Critically ill patients often experience dysglycaemia which is strongly associated with increased morbidity and mortality. While exogenous insulin therapy is used to manage hyperglycaemia, it has been demonstrated to increase the frequency of hypoglycaemic episodes and variability in blood glucose, both of which have been shown to increase mortality. Enteral feeding may worsen glycaemic control due to its carbohydrate content. This study aims to determine if the use of a reduced carbohydrate formula improves overall glycaemic control when compared to standard care in critically ill patients with hyperglycaemia.

This is the protocol for a multicentre, prospective randomised controlled trial conducted at 7 intensive care units (ICU). One hundred and sixty patients admitted to ICU, receiving or about to receive enteral nutrition expected to continue until the day after tomorrow, who have had two consecutive blood glucose levels >10 mmol/L or have received insulin based on local protocols within the previous 24-h period, and who meet none of the exclusion criteria, will be eligible. Patients in the standard care arm will receive enteral nutrition as per usual site practice and patients in the intervention arm will receive Glucerna Select® to achieve a caloric equivalent to that prescribed or delivered prior to study recruitment. All other aspects of nutrition management remain as per routine clinical practice. The primary outcome measure is units of insulin administered per day in the ICU to a maximum of seven days post randomisation. Key secondary outcome measures include measures of glycaemic control, nutrition provision, nutrition tolerance and clinical outcomes such as infectious complications, duration of ventilation, ICU and hospital stay as well as in hospital mortality.

This study will provide data on whether the use of a reduced carbohydrate enteral nutrition formula reduces insulin administration thereby improving dysglycaemia in critically ill patients. It will also be used to refine the design of a larger multi-centre trial to definitively ascertain the impact of using reduced carbohydrate enteral formula on clinical outcomes.

Ethical approval was obtained from the local Research Ethics Committee (HREC Approval HREC/2021/QMS/74667). The trial was registered on the Clinical Trials Registry with registration number ACTRN12621000859886.

Advanced glycation end-products (AGEs) can enter patients' circulation through exogenous sources, such as enteral nutrition formulae. Circulating AGEs, specifically carboxymethyllysine, can promote insulin resistance and activation of pro-inflammatory pathways leading to oxidative stress, cell death, and organ failure. Suboptimal kidney function increases the risk of elevated circulating AGEs because levels are controlled through urinary excretion. Our aim was to determine associations between carboxymethyllysine intake and glycemic control as well as clinical outcomes in critically ill patients and explore these in the subset of patients with an acute kidney injury (AKI).

This was a retrospective cohort study. Data were extracted from electronic medical records. Patients were eligible if they were ≥18 years and received enteral nutrition, with known carboxymethyllysine content, for ≥3 days. AKI was defined using the Kidney Disease: Improving Global Outcomes guidelines. Linear and logistic regression models were used to determine adjusted associations.

Between 2015 and 2021, 2636 patients met the eligibility criteria, with 848 (32%) patients having an AKI. Most were male (n = 1752, 67%) with a median (interquartile range) Acute Physiology And Chronic Health Evaluation III score of 59 (45-77). For every 10-μmol increase in carboxymethyllysine provision, mean blood glucose increased by 0.05 mmol (95% CI, 0.03-0.07), and the odds of dying increased by 16% (odds ratio = 1.16; 95% CI, 1.06-1.27). A subgroup analysis indicated these associations persisted in patients with AKI but not in those without.

Carboxymethyllysine intake was associated with increased mean blood glucose and odds of dying in our study cohort.

Nutrition therapy is important in the management of critically ill patients and is continuously evolving as new evidence emerges. The Japanese Critical Care Nutrition Guideline 2024 (JCCNG 2024) is specific to Japan and is the latest set of clinical practice guidelines for nutrition therapy in critical care that was revised from JCCNG 2016 by the Japanese Society of Intensive Care Medicine. An English version of these guidelines was created based on the contents of the original Japanese version. These guidelines were developed to help health care providers understand and provide nutrition therapy that will improve the outcomes of children and adults admitted to intensive care units or requiring intensive care, regardless of the disease. The intended users of these guidelines are all healthcare professionals involved in intensive care, including those who are not familiar with nutrition therapy. JCCNG 2024 consists of 37 clinical questions and 24 recommendations, covering immunomodulation therapy, nutrition therapy for special conditions, and nutrition therapy for children. These guidelines were developed in accordance with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system by experts from various healthcare professionals related to nutrition therapy and/or critical care. All GRADE-based recommendations, good practice statements (GPS), future research questions, and answers to background questions were finalized by consensus using the modified Delphi method. Strong recommendations for adults include early enteral nutrition (EN) within 48 h and the provision of pre/synbiotics. Weak recommendations for adults include the use of a nutrition protocol, EN rather than parenteral nutrition, the provision of higher protein doses, post-pyloric EN, continuous EN, omega-3 fatty acid-enriched EN, the provision of probiotics, and indirect calorimetry use. Weak recommendations for children include early EN within 48 h, bolus EN, and energy/protein-dense EN formulas. A nutritional assessment is recommended by GPS for both adults and children. JCCNG 2024 will be disseminated through educational activities mainly by the JCCNG Committee at various scientific meetings and seminars. Since studies on nutritional treatment for critically ill patients are being reported worldwide, these guidelines will be revised in 4 to 6 years. We hope that these guidelines will be used in clinical practice for critically ill patients and in future research.

