Abstract

ObjectiveThe hyperglycemic response to surgery may be a risk factor for cognitive dysfunction. We hypothesize that strict maintenance of normoglycemia during cardiac surgery preserves postoperative cognitive function.MethodsAs part of a larger randomized, single-blind, interventional efficacy study on the effects of hyperinsulinemic glucose control in cardiac surgery (NCT00524472), consenting patients were randomly assigned to receive combined administration of insulin and glucose, titrated to preserve normoglycemia (3.5–6.1 mmol L−1; experimental group), or standard metabolic care (blood glucose 3.5–10 mmol L−1; control group), during open heart surgery. The patients’ cognitive function was assessed during three home visits, approximately two weeks before the operation, and two months and seven months after surgery. The following tests were performed: Rey Auditory Verbal Learning Task (RAVLT for verbal learning and memory), Digit Span Task (working memory), Trail Making A & B (visuomotor tracking and attention), and the Word Pair Task (implicit memory). Questionnaires measuring specific traits known to affect cognitive performance, such as self-esteem, depression, chronic stress and social support, were also administered. The primary outcome was to assess the effect of hyperinsulinemic-normoglycemic clamp therapy versus standard therapy on specific cognitive parameters in patients receiving normoglycemic clamp, or standard metabolic care.ResultsTwenty-six patients completed the study with 14 patients in the normoglycemia and 12 patients in the control group. Multiple analysis of covariance (MANCOVA) for the RAVLT showed a significant effect for the interaction of group by visit (F = 4.07, p = 0.035), and group by visit by recall (F = 2.21, p = 0.04). The differences occurred at the second and third visit. MANCOVA for the digit span task, trail making and word pair association test showed no significant effect.ConclusionsPreserving intraoperative normoglycemia by intravenous insulin and glucose may prevent the impairment of memory function, both short and long-term, after cardiac surgery.

Highlights

  • Hyperglycemia is a typical feature of the body’s metabolic response to major surgical tissue trauma

  • Hyperglycemia is associated with poor outcomes after open heart surgery and postoperative cognitive dysfunction (POCD) [2]

  • In 2004 we introduced the ‘Glucose and Insulin administration while maintaining normoglycemia’ (GIN) concept in cardiac surgery [1]

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Summary

Methods

Patients in this study participated in a larger registered Randomized Controlled Trial on the effect of intraoperative GIN therapy on outcomes after cardiac surgery (NCT005244) [7]. To investigate the effect of cardiac surgery and GIN on the preservation of verbal memory, we ran a three factor (group by visit by recall) mixed design MANCOVA with the total number of recalled words as dependent variable, the repeated recall and the visit as repeated measures, and the group (GIN versus control) as independent variable. We ran a three factor (group by visit by direction) mixed design MANCOVA with the digit span score as the dependent variable, the direction and the visit as a repeated measures, and the group (GIN versus control) as an independent variable. We ran three three factor (group by visit by recall) mixed design MANCOVAs with the number of recalled words as the dependent variable, the recall (immediate versus delayed) and the visit as repeated measures, and the group (GIN versus control) as independent variable.

Results
Introduction
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