Sedation Intensity in Patients with Moderate to Severe Traumatic Brain Injury in the Intensive Care Unit: A TRACK-TBI Cohort Study.

BACKGROUND: Interventions to reduce intracranial pressure (ICP) in patients with traumatic brain injury (TBI) are multimodal but variable, including sedation-dosing strategies. This article quantifies the different sedation intensities administered in patients with moderate to severe TBI (msTBI) using the therapy intensity level (TIL) across different intensive care units (ICUs), including the use of additional ICP-lowering therapies. METHODS: Within the prospective Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, we performed a retrospective analysis of adult patients with msTBI admitted to an ICU for a least 5 days from seven US level 1 trauma centers who received invasive ICP monitoring and intravenous sedation. Sedation intensity was classified prospectively as one of three ordinal levels as part of the validated TIL score, which were collected at least once a day. RESULTS: A total of 127 patients met inclusion criteria (mean age 41.6 ± 17.7 years; 20% female). The median Injury Severity Score was 27 (interquartile range 17-33), with a median admission Glasgow Coma Score of 3 (interquartile range 3-7); 104 patients had severe TBI (82%), and 23 patients had moderate TBI (18%). The sedation intensity score was highest on the first ICU day (2.69 ± 1.78), independent of patient severity. Time to reaching each sedation intensity level varied by site. Sedation level I was reached within 24 h for all sites, but sedation levels II and III were reached variably between days 1 and 3. Sedation level III was never reached by two of seven sites. The total TIL score was highest on the first ICU day, with a modest decrease for each subsequent ICU day, but there was high site-specific practice-pattern variation. CONCLUSIONS: Intensity of sedation and other therapies for elevated ICP for patients with msTBI demonstrate large practice-pattern variation across level 1 trauma centers within the TRACK-TBI cohort study, independent of patient severity. Optimizing sedation strategies using patient-specific physiologic and pathoanatomic information may optimize patient outcomes.

Pilot study evaluating treatment with sumatriptan for moderate to severe post-traumatic headache: A phase 2 open-label study.

OBJECTIVE: Our primary outcome was to determine the feasibility of patients with post-traumatic headache (PTH) keeping a daily headache diary and using sumatriptan as directed. Secondary outcomes include determining if sumatriptan is effective in aborting PTH and whether headache resolution is dependent on PTH phenotype. BACKGROUND: PTH is prevalent and persistent after traumatic brain injury, yet there have been few studies evaluating the effects of pharmacological treatments in individuals with PTH. METHODS: This is a single-arm, prospective, non-randomized phase 2 clinical trial registered at Clinicaltrials.gov (NCT01854385) and conducted from 2013 to 2017. Data analysis was completed in 2022. Of the 299 participants screened, 40 were enrolled in the study. Participants kept a headache diary documenting headache characteristics and severity. Headache characteristics were used to determine PTH phenotypes of migraine-like, probable migraine-like, or non-migraine-like. Participants reported whether sumatriptan was used for their headache, their response to the medication, if a second dose was taken, and their response to the second dose. RESULTS: A total of 15 participants out of the 40 enrolled (mean [SD] age, 41.9 [14.2] years, and 53% [21/40] male), met the criteria for the use of sumatriptan, and completed all assessments. Average headache diary compliance rate for the final month of the study was 80% (372/465). While sumatriptan was used for only 19% (122/654) of all reported headaches, 72% (88/122) of those headaches resolved within 2 h of taking the medication. Resolution of headaches with sumatriptan was not significantly different among headache phenotypes (migraine-like: 22/38 [58%], probable migraine-like: 24/29 [83%], non-migraine-like: 6/15 [40%]; p = 0.154). CONCLUSIONS: A daily headache diary is feasible for tracking headache symptoms. Preliminary results also suggest that sumatriptan, a migraine-specific medication, may be beneficial for the treatment of PTH of different clinical phenotypes. Future studies, such as a phase 3 clinical trial with a larger sample size, are needed to better understand the efficacy of sumatriptan in the treatment of PTH.

Preoperative Opioid Use Increases Postoperative Opioid Demand, but Not Length of Stay After Spine Trauma Surgery.

BACKGROUND: Preoperative opioid use has been well-studied in elective spinal surgery and correlated with numerous postoperative complications including increases in immediate postoperative opioid demand (POD), continued opioid use postoperatively, prolonged length of stay (LOS), readmissions, and disability. There is a paucity of data available on the use of preoperative opioids in surgery for spine trauma, possibly because there are minimal options for opioid reduction prior to emergent spinal surgery. Nevertheless, patients with traumatic spinal injuries are at a high risk for adverse postoperative outcomes. This study investigated the effects of preoperative opioid use on POD and LOS in spine trauma patients. METHODS: 130 patients were grouped into two groups for primary comparison: Group 1 (preoperative opioid use, N = 16) and Group 2 (no opioid use, N = 114). Two subgroups of Group 2 were used for secondary analysis against Group 1: Group 3 (no substance abuse, N = 95) and Group 4 (other substance abuse, N = 19). Multivariable analysis was used to determine if there were significant differences in POD and LOS. RESULTS: Primary analysis demonstrated that preoperative opioid users required an estimated 97.5 mg/day more opioid medications compared to non-opioid users (P < 0.001). Neither primary nor secondary analysis showed a difference in LOS in any of the comparisons. CONCLUSIONS: Preoperative opioid users had increased POD compared to non-opioid users and patients abusing other substances, but there was no difference in LOS. We theorize the lack of difference in LOS may be due to the enhanced perioperative recovery protocol used, which has been demonstrated to reduce LOS.