Enteral nutrition (EN) has been reported to have some physiological importance for critically ill patients. However, the advantage of EN over parenteral nutrition remains controversial in recent paradigms. To maximize the benefits and efficiency of EN, implementing measures based on comprehensive evidence is essential. Here, we systematically reviewed EN-related studies and integrated them into the best and most up-to-date EN practices. We extracted studies from 13 systematic reviews during the development of Japanese Critical Care Nutrition Guidelines, summarizing findings on the assessment of enteral feeding intolerance (EFI), the timing of EN, formula composition and nutrients, and method of administration in critically ill adult patients. Multifaceted EFI assessment may be needed in patients for high-risk patients. Early EN may reduce infectious complications, and initiating EN even earlier may offer an additional advantage. High protein intake (≥1.2 g/kg/day) could maintain muscle mass and physical function without increasing gastrointestinal complications. Probiotics, prebiotics, and synbiotics may serve as beneficial options for preventing infection and gastrointestinal complications, although their efficacy depends on the strains, types, and combinations used. For patients with EFI, post-pyloric feeding could be an effective approach, while intermittent feeding may be a safer approach. Both methods should be utilized to achieve nutritional targets. Integrating these nutritional interventions into EN strategies may help maximize their effectiveness and minimize complications. However, careful consideration regarding timing, dosage, nutrient selection, administration methods, and patient selection is required.

A wide range of factors contribute to the overlap of hyperglycemia-acute or chronic-and sarcopenia, as well as their associated adverse consequences, which can lead to impaired physical function, reduced quality of life, and increased mortality risk. These factors include malnutrition (both overnutrition and undernutrition) and low levels of physical activity. Hyperglycemia and sarcopenia are interconnected through a vicious cycle of events that mutually reinforce and worsen each other. To explore this association, our review compiles evidence on: (i) the impact of hyperglycemia on motor and muscle function, with a focus on the mechanisms underlying biochemical changes in the muscles of individuals with or at risk of diabetes and sarcopenia; (ii) the importance of the clinical assessment and control of sarcopenia under hyperglycemic conditions; and (iii) the potential benefits of medical nutrition therapy and increased physical activity as muscle-targeted treatments for this population. Based on the reviewed evidence, we conclude that a regular intake of key functional nutrients, together with structured and supervised resistance and/or aerobic physical activity, can help maintain euglycemia and improve muscle status in all patients with hyperglycemia and sarcopenia.

High-fat, low-carbohydrate enteral nutrition has gained attention, with expectations of an improved respiratory condition, fewer complications, and lower mortality. The present study performed a systematic review and meta-analysis of randomized controlled trials to examine the effects of high-fat, low-carbohydrate enteral nutrition in critically ill adult patients.

We searched MEDLINE via Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), and ICHUSHI for randomized controlled trials comparing high-fat, low-carbohydrate enteral nutrition to standard enteral nutrition in critically ill adult patients who received enteral nutrition. The primary outcome was mortality. Secondary outcomes included intensive care unit (ICU) mortality, length of ICU stay, length of mechanical ventilation, and adverse events of diarrhea and gastric residual volume. We examined the risk of bias using the Cochrane risk-of-bias tool for randomized trials version 2. We assessed the overall certainty of evidence based on the Grading of Recommendations Assessment, Development, and Evaluation methodology. Synthesis results were calculated with risk ratios and 95% confidence intervals using a Mantel-Haenszel random-effects model.

Eight trials with 607 patients were included. The effects of high-fat, low-carbohydrate enteral nutrition on mortality did not significantly differ from those of standard enteral nutrition (62/280 [22.1%] vs. 39/207 [18.8%], risk ratios = 1.14, 95% confidence intervals 0.80 to 1.62, P = 0.47). No significant differences were observed in ICU mortality, ICU length of stay, diarrhea, or gastric residual volume between the two groups. However, high-fat, low-carbohydrate enteral nutrition was associated with a significantly shorter duration of mechanical ventilation (mean difference -1.72 days, 95% confidence intervals -2.93 to -0.50, P = 0.005).

