Conventional Glucose Management Research Articles

Comparison of in-patient glucose team based management with conventional blood glucose management- a retrospective study from China

BackgroundGlycemic control for patients with diabetes in the surgical department is often unsatisfactory. Compounding this issue is the fact that conventional glucose management models are often inefficient and difficult to monitor over time.ObjectiveTo investigate the impact of inpatient glucose team-based management on glycemic control and hospital days in surgical patients with diabetes.MethodsA retrospective analysis was conducted on 4156 patients with diabetes in the surgical department who received inpatient management of diabetes at a tertiary medical center from June 2020 to May 2022. Based on whether they received inpatient glucose team-based management, the surgical patients with diabetes were divided into two groups: the inpatient glucose team-based management (GM group, consisting of 1698 participants) and the conventional blood glucose management group (control group, consisting of 2458 participants). We compared the two groups in terms of glycemic control, hospital days, and health-care costs. Multiple logistic regression analysis was performed to build the hospital days prediction model and nomogram. Finally, the performance of the model was evaluated.ResultsThe rate of glucose detection was higher in the GM group at 2 h postprandial (P < 0.01). The incidence of hypoglycemia and severe hyperglycemia, blood glucose attainment time, pre-operative preparation days, hospital days, and health-care costs were lower in the GM group than in the control group (P < 0.01). The linear regression model revealed that blood glucose attainment time, incidence of hypoglycemia (< 3.9mmol/L), preoperative preparation days, perioperative complications, and health-care costs were the factors influencing the hospital days (Total Point 83.4 points, mean hospital days 9.37 days). Receiver operating characteristic (ROC) curve analysis demonstrated that the nomogram had good accuracy for predicting hospital days (area under the ROC curve 0.83, 95% confidence interval [CI], 0.74 to 0.92).ConclusionInpatient glucose team-based management demonstrated significant improvements in glycemic control among surgical patients with diabetes, resulting in reduced hospital days and associated costs. The developed nomogram also exhibited promising potential in predicting hospital days, offering valuable clinical applications.

Comparison of intensive insulin therapy and conventional glucose management in patients undergoing coronary artery bypass grafting.

Background and Aims:Hyperglycemia during cardiac surgery is a risk factor for postoperative outcomes. Because incidence of diabetes mellitus is increasing in Indian population, we tried to evaluate the western protocol for strict control of blood sugar perioperatively. The main aim of the study was to evaluate glycemic control during coronary artery bypass grafting and to determine whether intensive insulin therapy (IIT) is better than the conventional one.Material and Methods:A prospective randomized comparative study was conducted to evaluate IIT and conventional management of glucose in 40 patients undergoing on-pump coronary artery bypass grafting. Outcomes measured were incidence of hyperglycemia or hypoglycemia, incidence of hypokalemia, prolonged intubation, wound infections, strokes, acute renal failure, new onset arrhythmias, length of stay in ICU and hospital, cardiac arrest and mortality. The statistical analysis was done by using Chi-square test, and paired and unpaired t test.Results:The diabetic patients had significantly higher mean blood sugar and insulin requirement. The incidence of hyperglycemia was significantly higher in conventional management of blood sugar (P = 0.001), whereas hypoglycemia (P = 0.047) and hypokalemia (P = 0.020) were significantly higher in IIT. There were no significant difference in the incidence of prolonged intubation, wound infection, length of ICU and hospital stay, strokes, acute renal failure, new onset arrhythmias, cardiac arrest, and mortality.Conclusion:The IIT did not improve the morbidity and mortality in our patients undergoing coronary artery bypass grafting.

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

BackgroundGeneral supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers.MethodsWe performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment.ResultsThe survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate).The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%).ConclusionsPractice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome.

Glycemia in Acute Stroke II study: a call to improve post-stroke hyperglycemia management in clinical practice.

