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Local Anesthetic Toxicity

  • David L. Brown

Abstract

Effective regional block is not possible without the use of local anesthetics. Even though local anesthetics have been used for more than 115 years, details about balancing risks of their toxic effects with the benefits of their therapeutic effects remain poorly focused for many clinicians. In this chapter, the most frequent toxic effect of local anesthetics — local anesthetic systemic toxicity — will be covered, as will the less-frequent clinical situations of allergy to local anesthetics and myelotoxicity.

Keywords

Local Anesthetic Sodium Channel Regional Anesthesia Local Anesthetic Agent Regional Block 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Feldman HS. Toxicity of local anesthetic agents. In: Rice SA, Fish KJ, eds. Anesthetic Toxicity. New York: Raven Press; 1994:107–133.Google Scholar
  2. 2.
    Holmstedt B, Fredga A. Sundry episodes in the history of coca and cocaine. J Ethnopharmacol 1981;3:113–147.PubMedCrossRefGoogle Scholar
  3. 3.
    Fink BR. History of neural blockade. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and Management of Pain. Philadelphia: JB Lippincott; 1988: 3–15.Google Scholar
  4. 4.
    Mattison JB. Cocaine poisoning. Med Surg Rep 1891;60:645–650.Google Scholar
  5. 5.
    Reclus P. Analgésie locale par la cocaïne. Rev Chir 1889;9:913.Google Scholar
  6. 6.
    Braun H. Ueber einige neuerörtliche Anesthetica (Stovain, Alypin, Novocain). Dtsch Klin Wochenschr 1905;31:1667.CrossRefGoogle Scholar
  7. 7.
    Eggleston C, Hatcher RA. A further contribution to the pharmacology of the local anesthetics. J Pharmacol Exp Ther 1919;13:433.Google Scholar
  8. 8.
    Tatum AL, Atkinson AJ, Collins KH. Acute cocaine poisoning, its prophylaxis and treatment in laboratory animals. J Pharmacol Exp Ther 1925;26:325–335.Google Scholar
  9. 9.
    Englesson S. The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. Acta Anaesthesiol Scand 1974;18:79–87.PubMedCrossRefGoogle Scholar
  10. 10.
    Tanaka K, Yamasaki M. Blocking of cortical inhibitory synapses by intravenous lidocaine. Nature 1966;209:207–208.PubMedCrossRefGoogle Scholar
  11. 11.
    Wagman IH, DeJong RH, Prince DA. Effects of lidocaine on the central nervous system. Anesthesiology 1967;28:155–172.PubMedCrossRefGoogle Scholar
  12. 12.
    Truex RC, Carpenter MB. The basal ganglia and rhinencephalon, olfactory and limbic system pathways. In: Human Neuroanatomy. 6th ed. Baltimore: Williams & Wilkins; 1971: 498–542.Google Scholar
  13. 13.
    Garfield JM, Gugino L. Central effects of local anesthetic agents. In: Strichartz G, ed. Local Anesthetics. Vol 81. New York: Springer-Verlag; 1987:253–284.Google Scholar
  14. 14.
    Green JD, Duisberg REH, McGrath WB. Focal epilepsy of psychomotor type. A preliminary report of observations on effects of surgical therapy. J Neurosurg 1951;8:157–172.PubMedCrossRefGoogle Scholar
  15. 15.
    Pool JL. Neurophysiological symposium: visceral brain in man. J Neurosurg 1954;11: 45–63.PubMedCrossRefGoogle Scholar
  16. 16.
    MacLean PD, Delgado JMR. Electrical and chemical stimulation of fronto-temporal portion of limbic system in the waking animal. Electroencephalogr Clin Neurophysiol 1952;5:91–100.Google Scholar
  17. 17.
    Feindel W, Penfield W. Localization of discharge in temporal lobe automatism. AMA Arch Neurol Psychiatry 1954;72:605–630.Google Scholar
  18. 18.
    Eidelberg E, Lesse H, Gaulta FP. An experimental model of temporal lobe epilepsy. Studies of the convulsant properties of cocaine. In: Glaser GH, ed. EEG and Behavior. New York: Basic Books; 1963:Chapter 10.Google Scholar
  19. 19.
    DeJong RH. Central nervous system effects. In: DeJong RH, ed. Local Anesthetics. 2nd ed. Springfield, IL: Charles C. Thomas; 1977:84–114.Google Scholar
  20. 20.
