Pharmacology NotesPostoperative glycemic control in cardiac surgery patientsTheresa Breithaupt, PharmD, BCPS              ...
glucose, and those in the control arm received sliding-scale             reduction in the incidence of sternal wound infec...
Studies showing no benefit with intensive blood glucose                and 180 mg/dL in critically ill patients, with poss...
with diabetes undergoing coronary artery bypass grafting. J Thorac Car-      19. Guvener M, Pasaoglu I, Demircin M, Oc M. ...
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Postoperative glycemic control in cardiac surgery patients

  1. 1. Pharmacology NotesPostoperative glycemic control in cardiac surgery patientsTheresa Breithaupt, PharmD, BCPS evaluated in diabetic patients, and recent literature includes bothGlycemic control in postoperative cardiac patients is necessary to improve diabetic and nondiabetic patients undergoing cardiac surgery.outcomes in wound infection and overall mortality. In recent years, clinical These studies attempt to define optimal postoperative bloodtrials evaluating blood glucose control in critically ill patients advocated for glucose goal ranges in both populations.intense blood glucose management and found a significant reduction in Initial research assessed benefits of blood glucose manage-morbidity and mortality. Some organizations published recommendations ment for prevention of sternal wound infection in diabeticregarding blood glucose management in critically ill patients reflecting this patients undergoing open heart surgery (6). An early study byinformation. However, recent clinical trials evaluating blood glucose target Zerr et al compared an insulin infusion protocol to maintainranges in critically ill patients have found conflicting results, which has postoperative blood glucose <200 mg/dL to usual blood glu-prompted reevaluation of current goals and guidelines, allowing for less cose control (6). The study involved 1585 diabetic patients:stringent blood glucose target ranges. With the inconsistency of clinical 990 patients before the insulin infusion protocol from 1987 totrials evaluating a target blood glucose range for critically ill patients, 1991 and 595 patients after protocol initiation from 1991 tospecifically postoperative cardiac surgery patients, the target blood glu- 1993. The average blood glucose value in the protocol arm wascose range is still not clearly defined. Additional comparisons of specific 172 mg/dL compared with 206 mg/dL in the control arm. Onglucose ranges would allow for a clearer definition of recommended blood postoperative day 2, the average blood glucose was 176 mg/dLglucose goals to target in postoperative cardiac patients. in the protocol arm and 195 mg/dL in the control arm. The incidence of deep wound infections, including both the sternal site and the leg incision, decreased from 2.4% in the controlB lood glucose management in critically ill patients remains arm to 1.5% in the treatment arm (P < 0.02); for the sternal an ongoing controversy. In recent years, clinical trials site alone, the rates were 2.8% and 0.74%, respectively. Elevated evaluating blood glucose control in critically ill patients mean blood glucose levels within the first 48 hours after surgery advocated for intense blood glucose management, with were found to be associated with deep sternal wound infectionstarget blood glucose levels between 80 and 110 mg/dL (1). In- and to be an independent risk factor for deep sternal woundtense blood glucose control resulted in a reduction in morbidity development (6).and mortality in the critically ill patient population, with a large Furnary et al conducted a follow-up study evaluating deepportion of these patients being cardiovascular surgery patients. sternal wound infections in diabetic patients undergoing cardiacClinical trials evaluating other patient populations have shown surgery; the standard arm received sliding-scale insulin every 4a reduction in morbidity with a lesser impact on mortality using hours to maintain blood glucose <200 mg/dL, and the studytight blood glucose control (2). Additional clinical trials con- arm received a continuous insulin infusion to maintain bloodducted to evaluate the benefit of tight blood glucose control have glucose <200 mg/dL (7). The researchers found a significantshown a negative impact on mortality due to hypoglycemia and decrease in deep sternal wound infections in the study armcontribute to the body of evidence disputing the need for tight (P = 0.005).blood glucose control (3). Given the conflicting results from Another study by the same investigators evaluated hospitalthese recent trials, the target blood glucose range for critically mortality in diabetic patients undergoing coronary artery bypassill patients, specifically postoperative cardiac surgery patients, graft surgery (CABG) (8). Subjects in the study arm received