Enteral Formulations Research Articles

Enteral Nutrition Therapy: Historical Perspective, Utilization, and Complications.

Enteral nutrition (EN) therapy can provide vital nutrition support for patients with various medical conditions as long as it is indicated and supported by ethical reasoning. This review seeks to offer a detailed account of the history of EN development, highlighting key milestones and recent advances in the field. Additionally, it covers common complications associated with EN and their management. After years of research and development, we have reached newer generations of enteral feeding formulations, more options for enteral tubes and connectors, and a better understanding of EN therapy challenges. Given the availability of many different formulas, selecting a feeding formula with the best evidence for specific indications for enteral feeding is recommended. Initiation of enteral feeding with standard polymeric formula remains the standard of care. Transition to small-bore connectors remains suboptimal. Evidence-based practices should be followed to recognize and reduce possible enteral feeding complications early.

Instruments to evaluate the profile of food and enteral formulation hardlers

To know the profile of food and enteral formulation handlers is important to promote more effective health education actions for these individuals. This study aimed to develop instruments to evaluate the profile of food handlers in households (PFH) and in food service establishments (PFSE), as well as the profile of handlers of enteral formulations in households (PEFHH). A scoping review was carried out to identify questions about the profile of food and enteral formulation handlers evaluated in studies in thein the main national and international databases. From 47 selected articles, 66 questions were identified. Of these, 17, 22, and 18 questions were established to assess the PFH, PFSE, and PEFHH, respectively. The instrument questions were subdivided by subject into personal data, sociodemographic and professional characteristics, and general information. Some questions differ between instruments due to segment specificities. The proposed instruments are novel tools. Through a scoping review and expert consultations, a comprehensive set of questions was identified and organized into instruments tailored to each specific segment. These tools will be valuable for nutritionists, researchers, and other professionals involved in assessing and addressing the needs of food handlers.

Assessment of the risk of contamination of enteral nutrition bottles based on the simulation of home use conditions and hygiene procedures.

Home-prepared enteral formulations are supplied to patients through enteral nutrition bottles, via a gravity bag or other container, which may be inadequately sanitized and reused more times than recommended by the manufacturer. Such procedures increase the risk of contamination and can compromise the patient's clinical outcome. In light of this, the present study aimed to assess the risk of contamination of enteral nutrition bottles by simulating home use conditions and hygiene procedures. A simulation of bottle usage was conducted across the three categories of enteral nutrition (homemade enteral preparations, blended enteral preparations, and commercial enteral formulas) for 3 days, using three hygiene procedures reported by caregivers: use of detergent (DET); use of detergent and boiling water (DET+BW); and use of detergent and bleach (DET+BL). The microbiological contamination was determined by the analysis of aerobic mesophilic microorganisms. The bottles that were used for 3 days, regardless of the enteral nutrition category, were within the acceptable limit for aerobic mesophilic microorganisms (between <4 and 8.0 colony-forming units [CFU]/cm2) when sanitized using the DET+BW and DET+BL procedures. The enteral nutrition bottles, when cleaned using the DET procedure during the 3 days of usage, showed low microbial contamination (between <4 and 3.0 CFU/cm2) in blended preparation and commercial formula only. Thus, regardless of the enteral nutrition category, we found that the bottles can be used for 3 days, as long as the DET+BW or DET+BL hygiene procedure is applied and safe food handling measures are adopted.

Costliness of Iron Repletion Methods in Iron Deficient Adolescent Females Depends on Patient-Specific Factors

Background: Iron deficiency anemia is common in adolescent females. Treatment is possible with either enteral (PO) or intravenous (IV) formulations. The cost-effectiveness of each method is unknown. In addition, treatment cost-effectiveness likely differs between three distinct adolescent female subgroups with iron deficiency: average BMI with moderate anemia, average BMI with severe anemia, and obese BMI with moderate anemia. Methods: A decision analysis model evaluated PO ferrous sulfate, IV iron sucrose, and IV ferric carboxymaltose use in adolescent female subgroups, comparing costs associated with each treatment strategy from a healthcare perspective. In the PO iron strategy, initial PO therapy failure prompted conversion to IV iron sucrose use. Literature review was performed to obtain model parameters. The effectiveness term in the model was the likelihood of successful iron repletion, which was assumed to be identical for each strategy in the base case analysis. Model time horizon was three months. One-way sensitivity analyses evaluated model uncertainty. Results: In moderate anemia and average BMI, IV iron sucrose was least costly at $531.79 (compared to $592.12 for PO iron and $855.78 for IV ferric carboxymaltose). Varying the PO iron success likelihood and clinic visit frequency could favor the PO iron strategy. With severe anemia and average BMI, IV ferric carboxymaltose was least costly at $855.78 (vs. $1013.44 for IV iron sucrose and $902.78 for PO iron). Variation in infusions needed for IV iron sucrose (and therefore anemia severity) alters the preferred strategy, with IV iron sucrose favored if 1-4 infusions are required, PO iron favored if 5-6 infusions required, and IV ferric carboxymaltose preferred if 7 or more infusions are needed. In the moderately anemic obese group, PO iron was preferred, costing $763.90 compared to $798.12 for IV iron sucrose and $855.78 for IV ferric carboxymaltose. In a one-way sensitivity analysis, PO iron was favored at a weight &amp;gt;74kg (base case value 90); below this weight, IV iron sucrose was preferred. Conclusion: The cost-effectiveness of different iron repletion strategies depends on the adolescent female subgroup affected. Patient weight and anemia severity are important clinical characteristics to consider when assessing which method is the most cost-effective.

