Editorial Views  |   February 2009
Perioperative Glucose Control: What Is Enough?
Author Affiliations & Notes
  • Brenda G. Fahy, M.D.
  • Ann M. Sheehy, M.D.
  • Douglas B. Coursin, M.D.
  • *Department of Anesthesiology, University of Kentucky Chandler Medical Center, Lexington, Kentucky. . †Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. ‡Department of Medicine and Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health.
Article Information
Editorial Views / Critical Care / Endocrine and Metabolic Systems
Editorial Views   |   February 2009
Perioperative Glucose Control: What Is Enough?
Anesthesiology 2 2009, Vol.110, 204-206. doi:10.1097/ALN.0b013e3181948aae
Anesthesiology 2 2009, Vol.110, 204-206. doi:10.1097/ALN.0b013e3181948aae
TYPE 2 diabetes mellitus, impaired fasting glucose/impaired glucose tolerance, and stress-induced hyperglycemia (SIH) are ubiquitous in the adult population and represent major public health concerns.1 Almost 10% of adult Americans have type 2 diabetes mellitus, an additional 20–25% have impaired glucose tolerance/impaired fasting glucose, and an unknown number develop SIH. Upwards of one third of affected patients are unaware of the presence of dysglycemia and its systemic effects.1 Projections predict a continued, dramatic increase in the incidence and prevalence of type 2 diabetes over the next several decades, with its deleterious impact on quality of life and life expectancy. In this issue of Anesthesiology, Drs. Lipshutz and Gropper address the impact of dysglycemia on perioperative management.2 
Patients with diabetes require acute and critical care, procedural interventions, and hospitalizations more commonly than those with normal glucose tolerance.3 When patients with diabetes require hospitalization or undergo certain procedures, they sustain greater morbidity and mortality.4 Studies from this decade have shown that a minimalist approach to glucose control in selected perioperative and critically ill patient populations is unwarranted, and improved glucose control leads to less morbidity and better outcomes,4–6 particularly in those with SIH.7 Key questions remain unanswered. How tight should glycemic control be? Are all hyperglycemic patients at equal risk for morbid and lethal events at a given degree of dysglycemia? What is the incidence and degree of morbidity when tight glycemic control (TGC) is universally applied? Identification of the dysglycemic patient and application of reliable glucose monitoring and glucose management techniques to a proper endpoint are crucial to achieving adequate perioperative glucose control. Identification of new-onset glucose intolerance in the perioperative patient should be followed by appropriate referral to the patient’s primary care provider for ambulatory unstressed diabetes testing.
Drs. Lipshutz and Gropper emphasize that the current data reporting the benefits in reducing morbidity and mortality in intensive care unit patients using intensive insulin therapy to provide TGC be interpreted with care in light of risks reported when this approach is applied universally. They comment on the potential differences in glucose control and outcome related to type 1 versus  type 2 diabetes or SIH, the effect of glucose variability during the course of intense monitoring and therapy, and the current risk-benefit data on TGC in various populations. They caution about extrapolating intensive care unit studies directly to the perioperative patient. We would go a step further and caution against a sudden call for intraoperative normalization of blood glucose (80–110 mg/dL; 4.4–6.1 mmol). Additional data should be obtained before implementing rigid perioperative standards of glucose management while tying reimbursement for care of the hyperglycemic perioperative patient to potentially unsubstantiated goals.8–10 
This thorough review briefly comments on the importance of glucose monitoring, quality control of bedside glucose measurements versus  laboratory techniques, and attempts at developing continuous and closed loop systems to control glucose. The reliability of glucose measurements is important to remember when controlling glucose levels during the dynamic perioperative period. Practical pitfalls in glucose monitoring secondary to sample site and source, technique of monitoring, impact of concurrent pathophysiologic states and interfering substances such as nonglucose sugars, and various medications are now recognized.11–13 
The source of glucose monitoring, point-of-care device, blood gas analyzer, or central laboratory evaluation may explain some of the conflicting results reported when intensive insulin therapy and TGC protocols are instituted.11–13 Point-of-care glucose monitoring using finger-stick capillary blood, the most common approach to perioperative evaluation, is based on application of ambulatory technology using photoreflectometry or electrochemical reaction. The Food and Drug Administration mandates a ± 20% agreement between the point-of-care device and laboratory gold standard.1Differences between laboratory and point-of-care–derived values are particularly important in intensive care unit patients who are anemic, hypothermic, or hypoperfused. Potentially critical disagreements between the central laboratory value and point-of-care measurement may lead to inappropriate insulin management.11–13 Certain operative patients, particularly those in shock or actively hemorrhaging, are likely to be affected.
