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Introduction: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of dexamethasone on lactate and glucose levels in patients undergoing cardiac surgery., Methods: The Dexamethasone for Cardiac Surgery (DECS) trial was a multicenter randomized trial on the effect of dexamethasone 1 mg/kg versus placebo on clinical outcomes after cardiac surgery in adults. Here we report a pre-planned secondary analysis of data from DECS trial participants included at the University Medical Center Groningen. The use of a computer-assisted glucose regulation protocol--Glucose Regulation for Intensive care Patients (GRIP)--was part of routine postoperative care. GRIP aimed at glucose levels of 4 to 8 mmol/L. Primary outcome parameters were area under the lactate and glucose curves over the first 15 hours of ICU stay (AUC₁₅). ICU length of stay and mortality were observed as well., Results: The primary outcome could be determined in 497 patients of the 500 included patients. During the first 15 hours of ICU stay, lactate and glucose levels were significantly higher in the dexamethasone group than in the placebo group: lactate AUC₁₅ 25.8 (13.1) versus 19.9 (11.2) mmol/L × hour, P <0.001 and glucose AUC₁₅ 126.5 (13.0) versus 114.4 (13.9) mmol/L × hour, P <0.001. In this period, patients in the dexamethasone group required twice as much insulin compared with patients who had received placebo. Multivariate and cross-correlation analyses suggest that the effect of dexamethasone on lactate levels is related to preceding increased glucose levels. Patients in the placebo group were more likely to stay in the ICU for more than 24 hours (39.2%) compared with patients in the dexamethasone group (25.0%, P = 0.001), and 30-day mortality rates were 1.6% and 2.4%, respectively (P = 0.759)., Conclusions: Intraoperative high-dose dexamethasone increased postoperative lactate and glucose levels in the first 15 hours of ICU stay. Still, patients in the dexamethasone group had a shorter ICU length of stay and similar mortality compared with controls., Trial Registration: ClinicalTrials.gov NCT00293592 . Registered 16 February 2006.

Multiple biomarkers improve prognostication for long-term mortality in ST-segment elevation myocardial infarction (STEMI). However, one-third of mortality after STEMI occurs within initial discharge. Our objective was to determine whether multiple biomarkers (glucose, N-terminal pro-brain natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR)) predict both short-term as long-term mortality in STEMI. We used a patient-pooled dataset of consecutive STEMI patients, with complete biomarkers, who underwent primary percutaneous coronary intervention (PCI) in two single centers (Amsterdam and Groningen). With a previously developed multimarker risk score, based on three biomarkers, patients were indicated as low-, intermediate- or high risk. Cumulative 4-year mortality was estimated with the Kaplan-Meier method and compared with a log-rank test. We compared short-term and long-term mortality with a landmark set at 30 days because previous studies have shown that mortality largely occurs within 30 days. A total of 2,355 STEMI-patients were treated with primary PCI. The mortality rates in the low- (n = 1,531), intermediate- (n = 403) and high-risk (n = 421) groups were 4.8, 16.1, and 43.9 %, respectively. The differences were observed at a follow-up up to 30 days (log-rank p < 0.001) as well as after 30 days (log-rank p < 0.001). A multimarker risk score, based on admission levels of glucose, NT-proBNP, and eGFR identifies STEMI patients at low-, intermediate-, and high-risk for short-term and long-term mortality.

Background: In nondiabetic patients with ST-segment-elevation myocardial infarction, acute hyperglycemia is associated with adverse outcome. Whether this association is due merely to hyperglycemia as an acute stress response or whether longer-term glycometabolic derangements are also involved is uncertain. It was our aim to determine the association between both acute and chronic hyperglycemia (hemoglobin A(₁c) [HbA(₁c)]) and outcome in nondiabetic patients with ST-segment-elevation myocardial infarction., Methods and Results: This observational study included consecutive patients (n=4176) without known diabetes mellitus admitted with ST-segment-elevation myocardial infarction. All patients were treated with primary percutaneous intervention. Both glucose and HbA(1c) were measured on admission. Main outcome measure was total long-term mortality; secondary outcome measures were 1-year mortality and enzymatic infarct size. One-year mortality was 4.7%, and mortality after total follow-up (3.3 ± 1.5 years) was 10%. Both elevated HbA(1c) levels (P<0.001) and elevated admission glucose (P<0.001) were associated with 1-year and long-term mortality. After exclusion of early mortality (within 30 days), HbA(₁c) remained associated with long-term mortality (P<0.001), whereas glucose lost significance (P=0.09). Elevated glucose, but not elevated HbA(₁c), was associated with larger infarct size. After multivariate analysis, HbA(₁c) (hazard ratio, 1.2 per interquartile range; P<0.01), but not glucose, was independently associated with long-term mortality., Conclusions: In nondiabetic patients with ST-segment-elevation myocardial infarction, both elevated admission glucose and HbA(₁c) levels were associated with adverse outcome. Both of these parameters reflect different patient populations, and their association with outcome is probably due to different mechanisms. Measurement of both parameters enables identification of these high-risk groups for aggressive secondary risk prevention.