Prior traumatic brain injury is a risk factor for in-hospital mortality in moderate to severe traumatic brain injury: a TRACK-TBI cohort study.

Objectives: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort. Methods: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury. Results: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months. Conclusions: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed. Level of evidence: IV. Trial registration number: NCT02119182.

Extracranial Complications in Monitored and Non-Monitored Patients with Traumatic Brain Injury in the BEST TRIP Trial and a Companion Observational Cohort.

INTRODUCTION: Extracranial complications occur commonly in patients with traumatic brain injury (TBI) and can have implications for patient outcome. Patient-specific risk factors for developing these complications are not well studied, particularly in low and middle-income countries (LMIC). The study objective was to determine patient-specific risk factors for development of extracranial complications in TBI. METHODS: We assessed the relationship between patient demographic and injury factors and incidence of extracranial complications using data collected September 2008-October 2011 from the BEST TRIP trial, a randomized controlled trial assessing TBI management protocolized on intracranial pressure (ICP) monitoring versus imaging and clinical exam, and a companion observational patient cohort. RESULTS: Extracranial infections (55%), respiratory complications (19%), hyponatremia (27%), hypernatremia (27%), hospital acquired pressure ulcers (6%), coagulopathy (9%), cardiac arrest (10%), and shock (5%) occurred at a rate of ≥5% in our study population; overall combined rate of these complications was 82.3%. Tracheostomy in the intensive care unit (p<0.001), tracheostomy timing (p=0.025), mannitol and hypertonic saline doses (p<0.001), brain-specific therapy days and brain-specific therapy intensity (p<0.001), extracranial surgery (p<0.001), and neuroworsening with pupil asymmetry (p=0.038) were all significantly related to the development of one of these complications by univariable analysis. Multivariable analysis revealed ICP monitor use and brain-specific therapy intensity to be the most common factors associated with individual complications. CONCLUSIONS: Extracranial complications are common following TBI. ICP monitoring and treatment are related to extra-cranial complications. This supports the need for reassessing the risk-benefit balance of our current management approaches in the interest of improving outcome.

Association of early dexmedetomidine exposure with brain injury biomarker levels following moderate - Severe traumatic brain injury: A TRACK-TBI study.

BACKGROUND: Traumatic brain injury (TBI) triggers autonomic dysfunction and inflammatory response that can result in secondary brain injuries. Dexmedetomidine is an alpha-2 agonist that may modulate autonomic function and inflammation and has been increasingly used as a sedative agent for critically ill TBI patients. We aimed to investigate the association between early dexmedetomidine exposure and blood-based biomarker levels in moderate-to-severe TBI (msTBI). METHODS: We conducted a retrospective cohort study using data from the Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study (TRACK-TBI), which enrolled acute TBI patients prospectively across 18 United States Level 1 trauma centers between 2014-2018. Our study population focused on adults with msTBI defined by Glasgow Coma Scale score 3-12 after resuscitation, who required mechanical ventilation and sedation within the first 48 h of ICU admission. The study's exposure was early dexmedetomidine utilization (within the first 48 h of admission). Primary outcome included brain injury biomarker levels measured from circulating blood on day 3 following injury, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B) and the inflammatory biomarker C-reactive protein (CRP). Secondary outcomes assessed biomarker levels on days 5 and 14. Linear mixed-effects regression modelling of the log-transformed response variable was used to analyze the association of early dexmedetomidine exposure with brain injury biomarker levels. RESULTS: Among the 352 TRACK-TBI subjects that met inclusion criteria, 50 (14.2 %) were exposed to early dexmedetomidine, predominantly male (78 %), white (81 %), and non-Hispanic (81 %), with mean age of 39.8 years. Motor vehicle collisions (27 %) and falls (22 %) were common causes of injury. No significant associations were found between early dexmedetomidine exposure with day 3 brain injury biomarker levels (GFAP, ratio = 1.46, 95 % confidence interval [0.90, 2.34], P = 0.12; UCH-L1; ratio = 1.17 [0.89, 1.53], P = 0.26; NSE, ratio = 1.19 [0.92, 1.53], P = 0.19; S100B, ratio = 1.01 [0.95, 1.06], P = 0.82; hs-CRP, ratio = 1.29 [0.91, 1.83], P = 0.15). The hs-CRP level at day 14 in the dexmedetomidine group was higher than that of the non-exposure group (ratio = 1.62 [1.12, 2.35], P = 0.012). CONCLUSIONS: There were no significant associations between early dexmedetomidine exposure and day 3 brain injury biomarkers in msTBI. Our findings suggest that early dexmedetomidine use is not correlated with either decrease or increase in brain injury biomarkers following msTBI. Further research is necessary to confirm these findings.

