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Background: Neuromonitoring devices are often used in traumatic brain injury. The objective of this report is to raise awareness concerning variations in optimal cerebral perfusion pressure (CPPopt) determination using exploratory information provided by two neuromonitoring monitors that are part of research programs (Moberg CNS Monitor and RAUMED NeuroSmart LogO)., Methods: We connected both monitors simultaneously to a parenchymal intracranial pressure catheter and recorded the pressure reactivity index (PRx) and the derived CPPopt estimates for a patient with a severe traumatic brain injury. These estimates were available at the bedside and were updated at each minute., Results: Using the Bland and Altman method, we found a mean variation of - 3.8 (95% confidence internal from - 8.5 to 0.9) mm Hg between the CPPopt estimates provided by the two monitors (limits of agreement from - 26.6 to 19.1 mm Hg). The PRx and CPPopt trends provided by the two monitors were similar over time, but CPPopt trends differed when PRx values were around zero. Also, almost half of the CPPopt estimates differed by more than 10 mm Hg., Conclusions: These wide variations recorded in the same patient are worrisome and reiterate the importance of understanding and standardizing the methodology and algorithms behind commercial neuromonitoring devices prior to incorporating them in clinical use., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Patients with traumatic brain injury (TBI) with large contusions make up a specific TBI subtype. Because of the risk of brain edema worsening, elevated cerebral perfusion pressure (CPP) may be particularly dangerous. The pressure reactivity index (PRx) and optimal cerebral perfusion pressure (CPPopt) are new promising perfusion targets based on cerebral autoregulation, but they reflect the global brain state and may be less valid in patients with predominant focal lesions. In this study, we aimed to investigate if patients with TBI with significant contusions exhibited a different association between PRx, CPP, and CPPopt in relation to functional outcome compared to those with small/no contusions., Methods: This observational study included 385 patients with moderate to severe TBI treated at a neurointensive care unit in Uppsala, Sweden. The patients were classified into two groups: (1) significant contusions (> 10 mL) and (2) small/no contusions (but with extra-axial or diffuse injuries). The percentage of good monitoring time (%GMT) with intracranial pressure > 20 mm Hg; PRx > 0.30; CPP < 60 mm Hg, within 60-70 mm Hg, or > 70 mm Hg; and ΔCPPopt less than - 5 mm Hg, ± 5 mm Hg, or > 5 mm Hg was calculated. Outcome (Glasgow Outcome Scale-Extended) was assessed after 6 months., Results: Among the 120 (31%) patients with significant contusions, a lower %GMT with CPP between 60 and 70 mm Hg was independently associated with unfavorable outcome. The %GMTs with PRx and ΔCPPopt ± 5 mm Hg were not independently associated with outcome. Among the 265 (69%) patients with small/no contusions, a higher %GMT of PRx > 0.30 and a lower %GMT of ΔCPPopt ± 5 mm Hg were independently associated with unfavorable outcome., Conclusions: In patients with TBI with significant contusions, CPP within 60-70 mm Hg may improve outcome. PRx and CPPopt, which reflect global cerebral pressure autoregulation, may be useful in patients with TBI without significant focal brain lesions but seem less valid for those with large contusions. However, this was an observational, hypothesis-generating study; our findings need to be validated in prospective studies before translating them into clinical practice., (© 2024. The Author(s).)

Background: Traumatic brain injury (TBI) poses a significant challenge to healthcare providers, necessitating meticulous management of hemodynamic parameters to optimize patient outcomes. This article delves into the critical task of defining and meeting continuous arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) targets in the context of severe TBI in neurocritical care settings., Methods: We narratively reviewed existing literature, clinical guidelines, and emerging technologies to propose a comprehensive approach that integrates real-time monitoring, individualized cerebral perfusion target setting, and dynamic interventions., Results: Our findings emphasize the need for personalized hemodynamic management, considering the heterogeneity of patients with TBI and the evolving nature of their condition. We describe the latest advancements in monitoring technologies, such as autoregulation-guided ABP/CPP treatment, which enable a more nuanced understanding of cerebral perfusion dynamics. By incorporating these tools into a proactive monitoring strategy, clinicians can tailor interventions to optimize ABP/CPP and mitigate secondary brain injury., Discussion: Challenges in this field include the lack of standardized protocols for interpreting multimodal neuromonitoring data, potential variability in clinical decision-making, understanding the role of cardiac output, and the need for specialized expertise and customized software to have individualized ABP/CPP targets regularly available. The patient outcome benefit of monitoring-guided ABP/CPP target definitions still needs to be proven in patients with TBI., Conclusions: We recommend that the TBI community take proactive steps to translate the potential benefits of personalized ABP/CPP targets, which have been implemented in certain centers, into a standardized and clinically validated reality through randomized controlled trials., (© 2024. The Author(s).)

Background: Today, invasive intracranial pressure (ICP) measurement remains the standard, but its invasiveness limits availability. Here, we evaluate a novel ultrasound-based optic nerve sheath parameter called the deformability index (DI) and its ability to assess ICP noninvasively. Furthermore, we ask whether combining DI with optic nerve sheath diameter (ONSD), a more established parameter, results in increased diagnostic ability, as compared to using ONSD alone., Methods: We prospectively included adult patients with traumatic brain injury with invasive ICP monitoring, which served as the reference measurement. Ultrasound images and videos of the optic nerve sheath were acquired. ONSD was measured at the bedside, whereas DI was calculated by semiautomated postprocessing of ultrasound videos. Correlations of ONSD and DI to ICP were explored, and a linear regression model combining ONSD and DI was compared to a linear regression model using ONSD alone. Ability of the noninvasive parameters to distinguish dichotomized ICP was evaluated using receiver operating characteristic curves, and a logistic regression model combining ONSD and DI was compared to a logistic regression model using ONSD alone., Results: Forty-four ultrasound examinations were performed in 26 patients. Both DI (R =  - 0.28; 95% confidence interval [CI] R <  - 0.03; p = 0.03) and ONSD (R = 0.45; 95% CI R > 0.23; p < 0.01) correlated with ICP. When including both parameters in a combined model, the estimated correlation coefficient increased (R = 0.51; 95% CI R > 0.30; p < 0.01), compared to using ONSD alone, but the model improvement did not reach statistical significance (p = 0.09). Both DI (area under the curve [AUC] 0.69, 95% CI 0.53-0.83) and ONSD (AUC 0.72, 95% CI 0.56-0.86) displayed ability to distinguish ICP dichotomized at ICP ≥ 15 mm Hg. When using both parameters in a combined model, AUC increased (0.80, 95% CI 0.63-0.90), and the model improvement was statistically significant (p = 0.02)., Conclusions: Combining ONSD with DI holds the potential of increasing the ability of optic nerve sheath parameters in the noninvasive assessment of ICP, compared to using ONSD alone, and further study of DI is warranted., (© 2024. The Author(s).)

The neurological examination has remained key for the detection of worsening in neurocritical care patients, particularly after traumatic brain injury (TBI). New-onset, unreactive anisocoria frequently occurs in such situations, triggering aggressive diagnostic and therapeutic measures to address life-threatening elevations in intracranial pressure (ICP). As such, the field needs objective, unbiased, portable, and reliable methods for quickly assessing such pupillary changes. In this area, quantitative pupillometry (QP) proves promising, leveraging the analysis of different pupillary variables to indirectly estimate ICP. Thus, this scoping review seeks to describe the existing evidence for the use of QP in estimating ICP in adult patients with TBI as compared with invasive methods, which are considered the standard practice. This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and EMBASE. The search was limited to studies of adult patients with TBI published in any language between 2012 and 2022. Eight studies were included for analysis, with the vast majority being prospective studies conducted in high-income countries. Among QP variables, serial rather than isolated measurements of neurologic pupillary index, constriction velocity, and maximal constriction velocity demonstrated the best correlation with invasive ICP measurement values, particularly in predicting refractory intracranial hypertension. Neurologic pupillary index and ICP also showed an inverse relationship when trends were simultaneously compared. As such, QP, when used repetitively, seems to be a promising tool for noninvasive ICP monitoring in patients with TBI, especially when used in conjunction with other clinical and neuromonitoring data., (© 2024. The Author(s).)

