Despite improvements in management, mortality in severe traumatic brain injury (TBI) remains 25% and only 40% of patients survive without major handicap. Medical/surgical interventions aim to maintain adequate brain perfusion, which is critically dependent on cerebral perfusion pressure (CPP); calculated as the difference between mean arterial pressure (MAP) and intracranial pressure (ICP). Current guidelines aim for a CPP above 50 mmHg, based on population means. However, this 'one size fits all' approach is flawed, because the relation between CPP and brain perfusion varies between individuals. Further, this approach takes no account of autoregulation, a key protective mechanism that maintains cerebral perfusion despite CPP fluctuations.

Autoregulation is variably preserved following TBI, and there are large between patient variances in the 'optimal' CPP (CPPopt) at which autoregulation operates best. Individual CPPopt can be retrieved automatically by plotting autoregulation data against the CPP over a certain time window. The investigators have shown that maintenance of CPP close to CPPopt is associated with improved outcomes. These data pose the hypothesis that optimisation of management in individuals may be achieved by using the zone of optimal autoregulation as a basis for defining individualised CPP targets.

The investigators propose, together with collaborators in the CPPopt study group (Maastricht, Cambridge, Leuven and Aachen) to set up a pilot (multicenter) feasibility study to develop a protocol for a definitive outcome randomized controlled trial (RCT). This study aims to develop protocols for CPPopt guided critical care, and show that they maintain patients closer to their optimum perfusion levels than standard protocols which keep above a population CPP threshold of 60 mmHg.

Hence, the main objective is to offer clinicians monitoring and therapy algorithms that achieve individualized optimal CPPopt targets and potentially improve TBI outcome.

Inclusion Criteria:

• Any adult severe TBI patient requiring multimodality monitoring and ICP-directed therapy for at least 24 hrs on the assessment of the recruiting team.
• Start randomization within 24 hrs after ICU admission.
• Deferred informed consent or deferred proxy assent from relatives/legal representative (consultee).
• Exception for enrolling a patient past the 24 hour window: A patient who is admitted to the hospital and later experiences neuro-worsening that is not due to a systemic insult, (e.g. myocardial infarction, arrhythmia, pulmonary embolus, systemic hemorrhage) but due to a presumptive intracranial cause, and subsequently requires an ICP monitor, may be screened for enrolment. Consent, randomization, and monitor placement must be done within 48 hours from injury in order for the patient to qualify.

Exclusion Criteria:

• Patients < 18 years old.
• Known pregnancy.
• Moribund at presentation (e.g. bilaterally absent pupillary responses)
• Patients with primary decompressive craniectomy.
• Patients already enrolled in > 1 other research studies.