局部麻醉药心脏毒性不良反应的研究进展_West China Medical Journal

Authors：

王琦 ^1,2,1,2 ,  张文胜 ^1,2,1,2

1. ;
2. ;

Corresponding author：

张文胜, Email: zhangws@vip.163.com

Keywords：

局部麻醉药; 心脏毒性; 布比卡因

DOI：

10.7507/1002-0179.201603310

Video：

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自局部麻醉药应用于临床以来，临床上出现了许多局部麻醉药心脏毒性不良反应的案例，但目前对这方面的认识仍然存在争议。该文对局部麻醉药心脏毒性不良反应的构效关系、量效关系、诊断、预防及治疗方面的研究进展进行了综述。

Citation： 王琦, 张文胜. 局部麻醉药心脏毒性不良反应的研究进展. West China Medical Journal, 2017, 32(10): 1597-1601. doi: 10.7507/1002-0179.201603310 Copy

1.	Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology, 1979, 51(4): 285-287.
2.	Liu P, Feldman HS, Covino BM, et al. Acute cardiovascular toxicity of intravenous amide local anesthetics in anesthetized ventilated dogs. Anesth Analg, 1982, 61(4): 317-322.
3.	Tsuchiya H, Ueno T, Mizogami M, et al. Local anesthetics structure-dependently interact with anionic phospholipid membranes to modify the fluidity. Chem Biol Interact, 2010, 183(1): 19-24.
4.	Tsuchiya H, Mizogami M. R (+) -, Rac-, and S (-) -Bupivacaine stereostructure-specifically interact with membrane lipids at cardiotoxically relevant concentrations. Anesth Analg, 2012, 114(2): 310-312.
5.	Huang YF, Pryor ME, Mather LE, et al. Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep. Anesth Analg, 1998, 86(4): 797-804.
6.	Graf BM, Abraham I, Eberbach N, et al. Differences in cardiotoxicity of bupivacaine and ropivacaine are the result of physicochemical and stereoselective properties. Anesthesiology, 2002, 96(6): 1427-1434.
7.	Kariya N, Cosson C, Mazoit JX. Comparative effect of lidocaine, bupivacaine and RAC 109 on myocardial conduction and contractility in the rabbit. Eur J Pharmacol, 2012, 691(1-3): 110-117.
8.	Valenzuela C, Snyders DJ, Bennett PB, et al. Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig ventricular myocytes. Circulation, 1995, 92(10): 3014-3024.
9.	Valenzuela C, Delpón E, Tamkun MM, et al. Stereoselective block of a human cardiac potassium channel (Kv1.5) by bupivacaine enantiomers. Biophys J, 1995, 69(2): 418-427.
10.	Groban L, Deal DD, Vernon JC, et al. Ventricular arrhythmias with or without programmed electrical stimulation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine. Anesth Analg, 2000, 91(5): 1103-1111.
11.	Fujita Y. Comparative direct effects of lidocaine and bupivacaine on regional myocardial function in dogs at noncardiovascular toxic levels. Anesth Analg, 1994, 78(6): 51-52.
12.	Ohmura S, Kawada M, Ohta T, et al. Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats. Anesth Analg, 2001, 93(3): 743-748.
13.	Mio Y, Fukuda N, Kusakari Y, et al. Bupivacaine attenuates contractility by decreasing sensitivity of myofilaments to Ca<sup>2+</sup> in rat ventricular muscle. Anesthesiology, 2002, 97(5): 1168-1177.
14.	Groban L, Deal DD, Vernon JC, et al. Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs. Anesth Analg, 2001, 92(1): 37-43.
15.	Santos AC, Dearmas PI. Systemic toxicity of levobupivacaine, bupivacaine, and ropivacaine during continuous intravenous infusion to nonpregnant and pregnant ewes. Anesthesiology, 2001, 95(5): 1256-1264.
16.	Nancarrow C, Rutten AJ, Runciman WB, et al. Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep. Anesth Analg, 1989, 69(3): 276-283.
17.	Kiuchi MG, Zapata-Sudo G, Trachez MM, et al. The influence of age on bupivacaine cardiotoxicity. Anesth Analg, 2011, 112(3): 574-580.
18.	Morishima HO, Pedersen H, Finster M, et al. Toxicity of lidocaine in adult, newborn, and fetal sheep. Anesthesiology, 1981, 55(1): 57-61.
19.	Orebaugh SL, Williams BA, Vallejo M, et al. Adverse outcomes associated with stimulator-based peripheral nerve blocks with <italic>versus</italic> without ultrasound visualization. Reg Anesth Pain Med, 2009, 34(3): 251-255.
20.	Neal JM, Bernards CM, Butterworth JF, et al. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med, 2010, 35(2): 152-161.
