Comparison of three protocols for tight glycemic control in cardiac surgery patients.
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ABSTRACT: Objective
We performed a randomized trial to compare three insulin-titration protocols for tight glycemic control (TGC) in a surgical intensive care unit: an absolute glucose (Matias) protocol, a relative glucose change (Bath) protocol, and an enhanced model predictive control (eMPC) algorithm.Research design and methods
A total of 120 consecutive patients after cardiac surgery were randomly assigned to the three protocols with a target glycemia range from 4.4 to 6.1 mmol/l. Intravenous insulin was administered continuously or in combination with insulin boluses (Matias protocol). Blood glucose was measured in 1- to 4-h intervals as requested by the protocols.Results
The eMPC algorithm gave the best performance as assessed by time to target (8.8 +/- 2.2 vs. 10.9 +/- 1.0 vs. 12.3 +/- 1.9 h; eMPC vs. Matias vs. Bath, respectively; P < 0.05), average blood glucose after reaching the target (5.2 +/- 0.1 vs. 6.2 +/- 0.1 vs. 5.8 +/- 0.1 mmol/l; P < 0.01), time in target (62.8 +/- 4.4 vs. 48.4 +/- 3.28 vs. 55.5 +/- 3.2%; P < 0.05), time in hyperglycemia >8.3 mmol/l (1.3 +/- 1.2 vs. 12.8 +/- 2.2 vs. 6.5 +/- 2.0%; P < 0.05), and sampling interval (2.3 +/- 0.1 vs. 2.1 +/- 0.1 vs. 1.8 +/- 0.1 h; P < 0.05). However, time in hypoglycemia risk range (2.9-4.3 mmol/l) in the eMPC group was the longest (22.2 +/- 1.9 vs. 10.9 +/- 1.5 vs. 13.1 +/- 1.6; P < 0.05). No severe hypoglycemic episode (<2.3 mmol/l) occurred in the eMPC group compared with one in the Matias group and two in the Bath group.Conclusions
The eMPC algorithm provided the best TGC without increasing the risk of severe hypoglycemia while requiring the fewest glucose measurements. Overall, all protocols were safe and effective in the maintenance of TGC in cardiac surgery patients.
SUBMITTER: Blaha J
PROVIDER: S-EPMC2671097 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In some studies, tight glycemic control with insulin improved outcomes in adults undergoing cardiac surgery, but these benefits are unproven in critically ill children at risk for hyperinsulinemic hypoglycemia. We tested the hypothesis that tight glycemic control reduces morbidity after pediatric cardiac surgery.In this two-center, prospective, randomized trial, we enrolled 980 children, 0 to 36 months of age, undergoing surgery with cardiopulmonary bypass. Patients were randomly assigned to either tight glycemic control (with the use of an insulin-dosing algorithm targeting a blood glucose level of 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) or standard care in the cardiac intensive care unit (ICU). Continuous glucose monitoring was used to guide the frequency of blood glucose measurement and to detect impending hypoglycemia. The primary outcome was the rate of health care-associated infections in the cardiac ICU. Secondary outcomes included mortality, length of stay, organ failure, and hypoglycemia.A total of 444 of the 490 children assigned to tight glycemic control (91%) received insulin versus 9 of 490 children assigned to standard care (2%). Although normoglycemia was achieved earlier with tight glycemic control than with standard care (6 hours vs. 16 hours, P<0.001) and was maintained for a greater proportion of the critical illness period (50% vs. 33%, P<0.001), tight glycemic control was not associated with a significantly decreased rate of health care-associated infections (8.6 vs. 9.9 per 1000 patient-days, P=0.67). Secondary outcomes did not differ significantly between groups, and tight glycemic control did not benefit high-risk subgroups. Only 3% of the patients assigned to tight glycemic control had severe hypoglycemia (blood glucose <40 mg per deciliter [2.2 mmol per liter]).Tight glycemic control can be achieved with a low hypoglycemia rate after cardiac surgery in children, but it does not significantly change the infection rate, mortality, length of stay, or measures of organ failure, as compared with standard care. (Funded by the National Heart, Lung, and Blood Institute and others; SPECS ClinicalTrials.gov number, NCT00443599.).
