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Tight Blood Glucose Control in Cardiac Surgery Patients

Alyson P. Lozicki, PharmD

July 20, 2018

Question: Does intensive, perioperative glucose control benefit patients with or without diabetes undergoing cardiac surgery?

Response from Expert Alyson P. Lozicki, PharmD
Drug Information Research Fellow

Perioperative hyperglycemia (occurring intraoperatively or in the immediate postoperative period) develops in a large proportion of patients undergoing cardiac surgery and is associated with an increased risk for poor neurologic and cardiac outcomes, increased length of hospitalization, and increased mortality. Although the frequency is much greater in patients with diabetes than without, an estimated 30% of patients with no history of diabetes before surgery develop perioperative hyperglycemia, and recent evidence suggests the risk for complications is even greater for these patients.[1,2]

The Society of Thoracic Surgeons recommends targeting a blood glucose level < 180 mg/dL for the duration of stay in the intensive care unit (ICU) in cardiac surgery patients with and without diabetes.[3] Similarly, the American Diabetes Association (ADA) recommends maintaining blood glucose at a range of 140-180 mg/dL for diabetic patients in critical care. The ADA further notes that a broader blood glucose range of 80-180 mg/dL may be appropriate in the perioperative setting but is not strongly advised.[4] Despite these recommendations, there is still much debate whether intensive glucose control in surgical patients will improve cardiac outcomes and reduce complications and, if so, whether the benefits outweigh the risks of hypoglycemia and related complications.

There is a wealth of review literature evaluating the outcomes of tight perioperative blood glucose control in adult cardiac surgery patients. Although some individual studies have demonstrated clinical benefit with strict glucose control, the results are conflicting overall. Differences in patient characteristics, study design, outcomes measured, definition of the perioperative period, and target glucose ranges make it difficult to determine an optimal glucose target in patients undergoing cardiac surgery. Most studies in this setting have consistently shown no difference in clinical outcomes with tight versus standard glucose control in patients with diabetes, but trends in the most recent literature suggest that tight glucose control may reduce the risk for perioperative complications in nondiabetic patients.[5,6,7,8,9,10]

The most robust evidence comes from a randomized controlled trial by Umpierrez and colleagues.[10] The GLUCO-CABG trial compared a postoperative intensive glucose target (100-140 mg/dL) with a standard target of (141-180 mg/dL) in patients with diabetes (n = 152) and without diabetes (n =150) undergoing coronary artery bypass grafting (CABG).[10]

The composite primary outcome was the difference in hospital mortality and perioperative complications, which included sternal wound infection, bacteremia, respiratory failure, pneumonia, acute kidney injury, acute myocardial infarction, congestive heart failure, and cardiac arrhythmia. Glycemic targets were maintained from the immediate postoperative period throughout the duration of stay in the ICU, and then patients were transitioned to a single subcutaneous insulin protocol that targeted a blood glucose level < 140 mg/dL before meals while in the hospital and for 90 days after discharge.

There was no difference in the composite primary outcome at 90 days between intensive and standard control (42% vs 52%, respectively; P = .08). A significant difference in the rate of hypoglycemic events in the ICU was also lacking. However, a subgroup analysis revealed that whereas the level of glucose control did not affect perioperative complications in patients with diabetes, an intensive glucose target reduced the relative risk for perioperative complications by 38% compared with standard control in patients without diabetes (34% vs 55%, respectively; P = .008; number needed to treat, 5). These data suggest that for every five nondiabetic patients managed on intensive glucose control, perioperative complications would be prevented in one additional patient compared with standard control.

Overall, the results of this trial suggest that there is no overall clinical benefit of intensive perioperative glucose control after major cardiac surgery. However, patients with no history of diabetes may see improved clinical outcomes with a glucose target of 100-140 mg/dL while in intensive care.

A prespecified secondary outcome of the GLUCO-CABG trial was the effect of strict glucose control on markers of inflammation and oxidative stress, and the results were consistent with the primary outcome.[11] There was no overall between-group difference in biomarkers. But a subgroup analysis revealed higher levels of cortisol, C-reactive protein, interleukin-6, and DCF (a marker of intracellular H2O2 and oxidative stress) in patients who experienced complications compared with those with no complications regardless of preexisting diabetes (P < 0.02 for all markers).

Furthermore, in nondiabetic patients with complications, markers of oxidative stress (DCF and TBARS [thiobarbituric acid-reactive substances]) were significantly higher than in those without complications (P < .005 and P = .003, respectively). This difference was not demonstrated in diabetic patients who experienced complications. A correlation between insulin control and levels of inflammatory markers in the nondiabetic patient subgroup was not addressed.

Other studies assessing the effect of glucose control on cytokines and C-reactive protein have demonstrated similar results.[12,13] However, additional studies are needed to observe the relationship between perioperative glycemic control and markers of inflammation and oxidative stress in a larger number of nondiabetic patients.

Although it remains unclear whether there is a significant overall difference in outcomes with the implementation of strict glucose targets < 140 mg/dL versus the standard recommendation of 140-180 mg/dL in the postoperative period after cardiac surgery, there may be a decreased risk for complications in nondiabetic patients. More substantial evidence is needed to support this hypothesis, and a clear mortality benefit in this group is still unclear. The feasibility of screening, implementation of nursing protocols, and adequate monitoring to prevent hypoglycemia and related complications are also important considerations.


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