Does Perioperative Hyperglycemia Increase Risk? Should We Have Aggressive Glucose Control Perioperatively?

INTRODUCTION

The prevalence of diabetes mellitus in the United States is such that in 2020, the Centers for Disease Control and Prevention (CDC) estimated that 26.9 million individuals, or 8.2% of the US population, carried a formal diagnosis of the condition. In the context of glycemic control in the perioperative period, our clinical bias is toward heightened awareness in this particular patient population where perturbations in glucose homeostasis are anticipated. The CDC further estimated, however, that in 2020, an additional 7.3 million individuals (2.8% of the US adult population) are undiagnosed diabetics, and 88 million individuals aged 18 or older can be classified as prediabetic.

It is well documented that the physiologic stress of surgery and anesthesia elicits a complex counterregulatory hormonal response that disrupts the balance between hepatic glucose production and peripheral glucose utilization. This surgical stress response stimulates a propensity toward the development of hyperglycemia in all patients, irrespective of diabetic diagnosis or predisposition. Broadly, perioperative hyperglycemia is associated with increased morbidity and mortality. And while the mechanistic underpinnings of that association are still poorly understood, it is clear that minimizing gross disturbances (both high and low) in plasma glucose levels should be an important guiding principle for perioperative care of the surgical patient.

Operationalizing the objective of defining and maintaining perioperative euglycemia has proven challenging, with wide debate regarding the optimal glycemic target and management strategy. This chapter discusses the impact of perioperative hyperglycemia on patient outcomes and reviews the evidence informing current perioperative glycemic control recommendations from relevant medical societies.

OPTIONS

Recognizing that perioperative hyperglycemia is associated with an increased risk of adverse clinical outcomes, the goal for glycemic management is to maintain normal metabolic processes in as safe a manner as possible. In practice, this equates to avoiding profound hyperglycemia while mitigating the risk of iatrogenic hypoglycemia. Because perioperative glycemic control is highly dependent on the complex interplay of patient characteristics, the surgical procedure, anesthetic technique, and postoperative factors, explicit targets for particular phases of perioperative care continue to be debated. Current guidelines for the management of inpatient hyperglycemia suggest a blood glucose concentration of 180 mg/dL as a threshold for increasing risk. Although randomized controlled trials demonstrate that at this specific target the risk of intervention-derived hypoglycemia is significantly reduced, the potential harm associated with severe hypoglycemia (serum glucose concentration <40 mg/dL) should not be underestimated.

Any perioperative approach to maintaining euglycemia begins with the identification of patients at risk and subjecting them to frequent and accurate blood glucose monitoring. This extends beyond the patient population with a formal diagnosis of diabetes, because several studies have shown that adverse events are more common in patients with perioperative hyperglycemia without a diagnosis of diabetes compared with those with known disease. ^, Evidence is clear that the correction of hyperglycemia with insulin administration decreases complications and mortality in a wide variety of surgical patients. ^, Nevertheless, the optimal modality of insulin delivery (e.g., subcutaneous vs. intravenous [IV]) will differ depending on the clinical circumstance. Although perioperative glucose control regimens continue to evolve based on novel evidence, current best practices share the following thematic principles:

1.
Avoidance of marked hyperglycemia (>180 mg/dL) or hypoglycemia (<60 mg/dL)
2.
Prevention of unintended metabolic disturbances (e.g., ketoacidosis/hyperosmolar states)
3.
Applicable across the spectrum of the perioperative environment
4.
Communicate clearly defined goals of therapy

Preoperative Glycemic Optimization

Although no prospective randomized trials have determined the importance of preoperative glycemic control as it pertains to clinical outcome, there are signals that optimizing preoperative glucose levels may prove beneficial. Available evidence demonstrates that elevated levels of both baseline preoperative glucose and glycated hemoglobin (Hb A _1c ) levels are associated with higher rates of postoperative adverse events and mortality in cardiac and noncardiac surgery. A retrospective analysis of 61,000 patients undergoing elective noncardiac surgery showed that 1-year mortality was significantly related to preoperative blood glucose, with a crude incidence of mortality more than doubling in patients with preoperative blood glucose levels greater than 180 mg/dL compared with patients with a level of 85 mg/dL (3.5% vs. >9%). An analysis of more than 3000 patients undergoing elective coronary artery bypass grafting (CABG) demonstrated that a higher HbA1c was associated with an increased incidence of in-hospital mortality, myocardial infarction (MI), and sternal wound infection. The magnitude of the observed effect was such that a HbA1c greater than 8.6% was associated with a fourfold increase in mortality. The authors note that for each unit increase in preoperative HbA1c, there was a significantly increased risk of each individual adverse outcome.