Background: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO 2 ) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation., Methods: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO 2 . Autoregulatory function was measured by interrogating changes in ICP and PbtO 2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP., Results: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO 2  < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO 2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05)., Conclusions: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Intracranial hypertension (IH) is a key driver of secondary brain injury in patients with traumatic brain injury. Lowering intracranial pressure (ICP) as soon as IH occurs is important, but a preemptive approach would be more beneficial. We systematically reviewed the artificial intelligence (AI) models, variables, performances, risks of bias, and clinical machine learning (ML) readiness levels of IH prediction models using AI. We conducted a systematic search until 12-03-2023 in three databases. Only studies predicting IH or ICP in patients with traumatic brain injury with a validation of the AI model were included. We extracted type of AI model, prediction variables, model performance, validation type, and prediction window length. Risk of bias was assessed with the Prediction Model Risk of Bias Assessment Tool, and we determined the clinical ML readiness level. Eleven out of 399 nonduplicate publications were included. A gaussian processes model using ICP and mean arterial pressure was most common. The maximum reported area under the receiver operating characteristic curve was 0.94. Four studies conducted external validation, and one study a prospective clinical validation. The prediction window length preceding IH varied between 30 and 60 min. Most studies (73%) had high risk of bias. The highest clinical ML readiness level was 6 of 9, indicating "real-time model testing" stage in one study. Several IH prediction models using AI performed well, were externally validated, and appeared ready to be tested in the clinical workflow (clinical ML readiness level 5 of 9). A Gaussian processes model was most used, and ICP and mean arterial pressure were frequently used variables. However, most studies showed a high risk of bias. Our findings may help position AI for IH prediction on the path to ultimate clinical integration and thereby guide researchers plan and design future studies., (© 2024. The Author(s).)

Background: Intrahospital transportation (IHT) of patients with traumatic brain injury (TBI) is common and may have adverse consequences, incurring inherent risks. The data on the frequency and severity of clinical complications linked with IHT are contradictory, and there is no agreement on whether it is safe or potentially challenging for neurocritical care unit patients. Continuous intracranial pressure (ICP) monitoring is essential in neurointensive care. The role of ICP monitoring and management of cerebral autoregulation impairments in IHT of patients with severe TBI is underinvestigated. The purpose of this nonrandomized retrospective single-center study was to assess the dynamics of ICP and an improved pressure reactivity index (iPRx) as a measure of autoregulation during IHT., Methods: Seventy-seven men and fourteen women with severe TBI admitted in 2012-2022 with a mean age of 33.2 ± 5.2 years were studied. ICP and arterial pressure were invasively monitored, and cerebral perfusion pressure and iPRx were calculated from the measured parameters. All patients were subjected to dynamic helical computed tomography angiography using a 64-slice scanner Philips Ingenuity computed tomography scan 1-2 days after TBI. Statistical analysis of all results was done using a paired t-test, and p was preset at < 0.05. The logistic regression analysis was performed for cerebral ischemia development dependent on intracranial hypertension and cerebrovascular reactivity., Results: IHT led to an increase in ICP in all the patients, especially during vertical movement in an elevator (maximum 75.2 mm Hg). During the horizontal transportation on the floor, ICP remained increased (p < 0.05). The mean ICP during IHT was significantly higher (26.1 ± 13.5 mm Hg, p < 0.001) than that before the IHT (19.9 ± 5.3 mm Hg). The mean iPRx after and before IHT was 0.52 ± 0.04 and 0.23 ± 0.14, respectively (p < 0.001)., Conclusions: Both horizontal and vertical transportation causes a significant increase in ICP and iPRx in patients with severe TBI, potentially leading to the outcome worsening., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Transcranial Doppler (TCD) is a noninvasive bedside tool for cerebral hemodynamic assessments in multiple clinical scenarios. TCD, by means of measuring systolic and diastolic blood velocities, allows the calculation of the pulsatility index (PI), a parameter that is correlated with intracranial pressure (ICP). Nevertheless, the predictive value of the PI for raised ICP appears to be low, as it is subjected to several, often confounding, factors not related to ICP. Recently, the pulsatile apparent resistance (PaR) index was developed as a PI corrected for arterial blood pressure, reducing some of the confounding factors influencing PI. This study compares the predictive value of PaR versus PI for intracranial hypertension (IH) (ICP > 20 mm Hg) in patients with traumatic brain injury., Methods: Patients with traumatic brain injury admitted to the neurocritical care unit who required invasive ICP monitoring were included prospectively within 5 days of admission. TCD measurements were performed in both middle cerebral arteries, allowing calculations of the PI and PaR. The optimal cutoff, discriminative power of these parameters for ICP ≥ 20 mm Hg, was assessed by calculating the area under the receiver operator characteristics curve (AUC)., Results: In total, 93 patients were included. A total of 20 (22%) patients experienced IH during the recording sessions. The discriminative power was low for PI (AUC 0.63) but slightly higher for PaR (AUC 0.77). Nonparametric analysis indicated significant difference for PaR when comparing patients with (median 0.169) and without IH (median - 0.052, p = 0.001), whereas PI medians for patients with and without IH were 0.86 and 0.77, respectively (p =  0.041). Regarding subanalyses, the discriminative power of these parameters increased after exclusion of patients who had undergone a neurosurgical procedure. This was especially true for the PaR (AUC 0.89) and PI (AUC 0.72). Among these patients, a PaR cutoff value of - 0.023 had 100% sensitivity and 52.9% specificity., Conclusions: In the present study, discriminative power of the PaR for discriminating IH was superior to the PI. The PaR seems to be a reliable noninvasive parameter for detecting IH. Further studies are warranted to define its clinical application, especially in aiding neurosurgical decision making, following up in intensive care units, and defining its ability to indicate responses according to the therapies administered., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Paroxysmal sympathetic hyperactivity (PSH) occurs in a subset of patients with traumatic brain injury (TBI) and is associated with worse outcomes. Sepsis is also associated with worse outcomes after TBI and shares several physiologic features with PSH, potentially creating diagnostic confusion and suboptimal management of each. This is the first study to directly investigate the interaction between PSH and infection using robust diagnostic criteria., Methods: We performed a retrospective cohort study of patients with TBI admitted to a level I trauma center intensive care unit with hospital length of stay of at least 2 weeks. From January 2016 to July 2018, 77 patients diagnosed with PSH were 1:1 matched by age and Glasgow Coma Scale to 77 patients without PSH. Trauma infectious diseases subspecialists prospectively documented assessments corroborating diagnoses of infection. Extracted data including incidence, timing, classification, and anatomical source of infections were compared according to PSH diagnosis. We also evaluated daily PSH clinical feature severity scores and systemic inflammatory response syndrome (SIRS) criteria and compared values for patients with and without confirmed infection, stratified by PSH diagnosis., Results: During the first 2 weeks of hospitalization, there were no differences in rates of suspected (62%) nor confirmed (48%) infection between patients with PSH and controls. Specific treatments for PSH were initiated on median hospital day 7 and for confirmed infections on median hospital day 8. SIRS criteria could identify infection only in patients who were not diagnosed with PSH., Conclusions: In the presence of brain injury-induced autonomic nervous system dysregulation, the initiation and continuation of antimicrobial therapy is a challenging clinical decision, as standard physiologic markers of sepsis do not distinguish infected from noninfected patients with PSH, and these entities often present around the same time. Clinicians should be aware that PSH is a potential driver of SIRS, and familiarity with its diagnostic criteria as proposed by the PSH assessment measure is important. Management by a multidisciplinary team attentive to these issues may reduce rates of inappropriate antibiotic usage and misdiagnoses., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Introduction: Neuromonitoring represents a cornerstone in the comprehensive management of patients with traumatic brain injury (TBI), allowing for early detection of complications such as increased intracranial pressure (ICP) [1]. This has led to a search for noninvasive modalities that are reliable and deployable at bedside. Among these, ultrasonographic optic nerve sheath diameter (ONSD) measurement is a strong contender, estimating ICP by quantifying the distension of the optic nerve at higher ICP values. Thus, this scoping review seeks to describe the existing evidence for the use of ONSD in estimating ICP in adult TBI patients as compared to gold-standard invasive methods., Materials and Methods: This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and EMBASE. The search was limited to studies of adult patients with TBI published in any language between 2012 and 2022. Sixteen studies were included for analysis, with all studies conducted in high-income countries., Results: All of the studies reviewed measured ONSD using the same probe frequency. In most studies, the marker position for ONSD measurement was initially 3 mm behind the globe, retina, or papilla. A few studies utilized additional parameters such as the ONSD/ETD (eyeball transverse diameter) ratio or ODE (optic disc elevation), which also exhibit high sensitivity and reliability., Conclusion: Overall, ONSD exhibits great test accuracy and has a strong, almost linear correlation with invasive methods. Thus, ONSD should be considered one of the most effective noninvasive techniques for ICP estimation in TBI patients., (© 2023. The Author(s).)

