Intensive versus conventional glucose control in critically ill patients. Strict versus liberal target range for perioperative glucose in patients undergoing coronary artery bypass grafting: a prospective randomized controlled trial. Intensive versus conventional insulin therapy in type 2 diabetes patients undergoing D2 gastrectomy for gastric cancer: a randomized controlled trial. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Insulin infusion improves neutrophil function in diabetic cardiac surgery patients. Continuous insulin infusion improves postoperative glucose control in patients with diabetes mellitus undergoing coronary artery bypass surgery. Effects of aggressive versus moderate glycemic control on clinical outcomes in diabetic coronary artery bypass graft patients. Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized trial. Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events. Continuous perioperative insulin infusion decreases major cardiovascular events in patients undergoing vascular surgery: a prospective, randomized trial. Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial.
The optimal target range for blood glucose in critically ill patients remains unclear.
                Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization.
                Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39).
                In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.)
                2009 Massachusetts Medical Society The purpose of this study was to test the hypothesis that a liberal blood glucose strategy (121-180 mg/dL) is not inferior to a strict blood glucose strategy (90-120 mg/dL) for outcomes in patients after first-time isolated coronary artery bypass grafting and is superior for glucose control and target blood glucose management.
                A total of 189 patients undergoing coronary artery bypass grafting were investigated in this prospective randomized study to compare 2 glucose control strategies on patient perioperative outcomes. Three methods of analyses (intention to treat, completer, and per protocol) were conducted. Observed power was robust (>80%) for significant results.
                The groups were similar on preoperative hemoglobin A(1c) and number of diabetic patients. The liberal group was found to be noninferior to the strict group for perioperative complications and superior on glucose control and target range management. The liberal group had significantly fewer patients with hypoglycemic events (<60 mg/dL; P < .001), but severe hypoglycemic events (<40 mg/dL) were rare and no group differences were found (P = .23). These results were found with all 3 methods of analysis except for blood glucose variability, maximum blood glucose, and perioperative atrial fibrillation.
                This study demonstrated that maintenance of blood glucose in a liberal range after coronary artery bypass grafting led to similar outcomes compared with a strict target range and was superior in glucose control and target range management. On the basis of the results of this study, a target blood glucose range of 121 to 180 mg/dL is recommended for patients after coronary artery bypass grafting as advocated by the Society of Thoracic Surgeons.
                Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved. This study was to compare the effect of intensive insulin therapy (IIT) to conventional insulin therapy (CIT) on postoperative outcomes among type 2 diabetes mellitus (DM) patients who underwent D2 gastrectomy for gastric cancer.
                We randomly assigned gastric cancer patients with type 2 DM who underwent radical gastrectomy to receive IIT (maintenance of blood glucose at a level between 4.4 and 6.1 mmol/l) with insulin infusion or CIT (maintenance of blood glucose at a level between 10 and 11.1 mmol/l) during the postoperative period.
                Of the 179 eligible patients, 92 patients were assigned to receive IIT and 87 patients to receive CIT. Mean blood glucose concentrations were lower in the intensive group (IG) than in the conventional group (CG) (5.5 ± 0.8 vs. 9.9 ± 1.0 mmol/l, P < 0.001). Hypoglycemia occurred in 6 patients (6.5%) in the IG (P = 0.029) versus in 1 patient (1.1%) in the CG. Hospital mortality did not differ significantly between two groups (4.3% vs. 5.7%, P = 0.742). However, IIT significantly reduced morbidity (from 18.4 to 7.6%, P = 0.031). Also, IIT shortened the days to suture removal, postoperative hospital stay, and postoperative duration of antibiotic use. The HOMA-IR score was lower at all time points in IG. Moreover, IIT increased the postoperative HLA-DR expression on monocytes on postoperative days 3 and 5.
                IIT significantly reduced short-term morbidity but not mortality among type 2 DM patients who underwent D2 gastrectomy for gastric cancer. Furthermore, a possible mechanism of suppression of the insulin resistance and improvement of HLA-DR expression may partially explain the benefits of IIT. An optimal target for glucose control in ICU patients remains unclear. This prospective randomized controlled trial compared the effects on ICU mortality of intensive insulin therapy (IIT) with an intermediate glucose control.
