Enteral Delivery Research Articles

T Lymphocyte Numbers in Human Gut Associated Lymphoid Tissue Are Reduced Without Enteral Nutrition

Background: Clinically, in the absence of enteral nutrition, the morbidity of infectious complication is high. Although experiments using mice have shown alterations in gut‐associated lymphoid tissue (GALT) to be an important mechanism underlying impaired host defense, there are no clinical studies on the effects of nutritional routes on GALT. Methods: A total of 27 colon cancer cases who underwent right colectomy or hemicolectomy were reviewed. Six patients did not receive enteral nutrition for 4 to 28 days before surgery because of bowel obstruction (parenteral nutrition [PN] group). Twenty‐one patients were enterally fed before surgery (enteral nutrition [EN] group). The terminal ileum from resected specimens was examined microscopically. T‐cell numbers in intraepithelial spaces (IE) and the lamina propria (LP) were determined immunohistochemically in blinded fashion. Results: There were no significant differences in baseline characteristics between the 2 groups. T‐cell number in the LP was significantly lower in the PN group than in the EN group, with no difference in IE cell numbers. Conclusions: Lack of enteral delivery of nutrients reduces GALT cell number in patients with colon cancer, as is the case in mice.

MAPPING OF MULTIDRUG RESISTANCE GENE 1 AND MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN ISOFORM 1 TO 5 mRNA EXPRESSION ALONG THE HUMAN INTESTINAL TRACT

Efflux transporters such as P-glycoprotein and multidrug resistance-associated proteins (MRPs) in the intestinal wall restrict intestinal drug transport. To overcome this limitation for enteral drug absorption, galenical targeting approaches have been proposed for site-specific luminal drug release in segments of the gut, where expression of the respective absorption-limiting transporter is minimal. Therefore, expression of multidrug resistance gene 1 (MDR1) and MRP1-5 was systematically investigated in 10 healthy subjects. Biopsies were taken from different segments of the gastrointestinal tract (from duodenum and terminal ileum, as well as ascending, transverse, descending, and sigmoid colon). Gene expression was investigated by quantitative real-time PCR (TaqMan). MRP3 appeared to be the most abundantly expressed transporter in investigated parts of the human intestine, except for the terminal ileum, where MDR1 showed the highest expression. The ranking of transporter gene expression in the duodenum was MRP3 >> MDR1 > MRP2 > MRP5 > MRP4 > MRP1. In the terminal ileum, the ranking order was as follows: MDR1 > MRP3 >> MRP1 approximately MRP5 approximately MRP4 > MRP2. In all segments of the colon (ascending, transverse, descending, and sigmoid colon), the transporter gene expression showed the following order: MRP3 >> MDR1 > MRP4 approximately MRP5 > MRP1 >> MRP2. We have shown, for the first time, systematic site-specific expression of MDR1 and MRP mRNA along the gastrointestinal tract in humans. All transporters showed alterations in their expression levels from the duodenum to sigmoid colon. The most pronounced changes were observed for MRP2, with high levels in the small intestine and hardly any expression in colonic segments. This knowledge may be useful to develop new targeting strategies for enteral drug delivery.

Enteral nutrition in critically ill patients with severe hemodynamic failure after cardiopulmonary bypass

The study was designed to investigate and quantify nutritional support, and particularly enteral nutrition (EN), in critically ill patients with severe hemodynamic failure. Prospective, descriptive study in a surgical intensive care unit (ICU) in a university teaching hospital: patients aged 67+/-13 yrs (mean+/-SD) admitted after cardiac surgery with extracorporeal circulation, staying 5 days in the ICU with acute cardiovascular failure. Severity of disease was assessed with SAPS II, and SOFA scores. Variables were energy delivery and balance, nutrition route, vasopressor doses, and infectious complications. Artificial feeding delivered according to ICU protocol. EN was considered from day 2-3. Energy target was set 25 kcal/kg/day to be reached stepwise over 5 days. Seventy out of 1114 consecutive patients were studied, aged 67+/-17 years, and staying 10+/-7 days in the ICU. Median SAPS II was 43. Nine patients died (13%). All patients had circulatory failure: 18 patients required intra-aortic balloon-pump support (IABP). Norepinephrine was required in 58 patients (83%). Forty patients required artificial nutrition. Energy delivery was very variable. There was no abdominal complication related to EN. As a mean, 1360+/-620 kcal/kg/day could be delivered enterally during the first 2 weeks, corresponding to 70+/-35% of energy target. Enteral nutrient delivery was negatively influenced by increasing dopamine and norepinephrine doses, but not by the use of IABP. EN is possible in the majority of patients with severe hemodynamic failure, but usually results in hypocaloric feeding. EN should be considered in patients with careful abdominal and energy monitoring.

