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Nutrition in Clinical Practice Guidelines for Traumatic Brain Injury

Evidence-based guidelines (EBGs) are a common tool used in evidence-based medicine by health-care practitioners. Evidence-based medicine is founded on the following two principles (Guyatt et al., 2000; Sackett et al., 1996): (1) there is a hierarchy of strength of evidence behind recommendations, and (2) the clinician uses judgment when weighing the trade-offs associated with alternative management strategies, including consideration of patient values and preferences as well as societal values.

As will be obvious in Chapters 616, much of the available evidence suggesting potential benefits of specific nutritional interventions in traumatic brain injury (TBI) comes from findings in animal models and, in a handful of cases, randomized human trials. The committee has defined a research agenda for the many questions that still remain. This research agenda provides an opportunity for those developing clinical guidelines to be made cognizant of the questions that remain to be elucidated.

This chapter includes a brief summary of the nutrition-related recommendations from selected clinical guidelines for severe trauma patients, including TBI patients, and for patients with mild or moderate TBI.

EVIDENCE-BASED CLINICAL GUIDELINES

Hierarchy of Strength of Evidence

There is a hierarchy of strength of evidence behind recommendations in evidence-based clinical guidelines. The hierarchy of strength of evidence (i.e., which studies are best able to answer the question with certainty) varies, depending on the type of question being asked. Many questions addressed in EBGs are treatment questions best answered by a systematic review of randomized controlled human trials, or by several large, well-designed, randomized controlled human trials designed to answer the specific inquiry with consistent results (Howick et al., 2011). The EBGs are usually based on one or more systematic reviews, and these appear at the top of the hierarchy of evidence for treatment. Other questions are better



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2 Nutrition in Clinical Practice Guidelines for Traumatic Brain Injury Evidence-based guidelines (EBGs) are a common tool used in evidence-based medicine by health-care practitioners. Evidence-based medicine is founded on the following two principles (Guyatt et al., 2000; Sackett et al., 1996): (1) there is a hierarchy of strength of evidence behind recommendations, and (2) the clinician uses judgment when weighing the trade-offs associated with alternative management strategies, including consideration of patient values and preferences as well as societal values. As will be obvious in Chapters 6–16, much of the available evidence suggesting potential benefits of specific nutritional interventions in traumatic brain injury (TBI) comes from find - ings in animal models and, in a handful of cases, randomized human trials. The committee has defined a research agenda for the many questions that still remain. This research agenda provides an opportunity for those developing clinical guidelines to be made cognizant of the questions that remain to be elucidated. This chapter includes a brief summary of the nutrition-related recommendations from selected clinical guidelines for severe trauma patients, including TBI patients, and for pa- tients with mild or moderate TBI. EVIDENCE-BASED CLINICAL GUIDELINES Hierarchy of Strength of Evidence There is a hierarchy of strength of evidence behind recommendations in evidence-based clinical guidelines. The hierarchy of strength of evidence (i.e., which studies are best able to answer the question with certainty) varies, depending on the type of question being asked. Many questions addressed in EBGs are treatment questions best answered by a systematic review of randomized controlled human trials, or by several large, well-designed, random- ized controlled human trials designed to answer the specific inquiry with consistent results (Howick et al., 2011). The EBGs are usually based on one or more systematic reviews, and these appear at the top of the hierarchy of evidence for treatment. Other questions are better 23

