He Y L, Ueyama H, Tashiro C, Mashimo T, Yoshiya I
Department of Anesthesiology, Hyogo College of Medicine, Nishinomiya City, Japan.
Anesthesiology. 2000 Oct;93(4):986-91. doi: 10.1097/00000542-200010000-00019.
The lungs have been mentioned as a possible site contributing to the extrahepatic clearance of propofol. The objective of the present study was to clarify the pulmonary disposition of propofol directly in human lungs by investigating both the first-pass uptake and pulmonary extraction at pseudo-steady state.
Nine patients were enrolled in the first-pass uptake study. Propofol (5 mg) and indocyanine green (ICG; 15 mg) were simultaneously administered via a central venous catheter within 1 s, and sequential arterial blood samples were obtained from the radial artery at 1-s intervals up to 45 s. Eleven patients were included in the infusion study, and propofol was infused via the jugular vein at a rate of 50 microgram. kg-1. min-1. Blood samples were simultaneously collected from pulmonary and radial arteries up to 60 min.
A pronounced difference in the dilution curves between propofol and ICG was observed, and 28.4 +/- 11.6% (mean +/- SD) of propofol was taken up during the single passage through the human lung. The mean pulmonary transit time of propofol (31.3 +/- 6.0 s) was significantly longer than that of ICG (22.4 +/- 2.7 s; P < 0.01), indicating that some of the propofol trapped by lungs returned to the circulation by back diffusion. In the constant infusion study, no significant differences were observed with the plasma concentrations of propofol between pulmonary and radial arteries except for that at 2 min. The area under the curve of pulmonary and radial arterial concentration curves to 60 min were 59.1 +/- 14.8 and 56.8 +/- 12.5 microg. ml-1. min-1, respectively. No significant difference was observed with the area under the curve, suggesting that metabolism was not involved in the pulmonary uptake in human lungs.
Most of the propofol that undergoes pulmonary uptake during the first pass was released back to the circulation by back diffusion. Metabolism was not involved in the pulmonary uptake in human lungs.
肺被认为可能是有助于丙泊酚肝外清除的一个部位。本研究的目的是通过研究伪稳态下的首过摄取和肺摄取率，直接阐明丙泊酚在人肺中的处置情况。
9例患者参与首过摄取研究。丙泊酚（5毫克）和吲哚菁绿（ICG；15毫克）在1秒内通过中心静脉导管同时给药，并在45秒内每隔1秒从桡动脉采集动脉血样。11例患者纳入输注研究，丙泊酚通过颈静脉以50微克·千克⁻¹·分钟⁻¹的速率输注。同时从肺和桡动脉采集血样，持续60分钟。
观察到丙泊酚和ICG稀释曲线有明显差异，单次通过人肺时，28.4±11.6%（均值±标准差）的丙泊酚被摄取。丙泊酚的平均肺转运时间（31.3±6.0秒）显著长于ICG（22.4±2.7秒；P<0.01），表明肺滞留的部分丙泊酚通过反向扩散返回循环。在持续输注研究中，除2分钟时外，肺和桡动脉的丙泊酚血浆浓度无显著差异。至60分钟时肺和桡动脉浓度曲线下面积分别为59.1±14.8和56.8±12.5微克·毫升⁻¹·分钟⁻¹。曲线下面积无显著差异，提示代谢不参与人肺的肺摄取。
首过过程中发生肺摄取的大部分丙泊酚通过反向扩散释放回循环。代谢不参与人肺的肺摄取。
