Toxicity Due to Local Anesthetic Agents: Literature Review
Keywords:
Anesthetics Local, Toxicity, Cardiotoxins, Neurotoxicity Syndromes, Fat Emulsions Intravenous
Abstract
Local anesthetics (LA) are drugs widely used in the practice of anesthesia, with low incidence of adverse events; however, in case of toxicity, mortality is very high. Currently, the systemic toxicity rates have dropped from 0.2 % to 0.01 %, thanks to the use of preventive measures and to the development of safer drugs. In view of the high risk of latent mortality, studies in humans are not feasible and hence the available sources of information are extrapolated animal studies or case reports.
Severe LA toxicity manifestations occur mainly as a result of intravascular administration rather than due to tissue absorption; hence, bupivacaine is the LA that exhibits the highest risk. Clinically there are awareness disorders and tonic-clonic seizures followed by cardiovascular involvement resulting from conduction blocks and difficult to manage cardiovascular collapse.
With regards to management, prevention is the key, followed by an adequate anesthetic technique; rapid identification and diagnosis and early application of ACLS rescue measures. More recently, the concomitant use of 20 % lip-id emulsions has been supported by successful resuscitation case reports.
References
1. Heavner JE. Local Anesthetics, Curr Opin Anesthesiol, 2007, 20336-342.
2. Veering BT. Complications and local anaesthetic toxicity in regional anaesthesia. Curr Opin Anaesth, 2003;16:455-9.
3. Leone S, Di Cianni S, Casati A, et al. Pharmacology, toxicology and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine. Acta Biomed, 2008;79:92-105.
4. Mulroy MF. Sistemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Regional Anesthesia and Pain Medicine, 2002;27(6):556-561
5. Reynolds F. Maximum Recommended Doses of Local Anesthetics: A Constant Cause of Confusion. To the editor. Regional Anesthesia and Pain Medicine. 2005; 30(3):314-6.
6. Mather LE, Copeland SE, Ladd LA. Acute Toxicity of Local Anesthetics: Underlying Pharmacokinetic and Pharmacodynamic Concepts. Reg Anesth Pain Med 2005;30:553-66.
7. Brown DL, Ransom DM, Hall JA, et al. Regional Anesthesia and Local Anesthetic-Induced Systemic Toxicity: Seizure Frequency and Accompanying Cardiovascular Change. Anesth Analg 1995;81:321-8.
8. Cox B, Duriex ME, Marcus MA. Toxicity of local anaesthetics. Best Pract Res Clin Anaesthesiol. 2003 Mar;17(1):111-36
9. Faccenda KA, Finucane BT. Complications of regional anaesthesia, incidence and prevention. Drug Saf. 2001;24(6):413-4.
10. Felice KL, Schumann HM. Intravenous Lipid Emulsion for Local Anesthetic Toxicity: A Review of the Literature. J Med Toxicol, 2008;4(3):184-91.
11. Barrington MJ, Watts SA, Gledhill SR, et al. Preliminary Results of the Australasian Regional Anaesthesia Collaboration A Prospective Audit of More Than 7000 Peripheral Nerve and Plexus Blocks for Neurologic and Other Complications. Reg Anesth Pain Med 2009;34:534-41.
12. Kindler CH, Yost CE. Two-pore domain potassium channels: new sites of local anesthetic action and toxicity. Reg Anesth Pain Med 2005;30:260-274.
13. Hollmann MW, Herroeder S, Kurz KS, et al. Time-dependent inhibition of G-protein coupled receptor signaling by local anesthetics. Anesthesiology. 2004; 100:852-860.
14. Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: A multi-factorial concept. Reg Anesth Pain Med 2004;29:564-575.
15. Niesel HC. Local anesthetics maximum recommended doses. Anaesthesiol Reanim. 1997;22(3):60-2.
16. Kucera IJ, Lambert TJ, Klein JA, et al. Liposuction: contemporary issues for the anesthesiologist. Journal of Clinical Anesthesia 2006;18:379-87.
17. Weinberg GL. Lipid Infusion Therapy: Translation to Clinical Practice, Anesth Analg 2008;106:5 1340-42.
18. Mazoit J, Le Guen R, Beloeil H, et al. Binding of Long-lasting Local Anesthetics to Lipid Emulsions, Anesthesiology 2009; 110:380-6.
19. Foxall G, McCahon R, Lamb J, et al. Levobupivacaine-induced seizures and cardiovascular collapse treated with Intralipid. Anaesthesia. 2007;62:516-518.
