Clinical trial NCT04013698: Influence of Respiratory Mechanics on Brain-specific Monitoring in Brain-injured Patients
Official title: Effects of Chest Wall and Lung Elastances on Intracranial Pressure and Brain-specific Multimodal Monitoring in Ventilated Brain Injured Patients
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Brain Injuries
Keywords: ventilation
brain injuries
PEEP
esophageal pressure
Lead sponsor: University of Lausanne Hospitals
Sponsor class: OTHER
First posted: 2019-07-10
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients included will receive volume assist-control ventilation with PEEP set at 5 cmH2O and 15 cmH2O in a randomized order (crossover design). Each setting will be applied during 45 minutes.
Primary purpose: OTHER

Brief summary: Increase in intracranial pressure (ICP) could be associated with increase in positive end-expiratory pressure (PEEP) level. Data are however disparate and interactions between ventilation with high PEEP and intracranial circulation are still debated. Individual patient's chest wall elastance could have a key role in determining the effects of PEEP on ICP, since it dictates which proportion of the applied PEEP is transmitted to the pleural space, thus increasing central venous pressure (CVP) and reducing cerebral venous return. Measurement of esophageal pressure with a dedicated probe allows partitioning of respiratory system elastance into its lung and chest wall components, thus permitting to study this phenomenon. Multimodal intracranial monitoring permits to study the effects of PEEP on more advanced brain-specific indices such as brain tissue oxygen (PtiO2), cerebral microdialysis data, transcranial doppler ultrasound-derived flow measurements and automated pupillometry, besides ICP.

This study aims to test the association between the ratio of chest wall to respiratory system elastance and PEEP-induced variations in ICP and brain-specific multimodal monitoring indices. This study will evaluate the relative role of other selected measures of respiratory mechanics, hemodynamic variables and intracranial compliance, in order to establish the role of individual respiratory mechanics in the interplay of physiological factors affecting the effects of positive pressure ventilation on the brain.

Patients will undergo two periods of ventilation at two different levels of PEEP (5 and 15 cmH2O) in a randomized cross-over order. At the end of each period, cardiorespiratory clinical data, ICP and other advanced multimodal neuromonitoring data (brain tissue oxygen tension, cerebral microdyalisis analytes, transcranial doppler ultrasound and automated infrared pupillometry data) will be collected. Systematic respiratory mechanics assessment (including calculation of chest wall and lung elastances and estimation of the amount of recruitment versus overdistension due to PEEP by means of a single-breath derecruitment trial), echocardiography and arterial blood gas analysis will be performed.


Eligibility criteria: Inclusion Criteria:

* Acute brain injury of any etiology requiring multimodal brain monitoring (intraparenchymal intracranial pressure, brain-tissue oxygen tension and cerebral microdialysis)
* Controlled mechanical ventilation via endotracheal tube
* Patient needing deep sedation

Exclusion Criteria:

* pregnancy
* contraindications to nasogastric probe placement: basilar skull or significant naso-facial fractures, significant esophageal or gastric trauma or bleeding, previous esophageal surgery, significant bleeding diathesis (spontaneous aPTT \> 60 sec, PT \< 40%, INR \> 1.8, platelets \< 50000/mm3), known esophageal or gastric varices
* decompressive craniectomy
* intracranial pressure monitoring method other than intraparenchymal (e.g. connected to external ventricular drain)
* severe relevant physiological instability contraindicating an increase in PEEP: severe baseline intracranial pressure elevation (\> 20 mmHg), severe hemodynamic instability (defined as norepinephrine requirements \> 0.5 μg/kg/min or cardiogenic shock, defined as any use of dobutamine)
* conditions that interfere with accurate measurements of respiratory mechanics: bronchopleural fistula, pneumothorax.
* Withhold of life-sustaining therapy for medical reasons

Primary outcomes:
measure: Correlation between Ers/Ecw and change in ICP between the two PEEP levels
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Secondary outcomes:
measure: Correlation between Ecw/Ers and the following neuromonitoring indices at the two PEEP levels: PtiO2, LPR, NPI; MFV, DFV and PI.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Effect of the two different levels of PEEP on NPI.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Effect of the two different levels of PEEP on the following transcranial doppler ultrasound variables: MFV, DFV and PI.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Effect of the two different levels of PEEP on LPR.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Effect of the two different levels of PEEP on PtiO2.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Effect of the two different levels of PEEP on the following intravascular pressures: CVP, MAP, CPP.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Effect of the two different levels of PEEP on the following echocardiographic measurements: LVOT VTI, CO.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Effect of the two different levels of PEEP on the dose of vasopressors/inotropes and volume of fluid boluses administered.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between Ers/Ecw and the following parameters at the two PEEP levels: LVOT VTI, CO; CVP, MAP, CPP; dose of vasopressors/inotropes and volume of fluid boluses administered.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between Pes_end-exp and the following parameters at the two PEEP levels: ICP, PtiO2, LPR, NPI, MFV, DFV, PI; CVP, MAP, CPP, LVOT VTI, CO, dose of vasopressors/inotropes and volume of fluid boluses administered.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between Rec/PEEPvol and the following parameters at the two PEEP levels: ICP, PtiO2, LPR, NPI, MFV, DFV, PI; CVP, MAP, CPP, LVOT VTI, CO, dose of vasopressors/inotropes and volume of fluid boluses administered.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between Vd/Vt and the following parameters at the two PEEP levels: ICP, PtiO2, LPR, NPI, MFV, DFV, PI; CPP
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between baseline PI at transcranial doppler ultrasound and the following parameters at the two PEEP levels: ICP, PtiO2, LPR, NPI, MFV, DFV, PI; LVOT VTI, CO, MAP, CPP.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between CVP and the following parameters at the two PEEP levels : ICP, PtiO2, LPR, NPI, MFV, DFV, PI; LVOT VTI, CO, MAP, CPP, dose of vasopressors/inotropes and volume of fluid boluses administered.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between LVOT VTI and the following parameters at the two PEEP levels: PtiO2, LPR, NPI, MFV, DFV, PI; MAP, CPP, dose of vasopressors/inotropes and volume of fluid boluses administered.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between PtiO2 and the following parameters at the two PEEP levels: ICP, MAP, dose of vasopressors/inotropes and volume of fluid boluses administered.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between LPR and the following parameters at the two PEEP levels: ICP, MAP, dose of vasopressors/inotropes and volume of fluid boluses administered.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between NPI and the following parameters at the two PEEP levels: ICP, MAP, dose of vasopressors/inotropes and volume of fluid boluses administered.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
measure: Correlation between doppler indices (MFV, DFV and PI) and the following parameters at the two PEEP levels: ICP, MAP, dose of vasopressors/inotropes and volume of fluid boluses administered.
timeFrame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Lausanne University Hospitals
state: Vaud
Study officials:
affiliation: University of Lausanne Hospitals
name: Lise Piquilloud, MER&PD
role: PRINCIPAL_INVESTIGATOR
References: