INTRODUCTION — Enteral nutrition support refers to the provision of calories, protein, electrolytes, vitamins, minerals, trace elements, and fluids via an intestinal route. The available formulations, components, delivery, and complications of enteral nutrition are reviewed here. The goals, outcomes, indications, contraindications, nutritional requirements, and timing of initiation of enteral nutrition are discussed separately. (See "Nutrition support in critically ill patients: An overview".)
INDICATIONS AND CONTRAINDICATIONS — The indications and contraindications for enteral nutrition are described elsewhere. (See "Nutrition support in critically ill patients: An overview".)
INITIATION — To initiate enteral nutrition, appropriate access must be obtained and the prescription needs to be determined. The prescription includes the formulation, composition, delivery strategy, and delivery rate [1]. Determination of the presence of gut contractility is subjective and not an absolute requirement prior to initiation. Enteral nutrition is typically not initiated until patients are relatively hemodynamically stable (which includes those on weaning or modest vasopressor support).
Access — Enteral nutrition is most commonly delivered into the stomach (gastric feeding). However, it can also be administered into more distal parts of the alimentary tract (post-pyloric), particularly in those intolerant of gastric enteral nutrition (eg, those with delayed gastric emptying or gastric outlet obstruction).
Gastric — Gastric feeding is typically delivered via an orogastric or nasogastric tube. Such tubes are available in two varieties:
●Sump tubes are larger and stiffer. They are generally inserted for gastric decompression and then used for short periods to deliver enteral nutrition when gastric decompression is no longer necessary. Concerns about longer-term use include nasal and esophageal erosion and sinusitis.
●Feeding tubes are of smaller diameter, more flexible, and often require a stylet for insertion. A feeding tube's position should be confirmed radiographically before it is used because it is frequently misplaced into an airway [2]. Once its position is confirmed, the stylet should be removed and never replaced. Trying to replace the stylet while the tube is in the patient can lead to the stylet protruding from the outlet of the tube and result in inadvertent bowel puncture. Some feeding tubes cannot be used for gastric decompression because the soft walls tend to collapse when suction is applied.
Feeding via tube through percutaneous endoscopic gastrostomy (PEG), percutaneous radiologic gastrostomy, and surgical gastrostomy are alternative approaches to delivering gastric feedings. A surgical gastrostomy tube can be inserted laparoscopically or by an open surgical approach. (See "Gastrostomy tubes: Uses, patient selection, and efficacy in adults" and "Gastrostomy tubes: Complications and their management".)
Post-pyloric — Guidelines recommend post-pyloric feeding for those at high risk for aspiration [1,3]. The reduction in the incidence of pneumonia is small [4]. Post-pyloric tube placement is often challenging and may need to be reserved for patients with documented delayed gastric emptying or gastric outlet obstruction.
Several techniques have been described for blind insertion of feeding tubes that terminate beyond the pylorus, usually ending in the first or second part of the duodenum [5]. All are technically difficult and require advanced training. As an example, the Corpak 10-10-10 protocol involves administering metoclopramide 10 minutes prior to tube insertion and then gently advancing the feeding tube from the stomach in 5 cm increments [6]. After each increment of advancement, the wire is withdrawn slightly to check for resistance, with resistance indicating possible coiling or kinking of the feeding tube. Post-pyloric positioning is confirmed radiographically.
Alternative approaches to blind insertion are available. These require specific technology that either helps monitor the position of the tube, or helps pull the tube into the small intestine. These include tubes with radio emitters on the tip of the guidewire the position of which is monitored, as well as fiberoptic guidewires that enable the mucosa to be visualized. Other alternatives include endoscopically placed nasal tube, percutaneous endoscopic, percutaneous radiological, or surgical feeding enterostomy.
Historically, many feeding tubes were manufactured with weighted ends with the theory that the weight would increase the possibility that the tube would migrate past the pylorus. Randomized trials have shown that these tubes pass less frequently and remain post-pyloric for shorter durations than do unweighted tubes [6,7].
Tubes used for post-pyloric feeding may have two ports, a proximal port to drain the stomach and a distal port to deliver enteral nutrition into the distal duodenum or proximal jejunum. These tubes transit through the stomach and into the small bowel, but most often require endoscopic placement. Post-pyloric feeding tubes are most useful in patients with the prolonged inability to tolerate gastric feedings, gastric outlet obstruction, duodenal obstruction, a gastric or duodenal fistula, severe gastroesophageal reflux, or the inability to have a gastric enteral access tube due to altered anatomy [8].
Formulations — There are many products available for enteral nutrition. Common differences between formulas include osmolarity, caloric density, and amount of protein per calorie, as well as electrolyte, vitamin, and mineral content. Most are formulated to provide 100 percent of recommended daily vitamin and mineral dose when a minimum of approximately 1000 or more kilocalories are delivered per day. In addition, there may be differences related to whether they are intact or predigested, fiber is present or absent, and disease-specific nutrients are present or absent [9,10]. Standard enteral nutrition provides sufficient nourishment for most critically ill patients if given with caloric adequacy, although concentrated and predigested enteral nutrition may be preferable for selected patients [1].
