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Coma and disorders of consciousness (DoC) are highly prevalent and constitute a burden for patients, families, and society worldwide. As part of the Curing Coma Campaign, the Neurocritical Care Society partnered with the National Institutes of Health to organize a symposium bringing together experts from all over the world to develop research targets for DoC. The conference was structured along six domains: (1) defining endotype/phenotypes, (2) biomarkers, (3) proof-of-concept clinical trials, (4) neuroprognostication, (5) long-term recovery, and (6) large datasets. This proceedings paper presents actionable research targets based on the presentations and discussions that occurred at the conference. We summarize the background, main research gaps, overall goals, the panel discussion of the approach, limitations and challenges, and deliverables that were identified. Supplementary Information The online version contains supplementary material available at 10.1007/s12028-021-01260-x.

Severe traumatic brain injury (sTBI) remains prevalent in the young adult population. Indeed, far from descending, the incidence of sTBI remains high. One of the key bases of treatment is to avoid, detect and correct secondary injuries of systemic origin, which aggravate the primary lesion. Much of this can be achieved by maintaining an adequate physiological microenvironment allowing recovery of the damaged brain tissue. General care measures are nonspecific actions designed to meet that objective. The available guidelines on the management of sTBI have not included the topics contemplated in this consensus. In this regard, a group of members of the Latin American Brain Injury Consortium (LABIC), involved in the different aspects of the acute management of sTBI (neurosurgeons, intensivists, anesthesiologists, neurologists, nurses and physiotherapists) were gathered. An exhaustive literature search was made of selected topics in the LILACS, PubMed, Embase, Scopus, Cochrane Controlled Register of Trials and Web of Science databases. To establish recommendations or suggestions with their respective strength or weakness, the GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was applied. Additionally, certain recommendations (included in complementary material) were not assessed by GRADE, because they constitute a set of therapeutic actions of effective compliance, in which it was not possible to apply the said methodology. Thirty-two recommendations were established, 16 strong and 16 weak, with their respective levels of evidence. This consensus attempts to standardize and establish basic general care measures in this particular patient population.

Resumen El traumatismo craneoencefalico grave (TCEg) continua siendo prevalente en la poblacion adulta joven. Lejos de descender, su incidencia se mantiene elevada. Uno de los pilares en los que se asienta su tratamiento es evitar, detectar y corregir complicaciones secundarias de origen sistemico que agravan la lesion primaria. Gran parte de este objetivo se logra manteniendo un microambiente fisiologico adecuado que permita la recuperacion del tejido cerebral lesionado. Las medidas de cuidados generales son acciones inespecificas destinadas a cumplir dicho objetivo. Las guias disponibles de manejo del TCEg no han incluido la mayoria de los topicos motivo de este consenso. Para ello, hemos reunido un grupo de profesionales miembros del Consorcio latinoamericano de Injuria Cerebral (LABIC), involucrados en los diferentes aspectos del manejo agudo del TCEg (neurocirujanos, intensivistas, anestesiologos, neurologos, enfermeros, fisioterapeutas). Se efectuo una busqueda bibliografica en las bases de datos LILACS, PubMed, Embasse, Scopus, Cochrane Controlled Register of Trials y Web of Science de los topicos seleccionados. Para establecer recomendaciones o sugerencias con su respectiva fortaleza o debilidad, fue aplicada la metodologia Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Adicionalmente, ciertas recomendaciones (incluidas en material complementario) no fueron valoradas por GRADE, por ser las mismas un conjunto de acciones terapeuticas de cumplimento efectivo, en las que no fue posible aplicar dicha metodologia. Fueron establecidas 32 recomendaciones; 16 fuertes y 16 debiles, con su respectivo nivel de evidencia. El presente consenso intenta homogeneizar y establecer medidas de cuidados generales basicas en esta poblacion de individuos.

Continuous monitoring of cerebral oxygenation and its application to the management of the severe neurological patient is a challenge for the management of patients with acute critical brain damage. Although several techniques have been described for monitoring brain, brain tissue oxygen monitoring provides relevant information about oxygen levels of brain tissue. However, the development of this technique has been associated with the need to answer not only some technical aspects of it as well as the meaning of the changes of the cerebral oxygenation in the neurocritical patient. The consensus document responds to various questions related to the monitoring of cerebral oxygenation by means of a cerebral oxygen tissue pressure sensor. For this purpose, a list of questions was prepared and a reviewed of the medical literature was made. The quality of the evidence and the degree of recommendation was evaluated using the GRADE methodology.

