Moderate glucose control is associated with increased mortality compared with tight glucose control in critically ill patients without diabetes.
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ABSTRACT: Background
Optimal glucose management in the ICU remains unclear. In 2009, many clinicians at Intermountain Healthcare selected a moderate glucose control (90-140 mg/dL) instead of tight glucose control (80-110 mg/dL). We hypothesized that moderate glucose control would affect patients with and without preexisting diabetes differently.Methods
We performed a retrospective cohort analysis of all patients treated with eProtocol-insulin from November 2006 to March 2011, stratifying for diabetes. We performed multivariate logistic regression for 30-day mortality with covariates of age, modified APACHE (Acute Physiology and Chronic Health Evaluation) II score, Charlson Comorbidity score, and target glucose.Results
We studied 3,529 patients in 12 different ICUs in eight different hospitals. Patients with diabetes had higher mean glucose (132 mg/dL vs 124 mg/dL) and greater glycemic variability (SD = 41 mg/dL vs 29 mg/dL) than did patients without diabetes (P < .01 for both comparisons). Tight glucose control was associated with increased frequency of moderate and severe hypoglycemia (30.3% and 3.6%) compared with moderate glucose control (14.3% and 2.0%, P < .01 for both). Multivariate analysis demonstrated that the moderate glucose target was independently associated with increased risk of mortality in patients without diabetes (OR, 1.36; 95% CI, 1.01-1.84; P = .05) but decreased risk of mortality in patients with diabetes (OR, 0.65; 95% CI, 0.45-0.93; P = .01).Conclusions
Moderate glucose control (90-140 mg/dL) may confer greater mortality in critically ill patients without diabetes compared with tight glucose control (80-110 mg/dL). A single glucose target does not appear optimal for all critically ill patients. These data have important implications for the design of future interventional trials as well as for the glycemic management of critically ill patients.
SUBMITTER: Lanspa MJ
PROVIDER: S-EPMC3747722 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:BACKGROUND:In 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. METHODS:In 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. RESULTS:The 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. CONCLUSIONS:Critically 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:ObjectiveIntensive insulin therapy is associated with the risk of hypoglycemia and increased costs of material and personnel. We therefore evaluated the safety and efficiency of a computer-assisted glucose control protocol in a large population of critically ill patients.Design and settingObservational cohort study in three intensive care units (32 beds) in a 1,300-bed university teaching hospital.PatientsAll 2,800 patients admitted to the surgical, neurosurgical, and cardiothoracic units; the study period started at each ICU after implementation of Glucose Regulation for Intensive Care Patients (GRIP), a freely available computer-assisted glucose control protocol.Measurements and resultsWe analysed compliance in relation to recommended insulin pump rates and glucose measurement frequency. Patients were on GRIP-ordered pump rates 97% of time. Median measurement time was 5min late (IQR 20min early to 34 min late). Hypoglycemia was uncommon (7% of patients for mild hypoglycemia, < 3.5mmol/l; 0.86% for severe hypoglycemia, < 2.2 mmol/l). Our predefined target range (4.0-7.5 mmol/l) was reached after a median of 5.6 h (IQR 0.2-11.8) and maintained for 89% (70-100%) of the remaining stay at the ICU. The number of measurements needed was 5.9 (4.8-7.3) per patient per day. In-hospital mortality was 10.1%.ConclusionsOur computer-assisted glucose control protocol provides safe and efficient glucose regulation in routine intensive care practice. A low rate of hypoglycemic episodes was achieved with a considerably lower number of glucose measurements than used in most other schemes.
| S-EPMC2491417 | biostudies-literature
Project description:Tight glucose control (TGC) to normal-for-age fasting blood glucose levels reduced morbidity and mortality in surgical adult and pediatric intensive care unit (ICU) patients. In adults, TGC did not affect the illness-induced alterations in thyroid hormones. With better feeding in children than in adult patients, we hypothesized that TGC in pediatric ICU patients reactivates the thyroid axis.The aim of this study was to assess the impact of TGC on the thyroid axis in pediatric ICU patients and to investigate how these changes affect the TGC outcome benefit.We conducted a preplanned analysis of all patients not treated with thyroid hormone, dopamine, or corticosteroids who were included in a randomized controlled trial on TGC (n=700).Serum TSH, T4, T3, and rT3 were measured upon admission and on ICU day 3 or the last ICU day for patients discharged earlier. Changes from baseline were compared for the TGC and usual care groups. The impact on the outcome benefit of TGC was assessed with multivariable Cox proportional hazard analysis, correcting for baseline risk factors.TGC further lowered the T)/rT3 ratio (P=0.03), whereas TSH (P=0.09) and T4 (P=0.3) were unaltered. With TGC, the likelihood of earlier live discharge from the ICU was 19% higher at any time (hazard ratio, 1.190; 95% confidence interval, 1.010-1.407; P=0.03). This benefit was statistically explained by the further reduction of T3/rT3 with TGC because an increase in T3/rT3 was strongly associated with a lower likelihood for earlier live discharge (hazard ratio per unit increase, 0.863; 95% confidence interval, 0.806-0.927; P<0.0001).TGC further accentuated the peripheral inactivation of thyroid hormone. This effect, mimicking a fasting response, statistically explained part of the clinical outcome benefit of TGC.
