Perioperative Glucose Management in Cardiothoracic Surgery Kelly Grogan, MD Associate Professor Medical University of South Carolina Department of Anesthesiology and Perioperative Medicine

Disclosures No conflict of interest

Discussion Review of the literature Moderate versus intensive glucose control Current guidelines/ recommendations Review of new quality measure Are you there already? Questions

Hyperglycemia and Cardiac Surgery – Observational Data - Postoperative Observational studies have suggested that hyperglycemia (>200 mg/dL) after cardiothoracic surgery is associated with a 2-fold increased risk of wound infection Reducing serum glucose reduces surgical site infection rates and cardiac-related mortality Elevates risk of poor outcomes in the setting of hyperglycemia has been reported repeatedly, independent of diabetes status Direct correlation between the risk and degree of hyperglycemia Fish and colleagues predicted 10 fold increase in complications from post-op glucose level of >250 mg/dL Fish – retrospectively reviewed the importance of blood glucose levels in the intraoperative and immediate postoperative period to predict the morbitiy in 200 consecutive CABG patients Latham R et al. Infect Control Hosp Epidemiol 2001;22:607-612. Zerr KJ et al. Ann Thorac Surg 1997;63:356-61. Furnary AP et al. Ann Thorac Surg 1999;67:352-62. Ascione R et al. Circulation 2008;118:113-123. Jones KW et al. J Diabetes Complications 2008;22:365-70. Fish LH et al. Am J Cardiol 2003;92:74-6.

Hyperglycemia and Cardiac Surgery – Observational Data - Intraoperative Mounting evidence regarding the importance of intraoperative glucose control Higher glucose levels during surgery are an independent predictor of mortality in patients with and without diabetes Duncan et al found that: Severe intraoperative hyperglycemia (average glucose >200 mg/dL) increased morbidity and mortality following cardiac surgery Patients with glucose <140 mg/dL had similar worse outcomes Glucose between 141-170 mg/dL had best outcomes Doenst – effects of hyperglycemia on the clinical outcomes of 6280 patients undergoing cardiac surgery Gahdhi – performed retrospective, observational study of 409 cardiac surgery patients; intraoperative hyperglycemia was an independent predictor of complications including death Doenst T et al. J Thorac Cardiovasc Surg 2005;130:1144. Ouattara A et al. Anesthesiology 2005;103:687-94. Gandhi GY et al. Mayo Clin Proc 2005;80:862-6. Duncan AE et al. Anesthesiology 2010;112:860-71.

Hyperglycemia and Cardiac Surgery: Observational - Preoperative Poor preoperative glucose control has been associated with increased morbidity, including increased DSWI and prolonged LOS Abnormal glucose values prior to surgery may also be predictors of decreased survival postoperatively Anderson and colleagues: 1375 CABG patients Elevated preop fasting glucose had: 1-year mortality that was twice as great as patients with normal fasting 1-year mortality equal to that of patients with diabetes Furnary Ap et al. Endocr Pract 2004;10(suple)2:21-33. Lazar HL et al. Circulation 2004;109:1497-502. Anderson et al. Eur J Cardiothorac Surg 2005;28:425-30.

Hyperglycemia and Cardiac Surgery – Interventions Portland Diabetic Project Prospective, nonrandomized, interventional study investigating relationship between hyperglycemia and M&M since 1987 Implemented in graded steps initiated in ICU and now continues until 7:00 am of the 3rd postoperative day Continuous insulin infusion resulted in significantly lower mean glucose levels than intermittent SQ insulin Most recent update includes data on 4864 diabetic patients who underwent open heart surgery Increasing blood glucose levels were found to be independently and directly associated with increasing rates of death, DSWIs, length of stay and hospital cost Concluded that both a target blood glucose level of less than 150 mg/dL and a 3-day postoperative duration were important variables in improving outcome Furnary AP et al. J Thorac Cardiovasc Surg 2003;125:1007-21. Furnary AP et al. Endocr Pract 2004;10:21-33.

Hyperglycemia and Cardiac Surgery – Interventions Lazar and colleagues 141 CABG pts with DM Modified glucose-insulin-potassium solution Goal 120-180 mg/dL versus <250 mg/dL with SSI GIP had better glucose control, higher cardiac indices, lower infections, less arrhythmias, shorter hospital LOS, and 5 year survival advantage Van den Bergue et al 1548 ventilated ICU patients; 62% cardiac surgery; 12% diabetics Conventional (180-200 mg/dL) vs intensive (80-110 mg/dL) Mortality reduction in pts requiring >3 days ICU care Lazar et al. Circulation 2004;109:1497-502. Van den Bergue G et al. N Engl J Med 2001;345:1359-67.

