Intensive insulin therapy in brain injury: a meta-analysis

Many studies have addressed the question of whether intensive insulin therapy (IIT) provides better outcomes for brain-injured patients than does conventional insulin therapy (CIT), with conflicting results. We performed a systematic review and meta-analysis of the literature to estimate the effect of IIT on patients with brain injury. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and citations of key articles and selected "all randomized controlled trials" (RCTs) comparing the effect of IIT to CIT among adult patients with acute brain injury (traumatic brain injury, stroke, subarachnoid hemorrhage, and encephalitis). Of the 2807 studies, we identified 9 RCTs with a total of 1160 patients for analysis. IIT did not appear to decrease the risk of in-hospital or late mortality (RR=1.04, 95% CI=0.75, 1.43 and RR=1.07, 95%CI=0.91, 1.27 respectively). No significant heterogeneity was found (I(2)=0.0%). IIT also did not have a protective effect on long-term neurological outcomes (LTNO) (RR=1.10, 95% CI=0.96, 1.27). IIT, however, did decrease the rate of infections (RR=0.76, 95% CI=0.58, 0.98). Heterogeneity was present (I(2)=64%), which was eliminated upon sensitivity analysis bringing the RR to 0.66 (95% CI=0.55, 0.80, I(2)=0%). IIT increased the rate of hypoglycemic episodes (RR=1.72, 95% CI=1.20, 2.46) however there was intractable heterogeneity present (I(2)=89%), which did not resolve upon sensitivity analysis. We found no evidence of publication bias by Egger's test (p=0.50). To conclude, IIT has no mortality or LTNO benefit to patients with brain injury, but is beneficial at decreasing infection rates.