| S-EPMC3462949 | 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:This meta-analysis aims to update the evidence for the effects of intensive glucose control (IGC) on the outcomes among critically ill patients. We performed a systematic literature review from inception through December, 2017 by two independent authors by searching PubMed, EMBASE and Cochrane Library. Randomized clinical trials of the effects of IGC compared with conventional glucose control were selected. Random-effect models were applied to calculate summary relative risks (RRs) for the related outcomes. Of 4247 records identified, we abstracted data from 27 relevant trials for meta-analysis. Compared with patients receiving conventional glucose control (controls), patients with IGC did not have significantly decreased risk of short-term mortality (in-hospital mortality or intensive care unit (ICU) mortality) (RR 0.99, 95% CI 0.92-1.06) or 3- to 6-month mortality (RR 1.02, 95% CI 0.97-1.08). These results remained constant among different study settings including surgical ICUs, medical ICUs or mixed ICUs. Similarly, we also found that patients with IGC did not have significantly lower risk of sepsis (RR 1.00, 95% CI 0.89-1.11) or new need for dialysis (RR 0.97, 95% CI 0.84-1.11). However, patients with IGC had almost 4-fold increase in risk of hypoglycemia (RR 4.86, 95% CI 3.16-7.46). In conclusion, in this updated meta-analysis of published trials, critically ill patients receiving IGC were found to be at neutral risk for short-term or 3- 6-month mortality, risk of sepsis or new need for dialysis, but at higher risk of hypoglycemia.
| S-EPMC6240146 | biostudies-literature
Project description:IntroductionSevere hypoglycemia (blood glucose concentration (BG) < 40 mg/dL) is independently associated with an increased risk of mortality in critically ill patients. The association of milder hypoglycemia (BG < 70 mg/dL) with mortality is less clear.MethodsProspectively collected data from two observational cohorts in the USA and in The Netherlands, and from the prospective GLUCONTROL trial were analyzed. Hospital mortality was the primary endpoint.ResultsWe analyzed data from 6,240 patients: 3,263 admitted to Stamford Hospital (ST), 2,063 admitted to three institutions in The Netherlands (NL) and 914 who participated in the GLUCONTROL trial (GL). The percentage of patients with hypoglycemia varied from 18% to 65% among the different cohorts. Patients with hypoglycemia experienced higher mortality than did those without hypoglycemia even after stratification by severity of illness, diagnostic category, diabetic status, mean BG during intensive care unit (ICU) admission and coefficient of variation (CV) as a reflection of glycemic variability. The relative risk (RR, 95% confidence interval) of mortality associated with minimum BG < 40, 40 to 54 and 55 to 69 mg/dL compared to patients with minimum BG 80 to 109 mg/dL was 3.55 (3.02 to 4.17), 2.70 (2.31 to 3.14) and 2.18 (1.87 to 2.53), respectively (all P < 0.0001). The RR of mortality associated with any hypoglycemia < 70 mg/dL was 3.28 (2.78 to 3.87) (P < 0.0001), 1.30 (1.12 to 1.50) (P = 0.0005) and 2.11 (1.62 to 2.74) (P < 0.0001) for the ST, NL and GL cohorts, respectively. Multivariate regression analysis demonstrated that minimum BG < 70 mg/dL, 40 to 69 mg/dL and < 40 mg/dL were independently associated with increased risk of mortality for the entire cohort of 6,240 patients (odds ratio (OR) (95% confidence interval (CI)) 1.78 (1.39 to 2.27) P < 0.0001), 1.29 (1.11 to 1.51) P = 0.0011 and 1.87 (1.46 to 2.40) P < 0.0001) respectively.ConclusionsMild hypoglycemia was associated with a significantly increased risk of mortality in an international cohort of critically ill patients. Efforts to reduce the occurrence of hypoglycemia in critically ill patients may reduce mortality.