Successful enteral administration of crushed posaconazole delayed-release tablets in children.

Erratic absorption of posaconazole oral suspension necessitates frequent dosing and administration with meals or supplements. Alternative enteral formulations are desirable for patients intolerant to enteral nutrition. Crushed posaconazole delayed-release tablets (POS-DRT) show promise in adults; limited evidence exists in children. We used crushed POS-DRT in 10 encounters with nine pediatric patients, achieving target POS concentrations in 90% of encounters. This highlights crushed POS-DRT as a potential enteral option for pediatric antifungal prophylaxis and treatment.

The importance of providing dietary fiber in medical and surgical critical care.

The early provision of soluble/insoluble fiber to the patient who is critically ill has been controversial in the past. Especially in the setting of hemodynamic instability, dysmotility, or impaired gastrointestinal transit, fear of inspissation of formula with precipitation of nonocclusive mesenteric ischemia (NOMI)/nonocclusive bowel necrosis (NOBN) limited its utilization by medical and surgical intensivists. The incidence of NOMI/NOBN has been estimated at 0.2%-0.3% for all intensive care unit (ICU) patients receiving enteral nutrition (EN), and the occurrence of inspissated formula is even less. The science supporting a benefit from providing fiber has recently increased exponentially. The fermentation of soluble fibers leading to the production of short chain fatty acids supports gut barrier function, modulates immune responses, and promotes refaunation of commensal organisms. The "butyrate effect" refers to local (gastrointestinal tract) and systemic anti-inflammatory responses mediated by the M2 polarization of macrophages, inhibition of histone deacetylase, and stimulation of ubiquitous G protein receptors. Both soluble and insoluble fiber have been shown to promote intestinal motility, reduce feeding intolerance, and shorten hospital length of stay. The benefit of providing dietary fiber early upon admission to the ICU outweighs its minimal associated risk. The point at which the intensivist determines that is safe to initiate EN, both soluble and insoluble fiber should be included in the enteral formulation.

Microbiological contamination present in enteral tube feeding prepared in hospitals and/or at home: a systematic review.

The safety of enteral formulas is important to restore and maintain the health of patients. A systematic review of the literature was conducted to assess the microbiological contamination present in enteral tube feeding prepared in hospitals and/or at home. A systematic search was conducted of the Medline, Scopus, BVS, CAPES/MEC, Embase, Science Direct, and SciELO databases and gray literature. Eligible studies that analyzed the contamination of enteral formulas manipulated in hospitals and/or at home were selected; a quality assessment tool was used. Twenty-three studies evaluated 1099 enteral formulations. Of these, 44.67% of enteral formulas (n = 491) exceeded the acceptable bacterial count. Samples of homemade enteral formulation preparations (86.03%; n = 191) had the highest bacterial counts, followed by mixed preparations (79.72%; n = 59), and commercial formulas (30.01%; n = 241). The number of samples of enteral formulations that exceeded the bacterial count at home was 70.79% (n = 160 at the hospital was 37.91% (n = 331). Total coliforms (82.68%; n = 406) and mesophilic aerobes (79.22%; n = 389) were the most common microorganisms. Samples with bacterial pathogens were also identified, with Bacillus cereus (4.07%; n = 20) and Listeria monocytogenes (3.66%; n = 18) being the most prevalent. A high number of samples of enteral formulations exceeded the bacterial count, but the risk to patient's health when consuming enteral tube feeding prepared in hospitals or at home may be low. This is because the bacteria present in the samples are not considered potential causes of disease but rather indicators of hygiene conditions. PROSPERO registration no. CRD42022367573.

