What Is the Role of Parenteral and Enteral Nutrition in Patients With Cancer and With Noncancer Illness?

Enteral Nutrition

Percutaneous endoscopic gastrostomy (PEG) and percutaneous endoscopic jejunostomy (PEJ), defined by where the tube terminates, are endoscopic procedures for inserting a plastic tube through the abdominal wall into the gastrointestinal tract. In the case of endoscopic PEG placement, an endoscope is introduced into the stomach where a light identifies the stomach’s position through the abdominal wall. A guide wire is inserted through the abdominal wall into the stomach, grasped via the endoscope, and pulled back up through the esophagus. The wire is attached to the gastrostomy tube (G-tube), which is then pulled back into the stomach and out through the skin. Other surgical and radiological approaches exist, all of which also require sedation and incision through the abdominal wall. When the procedure is complete, a balloon or internal bumper remains inside the lumen of the stomach to seal the entry point and prevent the tube from being inadvertently removed, while an external bumper is attached just over the skin to prevent further movement into the body. Artificial nutrition via the tube is usually started 24 hours after placement, though meta-analysis and a further retrospective comparative study of early versus delayed initiation supports starting as soon as 4 hours after the procedure. Contraindications to gastrostomy include active coagulopathy, thrombocytopenia, abdominal wall abnormalities, peritoneal carcinomatosis, organomegaly, large ascites, varices, recent myocardial infarction, hemodynamic instability, and sepsis.

Mounting evidence of a lack of benefit of enteral feeding in people with advanced dementia led to the 2014 American Board of Internal Medicine (ABIM) and American Geriatrics Society (AGS) Choosing Wisely campaign to recommend against the placement of tubes for AN and AH in these patients. Even prior to the 2014 recommendation, the prevalence of G-tube placement declined over 30% in Medicare patients from 1994 to 2012. The proportion of U.S. nursing home residents with advanced dementia and eating dependency receiving tubes for AN and AH decreased by approximately 50% between 2000 and 2014. Despite these recommendations, many patients with advanced dementia continue to receive EN despite evidence of increased harm at least in part because providers significantly underestimate complications and do not routinely use evidence-based decision aids. Financial incentives likely contribute to the continued use of tubes for AN and AH.

In general, the evidence for patients for whom enteral feeding is appropriate has been narrowed to specific diseases and situations. In the palliative care setting, G-tubes are considered most commonly for patients with neurological disorders (especially ALS and stroke), oropharyngeal and esophageal obstruction (usually due to cancer), and any advanced illness (other than dementia) if they are losing weight. They also may be placed to facilitate medication administration, or to relieve a permanent bowel obstruction (venting gastrostomy). Near the end of life, questions often arise about the effectiveness and appropriateness of gastrostomy.

Health care providers and family caregiver/surrogate expectations of benefit are frequently incongruent with respect to clinical outcomes for G-tubes. Health care provider expectations for these devices include improving nutrition (93%), hydration (60%), and survival (58% predict 1 to 2 months without versus 1 to 3 years with placement); providing medications (55%); preventing aspiration (49%); facilitating nursing home placement (22%); diminishing pain (14%); and decreasing obstruction (12%). Surrogate decision makers’ expectations of benefit from PEG placement include improved nutrition (96%), health (93%), survival (90%), quality of life (87%), and comfort (79%); fewer problems eating (83%); fewer choking episodes (79%); and the patient not feeling hungry or thirsty (70%). Surrogates report understanding the benefits of gastrostomy more than the risks. Of note, only 40% believed that the G-tube improved the patient’s quality of life when surveyed 2 or more months after placement.

PEG complications can generally occur in three categories: complications of upper endoscopy, complications of the PEG placement itself, and post-procedural complications resulting from presence of the tube in the body. While serious complications are rare, overall long-term complications are common, with estimates ranging from 32% to 70%. In healthy outpatients, mortality related to upper endoscopy is very low (< 0.01%). The risk of aspiration (0.3%–1%), severe hemorrhage (0.02%–0.06%), and perforation (0.008%–0.04%) is also low. Complications related to the PEG procedure itself include pneumoperitoneum (~50%, generally benign), bowel injury, fistula formation, liver/spleen injury, and hemorrhage. Postprocedural complications include peptic ulcer disease (15%), diarrhea, tube dislodgement (1.6%–4.4%), infection (3% with prophylactic antibiotics), gastrointestinal bleeding (2.5%), ileus/gastroparesis (1%–2%), peristomal leakage (1%–2%), peristomal pain, gastric outlet obstruction, volvulus, and buried bumper syndrome (1.5%–1.9%) in which the internal bumper is pulled too tight against the stomach wall and gradually erodes into the extragastric tissue.

