七氟醚和依托咪酯镇静催眠效应的相互作用

目的 评价七氟醚和依托咪酯镇静催眠效应的相互作用.方法 择期全麻手术患者24例,ASA Ⅰ或Ⅱ级,年龄18～59岁,体重指数17～27 kg/m2.试验Ⅰ 12例患者靶控输注依托咪酯,效应室靶浓度依次为0.05、0.1、0.2、0.3、0.4、0.5 μg/ml.效应室浓度依次达到预设浓度2 min时,记录反应熵(RE)、状态熵(SE)和警觉/镇静(OAA/S)评分,然后停止输注依托咪酯.随机分为3组(n=4),A1组、B1组、C1组吸入七氟醚,呼气末浓度分别为0.5%、1%、2%.七氟醚呼气末浓度达预定浓度的95%或以上时,靶控输注依托咪酯,效应室靶浓度依次为0.2、0.3、0.4、0.5 μg/ml.效应室浓度依次达到预设浓度2 min时,记录RE、SE和OAA/S评分.试验Ⅱ 12例患者吸入七氟醚,呼气末浓度依次为0.5%、1%、2%、3%、4%、5%.依次达到预定呼气末浓度时,记录RE、SE和OAA/S评分,然后停止吸人七氟醚,吸氧洗脱七氟醚.随机分为3组(n=4),A2组、B2组、C2组靶控输注依托咪酯,效应室靶浓度分别为0.05、0.1、0.2 μg/ml.效应室浓度达到预设浓度2 min时,吸入七氟醚,呼气末浓度依次为0.5%、1%、2%、3%、4%、5%.依次达到预定呼气末浓度时,记录RE、SE和OAA/S评分.采用反应曲面法评价RE、SE和OAA/S评分,判断七氟醚和依托咪酯镇静催眠效应的相互作用.结果 RE和SE的相互作用指数的拟合值及其95%可信区间分别为0.32(-0.07～0.71)、0.25(-0.12～0.63)(P>0.05).OAA/S评分的相互作用指数的拟合值及其95%可信区间为2.25(0.58～3.93)(P<0.05).结论 以脑电熵指数反映镇静催眠效应时七氟醚和依托咪酯为相加作用;以OAA/S评分反映镇静催眠效应时七氟醚和依托咪酯为协同作用.

Sedative and hypnotic interactions between sevoflurane and etomidate

Objective To evaluate sedative and hypnotic interactions between sevoflurane and etomidate. Methods Twenty-four ASA Ⅰ or Ⅱ patients aged 18-59 yr with body mass index 17-27 kg/m2 undergoing elective surgery under general anesthesia were included in this study. Part Ⅰ Twelve patients received etemidate by TCI at target effect-site concentrations (Ce) of 0.05, 0.1, 0.2, 0.3, 0.4 and 0.5 μg/ml in turn. When the preset concentrations were reached for 2 min, the spectral entropy index (response entropy, RE; state entropy, SE) and Observer's Assessment of Alertuess/Sedation (OAA/S) score were recorded and TCI of etomidate was stopped. The patients were randomly divided into 3 groups ( n = 4 each), inhaling sevoflurane with end-tidal concentrations of 0.5% (group A1 ), 1% (group B1 ) and 2% (group C1 ). When the sevoflurane concentration reached 95% predetermined end-tidal concentration or more, etomidate was administered via TCI at Ce of 0.05, 0.1, 0.2, 0.3, 0.4 and 0.5 μg/ml in turn. When the preset concentrations were reached for 2 min, RE, SE and OAA/S score were recorded. Part Ⅱ Twelve patients inhaled sevoflurane with end-tidal concentrations of 0.5%, 1%, 2%, 3%, 4% and 5% in turn. When the predetermined end-tidal concentrations were reached, RE, SE and OAA/S score were recorded and inhalation of sevoflurane was stopped. Sevoflurane was washed out. Then the patients were randomly divided into 3 groups ( n = 4 each), receiving etomidate by TCI at Ce of 0.05 μg/ml (group A2), 0.1 μg/ml ( group B2) and 0.2 μg/ml ( group C2) respectively. The patients inhaled sevoflurane with end-tidal concentrations of 0.5%, 1%, 2%, 3%, 4% and 5% in turn 2 min after the preset concentrations were reached. When the predetermined end-tidal concentrations were reached, RE, SE and OAA/S score were recorded. Response surface pharmacodynamic interaction models were constructed to evaluate RE, SE and OAA/S score and determine sedative and hypnotic interactions between sevoflurane and etomidate. Results The fitted values of the interaction index a of RE and SE (95% confidence intervals, 95% CI) were 0.32 ( - 0.07-0.71 ) and 0.25 (-0.12-0.63) respectively (P > 0.05). The fitted value of the interaction index a of OAA/S score (95% CI) was 2.25 (0.58-3.93) (P <0.05).Conclusion The interaction between etomidate and sevoflurane is additive and synergistic for sedation and hypnosis assessed by spectral entropy index and by OAA/S score respectively.