Collaborative Care for Chronic Pain After Traumatic Brain Injury: A Randomized Clinical Trial.

Importance: Chronic pain after traumatic brain injury (TBI) is prevalent and associated with poor outcomes. By providing multidisciplinary care through expert consultation, a collaborative care (CC) treatment approach may reduce pain interference. Objective: To compare CC with usual care (UC) in decreasing pain interference. Design, Setting, and Participants: This randomized clinical trial was conducted from July 2018 through April 2021 at 2 hospital-based academic rehabilitation medicine clinics in Seattle, Washington. Participants included adults with mild-to-severe TBI (at least 6 months before enrollment) and chronic pain. Data analysis was performed from March 30, 2022, to August 30, 2023. Intervention: The CC intervention (called TBI Care) included up to 12 in-person or telephone visits over 16 weeks with a care manager (CM) who provided person-centered cognitive behavioral treatment. The CM met weekly with members of the expert team to review participants and discuss recommendations to optimize treatment. Main Outcomes and Measures: The primary outcome was pain interference on the Brief Pain Inventory at treatment conclusion (4 months after randomization). Secondary outcomes included pain interference at 8 months; pain severity; symptoms of depression, anxiety, and sleep disturbance; pain-related emergency department visits; community participation; and participant satisfaction. Linear mixed-effects regression was used for analysis. Results: A total of 1379 individuals were screened for eligibility, and 158 were randomized (79 to CC and 79 to UC). The participants were mostly women (92 participants [58%]) with a mean (SD) age of 46.8 (13.2) years and a mean (SD) of 15.3 (3.0) years of education. TBI occurred a mean (SD) of 4.0 (5.9) years (median [IQR], 1.9 [0.8-4.5] years) before enrollment. All TBI severities were included, and of 149 participants for whom TBI severity was known, the majority (97 participants [65%]) had mild TBI. In the CC group, 71 participants (90%) completed at least 11 sessions, and, at 4 months, this group had significantly lower pain interference scores compared with the UC group (mean [SD], 3.46 [2.17] vs 5.03 [2.28]). This difference was maintained at 8 months after randomization, with mean (SD) TBI care pain interference scores of 3.61 (2.22) for CC vs 4.68 (2.51) for UC. At 4 months, there was significantly lower pain severity in the CC group vs UC group (mean [SD] score, 3.63 [1.95] vs 4.90 [1.96]), as well as symptoms of depression (mean [SD] score, 8.07 [5.34] vs 11.31 [6.37]) and anxiety (mean [SD], 6.20 [5.17] vs 9.58 [6.00]). Satisfaction with pain treatment (mean [SD] score, 2.99 [1.23] vs 2.52 [1.25]), clinical care (mean [SD] score, 3.28 [1.00] vs 2.84 [1.26]), and overall health care (mean [SD] score, 3.25 [0.88] vs 2.82 [1.00]) were significantly higher in the CC group vs the UC group; global impression of change was significantly lower in the CC group vs the UC group (mean [SD] score, 2.74 [1.02] vs 3.47 [1.26]) (lower scores denote a better impression of change). Conclusions and Relevance: In this randomized clinical trial of CC compared with UC for patients with TBI, CC was effective at reducing pain interference and was sustained at 8-month follow-up. Further research is needed to examine the implementation and cost-effectiveness of CC for TBI in other health care settings. Trial Registration: ClinicalTrials.gov Identifier: NCT03523923.

Predictors of Physical Activity One Year After Moderate to Severe Traumatic Brain Injury.

