There are insufficient data to support a Level I recommendation for this topic.

Patients should be fed to attain full caloric replacement by day 7 post-injury.

There are still few studies specifically addressing the impact of nutrition on traumatic brain injury (TBI) outcome. The effects of TBI on metabolism and nitrogen wasting have been studied most thoroughly. Prior to the 1980s, there were occasional case reports of hypermetabolism in TBI. The general attitude toward nutritional replacement was based on the assumption that, due to coma, metabolic requirements were reduced. However, over the last 25 years, numerous studies have documented hypermetabolism and nitrogen wasting in TBI patients. Data measuring metabolic expenditure in rested comatose patients with isolated TBI yielded a mean increase of approximately 140% of the expected metabolic expenditure with variations from 120% to 250% of that expected. These findings were consistent whether corticosteroids were used or not. Since the 2000 guidelines, two Class II studies have been conducted.

For this update, Medline was searched from 1996 through April of 2006 (see Appendix B for search strategy), and results were supplemented with literature recommended by peers or identified from reference lists. Of 33 potentially relevant studies, 4 were added to the existing tables and used as evidence for this question (Evidence Table I).

Researchers found that, in TBI patients, paralysis with pancuronium bromide or barbiturate coma decreased metabolic expenditure from a mean of 160% of that expected to 100-120%. This finding suggests that a major part of the increased metabolic expenditure is related to muscle tone. Even with paralysis, energy expenditure remained elevated by 20-30% in some patients. In the first 2 weeks after injury, energy expenditure seems to rise regardless of neurological course.

Nitrogen balance is an important measure of the adequacy of caloric intake and metabolism. The acceptable amount of nitrogen loss has not been quantified and has not been subjected to Class I studies relating it to global outcome. Randomized controlled trials (RCTs) measuring nitrogen balance or the degree of nitrogen loss as a surrogate of outcome have been performed but because they do not measure patient outcomes, they are not included as evidence for this topic. However, data from these studies suggest that at a high range of nitrogen intake (>17 g/day), less than 50% of administered nitrogen is retained after TBI. Therefore, the level of nitrogen intake that generally results in <10 g nitrogen loss per day is 15-17 g N/day or 0.3-0.5 g N/kg/day. This value is about 20% of the caloric composition of a 50-kcal/kg/day feeding protocol. Twenty percent is the maximal protein content of most enteral feedings designed for the hypermetabolic patient. Twenty percent is the maximal amino acid content of most parenteral formulations for trauma patients which generally contain > 15% protein calories.

Two studies evaluated the relationship of caloric intake to patient outcomes. One Class II study found that the consequence of severe undernutrition for a 2-week period after injury was a significantly greater mortality rate as compared to full replacement of measured calories by 7 days. A subsequent Class III study found no difference in morbidity at 6 months with full replacement at 3 versus 9 days.

To achieve full caloric replacement by 7 days, nutritional replacement is usually begun no later than 72 h after injury. One Class II study demonstrated fewer infective and overall complications by starting feeding (jejunal and/or gastric) at a rate that met the estimated energy and nitrogen requirements starting on day 1 after injury. The study also showed that these patients had a higher percentage of energy and nitrogen requirements met by the end of the first week. There was a trend towards improvement at 3 months but no difference in outcome at 6 months as measured by the Glasgow Outcome Scale (GOS) score. There is evidence to suggest that 2-3 days are required to gradually increase feedings to full replacement whether feeding is by jejunal or gastric route. Intravenous hyperalimentation is also started at levels below resting metabolism expenditure and advanced over 3 days. Whichever method is used, feedings are usually begun within 72 h of injury in order to achieve full nutritional support.

There have been no published studies comparing different specific formulations for parenteral or enteral nutrition in the setting of human TBI. Except for the protein content, the appropriate combination of the core components of nutritional support (carbohydrates, lipids, and proteins) are based on the critical care literature. As discussed above, the recommended amount of protein in enteral and parenteral formulations should make up about 15% of the total calories. The use of branch chain amino acids has not been studied in TBI. There is evidence in critical care literature that branch chain amino acids improve outcome in septic patients. Glutamine supplementation may also be beneficial by decreasing the infection rate, but it has yet to be adequately studied in TBI patients. Immune enhancing and immune modulating diets containing glutamine, arginine, omega-3 fatty acids, and nucleotides have been studied in the critical care and surgical settings but not in TBI patients specifically.

