Timothy O. Lipman

Does enteral nutrition affect clinical outcome? A systematic review of the randomized trials.

BACKGROUND:Both parenteral nutrition (PN) and enteral nutrition (EN) are widely advocated as adjunctive care in patients with various diseases. A systematic review of 82 randomized controlled trials (RCTs) of PN published in 2001 found little, if any, effect on mortality, morbidity, or duration of hospital stay; in some situations, PN increased infectious complication rates.OBJECTIVE:The objective was to assess the effect of EN or volitional nutrition support (VNS) in individual disease states from available RCTs.DESIGN:We conducted a systematic review. RCTs comparing EN or VNS with untreated controls, or comparing EN with PN, were identified and separated according to the underlying disease state. Meta-analysis was performed when at least three RCTs provided data. The evidence from the RCTs was summarized into one of five grades. A or B, respectively, indicated the presence of strong or weak (low-quality RCTs) evidence supporting the use of the intervention. C indicated a lack of adequate evidence to make any decision about efficacy. D indicated that limited data could not support the intervention. E indicated either that strong data found no effect, or that either strong or weak data suggested that the intervention caused harm.PATIENTS AND SETTINGS:RCTs could include either hospitalized or nonhospitalized patients. The EN or VNS had to be provided as part of a treatment plan for an underlying disease process.INTERVENTIONS:The RCT had to compare recipients of either EN or VNS with controls not receiving any type of artificial nutrition or had to compare recipients of EN with recipients of PN.OUTCOME MEASURES:These were mortality, morbidity (disease specific), duration of hospitalization, cost, or interventional complications.SUMMARY OF GRADING:A: No indication was identified. B: EN or VNS in the perioperative patient or in patients with chronic liver disease; EN in critically ill patients or low birth weight infants (trophic feeding); VNS in malnourished geriatric patients. (The low-quality trials found a significant difference in survival favoring the VNS recipients in the malnourished geriatric patient trials; two high-quality trials found nonsignificant differences that favored VNS as well.) C: EN or VNS in liver transplantation, cystic fibrosis, renal failure, pediatric conditions other than low birth weight infants, well-nourished geriatric patients, nonstroke neurologic conditions, AIDS; EN in acute pancreatitis, chronic obstructive pulmonary disease, nonmalnourished geriatric patients; VNS in inflammatory bowel disease, arthritis, cardiac disease, pregnancy, allergic patients, preoperative bowel preparation. D: EN or VNS in patients receiving nonsurgical cancer treatment or in patients with hip fractures; EN in patients with inflammatory bowel disease; VNS in patients with chronic obstructive pulmonary disease. EN in the first week in dysphagic, or VNS at any time in nondysphagic, stroke patients who are not malnourished; dysphagia persisting for weeks will presumably ultimately require EN.CONCLUSIONS:There is strong evidence for not using EN in the first week in dysphagic, and not using VNS at all in nondysphagic, stroke patients who are not malnourished. There is reasonable evidence for using VNS in malnourished geriatric patients. The recommendations to consider EN/VNS in perioperative/liver/critically ill/low birth weight patients are limited by the low quality of the RCTs. No evidence could be identified to justify the use of EN/VNS in other disease states.

Grains or Veins: Is Enteral Nutrition Really Better Than Parenteral Nutrition? A Look at the Evidence

BACKGROUND Enteral nutrition is said to be better than parenteral nutrition for providing nutrition support to humans. PURPOSE To assess the literature documenting the assertions that enteral nutrition is superior to parenteral nutrition with respect to cost, safety, physiology, intestinal structure and function, bacterial translocation, and outcome. DATA IDENTIFICATION Sources included MEDLINE search, personal files, and references from human comparative studies of enteral vs parenteral nutrition. STUDY SELECTION The goal was to include all human studies directly addressing questions of comparative efficacy of enteral and parenteral nutrition. Emphasis was given to prospective randomized controlled studies where available. Retrospective comparisons were not included. DATA EXTRACTION An attempt was made to briefly summarize methodology and findings of relevant studies. No general attempt was made to assess quality of individual studies. RESULTS OF DATA SYNTHESIS Enteral nutrition appears to be less expensive than parenteral nutrition, but new economic analyses are needed given the newer aggressive access techniques for enteral nutrition. Enteral nutrition is associated with meaningful morbidity and mortality. The little comparative data existent suggest no differences in safety. Comparative studies of physiology and metabolism as well as comparative and noncomparative studies of intestinal function and structure do not support putative advantages of enteral nutrition. There is no evidence that enteral nutrition prevents bacterial translocation in humans. Enteral nutrition probably reduces septic morbidity compared with parenteral nutrition in abdominal trauma. Otherwise, there is no evidence that enteral nutrition consistently improves patient outcome compared with parenteral nutrition. CONCLUSIONS With the exception of decreased cost and probable reduced septic morbidity in acute abdominal trauma, the available literature does not support the thesis that enteral nutrition is better than parenteral nutrition in humans.