The aim of the study was to analyze the effect of conventional glucose management, which aimed to maintain glucose levels <155mg/dL (8.5mmol/L), on glucose control and the outcomes of patients with acute ischaemic stroke (IS) in a clinical practice setting. This was a multicenter, prospective cohort study of patients with acute IS. Patients were classified into four groups based on their initial 48-h capillary glucose levels and the administration of and response to corrective treatment: (i) untreated and maximum glucose levels <155mg/dL (8.5mmol/L) within the first 48h; (ii) treated and good responders [glucose levels persistently <155mg/dL (8.5mmol/L)]; (iii) treated and non-responders [any glucose values ≥155mg/dL (8.5mmol/L) during the 24h after the start of corrective treatment]; and (iv) untreated with any glucose value ≥155mg/dL (8.5mmol/L). The primary outcome was death or dependence at 3months (blinded rater). A total of 213 patients were included. Ninety-seven (45.5%) patients developed glucose levels ≥155mg/dL (8.5mmol/L), 69 (71.1%) underwent corrective treatment and 31 patients underwent no corrective treatment at the physician's discretion [28 of whom had isolated values ≥155mg/dL (8.5mmol/L)]. Only 11 (16%) patients responded to conventional treatment, whereas 58 (84%) patients were non-responsive. Non-responders showed a twofold higher risk of death or dependence at 3months (odds ratio, 2.472; 95% confidence interval, 1.096-5.576; P=0.029). Lack of response to conventional treatment for glucose management in acute IS is frequent and associated with poor outcomes.

Metabolic Profiling of Children Undergoing Surgery for Congenital Heart Disease.

Inflammation and metabolism are closely interlinked. Both undergo significant dysregulation following surgery for congenital heart disease, contributing to organ failure and morbidity. In this study, we combined cytokine and metabolic profiling to examine the effect of postoperative tight glycemic control compared with conventional blood glucose management on metabolic and inflammatory outcomes in children undergoing congenital heart surgery. The aim was to evaluate changes in key metabolites following congenital heart surgery and to examine the potential of metabolic profiling for stratifying patients in terms of expected clinical outcomes. Laboratory and clinical study. University Hospital and Laboratory. Of 28 children undergoing surgery for congenital heart disease, 15 underwent tight glycemic control postoperatively and 13 were treated conventionally. Metabolic profiling of blood plasma was undertaken using proton nuclear magnetic resonance spectroscopy. A panel of metabolites was measured using a curve-fitting algorithm. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The data were assessed with respect to clinical markers of disease severity (Risk Adjusted Congenital heart surgery score-1, Pediatric Logistic Organ Dysfunction, inotrope score, duration of ventilation and pediatric ICU-free days). Changes in metabolic and inflammatory profiles were seen over the time course from surgery to recovery, compared with the preoperative state. Tight glycemic control did not significantly alter the response profile. We identified eight metabolites (3-D-hydroxybutyrate, acetone, acetoacetate, citrate, lactate, creatine, creatinine, and alanine) associated with surgical and disease severity. The strength of proinflammatory response, particularly interleukin-8 and interleukin-6 concentrations, inversely correlated with PICU-free days at 28 days. The interleukin-6/interleukin-10 ratio directly correlated with plasma lactate. This is the first report on the metabolic response to cardiac surgery in children. Using nuclear magnetic resonance to monitor the patient journey, we identified metabolites whose concentrations and trajectory appeared to be associated with clinical outcome. Metabolic profiling could be useful for patient stratification and directing investigations of clinical interventions.

Effects of tight computerized glucose control on neurological outcome in severely brain injured patients: a multicenter sub-group analysis of the randomized-controlled open-label CGAO-REA study.

IntroductionHyperglycemia is a marker of poor prognosis in severe brain injuries. There is currently little data regarding the effects of intensive insulin therapy (IIT) on neurological recovery.MethodsA sub-group analysis of the randomized-controlled CGAO-REA study (NCT01002482) in surgical intensive care units (ICU) of two university hospitals. Patients with severe brain injury, with an expected ICU length of stay ≥48 hours were included. Patients were randomized between a conventional glucose management group (blood glucose target between 5.5 and 9 mmol.L−1) and an IIT group (blood glucose target between 4.4 and 6 mmol.L−1). The primary outcome was the day-90 neurological outcome evaluated with the Glasgow outcome scale.ResultsA total of 188 patients were included in this analysis. In total 98 (52%) patients were randomized in the control group and 90 (48%) in the IIT group. The mean Glasgow coma score at baseline was 7 (±4). Patients in the IIT group received more insulin (130 (68 to 251) IU versus 74 (13 to 165) IU in the control group, P = 0.01), had a significantly lower morning blood glucose level (5.9 (5.1 to 6.7) mmol.L−1 versus 6.5 (5.6 to 7.2) mmol.L−1, P <0.001) in the first 5 days after ICU admission. The IIT group experienced more episodes of hypoglycemia (P <0.0001). In the IIT group 24 (26.6%) patients had a favorable neurological outcome (good recovery or moderate disability) compared to 31 (31.6%) in the control group (P = 0.4). There were no differences in day-28 mortality. The occurrence of hypoglycemia did not influence the outcome.ConclusionsIn this sub-group analysis of a large multicenter randomized trial, IIT did not appear to alter the day-90 neurological outcome or ICU morbidity in severe brain injured patients or ICU morbidity.