Impact of pin‐to‐plate cold plasma depolymerization on the gelation and functional attributes of guar galactomannan

AbstractThe present study aimed to investigate the impact of pin‐to‐plate cold plasma on the gelation and functional attributes of guar seed galactomannan. The guar galactomannan was subjected to 170 and 230 V treatment for 30 and 60 min and investigated for the gel characteristics and functional properties. The cold plasma treatment incurred galactomannan chain depolymerization with a reduction in the degree of polymerization (DP) ranging from 7.33% to 48.99%. The water contact angle (WCA) reduced from 110.93° to 95.54°, thus increasing the hydration capacity (36.73–45.90 g/g). These mechanisms diminish the gel viscosity (from 798. 227 cP of UT to 334.65 cP at 230‐60) and the viscoelastic moduli (G′ andG″) indicating the low strength of gels from plasma‐treated galactomannan (PT‐GG). This further influenced the least gelation concentration, foam capacity, and foam stability. However, the critical strain (from 11.83% [UT] to 41% [230‐60]), cross‐over frequency (from 3.39 Hz [UT] to 15.3 Hz [230‐60]), and degradation activation energy (from 18.445 kJ/mol [UT] to 21.721 kJ/mol [230‐60]) of the PT‐GG were increased (from 18.445 kJ/mol [UT] to 21.721 kJ/mol [230‐60]) signifying the increased stability of gels by intramolecular and electrostatic forces. Thus, the cold plasma‐induced depolymerization and hydrophilic modification of galactomannan influence the gelation and functional attributes which widen the potential applications of the hydrocolloid.Practical ApplicationsDepolymerized guar gum is industrially known for its specific applications such as low‐viscosity source of dietary fiber, stabilizers, complex forming, and encapsulating agents. This study shows the potential of cold plasma processing as an eco‐friendly sustainable technology for producing depolymerized guar gum which can be applied as a source of fiber in enteral feed formulations, stabilizers in low viscous spreads and sauces, and also in thermo‐reversible gel networks due to its thermal gel transition attributes.

Checklist to assess food safety when handling home enteral nutrition.

Identifying food safety risks when handling enteral formulations at home is important to restore and maintain the health of patients. Therefore, this study developed and validated a food safety assessment checklist for handling home enteral nutrition (HEN). This methodological study developed a checklist based on a literature review and interviews with food safety professionals. The content validation, which was conducted by food safety and enteral feeding experts, assessed the relevance, clarity, and simplicity of the checklist using the content validity index of items (CVI-I), categories (CVI-C), and the entire instrument (CVI-EI). Each item was rated as either essential, necessary, or recommended according to the risk in relation to foodborne diseases. The Food Safety for Handling Home Enteral Nutrition checklist (FSHEN checklist) that was developed includes 40 items and the following eight categories: physical structure; cleaning of facilities, equipment, furniture, and utensils; pests and waste; water supply; food handlers; ingredients and packaging; handling of enteral formulations; and the bottling and storage of enteral formulations. The CVI-EI was above the recommendation (≥0.93) for the three assessed criteria, as was the CVI-C in terms of clarity (≥0.95), relevance (≥0.98), and simplicity (≥0.84). A total of 52.5% of the items were rated as essential, 32.5% as necessary, and 15% as recommended. The FSHEN checklist is relevant, clear, and easy to use. It can help health professionals and individuals working in the field to assess and prioritize items to improve food safety in the management of HEN.

Enteral nutrition product formulations: A review of available products and indications for use.

When oral nutrition is not feasible, enteral nutrition (EN) therapy is often considered the preferred route of nutrition support to meet the nutrient needs of individuals with a functional gastrointestinal tract across multiple levels of care (critical care, acute care, and home care). Enteral formulations have progressively evolved over the last 50 years from the simple blending of hospital food thin enough to run through a feeding tube, to the development of commercial standard formulas, followed by specialized formulas with immune-modulating and disease-specific qualities, to the most recent shift to food-based or blenderized EN composed of natural, whole foods with perceived health benefits. With the vast number of enteral formulations on the market, clinicians may be overwhelmed trying to determine proven vs theoretical benefits. This review is intended to explore differences in enteral formulations, identify implications for clinical practice, and review evidenced-based clinical guidelines to assist clinicians in enteral formula selection.

