Search

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.

The avid consumption of glucose with concomitant lactate production by malignant cells, even under aerobic conditions, is called the Warburg effect, or aerobic glycolysis. This metabolic state is a final common pathway that apparently serves various invasive purposes. As most invasive tumours display the Warburg effect, this has proven of great clinical importance in detecting malignancies with 18-fluorine 2-deoxyglucose positron emission tomography (FDG-PET) scans. However, using the Warburg effect to target malignancies has proven more difficult. Since hypoglycaemia has been shown to be tumouricidal for cancers that display the Warburg effect, various schemes to block glucose utilization have been investigated. But in vivo it is difficult to selectively target glucose utilization in malignant cells without harming normal cells. Cancer cells produce large amounts of lactate under the Warburg effect, without fully oxidizing it to CO(2). In contrast normal cells can completely oxidize lactate under aerobic conditions. Recent studies have demonstrated that vital organs such as the brain, heart, liver, kidneys and muscle are capable of oxidizing lactate as a fuel alternative to glucose. It has also been shown that during hypoglycaemia intravenous lactate can serve as a salvage fuel in man. Other clinical studies showed that patients can effectively metabolize large amounts of exogenous lactate. All this appears to reflect the recently recognized major physiological role of lactate as a glucose alternative. Consequently, lactate is the most logical candidate to serve as a salvage fuel when local or systemic hypoglycemia is induced. Thus, we hypothesize that the combination of hypoglycaemia induced by insulin and concomitant lactate administration will selectively suppress cancers manifesting the Warburg effect, since such cancers will have great difficulty in metabolizing lactate. This metabolic therapy could be modulated in many ways both in amplitude, in duration and in timing with respect to other therapies. The validated isolated limb perfusion (ILP) model for sarcoma appears an attractive model to evaluate local therapy with insulin and lactate and test its (adjuvant) tumouricidal effects in animals and man. Such effects could be evaluated with modern metabolic detection techniques such as FDG-PET and magnetic resonance imaging in local models both in animals and humans. Subsequently the systemic effects of hypoglycaemia combined with sodium lactate administration could be evaluated.

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. [ABSTRACT FROM AUTHOR]

Background: Favorable clinical outcomes have been observed with glucose-insulin-potassium infusion (GIK) in acute myocardial infarction (MI). The mechanisms of this beneficial effect have not been delineated clearly. GIK has metabolic, anti-inflammatory and profibrinolytic effects and it may preserve the ischemic myocardium. We sought to assess the effect of GIK infusion on infarct size and left ventricular function, as part of a randomized controlled trial. Methods: Patients (n = 940) treated for acute MI by primary percutaneous coronary intervention (PCI) were randomized to GIK infusion or no infusion. Endpoints were the creatinine kinase MB-fraction (CK-MB) and left ventricular ejection fraction (LVEF). CK-MB levels were determined 0, 2, 4, 6, 24, 48, 72 and 96 hours after admission and the LVEF was measured before discharge. Results: There were no differences between the two groups in the time course or magnitude of CK-MB release: the peak CK-MB level was 249 ± 228 U/L in the GIK group and 240 ± 200 U/L in the control group (NS). The mean LVEF was 43.7 ± 11.0 % in the GIK group and 42.4 ± 11.7% in the control group (P = 0.12). A LVEF ≤ 30% was observed in 18% in the controls and in 12% of the GIK group (P = 0.01). Conclusion: Treatment with GIK has no effect on myocardial function as determined by LVEF and by the pattern or magnitude of enzyme release. However, left ventricular function was preserved in GIK treated patients. [ABSTRACT FROM AUTHOR]

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 A1c [HbA1c]) and outcome in nondiabetic patients with ST-segment-elevation myocardial infarction. Methods and Results--This observational study included consecutive patients (n=4 176) without known diabetes mellitus admitted with ST-segment-elevation myocardial infarction. All patients were treated with primary percutaneous intervention. Both glucose and HbA1c 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 HbA1c 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), HbA1c remained associated with long-term mortality (P<0.001), whereas glucose lost significance (P0.09). Elevated glucose, but not elevated HbA1c, was associated with larger infarct size. After multivariate analysis, HbA1c (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 HbA1c 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. [ABSTRACT FROM AUTHOR]

The article provides information on a study which investigated the relation between insulin administration and renal potassium excretion in a cohort of intensive care unit (ICU) patients. The prospective observational study was conducted at 12-bed surgical ICU unit of a university teaching hospital. It made use of a computer-assisted decision support system to regulate potassium and glucose levels with periodic adjustments of continuous and insulin infusion.