Society of Critical Care Medicine Guidelines on Glycemic Control for Critically Ill Children and Adults 2024.

RATIONALE: Maintaining glycemic control of critically ill patients may impact outcomes such as survival, infection, and neuromuscular recovery, but there is equipoise on the target blood levels, monitoring frequency, and methods. OBJECTIVES: The purpose was to update the 2012 Society of Critical Care Medicine and American College of Critical Care Medicine (ACCM) guidelines with a new systematic review of the literature and provide actionable guidance for clinicians. PANEL DESIGN: The total multiprofessional task force of 22, consisting of clinicians and patient/family advocates, and a methodologist applied the processes described in the ACCM guidelines standard operating procedure manual to develop evidence-based recommendations in alignment with the Grading of Recommendations Assessment, Development, and Evaluation Approach (GRADE) methodology. Conflict of interest policies were strictly followed in all phases of the guidelines, including panel selection and voting. METHODS: We conducted a systematic review for each Population, Intervention, Comparator, and Outcomes question related to glycemic management in critically ill children (≥ 42 wk old adjusted gestational age to 18 yr old) and adults, including triggers for initiation of insulin therapy, route of administration, monitoring frequency, role of an explicit decision support tool for protocol maintenance, and methodology for glucose testing. We identified the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as a good practice statement. In addition, "In our practice" statements were included when the available evidence was insufficient to support a recommendation, but the panel felt that describing their practice patterns may be appropriate. Additional topics were identified for future research. RESULTS: This guideline is an update of the guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. It is intended for adult and pediatric practitioners to reassess current practices and direct research into areas with inadequate literature. The panel issued seven statements related to glycemic control in unselected adults (two good practice statements, four conditional recommendations, one research statement) and seven statements for pediatric patients (two good practice statements, one strong recommendation, one conditional recommendation, two "In our practice" statements, and one research statement), with additional detail on specific subset populations where available. CONCLUSIONS: The guidelines panel achieved consensus for adults and children regarding a preference for an insulin infusion for the acute management of hyperglycemia with titration guided by an explicit clinical decision support tool and frequent (≤ 1 hr) monitoring intervals during glycemic instability to minimize hypoglycemia and against targeting intensive glucose levels. These recommendations are intended for consideration within the framework of the patient's existing clinical status. Further research is required to evaluate the role of individualized glycemic targets, continuous glucose monitoring systems, explicit decision support tools, and standardized glycemic control metrics.

Nutrition support, carbohydrate feeding and insulin sensitivity in the critically ill patient: a complex relationship.

PURPOSE OF REVIEW: This review aims to summarize recent studies that highlight the complex relationship between nutrition, carbohydrate, insulin provision and glycaemic control in the critically ill patient population. RECENT FINDINGS: Results of observational studies concur to support early hypoglycaemia and persisting hyperglycaemia as life-threatening events. In contrast, interventional studies indicate that early macronutrient restriction appears to reduce the benefits related to insulin therapy. This restriction is however associated with improved outcomes in itself. The potential role of modified enteral solutions as an adjunctive treatment to attenuate hyperglycaemia warrants further research. The selection of a therapeutic modality may also differ according to the characteristics of the setting, such as the nurse-to-patient ratio, the type and accuracy of meters, including near-continuous glucose monitoring and the availability of computer-guided protocols. SUMMARY: There appears to be significant interplay between nutrition, including carbohydrate provision, blood glucose control and clinical outcomes. Individualized care is probably needed to define the optimal glucose target and nutritional intervention. This can differ according to the preexistence of chronic hyperglycaemia, the timing from the onset of critical illness and the clinical condition itself.

The need for biomarkers to determine response to enteral nutrition during and after critical illness: an update.

PURPOSE OF REVIEW: Biomarkers proposed to provide prognosis or to determine the response to enteral nutrition have been assessed in a number of experimental and clinical studies which are summarized in the current review. RECENT FINDINGS: There are several pathophysiological mechanisms identified which could provide biomarkers to determine response to enteral nutrition. Several biomarkers have been studied, most of them insufficiently and none of them has made its way to clinical practice. Available studies have mainly assessed a simple association of a biomarker with outcomes, but are less focused on dynamic changes in the biomarker levels. Importantly, studies on pathophysiology and clinical features of gastrointestinal dysfunction, including enteral feeding intolerance, are also needed to explore the mechanisms potentially providing specific biomarkers. Not only an association of the biomarker with any adverse outcome, but also a rationale for repeated assessment to assist in treatment decisions during the course of illness is warranted. SUMMARY: There is no biomarker currently available to reliably provide prognosis or determine the response to enteral nutrition in clinical practice, but identification of such a biomarker would be valuable to assist in clinical decision-making.

