右美托咪啶预注对利多卡因心脏毒性的实验研究
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摘要
目的：通过右美托咪啶预注预防利多卡因心脏毒性反应的可行性。
方法：成熟Wistar大鼠,30只,随机分为3组,每组10只大鼠。A组为右美托咪啶0μg/kg组,B组为右美托咪啶5μg/kg组,C组为右美托咪啶10μg/kg组。行10%水合氯醛4ml/kg腹腔麻醉,经右侧股动脉直接测压、经左侧股静脉置入导管给药。在实验组中,通过左侧股静脉10mmin泵入相对剂量的右美托咪啶1ml。10mmin后以1ml/h泵入2%利多卡因,直至动物产生中毒症状为止,动物一旦产生中毒症状,立即停止用药。利多卡因中毒的界定：ECG波形中发生改变,增宽幅度>基础值20%或出现心律失常、心率变化>基础值25%、MAP下降>25%可定义为利多卡因中毒。动物产生利多卡因等局麻药中毒症状时通过右侧股动脉抽取动脉血,高效液相色谱法测定血中利多卡因浓度。分析给入不同浓度右美托咪啶与血中利多卡因浓度的关系。
结果：A、B、C三组中实验大鼠的体重和血流动力学指标(基础值)无统计学差异(P>0.05)；A组大鼠利多卡因中毒时血药浓度为1.049±0.883μg/ml, B组大鼠利多卡因中毒时血药浓度为5.460±1.814μg/ml,C组大鼠利多卡因中毒时血药浓度为6.066±2.715μg/ml。.
结论：右美托咪啶对利多卡因引起的心脏毒性反应有较好的预防作用。
Objective:To investigate the effect of dexemedetomidine pre-injection on prevention of lidocaine cardiac toxicity in mature Wistar rats.
Methods:Thirty mature Wistar rats were randomized to three groups of 10 rats each to receive pre-injection with dexmedetomidine 0μg/kg (Group A), dexmedetomidine 5μg/kg (Group B), or dexmedetomidine 10μg/kg (Group C). All groups underwent intraperitoneal anesthesia with 4ml/kg 10% Chloral hydrate, noninvasive blood pressure was applied to the rignt femoral,a catheter was inserted in the left femoral vein devoted to medcine infusion.In the experiment groups,1 ml relative dose was infused through the left femoral vein in 10 minutes and then with a continuous lml/h 2% lidocaine infusion with a pump until the rats had the manifestations of poisoning, definded as the ECG waveform changed, including that broadening range>20% of baseline values or arrhythmia, heart rate> 25% of baseline values, MAP decreased>25%.Hardly rats produced poisoning symptoms of local anesthetic when the arterial blood was collected through the right femoral artery, measured the determination of lidocaine concentrations in blood with the High Performance Liquid Chromatography. To analysis the relationship between different concentrations of dexmedetomidine and blood lidocaine concentration.
Results:The rats in three groups were similar with regard to weights and hemodynamics (baseline) and there was no significant difference (P>0.05). A group blood concentration of lidocaine poisoning was 1.049±0.883μg/ml, B group blood concentration of lidocaine poisoning was 5.460±1.814μg/ml, C group blood concentration of lidocaine poisoning was 6.066±2.715μg/ml.
Conclusion:Pre-injection with dexmedetomidine had a good preventive effect on lidocaine induced cardiac toxicity.
方法：成熟Wistar大鼠,30只,随机分为3组,每组10只大鼠。A组为右美托咪啶0μg/kg组,B组为右美托咪啶5μg/kg组,C组为右美托咪啶10μg/kg组。行10%水合氯醛4ml/kg腹腔麻醉,经右侧股动脉直接测压、经左侧股静脉置入导管给药。在实验组中,通过左侧股静脉10mmin泵入相对剂量的右美托咪啶1ml。10mmin后以1ml/h泵入2%利多卡因,直至动物产生中毒症状为止,动物一旦产生中毒症状,立即停止用药。利多卡因中毒的界定：ECG波形中发生改变,增宽幅度>基础值20%或出现心律失常、心率变化>基础值25%、MAP下降>25%可定义为利多卡因中毒。动物产生利多卡因等局麻药中毒症状时通过右侧股动脉抽取动脉血,高效液相色谱法测定血中利多卡因浓度。分析给入不同浓度右美托咪啶与血中利多卡因浓度的关系。
结果：A、B、C三组中实验大鼠的体重和血流动力学指标(基础值)无统计学差异(P>0.05)；A组大鼠利多卡因中毒时血药浓度为1.049±0.883μg/ml, B组大鼠利多卡因中毒时血药浓度为5.460±1.814μg/ml,C组大鼠利多卡因中毒时血药浓度为6.066±2.715μg/ml。.
结论：右美托咪啶对利多卡因引起的心脏毒性反应有较好的预防作用。
Objective:To investigate the effect of dexemedetomidine pre-injection on prevention of lidocaine cardiac toxicity in mature Wistar rats.
