A model of the ventilatory depressant potency of remifentanil in the non-steady state

被引:57
作者
Bouillon, T
Bruhn, J
Radu-Radulescu, L
Andresen, C
Cohane, C
Shafer, SL
机构
[1] Univ Bern, Inselspital, Dept Anesthesia, CH-3010 Bern, Switzerland
[2] Bonn Univ Hosp, Dept Anesthesia, Bonn, Germany
[3] Duke Univ, Dept Anesthesia, Durham, NC 27706 USA
[4] Palo Alto Hlth Care Syst, Dept Anesthesia, Palo Alto, CA USA
[5] Stanford Univ, Sch Med, Stanford, CA 94305 USA
[6] PAVAHCS, Anesthesiol Serv 112A, Palo Alto, CA 94304 USA
[7] Univ Calif San Francisco, San Francisco, CA 94143 USA
关键词
D O I
10.1097/00000542-200310000-00007
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background: The C-50 of remifentanil for ventilatory depression has been previously determined using inspired carbon dioxide and stimulated ventilation, which may not describe the clinically relevant situation in which ventilatory depression occurs in the absence of inspired carbon dioxide. The authors applied indirect effect modeling to non-steady state PaCO2 data in the absence of inspired carbon dioxide during and after administration of remifentanil. Methods: Ten volunteers underwent determination of carbon dioxide responsiveness using a rebreathing design, and a model was fit to the end-expiratory carbon dioxide and minute ventilation. Afterwards, the volunteers received remifentanil in a stepwise ascending pattern using a computer-controlled infusion pump until significant ventilatory depression occurred (end-tidal carbon dioxide [PeCO(2)] > 65 mmHg and/or imminent apnea). Thereafter, the concentration was reduced to 1 ng/ml. Remifentanil pharmacokinetics and PaCO2 were determined from frequent arterial blood samples. An indirect response model was used to describe the PaCO2 time course as a function of remifentanil concentration. Results: The time course of hypercarbia after administration of remifentanil was well described by the following pharmacodynamic parameters: F (gain of the carbon dioxide response), 4.30; k(c0) carbon dioxide, 0.92 min(-1); baseline PaCO2,42.4 mmHg; baseline minute ventilation, 7.06 1/min; k(el,CO2), 0.08 min(-1); C-50 for ventilatory depression, 0.92 ng/ml; Hill coefficient, 1.25. Conclusion: Remifentanil is a potent ventilatory depressant. Simulations demonstrated that remifentanil concentrations well tolerated in the steady state will cause a clinically significant hypoventilation following bolus administration, confirming the acute risk of bolus administration of fast-acting opioids in spontaneously breathing patients.
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页码:779 / 787
页数:9
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