Effect of midazolam on inflammatory mediators in patients with moderate and severe brain injury / 中国中西医结合急救杂志

ABSTRACT

Objective To investigate the effect of midazolam on inflammatory response in patients with moderate and severe craniocerebral injury and its protective effect on the brain and mechanism.Methods A prospective study was conducted.One hundred and twenty patients with moderate and severe craniocerebral injury admitted to the Intensive Care Unit (ICU) of Jiangsu Subei Peoples' Hospital from April 2013 to July 2016 were enrolled,and they were divided into a conventional treatment group (58 cases) and a midazolam group (62 cases) according to the random number table method.Both groups were given conventional western medicine treatment,and in cases with surgical indications,operations were performed;in midazolam group,additionally intravenous injection of midazolam 2-3 mg was given firstly,and then continuous intravenous infusion of the drug 0.05-0.10 mg· kg-1· h-1 was applied by a pump,and in operative patients,the above management was given 3 hours after operation.The mean arterial pressure (MAP),heart rate (HR),Riker sedation agitation score (SAS) and electroencephalogram bispectral index (BIS) were measured before and after treatment for 24,48 and 72 hours,respectively.The levels of interleukin-6 (IL-6) and soluble nerve chemotactic protein (sFkn) in plasm and cerebrospinal fluid (CSF) were measured by double antibody sandwich enzyme linked immunosorbent assay (ELISA) at each time point;the incidence of epilepsy and 28-day mortality were recorded.Results Before and after treatment,the MAP and HR in the two groups of patients were stable,the difference being not statistically significant (both P ＞ 0.05).Compared with those before treatment,after treatment the SAS score and BIS in two groups of patients were gradually decreased,and at 72 hours reached the lowest levels (SAS scoreconventional treatment group was 3.8 ± 1.0 vs.5.7 ± 2.0,midazolam group was 3.6 ± 0.9 vs.5.8 ± 1.7;BISconventional treatment group was 69± 12 vs.82± 12,midazolam group was 72± 15 vs.82± 12,all P ＜ 0.05),but there were no significant differences between the two groups (all P ＞ 0.05),suggesting that the two groups had achieved the desired goal of sedation.ELISA results showedcompared with those before treatment,after treatment for 24 hours,the CSF IL-6,sFkn and plasm sFkn levels were temporarily increased in short term,and then showed a tendency of gradually decreasing,and the plasm IL-6 presented persistently descending in the conventional treatment group,while in the midazolam group,since 24 hours after treatment,each index showed a trend of decrease and continued to 72 hours.After treatment at each time point,the CSF and plasm levels of IL-6 and sFkn were significantly lower in midazolam group than those of the conventional treatment group,and reached to the minimal levels at 72 hours [CSFIL-6 (ng/L) was 251.6 ± 145.7 vs.347.3 ± 146.4,sFkn (ng/L)289.7 ± 79.3 vs.423.6 ± 132.8;plasmIL-6 (ng/L) was 54.4± 27.3 vs.85.6 ± 41.8,SFkn (ng/L)919.9±426.3 vs.1 199.4 ± 414.8,all P ＜ 0.05].The incidence of epilepsy in the midazolam group was obviously lower than that in the conventional treatment group [1.61％ (1/62) vs.10.34％ (6/58),P ＜ 0.05],but there was no significant difference between midazolam group and the conventional treatment group in the 28-day mortality [11.29％ (7/62) vs.10.34％ (6/58),P ＞ 0.05].Conclusion Midazolam can reduce the incidence of epilepsy in patients with moderate and severe traumatic brain injury,and its brain protective effect may be related to the decrease of CSF and plasm IL-6 and sFkn levels.