Standard — The following characteristics are typical of standard enteral nutrition:
●Isotonic to serum
●Caloric density of approximately 1 kcal/mL
●Lactose-free
●Intact (nonhydrolyzed) protein content of about 40 g/1000 mL (40 g/1000 kcal)
●Nonprotein calorie to nitrogen ratio of approximately 130
●Mixture of simple and complex carbohydrates
●Long-chain fatty acids (although some are now including medium-chain and omega-3 fats)
●Essential vitamins, minerals, and micronutrients
The daily amount of enteral nutrition is tailored to the nutritional and fluid needs of each patient. Most patients require supplementation of water, in addition to the feeds. All feeding tubes should have periodic water flushes to minimize clogging. Only water should be used for flushing. Acidic fluids should be specifically avoided as they increase clogging [11]. (See 'Amount and rate' below.)
Concentrated — Critically ill patients frequently require volume restriction (eg, patients with respiratory failure, or volume overload). Concentrated enteral nutrition may be useful for such patients.
The standard composition of concentrated enteral nutrition is similar to that of standard enteral nutrition, except that it is mildly hyperosmolar to serum and has a caloric density of 1.2, 1.5, or 2.0 kcal/mL. The delivery of energy-dense enteral formula does not appear to infer benefit when compared with standard formulations. In a randomized trial of 3957 medical ICU patients who were mechanically ventilated and undergoing enteral feeding, despite administering an extra 600 kcal per day, an energy-dense formula (1.5 kcal/mL) did not result in a mortality benefit when compared with a standard formulation (1.0 kcal/mL) administered at the same rate (1 mL/kg of ideal body weight per hour) [12]. Similarly, no difference in ventilator-free days, duration of hospital stay, or infections was reported.
Historically, the hyperosmolality of concentrated enteral nutrition was thought to predispose patients to diarrhea or symptoms similar to dumping syndrome if infused rapidly. Current adult formulations rarely exceed approximately 750 mOsm/L and are rarely the primary cause of diarrhea. Dumping syndrome is characterized by symptoms of nausea, shaking, diaphoresis, and diarrhea shortly after eating foods containing high amounts of refined sugars. Concentrated enteral nutrition is less likely to be tolerated if it is delivered rapidly in tubes placed beyond the pylorus [13]. (See "Postgastrectomy complications".)
Predigested — Predigested enteral nutrition (previously called chemically defined, semi-elemental, or elemental) differs from standard enteral nutrition in that the protein is hydrolyzed to short-chain peptides and the carbohydrates are in a less complex form. The total amount of fat may be decreased, with an increased proportion of medium-chain triglycerides, or the triglycerides altered or structured to contain various mixes of fatty acids.
The use of predigested enteral nutrition is weakly supported by data. These have been proposed as potentially beneficial in patients with the following problems:
●Thoracic duct leak, chylothorax, or chylous ascites, since the medium-chain triglycerides do not enter the lymphatic capillaries in the small intestine. This is theoretical. Whether a reduction in chyle volume has not been tested, and the presence of food in the gut, rather than the components of it, may be more important in determining chyle volume.
●Digestive defects (eg, malabsorptive syndromes that are unresponsive to supplementation of pancreatic enzymes).
●Failure to tolerate standard enteral nutrition, such as persistent diarrhea.
Predigested enteral nutrition usually has a caloric density of 1 or 1.5 kcal/mL. It is not recommended as an initial tube feed in critically ill patients [1]. These are often used, without strong evidence, in patients with marginal gut function or a short gut because it is believed to be better tolerated. Patients who tolerate predigested enteral nutrition can then be transitioned to standard enteral nutrition.
The original formulations of predigested enteral nutrition included amino acids instead of peptides or proteins. These formulations are less commonly used today, since amino acid-based feedings are more hypertonic and may be less well tolerated.
Overall, studies of predigested feed products have not demonstrated differences in mortality, infectious complications, or the incidence of diarrhea when compared to standard enteral nutrition [14,15].
Critical illness — A variety of enteral feeding formulations were developed for patients with specific critical illnesses [16-18]. However, no such formulation has consistently demonstrated a beneficial effect on clinical outcomes. As a result, disease-specific enteral nutrition is not recommended over the traditional types of enteral nutrition. The exceptions are renal formulae for patients requiring fluid and electrolyte restriction, and glycemic control formulae for patients receiving bolus feeding.
Composition
Carbohydrate/fat — Enteral nutrition can deliver the same caloric density using different proportions of carbohydrate and fat. Low carbohydrate/high fat and high carbohydrate/low fat formulations exist, but neither is recommended for routine enteral nutrition.
Standard enteral nutrition delivers 49 to 53 percent of calories as carbohydrate and 29 to 30 percent of calories as fat. In contrast, low carbohydrate/high fat enteral nutrition typically delivers 28 to 40 percent of calories as carbohydrate and 40 to 55 percent of calories as fat. High carbohydrate/low fat enteral nutrition delivers only 15 percent of calories as fat.
Low carbohydrate/high fat enteral nutrition was developed with the intention of reducing the work of breathing and facilitating weaning from the ventilator. The rationale was that low carbohydrate enteral nutrition would lead to the production of less carbon dioxide; thus, a smaller minute ventilation would be necessary to maintain an acceptable arterial carbon dioxide tension (PaCO2) and prevent the need for, or reduce the amount of time of dependence on mechanical ventilation. Clinical studies have failed to uphold this theory. Excess total calories delay weaning, but enteral nutrition that is low in carbohydrate and high in fat does not seem to improve PaCO2 or weaning time [16,19]. Moreover, low carbohydrate/high fat enteral nutrition does not affect mortality, infectious complications, or ICU length of stay, compared to standard enteral nutrition [20,21].
