Severe Traumatic Brain Injury In Adults Research Articles

Severe Traumatic Brain Injury Outcomes in Patients with Premorbid Psychiatric Illness

ObjectiveIndividuals with psychiatric illnesses (PI) have increased rates of traumatic brain injury (TBI). Nonetheless, the influence of underlying PI on TBI outcomes is poorly understood. MethodsWe analyzed the medical records of 633 adult-severe TBI (sTBI) patients admitted to our institution between 2010-2021. We identified patients with premorbid PI (Psych(+) group, n=129) and a subset with only a substance use disorder (SUD(+) group, n=60) and compared them to patients without PI (Psych(-) group, n=480). Outcome measures included discharge Glasgow Coma Scale (GCS), length of stay (LOS), in-hospital survival, and Glasgow Outcome Scale-Extended (GOS-E). ResultsThe Psych(+) group had increased in-hospital survival (69.8% v. 55.0%, P=0.003) and fewer patients with severe (3-8) discharge-GCS (28.7% v. 46.0%, P<0.001). The SUD(+) group had increased in-hospital survival (70.0% v. 55.0%, P=0.028) and fewer patients with severe discharge-GCS (28.3% v. 46.0%, P=0.009). However, the Psych(+) (21.0 v. 10.0 days, P<0.001) and SUD(+) (16.0 v. 10.0 days, P=0.011) groups had longer LOS. The Psych(+) group had a higher mean GOS-E at discharge (2.7 v. 2.4, P=0.004), six-months (3.8 v. 3.0, P=0.006) and one-year (3.4 v. 2.3, P=0.027). The SUD(+) group also had a higher mean GOS-E at discharge (2.8 v. 2.4, P=0.034), six months (3.8 v. 3.0, P=0.035), and one year (3.5 v. 2.3, P=0.008). Additionally, there were no significant differences in injury severity or CT scan findings. ConclusionsIndividuals with PI and SUD appeared to have better outcomes but more complicated hospital stays following sTBI. Future studies should investigate the mechanisms underlying these outcomes.

785 Variability in Withdrawal of Life Sustaining Treatment Decision for Patients With Severe Traumatic Brain Injury: An Analysis of 510 North American Trauma Centers

INTRODUCTION: Withdrawal of life sustaining treatment (WLST) in severe traumatic brain injury (TBI) is complex with a paucity of standardized guidelines to inform practice patterns. We hypothesized presence of variability in WLST decision-making across centers, which could have important implications for equitable trauma care provision. METHODS: This retrospective study utilized data from adult severe TBI patients treated at trauma centers participating in the Trauma Quality Improvement Program between 2017-2020. Multivariable hierarchical logistic regression was used to adjust for patient, injury and hospital attributes influencing WLST. Residual between-center variability was characterized using the median odds ratio. Disparate WLST practices were further assessed by ranking centers' tendencies for WLST and assessing mortality between quartiles. RESULTS: We identified a total of 85511 subjects with severe TBI treated across 510 trauma centers, of which 20,300 (24%) had WLST. Patient-level factors associated with increased likelihood of WLST were advanced age, white race, treatment in a non-profit trauma center or self-pay/ Medicare insurance status (compared to private insurance). Black race was associated with reduced tendency for WLST. Higher severity intracranial and extracranial injuries also increased likelihood for WLST.After adjustment for patient and hospital attributes, the median odds ratio was 1.44 (1.40-1.48 95%CI), suggesting substantial residual variation in WLST between centers. When centers were grouped into quartiles by their propensity for WLST, there was a 1.37 (1.30-1.42 95%CI) increased adjusted odds of mortality between fourth versus first quartile centers. CONCLUSIONS: We highlighted the presence of disparate WLST practice patterns between trauma centers after adjustment for case-mix and hospital attributes. These findings highlight a strong need for examination of center-level factors contributing to heterogenous WLST practices to ultimately improve equity of care provision for severe TBI patients.