anis still not clearly defined. insulin infusion for 72 hours after surgery to maintain blood Blood glucose disturbances from cardiac bypass pump expo-sure are well documented (4). However, the ability of hypergly- From the Department of Pharmacy Services, Baylor University Medical Center,cemia to impair leukocyte function via impaired phagocytosis Dallas, Texas.and bacterial killing and lead to infection—specifically surgical Corresponding author: Theresa Breithaupt, PharmD, BCPS, Department ofor sternal wound infections—was not well established until Pharmacy Services, Baylor University Medical Center, 3500 Gaston Avenue,later (5). Postoperative blood glucose management has been Dallas, Texas 75246 (e-mail: (Bayl Univ Med Cent) 2010;23(1):79–82 79
  2. 2. glucose, and those in the control arm received sliding-scale reduction in the incidence of sternal wound infections was ob-insulin to maintain blood glucose. Blood glucose goals were served (0.4% to 0%) when the insulin infusion was initiatedgradually lowered throughout the study: from 1991 to 1998, at a blood glucose of >125 mg/dL. The same rate of sternalthe goal was 150 to 200 mg/dL (group 1); from 1999 to 2000, wound infections was maintained in the final phase of the study125 to 175 mg/dL (group 2); and in 2001, 100 to 150 mg/dL when the insulin infusion was initiated at a blood glucose >110(group 3). The overall mortality in the continuous insulin infu- mg/dL (12).sion arm, including all three groups, was 2.5% compared with A trial by LeComte et al evaluated additional endpoints,5.3% in the control group (P < 0.0001). The blood glucose including incidence of renal failure in patients with intensivegoals were gradually decreased within each range to allow nurses blood glucose control utilizing an insulin infusion (80–110to become comfortable with the protocol as well as to ensure mg/dL) versus those patients without intensive blood glucosepatient safety. Overall mortality was decreased in the insulin control. To maintain blood glucose, all patients were initiatedinfusion group; however, it was unclear if mortality decreased intraoperatively on fluids that contained dextrose. A significantwith each incremental decrease in blood glucose goals. decrease in the incidence of postoperative renal injury and renal In 1991, the American College of Cardiology (ACC) and failure was found, but only in nondiabetic patients (13). InAmerican Heart Association (AHA) Guidelines for Coronary the nondiabetic patients, 30-day mortality was also decreasedArtery Bypass Graft Surgery made no recommendations related (P < 0.05).to blood glucose control in CABG patients, although the in- Based on much of the new information at that time, thecreased risk of sternal wound infections in diabetics was noted AHA/ACC guidelines were reevaluated in 2004, and recom-(9). In the 1999 version, the guidelines recommended an insulin mendations similar to those published in 1999 were main-infusion maintaining blood glucose <200 mg/dL (10). tained, that blood glucose should be <200 mg/dL (10, 14). One of the first trials evaluating intensive blood glucose These guidelines did not recommend intensive blood glucosecontrol, blood glucose 80 to 110 mg/dL, produced significant control (80–100 mg/dL). However, in 2007, guidelines frombenefits. The trial was conducted by van den Berghe et al. Ap- the American Association of Clinical Endocrinologists (AACE)proximately 1500 critically ill patients were included in this for in-hospital management of blood glucose in critically illrandomized trial, consisting of both diabetic and nondiabetic patients suggested a goal blood sugar of 80 to 110 mg/dL (15).patients, the majority of whom underwent cardiac surgery. A This was a significant decrease in the suggested blood glucosecontinuous insulin infusion was used to maintain blood glucose target range. The recommendations seem to be based uponat two different levels: from 80 to 110 mg/dL in the intensive known deleterious outcomes of patients with elevated bloodtreatment arm and from 180 and 200 mg/dL in the conven- glucose (16–19) as well as many other studies showing benefittional arm. The average blood glucose levels in the intensive in patients undergoing cardiac surgery with controlled bloodand conventional treatment arms were 143 and 173 mg/dL, glucose and the studies showing survival rates with various glu-respectively. There was a significant reduction in overall mortal- cose ranges (1, 6, 8, 11–13, 20, 21).ity in the intensive arm (4.6%) compared with the conventional The Normoglycemia in Intensive Care Evaluation–Survivalarm (8%) (P < 0.04), in addition to decreases in the incidence Using Glucose Algorithm Regulation (NICE-SUGAR) trialof septicemia, number of blood transfusions, length of stay compared intensive blood glucose control (81–108 mg/dL) within the intensive care unit (ICU), incidence of renal failure, conventional control (<180 mg/dL) (3). The trial included criti-number of bloodstream infections, and other morbidities (1). cally ill patients; approximately 37% were operative admissionsThis trial showed the largest positive impact on mortality and to the ICU. The number of cardiovascular surgery patients wasled to further trials evaluating various blood glucose goals in not defined. Approximately 6000 critically ill patients admit-cardiac surgery patients; however, none were able to recreate ted to the ICU were enrolled, with 3054 in the intensive armsuch a widely noticeable impact on patient outcomes. and 3050 in the conventional arm. Within the conventional Another study assessing effects of tight blood glucose con- arm, a continuous insulin drip was initiated if blood glucosetrol, 120 to 200 mg/dL, using continuous insulin infusion in rose above 180 mg/dL and was discontinued if the blood glu-diabetic patients after cardiac surgery reported decreases in cose fell below 144 mg/dL. A similar percentage of patients inlength of stay and deep surgical wound infections; however, both arms had a history of diabetes at baseline. At 90 days, thethe differences were not significant (11). A study by Carr et al primary outcome was assessed, and mortality was greater inevaluating the effect of lower blood glucose goals (<130 mg/dL) the intensive glucose control arm—28% compared with 25%demonstrated a significant benefit with intensive blood glucose in the conventional arm (P = 0.02). The absolute difference incontrol in patient morbidity outcomes; however, mortality was mortality was 2.6%. The results were drastically different thannot assessed (12). In that study, both diabetic and nondiabetic previous evidence supporting the practice of intensive glucosepatients were included, with a continuous insulin infusion initi- control and prompted reevaluation of blood glucose goals forated at decreasing blood glucose ranges set over specified time critically ill patients. The NICE-SUGAR trial provided evidenceperiods. In the last two phases of the study, insulin infusions against intensive blood glucose control due to increased mortal-were initiated when blood glucose was >125 mg/dL and 110 ity in these patients. However, only a minority of the patientsmg/dL. Patient glucose levels were considered well controlled were operative admissions, and even fewer were postoperativeif they were <130 mg/dL for more than 50% of the time. A cardiac patients.80 Baylor University Medical Center Proceedings Volume 23, Number 1
  3. 3. Studies showing no benefit with intensive blood glucose and 180 mg/dL in critically ill patients, with possibly increasedcontrol raise questions about target blood glucose ranges in benefit in maintaining a blood glucose closer to 140 mg/dL.cardiac surgery patients. A metaanalysis in 2008 evaluated ben- Maintenance of blood glucose below 110 mg/dL is no longerefits of intensive blood glucose control in critically ill patients, recommended (27). In addition, the Society of Thoracic Sur-evaluating intensive control in medical ICU patients, surgical geons published guidelines regarding blood glucose manage-ICU patients, and patients in a combined medical-surgical ICU. ment during cardiac surgery, recommending maintenance ofThe metaanalysis showed no overall benefit in intensive blood blood glucose <180 mg/dL utilizing an insulin infusion. Inglucose goals when all ICUs were included or when only the patients who spend >3 days in the ICU, require an intraaorticsurgical ICU was evaluated (22). However, the surgical ICU balloon pump, inotropic medications, or left ventricular assiststudies included in the metaanalysis were not specifically evalu- devices, receive antiarrhythmic drugs, or are on dialysis, a bloodating cardiac ICU or cardiac surgery patients. glucose level of <150 mg/dL is recommended (28). The Joint A recent study in 2009 evaluated blood glucose target rang- Commission and the Surgical Care Improvement Project havees: a treated range of 80 to 130 mg/dL and a control group of also issued requirements that morning blood glucose on post-160 to 200 mg/dL (23). No difference between the two groups operative day 1 and 2 be <200 mg/dL (29). These new bloodwas found in various clinical outcomes, including mortality, glucose goals are more lenient than the intensive blood sugarlength of stay, and infection rate. goals utilized in many institutions. Intraoperative blood glucose control has been evaluated in Based on recent information, the new Society of Thoracicpatients undergoing cardiopulmonary bypass surgery to deter- Surgeons guidelines and the AACE/ADA consensus statementmine if elevated blood glucose during bypass affects mortality seem appropriate and allay the concern for hypoglycemia withand if tight blood glucose control during surgery allows for the new recommended range of <180 and 140 to 180 mg/dL.improved glucose control postoperatively. Lazar et al evaluated More studies analyzing blood glucose target ranges seem neces-a glucose-insulin-potassium (GIK) infusion in diabetics during sary to further recommend an intensive blood glucose goal rangesurgery and postoperatively for tight control of blood glucose of 80 to 110 mg/dL, especially in the cardiac surgery population.