20. Chazalon P, Tourtier JP, Villevielle T, et al. Ropiva-caine-induced Cardiac Arrest after Peripheral Nerve Block: Successful Resuscitation. Anesthesiology 2003; 99:1449-51.
21. Huet O, Eyrolle LJ, Mazoit JX, et al. Cardiac Arrest after Injection of Ropivacaine for Posterior Lumbar Plexus Blockade Anesthesiology 2003; 99:1451-3.
22. Tasch MD, Butterworth JF. Toxicity of local anesthetics, ASA REFRESHING COURSE, 2006.
23. Zink W, Graf BM. The toxicity of local anesthetics: the place of ropivacaine and levobupivacaine. Current Opinion in Anaesthesiology. 2008;21:645-650.
24. Harmatz A. Local Anesthetics: Uses and Toxicities. Surg Clin N Am 2009;89:587-98.
25. Heavner JE. Cardiac toxicity of local anesthetics in the intact isolated heart model: a review. Reg Anesth Pain Med 2002;27:545-555.
26. Liu P, Feldmahn S, Covino BM, et al. Acute cardiovascular toxicity of intravenous amide local anesthetics in anesthetized ventilated dogs. Anesth Analg 1982;61:317-22.
27. Simon L, Kariya N, Pelle-Lancien E, et al. Bupivacaine-Induced QRS Prolongation is Enhanced by Lidocaine and by Phenytoin in Rabbit Hearts. Anesth Analg 2002;94:203-7.
28. Mets B, Janicki PK, James MF, et al. Lidocaine and Bupivacaine Cardiorespiratory Toxicity Is Additive: A Study in Rats. Anesth Analg 1992;75:611-4.
29. Thomas RD, Behbehani MM, Coyle DE, et al. Cardiovascular Toxicity of Local Anesthetics: An Alternative Hypothesis. Anesth Analg 1986;65:444-50.
30. Weinberg GL. Current Concepts in Resuscitation of Patients With Local Anesthetic Cardiac Toxicity. Reg Anesth Pain Med. 2002; 27(6): 568-75.
31. The Association of Anaesthetists of Great Britain & Ireland 2007. Guidelines for the Management of Severe Local Anaesthetic Toxicity. http://www.aagbi.org/publications/guidelines/docs/latoxicity07.pdf. 2007.
32. Copeland SE, Ladd LA, Gu X, et al. The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses. Anesth Analg 2008;106:1440-9.
33. Copeland SE, Ladd LA, Gu X, et al. The Effects of General Anesthesia on the Central Nervous and Cardiovascular System Toxicity of Local Anesthetics. Anesth Analg 2008;106:1429-39.
34. Corcoran W, Butterworth J, Weller RS, et al. Local Anesthetic-Induced Cardiac Toxicity: A Survey of Contemporary Practice Strategies Among Academic Anesthesiology Departments. Anesth Analg 2006;103:1322-26.
35. Hicks SD, Salcido DD, Logue ES, et al. Lipid emulsion combined with epinephrine and vasopressin does not improve survival in a swine model of bupivacai-neinduced cardiac arrest. Anesthesiology 2009;111:138-46.
36. Hiller DB, Di Gregorio G, Ripper R, et al. Epinephrine Impairs Lipid Resuscitation from Bupivacaine Overdose A Threshold Effect. Anesthesiology 2009;111:498-505.
37. Zausig YA, Zink W, Keil M, et al. Lipid Emulsion Improves Recovery from Bupivacaine-Induced Cardiac Arrest, but Not from Ropivacaine- or Mepivacaine-Induced Cardiac Arrest. Anesth Analg 2009;109:1323-6.
38. Picard J, Ward SC, Zumpe R, et al. Guidelines and the adoption of "lipid rescue" therapy for local anaesthetic toxicity. Anaesthesia 2009; 64:122-125.
39. Picard J, Harrop-Griffiths W. Lipid emulsion to treat drug overdose: past, present and future. Anaesthesia 2009; 64:119-121.
40. Cave G, Harvey MG, Winterbottom T. Evaluation of the Association of Anaesthetists of Great Britain and Ireland lipid infusion protocol in bupivacaine induced cardiac arrest in rabbits. Anesthesia. 2009;64(7):732-7.
41. Leskiw U , Weinberg GL. Lipid resuscitation for local anesthetic toxicity: is it really lifesaving?. Curr Opin Anaesthesio. 2009;22:667-71.