High carbohydrate/low fat enteral nutrition has been scarcely studied. One trial randomly assigned 43 burn patients to receive either standard enteral nutrition or low fat/high carbohydrate enteral nutrition [22]. There was no difference in mortality or ICU length of stay.
Protein — Most guidelines suggest high-protein enteral nutrition (1.2 to 2 g per kg of ideal body weight per day) in patients with critical illness based upon observational studies that report improved mortality associated with this strategy [1,23-25].
High-protein enteral nutrition has been associated, in observational studies, with improved mortality in critically ill patients. As an example, in one prospective observational cohort study of 886 mechanically ventilated patients in medical-surgical intensive care units, a 50 percent reduction in 28-day mortality was reported in patients who reached their protein target compared to patients who only met their energy needs (hazard ratio 0.47, 95% CI 0.31-0.73) [24]. Randomized studies will be needed to confirm these results, as they could equally suggest that sicker patients are harder to feed.
Low-protein enteral nutrition is not recommended for routine use for patients with acute or chronic renal disease. Low-protein enteral nutrition was originally developed for patients with renal disease because of the widespread belief that protein restriction delays the progression of renal disease. However, clinical trials have shown that patients with renal failure can tolerate protein intake as high as 2.5 g per kg per day during critical illness [26]. Many renal formulas now have an increased content of protein in the hope of countering the catabolism of acute illness and/or dialysis. However, there is a significant lack of outcomes data relating to how much protein is desirable in patients with renal disease.
Renal formulas may be helpful in managing patients who require fluid and/or electrolyte restriction, such as patients with acute renal failure complicated by fluid overload, hyperkalemia, and/or hyperphosphatemia, or those on hemodialysis with difficulties managing electrolytes and volume. Standard feedings, however, are acceptable in patients with renal failure when electrolytes and volume are adequately managed. There are concerns that all enteral formulas exceed calcium removal capacity in patients on hemodialysis.
In contrast, these volume and electrolyte restricted formulas are likely to be inappropriate for patients on continuous renal replacement (CRRT). This technique is highly effective at removing electrolytes such as potassium and phosphate. We prefer standard feeds, fluid-restricted if necessary, for patients on CRRT.
Standard enteral nutrition delivers an intact (nonhydrolyzed) protein content of about 40 g/1000 kcal. In contrast, most renal enteral nutrition formulas deliver a protein content of 44 g/1000 kcal.
Peptides — Enteral nutrition has been developed that includes peptides instead of intact proteins. These are also referred to as predigested, or semi-elemental. The intended purpose of such nutrition is to improve absorption by bypassing hydrolysis of the intact protein to peptides. However, pooled analyses of randomized trials demonstrated no significant difference in mortality, infectious complications, or the incidence of diarrhea when peptide-based enteral nutrition was compared to standard enteral nutrition [15].
Due to their lack of benefit and higher cost, enteral nutrition with peptides instead of intact proteins is not recommended for routine use. However, there may be circumstances in which peptides may be preferable to intact proteins. Patients in these situations may also benefit from less complex carbohydrates and fats; thus, a predigested formulation may be considered. (See 'Predigested' above.)
Omega-3 fatty acids and antioxidants — Supplementation of enteral nutrition with antioxidants plus omega-3 fatty acids is not recommended in critically ill patients because data from large randomized trials and meta-analyses suggest that it is unlikely to be beneficial and may be harmful.
Supplementation of enteral formulas with antioxidants plus omega-3 fatty acids was proposed with the hope it would have an antiinflammatory effect in the lung [27]. This led to the evaluation of these feeding products in patients with acute lung injury or acute respiratory distress syndrome (ALI/ARDS). Evidence from randomized trials and meta-analyses is conflicting [17,28-32]:
●Trials suggesting no benefit and possible harm include a multicenter trial conducted by the ARDS Clinical Trials Network, 272 patients who were receiving mechanical ventilation due to ALI/ARDS were randomly assigned to receive either enteral nutrition supplemented with omega-3 fatty acids plus antioxidants or a control enteral feed [28]. The study was stopped early due to no effect and potential harm; patients receiving omega-3 fatty acids plus antioxidants had fewer ventilator-free days (14 versus 17.2 days), fewer ICU-free days (14 versus 16.7 days), and fewer organ failure-free days (12.3 versus 15.5 days). However, there was also a trend toward increased mortality (27 versus 16 percent). In the only trial comparing enteral feeds supplemented with omega-3 fatty acids alone (ie, no additional antioxidants) to control enteral feed, no differences were seen in inflammatory markers, duration of mechanical ventilation or mortality [31]. Similarly, meta-analyses reported no benefit from omega-3 fatty acids in patients with sepsis [33], patients undergoing cardiac surgery [34], and patients with ARDS [35].
