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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