Glucose Algorithm Regulation Research Articles

Clinical challenges of glycemic control in the intensive care unit: A narrative review.

Glucose control in patient admitted to the intensive care unit has been a topic of much debate over the past 20 years. The harmful effects of uncontrolled hyperglycemia and hypoglycemia in critically ill patients is well established. Although a large clinical trial in 2001 demonstrated significant mortality and morbidity benefits with tight glucose control in this patient population, the results could not be replicated by other investigators. The "Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation" trial in 2009 established that tight glucose control was not only of no benefit, but in fact harmful due to the significant risk of hypoglycemia. The current guidelines suggest a moderate approach with the initiation of intravenous insulin therapy in critically ill patients when the blood glucose level is above 180 mg/dL. The most important factor that underpins glycemic management in intensive care unit patients is the consequent prevention of hypoglycemia. Robust glucose monitoring strategies and insulin protocols need to be implemented in order to achieve this goal.

Effect of published scientific evidence on glycemic control in adult intensive care units.

Little is known about the deadoption of ineffective or harmful clinical practices. A large clinical trial (the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation [NICE-SUGAR] trial) demonstrated that strict blood glucose control (tight glycemic control) in patients admitted to adult intensive care units (ICUs) should be deadopted; however, it is unknown whether deadoption occurred and how it compared with the initial adoption. To evaluate glycemic control in critically ill patients before and after the publication of clinical trials that initially suggested that tight glycemic control reduced mortality (Leuven I) but subsequently demonstrated that it increased mortality (NICE-SUGAR). Interrupted time-series analysis of 353,464 patients admitted to 113 adult ICUs from January 1, 2001, through December 31, 2012, in the United States using data from the Acute Physiology and Chronic Health Evaluation database. The physiologically most extreme blood glucose level on day 1 of ICU admission defined glycemic control as tight control (glucose level, 80-110 mg/dL; to convert to millimoles per liter, multiply by 0.0555), hypoglycemia (glucose level, <70 mg/dL), and hyperglycemia (glucose level, ≥180 mg/dL). Temporal changes in each marker were examined using mixed-effects segmented linear regression. Before the publication of Leuven I, 17.2% (95% CI, 16.2%-18.2%) of ICU admissions had tight glycemic control, 3.0% (95% CI, 2.6%-3.5%) had hypoglycemia, and 40.2% (95% CI, 38.8%-41.5%) had hyperglycemia. After the publication of Leuven I, there were significant increases in the relative proportion of admissions with tight glycemic control (1.7% per quarter; 95% CI, 1.2%-2.3%; P<.001) and hypoglycemia (2.5% per quarter; 95% CI, 1.9%-3.2%; P<.001) and decreases in those with hyperglycemia (0.6% per quarter; 95% CI, 0.4%-0.9%; P<.001). Following the publication of NICE-SUGAR, there was no change in the proportion of patients with tight glycemic control or hyperglycemia. There was an immediate decrease in the relative proportion of patients with hypoglycemia (22.4%; 95% CI, 13.2%-30.1%; P<.001) but no subsequent change over time. Among patients admitted to adult ICUs in the United States, there was a slow steady adoption of tight glycemic control following publication of a clinical trial that suggested benefit, with little to no deadoption following a subsequent trial that demonstrated harm. There is an urgent need to understand and promote the deadoption of ineffective clinical practices.

Glucose control in the intensive care unit by use of continuous glucose monitoring: what level of measurement error is acceptable?

Accuracy and frequency of glucose measurement is essential to achieve safe and efficacious glucose control in the intensive care unit. Emerging continuous glucose monitors provide frequent measurements, trending information, and alarms. The objective of this study was to establish the level of accuracy of continuous glucose monitoring (CGM) associated with safe and efficacious glucose control in the intensive care unit. We evaluated 3 established glucose control protocols [Yale, University of Washington, and Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR)] by use of computer simulations. Insulin delivery was informed by intermittent blood glucose (BG) measurements or CGM levels with an increasing level of measurement error. Measures of glucose control included mean glucose, glucose variability, proportion of time glucose was in target range, and hypoglycemia episodes. Apart from the Washington protocol, CGM with mean absolute relative deviation (MARD) ≤ 15% resulted in similar mean glucose as with the use of intermittent BG measurements. Glucose variability was also similar between CGM and BG-informed protocols. Frequency and duration of hypoglycemia were not worse by use of CGM with MARD ≤ 10%. Measures of glucose control varied more between protocols than at different levels of the CGM error. The efficacy of CGM-informed and BG-informed commonly used glucose protocols is similar, but the risk of hypoglycemia may be reduced by use of CGM with MARD ≤ 10%. Protocol choice has greater influence on glucose control measures than the glucose measurement method.