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24 NUTRITION AND TRAUMATIC BRAIN INJURY answered by different types of research designs. For example, systematic reviews of cross- sectional studies would best respond to diagnostic issues. Questions about the likelihood of causing harm would be best answered by either a systematic review of randomized n-of-1 trials for common harms and rare harms, by a systematic review of case-control studies, or by studies revealing dramatic effects. Prognosis questions would be best answered by systematic review of inception cohort studies. There often is no best evidence, but a clinical guideline is still needed by health-care practitioners. Therefore, in addition to attending to the kind of study needed, the reviewer needs to explicitly describe the strength of the evi- dence supporting a specific guideline. Such description provides the health-care practitioner an indication of the level of certainty of a guideline recommendation (ADA, 2010; Howick et al., 2011). Guidelines with weak supporting evidence need to be updated as new evidence becomes available. The Bradford-Hill criteria provide a framework for epidemiological research demon- strating causality between environment and disease states (Hill and Bradford, 1965). These criteria can be applied to the development of EBGs because they help determine whether an association between an intervention and an outcome is causal. For the task of this commit- tee, establishing a causal relationship between a nutritional intervention and a TBI outcome would rely on the following: strength of evidence, consistency of evidence, specificity, tem- poral relationship (temporality), biological gradient (dose-response relationship), plausibil- ity (biological plausibility), coherence with existing knowledge, experimental testing, and analogy (consideration of alternative explanations). Use of Clinical Judgment The second principle of evidence-based medicine is that the clinician uses judgment when weighing the trade-offs associated with alternative management strategies, including consideration of patient values and preferences as well as societal values (Guyatt, 2002; Guyatt et al., 2000). DEVELOPMENT OF EVIDENCE-BASED GUIDELINES Evidence-based guidelines are developed by professional organizations, health-care organizations, or other nonprofit, disease- or condition-specific organizations (DoD, 2008; Grilli et al., 2000; Knuth et al., 2005; Thomas et al., 1999). There are well-established pro- cedures to systematically review and synthesize the research best suited to answer the clinical questions faced by health-care practitioners. More than 40 clinical guidelines for TBI were identified at the National Guideline Clearinghouse online database.1 However, many of these guidelines focus on emergency department treatment or evaluating for the presence or ab- sence of TBI in primary care or sports settings, and only a few address nutritional concerns. In addition to guidelines developed specifically for TBI, generic evidence-based clinical practice guidelines for critical care of adults in intensive care units may also be appropri- ate in acute TBI. For mild TBI, other EBGs might also be appropriate based on additional conditions, such as obesity. For this report, EBGs from the following organizations were selected for more compre- hensive evaluation because of their relevance to TBI: the American Society of Parenteral and Enteral Nutrition (ASPEN), the Society of Critical Care Medicine (SCCM), the American Dietetic Association (ADA), the Brain Trauma Foundation, the National Neurotrauma Soci- 1 Available online: http://www.guideline.gov/ (accessed October 26, 2010).

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25 NUTRITION IN CLINICAL PRACTICE GUIDELINES FOR TBI ety, the American Association of Neuroscience Nurses (AANN), the Department of Defense (DoD), and the U.S. Department of Veterans Affairs (VA) (ADA, 2006; Bratton et al., 2007; Kattelmann et al., 2006; Knuth et al., 2005; McClave et al., 2009; VA/DoD, 2009). The following section summarizes the nutrition components of these EBGs. For this chapter, the EBGs were divided into two types: those for patients with severe TBI in the acute phase who are in the intensive care unit (ICU) critical-care setting, and those for patients with mild TBI, who are more likely to be outpatients. EBGS FOR SEVERE TBI IN THE ACUTE STAGES DoD’s Guidelines for the Field Management of Combat-Related Head Trauma (Knuth et al., 2005) address assessment of oxygenation and blood pressure, Glasgow Coma Scale, airway, ventilation, fluid treatment, pain management and sedation, triage for transport, and brain-targeted therapy. The only nutrition-related content is the discussion of assessment of nausea as a side effect of pain medication. Nutrition needs are not specifically addressed. In contrast, other guidelines do recognize the importance of nutrition to accelerate progress in trauma patients. For example, the SCCM/ASPEN Guidelines for Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient include recom- mendations for timing of initiation of enteral nutrition, use of parenteral nutrition, dosage of enteral feeding, monitoring, intolerance and adequacy of enteral nutrition, selection of appropriate enteral formulation, adjunctive therapies, and maximizing the efficacy of par- enteral nutrition, as well as specific recommendations for the following medical conditions: pulmonary failure, renal failure, hepatic failure, acute pancreatitis, and end-of-life treat- ments (McClave et al., 2009). The ADA Critical Illness Evidence-Based Nutrition Practice Guideline also includes recommendations for assessing nutritional issues in trauma patients. The recommendations address energy expenditure and needs, choosing enteral versus parenteral nutrition, timing of feeding, feeding tube site, use of immune-enhancing formulas, use of blue dye in enteral nutrition to detect aspiration, monitoring criteria and blood glucose control, and special considerations for persons with diabetes (Kattelmann et al., 2006). The third edition of the Guidelines for the Management of Severe Traumatic Brain Injury from the Brain Trauma Foundation includes a recommended time frame for patients to attain adequate energy (within seven days), but concludes there is insufficient evidence to make recommendations on how to determine whether enteral or parenteral nutrition is preferred or whether the use of vitamin, minerals, or other supplements is warranted (Brat- ton et al., 2007). Nursing interventions to maintain adequate nutrition are considered in the AANN EGB. The Nursing Management of Adults with Severe Traumatic Brain Injury guidelines include four main recommendations for adequate nutrition and glycemic control: timing of feeding, feeding tube site, the effect of certain agents on feeding tolerance, and the administration of intensive insulin therapy (Mcilvoy and Meyer, 2008). Extracts from these guidelines related to nutrition appear in Appendix B, Table B-1. The following are key recommendations pertinent to TBI patients. Estimating Energy Needs The ASPEN and ADA EBGs discuss the need to determine energy requirements at the time of initiation of nutritional therapy. Both indicate that predictive equations should be