Route of nutrient delivery

Nutritional intervention early in the course of critical illness in humans and animals can have a significant impact on morbidity and mortality. Enteral delivery of nutrients is less technically demanding, more physiologic, and less expensive than parenteral nutrition. Furthermore, as complete bowel rest during critical illness can be associated with detrimental intestinal structural and functional changes ultimately resulting in bacterial translocation from the gut, direct delivery of nutrients to the gastrointestinal tract is preferred in patients with sufficient gastrointestinal function to allow digestion and absorption of nutrients. Once the decision to “feed the gut” has been established, there are several routes of enteral nutrient delivery available. A sound knowledge of gastrointestinal function, anticipated duration of enteral support, and co-moribund conditions will help the clinician tailor a plan of nutrient delivery that optimally meets each patient’s needs. This article will review available routes of nutrient delivery to the gastrointestinal tract, and discuss indications and contraindications for each.

Enteral nutrient delivery increases with higher calorie prescriptions during the first five days of enteral nutrition

Enteral nutrient delivery increases with higher calorie prescriptions during the first five days of enteral nutrition

Enteral nutrition practice in a surgical intensive care unit: what proportion of energy expenditure is delivered enterally?

The object of this study was to document enteral feeding practice in critically ill patients in a surgical intensive care unit. We asked what proportion of measured energy expenditure is delivered enterally. Patient, material, and therapy-related factors should be assessed and related to enteral nutrition. Sixty patients receiving enteral nutrition for a period of at least 10 days were included in the study. Mean daily energy expenditure was 27.8+8.7kcal/kg. Mean daily enteral delivered calories reached 19.7±10.3kcal/kg ( P<0.05). Twenty-one out of 60 (35%) patients were fed isocalorically; 46% of enteral nutrition days failed to reach 80% of energy expenditure. Ten out of 30 patients (33%) fed over a gastric tube were nourished isocalorically in comparison to 8 out of 20 patients (40%) fed over a duodenal tube. Factors associated with hypocaloric enteral feeding in multiple logistic regression were abdominal, pelvic and lumbal spine trauma, gastrointestinal intolerance, problems with the feeding tube, additional surgical interventions, airway management and use of fentanyl. In the course of the study, gastrointestinal complications were the cause for more than 50% of insufficient enteral delivery cases, while therapy and material related reasons contribute to only a minor part. Abdominal, pelvic and lumbal spine traumas are associated with a higher possibility towards developing problems with enteral delivery, as shown by odds-ratios greater than eight. These diagnoses amounted in our investigation to nearly 40% and make a great difference to medical patients. Therefore, recommendations for optimising enteral feeding must take the concerned patient collective into account.