Acute Brain-Derived Neurotrophic Factor DNA Methylation Trajectories in Cerebrospinal Fluid and Associations With Outcomes Following Severe Traumatic Brain Injury in Adults

Background. Epigenetic biomarkers have the potential to explain outcome heterogeneity following traumatic brain injury (TBI) but are largely unexplored. Objective. This exploratory pilot study characterized brain-derived neurotrophic factor (BDNF) DNA methylation trajectories following severe TBI. Methods. Brain-derived neurotrophic factor DNA methylation trajectories in cerebrospinal fluid (CSF) over the first 5 days following severe TBI in 112 adults were examined in association with 3- and 12-month outcomes. Results. Group-based trajectory analysis revealed low and high DNA methylation groups at two BDNF cytosine-phosphate-guanine (CpG) targets that showed suggestive associations (P < .05) with outcomes. Membership in the high DNA methylation groups was associated with better outcomes after controlling for age, sex, and injury severity. Associations of age × trajectory group interactions with outcomes at a third CpG site revealed a pattern of the same or better outcomes with higher ages in the high DNA methylation group and worse outcomes with higher ages in the low DNA methylation group. Conclusions. Although no observed associations met the empirical significance threshold after correcting for multiple comparisons, suggestive associations of the main effect models were consistent in their direction of effect and were observed across two CpG sites and two outcome time points. Results suggest that higher acute CSF BDNF DNA methylation may promote recovery following severe TBI in adults, and this effect may be more robust with higher age. While the results require replication in larger and racially diverse independent samples, BDNF DNA methylation may serve as an early postinjury biomarker helping to explain outcome heterogeneity following TBI.

Cerebrovascular Autoregulation Monitoring in the Management of Adult Severe Traumatic Brain Injury: A Delphi Consensus of Clinicians

BackgroundSeveral methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty.AimTo formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities.MethodsA group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants.ResultsConsensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence.ConclusionThe Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

VENTILatOry strategies in patients with severe traumatic brain injury: the VENTILO Survey of the European Society of Intensive Care Medicine (ESICM)

BackgroundSevere traumatic brain injury (TBI) patients often develop acute respiratory failure. Optimal ventilator strategies in this setting are not well established. We performed an international survey to investigate the practice in the ventilatory management of TBI patients with and without respiratory failure.MethodsAn electronic questionnaire, including 38 items and 3 different clinical scenarios [arterial partial pressure of oxygen (PaO2)/inspired fraction of oxygen (FiO2) > 300 (scenario 1), 150–300 (scenario 2), < 150 (scenario 3)], was available on the European Society of Intensive Care Medicine (ESICM) website between November 2018 and March 2019. The survey was endorsed by ESICM.ResultsThere were 687 respondents [472 (69%) from Europe], mainly intensivists [328 (48%)] and anesthesiologists [206 (30%)]. A standard protocol for mechanical ventilation in TBI patients was utilized by 277 (40%) respondents and a specific weaning protocol by 198 (30%). The most common tidal volume (TV) applied was 6–8 ml/kg of predicted body weight (PBW) in scenarios 1–2 (72% PaO2/FIO2 > 300 and 61% PaO2/FiO2 150–300) and 4–6 ml/kg/PBW in scenario 3 (53% PaO2/FiO2 < 150). The most common level of highest positive end-expiratory pressure (PEEP) used was 15 cmH2O in patients with a PaO2/FiO2 ≤ 300 without intracranial hypertension (41% if PaO2/FiO2 150–300 and 50% if PaO2/FiO2 < 150) and 10 cmH2O in patients with intracranial hypertension (32% if PaO2/FiO2 150–300 and 33% if PaO2/FiO2 < 150). Regardless of the presence of intracranial hypertension, the most common carbon dioxide target remained 36–40 mmHg whereas the most common PaO2 target was 81–100 mmHg in all the 3 scenarios. The most frequent rescue strategies utilized in case of refractory respiratory failure despite conventional ventilator settings were neuromuscular blocking agents [406 (88%)], recruitment manoeuvres [319 (69%)] and prone position [292 (63%)].ConclusionsVentilatory management, targets and practice of adult severe TBI patients with and without respiratory failure are widely different among centres. These findings may be helpful to define future investigations in this topic.

