Routes and Timing of Non-Oral Nutritional Interventions

Routes of nutrient administration

In the early stages of recovery a significant percentage of patients will be comatose and mechanically ventilated, precluding oral feeding. While enteral feeding is the preferred route of nutrient administration, feeding intolerance due to gastroparesis and ileus are common. Enteral feeding has been associated with a decrease in bacterial translocation and a reduced incidence of infection.

Enteral feeding intolerance may be related to increased intracranial pressure (Ott et al. 1990). Medications may also play a role in delayed gastric emptying. Although the placement of feeding tubes into the small bowel may theoretically improve tolerance, placement can be difficult and empirical evidence of superiority is lacking. If intolerance is prolonged, parenteral feeding may be indicated (Cerra et al. 1997), although the risk of hyperglycemia and cerebral edema are increased. 

Table: Enteral Nutrition vs. Total Parenteral Nutrition  


An RCT assessing the effect of glycemic control on parenteral nutrition complications in hospitalized, patients with brain injury revealed that treatment using an insulin infusion significantly decreased blood glucose levels when compared to a conventional glucose treatment (Mousavi et al. 2014). The experimental group also had significantly lower concentrations of C-reactive protein, as well as triglycerides compared to the control group (Mousavi et al. 2014). The study authors concluded that although more research is needed, insulin infusions improved some parenteral nutrition complications (Mousavi et al. 2014).

In a prospective study comparing total enteral feeding at various time points (within 3 days, 4-7 days, and after 7 days) there were unfavourable outcomes associated with total enteral feeding after 3 days (Dhandapani et al. 2012).  Those who began later lost significantly more mid-arm circumference and mid arm muscle circumference and had more malnutrition.  At the 3 and 6th month follow-up those receiving total enteral feeding within the first 7 days were more likely to have favorable outcomes on the Glasgow Outcome Scale (Dhandapani et al. 2012).

Nataloni et al. (1999) studied the effects of enteral, parenteral or both enteral and parenteral nutrition on a group of ABI patients while in the ICU.  Even though there was a negative nitrogen balance in all groups, all showed improvement over the course of the study. A positive nitrogen balance was only seen in the enteral group. In respect to nitrogen balances, Justo Meirelles and de Aguilar-Nascimento (2011) also evaluated the effects of enteral and parenteral nutrition in 22 patients with moderately severe TBI and found that parenteral nutrition delivered nitrogen more effectively. Both groups received increasing quantities of nitrogen each day, with those in the TPN group receiving significantly more. Despite the increased daily loss of nitrogen, all patients showed significant improvement in nitrogen balance as a result of nutritional therapy (Justo Meirelles & de Aguilar-Nascimento 2011). Other studies have found no difference in nitrogen balance between early parenteral nutrition and enteral feeding (Borzotta et al. 1994; Hadley et al. 1986).

In an early study by Rapp et al. (1983) fewer deaths occurred among individuals receiving total parenteral nutrition compared to standard enteral nutrition (0 vs. 44%, p<0.0001). However, there were no significant differences in terms of serum albumin levels over time. This is contrary to a later study which found patients who received enteral nutrition showed significant increases in serum pre-albumin and retinol-binding protein compared to the parenteral or enteral and parenteral groups (Nataloni et al. 1999).

Hausmann et al. (1985) conducted an RCT to investigate the effects of combined enteral –parenteral nutrition (CN) and a total parenteral nutrition (TPN) had on protein catabolism. Findings from the study noted the difference in the nitrogen balance between the two feeding regimes; however, these differences were not significant. In the CN group the mortality rate was 40% and in the TPN group it was 20%. Again these differences were not found to be significant. Study authors found no relevant differences in the metabolic data between each of these treatments (Hausmann et al. 1985).


There is Level 2 evidence suggesting enteral nutrition and parenteral nutrition is effective in providing an increase in calories to patients with ABI.

There is conflicting data when looking at the nitrogen balance of patients with ABI as to which method of feeding is most effective.

Based on a single RCT, there is Level 2 evidence that TPN can safely be administered without causing serum hyperosmolality or influencing intracranial pressure levels in patients post ABI. 



Both enteral and parenteral feeding are safe and have been shown to provide an increase in caloric intake; however, there is conflicting data as to which method allows for the greatest increase in nitrogen balance.

 Enteral feeds are less expensive and maybe more effective than parenteral feeds.

Further research is needed to investigate the effect of both feeding routes on nitrogen balance and mortality.


Enhanced Enteral Nutrition

Enteral feeding solutions enriched with immune-enhancing nutrients may decrease the occurrence of sepsis and reduce the inflammatory response. Theoretically, glutamine may improve the nutrition of both the gut mucosa and immune cells, while probiotic bacteria could favorably alter the intraluminal environment, competing for nutrients and adhesion sites with pathogenic bacteria. These co-operative actions may reduce the rate of bacterial translocation and, thus, decrease both the incidence of infection and the length of hospitalization (Falcao de Arruda & de Aguilar-Nascimento 2004).