The Art and Science

Carol Parrish has provided an excellent review regarding enteral nutrition delivery. The article not only references key articles regarding enteral delivery but also incorporates the collected experience of the author. As a practicing gastroenterologist with an interest in nutrition support, I would agree with the comments made by the author in this paper. I think all of us have developed our own clinical instinct for the care of our patients as a result of our collected individualized clinical experiences over time. Having said that, I think we would all acknowledge that there is more than one best way to care for a patient. This is perhaps more true in nutrition support, given the lack of prospective, controlled studies in many instances. Also, as nutrition support providers, we have to interact daily with our medical/surgical colleagues, patients, and families. Each usually have their own ideas regarding nutrition, which is sometimes based on experience and sometimes not. As a consulting service, we have to be good listeners, understand the information presented to us, and most importantly, be good communicators. I believe it is our role as nutrition support providers to first guide all parties in the direction of what is safe for the patient, ie, first do no harm. I do not believe one should ever be criticized for erring on the side of safety for a patient. An example may be when tube feeds are held for 1 or 2 days because of reduced bowel sounds and mild abdominal distention, and you are not sure in which clinical direction the patient may turn. Although you may not agree with the decision to hold the feeding, it may ultimately be in the best interest of the patient. When to advance and when to hold enteral feeding is based on more than one piece of clinical information in my opinion. The decision first begins with accurate clinical information. It has been my observation that this is where most confusion begins. Examples may include incorrect charting of residual volumes, failure to discriminate stool incontinence from diarrhea, and failure to perform a careful abdominal examination. The clinical finding that concerns me the most is abdominal distention with abdominal pain on gentle palpation. Regardless of residual volumes or bowel sounds, I will usually suggest reduction or discontinuation of feedings. There are many variables (medications, postoperative ileus, diabetes) of hospitalized patients that can affect gastric function, and hence, residual volumes. Therefore, in my opinion, no set residual volume should be used because of patient variability. However, I do believe each specific institution needs to feel comfortable with a set number so the nursing staff can follow protocol. In terms of the art of enteral delivery, we should not forget our patient’s preference. We have recently published results showing that patients overwhelmingly prefer total parenteral nutrition (TPN) to nasal gastric feeding. 1 Perceived comfort was the primary reason for their answer. Gender, education level, physician’s recommendation, and cost did not influence patient’s preference. Although we advocate enteral nutrition in most circumstances, the results of this study have helped us become more aware of patients’ preferences, an important contribution to our efforts to provide the best care possible.

Effect of enteral vs. parenteral glucose delivery on initial splanchnic glucose uptake in nondiabetic humans.

To determine if enteral delivery of glucose influences splanchnic glucose metabolism, 10 subjects were studied when glucose was either infused into the duodenum at a rate of 22 micromol x kg(-1) x min(-1) and supplemental glucose given intravenously or when all glucose was infused intravenously while saline was infused intraduodenally. Hormone secretion was inhibited with somatostatin, and glucose (approximately 8.5 mmol/l) and insulin (approximately 450 pmol/l) were maintained at constant but elevated levels. Intravenously infused [6,6-(2)H(2)]glucose was used to trace the systemic appearance of intraduodenally infused [3-(3)H]glucose, whereas UDP-glucose flux (an index of hepatic glycogen synthesis) was measured using the acetaminophen glucuronide method. Despite differences in the route of glucose delivery, glucose production (3.5 +/- 1.0 vs. 3.3 +/- 1.0 micromol x kg(-1) x min(-1)) and glucose disappearance (78.9 +/- 5.7 vs. 85.0 +/- 7.2 micromol x kg(-1) x min(-1)) were comparable on intraduodenal and intravenous study days. Initial splanchnic glucose extraction (17.5 +/- 4.4 vs. 14.5 +/- 2.9%) and hepatic UDP-glucose flux (9.0 +/- 2.0 vs. 10.3 +/- 1.5 micromol x kg(-1) x min(-1)) also did not differ on the intraduodenal and intravenous study days. These data argue against the existence of an "enteric" factor that directly (i.e., independently of circulating hormone concentrations) enhances splanchnic glucose uptake or hepatic glycogen synthesis in nondiabetic humans.

Alcohol-induced free radicals in mice: Direct toxicants or signaling molecules?

Tumor necrosis factor α (TNF-α) and free radicals are produced in early alcohol-induced liver injury. Recently, pathology caused by alcohol was blocked nearly completely in tumor necrosis factor α receptor 1 (TNF-R1) knockout mice. With this model, it is now possible to evaluate whether free radicals are directly toxic or act as redox regulators of TNF-α production. Specifically, if free radicals were directly toxic, a parallel decrease in free radicals and pathology in TNF-R1 knockout mice would be predicted. If they only affect TNF-α production, radicals would be expected to remain high while pathology is diminished. Accordingly, free radical production in TNF-R1 knockout mice was studied here. The enteral alcohol delivery model used mice lacking TNF-R1 (p55) and wild-type control C57Bl/6J mice. Animals received a liquid diet continuously with either ethanol or isocaloric maltose-dextrin as control for 4 weeks. Urine ethanol levels fluctuated from 10 to 500 mg/dL in a cyclic pattern in mice receiving ethanol. Ethanol elevated liver:body weight ratios, serum alanine transaminase (ALT) levels, and pathology scores in wild-type mice. These parameters were blunted nearly completely in TNF-R1 knockout mice. Ethanol treatment increased free radical production in wild-type mice compared with animals fed a high-fat control diet. There were no differences in intensity of free radical signals regardless of the presence or absence of TNF-R1; however, pathology differed markedly between these groups. These findings are consistent with the hypothesis that free radicals act as redox signals for TNF-α production and do not directly damage cells in early alcohol-induced hepatic injury. (HEPATOLOGY 2001;34:935-942.)

