1. Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock Dellinger RP, Levy MM, Rhodes A, Annane D, Carcillo JA, Gerlach H, Opal S, Sevransky J, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally M, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld G, Webb S, Beale RJ, Vincent JL, Moreno R, and the SSC Management Guidelines Committee Crit Care Med. 2013;41:580–637 Intensive Care Med. 2013;39:165-228

2. Glucose Control Crit Care Med. 2013;41:580–637 Intensive Care Med. 2013;39:165-228 Surviving Sepsis Campaign (SSC) 2012 Guidelines

3. Surviving Sepsis Campaign 2012 Guidelines – Glucose Control We recommend protocolized approach to blood glucose management, commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dL. This protocolized approach should target upper blood glucose <180 mg/dL rather than upper target blood glucose <110 mg/dL. Grade 1A NICE-SUGAR. N Engl J Med. 2009;360:1283–1297 van den Berghe G. N Engl J Med. 2001;345:1359–1367 Dellinger P. Crit Care Med. 2013;41:580–637 Dellinger P. Intensive Care Med 2013;39:165-228

4. Surviving Sepsis Campaign 2012 Guidelines – Glucose Control Large randomized single-center trial (predominantly cardiac surgical ICU) demonstrated reduced ICU mortality with intensive intravenous insulin targeting blood glucose to 80–110 mg/dL. van den Berghe G. N Engl J Med. 2001;345:1359–1367 Second randomized trial of intensive insulin therapy using this protocol enrolled medical ICU patients with anticipated ICU LOS of >3 days; overall mortality was not reduced. van den Berghe G. N Engl J Med 2006;354:449–461 Dellinger P. Crit Care Med 2013; 41:580–637 Dellinger P. Intensive Care Med 2013;39:165-228

5. van den Berghe et al. N Engl J Med. 2001;345:1359 P = 0.005 P = 0.01 Intensive Insulin Therapy in Critically Ill Patients

6. van den Berghe et al. N Engl J Med. 2006;354:449 P = 0.40 P = 0.02

7. But…

8. Surviving Sepsis Campaign 2012 Guidelines – Glucose Control Subsequent RCTs studied mixed populations of surgical and medical ICU patients and found that intensive insulin therapy did not significantly decrease mortality, whereas the NICE-SUGAR trial demonstrated an increased mortality. Brunkhorst FM. VISEP. N Engl J Med. 2008;358:125–139 Preiser JC. Glucontrol. Intensive Care Med. 2009;35:1738 Annane D. COIITSS. JAMA.2010;303:341–348 NICE-SUGAR. N Engl J Med. 2009;360:1283–1297 Dellinger P. Crit Care Med. 2013;41:580–637 Dellinger P. Intensive Care Med. 2013;39:165-228

9. VISEP Intensive Insulin Trial Brunkhorst FM. N Engl J Med. 2008;358:125 P=0.36

10. Preiser JC. Glucontrol. Intensive Care Med.2009;35:1738 Intensive vs. Conventional Glucose Control in Critically Ill Patients

11. Intensive Insulin Therapy for Septic Shock - COIITSS Study Annane D. JAMA. 2010;303:341-348 P=0.57

12. NICE-SUGAR. N Engl J Med. 2009;360:1283 Tight glycemic control= 81-108 mg/dL vs. <180 mg/dL P=0.03 Intensive vs. Conventional Glucose Control in Critically Ill Patients

13. Surviving Sepsis Campaign 2012 Guidelines - Glucose Control As there is no evidence that targets between 140 and 180 mg/dL are different from targets of 110 to 140 mg/dL, the recommendations use an upper target blood glucose ≤180 mg/dL without a lower target other than hypoglycemia. Treatment should avoid hyperglycemia (>180 mg/dL), hypoglycemia, and wide swings in glucose levels. Dellinger P. Crit Care Med. 2013;41:580–637 Dellinger P. Intensive Care Med. 2013;39:165-228

14. Tight Glycemic Control in the ICU: Systematic Review and Meta-analysis Marik PE. Chest. 2010;137:544

15. 5.1% 0.8% 18.7% 3.1% 17% 4.1% 8.7% 2.7% 16.4% 7.8% 6.8% 0.5% Severe Hypoglycemia ≤40mg/dL (2.2 mmol/L) Treatment vs control P<0.001

16. Surviving Sepsis Campaign 2012 Guidelines - Glucose Control Mortality in clinical trials of intensive insulin therapy by high or moderate control groups

17. We recommend blood glucose values be monitored every 1-2 hours until values and insulin infusion rates are stable, then every 4 hours thereafter. Grade 1C Dellinger P. Crit Care Med. 2013;41:580–637 Dellinger P. Intensive Care Med. 2013;39:165-228 Surviving Sepsis Campaign 2012 Guidelines - Glucose Control

18. We recommend that glucose levels obtained with point-of-care testing of capillary blood be interpreted with caution, as such measurements may not accurately estimate arterial blood or plasma glucose values. No Grade Dellinger P. Crit Care Med. 2013;41:580–637 Dellinger P. Intensive Care Med. 2013;39:165-228 Surviving Sepsis Campaign 2012 Guidelines - Glucose Control

19. Capillary point-of-care testing found to be inaccurate with frequent false glucose elevations over range of glucose levels, but especially in hypoglycemic and hyperglycemic glucose ranges and in hypotensive patients or patients receiving catecholamines.. Hoedemaekers CW. Crit Care Med. 2008;36:3062–3066 Khan AI. Arch Pathol Lab Med. 2006;130:1527–1532 Desachy A. Mayo Clin Proc. 2008;83:400–405 Fekih Hassen M. Diabetes Res Clin Pract. 2010;87:87–91 Dellinger P. Crit Care Med. 2013;41:580–637 Dellinger P. Intensive Care Med. 2013;39:165-228 Surviving Sepsis Campaign 2012 Guidelines - Glucose Control