Effects of hyperglycemia and insulin therapy on outcome in a hyperglycemic septic model of critical illness

J Trauma. 2006 Apr;60(4):865-72. doi: 10.1097/01.ta.0000215565.29846.ab.

Abstract

Background: The effects of hyperglycemia and insulin therapy on septic outcome have not been well studied.

Methods: Septic hyperglycemia was induced by infusion of TPN (254 kcal/kg x d) immediately following cecal ligation and puncture (CLP) surgery in rats. Animals (N = 109) were monitored for blood glucose and followed for survival for 4 days. Separate cohorts (N = 36) were sacrificed at 22 hours post-CLP and analyzed for cytokines/chemokines, hormones, and organ damage markers. The effects of insulin treatment on 4 day survival were also examined (N = 60).

Results: Hyperglycemic septic animals had significantly higher blood glucose (p < 0.0001), plasma proinflammatory cytokine levels, serum organ damage markers (p < 0.05) and reduced mean survival time (p < 0.001). Insulin treatment (2 IU/kg/hr) resulted in significantly lower blood glucose (p < 0.01) and improved 4 day survival (p < 0.03).

Conclusions: Hyperglycemia is associated with greater morbidity and mortality in sepsis. Insulin therapy significantly improved survival suggesting that management of hyperglycemia with insulin may improve outcome in septic patients.

MeSH terms

  • Animals
  • Blood Glucose*
  • Disease Models, Animal*
  • Female
  • Hyperglycemia / drug therapy*
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Parenteral Nutrition, Total
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / blood*
  • Sepsis / metabolism

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin