Mobilising Patients With Severe Brain Injury in Intensive Care

Study Overview
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Brief Summary
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Introduction Patients with severe brain injury are often restricted to bed rest during the early period of brain injury which may lead to unwanted secondary complications. There is lack of evidence of when to initiate the first mobilisation. The Sara Combilizer® is an easy and efficient tool for mobilising patients with severe injuries, including brain injury. Through a randomised cross-over trial the investigators will investigate the impact of early mobilisation on patients with severe acquired brain injury caused by traumatic brain injury, subarachnoid brain injury or intracranial haematoma. The investigators hypothesise that mobilisation using the Sara Combilizer® does not affect partial oxygenation of brain tissue.

Detailed Description
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The primary purpose of this study is to quantify cerebral oxygenation, when mobilising patients with severe brain injury using a Sara Combilizer® to the seated position and during passive standing. This study is conducted at the Department of Neurointensive care and Neuroanaesthesiology, Rigshospitalet, Copenhagen. Based on the International Conference on harmonisation-Good Clinical Practice guidelines and the Danish Good Clinical Practice administrative order, a table regarding the responsibilities of sponsor/investigators before, during and after the clinical trial, will be filled and signed in order to avoid misunderstandings. This table can be found in the Trial Master File (TMF) located at the primary investigator's office and the sponsor's office. This study is designed as a cross-over study with patients randomly assigned to (1) an initial intervention protocol on the first day and with a passive sedentary protocol on the second, or (2) an initial passive sedentary protocol on the first day followed by an intervention protocol on the second day. Randomisation Included patients will, after stabilisation of ICP, be randomised to start with either the intervention or sedentary protocol, with the opposite protocol on the second day. A computer-generated randomisation algorithm will be created in REDCap, with age and Glasgow Coma Score (GCS) as dichotomised stratification variables. Age will be divided into young (18 to 60 years) and old (61+ years), and the GCS into severe brain injury (GCS 3-8) and moderate to mild injury (GCS 9-15). The following four composite groups of age and GCS will ensure an equal distribution of the patients within each stratum.

Official Title
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Mobilising Patients With Severe Brain Injury in Intensive Care

Conditions
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Brain Injury Traumatic Severe, Subarachnoid Hemorrhage, Intracranial Hematoma

Intervention / Treatment
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* Device: Mobilisation using the Sara Combilizer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Traumatic brain injury, subarachnoid haemorrhage, intracranial haematoma Sedated for at least 48 hours after admission Equipment measuring partial brain tissue oxygenation and intracranial pressure Understands spoken and written Danish Exclusion Criteria: Unstable spinal cord injury Unstable injury in the lower extremities prohibiting mobilisation No consent from nearest relative