Background: Severe traumatic brain injury (TBI) is a major contributor to disability and mortality in the industrialized world. Outcomes of severe TBI are profoundly heterogeneous, complicating outcome prognostication. Several prognostic models have been validated for acute prediction of 6-month global outcomes following TBI (e.g., morbidity/mortality). In this preliminary observational prognostic study, we assess the utility of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) Lab model in predicting longer term global and cognitive outcomes (7-10 years post injury) and the extent to which cerebrospinal fluid (CSF) biomarkers enhance outcome prediction., Methods: Very long-term global outcome was assessed in a total of 59 participants (41 of whom did not survive their injuries) using the Glasgow Outcome Scale-Extended and Disability Rating Scale. More detailed outcome information regarding cognitive functioning in daily life was collected from 18 participants surviving to 7-10 years post injury using the Cognitive Subscale of the Functional Independence Measure. A subset (n = 10) of these participants also completed performance-based cognitive testing (Digit Span Test) by telephone. The IMPACT lab model was applied to determine its prognostic value in relation to very long-term outcomes as well as the additive effects of acute CSF ubiquitin C-terminal hydrolase-L1 (UCH-L1) and microtubule associated protein 2 (MAP-2) concentrations., Results: The IMPACT lab model discriminated favorable versus unfavorable 7- to 10-year outcome with an area under the receiver operating characteristic curve of 0.80. Higher IMPACT lab model risk scores predicted greater extent of very long-term morbidity (β = 0.488 p = 0.000) as well as reduced cognitive independence (β =  - 0.515, p = 0.034). Acute elevations in UCH-L1 levels were also predictive of lesser independence in cognitive activities in daily life at very long-term follow-up (β = 0.286, p = 0.048). Addition of two CSF biomarkers significantly improved prediction of very long-term neuropsychological performance among survivors, with the overall model (including IMPACT lab score, UCH-L1, and MAP-2) explaining 89.6% of variance in cognitive performance 7-10 years post injury (p = 0.008). Higher acute UCH-L1 concentrations were predictive of poorer cognitive performance (β =  - 0.496, p = 0.029), whereas higher acute MAP-2 concentrations demonstrated a strong cognitive protective effect (β = 0.679, p = 0.010)., Conclusions: Although preliminary, results suggest that existing prognostic models, including models with incorporation of CSF markers, may be applied to predict outcome of severe TBI years after injury. Continued research is needed examining early predictors of longer-term outcomes following TBI to identify potential targets for clinical trials that could impact long-ranging functional and cognitive outcomes., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Traumatic brain injury (TBI) is an extremely heterogeneous and complex pathology that requires the integration of different physiological measurements for the optimal understanding and clinical management of patients. Information derived from intracranial pressure (ICP) monitoring can be coupled with information obtained from heart rate (HR) monitoring to assess the interplay between brain and heart. The goal of our study is to investigate events of simultaneous increases in HR and ICP and their relationship with patient mortality.., Methods: In our previous work, we introduced a novel measure of brain-heart interaction termed brain-heart crosstalks (ct np ), as well as two additional brain-heart crosstalks indicators [mutual information ([Formula: see text]) and average edge overlap (ω ct )] obtained through a complex network modeling of the brain-heart system. These measures are based on identification of simultaneous increase of HR and ICP. In this article, we investigated the relationship of these novel indicators with respect to mortality in a multicenter TBI cohort, as part of the Collaborative European Neurotrauma Effectiveness Research in TBI high-resolution work package., Results: A total of 226 patients with TBI were included in this cohort. The data set included monitored parameters (ICP and HR), as well as laboratory, demographics, and clinical information. The number of detected brain-heart crosstalks varied (mean 58, standard deviation 57). The Kruskal-Wallis test comparing brain-heart crosstalks measures of survivors and nonsurvivors showed statistically significant differences between the two distributions (p values: 0.02 for [Formula: see text], 0.005 for ct np and 0.006 for ω ct ). An inverse correlation was found, computed using the point biserial correlation technique, between the three new measures and mortality: - 0.13 for ct np (p value 0.04), - 0.19 for ω ct (p value 0.002969) and - 0.09 for [Formula: see text] (p value 0.1396). The measures were then introduced into the logistic regression framework, along with a set of input predictors made of clinical, demographic, computed tomography (CT), and lab variables. The prediction models were obtained by dividing the original cohort into four age groups (16-29, 30-49, 50-65, and 65-85 years of age) to properly treat with the age confounding factor. The best performing models were for age groups 16-29, 50-65, and 65-85, with the deviance of ratio explaining more than 80% in all the three cases. The presence of an inverse relationship between brain-heart crosstalks and mortality was also confirmed., Conclusions: The presence of a negative relationship between mortality and brain-heart crosstalks indicators suggests that a healthy brain-cardiovascular interaction plays a role in TBI., (© 2021. The Author(s).)

Traumatic brain injury (TBI) is the leading cause of mortality and disability among trauma-related injuries. Neuromonitoring plays an essential role in the management and prognosis of patients with severe TBI. Our bibliometric study aimed to identify the knowledge base, define the research front, and outline the social networks on neuromonitoring in severe TBI. We conducted an electronic search for articles related to neuromonitoring in severe TBI in Scopus. A descriptive analysis retrieved evidence on the most productive authors and countries, the most cited articles, the most frequently publishing journals, and the most common author's keywords. Through a three-step network extraction process, we performed a collaboration analysis among universities and countries, a cocitation analysis, and a word cooccurrence analysis. A total of 1884 records formed the basis of our bibliometric study. We recorded an increasing scientific interest in the use of neuromonitoring in severe TBI. Czosnyka, Hutchinson, Menon, Smielewski, and Stocchetti were the most productive authors. The most cited document was a review study by Maas et al. There was an extensive collaboration among universities. The most common keywords were "intracranial pressure," with an increasing interest in magnetic resonance imaging and cerebral perfusion pressure monitoring. Neuromonitoring constitutes an area of active research. The present findings indicate that intracranial pressure monitoring plays a pivotal role in the management of severe TBI. Scientific interest shifts to magnetic resonance imaging and individualized patient care on the basis of optimal cerebral perfusion pressure., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background and Objective: The temporal bone window (TBW) for transcranial Doppler (TCD) often fails to insonate the anterior cerebral artery (ACA). The frontal bone window (FBW) has never been evaluated in intensive care units (ICU). The main objective was to determine the ability of the FBW to assess ACA velocities in critically ill patients., Methods: A prospective study was conducted in two ICUs of the Montpellier University Hospital (France), between November 2014 and September 2016. Adult patients admitted to ICU for brain injury, with a Glasgow Coma Scale score ≤ 13, were enrolled within 3 days after admission. A first TCD examination was carried out bilaterally through the TBW and FBW by an intensivist expert in TCD, repeated by the same examiner, and 15 min later by an intensivist certified in TCD, designated as non-expert, blinded. The success of the FBW examinations was defined by the ability to measure the ACA velocities. Intra- and interobserver agreements were analyzed according to the Bland and Altman method., Results: A total of 147 patients were analyzed. The FBW succeeded in insonating the ACA in 66 patients [45%, CI (37-53)], 45 bilaterally and 21 unilaterally. For 16 patients (11%), the FBW was the only way to measure ACA velocities. By combining the two techniques, the ACA success rate increased from 62% CI (54-70) to 73% CI (65-79) (P = 0.05). Intra- and interobserver mean biases and 95% limits of agreement for ACA systolic velocity measurements through the FBW were 1 (- 33 to 35) and 2 (- 34 to 38) cm s -1 , respectively. For paired TBW and FBW measures of ACA velocities, mean biases (± SD) for ACA systolic, and mean and diastolic velocities were relatively close to zero, but negatives (- 7 ± 33, - 2 ± 19, - 1 ± 15 cm s -1 , respectively), highlighting that ACA velocities were lower with the FBW (A2 segment) than TBW (A1 segment). The correlation coefficient for ACA systolic velocities measured by the FBW and TBW was R = 0.47, CI (0.28-0.62). No risk factors for failure of the FBW were identified., Conclusions: In ICU, the FBW was able to insonate the ACA in 45% of patients admitted for brain injury, without the use of contrast agents. The FBW could improve the detection of ACA vasospasms.

For years, the use of ketamine as an anesthetic to patients suffering from acute brain injury has been debated because of its possible deleterious effects on the cerebral circulation and thus on the cerebral perfusion. Early studies suggested that ketamine could increase the intracranial pressure thus lowering the cerebral perfusion and hence reduce the oxygen supply to the injured brain. However, more recent studies are less conclusive and might even indicate that patients with acute brain injury could benefit from ketamine sedation. This systematic review summarizes the evidence regarding the use of ketamine in patients suffering from traumatic brain injury. Databases were searched for studies using ketamine in acute brain injury. Outcomes of interest were mortality, intracranial pressure, cerebral perfusion pressure, blood pressure, heart rate, spreading depolarizations, and neurological function. In total 11 studies were included. The overall level of evidence concerning the use of ketamine in brain injury is low. Only two studies found a small increase in intracranial pressure, while two small studies found decreased levels of intracranial pressure following ketamine administration. We found no evidence of harm during ketamine use in patients suffering from acute brain injury.