| S-EPMC3501680 | biostudies-literature
Project description:Our previous randomized, clinical trial showed that postoperative tight glycemic control (TGC) for children undergoing cardiac surgery did not reduce the rate of health care-associated infections compared with standard care (STD). Heterogeneity of treatment effect may exist within this population.We performed a post hoc exploratory analysis of 980 children from birth to 36 months of age at the time of cardiac surgery who were randomized to postoperative TGC or STD in the intensive care unit. Significant interactions were observed between treatment group and both neonate (age ?30 days; P=0.03) and intraoperative glucocorticoid exposure (P=0.03) on the risk of infection. The rate and incidence of infections in subjects ?60 days old were significantly increased in the TGC compared with the STD group (rate: 13.5 versus 3.7 infections per 1000 cardiac intensive care unit days, P=0.01; incidence: 13% versus 4%, P=0.02), whereas infections among those >60 days of age were significantly reduced in the TGC compared with the STD group (rate: 5.0 versus 14.1 infections per 1000 cardiac intensive care unit days, P=0.02; incidence: 2% versus 5%, P=0.03); the interaction of treatment group by age subgroup was highly significant (P=0.001). Multivariable logistic regression controlling for the main effects revealed that previous cardiac surgery, chromosomal anomaly, and delayed sternal closure were independently associated with increased risk of infection.This exploratory analysis demonstrated that TGC may lower the risk of infection in children >60 days of age at the time of cardiac surgery compared with children receiving STD. Meta-analyses of past and ongoing clinical trials are necessary to confirm these findings before clinical practice is altered.http://www.clinicaltrials.gov. Unique identifier: NCT00443599.
| S-EPMC4043858 | biostudies-literature
Project description:The benefit results of postoperative tight glycemic control (TGC) were controversial and there was a lack of well-powered studies that support current guideline recommendations.The EMBASE, MEDLINE, and the Cochrane Library databases were searched utilizing the key words "Blood Glucose", "insulin" and "Postoperative Period" to retrieve all randomized controlled trials evaluating the benefits of postoperative TGC as compared to conventional glycemic control (CGC) in patients undergoing surgery.Fifteen studies involving 5053 patients were identified. As compared to CGC group, there were lower risks of total postoperative infection (9.4% vs. 15.8%; RR 0.586, 95% CI 0.504 to 0.680, p?<? 0.001) and wound infection (4.6% vs. 7.2%; RR 0.620, 95% CI 0.422 to 0.910, p?=?0.015) in TGC group. TGC also showed a lower risk of postoperative short-term mortality (3.8% vs. 5.4%; RR 0.692, 95% CI 0.527 to 0.909, p?=?0.008), but sensitivity analyses showed that the result was mainly influenced by one study. The patients in the TGC group experienced a significant higher rate of postoperative hypoglycemia (22.3% vs. 11.0%; RR 3.145, 95% CI 1.928 to 5.131, p?<? 0.001) and severe hypoglycemia (2.8% vs. 0.7%; RR 3.821, 95% CI 1.796 to 8.127, p?<? 0.001) as compared to CGC group. TGC showed less length of ICU stay (SMD, -?0.428 days; 95% CI, -?0.833 to -?0.022 days; p?=?0.039). However, TGC showed a neutral effect on neurological dysfunction (1.1% vs. 2.4%; RR 0.499, 95% CI 0.219 to 1.137, p?=?0.098), acute renal failure (3.3% vs. 5.4%, RR 0.610, 95% CI 0.359 to 1.038, p?=?0.068), duration of mechanical ventilation (p?=?0.201) and length of hospitalization (p?=?0.082).TGC immediately after surgery significantly reduces total postoperative infection rates and short-term mortality. However, it might limit conclusion regarding the efficacy of TGC for short-term mortality in sensitivity analyses. The patients in the TGC group experienced a significant higher rate of postoperative hypoglycemia. This study may suggest that TGC should be administrated under close glucose monitoring in patients undergoing surgery, especially in those with high postoperative infection risk.