42. Weinberg G. Lipid infusion resuscitation for local anesthetic toxicity: Proof of clinical efficacy. Anesthesiology 2006; 105:7-8.
43. Spence A. Lipid reversal of central nervous system symptoms of bupivacaine toxicity. Anesthesiology 2007; 107:516-517.
44. Shah S, Gopalakrishnan S, Apuya J, et al. Use of Intralipid in an infant with impending cardiovascular collapse due to local anesthetic toxicity Anesth 2009:23:439-41.
45. Rosenblatt MA, Abel M, Fischer GW, et al. Successful Use of a 20% Lipid Emulsion to Resuscitate a Patient after a Presumed Bupivacaine-related Cardiac Arrest. Anesthesiology 2006;105:217-8.
46. 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;106:1572-4.
47. Warren JA, Thoma RB, Georgescu A, et al. Intravenous Lipid Infusion in the Successful Resuscitation of Local Anesthetic-Induced Cardiovascular Collapse After Supraclavicular Brachial Plexus Block. Anesth Analg 2008;106:1578-80.
48. Gregorio GD, Schawartz D, Ripper R, et al. Lipid emulsion is superior to vasopressin in a rodent model of resuscitation from toxin-induced cardiac arrest. Crit Care Med 2009; 37:993-999.
49. Picard J, Ward SC, Zumpe R, et al. Guidelines and the adoption of 'lipid rescue' therapy for local anaesthetic toxicity. Anaesthesia. 2009 Feb;64(2):122-5.
50. Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion. Anaesthesia 2006;61:800-1.
51. Litz R, Roessel T, Heller AR, et al. Reversal of Central Nervous System and Cardiac Toxicity After Local Anesthetic Intoxication by Lipid Emulsion Injection. Anesth Analg 2008;106:1575-7.
52. Corman SL, Skledar SJ. Use of Lipid Emulsion to Reverse Local Anesthetic-Induced Toxicity Corman and Skledar. Ann Pharmacother 2007;41:1873-7.
53. Weinberg GL. Limits to Lipid in the Literature and Lab: What We Know, What We Don't Know. Anesth Analg 2009;108(4):1062-4.
54. Brull SJ. Lipid Emulsion for the Treatment of Local Anesthetic Toxicity: Patient Safety Implications. Anesth Analg. 2008;106:1337-8.
55. Marwick PC, Levin AI, Coetzee AR. Recurrence of Cardiotoxicity After Lipid Rescue from Bupivacaine-Induced Cardiac Arrest. Anesth Analg 2009;108: 1344-6.
2. Veering BT. Complications and local anaesthetic toxicity in regional anaesthesia. Curr Opin Anaesth, 2003;16:455-9.
3. Leone S, Di Cianni S, Casati A, et al. Pharmacology, toxicology and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine. Acta Biomed, 2008;79:92-105.
4. Mulroy MF. Sistemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Regional Anesthesia and Pain Medicine, 2002;27(6):556-561
5. Reynolds F. Maximum Recommended Doses of Local Anesthetics: A Constant Cause of Confusion. To the editor. Regional Anesthesia and Pain Medicine. 2005; 30(3):314-6.
6. Mather LE, Copeland SE, Ladd LA. Acute Toxicity of Local Anesthetics: Underlying Pharmacokinetic and Pharmacodynamic Concepts. Reg Anesth Pain Med 2005;30:553-66.
7. Brown DL, Ransom DM, Hall JA, et al. Regional Anesthesia and Local Anesthetic-Induced Systemic Toxicity: Seizure Frequency and Accompanying Cardiovascular Change. Anesth Analg 1995;81:321-8.
8. Cox B, Duriex ME, Marcus MA. Toxicity of local anaesthetics. Best Pract Res Clin Anaesthesiol. 2003 Mar;17(1):111-36
9. Faccenda KA, Finucane BT. Complications of regional anaesthesia, incidence and prevention. Drug Saf. 2001;24(6):413-4.
10. Felice KL, Schumann HM. Intravenous Lipid Emulsion for Local Anesthetic Toxicity: A Review of the Literature. J Med Toxicol, 2008;4(3):184-91.
11. Barrington MJ, Watts SA, Gledhill SR, et al. Preliminary Results of the Australasian Regional Anaesthesia Collaboration A Prospective Audit of More Than 7000 Peripheral Nerve and Plexus Blocks for Neurologic and Other Complications. Reg Anesth Pain Med 2009;34:534-41.