Moderate vs Intensive Therapy Randomized Control Trials NICE SUGAR Finfer S et al.NEJM. 2009;360:1283-97. 6100 critically ill subjects in randomized, prospective, and blinded evaluation of IIT versus conventional management Mortality from cardiovascular causes was more common in the IIT group (42% vs 36%, p<0.02) as was severe hypoglycemia (6.8% vs 0.5%, p<0.001) Concluded that glucose <180 mg/dL or less resulted in lower mortality that did target 81-108 mg/dL Recent trials in critically ill patients have failed to show a significant improvement in mortality with intensive glycemic control and have highlighted the risks of severe hypoglycemia NICE SUGAR – 6100 subjects randomized, prospective, and blinded evaluation of IIT vs conventional; mortality (42 vs 36%) and severe hypoglycemia (6.8 vs 0.5%); concluded that IIT increased mortality and that glucose target <180 mg/dl or less resulted in less mortality VISEP – attempted to evaluate role of IIT in pts with severe sepsis using Leuven Protocol – stopped early cause of hypoglycemia (17 vs 4.1%) Glucontrol – 8.7 vs 2.7& hypoglycemia; stopped early cause of rate of hypoglycemia D’Ancona – Iatrogenic hypoglycemia secondary to tight glucose control was an independent determinant for mortality and cardiac morbidity Weiner – 8432 critically ill patients in 29 RCTs; no significant difference in mortality Griesdale – 13567 critically ill patients; significantly increased incidence of hypoglycemia. In the 14 of 26 that reported hypoglycemia, there was a 6 fold increase in the rate of occurrence Haga – Systematic review and meta-analysis of the cardiac surgery patient population found that there may be some benefit to tight glycemic control during and after cardiac surgery, results limited by few eligible trials and comparable outcomes that could be reviewed, small pt numbers, and poorly defined outcomes Higher incidence of mortality and severe hypoglycemia associated with intensive insulin therapy raise the possibility that serious adverse events may, at least in part, outweigh benefit derived from strict glycemic control.

Moderate vs Intensive Therapy Randomized Control Trials VISEP Brunkhorst FM et al. NEJM 2008;358:12539. Used the Leuven protocol and attempted to evaluate role of IIT versus conventional therapy in patients with severe sepsis Discontinued early due to high rates of severe hypoglycemia in IIT vs conventional group (17.0% vs 4.1%, p<0.001) Glucontrol Preiser J et al. Intensive Care Med 2009;35:1738-48. Also stopped early due to increased rates of hypoglcemia (8.7% vs 2.7%, p<0.001) Recent trials in critically ill patients have failed to show a significant improvement in mortality with intensive glycemic control and have highlighted the risks of severe hypoglycemia NICE SUGAR – 6100 subjects randomized, prospective, and blinded evaluation of IIT vs conventional; mortality (42 vs 36%) and severe hypoglycemia (6.8 vs 0.5%); concluded that IIT increased mortality and that glucose target <180 mg/dl or less resulted in less mortality VISEP – attempted to evaluate role of IIT in pts with severe sepsis using Leuven Protocol – stopped early cause of hypoglycemia (17 vs 4.1%) Glucontrol – 8.7 vs 2.7& hypoglycemia; stopped early cause of rate of hypoglycemia D’Ancona – Iatrogenic hypoglycemia secondary to tight glucose control was an independent determinant for mortality and cardiac morbidity Weiner – 8432 critically ill patients in 29 RCTs; no significant difference in mortality Griesdale – 13567 critically ill patients; significantly increased incidence of hypoglycemia. In the 14 of 26 that reported hypoglycemia, there was a 6 fold increase in the rate of occurrence Haga – Systematic review and meta-analysis of the cardiac surgery patient population found that there may be some benefit to tight glycemic control during and after cardiac surgery, results limited by few eligible trials and comparable outcomes that could be reviewed, small pt numbers, and poorly defined outcomes Higher incidence of mortality and severe hypoglycemia associated with intensive insulin therapy raise the possibility that serious adverse events may, at least in part, outweigh benefit derived from strict glycemic control.