Toward nutrition improving outcome of critically ill patients: How to interpret recent feeding RCTs?

Although numerous observational studies associated underfeeding with poor outcome, recent randomized controlled trials (RCTs) have shown that early full nutritional support does not benefit critically ill patients and may induce dose-dependent harm. Some researchers have suggested that the absence of benefit in RCTs may be attributed to overrepresentation of patients deemed at low nutritional risk, or to a too low amino acid versus non-protein energy dose in the nutritional formula. However, these hypotheses have not been confirmed by strong evidence. RCTs have not revealed any subgroup benefiting from early full nutritional support, nor benefit from increased amino acid doses or from indirect calorimetry-based energy dosing targeted at 100% of energy expenditure. Mechanistic studies attributed the absence of benefit of early feeding to anabolic resistance and futile catabolism of extra provided amino acids, and to feeding-induced suppression of recovery-enhancing pathways such as autophagy and ketogenesis, which opened perspectives for fasting-mimicking diets and ketone supplementation. Yet, the presence or absence of an anabolic response to feeding cannot be predicted or monitored and likely differs over time and among patients. In the absence of such monitor, the value of indirect calorimetry seems obscure, especially in the acute phase of illness. Until now, large feeding RCTs have focused on interventions that were initiated in the first week of critical illness. There are no large RCTs that investigated the impact of different feeding strategies initiated after the acute phase and continued after discharge from the intensive care unit in patients recovering from critical illness.

Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study.

BACKGROUND: Current guidelines suggest the introduction of early nutrition support within the first 48 h of admission to the intensive care unit (ICU) for patients who cannot eat. In that context, we aimed to describe nutrition practices in the ICU and study the association between the introduction of early nutrition support (< 48 h) in the ICU and patient mortality at day 28 (D28) using data from a multicentre prospective cohort. METHODS: The 'French-Speaking ICU Nutritional Survey' (FRANS) study was conducted in 26 ICUs in France and Belgium over 3 months in 2015. Adult patients with a predicted ICU length of stay > 3 days were consecutively included and followed for 10 days. Their mortality was assessed at D28. We investigated the association between early nutrition (< 48 h) and mortality at D28 using univariate and multivariate propensity-score-weighted logistic regression analyses. RESULTS: During the study period, 1206 patients were included. Early nutrition support was administered to 718 patients (59.5%), with 504 patients receiving enteral nutrition and 214 parenteral nutrition. Early nutrition was more frequently prescribed in the presence of multiple organ failure and less frequently in overweight and obese patients. Early nutrition was significantly associated with D28 mortality in the univariate analysis (crude odds ratio (OR) 1.69, 95% confidence interval (CI) 1.23-2.34) and propensity-weighted multivariate analysis (adjusted OR (aOR) 1.05, 95% CI 1.00-1.10). In subgroup analyses, this association was stronger in patients ≤ 65 years and with SOFA scores ≤ 8. Compared with no early nutrition, a significant association was found of D28 mortality with early enteral (aOR 1.06, 95% CI 1.01-1.11) but not early parenteral nutrition (aOR 1.04, 95% CI 0.98-1.11). CONCLUSIONS: In this prospective cohort study, early nutrition support in the ICU was significantly associated with increased mortality at D28, particularly in younger patients with less severe disease. Compared to no early nutrition, only early enteral nutrition appeared to be associated with increased mortality. Such findings are in contrast with current guidelines on the provision of early nutrition support in the ICU and may challenge our current practices, particularly concerning patients at low nutrition risk. Trial registration ClinicalTrials.gov Identifier: NCT02599948. Retrospectively registered on November 5th 2015.

Severe vitamin D deficiency in patients admitted to the emergency department with severe sepsis is associated with an increased 90-day mortality.

