Virginie Williams

OBJECTIVES: In critically ill patients with acute brain injury (ABI), maintaining intracranial pressure (ICP) and brain tissue oxygenation (PbtO₂) within targets could prevent secondary neurologic injury. Tight control of CO ₂ (Paco ₂), a potent regulator of cerebrovascular tone, is generally advocated, but its vasomotor effect may be short-lived. Our aim was to compare the effect of the synchronous Paco ₂ vs. its variation from a previous baseline on PbtO₂ and ICP. DESIGN: We performed a post hoc analysis of a prospective cohort study collecting arterial blood gas (ABG) values alongside synchronous neuromonitoring variables. Linear mixed-effects models were fitted to evaluate the association between Paco ₂ and/or Paco ₂ variation from its average of the last 8–24 hr vs. PbtO₂ and ICP, while controlling for cerebral perfusion pressure and Pao ₂. SETTING: Mixed medical-surgical ICU of Sacré-Coeur Hospital, an academic trauma center in Montreal, Canada. PATIENTS: All consecutive adult patients admitted for ABI with ICP and PbtO₂ monitoring between May 2017 and November 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 78 patients with 3047 ABG-neuromonitoring couplets. The model using the variation of Paco ₂ from its average of the last 24 hr displayed the best performance for the prediction of PbtO₂ (coefficient 0.37; 95% CI 0.21–0.53). The strongest predictor of ICP was the variation of Paco ₂ from its average of the last 8 hr (coefficient 0.17; 95% CI 0.10–0.23). CONCLUSIONS: Variation in Paco ₂ from baseline is a more significant determinant of PbtO₂ and ICP than the absolute Paco ₂ value at a given time. There may be a baseline vasomotor reset when patients are exposed to a given level of CO₂ for 8 to 24 hr. Therefore, sustained intentional manipulation of Paco ₂ is unlikely to have lasting effects and slower correction rates of high or low Paco ₂ could help prevent brain tissue hypoxia or intracranial hypertension, respectively.

Introduction Therapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and assess the effect of a multi-session transcranial alternating current stimulation (tACS) intervention in subacute brain-injured patients on recovery of consciousness, related brain oscillations and brain network dynamics. Methods and analyses The study is comprised of two phases: a validation phase (n=12) and a randomised controlled trial (n=138). Both phases will be conducted in medically stable brain-injured adult patients (traumatic brain injury and hypoxic-ischaemic encephalopathy), with a Glasgow Coma Scale score ≤12 after continuous sedation withdrawal. Recruitment will occur at the intensive care unit of a Level 1 Trauma Centre in Montreal, Quebec, Canada. The intervention includes a 20 min 10 Hz tACS at 1 mA intensity or a sham session over parieto-occipital cortical sites, repeated over five consecutive days. The current’s frequency targets alpha brain oscillations (8–13 Hz), known to be associated with consciousness. Resting-state electroencephalogram (EEG) will be recorded four times daily for five consecutive days: pre and post-intervention, at 60 and 120 min post-tACS. Two additional recordings will be included: 24 hours and 1-week post-protocol. Multimodal measures (blood samples, pupillometry, behavioural consciousness assessments (Coma Recovery Scale-revised), actigraphy measures) will be acquired from baseline up to 1 week after the stimulation. EEG signal analysis will focus on the alpha bandwidth (8–13 Hz) using spectral and functional network analyses. Phone assessments at 3, 6 and 12 months post-tACS, will measure long-term functional recovery, quality of life and caregivers’ burden. Ethics and dissemination Ethical approval for this study has been granted by the Research Ethics Board of the CIUSSS du Nord-de-l’Île-de-Montréal (Project ID 2021–2279). The findings of this two-phase study will be submitted for publication in a peer-reviewed academic journal and submitted for presentation at conferences. The trial’s results will be published on a public trial registry database (ClinicalTrials.gov). Trial registration number NCT05833568.

Background: Agitated behaviors are problematic in intensive care unit (ICU) patients recovering from traumatic brain injury (TBI) as they create substantial risks and challenges for healthcare providers. To date, there have been no studies evaluating their epidemiology and impact in the ICU. Prior to planning a multicenter study, assessment of recruitment, feasibility, and pilot study procedures is needed. In this pilot study, we aimed to evaluate the feasibility of conducting a large multicenter prospective cohort study. Methods: This feasibility study recruited adult patients admitted to the ICU with TBI and an abnormal cerebral CT scan. In all patients, we documented Richmond Agitation Sedation Score (RASS) and agitated behaviors every 8-h nursing shift using a dedicated tool documenting 14 behaviors. Our feasibility objectives were to obtain consent from at least 2 patients per month; completion of screening logs for agitated behaviors by bedside nurses for more than 90% of 8-h shifts; completion of data collection in an average of 6 h or less; and obtain 6-month follow-up for surviving patients. The main clinical outcome was the incidence of agitation and individual agitated behaviors. Results: In total, 47 eligible patients were approached for inclusion and 30 (64% consent rate) were recruited over a 10-month period (3 patients/month). In total, 794 out of 827 (96%) possible 8-h periods of agitated behavior logs were completed by bedside nurses, with a median of 24 observations (IQR 28.0) per patient. During the ICU stay, 17 of 30 patients developed agitation (56.7%; 95% CI 0.37–0.75) defined as RASS ≥ 2 during at least one observation period and for a median of 4 days (IQR 5.5). At 6 months post-TBI, among the 24 available patients, an unfavorable score (GOS-E < 5 including death) was reported in 12 patients (50%). In the 14 patients who were alive and available at 6 months, the median QOLIBRI score was 74.5 (IQR 18.5). Conclusions: This study demonstrates the feasibility of conducting a larger cohort study to evaluate the epidemiology and impact of agitated behaviors in critically ill TBI patients. This study also shows that agitated behaviors are frequent and are associated with adverse events.