Effect of Primary and Secondary Repellents on European Starlings: An Initial Assessment

Wildlife managers need chemical repellents that are effective at deterring damage by birds, but these repellents must be environmentally and toxicologically safe. The number of commercially available bird repellents has been reduced because of concerns about environmental safety. Currently, there are 2 categories of avian repellents. Chemicals that are reflexively avoided by birds because they irritate the peripheral chemical senses are referred to as primary repellents. Chemicals that cause gastrointestinal illness and learned avoidance of ancillary sensory cues that are paired with the illness are known as secondary repellents. Secondary repellents most often identified as the most effective avian repellents are derived from synthetic agrichemical pesticides and generally are regulated against because of their toxicity and concerns about the consequences of adding them to the environment. Primary repellents are usually derived from natural products and human food and flavor ingredients, and their use as bird repellents has been promoted as fulfilling the need for environmentally safe repellents. However, primary repellents are considered to be less potent than secondary repellents. We found that if the primary repellent, methyl anthranilate, was delivered enterically in European starlings (Sturnus vulgaris), we could achieve the same level of repellency as with the secondary repellent, methiocarb. Equal repellent effects for the 2 chemicals were found despite differences in their mode of action. Also, birds given an enteric delivery of the primary repellent methyl anthranilate showed fewer signs of behavioral distress (e.g., immobility and regurgitation) relative to those birds given the secondary repellent, methiocarb. By redirecting the site of action of a primary repellent, we have shown the feasibility to optimally combine the potency levels of secondary repellents with the biological and environmental safety attributes of primary repellents, without sacrificing efficacy. Primary repellents may he converted to secondary repellents via gastrointestinal delivery, thus potentially increasing efficacy and economic viability of these chemicals. Formulations that mask the irritating qualities of primary repellents are needed so that the chemical will be freely consumed by the target animal and exert its effect in the gastrointestinal tract.

Reduced Early Alcohol-Induced Liver Injury in CD14-Deficient Mice

Activation of Kupffer cells by gut-derived endotoxin is associated with alcohol-induced liver injury. Recently, it was shown that CD14-deficient mice are more resistant to endotoxin-induced shock than wild-type controls. Therefore, this study was designed to investigate the role of CD14 receptors in early alcohol-induced liver injury using CD14 knockout and wild-type BALB/c mice in a model of enteral ethanol delivery. Animals were given a high-fat liquid diet continuously with ethanol or isocaloric maltose-dextrin as control for 4 wk. The liver to body weight ratio in wild-type mice (5.8 +/- 0.3%) was increased significantly by ethanol (7.3 +/- 0.2%) but was not altered by ethanol in CD14-deficient mice. Ethanol elevated serum alanine aminotransferase levels nearly 3-fold in wild-type mice, but not in CD14-deficient mice. Wild-type and knockout mice given the control high-fat diet had normal liver histology, whereas ethanol caused severe liver injury (steatosis, inflammation, and necrosis; pathology score = 3.8 +/- 0.4). In contrast, CD14-deficient mice given ethanol showed minimal hepatic changes (score = 1.6 +/- 0.3, p < 0.05). Additionally, NF-kappa B, TGF-beta, and TNF-alpha were increased significantly in wild-type mice fed ethanol but not in the CD14 knockout. Thus, chronic ethanol feeding caused more severe liver injury in wild-type than CD14 knockouts, supporting the hypothesis that endotoxin acting via CD14 plays a major role in the development of early alcohol-induced liver injury.