Review: Bacterial Translocation and Enteral Nutrition in Humans: An Outsider Looks In

PURPOSE To assess the literature documenting the existence of bacterial translocation in humans, the effects of enteral nutrition on bacterial translocation in humans, and the hypothesis that enteral nutrition prevents bacterial translocation in humans. DATA IDENTIFICATION Sources included Medline search, references from review articles, and references from animal and human studies. STUDY SELECTION The goal was to include all animal and human studies directly addressing questions of bacterial translocation and nutritional status or nutritional support. DATA EXTRACTION An attempt was made to briefly summarize methodology and findings of relevent studies. No general attempt was made to assess quality of individual studies. RESULTS OF DATA SYNTHESIS Bacterial translocation is a well documented phenomenon in animal models. Starvation and malnutrition of themselves do not induce bacterial translocation, but may facilitate translocation in the presence of other systemic insults. Parenteral nutrition and many forms of enteral nutrition may induce and/or facilitate bacterial translocation. Chow and certain fiber sources seem protective. Moderate direct and several lines of indirect evidence support the existence of bacterial translocation in humans. There is no direct evidence and questionable indirect evidence suggesting that enteral nutrition prevents or modifies bacterial translocation in humans. CONCLUSIONS The hypothesis relating enteral nutrition and bacterial translocation in critically ill patients remains attractive, but unproven.

Central Venous Catheter Care in Parenteral Nutrition: A Review

Central venous catheter care in parenteral nutrition has been described in numerous publications. These descriptions include care of both short- and long-term catheters. Important aspects in the prevention of infection in central venous catheters used for parenteral nutrition have included: the method of central venous access, subcutaneous tunneling, dressing change techniques, therapeutic uses of the catheter, and catheter-intravenous tubing connection care. Methods of predicting infection and evaluating catheter sepsis have been described. The efficacy of intervention by specialized nutrition support teams in infection control related to these catheters has been demonstrated. Newer partially implantable and completely implantable venous access devices have been used for parenteral nutrition. Methods of infection control and prevention of mechanical damage of these types of catheters have been examined with various results. Care and composition of central venous catheters have been shown to have some role in thrombus formation in the central veins. The use of heparin to prevent thrombosis and catheter occlusion, and the varying degrees of success obtained, have been described. Medical treatment of the occluded catheter with urokinase may be a necessary alternative to discontinuance of that catheter. Overall consideration of research methods used to reach conclusions for catheter care should be considered in the evaluation of appropriate care in each situation.

Plasma zinc and vitamin a in human squamous carcinoma of the esophagus

Zinc deficiency enhances experimental esophageal tumor induction. Vitamin A supplementation inhibits carcinogenesis in animals. Plasma zinc and plasma vitamin A levels are reduced in several human squamous cancers, but have not been studied in a US population with esophageal cancer. Therefore, we measured plasma zinc and vitamin A in patients with newly diagnosed esophageal cancer. In addition, we assessed hepatic and nutritional status and attempted to control for other factors known to influence plasma zinc and vitamin A levels. Plasma zinc and vitamin A were both significantly less in esophageal carcinoma than in age‐matched healthy controls (plasma zinc 65.7 ± 3.3 μg/dl [mean ± SEM] in esophageal cancer versus 80.5 ± 2.4 μg/dl in controls, P < 0.01; plasma vitamin A 32.6 ± 3.4 μ/dl in esophageal cancer versus 60.2 ± 4.2 in controls, P < 0.001). Overall, 15 of 17 patients with esophageal cancer had decreased plasma zinc and/or decreased plasma vitamin A. Our findings are compatible with a hypothesis that zinc or vitamin A deficiency may be co‐factors in the induction of human esophageal carcinoma.

