The goal of this clinical trial is to learn if the new ventilation mode flow-controlled ventilation (FCV) is a more protective mode of ventilation for adult patients after severe burn injury. The main question it aims to answer is:

Does FCV reduce the mechanical power (a key determinant of ventilator-induced lung injury) compared to conventional pressure-controlled ventilation (PCV) during ventilation of patients with burn injury?

Researchers will compare FCV with PCV for up to 70 hours of ventilation to see if the mechanical power is reduced during ventilation of participants being in need of ventilation after severe burn injury.

Ventilation of participants will be controlled by either FCV or PCV. Group-specific ventilation will have the following characteristics:

• FCV: Control of airway flows during inspiration and expiration, use of individualized lower and upper airway pressures and no fixed values for the volumes being inspired and expired (tidal volumes)
• PCV: No control of airway flows during expiration, use of individualized lower airway pressures and upper airway pressures for a fixed tidal volume during each breath (6-8 ml/kg ideal body weight)

In total, at least 24 participants in need of ventilation after severe burn injury will be ventilated either with FCV (12 participants) or PCV (12 participants) for up to 70 hours.

During ventilation mechanical power is computed according to certain ventilation parameters. Additionally, we evaluate organ functions of the cardiovascular systems, the lungs and other organs during and after the group-specific ventilation.

Invasive ventilation can cause ventilator-induced lung injury. There is growing evidence that high mechanical power during (prolonged) controlled ventilation is associated with ventilator-induced lung injury and pulmonary complications.

Large animal model and perioperative clinical trial data have shown that the individualized application of the flow-controlled ventilation (FCV) mode can reduce mechanical power compared to conventional pressure-controlled ventilation (PCV).

Burn patients with or without inhalational injury are at high risk of pulmonary complications like pneumonias or the acute respiratory distress syndrome due to the hyperinflammatory state and also the intensive care treatment after a burn injury. If these patients need mechanical ventilation, this might aggravate lung injury.

With the study BIFLOWBURN we want to test the hypothesis that the mechanical power during controlled ventilation of burn patients is reduced with the individualized application of FCV compared to conventional PCV via Biphasic Positive Airway Pressure (BIPAP) ventilation.

BIFLOWBURN is a single-center, randomized, parallel-group trial with two intervention arms:

• Controlled BIPAP ventilation (n=12) with a compliance-guided positive end-expiratory pressure (PEEP) and driving pressure (ΔP) for tidal volumes of 6-8 ml/kg predicted body weight compared to
• optimized FCV (n=12) with a compliance-guided PEEP and a compliance-guided ΔP, resulting in liberal tidal volumes.

The group-specific controlled ventilation mode will be applied for a maximum of 70 hours.

As the primary study endpoint, the mechanical power in joules per minute (J/min) is computed during group-specific controlled ventilation.

As secondary study aims, clinically relevant patient outcomes are analyzed as explorative secondary outcomes, e.g., lung function, ventilatory parameters, the incidences of pulmonary and extra-pulmonary complications as well as different intensive care scores for the assessment of organ dysfunctions.

As an additional sub-study with an exploratory approach, parameters of different advanced haemodynamic monitoring techniques are assessed. Within a further ancillary study, biomarkers of acute lung injury and/or the burn inhalational injury will be characterized by molecular biological methods.

BIFLOWBURN is the first randomized controlled trial which assesses mechanical power during the ventilation of burn patients by comparing the alternative mode of flow-controlled ventilation with a conventional ventilation mode.

Inclusion Criteria:

• Body weight ≥ 40 kg
• Invasive ventilation time ≤ 24 hours before admission to the burn ICU or indication for intubation and invasive ventilation within 48 hours after admission to the burn ICU
• Estimated (further) invasive ventilation time ≥ 24 hours
• Intervention start within 48 hours after admission to the burn ICU
• Establishment of a central venous line and invasive blood pressure monitoring as part of the intensive care therapy before the intervention start
• Signed informed consent from the participant, legal guardian, next of kin in incompetent patients, or an intensivist in charge and independent from the Trial Management Committee in incompetent patients without a representative of the patients will

Exclusion Criteria:

• Participation in another interventional trial
• Duration of invasive ventilation > 24 hours at the time point of admission to the burn ICU
• Estimated (further) invasive ventilation time < 24 hours
• Patients being treated in the burn ICU for (suspected) severe skin reactions such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
• Lack of consent from the participant, legal guardian, next of kin, or intensivist in charge to participate in the study

Before the enrolment of the last participant, the study protocol including the statistical analysis plan will be published in an appropriate journal after peer-reviewing.

After pseudonymisation, data is transferred and processed with the web-based application software REDCap™. This enables data sharing of complete deidentified data sets of all primary and secondary study outcome data with the scientific community upon personal request with a reasonable proposal to the principal investigator.

Beginning immediately after publication of the respective main study and explorative ancillary studies with no end date.

IPD can be accessed by peers and other investigators upon personal request to the principal investigator with a reasonable proposal including a detailed description of the planned analyses. The Trial Management Committee will critically review this proposal together with the principal investigator.

Due to different ventilators during the interventions, outcome assessors can only be blinded after intervention withdrawal. Participants are blinded throughout the study.