Table: Enhanced Feeding Solutions


There is Level 1b evidence, based on a single RCT, that enhanced enteral nutrition can reduce the incidence of infection, and reduce both the ventilator dependency period and length of stay.

Timing of Enteral Nutrition

Early enteral feeding is desirable as a means to prevent intestinal mucosal atrophy and to preserve gut integrity; although, as previously noted, feeding intolerance occurs frequently. The following table contains literature surrounding the timing of enteral feeding. 

Table: Timing of Enteral Feeding

Chourdakis et al. (2012) compared delayed enteral feeding with early enteral feeding in 59 individuals post severe TBI. Although rates of complications were comparable between groups, the length of feeding for the early enteral feeding group was significantly shorter than the length of feeding for the delayed group (p<0.024). Hormonal measurements also indicated that those in the early group showed significant improvement on several of hormonal measures (Chourdakis et al. 2012). Similarly, Minard et al. (2000) found timing had no significant impact on mortality, length of stay or complications. Further, enhanced enteral nutrition was shown to accelerate neurologic recovery while reducing complications and also inflammatory post injury responses (Taylor & Fettes 1998; Taylor et al. 1999).

A Cochrane review by Yanagawa, Bunn, Roberts, Wentz, and Pierro (2000) identified six RCTs that addressed the timing to initiation of feeding and mortality as an outcome. The relative risk for death associated with early nutritional support was 0.71 (95% CI 0.43-1.16). The pooled relative risk from three trials, which also assessed death and disability, for early feeding was 0.75 (0.50-1.11). Although the results were not statistically significant, it was concluded that early feeding may be associated with a trend towards better outcomes in terms of survival and disability (Yanagawa et al. 2000). 


There is Level 1b evidence suggesting the early enteral nutrition results in a better hormonal profile of patients with TBI and may contribute to better clinical outcomes.

There is Level 2 evidence suggesting that initiating enteral feeding at goal rate will increase the percentage of prescribed energy and protein actually received.

Timing of Parenteral Nutrition

Early parenteral nutrition support provided directly following injury could assist in the maintenance of immunocompetence and help reduce the incidence of infection following ABI (Sacks et al. 1995). 

Table: Timing of Parenteral Feeding

The study by Sacks et al. (1995) found that in individuals with closed head injuries early parenteral nutrition was beneficial in modifying immunologic function. More specifically, it aided in improving CD4 cells, CD4-CD8 ratios, and T-lymphocyte responsiveness to Con A.

There is Level 2 evidence that early parenteral nutrition support of closed head-injury patients appears to modify immunologic function by increasing CD4 cells, CD4-CD8 ratios, and T-lymphocyte responsiveness to Con A. 


 Early parenteral nutrition support of ABI patients appears to modify immunologic function.


 Types of Enteral Feeding Tubes

Early enteral feeding has been associated with improved outcomes; however, the effectiveness of the intervention may vary depending on the mode of feeding. Nasogastric feeding tubes have been associated with increased incidence of pneumonia, while theoretically, feeding tubes placed more remotely decrease the risk. Gastronomies are proved to be a safe and dependable process used to provide enteral access for meeting nutritional needs of patients with ABI and delivering essential medications (Harbrecht et al. 1998).

Table: Early Gastrostomy


There is Level 1b evidence that the risk of developing pneumonia is higher among ventilated patients (stroke and head injury) fed by a naso-gastric tube compared with a gastrostomy tube.


 There is an increased risk of developing pneumonia for ventilated patients fed by a naso-gastric versus a gastrostomy tube.


 Metoclopramide and Enteral Feeding

Individuals who sustain a severe TBI often show signs of gastroparesis. For many individuals with a severe ABI, their energy requirements may reach 60% more than predicted. Metoclopramide has been used, and continues to be used, despite the inconsistent findings supporting its use (Nursal et al. 2007). To enhance the effectiveness of enteral nutrition metoclopramide has been used with limited success (Nursal et al. 2007).

Table: Metoclopramide and Enteral Nutrition

In a single RCT by Nursal et al. (2007) compared a control group and a treatment group that had been receiving 10 mg of metoclopramide. When looking at the absorption parameters of the two groups a small non-significant difference was found, with the levels in the treatment group being slightly more pronounced. Overall, the study showed no advantages to metoclopramide in a TBI population. 


There is Level 1b evidence indicating that metoclopramide is not effective as an aid to gastric emptying. 


 The therapeutic benefits of using metoclopramide to aid in gastric emptying are minimal.