The Brain Trauma Foundation (BTF) and BTF Center for Guidelines Management (Center) convened a virtual meeting of previous participants in the development of guidelines for prehospital management of traumatic brain injury (TBI), as well as with colleagues new to the project. They specified topics for inclusion in the current update, and agreed to include pediatric literature as a separate section for each topic. Further refinement of topics and scope was accomplished in a subsequent work meeting of participants with BTF and Center staff. The group agreed to maintain the distinction between Assessment topics and Treatment topics, as follows:

The group further agreed to eliminate the topic of Brain Targeted Therapy, and distribute the content as follows:

Cerebral Herniation: This is a new chapter to include hyperventilation, mannitol, and hyperosmolar therapy.
Fluid Resuscitation: Hyperosmolar and non-hyperosmolar therapies are addressed in this chapter.
Airway/Ventilation/Oxygenation: Sedation is addressed in this chapter.

A preliminary search revealed an insufficient literature base to support a Prevention topic. Thus the group agreed to summarize the descriptive findings and discuss future research for Prevention in the Introduction section of the Guidelines.

Four participants were assigned to work on each topic - two for the adult section and two for the pediatric section. Participants finalized the scope of each topic and provided terms for the electronic literature search.

Inclusion Criteria

• human subjects/li>
• traumatic brain injury/li>
• English language/li>
• ≥25 subjects/li>
• Randomized controlled trials (RCTs), cohort studies, case-control studies, case series, databases, registries/li>

Exclusion Criteria

• 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)
• statistics used in the analysis were not appropriate to the research design, variables, and/or sample size
• case studies, editorials, comments, letters

Center staff worked with a doctoral-level research librarian to construct electronic search strategies for each topic from 1996 through April to August of 2005 (see Appendix B). They used strategies with the highest likelihood of capturing most of the targeted literature, which resulted in the acquisition of a large proportion of non-relevant citations. A set of abstracts was sent to the participants for each topic. Blinded to each others' work, they read the abstracts and eliminated citations using the criteria specified above.

Center staff compared the participants' selections, identified discrepancies, and worked with authors to resolve them. A set of full-text publications was sent to each participant. They read the publications and determined the final library of studies that would be used as evidence. 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 2005 through July of 2006 to capture any relevant Class I or II literature that might have been published since the first literature search in 2005. 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.

Remaining blinded to each other's work, participants read each publication and abstracted data using a predetermined format. They drafted chapters and the entire team gathered for a 2-day work session to discuss the literature base, and to achieve consensus on classification of quality of evidence, and strength of recommendations.

After the work meeting, participants revised each topic based on the group's recommendations. Virtual meetings were convened, during which a subset of approximately five members of the team edited each topic online. Final versions were circulated to the Review Committee. Critiques from the Review Committee were addressed by participants and incorporated, or not, based upon their accuracy and consistency with the pre-specified systematic process.

Different criteria are used to evaluate the quality of the evidence in assessment topics vs. treatment topics. Quality criteria for assessment topics are in Table 1, and those for treatment topics are in Table 2. These are based on 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.

Publications contained in the evidence tables was assessed by two epidemiologists who were blinded to each other's work as well as to the identification of the studies, authors, and journals They applied the criteria in Tables 1 and 2 to each study to provide the quality assessment and derive the classification of level of evidence.

At the end of each recommendation section in this document, the recommendations are categorized in terms of Strength and Quality of Evidence. The strength of the recommendation is derived from the overall quality of the body of evidence used to assess the topic.

Strength of Recommendations

Consistent with methods generated by the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) working group, recommendations in this document are categorized as either strong or weak. As stated in the American Thoracic Society's official statement, in which they endorsed the GRADE methods for their guidelines endeavors, "The strength of a recommendation reflects the degree of confidence that the desirable effects of adherence to a recommendation outweigh the undesirable effects."

Strong recommendations are derived fromhigh quality evidence that provide precise estimates of the benefits or downsides of the topic being assessed. With weak recommendations, (1) there is lack of confidence that the benefits outweigh the downsides, (2) the benefits and downsides may be equal, and/or (3) there is uncertainty about the degree of benefits and downsides.

Quality of Body of Evidence

The underlying methods for assessing and classifying the quality of evidence of individual studies are represented in Tables 1 and 2. However, ultimately the individual studies must be considered in aggregate, whether through meta-analyses or through qualitative assessment. Thus, the strength of recommendations must be derived from the quality of the overall body of evidence used to address the topic.

The quality of the overall body of evidence for each recommendation in this document is classified as high, moderate, or low. Factors that may decrease the quality include potential bias, differing findings across studies,the use of indirect evidence, or lack or precision. For example, if two or more Class I studies demonstrate contradictory findings for a particular topic, the overall quality most probably will be low because there is uncertainty about the effect. Similarly, Class I or II studies that provide indirect evidence may only constitute low quality evidence, overall.

Indirect Evidence

Well controlled studies conducted in the field are rare. One alternative is to apply evidence from studies conducted in other environments to field practice, or from other pathologies to TBI. In this document, indirect evidence from inhospital populations or from physiological studies was used, after careful consideration of the quality of the study for its own population, and then of its usefulness as indirect evidence.We used the following sequential process of questions:

1. To what extent does the physiology of the field application approximate the physiology of the inhospital application?
2. What are the differences in patients, settings, treatments, and measurements between the field and inhospital settings?
3. To what extent would those differences influence the physiology of the intervention?
4. To what extent and in what direction would those differences influence the observed effect?
5. What is the quality of the publication?
6. Consider all of the above (1) to determine if the publication can be used as indirect evidence, and if so, (2) to determine the quality of the evidence.

In this document, indirect evidence used to support a recommendation is identified as such.