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a Department of Cardiothoracic Surgery, the Boston Medical Center, Boston, Massachusetts
b Division of Endocrinology, the Boston Medical Center, Boston, Massachusetts
c The School of Public Health and Health Sciences, The University of Massachusetts, Amherst, Massachusetts
d The Starr-Wood Cardiac Group, Portland, Oregon
e The Baystate Medical Center, Springfield, Massachusetts
f Division of Endocrinology, Ronald Regan Medical Center, David Geffen School of Medicine, Los Angeles, California
g Division of Cardiovascular Surgery, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
h University of Florida College of Medicine, Jacksonville, Florida
i Department of Cardiothoracic Surgery, University Hospital, Linkoping, Sweden
j Division of Cardiology, The University of Texas School of Medicine, Houston, Texas
k The Division of Cardiothoracic Surgery, Ronald Regan Medical Center, David Geffen School of Medicine, Los Angeles, California
* Address correspondence to Dr Lazar, Department of Cardiothoracic Surgery, Boston Medical Center, 88 East Newton St, Boston, MA 02118 (Email: harold.lazar{at}bmc.org).
| Introduction |
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Despite the emerging recognition of the importance of glycemic control, there are no specific guidelines for cardiac surgeons as to what the optimal level of glucose should be during the perioperative period, and the best method to achieve these target values. What follows is an executive summary of guidelines for the management of hyperglycemia in both patients with and without diabetes undergoing adult cardiac surgical procedures, derived from evidence-based recommendations (Table 1).
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| I. Detrimental Effects of Hyperglycemia in the Perioperative Period |
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Collectively, these studies strongly suggest that increased fasting glucose levels prior to surgery, and persistently elevated glucose levels during and immediately after cardiac surgery, are predictive of increased perioperative morbidity and mortality in patients with and without diabetes. The next section will review those studies showing that lowering perioperative glucose levels with insulin therapy will decrease morbidity and mortality in cardiac surgical patients.
| II. Beneficial Effects of Glycemic Control on Clinical Outcomes During Cardiac Surgery |
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One of the earliest studies to examine the effects of glycemic control during cardiac surgery was reported by Furnary and coworkers [9]. The study involved 3,554 patients undergoing CABG surgery from 1987 to 2001. Patients were divided into three groups based on the year of surgery, the method of glycemic control, and the targeted glucose levels. From 1987 to 1991, patients received subcutaneous insulin, given every 4 hours to keep serum glucose < 200 mg/dL. From 1991 to 1998, a continuous intravenous (IV) insulin infusion was used to keep serum glucose between 150 and 200 mg/dL. From 1998 to 2001, the Portland protocol was instituted, which used a continuous insulin drip to keep serum glucose between 100 and 150 mg/dL. Continuous insulin infusions resulted in significantly lower mean glucose levels than could be obtained with intermittent subcutaneous insulin therapy. The perioperative mortality in CABG patients with diabetes was decreased by 50% after 1992 (4.5% vs 1.9%; p < 0.0001) when continuous insulin protocols were instituted, and it was similar to that for nondiabetic CABG patients. There was also a significant decrease in the incidence of deep sternal wound infections (p < 0.001). Furnary and coworkers [10] expanded their original series to include an additional 1,980 patients managed with the Portland protocol from 2001 to 2005. They introduced a new method to assess glycemic control called 3-blood glucose, or "3-BG," consisting of the average of all glucose values obtained on the day of surgery and the first and second postoperative days. An increase in 3-BG was an independent predictor of perioperative mortality (p < 0.001). Mean 3-BG was also significantly related to the incidence of deep sternal wound infections, hospital length of stay, blood transfusions, new onset atrial fibrillation, and low cardiac output syndrome.