Cerebral edema is nonspecific pathological swelling of the brain that may develop in a focal or diffuse pattern (Cook et al., 2020). Cerebral edema is a frequent and serious complication in traumatic brain injury (TBI) patients (Winkler, Minter, Yue, & Manley, 2016). The simplest description of cerebral edema is an accumulation of excessive fluid, extracellular or within brain cells, classified as cytotoxic (due to energy failure, loss of ion gradients, and shift of water from the extracellular to intracellular space) or vasogenic (due to leaking capillaries and increased water in interstitial spaces) (Klatzo, 1987). The identification and treatment of cerebral edema are central to the management of critical intracranial pathologies. The use of dexamethasone has a role in some pathologies.

Globally, intracranial pressure (ICP) monitoring use in severe traumatic brain injury (sTBI) is inconsistent and susceptible to resource limitations and clinical philosophies. For situations without monitoring, there is no published comprehensive management algorithm specific to identifying and treating suspected intracranial hypertension (SICH) outside of the one ad hoc Imaging and Clinical Examination (ICE) protocol in the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST:TRIP) trial. As part of an ongoing National Institutes of Health (NIH)-supported project, a consensus conference involving 43 experienced Latin American Intensivists and Neurosurgeons who routinely care for sTBI patients without ICP monitoring, refined, revised, and augmented the original BEST:TRIP algorithm. Based on BEST:TRIP trial data and pre-meeting polling, 11 issues were targeted for development. We used Delphi-based methodology to codify individual statements and the final algorithm, using a group agreement threshold of 80%. The resulting CREVICE (Consensus REVised ICE) algorithm defines SICH and addresses both general management and specific treatment. SICH treatment modalities are organized into tiers to guide treatment escalation and tapering. Treatment schedules were developed to facilitate targeted management of disease severity. A decision-support model, based on the group's combined practices, is provided to guide this process. This algorithm provides the first comprehensive management algorithm for treating sTBI patients when ICP monitoring is not available. It is intended to provide a framework to guide clinical care and direct future research toward sTBI management. Because of the dearth of relevant literature, it is explicitly consensus based, and is provided solely as a resource (a "consensus-based curbside consult") to assist in treating sTBI in general intensive care units in resource-limited environments.

Introduction: Delayed extubation in neurocritical care patients is associated with an increased length of stay in the intensive care unit (ICU), a greater incidence of ventilator-associated pneumonia (VAP), and a poor outcome. There is no evidence available to support use of certain variables over others as predictors of successful extubation in these patients.

Background Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place. Methods Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting. Results We established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms. Conclusions These protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference. Electronic supplementary material The online version of this article (10.1007/s00134-019-05900-x) contains supplementary material, which is available to authorized users.

Traumatic brain injury (TBI) disproportionately affects lower- and middle-income countries (LMIC). The factors influencing outcomes in LMIC have not been examined as rigorously as in higher-income countries.This study was conducted to examine clinical and demographic factors influencing TBI outcomes in Latin American LMIC. Data were prospectively collected during a randomized trial of intracranial pressure monitoring in severe TBI and a companion observational study. Participants were aged ≥13 years and admitted to study hospitals with Glasgow Coma Scale score ≤8. The primary outcome was Glasgow Outcome Scale, Extended (GOS-E) score at 6 months. Predictors were analyzed using a multivariable proportional odds model created by forward stepwise selection.A total of 550 patients were identified. Six-month outcomes were available for 88%, of whom 37% had died and 44% had achieved a GOS-E score of 5-8. In multivariable proportional odds modeling, higher Glasgow Coma Scale motor score (odds ratio [OR], 1.41 per point; 95% confidence interval [CI], 1.23-1.61) and epidural hematoma (OR, 1.83; 95% CI, 1.17-2.86) were significant predictors of higher GOS-E score, whereas advanced age (OR, 0.65 per 10 years; 95% CI, 0.57-0.73) and cisternal effacement (P0.001) were associated with lower GOS-E score. Study site (P0.001) and race (P = 0.004) significantly predicted outcome, outweighing clinical variables such as hypotension and pupillary examination.Mortality from severe TBI is high in Latin American LMIC, although the rate of favorable recovery is similar to that of high-income countries. Demographic factors such as race and study site played an outsized role in predicting outcome; further research is required to understand these associations.

Background Severe traumatic brain injury (sTBI) is a significant global health problem disproportionately affecting low- and middle-income countries (LMICs). Management of intracranial hypertension in sTBI is crucial to survival and optimal recovery. Practitioners in high-income countries routinely use intracranial pressure (ICP) monitors although their usefulness has been questioned. ICP monitors are usually unavailable in LMICs. No consensus-based/tested protocols or literature exists for sTBI treatment without ICP monitoring. Methods Investigators developed serial SurveyMonkey surveys for Latin American neurointensivists and neurosurgeons to determine current practice. These clinicians had extensive routine ongoing experience in sTBI without ICP monitoring. Surveys were administered and analyzed before/during/after a 2015 Buenos Aires consensus conference. Investigators identified areas of convergence blinded from colleagues' responses. A 47-clinician task force, representing 15 countries, who routinely manage patients with sTBI without monitors developed consensus-based treatment guidelines during a 3-day facilitated conference. Results Elements were added to the protocol at an 80% agreement threshold. Follow-on surveys resolved remaining elements to 97% agreement. The protocol addresses both tapering (on improvement) and neuroworsening. Staged treatment options were identified, plus unique clinical practice issues. This process introduced a research method to a large multidisciplinary group of LMIC clinicians. This report describes the process used to develop an LMIC-specific protocol that is transferable to other diseases/injuries. The protocol is being tested in 5 LMICs. Conclusions We derived consensus-based guidelines for sTBI treatment without ICP monitoring, and introduced a research method to a large multidisciplinary group of LMIC clinicians naive to such methods.

