Biphasic Positive Airway Pressure Ventilation Versus Flow-Controlled Ventilation in Burn Patients

Official title

Biphasic Positive Airway Pressure Ventilation Versus Flow-Controlled Ventilation in Burn Patients: A Monocentric, Randomized Controlled, Parallel Group Trial

Overview

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.

Detailed description

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.

Interventions

• Other Individualized flow-controlled ventilation strategy
  1. Compliance-guided PEEP trial: An incremental PEEP trial from 5 to 15 cmH2O in 2 cmH2O steps with a constant driving pressure (ΔP) will be performed. At the first PEEP level, the tidal volume is set to 6-8 ml/kg PBW. The best PEEP level is defined as the one with the highest dynamic compliance. Participants are ventilated with this PEEP level + 1-2 cmH2O for a reduction of lung de-recruitment and atelectrauma. 2. Compliance-guided driving pressure (ΔP) trial: In the FCV group, an additional in
• Other Pressure-controlled ventilation strategy via the application of Biphasic Positive Airway Pressure ventilation
  1. Compliance-guided PEEP trial: An incremental PEEP trial from 5 to 15 cmH2O in 2 cmH2O steps with a constant driving pressure (ΔP)will be performed. At the first PEEP level, the tidal volume is set to 6-8 ml/kg PBW. The best PEEP level is defined as the one with the highest dynamic compliance. Participants are ventilated with this PEEP level + 1-2 cmH2O for a reduction of lung de-recruitment and atelectrauma. 2. The driving pressure (ΔP) is set to achieve a tidal volume of 6-8 ml/kg predicted

Primary outcome measures

• Mechanical power [Time frame: Mechanical power will be assessed hourly during up to 70 hours of controlled, group-specific ventilation.]

Secondary outcome measures (12)

• Dissipated energy/power [Time frame: The dissipated energy/power will be assessed at least hourly/continously during up to 70 hours of controlled, group-specific ventilation.]
• Respiratory rate [Time frame: Respiratory rates will be assessed hourly during up to 70 hours of controlled, group-specific ventilation.]
• Tidal volume [Time frame: Tidal volumes will be assessed hourly during up to 70 hours of controlled, group-specific ventilation.]
• Minute volume [Time frame: Minute volumes will be assessed hourly during up to 70 hours of controlled, group-specific ventilation.]
• Airway pressures [Time frame: Airway pressures will be assessed hourly during up to 70 hours of controlled, group-specific ventilation.]
• Dynamic compliance [Time frame: Dynamic compliances will be assessed hourly during up to 70 hours of controlled, group-specific ventilation.]
• Airway resistance [Time frame: Airway resistances will be assessed hourly during up to 70 hours of controlled, group-specific ventilation.]
• Oxygenation indices [Time frame: Oxygenation indices will be assessed every 4-8 hours with arterial blood gas analyses during up to 70 hours of controlled, group-specific ventilation.]
• Pulmonary complications [Time frame: Pulmonary complications will be assessed within the first ten days after randomization.]
• Extra-pulmonary complications [Time frame: Extra-pulmonary complications will be assessed within the first ten days after randomization.]
• Sequential Organ Failure Assessment (SOFA) Score [Time frame: The Sequential Organ Failure Assessment (SOFA) Score will be assessed daily within the first ten days after randomization.]
• Lung Injury Score (Murray) [Time frame: The Lung Injury Score will be assessed daily within the first ten days after randomization.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Germany · 1 center

• BG University Hospital Bergmannsheil, Ruhr University Bochum — Bochum

Publications

• Bittner E, Sheridan R. Acute Respiratory Distress Syndrome, Mechanical Ventilation, and Inhalation Injury in Burn Patients. Surg Clin North Am. 2023 Jun;103(3):439-451. doi: 10.1016/j.suc.2023.01.006. Epub 2023 Mar 21. PMID 37149380
• Van Oosten JP, Francovich JE, Somhorst P, van der Zee P, Endeman H, Gommers DAMPJ, Jonkman AH. Flow-controlled ventilation decreases mechanical power in postoperative ICU patients. Intensive Care Med Exp. 2024 Mar 19;12(1):30. doi: 10.1186/s40635-024-00616-9. PMID 38502268
• Spraider P, Abram J, Martini J, Putzer G, Glodny B, Hell T, Barnes T, Enk D. Flow-controlled versus pressure-controlled ventilation in cardiac surgery with cardiopulmonary bypass - A single-center, prospective, randomized, controlled trial. J Clin Anesth. 2023 Dec;91:111279. doi: 10.1016/j.jclinane.2023.111279. Epub 2023 Oct 3. PMID 37797394
• Abram J, Martini J, Spraider P, Putzer G, Ranalter M, Wagner J, Glodny B, Hell T, Barnes T, Enk D. Individualised flow-controlled versus pressure-controlled ventilation in a porcine oleic acid-induced acute respiratory distress syndrome model. Eur J Anaesthesiol. 2023 Jul 1;40(7):511-520. doi: 10.1097/EJA.0000000000001807. Epub 2023 Feb 7. PMID 36749046
• Urner M, Juni P, Hansen B, Wettstein MS, Ferguson ND, Fan E. Time-varying intensity of mechanical ventilation and mortality in patients with acute respiratory failure: a registry-based, prospective cohort study. Lancet Respir Med. 2020 Sep;8(9):905-913. doi: 10.1016/S2213-2600(20)30325-8. Epub 2020 Jul 28. PMID 32735841
• Santer P, Wachtendorf LJ, Suleiman A, Houle TT, Fassbender P, Costa EL, Talmor D, Eikermann M, Baedorf-Kassis E, Schaefer MS. Mechanical Power during General Anesthesia and Postoperative Respiratory Failure: A Multicenter Retrospective Cohort Study. Anesthesiology. 2022 Jul 1;137(1):41-54. doi: 10.1097/ALN.0000000000004256. PMID 35475882
• Cressoni M, Gotti M, Chiurazzi C, Massari D, Algieri I, Amini M, Cammaroto A, Brioni M, Montaruli C, Nikolla K, Guanziroli M, Dondossola D, Gatti S, Valerio V, Vergani GL, Pugni P, Cadringher P, Gagliano N, Gattinoni L. Mechanical Power and Development of Ventilator-induced Lung Injury. Anesthesiology. 2016 May;124(5):1100-8. doi: 10.1097/ALN.0000000000001056. PMID 26872367

Identifiers

NCT: NCT07041957 · 23-7944 · 23-7944

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