Influence of mild-moderate hypocapnia on intracranial pressure slow waves activity in TBI

BackgroundIn traumatic brain injury (TBI) the patterns of intracranial pressure (ICP) waveforms may reflect pathological processes that ultimately lead to unfavorable outcome. In particular, ICP slow waves (sw) (0.005–0.05 Hz) magnitude and complexity have been shown to have positive association with favorable outcome. Mild-moderate hypocapnia is currently used for short periods to treat critical elevations in ICP. Our goals were to assess changes in the ICP sw activity occurring following sudden onset of mild-moderate hypocapnia and to examine the relationship between changes in ICP sw activity and other physiological variables during the hypocapnic challenge.MethodsICP, arterial blood pressure (ABP), and bilateral middle cerebral artery blood flow velocity (FV), were prospectively collected in 29 adult severe TBI patients requiring ICP monitoring and mechanical ventilation in whom a minute volume ventilation increase (15–20% increase in respiratory minute volume) was performed as part of a clinical CO2-reactivity test. The time series were first treated using FFT filter (pass-band set to 0.005–0.05 Hz). Power spectral density analysis was performed. We calculated the following: mean value, standard deviation, variance and coefficient of variation in the time domain; total power and frequency centroid in the frequency domain; cerebrospinal compliance (Ci) and compensatory reserve index (RAP).ResultsHypocapnia led to a decrease in power and increase in frequency centroid and entropy of slow waves in ICP and FV (not ABP). In a multiple linear regression model, RAP at the baseline was the strongest predictor for the decrease in the power of ICP slow waves (p < 0.001).ConclusionIn severe TBI patients, a sudden mild-moderate hypocapnia induces a decrease in mean ICP and FV, but also in slow waves power of both signals. At the same time, it increases their higher frequency content and their morphological complexity. The difference in power of the ICP slow waves between the baseline and the hypocapnia period depends on the baseline cerebrospinal compensatory reserve as measured by RAP.

Feasibility of individualised severe traumatic brain injury management using an automated assessment of optimal cerebral perfusion pressure: the COGiTATE phase II study protocol

IntroductionIndividualising therapy is an important challenge for intensive care of patients with severe traumatic brain injury (TBI). Targeting a cerebral perfusion pressure (CPP) tailored to optimise cerebrovascular autoregulation has been...

Effect of American College of Surgeons Level 1 Trauma Center Designation on Management of Adult Severe TBI Patients

Abstract INTRODUCTION Severe traumatic brain injury (TBI) remains a leading cause of morbidity and mortality. There is a wide variability in treatment paradigm for patients with severe TBI. American College of Surgeons (ACS) level 1 trauma centers have access to 24 h neurosurgical coverage. In this study, we use the National Trauma Database (NTDB) to evaluate if ACS trauma center designation correlates with the management and outcomes of severe TBI in adults. METHODS Adult patients (&lt;65 yr) with a severe isolated nonpenetrating TBI were identified in the NTDB from years 2007 to 2014. ICD-9 procedure codes were used to identify primary treatment approaches: intracranial pressure monitoring and cranial surgery. Multivariate logistic regression was used to determine the impact of ACS designation on procedures and patient outcomes. Patient and injury characteristics were included in the analysis. RESULTS A total of 54 769 TBI patients were identified. Among those, 22 316 (42%) were treated at an ACS level 1 trauma center and 31 835 (58%) were treated elsewhere. Level 1 designated patients had significantly more intracranial pressure (ICP) monitors placed (12.3% vs10.8%; P &lt; .0001) and more cranial surgeries performed (17.7% vs 15.7%; P &lt; .0001). A greater percentage of patients were admitted to the intensive care unit (ICU; 89.9% vs 83.9%; P &lt; .0001) and had a longer hospital stay (16.1 vs 15.2; P &lt; .0001) at ACS level 1 trauma centers. In a regression analysis, patients at level 1 centers were associated with a 14% and 17% increased odds of obtaining a cranial surgery or ICP monitor, respectively. Patients treated at a level 1 center were associated with a 6% decrease in odds of mortality (P = .01). CONCLUSION ACS level 1 designation did correlate with increased rates of neurosurgical intervention and ICU admissions. This translated into patient outcomes as those treated at level 1 facilities were associated with lower rates of mortality.