Continuous Insulin Infusion: When, Where, and How?

The association between inpatient hyperglycemia and adverse patient outcomes is well documented.1–7 Thus, focus on inpatient glycemic control has increased in the past decade. However, optimal glycemic targets remain controversial, and significant barriers to optimal glycemic control persist. After publication of the initial van den Berghe trial in surgical intensive care patients,1 several professional organizations published guidelines supporting near-normal glycemic targets.8,9 Subsequent trials documented an increased risk for hypoglycemia with tight glycemic control, suggesting that more modest glycemic targets may be optimal.10–13 The Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study,14 a large, randomized trial involving > 6,100 medical and surgical patients, documented higher 90-day mortality rates in patients managed with tight glycemic control than in those receiving conventional glucose management. Although hypoglycemia was more common among patients in the intensive treatment group, the association of hypoglycemia with an increased hazard ratio for death was similar in the two groups, suggesting that hypoglycemia contributed to the excess mortality in the intensively treated group.15 The increased risk for hypoglycemia and mortality with tight glycemic control does not justify ignoring glycemic control, but it does justify setting more moderate targets. The American Diabetes Association (ADA), the American Association of Clinical Endocrinologists (AACE), the Surviving Sepsis Campaign, and the Institute for Healthcare Improvement all updated their guidelines for glycemic control in 2009 in response to data from NICE-SUGAR.16–18 All four sets of guidelines recommend initiating insulin therapy in patients with persistent hyperglycemia (blood glucose > 180 mg/dl). After insulin is initiated, the target blood glucose range should be 140–180 mg/dl for the majority of patients. However, a more stringent goal of 110–140 mg/dl may be appropriate for certain patients, provided it can be achieved without …

Intensive insulin therapy for septic patients: a meta-analysis of randomized controlled trials.

Background. Studies on the effect of intensive insulin therapy (IIT) in septic patients with hyperglycemia have given inconsistent results. The primary purpose of this meta-analysis was to evaluate whether it is effective in reducing mortality. Methods. We searched PubMed, Embase, the Cochrane Library, clinicaltrials.gov, and relevant reference lists up to September 2013 and including randomized controlled trials that compared IIT with conventional glucose management in septic patients. Study quality was assessed using the Cochrane Risk of Bias Tool. And our primary outcome measure was pooled in the random effects model. Results. We identified twelve randomized controlled trials involving 4100 patients. Meta-analysis showed that IIT did not reduce any of the outcomes: overall mortality (risk ratio [RR] = 0.98, 95% CI [0.85, 1.15], P = 0.84), 28-day mortality (RR = 0.66, 95% CI [0.40, 1.10], P = 0.11), 90-day mortality (RR = 1.10, 95% CI [0.97, 1.26], P = 0.13), ICU mortality (RR = 0.94, 95% CI [0.77, 1.14], P = 0.52), hospital mortality (RR = 0.98, 95% CI [0.86, 1.11], P = 0.71), severity of illness, and length of ICU stay. Conversely, the incidence of hypoglycemia was markedly higher in the IIT (RR = 2.93, 95% CI [1.69, 5.06], P = 0.0001). Conclusions. For patients with sepsis, IIT and conservative glucose management show similar efficacy, but ITT is associated with a higher incidence of hypoglycemia.