●In contrast, an earlier trial randomly assigned 146 patients with ARDS to receive either a high fat antioxidant supplemented enteral feed with a significant component of the fats from omega-3 fatty acids, or a control high fat enteral feed with most of the fat from omega-6 rich oils and no additional antioxidant [29]. Enteral nutrition with antioxidants plus omega-3 fatty acids significantly decreased the number of days on the ventilator, the number of days in the ICU, and the frequency of new organ failure. There was also a nonstatistically significant reduction in mortality (16 versus 25 percent, relative risk 0.63, 95% CI 0.32-1.22). These results should be interpreted with caution, since the enteral feed that was used as a “control” is a nonstandard feed containing high amounts of omega-6 fatty acids. Two subsequent trials that used the same control enteral feed after it had been reformulated to contain less long-chain fatty acids and more medium-chain fatty acids reported similar results [17,30]. All of these trials used the same combination of antioxidants and omega-3 fatty acids and researchers received funding from the maker of the product.
Glutamine — Glutamine-enriched enteral nutrition is not recommended for routine use in most critically ill patients because trials have not found consistent improvement in clinical outcomes and have shown a potential for harm.
Glutamine supplementation of enteral nutrition has been evaluated in several meta-analyses and randomized trials of critically ill patients, most of which reported no convincing improvement in mortality or reduction in infectious complications [36]. Additionally, one large multicenter randomized study of glutamine supplementation in critically ill patients reported potential harm with a trend toward increased 28-day mortality in those receiving glutamine-enriched enteral nutrition [3].
Glutamine is a precursor for nucleotide synthesis and an important fuel source for rapidly dividing cells that is rapidly depleted in catabolic patients. It is metabolized by the liver, kidneys, and splanchnic tissue into glutamate and ammonia. Accumulation of glutamine and its byproducts may lead to adverse effects, such as encephalopathy.
Ornithine ketoglutarate — Ornithine ketoglutarate (OKG) is a glutamine precursor that efficiently restores pools of glutamine in catabolic patients. It is not recommended as an enteral nutrition supplement because clinical trials in burn patients failed to show any clinical benefit. A meta-analysis of three such randomized trials (163 burn patients) found no difference in mortality [37].
Arginine — Arginine is considered conditionally essential during critical illness, because it is utilized more quickly. It is required for normal immune function and healing, and it has important roles in nitrogen metabolism, ammonia metabolism, and the generation of nitric oxide. Despite this, arginine-enriched enteral nutrition is not recommended for routine use in critically ill patients.
Arginine-enriched enteral nutrition has been extensively compared to standard enteral nutrition, with inconsistent results. Whereas one randomized trial found that arginine-enriched enteral nutrition reduced infections and length of stay in burn patients [17], other studies suggested that arginine-enriched enteral nutrition was not beneficial and potentially harmful [38]. In a meta-analysis of 14 randomized trials (1624 patients) that compared arginine-enriched enteral nutrition to standard enteral nutrition in critically ill patients, there was no effect on mortality [39]. Similarly, a meta-analysis of 10 randomized trials (1154 patients) found no effect on infectious complications [39].
Prebiotics/probiotics — Prebiotics are nondigestible carbohydrates (fiber) that are used as enteral nutrition supplements with the hope of promoting the growth of beneficial bacteria in the bowel and of hindering the growth of harmful bacteria. Probiotics (eg, Lactobacillus species) are living microorganisms that are purported to provide a health benefit to the host when ingested. Routine supplementation of enteral nutrition with prebiotics or probiotics is not recommended because the pooled results from randomized trials demonstrate no effect on mortality or infectious complications [40-42]. At least one trial has found potential harm from probiotics [43,44].
Fiber — Fiber is frequently added to correct diarrhea or constipation in patients who are already receiving enteral nutrition [1]. However, there is no evidence that routine supplementation of enteral nutrition with fiber can prevent either problem [42,45-50], and therefore its routine use for prophylaxis of diarrhea or constipation is not recommended [51]. However, based on consensus opinion, switching to a mixed fiber-containing formula is appropriate when there is persistent diarrhea [51]. There is concern that fiber-containing formulas should be avoided in patients on vasopressors because bezoars have been reported in this setting [52], but this complication is rare.
We avoid fiber in patients we deem at very high risk for bowel dysmotility. For example, those on moderate doses of vasopressors or barbiturates for longer periods of time may have slow mid-gut transit, but there are others who routinely use fiber-containing formulas.
Most fiber-containing formulas contain a mixture of soluble fibers. Less soluble or gelatinous fibers such as that from psyllium may help solidify stool, but have been associated with clogging of the feeding tube. Highly soluble fibers, such as guar gum, wheat dextrin, inulin or fructooligosaccharides do not gelatinize when dissolved, and so should not increase tube clogging. Their effect is primarily osmotic. Support for the use of highly soluble fibers in those with diarrhea is weak, and based upon three [47,49,50] of five randomized trials [42,49,50] that showed a reduction in diarrhea using this type of fiber supplementation. None show changes in any other outcome. It is theorized that their fermentation to short chain fats improves colonic biology. But we theorize that because they do not gel, they may be equally likely to make diarrhea worse due to their osmotic effect, and suggest their discontinuation be considered when diarrhea persists in patients receiving them.
