POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients II (POSITiVE II) - a randomized clinical trial

1.1 Postoperative ventilation
Postoperative ventilation is often needed after cardiac surgery. Over the last
decades it has become increasingly clear that ventilation has a strong
potential to injure the lungs, and emphasis has been put on using lung-
protective ventilator settings. Lung-protective ventilation consists of
ventilation using a properly-sized tidal volume (VT) to prevent volutrauma and
barotrauma, applying low pressures and energy to avoid energy trauma, and
restrictions in the use of oxygen to minimize the risk of chemotrauma.

1.2 ICU nursing staff workload
Applying lung-protective ventilation can be challenging and is often time-
consuming, as it requires complex titrations of ventilator settings according
to changing and individual needs of a patient, also in patients after cardiac
surgery. This is important in intensive care units (ICUs) that are facing
increasing challenges due to shortages in nursing staff, in particular during
surges of patients in need for respiratory support, as witnessed in the recent
coronavirus disease 2019 pandemic. Diminished ICU nursing staff is a growing
problem, and every effort should be taken to reduce the workload of often
overtasked and overcharged ICU nurses.

1.3 Automated, or closed-loop ventilation
Automated, or closed-loop ventilation is increasingly attractive for clinical
use, as it improves the quality of ventilation and potentially offers support
to diminished ICU nursing staff. Closed-loop modes are progressively available
on ventilators for use in critically ill patients. With INTELLiVENT-Adaptive
Support Ventilation (ASV), one of the most sophisticated forms of closed-loop
ventilation, those ventilator settings that are typically under control of the
ICU nursing staff are under control of algorithms that form the basis of this
form of closed-loop ventilation. INTELLiVENT-ASV targets ventilation and
oxygenation goals based on lung mechanics, whereby it adjusts, breath-by-
breath, VT, respiratory rate (RR), positive end-expiratory pressure (PEEP), and
fraction of oxygen in inspired air (FiO2). Furthermore, INTELLiVENT-ASV
facilitates weaning by using a weaning protocol and spontaneous breathing
trials. Several studies have shown INTELLiVENT-ASV to be safe and effective
with regard to lung-protective ventilation.

The here proposed randomized clinical trial, named *POStoperative INTELLiVENT-
adaptive support VEntilation in cardiac surgery patients II* (POSITiVE II),
compares INTELLiVENT-ASV with conventional ventilation in patients planned for
elective cardiac surgery and expected to need postoperative ventilation in an
intensive care unit for at least 2 hours.
2.1 Primary objective
The primary objective is to compare the two ventilation strategies with respect
to quality of ventilation.
2.2 Secondary objectives
One major secondary objective is to compare the two ventilation strategies with
respect to ICU nursing staff workload, using time and motion observations; we
will also compare the two ventilation strategies with respect to patient-
centered endpoints like duration of ventilation, and length of stay in ICU.
2.3 Hypotheses
We hypothesize that INTELLiVENT-ASV is superior to conventional ventilation
with respect to the quality of ventilation in postoperative ventilation in
patients after cardiac surgery. We further hypothesize that INTELLiVENT-ASV is
non-inferior to, i.e., as good as conventional ventilation with respect to
duration of ventilation and length of stay in ICU.

*POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery
patients II* (POSITiVE II) is an investigator-initiated, international,
multicenter, parallel, randomized clinical trial in patients after cardiac
surgery. The study will be conducted according to the Good Clinical Practice-
guidelines and comply with the principles of the Declaration of Helsinki,
national and international regulatory requirements and general data protection
regulations. The study is registered in a public registry and the study
protocol with its statistical analysis plan will be prepublished.

The intervention tested is named *INTELLiVENT-ASV*, a closed-loop mode of
ventilation available at Hamilton Medical AG ventilators (Hamilton Medical AG,
Bonaduz, Switzerland) and intended to be used in patients that need ventilation
in an intensive care unit (ICU). INTELLiVENT-ASV is a fully automated mode of
ventilation, targeting the lowest work and force of breathing, through breath-
by-breath adaptation of tidal volume (VT) and respiratory rate (RR), and
positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (FiO2)
based on patient activity, airway pressures and continuous pulse oximetry
readings and end- tidal carbon dioxide monitoring. It also uses a weaning
protocol and spontaneous breathing trials to facilitate weaning.

Patient burden and risks are low, the collection of general data from hospital
charts and (electronic) medical records systems causes no harm to the patients;
the patient will not experience any discomfort because they are still sedated
during postoperative ventilation in the ICU. INTELLiVENT-ASV and conventional
ventilation are standard care, but will be protocolized in this study.