To achieve nutritional goals and avoid complications of enteral nutrition, reasonable measures to take include withdrawing medications that complicate gastric motility, trans- or post-pyloric feeding enterally, and monitoring GRV regularly.

All critically ill patients should be screened for nutritional risk; subsequently, all patients identified as being at nutritional risk should undergo nutritional assessment. Nutritional support is generally recommended for critically ill patients who are not expected to meet their nutritional needs for 5 to 10 days. When nutritional support is warranted, enteral nutritional support is preferred over parenteral nutritional support.1

Common observations in critically ill patients with systemic inflammatory response syndrome and/or sepsis include protein catabolism, hypermetabolism, lipolysis, hyperglycemia, and insulin resistance.2,3 Inadequate nutritional support coinciding with the common manifestations of critical illness may contribute to significant loss of lean body mass. Nutritional support is recommended in order to attenuate the progressive loss of lean body mass. Published positive outcomes associated with early enteral feeding include cost-savings, enhanced safety, decreased lengths of stay, and decreased complication rates (for postoperative complications and infections).4-6

Although some studies7,8 challenged the presumed advantages of enteral feeding, Marik and Zaloga9 conducted meta-analysis of prospective, randomized studies comparing early vs late enteral feeding demonstrating the benefits of early nutrition. Early enteral feeding was defined in the meta-analysis as beginning within 36 hours of surgery or hospital admission. Positive outcomes associated with early enteral nutritional support included decreased infection rates and decreased lengths of stay. No significant impact of early enteral nutrition on outcomes was reported for noninfectious complications or mortality. The authors reported that the meta-analysis did not include trials with nonsurgical patients, since there were no published reports for that patient population that met their inclusion criteria. They also cautioned readers that interpretation of the results is necessary due to heterogeneity in the primary clinical trials.

The preferred feeding site for enteral nutrition remains controversial. In general, feeding into the small bowel (versus the stomach) warrants an assessment of aspiration risk, gastrointestinal anatomy, gastric emptying ability, tracheal aspiration, gastroparesis, anticipation of early postoperative feeding following major gastrointestinal surgery, reflux esophagitis, previous gastric surgery that prohibits gastric feeding, and gastric-outlet obstruction.1

Specialized Nutritional Support
The American Society for Parenteral and Enteral Nutrition’s board of directors and clinical guidelines task force described specialized nutritional support as “the provision of nutrients orally, enterally, or parenterally with therapeutic intent.”1 Specialized nutritional support is not intended for universal use in the treatment use of all critically ill patients; instead, it is for specific situations.

Overfeeding critically ill patients with adult respiratory distress syndrome (ARDS) or chronic obstructive pulmonary disease is associated with excess carbon dioxide production. It is challenging to assess energy and nutrient needs for a critically ill patient to avoid overfeeding.

Commercial enteral-nutrition formulae that are high in fat and low in carbohydrate were created for their presumed respiratory quotient (RQ) advantage. High-fat, low-carbohydrate nutrient regimens are not universally indicated for therapeutic use in pulmonary disease patients since positive clinical outcomes were not consistently demonstrated.10,11

Other commercial enteral-nutrition formulae were developed for immune-modulation purposes. ARDS is associated with inflammatory cytokines (interleukins 1, 6, and 8); therefore, enteral-nutrition formulae with W-3 fatty acids (borage oil and fish oil) were developed to attenuate the inflammatory response in patients with early ARDS. An enteral-nutrition formula with certain antioxidants and fatty acids (g-linolenic acid and eicosapentenoic acid) was demonstrated as improving outcomes for early ARDS patients.12 Some positive outcomes (decreased infectious complications) were reported in a meta-analysis of immune-enhancing enteral formulae by Heyland et al.13 The immune-enhancing enteral formulae included supplemental W-3 fatty acids, nucleotides, arginine, and glutamine. It is important to note that many studies of immune-modulating enteral-nutrition formulae contained more than one nutrient intended for modulation; therefore, efficacy evaluation for specific supplements remains challenging.

