The Brain Trauma Foundation (BTF) and BTF Center for Guidelines Management (Center) convened a virtual meeting of previous guideline authors and colleagues new to the project. This group agreed that separate guidelines should be provided for prehospital and prognosis topics. Thus, these were eliminated from the current update. They specified which previous topics would be maintained and agreed upon new topics to include. Previous topics which were updated are Blood Pressure and Oxygenation, Indications for Intracranial Pressure (ICP) Monitoring, ICP Treatment Threshold, ICP Monitoring Technology, Cerebral Perfusion Thresholds, Nutrition, Antiseizure Prophylaxis, Hyperventilation, and Steroids. New topics are Prophylactic Hypothermia, Brain Oxygen Monitoring and Thresholds, Infection Prophylaxis, and Deep Vein Thrombosis Prophylaxis. The previous topic of Mannitol was expanded to Hyperosmolar Therapy, and the previous topic of Barbiturates was expanded to Anesthetics, Analgesics, and Sedatives.

• Human subjects
• Traumatic brain injury
• English language
• Adults (age ≥ 18 years)
• In-hospital (e.g., no studies from the prehospital setting)
• ≥25 subjects
• Randomized controlled trials (RCTs), cohort studies, case-control studies, case series, databases, registries

• Sample contained >15% of pediatric patients or >15% of patients with pathologies other than TBI, and the data were not reported separately (see Appendix C)
• Wrong independent variable (e.g., the intervention was not specific to the topic)
• Wrong dependent variable (e.g., outcomes were not mortality or morbidity, or did not associate with clinical outcomes)
• Case studies, editorials, comments, letters

Center staff worked with a doctoral level research librarian to construct electronic search strategies for each topic (see Appendix B). For new topics, the literature was searched from 1966 to 2004, and for previous topics from 1996 to 2004. Strategies with the highest likelihood of capturing most of the targeted literature were used, which resulted in the acquisition of a large proportion of nonrelevant citations. Two authors were assigned to each topic, and a set of abstracts was sent to each. Blinded to each others' work, they read the abstracts and eliminated citations using the pre-determined inclusion/exclusion criteria.

Center staff compared the selections, and identified and resolved discrepancies either through consensus or through use of a third reviewer. A set of full-text publications was then sent to each author. Again blinded to each others' work, they read the publications and selected those that met the inclusion criteria.

Results of the electronic searches were supplemented by recommendations of peers and by reading reference lists of included studies. A second search was conducted from 2004 through April 2006 to capture any relevant Class I or II literature (see Quality Assessment section of this chapter) that might have been published since the first literature search in 2004. Relevant publications were added to those from the original search, constituting the final library of studies that were used as evidence in this document. The yield of literature from each phase of the search is presented in Appendix D.

Two authors independently abstracted data from each publication using an evidence table template (see Appendix E). They compared results of their data abstraction and through consensus finalized the data tables. Due to methodological heterogeneity of studies within topics, and to the lack of literature of adequate quality, data were not combined quantitatively for all but one topic. The exception was Prophylactic Hypothermia, for which a metaanalysis was performed.

Authors drafted manuscripts for each topic. The entire team gathered for a 2-day work session to discuss the literature base and to achieve consensus on classification of evidence and level of recommendations. Some topics, while considered important, were eliminated due to lack of a literature base (e.g., At-Risk Non-Comatose Patient, Hyperacute Rehabilitation, ICP in the Elderly, and Decompressive Therapies). Manuscripts were revised. Virtual meetings were held with a subset of the co-authors to complete the editing and consensus processes. The final draft manuscript was circulated to the peer review panel.

In April of 2004, the Brain Trauma Foundation established a collaboration with the Evidence-Based Practice Center (EPC) from Oregon Health & Science University (OHSU). Center staff worked with two EPC epidemiologists to develop criteria and procedures for the quality assessment of the literature. Criteria for classification of evidence based on study design and quality are in Table 1, and are derived from criteria developed by the U.S. Preventive Services Task Force, the National Health Service Centre for Reviews and Dissemination (U.K.), and the Cochrane Collaboration. These criteria were used to assess the literature for all topics except ICP Monitoring Technology. Quality criteria specific to technology assessment were used to assess the ICP Monitoring Technology topic.

Two investigators independently read the studies included in the Evidence Tables (both new studies and those maintained from the previous edition) and classified them as Class I, II, or III, based on the design and quality criteria in Table 1. Discrepancies were resolved through consensus, or through a third person's review.

Class I Evidence is derived from randomized controlled trials. However, some may be poorly designed, lack sufficient patient numbers, or suffer from other methodological inadequacies that render them Class II or III.

Class II Evidence is derived from clinical studies in which data were collected prospectively, and retrospective analyses that were based on reliable data. Comparison of two or more groups must be clearly distinguished. Types of studies include observational, cohort, prevalence, and case control. Class II evidence may also be derived from flawed RCTs.

Class III Evidence is derived from prospectively collected data that is observational, and retrospectively collected data. Types of studies include case series, databases or registries, case reports, and expert opinion. Class III evidence may also be derived from flawed RCTs, cohort, or case-control studies.

Quality criteria typically used for literature about technology assessment are presented in Table 2, and are derived from criteria developed by the U.S. Preventive Services Task Force. As indicated in Table 2, a key criterion for establishing Class I evidence for technology assessment is the application of the device in patients with and without the disease. Thus, the ability to use these criteria in evaluating ICP monitoring technology is limited, in that it would not be ethical to test the monitors in people without probable elevated ICP. Criteria were applied when feasible to estimate the reliability of the findings from each study included for this topic; however, levels of recommendation were not applied.

Levels of recommendation are Level I, II, and III, derived from Class I, II, and III evidence, respectively. Level I recommendations are based on the strongest evidence for effectiveness, and represent principles of patient management that reflect a high degree of clinical certainty. Level II recommendations reflect a moderate degree of clinical certainty. For Level III recommendations, the degree of clinical certainty is not established.

To determine the recommendation level derived from a meta-analysis, three criteria are considered:

• Are all included studies of the same quality class?
• Are the findings of the studies in the same or contradictory directions?
• What are the results of analyses that examine potential confounding factors?

Thus, a meta-analysis containing only Class II studies may be used to make a Level III recommendation if the answers to the above questions render uncertainty in the confidence of the overall findings.