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26 NUTRITION AND TRAUMATIC BRAIN INJURY used with caution and that indirect calorimetry is more accurate in determining resting metabolic rate (ADA, 2006; McClave et al., 2009). There is no clear consensus, however, on the best method to determine energy needs or how frequently they should be adjusted or remeasured. The ADA EBGs evaluated various formulas for estimating resting metabolic rate in the ICU patient population, and concluded that measurement was preferable to estimation formulas. If estimation is needed, the fol- lowing formulas for nonobese patients are recommended in the following order, based on their accuracy: the Penn State equation (2003a) is the most accurate, with ~79 percent accuracy,2 followed by Swinamer (55 percent accuracy) and Ireton-Jones, 1992 (52 percent accuracy). An estimation of resting metabolic rate was considered accurate if it was within 10 percent of the measured rate. These estimation formulas are preferred over the more traditional Harris-Benedict formula (ADA, 2006). The recommendations are summarized in Box 2-1. However, it should be noted that these are recommendations for estimating the resting metabolic rate, and although they present a good starting point for determining total energy needs, they are not specific for TBI patients and do not account for injury factors. Meeting Energy Needs Enteral Nutrition The ASPEN and ADA EBGs recommend enteral feeding be started early, within the first 24–48 hours of admission, and advanced toward optimal nutrition goals over the next 48–72 hours (ADA, 2006; McClave et al., 2009). The European Society for Parenteral and Enteral Nutrition also supports early feeding (< 24 hours if patients are hemodynamically stable and have functioning gastrointestinal tracts); however, they note there are no data to document improvement in relevant outcome parameters associated with early enteral feeding (Kreymann et al., 2006). Continuous intragastric feeding and initiating adequate nutrition within 72 hours of injury are recommended by the AANN to improve feeding tolerance and outcomes, respectively (Mcilvoy and Meyer, 2008). The Brain Trauma Foundation guidelines emphasize the need for feeding at least by the end of the first week postinjury, and indicate that feeding prior to seven days improves outcomes (Bratton et al., 2007). By the end of the first week of hospitalization, it is recommended that patients receive greater than 50 to 65 percent of their energy needs in order to achieve the clinical benefit of enteral nutrition. Parenteral Nutrition ASPEN supports the concept of permissive mild underfeeding (i.e., the restriction of nutrient intake, specifically in critically ill patients, over a short term) with a recommenda- tion to meet at least 80 percent of energy requirements as the ultimate goal for patients receiving parenteral nutrition (see Appendix B, Recommendation G.2). As the patient stabi- lizes, parenteral nutrition may be increased to meet energy needs. The ASPEN guideline has different goals for parenteral feeding than for enteral feeding. A separate recommendation (see Appendix B, Recommendation C.2) is made for enteral feeding that specifies a goal of providing from 50 to 65 percent of calories within the first week to achieve clinical benefit (McClave et al., 2009). 2 The 2003a Penn State equation has been updated since the ADA guidelines were published in 2006.