Intensive glucose regulation does not reduce enzymatic infarct size in hyperglycemic acute coronary syndromes: results of the randomized BIOMArCS-2 glucose trial

Background: Elevated admission plasma glucose (APG) in acute coronary syndrome (ACS) patients is associated with increased mortality. Clinical trials of glucose regulation provided inconsistent results with respect to cardiovascular outcomes. Target glucose levels might have been suboptimal. Aim: To study the effectiveness and safety of intensive glucose management in ACS patients with hyperglycemia, aiming at a strict blood glucose normalization. Methods: BIOMArCS-2 Glucose is a single-centre, prospective, open-label, randomized, clinical trial that enrolled 294 ACS patients with an APG 7.8-16 mmol/l. Patients were randomized to an intensive glucose management strategy, aiming at a plasma glucose 4.7-6.1 mmol/l by using intravenous insulin, or conventional expectative glucose management. Endpoints were high sensitivity Troponin T 72 hours after admission (hsTropT72) (primary), the area under the curve (AUC) of CKMB release, and myocardial perfusion scintigraphy (MPS) parameters at 6 weeks follow-up. Results: In the intensive arm hsTropT72 was 1197 ng/L (541-2296) vs. 1354 ng/L (530-3057) in the conventional arm, p-value 0.41. Median AUC-CKMB was 2372 U/L (1242 – 5004) vs. 3171 U/L (1620 – 5337), p-value 0.18. The median extent of myocardial injury measured by MPS was comparable (2% vs. 4%, p value 0.07). Severe hypoglycemia (<2.8 mmol/l) was rare and occurred in 13 patients. Before discharge, death or spontaneous recurrent MI occurred in 8 (5.7%) vs. 1 patients, p-value 0.04. ![Figure][1] Treatment effect for subgroups Conclusion: Intensive glucose regulation did not reduce enzymatic infarct size in troponin positive ACS patients treated with PCI. The benefit of a possible smaller infarct size needs to be carefully weighed against the risk of death or recurrent myocardial infarction. [1]: pending:yes

Design and rationale of safe pediatric euglycemia After cardiac surgery

To describe the design of a clinical trial testing the hypothesis that children randomized to tight glycemic control with intensive insulin therapy after cardiac surgery will have improved clinical outcomes compared to children randomized to conventional blood glucose management. Two-center, randomized controlled trial. Cardiac ICUs at two large academic pediatric centers. Children from birth to those aged 36 months recovering in the cardiac ICU after surgery with cardiopulmonary bypass. Subjects in the tight glycemic control (intervention) group receive an intravenous insulin infusion titrated to achieve normoglycemia (target blood glucose range of 80-110 mg/dL; 4.4-6.1 mmol/L). The intervention begins at admission to the cardiac ICU from the operating room and terminates when the patient is ready for discharge from the ICU. Continuous glucose monitoring is performed during insulin infusion to minimize the risks of hypoglycemia. The standard care group has no target blood glucose range. The primary outcome is the development of any nosocomial infection (bloodstream, urinary tract, and surgical site infection or nosocomial pneumonia). Secondary outcomes include mortality, measures of cardiorespiratory function and recovery, laboratory indices of nutritional balance, immunologic, endocrinologic, and neurologic function, cardiac ICU and hospital length of stay, and neurodevelopmental outcome at 1 and 3 yrs of age. A total of 980 subjects will be enrolled (490 in each treatment arm) for sufficient power to show a 50% reduction in the prevalence of the primary outcome. Pediatric cardiac surgery patients may recognize great benefit from tight glycemic control in the postoperative period, particularly with regard to reduction of nosocomial infections. The Safe Pediatric Euglycemia after Cardiac Surgery trial is designed to provide an unbiased answer to the question of whether this therapy is indeed beneficial and to define the associated risks of therapy.

