasal cannula”) had been reported to decrease the likelihood of the patient needing to be put back on the breathing machine. The PROPER Trial assessed over 750 intensive care unit patients to determine whether additional oxygen support with non-invasive ventilation or high flow nasal cannula reduced the need to go back on a breathing machine within 96 hours after initially being taken off. The results showed that receiving the additional support did not prevent the need to go back on a breathing machine. These findings suggest doctors can provide support with the devices for some patients who they think will benefit, but do not need to provide support with these devices for every patient.

Rationale: Respiratory support (noninvasive ventilation or high-flow nasal cannula) applied at the time of extubation has been reported to reduce reintubation rates, but concerns regarding effectiveness have limited uptake into practice.

Objectives: To determine if providing postextubation respiratory support to all patients undergoing extubation in a medical ICU would decrease the incidence of reintubation.

Methods: We conducted a pragmatic, two-armed, cluster-crossover trial of adults undergoing extubation from invasive mechanical ventilation between October 1, 2017, and March 31, 2019, in the medical ICU of an academic medical center. Patients were assigned to either protocolized postextubation respiratory support (a respiratory therapist-driven protocol in which patients with suspected hypercapnia received noninvasive ventilation and patients without suspected hypercapnia received high-flow nasal cannula) or usual care (postextubation management at the discretion of treating clinicians). The primary outcome was reintubation within 96 hours of extubation.

Measurements and Main Results: A total of 751 patients were enrolled. Of the 359 patients assigned to protocolized support, 331 (92.2%) received postextubation respiratory support compared with 66 of 392 patients (16.8%) assigned to usual care, a difference driven by differential use of high-flow nasal cannula (74.7% vs. 2.8%). A total of 57 patients (15.9%) in the protocolized support group experienced reintubation compared with 52 patients (13.3%) in the usual care group (odds ratio, 1.23; 95% confidence interval, 0.82 to 1.84; P = 0.32).

Conclusions: Among a broad population of critically ill adults undergoing extubation from invasive mechanical ventilation at an academic medical center, protocolized postextubation respiratory support, primarily characterized by an increase in the use of high-flow nasal cannula, did not prevent reintubation compared with usual care.Clinical trial registered with www.clinicaltrials.gov (NCT0328831).

Trial registration: ClinicalTrials.gov NCT03288311.

Keywords: invasive mechanical ventilation; noninvasive respiratory support; reintubation.

Manuscript Title: “Protocolized Postextubation Respiratory Support to Prevent Reintubation: A Randomized Clinical Trial.”

Journal: American Journal of Respiratory and Critical Care Medicine

PMID: 33794131