Second pilot trials of the STAR-Liege protocol for tight glycemic control in critically ill patients.
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ABSTRACT: Background
Critically ill patients often present increased insulin resistance and stress-induced hyperglycemia. Tight glycemic control aims to reduce blood glucose (BG) levels and variability while ensuring safety from hypoglycemia. This paper presents the results of the second Belgian clinical trial using the customizable STAR framework in a target-to-range control approach. The main objective is reducing measurement frequency while maintaining performance and safety of the glycemic control.Methods
The STAR-Liege 2 (SL2) protocol targeted the 100-140 mg/dL glycemic band and offered 2-hourly and 3-hourly interventions. Only insulin rates were adjusted, and nutrition inputs were left to the attending clinicians. This protocol restricted the forecasted risk of BG?ResultsDuring the SL2 trial, 91 measurements were taken over 194 hours. BG levels were tightly distributed: 54.9% of BG within 100-140 mg/dL, 40.7% were???140 mg/dL and 4.4% were??0.05) with significantly reduced measurement frequency for SL2 (p?ConclusionsThe SL2 protocol succeeded in reducing clinical workload while maintaining safety and effectiveness of the glycemic control. SL2 was also shown to be safer and tighter than hospital control. Overall results validate the efficacy of significantly customizing the STAR framework.
SUBMITTER: Penning S
PROVIDER: S-EPMC3511234 | biostudies-literature | 2012 Aug
REPOSITORIES: biostudies-literature
Publications
Second pilot trials of the STAR-Liege protocol for tight glycemic control in critically ill patients.
Penning Sophie S Le Compte Aaron J AJ Massion Paul P Moorhead Katherine T KT Pretty Christopher G CG Preiser Jean-Charles JC Shaw Geoffrey M GM Suhaimi Fatanah F Desaive Thomas T Chase J Geoffrey JG
Biomedical engineering online 20120823
<h4>Background</h4>Critically ill patients often present increased insulin resistance and stress-induced hyperglycemia. Tight glycemic control aims to reduce blood glucose (BG) levels and variability while ensuring safety from hypoglycemia. This paper presents the results of the second Belgian clinical trial using the customizable STAR framework in a target-to-range control approach. The main objective is reducing measurement frequency while maintaining performance and safety of the glycemic con ...[more]
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Project description:BackgroundIn multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies involving critically ill children who have not undergone cardiac surgery are lacking.MethodsIn a 35-center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower-target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher-target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)-free days to day 28.ResultsThe trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower-target group and 353 to the higher-target group. In the intention-to-treat analysis, the median number of ICU-free days did not differ significantly between the lower-target group and the higher-target group (19.4 days [interquartile range {IQR}, 0 to 24.2] and 19.4 days [IQR, 6.7 to 23.9], respectively; P=0.58). In per-protocol analyses, the median time-weighted average glucose level was significantly lower in the lower-target group (109 mg per deciliter [IQR, 102 to 118]; 6.1 mmol per liter [IQR, 5.7 to 6.6]) than in the higher-target group (123 mg per deciliter [IQR, 108 to 142]; 6.8 mmol per liter [IQR, 6.0 to 7.9]; P<0.001). Patients in the lower-target group also had higher rates of health care-associated infections than those in the higher-target group (12 of 349 patients [3.4%] vs. 4 of 349 [1.1%], P=0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients [5.2%] vs. 7 [2.0%], P=0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator-free days.ConclusionsCritically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter. (Funded by the National Heart, Lung, and Blood Institute and others; HALF-PINT ClinicalTrials.gov number, NCT01565941 .).
| S-EPMC5444653 | biostudies-literature
Project description:BACKGROUND:Hyperglycemia is prevalent in patients in the pediatric intensive care unit. The purpose of this study was to describe the benefits and risks of tight glucose control (TGC) in critically ill children. METHODS:A systemic review and meta-analysis of the literature was carried out on randomized controlled trials of TGC in critically ill children admitted to the pediatric intensive care unit. The databases searched were Medline, Embase, and CENTRAL databases until May 1, 2017. Paired reviewers independently screened citations, assessed risk of bias of included studies, and extracted data. A random-effects model was used to report all outcomes. The Grading of Recommendations Assessment, Development and Evaluation system was used to quantify absolute effects and quality of evidence. The primary outcome was hospital mortality. The secondary outcomes were hypoglycemia (any, severe), sepsis, new need for dialysis, and seizures. RESULTS:A total of 4030 patients were included from six studies. All six studies were rated as at low risk of bias. Our meta-analysis showed that TGC did not result in a decrease in risk of hospital mortality (odds ratio (OR), 0.95; 95% confidence interval (CI), 0.62-1.45; I2 = 40%; moderate quality), sepsis (OR, 0.82; 95% CI, 0.63-1.08), or seizures (OR, 0.98; 95% CI, 0.59-1.63). TGC was associated with a decrease in new need for dialysis (OR, 0.63; 95% CI, 0.45-0.86). However, TGC was associated with a significant increase in any hypoglycemia (OR, 4.39; 95% CI, 2.39-8.06) and severe hypoglycemia (OR, 4.11; 95% CI, 2.67-6.32). CONCLUSIONS:Among critically ill children with hyperglycemia, TGC does not result in a decrease in hospital mortality, but appears to reduce a new need for dialysis. However, TGC is associated with higher incidence of hypoglycemia. SYSTEMATIC REVIEW REGISTRATION:PROSPERO registration number CRD42017074039 .