Further evidence to support the role of insulin therapy in the CABG patient with diabetes was presented by Lazar and coworkers [11] using a modified glucose-insulin–potassium solution. In this trial involving 141 patients with diabetes undergoing isolated CABG surgery, patients were prospectively randomized to receive glucose-insulin–potassium to keep serum glucose between 120 and 180 mg/dL, or sliding scale insulin coverage to maintain glucose < 250 mg/dL. The glucose-insulin–potassium was started on induction of anesthesia and continued for 12 hours in the intensive care unit (ICU). The glucose-insulin–potassium-treated patients achieved significantly better glycemic control immediately prior to cardiopulmonary bypass (169 mg/dL vs 209 mg/dL; p < 0.0001), and after 12 hours in the ICU (134 mg/dL vs 266 mg/dL; p < 0.0001). Patients treated with tight glycemic control had significantly higher cardiac indices (p < 0.0001) and less need for inotropic support (p < 0.05) and pacing (p < 0.05). Tighter glycemic control also resulted in a lower incidence of infections (0% vs 13%; p = 0.01) and atrial fibrillation (15% vs 60%; p = 0.007). This all contributed to a shorter hospital length of stay (6.5 days vs 9.2 days; p = 0.0003). After 5 years, the Kaplan-Meier curves showed a significant survival advantage (p = 0.04) for patients receiving better glycemic control. They had a significantly lower incidence of recurrent ischemia (p = 0.01) and wound infections (p = 0.03), and were able to maintain a lower angina class (p = 0.03).
The importance of tight glycemic control in patients undergoing CABG surgery was also demonstrated in a study by Van den Berghe and coworkers [12] involving 1,548 ventilated patients admitted to a surgical ICU. In this prospective, randomized study, 62% of patients had undergone cardiac surgery, and only 13% had a prior history of diabetes. During their ICU stay, patients were randomized to a conventional therapeutic group in which insulin was administered only if serum glucose exceeded 215 mg/dL to maintain a target goal of 180 to 200 mg/dL, and an intensive group that received a continuous insulin infusion to maintain glucose levels between 80 and 110 mg/dL. Intensive insulin therapy resulted in a significant reduction in mortality (10% vs 20%; p = 0.005), exclusively in those patients who required
5 days of ICU care with multiorgan failure and sepsis. Similarly, cardiac surgical mortality was only reduced in those patients requiring
3 days of ICU care. Hospital mortality for all cardiac surgical patients, irrespective of their ICU stay, was reduced from 5.1% to 2.1% (p < 0.05). Intensive glycemic control had no effect on morbidity and mortality in those patients spending
3 days in the ICU. In a further attempt to identify those patients who might benefit most from tight glycemic control, D'Alessandro and coworkers [13] sought to correlate the effect of tight glycemic control with expected EuroScore outcomes in CABG patients with diabetes. Three hundred patients with diabetes undergoing CABG surgery from January 2003 to June 2004 receiving tight glycemic control (150 to 200 mg/dL in the operating room;
140 mg/dL in the ICU) were matched with 300 CABG patients with diabetes treated from March 2001 to September 2002, when insulin protocols were not present, using propensity-based analyses. The group with tight glycemic control had an observed mortality that was significantly lower than expected (1.3% vs 4.3%; p = 0.01). Mortality was especially lower in the higher risk cohort (EuroScore > 4; 2.5% vs 8.0%; p = 0.03). In contrast, there was no difference between observed and expected mortality in the group without tight glycemic control in patients with EuroScore < 4. Two additional studies have shown the importance of glycemic control in lowering sternal wound infections. Zerr and coworkers [14] studied the effects of glycemic control on the incidence of sternal wound infections in 1,585 CABG patients with diabetes. Sternal wound infections increased from 1.3% in patients with mean glucose values of 100 to 150 mg/dL to 6.7% in patients with levels of 250 to 300 mg/dL. In a retrospective study involving CABG patients with diabetes, Hruska and coworkers [15] found that a continuous insulin infusion maintaining glucose levels between 120 to 160 mg/dL significantly decreased the incidence of sternal wound infections compared with intermittent subcutaneous injections.
| III. Glycemic Control in Patients Without Diabetes During Cardiac Surgery |
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200 mg/dL. In this study, intraoperative glycemic control failed to improve short-term or long-term clinical outcomes in a group of patients without diabetes. Gandhi and coworkers [17] looked at the effects of intensive intraoperative insulin therapy in 400 elective CABG patients. Patients were prospectively randomized to a continuous insulin group to maintain serum glucose between 80 and 100 mg/dL, or a conventional group targeted to keep serum glucose < 200 mg/dL using intermittent boluses of intravenous (IV) insulin. The incidence of diabetes was 20% in both groups. There was no difference in the primary outcome between the groups, which consisted of the composite incidence of death, sternal wound infections, prolonged ventilation, cardiac arrhythmias, strokes, and renal failure within 30 days of surgery. There was also no difference in ICU or hospital stay between the groups. There was a tendency for more deaths (p = 0.06) and strokes (p = 0.02) in the intensive insulin group. This study was limited in that it included patients both with and without diabetes, and both groups received intensive insulin therapy in the immediate postoperative period.