The imaging and clinical examination (ICE) algorithm used in the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial is the only prospectively investigated clinical protocol for traumatic brain injury management without intracranial pressure (ICP) monitoring. As the default literature standard, it warrants careful evaluation. We present the ICE protocol in detail and analyze the demographics, outcome, treatment intensity, frequency of intervention usage, and related adverse events in the ICE-protocol cohort. The 167 ICE protocol patients were young (median 29 years) with a median Glasgow Coma Scale motor score of 4 but with anisocoria or abnormal pupillary reactivity in 40%. This protocol produced outcomes not significantly different from those randomized to the monitor-based protocol (favorable 6-month extended Glasgow Outcome Score in 39%; 41% mortality rate). Agents commonly employed to treat suspected intracranial hypertension included low-/moderate-dose hypertonic saline (72%) and mannitol (57%), mild hyperventilation (adjusted partial pressure of carbon dioxide 30-35 mm Hg in 73%), and pressors to maintain cerebral perfusion (62%). High-dose hyperosmotics or barbiturates were uncommonly used. Adverse event incidence was low and comparable to the BEST TRIP monitored group. Although this protocol should produce similar/acceptable results under circumstances comparable to those in the trial, influences such as longer pre-hospital times and non-specialist transport personnel, plus an intensive care unit model of aggressive physician-intensive care by small groups of neurotrauma-focused intensivists, which differs from most high-resource models, support caution in expecting the same results in dissimilar settings. Finally, this protocol's ICP-titration approach to suspected intracranial hypertension (vs. crisis management for monitored ICP) warrants further study.

Intracranial hypertension is one of leading causes of mortality after acute brain injury. Its causes and origins are multiple. The approach should be based on the underlying pathophysiology. There are different therapeutic modalities to control increased intracranial pressure (ICP), but all share the objective of normalizing basic physiologic variables. ICP control should be combined with adequate cerebral perfusion pressure. The classic approach to ICP control is unidirectional and sequential escalation of therapy. The nonresponse to classic therapy signaled a refractory condition. Multimodal monitoring has emerged as a useful tool, taking into account the analysis of ICP, oxygenation, and cerebral metabolism.

Brain injury; Head trauma; Algorithm Daño cerebral; Trauma en la cabeza; Algoritmo Lesió cerebral; Trauma al cap; Algoritme Background: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation’s sTBI Management Guidelines, as they were not evidence-based. Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists’ decision tendencies were the focus of recommendations. Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management. We thank our financial supporters who include Adler/Geirsch Attorney at Law, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Neurotrauma and Critical Care, Bard, the Brain Trauma Foundation, DePuy, Hemedex, Integra, the Neurointensive Care Section of the European Society of Intensive Care Medicine, Neurosurgical Society of Australasia, Medtronic, Moberg Research, Natus, Neuroptics, Raumedic, Sophysa, Stryker, and Zoll.

Importance: There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries. Objective: To formulate a consensus statement of recommendations on determination of BD/DNC based on review of the literature and expert opinion of a large multidisciplinary, international panel. Process: Relevant international professional societies were recruited to develop recommendations regarding determination of BD/DNC. Literature searches of the Cochrane, Embase, and MEDLINE databases included January 1, 1992, through April 2020 identified pertinent articles for review. Because of the lack of high-quality data from randomized clinical trials or large observational studies, recommendations were formulated based on consensus of contributors and medical societies that represented relevant disciplines, including critical care, neurology, and neurosurgery. Evidence Synthesis: Based on review of the literature and consensus from a large multidisciplinary, international panel, minimum clinical criteria needed to determine BD/DNC in various circumstances were developed. Recommendations: Prior to evaluating a patient for BD/DNC, the patient should have an established neurologic diagnosis that can lead to the complete and irreversible loss of all brain function, and conditions that may confound the clinical examination and diseases that may mimic BD/DNC should be excluded. Determination of BD/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there is no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation; (2) pupils are fixed in a midsize or dilated position and are nonreactive to light; (3) corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is no facial movement to noxious stimulation; (5) the gag reflex is absent to bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to deep tracheal suctioning; (7) there is no brain-mediated motor response to noxious stimulation of the limbs; and (8) spontaneous respirations are not observed when apnea test targets reach pH

