Influence of Respiratory Mechanics on Brain-specific Monitoring in 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.


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