Diabetes and periodontal therapy

This issue of The Journal of the American Dental Association (JADA) contains a report1 of the periodontal treatment response among people who participated in the Diabetes and Periodontal Therapy Trial (DPTT).2 The DPTT is a large, multicenter randomized controlled clinical trial that was designed to study the effect of nonsurgical periodontal therapy among people who have type 2 diabetes mellitus and periodontitis. The periodontal treatment consisted of two or more sessions of scaling and root planing (totaling more than 2.5 hours and involving the use of local anesthetic) and follow-up supportive periodontal care. The main conclusion of this six-month trial was that nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes who had periodontitis.2 This trial has received considerable attention because its findings are contrary to what many people anticipated—and because it did not support results of smaller clinical trials and meta-analyses that showed improvements in hemoglobin A1c (HbA1c) levels as a result of nonsurgical periodontal therapy.3 We wish to address the generalizability of the DPTT. As reported by the authors in this issue of JADA,1 the patient sample of the DPTT reflects the population of people with diabetes in the United States. The DPTT included participants who had type 2 diabetes with HbA1c levels between 7 percent and less than 9 percent; 72 percent of the participants were obese (body mass index [BMI] greater than 30 kilograms per square meter).1 The National Health and Nutrition Examination Survey is a population-based survey of people with diabetes in the United States; its results demonstrated that only 12.6 percent of people with diabetes in the United States are estimated to have HbA1c levels greater than 9 percent and 62.4 percent to have a BMI of 30 or greater.4,5 The DPTT does not address the possible effect of periodontal treatment in the 12 percent of the population with HbA1c levels greater than 9 percent or the 50 percent of the population with HbA1c levels less than 7 percent, because efforts were made to exclude these patients. However, the magnitude of obesity was not constrained by trial entry criteria. Patients with type 2 diabetes who have HbA1c levels higher than 9 percent and a BMI of less than 30 are rare. Because the participant sample was typical of patients with diabetes both in terms of HbA1c and obesity, the results of the DPTT should be viewed as fully generalizable to patients with diabetes in the United States.

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 …

Even silent hypoglycemia induces cardiac arrhythmias.

While many studies have shown that intensive glycemic control can prevent the microvascular complications of diabetes, the benefits of intensive glycemic control in preventing macrovascular complications, including heart attacks, strokes, and overall mortality, have been less clear. Intensive glycemic control almost always increases the frequency and severity of hypoglycemic episodes. What remains unclear is whether hypoglycemia directly contributes to, or is merely associated with, the increased mortality noted in recent large trials (e.g., Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation [NICE-SUGAR], Control of Hyperglycaemia in Paediatric intensive care [CHiP], Action to Control Cardiovascular Risk in Diabetes [ACCORD]) (1–3). In the intensive care setting, noniatrogenic hypoglycemia serves as a harbinger of mortality, but it is unlikely to be a direct cause of mortality (4). By contrast, in the outpatient setting, insulin-induced hypoglycemia can be lethal. Among people with diabetes, the mortality rate due to hypoglycemia has been reported to be as high as 10% (5). Indeed, insulin-induced hypoglycemia has been considered responsible for nocturnal deaths in diabetic patients (6), and has been documented to be associated with the “dead-in-bed” syndrome (7). Therefore in the outpatient setting, the microvascular benefits of intensive glycemic control in people with diabetes have to be weighed against the apparent increased mortality associated with iatrogenic hypoglycemia. The mechanism(s) by which hypoglycemia may increase mortality remains unknown. In patients with cardiac disease, hypoglycemia has been associated with ischemic chest pain (8). Hypoglycemia also increases markers of thrombosis and inflammation, potentially increasing the risk of acute thrombotic events or accelerating development of atherosclerosis (9). Although hypoglycemia-associated …