OBJECTIVE: To report the ESICM consensus and clinical practice recommendations on fluid therapy in neurointensive care patients. DESIGN: A consensus committee comprising 22 international experts met in October 2016 during ESICM LIVES2016. Teleconferences and electronic-based discussions between the members of the committee subsequently served to discuss and develop the consensus process. METHODS: Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles generated. The consensus focused on three main topics: (1) general fluid resuscitation and maintenance in neurointensive care patients, (2) hyperosmolar fluids for intracranial pressure control, (3) fluid management in delayed cerebral ischemia after subarachnoid haemorrhage. After an extensive literature search, the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were applied to assess the quality of evidence (from high to very low), to formulate treatment recommendations as strong or weak, and to issue best practice statements when applicable. A modified Delphi process based on the integration of evidence provided by the literature and expert opinions-using a sequential approach to avoid biases and misinterpretations-was used to generate the final consensus statement. RESULTS: The final consensus comprises a total of 32 statements, including 13 strong recommendations and 17 weak recommendations. No recommendations were provided for two statements. CONCLUSIONS: We present a consensus statement and clinical practice recommendations on fluid therapy for neurointensive care patients.

OBJECTIVEWhile existing guidelines support the treatment of intracranial hypertension in severe traumatic brain injury (TBI), it is unclear when to suspect and initiate treatment for high intracranial pressure (ICP). The objective of this study was to derive a clinical decision rule that accurately predicts intracranial hypertension.METHODSUsing Delphi methods, the authors identified a set of potential predictors of intracranial hypertension and a clinical decision rule a priori by consensus among a group of 43 neurosurgeons and intensivists who have extensive experience managing severe TBI without ICP monitoring. To validate these predictors, the authors used data from a Latin American trial (n = 150; BEST TRIP). To report on the performance of the rule, they calculated sensitivity, specificity, and positive and negative predictive values with 95% confidence intervals. In a secondary analysis, the rule was validated using data from a North American trial (n = 131; COBRIT).RESULTSThe final predictors and the clinical decision rule were approved by 97% of participants in the consensus working group. The predictors are divided into major and minor criteria. High ICP would be considered suspected in the presence of 1 major or ≥ 2 minor criteria. Major criteria are: compressed cisterns (CT classification of Marshall diffuse injury [DI] III), midline shift > 5 mm (Marshall DI IV), or nonevacuated mass lesion. Minor criteria are: Glasgow Coma Scale (GCS) motor score ≤ 4, pupillary asymmetry, abnormal pupillary reactivity, or Marshall DI II. The area under the curve for the logistic regression model that contains all the predictors was 0.86. When high ICP was defined as > 22 mm Hg, the decision rule performed with a sensitivity of 93.9% (95% CI 85.0%–98.3%), a specificity of 42.3% (95% CI 31.7%–53.6%), a positive predictive value of 55.5% (95% CI 50.7%–60.2%), and a negative predictive value of 90% (95% CI 77.1%–96.0%). The sensitivity of the clinical decision rule improved with higher ICP cutoffs up to a sensitivity of 100% when intracranial hypertension was defined as ICP > 30 mm Hg. Similar results were found in the North American cohort.CONCLUSIONSA simple clinical decision rule based on a combination of clinical and imaging findings was found to be highly sensitive in distinguishing patients with severe TBI who would suffer intracranial hypertension. It could be used to identify patients who require ICP monitoring in high-resource settings or start ICP-lowering treatment in environments where resource limitations preclude invasive monitoring.Clinical trial registration no.: NCT02059941 (clinicaltrials.gov).

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.

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.

Widely-varying published and presented analyses of the Benchmark Evidence From South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi method-based approach employed iterative pre-meeting polling to codify the group's general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of more than 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83% to 100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that the BEST TRIP trial: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation.

Intracranial pressure (ICP) monitoring is considered the standard of care for severe traumatic brain injury (TBI) and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed.The objective was to compare efficacy of guideline-based management in which a protocol for monitoring intraparenchymal ICP was used (ICP group) or a protocol in which treatment was based on imaging and clinical examination (exam group).A multicenter randomized controlled trial was conducted.The trial was set in ICUs in Bolivia or Ecuador.Patients had severe TBI (n = 324) and were 13 years of age or older.Patients were randomly allocated to ICP monitoring or clinical exam-based monitoring.The primary outcome was a composite of survival time, impaired consciousness, functional status at 3 and 6 months, and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of the protocol assignment. This composite measure was based on performance across 21 measures of functional and cognitive status and was calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance).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 versus 53 in the imaging-clinical examination group; P = 0.49). Six-month mortality rates were 39% in the pressure-monitoring group and 41% in the imaging-clinical examination group (P = 0.60). The median lengths of stay in the ICU were 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 (for example, 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 versus 3.4, P = 0.002). The distributions of serious adverse events were similar in the two groups.For patients with severe TBI, care focused on maintaining monitored ICP at 20 mmHg or less was not shown to be superior to care based on imaging and clinical examination.

