Myburgh J A, Upton R N, Grant C, Martinez A
Department of Anaesthesia and Intensive Care, University of Adelaide, Royal Adelaide Hospital, Australia.
Intensive Care Med. 2001 Jan;27(1):276-82. doi: 10.1007/s001340000793.
To determine the effects of exogenous ramped infusions of epinephrine, norepinephrine and dopamine on arterial and effluent brain blood concentrations of propofol under steady state intravenous anesthesia.
Prospective, randomized animal study.
University research laboratory.
Five adult female merino sheep.
Induction (5 mg/kg) and continuous infusion of propofol (15 mg/min) with controlled mechanical ventilation to maintain PaCO2 40 mmHg. After 1 h of continuous anesthesia, each animal randomly received ramped infusions of epinephrine, norepinephrine (10, 20, 40 microg/min) and dopamine (10, 20, 40 microg x kg x min) in 3 x 5 min intervals followed by a 30-min washout period.
Arterial and sagittal sinus whole blood for determination of propofol concentrations using high-pressure liquid chromatography. Cardiac output using a thermodilution method. Level of consciousness using an observational scale.
All three drugs significantly and transiently increased cardiac output in a dose-dependent fashion to a maximum of 146-169% of baseline. Baseline arterial and sagittal sinus propofol concentrations were not statistically different prior to catecholamine infusions. All three drugs significantly reduced mean arterial propofol concentrations (95 % CI, p < 0.05): epinephrine to 41.8% of baseline (11.4-72), norepinephrine to 63 % (27-99) and dopamine to 52.9 % (18.5-87.3). There were parallel reductions of concentrations in sagittal sinus blood leaving the brain. The lowest blood concentrations were associated with emergence from anesthesia. Arterial concentrations were inversely related to the simultaneously determined cardiac output (r2 = 0.74, p < 0.0001). Comparison of the data with the predictions of a previously developed recirculatory model of propofol disposition in sheep showed the data were consistent with a mechanism based on increased first pass dilution and clearance of propofol secondary to the increased cardiac output.
Catecholamines produced circulatory changes that reversed propofol anesthesia. These observations have potential clinical implications for the use of propofol in hyperdynamic circulatory conditions, either induced by exogenous catecholamine infusions or pathological states.
确定在稳态静脉麻醉下，外源性递增输注肾上腺素、去甲肾上腺素和多巴胺对动脉血及脑流出液中丙泊酚浓度的影响。
前瞻性随机动物研究。
大学研究实验室。
5只成年雌性美利奴羊。
诱导（5mg/kg）并持续输注丙泊酚（15mg/min），同时进行控制机械通气以维持动脉血二氧化碳分压（PaCO2）为40mmHg。持续麻醉1小时后，每只动物随机接受以3个5分钟间隔递增输注肾上腺素、去甲肾上腺素（10、20、40μg/min）和多巴胺（10、20、40μg·kg·min），随后有30分钟的洗脱期。
采集动脉血和矢状窦全血，采用高压液相色谱法测定丙泊酚浓度。采用热稀释法测量心输出量。使用观察量表评估意识水平。
所有三种药物均以剂量依赖方式显著且短暂地增加心输出量，最高可达基线的146 - 169%。在输注儿茶酚胺之前，基线动脉血和矢状窦丙泊酚浓度无统计学差异。所有三种药物均显著降低平均动脉丙泊酚浓度（95%可信区间，p < 0.05）：肾上腺素降至基线的41.8%（11.4 - 72），去甲肾上腺素降至63%（27 - 99），多巴胺降至52.9%（18.5 - 87.3）。离开大脑的矢状窦血中浓度也有相应降低。最低血药浓度与麻醉苏醒相关。动脉血浓度与同时测定的心输出量呈负相关（r2 = 0.74，p < 0.0001）。将数据与先前建立的绵羊丙泊酚处置再循环模型的预测结果进行比较，结果表明这些数据与基于心输出量增加导致丙泊酚首过稀释和清除增加的机制一致。
儿茶酚胺引起的循环变化可逆转丙泊酚麻醉。这些观察结果对于在外源性儿茶酚胺输注或病理状态诱导的高动力循环状态下使用丙泊酚具有潜在的临床意义。