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27 NUTRITION IN CLINICAL PRACTICE GUIDELINES FOR TBI BOX 2-1 Critical Illness Recommendations from the ADA Evidence Analysis Librarya Regarding Determining Resting Metabolic Rate (RMR) Indirect calorimetry to determine RMR Indirect calorimetry is the standard for determination of RMR in critically ill patients, because RMR based on measurement is more accurate than estimation using predictive equations. Rating: Strongb Imperativec RMR predictive equations for nonobese patients If predictive equations are needed in nonobese, critically ill patients, consider using one of the fol- lowing, as they have the best prediction accuracyd of equations studied (listed in order of accuracy): Penn State, 2003ae (79%), Swinamer (55%), and Ireton-Jones, 1992 (52%). In some individuals, errors between predicted and actual energy needs will result in under- or over-feeding. Rating: Fairf Conditionalg Inappropriate RMR predictive equations for this population The Harris-Benedict (with or without activity and stress factors), the Ireton-Jones, 1997 and the Fick equation should not be considered for use in RMR determination in critically ill patients, as these equations do not have adequate prediction accuracy. In addition, the Mifflin-St. Jeor equation should not be considered for use in critically ill patients, because it was developed for healthy people and has not been well researched in the critically ill population. Rating: Strong Imperative RMR predictive equations for obese patients If predictive equations are needed for critically ill, mechanically ventilated individuals who are obese, consider using Ireton-Jones, 1992 or Penn State, 1998, as they have the best prediction accuracy of equations studied. In some individuals, errors between predicted and actual energy needs will result in under- or over-feeding. Rating: Fair Conditional a Available online: http://www.adaevidencelibrary.com/template.cfm?key=1309&cms_preview=1 (accessed No- vember 30, 2010). b A Strong recommendation means that the workgroup believes that the benefits of the recommended approach clearly exceed the harms (or that the harms clearly exceed the benefits in the case of a strong negative recom- mendation), and that the quality of the supporting evidence is excellent/good (grade I or II). In some clearly identified circumstances, strong recommendations may be made based on lesser evidence when high-quality evidence is impossible to obtain and the anticipated benefits strongly outweigh the harms. Practitioners should follow a Strong recommendation unless a clear and compelling rationale for an alternative approach is present. c Imperative recommendations “require,” or “must,” or “should achieve certain goals,” but do not contain conditional text that would limit their applicability to specified circumstances. d A formula was considered accurate if it predicted resting metabolic rate within +/– 10% of measured resting metabolic rate. e The 2003a Penn State equation has been updated since these 2006 ADA guidelines. f A Fair recommendation means that the workgroup believes that the benefits exceed the harms (or that the harms clearly exceed the benefits in the case of a negative recommendation), but the quality of evidence is not as strong (grade II or III). In some clearly identified circumstances, recommendations may be made based on lesser evidence when high-quality evidence is impossible to obtain and the anticipated benefits outweigh the harms. Practitioners should generally follow a Fair recommendation but remain alert to new information and be sensitive to patient preferences. g Conditional statements clearly define a specific situation, while imperative statements are broadly applicable to the target population without restraints on their pertinence.

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28 NUTRITION AND TRAUMATIC BRAIN INJURY Serum Glucose Control ASPEN, ADA, and AANN EBGs discuss serum glucose control. ASPEN recommends moderate glucose control, indicating that 110–150 mg/dL may be most appropriate (McClave et al., 2009). AANN supports the intravenous administration of intensive insulin therapy for elevated serum glucose (greater than 110 mg/dL) to improve glycemic control and possibly even reduce intracranial pressure (Mcilvoy and Meyer, 2008). The ADA recommendation is currently under revision. Antioxidants and Immune-Enhancing Formulas ASPEN EBGs recommend that immune-modulating enteral formulations (supplemented with agents such as arginine, glutamine, nucleic acid, omega-3 fatty acids, and antioxidants) be used for appropriate patient populations (including major elective surgery and trauma cases) while urging caution in their use for patients with severe sepsis. ADA indicates that in trauma patients, any benefit of immune-enhancing formulas has not been associated with reduced mortality, reduced length of stay, reduced complications from infections, or fewer days on mechanical ventilation (ADA, 2006). ASPEN recommends that a combination of antioxidant vitamins and trace minerals (specifically including selenium) be provided to all critically ill patients receiving specialized nutrition therapy (McClave et al., 2009). Neither ADA nor ASPEN address the specific needs of TBI patients. EBGS FOR MODERATE OR MILD TBI AND CONCUSSION DoD’s Updated Mild Traumatic Brain Injury (mTBI) in Non-Deployed Medical Activi- ties (2008) addresses the assessment of TBI (and classification into acute [injury to 7 days], subacute [8–90 days], and chronic [> 90 days]), visual complaints, balance and hearing, use of imaging, medication management, and specialty referral and duty restrictions. The guideline recommends a multidisciplinary team with some identified specialties, but does not specify a practitioner with nutrition expertise (e.g., a registered dietitian) as a member of that team. The VA/DoD Evidence-Based Clinical Practice Guideline for Management of Concussion/ Mild Traumatic Brain Injury (2009) includes a consensus document with definitions, clas- sification and taxonomy, and guidelines and tools for initial presentation including screening and management of symptoms and follow-up of persistent symptoms for individuals with mild TBI. The guidance acknowledges the two previously developed DoD guidelines for management of mild TBI in theater and in nondeployed circumstances. A summary of the nutrition-related content of this guideline is included in Appendix B, Table B-2. Key recom- mendations are summarized here. Nutrition-related assessment factors include nausea and vomiting as well as changes in appetite, taste, or smell. DoD guidance for nondeployed settings also mentions the need to assess weight status and, in cases with a body mass index greater than 30, consider referral to polysomnogram (sleep study) to evaluate for sleep apnea. Nutritional interventions mentioned in DoD guidance include the use of novel therapy (unspecified nutrition supplements). The VA/DoD guideline addresses limiting caffeine, alco- hol, and herbal supplements, specifically some “energy” products that may interact with psy- chiatric medication and lead to hypertensive crisis. The VA/DoD guideline also mentions that nutritional supplements are being explored for potential treatment applications, and should only be included as part of a research protocol with institutional review board oversight.