Diffusion tensor imaging changes following mild, moderate and severe adult traumatic brain injury: a meta-analysis.

Diffusion tensor imaging quantifies the asymmetry (fractional anisotropy; FA) and amount of water diffusion (mean diffusivity/apparent diffusion coefficient; MD/ADC) and has been used to assess white matter damage following traumatic brain injury (TBI). In healthy brains, diffusion is constrained by the organization of axons, resulting in high FA and low MD/ADC. Following a TBI, diffusion may be altered; however the exact nature of these changes has yet to be determined. A meta-analysis was therefore conducted to determine the location and extent of changes in DTI following adult TBI. The data from 44 studies that compared the FA and/or MD/ADC data from TBI and Control participants in different regions of interest (ROIs) were analyzed. The impact of injury severity, post-injury interval (acute: ≤ 1 week, subacute: 1 week-3 months, chronic: > 3 months), scanner details and acquisition parameters were investigated in subgroup analyses, with the findings indicating that mild TBI should be examined separately to that of moderate to severe injuries. Lower FA values were found in 88% of brain regions following mild TBI and 92% following moderate-severe TBI, compared to Controls. MD/ADC was higher in 95% and 100% of brain regions following mild and moderate-severe TBI, respectively. Moderate to severe TBI resulted in larger changes in FA and MD/ADC than mild TBI. Overall, changes to FA and MD/ADC were widespread, reflecting more symmetric and a higher amount of diffusion, indicative of white matter damage.

Time course of cerebrospinal fluid inflammatory biomarkers and relationship to 6-month neurologic outcome in adult severe traumatic brain injury

ObjectiveActivation of the inflammatory cascade is a known pathophysiologic process in severe traumatic brain injury (TBI) with yet non-standardized scientific data regarding relationship to outcome. The understanding of the time course of expression of cerebrospinal fluid (CSF) biomarker levels following severe TBI is an important step toward using these biomarkers to measure injury severity and/or early response to therapeutic interventions. The objective of the current study is to report the time course and values of a battery of CSF inflammatory biomarkers following severe TBI in our reasonably sized patient cohort. Patients and methodsOur patient cohort consists of 32 consented patients, who met the study's inclusion criteria for data collection from 2000 to 2010. The time course and values of a battery of CSF biomarkers (IL-1β, IL-6, TNF-α, IFN-γ, IL-12p70, IL-10, and IL-8) following severe TBI in this patient cohort was characterized. Additionally, the correlation of biomarker concentration with 6-month neurological outcome was assessed. Serial CSF sampling through an external ventricular drain was performed over the first five days following injury. Concentration of a panel of inflammatory biomarkers (IL-1β, IL-6, TNF-α, IFN-γ, IL-12p70, IL-10, and IL-8) were evaluated using Meso Scale Discovery's Multi-Array technology. Glasgow Outcome Scale (GOS) score at six months following injury was dichotomized into poor outcome (GOS 1-3) and favorable outcome (GOS 4-5). Statistical analyses were performed using Kruskal-Wallis test and linear regression analysis. ResultsThe result shows that CSF concentrations of inflammatory biomarkers had a significant association with 6-month neurological outcome (p-values≤0.05 for each marker), with the favorable outcome group having lower concentrations of these biomarkers on average, in comparison to the poor neurologic outcome group over the first five days after TBI. All inflammatory biomarkers decreased to normal levels by post-trauma day 5, except for IL-6 and IL-8. Upregulation and increased expression of key inflammatory markers following severe TBI were significant predictors of worse 6-month neurologic outcome. Additionally, post-trauma day 5 concentrations of IL-6 and IL-8 remained elevated over normal CSF values. ConclusionThe study shows that inflammatory biomarkers in CSF are potential biomarkers of injury severity and progression and/or recovery; they could prove beneficial in the future assessment of injury severity and response to therapy after severe TBI.

