靶控输注异丙酚在脑脊液中药物浓度的实验研究

Cerebrospinal fluid concentrations of propofol during target-controlled infusion

目的 研究靶控效应室浓度输注异丙酚时脑脊液浓度、效应室浓度以及BIS之间的相互关系,探讨靶控效应室浓度输注的准确性。方法 选择成年健康杂种犬12只,以3μg/ml为效应室靶浓度进行靶控输注15min。取脑脊液用高效液相色谱荧光检测法测定异丙酚的浓度。同时监测BIS以及血液动力学和呼气末CO2。结果 靶控效应室浓度输注后,模拟血浆浓度与效应室浓度在10.9min时达到平衡,并维持在3μg/ml的靶浓度水平。15min停止输注后模拟血浆和效应室浓度逐渐衰减。脑脊液峰值浓度约为0.29±0.14μg/ml,但各时点的浓度值均比效应室浓度低（P<0.05）,平均为效应室浓度的18·7％。BIS与脑脊液浓度均在5min达到峰值,而效应室浓度相对滞后。且BIS与脑脊液浓度的相关性（γ=0.9195）优于效应室浓度（γ=0.554）。给药后犬的血压下降但未出现严重的心血管副作用。结论 靶控效应室浓度输注异丙酚时,效应室浓度与BIS的变化不完全一致可能是药代动力学参数造成的差异。脑脊液浓度与BIS相关较好,比血药浓度更能反映效应部位的药代学特征。

Objective To investigate the relationship between bispectral index (BIS) and cerebrospinal fluid (CSF) concentrations of propofol or effect-site concentrations during target-controlled infusion (TCI) of propofol and evaluate the accuracy of the infusion system targeting at effect-site concentration.Methods Twelve healthy mongrel dogs weighing (17.04± 1.53) kg were anesthetized with intramuscular ketamine 5 mg·kg-1 followed by enflurane inhalation. A catheter was inserted into subarachnoid space and advanced to the base of skull for the collection of CSF. BIS, hemodynamics and PETCO2 were monitored continuously during the experiment. Target effect-site propofol concentration was set at 3 μg·ml-1 and infusion was continued for 15 min. CSF was collected at 1, 3, 5, 10, 15, 20, 30, 45 and 60 min after infusion was started for determination of propofol concentration by high performance liquid chromatography with fluorescence detection. Results The equilibrium between predicted plasma and effect-site concentration was reached at 10.9 min and the target effect-site concentration was maintained at 3 μg·ml-1 .The peak CSF concentration of propofol was (0.29± 0.14)μg·ml-1 .CSF concentrations were much lower than the effect-site concentrations at all sampling times (about 18.7% of the effect-site concentration on average) . BIS was consistent with the CSF concentrations of propofol. Both of them reached the lowest or peak values at 5 min after infusion was started, while the peak effect-site concentration was reached relatively later. BIS was found to be better correlated with CSF concentration (γ = 0.9195) than with the effect-site concentration (γ = 0.554) . The dogs developed hypotension as expected but no other severe adverse effect was observed. Conclusion The inconsistency of BIS with effect-site concentration during TCI of propofol may result from its pharmacokinetic parameters. Good correlation between BIS and CSF concentration indicates that CSF concentration can reflect the pharmacokinetic profileof propofol at effect-site more accurately than the plasma concentration during TCI of propofol targeting at effect-site concentration.