Timely Bolus Insulin for Glucose Control during Cardiopulmonary Bypass

Hyperglycemia during cardiopulmonary bypass (CPB) with glucose containing cardioplegia is common; normoglycemia is difficult to maintain and failure to do so may result in worse outcomes. The purpose of this quality improvement initiative was to show that a simple timely insulin bolus is more effective for glucose control during CPB with glucose containing cardioplegia than conventional (not standardized) glucose management in historical case-matched controls. A single bolus of insulin (.2 international units per kilogram; iu/kg) was administered, at the time of aortic cannulation, to 211 consecutive patients undergoing cardiac surgery with CPB and glucose containing cardioplegia. A further .1 iu/kg bolus of insulin was given for blood glucose (BG) measurements greater than 10.0 mmol/L (180 mg/dL) during CPB. The control group of 211 historical case-matched patients had glucose management according to anesthesiologist preference (insulin as a bolus, bolus plus infusion, infusion only, or no insulin). The frequency of hyperglycemia (BG &gt; 11.0 mmol/L; 198 mg/dL) during CPB was significantly less in the study group (22; 10.5%) than in the control group (117; 55.5%) (p &lt; .0001). Hyperglycemia in the first 6 hours in the intensive care unit was also significantly less frequent in the study group (5; 2.4%) than in the control group (14; 6.6%) (p = .03). Severe hypoglycemia (BG &lt; 2.8 mmol/L; 50.4 mg/dL) occurred in one patient (.47%) in the timely bolus insulin group and five patients (2.3%) in the control group (p = .09). The timely bolus insulin method is more efficacious, but equally safe, in preventing hyperglycemia during CPB with glucose containing cardioplegia, compared with conventional (not standardized) insulin treatment in historical case-matched controls.

Intensive management of hyperglycaemia in acute coronary syndromes. Study design and rationale of the BIOMArCS 2 glucose trial

Elevated admission plasma glucose is associated with increased mortality in patients who are admitted with an acute coronary syndrome. This may be mediated by increased inflammation, apoptosis and coagulation, and by a disturbed endothelial function that can be found in hyperglycaemic patients. Insulin has several characteristics that may potentially counteract these mechanisms. The BIOMArCS programme is a multi-centre initiative and currently consists of three different studies. The effects of acute coronary syndrome on acute biomarkers washout are studied in the BIOMArCS pilot and the value of biomarkers in predicting upcoming acute coronary syndrome events is studied in BIOMArCS 1. The third study (BIOMArCS 2 glucose), which will be presented here, investigates the effectiveness and safety of intensive glucose level control compared with conventional glucose management in patients with acute coronary syndrome and an admission plasma glucose of 7.8-16 mmol/l. In BIOMArCS 2 glucose, a total of 300 patients without insulin-treated diabetes mellitus will be randomized in a 1:1 ratio to either intensive or conventional glucose management on top of standard medical care. The primary endpoint is infarct size as expressed by the cardiac troponin T level 72 h after admission. To study the metabolic effects of insulin administration, we will investigate biomarker washout patterns of various metabolic mechanisms up to 7 days after admission. These markers will address inflammation, oxidative stress, hypercoagulability, endothelial activation and vasodilatation. Current acute coronary syndrome guidelines lack a clear strategy for hyperglycaemia treatment. This study will extend our knowledge on this matter as it may clarify mechanisms and generate hypotheses of if and how myocardial infarct size may be limited by glucose management at admission.

Muscle atrophy and preferential loss of myosin in prolonged critically ill patients*

Muscle weakness contributes to prolonged rehabilitation and adverse outcome of critically ill patients. Distinction between a neurogenic and/or myogenic underlying problem is difficult using routine diagnostic tools. Preferential loss of myosin has been suggested to point to a myogenic component. We evaluated markers of muscle atrophy and denervation, and the myosin/actin ratio in limb and abdominal wall skeletal muscle of prolonged critically ill patients and matched controls in relation to insulin therapy and known risk factors for intensive care unit-acquired weakness. Secondary analysis of two large, prospective, single-center randomized clinical studies. University hospital surgical and medical intensive care unit. Critically ill patients and matched controls. Intensive care unit patients had been randomized to blood glucose control to 80-110 mg/dL with insulin infusion or conventional glucose management, where insulin was only administered when glucose levels rose above 215 mg/dL. As compared with controls, rectus abdominis and vastus lateralis muscle of critically ill patients showed smaller myofiber size, decreased mRNA levels for myofibrillar proteins, increased proteolytic enzyme activities, and a lower myosin/actin ratio, virtually irrespective of insulin therapy. Increased forkhead box O1 action may have played a role. Most alterations were more severe in patients treated with corticosteroids. Duration of corticosteroid treatment, independent of duration of intensive care unit stay or other risk factors, was a dominant risk factor for a low myosin/actin ratio. The immature acetylcholine receptor subunit γ messenger RNA expression was elevated in vastus lateralis, independent of the myosin/actin ratio. Both limb and abdominal wall skeletal muscles of prolonged critically ill patients showed downregulation of protein synthesis at the gene expression level as well as increased proteolysis. This affected myosin to a greater extent than actin, resulting in a decreased myosin/actin ratio. Muscle atrophy was not ameliorated by intensive insulin therapy, but possibly aggravated by corticosteroids.

