Introduction: Optimal glycemic control in cardiac surgery patients remains a laudable but confusing practice. Existing studies have primarily employed two maintenance strategies using either intensive insulin therapy (IIT) (maintain glucose < 120 mg/dl) or conventional insulin therapy (CIT) (<200 mg/dl) with conflicting outcomes. This meta-analysis evaluates the impact of IIT and CIT in regards to the incidence of mortality, length of stay (LOS), intensive care unit (ICU) LOS, atrial fibrillation (AF), and infections. Methods: A comprehensive literature search in PubMed, Google Scholar and the Cochrane Central Registry of Controlled Trials was completed between 1966 and 2016. Keywords searched were “insulin”, “bypass”, “coronary”, “CABG”, “glucose”, “artery”, “intensive”, “cardiac”, and “surgery”. Eligible studies were randomized control trials (RCTs) comparing IIT (BGL 80-120 mg/dL) and CIT (BGL < 200 mg/dL). Primary outcomes were mortality, ICU LOS, and hospital LOS. Results: 8 RCTs were included in this study. IIT strategies did not significantly affect overall mortality (RR = 0.905, 95% CI = 0.604 to 1.356; p = 0.628), ICU LOS (MD = -0.073 days, 95% CI = -0.324 to 0.178; p = 0.568), or hospital LOS (MD = 0.269, 95% CI = -2.158 to 2.696; p = 0.828). No difference in AF rates (RR = 0.887, 95% CI = 0.681 to 1.155; p = 0.375) or deep sternal infection (RR = 0.985, 95% CI = 0.357 to 2.720; p = 0.977) were observed. Conclusion: IIT targeting blood sugar levels of 80 - 120 mg/dl have no effect on perioperative outcomes in cardiac surgery patients. IIT is associated with similar mortality, ICU LOS, hospital LOS, AF rates, and deep sternal infection rates compared to more liberal glycemic strategies. IIT should not replace CIT as the standard of care in cardiac surgery patients.
References
[1]
Schmeltz, L.R., DeSantis, A.J., Thiyagarajan, V., et al. (2007) Reduction of Surgical Mortality and Morbidity in Diabetic Patients Undergoing Cardiac Surgery with a Combined Intravenous and Subcutaneous Insulin Glucose Management Strategy. Diabetes Care, 30, 823-828.
[2]
Furnary, A.P., Wu, Y. and Bookin, S.O. (2004) Effect of Hyperglycemia and Continuous Intravenous Insulin Infusion on Outcomes of Cardiac Surgical Procedures: The Portland Diabetic Project. Endocrine Practice, 10, 21-33. http://dx.doi.org/10.4158/EP.10.S2.21
[3]
Donner, T.W. and Flammer, K.M. (2008) Diabetes Management in the Hospital. Medical Clinics of North America, 92, 407-425. http://dx.doi.org/10.1016/j.mcna.2007.10.001
[4]
Van den Berghe, G., Wouters, P.J., Bouillon, R., et al. (2003) Outcome Benefit of Intensive Insulin Therapy in the Critically Ill: Insulin Dose versus Glycemic Control. Critical Care Medicine, 31, 359-366. http://dx.doi.org/10.1097/01.CCM.0000045568.12881.10
[5]
American Diabetes Association (2005) Diabetes Mellitus and Other Categories of Description of Diabetes. American Diabetes Association, 28, s5-s10. http://dx.doi.org/10.2337/diacare.27.2007.S5
van den Berghe, G., Wouters, P., Weekers, F., et al. (2001) Intensive Insulin Therapy in the Critically Ill Patients. New England Journal of Medicine, 345, 1359-1367. http://dx.doi.org/10.1056/NEJMoa011300
[8]