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29 NUTRITION IN CLINICAL PRACTICE GUIDELINES FOR TBI Although all of the guidelines acknowledged nausea and vomiting as side effects of med- ications used in treating TBI, none specifically addressed their impact on weight in the longer term or a need for referral for complete nutritional assessment by a registered dietitian. CONCLUSIONS AND RECOMMENDATIONS Medical and nutrition care in the field, military treatment facilities, VA medical facili- ties, and in the home environment after discharge from medical treatment facilities are in- creasingly guided by EBGs. The TBI-specific EBGs currently available are extremely limited in their discussion of nutrition assessment, nutrition-specific interventions, and nutrition monitoring and evaluation criteria. The generic critical-illness EBGs that may apply do not specifically identify any unique nutritional concerns of TBI patients. There is general agree- ment among the existing EBGs on the need to determine energy requirements and to meet those needs in acute TBI early in treatment, the preference of use of enteral nutrition over parenteral nutrition when possible (in U.S. guidelines), and the need to maintain serum glu- cose control. The consensus is less clear on the use of antioxidants and immune-enhancing formulas, the method or frequency of determining energy requirements, and the percentage of energy needs that should be met in acute TBI treatment. The body of research to support clinical practice guidelines specific to the nutrition care of TBI patients is extremely limited. To aid those preparing such guidelines, specific ques- tions of interest for future research are included in Appendix C, Table B-3. The questions are based on the recommendations of the committee (Chapters 6–16) and have been tabulated in the Population, Intervention, Comparator, Outcome format. The general topics are: • Identification of specific nutrients, dietary supplements, and food components that promise benefits in providing resilience or treating TBI and for which nutritional status should be assessed in the military population. • Determination of optimal feeding regimens (e.g., energy needs and sources, route of administration, novel nutrition therapies) at various points (e.g., less than 24 hours, 24 hours to 7 days, post 7 days, chronic home care) within the nutrition care treat- ment cycle for varying levels of severity of TBI injury. • Identification of biomarkers and assessment indicators to reflect level of mitochon- drial function and inflammatory responses. RECOMMENDATION 2-1. Evidence-based nutrition guidelines specific for severe TBI should be updated. These guidelines should address unique nutritional concerns of severe TBI when different from generic critical-illness nutrition guidelines (e.g., meeting energy needs and benefits of specific nutrients, food components, or diets). In addition, current guidelines to manage mild and moderate TBI should include recommendations for nutritional interventions. The guidelines should be developed in a collaborative man- ner with the various key stakeholders (e.g., ADA, VA, DoD). REFERENCES ADA (American Dietetic Association). 2006. Critical illness evidence-based nutrition practice guideline. American Dietetic Association. http://www.adaevidencelibrary.com/topic.cfm?cat=2799 (accessed October 26, 2010). ADA. 2010. ADA method of creating evidence-based nutrition practice guidelines. American Dietetic Association. http://www.adaevidencelibrary.com/category.cfm?cid=16&cat=0&library=EBG (accessed October 26, 2010).