Glycaemic Control and Long-Term Outcomes following Transition from Modified Intensive Insulin Therapy to Conventional Glycaemic Control

This retrospective observational cohort study compared glycaemic control and long-term outcomes following transition from a modified intensive insulin therapy (mIIT) regimen to conventional glycaemic control (CGC) in adult patients admitted to a tertiary adult general intensive care unit, during two 24-month periods, before and after the publication of the Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR) trial. The before NICE-SUGAR cohort received mIIT (target glycaemic ranges 4.4 to 7.0 mmol/l), while the after NICE-SUGAR cohort received CGC (target glycaemic range 7.1 to 9.0 mmol/l). A total of 5202 patients were included in the study. With transition from mIIT to CGC, the mean time-weighted glucose increased from 6.94 mmol/l to 8.2 mmol/l (P <0.0001). A similar increase was observed in other glycaemic indices (mean, highest and lowest glucose values, P <0.0001 for all). The adjusted 90-day odds ratio for mortality decreased by 47% with transition from mIIT to CGC (odds ratio 1.47 (95% confidence interval, 1.22 to 1.78) (P <0.0001). The rate of severe and moderate hypoglycaemia also decreased from 1.2 to 0.4% (P=0.004) and from 23.3 to 5.9% (P <0.0001), respectively. mIIT was associated with an increased risk of moderate and severe hypoglycaemia compared to CGC (odds ratio 3.1 (1.51 to 6.39) (P=0.002), 6.29 (5.1 to 7.75) (P <0.0001)). Changes in recommended glycaemic control were translated into practice, with increased glycaemic indices and decreased rates of severe and moderate hypoglycaemia after the introduction of CGC. The associated decrease in 90-day mortality suggests mIIT was not superior to CGC, despite a lower hypoglycaemia rate than in previous IIT trials. Our findings support the continued use of CGC.

The benefits of tight glycemic control in critical illness: Sweeter than assumed?

Hyperglycemia has long been observed amongst critically ill patients and associated with increased mortality and morbidity. Tight glycemic control (TGC) is the clinical practice of controlling blood glucose (BG) down to the “normal” 4.4–6.1 mmol/L range of a healthy adult, aiming to avoid any potential deleterious effects of hyperglycemia. The ground-breaking Leuven trials reported a mortality benefit of approximately 10% when using this technique, which led many to endorse its benefits. In stark contrast, the multi-center normoglycemia in intensive care evaluation–survival using glucose algorithm regulation (NICE-SUGAR) trial, not only failed to replicate this outcome, but showed TGC appeared to be harmful. This review attempts to re-analyze the current literature and suggests that hope for a benefit from TGC should not be so hastily abandoned. Inconsistencies in study design make a like-for-like comparison of the Leuven and NICE-SUGAR trials challenging. Inadequate measures preventing hypoglycemic events are likely to have contributed to the increased mortality observed in the NICE-SUGAR treatment group. New technologies, including predictive models, are being developed to improve the safety of TGC, primarily by minimizing hypoglycemia. Intensive Care Units which are unequipped in trained staff and monitoring capacity would be unwise to attempt TGC, especially considering its yet undefined benefit and the deleterious nature of hypoglycemia. International recommendations now advise clinicians to ensure critically ill patients maintain a BG of <10 mmol/L. Despite encouraging evidence, currently we can only speculate and remain optimistic that the benefit of TGC in clinical practice is sweeter than assumed.

In-Hospital Management of Diabetes.

In-Hospital Management of Diabetes.

In-hospital Management of Diabetes

In-hospital Management of Diabetes

Glycaemic control in Australia and New Zealand before and after the NICE-SUGAR trial: a translational study.