| IV. Management of Hyperglycemia Using Insulin Protocols in the Perioperative Period Recommendations: Class I |
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180 mg/dL (level of evidence = B). Intravenous insulin therapy is the preferred method of insulin delivery during the perioperative period. It allows for rapid titration, which facilitates glycemic control during periods of malabsorption, insulin deficiency, and resistance [18]. Table 2 describes various protocols that are readily available for use and target glucose values that can be achieved. Choosing an insulin infusion protocol is dependent on the needs and resources of the institution. To ensure safe and effective implementation of any protocol, those individuals involved in the patients' care must be comfortable using it. The success of any protocol can be determined by outcomes such as the time needed to achieve the target value, specific BG concentrations, average BG control, percentage of values in the desired range, or an area under-the-curve calculation reported as the percentage of time spent in a determined range [19]. This issue is addressed specifically on the American Association of Clinical Endocrinologists website for hospital management of hyperglycemia [20, 21]. For safety tracking, the number of episodes (or percent) of hypoglycemic events and any clinical consequences should be monitored.
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| V. Preoperative Management and Assessment for Patients With Diabetes Recommendations: Class I |
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| Class IIA |
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180 mg/dL (level of evidence = B). Efforts should be made to optimize glucose control prior to surgery, because poor preoperative glycemic control has been associated with increased morbidity, including a higher incidence of deep sternal wound infections and prolonged postoperative length of stay [10, 11]. In general, all oral diabetes medications should be withheld within the 24 hours prior to surgery, especially sulfonylureas (eg, glipizide) and glinides (eg, nateglinide or repaglinide). These drugs can induce hypoglycemia in the absence of food. Patients who are taking insulin and who are admitted on the day of surgery should be instructed to continue their basal insulin dose (eg, glargine, detemir, or NPH) and hold their nutritional insulin (eg, lispro, aspart, glulisine, or regular) unless instructed otherwise by their primary physician. The NPH insulin may be reduced by one half or one third prior to surgery to avoid hypoglycemia.
To achieve rapid control in a hospitalized patient with hyperglycemia (glucose persistently > 180 mg/dL for > 12 hours before surgery), insulin therapy either with intravenous variable-rate continuous infusion or subcutaneous basal plus rapid-acting insulin should be used depending on the availability of either therapy. For the patient noted to be hyperglycemic in the preoperative area on the day of surgery, IV insulin therapy is an effective way to achieve rapid control. Patients with a known history of diabetes (either type 1 or type 2) can be started immediately on IV therapy in the preoperative area. All preoperative medications should be reviewed to determine the potential for insulin resistance. These include steroids, protease inhibitors, and anti-psychotic drugs. Finally, patients with renal insufficiency should be identified, because insulin clearance is impaired and the risk for hypoglycemia is increased.
The hemaglobin A1c (HbA1c), a glycosylated hemoglobin, is an accurate indicator of glycemic control for a 2-month to 3-month period. The American Diabetes Association has reported that adequate glycemic control is associated with an HbA1c
7% [21]. Obtaining an HbA1c prior to surgery in diabetic patients or those patients at risk for postoperative hyperglycemia will help to optimize glycemic control in those patients with elevated HbA1c levels. It will also identify those patients who might require more aggressive glycemic control upon hospital discharge.
| VI. Intraoperative Control Recommendations: Class I |
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180 mg/dL. However, in those patients with persistently elevated serum glucose (> 180 mg/dL) after cardiopulmonary bypass, a continuous insulin drip should be instituted, and an endocrinology consult should be obtained (level of evidence = B).
180 mg/dL (level of evidence = C). Patients receiving IV infusions of insulin should have their blood glucose monitored every 30 to 60 minutes. More frequent monitoring, as often as every 15 minutes, should be made during periods of rapidly fluctuating sensitivity, such as during the administration of cardioplegia and systemic cooling and rewarming. Patients with IV insulin infusions initiated in the preoperative period should have them continued in the operating room (OR) to maintain serum glucose < 180 mg/dL.