Van Den Berghe, G., Wilmer, A., Milants, I., et al. (2006) Intensive Insulin Therapy in Mixed Medical/Surgical. Heal, 55, 3151-3159. http://dx.doi.org/10.2337/db06-0855
[9]
Finfer, S., Chittock, D.R., Su, S.Y.-S., et al. (2009) Intensive versus Conventional Glucose Control in Critically Ill Patients. New England Journal of Medicine, 360, 1283-1297. http://dx.doi.org/10.1056/NEJMoa0810625
[10]
Haga, K.K., McClymont, K.L., Clarke, S., et al. (2011) The Effect of Tight Glycaemic Control, during and after Cardiac Surgery, on Patient Mortality and Morbidity: A Systematic Review and Meta-Analysis. Journal of Cardiothoracic Surgery, 6, 3. http://dx.doi.org/10.1186/1749-8090-6-3
[11]
Liberati, A., Altman, D.G., Tetzlaff, J., et al. (2009) Annals of Internal Medicine Academia and Clinic the PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Annals of Internal Medicine, 151, W65-W94. http://dx.doi.org/10.1371/journal.pmed.1000100
[12]
Nashef, S.A.M., Roques, F., Michel, P., Gauducheau, E., Lemeshow, S. and Salamon, R. (1999) European System for Cardiac Operative Risk Evaluation (EuroSCORE). European Journal Cardio-Thoracic Surgery, 16, 9-13. http://dx.doi.org/10.1016/S1010-7940(99)00134-7
[13]
Al-Sarraf, N., Thalib, L., Hughes, A., et al. (2011) Cross-Clamp Time Is an Independent Predictor of Mortality and Morbidity in Low- and High-Risk Cardiac Patients. International Journal of Surgery, 9, 104-109. http://dx.doi.org/10.1016/j.ijsu.2010.10.007
[14]
El-Chami, M.F., Kilgo, P., Thourani, V., et al. (2010) New-Onset Atrial Fibrillation Predicts Long-Term Mortality After Coronary Artery Bypass Graft. Journal of the American College of Cardiology, 55, 1370-1376. http://dx.doi.org/10.1016/j.jacc.2009.10.058
[15]
Doenst, T., Borger, M.A., Weisel, R.D., Yau, T.M., Maganti, M. and Rao, V. (2008) Relation between Aortic Cross-Clamp Time and Mortality—Not as Straightforward as Expected. European Journal Cardio-Thoracic Surgery, 33, 660-665. http://dx.doi.org/10.1016/j.ejcts.2008.01.001
[16]
Krinsley, J.S., Egi, M., Kiss, A., et al. (2013) Diabetic Status and the Relation of the Three Domains of Glycemic Control to Mortality in Critically Ill Patients: An International Multicenter Cohort Study. Critical Care, 17, R37. http://dx.doi.org/10.1186/cc12547
[17]
Arabi, Y.M., Tamim, H.M. and Rishu, A.H. (2009) Hypoglycemia with Intensive Insulin Therapy in Critically ill Patients: Predisposing Factors and Association with Mortality. Critical Care Medicine, 37, 2536-2544. http://dx.doi.org/10.1097/CCM.0b013e3181a381ad
[18]
Stamou, S.C., Nussbaum, M., Carew, J.D., et al. (2011) Hypoglycemia with Intensive Insulin Therapy after Cardiac Surgery: Predisposing Factors and Association with Mortality. The Journal of Thoracic and Cardiovascular Surgery, 142, 166-173. http://dx.doi.org/10.1016/j.jtcvs.2010.09.064
[19]
Boucai, L., Southern, W.N. and Zonszein, J. (2011) Hypoglycemia-Associated Mortality Is Not Drug-Associated but Linked to Comorbidities. American Journal of Medicine, 124, 1028-1035. http://dx.doi.org/10.1016/j.amjmed.2011.07.011
[20]
Kosiborod, M., Inzucchi, S.E., Goyal, A., et al. (2009) Relationship between Spontaneous and Iatrogenic Hypoglycemia and Mortality in Patients Hospitalized with Acute Myocardial Infarction. JAMA, 301, 1556-1564. http://dx.doi.org/10.1001/jama.2009.496
[21]