Background: Early delivery of calories is important in critically ill patients, and the administration of parenteral nutrition (PN) is sometimes required to achieve this goal. However, PN can induce acute hyperglycemia, which is associated with adverse outcome. We hypothesized that initiation of PN using a rapid "step-up" approach, coupled with a computerized insulin-dosing protocol, would result in a desirable caloric intake within 24 hours without causing hyperglycemia., Methods: In our surgical intensive care unit (ICU), glucose is regulated by a nurse-centered computerized glucose regulation program. When adequate enteral feeding was not possible, PN was initiated according to a simple step-up rule at an infusion rate of 10 mL/h (approximately 10 kcal/h) and subsequently increased by steps of 10 mL/h every 4 hours, provided glucose was <10 mmol/L, until the target caloric intake (1 kcal/kg/h) was reached. All glucose levels and insulin doses were collected during the step-up period and for 24 hours after achieving target feeding., Results: In all 23 consecutive patients requiring PN, mean intake was 1 kcal/kg/h within 24 hours. Of the 280 glucose samples during the 48-hour study period, mean ± standard deviation glucose level was 7.4 ± 1.4 mmol/L. Only 4.5% of glucose measurements during the step-up period were transiently ≥10 mmol/L. After initiating PN, the insulin requirement rose from 1.1 ± 1.5 units/h to 2.9 ± 2.5 units/h (P < .001)., Conclusions: This proof of concept study shows that rapid initiation of PN using a step-up approach coupled with computerized glucose control resulted in adequate caloric intake within 24 hours while maintaining adequate glycemic control.

Current care guidelines recommend glucose control (GC) in critically ill patients. To achieve GC, many ICUs have implemented a (nurse-based) protocol on paper. However, such protocols are often complex, time-consuming, and can cause iatrogenic hypoglycemia. Computerized glucose regulation protocols may improve patient safety, efficiency, and nurse compliance. Such computerized clinical decision support systems (Cuss) use more complex logic to provide an insulin infusion rate based on previous blood glucose levels and other parameters. A computerized CDSS for glucose control has the potential to reduce overall workload, reduce the chance of human cognitive failure, and improve glucose control. Several computer-assisted glucose regulation programs have been published recently. In order of increasing complexity, the three main types of algorithms used are computerized flowcharts, Proportional-Integral-Derivative (PID), and Model Predictive Control (MPC). PID is essentially a closed-loop feedback system, whereas MPC models the behavior of glucose and insulin in ICU patients. Although the best approach has not yet been determined, it should be noted that PID controllers are generally thought to be more robust than MPC systems. The computerized Cuss that are most likely to emerge are those that are fully a part of the routine workflow, use patient-specific characteristics and apply variable sampling intervals.

Objective: Intensive insulin therapy is associated with the risk of hypoglycemia and increased costs of material and personnel. We therefore evaluated the safety and efficiency of a computer-assisted glucose control protocol in a large population of critically ill patients., Design and Setting: Observational cohort study in three intensive care units (32 beds) in a 1,300-bed university teaching hospital., Patients: All 2,800 patients admitted to the surgical, neurosurgical, and cardiothoracic units; the study period started at each ICU after implementation of Glucose Regulation for Intensive Care Patients (GRIP), a freely available computer-assisted glucose control protocol., Measurements and Results: We analysed compliance in relation to recommended insulin pump rates and glucose measurement frequency. Patients were on GRIP-ordered pump rates 97% of time. Median measurement time was 5min late (IQR 20min early to 34 min late). Hypoglycemia was uncommon (7% of patients for mild hypoglycemia, < 3.5mmol/l; 0.86% for severe hypoglycemia, < 2.2 mmol/l). Our predefined target range (4.0-7.5 mmol/l) was reached after a median of 5.6 h (IQR 0.2-11.8) and maintained for 89% (70-100%) of the remaining stay at the ICU. The number of measurements needed was 5.9 (4.8-7.3) per patient per day. In-hospital mortality was 10.1%., Conclusions: Our computer-assisted glucose control protocol provides safe and efficient glucose regulation in routine intensive care practice. A low rate of hypoglycemic episodes was achieved with a considerably lower number of glucose measurements than used in most other schemes.

Background: Intensive insulin therapy to maintain normoglycemia after cardiac surgery reduces morbidity and mortality. We investigated the magnitude and duration of hyperglycemia caused by dexamethasone administered after cardiopulmonary bypass., Methods: A single-center before-after cohort study was performed. All consecutive patients undergoing coronary artery bypass grafting with cardiopulmonary bypass during a 6-month period were included. Insulin administration was guided by a sliding scale protocol. Halfway the observation period, the dexamethasone protocol was changed. The single dose (1D) group received a pre-operative dose of dexamethasone of 1 mg/kg. The double dose group (2D) received an additional dose of 0.5 mg/kg of dexamethasone post-operatively at ICU admission., Results: We included 116 patients in the 1D group and 158 patients in the 2D group. There were no significant baseline differences between the groups. Median Euroscore was 5. In univariable analysis, the glucose level was different between groups 1D and 2D at 4, 6, 9, 12 and 24 hours after ICU admission (all p < 0.001). Insulin infusion was higher in the 1D group. Corrected for insulin dose in multivariable linear analysis, the difference in glucose between the 1D and 2D groups was 1.5 mmol/L (95% confidence interval 1.0-2.0, p < 0.001) 12 hours after ICU admission., Conclusion: Dexamethasone exerts a hyperglycemic effect in cardiac surgery patients. Patients receiving high-dose corticosteroid therapy should be monitored and treated more intensively for hyperglycemic episodes.