Intragastric or Transpyloric Support
Accepting that early enteral nutrition is preferred to parenteral nutrition for critically ill patients, one must address the potential complications of enteral feeding and the practicality of meeting nutritional goals. Critically ill patients experience gastrointestinal motility dysfunction, resulting in intolerance of intragastric enteral nutrition. Because current enteral-nutrition guidelines do not report a gastric residual volume (GRV) threshold that is associated with aspiration pneumonia, the practice of withholding intragastric enteral nutrition varies by practice site.14,15 A survey of 219 intensive care unit (ICU) nurses working in university medical centers found that 50% of the respondents would stop enteral nutrition for a GRV of more than 100 mL.16 Some groups recommend continued feeding until the GRV is more than 300 mL.17 Others recommend cessation at 100 mL to 150 mL and resumption at less than 75 mL.18 When high residuals prompt health care providers to stop enteral nutrition, patients fail to reach nutritional goals. In a prospective study19 of medical and surgical ICU patients, only 42% of patients reached targeted levels of enteral nutrition. High GRVs were cited in 51% of cases as the reason for stopping nutritional support.

Additional, nonspecific measures used to evaluate enteral feeding intolerance include abdominal tenderness, distention, absence of bowel sounds, and bowel movements.18,20,21 Clinicians working without a sensitive, specific marker of enteral-nutrition intolerance clearly face a dilemma when feeding patients enterally.

Despite the absence of definitive evidence associating GRV and pneumonia, a recent report strengthens the hypothesis that decreasing duodenogastric reflux, gastric colonization, and gastroesophageal regurgitation reduces pulmonary aspiration and the morbidity attributable to nosocomial pneumonia.22 Moreover, it has been proposed that feeding in the transpyloric position should further reduce the amount of aspiration and associated complications. Heyland et al,23 using a radiolabeled feeding additive, found reduced gastroesophageal regurgitation in patients fed in the transpyloric position; however, comparative trials of gastric versus transpyloric feeding in ICU patients by Kerns,24 Monteclavo,25 and Spain et al26 failed to show significant decreases in pneumonia, mechanical-ventilation time, ICU lengths of stay, mortality, or aspiration. To account for this apparent inconsistency, it has been suggested that transpyloric feeding decreases the proportion of GVR that is enteral nutrition; however, transpyloric feeding may increase gastric secretions.27 Increased gastric secretions in a patient with impaired gastric emptying then contribute to aspiration.27 Only Monteclavo reported the ability to supply more calories per day, with increased prealbumin concentrations, to patients fed in the transpyloric position than to those fed in the gastric position.25

Promotility agents
Impaired gastric emptying has been demonstrated in patients with diabetes mellitus, head injury, burn injury, abdominal surgery, and sepsis, as well as those in the recumbent position.23 Normal gastric peristalsis requires coordination between the central nervous system and the enteric nervous system through sympathetic and parasympathetic afferent and efferent neurons. Peristalsis occurs when afferent ascending neurons signal contraction through chemical mediators (serotonin, substance P, and acetylcholine). A simultaneous, descending cholinergic stimulus causing relaxation is mediated by vasoactive intestinal peptide, adenosine triphosphate, and nitric oxide. Coordination of contraction and relaxation propels gastric contents antegrade. This activity is greatly depressed in critically ill patients. It is estimated that about 50% of mechanically ventilated patients have delayed gastric emptying.28 Medications commonly used in ICU patients also contribute to gastroparesis and aspiration.22

The prokinetic agents cisapride, metoclopramide, and erythromycin have been used with varying degrees of success for the treatment of delayed gastric motility.

Cisapride is thought to enhance gastric motility though serotonergic release. Despite its efficacy in diabetic gastroparesis,31,32 studies of ICU patients did not demonstrate significant improvement in gastric emptying.33,34 Cisapride may benefit ICU patients by enhancing lower esophageal sphincter tone, thus decreasing aspiration contents; however, due to its potential arrhythmogenic potential, cisapride was removed from the US market and is no longer recommended.

