The Harris–Benedict equation estimates basal energy expenditure (BEE) to determine caloric requirements. The Harris–Benedict equations are specific to men and women based on weight, body mass index (BMI), and height and are as follows:

Weight is in kilograms (kg), height in centimeters (cm), and age in years. The BEE represents energy requirements in the fasting, resting, and non-stressed state, so it may not be completely accurate in trauma or surgical patients. In the presence of metabolic stress, the BEE must be multiplied by an empirically derived stress factor; this factor may grossly overestimate the true caloric needs of the individual and remains the source of controversy in using this formula in the critically ill. Overestimation of caloric needs results in complications such as overfeeding, hypercapnia, hyperglycemia, and hepatic steatosis. The new multiplication constants to estimate the stressed caloric needs range from 1.2 to 1.6 times the BEE. These new recommendations better estimate the caloric needs of even the most stressed patient scenarios, such as burns.

Indirect calorimetry is a tool used to measure resting energy expenditure (REE) and relies on the relationship of oxygen consumption and carbon dioxide production. Because of the components necessary to calculate the REE, patients should be ventilated for best accuracy, although there is support to use it even in spontaneously breathing patients. It is recommended that steady state be achieved, defined as a change in either parameter of less than 10% over 5 min or more [23]. The REE obtained should then be used to estimate the patient’s baseline nutritional goal. Indirect calorimetry may be helpful when overfeeding would be undesirable (as in diabetes, obesity, or chronic obstructive pulmonary disease), underfeeding would be especially detrimental (renal failure, large wounds), physical or clinical factors promote energy expenditure that deviates from normal, drugs are used that may significantly alter energy expenditure (paralytic agents, beta-blockers, corticosteroids), patient response to calculated regimens is suboptimal, or body habitus makes energy expenditure predictions challenging (morbid obesity, quadriplegia).

The respiratory quotient is another derivative from the components of the indirect calorimetry. The formula is below:

Respiratory quotient (RQ)  =  V_O2/V_CO2  =  CO₂ production/O₂ consumption.

The RQ is a gross measurement of substrate utilization [24]. When an RQ value ≥1 is obtained, CO₂ production may be increased by one of the two mechanisms: either a high proportion of nonprotein calories are being supplied as glucose (carbohydrates have RQ of 1) or less commonly, the patient is being provided excess calories. Failure to wean with a persistently elevated PCO₂ on an arterial blood gas should prompt measurement of the RQ. An RQ of 0.85 provides optimal utilization, while <0.7 suggests gross underfeeding and ketone utilization.

Both basic and clinical research suggests that the beneficial effects of enteral nutrition can be amplified by supplementing formulas with specific nutrients that exert immune-enhancing effects, including glutamine, arginine, nucleotides, and omega-3 fatty acids. There are numerous prospective randomized controlled trials comparing immune-enhancing enteral diets to standard enteral diet and most, but not all, demonstrate improved outcomes. The majority of trials are in trauma and cancer patients, though a few trials include mixed intensive care unit (ICU) and septic ICU patients.

The concept of pharmaconutrition allows the separation of nutritional support from the provision of key nutrients that may modulate the inflammatory and immune response associated with critical illness. This came about after the realization that the greatest benefit in clinical outcomes was from studies utilizing specific nutrients [16]. This is likely due to their effects on the enteric inflammatory response and the way in which they work to block inflammatory stimulation. Any event that stimulates a gastrointestinal inflammatory response and a change in gut perfusion alters the way that the gastrointestinal tract utilizes nutrients. Providing intraluminal alimentation to stressed mucosa of the gut improves intestinal transit [26]. Pharmaconutrients alone or as supplementation have been shown to decrease infectious complications and complication-associated length of hospital stay [27].

Glutamine is the primary fuel source for the enterocyte and is preferred to glucose as a fuel source in times of stress [28]. It is released from muscle during the stress response and then exploited as a signal mechanism, promoting immune regulation and cellular protection, and as a nutrient and source of energy [29]. But in addition, glutamine has anti-catabolic and antioxidant properties that enhance its use and its receipt at enterocytes. Furthermore it increases plasma concentration of arginine [30], which will be addressed later. Although glutamine can be provided both enterally and parenterally, it demonstrates the most benefit of barrier to infection and control of the immune response when given enterally [30]. Meta-analysis and prospective randomized trials for trauma and burn patients showed benefit of glutamine in these patient populations in terms of decreasing infectious complications and enhancing the gut’s use of other enteric nutrients [31–35]. Based on the available data, glutamine, despite the administration route, appears to lower infectious complications, decrease hospital length of stay, and enhance nutrient use in the critically ill patient [36, 37]. Heat-shock proteins, which serve as molecular regulators of denatured proteins, are induced by glutamine, which may be another way in which glutamine modulates the cyto-protection and inflammatory response [38–40]. Equally important is the lack of data showing adverse effect of using glutamine in either form.

