Enteral Formulations Research Articles

Strategies To Reduce Postoperative Pulmonary Complications after Noncardiothoracic Surgery: Systematic Review for the American College of Physicians

Postoperative pulmonary complications are as frequent and clinically important as cardiac complications in terms of morbidity, mortality, and length of stay. However, there has been much less research and no previous systematic reviews of the evidence of interventions to prevent pulmonary complications. To systematically review the literature on interventions to prevent postoperative pulmonary complications after noncardiothoracic surgery. MEDLINE English-language literature search, 1 January 1980 through 30 June 2005, plus bibliographies of retrieved publications. Randomized, controlled trials (RCTs); systematic reviews; or meta-analyses that met predefined inclusion criteria. Using standardized forms, the authors abstracted data on study methods, quality, intervention and control groups, patient characteristics, surgery, postoperative pulmonary complications, and adverse events. The authors qualitatively synthesized, without meta-analysis, evidence from eligible studies. Good evidence (2 systematic reviews, 5 additional RCTs) indicates that lung expansion interventions (for example, incentive spirometry, deep breathing exercises, and continuous positive airway pressure) reduce pulmonary risk. Fair evidence suggests that selective, rather than routine, use of nasogastric tubes after abdominal surgery (2 meta-analyses) and short-acting rather than long-acting intraoperative neuromuscular blocking agents (1 RCT) reduce risk. The evidence is conflicting or insufficient for preoperative smoking cessation (1 RCT), epidural anesthesia (2 meta-analyses), epidural analgesia (6 RCTs, 1 meta-analysis), and laparoscopic (vs. open) operations (1 systematic review, 1 meta-analysis, 2 additional RCTs), although laparoscopic operations reduce pain and pulmonary compromise as measured by spirometry. While malnutrition is associated with increased pulmonary risk, routine total enteral or parenteral nutrition does not reduce risk (1 meta-analysis, 3 additional RCTs). Enteral formulations designed to improve immune status (immunonutrition) may prevent postoperative pneumonia (1 meta-analysis, 1 additional RCT). The overall quality of the literature was fair: Ten of 20 RCTs and 6 of 11 systematic reviews were good quality. Few interventions have been shown to clearly or possibly reduce postoperative pulmonary complications.

Nutrients with immune-modulating effects: what role should they play in the intensive care unit?

This review will summarize recent clinical and experimental data on the use of immune-modulating nutrients in critical illness. It will present the concept of these nutrients as pharmacologic agents or 'nutraceuticals' administered in addition to protein, calorie, vitamin, and trace element sources. Studies have defined the physiologic roles of arginine in critical illness, such as its role as a precursor for the production of nitric oxide. Investigations have determined that, in critical illness, glutamine levels decrease and severe glutamine deficiency is associated with increased mortality. Experimental studies have revealed that glutamine attenuates proinflammatory cytokine responses, improves gut barrier and immune cell functions, increases the ability to mount a stress response, and decreases mortality. Clinical trials and meta-analyses of studies testing immune-modulating nutritional formulations have reported numerous benefits but also some conflicting results. Dose and route of administration are key factors that influence the benefit, or lack thereof, of these nutraceuticals. Cumulative studies of enteral immune-modulating nutritional formulations report benefits in surgical critically ill patients such as burn, trauma, or gastrointestinal surgery populations. Conflicting data in patients with sepsis warrant concern and further evaluation; in particular, controversy seems to stem around the use of arginine. Glutamine is beneficial when given in high doses or via the parenteral route (>0.20-0.30 g/kg per day or >or=30 g/day). Providing both omega-3 and omega-6 polyunsaturated fatty acids is important in immune modulation. The best doses and combinations of immune-modulating components remain unclear.

Are there any real differences between enteral feed formulations used in the critically ill?