Insensitivity of Guaiac Slide Tests for Detection of Blood in Gastric Juice

Two guaiac slide tests (Hemoccult and Fe-Cult) were evaluated for their ability to detect blood in gastric juice and other fluid mixtures relevant to clinical testing in upper gastrointestinal hemorrhage. Blood was added to these fluid mixtures in various amounts sufficient to yield concentrations from 20 microL blood/dL to 4000 microL/dL. With these agents we frequently could not detect blood in unbuffered gastric juice at concentrations as great as 4000 microL/dL. Buffering of gastric juice to pH 4 with either of two antacids only slightly restored sensitivity for blood detection. In contrast, blood in gastric juice obtained from subjects previously given intravenous cimetidine tested positive at concentrations as low as 50 microL/dL. The ability of both test agents to detect blood in gastric juice was considerably enhanced by neutralizing gastric juice with 0.1 N NaOH.

Nasopulmonary Intubation with Feeding Tubes: Case Reports and Review of the Literature

Pulmonary aspiration of regurgitated feeding material is a recognized complication of enteral nutrition by feeding tube. Nasopulmonary intubation with feeding tubes has been reported infrequently. We present two patients with such complications. In one, nasopulmonary intubation resulted in a pneumothorax. In the other unrecognized misplacement resulted in pneumonia and hydrothorax. Similar cases in the literature are discussed. Common features of this complication are: (1) patients who are obtunded, debilitated, or without gag reflex; (2) previous successful insertion of a tube; (3) successful passage past endotracheal tubes and tracheostomies; and (4) positive auscultation of insufflated air over the left upper quadrant. Complete prevention of this complication probably is not possible, but health care personnel should be aware of this potential problem in the patient at risk.

Bacterial Safety of Reconstituted Continuous Drip Tube Feeding

Chemically defined diets require reconstitution and transfer to a delivery system. When reconstituted High Vivonex was noted in our Medical Center to be bacteriologically contaminated, we instituted a series of control procedures. We then reevaluated bacterial growth in reconstituted High Nitrogen Vivonex and diluted Isocal under ward conditions. The mixtures were prepared with sterile water versus tap water, using a hand washed blender versus a machine washed blender. We also investigated the bacteriological effect of blast freezing reconstituted High Nitrogen Vivonex. All preparations of the nonfrozen High Nitrogen Vivonex showed occasional low level contamination, although quantitative cultures did not show logarithmic growth over eight hours of observation. No growth occurred in the blast frozen High Nitrogen Vivonex or in the Isocal. We conclude that reconstituted High Nitrogen Vivonex and diluted Isocal may be prepared and hung safely for eight hours, and that blast freezing of High Nitrogen Vivonex is bacteriologically safe. As a result of our initial findings of bacteriologic contamination, we believe a program for bacterial monitoring of the tube feeding is desirable.

The presence and effect of bias in trials of early enteral nutrition in critical care.

BACKGROUND Randomized trials suggest that early enteral nutrition is beneficial in critically ill adults. However, methodologic bias can overestimate benefit. OBJECTIVE To assess the potential effect of methodologic bias on these trials. STUDY DESIGN Systematic review and meta-analysis. DATA SOURCE Randomized trials identified in electronic searches of PUBMED, EMBASE, and the Cochrane Library, and in various handsearches. METHODS The primary (mortality, morbidity) and secondary (time on ventilator or in intensive care unit/hospital, cost) outcomes were abstracted from each identified trial comparing early enteral nutrition to no/delayed enteral nutrition. Each trial was assessed for six domains of methodologic bias (sequence generation, allocation concealment, blinding, intention-to-treat, selective outcome reporting, other). No low risk of bias trial (adequate in all six domains) was identified, so such trials could not be compared to the others. Instead, meta-analyses of trials with more or fewer risks were compared in the following ways: adequate methodology to deal with ≥3 or ≤2 domains; Jadad scores ≥3 or ≤2; adequate versus not adequate for each domain. DATA SYNTHESIS In the 15 identified trials, early enteral nutrition appeared to improve mortality and infectious morbidity. Mortality benefit was observed only in trials with more risks of bias; infectious morbidity benefit was observed in some analyses of trials with fewer bias risks. LIMITATIONS Small numbers of trials and missing information. CONCLUSIONS The benefits attributed to early enteral nutrition were either seen only in trials with high risks of bias or may result from residual risks of bias.

The chicken soup paradigm and nutrition support: rethinking terminology

The language used to describe the provision of artificial nutrition needs to be rethought and probably changed.