Ventilator Study in the NICU

Official title

Titration of End-expiratory Lung Volume Using the Capnodynamic Method in Intubated Neurointensive Care Patients - Effects on Driving Pressure, Compliance, and Mixed Venous Oxygen Saturation

Overview

Background: Optimal adjustment of mechanical ventilation in intensive care patients is crucial to ensure effective ventilation and to reduce the risk of ventilator-associated complications such as pneumonia and ventilator-induced lung injury. Current monitoring methods may often be insufficient to achieve truly optimal ventilator settings in routine clinical practice. By applying a specific breathing pattern, additional key ventilation-related parameters can be monitored and adjusted using a novel carbon dioxide-based method. This approach has the potential to substantially improve ventilation in critically ill patients. The carbon dioxide-based method utilizes a modified intensive care ventilator (Servo-i®, Getinge) equipped with CE-marked research software. The software modifies the breathing pattern by introducing three slightly prolonged expiratory pauses in three out of nine breaths. This ventilator has been used in multiple large-animal studies and clinical trials, including two conducted by the present research group. Study Design: The study will include adult patients receiving mechanical ventilation in a neurointensive care unit due to brain injury. Patients must be in a stable phase with regard to neurological status and circulation and require controlled mechanical ventilation. Informed consent will be obtained from the patient after recovery when applicable. Part 1 (Pilot Study): This is an observational study including 15 patients, aiming to establish reference values for parameters obtained using the carbon dioxide-based method, such as end-expiratory lung volume and mixed venous oxygen saturation. Patients will be switched to the research ventilator for 15-20 minutes, during which measurements from the carbon dioxide-based method and standard vital sign monitoring will be collected. Ventilator settings will be identical to those used on the patient's conventional ventilator. After completion of the protocol, patients will be switched back to their standard ventilator. Part 2 (Main Study): This is an interventional study with a within-subject (self-controlled) design, including 15 mechanically ventilated patients with stable brain injury. The aim is to optimize ventilator settings using the carbon dioxide-based method to achieve more lung-protective ventilation. Patients will be transferred to the research ventilator using the same procedure as in the pilot study, initially maintaining the same ventilator settings. After a 10-minute stabilization period, ventilatory parameters will be recorded and an arterial blood gas sample obtained (baseline). The specific breathing pattern will then be initiated, and ventilation will be adjusted based on additional parameters provided by the capnodynamic method (end-expiratory lung volume, cardiac output, and mixed venous oxygen saturation). Measurements and arterial blood gases will be repeated immediately after initiation of the breathing pattern and again 15 minutes after ventilator adjustments. The study will then conclude, and the patient will be returned to their standard ventilator using the optimized ventilator settings to potentially ensure patient benefit.

Detailed description

The primary outcome measure is a reduction in driving pressure, as it is well established that a driving pressure \>15 cmH₂O is associated with an increased risk of lung injury (ventilator-induced lung injury, VILI). Clinical observations in the intended study population show driving pressures of approximately 19 cmH₂O with an estimated standard deviation of 2 cmH₂O (study baseline). When these values are entered into a power calculation for a paired two-sided t-test, a sample size of approximately 10 patients is obtained. To account for potential dropouts, the study group size is set at 15 patients. The significance level is \<0.05, with a power of 80%.

Interventions

• Device Capnodynamic method
  Applying the capnodynamic method using a modified intensive care ventilator and subsequently use additional parameters like effective lung volume (ELV) in order to adjust ventilator settings to minimize driving pressure.

Primary outcome measures

• Driving pressure (deltaP) cmH2O. [Time frame: Study protocols will have a time frame och 15-30 minutes.]

Secondary outcome measures (1)

• ELV (ml) [Time frame: 15-30 minutes]

Eligibility criteria

Inclusion criteria

• Stable with regard to intracranial pressure
• Hemodynamically stable

Exclusion criteria

• Ongoing instability with regard to intracranial pressure and circulation
• Spontaneous breathing / patient-triggered ventilation
• If the patient subsequently declines consent

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 1 center

• Karolinska University Hospital, Neurointensive care unit — Stockholm

Publications

• Iavarone IG, Rocco PRM, Grieco DL, Rosa T, Pellegrini M, Badenes R, Stevens RD, Asehnoune K, Robba C, Camporota L, Roquilly A. Pathophysiology and clinical applications of PEEP in acute brain injury. Intensive Care Med. 2025 Nov;51(11):2104-2116. doi: 10.1007/s00134-025-08111-9. Epub 2025 Sep 22. PMID 40982016
• Sigmundsson TS, Ohman T, Hallback M, Suarez-Sipmann F, Wallin M, Oldner A, Hallsjo-Sander C, Bjorne H. Comparison between capnodynamic and thermodilution method for cardiac output monitoring during major abdominal surgery: An observational study. Eur J Anaesthesiol. 2021 Dec 1;38(12):1242-1252. doi: 10.1097/EJA.0000000000001566. PMID 34155171
• Ohman T, Sigmundsson TS, Hallback M, Suarez Sipmann F, Wallin M, Oldner A, Bjorne H, Hallsjo Sander C. Clinical and experimental validation of a capnodynamic method for end-expiratory lung volume assessment. Acta Anaesthesiol Scand. 2020 May;64(5):670-676. doi: 10.1111/aas.13552. Epub 2020 Jan 30. PMID 31965563
• Sander CH, Sigmundsson T, Hallback M, Sipmann FS, Wallin M, Oldner A, Bjorne H. A modified breathing pattern improves the performance of a continuous capnodynamic method for estimation of effective pulmonary blood flow. J Clin Monit Comput. 2017 Aug;31(4):717-725. doi: 10.1007/s10877-016-9891-z. Epub 2016 Jun 1. PMID 27251701
• Hallsjo Sander C, Hallback M, Suarez Sipmann F, Wallin M, Oldner A, Bjorne H. A novel continuous capnodynamic method for cardiac output assessment in a porcine model of lung lavage. Acta Anaesthesiol Scand. 2015 Sep;59(8):1022-31. doi: 10.1111/aas.12559. Epub 2015 Jun 4. PMID 26041115
• Hallsjo Sander C, Hallback M, Wallin M, Emtell P, Oldner A, Bjorne H. Novel continuous capnodynamic method for cardiac output assessment during mechanical ventilation. Br J Anaesth. 2014 May;112(5):824-31. doi: 10.1093/bja/aet486. Epub 2014 Feb 18. PMID 24554544

Identifiers

NCT: NCT07585019 · CIV-ID CIV-26-01-055996 · 2026-01383-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