BACKGROUND: The role of vitamin D in the response to infection has been increasingly acknowledged. However, the influence of severe vitamin D deficiency on the outcome of patients admitted for severe sepsis is unknown. Hence, this study aimed to investigate the association between severe vitamin D deficiency and sepsis-related outcomes in patients presenting to the ED. METHODS: This single centre prospective study included patients presenting to the ED with severe sepsis from April 2014 until December 2017. 25-Hydroxy vitamin D (25(OH)D) was measured in a blood sample drawn within 24 hours of admission to the ED, and severe vitamin D deficiency was defined as 25(OH)D <12 ng/mL. 90-day mortality was compared between patients with and without severe vitamin D deficiency by a multivariable analysis adjusting for confounders and according to a Kaplan-Meier survival analysis. RESULTS: 263 patients were initially screened and 164 patients with severe sepsis were included in this study, 18% of whom had septic shock. Severe vitamin D deficiency was present in 46% of patients. The overall 90-day mortality rate was 26.2% and the median length of stay was 14 days. In a logistic regression accounting for sepsis severity and age-adjusted comorbidities, severe vitamin D deficiency was associated with increased mortality (OR=2.69 (95% CI 1.03 to 7.00), p=0.043), and lower chances of hospital discharge (sub-HR=0.66 (95% CI 0.44 to 0.98)). In the subgroup of patients admitted to the intensive care unit, severe vitamin D deficiency was associated with an increased 28-day adjusted mortality (HR=3.06 (95% CI 1.05 to 8.94), p=0.04) and lower chances of discharge (sub-HR=0.51 (95% CI 0.32 to 0.81)). CONCLUSIONS: Severe vitamin D deficiency at ED admission is associated with higher mortality and longer hospital stay in patients with severe sepsis.

Relative Hypoglycemia and Lower Hemoglobin A1c-Adjusted Time in Band Are Strongly Associated With Increased Mortality in Critically Ill Patients.

OBJECTIVES: To determine the associations of relative hypoglycemia and hemoglobin A1c-adjusted time in blood glucose (BG) band (HA-TIB) with mortality in critically ill patients. DESIGN: Retrospective cohort investigation. SETTING: University-affiliated adult medical-surgical ICU. PATIENTS: Three thousand six hundred fifty-five patients with at least four BG tests and hemoglobin A1c (HbA1c) level admitted between September 14, 2014, and November 30, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were stratified for HbA1c bands of <6.5%; 6.5-7.9%; greater than or equal to 8.0% with optimal affiliated glucose target ranges of 70-140, 140-180, and 180-250 mg/dL, respectively. HA-TIB, a new glycemic metric, defined the HbA1c-adjusted time in band. Relative hypoglycemia was defined as BG 70-110 mg/dL for patients with HbA1c ≥ 8.0%. Further stratification included diabetes status-no diabetes (NO-DM, n = 2,616) and preadmission treatment with or without insulin (DM-INS, n = 352; DM-No-INS, n = 687, respectively). Severity-adjusted mortality was calculated as the observed:expected mortality ratio (O:EMR), using the Acute Physiology and Chronic Health Evaluation IV prediction of mortality. Among NO-DM, mortality and O:EMR, decreased with higher TIB 70-140 mg/dL ( p < 0.0001) and were lowest with TIB 90-100%. O:EMR was lower for HA-TIB greater than or equal to 50% than less than 50% and among all DM-No-INS but for DM-INS only those with HbA1 greater than or equal to 8.0%.Among all patients with hba1c greater than or equal to 8.0% And no bg less than 70 mg/dl, mortality was 18.0% For patients with relative hypoglycemia (bg, 70-110 mg/dl) ( p < 0.0001) And was 0.0%, 12.9%, 13.0%, And 34.8% For patients with 0, 0.1-2.9, 3.0-11.9, And greater than or equal to 12.0 Hours of relative hypoglycemia ( p < 0.0001). CONCLUSIONS: These findings have considerable bearing on interpretation of previous trials of intensive insulin therapy in the critically ill. Moreover, they suggest that BG values in the 70-110 range may be deleterious for patients with HbA1c greater than or equal to 8.0% and that the appropriate target for BG should be individualized to HbA1c levels. These conclusions need to be tested in randomized trials.

Nutritional therapy in critically ill patients with diabetes.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial.