High-fat, low-carbohydrate enteral nutrition may not affect mortality, but may decrease the duration of mechanical ventilation in critically ill adult patients. Limitations include the small number of studies and potential for bias. Further research is needed to confirm these results and investigate effects on other outcomes and in a subgroup of patients requiring mechanical ventilation.

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.

The coronavirus disease 2019 (COVID-19) pandemic challenges our collective understanding of transmission, prevention, complications, and clinical management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Risk factors for severe infection, morbidity, and mortality are associated with age, environment, socioeconomic status, comorbidities, and interventional timing. Clinical investigations report an intriguing association of COVID-19 with diabetes mellitus and malnutrition but incompletely describe the triphasic relationship, its mechanistic pathways, and potential therapeutic approaches to address each malady and their underlying metabolic disorders. This narrative review highlights common chronic disease states that interact epidemiologically and mechanistically with the COVID-19 to create a syndromic phenotype-the COVID-Related Cardiometabolic Syndrome-linking cardiometabolic-based chronic disease drivers with pre-, acute, and chronic/post-COVID-19 disease stages. Since the association of nutritional disorders with COVID-19 and cardiometabolic risk factors is well established, a syndromic triad of COVID-19, type 2 diabetes, and malnutrition is hypothesized that can direct, inform, and optimize care. In this review, each of the three edges of this network is uniquely summarized, nutritional therapies discussed, and a structure for early preventive care proposed. Concerted efforts to identify malnutrition in patients with COVID-19 and elevated metabolic risks are needed and can be followed by improved dietary management while simultaneously addressing dysglycemia-based chronic disease and malnutrition-based chronic disease.

There has been a significant increase in nutrition therapy related studies within the critical care cohort in recent years. Management of patients with both diabetes and stress hyperglycaemia through targeted nutrition interventions is no exception. The aim of this review is to outline current available diabetes specific nutrition formula, its impact on gastric emptying and subsequently glycaemic control as well as explore recent literature on the efficacy of utilizing nutrition support to optimize glycaemic control in critically ill patients.

Studies explored within this review were similar in terms of outcomes measures, focusing primarily on insulin use and glycaemic control. Although there were promising results in terms of the impact of diabetes-specific nutrition formula on these outcome measures, there were no significant associations with clinical outcomes.

The use of diabetes-specific formulae in critically ill patients with pre-existing diabetes and stress hyperglycaemia can be considered a logical approach to minimize the risks associated with high doses of insulin. Additional research is required to address the effects of these formulae on the dysglycaemia, nursing workload, safety of glycaemic control and cost-effectiveness.

Hyperglycaemia occurs frequently in the critically ill. Dietary intake of advanced glycation end-products (AGEs), specifically Nε-(carboxymethyl)lysine (CML), may exacerbate hyperglycaemia through perturbation of insulin sensitivity. The present study aimed to determine whether the use of nutritional formulae, with varying AGE loads, affects the amount of insulin administered and inflammation.

Exclusively tube fed patients (n = 35) were randomised to receive Nutrison Protein Plus Multifibre®, Diason® or Glucerna Select®. Insulin administration was standardised according to protocol based on blood glucose (<10 mmol L^-1 ). Samples were obtained at randomisation and 48 h later. AGEs in nutritional formula, plasma and urine were measured using mass spectrometry. Plasma inflammatory markers were measured using an enzyme-linked immunosorbent assay and multiplex bead-based assays.

AGE concentrations of CML in nutritional formulae were greatest with delivery of Nutrison Protein Plus® (mean [SD]; 6335 pmol mol^-1 [2436]) compared to Diason® (4836 pmol mol^-1 [1849]) and Glucerna Select® (4493 pmol mol^-1 [1829 pmol mol^-1 ]) despite patients receiving similar amounts of energy (median [interquartile range]; 12 MJ [8.2-13.7 MJ], 11.5 MJ [8.3-14.5 MJ], 11.5 MJ [8.3-14.5 MJ]). More insulin was administered with Nutrison Protein Plus® (2.47 units h^-1 [95% confidence interval (CI) = 1.57-3.37 units h^-1 ]) compared to Diason® (1.06 units h^-1 [95% CI = 0.24-1.89 units h^-1 ]) or Glucerna Select® (1.11 units h^-1 [95% CI = 0.25-1.97 units h^-1 ]; p = 0.04). Blood glucose concentrations were similar. There were associations between greater insulin administration and reductions in circulating interleukin-6 (r = -0.46, p < 0.01), tumour necrosis factor-α (r = -0.44, p < 0.05), high sensitivity C-reactive protein (r = -0.42, p < 0.05) and soluble receptor for advanced glycation end-products (r = -0.45, p < 0.01) concentrations.

