Intraoperative maintenance of normoglycemia with insulin and glucose preserves verbal learning after cardiac surgery

Abstract

Objective: The 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.

Methods: As 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.

Results: Twenty-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.

Conclusions: Preserving intraoperative normoglycemia by intravenous insulin and glucose may prevent the impairment of memory function, both short and long-term, after cardiac surgery.

Figure 1. Schema illustrating the attrition in the GIN and control group over the course of the experiment.

Figure 2. Performance of the subjects in the two groups over the course of the experiment.

GIN: Experimental group with variable insulin infusion; Control: Best practice treatment; Pre-surgery: Neuropsychological assessment before surgery; Post surgery 1: Neuropsychological assessment approximately two months after surgery; Post surgery 2: Neuropsychological assessment approximately seven months after surgery; x-axis legend 1–1 to 3–7: days and iteration of verbal learning task.