                Adult patients admitted to the 21 participating medico-surgical ICUs were randomized to group 1 (target BG 7.8-10.0 mmol/L) or to group 2 (target BG 4.4-6.1 mmol/L).
                While the required sample size was 1,750 per group, the trial was stopped early due to a high rate of unintended protocol violations. From 1,101 admissions, the outcomes of 542 patients assigned to group 1 and 536 of group 2 were analysed. The groups were well balanced. BG levels averaged in group 1 8.0 mmol/L (IQR 7.1-9.0) (median of all values) and 7.7 mmol/L (IQR 6.7-8.8) (median of morning BG) versus 6.5 mmol/L (IQR 6.0-7.2) and 6.1 mmol/L (IQR 5.5-6.8) for group 2 (p < 0.0001 for both comparisons). The percentage of patients treated with insulin averaged 66.2 and 96.3%, respectively. Proportion of time spent in target BG was similar, averaging 39.5% and 45.1% (median (IQR) 34.3 (18.5-50.0) and 39.3 (26.2-53.6)%) in the groups 1 and 2, respectively. The rate of hypoglycaemia was higher in the group 2 (8.7%) than in group 1 (2.7%, p < 0.0001). ICU mortality was similar in the two groups (15.3 vs. 17.2%).
                In this prematurely stopped and therefore underpowered study, there was a lack of clinical benefit of intensive insulin therapy (target 4.4-6.1 mmol/L), associated with an increased incidence of hypoglycaemia, as compared to a 7.8-10.0 mmol/L target. (ClinicalTrials.gov # NCT00107601, EUDRA-CT Number: 200400391440). Diabetic patients are at increased risk of wound infection after major surgery, but the effect of perioperative glucose control on postoperative wound infection rates after surgery is uncertain. We tested the effect of an insulin infusion on perioperative neutrophil function in diabetic patients scheduled for coronary artery bypass surgery. Participants (n = 26) were randomly allocated to receive either aggressive insulin therapy (AIT) or standard insulin therapy (SIT) during surgery. Blood was drawn for neutrophil testing before surgery, 1 h after the completion of cardiopulmonary bypass, and on the first postoperative day. Neutrophil phagocytic activity decreased to 75% of baseline activity in the AIT group and to 47% of baseline activity in the SIT group (P < 0.05 between groups). No important differences in neutrophil antibody-dependent cell cytotoxicity were found. This study documents a potentially beneficial effect of continuous insulin therapy in diabetic patients who require major surgery.
                A continuous insulin infusion and glucose control during surgery improves white cell function in diabetic patients and may increase resistance to infection after surgery. Postoperative glucose control directly affects the incidence of deep sternal wound infection and death after patients with diabetes have undergone coronary artery bypass grafting. We compared the effect upon glucose control of continuous insulin infusion with that of glucometer-guided insulin injection after coronary artery bypass. Our prospective, randomized, controlled study involved patients with diabetes mellitus who underwent coronary artery bypass grafting in our hospital from January 2001 through January 2003. Immediately after surgery, patients were randomly assigned to receive continuous insulin infusion or conventional glucometer-guided injection to maintain blood glucose at a level between 150 and 200 mg/dL. The adequacy of postoperative blood glucose control and clinical outcome were evaluated. Of 93 patients studied, the incidence of sternal wound infection was 3.9% among infusion patients and 4.8% among injection patients (P=0.587). There was no significant difference in mortality rates (infusion, 3.9%; injection, 2.4%; P=0.573). Satisfactory blood glucose levels were achieved in significantly more patients undergoing infusion than injection (64.7% vs 28.6%, P <0.001). In the injection group, significantly more blood glucose measurements were required to achieve control (23.4 vs 16.5, P=0.001), and good control was attained much sooner in the infusion group (21.4 vs 30.5 hr, P=0.013). We conclude that continuous insulin infusion provides better control of postoperative blood glucose levels after coronary artery bypass grafting in patients with diabetes than does glucometer-guided insulin injection. This study sought to determine whether aggressive glycemic control (90-120 mg/dL) would result in more optimal clinical outcomes and less morbidity than moderate glycemic control (120-180 mg/dL) in diabetic patients undergoing coronary artery bypass graft (CABG) surgery.