OBJECTIVE: To determine patterns of hyperglycemic (HG) control in acute stroke. METHODS: Anonymous survey through Internet questionnaire. Participants included Latin-American physicians specialized in neurocritical care. RESULTS: The response rate was 74%. HG definition varied widely. Fifty per cent considered it when values were >140 mg/dL (7.8 mmol/L). Intravenous (IV) regular insulin was the drug of choice for HG correction. One fifth of the respondents expressed adherence to a protocol. Intensive insulin therapy (IIT) was used by 23%. Glucose levels were measured in all participants at admission. Routine laboratory test was the preferred method for monitoring. Reactive strips were more frequently used when monitoring was intensive. Most practitioners (56.7%) monitored glucose more than two times daily throughout the Intensive Care Unit stay. CONCLUSIONS: There is considerable variability and heterogeneity in the management of elevated blood glucose during acute phase of stroke by the surveyed Latin-American physicians. OBJETIVO: Determinar patrones de control de hiperglucemia (HG) en el ictus agudo. MÉTODOS: Encuesta anónima, mediante cuestionario vía Internet. Los participantes incluyan médicos latinoamericanos especializados en cuidados neurocríticos. RESULTADOS: Las encuestas fueron respondidas por el 74% de los convocados. Las definiciones de hiperglucemia fueron variadas. El 50% de los que respondieron consideran HG cuando glucemia >140 mg/dL (7.8 mmol/L). Insulina regular intravenosa fue la droga de elección para su control. Solo la quinta parte de los encuestados manifestaron adherencia a un protocolo. El 23% emplea el régimen insulínico intensivo (TII). Glucemia fue obtenida a la admisión a la Unidad de Terapia Intensiva (UCI) por el total de los participantes. Test rutinario de laboratorio fue el método preferido para la monitorización. Tiras reactivas fueron utilizadas con mayor frecuencia cuando se aplicó monitoreo intensivo. El 56.7% monitoriza glucemia más de dos veces al día durante la estadía en UCI. CONCLUSIONES: Existe una considerable variabilidad y heterogeneidad en el manejo de la hiperglucemia durante la fase aguda del ictus entre los médicos latinoamericanos encuestados.

Cerebral autoregulation (CA) is the mechanism responsible for maintaining a relatively constant cerebral blood flow (CBF) over a wide range of arterial blood pressure. CA depends on several mechanisms to maintain a suitable CBF based on cerebral metabolic demands. These mechanisms protect the brain from oligemia or hyperemia. Under specific conditions, the range of CA is severely compromised, increasing the risk of cerebral swelling (1).

BACKGROUND : Previous studies indicate that age, Glasgow Coma Scale score (GCS), arterial hypotension, computed tomography (CT) findings, and pupillary reactivity are strong predictors of outcome for patients with severe traumatic brain injury (TBI). However, the predictive validity of these variables has never been rigorously tested in patients from the developing world. The objective of this study was to evaluate the prognostic value of these variables in a resource-limited setting and to test their predictive power by using them to create an outcome model. METHODS : The study was conducted at Hospital Emergencias "Dr. Clemente Alvarez" in Rosario, Argentina. All patients with severe TBI meeting criteria between August 2000 and February 2003 were included. Outcome at 6 months postinjury was measured by mortality and by the Extended Glasgow Outcome Scale score. Two logistic regression models were created for predicting mortality and outcome. RESULTS : Outcome measures were acquired for 100% of the sample (N = 148). There was 58% mortality; 30% had moderate to good recovery, and 12% were severely disabled. The model accurately predicted 83.9% of mortality, and 81.1% of outcome. Because of variation in timing of CT scans, the models were recalculated without the CT variable. The accuracy of prediction was 79.7% and 79% for mortality and Extended Glasgow Outcome Scale, respectively. CONCLUSIONS : This study provides rigorous, prospective data that (1) validates the generalizability of the five World Health Organization/Organization Mondiale de la Sante TBI prognostic predictors outside of the developed world, and (2) provides outcome benchmarks for mortality and morbidity from severe TBI in developing countries.