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30 NUTRITION AND TRAUMATIC BRAIN INJURY Bratton, S. L., R. M. Chestnut, J. Ghajar, F. F. McConnell Hammond, O. A. Harris, R. Hartl, G. T. Manley, A. Nemecek, D. W. Newell, G. Rosenthal, J. Schouten, L. Shutter, S. D. Timmons, J. S. Ullman, W. Videtta, J. E. Wilberger, and D. W. Wright. 2007. Guidelines for the management of severe traumatic brain injury. XII. Nutrition. Journal of Neurotrauma 24(Suppl 1):S77–S82. DoD (Department of Defense). 2008. Updated mild traumatic brain injury (mTBI) clinical guidance in non- deployed medical activities. http://www.dvbic.org/images/pdfs/Providers/mTBI_recs_for_ CONUS.aspx (ac- cessed January 19, 2011). Grilli, R., N. Magrini, A. Penna, G. Mura, and A. Liberati. 2000. Practice guidelines developed by specialty societ- ies: The need for a critical appraisal. Lancet 355(9198):103–106. Guyatt, G. 2002. Users’ guide to the medical literature: Essentials of evidence-based clinical practice. Chicago, IL: American Medical Association. Guyatt, G. H., R. B. Haynes, R. Z. Jaeschke, D. J. Cook, L. Green, C. D. Naylor, M. C. Wilson, and W. S. Richardson. 2000. Users’ guides to the medical literature: XXV. Evidence-based medicine: Principles for ap- plying the users’ guides to patient care. The Journal of the American Medical Association 284(10):1290–1296. Hill, G. B., and A. Bradford. 1965. The environment and disease: Association or causation? Presented at the Pro- ceedings of Royal Society of Medicine. Howick, J., I. Chalmers, P. Glasziou, T. Greenhalgh, C. Henegham, A. Liberati, I. Moschetti, B. Phillips, H. Thornton, O. Goddard, and M. Hodgkinson. 2011. The Oxford 2011 table of evidence. Oxford Centre for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o=5653 (accessed January 19, 2011). Kattelmann, K. K., M. Hise, M. Russell, P. Charney, M. Stokes, and C. Compher. 2006. Preliminary evidence for a medical nutrition therapy protocol: Enteral feedings for critically ill patients. Journal of the American Dietetic Association 106(8):1226–1241. Knuth, T., P. Letarte, G. Ling, L. Moores, P. Rhee, D. Tauber, and A. Trask. 2005. Guidelines for the field manage- ment of combat-related head trauma. New York: Brain Trauma Foundation. Kreymann, K. G., M. M. Berger, N. E. P. Deutz, M. Hiesmayr, P. Jolliet, G. Kazandjiev, G. Nitenberg, G. van den Berghe, J. Wernerman, C. Ebner, W. Hartl, C. Heymann, and C. Spies. 2006. ESPEN guidelines on enteral nutrition: Intensive care. Clinical Nutrition 25(2):210–223. McClave, S. A., R. G. Martindale, V. W. Vanek, M. McCarthy, P. Roberts, B. Taylor, J. B. Ochoa, L. Napolitano, and G. Cresci. 2009. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and En- teral Nutrition (ASPEN). Journal of Parenteral and Enteral Nutrition 33(3):277–316. Mcilvoy, L., and K. Meyer. 2008. Nursing management of adults with severe traumatic brain injury. Glenview, IL: American Association of Neuroscience Nurses. Sackett, D. L., W. M. Rosenberg, J. A. Gray, R. B. Haynes, and W. S. Richardson. 1996. Evidence based medicine: What it is and what it isn’t. British Medical Journal 312(7023):71–72. Thomas, L., N. Cullum, E. McColl, N. Rousseau, J. Soutter, and N. Steen. 1999. Guidelines in professions allied to medicine. Cochrane Database of Systematic Reviews Issue 1. Art No.:CD000349. VA/DoD (Department of Veterans Affairs and Department of Defense). 2009. VA/DoD clinical practice guideline for management of concussion/mild traumatic brain injury. http://www.healthquality.va.gov/mtbi/concus- sion_mtbi_full_1_0.pdf (accessed January 19, 2011).