                Maintaining serum glucose levels between 120 and 180 mg/dL with continuous insulin infusions decreases morbidity in diabetic patients undergoing CABG surgery. Studies in surgical patients requiring prolonged ventilation suggest that aggressive glycemic control (<120 mg/dL) may improve survival; however, its effect in diabetic CABG patients is unknown.
                Eighty-two diabetic patients undergoing CABG were prospectively randomized to aggressive glycemic control (90-120 mg/dL) or moderate glycemic control (120-180 mg/dL) using continuous intravenous insulin solutions (100 units regular insulin in 100 mL: normal saline) beginning at the induction of anesthesia and continuing for 18 hours after CABG. Primary end points were the incidence of major adverse events (major adverse events = 30-day mortality, myocardial infarction, neurologic events, deep sternal infections, and atrial fibrillation), the level of serum glucose, and the incidence of hypoglycemic events.
                There were no differences in the incidence of major adverse events between the groups (17 moderate vs 15 aggressive; P = 0.91). Patients with aggressive control had a lower mean glucose at the end of 18 hours of insulin infusion (135 ± 12 mg/dL moderate vs 103 ± 17 mg/dL aggressive; P < 0.0001). Patients with aggressive control had a higher incidence of hypoglycemic events (4 vs 30; P < 0.0001).
                In diabetic patients undergoing CABG surgery, aggressive glycemic control increases the incidence of hypoglycemic events and does not result in any significant improvement in clinical outcomes that can be achieved with moderate control. Clinical Trials.gov (ID #NCT00460499). It is not known whether rigorous intraoperative glycemic control reduces death and morbidity in cardiac surgery patients.
                To compare outcomes of intensive insulin therapy during cardiac surgery with those of conventional intraoperative glucose management.
                A randomized, open-label, controlled trial with blinded end point assessment.
                Tertiary care center.
                Adults with and without diabetes who were undergoing on-pump cardiac surgery.
                The primary outcome was a composite of death, sternal infections, prolonged ventilation, cardiac arrhythmias, stroke, and renal failure within 30 days after surgery. Secondary outcome measures were length of stay in the intensive care unit and hospital.
                Patients were randomly assigned to receive continuous insulin infusion to maintain intraoperative glucose levels between 4.4 (80 mg/dL) and 5.6 mmol/L (100 mg/dL) (n = 199) or conventional treatment (n = 201). Patients in the conventional treatment group were not given insulin during surgery unless glucose levels were greater than 11.1 mmol/L (>200 mg/dL). Both groups were treated with insulin infusion to maintain normoglycemia after surgery.
                Mean glucose concentrations were statistically significantly lower in the intensive treatment group at the end of surgery (6.3 mmol/L [SD, 1.6] [114 mg/dL {SD, 29}] in the intensive treatment group vs. 8.7 mmol/L [SD, 2.3] [157 mg/dL {SD, 42}] in the conventional treatment group; difference, -2.4 mmol/L [95% CI, -2.8 to -1.9 mmol/L] [-43 mg/dL {CI, -50 to -35 mg/dL}]). Eighty two of 185 patients (44%) in the intensive treatment group and 86 of 186 patients (46%) in the conventional treatment group had an event (risk ratio, 1.0 [CI, 0.8 to 1.2]). More deaths (4 deaths vs. 0 deaths; P = 0.061) and strokes (8 strokes vs. 1 strokes; P = 0.020) occurred in the intensive treatment group. Length of stay in the intensive care unit (mean, 2 days [SD, 2] vs. 2 days [SD, 3]; difference, 0 days [CI, -1 to 1 days]) and in the hospital (mean, 8 days [SD, 4] vs. 8 days [SD, 5]; difference, 0 days [CI, -1 to 0 days]) was similar for both groups.
                This single-center study used a composite end point and could not examine whether outcomes differed by diabetes status.