We read with interest the editorial critique of Sahuquillo and Biestro[10] regarding the BEST TRIP trial,[2] and appreciate Hunt's editorial response.[6] However, we believe that the several oversights and misinterpretations that flaw the structure of the editorial, although resolvable by careful reading of the paper, will benefit by clarification by us who were directly involved with the study. Our major concerns are regarding the misrepresentation of the study's focus and the sterile analysis of equipoise. As stated in the BEST TRIP report, this was not a study of intracranial pressure (ICP) monitoring per se. It was designed as an investigation of two protocols of aggressive treatment of intracranial hypertension, one driven by monitored ICP and based on recommendations from the Guidelines for the Management of Acute Brain Injury in Adults[1] and the other based on current practices at the study (non-monitoring) institutions, which were guided by serial neurological examination and CT imaging. There was no placebo group in this study; both groups were afforded highly aggressive neurological management. As presented in the BEST TRIP report, there was no difference in the incidence of pre-specified clinical neurological deterioration criteria (one hallmark of inadequate ICP management) between the monitor-driven and the non–monitor-driven protocols. Recognizing the absence of a placebo control group renders specious the suggested parallels between the BEST TRIP trial and ethically questionable studies such as the African zidovudine studies and the Tuskegee and Willowbrook investigations. From a position of academics in high-income countries (HICs), it is argued that ICP monitoring is the standard of care. However, the guidelines themselves note that the weakness of the literature supporting ICP monitoring reflects the lack of randomized control trial (RCT)-level data. There is no doubt that elevated ICP is a bad prognostic indicator; the evidentiary frisson exists because it has not been definitively shown that lowering ICP improves recovery. The correlative nature of the available Class II and III studies cannot differentiate treatment-related selection of patient subgroups with different prognoses versus actually increasing recovery. An objective indication that there is no consensus on ICP monitoring, even in HICs, is the wide variation of its routine use in actual practice (77.4% in the US,[5] 44.5% in Australia and New Zealand,[7] 63% in Canada,[9] and 37% in Europe[12]). Perhaps naively, we believe that these frequencies reflect clinical or global equipoise at HIC centers rather than non-compliance with a true standard of practice. In low- and-middle-income countries (LMICs), although ICP monitoring is generally available (via ventriculostomy), it is rarely used, with availability of neurological surgeons, expense, complications, and labor intensity quoted as reasons. As a result, aggressive treatment of suspected intracranial hypertension is based on serial imaging and neurological examination. The widespread environment of competition for funding and resources in LMICs places the implications of the lack of scientific rigor in a unique context quite different from that in HICs. It is perhaps germane to realize that most, if not all, of the authors of the guidelines have never managed a severe traumatic brain injury (TBI) patient without an ICP monitor. This brings us to our second major area of concern with the Sahuquillo and Biestro critique, which revolves around the sterility of their analysis of equipoise. As noted in the commentary of Hunt, equipoise may be considered to have superficial and deep aspects. Superficially, it is likely true that our Latin American investigators would have been using ICP monitoring before the trial if it were readily available. Of course, cardiac surgeons would have routinely employed internal mammary artery ligation for angina in the 1950s[3] and intensivists would have chosen pulmonary artery catheterization for managing critically ill ICU patients four decades later.[4,8,11] We would all likely benefit from confessing to “medical magpie-ism” and admitting that practice in the high-resource environment of HICs greatly facilitates (and obscures) such a non-scientific proclivity. However, the benefits of living in a high-resource environment also strongly inhibits us from understanding the profoundly different visceral viewpoint that arises from having experienced one's entire medical career in LMICs. Indeed, the BEST TRIP investigators from the US and Argentina were initially taken aback when the site investigators involved in designing a multicenter prospective observational study suggested that they would be interested in performing an RCT involving ICP-monitor-driven care. Not until after much discussion among ourselves and with our site PIs did we realize that their position of equipoise, although difficult for us initially to understand, was internally valid. Without the indispensable experience that we had gained over a decade of working in Latin America, learning and experiencing their reality, it is quite possible that some of the BEST TRIP authors might have co-authored the editorial critique of Sahuquillo and Biestro. It is notable that this trial was evaluated and approved by ethical committees and FWA-approved IRBs in all participating Latin American institutions, as well as by the IRB at the University of Washington in the US. Although there were myriad ethical questions from each entity during these reviews, none found the study unacceptable based on ethical concerns. As far as conflict of interest is concerned, the site PIs who suggested and performed this study had no interest in its implications in HICs, but were very much interested in finding whether the application of our current ICP-monitor-driven protocols in their environment would warrant the required resources. Although the editorial states that “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 …,” we fail to see how demonstrating inadequacies in our use of an important monitoring device is not relevant to the health needs of both the US and Latin American countries involved in the study. We also take issue with their strong implication that this study was influenced by industry. Given the highly limited funding that comes with Fogarty International Center directed/NIH sponsored research awards, there was no way for us to purchase the required monitors. Integra Life Sciences responded positively to our request that they would supply the necessary hardware, despite explicit prohibitions against their having input into the design, execution, analysis, or publication of the study results. This is collaboration, not collusion, and allegations otherwise would benefit from supporting evidence. In contrast to the implications of the editorial, the BEST TRIP publication explicitly cautions against ready generalization of the results to HIC centers. This is based on the many important differences between these environments and our inability to adequately control for them in our analyses. As the editorial correctly states, the logical next step would be repeating the study at trauma centers in HICs. However, it also posits, “these countries would never allow such a trial to be conducted,” which we believe is incorrect. As noted above, there were sizeable percentages of HIC trauma centers not monitoring prior to the trial, and we perceive an increasing willingness for practitioners who do not routinely monitor to publically admit this following the BEST TRIP publication. A shift in HIC-equipoise balance might not be required to perform such a study. Finally, our site PIs almost to a person took umbrage at the implication in this editorial that the study ICUs were of limited quality due to lack of resources. Anyone who has spent time in these ICUs will immediately recognize the high level of education, diligence, and application represented by the involved intensivists, which is clearly reflected in the data presented in the BEST TRIP publication and the online supplement. We offer a standing invitation to Professor Sahuquillo and Dr. Biestro to visit any or all of the BEST TRIP ICUs toward rectifying their difficulty in differentiating resource limitations and quality of care. We believe that proper response to a careful, thorough reading of the BEST TRIP report is to recognize the critical value of aggressive and attentive management of TBI patients in all settings and to admit that our field's employment of ICP monitoring is under-developed at present, rather than to deny the study's findings. Refinements in threshold setting, TBI subgroup identification, and integration of ICP data with other monitored values and trends appear wanting, but there is no evidence that ICP monitoring should be abandoned. On the larger stage, it is also important to realize that the medical and ethical literature almost exclusively emanates from academic centers in HICs. The only valid method for assessing the generalizability of this literature to LMICs is to make an unbiased, protracted effort to understand their reality, as perceived by them. In this light, it is notable that none of our Latin American colleagues have ever expressed regret that they suggested this study or participated in its execution.