Current Literature: Bacterial Contamination of Ready‐to‐use 1‐L Feeding Bottles and Administration Sets in Severely Compromised Intensive Care Patients

Objective: In intensive care patients, enteral feeding requires sterile feedings because of infectious complications and adequate supplements to meet nutritional needs. Heretofore, prepacked, large‐volume formula containers were developed, but bacterial contamination occurred in 4% to 15%. Our objective was to investigate the microbial contamination rate of 1‐L feeding bottles and newly designed administration sets over hanging times of 24 hours in the intensive care unit (ICU). Design and Setting: A prospective observational cohort study of patients admitted to the ICU of a university hospital. Patients: All consecutive patients fed via a nasojejunal tube for at least 4 days. Measurements: Cultures of feeding bottles, administration sets, and gastric and tracheobronchial aspirates at day 0, 1, 2, 4, and 7. Results: A total of 4% of feeding bottles and 74% of infusion sets contained &gt;10(2) colony forming units (CFU)/mL. Gastric and bronchial aspirates were positive in 90% and 92%, respectively. Bacterial counts of feeding bottles were 10(2)‐10(5) CFU/mL, and the main bacteria isolated included Enterobacter cloacae, Klebsiella oxytoca, and enterococci. One‐third of all cultured bacteria in feeding bottles, administration sets, stomach, and lungs belonged to the Enterobacteriaceae family, which was held responsible for the nosocomial infections in the ICU. None of the 1‐L feeding bottles with a hanging time of 19 to 24 hours was contaminated. Only bottles that had to be exchanged because of need for a faster rate of infusion proved to be contaminated, apparently without clinical consequences. With time and the increasing severity of disease, the administration sets became contaminated at an increasingly faster rate and with higher bacterial counts mainly through retrograde growth of endogenous bacteria. The final step of bottle contamination might have been the bacterial transfer by nurses' hands. Conclusion: Despite an almost ideal design of the enteral nutrition delivery system, a 4% contamination rate of initially sterile feedings with clinically relevant bacteria and the fact that only manipulated systems showed bacterial growth are of concern. (Crit Care Med 28:67–73, 2000)

Closed versus Open Enteral Delivery Systems: A Quality Improvement Study

The purpose of this study was to review the compliance rate with maximum enteral feeding hang‐time policy and to determine the incidence of tube feeding (TF) contamination. This study found the compliance rate for the maximum TF bag hang‐time was 67% for open delivery system (OS) and 88% for the closed delivery system (CS). The 10 CS bags cultured had hang‐times from 20.8 to 45.8 hours and were all sterile. The 8 OS bags cultured had hang‐times from 6.8 to 26.6 hours with 2 bags being contaminated. The maximum hang‐time for the CS was increased from 24 to 48 hours. The study was repeated with 100% compliance for the CS and still only 50% compliance for the OS. The 14 CS bags cultured had hang‐times from 22.0 to 47.3 hours and were all sterile except for 1 bag that had methylene blue dye added to it. The 9 OS bags cultured had hang‐times from 7.5 to 13.3 hours, and all were sterile. The findings of this study led us to conclude that closed enteral delivery systems should be used whenever possible.

The dose-related hypoglycemic effects of insulin emulsions incorporating highly purified EPA and DHA

The dose-related pharmacological effects of insulin emulsion incorporating highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were investigated. Water-in-oil-in-water multiple emulsions (insulin dose, 0, 10, 25 and 50 IU/kg) incorporating 2% DHA or EPA were administered directly into the colonic and rectal loops in situ. Serum insulin levels rose and serum glucose levels decreased in an insulin dose-related fashion. The relationship of insulin dose and C max or AUC insulin was linear at the rectum, but a non-linear relationship was observed at the colon. The trend was more predominant in DHA. In the in vivo rectal absorption experiment using emulsions incorporating 2% DHA, 5 IU/kg of insulin emulsion produced a rapid, transitory increase in serum insulin levels and strong reduction of serum glucose levels. The pharmacological availability determined from the dose–response curve by s.c. administration of insulin reached 43.2±26.3% (mean±S.D.). Mucosal irritation caused by administration of emulsions incorporating 2% EPA or DHA was evaluated by a lactate dehydrogenase (LDH) release study, and compared with those of the emulsion incorporating 2% oleic or linolenic acid. Only when emulsion incorporating 2% oleic acid was applied in the intestine did significant LDH release into the mesenteric veins occur. Our results indicate that emulsion incorporating highly purified long-chain polyunsaturated fatty acid, especially DHA, has the potential of becoming the formulation for enteral delivery of insulin.

