Skip to main content

Local Anesthetic Toxicity: Prevention and Management

  • Chapter
  • First Online:
Complications of Regional Anesthesia

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Reg Anesth Pain Med. 2002;27:556–61.

    Article  CAS  PubMed  Google Scholar 

  2. Brown DL, Ransom DM, Hall JA, Leicht CH, Schroeder DR, Offord KP. Regional anesthesia and local anesthetic-induced systemic toxicity: seizure frequency and accompanying cardiovascular changes. Anesth Analg. 1995;81:321–8.

    CAS  PubMed  Google Scholar 

  3. Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K. Serious complications related to regional anesthesia: results of a prospective survey in France. Anesthesiology. 1997;87:479–86.

    Article  CAS  PubMed  Google Scholar 

  4. Barrington MJ, Kluger R. Ultrasound guidance reduces the risk of local anesthetic systemic toxicity following peripheral nerve blockade. Reg Anesth Pain Med. 2013;38:289–99.

    Article  PubMed  Google Scholar 

  5. Sites BD, Taenzer AH, Herrick MD, Gilloon C, Antonakakis J, Richins J, Beach ML. Incidence of local anesthetic systemic toxicity and postoperative neurologic symptoms associated with 12,668 ultrasound-guided nerve blocks: an analysis from a prospective clinical registry. Reg Anesth Pain Med. 2012;37:478–82.

    Article  CAS  PubMed  Google Scholar 

  6. Fink BR. Leaves and needles: the introduction of surgical local anesthesia. Anesthesiology. 1985;63:77–83.

    Article  CAS  PubMed  Google Scholar 

  7. Anonymous: Cocaine. Br Med J 1979 Apr 14; 1(6169):971–2

    Google Scholar 

  8. Link WJ. Alfred Einhorn, Sc. D.: inventor of novocaine. Dent Radiogr Photogr. 1959;32:1–20.

    Google Scholar 

  9. Verfahren zur Darstellung von p-Aminobenzoesaurealkaminestern. Meister Lucius und Bruning in Hochst A.M. (179 627 (klasse 12q. Gruppe 6)). 11-27-1904.

    Google Scholar 

  10. Guptill A. Novocain as a skin irritant. Dent Cosmos. 1920;62:1460–1.

    CAS  Google Scholar 

  11. Lofgren N, Lundquist B. Studies on local anesthetics II. Sven Kem Tidskr. 1946;58:206.

    CAS  Google Scholar 

  12. Ekenstam B, Egner B, Petterson G. Local anaesthetics: I. N-alkyl pyrrolidine and N-alkyl piperidine carboxylic acid amides. Acta Chem Scand. 1957;11:1183–90.

    Article  Google Scholar 

  13. Moore DC, Bridenbaugh LD, Thompson GE, Balfour RI, Horton WG. Bupivacaine: a review of 11,080 cases. Anesth Analg. 1978;57:42–53.

    Article  CAS  PubMed  Google Scholar 

  14. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology. 1979;51:285–7.

    Article  CAS  PubMed  Google Scholar 

  15. Reiz S, Nath S. Cardiotoxicity of local anaesthetic agents. Br J Anaesth. 1986;58:736–46.

    Article  CAS  PubMed  Google Scholar 

  16. Marx GF. Cardiotoxicity of local anesthetics--the plot thickens. Anesthesiology. 1984;60:3–5.

    Article  CAS  PubMed  Google Scholar 

  17. Heath ML. Bupivicaine toxicity and bier blocks. Anesthesiology. 1983;59:481.

    Article  CAS  PubMed  Google Scholar 

  18. Rousso M, Wexler MR, Weinberg H, Magora F. Regional anesthesia for hand surgery. Prog Surg. 1979;16:44–52.

    Article  CAS  PubMed  Google Scholar 

  19. Casati A, Putzu M. Bupivacaine, levobupivacaine and ropivacaine: are they clinically different? Best Pract Res Clin Anaesthesiol. 2005;19:247–68.