| S-EPMC3387616 | biostudies-literature
Project description:IntroductionThe purpose of this research is to provide recommendations for the management of glycemic control in critically ill patients.MethodsTwenty-one experts issued recommendations related to one of the five pre-defined categories (glucose target, hypoglycemia, carbohydrate intake, monitoring of glycemia, algorithms and protocols), that were scored on a scale to obtain a strong or weak agreement. The GRADE (Grade of Recommendation, Assessment, Development and Evaluation) system was used, with a strong recommendation indicating a clear advantage for an intervention and a weak recommendation indicating that the balance between desirable and undesirable effects of an intervention is not clearly defined.ResultsA glucose target of less than 10 mmol/L is strongly suggested, using intravenous insulin following a standard protocol, when spontaneous food intake is not possible. Definition of the severe hypoglycemia threshold of 2.2 mmol/L is recommended, regardless of the clinical signs. A general, unique amount of glucose (enteral/parenteral) to administer for any patient cannot be suggested. Glucose measurements should be performed on arterial rather than venous or capillary samples, using central lab or blood gas analysers rather than point-of-care glucose readers.ConclusionsThirty recommendations were obtained with a strong (21) and a weak (9) agreement. Among them, only 15 were graded with a high level of quality of evidence, underlying the necessity to continue clinical studies in order to improve the risk-to-benefit ratio of glucose control.
| S-EPMC3219261 | biostudies-literature
Project description:IntroductionThis was a planned substudy from the European observational Sepsis Occurrence in Acutely ill Patients (SOAP) study to investigate the possible impact of insulin-treated diabetes on morbidity and mortality in ICU patients.MethodsThe SOAP study was a cohort, multicenter, observational study which included data from all adult patients admitted to one of 198 participating ICUs from 24 European countries during the study period. For this substudy, patients were classified according to whether or not they had a known diagnosis of insulin-treated diabetes mellitus. Outcome measures included the degree of organ dysfunction/failure as assessed by the sequential organ failure assessment (SOFA) score, the occurrence of sepsis syndromes and organ failure in the ICU, hospital and ICU length of stay, and all cause hospital and ICU mortality.ResultsOf the 3147 patients included in the SOAP study, 226 (7.2%) had previously diagnosed insulin-treated diabetes mellitus. On admission, patients with insulin-treated diabetes were older, sicker, as reflected by higher simplified acute physiology system II (SAPS II) and SOFA scores, and more likely to be receiving hemodialysis than the other patients. During the ICU stay, more patients with insulin-treated diabetes required renal replacement therapy (hemodialysis or hemofiltration) than other patients. There were no significant differences in ICU or hospital lengths of stay or in ICU or hospital mortality between patients with or without insulin-treated diabetes. Using a Cox proportional hazards regression analysis with hospital mortality censored at 28-days as the dependent factor, insulin-treated diabetes was not an independent predictor of mortality.ConclusionsEven though patients with a history of insulin-treated diabetes are more severely ill and more likely to have renal failure, insulin-treated diabetes is not associated with increased mortality in ICU patients.
| S-EPMC2875526 | biostudies-literature
Project description:BackgroundCritically 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.MethodsThe 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?<?90 mg/dL to a 5% level using a stochastic model of insulin sensitivity to assess patient-specific responses to insulin and its future likely variability to optimize insulin interventions. The clinical trial was performed at the Centre Hospitalier Universitaire de Liege and included 9 patients. Results are compared to 24-hour pre-trial and 24-hour post-trial, but also to the results of the first pilot trial performed in Liege, STAR-Liege 1 (SL1). This trial was approved by the Ethics Committee of the Medical Faculty of the University of Liege (Liege, Belgium).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?<?100 mg/dL with no BG?<?70 mg/dL. Comparing these results with 24-hour pre-trial and post-trial shows that SL2 reduced high and low BG levels and reduced glycemic variability. Nurses selected 3-hourly measurement only 5 of 16 times and overrode 12% of 91 recommended interventions (35% increased insulin rates and 65% decreased insulin rates). SL1 and SL2 present similar BG levels distribution (p?>?0.05) with significantly reduced measurement frequency for SL2 (p?<?0.05).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.
| S-EPMC3511234 | biostudies-literature