18. Intensive Insulin Therapy in the ICU

Background 

  • Elevated blood glucose is common in the ICU due to insulin resistance, increased catecholamines, and increased cortisol. 
  • Hyperglycemia in the critically ill patient is associated with worse outcomes (increased mortality) from observational data. However, hypoglycemia is also associated with adverse outcomes. 

Evidence for Insulin Therapy 

  • Intensive insulin therapy: 
    • One early RCT showed a mortality benefit to tight blood glucose control (the Leuven protocol for intensive insulin therapy, goal BG 110-140). However, this may not be generalizable to most ICU patients as it used a nutritional strategy that is not the standard of care (van den Berghe et al. 2006). 
  • Conventional insulin therapy: 
    • Several RCTs and meta-analyses have demonstrated no mortality benefit or increased mortality with intensive insulin therapy. 
    • NICE-SUGAR trial: multi-center RCT of 6,104 MICU and SICU patients demonstrated increased 90-day mortality with tight (81-108) vs conventional (target <180) control (27.5% vs. 24.9%, p=0.02). 
    • VISEP trial: multi-center RCT of MICU and SICU patients with severe sepsis. Stopped early after demonstrating increased hypoglycemia and serious adverse events with tight control. 
    • Glucontrol trial: multi-center RCT of MICU and SICU patients. Stopped early due to protocol violations but demonstrated increased hypoglycemia and no mortality benefit to tight (80-110) vs conventional (<180) control.  

Conclusions 

  • Although one early trial showed a mortality benefit to intensive insulin therapy (goal BG 80-110), since then multiple RCTs and meta-analyses (most notably NICE-SUGAR and VISEP trials) have shown no mortality benefit or increased mortality and increased hypoglycemia with intensive insulin therapy compared with conventional glucose control.  
  • Although there is variation in the lower end of target BG among society recommendations, guidelines (Surviving Sepsis 2016, SCCM 2012, ACP, ADA/AACE consensus statement 2009) recommend a target upper limit of BG <180.  

Keywords: NICE SUGAR, insulin, intensive insulin, glycemic control, hyperglycemia, hypoglycemia 

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Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360:1283-97. 

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Moghissi ES, Korytkowski MT, DiNardo M, et al.; American Association of Clinical Endocrinologists; American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care 2009;32:1119–1131. 

Preiser JC, Devos P, Ruiz-Santana S, et al. 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. Jacobi J, et al. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. Crit Care Med. 2012;40: 3251-3276. 

Van den Berghe, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345:1359.