    Stein PA, Michenfelder JD. Neurotoxicity of anesthetics. Anesthesiology 1979;50:437–453.CrossRefGoogle Scholar
  21. 21.
    Moore DC. Administer oxygen first in the treatment of local anesthetic-induced convulsions. Anesthesiology 1980;53:346–347.PubMedCrossRefGoogle Scholar
  22. 22.
    Maekawa T, Oshibuchi T, Takao, Takeshita H, Imamura A. Cerebral energy state and glycolytic metabolism during lidocaine infusion in the rat. Anesthesiology 1981;54:278–283PubMedCrossRefGoogle Scholar
  23. 23.
    DeJong RH, Heavner JE. Diazepam prevents local anesthetic seizures. Anesthesiology 1971;34:523–531.CrossRefGoogle Scholar
  24. 24.
    Brown DL, Ransom DM, Hall J A, Leicht CH, Schroeder DR, Offord KP. Regional anesthesia and local anesthetic-induced systemic toxicity: seizure frequency and accompanying cardiovascular changes. Anesth Analg 1995;81:321–328.PubMedGoogle Scholar
  25. 25.
    Löfström JB. Physiologic disposition of local anesthetics. Reg Anesth 1982:33–38.Google Scholar
  26. 26.
    Covino BG. Pharmacology of local anesthetic agents. In: Rogers MC, Tinker JH, Covino BG, et al., eds. Principles and Practice of Anesthesiology. St. Louis: Mosby Year Book; 1993:1235–1257.Google Scholar
  27. 27.
    Scott DB. Toxic effects of local anaesthetic agents on the central nervous system. Br J Anaesth 1986;58:732–735.PubMedCrossRefGoogle Scholar
  28. 28.
    Gerard JL, Edouard A, Berdeaux A, Duranteau J, Ahmad R. Interaction of intravenous diazepam and dupivacaine in conscious dogs. Reg Anesth 1989;14:298–303.PubMedGoogle Scholar
  29. 29.
    Bernards CM, Carpenter RL, Rupp SM, et al. Effect of midazolam and diazepam premedication on central nervous system and cardiovascular toxicity of bupivacaine in pigs. Anesthesiology 1989;70:318–323.PubMedCrossRefGoogle Scholar
  30. 30.
    Ausinsch B, Malagodi MH, Munson ES. Diazepam in the prophylaxis of lignocaine seizures. Br J Anaesth 1976;48:309.PubMedCrossRefGoogle Scholar
  31. 31.
    Englesson S. The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. I. An experimental study in cats. Acta Anaesthesiol Scand 1974;18: 79–87.PubMedCrossRefGoogle Scholar
  32. 32.
    Covino BG. Toxicity and systemic effects of local anesthetic agents. In: Brown DL, ed. Local Anesthesia. Vol 81. New York: Springer-Verlag; 1987:187–212.Google Scholar
  33. 33.
    Concepcion M. Acute complications and side effects of regional anesthesia. In: Regional Anesthesia and Analgesia. Philadelphia: WB Saunders; 1996:Chapter 23.Google Scholar
  34. 34.
    Heavner JE. Cardiac toxicity of local anesthetics in the intact isolated heart model: a review. Reg Anesth Pain Med 2002;27:545–555.PubMedGoogle Scholar
  35. 35.
    Lynch C III. Depression of myocardial contractility in vitro by bupivacaine, etidocaine, and lidocaine. Anesth Analg 1986;65:551–559.PubMedGoogle Scholar
  36. 36.
    Moller RA, Covino BG. Cardiac electrophysiologic effects of lidocaine and bupivacaine. Anesth Analg 1988;67:107–114.PubMedCrossRefGoogle Scholar
  37. 37.
    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.PubMedCrossRefGoogle Scholar
  38. 38.
    Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine [editorial]. Anesthesiology 1979;51:285–287.PubMedCrossRefGoogle Scholar
  39. 39.
    Blair MR. Cardiovascular pharmacology of local anaesthetics. Br J Anaesth 1975;47: 247–252.PubMedGoogle Scholar
  40. 40.
    Scott DB. “Maximal recommended doses” of local anaesthetic drugs. Br J Anaesth 1989; 63(4):373–374.PubMedCrossRefGoogle Scholar
  41. 41.
    Strichartz GR, Berde CB. Local anesthetics. In: Miller RD, ed. Anesthesia. 4th ed. New York: Churchill Livingstone; 1994:489–521.Google Scholar
  42. 42.