Arginine is another modulator of immune response of the enteric system. It is produced both endogenously from glutamine and the urea cycle, and obtained from the diet. When there is normal physiology without ongoing stress response, arginine serves to enhance immune function, contribute to wound healing, and stimulate anabolic hormones. l-arginine is a substrate for nitric oxide, which itself enhances the inflammatory response. l-arginine and its pathway to creating nitric oxide is a potential target for modification of immune activation. Specifically in trauma patients it has been shown that the release of IL-4, IL-10, and transforming growth factor beta increases arginase I expression, which corresponds to increased immune cell arginase activity and decreased plasma arginine and citrulline levels [41, 42]. By shunting arginine use in this way, it can no longer be used as a substrate for nitric oxide synthase dimerization and nitric oxide production. Therefore, administration of supplemental arginine in the critically ill patient may reduce the amount of nitric oxide produced in the post-injury period. Arguing against this data is work from another group suggesting that arginine supplementation increases nitric oxide production, thereby amplifying the systemic inflammatory response syndrome (SIRS) response and increasing mortality in the trauma or critically ill patient [43, 44]. There exists data supporting and refuting the use of arginine supplementation for both enteral and parenteral routes of administration [45–48]. It is clear, however, that arginine supplementation in elective surgical patients is beneficial. A recent meta-analysis by Drover et al. demonstrated a significant decrease in postoperative complications and hospital length of stay when patients undergoing gastrointestinal surgery received pre-, peri-, or postoperative arginine supplementation [49]. The effect was greatest when the supplementation included arginine as well as omega-3 fatty acids and nucleotides.

Nucleotides play an active role in cellular proliferation and immune modulation and are building blocks for several intrinsic cellular molecules. They are produced de novo and by salvage pathways. T cell proliferation and appropriate recognition of antigen are thought to be dependent on the presence of nucleotide because it has been shown that artificial decrease in interleukin-2 is corrected by addition of supplemental nucleotide [50]. They are either purine or pyridimine derived with a ribose and one or more phosphate groups [51]. Similar to glutamine and arginine, intravenous (IV) and enteral forms are available. Infusions of nucleotides decrease bacterial translocation and decrease graft rejection [50, 52]. These references also show that parenteral doses of nucleotides, administered with TPN, decrease associated gut atrophy.

Omega-3 fatty acids are the active components of fish oils and have significant anti-inflammatory properties [53], the mechanism of which is likely a combination of functions including arachidonic acid displacement from cellular membranes, production of prostaglandins, and reduced activation of various nuclear factors [54]. Specifically, they target and down-regulate NF-κB and AP-1 [54] on the nuclear membrane and they down-regulate iNOS, thereby reducing production of nitric oxide. While there are no studies of critically ill patients who received only omega-3 fatty acid and no additional supplementation, there are three prospective randomized studies that included omega-3 fatty acid in the supplementation package and had a significant improvement in respiratory function of their critically ill patients [55–57].

Beyond activation of the immune system, the critically ill and traumatic patient suffers damage at the cellular level secondary to the effects of oxidation-induced injury. Antioxidants have been found to catalyze the breakdown of the substances that are implicated in causing this damage [58]. Superoxide dismutase, catalase, and glutathione peroxidase have been identified as antioxidants; cofactors include selenium, zinc, manganese, and iron. Supplementation of these substances decreases the inflammatory response and halts oxidative stress [59–61]. Similar to nucleotides, it has been shown that the number of days on mechanical ventilation and overall mortality can be reduced by supplementation of antioxidants and their cofactors [61–63]. The REDOX trial, a prospective randomized trial comparing enteral and parenteral glutamine and antioxidants in critically ill patients with organ failure, has just been completed. Thus far no adverse effects have been identified [58, 64].

While gastric and post-pyloric nutrition have been compared, statistically no difference is noted in the time to reach caloric goal, length of stay in the ICU, or length of ventilator time between the two [67]. There is a consistent delay in initiating gastric feeds when compared to post-pyloric feeds in surgical patients, but again, the ultimate outcomes data do not differ. In fact gastric feeds and post-pyloric feeds can achieve the same caloric supplementation in the same amount of time in the critically ill patients [68]. It has also been shown that initiating early enteric feeds (within 36 h) improves survival and decreases infectious complications [69].

If feeds are provided past the ligament of Treitz, enteral feeds do not require a hold for return to the operating room [70]. This is important in the surgical population where frequent trips to the operating room might otherwise greatly hamper uninterrupted full caloric nutrition in these patients. Aspiration during intubation remains a risk for patients who have been gastrically fed [71]. This same risk does not appear as evident even for patients who have continuous jejunal tube feeds running during their operations. There is no difference in aspiration risk in gastric or post-pyloric feeds with respect to aspiration risk or residuals [72].

