PRECISION-TBI: a study protocol for a vanguard prospective cohort study to enhance understanding and management of moderate to severe traumatic brain injury in Australia.

INTRODUCTION: Traumatic brain injury (TBI) is a heterogeneous condition in terms of pathophysiology and clinical course. Outcomes from moderate to severe TBI (msTBI) remain poor despite concerted research efforts. The heterogeneity of clinical management represents a barrier to progress in this area. PRECISION-TBI is a prospective, observational, cohort study that will establish a clinical research network across major neurotrauma centres in Australia. This network will enable the ongoing collection of injury and clinical management data from patients with msTBI, to quantify variations in processes of care between sites. It will also pilot high-frequency data collection and analysis techniques, novel clinical interventions, and comparative effectiveness methodology. METHODS AND ANALYSIS: PRECISION-TBI will initially enrol 300 patients with msTBI with Glasgow Coma Scale (GCS) <13 requiring intensive care unit (ICU) admission for invasive neuromonitoring from 10 Australian neurotrauma centres. Demographic data and process of care data (eg, prehospital, emergency and surgical intervention variables) will be collected. Clinical data will include prehospital and emergency department vital signs, and ICU physiological variables in the form of high frequency neuromonitoring data. ICU treatment data will also be collected for specific aspects of msTBI care. Six-month extended Glasgow Outcome Scores (GOSE) will be collected as the key outcome. Statistical analysis will focus on measures of between and within-site variation. Reports documenting performance on selected key quality indicators will be provided to participating sites. ETHICS AND DISSEMINATION: Ethics approval has been obtained from The Alfred Human Research Ethics Committee (Alfred Health, Melbourne, Australia). All eligible participants will be included in the study under a waiver of consent (hospital data collection) and opt-out (6 months follow-up). Brochures explaining the rationale of the study will be provided to all participants and/or an appropriate medical treatment decision-maker, who can act on the patient's behalf if they lack capacity. Study findings will be disseminated by peer-review publications. TRIAL REGISTRATION NUMBER: NCT05855252.

The pressure reactivity index as a measure of cerebral autoregulation and its application in traumatic brain injury management.

Severe traumatic brain injury (TBI) is a major cause of morbidity and mortality globally. The Brain Trauma Foundation guidelines advocate for the maintenance of a cerebral perfusion pressure (CPP) between 60 and 70 mmHg following severe TBI. However, such a uniform goal does not account for changes in cerebral autoregulation (CA). CA refers to the complex homeostatic mechanisms by which cerebral blood flow is maintained, despite variations in mean arterial pressure and intracranial pressure. Disruption to CA has become increasingly recognised as a key mediator of secondary brain injury following severe TBI. The pressure reactivity index is calculated as the degree of statistical correlation between the slow wave components of mean arterial pressure and intracranial pressure signals and is a validated dynamic marker of CA status following brain injury. The widespread acceptance of pressure reactivity index has precipitated the consideration of individualised CPP targets or an optimal cerebral perfusion pressure (CPPopt). CPPopt represents an alternative target for cerebral haemodynamic optimisation following severe TBI, and early observational data suggest improved neurological outcomes in patients whose CPP is more proximate to CPPopt. The recent publication of a prospective randomised feasibility study of CPPopt guided therapy in TBI, suggests clinicians caring for such patients should be increasingly familiar with these concepts. In this paper, we present a narrative review of the key landmarks in the development of CPPopt and offer a summary of the evidence for CPPopt-based therapy in comparison to current standards of care.

What Determines the Arterial Partial Pressure of Carbon Dioxide on Venovenous Extracorporeal Membrane Oxygenation?

Rapid reductions in P a CO 2 during extracorporeal membrane oxygenation (ECMO) are associated with poor neurologic outcomes. Understanding what factors determine P a CO 2 may allow a gradual reduction, potentially improving neurologic outcome. A simple and intuitive arithmetic expression was developed, to describe the interactions between the major factors determining P a CO 2 during venovenous ECMO. This expression was tested using a wide range of input parameters from clinically feasible scenarios. The difference between P a CO 2 predicted by the arithmetic equation and P a CO 2 predicted by a more robust and complex in-silico mathematical model, was <10 mm Hg for more than 95% of the scenarios tested. With no CO 2 in the sweep gas, P a CO 2 is proportional to metabolic CO 2 production and inversely proportional to the "total effective expired ventilation" (sum of alveolar ventilation and oxygenator ventilation). Extracorporeal blood flow has a small effect on P a CO 2 , which becomes more important at low blood flows and high recirculation fractions. With CO 2 in the sweep gas, the increase in P a CO 2 is proportional to the concentration of CO 2 administered. P a CO 2 also depends on the fraction of the total effective expired ventilation provided via the oxygenator. This relationship offers a simple intervention to control P a CO 2 using titration of CO 2 in the sweep gas.

A pilot study of high frequency accelerometry-based sedation and agitation monitoring in critically ill patients.

OBJECTIVE: The degree of sedation or agitation in critically ill patients is typically assessed with the Richmond Agitation and Sedation Scale (RASS). However, this approach is intermittent and subject to unrecognised variation between assessments. High frequency accelerometry may assist in achieving a quantitative and continuous assessment of sedation while heralding imminent agitation. DESIGN: We undertook a prospective, observational pilot study. SETTING: An adult tertiary intensive care unit in Melbourne, Australia. PARTICIPANTS: 20 patients with an admission diagnosis of trauma. MAIN OUTCOME MEASURES: Accelerometers were applied to patients' wrists and used to continuously record patient movement. Video data of patient behaviour were simultaneously collected, and observers blinded to accelerometry data were adjudicated the RASS score every 30 seconds. Exploratory analyses were undertaken. RESULTS: Patients were enrolled for a median duration of 9.7 hours (interquartile range [IQR], 0-22.8) and a total of 160 hours. These patients had a median RASS score of 0 (IQR, -4 to 0). A 2-minute moving window of amplitude variance was seen to reflect contemporaneous fluctuations in motor activity and was proportional to the RASS score. Furthermore, the moving window of amplitude variance was observed to spike immediately before ≥ 2 point increases in the RASS score. CONCLUSIONS: We describe a novel approach to the analysis of wrist accelerometry data in critically ill patients. This technique not only appears to provide novel and continuous information about the depth of sedation or degree of agitation, it is also notable in its aptitude to anticipate impending transitions to higher RASS values.