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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
PEEP level set for 45 minutes
PEEP level set for 45 minutes
Lausanne University Hospitals
Lausanne, Canton of Vaud, Switzerland
Correlation between Ers/Ecw and change in ICP between the two PEEP levels
Respiratory mechanics; intracranial pressure monitoring Ers/Ecw = chest wall to respiratory system elastances ratio; ICP = intracranial pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Correlation between Ecw/Ers and the following neuromonitoring indices at the two PEEP levels: PtiO2, LPR, NPI; MFV, DFV and PI.
Respiratory mechanics; brain tissue oxygen tension; cerebral microdyalisis analytes; automated infrared pupillometry; transcranial doppler ultrasound Ers/Ecw = chest wall to respiratory system elastances ratio; PtiO2 = brain tissue oxygen tension; LPR = lactate/pyruvate ratio; NPI = neurological pupil index; MFV = mean flow velocity; DFV = diastolic flow velocity; PI = pulsatility index
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Effect of the two different levels of PEEP on NPI.
Automated infrared pupillometry NPI = neurological pupil index PtiO2 = brain tissue oxygen tension; LPR = lactate/pyruvate ratio; NPI = neurological pupil index
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Effect of the two different levels of PEEP on the following transcranial doppler ultrasound variables: MFV, DFV and PI.
Transcranial doppler ultrasound MFV = mean flow velocity; DFV = diastolic flow velocity; PI = pulsatility index
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Effect of the two different levels of PEEP on LPR.
Cerebral microdyalisis analytes LPR = lactate/pyruvate ratio
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Effect of the two different levels of PEEP on PtiO2.
Brain tissue oxygen tension. PtiO2 = brain tissue oxygen tension
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Effect of the two different levels of PEEP on the following intravascular pressures: CVP, MAP, CPP.
Invasive intravascular pressures. CVP = central venous pressure; MAP = mean arterial pressure; CPP = cerebral perfusion pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Effect of the two different levels of PEEP on the following echocardiographic measurements: LVOT VTI, CO.
Echocardiography. LVOT VTI = left ventricle outflow tract velocity-time integral; CO = cardiac output (echocardiographically estimated).
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Effect of the two different levels of PEEP on the dose of vasopressors/inotropes and volume of fluid boluses administered.
Administered drugs and fluids.
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
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.
Respiratory mechanics; echocardiography; invasive intravascular pressures; administered drugs and fluids LVOT VTI = left ventricle outflow tract velocity-time integral; CO = cardiac output (echocardiographically estimated); CVP = central venous pressure; MAP = mean arterial pressure; CPP = cerebral perfusion pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
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.
Respiratory mechanics; intracranial pressure monitoring, Brain tissue oxygen tension; cerebral microdyalisis analytes; automated infrared pupillometry; transcranial doppler ultrasound; Echocardiography; invasive intravascular pressures; administered drugs and fluids. ICP = intracranial pressure; PtiO2 = brain tissue oxygen tension; LPR = lactate/pyruvate ratio; NPI = neurological pupil index; MFV = mean flow velocity; DFV = diastolic flow velocity; PI = pulsatility index; CVP = central venous pressure; MAP = mean arterial pressure; CPP = cerebral perfusion pressure; LVOT VTI = left ventricle outflow tract velocity-time integral; CO = cardiac output (echocardiographically estimated)
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
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.
