肝功能对患者意识消失时咪达唑仑浓度和脑电双频谱指数的影响

Relationship of liver function with midazolam concentration and bispetral index on loss of consciousness during general anesthesia

目的探索肝功能对意识消失时咪达唑仑浓度和双频谱脑电指数的影响。方法选择无听力障碍且近期未服用精神类药物的患者45例。肝功能正常（A组，n=15）和中度脂肪肝（B组，n=15）行择期腹腔镜下胆囊切除术；终末期肝病（C组，n=15）行肝脏移植手术。3组患者均予靶控输注咪达唑仑，同时进行双频谱脑电图监测（BIS），在患者意识消失时同时记录BIS值和抽取静脉血测量咪达唑仑血药浓度。用logistic回归分析咪达唑仑实测药物浓度与BIS的关系，计算50％患者意识消失时咪达唑仑的血药浓度（EC50）和BIS值（BIS50）。结果A、B组意识消失咪达唑仑EC50分别为310．4ng／ml和294.8ng／ml（P〉0．05），BIS50分别为51和52（P〉0.05）；C组患者意识消失时咪达唑仑EC50低于A、B组而BIS50高于A、B组（P〈0．01）。结论轻度肝功能异常不影响患者意识消失时咪达唑仑的EC50和BIS50，而终末期肝病患者对咪达唑仑中枢抑制更敏感，其BIS预测意识消失概率发生情况发生的敏感性受到影响。

Objective To investigate the relationship of liver function with midazolam concentration and bispectral index （BIS） on loss of consciousness during general anesthesia. Methods Forty-five patients underwent operation under general anesthesia were enrolled in the study including 15 cases with normal liver function （group A）, 15 cases with moderate fatty liver （group B） and 15 cases with end-stage liver disease （group C）. Midazolam was administered using a target-controlled infusion device to increase concentration gradually. At the time of loss of consciousness （LOC）, the BIS was recorded and the blood sample was withdrawn for measurement of midazolam concentration. Logistic regression analysis was used to calculate EC50 of midazolam and BIS50 at the time to LOC. Results The ECho of midazolam was 310.4 and 294.8 ng/ml （P 〉0.05）, BIS50 were 51 and 52 in Group A and B at the time to LOC. LOC occurred at the lower EC50 of midazolam and at a high BIS50 in group C compared with groups A and B （P〈0.01）. Conclusion Patients with end-stage liver disease are more sensitive to midazolam and the prediction of BIS for LOC was affected, while there are no changes in patients with minimally abnormal liver function.