| S-EPMC6013895 | biostudies-other
Project description:Hyperglycemia is common in patients undergoing cardiac surgery and is associated with poor outcomes. This is a review of the perioperative insulin protocol being used at Medanta, the Medicity, which has a large volume cardiac surgery setup. Preoperatively, patients are usually continued on their preoperative outpatient medications. Intravenous insulin infusion is intiated postoperatively and titrated using a column method with a choice of 7 scales. Insulin dose is calculated as a factor of blood glucose and patient's estimated insulin sensitivity. A comparison of this protocol is presented with other commonly used protocols. Since arterial blood gas analysis is done every 4 hours for first two days after cardiac surgery, automatic data collection from blood gas analyzer to a central database enables collection of glucose data and generating glucometrics. Data auditing has helped in improving performance through protocol modification.
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Project description:Critical illness is associated with significant catabolism, and persistent protein loss correlates with increased morbidity and mortality. Insulin is a potent anticatabolic hormone; high-dose insulin decreases skeletal muscle protein breakdown in critically ill pediatric surgical patients. However, insulin's effect on protein catabolism when given at clinically utilized doses has not been studied. The objective was to evaluate the effect of postoperative tight glycemic control and clinically dosed insulin on skeletal muscle degradation in children after cardiac surgery with cardiopulmonary bypass.Secondary analysis of a two-center, prospective randomized trial comparing tight glycemic control with standard care. Randomization was stratified by study center.Children 0-36 months who were admitted to the ICU after cardiac surgery requiring cardiopulmonary bypass.In the tight glycemic control arm, insulin was titrated to maintain blood glucose between 80 and 110 mg/dL. Patients in the control arm received standard care. Skeletal muscle breakdown was quantified by a ratio of urinary 3-methylhistidine to urinary creatinine.A total of 561 patients were included: 281 in the tight glycemic control arm and 280 receiving standard care. There was no difference in 3-methylhistidine to creatinine between groups (tight glycemic control, 249 ± 127 vs standard care, 253 ± 112, mean ± SD in ?mol/g; p = 0.72). In analyses restricted to the patients in tight glycemic control arm, higher 3-methylhistidine to creatinine correlated with younger age, as well as lower weight, weight-for-age z score, length, and body surface area (p < 0.005 for each) and lower postoperative day 3 serum creatinine (r = -0.17; p = 0.02). Sex, prealbumin, and albumin were not associated with 3-methylhistidine to creatinine. During urine collection, 245 patients (87%) received insulin. However, any insulin exposure did not impact 3-methylhistidine to creatinine (t test, p = 0.45), and there was no dose-dependent effect of insulin on 3-methylhistidine to creatinine (r = -0.03; p = 0.60).Although high-dose insulin has an anabolic effect in experimental conditions, at doses necessary to achieve normoglycemia, insulin appears to have no discernible impact on skeletal muscle degradation in critically ill pediatric cardiac surgical patients.
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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 .).
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Project description:Postoperative delirium is common in patients recovering from cardiac surgery. Tight glucose control has been shown to reduce mortality and morbidity. Therefore, the authors sought to determine the effect of tight intraoperative glucose control using a hyperinsulinemic-normoglycemic clamp approach on postoperative delirium in patients undergoing cardiac surgery.The authors enrolled 198 adult patients having cardiac surgery in this randomized, double-blind, single-center trial. Patients were randomly assigned to either tight intraoperative glucose control with a hyperinsulinemic-normoglycemic clamp (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin administration with blood glucose target, <150 mg/dl). Delirium was assessed using a comprehensive delirium battery. The authors considered patients to have experienced postoperative delirium when Confusion Assessment Method testing was positive at any assessment. A positive Confusion Assessment Method was defined by the presence of features 1 (acute onset and fluctuating course) and 2 (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness).Patients randomized to tight glucose control were more likely to be diagnosed as being delirious than those assigned to routine glucose control (26 of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after adjusting for preoperative usage of calcium channel blocker and American Society of Anesthesiologist physical status. Delirium severity, among patients with delirium, was comparable with each glucose management strategy.Intraoperative hyperinsulinemic-normoglycemia augments the risk of delirium after cardiac surgery, but not its severity.