We know that adequate nutritional support is essential in the treatment of critically ill patients, because it can, if applied appropriately, improve the clinical outcome. Increasing evidence seems to suggest that malnutrition itself is a predictor of poor outcome in intensive care, and significant underfeeding during intensive care stay increases the risk of bloodstream infections. The purpose of this review is to highlight recent advances in enteral nutrition in the critically ill adult patient. Recent studies suggest that tight glycaemic control is associated with improved outcome. Enteral feeding should be encouraged, using simple feeding protocols, and started early if safe to do so. Gastric residual volumes do not correlate with the risk of aspiration, and therefore should be used with caution in feeding protocols. Conflicting evidence exists for supplementation with antioxidant and immunonutrition in the critically ill. Glutamine and fish oil/borage oil should be considered for burns patients and patients with adult respiratory distress syndrome, respectively. This review offers information regarding the latest developments in nutritional support via the enteral route. Further research is needed to clarify the role of enteral supplements such as antioxidants and 'immune modulating substances'.

Selective uptake of glutamine in the gastrointestinal tract: Confirmation in a human study

Recent animal data suggest that the gut plays a far more important metabolic role than previously thought. During critical illness, disruption in bowel barrier function may result in a chronic hypermetabolic state and contribute to multiorgan failure. Animal studies have demonstrated that enterocytes of the gastrointestinal tract use glutamine as a respiratory fuel and during critical illness the consumption of glutamine by the gut significantly increases. The selective uptake of glutamine by the gut, to date, has not been confirmed in humans. Seven patients who sustained multisystem trauma necessitating laparotomy underwent portal venous catheterization. This was done by carefully reopening the obliterated umbilical vein and facilitating access to the left branch of the portal vein using a standard central venous catheter. Portal venous and systemic blood samples were recorded for 5 days after operation. Amino acid levels in both circulations were recorded at 48 h and 5 days. Using Student's t test for related samples, the differences between individual amino acids in portal and systemic circulations were compared. At 48 h, mean(s.d.) portal venous glutamine was 85(5) per cent of the systemic levels (253(80) compared with 296(90) mumol/ml, P less than 0.002). At 5 days, portal glutamine was 87(3) per cent of the systemic levels (255(69) compared with 292(83) mumol/ml, P less than 0.003). Levels of citrulline, a breakdown product of glutamine metabolism, were elevated in the portal venous circulation at 48 h (20(4) compared with 16(3) mumol/ml, P less than 0.005) and at 5 days (21(5) compared with 14(3) mumol/ml, P less than 0.002). No significant differences between any of the other amino acids analysed were identified. This study confirms, for the first time in humans, that selective uptake of glutamine occurs in the gut. In stressed states, glutamine deficiency is associated with gut mucosal atrophy. This has significant implications as glutamine is not provided in most commercially available parenteral and enteral nutrition formulations.

Standards for Specialized Nutrition Support: Home Care Patients

Standards for Specialized Nutrition Support: Home Care Patients

The impact of computerization of the nutrition support process on the nutrition support program in a tertiary care hospital in the Philippines: Report for the years 2000–2003

To improve hospital health care delivery by identifying malnutrition in all admitted patients and following up those identified to be malnourished and "at risk of developing malnutrition" a hospital nutrition support program based on the JCAHO system was initiated in 1999. Two major problems were encountered: first, the inability to perform a nutrition surveillance process due to failure by the staff to implement existing nutrition screening tools and second, the lack of awareness and support from the medical staff in this initiative. Two solutions were implemented in 2000: computerization of the nutrition screening and nutrition support process and synchronizing this with the whole nutrition support program. A computer program was developed which performs BMI-based nutrition screening, produces lists of all malnourished patients, and computes the different formulas for either nutritional requirement or parenteral and/or enteral formulation. It also generates patient status reports based on encoded data from the nutrition support team, which prioritized these patients for management based on the data output. From 2000 to 2003, improvement was seen in these areas: entry of height and weight in the patient record increased from 30% to 90%; nutrition surveillance shows nutritional status distribution to be: normal (58%), underweight (9%), overweight (25%), and obese (8%), referrals to the nutrition support team based on the screen notification increased from 37% to 100%, patient coverage by nutrition support services increased from 7374 (38.8%) in 2000 to 11,369 (83%) in 2003, and critical care patients seen increased from 10% in 2000 to 99% in 2003. More improvement is needed in physician response to nutrition support recommendations, which still remains low (11.2-24%). Computerization helps to improve nutrition support delivery in the hospital, but more cooperation and support from the medical staff is still needed for better results.

