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Purpose: "Glucosafe' is a new model-based decision support system for glycemic control in critical care. Safety and achievement of glycemic goals using the system are tested prospectively., Methods: Four penalty functions were developed to balance regimens of nutrition and insulin therapy against model-predicted glycemic outcome. The system advises the regimen where the penalty sum is minimal. An interactive interface allows advice alterations. Ten hyperglycemic patients (median Acute Physiology and Chronic Health Evaluation II, 12.5; interquartile range, 7.5-16.3) from a neuro and trauma intensive care unit were included for pilot testing using Glucosafe for 12 to 14 hours. Glycemic outcomes were compared to the 24-hour intervals before and after intervention., Results: Hypoglycemia (blood glucose [BG] <3.5 mmol/L) was not observed. Mean log-normal BG +/- standard deviation was reduced from 8.6 +/- 2.4 mmol/L preintervention to 7.0 +/- 1.1 mmol/L during the intervention. Nine patients reached the 4.4- to 6.1-mmol/L band after a mean 5 hours. At 5 hours intervention, mean log-normal BG was 6.7 mmol/L, 40% of measurements were in the 4.4- to 6.1-mmol/L band, and 84% were in the 4.4- to 7.75-mmol/L band., Conclusions: Safety was demonstrated with the developed penalty functions. The low BG variance achieved may permit minor adjustments of the penalty function values to reduce average BG if desired., (Copyright 2010 Elsevier Inc. All rights reserved.)