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Pharmacologic Agents for the Prevention and Treatment of Delirium in Patients Undergoing Cardiac Surgery: Systematic Review and Meta-analysis

COMMENT Delirium is commonly seen after cardiac surgery and is associated with increased morbidity and mortality. The inflammatory response to surgery is among others factors that cause delirium; however, the exact etiology is still unclear. Hyperglycemia can both lead to or be the result of perioperative inflammation. It is also well established that hyperglycemia is associated with increased morbidity and mortality, including neurological morbidity. Thus, tight glucose control with intensive insulin therapy should in theory reduce perioperative inflammation. In addition, insulin has been shown to have anti-inflammatory properties. As a result, it seems plausible that reducing hyperglycemia using tight glucose control would reduce delirium as a result of reduced inflammation. The authors randomized 203 patients to study the effects of intraoperative tight glycemic control using a hyperinsulinemicnormoglycemic clamp approach on the incidence and severity of postoperative delirium. The tight control blood glucose was targeted at 80 to 110 mg/dL versus less than 150 mg/dL in the standard group. This tight control was limited only to the duration of surgery, and standard management was used in the postoperative period. Intraoperative characteristics of the groups were evenly matched. Surprisingly, in contrast to the proposed hypothesis, patients randomized to the insulin group had a higher probability of receiving a diagnosis of delirium (26% in the insulin group vs 14% in the standard therapy group) with no difference in severity. The accompanying editorial by Berger et al discusses the more recent increased focus to study delirium as it is rather difficult to diagnose, leading to wide variations in the reported incidence. One major proven disadvantage of tight control is the possibility of hypoglycemia, and there was a trend toward increased delirium rates with each 10-mg/dL decrease in glucose levels despite the absence of severe hypoglycemia. Thus, it can be inferred that there was an increased incidence of mild hypoglycemia adversely affecting neurocognitive function. Unfortunately, the authors did not assess baseline neurocognitive function to make comparisons. The role of tight glycemic control has been the subject of a large number of trials in the perioperative period involving cardiac surgery and intensive care. van der Berge and colleagues demonstrated clinical outcome benefits with aggressive insulin therapy for tight glucose control after cardiac surgery, but later studies, including the NICE-SUGAR and other trials, proved that tight glucose control actually worsened clinical outcomes. It is thus well established that intensive insulin therapy and tight glucose control are not recommended. Instead, mild hyperglycemia seems to be well tolerated.