Patients with no history of diabetes prior to surgery, may exhibit transient elevation of BG > 180 mg/dL during cardiopulmonary bypass. These patients may have insulin resistance and should be treated with a single or intermittent dose of IV insulin to maintain glucose
180 mg/dL. Caution should be exercised in initiating a continuous IV insulin drip in these patients, because insulin requirements may decrease rapidly in the immediate postoperative period resulting in serious hypoglycemia [22]. However, those patients not known to have diabetes who have persistently elevated glucose values (> 180 mg/dL) during surgery should receive a continuous IV insulin drip. Because a large percentage of these patients may ultimately be found to have diabetes mellitus, an endocrinology consult should be obtained in the postoperative period.
| VII. Glycemic Control in the ICU Recommendation: Class I |
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3 days in the ICU because of ventilatory dependency or requiring the need for inotropes, intra-aortic balloon pump, or left ventricular assist device support, anti-arrhythmics, dialysis, or continuous veno-venous hemofiltration should have a continuous insulin infusion to keep blood glucose
150 mg/dL, regardless of diabetic status (level of evidence = B).
Patients with or without diabetes mellitus who have persistently elevated serum glucose > 180 mg/dL should receive intravenous insulin infusions to maintain serum glucose < 180 mg/dL [9–12]. Furthermore, those patients who require
3 days of ICU care due to prolonged ventilatory support, inotropic or mechanical support, renal insufficiency, or need for anti-arrhythmic therapy should have continuous IV insulin infusions to keep blood glucose < 150 mg/dL [10, 12]. When patients are receiving IV insulin infusions in the ICU, glucose levels should be monitored at least hourly until stable. This frequency avoids fluctuations in glucose levels and minimizes the risk of hypoglycemia, which is fortunately rare and has resulted in minimal morbidity [10–12].
When patients are ready to be discharged from the ICU, patients should be transitioned to a subcutaneous insulin-dosing schedule. Daily insulin requirements can be estimated by extrapolating the amount of insulin required in the preceding 24 hours and considering the patients' current nutritional intake [23].
| VIII. Glycemic Control in the Stepdown Units and on the Floor Recommendations: Class I |
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110 mg/dL should be achieved in the fasting and pre-meal states after transfer to the floor (level of evidence = C). | IX. Preparation for Hospital Discharge Recommendations: Class I |
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All patients with hyperglycemia after cardiac surgery should be assessed by an inpatient diabetes team to decide on a glycemic control program after discharge. When hyperglycemia is discovered for the first time in the perioperative period, or if insulin is first being administered, or when a new insulin protocol is instituted, the patient should receive specialized education prior to discharge. This can be provided by a certified diabetes educator, and supplemented by nurses or registered dieticians with expertise in diabetes. Education should be started at least 2 days prior to discharge, including techniques of glucose monitoring, administration of medications, nutrition, exercise, and lifestyle modification [25, 26]. Appropriate follow-up should be arranged with primary care physicians prior to discharge. Referring physicians should be informed of any changes made in the diabetes management plan.
| IX. Future Areas of Study |
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| Footnotes |
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For the full text of The Society of Thoracic Surgeons (STS) Guideline on Blood Glucose Management During Adult Cardiac Surgery, as well as other titles in STS Practice Guideline Series, visit http://www.sts.org/sections/aboutthesociety/practiceguidelines at the official website of STS at www.sts.org.
| References |
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This article has been cited by other articles:
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S. Akhtar, P. G. Barash, and S. E. Inzucchi Scientific Principles and Clinical Implications of Perioperative Glucose Regulation and Control Anesth. Analg., February 1, 2010; 110(2): 478 - 497. [Abstract] [Full Text] [PDF] |
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H. L. Lazar and M. McDonnell Reply. Ann. Thorac. Surg., October 1, 2009; 88(4): 1385 - 1386. [Full Text] [PDF] |
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A. M. Sheehy, D. B. Coursin, and M. T. Keegan Risks of tight glycemic control during adult cardiac surgery. Ann. Thorac. Surg., October 1, 2009; 88(4): 1384 - 1385. [Full Text] [PDF] |
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H. L. Lazar Reply Ann. Thorac. Surg., September 1, 2009; 88(3): 1049 - 1049. [Full Text] [PDF] |
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K. W. Lobdell Computerized euglycemia in cardiovascular and thoracic surgery. Ann. Thorac. Surg., September 1, 2009; 88(3): 1048 - 1049. [Full Text] [PDF] |
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