None listed
Conditions
Brief summary
The Problem: After the initial brain trauma (primary injury) additional brain injury occurs (secondary brain injury) which can significantly affect long-term outcomes of death and severe disability. We aim to reduce this secondary brain injury through a strategy of brain oxygen neuromonitoring and optimisation. Clinical monitoring has traditionally focused on measuring intracranial pressure (ICP), and optimising cerebral perfusion pressure (CPP). These are both insensitive to changes in brain oxygen. Neuronal health depends on a constant supply of oxygen, and in patients with the worst outcomes, brain ischemia is found. In comparison to standard ICP/CPP based care, the BONANZA study will assess the value of additional continuous monitoring of the partial pressure of brain tissue oxygen (PbtO2), in combination with a specific set of interventions that can be instituted when low brain oxygen levels are detected. Some centres use this approach as standard, but this number is currently small. Current data suggests this approach reduces the cerebral hypoxic burden post-TBI and may improve survival and functional outcomes. The solution: The BONANZA study will assess this management strategy and guide clinical practice and policy globally with significant impacts whether the approach proves beneficial or not. This study has now become truly global with sites in Australia, New Zealand, Switzerland, Belgium, UK, Finland, Spain, France and Germany. The Impact: If BONANZA demonstrates benefit, it will become the global standard of care benefiting patients, their families, clinicians and reducing healthcare costs. Equipoise currently exists to address this important evidence gap.
Interventions
Patients in the intervention arm will have continuous PbtO2 and ICP monitoring. Cerebral hypoxic episodes will be treated according to the BONANZA PbtO2 optimisation strategy. The PbtO2 treatment algorithm is a set of physiologic interventions that vary depending on the clinical scenario. The physiological interventions are tiered in a hierarchical fashion, with less aggressive interventions attempted before more aggressive manoeuvres.
Three abnormal clinical scenarios are possible:
1. Isolate
Patients in the intervention arm will have continuous PbtO2 and ICP monitoring. Cerebral hypoxic episodes will be treated according to the BONANZA PbtO2 optimisation strategy. The PbtO2 treatment algorithm is a set of physiologic interventions that vary depending on the clinical scenario. The physiological interventions are tiered in a hierarchical fashion, with less aggressive interventions attempted before more aggressive manoeuvres. Three abnormal clinical scenarios are possible: 1. Isolated intracranial hypertension: PbtO2 is greater than or equal to 20 mmHg and ICP is greater than target. 2. Isolated cerebral hypoxia: PbtO2 is less than 20 mmHg and ICP is within the satisfactory range. 3. Simultaneous cerebral hypoxia and intracranial hypertension: PbtO2 is less than 20 mmHg and ICP is greater than target. All therapies are administered when the patient is in intensive care. Tier 1 therapies include sedation and analgesia. A broad range of agents may be used, most commonly Propofol, Midazolam, Morphine and Fentanyl. Vasopressors or drugs that are used to improve blood pressure may also be given in order to improve blood flow to the brain. Commonly used vasopressors are Noradrenaline and Adrenaline. Osmotherapy may also be administered to reduce the water content of the brain and reduce brain swelling. Commonly used osmotics include Mannitol and Hpertonic saline. The doses of all these drugs mentioned are variable and are usually given via an infusion that is titrated according to the patients response. Tier 2 therapies include the use of neuromuscular blockade agents like Cisatracurium. The dose is variable and may be given intermittently as a bolus or via infusion depending on each patient scenario. Other tier 2 therapies include blood tranfusion, and adjustments to the ventilator in order to optimize levels of oxygen and carbon dioxide in the patients blood. Tier 3 therapies are largely optional and include lowering the patients temperature, further ventilator adjustments, the use of drugs known as barbiturates that will induce a deep coma in the patient and the consideration of surgery involving the removal of a portion of the skull to relieve pressure on the brain. These interventions are only delivered when the patient is in intensive care under the supervision of a trained intensivist. The clinical team in intensive care will determine and adjust the therapies according to the patient's clinical scenario and any surgery that may be performed will be undertaken by a neurosurgeon. The number of times an intervention is delivered will vary from patient to patient depending on their individual response and will continue for the duration of PbtO2 monitoring. PbtO2 monitoring will continue until the patient awakens (GCS motor score = 6), or the ICP monitor is removed. Removal of the probe will be at the discretion of the clinical team. The duration of ICP monitoring will be determined by the treating clinicians. Case report forms will capture interventions.
Sponsors
Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients = 18 years who have suffered a non-penetrating severe TBI, as defined by: 1. A post resuscitation GCS of 3-8 (motor sub-score less than 6) AND an abnormal CT scan (demonstrating intra-cranial trauma), OR 2. A post resuscitation GCS of 3-8 (motor sub-score less than 6), in the absence of confounders, AND a high index of suspicion for severe TBI (in the opinion of the treating neurosurgeon).
Exclusion criteria
a. Contraindication to placement of ICP and/or PbtO2 monitor (un-correctable coagulopathy). b. Intra-cranial monitoring is already in situ at the time of neurosurgical assessment. c. Pregnancy. d. Bilaterally absent pupillary response (e.g. both pupils must be visible and are fixed and dilated) in the absence of confounders (e.g. traumatic mydriasis, atropine, neuromuscular blockers). e. Characteristics that preclude accurate optimisation of PbtO2: - Refractory hypotension (e.g. SBP<90mmHg despite medical intervention) - Refractory systemic hypoxia (e.g. SaO2 <90% despite medical intervention) - Active CNS disease that is likely to impair accurate PbtO2 measurements (prior TBI, active CNS disease in vicinity of probe position). f. Non-survivable injury or no intention of aggressive intervention. g. Cardiac arrest as part of this traumatic event. h. Other issues prior to randomization that would preclude appropriate treatment, diagnosis, or follow-up such as known pre-existing neurologic disease with confounding residual deficits or known pre-existing condition resulting in an inability to perform activities of daily living without assistance. i. At the time of the decision to insert an ICP monitor, 12 or more hours has elapsed since the injury occurred.
Outcome results
None listed