Lee Bee B, Ngan Kee Warwick D, Plummer John L, Karmakar Manoj K, Wong April S Y
Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Anesth Analg. 2002 Nov;95(5):1402-7, table of contents. doi: 10.1097/00000539-200211000-00055.
The addition of epinephrine to ropivacaine has not been recommended because ropivacaine has intrinsic vasoconstrictor properties. However, few pharmacokinetic data are available on the addition of epinephrine to epidural ropivacaine in humans. In this prospective, double-blinded study, we randomized patients having elective abdominal hysterectomy to receive epidural ropivacaine 1.5 mg/kg, diluted in 15 mL, either with (epinephrine group, n = 12) or without (plain group, n = 12) epinephrine 5 microg/mL and then measured arterial and venous plasma concentrations of ropivacaine at intervals up to 180 min. We found that arterial and venous plasma ropivacaine concentrations were smaller in the epinephrine group compared with the plain group in the first 60 min after the drug administration (P < 0.01). Mean (+/- SD) maximum total plasma ropivacaine concentration was smaller in the epinephrine group (arterial, 0.92 +/- 0.32 microg/mL; venous, 0.82 +/- 0.33 microg/mL) compared with the plain group (1.31 +/- 0.39 microg/mL and 1.31 +/- 0.50 microg/mL, respectively; P = 0.01). Time to maximum total plasma ropivacaine concentration was not significantly different between groups (mean +/- SD; arterial, 16 +/- 2 min; venous, 23 +/- 2 min in the epinephrine group versus 9 +/- 2 min and 12 +/- 3 min, respectively, in the plain group; P = 0.08). Arterial plasma ropivacaine concentrations were larger than venous concentrations during the first hour (P < 0.01); the arterio-venous difference decreased exponentially, and the rate and magnitude of this decrease was unaffected by epinephrine. We conclude that the addition of epinephrine 5 microg/mL to ropivacaine reduced the early systemic plasma concentrations of ropivacaine after epidural injection and may be useful for decreasing the risk of toxicity from systemic absorption of epidural ropivacaine.
The addition of epinephrine 5 microg/mL to epidural ropivacaine reduced the systemic arterial and venous plasma concentrations of ropivacaine in the first hour and the maximum plasma concentration of ropivacaine. Epinephrine may be a useful additive for reducing the risk of systemic toxicity when large doses of ropivacaine are given epidurally.
由于罗哌卡因本身具有血管收缩特性，因此不建议在罗哌卡因中添加肾上腺素。然而，关于在人体硬膜外使用的罗哌卡因中添加肾上腺素的药代动力学数据却很少。在这项前瞻性双盲研究中，我们将择期行腹部子宫切除术的患者随机分为两组，一组接受1.5mg/kg罗哌卡因，用15mL稀释，其中添加肾上腺素5μg/mL（肾上腺素组，n = 12），另一组不添加肾上腺素（单纯组，n = 12），然后在长达180分钟的时间间隔内测量罗哌卡因的动脉和静脉血浆浓度。我们发现，给药后的前60分钟内，肾上腺素组的动脉和静脉血浆罗哌卡因浓度低于单纯组（P < 0.01）。与单纯组（分别为1.31±0.39μg/mL和1.31±0.50μg/mL）相比，肾上腺素组罗哌卡因的平均（±标准差）最大总血浆浓度较低（动脉，0.92±0.32μg/mL；静脉，0.82±0.33μg/mL；P = 0.01）。两组达到罗哌卡因最大总血浆浓度的时间无显著差异（平均±标准差；肾上腺素组动脉为16±2分钟，静脉为23±2分钟；单纯组动脉为9±2分钟，静脉为12±3分钟；P = 0.08）。给药后的第一个小时内，动脉血浆罗哌卡因浓度高于静脉浓度（P < 0.01）；动静脉差值呈指数下降，且这种下降的速率和幅度不受肾上腺素影响。我们得出结论，在罗哌卡因中添加5μg/mL肾上腺素可降低硬膜外注射后罗哌卡因早期的全身血浆浓度，可能有助于降低硬膜外罗哌卡因全身吸收所致毒性的风险。
在硬膜外罗哌卡因中添加5μg/mL肾上腺素可降低给药后第一个小时内罗哌卡因的全身动脉和静脉血浆浓度以及罗哌卡因的最大血浆浓度。当硬膜外给予大剂量罗哌卡因时，肾上腺素可能是一种有助于降低全身毒性风险的添加剂。