(goal blood glucose, 125–200 mg/dL) compared with standard Even throughout the Van Den Berghe trials, the average bloodtherapy with sliding-scale insulin (goal blood glucose, <250 sugar of patients in the intensive control arm was approximatelymg/dL). No impact on mortality was found; however, the GIK 140 mg/dL. Thus, aiming for blood glucose levels around 140infusion arm showed a significant decrease in infection rates, mg/dL appears reasonable. Mortality and morbidity benefitslength of stay, mechanical ventilator time, and incidence of atrial are seen with overall control of hyperglycemia; however, thefibrillation (24). Ouattara et al also evaluated intraoperative exact range is still not clearly defined, as previously thought.blood glucose control and outcomes on multiple morbidities; Additional comparisons of specific glucose ranges would allowmortality was not evaluated. An association was found between for a clearer definition of recommended blood glucose goals inincreased morbidity and poor intraoperative glycemic control postoperative cardiac patients, resulting in the best outcomes(25). and least incidence of hypoglycemia. Gandhi et al (26) also evaluated intensive blood glucosecontrol with an insulin infusion (goal blood glucose, 80–100 1. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetzmg/dL) compared with conventional treatment with an insulin M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001;345(19):1359–infusion (blood glucose goal, 150–200 mg/dL) in both dia- 1367.betic and nondiabetic patients. A composite outcome of death, 2. Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ,sternal wound infections, prolonged pulmonary ventilation, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R. Intensive insulincardiac arrhythmias, stroke, and acute renal failure within 30 therapy in the medical ICU. N Engl J Med 2006;354(5):449–461.days was evaluated. Mean blood glucose was 123 versus 148 3. NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blairmg/dL during bypass and 114 versus 157 mg/dL postopera- D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hébert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchelltively in the ICU in the intensive control and conventional I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ. Intensivearms, respectively. There was no significant difference between versus conventional glucose control in critically ill patients. N Engl J Medgroups in the primary composite outcome. Individual endpoints 2009;360(13):1283–1297.were analyzed separately, finding an increase in death, stroke, 4. Mills NL, Beaudet RL, Isom OW, Spencer FC. Hyperglycemia duringand heart block requiring pacemaker in the intensive insulin cardiopulmonary bypass. Ann Surg 1973;177(2):203–205. 5. Bagdade JD, Root RK, Bulger RJ. Impaired leukocyte function in patientscontrol arm. with poorly controlled diabetes. Diabetes 1974;23(1):9–15. With more conflicting evidence and literature reporting 6. Zerr KJ, Furnary AP, Grunkemeier GL, Bookin S, Kanhere V, Starr A.poor outcomes with intensive blood glucose control, recom- Glucose control lowers the risk of wound infection in diabetics after openmendations regarding blood glucose goals have been revised. heart operations. Ann Thorac Surg 1997;63(2):356–361.In 2007, the AACE recommended a goal blood sugar of 80 to 7. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection110 mg/dL in critically ill inpatients (15). However, consensus in diabetic patients after cardiac surgical procedures. Ann Thorac Surgstatements from the AACE and American Diabetes Associa- 1999;67(2):352–360; discussion 360–362.tion (ADA) published in 2009 now recommend utilization of 8. Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, Flotenan insulin infusion to maintain blood glucose between 140 HS, Starr A. Continuous insulin infusion reduces mortality in patientsJanuary 2010 Postoperative glycemic control in cardiac surgery patients 81