Metoclopramide, a dopamine-1 antagonist, is commonly used in non-ICU settings for diabetic gastroparesis and, at higher doses (1 mg/kg) in combination with dexamethasone, for preventing chemotherapy-induced nausea and vomiting.35,36 In the ICU setting, small studies37 have demonstrated the usefulness of metoclopramide in facilitating postpyloric intubation, but other, larger studies have yielded disappointing results.38,39 Despite this potential use, metoclopramide has failed to facilitate tolerance of enteral feeding or to reduce aspiration pneumonia rates in ICU patients consistently.40

Erythromycin is an antibiotic that stimulates the contraction of gastric muscles through the stimulation of motilin receptors predominating in the stomach.41 Erythromycin has consistently demonstrated its ability to increase gastric contractions and improve gastric emptying in ICU patients.42 Chapman43 reported that a single dose of 200 mg of intravenous (IV) erythromycin decreased GRV, allowing enteral nutrition to be continued in nine of 10 patients in the treatment group, versus five of 10 in the placebo group (P=.05). More recently, Boivin and Levy44 showed that gastric feeding, with erythromycin (200 mg IV) administered every 8 hours, was equal to transpyloric feeding in the time needed to reach the goal enteral-nutrition rate. Because the optimal dose of erythromycin is unknown, additional studies evaluating the dose-response relationship are needed. Drug interactions are common with erythromycin and need to be considered before selecting this therapy.

It is well appreciated that opioids used to treat pain in ICU patients decrease gastric motility and may result in opiate-induced ileus.45,46 Orally administered naloxone, an opiate antagonist, has been used in outpatients with terminal cancer to relieve gastric symptoms associated with opioids while sparing the opiates’ central analgesic activity.47-50 More recently, a novel, peripherally acting opiate antagonist, ADL 8-2698, was investigated in surgical patients who received opiates intraoperatively. Patients in the ADL 8-2698 group reported less postoperative nausea and vomiting. Subjects in the treatment group also had shorter intervals between surgery and passing flatus (by 21 hours) and first bowel movements (by 41 hours), compared with placebo.51 Patients in the treatment group were identified as ready for discharge 23 hours earlier (P=.03). Because administration of opiate antagonists, either enterally or parenterally, in an ICU population has not been evaluated in rigorous clinical trials, widespread use cannot be recommended.

Adverse effects
It is known that enteral nutrition increases oxygen consumption in healthy volunteers. Patients with limited oxygen reserves due to decreased perfusion or oxygen-carrying capacity may be at risk for the development of nonocclusive mesenteric ischemia (NOMI). Small-bowel obstruction resulting in necrosis has been reported as a complication of early enteral nutrition.52 Choban53 performed a retrospective review of enterally fed surgical patients with NOMI and identified several risk factors. Coronary artery disease, peripheral vascular disease, digoxin toxicity, and hypoperfusion were all associated with NOMI in patients who were enterally fed. It is unclear whether feeding at-risk patients places them at risk of additional ischemic episodes, or whether choosing an enteral-nutrition formula requiring less metabolic work for utilization can prevent ischemic complications in this population.

Enteral feeding is the preferred route of nutrition in critically ill patients. To avoid complications of enteral nutrition and to achieve nutritional goals, reasonable measures taken should include withdrawing medications that complicate gastric motility, trans- or postpyloric feeding enterally, monitoring GRV regularly, utilizing erythromycin for patients with increased GRV, and being constantly alert to the development of NOMI in high-risk populations. Enteral nutrition formulas that have a lower metabolic cost for metabolism or those with a lower carbon dioxide burden have not consistently demonstrated positive outcomes. Therefore, enteral nutrition formulas supplemented with therapeutic levels of nutrients for immune modulation may be used in select cases.

Katherine T. Ideno, MS, RD, CNSD, LD, is clinical nutrition manager, and Michael G. Liebl, RPh, BCPS, is pharmacological clinical specialist in critical care, both at The Methodist Hospital, Texas Medical Center, Houston.

The authors would like to give special thanks to Robert Levine, MD; Ken Hargett, RRT, RCP; Cyndy Bloss, PharmD, RPh, BCNSP; and Paula Hansen, BSN, MHA, CHE, CNAA, RN.

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