OBJECTIVE: To identify predictors of moderate to vigorous physical activity (MVPA) at 12-months post-moderate-severe traumatic brain injury (TBI). Setting: Four inpatient rehabilitation centers. PARTICIPANTS: Individuals enrolled in the TBI Model Systems with moderate to severe TBI, admitted to inpatient rehabilitation, and able to ambulate without physical assistance from another person. DESIGN: Prospective longitudinal cohort study. MVPA was measured by having participants wear an ActiGraph GT3X on their wrist for 7 consecutive days. MAIN ANALYSES: We used multivariate regression to predict minutes per week of MVPA at 12 months after TBI. Three classes of predictors were entered hierarchically-demographic and clinical variables (age, sex, body mass index, education, TBI severity, neighborhood walkability score, and self-reported preinjury physical activity [PA] level), baseline TBI-related comorbid conditions (eg, measures of sleep, pain, mood, fatigue, and cognition), and intention to exercise and exercise self-efficacy assessed approximately 1 week after discharge from inpatient rehabilitation. RESULTS: 180 participants (ages 17.7-90.3 years) were enrolled, and 102 provided at least 5 days of valid accelerometer data at 12 months. At 12 months, participants recorded an average of 703 (587) minutes per week of MVPA. In univariate and multivariate analyses, age was the only significant predictor of 12-month MVPA (r = -0.52). A sharp decline in MVPA was observed in the tertile of participants who were over the age of 61. CONCLUSIONS: Older adults with TBI are at elevated risk of being physically inactive. Assuming PA may enhance health after TBI, older adults are a logical target for prevention or early intervention studies. Studies with longer outcomes are needed to understand the trajectory of PA levels after TBI.

Recovery Potential in Patients Who Died After Withdrawal of Life-Sustaining Treatment: A TRACK-TBI Propensity Score Analysis.

Among patients with severe traumatic brain injury (TBI), there is high prognostic uncertainty but growing evidence that recovery of independence is possible. Nevertheless, families are often asked to make decisions about withdrawal of life-sustaining treatment (WLST) within days of injury. The range of potential outcomes for patients who died after WLST (WLST+) is unknown, posing a challenge for prognostic modeling and clinical counseling. We investigated the potential for survival and recovery of independence after acute TBI in patients who died after WLST. We used Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data and propensity score matching to pair participants with WLST+ to those with a similar probability of WLST (based on demographic and clinical characteristics), but for whom life-sustaining treatment was not withdrawn (WLST-). To optimize matching, we divided the WLST- cohort into tiers (Tier 1 = 0-11%, Tier 2 = 11-27%, Tier 3 = 27-70% WLST propensity). We estimated the level of recovery that could be expected in WLST+ participants by evaluating 3-, 6-, and 12-month Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale outcomes in matched WLST- participants. Of 90 WLST+ participants (80% male, mean [standard deviation; SD] age = 59.2 [17.9] years, median [IQR] days to WLST = 5.4 [2.2, 11.7]), 80 could be matched to WLST- participants. Of 56 WLST- participants who were followed at 6 months, 31 (55%) died. Among survivors in the overall sample and survivors in Tiers 1 and 2, more than 30% recovered at least partial independence (GOSE ≥4). In Tier 3, recovery to GOSE ≥4 occurred at 12 months, but not 6 months, post-injury. These results suggest a substantial proportion of patients with TBI and WLST may have survived and achieved at least partial independence. However, death or severe disability is a common outcome when the probability of WLST is high. While further validation is needed, our findings support a more cautious clinical approach to WLST and more complete reporting on WLST in TBI studies.

Feasibility of Brief, Hypnotic Enhanced Cognitive Therapy for SCI-related Pain During Inpatient Rehabilitation.

OBJECTIVES: (1) Adapt evidence-based hypnosis-enhanced cognitive therapy (HYP-CT) for inpatient rehabilitation setting; and (2) determine feasibility of a clinical trial evaluating the effectiveness of HYP-CT intervention for pain after spinal cord injury (SCI). STUDY DESIGN: Pilot non-randomized controlled trial. SETTING: Inpatient rehabilitation unit. PARTICIPANTS: English-speaking patients admitted to inpatient rehabilitation after SCI reporting current pain of at least 3 on a 0-10 scale. Persons with severe psychiatric illness, recent suicide attempt or elevated risk, or significant cognitive impairment were excluded. Consecutive sample of 53 patients with SCI-related pain enrolled, representing 82% of eligible patients. INTERVENTION: Up to 4 sessions of HYP-CT Intervention, each 30-60 minutes long. METHODS: Participants were assessed at baseline and given the choice to receive HYP-CT or Usual Care. MAIN OUTCOME MEASURES: Participant enrollment and participation and acceptability of intervention. Exploratory analyses examined the effect of intervention on pain and cognitive appraisals of pain. RESULTS: In the HYP-CT group, 71% completed at least 3 treatment sessions and reported treatment benefit and satisfaction with the treatment; no adverse events were reported. Exploratory analyses of effectiveness found pre-post treatment pain reductions after HYP-CT with large effect (P<.001; ß=-1.64). While the study was not powered to detect significant between-group differences at discharge, effect sizes revealed decreases in average pain (Cohen's d=-0.13), pain interference (d=-0.10), and pain catastrophizing (d=-0.20) in the HYP-CT group relative to control and increases in self-efficacy (d=0.27) and pain acceptance (d=0.15). CONCLUSIONS: It is feasible to provide HYP-CT to inpatients with SCI, and HYP-CT results in substantial reductions in SCI pain. The study is the first to show a psychological-based nonpharmacologic intervention that may reduce SCI pain during inpatient rehabilitation. A definitive efficacy trial is warranted.