21.	Ludot H, Tharin JY, Belouadah M, et al. Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child. Anesth Analg, 2008, 106(5): 1572-1574, table of contents.
22.	Weinberg G, Lin B, Zheng S, et al. Partitioning effect in lipid resuscitation: further evidence for the lipid sink. Crit Care Med, 2010, 38(11): 2268-2269.
23.	Ozcan MS, Weinberg G. Intravenous lipid emulsion for the treatment of drug toxicity. J Intensive Care Med, 2014, 29(2): 59-70.
24.	Fettiplace MR, Weinberg G. Past, present, and future of lipid resuscitation therapy. JPEN J Parenter Enteral Nutr, 2015, 39(1 suppl): 72S-83S.
25.	Partownavid P, Sharma S, Li J, et al. Involvement of opioid receptors in the lipid rescue of bupivacaine-induced cardiotoxicity. Anesth Analg, 2015, 121(2): 340-347.
26.	Chen Y, Xia Y, Liu L, et al. Lipid emulsion reverses bupivacaine-induced asystole in isolated rat hearts: concentration-response and time-response relationships. Anesthesiology, 2010, 113(6): 1320-1325.
27.	Fettiplace MR, Akpa BS, Ripper R, et al. Resuscitation with lipid emulsion: dose-dependent recovery from cardiac pharmacotoxicity requires a cardiotonic effect. Anesthesiology, 2014, 120(4): 915-925.
28.	The Association of Anaesthetists of Great Britain & Ireland. AAGBI safety guideline: management of severe local anaesthetic toxicity. (2010-03-04)[2017-09-20]. http://www.p-h-c.com.au/ doc/Local_Anaesthesia_Toxicity.pdf.
29.	Laine J, Lokajová J, Parshintsev J, et al. Interaction of a commercial lipid dispersion and local anesthetics in human plasma: implications for drug trapping by " lipid-sinks”. Anal Bioanal Chem, 2010, 396(7): 2599-2607.
30.	Liu L, Xia Y, Chen Y, et al. The comparative effects of lipid, epinephrine, and their combination in the reversal of bupivacaine-induced asystole in the isolated rat heart. Anesth Analg, 2012, 114(4): 886-893.
31.	Weinberg GL, Di Gregorio G, Ripper R, et al. Resuscitation with lipid <italic>versus</italic> epinephrine in a rat model of bupivacaine overdose. Anesthesiology, 2008, 108(5): 907-913.
32.	Heavner JE, Pitkänen MT, Shi B, et al. Resuscitation from bupivacaine-induced asystole in rats: comparison of different cardioactive drugs. Anesth Analg, 1995, 80(6): 1134-1139.
33.	Neustein S, Sampson I, Dimich I, et al. Milrinone is superior to epinephrine as treatment of myocardial depression due to ropivacaine in pigs. Can J Anaesth, 2000, 47(11): 1114-1118.
34.	Stehr SN, Christ T, Rasche B, et al. The effects of levosimendan on myocardial function in ropivacaine toxicity in isolated Guinea pig heart preparations. Anesth Analg, 2007, 105(3): 641-647.
35.	Aittomäki J, Liuhanen S, Sallisalmi M, et al. The effect of levosimendan on bupivacaine-induced severe myocardial depression in anesthetized pigs. Reg Anesth Pain Med, 2010, 35(1): 34-40.
36.	Gokahmetoglu G, Aksu R, Bicer C, et al. The effect of levosimendan combined with 20% lipid emulsion treatment on survival from bupivacaine induced toxicity in experiment. Bratisl Lek Listy, 2014, 115(5): 275-279.
37.	Toller WG, Stranz C. Levosimendan, a new inotropic and vasodilator agent. Anesthesiology, 2006, 104(3): 556-569.
38.	Yang S, Uugangerel T, Jang IK, et al. Insulin facilitates the recovery of myocardial contractility and conduction during cardiac compression in rabbits with Bupivacaine-Induced cardiovascular collapse. Anesthesiol Res Pract, 2012, 2012: 878764.
39.	Choi YS, Lee KH. Insulin effect on bupivacaine-induced cardiotoxicity in rabbits. Korean J Anesthesiol, 2011, 61(6): 493-496.
40.	Kim MH, Lee KH, Kim CS, et al. Insulin/glucose infusion successfully resuscitates bupivacaine-induced sudden-onset circulatory collapse in dogs. Can J Anaesth, 2013, 60(5): 471-478.
41.	Kim JT, Yang SM, Lee KH. The effects of an insulin-glucose-potassium (IGK) pretreatment on the bupivacaine cardiotoxicity. Korean J Anesthesiol, 2013, 64(1): 47-53.
42.	Clarkson CW, Hondeghem LM. Mechanism for bupivacaine depression of cardiac conduction:fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology, 1985, 52(4): 396-405.

1. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology, 1979, 51(4): 285-287.
2. Liu P, Feldman HS, Covino BM, et al. Acute cardiovascular toxicity of intravenous amide local anesthetics in anesthetized ventilated dogs. Anesth Analg, 1982, 61(4): 317-322.
3. Tsuchiya H, Ueno T, Mizogami M, et al. Local anesthetics structure-dependently interact with anionic phospholipid membranes to modify the fluidity. Chem Biol Interact, 2010, 183(1): 19-24.
4. Tsuchiya H, Mizogami M. R (+) -, Rac-, and S (-) -Bupivacaine stereostructure-specifically interact with membrane lipids at cardiotoxically relevant concentrations. Anesth Analg, 2012, 114(2): 310-312.
5. Huang YF, Pryor ME, Mather LE, et al. Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep. Anesth Analg, 1998, 86(4): 797-804.
6. Graf BM, Abraham I, Eberbach N, et al. Differences in cardiotoxicity of bupivacaine and ropivacaine are the result of physicochemical and stereoselective properties. Anesthesiology, 2002, 96(6): 1427-1434.
7. Kariya N, Cosson C, Mazoit JX. Comparative effect of lidocaine, bupivacaine and RAC 109 on myocardial conduction and contractility in the rabbit. Eur J Pharmacol, 2012, 691(1-3): 110-117.
8. Valenzuela C, Snyders DJ, Bennett PB, et al. Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig ventricular myocytes. Circulation, 1995, 92(10): 3014-3024.
9. Valenzuela C, Delpón E, Tamkun MM, et al. Stereoselective block of a human cardiac potassium channel (Kv1.5) by bupivacaine enantiomers. Biophys J, 1995, 69(2): 418-427.
10. Groban L, Deal DD, Vernon JC, et al. Ventricular arrhythmias with or without programmed electrical stimulation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine. Anesth Analg, 2000, 91(5): 1103-1111.
11. Fujita Y. Comparative direct effects of lidocaine and bupivacaine on regional myocardial function in dogs at noncardiovascular toxic levels. Anesth Analg, 1994, 78(6): 51-52.
12. Ohmura S, Kawada M, Ohta T, et al. Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats. Anesth Analg, 2001, 93(3): 743-748.
13. Mio Y, Fukuda N, Kusakari Y, et al. Bupivacaine attenuates contractility by decreasing sensitivity of myofilaments to Ca<sup>2+</sup> in rat ventricular muscle. Anesthesiology, 2002, 97(5): 1168-1177.
14. Groban L, Deal DD, Vernon JC, et al. Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs. Anesth Analg, 2001, 92(1): 37-43.
15. Santos AC, Dearmas PI. Systemic toxicity of levobupivacaine, bupivacaine, and ropivacaine during continuous intravenous infusion to nonpregnant and pregnant ewes. Anesthesiology, 2001, 95(5): 1256-1264.
16. Nancarrow C, Rutten AJ, Runciman WB, et al. Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep. Anesth Analg, 1989, 69(3): 276-283.
17. Kiuchi MG, Zapata-Sudo G, Trachez MM, et al. The influence of age on bupivacaine cardiotoxicity. Anesth Analg, 2011, 112(3): 574-580.
18. Morishima HO, Pedersen H, Finster M, et al. Toxicity of lidocaine in adult, newborn, and fetal sheep. Anesthesiology, 1981, 55(1): 57-61.
19. Orebaugh SL, Williams BA, Vallejo M, et al. Adverse outcomes associated with stimulator-based peripheral nerve blocks with <italic>versus</italic> without ultrasound visualization. Reg Anesth Pain Med, 2009, 34(3): 251-255.
20. Neal JM, Bernards CM, Butterworth JF, et al. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med, 2010, 35(2): 152-161.
21. Ludot H, Tharin JY, Belouadah M, et al. Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child. Anesth Analg, 2008, 106(5): 1572-1574, table of contents.
22. Weinberg G, Lin B, Zheng S, et al. Partitioning effect in lipid resuscitation: further evidence for the lipid sink. Crit Care Med, 2010, 38(11): 2268-2269.
23. Ozcan MS, Weinberg G. Intravenous lipid emulsion for the treatment of drug toxicity. J Intensive Care Med, 2014, 29(2): 59-70.
