Intensive insulin therapy on infection rate, days in NICU, in-hospital mortality and neurological outcome in severe traumatic brain injury patients: a randomized controlled trial.

Objective: Evaluate the impact of an intensive insulin therapy and conventional glucose control protocol during staying in neurological intensive care unit (NICU) on infection rate, days in NICU, in-hospital mortality and long-term neurological outcome in severe traumatic brain injury (TBI) patients.

Methods: A total of 240 patients with severe TBI (GCS score 3-8) admitted to NICU were prospectively enrolled and randomly assigned either to conventional insulin therapy or to intensive insulin therapy. Patients in intensive glucose control group (n=121) received continuous insulin infusion to maintain glucose levels between 4.4 m mol/l (80 mg/dl) and 6.1 m mol/l (110 mg/dl). Patients in the conventional treatment group (n=119) were not given insulin unless glucose levels were greater than 11.1 m mol/l (200mg/dl). Both groups were treated with insulin infusion to maintain normoglycemia after leaving NICU. Comparison was made against conventional insulin therapy using a randomized trial design. The primary outcomes is the mortality rate at 6 months follow-up. The second outcomes including ICU infection rate, duration of ICU stay, in-hospital mortality rate and neurologic outcome at 6 months follow-up.

Results: There was no significant difference in gender (66% vs. 67% male), age (46+/-11 years vs. 45+/-10 years), APACHE II score (30 vs. 29), TISS-28 score (47 vs. 46), and Glasgow Coma Score (GCS, 5.3 vs. 5.3) between the two groups. Overall mortality rates at 6 months follow-up were similar in the 2 groups (61 of 117, 52.1% vs. 62 of 116, 53.4%; P=0.8). The infection rate during the study was significantly higher in patients who received conventional insulin therapy than that in patients who received intensive insulin therapy (46.2% vs. 31.4%; P<0.05). The days stay in NICU was shorter in intensive insulin control group than that in conventional therapy group [4.2 days vs. 5.6 days (medians) P<0.05]. The in-hospital mortality during the study was similar in conventional and intensive therapy groups (34 of 119, 28.6% vs. 35 of 121, 28.9% in the conventional and intensive insulin therapy groups; P=0.85). The neurologic outcome according to Glasgow Outcome Score (GOS) at 6 months (GOS 5 and 4) was better in the intensive insulin therapy group (34 of 117, 29.1%) than that in the conventional therapy group (26 of 116, 22.4%, P<0.05).

Conclusions: Mortality rates at 6 months follow-up are not affected by intensive glucose control in patients with severe TBI. Intensive insulin therapy decreases infection rate and days in NICU and improves the neurological outcome at 6 months follow-up, while has no obvious influence on in-hospital mortality of severe TBI patients.