12. Kindler CH, Yost CE. Two-pore domain potassium channels: new sites of local anesthetic action and toxicity. Reg Anesth Pain Med 2005;30:260-274.
13. Hollmann MW, Herroeder S, Kurz KS, et al. Time-dependent inhibition of G-protein coupled receptor signaling by local anesthetics. Anesthesiology. 2004; 100:852-860.
14. Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: A multi-factorial concept. Reg Anesth Pain Med 2004;29:564-575.
15. Niesel HC. Local anesthetics maximum recommended doses. Anaesthesiol Reanim. 1997;22(3):60-2.
16. Kucera IJ, Lambert TJ, Klein JA, et al. Liposuction: contemporary issues for the anesthesiologist. Journal of Clinical Anesthesia 2006;18:379-87.
17. Weinberg GL. Lipid Infusion Therapy: Translation to Clinical Practice, Anesth Analg 2008;106:5 1340-42.
18. Mazoit J, Le Guen R, Beloeil H, et al. Binding of Long-lasting Local Anesthetics to Lipid Emulsions, Anesthesiology 2009; 110:380-6.
19. Foxall G, McCahon R, Lamb J, et al. Levobupivacaine-induced seizures and cardiovascular collapse treated with Intralipid. Anaesthesia. 2007;62:516-518.
20. Chazalon P, Tourtier JP, Villevielle T, et al. Ropiva-caine-induced Cardiac Arrest after Peripheral Nerve Block: Successful Resuscitation. Anesthesiology 2003; 99:1449-51.
21. Huet O, Eyrolle LJ, Mazoit JX, et al. Cardiac Arrest after Injection of Ropivacaine for Posterior Lumbar Plexus Blockade Anesthesiology 2003; 99:1451-3.
22. Tasch MD, Butterworth JF. Toxicity of local anesthetics, ASA REFRESHING COURSE, 2006.
23. Zink W, Graf BM. The toxicity of local anesthetics: the place of ropivacaine and levobupivacaine. Current Opinion in Anaesthesiology. 2008;21:645-650.
24. Harmatz A. Local Anesthetics: Uses and Toxicities. Surg Clin N Am 2009;89:587-98.
25. Heavner JE. Cardiac toxicity of local anesthetics in the intact isolated heart model: a review. Reg Anesth Pain Med 2002;27:545-555.
26. Liu P, Feldmahn S, Covino BM, et al. Acute cardiovascular toxicity of intravenous amide local anesthetics in anesthetized ventilated dogs. Anesth Analg 1982;61:317-22.
27. Simon L, Kariya N, Pelle-Lancien E, et al. Bupivacaine-Induced QRS Prolongation is Enhanced by Lidocaine and by Phenytoin in Rabbit Hearts. Anesth Analg 2002;94:203-7.
28. Mets B, Janicki PK, James MF, et al. Lidocaine and Bupivacaine Cardiorespiratory Toxicity Is Additive: A Study in Rats. Anesth Analg 1992;75:611-4.
29. Thomas RD, Behbehani MM, Coyle DE, et al. Cardiovascular Toxicity of Local Anesthetics: An Alternative Hypothesis. Anesth Analg 1986;65:444-50.
30. Weinberg GL. Current Concepts in Resuscitation of Patients With Local Anesthetic Cardiac Toxicity. Reg Anesth Pain Med. 2002; 27(6): 568-75.
31. The Association of Anaesthetists of Great Britain & Ireland 2007. Guidelines for the Management of Severe Local Anaesthetic Toxicity. http://www.aagbi.org/publications/guidelines/docs/latoxicity07.pdf. 2007.
32. Copeland SE, Ladd LA, Gu X, et al. The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses. Anesth Analg 2008;106:1440-9.
33. Copeland SE, Ladd LA, Gu X, et al. The Effects of General Anesthesia on the Central Nervous and Cardiovascular System Toxicity of Local Anesthetics. Anesth Analg 2008;106:1429-39.
34. Corcoran W, Butterworth J, Weller RS, et al. Local Anesthetic-Induced Cardiac Toxicity: A Survey of Contemporary Practice Strategies Among Academic Anesthesiology Departments. Anesth Analg 2006;103:1322-26.
35. Hicks SD, Salcido DD, Logue ES, et al. Lipid emulsion combined with epinephrine and vasopressin does not improve survival in a swine model of bupivacai-neinduced cardiac arrest. Anesthesiology 2009;111:138-46.
