The scope and purpose of this work is 2-fold: to synthesize the available evidence and to translate it into recommendations. This document provides recommendations only when there is evidence to support them. As such, they do not constitute a complete protocol for clinical use. Our intention is that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient. We think it is important to have evidence-based recommendations to clarify what aspects of practice currently can and cannot be supported by evidence, to encourage use of evidence-based treatments that exist, and to encourage creativity in treatment and research in areas where evidence does not exist. The communities of neurosurgery and neuro-intensive care have been early pioneers and supporters of evidence-based medicine and plan to continue in this endeavor. The complete guideline document, which summarizes and evaluates the literature for each topic, and supplemental appendices (A-I) are available online at https://www.braintrauma.org/coma/guidelines.

Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition

background It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival. We conducted a multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU. methods We randomly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days. The primary outcome measure was death from any cause during the 28-day period after randomization. results Of the 6997 patients who underwent randomization, 3497 were assigned to receive albumin and 3500 to receive saline; the two groups had similar baseline characteristics. There were 726 deaths in the albumin group, as compared with 729 deaths in the saline group (relative risk of death, 0.99; 95 percent confidence interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups (P=0.85). There were no significant differences between the groups in the mean (±SD) numbers of days spent in the ICU (6.5±6.6 in the albumin group and 6.2±6.2 in the saline group, P=0.44), days spent in the hospital (15.3±9.6 and 15.6±9.6, respectively; P = 0.30), days of mechanical ventilation (4.5±6.1 and 4.3±5.7, respectively; P = 0.74), or days of renal-replacement therapy (0.5±2.3 and 0.4±2.0, respectively; P = 0.41). conclusions In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days.

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A comparison of albumin and saline for fluid resuscitation in the intensive care unit

Traumatic brain injury (TBI) is a major health and socioeconomic problem that affects all societies. In recent years, patterns of injury have been changing, with more injuries, particularly contusions, occurring in older patients. Blast injuries have been identified as a novel entity with specific characteristics. Traditional approaches to the classification of clinical severity are the subject of debate owing to the widespread policy of early sedation and ventilation in more severely injured patients, and are being supplemented with structural and functional neuroimaging. Basic science research has greatly advanced our knowledge of the mechanisms involved in secondary damage, creating opportunities for medical intervention and targeted therapies; however, translating this research into patient benefit remains a challenge. Clinical management has become much more structured and evidence based since the publication of guidelines covering many aspects of care. In this Review, we summarise new developments and current knowledge and controversies, focusing on moderate and severe TBI in adults. Suggestions are provided for the way forward, with an emphasis on epidemiological monitoring, trauma organisation, and approaches to management.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(08)70164-9.pdf

Moderate and severe traumatic brain injury in adults.

The Glasgow Outcome Scale (GOS) is the most widely used outcome measure after traumatic brain injury, but it is increasingly recognized to have important limitations. It is proposed that shortcomings of the GOS can be addressed by adopting a standard format for the interview used to assign outcome. A set of guidelines are outlined that are directed at the main problems encountered in applying the GOS. The guidelines cover the general principles underlying the use of the GOS and common practical problems of applying the scale. Structured interview schedules are described for both the five-point GOS and an extended eight-point GOS (GOSE). An interrater reliability study of the structured interviews for the GOS and GOSE yielded weighted kappa values of 0.89 and 0.85, respectively. It is concluded that assessment of the GOS using a standard format with a written protocol is practical and reliable.

Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: Guidelines for their use

Nerve regeneration is a complex biological phenomenon. In the peripheral nervous system, nerves can regenerate on their own if injuries are small. Larger injuries must be surgically treated, typically with nerve grafts harvested from elsewhere in the body. Spinal cord injury is more complicated, as there are factors in the body that inhibit repair. Unfortunately, a solution to completely repair spinal cord injury has not been found. Thus, bioengineering strategies for the peripheral nervous system are focused on alternatives to the nerve graft, whereas efforts for spinal cord injury are focused on creating a permissive environment for regeneration. Fortunately, recent advances in neuroscience, cell culture, genetic techniques, and biomaterials provide optimism for new treatments for nerve injuries. This article reviews the nervous system physiology, the factors that are critical for nerve repair, and the current approaches that are being explored to aid peripheral nerve regeneration and spinal cord repair.

Neural tissue engineering: strategies for repair and regeneration.

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

http://ether.stanford.edu/library/neuroanesthesia/SNACC%20Reading%20List%20articles/Narayan_Clinical%20trials%20in%20head%20injury.pdf

Clinical trials in head injury

The rapid pace of recent advances in development and application of electrical stimulation of the nervous system and in neural regeneration has created opportunities to combine these two approaches to restoration of function. This paper relates the discussion on this topic from a workshop at the International Functional Electrical Stimulation Society. The goals of this workshop were to discuss the current state of interaction between the fields of neural regeneration and neural prostheses and to identify potential areas of future research that would have the greatest impact on achieving the common goal of restoring function after neurological damage. Identified areas include enhancement of axonal regeneration with applied electric fields, development of hybrid neural interfaces combining synthetic silicon and biologically derived elements, and investigation of the role of patterned neural activity in regulating various neuronal processes and neurorehabilitation. Increased communication and cooperation between the two communities and recognition by each field that the other has something to contribute to their efforts are needed to take advantage of these opportunities. In addition, creative grants combining the two approaches and more flexible funding mechanisms to support the convergence of their perspectives are necessary to achieve common objectives.

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William Heetderks

Papers

Clinical trials in head injury

At the interface: Convergence of neural regeneration and neural prostheses for restoration of function