Neonatal Nutrition and Consequences on Adult Health

After completing this article, readers should be able to: 1. Describe aberrations in adult health that can result from nutrition in the fetal period and in neonatal life. 2. Review the results of studies from human neonates regarding early nutritional interventions designed for “catch-up” growth. 3. Review results from animal studies regarding early nutrition and “programming” for adult metabolic syndrome. 4. Describe some of the potential epigenetic mechanisms that may be responsible for “programming.” 5. Examine methods for preventing growth delays, the consequences of undernutrition, and the metabolic syndrome related to adverse “programming.” One of the traditional goals of neonatal nutrition is to maintain growth within standardized limits. In the preterm infant, growth between the 10th and 90th percentiles of intrauterine rate has been an ideal goal. More recently, maintenance of lean body mass and bone density; prevention of complications such as chronic lung disease, necrotizing enterocolitis, and infection; and optimization of neurodevelopment and adult health through early nutritional programming have become recognized as more meaningful goals than mere somatic growth. To meet these goals, current nutritional practices require thorough scrutiny in terms of quantity and quality (composition) and how they are customized, if not for the individual patient (which would be ideal), at least for subgroups such as those who are small or appropriate for gestational age, sick or healthy, preterm or term, or male or female. Fetal nutrition and development frequently are used as a template for the low-birthweight infant. A large body of literature on the consequences of fetal undernutrition shows that infants born small for gestational age (SGA) not only have short-term morbidity, but long-term morbidity manifested in what has been termed the “metabolic syndrome.” This syndrome includes abdominal obesity, arterial hypertension, and insulin resistance. Other clinical manifestations can be observed, including thyroid dysfunction, hirsutism, ovarian hyperandrogenism and infertility, dyslipidemia (increased …

The Open Abdomen: Enteral Access Results in Cost Savings

Purpose To evaluate the cost savings of using enteral access for drug and nutrition delivery in patients requiring open peritoneal cavity management (laparosotomy). Methods A review of 14 patients who required laparostomy and received at least 4 consecutive days of enteral nutrition treated at our tertiary care facility between January 1999 and May 2001. Data collected included age, sex, reason for laparostomy, enteral formulation, medications, and side effects (diarrhea and gastric reflux). Cost savings were calculated as the difference between the cost of intravenous (IV) and enteral nutritional formulation and drug dosage costs. Results Patients were fed via nasojejunal feeding tube. Average duration of enteral nutrition (EN) was 19.1 ± 12.3 days. Gastric reflux and diarrhea occurred in five (36%) and six (42%) patients, respectively. These were easily treated and did not require conversion to IV nutrition or medications. Drug and electrolyte levels were therapeutic at appropriate enteral doses. A total of 267 days of EN were utilized in these 14 patients. The cost difference between the parenteral nutrition that would have been used during that time and the actual enteral formula utilized was $25,373. The use of enteral rather than IV medications also resulted in a cost savings of $7,058. Thus, the combined cost savings of enteral medication and nutrition therapy for the 14 patients was $32,431. Conclusion EN and drug therapy can be utilized in patients requiring open peritoneal cavity management. The resultant cost savings can be substantial, and these methods of cost reduction can also be applied to other patients.

New lipids in enteral feeding.