  4. 4. with diabetes undergoing coronary artery bypass grafting. J Thorac Car- 19. Guvener M, Pasaoglu I, Demircin M, Oc M. Perioperative hyperglycemia diovasc Surg 2003;125(5):1007–1021. is a strong correlate of postoperative infection in type II diabetic patients9. American College of Cardiology/American Heart Association Task Force after coronary artery bypass grafting. Endocr J 2002;49(5):531–537. on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures 20. Finney SJ, Zekveld C, Elia A, Evans TW. Glucose control and mortality (Subcommittee on Coronary Artery Bypass Graft Surgery). ACC/AHA in critically ill patients. JAMA 2003;290(15):2041–2047. guidelines and indications for coronary artery bypass graft surgery. Cir- 21. Hruska LA, Smith JM, Hendy MP, Fritz VL, McAdams S. Continuous culation 1991;83(3):1125–1173. insulin infusion reduces infectious complications in diabetics following10. Eagle KA, Guyton RA, Davidoff R, Ewy GA, Fonger J, Gardner TJ, Gott coronary surgery. J Card Surg 2005;20(5):403–407. JP, Herrmann HC, Marlow RA, Nugent WC, O’Connor GT, Orszulak 22. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose TA, Rieselbach RE, Winters WL, Yusuf S, Gibbons RJ, Alpert JS, Eagle control in critically ill adults: a meta-analysis. JAMA 2008;300(8):933– KA, Garson A Jr, Gregoratos G, Russell RO, Smith SC Jr; American 944. College of Cardiology/American Heart Association Task Force on Prac- 23. Chan RP, Galas FR, Hajjar LA, Bello CN, Piccioni MA, Auler JO Jr. tice Guidelines (Committee to Revise the 1991 Guidelines for Coronary Intensive perioperative glucose control does not improve outcomes of Artery Bypass Graft Surgery). ACC/AHA guidelines for coronary artery patients submitted to open-heart surgery: a randomized controlled trial. bypass graft surgery. J Am Coll Cardiol 1999;34(4):1262–1347. Clinics (Sao Paulo) 2009;64(1):51–60.11. Vora AC, Saleem TM, Polomano RC, Eddinger VL, Hollenbeak CS, 24. Lazar HL, Chipkin SR, Fitzgerald CA, Bao Y, Cabral H, Apstein CS. Girdharry DT, Joshi R, Martin D, Gabbay RA. Improved perioperative Tight glycemic control in diabetic coronary artery bypass graft patients glycemic control by continuous insulin infusion under supervision of an improves perioperative outcomes and decreases recurrent ischemic events. endocrinologist does not increase costs in patients with diabetes. Endocr Circulation 2004;109(12):1497–1502. Pract 2004;10(2):112–118. 25. Ouattara A, Lecomte P, Le Manach Y, Landi M, Jacqueminet S, Platonov12. Carr JM, Sellke FW, Fey M, Doyle MJ, Krempin JA, de la Torre R, Lid- I, Bonnet N, Riou B, Coriat P. Poor intraoperative blood glucose control dicoat JR. Implementing tight glucose control after coronary artery bypass is associated with a worsened hospital outcome after cardiac surgery in surgery. Ann Thorac Surg 2005;80(3):902–909. diabetic patients. Anesthesiology 2005;103(4):687–694.13. Lecomte P, Van Vlem B, Coddens J, Cammu G, Nollet G, Nobels F, 26. Gandhi GY, Nuttall GA, Abel MD, Mullany CJ, Schaff HV, O’Brien Vanermen H, Foubert L. Tight perioperative glucose control is associated PC, Johnson MG, Williams AR, Cutshall SM, Mundy LM, Rizza RA, with a reduction in renal impairment and renal failure in non-diabetic McMahon MM. Intensive intraoperative insulin therapy versus conven- cardiac surgical patients. Crit Care 2008;12(6):R154. tional glucose management during cardiac surgery: a randomized trial.14. Eagle KA, Guyton RA, Davidoff R, Edwards FH, Ewy GA, Gardner TJ, Ann Intern Med 2007;146(4):233–243. Hart JC, Herrmann HC, Hillis LD, Hutter AM Jr, Lytle BW, Marlow RA, 27. Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Nugent WC, Orszulak TA; American College of Cardiology; American Hirsch IB, Inzucchi SE, Ismail-Beigi F, Kirkman MS, Umpierrez GE; Heart Association. ACC/AHA 2004 guideline update for coronary artery American Association of Clinical Endocrinologists; American Diabe- bypass graft surgery. Circulation 2004;110(14):e340–e437. tes Association. American Association of Clinical Endocrinologists and15. American College of Endocrinology and American Association of Clinical American Diabetes Association consensus statement on inpatient glycemic Endocrinologists (AACE) diabetes road maps. Endocrine Practice 2007;13: control. Diabetes Care 2009;32(6):1119–1131. S5–S68. 28. Lazar HL, McDonnell M, Chipkin SR, Furnary AP, Engelman RM, Sadhu16. McAlister FA, Man J, Bistritz L, Amad H, Tandon P. Diabetes and coro- AR, Bridges CR, Haan CK, Svedjeholm R, Taegtmeyer H, Shemin RJ; nary artery bypass surgery: an examination of perioperative glycemic Society of Thoracic Surgeons Blood Glucose Guideline Task Force. The control and outcomes. Diabetes Care 2003;26(5):1518–1524. Society of Thoracic Surgeons practice guideline series: Blood glucose man-17. Szabó Z, Håkanson E, Svedjeholm R. Early postoperative outcome agement during adult cardiac surgery. Ann Thorac Surg 2009;87(2):663– and medium-term survival in 540 diabetic and 2239 nondiabetic pa- 669. tients undergoing coronary artery bypass grafting. Ann Thorac Surg 29. The Joint Commission. Specification Manual for National Hospital Quality 2002;74(3):712–719. Measures. Oakbrook Terrace, IL: The Joint Commission, 2009. Available18. Krinsley JS. Effect of an intensive glucose management protocol on the at mortality of critically ill adult patients. Mayo Clin Proc 2004;79(8):992– anceMeasurement/Current+NHQM+Manual.htm; accessed October 22, 1000. 2009.82 Baylor University Medical Center Proceedings Volume 23, Number 1