Vitamins and trace elements — Numerous clinical trials have examined the effect of antioxidants given as single nutrients (eg, selenium) [53] or as a combination of nutrients (selenium, copper, zinc, vitamin A, vitamin C, vitamin E, and N-acetylcysteine) on critically ill patients. The trials used a variety of methods to administer the nutrients, including supplementation of parenteral nutrition, a separate intravenous infusion, supplementation of enteral nutrition, and oral intake.
A meta-analysis of 21 randomized trials using antioxidant vitamins and trace elements demonstrated a reduction in mortality (risk ratio [RR] 0.82, 95% CI 0.72-0.93), duration of mechanical ventilation (weighed mean difference in days -0.67, 95% CI -1.22 0 -0.13), but no overall effect on ICU or hospital length of stay (LOS). There was no significant impact on mortality in studies with a lower mortality in the control group (RR 1.14, 95% 0.72-1.82), but there was a significant reduction in mortality in studies where the entrants had a higher risk of death (>10 percent mortality in control group; RR 0.79, 95% CI 0.68 -0.92) [54]. Regardless, routine supplementation of antioxidant vitamins is not recommended for critically ill patients, given other less supportive analyses. (See 'Omega-3 fatty acids and antioxidants' above.)
Few of the trials looked specifically at patients receiving enteral nutrition. Rather, most enrolled a heterogeneous sample of patients receiving either enteral or parenteral nutrition and did not look for differences in the effects of the vitamins and trace elements in these subgroups. As a result, it seems reasonable to provide vitamins and trace elements to critically ill patients, regardless of the type of nutrition support that they are receiving [1]. The optimal mixture of vitamins and trace elements is yet to be determined. Daily recommended allowances should not be routinely exceeded in the absence of well-designed and valid randomized trials.
Immune modulators — Supplementation of enteral nutrition with a combination of immune modulators (eg, glutamine, selenium, omega-3 fatty acids, and antioxidants) is not recommended in patients who are critically ill. While several meta-analyses of small randomized trials suggested that use of immune modulating nutrients reduced infections and improved recovery from critical illness, a large randomized trial has since reported no benefit and potential harm [55-58].
The effect of high-protein enteral nutrition containing immune modulating nutrients (IMHP) was examined in one multicenter, randomized, double-blind trial of 301 mechanically ventilated adult patients (MetaPlus) [58]. There was no difference reported in the rate of infections, duration of mechanical ventilation, or length of ICU or hospital stay. A higher six-month mortality rate was reported in a predefined subpopulation of medical patients with IMHP (54 versus 35 percent); this was not seen in the surgical or trauma patients. This study lends support to the lack of benefit and possible harmful effects of supplementation with immune modulators that was also seen in three large multicenter randomized trials that studied supplementation with some of the individual components in IMHP: glutamine, selenium, and omega-3 fatty acids [3,28,59].
Products supplemented with beta-hydroxy-beta-methylbutyrate (HMB) are available. There are, to our knowledge, no studies of these specific to critically ill patients. Given our prior experience with anabolic and immune modulating nutrients, routine use of these in the critically ill cannot be recommended until properly studied.
Continuous versus bolus — There is no evidence that either continuous or bolus (ie, intermittent) enteral nutrition is superior to the other. Two randomized trials compared the two approaches and found no differences in mortality, infections, or ICU length of stay [60-62]. Nonetheless, enteral nutrition is typically administered as a continuous or cycled infusion by many experts, particularly in patients at high risk of vomiting, reflux, and aspiration.
Amount and rate — The daily amount of enteral nutrition is tailored to the nutritional and fluid needs of each patient. A calorie goal of 18 to 25 kcal/kg/d is a reasonable initial range to use to meet the needs of a critically ill patient of normal weight. In practice, it is generally considered acceptable that enteral feeding be initiated in critically ill patients at a rate of 10 to 30 mL/hour (for standard enteral formulations), so called "trophic" feeding, for six days and then incrementally increased to the target rate. It is our practice to initiate feeds at 25 to 30 percent of estimated goal rate. In patients who are subjectively more critically ill, we do not attempt to increase further toward goal until the fifth to seventh day of critical illness. In less critically ill patients, advancement is made toward goal as tolerated, based on gastrointestinal symptoms and physical examination (ie, presence of abdominal distension). We do not use gastric residuals, unless greater than 500 mL, as criteria for tolerance, and are working toward cessation of routinely checking gastric volume (see 'Monitoring' below). Provided the enteral nutrition is paused infrequently, for issues such as gastric distension, diarrhea, or vomiting, this suggested approach should result in the patient ultimately reaching a stable target rate within a reasonable period of time. Initiating enteral nutrition as close as possible to target goal, or advancing more rapidly, is advocated by some for those who are malnourished, but randomized data are lacking to support this practice. (See "Nutrition support in critically ill patients: An overview", section on 'Nutritional requirements'.)
Two strategies have been used to initiate enteral nutrition, in general. They include incrementally increasing the infusion rate until the target maintenance rate is achieved, or initiating the infusion at the target maintenance rate. There is conflicting evidence regarding which approach is superior, with some trials suggesting that slowly increasing the infusion rate to the target is superior [63,64] and other trials finding that beginning at the target rate is more beneficial [65].