                Intensive insulin therapy during cardiac surgery does not reduce perioperative death or morbidity. The increased incidence of death and stroke in the intensive treatment group raises concern about routine implementation of this intervention. This study sought to determine whether tight glycemic control with a modified glucose-insulin-potassium (GIK) solution in diabetic coronary artery bypass graft (CABG) patients would improve perioperative outcomes.
                One hundred forty-one diabetic patients undergoing CABG were prospectively randomized to tight glycemic control (serum glucose, 125 to 200 mg/dL) with GIK or standard therapy (serum glucose <250 mg/dL) using intermittent subcutaneous insulin beginning before anesthesia and continuing for 12 hours after surgery. GIK patients had lower serum glucose levels (138+/-4 versus 260+/-6 mg/dL; P<0.0001), a lower incidence of atrial fibrillation (16.6% versus 42%; P=0.0017), and a shorter postoperative length of stay (6.5+/-0.1 versus 9.2+/-0.3 days; P=0.003). GIK patients also showed a survival advantage over the initial 2 years after surgery (P=0.04) and decreased episodes of recurrent ischemia (5% versus 19%; P=0.01) and developed fewer recurrent wound infections (1% versus 10%, P=0.03).
                Tight glycemic control with GIK in diabetic CABG patients improves perioperative outcomes, enhances survival, and decreases the incidence of ischemic events and wound complications. A growing body of evidence suggests that hyperglycemia is an independent predictor of increased cardiovascular risk. Aggressive glycemic control in the intensive care decreases mortality. The benefit of glycemic control in noncardiac surgery is unknown.
                In a single-center, prospective, unblinded, active-control study, 236 patients were randomly assigned to continuous insulin infusion (target glucose 100-150 mg/dl) or to a standard intermittent insulin bolus (treat glucose > 150 mg/dl) in patients undergoing peripheral vascular bypass, abdominal aortic aneurysm repair, or below- or above-knee amputation. The treatments began at the start of surgery and continued for 48 h. The primary endpoint was a composite of all-cause death, myocardial infarction, and acute congestive heart failure. The secondary endpoints were blood glucose concentrations, rates of hypoglycemia (< 60 mg/dl) and hyperglycemia (> 150 mg/dl), graft failure or reintervention, wound infection, acute renal insufficiency, and duration of stay.
                The groups were well balanced for baseline characteristics, except for older age in the intervention group. There was a significant reduction in primary endpoint (3.5%) in the intervention group compared with the control group (12.3%) (relative risk, 0.29; 95% confidence interval, 0.10-0.83; P = 0.013). The secondary endpoints were similar. Hypoglycemia occurred in 8.8% of the intervention group compared with 4.1% of the control group (P = 0.14). Multivariate analysis demonstrated that continuous insulin infusion was a negative independent predictor (odds ratio, 0.28; 95% confidence interval, 0.09-0.87; P = 0.027), whereas previous coronary artery disease was a positive predictor of adverse events.
                Continuous insulin infusion reduces perioperative myocardial infarction after vascular surgery. The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass.
                We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days). A p-value of <0.05 was considered significant.
                The anthropometric and clinical characteristics of the patients from each group were similar, except for weight and body mass index. The mean glucose level during the protocol period was 126.69 mg/dl in the treated group and 168.21 mg/dl in the control group (p<0.0016). There were no differences between groups regarding clinical outcomes, including the duration of mechanical ventilation, length of stay in the intensive care unit, blood transfusion, postoperative infection, hypoglycemic event, neurological dysfunction or 30-day mortality (p>0.05).
                In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily achieved and not to differentially affect clinical outcomes.
The included trials did not demonstrate significant differences for most of the outcomes when targeting intensive perioperative glycaemic control compared with conventional glycaemic control in patients with diabetes mellitus. However, posthoc analysis indicated that intensive glycaemic control was associated with an increased number of patients experiencing hypoglycaemic episodes. Intensive glycaemic control protocols with near-normal blood glucose targets for patients with diabetes mellitus undergoing surgical procedures are currently not supported by an adequate scientific basis. We suggest that insulin treatment regimens, patient- and health-system relevant outcomes, and time points for outcome measures should be defined in a thorough and uniform way in future studies.