IntroductionThere is no information on the uptake of Intensive Insulin Therapy (IIT) before the Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR) trial in Australia and New Zealand (ANZ) and on the bi-national response to the trial, yet such data would provide important information on the evolution of ANZ practice in this field. We aimed to study ANZ glycaemic control before and after the publication of the results of the NICE-SUGAR trial.MethodsWe analysed glucose control in critically ill patients across Australia and New Zealand during a two-year period before and after the publication of the NICE-SUGAR study. We used the mean first day glucose (Glu1) (a validated surrogate of ICU glucose control) to define practice. The implementation of an IIT protocol was presumed if the median of Glu1 measurements was <6.44 mmol/L for a given ICU. Hypoglycaemia was categorised as severe (glucose ≤2.2 mmol/L) or moderate (glucose ≤3.9 mmol/L).ResultsWe studied 49 ICUs and 176,505 patients. No ICU practiced IIT before or after NICE-SUGAR. Overall, Glu1 increased from 7.96 (2.95) mmol/L to 8.03 (2.92) mmol/L (P <0.0001) after NICE-SUGAR. Similar increases were noted in all patient subgroups studied (surgical, medical, insulin dependent diabetes mellitus, ICU stay >48/<48 hours). The rate of severe and moderate hypoglycaemia before and after NICE-SUGAR study were 0.59% vs. 0.55% (P =0.33) and 6.62% vs. 5.68% (P <0.0001), respectively. Both crude and adjusted mortalities declined over the study period.ConclusionsIIT had not been adopted in ANZ before the NICE-SUGAR study and glycaemic control corresponded to that delivered in the control arm of NICE-SUGAR trial. There were only minor changes in practice after the trial toward looser glycaemic control. The rate of moderate hypoglycaemia and mortality decreased along with such changes.

Anesthesia Literature Review

Anesthesia Literature Review

Improving IV Insulin Administration in a Community Hospital

Diabetes mellitus is a major independent risk factor for increased morbidity and mortality in the hospitalized patient, and elevated blood glucose concentrations, even in non-diabetic patients, predicts poor outcomes. The 2008 consensus statement by the American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA) states that "hyperglycemia in hospitalized patients, irrespective of its cause, is unequivocally associated with adverse outcomes." It is important to recognize that hyperglycemia occurs in patients with known or undiagnosed diabetes as well as during acute illness in those with previously normal glucose tolerance. The Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study involved over six thousand adult intensive care unit (ICU) patients who were randomized to intensive glucose control or conventional glucose control. Surprisingly, this trial found that intensive glucose control increased the risk of mortality by 14% (odds ratio, 1.14; p = 0.02). In addition, there was an increased prevalence of severe hypoglycemia in the intensive control group compared with the conventional control group (6.8% vs. 0.5%, respectively; p < 0.001). From this pivotal trial and two others, Wyoming Medical Center (WMC) realized the importance of controlling hyperglycemia in the hospitalized patient while avoiding the negative impact of resultant hypoglycemia. Despite multiple revisions of an IV insulin paper protocol, analysis of data from usage of the paper protocol at WMC shows that in terms of achieving normoglycemia while minimizing hypoglycemia, results were suboptimal. Therefore, through a systematical implementation plan, monitoring of patient blood glucose levels was switched from using a paper IV insulin protocol to a computerized glucose management system. By comparing blood glucose levels using the paper protocol to that of the computerized system, it was determined, that overall, the computerized glucose management system resulted in more rapid and tighter glucose control than the traditional paper protocol. Specifically, a substantial increase in the time spent within the target blood glucose concentration range, as well as a decrease in the prevalence of severe hypoglycemia (BG < 40 mg/dL), clinical hypoglycemia (BG < 70 mg/dL), and hyperglycemia (BG > 180 mg/dL), was witnessed in the first five months after implementation of the computerized glucose management system. The computerized system achieved target concentrations in greater than 75% of all readings while minimizing the risk of hypoglycemia. The prevalence of hypoglycemia (BG < 70 mg/dL) with the use of the computer glucose management system was well under 1%.

