Influence of Respiratory Mechanics on Brain-specific Monitoring in Brain-injured Patients (ABIVENT)

Effects of Chest Wall and Lung Elastances on Intracranial Pressure and Brain-specific Multimodal Monitoring in Ventilated Brain Injured Patients

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.

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.

Respiratory mechanics; intracranial pressure monitoring Ers/Ecw = chest wall to respiratory system elastances ratio; ICP = intracranial pressure

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

Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes

Automated infrared pupillometry NPI = neurological pupil index PtiO2 = brain tissue oxygen tension; LPR = lactate/pyruvate ratio; NPI = neurological pupil index

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

Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes

Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes

Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes

Invasive intravascular pressures. CVP = central venous pressure; MAP = mean arterial pressure; CPP = cerebral perfusion pressure

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).

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.

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

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)

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)

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

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

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

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

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

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

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

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

Recorded every minute during 10 minutes at the end of each 45-minute period (PEEP 5 and 15 cmH2O), 90 minutes

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