Managing Severe Traumatic Brain Injury Across Resource Settings: Latin American Perspectives.

Severe traumatic brain injury (sTBI) is a condition of increasing epidemiologic concern worldwide. Outcomes are worse as observed in low- and middle-income countries (LMICs) versus high-income countries. Global targets are in place to address the surgical burden of disease. At the same time, most of the published literature and evidence on the clinical approach to sTBI comes from wealthy areas with an abundance of resources. The available paradigms, including the Brain Trauma Foundation guidelines, the Seattle International Severe Traumatic Brain Injury Consensus Conference, Consensus Revised Imaging and Clinical Examination, and multimodality approaches, may fit differently depending on local resources, expertise, and sociocultural factors. A first step toward addressing heterogeneity in practice is to consider comparative effectiveness approaches that can capture actual practice patterns and record short-term and long-term outcomes of interest. Decompressive craniectomy (DC) decreases intracranial pressure burden and can be lifesaving. Nevertheless, completed randomized controlled trials took place within high-income settings, leaving important questions unanswered and making extrapolations to LMICs questionable. The concept of preemptive DC specifically to address limited neuromonitoring resources may warrant further study to establish a benefit/risk profile for the procedure and its role within local protocols of care.

Global neurotrauma research challenges and opportunities.

Traumatic injury to the brain or spinal cord is one of the most serious public health problems worldwide. The devastating impact of 'trauma', a term used to define the global burden of disease related to all injuries, is the leading cause of loss of human potential across the globe, especially in low- and middle-income countries. Enormous challenges must be met to significantly advance neurotrauma research around the world, specifically in underserved and austere environments. Neurotrauma research at the global level needs to be contextualized: different regions have their own needs and obstacles. Interventions that are not considered a priority in some regions could be a priority for others. The introduction of inexpensive and innovative interventions, including mobile technologies and e-health applications, focused on policy management improvement are essential and should be applicable to the needs of the local environment. The simple transfer of a clinical question from resource-rich environments to those of low- and middle-income countries that lack sophisticated interventions may not be the best strategy to address these countries' needs. Emphasis on promoting the design of true 'ecological' studies that include the evaluation of human factors in relation to the process of care, analytical descriptions of health systems, and how leadership is best applied in medical communities and society as a whole will become crucial.

Plasma Levels, Temporal Trends and Clinical Associations between Biomarkers of Inflammation and Vascular Homeostasis after Pediatric Traumatic Brain Injury.

Expression of inflammatory (interleukin-6 [IL-6]) and vascular homeostatic (angiopoietin-2 [AP-2], endothelin-1 [ET-1], endocan-2 [EC-2]) biomarkers in pediatric traumatic brain injury (TBI) was examined in this prospective, observational cohort study of 28 children hospitalized with mild, moderate, and severe TBI by clinical measures (age, sex, Glasgow Coma Scale score [GCS], Injury Severity Score [ISS], and cerebral autoregulation status). Biomarker patterns suggest an inverse relationship between GCS and AP-2, GCS and IL-6, ISS and ET-1, but a direct relationship between GCS and ET-1 and ISS and AP-2. Biomarker patterns suggest an inverse relationship between AP-2 and ET-1, AP-2 and EC-2, but a direct relationship between AP-2 and IL-6, IL-6 and EC-2, and IL-6 and ET-1. Plasma concentrations of inflammatory and vascular homeostatic biomarkers suggest a role for inflammation and disruption of vascular homeostasis during the first 10 days across the severity spectrum of pediatric TBI. Although not statistically significant, without impact on cerebral autoregulation, biomarker patterns suggest a relationship between inflammation and alterations in vascular homeostasis. The large variation in biomarker levels within TBI severity and age groups, and by sex suggests other contributory factors to biomarker expression.

Prevalence, Evolution, and Extent of Impaired Cerebral Autoregulation in Children Hospitalized With Complex Mild Traumatic Brain Injury.