Improving IV Insulin Administration in a Community Hospital

Diabetes mellitus is a major independent risk factor for increased morbidity and mortality in the hospitalized patient, and elevated blood glucose concentrations, even in non-diabetic patients, predicts poor outcomes.1-4 The 2008 consensus statement by the American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA) states that "hyperglycemia in hospitalized patients, irrespective of its cause, is unequivocally associated with adverse outcomes."5 It is important to recognize that hyperglycemia occurs in patients with known or undiagnosed diabetes as well as during acute illness in those with previously normal glucose tolerance. The Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study involved over six thousand adult intensive care unit (ICU) patients who were randomized to intensive glucose control or conventional glucose control.6 Surprisingly, this trial found that intensive glucose control increased the risk of mortality by 14% (odds ratio, 1.14; p=0.02). In addition, there was an increased prevalence of severe hypoglycemia in the intensive control group compared with the conventional control group (6.8% vs. 0.5%, respectively; p<0.001). From this pivotal trial and two others,7,8 Wyoming Medical Center (WMC) realized the importance of controlling hyperglycemia in the hospitalized patient while avoiding the negative impact of resultant hypoglycemia. Despite multiple revisions of an IV insulin paper protocol, analysis of data from usage of the paper protocol at WMC shows that in terms of achieving normoglycemia while minimizing hypoglycemia, results were suboptimal. Therefore, through a systematical implementation plan, monitoring of patient blood glucose levels was switched from using a paper IV insulin protocol to a computerized glucose management system. By comparing blood glucose levels using the paper protocol to that of the computerized system, it was determined, that overall, the computerized glucose management system resulted in more rapid and tighter glucose control than the traditional paper protocol. Specifically, a substantial increase in the time spent within the target blood glucose concentration range, as well as a decrease in the prevalence of severe hypoglycemia (BG < 40 mg/dL), clinical hypoglycemia (BG < 70 mg/dL), and hyperglycemia (BG > 180 mg/dL), was witnessed in the first five months after implementation of the computerized glucose management system. The computerized system achieved target concentrations in greater than 75% of all readings while minimizing the risk of hypoglycemia. The prevalence of hypoglycemia (BG < 70 mg/dL) with the use of the computer glucose management system was well under 1%.

Glycemic Targets and Approaches to Management of the Patient with Critical Illness

Hyperglycemia during critical illness is associated with adverse outcome. The proof-of-concept Leuven studies assessed causality, and revealed that targeting strict normoglycemia (80-110mg/dL) with insulin improved outcome compared with tolerating hyperglycemia to the renal threshold (215mg/dL). A large multicenter trial (NICE-SUGAR [Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation]) found an intermediate blood glucose target (140-180mg/dL) safer than targeting normoglycemia. Differences in design and in execution of glycemic control at the bedside may have contributed to these results. In NICE-SUGAR (Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation), the blood-glucose target range in the control group was lower, there were problems to reach and maintain normoglycemia in the intervention group, and inaccurate handheld blood glucose meters and variable blood sampling sites were allowed. Inaccurate tools led to insulin-dosing errors with consequently (undetected) hypoglycemia and unacceptable blood glucose variability. Also, the studies were done superimposed upon different nutritional strategies. Thus, such differences do not allow simple, evidence-based recommendations for daily practice, but an intermediate blood glucose target may be preferable while awaiting better tools to facilitate safely reaching normoglycemia.

Glycemic Control in the ICU

Hyperglycemia is common in critically ill patients, with approximately 90% of patients treated in an ICU developing blood glucose concentrations > 110 mg/dL (6.1 mmol/L). Landmark trials in Leuven, Belgium, suggested that targeting normoglycemia (a blood glucose concentration of 80-110 mg/dL [4.4-6.1 mmol/L]) reduced mortality and morbidity, but other investigators have not been able to replicate these findings. Recently, the international multicenter Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study reported increased mortality with this approach, and recent meta-analyses do not support intensive glucose control for critically ill patients. Although the initial trials in Leuven produced enthusiasm and recommendations for intensive blood glucose control, the results of the NICE-SUGAR study have resulted in the more moderate recommendation to target a blood glucose concentration between 144 mg/dL and 180 mg/dL (8-10 mmol/L). As critical care practitioners pay greater attention to glycemic control, it has become clear that currently used point-of-care measuring systems are not accurate enough to target tight glucose control. Unresolved issues include whether increased blood glucose variability is inherently harmful and whether even moderate hypoglycemia can be tolerated in the quest for tighter blood glucose control. Future research must first address whether intensive glucose control can be delivered safely, and whether computerized decision support systems and newer technologies that allow accurate and continuous or near-continuous measurement of blood glucose can make this possible. Until such time, clinicians would be well advised to abide by the age-old adage to "first, do no harm."