| S-EPMC4440226 | 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:IntroductionIntensive care unit mortality is strongly associated with organ failure rate and severity. The sequential organ failure assessment (SOFA) score is used to evaluate the impact of a successful tight glycemic control (TGC) intervention (SPRINT) on organ failure, morbidity, and thus mortality.MethodsA retrospective analysis of 371 patients (3,356 days) on SPRINT (August 2005 - April 2007) and 413 retrospective patients (3,211 days) from two years prior, matched by Acute Physiology and Chronic Health Evaluation (APACHE) III. SOFA is calculated daily for each patient. The effect of the SPRINT TGC intervention is assessed by comparing the percentage of patients with SOFA ?5 each day and its trends over time and cohort/group. Organ-failure free days (all SOFA components ?2) and number of organ failures (SOFA components >2) are also compared. Cumulative time in 4.0 to 7.0 mmol/L band (cTIB) was evaluated daily to link tightness and consistency of TGC (cTIB ?0.5) to SOFA ?5 using conditional and joint probabilities.ResultsAdmission and maximum SOFA scores were similar (P = 0.20; P = 0.76), with similar time to maximum (median: one day; IQR: 13 days; P = 0.99). Median length of stay was similar (4.1 days SPRINT and 3.8 days Pre-SPRINT; P = 0.94). The percentage of patients with SOFA ?5 is different over the first 14 days (P = 0.016), rising to approximately 75% for Pre-SPRINT and approximately 85% for SPRINT, with clear separation after two days. Organ-failure-free days were different (SPRINT = 41.6%; Pre-SPRINT = 36.5%; P < 0.0001) as were the percent of total possible organ failures (SPRINT = 16.0%; Pre-SPRINT = 19.0%; P < 0.0001). By Day 3 over 90% of SPRINT patients had cTIB ?0.5 (37% Pre-SPRINT) reaching 100% by Day 7 (50% Pre-SPRINT). Conditional and joint probabilities indicate tighter, more consistent TGC under SPRINT (cTIB ?0.5) increased the likelihood SOFA ?5.ConclusionsSPRINT TGC resolved organ failure faster, and for more patients, from similar admission and maximum SOFA scores, than conventional control. These reductions mirror the reduced mortality with SPRINT. The cTIB ?0.5 metric provides a first benchmark linking TGC quality to organ failure. These results support other physiological and clinical results indicating the role tight, consistent TGC can play in reducing organ failure, morbidity and mortality, and should be validated on data from randomised trials.
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Project description:Aims/introduction?-Glucosidase inhibitors (?GIs) are widely used for the primary treatment of type 2 diabetes. We compared the clinical effects of three ?GIs (miglitol, acarbose and voglibose) in patients with obese type 2 diabetes.Materials and methodsJapanese patients (n = 81) with obese type 2 diabetes (body mass index [BMI] ?25 kg/m(2)) were enrolled in this multicenter, open-label study. The participants were randomized into the miglitol (n = 18), acarbose (n = 22), voglibose (n = 19) or control (n = 22) groups. Glycemic control (fasting blood glucose and glycated hemoglobin [HbA1c]), bodyweight, BMI, serum insulin, serum lipids (low-density lipoprotein and high-density lipoprotein cholesterol, and triacylglycerols) and adipocytokines (leptin and adiponectin) were evaluated every 4 weeks for 12 weeks.ResultsIn the miglitol group, HbA1c was improved significantly from the baseline at all points. The changes in HbA1c at 8 and 12 weeks from baseline were greater in the miglitol group than the control group. The voglibose group showed significant improvements in HbA1c at 12 weeks. Bodyweight and BMI were decreased significantly in the miglitol group. In addition, significant correlations were observed between the decrements in HbA1c and bodyweights over 12 weeks in the miglitol (r = 0.759, P < 0.001) and voglibose groups (r = 0.667, P = 0.002). Serum lipid and adipocytokine levels were not altered in any groups.Conclusions?GIs, especially miglitol, can effectively control blood glucose and bodyweight in obese type 2 diabetes. This study was registered with UMIN (no. UMIN000006465).
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