Additionally the question of gastrointestinal prophylaxis in the patient who is ventilated and fed into the small bowel is significant. Gastric pH must be addressed in any patient intubated more than 48 h and undergoing non-gastric nutritional support. This is to prevent stress ulceration, which is a known complication of ICU patients. Because gastric tubes can be placed nasally and blindly by push technique easier than jejunal tubes, the natural tendency is toward placing nasogastric (NG) tubes for decompression and to pass a nasojejunal tube and feed it even if gastric. There may be a need for recommendations on post-pyloric feeds in ICU-level patients secondary to their frequent trips to the operating room, need for continuous uninterrupted feeds to prevent malnutrition, and prevention of aspiration. Equally one could argue for gastric feeds with head of bed elevation, which might cut the number of stress ulcers and reduce the number of procedures and sedation that ICU patients are getting for placement of endoscopic tubes.

The refeeding syndrome can occur in any nutritionally deplete individual regardless of the manner in which he or she is being fed. The syndrome is most frequently seen in patients who are alcoholics, have eating disorders, suffer from hyperemesis gravidarum, or who have experienced excessive, rapid weight loss following bariatric surgery. Symptoms are not limited to cardiac arrhythmias, organ failure, and death. The crux of the syndrome is that fat metabolism, which predominated in the unstressed, starved state, now with refeeding, switches to a primarily carbohydrate-based metabolism. The carbohydrate-based metabolism is responsible for a rapid uptake of electrolytes causing intra- and extracellular levels to drop quickly creating disturbances and related effects. Prevention is by recognizing inherent risks and repleting electrolytes before the syndrome can ensue. An additional strategy is to start feeds at one-third to one-half of goal and increase gradually. Electrolytes should be serially checked in high-risk patients.

There does not seem to be any decisive data regarding feeding the gut for patients on pressor therapy. Based on observational data, it appears that if vasopressors are being used for indications other than fulminant non-septic shock (such as phenylephrine for spinal perfusion), it is of little detriment to feed the gut. A nonocclusive pattern would be expected to involve the entire length of the bowel, and, if it were from feeds, would be expected to begin wherever feeds were initiated. For example, if the stomach is the point of nutritional entry, then any nonocclusive bowel necrosis would be expected to involve the stomach, even despite its robust blood supply. Patchy areas may result if the period of ischemia were short. However, the data appear to be lacking for definitive recommendations in such situations. The mortality for fulminant nonocclusive bowel necrosis approaches 50% [83].

Pancreatitis demands special attention. There is some debate in the literature of whether post-ligament of Treitz feeding prevents continued inflammation. Placement of endoscopic or push nasojejunal tubes has allowed the patient with pancreatitis to be fed enterally. There are several well-documented populations where outcomes have shown a positive benefit to enteral feeds as compared to nutrition provided by TPN [84, 85]. Despite previous concern that small bowel enteral feeds would still have some, even if minimal, effect on pancreatic stimulation, this has proven to be unfounded [86].

Although an uncommon phenomenon, chylothorax and even chyloperitoneum do require special attention. While overall this complication is more likely seen as a result of malignancy or operative management of malignancy, at our institution these are more often seen in the trauma population, after central line placements, with lumbar spine fractures, and iatrogenic. Recommendations include attempting nonoperative management with dietary modification and TPN, chest tube drainage to quantify the volume, followed by surgical ligation if the output continues of 1,500 ml/24-h periods or for more than 2 weeks [87]. When the volume of this problem is uncontrollable, TPN or enteral feeds with medium-chain fatty acids seem to be most effective in decreasing the output. We typically use elemental formulas, such as Vivonex, for several weeks to ensure adequate seal of the lymphatic chain. Because the majority of chylothoraces seen on our service are secondary to traumatic insult, we are less hasty to perform operative management if patients show response to dietary modification. Substantial loss of protein and albumin occurs during the leak and this can lead to significant malnutrition and immunologic derangement [88, 89].

Enterocutaneous fistulas drain bowel content to the atmosphere and are the bane of surgical complication. They are thought to be caused by anastomotic failure and breakdown, intra-abdominal abscesses, foreign body erosion (for example, drains), malignancy, or inflammatory processes, and there is some data that they can be due to prolonged wound vac usage [90, 91]. They additionally can occur without identifiable cause. The biggest problems associated with them are damage and excoriation to the skin, loss of electrolytes and fluid with dehydration risk, and understanding how to provide effective and usable nutritional support [92]. Spontaneous closure is more likely if the output is low, the surrounding bowel is healthy, and the fistula resulted as a postoperative complication [93]. There is no definitive data in the literature regarding medications or supplements that will decrease fistula output and promote ultimate closure; glutamine, use of TPN with avoidance of enteral nutrition, and specific dressings have all been credited with enabling closure [94–98]. Spontaneous closure does not occur often, and if does not occur, indicates need for planned, delayed, surgical closure [99–101]. Mortality is directly correlated with output volume and additional related complications [93]. High-output fistula is defined as volume loss greater than 500 ml per 24-h period. This fluid contains significant electrolytes, mimicking the makeup of the specific fluid in that part of the gastrointestinal system. These electrolytes must be accounted for and appropriately replaced to prevent dehydration and complications related to specific electrolyte loss [102, 103]. Significant albumin wasting is associated with increased morbidity and mortality [104, 105].