Background: Progressive hemorrhagic injury (PHI) is common in patients with severe traumatic brain injury (TBI) and is associated with poor outcomes. TBI-associated coagulopathy is frequent and has been described as risk factor for PHI. This coagulopathy is a dynamic process involving hypercoagulable and hypocoagulable states either one after the other either concomitant. Fibrin monomers (FMs) are a direct marker of thrombin action and thus reflect coagulation activation. This study sought to determine the ability of FM to predict PHI after severe TBI., Methods: We conducted a prospective, observational study including all severe TBI patients admitted in the trauma center. Between September 2011 and September 2016, we enrolled patients with severe TBI into the derivation cohort. Between October 2016 and December 2018, we recruited the validation cohort on the same basis. Study protocol included FM measurements and standard coagulation test at admission and two computed tomography (CT) scans (upon arrival and at least 6 h thereafter). A PHI was defined by an increment in size of initial lesion (25% or more) or the development of a new hemorrhage in the follow-up CT scan. Multivariate logistic regression analysis was applied to identify predictors of PHI., Results: Overall, 106 patients were included in the derivation cohort. Fifty-four (50.9%) experienced PHI. FM values were higher in these patients (151 [136.8-151] vs. 120.5 [53.3-151], p < 0.0001). The ROC curve demonstrated that FM had a fair accuracy to predict the occurrence of PHI with an area under curve of 0.7 (95% CI [0.6-0.79]). The best threshold was determined at 131.7 μg/ml. In the validation cohort of 54 patients, this threshold had a negative predictive value of 94% (95% CI [71-100]) and a positive predictive value of 49% (95% CI [32-66]). The multivariate logistic regression analysis identified 2 parameters associated with PHI: FM ≥ 131.7 (OR 6.8; 95% CI [2.8-18.1]) and Marshall category (OR 1.7; 95% CI [1.3-2.2]). Coagulopathy was not associated with PHI (OR 1.3; 95% CI [0.5-3.0]). The proportion of patients with an unfavorable functional neurologic outcome at 6-months follow-up was higher in patients with positive FM: 59 (62.1%) versus 16 (29.1%), p < 0.0001., Conclusions: FM levels at admission had a fair accuracy to predict PHI in patients with severe TBI. FM values ≥ 131.7 μg/ml are independently associated with the occurrence of PHI.

Background/objective: Lingering morbidities including physical, cognitive, emotional, and psychosocial sequelae, termed the Post-Intensive Care Syndrome, persist years after pediatric neurocritical care (PNCC) hospitalization. Sleep disturbances impact other Post-Intensive Care Syndrome domains and are under-evaluated to date due to a lack of appropriate measurement tools. The present study evaluated the validity of the Sleep Disturbance Scale for Children (SDSC) to address the growing need for assessing sleep problems after PNCC., Methods: We conducted a prospective observational study of youth aged 3-17 years with acquired brain injury (N = 69) receiving care through longitudinal PNCC programs at two tertiary academic medical centers. Parents completed the SDSC and provided proxy reports of internalizing symptoms, health-related quality of life (HRQOL), fatigue, pain behavior, and cognitive function within 3 months of hospital discharge. Evidence for the validity of the SDSC was established by utilizing the full sample for psychosocial measure comparisons and by comparing SDSC outcomes by severity (Low Risk, Mild-Moderate Risk, and High Risk defined by reported standardized T-scores)., Results: Internal consistency of the SDSC was good (α = .81). Within the full sample, increased sleep disturbances on the SDSC were significantly correlated with Post-Intensive Care Syndrome measures, including worse physical (r = .65), psychological (r = .62), and cognitive (r = - .74) sequelae. Youth in the High Risk group evidenced greater dysfunction in mental acuity, pain behavior, internalizing symptoms, and social engagement. Findings revealed both statistically and clinically significant impacts of sleep disturbances as measured by the SDSC on HRQOL., Conclusions: The SDSC is a valid and reliable measure for assessing sleep disturbances in children after PNCC. Results support the use of the SDSC to measure sleep disturbances after PNCC. Targeted interventions for sleep disturbances may be key to overall patient recovery.

Background: Measuring optic nerve sheath diameter (ONSD), an indicator to predict intracranial hypertension, is noninvasive and convenient, but the reliability of ONSD needs to be improved. Instead of using ONSD alone, this study aimed to evaluate the reliability of the ratio of ONSD to eyeball transverse diameter (ONSD/ETD) in predicting intracranial hypertension in traumatic brain injury (TBI) patients., Methods: We performed a prospective study on patients admitted to the Surgery Intensive Care Unit. The included 52 adults underwent craniotomy for TBI between March 2017 and September 2018. The ONSD and ETD of each eyeball were measured by ultrasound and computed tomography (CT) scan within 24 h after a fiber optic probe was placed into lateral ventricle. Intracranial pressure (ICP) > 20 mmHg was regarded as intracranial hypertension. The correlations between invasive ICP and ultrasound-ONSD/ETD ratio, ultrasound-ONSD, CT-ONSD/ETD ratio, and CT-ONSD were each analyzed separately., Results: Ultrasound measurement was successfully performed in 94% (n = 49) of cases, and ultrasound and CT measurement were performed in 48% (n = 25) of cases. The correlation efficiencies between ultrasound-ONSD/ETD ratio, ultrasound-ONSD, CT-ONSD/ETD ratio, and ICP were 0.613, 0.498, and 0.688, respectively (P < 0.05). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve for the ultrasound-ONSD/ETD ratio and CT-ONSD/ETD ratio were 0.920 (95% CI 0.877-0.964) and 0.896 (95% CI 0.856-0.931), respectively. The corresponding threshold values were 0.25 (sensitivity of 90%, specificity of 82.3%) and 0.25 (sensitivity of 85.7%, specificity of 83.3%), respectively., Conclusion: The ratio of ONSD to ETD tested by ultrasound may be a reliable indicator for predicting intracranial hypertension in TBI patients.

Background: Raised intracranial pressure (ICP) is a prominent cause of morbidity and mortality after severe traumatic brain injury (TBI). However, in the clinical setting, little is known about the cerebral physiological response to severe and prolonged increases in ICP., Methods: Thirty-three severe TBI patients from a single center who developed severe refractory intracranial hypertension (ICP > 40 mm Hg for longer than 1 h) with ICP, arterial blood pressure, and brain tissue oxygenation (P BT O 2 ) monitoring (subcohort, n = 9) were selected for retrospective review. Secondary parameters reflecting autoregulation (including pressure reactivity index-PRx, which was available in 24 cases), cerebrospinal compensatory reserve (RAP), and ICP pulse amplitude were calculated., Results: PRx deteriorated from 0.06 ± 0.26 a.u. at baseline levels of ICP to 0.57 ± 0.24 a.u. (p < 0.0001) at high levels of ICP (> 50 mm Hg). In 4 cases, PRx was impaired (> 0.25 a.u.) before ICP was raised above 25 mm Hg. Concurrently, P BT O 2 decreased from 27.3 ± 7.32 mm Hg at baseline ICP to 12.68 ± 7.09 mm Hg at high levels of ICP (p < 0.001). The pulse amplitude of the ICP waveform increased with increasing ICP but showed an 'upper breakpoint'-whereby further increases in ICP lead to decreases in pulse amplitude-in 6 out of the 33 patients., Discussion: Severe intracranial hypertension after TBI leads to decreased brain oxygenation, impaired pressure reactivity, and changes in the pulse amplitude of ICP. Impaired pressure reactivity may denote increased risk of developing refractory intracranial hypertension in some patients.

Background: Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI., Methods: We conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses., Results: We observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status., Conclusions: Our preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.

The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in the September of 2018 devoted a section to address the question, "What should a clinician do when spreading depolarizations are observed in a patient?" Discussants represented a wide range of expertise, including neurologists, neurointensivists, neuroradiologists, neurosurgeons, and pre-clinical neuroscientists, to provide both clinical and basic pathophysiology perspectives. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was formally collated, reviewed, and incorporated into the final document which was subsequently approved by all authors.