The best evidence suggests that initial low-volume enteral feeding has fewer undesirable effects than initial feeding at the target rate. The EDEN trial was a multicenter open-labelled trial that randomly assigned 1000 mechanically ventilated patients with acute lung injury to receive either full enteral feeding or low-volume enteral feeding (ie, full versus trophic feeding) for six days, after which both groups received full enteral feeding [66]. Full enteral feeding consisted of initiating enteral feeding at 25 mL per hour and then increasing the rate by 25 mL per hour every six hours until the target rate was achieved, as long as the gastric residual volume did not exceed 400 mL when checked prior to each rate increase. In contrast, low-volume enteral feeding consisted of initiating enteral feeding at approximately 10 to 30 mL per hour (approximately 30 percent of the maintenance target), continuing that rate for six days, and then advancing the infusion rate using the same protocol that was used in the full enteral feeding group. The trial found no differences in the number of ventilator-free days, 60-day mortality, frequency of infectious complications, or long-term physical or neurocognitive function [66,67]. However, the low-volume feeding group had less vomiting, smaller gastric residual volumes, lower mean plasma glucose levels, and less constipation. The low-volume feeding group also required fewer prokinetic agents and less insulin.
MONITORING — Patients on tube feeding are at risk for fluid imbalance, gut dysfunction, and electrolyte imbalance. Refeeding syndrome is often seen in chronically undernourished patients, especially those with electrolyte losses such as diarrhea, vomiting, or renal wasting. (See 'Complications' below and "Anorexia nervosa in adults and adolescents: The refeeding syndrome".)
It has long been standard clinical practice to check the patient's gastric residual volume (GRV) at regular intervals and/or prior to increasing the infusion rate of gastric tube feeding. This was done based on the theory that the risk of pneumonia would be minimized by recognizing gastric fluid accumulation and therefore predicting and reducing vomiting. However, this practice has now been shown to lack benefit, and is no longer recommended. If GRV is measured, volumes of less than 500 mL should not result in the holding of the feeds unless other signs of intolerance, such as distension, nausea, or vomiting, are present.
Studies have shown that measurement of gastric residuals correlates poorly with aspiration risk and is associated with a decrease in calorie delivery [68-70]. Further evidence against routine measurement of gastric residuals comes from an adequately powered, but unblinded trial in which 222 ICU patients were randomly assigned to monitoring of gastric residual volume every six hours, with adjustment of feeding rate for residuals over 250 mL, and another 227 patients received enteral feeding without monitoring of residuals (enteral feeds were only adjusted when patients experienced vomiting or regurgitation) [71]. The rate of ventilator associated pneumonia was not higher in the group without monitoring of gastric residuals. While there were almost twice as many vomiting episodes in the group without monitoring, the overall incidence of vomiting was relatively low. Other ICU outcomes such as duration of ICU-acquired infection, mechanical ventilation, hospital length of stay, and short-and long-term mortality were not different between the groups. Based on these findings, there is increasing consensus that the routine checking of gastric residual volumes is unnecessary in asymptomatic patients receiving tube feedings, and may inappropriately hamper calorie delivery. Gastric residuals should be measured if the patient exhibits a clinical change, such as abdominal pain, abdominal distension, or deterioration in hemodynamics or overall status.
COMPLICATIONS — There is a relative paucity of evidence regarding the frequency of adverse effects due to enteral nutrition. The limited evidence that exists suggests that the most common complications are aspiration, diarrhea, metabolic abnormalities, and mechanical complications.
Aspiration — Aspiration is discussed below. (See 'Prevention of aspiration' below.)
Diarrhea — Diarrhea is estimated to occur in approximately 15 to 18 percent of critically ill patients who receive enteral nutrition, compared to only 6 percent of such patients who do not receive enteral nutrition [72,73]. The precise mechanism is unknown, but alteration of intestinal transit or the intestinal microflora has been proposed. We have observed that feeding-related diarrhea is commonly associated with concomitant administration of medications that can cause diarrhea (eg, antibiotics, proton pump inhibitors) or medications in suspension. The latter are often administered using sorbitol, a non-absorbable sugar that induces diarrhea at high doses, as a vehicle. Concentrated feedings are only mildly hypertonic, and are unlikely to induce diarrhea.
Fiber is the best studied and most widely accepted therapeutic intervention for enteral nutrition-associated diarrhea if removal of potential culprit agents has been unsuccessful [50]. Fiber should be used with caution in patients with impaired peristalsis, such as those receiving pressors, and it is theorized that highly soluble short-chain fiber may worsen diarrhea via osmosis. (See 'Fiber' above.)
Enteral nutrition does not need to be interrupted for diarrhea and should be continued while the etiology is being investigated.
Metabolic — Adverse metabolic consequences of enteral nutrition include hyperglycemia, micronutrient deficiencies, and refeeding syndrome.
Refeeding syndrome is a potentially fatal condition resulting from rapid changes in fluids and electrolytes when malnourished patients are given oral, enteral, or parenteral feedings [74]. It is defined primarily by development of hypophosphatemia (including cardiovascular collapse, respiratory failure, rhabdomyolysis, seizures, and delirium when severe). Hypokalemia and hypomagnesemia also occur. Refeeding syndrome is described in greater detail elsewhere. (See "Anorexia nervosa in adults and adolescents: The refeeding syndrome".)