Despite the demonstrable risk of poor preoperative glycemic control in the surgical population, there exists very little evidence to suggest that achieving and maintaining a specific HbA1c or preoperative blood glucose level will improve postoperative outcomes. Many national and international societies offer various HbA1c thresholds for delaying elective surgery but imply an individualized approach regarding the decision. Noting that it may take up to 3 years to achieve a desired HbA1c concentration, the practicality of short-term interventions is uncertain and encourages further investigation into the interplay between antecedent glycemia, perioperative glucose control, and patient outcomes.

Intra- and Postoperative Glucose Control Regimens

Historically, hyperglycemia had been considered an adaptive response essential for survival and was not routinely controlled in critical illness. ^, As evidence mounted linking hyperglycemia with poor clinical outcomes, practice patterns shifted to emphasize the prevention and correction of hyperglycemia. The tools used to achieve that goal have evolved over time, with previously popularized techniques of employing a combination infusion of glucose, insulin, and potassium falling out of favor for separate infusions of insulin and glucose.

Given that the overwhelming majority of the literature investigating glucose control regimens focuses on interventions in the postoperative period, much of what is put into practice in the intraoperative phase of care has been extrapolated. The dramatic results of the 2001 Leuven trial of tight glycemic control in critically ill surgical patients (target blood glucose of 80–110 mg/dL) encouraged the adoption of intensive insulin therapy across the perioperative spectrum. Subsequent trials, however, have not been able to replicate the mortality benefit associated with aggressive glycemic control and have shown a significantly increased risk for severe hypoglycemia when intensive insulin therapy targets are introduced for critically ill surgical, medical, or pediatric patient populations. ^, With upward of 32% of patients experiencing a hypoglycemic event (blood glucose <60 mg/dL) in the context of an intensive insulin therapy regimen, society recommendations have liberalized therapeutic goals to minimize the risk for iatrogenic hypoglycemia. The American Association of Clinical Endocrinologists Task Force and the American Diabetes Association recommend target blood glucose levels between 140 and 180 mg/dL in critically ill patients. The Society of Thoracic Surgeons echo this guidance, offering a recommendation to maintain serum glucose levels less than or equal to 180 mg/dL for at least 24 hours after cardiac surgery. Further reinforcing this general approach, the Society for Ambulatory Anesthesia sets forth an intraoperative management goal of maintaining blood glucose levels less than 180 mg/dL.

Blood Glucose Measurement

The foundation of any perioperative glycemic management strategy is frequent and accurate measurement of blood glucose concentration. The frequency of testing should consider the patient’s preoperative metabolic status, existing glycemic control regimen, duration of surgery, invasiveness of the procedure, anesthetic technique, the expected duration of decreased oral intake, and the pharmacokinetics of the insulin analog being used temporarily in the perioperative period. Central laboratory testing provides the most accurate blood glucose measurement but is limited in its scope of application, primarily because of the temporal delay in receiving actionable results. Although point-of-care capillary blood glucose monitors are widely used in the perioperative environment and generally correlate well with reference laboratory values, clinicians should be aware of significant limitations in particular clinical scenarios. In critically ill surgical patients, point-of-care measurements derived from capillary blood have previously been shown to demonstrate greater than 20% variability compared with values obtained from whole blood. Furthermore, compared with central laboratory devices, point-of-care monitors lack accuracy in the context of anemia, hypoperfusion, or hypothermia. ^, As a result of changes in capillary perfusion that may underestimate or overestimate blood glucose concentration, evidence suggests that patients who demonstrate unstable hemodynamics or are receiving an insulin infusion should have blood glucose samples obtained from venous or arterial blood instead of fingerstick capillary blood.

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