Background: Neurocritical care is devoted to the care of critically ill patients with acute neurological or neurosurgical emergencies. There is limited information regarding epidemiological data, disease characteristics, variability of clinical care, and in-hospital mortality of neurocritically ill patients worldwide. We addressed these issues in the Point PRevalence In Neurocritical CarE (PRINCE) study, a prospective, cross-sectional, observational study., Methods: We recruited patients from various intensive care units (ICUs) admitted on a pre-specified date, and the investigators recorded specific clinical care activities they performed on the subjects during their first 7 days of admission or discharge (whichever came first) from their ICUs and at hospital discharge. In this manuscript, we analyzed the final data set of the study that included patient admission characteristics, disease type and severity, ICU resources, ICU and hospital length of stay, and in-hospital mortality. We present descriptive statistics to summarize data from the case report form. We tested differences between geographically grouped data using parametric and nonparametric testing as appropriate. We used a multivariable logistic regression model to evaluate factors associated with in-hospital mortality., Results: We analyzed data from 1545 patients admitted to 147 participating sites from 31 countries of which most were from North America (69%, N = 1063). Globally, there was variability in patient characteristics, admission diagnosis, ICU treatment team and resource allocation, and in-hospital mortality. Seventy-three percent of the participating centers were academic, and the most common admitting diagnosis was subarachnoid hemorrhage (13%). The majority of patients were male (59%), a half of whom had at least two comorbidities, and median Glasgow Coma Scale (GCS) of 13. Factors associated with in-hospital mortality included age (OR 1.03; 95% CI, 1.02 to 1.04); lower GCS (OR 1.20; 95% CI, 1.14 to 1.16 for every point reduction in GCS); pupillary reactivity (OR 1.8; 95% CI, 1.09 to 3.23 for bilateral unreactive pupils); admission source (emergency room versus direct admission [OR 2.2; 95% CI, 1.3 to 3.75]; admission from a general ward versus direct admission [OR 5.85; 95% CI, 2.75 to 12.45; and admission from another ICU versus direct admission [OR 3.34; 95% CI, 1.27 to 8.8]); and the absence of a dedicated neurocritical care unit (NCCU) (OR 1.7; 95% CI, 1.04 to 2.47)., Conclusion: PRINCE is the first study to evaluate care patterns of neurocritical patients worldwide. The data suggest that there is a wide variability in clinical care resources and patient characteristics. Neurological severity of illness and the absence of a dedicated NCCU are independent predictors of in-patient mortality.

Background/objective: Simplified continuous electroencephalogram (cEEG) monitoring has shown improvement in detecting seizures; however, it is insufficient in detecting abnormal EEG patterns, such as periodic discharges (PDs), rhythmic delta activity (RDA), spikes and waves (SW), and continuous slow wave (CS), as well as nonconvulsive status epilepticus (NCSE). Headset-type continuous video EEG monitoring (HS-cv EEG monitoring; AE-120A EEG Headset™, Nihon Kohden, Tokyo, Japan) is a recently developed easy-to-use technology with eight channels. However, its ability to detect abnormal EEG patterns with raw EEG data has not been comprehensively evaluated. We aimed to examine the diagnostic accuracy of HS-cv EEG monitoring in detecting abnormal EEG patterns and NCSE in patients with altered mental status (AMS) with unknown etiology. We also evaluated the time required to initiate HS-cv EEG monitoring in these patients., Methods: We prospectively observed and retrospectively examined patients who were admitted with AMS between January and December 2017 at the neurointensive care unit at Asakadai Central General Hospital, Saitama, Japan. We excluded patients whose data were missing for various reasons, such as difficulties in recording, and those whose consciousness had recovered between HS-cv EEG and conventional cEEG (C-cEEG) monitoring. For the included patients, we performed HS-cv EEG monitoring followed by C-cEEG monitoring. Definitive diagnosis was confirmed by C-cEEG monitoring with the international 10-20 system. As the primary outcome, we verified the sensitivity and specificity of HS-cv EEG monitoring in detecting abnormal EEG patterns including PDs, RDA, SW, and CS, in detecting the presence of PDs, and in detecting NCSE. As the secondary outcome, we calculated the time to initiate HS-cv EEG monitoring after making the decision., Results: Fifty patients (76.9%) were included in the final analyses. The median age was 72 years, and 66% of the patients were male. The sensitivity and specificity of HS-cv EEG monitoring for detecting abnormal EEG patterns were 0.974 (0.865-0.999) and 0.909 (0.587-0.998), respectively, and for detecting PDs were 0.824 (0.566-0.926) and 0.970 (0.842-0.999), respectively. We diagnosed 13 (26%) patients with NCSE using HS-cv EEG monitoring and could detect NCSE with a sensitivity and specificity of 0.706 (0.440-0.897) and 0.970 (0.842-0.999), respectively. The median time needed to initiate HS-cv EEG was 57 min (5-142)., Conclusions: HS-cv EEG monitoring is highly reliable in detecting abnormal EEG patterns, with moderate reliability for PDs and NCSE, and rapidly initiates cEEG monitoring in patients with AMS with unknown etiology.

Background: Arterial hyperglycemia is associated with poor outcome in traumatic brain injury (TBI), but the pathophysiology is not completely understood. Previous preclinical and clinical studies have indicated that arterial glucose worsens pressure autoregulation. The aim of this study was to evaluate the relationship of arterial glucose to both pressure reactivity and cerebral energy metabolism., Method: This retrospective study was based on 120 patients with severe TBI treated at the Uppsala University hospital, Sweden, 2008-2018. Data from cerebral microdialysis (glucose, pyruvate, and lactate), arterial glucose, and pressure reactivity index (PRx55-15) were analyzed the first 3 days post-injury., Results: High arterial glucose was associated with poor outcome/Glasgow Outcome Scale-Extended at 6-month follow-up (r = - 0.201, p value = 0.004) and showed a positive correlation with both PRx55-15 (r = 0.308, p = 0.001) and cerebral lactate/pyruvate ratio (LPR) days 1-3 (r = 0. 244, p = 0.014). Cerebral lactate-to-pyruvate ratio and PRx55-15 had a positive association day 2 (r = 0.219, p = 0.048). Multivariate linear regression analysis showed that high arterial glucose predicted poor pressure autoregulation on days 1 and 2., Conclusions: High arterial glucose was associated with poor outcome, poor pressure autoregulation, and cerebral energy metabolic disturbances. The latter two suggest a pathophysiological mechanism for the negative effect of arterial hyperglycemia, although further studies are needed to elucidate if the correlations are causal or confounded by other factors.

Background: Cerebral injury may alter the autoregulation of cerebral blood flow. One index for describing cerebrovascular state is the pressure reactivity (PR). Little is known of whether PR is associated with measures of brain metabolism and indicators of ischemia and cell damage. The aim of this investigation was to explore whether increased interstitial levels of glycerol, a marker of cell membrane damage, are associated with PR, and if prostacyclin, a membrane stabilizer and regulator of the microcirculation, may affect this association in a beneficial way., Materials and Methods: Patients suffering severe traumatic brain injury (sTBI) were treated according to an intracranial pressure (ICP)-targeted therapy based on the Lund concept and randomized to an add-on treatment with prostacyclin or placebo. Inclusion criteria were verified blunt head trauma, Glasgow Coma Score ≤ 8, age 15-70 years, and a first measured cerebral perfusion pressure of ≥ 10 mmHg. Multimodal monitoring was applied. A brain microdialysis catheter was placed on the worst affected side, close to the penumbra zone. Mean (glycerol mean ) and maximal glycerol (glycerol max ) during the 96-h sampling period were calculated. The mean PR was calculated as the ICP/mean arterial pressure (MAP) regression coefficient based on hourly mean ICP and MAP during the first 96 h., Results: Of the 48 included patients, 45 had valid glycerol and PR measurements available. PR was higher in the placebo group as compared to the prostacyclin group (p = 0.0164). There was a positive correlation between PR and the glycerol mean (ρ = 0.503, p = 0.01) and glycerol max (ρ = 0.490, p = 0.015) levels in the placebo group only., Conclusions: PR is correlated to the glycerol level in patients suffering from sTBI, a relationship that is not seen in the group treated with prostacyclin. Glycerol has been associated with membrane degradation and may support glycerol as a biomarker for vascular endothelial breakdown. Such a breakdown may impair the regulation of cerebrovascular PR.

Background: Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Low cerebral perfusion pressure (CPP, mean arterial pressure [MAP] minus intracranial pressure) after TBI is associated with cerebral ischemia, impaired cerebral autoregulation, and poor outcomes. Normalization of CPP and limitation of cerebral autoregulation impairment is a key therapeutic goal. However, some vasoactive agents used to elevate MAP such as phenylephrine (Phe) improve outcome in females but not male piglets after TBI while dopamine (DA) does so in both sexes. Clinical evidence has implicated neurological injuries as a cause of cardiac dysfunction, and we recently described cardiac dysfunction after TBI. Cardiac dysfunction may, in turn, influence brain health. One mechanism of myocyte injury may involve catecholamine excess. We therefore tested the hypothesis that TBI caused cardiac dysfunction and catecholamine excess which may reciprocally be modulated by vasoactive agent choice to normalize CPP and prevent impairment of cerebral autoregulation after injury., Methods: TBI was produced in anesthetized pigs equipped with a closed cranial window, and Phe or DA administered to normalize CPP., Results: Plasma cardiac enzymes troponin and creatine kinase and catecholamines epinephrine and norepinephrine were elevated by TBI, such release potentiated by Phe in males but blocked in female piglets and blocked in both sexes after DA. Cerebral autoregulation was impaired after TBI, worsened by Phe in males but protected in females and males treated with DA. Papaverine-induced dilation was unchanged by fluid percussion brain injury, DA, and Phe., Conclusions: These data indicate that pressor choice in elevation of CPP is important in limiting cardiac dysfunction and suggest that DA protects cerebral autoregulation in both sexes via reduction of cardiac biomarkers of injury and catecholamines released after TBI.