Careful patient monitoring using a variety of techniques including clinical and laboratory evaluation, bedside physiological monitoring with continuous or non-continuous techniques and imaging is fundamental to the care of patients who require neurocritical care. How best to perform and use bedside monitoring is still being elucidated. To create a basic platform for care and a foundation for further research 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 develop recommendations about physiologic bedside monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews as a background to the recommendations. In this article, we highlight the recommendations and provide additional conclusions as an aid to the reader and to facilitate bedside care.

BACKGROUND Although in the developed world the intracranial pressure (ICP) monitor is considered the standard of care for patients with severe traumatic brain injury (TBI), its usefulness to direct treatment decisions has never been tested rigorously. OBJECTIVE The primary focus was to conduct a high-quality, randomized, controlled trial to determine whether ICP monitoring used to direct TBI treatment improves patient outcomes. By providing education, equipment, and structure, the project will enhance the research capacity of the collaborating investigators and will foster the collaborations established during earlier studies. METHODS Study centers were selected that routinely treated ICP based on clinical examination and computed tomography imaging using internal protocols. We randomized patients to either an ICP monitor group or an imaging and clinical examination group. Treatment decisions for the ICP monitor group are guided by ICP monitoring based on established guidelines. Treatment decisions for the imaging and clinical examination group are made using a single protocol derived from those previously being used at those centers. EXPECTED OUTCOMES There are 2 study hypotheses: (1) patients with severe TBI whose acute care treatment is managed using ICP monitors will have improved outcomes and 2) incorporating ICP monitoring in the care of patients with severe TBI will minimize complications and decrease length of intensive care unit stay. DISCUSSION This clinical trial tests the effectiveness of a management protocol based on technology considered pivotal to brain trauma treatment in the developed world: the ICP monitor. A randomized, controlled trial of ICP monitoring has never been performed-a critical gap in the evidence base that supports the role of ICP monitoring in TBI care. As such, the results of this randomized, controlled trial will have global implications regardless of the level of development of the trauma system.

In patients with severe traumatic brain injury (TBI), the influence on important outcomes of the use of information from intracranial pressure (ICP) monitoring to direct treatment has never been tested in a randomized controlled trial (RCT). We are conducting an RCT in six trauma centers in Latin America to test this question. We hypothesize that patients randomized to ICP monitoring will have lower mortality and better outcomes at 6-months post-trauma than patients treated without ICP monitoring. We selected three centers in Bolivia to participate in the trial, based on (1) the absence of ICP monitoring, (2) adequate patient accession and data collection during the pilot phase, (3) preliminary institutional review board approval, and (4) the presence of equipoise about the value of ICP monitoring. We conducted extensive training of site personnel, and initiated the trial on September 1, 2008. Subsequently, we included three additional centers. A total of 176 patients were entered into the trial as of August 31, 2010. Current enrollment is 81% of that expected. The trial is expected to reach its enrollment goal of 324 patients by September of 2011. We are conducting a high-quality RCT to answer a question that is important globally. In addition, we are establishing the capacity to conduct strong research in Latin America, where TBI is a serious epidemic. Finally, we are demonstrating the feasibility and utility of international collaborations that share resources and unique patient populations to conduct strong research about global public health concerns.