Methods:Thirty mature Wistar rats were randomized to three groups of 10 rats each to receive pre-injection with dexmedetomidine 0μg/kg (Group A), dexmedetomidine 5μg/kg (Group B), or dexmedetomidine 10μg/kg (Group C). All groups underwent intraperitoneal anesthesia with 4ml/kg 10% Chloral hydrate, noninvasive blood pressure was applied to the rignt femoral,a catheter was inserted in the left femoral vein devoted to medcine infusion.In the experiment groups,1 ml relative dose was infused through the left femoral vein in 10 minutes and then with a continuous lml/h 2% lidocaine infusion with a pump until the rats had the manifestations of poisoning, definded as the ECG waveform changed, including that broadening range>20% of baseline values or arrhythmia, heart rate> 25% of baseline values, MAP decreased>25%.Hardly rats produced poisoning symptoms of local anesthetic when the arterial blood was collected through the right femoral artery, measured the determination of lidocaine concentrations in blood with the High Performance Liquid Chromatography. To analysis the relationship between different concentrations of dexmedetomidine and blood lidocaine concentration.
Results:The rats in three groups were similar with regard to weights and hemodynamics (baseline) and there was no significant difference (P>0.05). A group blood concentration of lidocaine poisoning was 1.049±0.883μg/ml, B group blood concentration of lidocaine poisoning was 5.460±1.814μg/ml, C group blood concentration of lidocaine poisoning was 6.066±2.715μg/ml.
Conclusion:Pre-injection with dexmedetomidine had a good preventive effect on lidocaine induced cardiac toxicity.
引文
[1]《围麻醉期风险与处理》,马武华,古妙宁.
[2]Guido Di Gregorio, MD, Joseph M. Neal, MD, Richard W. Rosenquist, MD and Guy L. Weinberg, MD. Clinical Presentation of Local Anesthetic Systemic Toxicity. Reg Anesth Pain Med 2010;35:181-187.
[3]《麻醉相关并发症处理学》,屠伟峰.
[4]Guy L. Weinberg, MD. Treatment of Local Anesthetic Systemic Toxicity (LAST). Reg Anesth Pain Med 2010;35:188-193.
[5]Michael F. Mulroy, MD and Michael R. Hejtmanek, MD. Prevention of Local Anesthetic Systemic Toxicity. Reg Anesth Pain Med 2010;35:177-180.
[6]John F. Butterworth, IV, MD.Models and Mechanisms of Local Anesthetic Cardiac Toxicity.
[7]Guido Di Gregorio, MD, Joseph M. Neal, MD, Richard W. Rosenquist, MD, and Guy L. Weinberg, MD. Clinical Presentation of Local Anesthetic Systemic Toxicity.
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[2]Guido Di Gregorio, MD, Joseph M. Neal, MD, Richard W. Rosenquist, MD and Guy L. Weinberg, MD. Clinical Presentation of Local Anesthetic Systemic Toxicity. Reg Anesth Pain Med 2010;35:181-187.
[3]《麻醉相关并发症处理学》,屠伟峰.
[4]Guy L. Weinberg, MD. Treatment of Local Anesthetic Systemic Toxicity (LAST). Reg Anesth Pain Med 2010;35:188-193.
[5]Michael F. Mulroy, MD and Michael R. Hejtmanek, MD. Prevention of Local Anesthetic Systemic Toxicity. Reg Anesth Pain Med 2010;35:177-180.
[6]John F. Butterworth, IV, MD.Models and Mechanisms of Local Anesthetic Cardiac Toxicity.
[7]Guido Di Gregorio, MD, Joseph M. Neal, MD, Richard W. Rosenquist, MD, and Guy L. Weinberg, MD. Clinical Presentation of Local Anesthetic Systemic Toxicity.
[8]M. D. Wiles1 and M. H. Nathanson.Local anaesthetics and adjuvants-future developments.
[9]Tim Smith. Systemic toxic effects of local anaesthetics. Anaesthesia & Intensive Care Medicine; 2007,8,4:155-158.
[10]Graf BM, Martin E. Peripheral nerve block. An overview of new developments in an old technique. Anaesthesist; 2001,50(5):312-22.
[11]Kim JT, Jung CW, Lee KH. The effect of insulin on the resuscitation of bupivacaine-induced severe cardiovascular toxicity in dogs. Anesth Analg 2004; 99:728-33.
[12]Weinberg GL, VadeBoncouer T, Ramaraju GA, et al. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology,1998; 88:1071-1075.
[13]Weinberg GL, Ripper R, Feinstein DL, Hoffman W:Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med,2003; 28:198-202.
[14]Weinberg GL, Ripper R, Murphy P, Edelman LB, Hoffman W, Strichartz G, Feinstein DL:Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart. Reg Anesth Pain Med 2006; 31:296-303.
[15]Weinberg GL, Di Gregorio G, Ripper R, Kelly K, Massad M, Edelman L, Schwartz D, Shah N, Zheng S, Feinstein DL. Resuscitation with lipid versus epinephrine in a rat model of bupivacaine overdose. Anesthesiology,2008, 108(5):907-913.
[16]Weinberg GL:Lipid rescue resuscitation from local anaesthetic cardiac toxicity. Toxicol Rev 2006; 25:139-45.
[17]Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology.2006 Jul;105(1):217-8.
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