LB1148: An Enteral Protease Inhibitor Significantly Accelerated the Return of Bowel Function after Bowel Resection

Introduction: Return of bowel function is a clinically accepted determinant of recovery after gastrointestinal (GI) surgery. Postoperative ileus presents significant clinical challenges that may prolong hospital stay, contribute to readmission, and increase morbidity and expense. The aim of this study was to determine if a novel enteral formulation of tranexamic acid, LB1148, could accelerate return of GI function in patients undergoing bowel resection surgery. Methods: We conducted a phase II multicenter, randomized, double-blind, placebo-controlled study of LB1148 for the restoration of postoperative bowel function in patients undergoing elective bowel resection. The study included both open and laparoscopic surgical approaches with anastomosis and or stoma creation. Primary outcome was recovery of bowel function as measured by time from end of surgery to oral food tolerance and passage of stool. Results: A total of 120 patients completed the study. Treatment groups were well balanced for patient demographics and included a broad range of baseline surgery characteristics, approaches, and methodologies. Median time to return of bowel function was 2.77 days vs 3.83 days in patients receiving LB1148 and placebo, respectively (hazard ratio=1.8; p = 0.0008). Key GI functional data will be presented based on laparoscopy and laparotomy with surgical characteristics including, right hemicolectomy, left hemicolectomy, and rectosigmoid surgery. The most common drug-related adverse events were GI disorders (LB1148 4.7% vs placebo 3.2%). No drug-related serious adverse events occurred in the trial. Conclusion: For patients undergoing elective bowel resection surgery, LB1148 was safe and well-tolerated and significantly accelerated the return of bowel function.

Is it Possible to Estimate the Bioequivalence between Parenteral and Enteral Formulations of Escin?

We suggest that enteral formulation of escin could be used instead of enteral formulation if it is not available.

Does the nutritional composition and category of administered enteral nutrition affect the nutritional status of patients receiving home nutritional therapy?

Home enteral nutrition is a nutritional intervention that can help in the recovery of health after hospital discharge. The objectives of this study were to evaluate the nutritional composition of different categories of enteral nutrition administered to patients at home, the relationship with their nutritional status, and to compare the nutritional recommendations to the nutritional content provided by the different categories of enteral nutrition. 111 samples of homemade enteral preparations (HEP), blended enteral preparations (BEP) and commercial enteral formulas (CEF) were collected from patients' homes. Physicochemical analyses were performed on the enteral formulations, and anthropometric and body composition evaluations were performed on the patients. Comparisons between the infused and prescribed nutritional content were performed. Shapiro-Wilk, Wilcoxon, and Kruskal-Wallis tests with post hoc DMS were conducted. The enteral nutrition categories demonstrated adequacy in relation to the physical analyses. The energy content was similar among the evaluated categories. The BEP and CEF presented higher levels of total solids, proteins, lipids, caloric density and non-protein calories; they also had a lower volume of infused/day content, and both were classified as normocaloric. The HEP were classified as hypocaloric. Regarding the infused content in relation to the recommended content, the HEP presented lower levels of protein and lipids; the CEF showed lower lipid and carbohydrate content, and the BEP presented adequacy in all nutrients. Most of the evaluated anthropometric parameters did not differ between the enteral nutrition categories. The anthropometric indicator of arm circumference (cm and %) was higher in patients receiving CEF and BEP, and the triceps skin fold (mm) was higher in patients receiving CEF and HEP. It is recommended to review the macronutrient content in nutritional prescriptions, regardless of the enteral nutrition category used. Most anthropometric parameters did not differ between the categories of enteral nutrition administered, especially those that were indicative of lean body mass.

Therapeutic Properties and Use of Extra Virgin Olive Oil in Clinical Nutrition: A Narrative Review and Literature Update

Extra virgin olive oil (EVOO) is a cornerstone of the Mediterranean diet (MedD). In this narrative review, we synthesize and illustrate the various characteristics and clinical applications of EVOO and its components—such as oleic acid, hydroxytyrosol, and oleuropein—in the field of clinical nutrition and dietetics. The evidence is split into diet therapy, oleic acid-based enteral nutrition formulations and oral supplementation formulations, oleic acid-based parenteral nutrition, and nutraceutical supplementation of minor components of EVOO. EVOO has diverse beneficial health properties, and current evidence supports the use of whole EVOO in diet therapy and the supplementation of its minor components to improve cardiovascular health, lipoprotein metabolism, and diabetes mellitus in clinical nutrition. Nevertheless, more intervention studies in humans are needed to chisel specific recommendations for its therapeutic use through different formulations in other specific diseases and clinical populations.

Unraveling the Metabolic Hallmarks for the Optimization of Protein Intake in Pre-Dialysis Chronic Kidney Disease Patients.