Effect of high ambient temperature on contamination and physical stability of one-liter Ready-to-Hang enteral delivery systems

The effect of high ambient temperature on the physical stability and bacterial contamination of 1-L, prefilled, closed enteral feeding systems was examined under simulated clinical conditions. One hundred Jevity Ready-to-Hang enteral feeding systems (Abbott Park, IL, USA) were placed in a 37°C incubator for 24 h. The Ready-to-Hang formula containers were visually inspected at 0 and 24 h. Formula samples were collected from the containers at 24 h and plated on trypticase soy agar. Two samples had insignificant bacterial growth of one colony-forming unit per milliliter that was not demonstrated in repeat culture. No growth was observed for any other sample. Additional samples collected from the two apparently contaminated delivery sets showed no growth. No set showed signs of formula instability, such as coagulation, clumping, or curdling. These findings suggest that, even at a high ambient temperature of 37°C, the risk of bacterial contamination or compromised physical integrity is very low with the use of 1-L, prefilled, closed enteral feeding systems.

How enteral feeding options influence corticosterone patterns in rats.

Even with all the nutritional research conducted to date, it is not clear which enteral nutrition delivery and composition options are most physiologically sound. Glucocorticoid temporal patterns are reported to be shifted or disrupted with restricted feeding schedules, but because of intermittent sampling, temporal patterns have not been completely depicted. The purpose of this study was to characterize corticosterone temporal patterns while systematically varying selected enteral feeding options in a well-established nutritional animal model. A 2 x 2 x 2 x 2 randomized block experimental design was used in which enteral feeding schedules, delivery methods, kilocalorie levels (kcal), and fiber contents were systematically varied in rats (n = 80), and plasma corticosterone was measured by 125I radioimmunoassay. Blood samples were drawn hourly over 24 h. With cosinor analysis, 24-h and 12-h corticosterone rhythmic components were tested in each feeding group. Five of 16 feeding groups had a significant (p < or = 0.05) 24-h rhythmic component, and 3 more showed a trend (p > 0.05 < 0.10); 7 of these groups were on 24-h feeding schedules. When rhythmic components were detectable, groups receiving high-fiber formula displayed more uniform rhythm characteristics than did no-fiber groups. Only 1 group had a significant 12-h rhythmic component, and 1 showed a trend. Both were on 12-h, high-fiber restricted kcal feedings. In this small animal sample, no one enteral feeding option guaranteed a 24-h corticosterone pattern. The option coming closest was formula delivered on a 24-h schedule. This temporal pattern is one aspect to consider in enteral nutrition. The underlying mechanisms have yet to be elucidated.

Bacterial contamination of ready-to-use 1-L feeding bottles and administration sets in severely compromised intensive care patients.

In intensive care patients, enteral feeding requires sterile feedings because of infectious complications and adequate supplements to meet nutritional needs. Heretofore, prepacked, large-volume formula containers were developed, but bacterial contamination occurred in 4% to 15%. Our objective was to investigate the microbial contamination rate of 1-L feeding bottles and newly designed administration sets over hanging times of 24 hrs in the intensive care unit (ICU). A prospective observational cohort study of patients admitted to the ICU of a university hospital. All consecutive patients fed via a nasojejunal tube for at least 4 days. Cultures of feeding bottles, administration sets, and gastric and tracheobronchial aspirates at day 0, 1, 2, 4, and 7. A total of 4% of feeding bottles and 74% of infusion sets contained >10(2) colony forming units (CFU)/mL. Gastric and bronchial aspirates were positive in 90% and 92%, respectively. Bacterial counts of feeding bottles were 10(2)-10(5) CFU/mL, and the main bacteria isolated included Enterobacter cloacae, Klebsiella oxytoca, and enterococci. One third of all cultured bacteria in feeding bottles, administration sets, stomach, and lungs belonged to the Enterobacteriaceae family, which was held responsible for the nosocomial infections in the ICU. None of the 1-L feeding bottles with a hanging time of 19-24 hrs was contaminated. Only bottles that had to be exchanged because of need for a faster rate of infusion proved to be contaminated, apparently without clinical consequences. With time and the increasing severity of disease, the administration sets became contaminated at an increasingly faster rate and with higher bacterial counts mainly through retrograde growth of endogenous bacteria. The final step of bottle contamination might have been the bacterial transfer by nurses' hands. Despite an almost ideal design of the enteral nutrition delivery system, a 4% contamination rate of initially sterile feedings with clinically relevant bacteria and the fact that only manipulated systems showed bacterial growth are of concern.