Moderate vs Intensive Therapy Meta Analysis/Systematic Reviews Weiner RS et al JAMA 2008;300:933-44. Meta analysis of RCTs comparing IIT (80-110 mg/dL) vs less intensive targets (180-200 mg/dL) in critically ill patients 8432 pts in 29 RCTs, no difference in mortality (21.6 vs 23.3%, respectively) Griesdale DE et al CMAJ 2009;180:821-7. Meta analysis of 13567 critically ill patients, IIT was shown to significantly increase risk of hypoglycemia (6 fold increase) Recent trials in critically ill patients have failed to show a significant improvement in mortality with intensive glycemic control and have highlighted the risks of severe hypoglycemia NICE SUGAR – 6100 subjects randomized, prospective, and blinded evaluation of IIT vs conventional; mortality (42 vs 36%) and severe hypoglycemia (6.8 vs 0.5%); concluded that IIT increased mortality and that glucose target <180 mg/dl or less resulted in less mortality VISEP – attempted to evaluate role of IIT in pts with severe sepsis using Leuven Protocol – stopped early cause of hypoglycemia (17 vs 4.1%) Glucontrol – 8.7 vs 2.7& hypoglycemia; stopped early cause of rate of hypoglycemia D’Ancona – Iatrogenic hypoglycemia secondary to tight glucose control was an independent determinant for mortality and cardiac morbidity Weiner – 8432 critically ill patients in 29 RCTs; no significant difference in mortality Griesdale – 13567 critically ill patients; significantly increased incidence of hypoglycemia. In the 14 of 26 that reported hypoglycemia, there was a 6 fold increase in the rate of occurrence Haga – Systematic review and meta-analysis of the cardiac surgery patient population found that there may be some benefit to tight glycemic control during and after cardiac surgery, results limited by few eligible trials and comparable outcomes that could be reviewed, small pt numbers, and poorly defined outcomes Higher incidence of mortality and severe hypoglycemia associated with intensive insulin therapy raise the possibility that serious adverse events may, at least in part, outweigh benefit derived from strict glycemic control.

Moderate versus Intensive Therapy Cardiac Surgery Haga KK et al. Cardiothorac Surg 2011;6:3. Systematic review and meta analysis “there may be some benefit to tight glycemic control during and after cardiac surgery” Results were limited by few eligible trials, small patient numbers, poorly defined outcomes D’Ancona G et al. Eur J Cardiothorac Surg 2011;40:360-6. Iatrogenic hypoglycemia secondary to tight glucose control was independent determinant for mortality and cardiac morbidity

Comparison of Glycemic Control Recommendations and Guidelines American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control (Moghessi et al, Endocr Pract 2009;15:353-69) Consensus statement recommendations for inpatient glucose management based on degree of illness Society of Thoracic Surgeons Practice Guidelines Series: Blood Glucose Management During Adult Cardiac Surgery (Lazar et al, Ann Thorac Surg 2009;87:663-9) Evidence-based recommendations for all patients undergoing cardiac surgery American College of Cardiology Foundation and American Heart Association Guidelines for Coronary Artery Bypass Grafting (Hillis et al, Circulation 2011;124:2610-2642) Recommendations for all patients undergoing CABG There is evolving literature that moderate glucose control provides the same benefit as tight glucose control but with a lower risk of hypoglycemic complications.

Intraoperative STS Practice Guideline Series AACE/ADA Consensus Statement ACCF/AHA CABG Guideline Diabetics – A glucose level ≤180 mg/dL is best achieved with IV insulin (level of evidence A) Nondiabetics – IV insulin is not necessary provided glucose levels remain ≤180 mg/DL (Class I; level of evidence B) No specific recommendations for intraoperative management Use of continuous IV insulin to achieve a glucose level ≤140 mg/dL has uncertain effectiveness (Class IIb; level of evidence B)

Postoperative/Inpatient Management – General Comments STS Practice Guidelines Series AACE/ADA Consensus Statement ACCF/AHA CABG Guideline Diabetics should have a glucose ≤180 mg/dL for at least 24 hrs postop; best achieved with IV insulin infusion Non-diabetics with persistently elevated blood glucose levels (≥180 mg/dL) treat with IV insulin infusion and obtain endocrinology consult (Class I; level of evidence B) Use of continuous IV insulin to achieve early postoperative glucose level ≤180 mg/dL while avoiding hypoglycemia is indicated to reduce the incidence of adverse events, including deep sternal wound infection after CABG (Class I; level of evidence B)

