Insulin for Perioperative Glucose Control: Settled Science?

We read with interest the recent Clinical Concepts and Commentary article on perioperative glucose control.¹  However, we worry that it overstates available evidence with respect to the benefit/risk ratio of using insulin to target specific intraoperative glucose levels in patients undergoing surgery.

The authors rightly note that most studies find a strong correlation between hyperglycemia and poor perioperative outcomes in cardiac and noncardiac surgery.²  However, they do not mention that this correlation may not be as tight in diabetic patients³  who are most likely to experience perioperative hyperglycemia. Although the mechanism for this variability is incompletely understood, one possibility is that poorly controlled diabetics “reset” their hypoglycemic response to a higher glucose threshold.⁴  A uniform target for glucose management thus ignores that, for some patient groups, aggressively targeting a single value may cause harm both chronically⁵  and in the perioperative period.⁶  Existing intensive care unit studies clearly demonstrate that overly tight glucose control can increase mortality so the risk/benefit of any specific glucose target should be empirically tested to permit the clinician to deliver optimal care. Studies of the 200 mg/dl threshold used in the Surgical Care Improvement Project Infection-4 metric find no benefit to Infection-4 compliance,⁷  indicating that 200 may not be the right number. More recent data further complicate benefit/risk balance, observing that although mixed perioperative hyperglycemia and hypoglycemia worsened mortality after cardiac surgery, hyperglycemia alone (more than 180 mg/dl) had no effect.⁶ 

Duggan et al. may also understate the risks of aggressive insulin therapy. The Medmarx adverse drug event database identifies insulin and heparin as the two drugs most associated with adverse events resulting from administration error.⁸  In cardiac surgery patients, aggressive insulin treatment does not improve cardiac function,⁹  may worsen delirium,¹⁰  and increases the risk of hypoglycemia.¹¹  For ambulatory surgery patients, the risk calculus is even more complex. Duggan et al. reference current Society for Ambulatory Anesthesia guidelines, which by definition are for patients going home after surgery.¹²  Should such patients really receive an intraoperative insulin infusion targeting a specific glucose level, only to go home afterward where control is likely to be less tight? And is the benefit from controlling glucose only in the operating room worth the risk? Society for Ambulatory Anesthesia guidelines suggest with a 2A level of evidence that “in patients with poorly controlled diabetes, if the decision to proceed with the surgery is made, the blood glucose levels should be maintained around their preoperative baseline values rather than temporarily (i.e., perioperatively) normalizing them.”¹²  Approximately 98,000 insulin dosing errors occur every year,¹³  and a dosing error causing a patient to not emerge from anesthesia due to severe intraoperative hypoglycemia is eerily plausible.

Although the authors argue that insulin “has been shown” to improve outcomes when administered perioperatively, few prospective, randomized trials exist, some trials do not control for diabetic status, and other nonrandomized trials find no effect of insulin use.¹⁴  In light of the potentially disastrous consequences of perioperative hypoglycemia and logistical issues, including postoperative step-down beds for aggressive hyperglycemia treatment, widespread implementation of intravenous insulin infusions targeting a specific glucose level may be concerning. We do not believe that any single threshold represents settled science, and we worry that risk/benefit ratios remain too imprecise to justify widespread adoption of single-target protocols.

This work was funded by the Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois.

Dr. Tung receives a salary as Critical Care and Resuscitation Executive Editor for the journal Anesthesia & Analgesia.