Essential role of tumor necrosis factor α in alcohol-induced liver injury in mice

Background & Aims: Tumor necrosis factor (TNF)-α is associated with increased mortality in alcoholics, but its role in early alcohol-induced liver injury is not fully understood. Recently, it was shown that injury induced by the enteral alcohol delivery model of Tsukamoto and French was reduced by antibodies to TNF-α. To obtain clear evidence for or against the hypothesis that TNF-α is involved, we studied TNF receptor 1 (TNF-R1, p55) or 2 (TNF-R2, p75) knockout mice. Methods: Long-term enteral alcohol delivery was modified for male gene–targeted mice lacking TNF-R1 and TNF-R2. Animals were given a high-fat liquid diet continuously with either ethanol or isocaloric maltose-dextrin as a control for 4 weeks. Results: Ethanol elevated serum levels of alanine aminotransferase nearly 3-fold in wild-type and TNF-R2 knockout mice but not in TNF-R1 knockout mice. Likewise, ethanol caused severe liver injury in wild-type mice (pathology score, 5.5 ± 0.6) and TNF-R2 knockout mice (pathology score, 5.0 ± 0.4), but not in TNF-R1 knockout mice (pathology score, 0.8 ± 0.4; P < 0.001). Conclusions: Long-term ethanol feeding caused liver injury in wild-type and TNF-R2 knockout mice but not in TNF-R1 knockout mice, providing solid evidence in support of the hypothesis that TNF-α plays an important role in the development of early alcohol-induced liver injury via the TNF-R1 pathway. Moreover, the long-term enteral ethanol feeding technique we described for the first time for knockout mice provides a useful new tool for alcohol research. GASTROENTEROLOGY 1999;117:942-952

Lack of enteral nutrition during critical illness is associated with profound decrements in biliary lipid concentrationsrted by the Dutch Organization for Scientific Research, project no. 902-23-097.rted by the Dutch Organization for Scientific Research, project no. 902-23-097.rted by the Dutch Organization for Scientific Research, project no. 902-23-097.

Food in the intestine drives the enterohepatic circulation of bile components. We investigated whether parenteral or enteral delivery of nutrients alters serum and biliary lipids in critically ill patients. Eight intensive care unit (ICU) patients who had received >/= 5 d of total parenteral nutrition (TPN) were compared with 8 ICU patients who had fasted for >/=5 d. Both groups were studied before and after 5 d of enteral nutrition (EN). Each patient served as his or her own control. Duodenal bile was analyzed for biliary lipid content and serum lipids were determined simultaneously. Duodenal bile samples from 18 healthy persons served as controls. Bile salt concentrations in all ICU patients were 17% of control values before EN (P < 0.005) and 34% of control values after 5 d of EN (P < 0.005). Phospholipid concentrations were 12% of control before EN (P < 0. 0005) but increased almost 4-fold after EN (P < 0.0005). Biliary cholesterol concentrations were 20% of control values before EN (P < 0.001) and did not improve afterward. No difference in bile composition was observed between fasted ICU patients and those who received TPN. The inverse correlation between the severity of illness and biliary lipid concentrations observed before EN disappeared with enteric stimulation. The low serum concentrations of HDL cholesterol and apolipoprotein A-I increased significantly with EN in all ICU patients. Lack of EN during critical illness was associated with profound decrements in biliary lipid concentrations that normalized partially after 5 d of EN. We hypothesize that loss of enteric stimulation in ICU patients impairs hepatic lipid metabolism.

Emergency Medication Security Potassium Chloride as Floorstock Nurses and Drug Interaction Screening Medication Use Evaluations Enteral Samples Hospice and Oncology Care Plans Handwritten Labels Equipment Delivery Verification of Physician Licensure

This column addresses questions from readers about any issue, process, standard, or future direction of the Joint Commission, whether it relates to home care, the hospital, or other practice environment. The objective is to give you a better insight into the Joint Commission accreditation process in your own practice site. Any question is fair game.