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Abstract Best practice guidelines have advanced severe traumatic brain injury (TBI) care; however, there is little that currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the S eattle I nternational severe traumatic B rain I njury C onsensus C onference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, and acceptability of neurological outcomes, as well as putative means of improving decisions that might limit care. A total of 97.6% of the 42 SIBICC panelists completed the survey. Responses to most questions were highly variable. Overall, panelists reported infrequent use of prognostic calculators, and observed variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a "nihilism guard." More than 50% of panelists felt that if it was certain to be permanent, a vegetative state or lower severe disability would justify a withdrawal of care decision, whereas 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, on average a 64-69% chance of a poor outcome was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes that might prompt consideration of care withdrawal; however, imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care-limiting decisions.

Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established. Citicoline, a naturally occurring endogenous compound, offers the potential of neuroprotection, neurorecovery, and neurofacilitation to enhance recovery after TBI. Citicoline has a favorable side-effect profile in humans and several meta-analyses suggest a benefit of citicoline treatment in stroke and dementia. COBRIT is a randomized, double-blind, placebo-controlled, multi-center trial of the effects of 90 days of citicoline on functional outcome in patients with complicated mild, moderate, and severe TBI. In all, 1292 patients will be recruited over an estimated 32 months from eight clinical sites with random assignment to citicoline (1000 mg twice a day) or placebo (twice a day), administered enterally or orally. Functional outcomes are assessed at 30, 90, and 180 days after the day of randomization. The primary outcome consists of a set of measures that will be analyzed as a composite measure using a global test procedure at 90 days. The measures comprise the following core battery: the California Verbal Learning Test II; the Controlled Oral Word Association Test; Digit Span; Extended Glasgow Outcome Scale; the Processing Speed Index; Stroop Test part 1 and Stroop Test part 2; and Trail Making Test parts A and B. Secondary outcomes include survival, toxicity, and rate of recovery.

Changes in the modes of cerebrovascular pressure transmission during cerebral vasodilation induced by hypercapnic challenge were examined as a means for developing the basis for a bedside method to evaluate regulation of cerebral blood flow. Recordings of arterial blood pressure (ABP) and intracranial pressure (ICP) obtained from a piglet preparation equipped with a cranial window were used to determine serial changes of the highest modal frequency (HMF) and dampening factor (DF) of a numerical system identification model of cerebrovascular pressure transmission. Resistance and compliance elements of a Windkessel model of ICP dynamics selected to provide the mathematical structure for the system identification modeling approach were also manipulated to obtain a match with HMF, DF, and the experimental and simulated recordings of ICP. During hypercapnic challenge, significant increases of ICP, pial arterial diameter (PAD) and partial pressure of arterial blood carbon dioxide increases, and a decrease of arterial pH were observed. Vasodilation changed the modes of the system identification model of cerebrovascular pressure transmission from a dominantly over-damped process to an under-damped one with a significant increase in HMF and decrease in DF. Simulations of the Windkessel circuit model required a decrease in the relative resistance and an increase in relative compliance of the arterial-arteriolar vascular bed consistent with the observed increases in PAD induced by vasodilation. Evaluation of changes in the modes of cerebrovascular pressure transmission may provide means of assessing the state of cerebrovascular vasodilation and autoregulation of cerebral blood flow in the clinical setting.