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Archived Comments for: Intensive glycemic control in traumatic brain injury: what is the ideal glucose range?

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  1. Blood glucose control following severe traumatic brain injury- unclear transition from beneficial to detrimental effects

    John F. Stover, Surgical Intensive Care Medicine, University Hospital Zuerich, Switzerland

    8 September 2008

    In contemporary critical care it is essential to avoid induction of additional damage. This is of utmost imortance in patients with acute brain injuries. In this context, control of arterial blood glucose should be integrated in daily clinical routine. For this, however, the optimal range has not yet been defined. In addition, we are still lacking insight into time- dependent changes possibly requiring temporally adapted blood glucose levels. During the early phase disturbances in endogenous hormonal regulation, adaptation to artificial nutrition, hemodynamic instability, and activation of the systemic inflammatory response predispose patients to unpredictable changes in arterial blood glucose. Consequently, the early phase is overshadowed by an increased risk of hyperglycemic as well as insulin- induced hypoglycemic episodes. Not even sophisticated protocols could prevent insulin- induced hypoglycemia [1- 7]. Over time, as the patients become more stable, they are less prone to e.g., insulin- induced hypoglycemia. This could explain why the beneficial effects reported by van den Berghe are not observed during the first 3 [1, 2] to 5 days [3]. In our retrospective analysis beneficial effects in terms of reduced rate in infections and elevated intracranial pressure exceeding 20 mmHg were only observed after the first week [8]. During the first week there was even a significant increase in infection rate and norepinephrine requirement in patients in whom arterial blood glucose was maintained between 3.5- 6.5 compared to 5- 8 mmol/ l [8]. To date, it remains unclear whether low arterial blood glucose must be maintained within tight limits during the first 3- 7 days in these patients with the increased risk of hypoglycemia to induce subsequent beneficial effects. Thus, detailed investigations are important to determine if low arterial blood glucose maintained within tight limits after the 3rd or 7th day allowing higher limits during the first 3- 7 days will result in significant improval and reduced complications and mortality.

    As pointed out by Paul M. Vespa [9] in his commentary to our retrospective analysis [8] the lowest possible blood glucose level void of detrimental effects must be determined for each individual patient. This is essential to define a detailed protocol for a prospective study to avoid adverse effects as e.g., induced cerebral metabolic distress [9], hypoglycaemia and rebound hyperglycemia. Increased rate of hypoglycemic episodes had resulted in premature termination of other trials [5] aimed at reproducing previously published positive effects of maintaining blood glucose between 4.4 and 6.1 mmol/ l [1- 3]. In an attempt to determine potentially optimal range in blood glucose levels we retrospectively investigated the concentration- dependent influence of arterial blood glucose on cerebral metabolic effects determined by microdialysis and changes in arterial- jugular venous differences (unpublished data). These new results strongly suggest that arterial blood glucose levels between 7 and 9 mmol/ l are superior to arterial blood glucose levels < 5 mmol/ l in terms of increased cerebral glucose uptake and improved cerebral metabolic stability.

    Despite its simple principle of action more detailed investigations are required to characterize time-, duration-, and concentration- dependent effects of maintaining arterial blood glucose levels within certain limits in patients prone to glucose- induced brain damage.


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    8. Meier R, Béchir M, Ludwig S, Sommerfeld J, Keel M, Steiger P, Stocker R, Stover JF. Differential temporal profile of lowered blood glucose levels (3.5 to 6.5 mmol/l versus 5 to 8 mmol/l) in patients with severe traumatic brain injury. Crit Care. 2008, 12: R98.

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    Competing interests