    DiFazio CA, Woods AM. Drugs commonly used for nerve blocking: pharmacology of local anesthetics. In: Prithi R, ed. Practical Management of Pain. 2nd ed. St. Louis: Mosby Year Book; 1992:685–700.Google Scholar
  43. 43.
    Braid DP, Scott DB. The systemic absorption of local analgesic drugs. Br J Anaesth 1965; 37:394–404.PubMedCrossRefGoogle Scholar
  44. 44.
    Rosenberg PH, Veering BT, Urmey WE. Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med 2004;29:564–575.PubMedGoogle Scholar
  45. 45.
    Braid DP, Scott DB. The effect of adrenaline on the systemic absorption of local anaesthetic drugs. Acta Anaesthesiol Scand 1996;(suppl 23):334–346.Google Scholar
  46. 46.
    Raj RP, Rosenblatt R, Miller J, Katx RL, Corden E. Dynamics of local anesthetic comounds in regional anesthesia. Anesth Analg 1977;56:110–117.PubMedCrossRefGoogle Scholar
  47. 47.
    Mather LE, Tucker GT, Murphy TM, Stanton-Hicks M, Bonica JJ. Effect of adding adrenaline to etidocaine and lignocaine in extradural anaesthesia. II. Pharmacokinetics. Br J Anaesth 1976;48:989–994.PubMedCrossRefGoogle Scholar
  48. 48.
    Wildsmith JAW, Tucker GT, Cooper S, Scott DB, Covino BG. Plasma concentrations of local anaesthetics after interscalene brachial plexus block. Br J Anaesth 1977;49:461–466.PubMedCrossRefGoogle Scholar
  49. 49.
    Wilkinson GR, Lund PC. Bupivacaine levels in plasma and cerebrospinal fluid following peridural administration. Anesthesiology 1970;33:482–486.PubMedCrossRefGoogle Scholar
  50. 50.
    Appleyard TN, Witt A, Atkinson RE, Nicholas ADG. Bupivacaine carbonate and bupivacaine hydrochloride: a comparison of blood concentrations during epidural blockade for vaginal surgery. Br J Anaesth 1974;46:503–533.CrossRefGoogle Scholar
  51. 51.
    Abdel-Salam AR, Vonwiller JB, Scott DB. Evaluation of etidocaine in extradural block. Br J Anaesth 1975;47:1081–1086.PubMedCrossRefGoogle Scholar
  52. 52.
    Pälve H, Kirvelä O, Olin H, Syvälahti E, Kanto J. Maximum recommended doses of lignocaine are not toxic. Br J Anaesth 1995;74:704–705.PubMedCrossRefGoogle Scholar
  53. 53.
    Samdal F, Amland PF, Bugge JF. Plasma lidocaine levels during suction-assisted lipectomy using large doses of dilute lidocaine with epinephrine. Plast Reconstr Surg 1994;93(6): 1217–1223.PubMedCrossRefGoogle Scholar
  54. 54.
    Moore DC, Batra MS. The components of an effective test dose prior to epidural block. Anesthesiology 1981;55(6):693–696.PubMedCrossRefGoogle Scholar
  55. 55.
    Auroy Y, Benhamou D, Bargue L, et al. Major complications in regional anesthesia in France: the SOS regional anesthesia hotline service. Anesthesiology 2002;97:1274–1280.PubMedCrossRefGoogle Scholar
  56. 56.
    Liu P, Feldman HS, Covino BM, Giasi R, Covino BG. Acute cardiovascular toxicity of intravenous amide local anesthetics in anesthetized ventilated dogs. Anesth Analg 1982; 61:317–322.PubMedGoogle Scholar
  57. 57.
    Feldman HS, Arthur GR, Covino BG. Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog. Anesth Analg 1989;69:794–801.PubMedGoogle Scholar
  58. 58.
    Feldman HS, Arthur GR, Pitkanen M, Hurley R, Doucette AM, Covino BG. Treatment of acute systemic toxicity after the rapid intravenous injection of ropivacaine and bupivacaine in the conscious dog. Anesth Analg 1991;73:373–384.PubMedCrossRefGoogle Scholar
  59. 59.
    Covino BG. Toxicity and systemic effects of local anesthetic agents. In: Strichartz G, ed. Local Anesthesia. New York: Springer-Ver lag; 1987:187–209.Google Scholar
  60. 60.
