J Korean Diabetes.  2015 Mar;16(1):18-24. 10.4093/jkd.2015.16.1.18.

Glycemic Targets for the Critically Ill Patient

• Kim HM
• Kim J

• KMID: 2137279
• DOI: http://doi.org/10.4093/jkd.2015.16.1.18

Abstract

Critically ill patients often experience hyperglycemia, which may be associated with increased morbidity and mortality. In 2001, van den Berghe et al. suggested significant benefit of normalization of blood glucose level in critically ill patients using intensive intravenous insulin therapy. Subsequent multicenter randomized studies, however, demonstrated adverse effects of tight glucose control. Therefore, while the need for glucose control in critically ill patients is generally accepted, the treatment thresholds for initiation of insulin therapy or target glucose values are still undetermined. Furthermore, occurrence of a hypoglycemic event during intensive insulin therapy is known to be an independent predictor of clinical outcome, and glycemic variability is an important variable of glucose management in the critically ill patients. Novel technological approaches such as a continuous glucose monitoring system (CGMS) might help to overcome some problems of tight glucose control by reducing the risk of hypoglycemia and minimizing glycemic variability.

Keyword

Critical illness; Hyperglycemia; Intensive care units

MeSH Terms

Blood Glucose
Critical Illness*
Glucose
Humans
Hyperglycemia
Hypoglycemia
Insulin
Intensive Care Units
Mortality
Blood Glucose
Glucose
Insulin

Reference

References

1. Levetan CS, Passaro M, Jablonski K, Kass M, Ratner RE. Unrecognized diabetes among hospitalized patients. Diabetes Care. 1998; 21:246–9.

2. 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 critically ill patients. N Engl J Med. 2001; 345:1359–67.

3. 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). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008; 358:125–39.

4. NICE-SUGAR Study Investigators. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hébert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009; 360:1283–97.

5. 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; 354:449–61.

6. Preiser JC, Devos P, Ruiz-Santana S, Mélot C, Annane D, Groeneveld J, Iapichino G, Leverve X, Nitenberg G, Singer P, Wernerman J, Joannidis M, Stecher A, Chioléro R. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med. 2009; 35:1738–48.

7. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a metaanalysis. JAMA. 2008; 300:933–44.

8. Kansagara D, Fu R, Freeman M, Wolf F, Helfand M. Intensive insulin therapy in hospitalized patients: a systematic review. Ann Intern Med. 2011; 154:268–82.

9. ACE/ADA Task Force on Inpatient Diabetes. American College of Endocrinology and American Diabetes Association Consensus statement on inpatient diabetes and glycemic control. Diabetes Care. 2006; 29:1955–62.

10. American Diabetes Association. 13. Diabetes Care in the Hospital, Nursing Home, and Skilled Nursing Facility. Diabetes Care. 2015; 38(Suppl 1):S80–5.

11. Korean Diabetes Association: Treatment guideline for diabetes. 4th ed.Seoul: Gold'Planning and Development;2011. p. p72–4.

12. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R. Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013; 39:165–228.

13. Writing Committee Members. Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM, Fesmire FM, Ganiats TG, Lincoff AM, Peterson ED, Philippides GJ, Theroux P, Wenger NK, Zidar JP, Anderson JL. American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/Non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2012; 126:875–910.

14. Qaseem A, Chou R, Humphrey LL, Shekelle P. Clinical Guidelines Committee of the American College of Physicians. Inpatient glycemic control: best practice advice from the Clinical Guidelines Committee of the American College of Physicians. Am J Med Qual. 2014; 29:95–8.

15. Todi S. Glycemic control in critically ill: A moving target. Indian J Crit Care Med. 2014; 18:229–33.

16. Rassias AJ, Marrin CA, Arruda J, Whalen PK, Beach M, Yeager MP. Insulin infusion improves neutrophil function in diabetic cardiac surgery patients. Anesth Analg. 1999; 88:1011–6.

17. Nielson CP, Hindson DA. Inhibition of polymorphonuclear leukocyte respiratory burst by elevated glucose concentrations in vitro. Diabetes. 1989; 38:1031–5.

18. Rayfield EJ, Ault MJ, Keusch GT, Brothers MJ, Nechemias C, Smith H. Infection and diabetes: the case for glucose control. Am J Med. 1982; 72:439–50.

19. Van den Berghe G. How does blood glucose control with insulin save lives in intensive care? J Clin Invest. 2004; 114:1187–95.

20. Amour J, Brzezinska AK, Jager Z, Sullivan C, Weihrauch D, Du J, Vladic N, Shi Y, Warltier DC, Pratt PF Jr, Kersten JR. Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms. Anesthesiology. 2010; 112:576–85.

21. Nazir FS, Alem M, Small M, Connell JM, Lees KR, Walters MR, Cleland SJ. Blunted response to systemic nitric oxide synthase inhibition in the cerebral circulation of patients with Type 2 diabetes. Diabet Med. 2006; 23:398–402.

22. Krinsley JS. Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proc. 2003; 78:1471–8.

23. Weston A, Caldera K, Doron S. Surgical care improvement project in the value-based purchasing era: more harm than good? Clin Infect Dis. 2013; 56:424–7.

24. Bagshaw SM, Egi M, George C, Bellomo R. Australia New Zealand Intensive Care Society Database Management Committee. Early blood glucose control and mortality in critically ill patients in Australia. Crit Care Med. 2009; 37:463–70.

25. Arabi YM, Tamim HM, Rishu AH. Hypoglycemia with intensive insulin therapy in critically ill patients: predisposing factors and association with mortality. Crit Care Med. 2009; 37:2536–44.

26. Boord JB, Graber AL, Christman JW, Powers AC. Practical management of diabetes in critically ill patients. Am J Respir Crit Care Med. 2001; 164:1763–7.

27. Egi M, Bellomo R, Stachowski E, French CJ, Hart G. Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology. 2006; 105:244–52.

28. Hermanides J, Vriesendorp TM, Bosman RJ, Zandstra DF, Hoekstra JB, Devries JH. Glucose variability is associated with intensive care unit mortality. Crit Care Med. 2010; 38:838–42.

29. Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab. 2001; 281:E924–30.

30. Schiekofer S, Andrassy M, Chen J, Rudofsky G, Schneider J, Wendt T, Stefan N, Humpert P, Fritsche A, Stumvoll M, Schleicher E, Häring HU, Nawroth PP, Bierhaus A. Acute hyperglycemia causes intracellular formation of CML and activation of ras, p42/44 MAPK, and nuclear factor kappaB in PBMCs. Diabetes. 2003; 52:621–33.

31. Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006; 295:1681–7.

32. Holzinger U, Warszawska J, Kitzberger R, Wewalka M, Miehsler W, Herkner H, Madl C. Realtime continuous glucose monitoring in critically ill patients: a prospective randomized trial. Diabetes Care. 2010; 33:467–72.

33. Haluzik M, Mraz M, Kopecky P, Lips M, Svacina S. Glucose control in the ICU: is there a time for more ambitious targets again? J Diabetes Sci Technol. 2014; 8:652–7.