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左西孟旦联合肾上腺素可改善布比卡因诱导的心脏骤停大鼠脂质复苏模型的抢救效果。

Levosimendan combined with epinephrine improves rescue outcomes in a rat model of lipid-based resuscitation from bupivacaine-induced cardiac arrest.

作者信息

Nan Fubei, Cai Xixi, Ye Yingchao, Xu Xuzhong, Li Zhengqian, Li Min, Chen Limei

机构信息

Department of Anaesthesiology, the First Affiliated Hospital, Wenzhou Medical University, Zhejiang, China.

Department of Anaesthesiology, Peking University Third Hospital ( PUTH ), No.49.North Garden Street, Haidian District, Beijing, China.

出版信息

BMC Anesthesiol. 2017 Sep 15;17(1):128. doi: 10.1186/s12871-017-0414-3.

DOI:10.1186/s12871-017-0414-3
PMID:28915792
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5602843/
Abstract

BACKGROUND

The effectiveness of a combination of a lipid emulsion with epinephrine in reversing local anesthetic-induced cardiac arrest has been confirmed. The combination of a lipid emulsion with levosimendan, was shown to be superior to administration of a lipid emulsion alone with regard to successful resuscitation. In this study, we compared the reversal effects of levosimendan, epinephrine, and a combination of the two agents in lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest.

METHODS

Fifty-four adult male Sprague-Dawley rats were subjected to bupivacaine (15 mg·kg) -induced asystole and were then randomly divided into 3 groups. A lipid emulsion was used as the basic treatment, and administration of drug combinations varied in each group as follows: (1) levosimendan combined with epinephrine (LiEL); (2) epinephrine (LiE); and (3) levosimendan (LiL). The resuscitation outcomes were recorded and included the rate of return of spontaneous circulation (ROSC) and survival at 40 min, time to first heartbeat, time to ROSC, and cumulative dose of epinephrine. We calculated the wet-to-dry ratio of the lung, blood gas values at 40 min and bupivacaine concentration of cardiac tissue and plasma.

RESULTS

The rates of ROSC in LiEL and LiE groups were higher than LiL group (P < 0.001; LiEL vs LiL, P = 0.001; LiE vs LiL, P = 0.007). The survival rate in LiEL group was higher than LiE group (P = 0.003; LiEL vs LiE, P = 0.008; LiEL vs LiL, P = 0.001). The time to first heart beat in LiEL group was shorter than LiE, LiL groups. (P < 0.001; LiE vs LiEL, P = 0.001; LiL vs LiEL, P < 0.001). The time to ROSC in LiEL group was shorter than LiE, LiL groups (P < 0.001; LiEL vs LiE, P < 0.001; LiEL vs LiL, P < 0.001). The result was similar for the bupivacaine concentration of cardiac tissue and plasma (cardiac tissue: P = 0.002; plasma: P = 0.011). Furthermore, there were significant differences in the blood-gas values at 40 min, wet-to-dry lung weight ratio, and ratio of damaged alveoli among groups. The LiEL group had the best result for all parameters (P < 0.01, P = 0.008, P < 0.001, respectively). Additionally, significantly less epinephrine was used in the LiEL group (P < 0.001).

CONCLUSIONS

Levosimendan combined with epinephrine may be superior to either drug alone for lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest. The drug combination was associated with a higher survival rate as well as decreased epinephrine consumption and lung damage.

摘要

背景

脂质乳剂与肾上腺素联合使用逆转局部麻醉药引起的心脏骤停的有效性已得到证实。脂质乳剂与左西孟旦联合使用在成功复苏方面优于单独使用脂质乳剂。在本研究中,我们比较了左西孟旦、肾上腺素以及两种药物联合在布比卡因诱导的心脏骤停大鼠模型中基于脂质的复苏中的逆转效果。

方法

54只成年雄性Sprague-Dawley大鼠接受布比卡因(15mg·kg)诱导的心脏停搏,然后随机分为3组。脂质乳剂用作基础治疗,每组药物组合的给药情况如下:(1)左西孟旦联合肾上腺素(LiEL);(2)肾上腺素(LiE);(3)左西孟旦(LiL)。记录复苏结果,包括自主循环恢复(ROSC)率和40分钟时的存活率、首次心跳时间、ROSC时间以及肾上腺素累积剂量。我们计算了肺的湿重与干重之比、40分钟时的血气值以及心脏组织和血浆中的布比卡因浓度。

结果

LiEL组和LiE组的ROSC率高于LiL组(P<0.001;LiEL与LiL比较,P = 0.001;LiE与LiL比较,P = 0.007)。LiEL组的存活率高于LiE组(P = 0.003;LiEL与LiE比较,P = 0.008;LiEL与LiL比较,P = 0.001)。LiEL组的首次心跳时间短于LiE组和LiL组(P<0.001;LiE与LiEL比较,P = 0.001;LiL与LiEL比较,P<0.001)。LiEL组的ROSC时间短于LiE组和LiL组(P<0.001;LiEL与LiE比较,P<0.001;LiEL与LiL比较,P<0.001)。心脏组织和血浆中的布比卡因浓度结果相似(心脏组织:P = 0.002;血浆:P = 0.011)。此外,各组在40分钟时的血气值、肺湿重与干重之比以及受损肺泡比例存在显著差异。LiEL组在所有参数方面结果最佳(分别为P<0.01、P = 0.008、P<0.001)。此外,LiEL组使用的肾上腺素明显更少(P<0.001)。

结论

在布比卡因诱导的心脏骤停大鼠模型中,左西孟旦联合肾上腺素在基于脂质的复苏方面可能优于单独使用任何一种药物。该药物组合与更高的存活率以及肾上腺素消耗减少和肺损伤减轻相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e5/5602843/97c5ffebae94/12871_2017_414_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e5/5602843/ea74b3d29724/12871_2017_414_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e5/5602843/996939565007/12871_2017_414_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e5/5602843/97c5ffebae94/12871_2017_414_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e5/5602843/ea74b3d29724/12871_2017_414_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e5/5602843/996939565007/12871_2017_414_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e5/5602843/97c5ffebae94/12871_2017_414_Fig3_HTML.jpg

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BMC Anesthesiol. 2017 Feb 2;17(1):18. doi: 10.1186/s12871-017-0309-3.
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Part 1: Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.第1部分:执行摘要:2015年美国心脏协会心肺复苏及心血管急救指南更新
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Epinephrine administration in lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest: optimal timing.
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Reg Anesth Pain Med. 2015 May-Jun;40(3):223-31. doi: 10.1097/AAP.0000000000000220.
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The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats.脂肪乳剂对布比卡因在大鼠体内药代动力学和组织分布的影响。
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