Perioperative glycemic management in 2011

The publication of Van den Berghe's landmark study in 2001 supported the use of intensive insulin therapy (IIT) to target normoglycemia in the critically ill and triggered a new era in glycemic management in the perioperative period and in the ICU. In 2009, the normoglycemia in intensive care evaluation-survival using glucose algorithm regulation (NICE-SUGAR) trial demonstrated increased mortality and incidence of hypoglycemia in patients managed with IIT, resulting in a shift toward higher blood glucose targets in this patient population. This review distills clinically pertinent principles from the related literature published in the months since the NICE-SUGAR trial. A target blood glucose level in the acute care setting supported by many of the pertinent societies and frequently quoted in the literature is 140-180 mg/dl. Hyperglycemia, hypoglycemia, and glucose variability are detrimental. Accurate and efficient glucose monitoring devices are essential. Insulin infusion protocols (IIPs) employed to achieve desired blood glucose targets must be individualized and validated for the ICU and institution in which they are being implemented. Appropriate glycemic management in the acute care setting can be achieved by targeting a reasonable blood glucose range and employing specific and institutionally validated IIPs.

Use of a Novel Fluorescent Glucose Sensor in Volunteer Subjects with Type 1 Diabetes Mellitus

Stress hyperglycemia in the critically ill has been found to be associated with increased morbidity and mortality. Studies have found significant improvements in morbidity and mortality in postsurgical patients whose glucose levels were closely maintained in the euglycemic range. However, subsequent studies, in particular the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study, found no improvement in subjects with tight glycemic control. In addition to differences in protocol design, patients in the tight glycemic control arm of the NICE-SUGAR study experienced high rates of hypoglycemia compared with other studies. One interpretation of the NICE-SUGAR study results is that it is difficult to achieve normal glycemia in critically ill patients with existing glucose monitoring technology. The purpose of the study reported here was to evaluate the safety and performance of a continuous intravascular glucose sensor that could be used in the future in critically ill patients. A first-generation prototype of an intravascular continuous glucose sensor was evaluated in 29 volunteer subjects with type 1 diabetes mellitus. The sensor operates on the principle of quenched fluorescence. The fluorescent emission from the sensor chemistry is nonlinear, resulting in improved accuracy in the hypoglycemic range. The duration of each study was 8 hours. Sensor output was compared with temporally correlated reference measurements made from venous samples on a laboratory glucose analyzer. Data were obtained from 18 of the 29 subjects in the study. Data were analyzed retrospectively using a factory calibration plus a one-point in vivo calibration. The mean absolute relative difference was 7.97%, and 95.1% of all the points were in zone A of the Clarke error grid. This pilot study was the first use in human subjects of a prototype of the GluCath Intravascular Continuous Glucose Monitoring System (GluCath System). The GluCath System is based on a novel fluorescent sensor chemistry. The study found the GluCath System had a high level of accuracy as compared with a laboratory reference analyzer.

Glycemic Control in the Intensive Care Unit and during the Postoperative Period

Glycemic Control in the Intensive Care Unit and during the Postoperative Period

Response to Cembrowski et al. regarding “Could Susceptibility to Low Hematocrit Interference Have Compromised the Results of the NICE-SUGAR Trial?”

To the Editor: Cembrowski et al. (1) hypothesize that the hematocrit effect (i.e., the tendency of many blood glucose meter systems toward a positive bias at low hematocrits) in the SureStep®Flexx® meter (LifeScan) may have caused false hyperglycemia, which, when treated with insulin, may have led to some of the hypoglycemic events observed in the NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) study. We believe that the authors' data do not support this assertion. First, the authors do not present any SureStep®Flexx® data related to hypoglycemic events, the hematocrit, or NICE-SUGAR. Therefore, there is no evidence that SureStep®Flexx® was associated with hypoglycemia during the NICE-SUGAR study. Second, …