The Cerebral-Respiratory Interaction During Spontaneous Breathing Ventilation in Neurosurgical Patients (CeRes-SB)

Study Overview
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Brief Summary
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Mechanical ventilation (MV) is a life-saving supportive therapy and one of the most common interventions implemented in intensive care. To date, only the inspiratory phase of breathing has been extensively investigated, and new MV methods have been implemented to reduce its harmful effects. Despite this, lung injury still occurs and propagates, causing multiorgan failure and patient deaths. The expiratory phase is considered unharmful and is not monitored or assisted during MV. In animal experiments, we recently showed that the loss of diaphragmatic contraction during expiration can harm the lungs during MV. During mechanical ventilation, the expiratory phase of breathing is completely disregarded. However, in all conditions that promote lung collapse, peripheral airways gradually compress and close throughout the expiration, potentially worsening lung injury. This cyclical lung collapse and consequent air-trapping may have an impact on the Starling resistor mechanisms that regulate venous return from the brain, potentially affecting cerebral perfusion and intracranial pressure. This study will investigate the incidence and the consequences of an uncontrolled expiration and expiratory lung collapse in spontaneously breathing critically ill neurosurgical patients during mechanical ventilation. Electrical impedance tomography measurements , oesophagus and gastric pressure, electrical activity of the diaphragm and intracranial pressure will be acquired in a synchronised manner during controlled mechanical ventilation, on a daily bases during assisted mechanical ventilation.

Official Title
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Investigating the Effects of Expiratory Flow Limitation and the Effects of Spontaneous Breathing on Intracranial Pressure. An Observational Clinical Study on Neurosurgical Patients.

Conditions
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Mechanical Ventilation Complication, Neurological Complication, Respiratory Complication

Intervention / Treatment
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* Other: Mechanically ventilated neurosurgical patients


Participation Criteria
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Eligibility Criteria
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Neurosurgical patients on mechanical ventilation and with ongoing intracerebral pressure monitoring will be included in the study Inclusion Criteria: Age >18 years; MV expected for more than 72 hours; Not pregnant; Informed consent from patient or next of kin. Exclusion Criteria: Previously demonstrated paralysis of the diaphragm or know pathology of the phrenic nerve or neuromuscular disorder; Chest tube; Patients with clinical conditions that contraindicate the insertion of esophageal/gastric catheters (e.g., esophagus rupture, esophageal bleeding); Pacemaker and/or implantable cardioverter defibrillator, these last being a contraindication for EIT; Hemicraniectomy. In case of late hemicraniectomy (after patient inclusion), the patient will drop-out from the study. Relative contraindication: in case of skull base fracture the patient can be included only if oesophageal/gastric and NAVA catheters can be inserted orally.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Mechanically ventilated neurosurgical patients<br>Observational study in mechanically ventilated neurosurgical patients | Other: Mechanically ventilated neurosurgical patients<br>* Observational study where respiratory variables and intracranial pressure will be measured during assisted mechanical ventilation. No intervention is planned.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of uncontrolled expiration | The incidence of uncontrolled expiration and consequent expiratory lung collapse (determined by changes in expiratory flow and time constant) during assisted ventilation in neurosurgical patients. | during the period of assisted mechanical ventilation, an average of 14 days | 
| Correlation between uncontrolled expiration and intracranial pressure | The influence of an uncontrolled expiration (defined by expiratory flow, expiratory EAdi and thoracic impedance) on intracranial pressure in neurosurgical patients. | During the period of assisted mechanical ventilation, an average of 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensive care unit (ICU) and hospital length of stay (LOS) | Correlation between lung collapse and LOS | At ICU/hospital discharge, an average of 30 days | 
| Number of days of mechanical ventilation | Correlation between lung collapse and days of mechanical ventilation | At ICU discharge, an average of 20 days | 
| 90-days mortality from intensive care unit admission | Correlation between lung collapse and 90-days mortality | 90 days after hospital discharge | 
| 30-day and 90-days neurological and functional outcomes | Correlation between lung collapse and 30-day and 90-days neurological and functional outcomes (Disability Rating Scale, clinical frailty score, Glasgow Outcome Scale) | 90 days after hospital discharge |