Respiratory mechanics; intracranial pressure monitoring, Brain tissue oxygen tension; cerebral microdyalisis analytes; automated infrared pupillometry; transcranial doppler ultrasound; Echocardiography; invasive intravascular pressures; administered drugs and fluids. Rec/PEEPvol = recruited volume to PEEP-related volume ratio; ICP = intracranial pressure; PtiO2 = brain tissue oxygen tension; LPR = lactate/pyruvate ratio; NPI = neurological pupil index; MFV = mean flow velocity; DFV = diastolic flow velocity; PI = pulsatility index; CVP = central venous pressure; MAP = mean arterial pressure; CPP = cerebral perfusion pressure; LVOT VTI = left ventricle outflow tract velocity-time integral; CO = cardiac output (echocardiographically estimated)
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Correlation between Vd/Vt and the following parameters at the two PEEP levels: ICP, PtiO2, LPR, NPI, MFV, DFV, PI; CPP
Respiratory mechanics; intracranial pressure monitoring, brain tissue oxygen tension; cerebral microdyalisis analytes; automated infrared pupillometry; transcranial doppler ultrasound; invasive intravascular pressures. Vd/Vt = dead space to tidal volume ratio; ICP = intracranial pressure; PtiO2 = brain tissue oxygen tension; LPR = lactate/pyruvate ratio; NPI = neurological pupil index; MFV = mean flow velocity; DFV = diastolic flow velocity; PI = pulsatility index; CVP = central venous pressure; CPP = cerebral perfusion pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
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.
Intracranial pressure monitoring, Brain tissue oxygen tension; cerebral microdyalisis analytes; automated infrared pupillometry; transcranial doppler ultrasound; Echocardiography; invasive intravascular pressures. PI = pulsatility index; ICP = intracranial pressure; PtiO2 = brain tissue oxygen tension; LPR = lactate/pyruvate ratio; NPI = neurological pupil index; MFV = mean flow velocity; DFV = diastolic flow velocity; PI = pulsatility index; LVOT VTI = left ventricle outflow tract velocity-time integral; CO = cardiac output (echocardiographically estimated); MAP = mean arterial pressure; CPP = cerebral perfusion pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
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.
Intracranial pressure monitoring, Brain tissue oxygen tension; cerebral microdyalisis analytes; automated infrared pupillometry; transcranial doppler ultrasound; Echocardiography; invasive intravascular pressures; administered drugs and fluids. CVP = central venous pressure; ICP = intracranial pressure; PtiO2 = brain tissue oxygen tension; LPR = lactate/pyruvate ratio; NPI = neurological pupil index; MFV = mean flow velocity; DFV = diastolic flow velocity; PI = pulsatility index; LVOT VTI = left ventricle outflow tract velocity-time integral; CO = cardiac output (echocardiographically estimated); MAP = mean arterial pressure; CPP = cerebral perfusion pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
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.
Brain tissue oxygen tension; cerebral microdyalisis analytes; automated infrared pupillometry; transcranial doppler ultrasound; echocardiography, invasive intravascular pressures; administered drugs and fluids. LVOT VTI = left ventricle outflow tract velocity-time integral; PtiO2 = brain tissue oxygen tension; LPR = lactate/pyruvate ratio; NPI = neurological pupil index; MFV = mean flow velocity; DFV = diastolic flow velocity; PI = pulsatility index; MAP = mean arterial pressure; CPP = cerebral perfusion pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Correlation between PtiO2 and the following parameters at the two PEEP levels: ICP, MAP, dose of vasopressors/inotropes and volume of fluid boluses administered.
Intracranial pressure monitoring, brain tissue oxygen tension; invasive intravascular pressures; administered drugs and fluids. PtiO2 = brain tissue oxygen tension; ICP = intracranial pressure; MAP = mean arterial pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Correlation between LPR and the following parameters at the two PEEP levels: ICP, MAP, dose of vasopressors/inotropes and volume of fluid boluses administered.
Intracranial pressure monitoring, cerebral microdyalisis analytes; invasive intravascular pressures; administered drugs and fluids. LPR = lactate/pyruvate ratio; ICP = intracranial pressure; MAP = mean arterial pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
Correlation between NPI and the following parameters at the two PEEP levels: ICP, MAP, dose of vasopressors/inotropes and volume of fluid boluses administered.
Intracranial pressure monitoring, automated infrared pupillometry; invasive intravascular pressures; administered drugs and fluids. NPI = neurological pupil index; ICP = intracranial pressure; MAP = mean arterial pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
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.
Intracranial pressure monitoring, transcranial doppler ultrasound; invasive intravascular pressures; administered drugs and fluids. MFV = mean flow velocity; DFV = diastolic flow velocity; PI = pulsatility index; ICP = intracranial pressure; MAP = mean arterial pressure
Time frame: Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes
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