Lipid sources for enteral nutrition continue to be an exciting area of investigation. It is timely to review recent developments which have largely contributed to thrust enteral feeding into a new era. Although much more research needs to be done, there is a better understanding of the competitive relationships between n-6/n-3 fatty acids in conditions of metabolic and immune stress as well as in autoimmune and degenerative diseases. Although structured lipids are more completely absorbed and cleared, other more important clinical benefits need to be documented before they can be considered cost-effective. Immune enhancing formulas are the subject of controversy and some have been shown to be more effective than others. Enteral formulations with short-chain fatty acids are promising but more experimental work on the normal, and the sick colon is needed. Finally, there are a few isolated studies suggesting that enteral feeding with liposomes and with lipolytic products may have advantages when the digestive phase needs to be circumvented. The era of nutrigenomics, in which the effect of specific lipids on genes and proteins is being explored, is with us. We can look forward to nutrigenetics when the effect of genetic variation on the interaction between diet and disease will guide our practice. Clinicians already have access to lipid sources and formulations which allow them to individualize enteral feeding programs. More clinical and technological research needs to be carried out, however, before products can be tailored to produce optimal effects in specific conditions.

Toxicity of Food Drug and Cosmetic Blue No. 1 Dye in Critically Ill Patients

Food Drug and Cosmetic Blue No. 1 dye (FD&C Blue No. 1) is commonly added to enteral nutrition formulations in order to facilitate the detection of gastric aspirate in tracheal secretions of critically ill patients. However, reports of systemic blue dye absorption and associated adverse outcomes are emerging. We report two cases of abnormal systemic absorption of FD&C Blue No. 1 in critically ill patients who subsequently died of refractory shock and metabolic acidosis. Risk factors and mechanisms of FD&C Blue No. 1 toxicity are discussed, and alternate approaches to gastric aspiration detection in critically ill patients are considered.

Controversy of immunonutrition for surgical critical-illness patients.

Specific nutrients such as arginine, glutamine, dietary nucleotides, and omega-3 fatty acids have been shown to influence infectious morbidity, antibiotic use, and hospital length of stay. The combination of these nutrients into one enteral formulation has become known as immune-enhancing diets. Consensus guidelines developed by a number of clinical investigators and published in 2001 concluded that immune-enhancing diets were beneficial in moderate to severely malnourished patients undergoing elective gastrointestinal surgery and patients sustaining severe blunt and penetrating torso trauma. The purpose of this article is to review data published between February 1, 2001, and January 31, 2003, to determine whether new studies substantiated or refuted the current recommendations for the use of immune-enhancing diets in surgical, critically injured, and critically ill patients. Results confirmed the benefits of preoperative administration of immune-enhancing diets in surgical patients but also demonstrated that postoperative administration offered no advantages. Decreased infectious complications were also observed in critically ill patients receiving immune-enhancing diets. Accumulating evidence supports the use of immune-enhancing diets in these specific patient populations.

Specialized enteral formulae for diabetic patients

This article reports on the 23rd Congress of the European Society of Parenteral and Enteral Nutrition (ESPEN), September 8 to 12, 2001, held in Munich, Germany. The debate, titled Do We Need 'Diabetes' Enteral Formulae, was moderated by Hans Hauner, MD. The speakers were John Writh, MD, who discussed the positive aspects of diabetic enteral formulae, and Burkhard Goke, MD, who was against specialized enteral diabetic formulations. The discussion was led by S. Muhlebach, MD, and Viviane Chaer Borges, RD. This article presents some relevant issues such as the ideal mix of fat and carbohydrate as an energy source, nutritional diabetic requirement, the role of fiber in the formulations, the interference of different types of carbohydrate on glycemia, and which composition of fatty acids in the enteral formulations is most beneficial for patients with type 2 diabetes.

An Enteral Therapy Containing Medium-Chain Triglycerides and Hydrolyzed Peptides Reduces Postprandial Pain Associated with Chronic Pancreatitis