Combat Deployed Service Members by Blast TBI and Service Separation Status 5-years Post-deployment: Comparison of Cognitive, Neurobehavioral, and Psychological Profiles of Those Who Left vs. Those Still Serving.

INTRODUCTION: Longitudinal research regarding the pre- and post-separation experience has been relatively limited, despite its potential as a major life transition. Separating from the military and re-integration to civilian life is noted to be a period of increased risk of significant adjustment challenges, which impacts a service member in a multitude of areas. Active duty service members with combat-related physical or mental health or pre-existing adjustment conditions may be more likely to separate from service and more at risk for post-military service adjustment problems. MATERIALS AND METHODS: This is a secondary data analysis from a prospective, observational, longitudinal, multicohort study involving deployed service members originally enrolled between 2008 and 2013 in combat or following medical evacuation to Landstuhl, Germany. Two combat-deployed cohorts were examined: non-head-injured control without blast exposure (n = 109) and combat-related concussion arising from blast (n = 165). Comprehensive clinical evaluations performed at 1 year and 5 year follow-up included identical assessment batteries for neurobehavioral, psychiatric, and cognitive outcomes. In addition to demographics collected at each study visit, the current analysis leveraged the Glasgow Outcome Scale Extended (GOS-E), a measure of overall global disability. For neurobehavioral impairment, the Neurobehavioral Rating Scale-Revised (NRS) was used as well as the Headache Impact Test (HIT-6) to assess headache burden. To compare psychiatric symptom burden between those separated to those still serving, the Clinician-Administered PTSD Scale for DSM-IV (CAPS) and Montgomery-Asberg Depression Rating Scale (MADRS) for depression were used as well as the Michigan Alcohol Screening Test (MAST) to be able to compare alcohol misuse across groups. Overall cognitive function/performance was defined for each service member by aggregating the 19 neuropsychological measures. RESULTS: Overall comparisons following adjustment by linear regression and correction for multiple comparisons by separation status subgroup for non-blast control or blast traumatic brain injury (TBI) identified significant differences at 5 years post-enrollment in measures of global disability, neurobehavioral impairment, and psychiatric symptom burden. Those who separated had worse global disability, worse neurobehavioral symptoms, worse Post-Traumatic Stress Disorder symptoms, and worse depression symptoms than active duty service members. While service members who sustain a mild blast TBI during combat are more likely to separate from service within 5 years, there is a proportion of those non-injured who also leave during this time frame. Clinical profiles of both groups suggest service members who separated have elevated psychiatric and neurobehavioral symptoms but not cognitive dysfunction. Interestingly, the symptom load in these same domains is lower for those without blast TBI who separated during this time frame. CONCLUSIONS: These results appear to support previous research depicting that, for some service members, transitioning out of the military and re-integrating into civilian life can be a challenging adjustment. Many factors, including personal and social circumstances, prior mental or emotional difficulties, availability of social or community support or resources, can influence the adjustment outcomes of veterans. Service members with prior adjustment difficulties and/or those with blast TBI history (and ongoing neurobehavioral symptoms) may find the transition from military to civilian life even more challenging, given the potential substantial changes in lifestyle, structure, identity, and support.

The Temporal Relationship Between Moderate to Vigorous Physical Activity and Secondary Conditions During the First Year After Moderate to Severe Traumatic Brain Injury.

OBJECTIVE: To determine the cross-sectional and temporal relationships between minutes per week of moderate to vigorous physical activity (MVPA) as measured by a wrist-worn accelerometer and secondary conditions in the first year after moderate to severe traumatic brain injury (TBI). DESIGN: Prospective longitudinal cohort study. SETTING: Four inpatient rehabilitation centers. PARTICIPANTS: Individuals (N = 180) with moderate-severe TBI enrolled in the TBI Model Systems Study. INTERVENTIONS: Participants wore a wrist accelerometer for 7 days immediately post discharge, and for 7 consecutive days at 6- and 12-months post injury. MAIN OUTCOME MEASURES: Minutes per week of MVPA from daily averages based on wrist worn accelerometer. Secondary conditions included depression (Patient Health Questionnaire-9), fatigue (PROMIS Fatigue), Pain (Numeric Rating Scale), Sleep (Pittsburgh Sleep Quality Index), and cognition (Brief Test of Adult Cognition by Telephone). RESULTS: At baseline, 6 and 12 months, 61%, 70% and 79% of the sample achieved at least 150 minutes per week of MVPA. The correlations between minutes of MVPA between baseline, 6 and 12 months were significant (r = 0.53-0.73), as were secondary conditions over these time points. However, no significant correlations were observed between minutes of MVPA and any secondary outcomes cross-sectionally or longitudinally at any time point. CONCLUSIONS: Given the robust relationships physical activity has with outcomes in the general population, further research is needed to understand the effect of physical activity in individuals with moderate-severe TBI.

Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

OBJECTIVE: To examine early sedation patterns, as well as the association of dexmedetomidine exposure, with clinical and functional outcomes among mechanically ventilated patients with moderate-severe traumatic brain injury (msTBI). DESIGN: Retrospective cohort study with prospectively collected data. SETTING: Eighteen Level-1 Trauma Centers, United States. PATIENTS: Adult (age > 17) patients with msTBI (as defined by Glasgow Coma Scale < 13) who required mechanical ventilation from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using propensity-weighted models, we examined the association of early dexmedetomidine exposure (within the first 5 d of ICU admission) with the primary outcome of 6-month Glasgow Outcomes Scale Extended (GOS-E) and the following secondary outcomes: length of hospital stay, hospital mortality, 6-month Disability Rating Scale (DRS), and 6-month mortality. The study population included 352 subjects who required mechanical ventilation within 24 hours of admission. The initial sedative medication was propofol for 240 patients (68%), midazolam for 59 patients (17%), ketamine for 6 patients (2%), dexmedetomidine for 3 patients (1%), and 43 patients (12%) never received continuous sedation. Early dexmedetomidine was administered in 77 of the patients (22%), usually as a second-line agent. Compared with unexposed patients, early dexmedetomidine exposure was not associated with better 6-month GOS-E (weighted odds ratio [OR] = 1.48; 95% CI, 0.98-2.25). Early dexmedetomidine exposure was associated with lower DRS (weighted OR = -3.04; 95% CI, -5.88 to -0.21). In patients requiring ICP monitoring within the first 24 hours of admission, early dexmedetomidine exposure was associated with higher 6-month GOS-E score (OR 2.17; 95% CI, 1.24-3.80), lower DRS score (adjusted mean difference, -5.81; 95% CI, -9.38 to 2.25), and reduced length of hospital stay (hazard ratio = 1.50; 95% CI, 1.02-2.20). CONCLUSION: Variation exists in early sedation choice among mechanically ventilated patients with msTBI. Early dexmedetomidine exposure was not associated with improved 6-month functional outcomes in the entire population, although may have clinical benefit in patients with indications for ICP monitoring.

Clinical Outcomes After Traumatic Brain Injury and Exposure to Extracranial Surgery: A TRACK-TBI Study.

Importance: Traumatic brain injury (TBI) is associated with persistent functional and cognitive deficits, which may be susceptible to secondary insults. The implications of exposure to surgery and anesthesia after TBI warrant investigation, given that surgery has been associated with neurocognitive disorders. Objective: To examine whether exposure to extracranial (EC) surgery and anesthesia is related to worse functional and cognitive outcomes after TBI. Design, Setting, and Participants: This study was a retrospective, secondary analysis of data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective cohort study that assessed longitudinal outcomes of participants enrolled at 18 level I US trauma centers between February 1, 2014, and August 31, 2018. Participants were 17 years or older, presented within 24 hours of trauma, were admitted to an inpatient unit from the emergency department, had known Glasgow Coma Scale (GCS) and head computed tomography (CT) status, and did not undergo cranial surgery. This analysis was conducted between January 2, 2020, and August 8, 2023. Exposure: Participants who underwent EC surgery during the index admission were compared with participants with no surgery in groups with a peripheral orthopedic injury or a TBI and were classified as having uncomplicated mild TBI (GCS score of 13-15 and negative CT results [CT- mTBI]), complicated mild TBI (GCS score of 13-15 and positive CT results [CT+ mTBI]), or moderate to severe TBI (GCS score of 3-12 [m/sTBI]). Main Outcomes and Measures: The primary outcomes were functional limitations quantified by the Glasgow Outcome Scale-Extended for all injuries (GOSE-ALL) and brain injury (GOSE-TBI) and neurocognitive outcomes at 2 weeks and 6 months after injury. Results: A total of 1835 participants (mean [SD] age, 42.2 [17.8] years; 1279 [70%] male; 299 Black, 1412 White, and 96 other) were analyzed, including 1349 nonsurgical participants and 486 participants undergoing EC surgery. The participants undergoing EC surgery across all TBI severities had significantly worse GOSE-ALL scores at 2 weeks and 6 months compared with their nonsurgical counterparts. At 6 months after injury, m/sTBI and CT+ mTBI participants who underwent EC surgery had significantly worse GOSE-TBI scores (B = -1.11 [95% CI, -1.53 to -0.68] in participants with m/sTBI and -0.39 [95% CI, -0.77 to -0.01] in participants with CT+ mTBI) and performed worse on the Trail Making Test Part B (B = 30.1 [95% CI, 11.9-48.2] in participants with m/sTBI and 26.3 [95% CI, 11.3-41.2] in participants with CT+ mTBI). Conclusions and Relevance: This study found that exposure to EC surgery and anesthesia was associated with adverse functional outcomes and impaired executive function after TBI. This unfavorable association warrants further investigation of the potential mechanisms and clinical implications that could inform decisions regarding the timing of surgical interventions in patients after TBI.