Prolonged ICU Stay of Critically Ill STS Practice Guidelines Series AACE/ADA Consensus Statement ACCF/AHA CABG Guideline All patients with persistently elevated glucose levels (≥180 mg/dL) should receive IV insulin infusions to maintain serum glucose ≤180 mg/dL for the duration of their IV care (Class I; level of evidence A) All patients who require >3 days in ICU* should have a continuous IV insulin infusion to maintain serum glucose ≤150 mg/dL (Class I; level of evidence B) Critically ill patients in the ICU should have IV insulin initiated for glucose levels ≤180 mg/dL with the goal of 140-180 mg/dL; target levels <110 mg/dL are not recommended *Vent dependency; inotropes; IABP; LVAD; antiarrhythmics; dialysis; CVVH

Stepdown and Floor Status STS Practice Guidelines Series AACE/ADA Consensus Statement ACCF/AHA CABG Guideline A target blood glucose level ≤180 mg/dL should be achieved in peak postprandial state (Class I; level of evidence B) A target blood glucose level ≤110 mg/dL should be achieved in the fasting and premeal states (Class I; level of evidence C) Based on clinical experience and judgment, premeal glucose levels should generally be ≤140 mg/dL with random glucose levels ≤180 mg/dL

New Quality Measure Performance Metric Name: Cardiac Surgery Patients with Controlled Postoperative Blood Glucose Description: Cardiac surgery patients with controlled postoperative blood glucose (less than or equal to 180 mg/dL) in the timeframe of 18-24 hours after Anesthesia End Time Is replacing the goal of controlled 6:00 am glucose of less than 200 mg/dl on postoperative day 1 and 2 with anesthesia end date being postoperative day zero (POD 0)

Rationale STS Workforce guidelines that recommend that all cardiac surgery patients, with and without diabetes, maintain serum glucose of <180 mg/dL Controlling glucose in the immediate time period after surgery may be challenging Cardiac surgery care teams should be able to reasonably control the blood glucose to levels of 180 mg/dL or less within the 18-24 hour post-operative time frame

Definitions Type of Measure Process Improvement Noted As An increase in the percentage Numerator Statement Cardiac surgery patients with controlled postoperative blood glucose (<180 mg/dL) in the timeframe of 18-24 hours after Anesthesia End Time Denominator Statement Cardiac surgery patients with no evidence of prior infection A measure used to assess a goal directed, interrelated series of actions, events, mechanisms, or steps, such as measure of performance that describes what is done to, for, or by patients, as in performance of a procedure.

Included Populations An ICD-9-CM Principal Procedure Code of selected surgeries (as defined in Appendix A, Table 5.10 for ICD-9-CM codes) An ICD-9-CM Principal Procedure Code of selected surgeries (as defined in Appendix A, Table 5.11 for ICD-9-CM codes)

Excluded Populations Patients less than 18 years of age Patients who have a length of stay greater than 120 days Patients who had a principal diagnosis suggestive of preoperative infectious disease (as defined in Appendix A, Table 5.09 for ICD-9-CM codes) Burn and transplant patients (as defined in Appendix A, Table 5.14 and 5.15 for ICD-9-CM codes) Patients enrolled in clinical trials Patients whose ICD-9-CM principal procedure occurred prior to the date of admission Patients with physician/APN/PA documented infection prior to surgical procedure of interest Patients who undergo CPR or surgery, discharge, expire, or leave AMA prior to 24 hours after Anesthesia End Time

Data Elements Anesthesia Start Date Admission Date Birthdate Clinical Trial Discharge Date ICD-9-CM Principal Diagnosis Code ICD-9-CM Principal Procedure Code Infection Prior to Anesthesia

UTD – unable to determine Surgery days – equal to the Anesthesia start date minus the admission date Glucose equals a 3 or 4, the case will proceed to a Measure Category assignment of D and will be in the measure population Glucose equals a 1 or 2, the case will proceed to a measure catetory assignment of E and will be in the numerator population

Where to begin? The Framework Administrative support Stakeholders Identify Define working groups Assess Current State Create/Identify Protocols and Algorithms Education Implement Evaluate Modify

Assessment of Current Processes What is the current level of glycemic control? How many measurements fall within goal?

Assessment of Current Processes What are the current practices and policies? Are they used consistently/ appropriately? Is glucose being measured sufficiently frequently? Insulin use patterns Incidence of hypoglycemic and it’s sequelae What are YOUR identified barriers to obtaining glycemic control?

Questions? Comments?