There are three options for the method of early feeding: gastric, jejunal, and parenteral. Some reports indicate that jejunal and parenteral replacement produce better nitrogen retention than gastric feeding. Gastric alimentation has been used by some investigators. Others have found altered gastric emptying or lower esophageal sphincter dysfunction to complicate gastric feeding. One study reported better tolerance of enteral feeding with jejunal rather than gastric administration. In studies of both gastric and jejunal administration, it has been possible to achieve full caloric feeding in most patients by 7 days after injury.

Percutaneous endoscopic gastrostomy is well tolerated in TBI patients, but there is the concern that early intragastric feeding may pose the risk of formation of residual, delayed gastric emptying, and aspiration pneumonia. However, one Class III found 111/114 (97%) patients tolerated intragastric feeding (started at an initial rate of 25 mL/h and increased by 25 mL/h every 12 h until target was reached) without complication.13 Another Class III study demonstrated better feeding tolerance with continuous compared to bolus feeding and were able to meet 75% of nutritional goals faster. In this study, the authors also identified other significant independent predictors of feeding intolerance (use of sucralfate, propofol, pentabarbitol and days of mechanical ventilation, older age, admission diagnosis of either intracerebral hemorrhage or ischemic stroke). Use of prokinetic agents failed to improve tolerance to gastric feeding. There was no difference in clinical outcome (GOS, ICU, and hospital length of stay) with continuous versus bolus feeding.

Jejunal feeding by gastrojejunostomy avoids gastric intolerance found in gastric feeding and the use of intravenous catheters required in total parenteral nutrition. Jejunal alimentation by endoscopic or fluroscopic, not blind, placement has practical advantages over gastric feeding. A higher percentage of patients tolerate jejunal better than gastric feeding early after injury (first 72 h) with less risk of aspiration. Increasingly, parenteral nutrition is started early after injury until either gastric feedings are tolerated or a jejunal feeding tube can be placed.

The risk of infection has not been shown to be increased with parenteral nutrition as compared to enteral nutrition in TBI patients. The primary advantage of parenteral nutrition is that it is well tolerated. While in laboratory animals, parenteral nutrition may aggravate brain swelling, the available evidence does not indicate this is a clinical problem. No clearly superior method of feeding has been demonstrated either in terms of nitrogen retention, complications, or outcome.

Hyperglycemia has been shown to aggravate hypoxic ischemic brain injury in an extensive body of experimental literature with animals. One such study of cortical contusion injury in rats found hyperglycemia to exacerbate cortical contusion injury with superimposed ischemia. In two Class III human studies, hyperglycemia has been associated with worsened outcome.

Zinc is the only supplement studied in detail in a TBI population. One small pilot Class II study reported a better 24-h peak GCS motor score at two time points after injury (days 15 and 21) with zinc supplementation. There was also a significant improvement in two visceral protein levels (serum prealbumin, retinol binding protein) and a trend towards lower mortality.

Data show that starved TBI patients lose sufficient nitrogen to reduce weight by 15% per week; 100-140% replacement of Resting Metabolism Expenditure with 15-20% nitrogen calories reduces nitrogen loss. Data in non-TBI injured patients show that a 30% weight loss increased mortality rate. The data support feeding at least by the end of the first week. It has not been established that any method of feeding is better than another or that early feeding prior to 7 days improves outcome. Based on the level of nitrogen wasting documented in TBI patients and the nitrogen sparing effect of feeding, it is a Level II recommendation that full nutritional replacement be instituted by day 7 post-injury.

Studies are needed to determine if specific nutritional formulations and the addition of vitamins and other supplements can improve outcome of TBI patients. There is still some debate with regards to the timing of feeding, rate of the achievement of target caloric intake and method of delivery that could be answered by well designed clinical trials.