Projets

“CPP OPtimal” To IndividuaLize Care Of Traumatic Brain Injury Patients (CO-PILOT Study)

Note: la description de certains programmes de recherche est en anglais seulement.

BACKGROUND

Abnormalities in cerebral perfusion pressure (CPP) are strongly associated with poor neurologic outcomes following severe traumatic brain injury (TBI).  Inadequate CPP may induce ischemic injury, while excessive CPP may exacerbate cerebral edema.  Current guidelines recommend maintenance of CPP at 60-70 mmHg.  However, the specific physiologic impact of changes in CPP is closely intertwined with the capacity of cerebral vasculature to “autoregulate” cerebral blood flow (CBF), such that it is unlikely that a single CPP target range is optimal for all patients.

CBF autoregulation can be assessed continuously by calculating the correlation coefficient between mean arterial pressure (MAP) and intracranial pressure (ICP), a parameter referred to as the “pressure reactivity index” (PRx). Observational studies have demonstrated that relative preservation of normal pressure reactivity (PRx < 0.20) is associated with a greater chance of favorable recovery.  There is usually a range of CPP where PRx is lowest, (autoregulation is best preserved).  This range is referred to as the “optimal CPP” or “CPPopt”, and can be identified graphically by comparing CPP (x-axis) and PRx (y-axis).  Numerous retrospective studies, as well as a systematic review, have suggested that the chance of poor outcome after TBI is associated with the magnitude of difference between actual CPP and CPPopt.  Some research suggests that time spent below CPPopt has greater prognostic significance than time above CPPopt, particularly when CPP is below the lower limit of autoregulatory capacity.

OBJECTIVES

(1) To assess the feasibility of regularly measuring CPPopt in a multi-center study.  Feasibility will be evaluated by determining the proportion of time that optimal CPPopt can be established, clinicians’ inter-observer agreement in doing so, and the difference between CPPopt vs. usual CPP targets; (2) To assess the association between deviation from CPPopt and neurologic outcomes; (3) To assess the association between time spent below the lower limit of autoregulation and neurologic outcome; and (4) To assess the association between deviation from CPPopt / time spent below the lower limit of autoregulation and the development of reduced brain tissue oxygen tension (PbtO2 < 20 mmHg) or regional oxygen saturation (rSO2¬ < 55%).  It is anticipated that the findings of this study will be used to plan a larger, multi-center randomized controlled trial.

NOVELTY

Previous studies assessing the relationship of PRx or CPPopt with neurologic outcomes have largely been retrospective and single-center.  A prospective multi-center study where CPP¬opt is regularly determined has never been performed.

METHODS

This will be a prospective, multi-center cohort study involving consecutive patients with severe TBI who undergo insertion of an arterial catheter and intracranial pressure (ICP) monitor.  Participating centers will have access to software (ICM+, Cambridge, UK) that continuously calculates PRx, and graphically displays the relationship between PRx and CPP.  Investigators will determine CPPopt at least twice per day for the first week after TBI and record the concomitant actual CPP goal that is being targeted.  Extended GOS (GOS-e) scores will be determined after 6

OUTCOMES

Outcomes will include: proportion of time that CPPopt can be determined (hypothesized to be > 80%); interobserver agreement (a second investigator will retrospectively review the same tracings that were prospectively reviewed at the bedside); association between > 5 mmHg deviation from CPPopt and poor 6-month neurologic outcome (GOS-e 1-4); association between time spent below the lower limit of autoregulation (PRx > 0.3) and poor 6-month neurologic outcome (GOS-e 14); and the association between > 5 mmHg deviation from CPPopt / time spent below the lower limit of autoregulation and either PbtO2 < 20 or rSO2 < 55%.

SAMPLE SIZE

Given that this will be a pilot study, the goal sample size is based primarily on what is realistic in a one-year time frame.  At Foothills Medical Center, it is estimated that about 15-20 patients per year will meet eligibility criteria.  With a consent rate of approximately 75%, we would recruit about 10-15 patients per year.  With 3-5 centers, we would expect to enroll a total of about 4060 patients.