Within the last couple of decades, advances in critical care medicine have led to increased survival of critically ill patients, as well as the discovery of notable, long-term health challenges in survivors and their loved ones. The terms post-intensive care syndrome (PICS) and PICS-family (PICS-F) have been used in non-neurocritical care populations to characterize the cognitive, psychiatric, and physical sequelae associated with critical care hospitalization in survivors and their informal caregivers (e.g., family and friends who provide unpaid care). In this review, we first summarize the literature on the cognitive, psychiatric, and physical correlates of PICS and PICS-F in non-neurocritical patient populations and draw attention to their long-term negative health consequences. Next, keeping in mind the distinction between disease-related neurocognitive changes and those that are associated directly with the experience of a critical illness, we review the neuropsychological sequelae among patients with common neurocritical illnesses. We acknowledge the clinical factors contributing to the difficulty in studying PICS in the neurocritical care patient population, provide recommendations for future lines of research, and encourage collaboration among critical care physicians in all specialties to facilitate continuity of care and to help elucidate mechanism(s) of PICS and PICS-F in all critical illness survivors. Finally, we discuss the importance of early detection of PICS and PICS-F as an opportunity for multidisciplinary interventions to prevent and treat new neuropsychological deficits in the neurocritical care population.

Background: The underlying physiology of the intracranial pressure (ICP) curve morphology is still poorly understood. If this physiology is explained it could be possible to extract clinically relevant information from the ICP curve. The venous outflow from the cranial cavity is pulsatile, and in theory the pulsatile component of venous outflow from the cranial cavity should be attenuated with increasing ICP. In this study, we explored the relationship between ICP and the pulsatility of the venous outflow from the intracranial cavity., Methods: Thirty-seven neuro-intensive care patients that had been examined with phase-contrast magnetic resonance imaging regarding cerebral blood flow (CBF) through the internal carotid and vertebral arteries and venous flow in the internal jugular veins were retrospectively included. The pulsatility of the jugular flow was determined by calculating the venous pulsatile index. The results were correlated to clinical data registered in the patient data monitoring system, including ICP and cerebral perfusion pressure (CPP)., Results: CBF was 996 ± 298 ml/min, and the flow in the internal jugular veins equaled 67 ± 17% of the CBF, with a range of 22-97%. The venous pulsatile index correlated negatively to ICP (R = - 0.47 p = 0.003). The lowest flow in the internal jugular veins over the cardiac cycle (F min ) was not correlated to ICP. Temperature, end-tidal CO 2 , MAP, and CPP were not correlated to venous pulsatility., Conclusion: An increase in ICP correlates to a lower pulsatility of the venous outflow from the cranial cavity. A lower pulsatility could be due to increased pressure requirements to compress intracranial veins with increasing ICP.

Background: Intracranial pressure (ICP) monitoring is central to the care of severe traumatic brain injury (TBI). External ventricular drains (EVD) allow ICP control via cerebrospinal fluid drainage, whereas intraparenchymal monitors (IPM) for ICP do not, but it is unclear whether EVD placement improves outcomes. To evaluate whether there exists a difference in patient outcomes with the use of EVD versus IPM in severe TBI patients, we conducted a retrospective cohort study using data from the Citicoline Brain Injury Treatment trial., Methods: Adults with Glasgow Coma Score < 9 who had either an EVD or IPM placed within 6 h of study center arrival were included. We compared patients with EVD placement to those without on Glasgow Outcome Scale-Extended (GOS-E) and neuropsychological performance at 180 days, mortality, and intensive care unit length of stay. We used regression models with propensity score weighting for probability of EVD placement to test for association between EVD use and outcomes. Of 224 patients included, 45% received an EVD., Results: EVD patients had lower GOS-E at 180 days [3.8 ± 2.2 vs 4.9 ± 2.2, p = 0.002; weighted difference - 0.97, 95% CI (- 1.58, - 0.37)], higher in-hospital mortality [23% vs 10%, p = 0.014; weighted OR 2.46, 95% CI (1.20, 5.05)], and did significantly worse on all 8 neuropsychological measures. Additional sensitivity analysis was performed to minimize confounding effects supported our initial results., Conclusions: Our retrospective data analysis suggests that early placement of EVDs in severe TBI is associated with worse functional and neuropsychological outcomes and higher mortality than IPMs and future prospective trials are needed to determine whether these results represent an important consideration for clinicians.

Objective: This study applied a new external ventricular catheter, which allows intracranial pressure (ICP) monitoring and cerebral spinal fluid (CSF) drainage simultaneously, to study cerebral vascular responses during acute CSF drainage., Methods: Six patients with 34 external ventricular drain (EVD) opening sessions were retrospectively analyzed. A published algorithm was used to extract morphological features of ICP recordings, and a template-matching algorithm was applied to calculate the likelihood of cerebral vasodilation index (VDI) and cerebral vasoconstriction index (VCI) based on the changes of ICP waveforms during CSF drainage. Power change (∆P) of ICP B-waves after EVD opening was also calculated. Cerebral autoregulation (CA) was assessed through phase difference between arterial blood pressure (ABP) and ICP using a previously published wavelet-based algorithm., Results: The result showed that acute CSF drainage reduced mean ICP (P = 0.016) increased VCI (P = 0.02) and reduced ICP B-wave power (P = 0.016) significantly. VCI reacted to ICP changes negatively when ICP was between 10 and 25 mmHg, and VCI remained unchanged when ICP was outside the 10-25 mmHg range. VCI negatively (r = - 0.44) and VDI positively (r = 0.82) correlated with ∆P of ICP B-waves, indicating that stronger vasoconstriction resulted in bigger power drop in ICP B-waves. Better CA prior to EVD opening triggered bigger drop in the power of ICP B-waves (r = - 0.612)., Conclusions: This study demonstrates that acute CSF drainage reduces mean ICP, and results in vasoconstriction which can be detected through an index, VCI. Cerebral vessels actively respond to ICP changes or cerebral perfusion pressure (CPP) changes in a certain range; beyond which, the vessels are insensitive to the changes in ICP and CPP.

Background: An external ventricular drain (EVD) is the gold standard for measurement of intracranial pressure (ICP) and allows for drainage of cerebrospinal fluid (CSF). Different causes of elevated ICP, such as CSF outflow obstruction or cerebral swelling, respond differently to CSF drainage. This is a widely recognized but seldom quantified distinction. We sought to define an index to characterize the response to CSF drainage in neurocritical care patients., Methods: We studied consecutive patients admitted to the neurointensive care unit who had an EVD. The EVD was closed for 30 min prior to assessment. We documented pre-drainage ICP, opened EVD to drainage allowing CSF to drain until it ceased, and recorded post-drainage ICP at EVD closure. We calculated the pressure equalization (PE) ratio as the difference between pre-drainage ICP and post-drainage ICP divided by the difference between pre-drainage ICP and EVD height., Results: We studied 60 patients (36 traumatic brain injury [TBI], 24 non-TBI). As expected, TBI patients had more signs of cerebral swelling on CT and smaller ventricles. Although TBI patients had significantly higher pre-drainage ICP (26 ± 10 mm Hg) than non-TBI patients (19 ± 5 mm Hg, p < 0.001) they drained less CSF (7 cc vs. 4 cc, p < 0.01). PE ratio was substantially higher in non-TBI than in TBI patients (0.86 ± 0.36 vs. 0.43 ± 0.31, p < 0.0001), indicating that non-TBI patients were better able to equalize pressure with EVD height than TBI patients., Conclusions: PE ratio reflects the ability to equalize pressure with the preset height of the EVD and differs substantially between TBI and non-TBI patients. A high PE ratio likely indicates CSF outflow obstruction effectively treated by CSF diversion, while a lower PE ratio occurs when cerebral swelling predominates. Further studies could assess whether the PE ratio would be useful as a surrogate marker for cerebral edema or the state of intracranial compliance.

Background: Patients with severe acute brain injury (ABI) often require intrahospital transports (IHTs) for repeated computed tomography (CT) scans. IHTs are associated with serious adverse events (AE) that might pose a risk for secondary brain injury. The goal of this study was to assess IHT-related alterations of cerebral metabolism in ABI patients., Methods: We included mechanically ventilated patients with ABI who had continuous multimodality neuromonitoring during an 8-h period before and after routine IHT. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PtiO 2 ) as well as cerebral and subcutaneous microdialysis parameters (lactate, pyruvate, glycerol, and glutamate) were recorded. Values were compared between an 8-h period before (pre-IHT) and after (post-IHT) the IHT., Results: A total of 23 IHT for head CT scans in 18 patients were analyzed. Traumatic brain injury (n = 7) was the leading cause of ABI, followed by subarachnoid hemorrhage (n = 6) and intracerebral hemorrhage (n = 5). The analyzed microdialysis parameters in the brain tissue as in the subcutaneous tissue did not show significant changes between the pre-IHT and post-IHT period. In addition, we observed no significant increase in ICP or decrease in CPP and PtiO 2 in the 8-h period after IHT., Conclusions: While the occurrence of AE during IHT is a known risk factor for ABI patients, our results demonstrate that IHTs do not alter the brain tissue chemistry in a significant manner. This fact may help assess the risk for routine IHT more accurately.