Background/Aim: Pain in patients with chronic pancreatitis is difficult to manage. We examined if an enteral formulation containing medium-chain triglycerides (MCT) and hydrolyzed peptides would (1) minimally stimulate the exocrine pancreas by blunting cholecystokinin release and (2) decrease pain in patients with chronic pancreatitis. Methods: In the first part of the study, on separate days, 6 healthy controls consumed a standard enteral formulation, an enteral formulation containing MCT and hydrolyzed peptides, and a high-fat meal. Baseline and postprandial plasma cholecystokinin (CCK) concentrations were analyzed. Subsequently, 8 patients with chronic pancreatitis were enrolled and instructed to complete a visual analog pain assessment for a baseline period of 2 weeks followed by three cans per day of the enteral formulation containing MCT and hydrolyzed peptides for 10 weeks. Results: Mean CCK levels for our control subjects were 0.46 ± 0.29 pM at baseline, 10.75 ± 0.45 pM in response to the high-fat meal, and 7.9 ± 1.25 pM in response to the standard enteral formulation. Of note, CCK levels were 1.43 ± 0.72 pM in response to the enteral supplement containing MCT and hydrolyzed peptides. In patients with chronic pancreatitis, the average improvement in pain scores from baseline to the conclusion of the study was 61.8% (p = 0.01). This corresponded to a clinical improvement in 6 of the 8 patients. Conclusions: A complete enteral supplement containing MCT and hydrolyzed peptides minimally increases plasma CCK levels. This therapy may be effective in reducing postprandial pain associated with chronic pancreatitis.

Procalcitonin and enteral nutrition tolerance in critically ill patients.

Serum procalcitonin concentrations have been reported to be elevated in patients with bacterial infection. Early enteral nutrition (EN) has been shown to decrease infections in trauma patients. The purpose of this study was to characterize procalcitonin and other serum proteins during EN of trauma patients based on EN tolerance and presence of infection. Twenty traumatized patients received a high-protein enteral formulation within 5 days of injury. Serum for procalcitonin, C-reactive protein, and prealbumin was analyzed on days 1 and 7 of EN. The procalcitonin/prealbumin and C-reactive protein/prealbumin ratios were calculated the same days. Patients who were infected during the study were compared with those not infected, and enteral-tolerant patients were compared with enteral-intolerant patients using these measurements. In the 20 trauma patients, procalcitonin (10.35 +/- 27.87 versus 1.03 +/- 1.24 ng/mL, p < .001) and procalcitonin/prealbumin ratio (1.70 +/- 4.20 versus 0.18 +/- 0.28, p < .01) decreased significantly over the 7-day period of EN. In the 12 patients who had infection, procalcitonin (16.33 +/- 35.31 versus 1.37 +/- 1.41 ng/mL, p < .004) and procal- citonin/prealbumin ratio (2.74 +/- 5.31 versus 0.26 +/- 0.33, p < .01) decreased significantly over the 7-day period of enteral nutrition. There were no significant changes in the measurements for 8 patients without infection. In the 15 patients who were enteral-tolerant, procalcitonin (12.56 +/- 32.84 versus 1.07 +/- 1.23 ng/mL, p < .004) and procalcitonin/prealbumin ratio (2.03 +/- 4.93 versus 0.20 +/- 0.29, p < .01) decreased significantly. Procalcitonin serum concentrations decrease significantly during EN in enteral-tolerant, critically ill patients with infection.

Enteral feeding and Crohn disease

Enteral nutrition is an established therapeutic option in the treatment of patients with Crohn disease. The mode of action for enteral nutrition remains unknown but research efforts have begun to elucidate the complex interaction between nutritional luminal contents, intestinal epithelium, and mucosal immune response. Trials of novel enteral diet formulations have been conducted to explore the antiinflammatory role of specific nutrients.

Microbiological quality of reconstituted enteral formulations used in hospitals

Contamination of enteral feeds may occur during preparation, storage, decanting, and administration to patients. The aim of this study was to investigate the microbiological quality of reconstituted enteral feeds, residual feeds from feed delivery systems, and the water used to reconstitute powdered feeds in hospital. Hazard Analysis Critical Control Points (HACCP) system was implemented to control microbiological contamination of the enteral feeding formulations. Before the implementation of the HACCP system microbiological analyses of feeds showed the presence of indicator organisms such as coliforms and Enterococcus spp. and unacceptably high levels of mesophilic aerobic microorganisms (>10 4 cfu/mL). After the implementation of the HACCP, the microbial quality of the feeds improved significantly, with counts of <10 1 cfu/mL. Blenders used in reconstituting feeds were found to be the main source of bacterial contamination.