| S-EPMC5835325 | biostudies-literature
Project description:Hyperglycemia is common in critically ill patients and can be caused by various mechanisms, including nutrition, medications, and insufficient insulin. In the past, hyperglycemia was thought to be an adaptive response to stress, but hyperglycemia is no longer considered a benign condition in patients with critical illnesses. Indeed, hyperglycemia can increase morbidity and mortality in critically ill patients. Correction of hyperglycemia may improve clinical outcomes. To date, a definite answer with regard to glucose management in general intensive care unit patients, including treatment thresholds and glucose target is undetermined. Meta-analyses of randomized controlled trials suggested no survival benefit of tight glycemic control and a significantly increased incidence of hypoglycemia. Studies have shown a J- or U-shaped relationship between average glucose values and mortality; maintaining glucose levels between 100 and 150 mg/dL was likely to be associated with the lowest mortality rates. Recent studies have shown glycemic control < 180 mg/dL is not inferior to near-normal glycemia in critically ill patients and is clearly safer. Glycemic variability is also an important aspect of glucose management in the critically ill patients. Higher glycemic variability may increase the mortality rate, even in patients with the same mean glucose level. Decreasing glucose variability is an important issue for glycemic control in critically ill patients. Continuous measurements with automatic closed-loop systems could be considered to ensure that blood glucose levels are controlled within a specific range and with minimal variability.
| S-EPMC3956063 | biostudies-other
Project description:IntroductionTight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible, model-based TGC approach directly accounting for intra- and inter- patient variability with a stochastically derived maximum 5% risk of blood glucose (BG) < 4.0 mmol/L. This research assesses the safety, efficacy, and clinical burden of a STAR TGC controller modulating both insulin and nutrition inputs in pilot trials.MethodsSeven patients covering 660 hours. Insulin and nutrition interventions are given 1-3 hourly as chosen by the nurse to allow them to manage workload. Interventions are calculated by using clinically validated computer models of human metabolism and its variability in critical illness to maximize the overlap of the model-predicted (5-95th percentile) range of BG outcomes with the 4.0-6.5 mmol/L band while ensuring a maximum 5% risk of BG < 4.0 mmol/L. Carbohydrate intake (all sources) was selected to maximize intake up to 100% of SCCM/ACCP goal (25 kg/kcal/h). Maximum insulin doses and dose changes were limited for safety. Measurements were made with glucometers. Results are compared to those for the SPRINT study, which reduced mortality 25-40% for length of stay ≥3 days. Written informed consent was obtained for all patients, and approval was granted by the NZ Upper South A Regional Ethics Committee.ResultsA total of 402 measurements were taken over 660 hours (~14/day), because nurses showed a preference for 2-hourly measurements. Median [interquartile range, (IQR)] cohort BG was 5.9 mmol/L [5.2-6.8]. Overall, 63.2%, 75.9%, and 89.8% of measurements were in the 4.0-6.5, 4.0-7.0, and 4.0-8.0 mmol/L bands. There were no hypoglycemic events (BG < 2.2 mmol/L), and the minimum BG was 3.5 mmol/L with 4.5% < 4.4 mmol/L. Per patient, the median [IQR] hours of TGC was 92 h [29-113] using 53 [19-62] measurements (median, ~13/day). Median [IQR] results: BG, 5.9 mmol/L [5.8-6.3]; carbohydrate nutrition, 6.8 g/h [5.5-8.7] (~70% goal feed median); insulin, 2.5 U/h [0.1-5.1]. All patients achieved BG < 6.1 mmol/L. These results match or exceed SPRINT and clinical workload is reduced more than 20%.ConclusionsSTAR TGC modulating insulin and nutrition inputs provided very tight control with minimal variability by managing intra- and inter- patient variability. Performance and safety exceed that of SPRINT, which reduced mortality and cost in the Christchurch ICU. The use of glucometers did not appear to impact the quality of TGC. Finally, clinical workload was self-managed and reduced 20% compared with SPRINT.