The Roles of Protocols and Protocolization in Improving Outcome From Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Our Phase-I parallel-cohort study suggested that managing severe traumatic brain injury (sTBI) in the absence of intracranial pressure (ICP) monitoring using an ad hoc Imaging and Clinical Examination (ICE) treatment protocol was associated with superior outcome vs nonprotocolized management but could not differentiate the influence of protocolization from that of the specific protocol. Phase II investigates whether adopting the Consensus REVised Imaging and Clinical Examination (CREVICE) protocol improved outcome directly or indirectly via protocolization. METHODS: We performed a Phase-II sequential parallel-cohort study examining adoption of the CREVICE protocol from no protocol vs a previous protocol in patients with sTBI older than 13 years presenting ≤24 hours after injury. Primary outcome was prespecified 6-month recovery. The study was done mostly at public South American centers managing sTBI without ICP monitoring. Fourteen Phase-I nonprotocol centers and 5 Phase-I protocol centers adopted CREVICE. Data were analyzed using generalized estimating equation regression adjusting for demographic imbalances. RESULTS: A total of 501 patients (86% male, mean age 35.4 years) enrolled; 81% had 6 months of follow-up. Adopting CREVICE from no protocol was associated with significantly superior results for overall 6-month extended Glasgow Outcome Score (GOSE) (protocol effect = 0.53 [0.11, 0.95], P = .013), mortality (36% vs 21%, HR = 0.59 [0.46, 0.76], P < .001), and orientation (Galveston Orientation and Amnesia Test discharge protocol effect = 10.9 [6.0, 15.8], P < .001, 6-month protocol effect = 11.4 [4.1, 18.6], P < .005). Adopting CREVICE from ICE was associated with significant benefits to GOSE (protocol effect = 0.51 [0.04, 0.98], P = .033), 6-month mortality (25% vs 18%, HR = 0.55 [0.39, 0.77], P < .001), and orientation (Galveston Orientation and Amnesia Test 6-month protocol effect = 9.2 [3.6, 14.7], P = .004). Comparing both groups using CREVICE, those who had used ICE previously had significantly better GOSE (protocol effect = 1.15 [0.09, 2.20], P = .033). CONCLUSION: Centers managing adult sTBI without ICP monitoring should strongly consider protocolization through adopting/adapting the CREVICE protocol. Protocolization is indirectly supported at sTBI centers regardless of resource availability.

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

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 (PbtO2) 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 PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 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 (PbtO2 < 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 PbtO2 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.

Profiles of Cognitive Functioning at 6 Months After Traumatic Brain Injury Among Patients in Level I Trauma Centers: A TRACK-TBI Study.

Importance: Cognitive dysfunction is common after traumatic brain injury (TBI), with a well-established dose-response relationship between TBI severity and likelihood or magnitude of persistent cognitive impairment. However, patterns of cognitive dysfunction in the long-term (eg, 6-month) recovery period are less well known. Objective: To characterize the prevalence of cognitive dysfunction within and across cognitive domains (processing speed, memory, and executive functioning) 6 months after injury in patients with TBI seen at level I trauma centers. Design, Setting, and Participants: This prospective longitudinal cohort study used data from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) and included patients aged 17 years or older presenting at 18 US level I trauma center emergency departments or inpatient units within 24 hours of head injury, control individuals with orthopedic injury recruited from the same centers, and uninjured friend and family controls. Participants were enrolled between March 2, 2014, and July 27, 2018. Data were analyzed from March 5, 2020, through October 3, 2023. Exposures: Traumatic brain injury (Glasgow Coma Scale score of 3-15) or orthopedic injury. Main Outcomes and Measures: Performance on standard neuropsychological tests, including premorbid cognitive ability (National Institutes of Health Toolbox Picture Vocabulary Test), verbal memory (Rey Auditory Verbal Learning Test), processing speed (Wechsler Adult Intelligence Scale [4th edition] Processing Speed Index), and executive functioning (Trail Making Test). Results: The sample included 1057 persons with TBI (mean [SD] age, 39.3 [16.4] years; 705 [67%] male) and 327 controls without TBI (mean [SD] age, 38.4 [15.1] years; 222 [68%] male). Most persons with TBI demonstrated performance within 1.5 SDs or better of the control group (49.3% [95% CI, 39.5%-59.2%] to 67.5% [95% CI, 63.7%-71.2%] showed no evidence of impairment). Similarly, 64.4% (95% CI, 54.5%-73.4%) to 78.8% (95% CI, 75.4%-81.9%) of participants demonstrated no evidence of cognitive decline (defined as performance within 1.5 SDs of estimated premorbid ability). For individuals with evidence of either cognitive impairment or decline, diverse profiles of impairment across memory, speed, and executive functioning domains were observed (ie, the prevalence was >0 in each of the 7 combinations of impairment across these 3 cognitive domains for most TBI subgroups). Conclusions and Relevance: In this cohort study of patients seen at level I trauma centers 6 months after TBI, many patients with TBI demonstrated no cognitive impairment. Impairment was more prevalent in persons with more severe TBI and manifested in variable ways across individuals. The findings may guide future research and treatment recommendations.