Fluid/water — All feeding products consist of only 70 to 80 percent water. As a result, they are unable to meet patients' normal water requirements alone (enteral nutrition providing 25 kcal/kg with a 1 kcal/mL formula provides an average of only 20 mL/kg of water). This may be beneficial for patients who require fluid restriction, but most patients require another source of water. Feeding tubes must be flushed regularly with water to avoid clogging, as well as with medication, and patients in ICUs are rarely without sources of intravenous fluids. This may suffice, but volume status should be monitored regularly.
Mechanical — Constipation is a well-known consequence of enteral nutrition support. Fecal impaction is less common. Development of a fiber bezoar is a rare complication that can occur among patients receiving enteral feedings with fiber. Fiber bezoars may be more prevalent when peristalsis is impaired, such as in patients on pressors [1,52,75]. Fiber should be used in such patients with caution. The risk factors for bezoar are poorly understood and the incidence is likely quite low. Either constipation or a fiber bezoar can cause impaction, bowel distention, perforation, and death if not treated early, although these sequelae are very rare. (See 'Fiber' above.) Patients who receive enteral feedings through a PEG tube are at risk for complications related to the PEG tube. (See "Gastrostomy tubes: Complications and their management".)
Insertion of a nasogastric or nasoenteric tube can also cause mechanical complications, such as insertion into the lung. Feeding through such tubes should not begin until its proper position has been confirmed radiographically.
PREVENTION OF ASPIRATION — A great deal of attention has been paid to aspiration in patients receiving enteral nutrition. While it is not controversial that patients receiving enteral nutrition tend to have more pneumonia, and an increased incidence of aspiration, causality is poorly established, and these may simply be reflective of the patient’s underlying condition(s).
Aspiration is likely more common because critically ill patients tend to be unable to protect their airways during critical illness. However, unless aspiration causes an overt untoward clinical outcome (eg, aspiration of a large volume causing hypoxia or pneumonitis), it is not clear that most aspiration (eg, microaspiration) causes harmful clinical outcomes. As support of this, nutrition early in the course of surgical critical illness has been associated with a decrease the rate of nosocomial pneumonia [76]. Moreover, the incidence of aspiration in the normal population approaches 50 percent [77], so a cause and effect relationship will require sophisticated study. Thus, while aspiration is predictive of pneumonia, it may only be an epiphenomenon in patients with other risks, is a poor surrogate, and should not be used as a clinical outcome in studies intended to reduce the risk of pneumonia. (See 'Monitoring' above and "Nutrition support in critically ill patients: An overview".)
Various strategies to reduce pneumonia have been studied, most using aspiration as the outcome. These include backrest elevation, post-pyloric feeding, enteral feeding via a percutaneous gastrostomy (PEG) tube, and administration of motility agents to promote gastric emptying [78]. The rationale for most of these strategies was the belief that reflux and aspiration of gastric contents increases the risk for nosocomial pneumonia. Numerous studies have failed to confirm this hypothesis and it now seems likely that aspiration of oropharyngeal secretions is the likely cause of nosocomial pneumonia.
Despite the lack of good prospective randomized data, adherence to the recommendation that all patients receiving enteral nutrition have their backrest elevated 30 to 45 degrees has been strongly advocated since the intervention is believed to be beneficial and easy to perform. This practice, however, is without the support of good randomized trials, and universal adherence is, in fact, difficult to obtain.
When backrest elevation is not possible, the backrest should be elevated as much as possible. We do not suggest routine post-pyloric feeding or insertion of a percutaneous or surgical feeding device, since related trials and meta-analyses show only trends toward benefit. However, post-pyloric feeding is considered appropriate in those at high risk of aspiration. Similarly, the administration of motility agents (eg, metoclopramide, erythromycin) solely for the purpose of decreasing aspiration should not be routinely performed since this approach does not appear to be beneficial. These can be administered on a case-by-case basis in those assessed to be at high risk of aspiration. (See 'Backrest elevation' below.)
The increasing prevalence in use of prone positioning in treating ARDS [79] raises concerns about reflux of and subsequent aspiration of gastric contents, and whether tube feeding is safe in this position. Several observational studies, and a meta-analysis [80] would suggest that there are no added risks to enteral nourishment while prone. In one prospective observational study, 34 proned patients were compared to a total of >1200 total ventilated patients. There were no differences in gastric residual volume per day of tube feeding (126.6 versus 189.2), incidence of high gastric residual events per day of tube feeding (0.06 vs 0.09; P = .39), vomiting episodes per day of tube feeding (0.016 versus 0.03), or regurgitation of feed (observation of feed product in mouth or nose) per day of tube feeding (0 versus 0.04) [81].
Backrest elevation — A randomized crossover trial of critically ill patients receiving enteral nutrition reported that aspiration was less common among patients in the semirecumbent position than the supine position [69]. This was supported by another clinical trial and several observational studies that reported a lower incidence of aspiration among patients whose backrest was elevated [82,83].
Reduction of aspiration is not an outcomes benefit unless it reduces the incidence of nosocomial pneumonia. In one small trial that randomly assigned 86 critically ill patients to receive care in the semirecumbent or supine position, there was a significant decrease in the incidence of pneumonia in the semirecumbent position among patients receiving enteral nutrition (9 versus 50 percent) [78]. More recently, however, analyses have failed to support these findings, and have questioned whether the practice has the potential to cause other problems (decubitus ulcers, interference with nursing care, etc) and have suggested a softening of the recommendations [84].