BACKGROUND: A defining feature of prolonged critical illness is muscle wasting, leading to impaired recovery. Supplementation with a tailored blend of amino acids may bolster the innate gut defence, promote intestinal mucosa repair and limit muscle loss. METHODS: This was a monocentric, randomized, double-blind, placebo-controlled study that included patients with sepsis or acute respiratory distress syndrome. Patients received a specific combination of five amino acids or placebo mixed with enteral feeding for 21 days. Markers of renal function, gut barrier structure and functionality were collected at baseline and 1, 2, 3 and 8 weeks after randomization. Muscle structure and function were assessed through MRI measurements of the anterior quadriceps volume and by twitch airway pressure. Data were compared between groups relative to the baseline. RESULTS: Thirty-five critically ill patients were randomized. The amino acid blend did not impair urine output, blood creatinine levels or creatinine clearance. Plasma citrulline levels increased significantly along the treatment period in the amino acid group (difference in means [95% CI] 5.86 [1.72; 10.00] nmol/mL P = 0.007). Alanine aminotransferase and alkaline phosphatase concentrations were lower in the amino acid group than in the placebo group at one week (ratio of means 0.5 [0.29; 0.86] (P = 0.015) and 0.73 [0.57; 0.94] (P = 0.015), respectively). Twitch airway pressure and volume of the anterior quadriceps were greater in the amino acid group than in the placebo group 3 weeks after randomization (difference in means 10.6 [0.99; 20.20] cmH20 (P = 0.035) and 3.12 [0.5; 5.73] cm3/kg (P = 0.022), respectively). CONCLUSIONS: Amino acid supplementation increased plasma citrulline levels, reduced alanine aminotransferase and alkaline phosphatase levels, and improved twitch airway pressure and anterior quadriceps volume. Trial registration ClinicalTrials.gov, NCT02968836. Registered November 21, 2016.

Impact of prolonged requirement for insulin on 90-day mortality in critically ill patients without previous diabetic treatments: a post hoc analysis of the CONTROLING randomized control trial.

BACKGROUND: Stress hyperglycemia can persist during an intensive care unit (ICU) stay and result in prolonged requirement for insulin (PRI). The impact of PRI on ICU patient outcomes is not known. We evaluated the relationship between PRI and Day 90 mortality in ICU patients without previous diabetic treatments. METHODS: This is a post hoc analysis of the CONTROLING trial, involving 12 French ICUs. Patients in the personalized glucose control arm with an ICU length of stay ≥ 5 days and who had never previously received diabetic treatments (oral drugs or insulin) were included. Personalized blood glucose targets were estimated on their preadmission usual glycemia as estimated by their glycated A1c hemoglobin (HbA1C). PRI was defined by insulin requirement. The relationship between PRI on Day 5 and 90-day mortality was assessed by Cox survival models with inverse probability of treatment weighting (IPTW). Glycemic control was defined as at least one blood glucose value below the blood glucose target value on Day 5. RESULTS: A total of 476 patients were included, of whom 62.4% were male, with a median age of 66 (54-76) years. Median values for SAPS II and HbA1C were 50 (37.5-64) and 5.7 (5.4-6.1)%, respectively. PRI was observed in 364/476 (72.5%) patients on Day 5. 90-day mortality was 23.1% in the whole cohort, 25.3% in the PRI group and 16.1% in the non-PRI group (p < 0.01). IPTW analysis showed that PRI on Day 5 was not associated with Day 90 mortality (IPTWHR = 1.22; CI 95% 0.84-1.75; p = 0.29), whereas PRI without glycemic control was associated with an increased risk of death at Day 90 (IPTWHR = 3.34; CI 95% 1.26-8.83; p < 0.01). CONCLUSION: In ICU patients without previous diabetic treatments, only PRI without glycemic control on Day 5 was associated with an increased risk of death. Additional studies are required to determine the factors contributing to these results.

Long-term outcomes after critical illness: recent insights.

Intensive care survivors often experience post-intensive care sequelae, which are frequently gathered together under the term "post-intensive care syndrome" (PICS). The consequences of PICS on quality of life, health-related costs and hospital readmissions are real public health problems. In the present Viewpoint, we summarize current knowledge and gaps in our understanding of PICS and approaches to management.

A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice.