Meyfroidt, G., Keenan, D.M., Wang, X., Wouters, P.J., Veldhuis, J.D. and van den Berghe, G. (2010) Dynamic Characteristics of Blood Glucose Time Series during the Course of Critical Illness: Effects of Intensive Insulin Therapy and Relative Association with Mortality. Critical Care Medicine, 38, 1021-1029. http://dx.doi.org/10.1097/CCM.0b013e3181cf710e
[22]
Lazar, H.L., Chipkin, S.R., Fitzgerald, C., Bao, Y., Cabral, H. and Apstein, C.S. (2004) Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events. Circulation, 109, 1497-1502. http://dx.doi.org/10.1161/01.CIR.0000121747.71054.79
[23]
Furnary, A.P. and Wu, Y. (2006) Eliminating the Diabetic Disadvantage: The Portland Diabetic Project. Seminars in Thoracic and Cardiovascular Surgery, 18, 302-308. http://dx.doi.org/10.1053/j.semtcvs.2006.04.005
[24]
Paparella, D., Yau, T.M. and Young, E. (2002) Cardiopulmonary Bypass Induced Inflammation: Pathophysiology and Treatment. An Update. European Journal Cardio-Thoracic Surgery, 21, 232-244. http://dx.doi.org/10.1016/S1010-7940(01)01099-5
[25]
Ndumele, C.E., Pradhan, A.D. and Ridker, P.M. (2006) Interrelationships between Inflammation, C-Reactive Protein, and Insulin Resistance. Journal of the CardioMetabolic Syndrome, 1, 107-196. http://dx.doi.org/10.1111/j.1559-4564.2006.05538.x
[26]
Hoedemaekers, C.W., Pickkers, P., Netea, M.G., van Deuren, M. and Van der Hoeven, J.G. (2005) Intensive Insulin Therapy Does Not Alter the Inflammatory Response in Patients Undergoing Coronary Artery Bypass Grafting: A Randomized Controlled Trial [ISRCTN95608630]. Critical Care, 9, R790-R797. http://dx.doi.org/10.1186/cc3911
[27]
Kalman, J.M., Munawar, M., Howes, L.G., et al. (1995) Atrial Fibrillation after Coronary Artery Bypass Grafting Is Associated with Sympathetic activation. Annals of Thoracic Surgery, 60, 1709-1715. http://dx.doi.org/10.1016/0003-4975(95)00718-0
[28]
Aviles, R.J., Martin, D.O., Apperson-Hansen, C., et al. (2003) Inflammation as a Risk Factor for Atrial Fibrillation. Circulation, 108, 3006-3010. http://dx.doi.org/10.1161/01.CIR.0000103131.70301.4F
[29]
Bruins, P., Te, V.H., Yazdanbakhsh, A.P., et al. (1997) Activation of the Complement System during and after Cardiopulmonary Bypass Surgery: Postsurgery Activation Involves C-Reactive Protein and Is Associated with Postoperative Arrhythmia. Circulation, 96, 3542-3548. http://dx.doi.org/10.1161/01.CIR.96.10.3542
[30]
Capes, S.E., Hunt, D., Malmberg, K., Pathak, P. and Gerstein, H.C. (2001) Stress Hyperglycemia and Prognosis of Stroke in Nondiabetic and Diabetic Patients: A Systematic Overview. Stroke, 32, 2426-2432. http://dx.doi.org/10.1161/hs1001.096194
[31]
Stegenga, M.E., van der Crabben, S.N., Blümer, R.M.E., et al. (2008) Hyperglycemia Enhances Coagulation and Reduces Neutrophil Degranulation, Whereas Hyperinsulinemia Inhibits Fibrinolysis during Human Endotoxemia. Blood, 112, 82-89. http://dx.doi.org/10.1182/blood-2007-11-121723
[32]
Azevedo, J.R.A., Azevedo, R.P., Lucena, L.C., Costa, N.N.R. and Sousa, W.S. (2009) Does Intensive Insulin Therapy Really Reduce the Incidence of Acute Renal Injury in Critically Ill Patients? An Analysis Using the RIFLE Criteria. Critical Care, 13, P37. http://dx.doi.org/10.1186/cc7839 http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed10&NEWS=N&AN=70339953