左旋布比卡因、布比卡因和罗哌卡因在连续静脉输注期间对非妊娠和妊娠母羊的全身毒性。

Systemic toxicity of levobupivacaine, bupivacaine, and ropivacaine during continuous intravenous infusion to nonpregnant and pregnant ewes.

作者信息

Santos A C, DeArmas P I

机构信息

Department of Anesthesiology, St. Luke's-Roosevelt Hospital Center, College of Physicians and Surgeons, Columbia University, New York, New York 10025, USA.

出版信息

Anesthesiology. 2001 Nov;95(5):1256-64. doi: 10.1097/00000542-200111000-00033.

DOI:10.1097/00000542-200111000-00033

PMID:11684998

Abstract

BACKGROUND

Levobupivacaine, the single levorotatory isomer of bupivacaine, is now available for clinical use. This study was undertaken to determine whether pregnancy affects the systemic toxicity of levobupivacaine and to compare the systemic toxicity of levobupivacaine with that of bupivacaine and ropivacaine.

METHODS

Chronically prepared nonpregnant and pregnant sheep were randomized to receive an intravenous infusion of 0.52% levobupivacaine, 0.52% bupivacaine, or 0.50% ropivacaine at a constant rate of 0.1 ml x kg(-1) x min(-1) until circulatory collapse. The investigators were blinded to the identity of the local anesthetic. Physiologic parameters, including cardiac rhythm, were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations. These were analyzed for total and free serum drug concentrations as well as arterial blood pH and gas tensions.

RESULTS

The doses of all three drugs required to produce convulsions were lower in pregnant than nonpregnant animals. However, as the infusion continued, there were no significant differences between pregnant and nonpregnant ewes in the dose of drug required to produce more advanced manifestations of toxicity: hypotension, apnea, and circulatory collapse. The mean cumulative dose and serum concentration at each toxic manifestation was lowest for bupivacaine, intermediate for levobupivacaine, and highest for ropivacaine in both pregnant and nonpregnant animals. For all three local anesthetics, there were no significant differences between pregnant and nonpregnant ewes in total and free serum drug concentrations, except that at circulatory collapse, these were higher in pregnant animals.

CONCLUSIONS

Pregnancy increases the risk of convulsions but not of more advanced manifestations of local anesthetic toxicity. The risk of toxicity is greatest with bupivacaine and least with ropivacaine. However, in actual clinical practice, the risk of systemic toxicity may also be affected by the relative potency and effectiveness of these drugs.

摘要

背景

左旋布比卡因是布比卡因的单一左旋异构体，现已可供临床使用。本研究旨在确定妊娠是否会影响左旋布比卡因的全身毒性，并比较左旋布比卡因与布比卡因和罗哌卡因的全身毒性。

方法

将长期制备的未孕和孕羊随机分组，以0.1 ml×kg⁻¹×min⁻¹的恒定速率静脉输注0.52%左旋布比卡因、0.52%布比卡因或0.50%罗哌卡因，直至循环衰竭。研究人员对局部麻醉药的身份不知情。在整个研究过程中监测包括心律在内的生理参数。在输注前和出现毒性表现时采集动脉血样。分析这些血样的总血清药物浓度、游离血清药物浓度以及动脉血pH值和血气张力。

结果

与未孕动物相比，孕羊发生惊厥所需的所有三种药物剂量均较低。然而，随着输注的持续，在出现更严重毒性表现（低血压、呼吸暂停和循环衰竭）所需的药物剂量方面，孕羊和未孕母羊之间没有显著差异。在孕羊和未孕动物中，每种毒性表现时的平均累积剂量和血清浓度，布比卡因最低，左旋布比卡因居中，罗哌卡因最高。对于所有三种局部麻醉药，孕羊和未孕母羊的总血清药物浓度和游离血清药物浓度没有显著差异，只是在循环衰竭时，孕羊的这些浓度更高。