Multidisciplinary teams should develop glucose control protocols, set reasonable goals for control, monitor the effectiveness of controlling glucose, and recognize and carefully monitor patients at high risk for hypoglycemia.14–17 The latter is especially important during the perioperative period, when early signs of hypoglycemia may be masked due to the administration of sedatives, analgesics, and anesthetics. The University of California, San Francisco group and others have reported their success with such an approach.14–17 Nonetheless, given concerns over reports of hypoglycemia with intensive insulin therapy that range from 5–18.7% and increased mortality when hypoglycemia (glucose < 40 mg/dL; 2.2 mmol) develops in critically ill patients, cautious application of TGC in the perioperative period should be the norm until more data are forthcoming.4,5,18,19 Further, the effort and resources required to maintain TGC are significant, and the potential for long-term morbidity secondary to hypoglycemia-induced neuropsychologic compromise has not been well studied.
The implications of establishing practice guidelines and applying them globally17 to complex perioperative populations that range from patients with neuroischemia, neurotrauma, cardiac compromise, and sepsis, to name but a few, are significant. Adding the variables discussed in this review, prior diabetes, type 1 versus  type 2, SIH, and a host of others such as obesity, age, and other end-organ compromise further complicate the potentially premature call for routine TGC in the perioperative period. The wisdom of applying glucose management standards to pay for performance remains to be proven and can be potentially dangerous at present and should await additional data. The application of these standards might even be dangerous to unique patients, and their use must await further study in diverse patient populations.
The Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE SUGAR) Trial2completed enrollment of 6100 patients in August 2008.20 Although an ICU trial, it is multicenter, international, prospective, and randomized, and it is the largest trial of its kind. It has the potential to further guide therapeutic interventions in patients with a broad spectrum of illnesses, including those in the perioperative period.
The development of a prospective multi-institutional database evaluating the incidence and evidence-based management of hypoglycemia or hyperglycemia across the heterogeneous perioperative population would address some major public health concerns. This database would facilitate identification of previously undiagnosed surgical patients with diabetes, aid in determination of the incidence and natural history of SIH in perioperative patients, and provide data on the impact of glycemic management and quality of long-term care of specific subsets of patients, including those undergoing primary neurologic, cardiac, or traumatic surgery. Unfortunately, at present, other than epidemiologic screens such as the National Health and Nutrition Examination Survey,3there is no program, federally or privately funded, available to generate such information. Hopefully, the drive for evidence-based medical care could facilitate such a vehicle to examine this and other important perioperative diagnoses and management strategies such as use of β-blockers, indication for statin administration, and application of genomic diagnostics to stratify care and optimize outcome.
*Department of Anesthesiology, University of Kentucky Chandler Medical Center, Lexington, Kentucky. . †Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. ‡Department of Medicine and Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health.
Cowie CC, Rust KF, Byrd-Holt DD, Eberhardt MS, Flegal KM, Engelgau MM, Saydah SH, Williams DE, Geiss LS, Gregg EW: Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health and Nutrition Examination Survey 1999–2002. Diabetes Care 2006; 29:1263–8Cowie, CC Rust, KF Byrd-Holt, DD Eberhardt, MS Flegal, KM Engelgau, MM Saydah, SH Williams, DE Geiss, LS Gregg, EW
Lipschutz AKM, Gropper MA: Perioperative glucose control: An evidence-based review. Anesthesiology 2009; 110:408–21Lipschutz, AKM Gropper, MA
Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE: Hyperglycemia: An independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002; 87:978–82Umpierrez, GE Isaacs, SD Bazargan, N You, X Thaler, LM Kitabchi, AE
Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R: Intensive insulin therapy in the surgical intensive care unit. N Engl J Med 2001; 345:1359–67Van den Berghe, G Wouters, P Weekers, F Verwaest, C Bruyninckx, F Schetz, M Vlasselaers, D Ferdinande, P Lauwers, P Bouillon, R
Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R: Intensive insulin therapy in the medical ICU. N Engl J Med 2006; 354:449–61Van den Berghe, G Wilmer, A Hermans, G Meersseman, W Wouters, PJ Milants, I Van Wijngaerden, E Bobbaers, H Bouillon, R
Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, Floten HS, Starr A: Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003; 125:1007–21Furnary, AP Gao, G Grunkemeier, GL Wu, Y Zerr, KJ Bookin, SO Floten, HS Starr, A
Egi M, Bellomo R, Stachowski E, French CJ, Hart GK, Hegarty C, Bailey M: Blood glucose concentration and outcome of critical illness: The impact of diabetes. Crit Care Med 2008; 36:2249–55Egi, M Bellomo, R Stachowski, E French, CJ Hart, GK Hegarty, C Bailey, M
Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof EL, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF, Smith SC Jacobs AK, Adams CD, Anderson JL, Antman EM, Buller CE, Creager MA, Ettinger SM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW: ACC/AHA 2007 Guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery. Circulation 2007; 116:e418–99Fleisher, LA Beckman, JA Brown, KA Calkins, H Chaikof, EL Fleischmann, KE Freeman, WK Froehlich, JB Kasper, EK Kersten, JR Riegel, B Robb, JF Smith, SC Jacobs, AK Adams, CD Anderson, JL Antman, EM Buller, CE Creager, MA Ettinger, SM Faxon, DP Fuster, V Halperin, JL Hiratzka, LF Hunt, SA Lytle, BW Nishimura, R Ornato, JP Page, RL Riegel, B Tarkington, LG Yancy, CW
Garber AJ, Moghissi ES, Bransome ED Jr, Clark NG, Clement S, Cobin RH, Furnary AP, Hirsch IB, Levy P, Roberts R, Van den Berghe G, Zamudio V: American College of Endocrinology Task Force on Inpatient Diabetes Metabolic Control: American College of Endocrinology position statement on inpatient diabetes and metabolic control. Endocr Pract 2004; 10:77–82Garber, AJ Moghissi, ES Bransome, ED Clark, NG Clement, S Cobin, RH Furnary, AP Hirsch, IB Levy, P Roberts, R Van den Berghe, G Zamudio, V American College of Endocrinology Task Force on Inpatient Diabetes Metabolic Control,
McCormick MT, Muir KW, Gray CS, Walters MR: Management of hyperglycemia in acute stroke: How, when, and for whom? Stroke 2008; 39:2177–85McCormick, MT Muir, KW Gray, CS Walters, MR
Desachy A, Vuagnat AC, Ghazali AD, Baudin OT, Longuet OH, Calvat SN, Gissot V: Accuracy of bedside glucometry in critically ill patients: Influence of clinical characteristics and perfusion index. Mayo Clin Proc 2008; 83:400–5Desachy, A Vuagnat, AC Ghazali, AD Baudin, OT Longuet, OH Calvat, SN Gissot, V
Kanji S, Buffie J, Hutton B, Bunting PS, Singh A, McDonald K, Fergusson D, McIntyre LA, Hebert PC: Reliability of point-of-care testing for glucose measurement in critically ill adults. Crit Care Med 2005; 33:2778–85Kanji, S Buffie, J Hutton, B Bunting, PS Singh, A McDonald, K Fergusson, D McIntyre, LA Hebert, PC
Fahy BG, Coursin DB: Critical glucose control: The devil is in the details. Mayo Clin Proc 2008; 83:394–7Fahy, BG Coursin, DB
Lipshutz AK, Fee C, Schell H, Campbell L, Taylor J, Sharpe BA, Nguyen J, Gropper MA: Strategies for success: A PDSA analysis of three QI initiatives in critical care. Jt Comm J Qual Patient Saf 2008; 34:435–4Lipshutz, AK Fee, C Schell, H Campbell, L Taylor, J Sharpe, BA Nguyen, J Gropper, MA
Vriesendorp TM, DeVries JH, van Santen S, Moeniralam HS, de Jonge E, Roos YB, Schultz MJ, Rosendaal FR, Hoekstra JB: Evaluation of short-term consequences of hypoglycemia in an intensive care unit. Crit Care Med 2006; 34:2714–8Vriesendorp, TM DeVries, JH van Santen, S Moeniralam, HS de Jonge, E Roos, YB Schultz, MJ Rosendaal, FR Hoekstra, JB
Soylemez Wiener R, Wiener DC, Larson RJ: Benefits and risks of tight glucose control in critically ill adults: A meta-analysis. JAMA 2008; 300:933–44Soylemez Wiener, R Wiener, DC Larson, RJ
Wilson M, Weinreb J, Hoo GW: Intensive insulin therapy in critical care: A review of 12 protocols. Diabetes Care 2007; 30:1005–11Wilson, M Weinreb, J Hoo, GW
Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K, German Competence Network Sepsis (SepNet): German Competence Network Sepsis (SepNet): Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358:125–39Brunkhorst, FM Engel, C Bloos, F Meier-Hellmann, A Ragaller, M Weiler, N Moerer, O Gruendling, M Oppert, M Grond, S Olthoff, D Jaschinski, U John, S Rossaint, R Welte, T Schaefer, M Kern, P Kuhnt, E Kiehntopf, M Hartog, C Natanson, C Loeffler, M Reinhart, K German Competence Network Sepsis (SepNet), German Competence Network Sepsis (SepNet),
Gandhi GY, Murad MH, Flynn DN, Erwin PJ, Cavalcante AB, Bay Nielsen H, Capes SE, Thorlund K, Montori VM, Devereaux PJ: The effect of perioperative insulin infusion of surgical morbidity and mortality: A systematic review and meta-analysis of randomized trials. Mayo Clin Proc 2008; 83:418–30Gandhi, GY Murad, MH Flynn, DN Erwin, PJ Cavalcante, AB Bay Nielsen, H Capes, SE Thorlund, K Montori, VM Devereaux, PJ
Finfer S, Delaney A: Tight glycemic control in critically ill adults. JAMA 2008; 300:963–5Finfer, S Delaney, A