Weinberg Guy L, Ripper Richard, Murphy Patricia, Edelman Lucas B, Hoffman William, Strichartz Gary, Feinstein Douglas L
Department of Anesthesiology, University of Illinois College of Medicine at Chicago, Chicago, IL 60612, USA.
Reg Anesth Pain Med. 2006 Jul-Aug;31(4):296-303. doi: 10.1016/j.rapm.2005.02.011.
Infusion of a lipid emulsion has been advocated for treatment of severe bupivacaine cardiac toxicity. The mechanism of lipid rescue is unknown. These studies address the possibility that lipid infusion reduces cardiac bupivacaine content in the context of cardiac toxicity.
We compared the effects of a 1% lipid emulsion with standard Krebs buffer after inducing asystole in isolated rat heart with 500 micromol/L bupivacaine. We compared times to first heart beat and recovery of 90% of baseline rate pressure product (RPP = heart rate x [left ventricular systolic pressure - left ventricular diastolic pressure]) between controls and hearts receiving 1% lipid immediately after bupivacaine. We also used minibiopsies to compare control bupivacaine tissue content with hearts getting lipid immediately after an infusion of radiolabeled bupivacaine. We then compared bupivacaine efflux from hearts with and without lipid infusion started 75 seconds after radiolabeled bupivacaine was administered.
Infusion of lipid resulted in more rapid return of spontaneous contractions and full recovery of cardiac function. Average (+/- SEM) times to first beat and to 90% recovery of rate pressure product were 44.6 +/- 3.5 versus 63.8 +/- 4.3 seconds (P < .01) and 124.7 +/- 12.4 versus 219.8 +/- 25.6 seconds (P < .01) for lipid and controls, respectively. Lipid treatment resulted in more rapid loss of bupivacaine from heart tissue (P < .0016). Late lipid infusion, 75 seconds after bupivacaine infusion ended, increased the release of bupivacaine measured in effluent for the first 15-second interval compared with controls (183 vs. 121 nmol, n = 5 for both groups, P < .008).
Lipid emulsion speeds loss of bupivacaine from cardiac tissue while accelerating recovery from bupivacaine-induced asystole. These findings are consistent with the hypothesis that bupivacaine partitions into the emulsion and supports the concept of a "lipid sink." However, the data do not exclude other possible mechanisms of action.
输注脂质乳剂已被推荐用于治疗布比卡因严重心脏毒性。脂质挽救的机制尚不清楚。这些研究探讨了在心脏毒性情况下脂质输注降低心脏布比卡因含量的可能性。
在用500微摩尔/升布比卡因诱导离体大鼠心脏心搏停止后，我们比较了1%脂质乳剂与标准 Krebs 缓冲液的效果。我们比较了对照组与布比卡因给药后立即接受1%脂质的心脏首次心跳时间以及心率血压乘积（RPP = 心率×[左心室收缩压 - 左心室舒张压]）恢复至基线值90%的时间。我们还使用微量活检来比较对照组布比卡因组织含量与输注放射性标记布比卡因后立即接受脂质的心脏的布比卡因组织含量。然后，我们比较了在给予放射性标记布比卡因75秒后开始和未开始脂质输注的心脏中布比卡因的流出情况。
输注脂质导致自发收缩恢复更快且心脏功能完全恢复。脂质组和对照组首次心跳的平均（±标准误）时间以及心率血压乘积恢复至90%的时间分别为44.6±3.5秒对63.8±4.3秒（P < .01）和124.7±12.4秒对219.8±25.6秒（P < .01）。脂质治疗使布比卡因从心脏组织中更快地清除（P < .0016）。与对照组相比，在布比卡因输注结束75秒后进行的晚期脂质输注增加了最初15秒内流出液中布比卡因的释放量（183对121纳摩尔，两组n均为5，P < .008）。
脂质乳剂加快布比卡因从心脏组织中的清除，同时加速布比卡因诱导的心搏停止后的恢复。这些发现与布比卡因分配到乳剂中的假设一致，并支持“脂质池”的概念。然而，数据并未排除其他可能的作用机制。