Independent risk factors for increased mortality after gastrostomy include low albumin (OR 2.1–3.0); age >80 (OR 1.8); heart failure (OR 1.5); previous subtotal gastrectomy (OR 2.6); platelets <100,000; C-reactive protein >5; diabetes; receiving a PEG in the hospital; poor functional status; and disorientation.

A 2015 Cochrane review found that complications in the first month and incidence of pneumonia at 6 months are no different between PEG and NG tube for enteral nutrition. Lower-quality evidence finds that PEG is associated with a lower prevalence of recurrent displacements and treatment interruptions but no difference in mortality, suggesting that a PEG should be used if enteral access is needed for more than 30 days. Separate Cochrane reviews favored PEG for stroke but found no difference for head and neck cancer. Patients and families may prefer a gastrostomy for social reasons, comfort, and convenience.

Parenteral Nutrition

PN provides macronutrients and essential micronutrients directly into the venous system. The parenteral route may be used to provide all required nutrition (total parenteral nutrition or TPN) or to supplement oral or tube feeding (partial parental nutrition or PPN). PN may be delivered through a peripheral or central intravenous catheter. Peripheral delivery can only accommodate lower osmolarity solutions (usually achieved with decreased dextrose concentrations), for shorter duration (<2 weeks), and may not be feasible in patients with poor peripheral access, high nutritional requirements, or fluid restrictions. For short- to medium-term administration, a directly inserted central line or peripherally inserted central catheter (PICC) may be used. If PN is likely to be needed for months or longer, a tunneled line or subcutaneous infusion port is preferred to reduce the risk of infection. PN formulas consist of dextrose, amino acids, electrolytes, vitamins, and trace mineral supplements. Chloride and acetate are titrated to create a physiologic pH. Lipid emulsions are commonly provided in a separate delivery bag. As with all nutritional supplementation, analysis of needs and current intake determines the composition of the formula for a particular patient. Once PN is started, it requires close clinical monitoring of electrolytes, blood glucose, and markers of nutritional status such as prealbumin. With longer-term use, intermittent monitoring of trace elements (Zn, Cu, Se) and vitamins (B12, folate, D) is also necessary.

While there are no absolute contraindications to providing PN, there are significant risks that must be considered whenever it is started. The major risks of PN may be divided into three categories: mechanical, infective, and metabolic. Mechanical risks are primarily those associated with placing an intravenous line and include bleeding, pneumothorax, improper placement, pain, air embolism, and arrhythmias. Once the line is in place, mechanical risks include thrombosis, line failure requiring replacement, phlebitis, and infiltration. The prevalence of most of these complications depends upon the location of the line and the technique used to place it, but generally the complications are significant (e.g., pneumothorax, line malposition, arterial puncture, brachial plexus lesions) in 1% to 4% of patients.

Despite recent advances in infection prevention, central venous catheters still carry a significant risk of infection, with resultant spread of organisms to the bloodstream and possible sepsis. Compared with those whose lines are used for other purposes, patients receiving PN are 2.5 to 4 times more likely to develop line infections and are at particular risk for fungemia. Mortality for each infection is high, estimated to be 12% to 30%. Finally, even with close monitoring, metabolic complications can occur including hyperglycemia, liver function abnormalities, refeeding syndrome (hypophosphatemia, hypomagnesemia, and hypokalemia), steatosis, cholestasis, and cholecystitis (4% after 3 months). Long-term use over years is also associated with end-stage liver disease (~50%) and metabolic bone disease (> 40%). In patients with limited prognoses, these longer-term risks, and even many of the short-term risks, are often of less concern.

Cancer Anorexia-Cachexia Syndrome

Upward of 80% of patients with advanced cancer develop cachexia, usually accompanied by anorexia, early satiety, anemia, and edema—often despite seemingly adequate nutritional intake. Together, these symptoms are referred to as cancer anorexia-cachexia syndrome (CACS). As with other forms of cachexia, the pathophysiology of this disorder is only partially understood but is probably related to complex host–cancer cytokine interactions that induce the body to favor catabolism over anabolism.

Key to any discussion of AN in CACS is the observation that nutritional support generally does not restore lean body mass because protein catabolism is rate limiting. Small studies of fish oil and eicosatetraenoic acid supplementation have shown a possible positive effect on muscle mass and weight loss, but generally CACS is not considered reversible. Studies of the potential for certain medications and nutritional supplements/formulas to interrupt this process are needed and ongoing.

Parenteral Versus Enteral Nutrition

In nearly all cases where the gut is functional, EN is preferred over PN because it is more physiologic, is associated with fewer complications, requires less monitoring, and costs much less. While superior to PN, EN results in a decrease in gut-associated lymphoid tissue (GALT) function, disrupts the mucosal barrier, and alters the intestinal microbiome. While it is likely that PN, by bypassing the gastrointestinal tract, leads to increased atrophy of this important immune tissue, higher infection rates in this group are largely related to vascular access. Both patients on PN and EN experience suppression of gut tissue immune activity, albeit this is likely greater in PN. Data pertaining to particular diseases and settings are discussed below. For simplicity, unless data pertain specifically to one type of percutaneous tube placement, we will use the term gastrostomy .

PN is generally considered when nutrition has been inadequate and oral or enteral feeding and/or supplementation efforts have either failed or are impractical. If the patient has a functioning gut, oral or enteral nutrition is nearly always preferred over PN. In the palliative care setting PN is typically considered for patients with malignant bowel obstruction and head and neck cancer, but may be requested in other situations. Importantly, PN does not have to be total, and should usually be supplemented by and eventually replaced with EN as soon as possible.

Given the high cost and serious complications associated with PN, there is significant concern for its use outside guidelines in the United States. The American Society for Parenteral and Enteral Nutrition (ASPEN) and the European Society for Clinical Nutrition and Metabolism (ESPEN) have both published recent evidence-based guidelines for the appropriate use of TPN. Even hospitals that have made previous efforts to control the ordering of inappropriate PN have recently been found to follow guidelines only 32% of the time. Use of PN outside guideline recommendations results in longer hospital stays and higher overall costs (~$4,000 per patient) without changes in outcome. In the United States, it is estimated that moving 10% of PN patients to EN would save $92 million annually from reduced adverse events and shorter hospital stays. There is also some evidence that using a specialized nutrition support team may reduce rates of inappropriate PN use.

Evidence for PN from the ASPEN and ESPEN guidelines is reviewed below, supplemented by meta-analyses or randomized clinical trials (RCTs) published since the guidelines. Where research has explored the potential benefits of avoiding EN, comparisons with PN are discussed. Except as specified, all other sections addressing PN assume that EN is not feasible and generally focus on when in an illness to start PN. They also assume that PN is otherwise consistent with the patient’s goals of care. In all cases, initiating PN during a proinflammatory phase of illness (e.g., early in sepsis treatment) or when the patient is hemodynamically unstable is associated with an increased risk of complications.

In general, the following discussion is limited to the use of PN in the palliative care setting. A Cochrane review examining the effect of medically assisted nutrition on the length and quality of life of palliative care patients found no RCTs or prospective controlled trials and concluded that there were insufficient data to make any recommendations. Three less rigorous prospective studies included in the review that examined home PN mostly in cancer patients showed an average survival of 3 to 4 months. There were no quantitative data on quality of life, but positive features of home PN identified in one qualitative study were assurance that nutrition was being met and a shift in the focus of eating from nutrition to comfort. Negative features were nausea, vomiting, drowsiness, headache, and restriction on family life and social involvement. Complications in this population were catheter sepsis (0.67 cases/year of treatment), deep vein thrombosis (0.16), and metabolic instability (0.50).

Cancer

While nutrition support in surgical oncology is generally beneficial, short term, and provided by NG tube, for nonsurgical cancer patients (excepting head and neck cancer patients, discussed below) the benefit of EN depends almost entirely on the patient’s functional and nutritional status. In patients with limited prognoses and poor quality of life, no data support improved survival, and patients with cancer who receive PEGs generally report poorer quality of life. Guidelines also recommend against EN for patients undergoing routine radiation, chemotherapy, or stem cell transplant. In contrast, enteral feeding is recommended for patients with head and neck cancer who have preserved function and maintain their quality of life if they are losing weight due to insufficient nutritional intake or are expected to consume less than 60% of their estimated energy expenditure for greater than 10 days (see also Chapter 49 ). As with other forms of nutrition support, while PN may stimulate tumor growth in many cancers, there is no evidence that this stimulation has any clinical effect, and it is not a contraindication to using PN in otherwise appropriate patients.

Noncancer Conditions