    Article  CAS  PubMed  Google Scholar 

  20. Aberg G. Toxicological and local anaesthetic effects of optically active isomers of two local anaesthetic compounds. Acta PharmacolToxicol(Copenh). 1972;31:273–86.

    Article  CAS  Google Scholar 

  21. Bruhova I, Tikhonov DB, Zhorov BS. Access and binding of local anesthetics in the closed sodium channel. Mol Pharmacol. 2008;74:1033–45.

    Article  CAS  PubMed  Google Scholar 

  22. Berde C. Local anesthetics in infants and children: an update. Paediatr Anaesth. 2004;14:387–93.

    Article  PubMed  Google Scholar 

  23. Mazoit JX. Pharmacology of local anesthetics. In: Bissonnette BJD, editor. Pediatric anesthesia: principles and practice. New York: McGraw-Hill; 2002. p. 302–37.

    Google Scholar 

  24. O’Donnell B, Riordan J, Ahmad I, Iohom G. Brief reports: a clinical evaluation of block characteristics using one milliliter 2 % lidocaine in ultrasound-guided axillary brachial plexus block. Anesth Analg. 2010;111:808–10.

    Article  PubMed  Google Scholar 

  25. Riazi S, Carmichael N, Awad I, Holtby RM, McCartney CJ. Effect of local anaesthetic volume (20 vs 5 ml) on the efficacy and respiratory consequences of ultrasound-guided interscalene brachial plexus block. Br J Anaesth. 2008;101:549–56.

    Article  CAS  PubMed  Google Scholar 

  26. Tucker GT. Pharmacokinetics of local anaesthetics. Br J Anaesth. 1986;58:717–31.

    Article  CAS  PubMed  Google Scholar 

  27. Rothstein P, Arthur GR, Feldman HS, Kopf GS, Covino BG. Bupivacaine for intercostal nerve blocks in children: blood concentrations and pharmacokinetics. Anesth Analg. 1986;65:625–32.

    Article  CAS  PubMed  Google Scholar 

  28. Burm AG, Vermeulen NP, van Kleef JW, de Boer AG, Spierdijk J, Breimer DD. Pharmacokinetics of lignocaine and bupivacaine in surgical patients following epidural administration. Simultaneous investigation of absorption and disposition kinetics using stable isotopes. Clin Pharmacokinet. 1987;13:191–203.

    Article  CAS  PubMed  Google Scholar 

  29. Stoelting RK, Hillier SC. Pharmacokinetics and pharmacodynamics of injected and inhaled drugs. In: Stoelting RK, Hillier SC, editors. Handbook of pharmacology and physiology in anesthetic practice. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 3–41.

    Google Scholar 

  30. Dalens BJ, Truchon R. Neural blockade for pediatric surgery. In: Cousins MJ, Bridenbaugh PO, Carr DB, Horlocker TT, editors. Cousins and Bridenbaugh’s neural blockade in clinical anesthesia and pain medicine. 4th ed. Philadelphia, Lippincott: Williams & Wilkins; 2009. p. 595–630.

    Google Scholar 

  31. Vasques F, Behr AU, Weinberg G, Ori C, Di GG. A review of local anesthetic systemic toxicity cases since publication of the American Society of Regional Anesthesia Recommendations: to whom it may concern. Reg Anesth Pain Med. 2015;40:698–705.

    Article  CAS  PubMed  Google Scholar 

  32. Gristwood RW, Greaves JL. Levobupivacaine: a new safer long acting local anaesthetic agent. ExpertOpinInvestigDrugs. 1999;8:861–76.

    CAS  Google Scholar 

  33. 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;62:396–405.

    Article  CAS  PubMed  Google Scholar 

  34. Valenzuela C, Delpon E, Tamkun MM, Tamargo J, Snyders DJ. Stereoselective block of a human cardiac potassium channel (Kv1.5) by bupivacaine enantiomers. BiophysJ. 1995;69:418–27.