Despite the recommendations for backrest elevation, it has proven difficult to consistently maintain the desired 45 degrees of backrest elevation. In one multicenter study, the average amount of backrest elevation was approximately 20 degrees, which did not confer any clinical benefits [85].
In another study [86], which set 30 degrees as the goal, mean compliance was only 53.6 percent. While this one study did not find an association between bedrest elevation and pressure ulcer formation, there remains concern that backrest elevation may predispose to pressure ulcers.
Post-pyloric feeding — Three meta-analyses of randomized trials that compared post-pyloric feeding to gastric feeding have been published. Two of the meta-analyses found no benefit from post-pyloric feeding [87,88], while the other found a reduction in the incidence of pneumonia [89]. When the latter meta-analysis was repeated after removing one controversial study, there was no benefit from post-pyloric feeding [1].
Surgical or percutaneous feeding — The outcomes after insertion of a percutaneous or surgical feeding device compared to outcomes during nasogastric or nasoenteric feeding in the critically ill are unknown. Long-term complications are not different when comparing nasal versus percutaneous tubes in non-critically ill patients with swallowing problems [90].
There is a growing practice of simultaneous insertion of percutaneous endoscopic gastrostomy (PEG) at the same time as tracheostomy [91]. While this practice may be convenient, especially in regions where post-discharge healthcare facilities do not accept nasal tubes, the benefit is unproven. Skilled nursing home (SNF) policies regarding types of feeding tubes vary by region and may affect the clinician’s decision to place a gastrostomy versus a nasal feeding tube. For example, one study reported that the rate of acceptance of patients with temporary nasal tubes was significantly lower in New York City compared with the national average (18 versus 62 percent) [92]. In keeping with this observation, it has been reported that gastrostomies are being inserted earlier during hospitalization and in sicker patients [91]. Although unproven and the reasons are not well-defined, it is postulated that this is for the purpose of meeting SNF admissions policies [93,94].
Motility agents — A trial that randomly assigned 305 critically ill patients to receive metoclopramide or placebo with their enteral nutrition found that metoclopramide did not alter mortality or the incidence of nosocomial pneumonia [95]. A subsequent meta-analysis that included the randomized trial and three others (494 patients) similarly found that metoclopramide and erythromycin did not change mortality or the incidence of nosocomial pneumonia [96].
Motility agents may help achieve the desired rate of feeding in a subgroup of patients with poor gastric emptying. However, given the uncertainty of what constitutes an optimal feeding rate and the lack of evidence that motility agents improve clinical outcomes, we believe that use of motility agents as a preventive measure to prevent pneumonia is not warranted.
PROTOCOLS — Clinical practice guidelines suggest that enteral nutrition protocols be designed and implemented [1].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Nutrition support (parenteral and enteral nutrition) in adults".)
SUMMARY AND RECOMMENDATIONS
●Enteral nutrition support refers to the provision of calories, protein, electrolytes, vitamins, minerals, and fluids via an enteral route. (See 'Introduction' above.)
●For most critically ill patients for whom enteral nutrition is prescribed, we suggest a standard formulation of enteral nutrition (Grade 2B). Exceptions include the following: patients who require volume restriction may benefit from concentrated enteral nutrition, patients who do not tolerate a standard formulation may benefit from predigested enteral nutrition, and patients with renal failure complicated by severe fluid and electrolyte abnormalities may benefit from concentrated, electrolyte-restricted (ie, renal) enteral nutrition. (See 'Formulations' above and 'Protein' above.)
●Routine supplementation of enteral nutrition with omega-3 fatty acids, antioxidants, glutamine, ornithine ketoglutarate (OKG), arginine, prebiotics, probiotics, fiber, beta-hydroxy-beta-methylbutyrate (HMB), or immune modulators is not indicated. Fiber is used with caution in patients on vasopressor agents. (See 'Composition' above.)
●In practice, it is generally considered acceptable that enteral feeding be initiated in critically ill patients at a rate of 10 to 30 mL/hour (standard formulation) for six days and then incrementally increased to the target rate in more severely critically ill patients. Provided the enteral nutrition is paused infrequently, for issues such as high gastric residuals, diarrhea, or vomiting, this suggested approach should result in the patient ultimately reaching a stable target rate within a reasonable period of time. (See 'Amount and rate' above.)
●Routine checking of gastric residual volumes is unnecessary in asymptomatic patients receiving tube feedings. Gastric residuals are measured if the patient exhibits a clinical change, such as abdominal pain, abdominal distension, or deterioration in hemodynamics or overall status. (See 'Monitoring' above.)
●For all critically ill patients receiving enteral nutrition, we suggest 30 to 45 degrees of backrest elevation (Grade 2C). When this degree of elevation is not possible, we elevate the backrest as much as possible. (See 'Prevention of aspiration' above.)
●For most critically ill patients receiving enteral nutrition, we suggest gastric feeding rather than post-pyloric feeding (Grade 2B). Gastric feeding can be delivered via an orogastric tube, a nasogastric tube, or a percutaneous gastric tube. Post-pyloric feeding should be used if gastric feeding is not tolerated or contraindicated, and may be considered in those at high risk of aspiration. (See 'Prevention of aspiration' above.)
