Diabetes confers an increased risk of perioperative morbidity and mortality, mostly from infection and cardiovascular events. It is not unusual for surgical patients with diabetes to have a number of comorbidities or underlying chronic vascular complications that put them at risk for cardiovascular events or an infectious complication. Silent ischemia, coronary artery disease, and autonomic neuropathy are common among patients with diabetes, and each can contribute to perioperative morbidity and mortality. These are important considerations since nearly one-fifth of surgical patients have diabetes and since a person with diabetes has a 50% risk of undergoing surgery at some point in his or her lifetime.1
This article reviews the preoperative evaluation of patients with diabetes, discusses the relation between glycemic control and perioperative outcomes, and examines targets and strategies for glycemic control in patients with type 1 and type 2 diabetes throughout the perioperative period.
The preoperative evaluation must consider first and foremost the status of the patient’s diabetes and his or her surgical risk factors. Also important are the characteristics of the procedure to be performed, the method of anesthesia to be used, and select laboratory values.
The type of diabetes and its treatment must be considered. Type 1 diabetes requires continuous insulin therapy to prevent ketoacidosis; patients with type 2 diabetes are usually treated with oral medications with or without insulin. Baseline control of blood glucose is a predictor of morbidity following surgery. Hypoglycemia is associated with increased morbidity in the inpatient setting, so a history of severe hypoglycemic events or of difficulty recognizing hypoglycemia (hypoglycemia unawareness) should be elicited in the preoperative evaluation. Complications of diabetes and other comorbidities also must be evaluated, along with their treatments.
Surgical risk factors
Patients with diabetes have surgical risk factors specific to their health—namely, cardiovascular risk factors that may or may not have been previously diagnosed. Patients with diabetes may have silent ischemia, atypical manifestations of coronary ischemia, or underlying cardiomyopathy. Many patients with type 2 diabetes have hypertension, which may complicate perioperative management. Other common surgical risk factors in this population include obesity, chronic kidney disease, and undiagnosed autonomic dysfunction, which may compromise hemodynamic stability in the perioperative period. Additionally, patients with long-standing diabetes experience reductions in pulmonary function (eg, forced expiratory volume, peak expiratory flow, and diffusion capacity for carbon monoxide) related to disease duration and vascular injury,2 which may complicate weaning from ventilatory support.
Characteristics of the procedure and anesthetic
Both surgery and anesthesia may induce an increase in levels of stress hormones (epinephrine, cortisol, growth hormone) and inflammatory cytokines (interleukin-6 and tumor necrosis factor–alpha), resulting in insulin resistance and impaired insulin secretion (even among patients who present with adequate insulin secretion). These in turn contribute to lipolysis and protein catabolism, leading to hyperglycemia and, if a patient is severely insulin deficient, ketoacidosis. Other factors that particularly affect insulin resistance and secretion include cardiovascular bypass surgery, sepsis, the need for total parenteral nutrition, and steroid therapy.
The characteristics of the surgical procedure, including the type of surgery as well as its urgency, duration, and timing (morning vs later in the day), are important in planning for perioperative glycemic management. For example, a short, minor procedure may require only observation, whereas more extensive procedures warrant periodic monitoring and active glycemic management with insulin infusions.
The type of anesthesia should also be considered. Compared with epidural anesthesia, general anesthesia is associated with greater stimulation of the sympathetic nervous system and increased catecholamine levels, resulting in more pronounced hyperglycemia.3
Preoperative testing and laboratory evaluation should include, at minimum, an electrocardiogram, a basic metabolic panel to assess renal function, electrolyte levels, and hemoglobin A1c measurement. For low-risk procedures in patients with adequate exercise tolerance, no diagnostic tests might be needed. In any case, knowledge of the hemoglobin A1c level may help not only to classify perioperative risk but also to determine postoperative care, including the choice of antiglycemic medications at discharge.
IMPORTANCE OF GLYCEMIC CONTROL
Preoperative glycemic control has a significant impact on the risk of infectious complications—including pneumonia, wound infection, urinary tract infection, and sepsis—in patients with diabetes across a variety of surgical procedures.4 Similarly, postoperative glycemic control—to a mean blood glucose level less than 200 mg/dL in the immediate postoperative period—significantly reduces the incidence of deep sternal wound infection after open heart surgery.5
Among patients undergoing cardiothoracic surgery, both cardiac-related and overall mortality are greater with increasing postoperative blood glucose levels, although a cause-and-effect relationship has not been established.6
Glycemic control matters regardless of diabetes status
Hyperglycemia affects mortality regardless of diabetes status. In a study of 779 consecutive patients admitted for acute myocardial infarction, mortality at 180 days was highly associated with hyperglycemia on admission independent of a history of diabetes; the highest mortality was among hyperglycemic patients without previously known diabetes.7 Similarly, a large study of glycemic control in intensive care unit (ICU) patients receiving insulin found that mortality in nondiabetic patients increased with median glucose level and was higher than mortality in diabetic patients.8 These findings suggest a need for vigilance in the perioperative and critical care management of all patients with hyperglycemia, regardless of preadmission diabetes diagnosis, as they carry significant morbidity and mortality risk.
GLYCEMIC CONTROL IN THE CRITICALLY ILL: SOME SUPPORT FOR A MODIFIED TARGET, BUT VIGILANCE FOR HYPOGLYCEMIA NEEDED
The landmark study by Van den Berghe et al of intensive insulin therapy in surgical ICU patients demonstrated significant reductions in morbidity and mortality when glucose levels were controlled aggressively (80 to 110 mg/dL; average, 103 mg/dL) compared with conventional control (180 to 200 mg/dL).9 The benefit of intensive glycemic control was evident on outcomes such as the occurrence of sepsis, need for dialysis, need for blood transfusion, and development of acute polyneuropathy. Intensive insulin therapy was also associated with cost savings compared with conventional insulin therapy in mechanically ventilated patients.10
However, a number of subsequent studies have clearly shown that as blood glucose levels approach normoglycemia, the risks of hypoglycemia, especially severe hypoglycemia, can offset the benefits of tight blood glucose control.
A follow-up study by Ven den Berghe et al in a medical ICU failed to show a mortality benefit from tight glycemic control, though patients in the intensive control arm experienced less renal injury, faster weaning from ventilation, and earlier discharge from the ICU and hospital.11
The recent NICE-SUGAR study of aggressive glucose control in the ICU randomized patients to a target blood glucose of 81 to 108 mg/dL (intensive group) or 180 mg/dL or less (control group).12 At study’s end, the groups’ mean blood glucose levels were 115 mg/dL and 144 mg/dL, respectively, while rates of severe hypoglycemia (blood glucose < 40 mg/dL) were 6.8% and 0.5%, respectively. Mortality rates were higher in the intensive therapy group (27.5%) than in the control group (24.9%), driven by severe hypoglycemic events. Notably, blood glucose monitoring in this and other studies was conducted at a frequency of anywhere between 1 and 4 hours.
The conclusions of the available data would support, for the time being, a modified glycemic target in critically ill patients, with strict avoidance of severe hypoglycemia. The recent consensus statement from the American Association of Clinical Endocrinologists and the American Diabetes Association recommends using insulin therapy if blood glucose levels exceed 180 mg/dL, with target glucose levels less than 180 mg/dL in critically ill patients and less than 140 mg/dL in non–critically ill patients.13 Development and implementation of safer insulin infusion algorithms and more frequent and accurate blood glucose monitoring in this setting should enable us to achieve better glycemic targets with lower risk.