Intensive vs conventional blood glucose control in critically ill patients

Hyperglycemia is common during critical illness and has been identified as a modifiable risk factor for increased morbidity and mortality in critically ill patients. Data from selected clinical trials suggest that intensive insulin therapy (IIT) and tight glycemic control (TGC) achieve a clinical benefit when targeting blood glucose (BG) in the range of 4.4– 6.1 mmol L. However, reports of recently conducted randomized trials have shown conflicting results. Consequently, the NICE-SUGAR (Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) trial was designed as a pragmatic multi-national multi-centre randomized ‘‘effectiveness’’ trial to evaluate the impact of IIT to achieve TGC on 90-day all cause mortality and several secondary morbidity outcomes. The NICESUGAR trial aimed to resolve existing concerns about the applicability of IIT to achieve TGC in critical illness. This article considers the NICE-SUGAR trial and discusses its key findings in the context of the published literature. As the optimum target range for blood glucose (BG) in critically ill patients remains unclear, the objective of this study was to evaluate whether intensive glucose control in critical illness is associated with improved clinical outcomes. The design was a multi-national multi-centre randomized controlled trial. The setting involved 42 participating intensive care units (ICUs) across Australia, New Zealand, Canada, and the United States. Critically ill adult subjects met the eligibility requirements if, within 24 hr after admission to an ICU, they were expected to require treatment in the ICU for three or more consecutive days. Subjects were randomized to receive either intensive glucose control with a target blood glucose range of 4.5–6.0 mmol L or conventional glucose control with a target blood glucose range of 10.0 mmol L or less. The primary endpoint was allcause mortality 90 days after randomization. Of the 6,104 subjects who were randomized, 3,054 patients were randomized to undergo intensive glucose control and 3,050 patients received conventional glucose management. Data with regard to the primary outcome at day 90 were available for over 98% of the subjects evaluated. The two groups had similar characteristics at baseline. The authors reported that 829 patients (27.5%) in the intensive-control group and 751 (24.9%) patients in the conventional-control group died (odds ratio [OR] for intensive control, 1.14; 95% confidence intervals [CI], 1.02–1.28; P = 0.02). The treatment effect was similar when comparing operative (surgical) patients and non-operative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P = 0.10). Severe hypoglycemia, defined as a blood glucose level \2.2 mmol L was reported in 206 (6.8%) of patients in the intensive-control group and 15 (0.5%) of patients in the conventional-control group (P 0.001). The groups were found to be similar regarding the median S. M. Bagshaw, MD (&) M. J. Jacka, MD University of Alberta, Edmonton, Canada e-mail: bagshaw@ualberta.ca