Acute Extra-Arachnoid Subdural Hematomas in Patients 50 Years and Older: When Subdurals Act Like Epidurals.

BACKGROUND: Some patients with subdural hematoma (SDH) with acute extra-arachnoid lesions and without concomitant subarachnoid blood or contusions may present in similarly grave neurological condition compared with the general population of patients with SDH. However, these patients often make an impressive neurological recovery. This study compared neurological outcomes in patients with extra-arachnoid SDH with all other SDH patients. METHODS: We compared a prospective series of extra-arachnoid SDH patients without subarachnoid hemorrhage or other concomitant intracranial injury with a Transforming Research and Clinical Knowledge in TBI control group with SDH only. We performed inverse probability weighting for key characteristics and ordinal regression with and without controlling for midline shift comparing neurological outcomes (Extended Glasgow Outcome Scale score) at 2 weeks. We used the Corticosteroid Randomization After Significant Head Injury prognostic model to predict mortality based on age, Glasgow Coma Scale score, pupil reactivity, and major extracranial injury. RESULTS: Mean midline shift was significantly different between extra-arachnoid SDH and control groups (7.2 mm vs. 2.7 mm, P < 0.001). After weighting for group allocation and controlling for midline shift, extra-arachnoid SDH patients had 5.68 greater odds (P < 0.001) of a better 2-week Extended Glasgow Outcome Scale score than control patients. Mortality in the extra-arachnoid SDH group was less than predicted by the Corticosteroid Randomization After Significant Head Injury prognostic model (10% vs. 21% predicted). CONCLUSIONS: Patients with extra-arachnoid SDH have significantly better 2-week neurological outcomes and lower mortality than predicted by the Corticosteroid Randomization After Significant Head Injury model. Neurosurgeons should consider surgery for this patient subset even in cases of poor neurological examination, older age, and large hematoma with high degree of midline shift.

Perioperative complications and secondary retethering after pediatric tethered cord release surgery.

OBJECTIVE: Tethered cord syndrome refers to a constellation of symptoms characterized by neurological, musculoskeletal, and urinary symptoms, caused by traction on the spinal cord, which can be secondary to various etiologies. Surgical management of simple tethered cord etiologies (e.g., fatty filum) typically consists of a single-level lumbar laminectomy, intradural exploration, and coagulation and sectioning of the filum. More complex etiologies such as lipomyelomeningoceles or scar formation after myelomeningocele repair involve complex dissection and dural reconstruction. The purpose of this study was to evaluate operative complications and long-term outcomes of secondary retethering related to pediatric tethered cord release (TCR) at a tertiary children's hospital. METHODS: Medical records of children who underwent surgery for TCR from July 2014 to March 2023 were retrospectively reviewed. Data collected included demographics, perioperative characteristics, surgical technique, and follow-up duration. Primary outcomes were 60-day postoperative complications and secondary retethering requiring repeat TCR surgery. Univariate and multivariate analyses were performed to identify risk factors associated with complications and secondary retethering. RESULTS: A total of 363 TCR surgeries (146 simple, 217 complex) in 340 patients were identified. The mean follow-up was 442.8 ± 662.2 days for simple TCRs and 733.9 ± 750.3 days for complex TCRs. The adjusted 60-day complication-free survival rate was 96.3% (95% CI 91.3%-98.4%) for simple TCRs and 88.7% (95% CI 82.3%-91.4%) for complex TCRs. Lower weight, shorter surgical times, and intensive care unit admission were associated with complications for simple TCRs. Soft-tissue drains increased complications for complex TCRs. The secondary retethering rates were 1.4% for simple TCRs and 11.9% for complex TCRs. The 1-, 3-, and 5-year progression-free survival rates in complex cases were 94.7% (95% CI 89.1%-97.4%), 77.7% (95% CI 67.3%-85.3%), and 62.6% (95% CI 46.5%-75.1%), respectively. Multivariate analysis revealed that prior detethering (OR 8.15, 95% CI 2.33-28.50; p = 0.001) and use of the operative laser (OR 10.43, 95% CI 1.36-80.26; p = 0.024) were independently associated with secondary retethering in complex cases. CONCLUSIONS: This is the largest series to date examining postoperative complications and long-term secondary retethering in TCR surgery. Simple TCR surgeries demonstrated safety, rare complications, and low secondary retethering rates. Complex TCR surgeries presented higher risks of complications and secondary retethering. Modifiable risk factors such as operative laser use influenced secondary retethering in complex cases.