Background: This study aims to determine the relationship between pupillary reactivity, midline shift and basal cistern effacement on brain computed tomography (CT) in moderate-to-severe traumatic brain injury (TBI). All are important diagnostic and prognostic measures, but their relationship is unclear., Methods: A total of 204 patients with moderate-to-severe TBI, documented pupillary reactivity, and archived neuroimaging were included. Extent of midline shift and basal cistern effacement were extracted from admission brain CT. Mean midline shift was calculated for each ordinal category of pupillary reactivity and basal cistern effacement. Sequential Chi-square analysis was used to calculate a threshold midline shift for pupillary abnormalities and basal cistern effacement. Univariable and multiple logistic regression analyses were performed., Results: Pupils were bilaterally reactive in 163 patients, unilaterally reactive in 24, and bilaterally unreactive in 17, with mean midline shift (mm) of 1.96, 3.75, and 2.56, respectively (p = 0.14). Basal cisterns were normal in 118 patients, compressed in 45, and absent in 41, with mean midline shift (mm) of 0.64, 2.97, and 5.93, respectively (p < 0.001). Sequential Chi-square analysis identified a threshold for abnormal pupils at a midline shift of 7-7.25 mm (p = 0.032), compressed basal cisterns at 2 mm (p < 0.001), and completely effaced basal cisterns at 7.5 mm (p < 0.001). Logistic regression revealed no association between midline shift and pupillary reactivity. With effaced basal cisterns, the odds ratio for normal pupils was 0.22 (95% CI 0.08-0.56; p = 0.0016) and for at least one unreactive pupil was 0.061 (95% CI 0.012-0.24; p < 0.001). Basal cistern effacement strongly predicted midline shift (OR 1.27; 95% CI 1.17-1.40; p < 0.001)., Conclusions: Basal cistern effacement alone is associated with pupillary reactivity and is closely associated with midline shift. It may represent a uniquely useful neuroimaging marker to guide intervention in traumatic brain injury.

Background: To explore the relationship between various autoregulatory indices in order to determine which approximate small vessel/microvascular (MV) autoregulatory capacity most accurately., Methods: Utilizing a retrospective cohort of traumatic brain injury patients (N = 41) with: transcranial Doppler (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we calculated various continuous indices of autoregulation and cerebrovascular responsiveness: A. ICP derived [pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP), PAx-correlation between pulse amplitude of ICP (AMP) and MAP, RAC-correlation between AMP and cerebral perfusion pressure (CPP)], B. TCD derived (Mx-correlation between mean flow velocity (FVm) and CPP, Mx&#95;a-correlation between FVm and MAP, Sx-correlation between systolic flow velocity (FVs) and CPP, Sx&#95;a-correlation between FVs and MAP, Dx-correlation between diastolic flow index (FVd) and CPP, Dx&#95;a-correlation between FVd and MAP], and LDF derived (Lx-correlation between LDF cerebral blood flow [CBF] and CPP, Lx&#95;a-correlation between LDF-CBF and MAP). We assessed the relationship between these indices via Pearson correlation, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC), and k-means cluster analysis (KMCA)., Results: LDF-based autoregulatory index (Lx) was most associated with TCD-based Mx/Mx&#95;a and Dx/Dx&#95;a across Pearson correlation, PCA, AHC, and KMCA. Lx was only remotely associated with ICP-based indices (PRx, PAx, RAC). TCD-based Sx/Sx&#95;a was more closely associated with ICP-derived PRx, PAx and RAC. This indicates that vascular-derived indices of autoregulatory capacity (i.e., TCD and LDF based) covary, with Sx/Sx&#95;a being the exception, whereas indices of cerebrovascular reactivity derived from pulsatile CBV (i.e., ICP indices) appear to not be closely related to those of vascular origin., Conclusions: Transcranial Doppler Mx is the most closely associated with LDF-based Lx/Lx&#95;a. Both Sx/Sx-a and the ICP-derived indices appear to be dissociated with LDF-based cerebrovascular reactivity, leaving Mx/Mx-a as a better surrogate for the assessment of cortical small vessel/MV cerebrovascular reactivity. Sx/Sx&#95;a cocluster/covary with ICP-derived indices, as seen in our previous work.

Background: Continuous monitoring of cerebral autoregulation is considered clinically useful due to its ability to warn against brain ischemic insults, which may translate to a relationship with adverse outcome. It is typically performed using the pressure reactivity index (PRx) based on mean arterial pressure and intracranial pressure. A new ORx index based on brain tissue oxygenation and cerebral perfusion pressure (CPP) has been proposed that similarly allows for evaluation of cerebrovascular reactivity. Conflicting results exist concerning its clinical utility., Methods: Retrospective analysis was performed in 85 patients with traumatic brain injury (TBI). ORx was calculated using three time windows of 5, 20, and 60 min. Correlation coefficients and individual "optimal CPP" (CPP opt ) were calculated using both PRx and ORx, and relation to patient outcome investigated., Results: Correlation coefficients for all comparisons between PRx and ORx indicated poor association between these indices (range from -0.04 to 0.07). PRx was significantly lower in patients with good outcome (p = 0.01), while none of the ORx indices proved to be significantly different in the two outcome groups. Higher mortality related to average CPP < CPP opt was found regardless of which index was used to calculate CPP opt ., Conclusion: In the TBI setting, ORx does not appear to correlate with vascular pressure reactivity as assessed with PRx. Its potential use for individualizing CPP thresholds remains unclear.

Objective: We introduced 'compensatory-reserve-weighted intracranial pressure (ICP),' named 'weightedICP' for brevity, as a variable that may better describe changes leading to mortality after traumatic brain injury (TBI) over the standard mean ICP., Methods: ICP was monitored prospectively in over 1023 sedated and ventilated patients. The RAP coefficient (R-correlation, A-amplitude, and P-pressure) was calculated as the running correlation coefficient between slow changes in the pulse amplitude of ICP and the mean ICP. RAP has a value of 0 on the linear part of the pressure-volume curve and a value of + 1 on the ascending exponential part. Then, RAP decreases towards zero or even becomes negative when ICP increases further-a phenomenon thought to be related to the critical closing of cerebral vessels. In this study, we investigated a derived variable called weightedICP, calculated as ICP*(1 - RAP)., Results: Mortality after TBI was associated with both elevated ICP and weightedICP. Analysis of variance showed higher values of test statistics for weightedICP (K = 93) than for ICP (K = 64) in outcome categorization. Additionally, receiver operator curve analysis indicated greater area under the curve for weightedICP (0.71) than for ICP (0.67) with respect to associated mortality; however, the difference was not statistically significant (p = 0.12). The best threshold (maximizing sensitivity and specificity) was 19.5 mm Hg for mean ICP, and 8 mm Hg for weightedICP. Mortality rate expressed as a function of mean ICP and weightedICP showed an ascending profile in both cases., Conclusion: The proposed variable shows a significant association with mortality following head injury. It is sensitive to both the rising absolute ICP and to the critical deterioration of pressure-volume compensation.

Background: Monitoring of intracranial pressure (ICP) is considered to be fundamental for the care of patients with severe traumatic brain injury (TBI) and is routinely used to direct medical and surgical therapy. Accordingly, some guidelines for the management of severe TBI recommend that treatment be initiated for ICP values >20 mmHg. However, it remained to be accounted whether there is a scientific basis to this instruction. The purpose of the present study was to clarify whether the basis of ICP values >20 mmHg is appropriate., Subject and Methods: We retrospectively reviewed 25 patients with severe TBI who underwent neuroimaging during ICP monitoring within the first 7 days. We measured cerebral blood flow (CBF), mean transit time (MTT), cerebral blood volume (CBV), and ICP 71 times within the first 7 days., Results: Although the CBF, MTT, and CBV values were not correlated with the ICP value at ICP values ≤20 mmHg, the CBF value was significantly negatively correlated with the ICP value (r = -0.381, P < 0.05) at ICP values >20 mmHg. The MTT value was also significantly positively correlated with the ICP value (r = 0.638, P < 0.05) at ICP values >20 mmHg., Conclusion: The cerebral circulation disturbance increased with the ICP value. We demonstrated the cerebral circulation disturbance at ICP values >20 mmHg. This study suggests that an ICP >20 mmHg is the threshold to initiate treatments. An active treatment intervention would be required for severe TBI when the ICP was >20 mmHg.