    Article  CAS  Google Scholar 

  35. Veering BT. Complications and local anaesthetic toxicity in regional anaesthesia. Curr Opin Anaesthesiol. 2003;16:455–9.

    Article  PubMed  Google Scholar 

  36. Groban L, Deal DD, Vernon JC, James RL, Butterworth J. Does local anesthetic stereoselectivity or structure predict myocardial depression in anesthetized canines? Reg Anesth Pain Med. 2002;27:460–8.

    PubMed  Google Scholar 

  37. Moore DC, Bridenbaugh LD. Oxygen: the antidote for systemic toxic reactions from local anesthetic drugs. JAMA. 1960;174:842–7.

    Article  CAS  PubMed  Google Scholar 

  38. Ludot H, Tharin JY, Belouadah M, Mazoit JX, Malinovsky JM. Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child. Anesth Analg. 2008;106:1572–4, table.

    Google Scholar 

  39. 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;105:217–8.

    Article  PubMed  Google Scholar 

  40. Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. 2003;28:198–202.

    Article  CAS  PubMed  Google Scholar 

  41. Weinberg GL. Current concepts in resuscitation of patients with local anesthetic cardiac toxicity. Reg Anesth Pain Med. 2002;27:568–75.

    Article  CAS  PubMed  Google Scholar 

  42. Fettiplace MR, Akpa BS, Ripper R, Zider B, Lang J, Rubinstein I, Weinberg G. Resuscitation with lipid emulsion: dose-dependent recovery from cardiac pharmacotoxicity requires a cardiotonic effect. Anesthesiology. 2014;120:915–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Fettiplace MR, Ripper R, Lis K, Lin B, Lang J, Zider B, Wang J, Rubinstein I, Weinberg G. Rapid cardiotonic effects of lipid emulsion infusion. Crit Care Med. 2013;41:e156–62.

    Article  PubMed  Google Scholar 

  44. Fettiplace MR, Lis K, Ripper R, Kowal K, Pichurko A, Vitello D, Rubinstein I, Schwartz D, Akpa BS, Weinberg G. Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion. J Control Release. 2015;198:62–70.

    Article  CAS  PubMed  Google Scholar 

  45. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998;88:1071–5.

    Article  CAS  PubMed  Google Scholar 

  46. Foxall G, McCahon R, Lamb J, Hardman JG, Bedforth NM. Levobupivacaine-induced seizures and cardiovascular collapse treated with Intralipid. Anaesthesia. 2007;62:516–8.

    Article  CAS  PubMed  Google Scholar 

  47. 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.

    Article  CAS  PubMed  Google Scholar 

  48. Warren JA, Thoma RB, Georgescu A, Shah SJ. Intravenous lipid infusion in the successful resuscitation of local anesthetic-induced cardiovascular collapse after supraclavicular brachial plexus block. Anesth Analg. 2008;106:1578–80, table.

    Google Scholar 

  49. Weinberg GL. Treatment of local anesthetic systemic toxicity (LAST). Reg Anesth Pain Med. 2010;35:188–93.

    Article  CAS  PubMed  Google Scholar 

  50. Long WB, Rosenblum S, Grady IP. Successful resuscitation of bupivacaine-induced cardiac arrest using cardiopulmonary bypass. Anesth Analg. 1989;69:403–6.

    CAS  PubMed  Google Scholar 

  51. Neal JM, Bernards CM, Butterworth JF, Di GG, Drasner K, Hejtmanek MR, Mulroy MF, Rosenquist RW, Weinberg GL. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med. 2010;35:152–61.

    Article  PubMed  Google Scholar 

  52. Hiller DB, Gregorio GD, Ripper R, Kelly K, Massad M, Edelman L, Edelman G, Feinstein DL, Weinberg GL. Epinephrine impairs lipid resuscitation from bupivacaine overdose: a threshold effect. Anesthesiology. 2009;111:498–505.