Guideline adherence and outcomes in severe adult traumatic brain injury for the CHIRAG (Collaborative Head InjuRy and Guidelines) study

Guideline adherence and outcomes in severe adult traumatic brain injury for the CHIRAG (Collaborative Head InjuRy and Guidelines) study

Guideline Adherence and Outcomes in Severe Adult Traumatic Brain Injury for the CHIRAG (Collaborative Head Injury and Guidelines) Study

We examined the effect of early intensive care unit (ICU) adherence to 2007 Brain Trauma Foundation Guideline indicators after traumatic brain injury (TBI) on inpatient mortality at a level 1 trauma center in India (Jay Prakash Narayan Apex Trauma Center [JPNATC]) and Harborview Medical Center (HMC) in U.S. among adults older than 18 years with severe TBI. At each site, ICU Guideline adherence in first 72 hours for 17 indicators was determined and expressed as a percentage. Outcomes were in-hospital mortality and Glasgow Outcome Scale (GOS) scores at 3, 6, and 12 months after discharge. JPNATC and HMC Guideline adherence rates were 74.9% [11.0] and 71.6 % (SD ±10.4), and overall in-hospital mortality was 24% and 27%, respectively. At JPNATC, less than 65% ICU Guideline adherence was associated with higher inpatient mortality (adjusted relative risk [aRR], 1.92; 95% confidence interval [CI], 1.11-3.33) and an increase in ICU Guideline adherence rate by 1% was associated with a 3% lower in-hospital mortality (aRR, 0.97; 95% CI, 0.95-0.99). Among patients discharged with a GOS score of 2-4 at JPNATC, 67% improved at 12 months (R(2)= 0.991; P < 0.01; 99% follow-up rate) compared with discharge, but 35%, 25%, and 14% of patients discharged with a GOS score of 3-5 deteriorated at 3, 6, and 12 months to a lower GOS at home. Achieving early ICU adherence to guideline indicators was feasible and associated with significantly lower in-hospital mortality at JPNATC. Although the intracranial pressure (ICP) monitoring rates varied, in-hospitals deaths were similar between the two institutions. Although long-term outcomes generally improved, patients discharged with favorable GOS score often deteriorated at home.

Guidelines for the diagnosis and treatment of severe traumatic brain injury. Part 2. Intensive care and neuromonitoring

Traumatic brain injury (TBI) is one of the major causes of death and disability in young and middle-aged people. The most problematic group is comprised of patients with severe TBI who are in a coma. The adequate diagnosis of primary brain injuries and timely prevention and treatment of the secondary injury mechanisms largely define the possibility of reducing mortality and severe disabling consequences. When developing these guidelines, we used our experience in the development of international and national recommendations for the diagnosis and treatment of mild traumatic brain injury, penetrating gunshot wounds to the skull and brain, severe traumatic brain injury, and severe consequences of brain injuries, including a vegetative state. In addition, we used international and national guidelines for the diagnosis, intensive care, and surgical treatment of severe traumatic brain injury, which had been published in recent years. The proposed guidelines concern intensive care of severe TBI in adults and are particularly intended for neurosurgeons, neurologists, neuroradiologists, anesthesiologists, and intensivists who are routinely involved in the treatment of these patients.

Guidelines for the management of severe traumatic brain injury. Part 3. Surgical management of severe traumatic brain injury (Options)

Traumatic brain injury (TBI) is one of the main causes of mortality and severe disability in young and middle age patients. Patients with severe TBI, who are in coma, are of particular concern. Adequate diagnosis of primary brain injuries and timely prevention and treatment of secondary injury mechanisms markedly affect the possibility of reducing mortality and severe disability. The present guidelines are based on the authors' experience in developing international and national recommendations for the diagnosis and treatment of mild TBI, penetrating gunshot wounds of the skull and brain, severe TBI, and severe consequences of brain injury, including a vegetative state. In addition, we used the materials of international and national guidelines for the diagnosis, intensive care, and surgical treatment of severe TBI, which were published in recent years. The proposed recommendations for surgical treatment of severe TBI in adults are addressed primarily to neurosurgeons, neurologists, neuroradiologists, anesthesiologists, and intensivists who are routinely involved in treating these patients.

Clinical applications of intracranial pressure monitoring in traumatic brain injury : report of the Milan consensus conference.

Intracranial pressure (ICP) monitoring has been for decades a cornerstone of traumatic brain injury (TBI) management. Nevertheless, in recent years, its usefulness has been questioned in several reports. A group of neurosurgeons and neurointensivists met to openly discuss, and provide consensus on, practical applications of ICP in severe adult TBI. A consensus conference was held in Milan on October 5, 2013, putting together neurosurgeons and intensivists with recognized expertise in treatment of TBI. Four topics have been selected and addressed in pro-con presentations: 1) ICP indications in diffuse brain injury, 2) cerebral contusions, 3) secondary decompressive craniectomy (DC), and 4) after evacuation of intracranial traumatic hematomas. The participants were asked to elaborate on the existing published evidence (without a systematic review) and their personal clinical experience. Based on the presentations and discussions of the conference, some drafts were circulated among the attendants. After remarks and further contributions were collected, a final document was approved by the participants. The group made the following recommendations: 1) in comatose TBI patients, in case of normal computed tomography (CT) scan, there is no indication for ICP monitoring; 2) ICP monitoring is indicated in comatose TBI patients with cerebral contusions in whom the interruption of sedation to check neurological status is dangerous and when the clinical examination is not completely reliable. The probe should be positioned on the side of the larger contusion; 3) ICP monitoring is generally recommended following a secondary DC in order to assess the effectiveness of DC in terms of ICP control and guide further therapy; 4) ICP monitoring after evacuation of an acute supratentorial intracranial hematoma should be considered for salvageable patients at increased risk of intracranial hypertension with particular perioperative features.

Subarachnoid hemorrhage prevalence and its association with short-term outcome in pediatric severe traumatic brain injury.

Subarachnoid hemorrhage (SAH) is an independent prognostic indicator of outcome in adult severe traumatic brain injury (sTBI). There is a paucity of investigations on SAH in pediatric sTBI. The goal of this study was to determine in pediatric sTBI patients SAH prevalence, associated factors, and its relationship to short-term outcome. We retrospectively analyzed 171 sTBI patients (pre-sedation GCS ≤8 and head MAIS ≥4) who underwent CT head imaging within the first 24h of hospital admission. Data were analyzed with both univariate and multivariate techniques. SAH was found in 42% of sTBI patients (n=71/171), and it was more frequently associated with skull fractures, cerebral edema, diffuse axonal injury, contusion, and intraventricular hemorrhage (p<0.05). Patients with SAH had higher Injury Severity Scores (p=0.032) and a greater frequency of fixed pupil(s) on admission (p=0.001). There were no significant differences in etiologies between sTBI patients with and without SAH. Worse disposition occurred in sTBI patients with SAH, including increased mortality (p=0.009), increased episodes of central diabetes insipidus (p=0.002), greater infection rates (p=0.002), and fewer ventilator-free days (p=0.001). In sTBI survivors, SAH was associated with increased lengths of stay (p<0.001) and a higher level of care required on discharge (p=0.004). Despite evidence that SAH is linked to poorer outcomes on univariate analyses, multivariate analysis failed to demonstrate an independent association between SAH and mortality (p=0.969). SAH was present in almost half of pediatric sTBI patients, and it was indicative of TBI severity and a higher level of care on discharge. SAH in pediatric patients was not independently associated with increased risk of mortality.

Is intracranial pressure monitoring still required in the management of severe traumatic brain injury? Ethical and methodological considerations on conducting clinical research in poor and low-income countries.

Long-term disabilities suffered by patients with severe traumatic brain injury (TBI) are a continuous challenge for health care systems and a burden for patients, their families, and the community in terms of suffering, disability, and monetary cost.[13,19] Approximately 50% of TBI comatose patients with an abnormal computed tomography (CT) scan also have high intracranial pressure (ICP).[22] Death, vegetative state, and severe disability are the expected outcomes in patients with persistent high ICP not controlled by medical and/or surgical treatment. As high ICP cannot be estimated reliably by clinical examination or even sequential imaging, ICP monitoring has been considered a necessary tool for its diagnosis and management. After decades of ongoing debate about how and when to monitor ICP, a consensus was finally reached in 1995 with the publication of the first evidence-based guidelines (EBGs) for the management of severe TBI in adults, developed under the sponsorship of the Brain Trauma Foundation (BTF).[3] Three consecutive versions of these guidelines have established–as a level II recommendation–that ICP should be monitored in “all salvageable patients with a severe TBI and an abnormal CT scan”.[3,30] BTF guidelines are endorsed by most scientific societies worldwide and they have been translated into many languages and disseminated and applied in the United States, Europe, South America, China, and Japan, thus defining the core principles for managing severe TBI. In keeping with the guidelines, care centered on ICP management is the standard for patients with severe TBI in both developed countries and those developing countries that can afford their costly management. A few studies have shown that good adherence to the BTF guidelines improve outcomes and reduce the cost of the acute care.[12,16,24,26] The recent publication of the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST TRIP) trial in the New England Journal of Medicine (NEJM) changed this calm scenario unexpectedly, particularly because some of the investigators coauthoring the paper were also active contributors to recent versions of the BTF guidelines.[7] This randomized clinical trial (RCT), which enrolled 324 patients in 6 hospitals in Bolivia and Ecuador, reported as its main conclusion that ICP-based management increased the 6-month favorable outcome only by a marginal and nonsignificant 5% difference when compared with patients for whom care was guided with serial CTs and clinical examination.[7] Despite some clarifications by the principal investigator,[6] the main message conveyed by this trial is that ICP monitoring does not make an outcome difference when managing TBI.[14] Consequently, the debate of whether or not ICP should be monitored has been effectively resuscitated and it is receiving wide media coverage and generating more heat than light among clinicians.[14] Some neurosurgeons and intensivists would even like to have a moratorium until class I evidence is obtained for ICP monitoring. BEST TRIP is a good example of research that has no practical relevance to the health needs of the host country, but it is apparently important to the foreign sponsors and researchers and therefore it provides a good opportunity to raise the issues of double standards, external validity, exploitation of vulnerable populations, the role of personal and clinical equipoise, and the value of biomedical research itself. There is a growing ethical concern for the obvious and hidden risks of conducting certain clinical trials in poor and low-income countries. These trials are frequently funded by pharmaceutical or medical device companies and approved by prestigious regulatory bodies that are based in Western Europe or the United States, countries where some of the trial designs and medical practices employed in these poorer countries would never be permissible.[8]

Intermittent Versus Continuous Cerebrospinal Fluid Drainage Management in Adult Severe Traumatic Brain Injury: Assessment of Intracranial Pressure Burden

There is clinical equipoise regarding whether neurointensive care unit management of external ventricular drains (EVD) in severe traumatic brain injury (TBI) should involve an open EVD, with continuous drainage of cerebrospinal fluid (CSF), versus a closed EVD, with intermittent opening as necessary to drain CSF. In a matched cohort design, we assessed the relative impact of continuous versus intermittent CSF drainage on intracranial pressure in the management of adult severe TBI. Sixty-two severe TBI patients were assessed. Thirty-one patients managed by open EVD drainage were matched by age, sex, and injury severity (initial Glasgow Coma Scale (GCS) score) to 31 patients treated with a closed EVD drainage. Patients in the open EVD group also had a parenchymal intracranial pressure (ICP) monitor placed through an adjacent burr hole, allowing real-time recording of ICP. Hourly ICP and other pertinent data, such as length of stay in intensive care unit (LOS-ICU), Injury Severity Score, and survival status, were extracted from our prospective database. With age, injury severity (initial GCS score), and neurosurgical intervention adjusted for, there was a statistically significant difference of 5.66 mmHg in mean ICP (p < 0.0001) between the open and the closed EVD groups, with the closed EVD group exhibiting greater mean ICP. ICP burden (ICP ≥ 20 mmHg) was shown to be significantly higher in the intermittent EVD group (p = 0.0002) in comparison with the continuous EVD group. Continuous CSF drainage via an open EVD seemed to be associated with more effective ICP control in the management of adult severe TBI.

Trends in survival and early functional outcomes from hospitalized severe adult traumatic brain injuries, pennsylvania, 1998 to 2007.

: To determine trends for in-hospital survival and functional outcomes at acute care hospital discharge for patients with severe adult traumatic brain injury (SATBI) in Pennsylvania, during 1998 to 2007. : Secondary analysis of the Pennsylvania trauma outcome study database. : Survival and functional status scores of 5 domains (feeding, locomotion, expression, transfer mobility, and social interaction) fitted into logistic regression models adjusted for age, sex, race, comorbidities, injury mechanism, extracranial injuries, severity scores, hospital stay, trauma center, and hospital level. Sensitivity analyses for functional outcomes were performed. : There were 26 234 SATBI patients. Annual numbers of SATBI increased from 1757 to 3808 during 1998 to 2007. Falls accounted for 47.7% of all SATBI. Survival increased significantly from 72.5% to 82.7% (odds ratio [OR] = 1.10, 95% CI: 1.08-1.11, P < .001). In sensitivity analyses, trends of complete independence in functional outcomes increased significantly for expression (OR = 1.01, 95% CI: 1.00-1.02, P = .011) and social interaction (OR = 1.01, 95% CI: 1.00-1.03, P = .002). There were no significant variations over time for feeding, locomotion, and transfer mobility. : Trends for SATBI served by Pennsylvania's established trauma system showed increases in rates but substantial reductions in mortality and significant improvements in functional outcomes at discharge for expression and social interaction.

Vasopressor use and effect on blood pressure after severe adult traumatic brain injury.

We describe institutional vasopressor usage, and examine the effect of vasopressors on hemodynamics: heart rate (HR), mean arterial blood pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PbtO(2)), and jugular venous oximetry (SjVO(2)) in adults with severe traumatic brain injury (TBI). We performed a retrospective analysis of 114 severely head injured patients who were admitted to the neurocritical care unit of Level 1 trauma center and who received vasopressors (phenylephrine, norepinephrine, dopamine, vasopressin or epinephrine) to increase blood pressure Phenylephrine was the most commonly used vasopressor (43%), followed by norepinephrine (30%), dopamine (22%), and vasopressin (5%). Adjusted for age, gender, injury severity score, vasopressor dose, baseline blood pressure, fluid administration, propofol sedation, and hypertonic saline infusion, phenylephrine use was associated with 8 mmHg higher mean arterial pressure (MAP) than dopamine (P = 0.03), and 12 mmHg higher cerebral perfusion pressure (CPP) than norepinephrine (P = 0.02) during the 3 h after vasopressor start. There was no difference in ICP between the drug groups, either at baseline or after vasopressor treatment. Most severe TBI patients received phenylephrine. Patients who received phenylephrine had higher MAP and CPP than patients who received dopamine and norepinephrine, respectively.