Background: Determination of relationships between transcranial Doppler (TCD)-based spectral pulsatility index (sPI) and pulse amplitude (AMP) of intracranial pressure (ICP) in 2 groups of severe traumatic brain injury (TBI) patients (a) displaying plateau waves and (b) with unstable mean arterial pressure (MAP)., Methods: We retrospectively reviewed patients with severe TBI and continuous TCD monitoring displaying either plateau waves or unstable MAP from 1992 to 1998. We utilized linear and nonlinear regression techniques to describe both cohorts: cerebral perfusion pressure (CPP) versus AMP, CPP versus sPI, mean ICP versus ICP AMP, mean ICP versus sPI, and AMP versus sPI., Results: Nonlinear regression techniques were employed to analyze the relationships with CPP. In plateau wave and unstable MAP patients, CPP versus sPI displayed an inverse nonlinear relationship (R 2  = 0.820 vs. R 2  = 0.610, respectively), with the CPP versus sPI relationship best modeled by the following function in both cases: PI = a + (b/CPP). Similarly, in both groups, CPP versus AMP displayed an inverse nonlinear relationship (R 2  = 0.610 vs. R 2  = 0.360, respectively). Positive linear correlations were displayed in both the plateau wave and unstable MAP cohorts between: ICP versus AMP, ICP versus sPI, AMP versus sPI., Conclusions: There is an inverse relationship through nonlinear regression between CPP versus AMP and CPP versus sPI display. This provides evidence to support a previously-proposed model of TCD pulsatility index. ICP shows a positive linear correlation with AMP and sPI, which is also established between AMP and sPI.

Background: Many demographic and physiological variables have been associated with TBI outcomes. However, with small sample sizes, making spurious inferences is possible. This paper explores the effect of sample sizes on statistical relationships between patient variables (both physiological and demographic) and outcome., Methods: Data from head-injured patients with monitored arterial blood pressure, intracranial pressure (ICP) and outcome assessed at 6 months were included in this retrospective analysis. A univariate logistic regression analysis was performed to obtain the odds ratio for unfavorable outcome. Three different dichotomizations between favorable and unfavorable outcomes were considered. A bootstrap method was implemented to estimate the minimum sample sizes needed to obtain reliable association between physiological and demographic variables with outcome., Results: In a univariate analysis with dichotomized outcome, samples sizes should be generally larger than 100 for reproducible results. Pressure reactivity index, ICP, and ICP slow waves offered the strongest relationship with outcome. Relatively small sample sizes may overestimate effect sizes or even produce conflicting results., Conclusion: Low power tests, generally achieved with small sample sizes, may produce misleading conclusions, especially when they are based only on p values and the dichotomized criteria of rejecting/not-rejecting the null hypothesis. We recommend reporting confidence intervals and effect sizes in a more complete and contextualized data analysis.

Background: Cerebral critical closing pressure (CrCP) is the level of arterial blood pressure (ABP) at which small brain vessels close and blood flow stops. This value is always greater than intracranial pressure (ICP). The difference between CrCP and ICP is explained by the tone of the small cerebral vessels (wall tension). CrCP value is used in several dynamic cerebral autoregulation models. However, the different methods for calculation of CrCP show frequent negative values. These findings are viewed as a methodological limitation. We intended to evaluate CrCP in patients with severe traumatic brain injury (TBI) with a new multiparameter impedance-based model and compare it with results found earlier using a transcranial Doppler (TCD)-ABP pulse waveform-based method., Methods: Twelve severe TBI patients hospitalized during September 2005-May 2007. Ten men, mean age 32 years (16-61). Four had decompressive craniectomies (DC); three presented anisocoria. Patients were monitored with TCD cerebral blood flow velocity (FV), invasive ABP, and ICP. Data were acquired at 50 Hz with an in-house developed data acquisition system. We compared the earlier studied "first harmonic" method (M1) results with results from a new recently developed (M2) "multiparameter method.", Results: M1: In seven patients CrCP values were negative, reaching -150 mmHg. M2: All positive values; only one lower than ICP (ICP 60 mmHg/ CrCP 57 mmHg). There was a significant difference between M1 and M2 values (M1 < M2) and between ICP and M2 (M2 > ICP)., Conclusion: M2 results in positive values of CrCP, higher than ICP, and are physiologically interpretable.

Background: In patients with traumatic brain injury (TBI), multicenter randomized controlled trials have assessed decompressive craniectomy (DC) exclusively as treatment for refractory elevation of intracranial pressure (ICP). DC reliably lowers ICP but does not necessarily improve outcomes. However, some patients undergo DC as treatment for impending or established transtentorial herniation, irrespective of ICP., Methods: We performed a population-based cohort study assessing consecutive patients with moderate-severe TBI. Indications for DC were compared with enrollment criteria for the DECRA and RESCUE-ICP trials., Results: Of 644 consecutive patients, 51 (8 %) were treated with DC. All patients undergoing DC had compressed basal cisterns, 82 % had at least temporary preoperative loss of ≥1 pupillary light reflex (PLR), and 80 % had >5 mm of midline shift. Most DC procedures (67 %) were "primary," having been performed concomitantly with evacuation of a space-occupying lesion. ICP measurements influenced the decision to perform DC in 18 % of patients. Only 10 and 16 % of patients, respectively, would have been eligible for the DECRA and RESCUE-ICP trials. DC improved basal cistern compression in 76 %, and midline shift in 94 % of patients. Among patients with ≥1 absent PLR at admission, DC was associated with lower mortality (46 vs. 68 %, p = 0.03), especially when the admission Marshall CT score was 3-4 (p = 0.0005). No patients treated with DC progressed to brain death. Variables predictive of poor outcome following DC included loss of PLR(s), poor motor score, midline shift ≥11 mm, and development of perioperative cerebral infarcts., Conclusions: DC is most often performed for clinical and radiographic evidence of herniation, rather than for refractory ICP elevation. Results of previously completed randomized trials do not directly apply to a large proportion of patients undergoing DC in practice.

Introduction: Mechanical ventilation with control of partial arterial CO2 pressures (PaCO2) is used to treat or stabilize intracranial pressure (ICP) in patients with traumatic brain injury (TBI). Pressure-regulated volume control (PRVC) is a ventilator mode where inspiratory pressures are automatically adjusted to deliver the patient a pre-set stable tidal volume (TV). This may result in a more stable PaCO2 and thus a more stable ICP compared with conventional pressure control (PC) ventilation. The aim of this study was to compare PC and PRVC ventilation in TBI patients with respect to ICP and PaCO2., Methods: This is a randomized crossover trial including eleven patients with a moderate or severe TBI who were mechanically ventilated and had ICP monitoring. Each patient was administered alternating 2-h periods of PC and PRVC ventilation. The outcome variables were ICP and PaCO2., Results: Fifty-two (26 PC, 26 PRVC) study periods were included. Mean ICP was 10.8 mmHg with PC and 10.3 mmHg with PRVC ventilation (p = 0.38). Mean PaCO2 was 36.5 mmHg (4.87 kPa) with PC and 36.1 mmHg (4.81 kPa) with PRVC (p = 0.38). There were less fluctuations in ICP (p = 0.02) and PaCO2 (p = 0.05) with PRVC ventilation., Conclusions: Mean ICP and PaCO2 were similar for PC and PRVC ventilation in TBI patients, but PRVC ventilation resulted in less fluctuation in both ICP and PaCO2. We cannot exclude that the two ventilatory modes would have impact on ICP in patients with higher ICP values; however, the similar PaCO2 observations argue against this.

Background: Approximately one-third of patients with isolated traumatic brain injury (iTBI) present with acute traumatic coagulopathy (ATC). ATC is associated with increased morbidity and mortality. Its effects on long-term functional and cognitive outcomes are not as well characterized., Methods: Data from the Citicoline Brain Injury Treatment Trial (COBRIT) were analyzed retrospectively. Exclusion criteria were renal failure or malignancy, and any extracranial injury severity score >3. ATC was defined as INR > 1.3, PTT > 38 s, or platelets < 100 K, determined at baseline, and during the first 7 days of hospitalization., Results: Six hundred forty-seven patients were included; 21 % were found to have ATC. Highest incidence occurred at baseline, and Day Two. Forty-two percent of ATC patients had a GCS < 8, compared with 11.3 % of non-ATC patients (p < 0.001). A significantly higher proportion of ATC patients was transfused blood products, required greater than 4L of fluids, demonstrated hyperthermia and hypothermia, were hypotensive and demonstrated elevated lactate when compared to non-ATC patients. In-hospital mortality, mean hospital length of stay, incidence of DVT and seizures were also significantly higher in ATC patients. A significantly lower portion of ATC patients had good outcomes on the GOS-E (i.e., score > 6), and the DRS (i.e., score < 2) at 180 days, for which ATC was found to be an independent predictor with binary logistic regression. ATC patients also performed significantly worse on several components of the CVLT-II at 180 days., Conclusions: ATC accompanying iTBI is associated with worse functional and cognitive outcomes at 180 days.