Reply

In their letter to the editor, Sheehy and colleagues [1Sheehy A.M. Coursin D.B. Keegan M.T. Risks of tight glycemic control during adult cardiac surgery (letter).Ann Thorac Surg. 2009; 88: 1384-1385Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] express their concern about hypoglycemia that occurs during tight glycemic control (TGC). They also draw our attention to the fact that large amounts of insulin administered intraoperatively may induce postcardiopulmonary bypass hypoglycemia. Finally, they note the importance of the methodology used for glucose measurement. We agree with the authors that adopting a tight glucose range is a cause of concern and, therefore, have made the focus of our guidelines the importance of avoiding glucose levels exceeding 180 mg/dL without strict guidance on a set goal range [2Lazar H.L. McDonnell M. Chipkin S.R. et al.The Society of Thoracic Surgeons Practice Guideline Series: blood glucose management during adult cardiac surgery.Ann Thorac Surg. 2009; 87: 663-669Abstract Full Text Full Text PDF PubMed Scopus (326) Google Scholar]. Our practice at the Boston Medical Center is to maintain blood glucose levels between 120 and 180 mg/dL during cardiac operations and in the postoperative period in the intensive care unit (ICU). Using this regimen, we have had a low incidence of hypoglycemia (< 80 mg/dL) and no complications related to this event. We also agree with the authors that the administration of large amounts of insulin intraoperatively, especially in patients who have had no preoperative history of diabetes, can result in severe hypoglycemia in the ICU. The key to avoiding this problem is frequent and judicious monitoring of serum glucose. In Section VI of the guidelines, “Intraoperative Control Recommendations,” we specifically mentioned, “patients receiving IV infusions of insulin should have their blood glucose monitored every 30 to 60 minutes. More frequent monitoring, as often as every 15 minutes, should be made during periods of rapidly fluctuating sensitivity, such as during the administration of cardioplegia and systemic cooling and rewarming.” Furthermore, we caution that “patients with no history of diabetes prior to surgery may exhibit transient elevation of blood glucose >180 mg/dl during cardiopulmonary bypass. These patients may have insulin resistance and should be treated with a single or intermittent dose of IV insulin to maintain glucose <180 mg/dl. Caution should be exercised in initiating a continuous IV insulin drip in these patients, because insulin requirements may decrease rapidly in the immediate postoperative period resulting in serious hypoglycemia.” In the study of Gandhi and colleagues [3Gandhi G.Y. Nuttall G.A. Abel M.D. et al.Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized trial.Ann Intern Med. 2007; 146: 233-243Crossref PubMed Scopus (481) Google Scholar], only 20% of patients had diabetes mellitus. The increased number of strokes seen in their study was unrelated to hypoglycemia because the frequency of hypoglycemia was low and not associated with any clinical event. It is also important to note that it is as yet unclear how, or if, hypoglycemia due to insulin therapy affects morbidity or mortality. Hypoglycemia in critically ill patients may be more reflective of widespread organ dysfunction and not insulin therapy [4Kosiborod M. Inzucchi S. Goyal A. et al.Relationship between spontaneous iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction.JAMA. 2009; 301: 1556-1564Crossref PubMed Scopus (282) Google Scholar]. Patients receiving TGC during cardiac operations receive this protocol for short periods, and their blood glucose levels are more frequently checked. This contrasts with the medical ICU, where TGC protocols are used in patients requiring long-term care in whom glucose monitoring is less frequent. Finally, although we have noted in our own practice fluctuations in glucose levels due to changes in temperature, cardiac index, and the need for inotropic support, glucose values obtained from arterial, venous, or subcutaneous sources appear to vary little and have had no effect on clinical outcomes. In summary, we agree with the authors that more moderate control is a more judicious approach, but that the potential side effects of hypoglycemia are negated by more frequent glucose monitoring, which is a key component of all surgical TGC protocols. Risks of Tight Glycemic Control During Adult Cardiac SurgeryThe Annals of Thoracic SurgeryVol. 88Issue 4PreviewThe recent guidelines of The Society of Thoracic Surgeons Practice Guideline Series on glucose control deserve cautionary comment [1]. Consideration of the adverse events reported by Gandhi and colleagues [2] (STS guideline reference 17), when tight glucose control (TGC) was maintained in cardiac surgical patients intraoperatively seems merited. The incidence and risks of hypoglycemia in TGC protocols in other critically ill adult patients should also be highlighted. Full-Text PDF

Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data

Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation - Survival Using Glucose Algorithm Regulation) study. We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83-1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5-8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44-0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78-1.28; mixed ICU: RR 0.99, 95% CI 0.86-1.12). The different targets of intensive insulin therapy (glucose level < or = 6.1 mmol/L v. < or = 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.

Intensive Intraoperative Insulin Therapy versus Conventional Glucose Management during Cardiac Surgery

Intensive Intraoperative Insulin Therapy versus Conventional Glucose Management during Cardiac Surgery

Intensive Intraoperative Insulin Therapy versus Conventional Glucose Management during Cardiac Surgery

Intensive Intraoperative Insulin Therapy versus Conventional Glucose Management during Cardiac Surgery

Intensive Intraoperative Insulin Therapy versus Conventional Glucose Management during Cardiac Surgery

To determine whether rigorous intraoperative glycemic control reduces death and morbidity in cardiac surgery patients, the authors randomly assigned 400 cardiac surgical patients to tight glycemic ...

Intensive Intraoperative Insulin Therapy versus Conventional Glucose Management during Cardiac Surgery

Intensive Intraoperative Insulin Therapy versus Conventional Glucose Management during Cardiac Surgery