A Meta-analysis: The Protective Effects Of α₂-adrenoceptor Agonists On Brain In Patients Undergoing Neurosurgical Procedures

Objective: To systematically evaluate the efficacy of α₂-adrenoceptor agonists used for patients undergoing neurosurgical procedures to improve brain injury.Method: Searched Pub-Med,the Cochrane Library,EBSCO,Ovid,Chinese Biological and Medical Database（CBM）,Wang Fang Data and Chinese Journal Database（CNKI）.Limits were set to literatures published in English or Chinese before December,2015.According to the inclusive and exclusive criteria,all randomized controlled trials about α₂-agonists used for patients undergoing neurosurgical procedures to improve brain injury were enrolled,and then the quality of eligible studies was assessed.Lastly,depending on the results of heterogeneity test,predefined outcomes were analyzed with a random-effects model or fixed-effects model by Revman5.2 software.For continuous data,the outcomes were calculated by mean difference（MD）or standard mean difference（SMD）and 95% Confidence Interval（the Confidence Interval,95% CI）,while odds ratio（OR）or relative ratio（RR）and 95%CI was used to expressed the pooled effects for dichotomous data.At the same time,Forest plot was also obtained.Result: Twenty-seven Randomized Controlled Trials including 1169 patients were included,24 of which were about Dexmedetomidine,3 about Clonidine.Findings for meta-analysis of various outcomes were summarized.Primary results shown that,compared with placebo,α₂-agonists reduced a surge of S100-β（SMD=-1.43,95%CI:-2.12^-0.73）and NSE（SMD=-1.51,95%CI:-2.41^-0.60）in patients with brain injury;suppressed the release of TNF-α（SMD=-2.05,95%CI:-2.82^-1.28）and IL-6（SMD=-1.79,95%CI:-2.88^-0.70）;decreased serum norepinephrine concentration（SMD=-0.61,95%CI:-1.14^-0.09）,cortisol concentration（SMD=-0.58,95%CI:-1.10^-0.06）and glucose level（SMD=-0.79,95%CI:-1.11^-0.46）;increased the scores of MMSE（MD=1.65,95%CI: 0.40 2.89）and improved postoperative cognitive function.In addition,Alpha-2 agonists could attenuate the increasing of MAP,HR and ICP without changing the cerebral perfusion pressure in response to stress reaction.However,on cerebral oxygen metabolism,we found that α₂-agonists had no significant effects in Ca O2,Da-jv O2 and CEO2,maintaining stable hemodynamics and intracranial homoeostasis.Conclusion: Alpha-2 adrenoceptor agonists could maintain stable hemodynamics and intracranial homoeostasis;reduce the release of inflammatory mediators and neuroendocrine hormones;improve postoperative cognitive function.They may be used in neurosurgical procedures to alleviate the second brain injury and exerte an effect on brain protection.