Intensive Insulin Therapy After Severe Traumatic Brain Injury: a Randomized Clinical Trial

Introduction: To investigate the risks and possible benefits of routine versus intensive insulin therapy, assessed by the frequency of hypoglycemic events defined as a glucose concentration less than 80 mg/dl (<4.44 mmol/l) in patients admitted to the intensive care unit (ICU) after severe traumatic brain injury (TBI).

Methods And Results: Ninety-seven patients admitted after severe TBI, were enrolled and randomly assigned to two groups of target glycemia. Insulin was infused at conventional rates when blood glucose levels exceeded 220 mg/dl (12.22 mmol/l) or at intensive rates, to maintain glycemia at 80-120 mg/dl (4.44-6.66 mmol/l). The following primary and outcome variables were measured during follow-up: hypoglycemic episodes, duration of ICU stay, infection rate, and 6-month mortality and neurologic outcome measured using the Glasgow Outcome Scale (GOS). Episodes of hypoglycemia (defined as blood glucose <80 mg/dl or 4.44 mmol/l) were significantly higher in patients receiving intensive insulin therapy: median (min-max) conventional insulin therapy 7 (range 0-11) vs. intensive insulin therapy 15 (range 6-33); P<0.0001. Duration of ICU stay was shorter in patients receiving intensive insulin therapy (7.3 vs. 10.0 days; P < 0.05); while infection rates during ICU stay (25.0% vs. 38.8%, P = 0.15), and GOS scores and mortality at 6 months were similar in the two groups.

Conclusions: Intensive insulin therapy significantly increases the risk of hypoglycemic episodes. Even though patients receiving intensive insulin therapy have shorter ICU stays and infection rates similar to those receiving conventional insulin therapy, both groups have similar follow-up mortality and neurologic outcome. Hence if intensive insulin therapy is to be used, great effort must be taken to avoid hypoglycemia.