    Article  CAS  PubMed  Google Scholar 

  53. Jin Z, Xia Y, Xia F, Wu C, Chen Z, Nan F, Wu B, Wan L, Wang X, Papadimos TJ, Xu X. Epinephrine administration in lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest: optimal timing. Reg Anesth Pain Med. 2015;40:223–31.

    Article  CAS  PubMed  Google Scholar 

  54. Gaba DM. Crisis resource management and teamwork training in anaesthesia. Br J Anaesth. 2010;105:3–6.

    Article  CAS  PubMed  Google Scholar 

  55. Neal JM, Hsiung RL, Mulroy MF, Halpern BB, Dragnich AD, Slee AE. ASRA checklist improves trainee performance during a simulated episode of local anesthetic systemic toxicity. Reg Anesth Pain Med. 2012;37:8–15.

    Article  PubMed  Google Scholar 

  56. Krombach JW, Marks JD, Dubowitz G, Radke OC. Development and implementation of checklists for routine anesthesia care: a proposal for improving patient safety. Anesth Analg. 2015;121:1097–103.

    Article  PubMed  Google Scholar 

  57. Mulroy MF, Weller RS, Liguori GA. A checklist for performing regional nerve blocks. Reg Anesth Pain Med. 2014;39:195–9.

    Article  CAS  PubMed  Google Scholar 

  58. Mauch J, Kutter AP, Madjdpour C, Spielmann N, Balmer C, Frotzler A, Bettschart-Wolfensberger R, Weiss M. Electrocardiographic changes during continuous intravenous application of bupivacaine in neonatal pigs. Br J Anaesth. 2010;105:437–41.

    Article  CAS  PubMed  Google Scholar 

  59. Barrington MJ, Watts SA, Gledhill SR, Thomas RD, Said SA, Snyder GL, Tay VS, Jamrozik K. 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.

    Article  PubMed  Google Scholar 

  60. Neal JM. Ultrasound-guided regional anesthesia and patient safety: an evidence-based analysis. Reg Anesth Pain Med. 2010;35:S59–67.

    Article  PubMed  Google Scholar 

  61. Zetlaoui PJ, Labbe JP, Benhamou D. Ultrasound guidance for axillary plexus block does not prevent intravascular injection. Anesthesiology. 2008;108:761.

    Article  PubMed  Google Scholar 

  62. Yoneyama T, Kudo T, Jinno F, Schmidt ER, Kondo T. Retrospective data analysis and proposal of a practical acceptance criterion for inter-laboratory cross-validation of bioanalytical methods using liquid chromatography/tandem mass spectrometry. AAPS J. 2014;16:1226–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Tran DQ, Dugani S, Dyachenko A, Correa JA, Finlayson RJ. Minimum effective volume of lidocaine for ultrasound-guided infraclavicular block. Reg Anesth Pain Med. 2011;36:190–4.

    Article  CAS  PubMed  Google Scholar 

  64. Cuvillon P, Nouvellon E, Ripart J, Boyer JC, Dehour L, Mahamat A, L’hermite J, Boisson C, Vialles N, Lefrant JY, de La Coussaye JE. A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks: a double-blind randomized study. Anesth Analg. 2009;108:641–9.

    Article  CAS  PubMed  Google Scholar 

  65. Mets B, Janicki PK, James MF, Erskine R, Sasman B. Lidocaine and bupivacaine cardiorespiratory toxicity is additive: a study in rats. Anesth Analg. 1992;75:611–4.

    Article  CAS  PubMed  Google Scholar 

  66. Baeriswyl M, Kirkham KR, Kern C, Albrecht E. The analgesic efficacy of ultrasound-guided transversus abdominis plane block in adult patients: a meta-analysis. Anesth Analg. 2015;121:1640–54.