OBJECTIVES: To examine cerebral autoregulation in children with complex mild traumatic brain injury. DESIGN: Prospective observational convenience sample. SETTING: PICU at a level I trauma center. PATIENTS: Children with complex mild traumatic brain injury (trauma, admission Glasgow Coma Scale score 13-15 with either abnormal head CT, or history of loss of consciousness). INTERVENTIONS: Cerebral autoregulation was tested using transcranial Doppler ultrasound between admission day 1 and 8. MEASUREMENTS AND MAIN RESULTS: The primary outcome was prevalence of impaired cerebral autoregulation (autoregulation index < 0.4),determined using transcranial Doppler ultrasonography and tilt testing. Secondary outcomes examined factors associated with and evolution and extent of impairment. Cerebral autoregulation testing occurred in 31 children 10 years (SD, 5.2 yr), mostly male (59%) with isolated traumatic brain injury (91%), median admission Glasgow Coma Scale 15, Injury Severity Scores 14.2 (SD, 7.7), traumatic brain injury due to fall (50%), preadmission loss of consciousness (48%), and abnormal head CT scan (97%). Thirty-one children underwent 56 autoregulation tests. Impaired cerebral autoregulation occurred in 15 children (48.4%) who underwent 19 tests; 68% and 32% of tests demonstrated unilateral and bilateral impairment, respectively. Compared with children on median day 6 of admission after traumatic brain injury, impaired autoregulation was most common in the first 5 days after traumatic brain injury (day 1: relative risk, 3.7; 95% CI, 1.9-7.3 vs day 2: relative risk, 2.7; 95% CI, 1.1-6.5 vs day 5: relative risk, 1.33; 95% CI, 0.7-2.3). Children with impaired autoregulation were older (12.3 yr [SD, 1.3 yr] vs 8.7 yr [SD, 1.1 yr]; p = 0.04) and tended to have subdural hematoma (64% vs 44%), epidural hematoma (29% vs 17%), and subarachnoid hemorrhage (36% vs 28%). Eight children (53%) were discharged home with ongoing impaired cerebral autoregulation. CONCLUSIONS: Impaired cerebral autoregulation is common in children with complex mild traumatic brain injury, despite reassuring admission Glasgow Coma Scale 13-15. Children with complex mild traumatic brain injury have abnormal cerebrovascular hemodynamics, mostly during the first 5 days. Impairment commonly extends to the contralateral hemisphere and discharge of children with ongoing impaired cerebral autoregulation is common.

Consensus statement from the International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury : Consensus statement.

BACKGROUND: Two randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries. RESULTS: The invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval. CONCLUSIONS: In this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction.

Primary External Ventricular Drainage Catheter Versus Intraparenchymal ICP Monitoring: Outcome Analysis.

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.

Transcranial Doppler Microemboli Monitoring for Stroke Risk Stratification in Blunt Cerebrovascular Injury.

OBJECTIVES: To assess whether microemboli burden, assessed noninvasively by bedside transcranial Doppler ultrasonography, correlates with risk of subsequent stroke greater than 24 hours after hospital arrival among patients with blunt cerebrovascular injury. The greater than 24-hour time frame provides a window for transcranial Doppler examinations and therapeutic interventions to prevent stroke. DESIGN: Retrospective cohort study. SETTING: Level I trauma center. PATIENTS: One thousand one hundred forty-six blunt cerebrovascular injury patients over 10 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 1,146 blunt cerebrovascular injury patients; 54 (4.7%) experienced stroke detected greater than 24 hours after arrival. Among those with isolated internal carotid artery injuries, five of nine with delayed stroke had positive transcranial Dopplers (at least one microembolus detected with transcranial Dopplers) before stroke, compared with 46 of 248 without (risk ratio, 5.05; 95% CI, 1.41-18.13). Stroke risk increased with the number of microemboli (adjusted risk ratio, 1.03/microembolus/hr; 95% CI, 1.01-1.05) and with persistently positive transcranial Dopplers over multiple days (risk ratio, 16.0; 95% CI, 2.00-127.93). Among patients who sustained an internal carotid artery injury with or without additional vessel injuries, positive transcranial Dopplers predicted stroke after adjusting for ipsilateral and contralateral internal carotid artery injury grade (adjusted risk ratio, 2.91; 95% CI, 1.42-5.97). No patients with isolated vertebral artery injuries had positive transcranial Dopplers before stroke, and positive transcranial Dopplers were not associated with delayed stroke among patients who sustained a vertebral artery injury with or without additional vessel injuries (risk ratio, 0.90; 95% CI, 0.21-3.83). CONCLUSIONS: Microemboli burden is associated with higher risk of stroke due to internal carotid artery injuries, but monitoring was not useful for vertebral artery injuries.

Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial.

OBJECTIVES: A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study. DESIGN: Randomized prospective clinical trial. SETTING: Ten ICUs in the United States. PATIENTS: One hundred nineteen severe traumatic brain injury patients. INTERVENTIONS: Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale-Extended. MEASUREMENTS AND MAIN RESULTS: A management protocol based on brain tissue oxygenation and intracranial pressure monitoring reduced the proportion of time with brain tissue hypoxia after severe traumatic brain injury (0.45 in intracranial pressure-only group and 0.16 in intracranial pressure plus brain tissue oxygenation group; p < 0.0001). Intracranial pressure control was similar in both groups. Safety and feasibility of the tiered treatment protocol were confirmed. There were no procedure-related complications. Treatment of secondary injury after severe traumatic brain injury based on brain tissue oxygenation and intracranial pressure values was consistent with reduced mortality and increased proportions of patients with good recovery compared with intracranial pressure-only management; however, the study was not powered for clinical efficacy. CONCLUSIONS: Management of severe traumatic brain injury informed by multimodal intracranial pressure and brain tissue oxygenation monitoring reduced brain tissue hypoxia with a trend toward lower mortality and more favorable outcomes than intracranial pressure-only treatment. A Phase III randomized trial to assess impact on neurologic outcome of intracranial pressure plus brain tissue oxygenation-directed treatment of severe traumatic brain injury is warranted.

Natural History and Management of Blunt Traumatic Pseudoaneurysms of the Internal Carotid Artery: The Harborview Algorithm Based Off a 10-Year Experience.

OBJECTIVE: To define the natural history of, and treatment strategy for, blunt traumatic internal carotid artery (ICA) pseudoaneurysms. BACKGROUND: The natural history and management of traumatic ICA pseudoaneurysms is controversial. METHODS: We retrospectively identified all traumatic ICA pseudoaneurysms diagnosed on head/neck computed tomographic angiography at a high-volume trauma center over a 10-year period. Radiographic and clinical data were recorded, and a treatment algorithm was derived. RESULTS: Forty-three pseudoaneurysms were diagnosed in 39 patients. All patients were treated with daily aspirin unless contraindicated, and 82% underwent daily transcranial Doppler ultrasonography with embolic monitoring. A rate of 8 or more emboli per hour was predictive of embolic stroke (P = 0.0076). Acute ischemic or embolic stroke was seen in 7 patients (16%) with an overall mortality in this subpopulation of 42% (n = 3). Four patients (9%) underwent acute surgical treatment (parent vessel sacrifice and/or arterial bypass) for ongoing ischemia. Long-term radiographic and clinical follow-up was obtained for 36 surviving patients (mean = 8 months; range: 1 week-5 years), all of whom were maintained on daily aspirin. No delayed ischemic or embolic events were reported. For ICA pseudoaneurysms treated with aspirin and observation alone, 9 (28%) increased in size, 17 (53%) decreased or stabilized, and 6 (19%) resolved. Enlargement of 5 mm or more in maximal diameter underwent delayed endovascular treatment with a 100% obliteration rate and no complications. CONCLUSIONS: Traumatic ICA pseudoaneurysms are safely treated with daily aspirin, embolic monitoring, and radiographic surveillance. Acute stroke or hemorrhage, or delayed radiographic progression, are indications for endovascular or surgical treatment.

A trial of intracranial-pressure monitoring in traumatic brain injury.

BACKGROUND: Intracranial-pressure monitoring is considered the standard of care for severe traumatic brain injury and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed. METHODS: We conducted a multicenter, controlled trial in which 324 patients 13 years of age or older who had severe traumatic brain injury and were being treated in intensive care units (ICUs) in Bolivia or Ecuador were randomly assigned to one of two specific protocols: guidelines-based management in which a protocol for monitoring intraparenchymal intracranial pressure was used (pressure-monitoring group) or a protocol in which treatment was based on imaging and clinical examination (imaging-clinical examination group). The primary outcome was a composite of survival time, impaired consciousness, and functional status at 3 months and 6 months and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of protocol assignment. This composite measure was based on performance across 21 measures of functional and cognitive status and calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance). RESULTS: There was no significant between-group difference in the primary outcome, a composite measure based on percentile performance across 21 measures of functional and cognitive status (score, 56 in the pressure-monitoring group vs. 53 in the imaging-clinical examination group; P=0.49). Six-month mortality was 39% in the pressure-monitoring group and 41% in the imaging-clinical examination group (P=0.60). The median length of stay in the ICU was similar in the two groups (12 days in the pressure-monitoring group and 9 days in the imaging-clinical examination group; P=0.25), although the number of days of brain-specific treatments (e.g., administration of hyperosmolar fluids and the use of hyperventilation) in the ICU was higher in the imaging-clinical examination group than in the pressure-monitoring group (4.8 vs. 3.4, P=0.002). The distribution of serious adverse events was similar in the two groups. CONCLUSIONS: For patients with severe traumatic brain injury, care focused on maintaining monitored intracranial pressure at 20 mm Hg or less was not shown to be superior to care based on imaging and clinical examination. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01068522.).

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

BACKGROUND: 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. METHODS: 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.

Intracranial pressure monitoring: fundamental considerations and rationale for monitoring.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. In large part critical care for TBI is focused on the identification and management of secondary brain injury. This requires effective neuromonitoring that traditionally has centered on intracranial pressure (ICP). The purpose of this paper is to review the fundamental literature relative to the clinical application of ICP monitoring in TBI critical care and to provide recommendations on how the technique maybe applied to help patient management and enhance outcome. A PubMed search between 1980 and September 2013 identified 2,253 articles; 244 of which were reviewed in detail to prepare this report and the evidentiary tables. Several important concepts emerge from this review. ICP monitoring is safe and is best performed using a parenchymal monitor or ventricular catheter. While the indications for ICP monitoring are well established, there remains great variability in its use. Increased ICP, particularly the pattern of the increase and ICP refractory to treatment is associated with increased mortality. Class I evidence is lacking on how monitoring and management of ICP influences outcome. However, a large body of observational data suggests that ICP management has the potential to influence outcome, particularly when care is targeted and individualized and supplemented with data from other monitors including the clinical examination and imaging.

Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

The International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: evidentiary tables: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.