The administration of greater AGE load in nutritional formula potentially increases the amount of insulin required to maintain blood glucose within a normal range during critical illness. There was an inverse relationship between exogenous insulin and plasma inflammatory markers.

The primary objective was to compare the intake of important micronutrients provided from enteral nutrition to critically ill patients with the Australia and New Zealand recommended dietary intakes. A secondary objective was to compare the upper levels of intake and investigate prespecified subgroups.

A systematic literature review was performed.

MEDLINE, EMBASE, CINAHL, and CENTRAL were used.

Databases were searched for randomised controlled trials that investigated an enteral nutrition intervention as the sole source of nutrition, were published in English between January 2000 and January 8th, 2021, and provided data to calculate micronutrient intake. The primary outcome was the % recommended dietary intake. The quality of individual trials was assessed using the Cochrane Risk of Bias Tool. Outcomes are presented as either mean ± standard deviation or median [interquartile range], with a p < 0.05 considered statistically significant.

Thirteen trials were included (n = 1538 patients). Trials investigating hypocaloric nutrition were excluded from the primary outcome assessment (conducted in nine trials (n = 1220)). All nine trials delivered ≥104% of the recommended dietary intakes and <100% of the upper level of intakes of all micronutrients. In subgroup analyses, trials with ≥80% target energy delivered a higher % of the recommended dietary intake of vitamin B12, thiamine, zinc, and vitamin C. Acute Physiology and Chronic Health Evaluation scores ≥20 delivered a higher % of the recommended dietary intake of vitamin B12 and vitamin A. Antioxidant formulas compared with standard formulas delivered a higher % recommended dietary intake of vitamin C and thiamine. In the four trials that investigated hypocaloric feeding compared with control, there was no difference in micronutrient intake. The quality was low.

Enteral nutrition delivery frequently met the recommended dietary intakes for all micronutrients investigated and did not exceed the upper levels of intake set for health.

CRD42020178333.

Effect size, α level, power, and sample size are misunderstood concepts that play a major role in the design and interpretation of studies. Effect size represents the magnitude of a change in an outcome or the strength of a relationship. Often, the effect size may be more important than just relying on the α level when interpreting results from a study because it informs a researcher of the actual magnitude of the difference or relationship. Confidence intervals can also assist in making this assessment. Power represents the probability of rejecting the null hypothesis when it is false. Effect size, power, and α level are all important in the calculation of sample size needed to conduct a study. Calculating the sample size a priori and including the required number of participants is essential. Studies with small sample sizes, relative to the needed number provided from a power analysis, may lead to false negative results. Studies with grossly large sample sizes may yield statistically significant findings with small effect sizes that may not be clinically relevant. It is beneficial when all four components are clearly presented in analytic studies. Failure to include these elements may limit the ability of other researchers to replicate the study's findings and lead to difficulty when interpreting the study's results.

Hyperglycemia is associated with increased morbidity and mortality. Low-carbohydrate, high-fat (LCHF) enteral formulas are marketed to improve glycemic control; however, given the multifactorial mechanisms contributing to hyperglycemia in patients who are critically ill, the effect that LCHF formulas may have on improving glycemic control in this patient population is unclear. Current guidelines for the use of LCHF formulas among patients who are critically ill are limited by a lack of evidence. This review explores recent research published in the past 7 years to determine whether LCHF enteral formulas improve glycemic control compared with standard enteral formulas in patients who are critically ill. Four randomized controlled trials met the inclusion criteria for this review. Their results suggest that LCHF formulas may improve glycemic control in patients who are critically ill with diabetes mellitus and/or who are hyperglycemic. Further large-scale randomized controlled trials are warranted to validate these findings among different subgroups of patients with critical illness. The potential benefits of LCHF formulas need to be weighed against specific limitations, including that LCHF formulas typically do not contain sufficient protein to meet the recommended needs of patients who are critically ill.

Food-based dietary management, enhanced with evidence-based commercial products, such as diabetes-specific nutrition formulas (DSNFs), can help control the development, progression, and severity of certain chronic diseases. In this review, evidence is detailed on the use of DSNFs in patients with or at risk for diabetes and cardiometabolic-based chronic disease. Many DSNF strategies target glycemic excursions and cardiovascular physiology, taking into account various elements of healthy eating patterns. Nevertheless, significant research, knowledge, and practice gaps remain. These gaps are actionable in terms of formulating and testing relevant and pragmatic research questions, developing an educational program for the uniform distribution of information, and collaboratively writing clinical practice guidelines that incorporate the evidence base for DSNF. In sum, the benefits of DNSF as part of validated clinical practice algorithms include mitigation of chronic disease progression, cost-savings for the healthcare system, and applicability on a global scale.