    Article  PubMed  Google Scholar 

  67. De Oliveira Jr GS, Castro-Alves LJ, Nader A, Kendall MC, McCarthy RJ. Transversus abdominis plane block to ameliorate postoperative pain outcomes after laparoscopic surgery: a meta-analysis of randomized controlled trials. Anesth Analg. 2014;118:454–63.

    Article  PubMed  Google Scholar 

  68. Dingeman RS, Barus LM, Chung HK, Clendenin DJ, Lee CS, Tracy S, Johnson VM, Dennett KV, Zurakowski D, Chen C. Ultrasonography-guided bilateral rectus sheath block vs local anesthetic infiltration after pediatric umbilical hernia repair: a prospective randomized clinical trial. JAMA Surg. 2013;148:707–13.

    Article  PubMed  Google Scholar 

  69. Naidu RK, Richebe P. Probable local anesthetic systemic toxicity in a postpartum patient with acute fatty liver of pregnancy after a transversus abdominis plane block. A A CaseRep. 2013;1:72–4.

    Google Scholar 

  70. Scherrer V, Compere V, Loisel C, Dureuil B. Cardiac arrest from local anesthetic toxicity after a field block and transversus abdominis plane block: a consequence of miscommunication between the anesthesiologist and surgeon. A A CaseRep. 2013;1:75–6.

    Google Scholar 

  71. Weiss E, Jolly C, Dumoulin JL, Meftah RB, Blanie P, Laloe PA, Tabary N, Fischler M, Le GM. Convulsions in 2 patients after bilateral ultrasound-guided transversus abdominis plane blocks for cesarean analgesia. Reg Anesth Pain Med. 2014;39:248–51.

    Article  CAS  PubMed  Google Scholar 

  72. Murouchi T, Iwasaki S, Yamakage M. Chronological changes in ropivacaine concentration and analgesic effects between transversus abdominis plane block and rectus sheath block. Reg Anesth Pain Med. 2015;40:568–71.

    Article  CAS  PubMed  Google Scholar 

  73. Hessian EC, Evans BE, Woods JA, Taylor DJ, Kinkel E, Bjorksten AR. Plasma ropivacaine concentrations during bilateral transversus abdominis plane infusions. Br J Anaesth. 2013;111:488–95.

    Article  CAS  PubMed  Google Scholar 

  74. SG DC-L, PW G, North J. Succinyldicholine and lignocaine by continuous intravenous drip; report of 1000 administrations. Anaesthesia. 1954;9:96–104.

    Article  Google Scholar 

  75. Marret E, Rolin M, Beaussier M, Bonnet F. Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery. Br J Surg. 2008;95:1331–8.

    Article  CAS  PubMed  Google Scholar 

  76. Ilfeld BM, Viscusi ER, Hadzic A, Minkowitz HS, Morren MD, Lookabaugh J, Joshi GP. Safety and side effect profile of liposome bupivacaine (Exparel) in peripheral nerve blocks. Reg Anesth Pain Med. 2015;40:572–82.

    Article  CAS  PubMed  Google Scholar 

  77. Bergese SD, Onel E, Morren M, Morganroth J. Bupivacaine extended-release liposome injection exhibits a favorable cardiac safety profile. Reg Anesth Pain Med. 2012;37:145–51.

    Article  CAS  PubMed  Google Scholar 

  78. McAlvin JB, Reznor G, Shankarappa SA, Stefanescu CF, Kohane DS. Local toxicity from local anesthetic polymeric microparticles. Anesth Analg. 2013;116:794–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Derek Dillane MB, BCh, BAO, MMedSci, FCARCSI .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Dillane, D. (2017). Local Anesthetic Toxicity: Prevention and Management. In: Finucane, B., Tsui, B. (eds) Complications of Regional Anesthesia. Springer, Cham. https://doi.org/10.1007/978-3-319-49386-2_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-49386-2_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-49384-8

  • Online ISBN: 978-3-319-49386-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics