Published in:
Open Access 01-12-2005 | Research
Intensive insulin therapy does not alter the inflammatory response in patients undergoing coronary artery bypass grafting: a randomized controlled trial [ISRCTN95608630]
Published in: Critical Care | Issue 6/2005
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Introduction
Strict control of plasma glucose in diabetic and non-diabetic patients has been shown to improve outcome in several clinical settings. There is extensive evidence that glucose can stimulate the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and IL-6, with no effect on the anti-inflammatory cytokine IL-10. We hypothesized that strict glucose regulation results in a change in cytokine balance from a pro-inflammatory state to a more balanced anti-inflammatory condition. In a randomized controlled trial we studied the effect of strict glycemic control on the local and systemic pro-inflammatory and anti-inflammatory balance in non-diabetic patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass.
Methods
After surgery patients were randomly assigned to intensive insulin therapy (blood glucose between 80 and 110 mg/dl) or conventional insulin therapy (blood glucose less than 200 mg/dl). At 0, 1, 2, 4, 8, 12, 16 and 24 hours after admission to the intensive care unit, plasma samples and samples from the mediastinal drains were obtained. We measured the concentrations of the pro-inflammatory cytokines TNF-α and IL-6 and the anti-inflammatory cytokine IL-10 by enzyme-linked immunosorbent assay.
Results
Both patient groups were comparable in demographics, clinical characteristics and peri-operative data. In the intensive treatment group, glucose levels were significantly lower than in the conventionally treated group. No differences were found between both groups in the concentrations of TNF-α, IL-6 and IL-10 in plasma samples or in fluid draining the mediastinal cavity. Levels of IL-6 and IL-10 were significantly higher in mediastinal fluid samples than in plasma samples, suggesting a compartmentalized production of cytokines.
Conclusion
The protective effect of intensive insulin therapy in patients after cardiac surgery with cardiopulmonary bypass is not related to a change in cytokine balance from a pro-inflammatory to an anti-inflammatory pattern. Systemic cytokine levels are not representative of the local inflammatory response.