Pavlin D J, Coda B, Shen D D, Tschanz J, Nguyen Q, Schaffer R, Donaldson G, Jacobson R C, Chapman C R
Department of Anesthesiology, University of Washington School of Medicine, Seattle 98195, USA.
Anesthesiology. 1996 Jan;84(1):23-37. doi: 10.1097/00000542-199601000-00004.
Propofol and alfentanil frequently are administered together for intravenous sedation. This study investigated pharmacokinetic and pharmacodynamic interactions between propofol and alfentanil, at sedative concentrations, with specific regard to effects on ventilation, analgesia, sedation, and nausea.
Ten male volunteers underwent steady-state infusions on 3 separate days consisting of propofol alone, alfentanil alone, or a combination of the two. Target plasma concentrations for propofol were 150, 300, and 600 ng/ml for 1 h at each concentration; for alfentanil it was 40 ng/ml for 3 h. Assessment included serial measurements of (1) ventilatory function (minute ventilation, carbon dioxide production, end-tidal carbon dioxide, ventilatory response to rebreathing 7% CO2); (2) analgesia (subjective pain report in response to graded finger shock and evoked potential amplitude); (3) sedation (subjective rating, observer scores, and digit symbol substitution test); (4) nausea (visual analog scale, 0-100 mm).
During combination treatment, propofol plasma concentration was 22% greater than during propofol alone using replicate infusion schemes (P < 0.009). End-tidal carbon dioxide was unchanged by propofol, and increased equally by alfentanil and alfentanil/propofol combined (delta end-tidal carbon dioxide 7.5 and 6.2 mmHg, respectively). Analgesia with propofol/alfentanil combined was greater than with alfentanil alone. (Pain report decreased 50% by PA vs. 28% for alfentanil, P < 0.05). Sedation was greater with propofol/alfentanil combined than with alfentanil or propofol alone (digit symbol substitution test 30 for propofol/alfentanil combined vs. 57 for alfentanil, and 46 for propofol, P < 0.05). Nausea occurred in 50% of subjects during alfentanil, but in none during propofol/alfentanil combination treatment.
The combination of propofol and alfentanil produced greater sedation and analgesia than that with either drug alone. Propofol offset the emetic effects of alfentanil. Equivalent depression of the carbon dioxide response curve, and elevation of end-tidal carbon dioxide occurred with propofol/alfentanil combined and alfentanil.
丙泊酚和阿芬太尼常联合用于静脉镇静。本研究调查了在镇静浓度下丙泊酚和阿芬太尼之间的药代动力学和药效学相互作用，特别关注对通气、镇痛、镇静和恶心的影响。
10名男性志愿者在3个不同的日子接受稳态输注，分别为单独输注丙泊酚、单独输注阿芬太尼或两者联合输注。丙泊酚的目标血浆浓度分别为150、300和600 ng/ml，每个浓度维持1小时；阿芬太尼的目标血浆浓度为40 ng/ml，维持3小时。评估包括连续测量：(1)通气功能（分钟通气量、二氧化碳产生量、呼气末二氧化碳分压、对7%二氧化碳重复呼吸的通气反应）；(2)镇痛（对分级手指电击的主观疼痛报告和诱发电位幅度）；(3)镇静（主观评分、观察者评分和数字符号替代试验）；(4)恶心（视觉模拟评分，0 - 100 mm）。
在联合治疗期间，使用重复输注方案时，丙泊酚血浆浓度比单独输注丙泊酚时高22%（P < 0.009）。丙泊酚对呼气末二氧化碳分压无影响，阿芬太尼和阿芬太尼/丙泊酚联合使用时呼气末二氧化碳分压升高程度相同（呼气末二氧化碳分压变化分别为7.5和6.2 mmHg）。丙泊酚/阿芬太尼联合使用时的镇痛效果优于单独使用阿芬太尼。（丙泊酚/阿芬太尼联合使用时疼痛报告下降50%，阿芬太尼单独使用时下降28%，P < 0.05）。丙泊酚/阿芬太尼联合使用时的镇静效果优于单独使用阿芬太尼或丙泊酚（数字符号替代试验中，丙泊酚/阿芬太尼联合使用时评分为30，阿芬太尼单独使用时为57，丙泊酚单独使用时为46，P < 0.05）。单独使用阿芬太尼时，50%的受试者出现恶心，但丙泊酚/阿芬太尼联合治疗期间无恶心发生。
丙泊酚和阿芬太尼联合使用产生的镇静和镇痛效果比单独使用任何一种药物都更强。丙泊酚抵消了阿芬太尼的催吐作用。丙泊酚/阿芬太尼联合使用和阿芬太尼对二氧化碳反应曲线的抑制作用相当，呼气末二氧化碳分压升高程度也相同。