| S-EPMC3224394 | biostudies-literature
Project description:AimWe explored the prospective relationship between continuous glucose monitoring (CGM) metrics and clinical outcomes in patients admitted to the intensive care unit (ICU).Materials and methodsWe enrolled critically ill patients admitted to the medical ICU. Patients with an Acute Physiology and Chronic Health Evaluation (APACHE) score ≤9 or ICU stay ≤48 h were excluded. CGM was performed for five days, and standardized CGM metrics were analyzed. The duration of ICU stay and 28-day mortality rate were evaluated as outcomes.ResultsA total of 36 patients were included in this study (age [range], 49-88 years; men, 55.6%). The average APACHE score was 25.4 ± 8.3; 33 (91.7%) patients required ventilator support, and 16 (44.4%) patients had diabetes. The duration of ICU stay showed a positive correlation with the average blood glucose level, glucose management indicator (GMI), time above range, and GMI minus (-) glycated hemoglobin (HbA1c). Eight (22.2%) patients died within 28 days, and their average blood glucose levels, GMI, and GMI-HbA1c were significantly higher than those of survivors (p<0.05). After adjustments for age, sex, presence of diabetes, APACHE score, and dose of steroid administered, the GMI-HbA1c was associated with the risk of longer ICU stay (coefficient=2.34, 95% CI 0.54-4.14, p=0.017) and higher 28-day mortality rate (HR=2.42, 95% CI 1.01-5.76, p=0.046).ConclusionThe acute glycemic gap, assessed as GMI-HbA1c, is an independent risk factor for longer ICU stay and 28-day mortality rate. In the ICU setting, CGM of critically ill patients might be beneficial, irrespective of the presence of diabetes.
| S-EPMC9114696 | biostudies-literature
Project description:Objective: Consensus guidelines recommend that intensive care unit (ICU) patients with blood glucose (BG) levels >180 mg/dL receive continuous intravenous insulin (CII). The effectiveness of CII at controlling BG levels among patients who are eating relative to those who are eating nothing by mouth (nil per os; NPO) has not been described. Methods: We conducted a retrospective cohort study of 260 adult patients (156 eating, 104 NPO) admitted to an ICU between January 1, 2014, and December 31, 2014, who received CII. Patients were excluded for a diagnosis of diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic syndrome, admission to an obstetrics service, or receiving continuous enteral or parenteral nutrition. Results: Among 22 baseline characteristics, the proportion of patients receiving glucocorticoid treatment (GCTx) (17.3% eating, 37.5% NPO; P<.001) and APACHE II score (15.0 ± 7.5 eating, 17.9 ± 7.9 NPO; P = .004) were significantly different between eating and NPO patients. There was no significant difference in the primary outcome of patient-day weighted mean BG overall (153 ± 8 mg/dL eating, 156 ± 7 mg/dL NPO; P = .73), or day-by-day BG (P = .37) adjusted for GCTx and APACHE score. Surprisingly, there was a significant difference in the distribution of BG values, with eating patients having a higher percentage of BG readings in the recommended range of 140 to 180 mg/dL. However, eating patients showed greater glucose variability (coefficient of variation 23.1 ± 1.0 eating, 21.2 ± 1.0 NPO; P = .034). Conclusion: Eating may not adversely affect BG levels of ICU patients receiving CII. Whether or not prandial insulin improves glycemic control in this setting should be studied. Abbreviations: BG = blood glucose; CII = continuous insulin infusion; CV = coefficient of variation; HbA1c = hemoglobin A1c; ICU = intensive care unit; NPO = nil per os; PDWMBG = patient day weighted mean blood glucose.
| S-EPMC7004843 | biostudies-literature
Project description:BackgroundRecent evidence suggests a potentially protective effect of increasing ketone body availability via accepting low macronutrient intake early after onset of critical illness. The impact of blood glucose control with insulin on circulating ketones is unclear. Whereas lowering blood glucose may activate ketogenesis, high insulin concentrations may have the opposite effect. We hypothesized that the previously reported protective effects of tight glucose control in critically ill patients receiving early parenteral nutrition may have been mediated in part by activation of ketogenesis.MethodsThis is a secondary analysis of 3 randomized controlled trials on tight versus liberal blood glucose control in the intensive care unit, including 700 critically ill children and 2748 critically ill adults. All patients received early parenteral nutrition as part of the contemporary standard of care. Before studying a potential mediator role of circulating ketones in improving outcome, we performed a time course analysis to investigate whether tight glucose control significantly affected ketogenesis and to identify a day of maximal effect, if any. We quantified plasma/serum 3-hydroxybutyrate concentrations from intensive care unit admission until day 3 in 2 matched subsets of 100 critically ill children and 100 critically ill adults. Univariable differences between groups were investigated by Kruskal-Wallis test. Differences in 3-hydroxybutyrate concentrations between study days were investigated by Wilcoxon signed-rank test.ResultsIn critically ill children and adults receiving early parenteral nutrition, tight glucose control, as compared with liberal glucose control, lowered mean morning blood glucose on days 1-3 (P < 0.0001) via infusing insulin at a higher dose (P < 0.0001). Throughout the study period, caloric intake was not different between groups. In both children and adults, tight glucose control did not affect 3-hydroxybutyrate concentrations, which were suppressed on ICU days 1-3 and significantly lower than the ICU admission values for both groups (P < 0.0001).ConclusionTight versus liberal glucose control in the context of early parenteral nutrition did not affect 3-hydroxybutyrate concentrations in critically ill patients. Hence, the protective effects of tight glucose control in this context cannot be attributed to increased ketone body availability.