The preferential use of the oral/enteral route in critically ill patients over gut rest is uniformly recommended and applied. This article provides practical guidance on enteral nutrition in compliance with recent American and European guidelines. Low-dose enteral nutrition can be safely started within 48 h after admission, even during treatment with small or moderate doses of vasopressor agents. A percutaneous access should be used when enteral nutrition is anticipated for ≥ 4 weeks. Energy delivery should not be calculated to match energy expenditure before day 4-7, and the use of energy-dense formulas can be restricted to cases of inability to tolerate full-volume isocaloric enteral nutrition or to patients who require fluid restriction. Low-dose protein (max 0.8 g/kg/day) can be provided during the early phase of critical illness, while a protein target of > 1.2 g/kg/day could be considered during the rehabilitation phase. The occurrence of refeeding syndrome should be assessed by daily measurement of plasma phosphate, and a phosphate drop of 30% should be managed by reduction of enteral feeding rate and high-dose thiamine. Vomiting and increased gastric residual volume may indicate gastric intolerance, while sudden abdominal pain, distension, gastrointestinal paralysis, or rising abdominal pressure may indicate lower gastrointestinal intolerance.

The Interaction of Acute and Chronic Glycemia on the Relationship of Hyperglycemia, Hypoglycemia, and Glucose Variability to Mortality in the Critically Ill.

OBJECTIVES: To determine the relationship between preadmission glycemia, reflected by hemoglobin A1c level, glucose metrics, and mortality in critically ill patients. DESIGN: Retrospective cohort investigation. SETTING: University affiliated adult medical-surgical ICU. PATIENTS: The investigation included 5,567 critically ill patients with four or more blood glucose tests and hemoglobin A1c level admitted between October 11, 2011 and November 30, 2019. The target blood glucose level was 90-120 mg/dL for patients admitted before September 14, 2014 (n = 1,614) and 80-140 mg/dL or 110-160 mg/dL for patients with hemoglobin A1c less than 7% or greater than or equal to 7% (n = 3,953), respectively, subsequently. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were stratified by hemoglobin A1c: less than 6.5.(n = 4,406), 6.5-7.9% (n = 711), and greater than or equal to 8.0% (n = 450). Increasing hemoglobin A1c levels were associated with significant increases in mean glycemia, glucose variability, as measured by coefficient of variation, and hypoglycemia (p for trend < 0.0001, < 0.0001, and 0.0010, respectively). Among patients with hemoglobin A1c less than 6.5%, mortality increased as mean glycemia increased; however, among patients with hemoglobin A1c greater than or equal to 8.0%, the opposite relationship was observed (p for trend < 0.0001 and 0.0027, respectively). Increasing glucose variability was independently associated with increasing mortality only among patients with hemoglobin A1c less than 6.5%. Hypoglycemia was independently associated with higher mortality among patients with hemoglobin A1c less than 6.5% and 6.5-7.9% but not among those with hemoglobin A1c greater than or equal to 8.0%. Mean blood glucose 140-180 and greater than or equal to 180 mg/dL were independently associated with higher mortality among patients with hemoglobin A1c less than 6.5% (p < 0.0001 for each). Among patients with hemoglobin A1c greater than or equal to 8.0% treated in the second era, mean blood glucose greater than or equal to 180 mg/dL was independently associated with decreased risk of mortality (p = 0.0358). CONCLUSIONS: Preadmission glycemia, reflected by hemoglobin A1c obtained at the onset of ICU admission, has a significant effect on the relationship of ICU glycemia to mortality. The different responses to increasing mean glycemia support a personalized approach to glucose control practices in the ICU.

Is slower advancement of enteral feeding superior to aggressive full feeding regimens in the early phase of critical illness.

PURPOSE OF REVIEW: An excessive caloric intake during the acute phase of critical illness is associated with adverse effects, presumably related to overfeeding, inhibition of autophagy and refeeding syndrome. The purpose of this review is to summarize recently published clinical evidence in this area. RECENT FINDINGS: Several observational studies, a few interventional trials, and systematic reviews/metaanalyses were published in 2017-2019. Most observational studies reported an association between caloric intakes below 70% of energy expenditure and a better vital outcome. In interventional trials, or systematic reviews, neither a benefit nor a harm was related to increases or decreases in caloric intake. Gastrointestinal dysfunction can be worsened by forced enteral feeding, whereas the absorption of nutrients can be impaired. SUMMARY: Owing to the risks of the delivery of an excessive caloric intake, a strategy of permissive underfeeding implying a caloric intake matching a maximum of 70% of energy expenditure provides the best risk-to-benefit ratio during the acute phase of critical illness.