Objective: To find out if there is an association between hyperglycaemia and mortality in mixed ICU patients., Design and Setting: Retrospective cohort study over a 2-year period at the medical ICU of a university hospital., Measurements: Admission glucose, maximum and mean glucose, length of stay, mortality, insulin therapy and Apache-II score., Results: In 1085 consecutive patients, ICU- and hospital mortality were 20 and 25%, respectively. The total number of blood glucose measurements was 10.012. Admission glucose was 7.9 +/- 4.5 mmol/l (mean +/- SD), mean glucose 7.5 +/- 2.9 and maximum glucose 10.0 +/- 5.4 mmol/l. Median ICU length of stay (LOS) was 3.0 days (range 2.0-6.0 days, IQR), and hospital LOS was 16 days (range 7-32 days). In 28% of patients insulin treatment was started. Median Apache-II score was 13. 68% of patients were mechanically ventilated. Univariate analysis showed an association with ICU mortality for mean glucose (non-survivors 8.6 +/- 4.3 vs 7.2 +/- 2.4 survivors), maximum glucose (11.7 +/- 5.9 vs 9.6 +/- 5.2, non-survivors vs survivors, respectively), use of insulin (mortality 29 vs 17% in patients not using insulin) and age (61 vs 55.7 years). Gender and a history of diabetes mellitus were not associated with mortality. In a multivariate model, the Apache-II score was the only variable associated with mortality independent of other variables, including mean blood glucose., Conclusion: In this retrospective study mean glucose level was not an independent risk factor for mortality in mixed ICU patients.

Background: Tight glucose control by intensive insulin therapy has become a key part of critical care and is an important field of study in acute coronary care. A balance has to be found between frequency of measurements and the risk of hypoglycemia. Current nurse-driven protocols are paper-based and, therefore, rely on simple rules. For safety and efficiency a computer decision support system that employs complex logic may be superior to paper protocols., Methods: We designed and implemented GRIP, a stand-alone Java computer program. Our implementation of GRIP will be released as free software. Blood glucose values measured by a point-of-care analyzer were automatically retrieved from the central laboratory database. Additional clinical information was asked from the nurse and the program subsequently advised a new insulin pump rate and glucose sampling interval., Results: Implementation of the computer program was uneventful and successful. GRIP treated 179 patients for a total of 957 patient-days. Severe hypoglycemia (< 2.2 mmol/L) only occurred once due to human error. With a median (IQR) of 4.9 (4.2-6.2) glucose measurements per day the median percentage of time in which glucose fell in the target range was 78%. Nurses rated the program as easy to work with and as an improvement over the preceding paper protocol. They reported no increase in time spent on glucose control., Conclusion: A computer driven protocol is a safe and effective means of glucose control at a surgical ICU. Future improvements in the recommendation algorithm may further improve safety and efficiency.

Introduction: Critically ill patients may benefit from strict glucose control. An objective measure of hyperglycaemia for assessing glucose control in acutely ill patients should reflect the magnitude and duration of hyperglycaemia, should be independent of the number of measurements, and should not be falsely lowered by hypoglycaemic values. The time average of glucose values above the normal range meets these requirements., Methods: A retrospective, single-centre study was performed at a 12-bed surgical intensive care unit. From 1990 through 2001 all patients over 15 years, staying at least 4 days, were included. Admission type, sex, age, Acute Physiology and Chronic Health Evaluation II score and outcome were recorded. The hyperglycaemic index (HGI) was defined as the area under the curve above the upper limit of normal (glucose level 6.0 mmol/l) divided by the total length of stay. HGI, admission glucose, mean morning glucose, mean glucose and maximal glucose were calculated for each patient. The relations between these measures and 30-day mortality were determined., Results: In 1779 patients with a median stay in the intensive care unit of 10 days, the 30-day mortality was 17%. A total of 65,528 glucose values were analyzed. Median HGI was 0.9 mmol/l (interquartile range 0.3-2.1 mmol/l) in survivors versus 1.8 mmol/l (interquartile range 0.7-3.4 mmol/l) in nonsurvivors (P < 0.001). The area under the receiver operator characteristic curve was 0.64 for HGI, as compared with 0.61 and 0.62 for mean morning glucose and mean glucose. HGI was the only significant glucose measure in binary logistic regression., Conclusion: HGI exhibited a better relation with outcome than other glucose indices. HGI is a useful measure of glucose control in critically ill patients.