The daily amount and quality of protein that should be administered by enteral nutrition in pre-dialysis chronic kidney disease (CKD) patients is a widely studied but still controversial issue. This is due to a compromise between the protein necessary to maintain muscular proteostasis avoiding sarcopenia, and the minimal amount required to prevent uremia and the accumulation of nitrogenous toxic substances in blood because of the renal function limitations. This review underlines some intracellular and extracellular features that should be considered to reconcile those two opposite factors. On one hand, the physiological conditions and usual side effects associated with CKD, mTOR and other proteins and nutrients involved in the regulation of protein synthesis in the muscular tissue are discussed. On the other hand, the main digestive features of the most common proteins used for enteral nutrition formulation (i.e., whey, casein and soy protein) are highlighted, due to the importance of supplying key amino acids to serum and tissues to maintain their concentration above the anabolic threshold needed for active protein synthesis, thereby minimizing the catabolic pathways leading to urea formation.

Macronutrients and energy in home-prepared enteral tube feeding: Comparison between food composition table estimates, nutrition labels, and laboratory analysis.

The effectiveness of home enteral nutrition depends on the supply and delivery of the prescribed nutrients. This study compared the macronutrient and energy values of home-prepared enteral tube feeding analyzed in the laboratory with the same information calculated from labels and food composition tables. A total of 107 enteral formulations were analyzed: 66 commercial enteral formulas (CEFs), 19 homemade enteral preparations, and 22 blended enteral preparations (BEPs). The values of macronutrients and energy and the ratio between the values found in the laboratory and the calculated values were all evaluated. The tolerance limit of acceptable variation was 20%. The results were subjected to chemometric methods using principal component analysis (PCA) and hierarchical cluster analysis (HCA). In the three categories of the enteral formulations, the calculated values for protein and fat were higher than those obtained in the laboratory. The calculated values for energy were higher than those obtained in the laboratory for the BEPs and CEFs. The CEFs had the highest percentage within the limit of acceptable variation for carbohydrate and protein, whereas the BEPs presented the lowest values for fat and energy. In the exploratory analysis of data using PCA and HCA, it was possible to verify similarities and discrepancies between the enteral formulations analyzed in the laboratory with those calculated from the labels and food composition tables. The enteral formulations showed differences between the values of macronutrients and energy analyzed in the laboratory and those calculated from labels and/or food composition tables.

Magnesium intake by enteral formulation affects serum magnesium concentration in patients undergoing hemodialysis.

Decreased serum magnesium levels are associated with mortality and fractures in patients with chronic kidney disease; however, there is no recommendation for Mg intake in these populations. This study used cross-sectional analysis to examine the association between Mg intake and serum Mg levels in patients undergoing hemodialysis. Sixty-one patients were included. The daily Mg intake was 185 mg (IQR: 151-203 mg), and serum Mg level was 2.4 mg/dL (IQR: 2.2-2.7 mg/dL). Multiple regression analysis showed that intake of enteral formulation by tube feeding was an independent factor associated with serum Mg level (B=0.90 [95% confidence interval: 0.61-1.20], p < 0.01). These findings may aid in serum Mg level management through diet and enteral formulation in patients undergoing hemodialysis.

WHO essential medicines for children 2011–2019: age-appropriateness of enteral formulations

IntroductionThe WHO Essential Medicine List for children (EMLc) is used for promoting access to medicines. The age-appropriateness of enteral (oral and rectal) formulations for children depend on their adaptability/flexibility to...

Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan

BackgroundA multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted.MethodsA multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE.ResultsPrescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified.ConclusionsNeonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.

Evaluation of slurry sampling preparation of enteral nutrition formulations for multielement determination using inductively coupled plasma optical emission spectrometry

An analytical procedure for the multielement determination in enteral nutrition formulations employing slurry sampling and inductively coupled plasma optical emission spectrometry (ICP OES) is proposed. A two-level full-factorial design was applied to assess the influence of the presence of stabilizing agents (HNO3, Triton X-100 and ethanol) on the composition of the slurry. Multiple response was established as a dependent variable. The experimental conditions for the preparation of the slurry were: 2.0 mL of sample and 8.0 mL of 10% (v/v) HNO3. The limits of detection (LOD) were 5; 9; and 10 µg L−1 for Cu, Fe, Zn, respectively. For P, and K, the LOD were 8 and 24 mg L−1, respectively. The method was applied for the analysis of three enteral nutrition formulation samples and the obtained concentrations ranges were (in mg L−1): 0.41–0.43 (Cu), 2.0–2.9 (Fe), 1.7–3.1 (Zn), 682–1409 (K), and 217–344 (P).