Continuous versus intermittent feeding of the critically ill: have we made progress?

PURPOSE OF REVIEW: Despite the lack of high-quality data for many years, the discussion on the best modality for enteral nutrition has been going on with little changes pertaining in recent guidelines. The present work aims to provide an overview on the different arguments in favour of either continuous or noncontinuous modes of enteral feed administration, emphasizing both clinical and pathophysiological aspects and comparing their relevance. RECENT FINDINGS: Different physiological effects deriving from enteral nutrition modes and that could impact on outcomes of care under critical illness settings are examined, such as glycaemic control and gastrointestinal motility. A further area of attention where recent efforts have been focusing is the issue of muscle and weakness under conditions of critical care. SUMMARY: A clinical equipoise continues to characterize the analysis that can be drawn from examining the most recent research work on the subject, allowing to infer that the most practical mode in terms of the interest of patient safety and comfort has to be privileged in day-to-day clinical care.

Biomarkers in critical care nutrition.

The goal of nutrition support is to provide the substrates required to match the bioenergetic needs of the patient and promote the net synthesis of macromolecules required for the preservation of lean mass, organ function, and immunity. Contemporary observational studies have exposed the pervasive undernutrition of critically ill patients and its association with adverse clinical outcomes. The intuitive hypothesis is that optimization of nutrition delivery should improve ICU clinical outcomes. It is therefore surprising that multiple large randomized controlled trials have failed to demonstrate the clinical benefit of restoring or maximizing nutrient intake. This may be in part due to the absence of biological markers that identify patients who are most likely to benefit from nutrition interventions and that monitor the effects of nutrition support. Here, we discuss the need for practical risk stratification tools in critical care nutrition, a proposed rationale for targeted biomarker development, and potential approaches that can be adopted for biomarker identification and validation in the field.

Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine.

BACKGROUND: Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. METHODS: This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. RESULTS: Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. CONCLUSIONS: Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.

Dynamic properties of glucose complexity during the course of critical illness: a pilot study.

Methods to control the blood glucose (BG) levels of patients in intensive care units (ICU) improve the outcomes. The development of continuous BG levels monitoring devices has also permitted to optimize these processes. Recently it was shown that a complexity loss of the BG signal is linked to poor clinical outcomes. Thus, it becomes essential to decipher this relation to design efficient BG level control methods. In previous studies the BG signal complexity was calculated as a single index for the whole ICU stay. Although, these approaches did not grasp the potential variability of the BG signal complexity. Therefore, we setup this pilot study using a continuous monitoring of central venous BG levels in ten critically ill patients (EIRUS platform, Maquet Critical CARE AB, Solna, Sweden). Data were processed and the complexity was assessed by the detrended fluctuation analysis and multiscale entropy (MSE) methods. Finally, recordings were split into 24 h overlapping intervals and a MSE analysis was applied to each of them. The MSE analysis on time intervals revealed an entropy variation and allowed periodic BG signal complexity assessments. To highlight differences of MSE between each time interval we calculated the MSE complexity index defined as the area under the curve. This new approach could pave the way to future studies exploring new strategies aimed at restoring blood glucose complexity during the ICU stay.

Updates in Glycemic Management in the Hospital.

PURPOSE OF REVIEW: To provide an update of glycemic management during metabolic stress related to surgery or critical illness. RECENT FINDINGS: There is a clear association between severe hyperglycemia, hypoglycemia, and high glycemic variability and poor outcomes of postoperative or critically ill patients. However, the impressive beneficial effects of tight glycemic management (TGM) by intensive insulin therapy reported in one study were never reproduced. Hence, the recommendation of TGM is now replaced by more liberal blood glucose (BG) targets (< 180 mg/dL or 10 mM). Recent data support the concept of targeting individualized blood glucose (BG) values according to the presence of diabetes mellitus/chronic hyperglycemia, the presence of brain injury, and the time from injury. A more liberal glycemic management goal is currently advised during metabolic stress and could be switched to individualized glycemic management once validated by prospective trials.