After adopting the Guidelines for the Management of Severe Head Injury, critical care physicians in Argentina reduced the mortality rate of patients with traumatic brain injury (TBI). However, there is no in-hospital or postdischarge rehabilitation services for persons with TBI in Argentina. Thus, severely disabled survivors were being discharged to home without follow-up or long-term care. Objectives The objectives of this project were to establish a structure for conducting research about TBI in Argentina, and to conduct a prospective, observational study of outcomes from TBI in hospitals that had adopted the acute care guidelines. The goal was to document outcomes for people treated in a medical system that does not provide TBI rehabilitation. The focus of this report is mortality and morbidity during the acute care and hospital ward treatment of TBI in Argentina. Methods We established a data-collection system in 5 hospitals in Argentina, using instruments and protocols developed by the NIDRR-funded TBI Model System program. Data-collection intervals were established to be comparable with intervals used in the TBI Model System program. The Argentine team consists of 11 neurocritical care physicians and 1 project manager/translator. All patient evaluation, data collection and entry, quality control, and local administration were conducted by this group. Results Over 31 months, 278 patients were entered into the study. Approximately 61% were discharged from acute care directly to home. The in-hospital mortality rate was 31%. Seventy-six percent of expired patients died from secondary complications such as sepsis and pneumonia, and 93% while in the hospital. Discussion TBI is a major public health concern in Argentina. However, rehabilitation for TBI is not a part of this country's medical system. The greatest proportion of expired patients in the Argentine sample died of secondary complications such as pneumonia or sepsis, which may have been avoided employing basic medical rehabilitation. The next research questions to be addressed in this population should be designed to identify solutions to the immediate need for rehabilitation, including treatment efficacy questions as well as questions about systems for delivering treatments.

The effect of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) has been reported by several investigators, without any consensus being reached. Acute neurological and neurosurgical patients suffer intracranial hypertension and acute lung injury with hypoxemia. Since PEEP may improve hypoxemia but elevate ICP and decrease CPP, it is important to determine the influence of varying levels of PEEP on ICP and CPP. The aim of the study was to investigate the changes in ICP and CPP associated with different levels of PEEP. Twenty patients requiring ICP monitoring and mechanical ventilation were enrolled. Patients had severe head injury (n = 10), spontaneous intracerebral haemorrhage (n = 5), and subarachnoid haemorrhage (n = 5). PEEP was raised from 5 (basal) to 15 cm H2O in steps of 5 cm H2O. After at least 10 minutes of each new PEEP setting, ICP and CPP were measured. PEEP at 10 and 15 cm H2O produced a significant (p

Objetivo. Revisar los estudios mas relevantes sobre la fisiopatologia de la hipoglucemia e hiperglucemia en pacientes neurocriticos, y la terapeutica para su control. Desarrollo. Las pruebas disponibles muestran que la hipoglucemia e hiperglucemia aumentan la lesion cerebral y empeoran el pronostico, pero no establecen los niveles adecuados de glucemia. El tratamiento intensivo de insulina, comparado con pautas mas laxas, no ha mejorado el pronostico, provocando mas episodios hipoglucemicos. Conclusiones. La hipoglucemia debe evitarse siempre. Los tratamientos intensivos para controlar la hiperglucemia no ofrecen ventaja e incrementan la posibilidad de hipoglucemia, y no se pueden recomendar en pacientes neurocriticos. No disponemos de evidencias que indiquen la glucemia optima, ni la pauta mas apropiada de insulina, indicandose generalmente su uso cuando la glucemia es superior a 180-200 mg/dL. Persiste aun la incertidumbre del valor del control farmacologico de la glucemia para mejorar el pronostico.

A variety of pharmacological agents have been advocated to treat pain and agitation in the traumatic brain injury (TBI) patient. It is felt beneficial to minimize painful or noxious stimuli as well as agitation as they may potentially contribute to elevations in ICP, raises in blood pressure, body temperature elevations and resistance to controlled ventilation. Until recently the primary concern over the utilization of these agents has been related to their tendency to obscure the neurologic exam, with a secondary concern over potential adverse hemodymanic effects. In the previous edition of these guidelines,2 little information was provided regarding analgesic and sedation utilization in severe TBI. It was noted that there have been relatively few outcome studies and therefore “decisions about . . . use . . . and the choice of agents are left to the practitioner to make based on individual circumstances.”

Pooled data indicate that prophylactic hypothermia is not significantly associated with decreased mortality when compared with normothermic controls. However, preliminary findings suggest that a greater decrease in mortality risk is observed when target temperatures are maintained for more than 48 h. Prophylactic hypothermia is associated with significantly higher Glasgow Outcome Scale (GOS) scores when compared to scores for normothermic controls.