36. Hiller DB, Di Gregorio G, Ripper R, et al. Epinephrine Impairs Lipid Resuscitation from Bupivacaine Overdose A Threshold Effect. Anesthesiology 2009;111:498-505.
37. Zausig YA, Zink W, Keil M, et al. Lipid Emulsion Improves Recovery from Bupivacaine-Induced Cardiac Arrest, but Not from Ropivacaine- or Mepivacaine-Induced Cardiac Arrest. Anesth Analg 2009;109:1323-6.
38. Picard J, Ward SC, Zumpe R, et al. Guidelines and the adoption of "lipid rescue" therapy for local anaesthetic toxicity. Anaesthesia 2009; 64:122-125.
39. Picard J, Harrop-Griffiths W. Lipid emulsion to treat drug overdose: past, present and future. Anaesthesia 2009; 64:119-121.
40. Cave G, Harvey MG, Winterbottom T. Evaluation of the Association of Anaesthetists of Great Britain and Ireland lipid infusion protocol in bupivacaine induced cardiac arrest in rabbits. Anesthesia. 2009;64(7):732-7.
41. Leskiw U , Weinberg GL. Lipid resuscitation for local anesthetic toxicity: is it really lifesaving?. Curr Opin Anaesthesio. 2009;22:667-71.
42. Weinberg G. Lipid infusion resuscitation for local anesthetic toxicity: Proof of clinical efficacy. Anesthesiology 2006; 105:7-8.
43. Spence A. Lipid reversal of central nervous system symptoms of bupivacaine toxicity. Anesthesiology 2007; 107:516-517.
44. Shah S, Gopalakrishnan S, Apuya J, et al. Use of Intralipid in an infant with impending cardiovascular collapse due to local anesthetic toxicity Anesth 2009:23:439-41.
45. Rosenblatt MA, Abel M, Fischer GW, et al. Successful Use of a 20% Lipid Emulsion to Resuscitate a Patient after a Presumed Bupivacaine-related Cardiac Arrest. Anesthesiology 2006;105:217-8.
46. 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;106:1572-4.
47. Warren JA, Thoma RB, Georgescu A, et al. Intravenous Lipid Infusion in the Successful Resuscitation of Local Anesthetic-Induced Cardiovascular Collapse After Supraclavicular Brachial Plexus Block. Anesth Analg 2008;106:1578-80.
48. Gregorio GD, Schawartz D, Ripper R, et al. Lipid emulsion is superior to vasopressin in a rodent model of resuscitation from toxin-induced cardiac arrest. Crit Care Med 2009; 37:993-999.
49. Picard J, Ward SC, Zumpe R, et al. Guidelines and the adoption of 'lipid rescue' therapy for local anaesthetic toxicity. Anaesthesia. 2009 Feb;64(2):122-5.
50. Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion. Anaesthesia 2006;61:800-1.
51. Litz R, Roessel T, Heller AR, et al. Reversal of Central Nervous System and Cardiac Toxicity After Local Anesthetic Intoxication by Lipid Emulsion Injection. Anesth Analg 2008;106:1575-7.
52. Corman SL, Skledar SJ. Use of Lipid Emulsion to Reverse Local Anesthetic-Induced Toxicity Corman and Skledar. Ann Pharmacother 2007;41:1873-7.
53. Weinberg GL. Limits to Lipid in the Literature and Lab: What We Know, What We Don't Know. Anesth Analg 2009;108(4):1062-4.
54. Brull SJ. Lipid Emulsion for the Treatment of Local Anesthetic Toxicity: Patient Safety Implications. Anesth Analg. 2008;106:1337-8.
55. Marwick PC, Levin AI, Coetzee AR. Recurrence of Cardiotoxicity After Lipid Rescue from Bupivacaine-Induced Cardiac Arrest. Anesth Analg 2009;108: 1344-6.
How to Cite
1.
Valencia Gómez RE, Garcia Araque HF. Toxicity Due to Local Anesthetic Agents: Literature Review. Colomb. J. Anesthesiol. [Internet]. 2011 Jan. 1 [cited 2024 Apr. 23];39(1):40-54. Available from: https://www.revcolanest.com.co/index.php/rca/article/view/711
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2011-01-01
How to Cite
1.
Valencia Gómez RE, Garcia Araque HF. Toxicity Due to Local Anesthetic Agents: Literature Review. Colomb. J. Anesthesiol. [Internet]. 2011 Jan. 1 [cited 2024 Apr. 23];39(1):40-54. Available from: https://www.revcolanest.com.co/index.php/rca/article/view/711
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Narrative review
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