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      Intensive glucose control for critically ill patients: an updated meta-analysis

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          Abstract

          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.

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          Most cited references28

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          Permissive underfeeding and intensive insulin therapy in critically ill patients: a randomized controlled trial.

          Nutritional support has been recognized as an essential part of intensive care unit management. However, the appropriate caloric intake for critically ill patients remains ill defined. We examined the effect of permissive underfeeding compared with that of target feeding and of intensive insulin therapy (IIT) compared with that of conventional insulin therapy (CIT) on the outcomes of critically ill patients. This study had a 2 × 2 factorial, randomized, controlled design. Eligible patients were randomly assigned to permissive underfeeding or target feeding groups (caloric goal: 60-70% compared with 90-100% of calculated requirement, respectively) with either IIT or CIT (target blood glucose: 4.4-6.1 compared with 10-11.1 mmol/L, respectively). Twenty-eight-day all-cause mortality was 18.3% in the permissive underfeeding group compared with 23.3% in the target feeding group (relative risk: 0.79; 95% CI: 0.48, 1.29; P = 0.34). Hospital mortality was lower in the permissive underfeeding group than in the target group (30.0% compared with 42.5%; relative risk: 0.71; 95% CI: 0.50, 0.99; P = 0.04). No significant differences in outcomes were observed between the IIT and CIT groups. In critically ill patients, permissive underfeeding may be associated with lower mortality rates than target feeding. This trial was registered at controlled-trials.com as ISRCTN96294863.
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            Hypoglycemia and outcome in critically ill patients.

            To determine whether mild or moderate hypoglycemia that occurs in critically ill patients is independently associated with an increased risk of death. Of patients admitted to 2 hospital intensive care units (ICUs) in Melbourne and Sydney, Australia, from January 1, 2000, to October 14, 2004, we analyzed all those who had at least 1 episode of hypoglycemia (glucose concentration, <81 mg/dL). The independent association between hypoglycemia and outcome was statistically assessed. Of 4946 patients admitted to the ICUs, a cohort of 1109 had at least 1 episode of hypoglycemia (blood glucose level, <81 mg/dL). Of these 1109 patients (22.4% of all admissions to the intensive care unit), hospital mortality was 36.6% compared with 19.7% in the 3837 nonhypoglycemic control patients (P<.001). Even patients with a minimum blood glucose concentration between 72 and 81 mg/dL had a greater unadjusted mortality rate than did control patients (25.9% vs 19.7%; unadjusted odds ratio, 1.42; 95% confidence interval, 1.12-1.80; P=.004.) Mortality increased significantly with increasing severity of hypoglycemia (P<.001). After adjustment for insulin therapy, hypoglycemia was independently associated with increased risk of death, cardiovascular death, and death due to infectious disease. In critically ill patients, an association exists between even mild or moderate hypoglycemia and mortality. Even after adjustment for insulin therapy or timing of hypoglycemic episode, the more severe the hypoglycemia, the greater the risk of death.
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              Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients.

              The role of intensive insulin therapy in medical surgical intensive care patients remains unclear. The objective of this study was to examine the effect of intensive insulin therapy on mortality in medical surgical intensive care unit patients. Randomized controlled trial. Tertiary care intensive care unit. Medical surgical intensive care unit patients with admission blood glucose of > 6.1 mmol/L or 110 mg/dL. A total of 523 patients were randomly assigned to receive intensive insulin therapy (target blood glucose 4.4-6.1 mmol/L or 80-110 mg/dL) or conventional insulin therapy (target blood glucose 10-11.1 mmol/L or 180-200 mg/dL). The primary end point was intensive care unit mortality. Secondary end points included hospital mortality, intensive care unit and hospital length of stay, mechanical ventilation duration, the need for renal replacement therapy and packed red blood cells transfusion, and the rates of intensive care unit acquired infections as well as the rate of hypoglycemia (defined as blood glucose < or = 2.2 mmol/L or 40 mg/dL). There was no significant difference in intensive care unit mortality between the intensive insulin therapy and conventional insulin therapy groups (13.5% vs. 17.1%, p = 0.30). After adjustment for baseline characteristics, intensive insulin therapy was not associated with mortality difference (adjusted hazard ratio 1.09, 95% confidence interval 0.70-1.72). Hypoglycemia occurred more frequently with intensive insulin therapy (28.6% vs. 3.1% of patients; p < 0.0001 or 6.8/100 treatment days vs. 0.4/100 treatment days; p < 0.0001). There was no difference between the intensive insulin therapy and conventional insulin therapy in any of the other secondary end points. Intensive insulin therapy was not associated with improved survival among medical surgical intensive care unit patients and was associated with increased occurrence of hypoglycemia. Based on these results, we do not advocate universal application of intensive insulin therapy in intensive care unit patients. Current Controlled Trials registry (ISRCTN07413772) http://www.controlled-trials.com/ISRCTN07413772/07413772; 2005.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                December 2018
                10 October 2018
                : 7
                : 12
                : 1288-1298
                Affiliations
                [1 ]Department of Endocrinology , The Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, Heilongjiang Province, People’s Republic of China
                [2 ]Higher Education Research and Teaching Quality Assessment Center , Qiqihar Medical College, Qiqihar, Heilongjiang Province, People’s Republic of China
                [3 ]Department of Clinical Laboratory , The Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, Heilongjiang Province, People’s Republic of China
                [4 ]Department of Nutrition and Food Hygiene , School of Public Health, Qiqihar Medical College, Qiqihar, Heilongjiang Province, People’s Republic of China
                Author notes
                Correspondence should be addressed to Y Cheng: chengyu19811009@ 123456sina.com
                Article
                EC-18-0393
                10.1530/EC-18-0393
                6240146
                30352416
                a157cb72-14a2-46ea-907e-ddd9661e8ad7
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 12 September 2018
                : 10 October 2018
                Categories
                Research

                intensive glucose control (igc),intensive care unit (icu),critically ill,meta-analysis

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