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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study is designed as a cross-over study with patients randomly assigned to (1) an initial intervention protocol on the first day and with a passive sedentary protocol on the second, or (2) an initial passive sedentary protocol on the first day followed by an intervention protocol on the second day.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention protocol<br>Phase 1. The patient will be positioned in a supine position for 20 minutes on the Sara Combilizer®. When necessary, the head of the patient can be elevated to a maximum of 30 degrees during the 20 minutes baseline measurements. Phase 2. The patient will be positioned in a seated position for 10 minutes with the trunk and head elevated to at least 70 degrees. Phase 3. The patient will be moved to the standing position for 20 minutes with an elevation angle of the Sara Combilizer of at least 70 degrees. If patients become haemodynamically unstable during the seated or standing position, they will be returned to the supine position, and the intervention will be terminated. Phase 4. The patient is returned to the phase 1 position (supine). Further measurements are made for at least 20 minutes. | Device: Mobilisation using the Sara Combilizer<br>* The mobilisation with the Sara Combilizer, will be done one time either 24 or 48 hours after stable intracranial pressure<br>* Other names: Arjo, Malmø, Sweden;|
| No Intervention: Sedentary protocol<br>The sedentary protocol will follow the same four phases as the intervention protocol only the patient will remain in the supine position on the Sara Combilizer®. Ideally, no interventions will occur during the 70-minute protocol. If medications are given or other interventions are necessary, this will be registered. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in partial oxygenation of brain tissue (PbtO2) | PbtO2 measures the partial pressure of oxygen in the extra-cellular fluid of the brain continuously. Therefore, this value represents the balance between oxygen delivered and consumed and reflects the perfusion of the capillaries in the area of interest. | Head-up tilt PbtO2 (delta between supine and standing values) compared to sedentary PbtO2 (delta by subtracting two values measured with the same duration and distance) measured continuously after 24 and 48 hours from stable intracranial pressure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean arterial pressure (MAP) | Arterial line | Head-up tilt MAP (delta between supine and standing values) compared to sedentary MAP (delta by subtracting two values measured with the same duration and distance) measured continuously after 24 and 48 hours from stable intracranial pressure | 
| Change in heart rate (HR) | Three-lead electrocardiography | Head-up tilt HR (delta between supine and standing values) compared to sedentary HR (delta by subtracting two values measured with the same duration and distance) measured continuously after 24 and 48 hours from stable intracranial pressure | 
| Change in intracranial pressure (ICP) | Electrode placed in the intraparenchymal area | Head-up tilt ICP (delta between supine and standing values) compared to sedentary ICP (delta by subtracting two values measured with the same duration and distance) measured continuously after 24 and 48 hours from stable intracranial pressure | 
| Change in middle cerebral artery flow velocity (MCAv) | Transcranial Doppler sonography using a 2 Megahertz probe. | Head-up tilt MCAv (delta between supine and standing values) compared to sedentary MCAv (delta by subtracting two values measured with the same duration and distance) measured continuously after 24 and 48 hours from stable intracranial pressure | 
| Change in microdialysis of cerebrospinal fluid: Glucose level (MDg) | Extracellular brain fluids through a small catheter with a semipermeable membrane. | Intervention protocol MDg (delta between supine and standing values) compared to sedentary MDg (calculated by subtracting baseline from after protocol values) measured continuously after 24 and 48 hours from stable intracranial pressure | 
| Change in microdialysis of cerebrospinal fluid: Lactate/pyruvate level (MDl/p) | Extracellular brain fluids through a small catheter with a semipermeable membrane. | Intervention protocol MDl/p (delta between supine and standing values) compared to sedentary MDl/p (calculated by subtracting baseline from after protocol values) measured continuously after 24 and 48 hours from stable intracranial pressure | 
| Change in cerebral perfusion pressure (CPP) | Cerebral perfusion pressure calculated from mean arterial pressure and intracranial pressure | Head-up tilt CPP (delta between supine and standing values) compared to sedentary CPP (delta by subtracting two values measured with the same duration and distance) measured continuously after 24 and 48 hours from stable intracranial pressure | 
| Change in mean flow index (Mx) | Pearson's correlation coefficient from mean flow velocity af the middle cerebral artery measured by transcranial Doppler and the cerebral perfusion pressure | Head-up tilt Mx (delta between supine and standing values) compared to sedentary Mx (delta by subtracting two values measured with the same duration and distance) measured continuously after 24 and 48 hours from stable intracranial pressure | 
| Change in pressure reactivity index (PRx) | Correlation between intracranial pressure and arterial blood pressure | Head-up tilt PRx (delta between supine and standing values) compared to sedentary PRx (delta by subtracting two values measured with the same duration and distance) measured continuously after 24 and 48 hours from stable intracranial pressure | 
| Change in artial arterial carbon dioxide (PaCO2) levels | Blood samples drawn from arterial line | Head-up tilt PaCO2 (delta between supine and standing values) compared to sedentary PaCO2 (delta by subtracting two values measured with the same duration and distance) measured continuously after 24 and 48 hours from stable intracranial pressure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acquired brain injury, Early mobilisation, Cerebral oxygenation