Determination of mono and disaccharide content of enteral formulations by gas chromatography

A quantitative GC method has been developed which allows determination of mono and disaccharides in enteral formulations. The method is based on the isolation of the mono and disaccharide fraction on a charcoal-celite column and conversion to trimethylsilylated oximes (TMS-oximes). The repeatability of the complete method and recovery were acceptable. In the five commercial samples assayed, maltose was the main sugar (5.24–8.85 gL−1) followed by glucose (1.06–2.41 gL−1) and lactose (0–1.17 gL−1) Low levels of fructose (0–0.18 gL−1) and sucrose (0–0.07 gL−1) were observed and galactose was detected in two of the samples. The presence of maltulose is reported in enteral formulations for the first time. Maltulose formed from maltose during processing, was present in variable amounts (0.12–1.07 gL−1) and could be a useful indicator for enteral formulation classification.

Phenytoin and enteral feedings: does evidence support an interaction?

To systematically review the reported interaction between oral dosage forms of phenytoin and enteral feeding formulations with respect to the evidence supporting or refuting its existence, proposed mechanism(s) underlying the interaction, and recommended interventions. We conducted a MEDLINE search (1966-April 2000) for English-language articles on phenytoin-enteral feeding interactions; the search terms used were phenytoin, enteral feeding, and/or interaction, and/or in vitro. This search was supplemented by a bibliographic review of all relevant articles. Prospective, randomized, controlled studies; prospective, nonrandomized, controlled studies; prospective, nonrandomized, uncontrolled studies; retrospective studies; clinical experience reports; case reports; in vitro studies; and letters were evaluated for relevant information. Data elements abstracted from these articles were study design, type (patients or healthy volunteers) and number of subjects involved, method of administration of phenytoin and enteral feeding, formulation of phenytoin, type of feeding (and whether it was continuous or interrupted), major findings, and proposed mechanisms of the interaction. Although four prospective, randomized, controlled trials in healthy human volunteers refute the existence of the interaction, there are numerous reports and studies showing dramatic decreases of serum phenytoin concentrations in patients when it is coadministered with enteral feeding formulations. Therefore, evidence supports the existence of this interaction in patients and in vitro studies, but not in healthy volunteers. Unfortunately, the exact mechanisms underlying this interaction remain unknown. Many methods have been devised to prevent and treat the interaction once it has occurred; however, a single, generally accepted, and practical intervention strategy is still lacking. The exact role of enteral feeding in this interaction is unclear due to the lack of prospective, randomized, controlled trials performed in patients. However, decreased serum phenytoin concentrations associated with enteral feeding may increase the risk of seizures. Clinicians should be aware of this potential drug-nutrient interaction and design a patient-specific care plan that includes consideration of the enteral feeding formulation and method of administration, as well as the phenytoin dosage form, schedule of administration, and monitoring.

Vegetable proteins

On the basis of the rate of animal growth, proteins have been traditionally classed as high quality, such as egg and milk protein, or low quality such as gluten. In general, vegetable proteins are of low quality but soy protein is an exception. The paper by Capristo et al. in this issue of the journal has shown that enteral formulations consisting of soy protein are as effective nutritionally as enteral formulations containing milk protein.

Proteins, peptides and amino acids in enteral nutrition: overview and some research challenges.

We have selectively reviewed various aspects of protein and amino acid metabolism and nutrition which we feel are relevant and important in any comprehensive consideration of proteins, peptides, and amino acids in enteral nutrition. These, together with various clinical aspects of the problem that we have not addressed, are covered in more specific detail elsewhere in this volume. Our hope is that by the time this workshop is at an end a reasonable picture of the state of the art will emerge in terms of an understanding of the physiology and biochemistry of protein, peptide, and amino acids in enteral nutrition. Simultaneously, we will need to know, through careful clinical investigation, how this knowledge can best be exploited for optimizing the design of the protein/peptide/amino acid component of enteral nutrition formulations. In doing so it should be possible to achieve a more effective enteral use of proteins, peptides, and amino acids in the comprehensive clinical management of individuals under various pathophysiological states.