24. Fettiplace MR, Weinberg G. Past, present, and future of lipid resuscitation therapy. JPEN J Parenter Enteral Nutr, 2015, 39(1 suppl): 72S-83S.
25. Partownavid P, Sharma S, Li J, et al. Involvement of opioid receptors in the lipid rescue of bupivacaine-induced cardiotoxicity. Anesth Analg, 2015, 121(2): 340-347.
26. Chen Y, Xia Y, Liu L, et al. Lipid emulsion reverses bupivacaine-induced asystole in isolated rat hearts: concentration-response and time-response relationships. Anesthesiology, 2010, 113(6): 1320-1325.
27. Fettiplace MR, Akpa BS, Ripper R, et al. Resuscitation with lipid emulsion: dose-dependent recovery from cardiac pharmacotoxicity requires a cardiotonic effect. Anesthesiology, 2014, 120(4): 915-925.
28. The Association of Anaesthetists of Great Britain & Ireland. AAGBI safety guideline: management of severe local anaesthetic toxicity. (2010-03-04)[2017-09-20]. http://www.p-h-c.com.au/ doc/Local_Anaesthesia_Toxicity.pdf.
29. Laine J, Lokajová J, Parshintsev J, et al. Interaction of a commercial lipid dispersion and local anesthetics in human plasma: implications for drug trapping by " lipid-sinks”. Anal Bioanal Chem, 2010, 396(7): 2599-2607.
30. Liu L, Xia Y, Chen Y, et al. The comparative effects of lipid, epinephrine, and their combination in the reversal of bupivacaine-induced asystole in the isolated rat heart. Anesth Analg, 2012, 114(4): 886-893.
31. Weinberg GL, Di Gregorio G, Ripper R, et al. Resuscitation with lipid <italic>versus</italic> epinephrine in a rat model of bupivacaine overdose. Anesthesiology, 2008, 108(5): 907-913.
32. Heavner JE, Pitkänen MT, Shi B, et al. Resuscitation from bupivacaine-induced asystole in rats: comparison of different cardioactive drugs. Anesth Analg, 1995, 80(6): 1134-1139.
33. Neustein S, Sampson I, Dimich I, et al. Milrinone is superior to epinephrine as treatment of myocardial depression due to ropivacaine in pigs. Can J Anaesth, 2000, 47(11): 1114-1118.
34. Stehr SN, Christ T, Rasche B, et al. The effects of levosimendan on myocardial function in ropivacaine toxicity in isolated Guinea pig heart preparations. Anesth Analg, 2007, 105(3): 641-647.
35. Aittomäki J, Liuhanen S, Sallisalmi M, et al. The effect of levosimendan on bupivacaine-induced severe myocardial depression in anesthetized pigs. Reg Anesth Pain Med, 2010, 35(1): 34-40.
36. Gokahmetoglu G, Aksu R, Bicer C, et al. The effect of levosimendan combined with 20% lipid emulsion treatment on survival from bupivacaine induced toxicity in experiment. Bratisl Lek Listy, 2014, 115(5): 275-279.
37. Toller WG, Stranz C. Levosimendan, a new inotropic and vasodilator agent. Anesthesiology, 2006, 104(3): 556-569.
38. Yang S, Uugangerel T, Jang IK, et al. Insulin facilitates the recovery of myocardial contractility and conduction during cardiac compression in rabbits with Bupivacaine-Induced cardiovascular collapse. Anesthesiol Res Pract, 2012, 2012: 878764.
39. Choi YS, Lee KH. Insulin effect on bupivacaine-induced cardiotoxicity in rabbits. Korean J Anesthesiol, 2011, 61(6): 493-496.
40. Kim MH, Lee KH, Kim CS, et al. Insulin/glucose infusion successfully resuscitates bupivacaine-induced sudden-onset circulatory collapse in dogs. Can J Anaesth, 2013, 60(5): 471-478.
41. Kim JT, Yang SM, Lee KH. The effects of an insulin-glucose-potassium (IGK) pretreatment on the bupivacaine cardiotoxicity. Korean J Anesthesiol, 2013, 64(1): 47-53.
42. Clarkson CW, Hondeghem LM. Mechanism for bupivacaine depression of cardiac conduction:fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology, 1985, 52(4): 396-405.

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局部麻醉药心脏毒性不良反应的研究进展

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