| S-EPMC8547101 | biostudies-literature
Project description:BackgroundEpithelial and endothelial barrier integrity, essential for homeostasis, is maintained by cellular boarder structures known as tight junctions (TJs). In critical illness, TJs may become disrupted, resulting in barrier dysfunction manifesting as capillary leak, pulmonary edema, gut bacterial translocation, and multiple organ failure. We aim to provide a clinically focused overview of TJ structure and function and systematically review and analyze all studies assessing markers of endothelial and epithelial TJ breakdown correlated with clinical outcomes in critically ill humans.MethodsWe systematically searched MEDLINE, EMBASE, and PubMed. Additional articles were identified by targeted searches. We included studies that looked at the relationship between biomarkers of endothelial or epithelial TJ structure or function and critical illness. Results were qualitatively analyzed due to sample size and heterogeneity.ResultsA total of 5297 abstracts met search criteria, of which 150 articles met requirements for full text review. Of these, 30 studies met inclusion criteria. Fifteen of the 30 reports investigated proteins of endothelial tight junctions and 15 investigated epithelial TJ markers, exclusively in the gastrointestinal epithelium. No studies investigated TJ-derived proteins in primary cardiac or pulmonary pathology.ConclusionsTJ integrity is essential for homeostasis. We identified multiple studies that indicate TJs are disrupted by critical illness. These studies highlight the significance of barrier disruption across many critical disease states and correlate TJ-associated markers to clinically relevant outcomes. Further study on the role of multiple tissue-specific claudins, particularly in the setting of respiratory or cardiac failure, may lead to diagnostic and therapeutic advances.Systematic review registrationThis systematic review is registered in the PROSPERO database: CRD42017074546 .
| S-EPMC6158145 | biostudies-literature
Project description:Evaluation of the functional outcomes of patients undergoing an early rehabilitation protocol for critically ill patients from admission to discharge from the intensive care unit.A retrospective cross-sectional study was conducted that included 463 adult patients with clinical and/or surgical diagnosis undergoing an early rehabilitation protocol. The overall muscle strength was evaluated at admission to the intensive care unit using the Medical Research Council scale. Patients were allocated to one of four intervention plans according to the Medical Research Council score, the suitability of the plan's parameters, and the increasing scale of the plan expressing improved functional status. Uncooperative patients were allocated to intervention plans based on their functional status. The overall muscle strength and/or functional status were reevaluated upon discharge from the intensive care unit by comparison between the Intervention Plans upon admission (Planinitial) and discharge (Planfinal). Patients were classified into three groups according to the improvement of their functional status or not: responsive 1 (Planfinal > Planinitial), responsive 2 (Planfinal = Planinitial) and unresponsive (Planfinal < Planinitial).In total, 432 (93.3%) of 463 patients undergoing the protocol responded positively to the intervention strategy, showing maintenance and/or improvement of the initial functional status. Clinical patients classified as unresponsive were older (74.3 ± 15.1 years of age; p = 0.03) and had longer lengths of intensive care unit (11.6 ± 14.2 days; p = 0.047) and hospital (34.5 ± 34.1 days; p = 0.002) stays.The maintenance and/or improvement of the admission functional status were associated with shorter lengths of intensive care unit and hospital stays. The results suggest that the type of diagnosis, clinical or surgical, fails to define the positive response to an early rehabilitation protocol.
| S-EPMC4489785 | biostudies-other
Project description:Acute glycemic control significantly affects the clinical outcomes of critically ill patients. This updated network meta-analysis examines the benefits and harms of four target blood glucose levels (< 110, 110-144, 144-180, and > 180 mg/dL). Analyzing data of 27,541 patients from 37 trials, the surface under the cumulative ranking curve for mortality and hypoglycemia was highest at a target blood glucose level of 144-180 mg/dL, while for infection and acute kidney injury at 110-144 mg/dL. Further evidence is needed to determine whether 110-144 or 144-180 mg/dL is superior as an optimal glucose target, considering prioritized outcomes.
| S-EPMC11017653 | biostudies-literature