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瑞芬太尼预处理对布比卡因致大鼠心脏毒性的影响。

Effects of Remifentanil Pretreatment on Bupivacaine Cardiotoxicity in Rats.

机构信息

Department of Anesthesiology and Reanimation, School of Medicine, Bulent Ecevit University, Zonguldak, Turkey.

出版信息

Cardiovasc Toxicol. 2018 Feb;18(1):56-62. doi: 10.1007/s12012-017-9413-3.

Abstract

Unintentional intravascular administration of bupivacaine may cause local anesthetic systemic toxicity (LAST). Although many systems are affected in LAST, the cardiovascular effects can be life-threatening. Remifentanil is a selective, ultra-short-acting, µ-opioid receptor agonist opioid. This study assessed the effects of combined pretreatment with intravenous lipid emulsion (ILE) and remifentanil on the cardiotoxicity caused by bupivacaine in an experimental model of anesthetized rats. The rats were divided into three groups. Group B received a saline pretreatment plus a bupivacaine, group L received ILE pretreatment plus a bupivacaine, and in group R, remifentanil was infused intravenously, plus ILE pretreatment plus a bupivacaine. The electrocardiogram tracing, invasive arterial pressure, and heart rate (HR) of rats were monitored continuously. Arterial blood gas analysis was performed in all groups. Arterial blood gas analysis revealed that the baseline pH (7.38 ± 0.31, 7.39 ± 0.41, and 7.37 ± 0.02 for groups B, L, and R, respectively), PaO (198.5 ± 9.45, 196.1 ± 32.3, and 197.7 ± 9.25 mmHg, respectively), and PaCO (37.8 ± 4.91, 37.4 ± 4.85, and 36.9 ± 4.42 mmHg, respectively) were similar in the groups (p > 0.05). Time to first alteration in QRS complex, time to first arrhythmia, time to 25, 50, and 75% reductions in HR, time to 25, 50, and 75% reductions in MAP, and time to asystole were recorded. Widening of the QRS complex was found 41.8 ± 16.6, 88.5 ± 7.91, and 103.0 ± 15.7 s after initiating the bupivacaine infusion in groups B, L, and R, respectively. Time elapsed until 25% reduction in HR was found 136.5 ± 50.7, 284.7 ± 31.7, and 292.0 ± 46.0 s for groups B, L, and R, respectively, and that until 25% reduction in MAP was found 101.7 ± 14.3, 245.0 ± 36.6, and 237.6 ± 52.6 s, respectively. Arrhythmia was observed after 135.2 ± 27.4, 172.4 ± 18.1, and 176.2 ± 23.0 s in groups B, L, and R, respectively. Finally, asystole occurred after 553.6 ± 74.4, 766.7 ± 64.8, and 800.1 ± 94.7 s in groups B, L, and R, respectively. This finding indicates that the survival time of rats administered pretreatment with ILE plus remifentanil and those given ILE was observed to be longer. Additionally, this study found that intravenous lipid emulsion plus remifentanil pretreatment did not result in better durations in terms of formation of bupivacaine intoxication and asystole compared to lipid pretreatment alone.

摘要

意外静脉内给予布比卡因可能导致局部麻醉药全身毒性(LAST)。尽管 LAST 会影响许多系统,但心血管效应可能危及生命。瑞芬太尼是一种选择性、超短效、µ-阿片受体激动剂类阿片类药物。本研究评估了静脉内给予脂肪乳剂(ILE)和瑞芬太尼预处理对麻醉大鼠布比卡因中毒的心脏毒性的影响。大鼠分为三组。B 组给予生理盐水预处理加布比卡因,L 组给予 ILE 预处理加布比卡因,R 组给予瑞芬太尼静脉输注,加 ILE 预处理加布比卡因。连续监测大鼠心电图描记、有创动脉压和心率(HR)。所有组均进行动脉血气分析。动脉血气分析显示,各组的基线 pH 值(分别为 7.38±0.31、7.39±0.41 和 7.37±0.02)、PaO(分别为 198.5±9.45、196.1±32.3 和 197.7±9.25mmHg)和 PaCO(分别为 37.8±4.91、37.4±4.85 和 36.9±4.42mmHg)相似(p>0.05)。记录首次 QRS 复合体改变、首次心律失常、HR 降低 25%、50%和 75%、MAP 降低 25%、50%和 75%、心动停止的时间。在 B、L 和 R 组中,开始输注布比卡因后分别发现 QRS 复合体增宽 41.8±16.6、88.5±7.91 和 103.0±15.7s。发现 HR 降低 25%的时间分别为 B、L 和 R 组的 136.5±50.7、284.7±31.7 和 292.0±46.0s,MAP 降低 25%的时间分别为 101.7±14.3、245.0±36.6 和 237.6±52.6s。B、L 和 R 组分别在 135.2±27.4、172.4±18.1 和 176.2±23.0s 观察到心律失常。最后,B、L 和 R 组分别在 553.6±74.4、766.7±64.8 和 800.1±94.7s 出现心动停止。这一发现表明,给予 ILE 加瑞芬太尼预处理的大鼠的存活时间比给予 ILE 预处理的大鼠更长。此外,本研究发现,与单独给予脂质预处理相比,静脉内给予脂肪乳剂加瑞芬太尼预处理并没有导致布比卡因中毒和心动停止的持续时间更好。

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