    Davis NL, deJong RH. Successful resuscitation following massive bupivacaine overdose. Anesth Analg 1982;61:62–64.PubMedGoogle Scholar
  61. 61.
    Moore DC, Bridenbaugh LD. Oxygen: the antidote for systemic toxic reactions from local anesthetic drugs. JAMA 1960;174:842–847.PubMedGoogle Scholar
  62. 62.
    Moore DC, Crawford RD, Scurlock JE. Severe hypoxia and acidosis following local anesthetic-induced convulsions. Anesthesiology 1980;53(3):259–260.PubMedCrossRefGoogle Scholar
  63. 63.
    Moore DC, Thompson GE, Crawford RD. Long-acting local anesthetic drugs and convulsions with hypoxia and acidosis. Anesthesiology 1982;56(3):230–232.PubMedCrossRefGoogle Scholar
  64. 64.
    Reis S, Nath S. Cardiotoxicity of local anaesthetic agents. Br J Anaesth 1986;58: 736–746.CrossRefGoogle Scholar
  65. 65.
    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.PubMedGoogle Scholar
  66. 66.
    Varshney M, Morey TE, Shah DO, et al. Pluronic microemulsions as nanoreservoirs for extraction of bupivacaine from normal saline. J Am Chem Soc 2004;126:5108–5112.PubMedCrossRefGoogle Scholar
  67. 67.
    Kim JT, Jung CW, Lee KH. The effect of insulin on the resuscitation of bupivacaine-induced severe cardiovascular toxicity in dogs. Anesth Analg 2004;99:728–733.PubMedCrossRefGoogle Scholar
  68. 68.
    Weinberg GL. Current concepts in resuscitation of patients with local anesthetic toxicity. Reg Anesth Pain Med 2002;27:568–575.PubMedGoogle Scholar
  69. 69.
    Bennett A. The physiological action of coca. Br Med J 1874;1:5–10.Google Scholar
  70. 70.
    Freud S. Über Coca. Zentralbl Ges Ther 1884;2:289–314.Google Scholar
  71. 71.
    Bull CS. The hydrochlorate of cocaine as a local anaesthetic in ophthalmic surgery. NY Med J 1884;40:643–644.Google Scholar
  72. 72.
    Hall RJ. Hydrochlorate of cocaine. NY Med J 1884;40:609–611.Google Scholar
  73. 73.
    Corning JL. Spinal anaesthesia and local medication of the cord. NY Med J 1885;42: 483–485.Google Scholar
  74. 74.
    Adriani J. Reactions to local anesthetics. JAMA 1966;196:119.CrossRefGoogle Scholar
  75. 75.
    Aldrete JA, Johnson DA. Evaluation of intracutaneous testing for investigation of allergy to local anesthetic agents. Anesth Analg 1970;49:173.PubMedGoogle Scholar
  76. 76.
    Incaudo G, Schatz M, Patterson R, et al. Administration of local anesthetics to patients with a history of prior adverse reaction. J Allergy Clin Immunol 1978;61:339.PubMedCrossRefGoogle Scholar
  77. 77.
    Brown DT, Beamish D, Wildsmith JAW. Allergic reaction to an amide local anaesthetic. Br J Anaesth 1981;53:435.PubMedCrossRefGoogle Scholar
  78. 78.
    Nagel JE, Fuscaldo JT, Fireman P. Paraben allergy. JAMA 1977;237:1594.PubMedCrossRefGoogle Scholar
  79. 79.
    DeShazo RD, Nelson HS. An approach to the patient with a history of local anaesthetic hypersensitivity: experience with 90 patients. J Allergy Clin Immunol 1979;63:387.PubMedCrossRefGoogle Scholar
  80. 80.
    Fisher MM. Intradermal testing in the diagnosis of acute anaphylaxis during anaesthesia-results of five years’ experience. Anaesth Intensive Care 1979;7:58.PubMedGoogle Scholar
  81. 81.
    Benoit PW, Belt WD. Some effects of local anesthetic agents on skeletal muscle. Exp Neurol 1972;34:264–278.PubMedCrossRefGoogle Scholar
  82. 82.
    Hall-Craggs ECB. Rapid degeneration and regeneration of a whole skeletal muscle following treatment with bupivacaine (Marcaine). Exp Neurol 1974;43:349–358.PubMedCrossRefGoogle Scholar
  83. 83.
    Johnson ME, Jones GH. Effects of Marcaine, a myotoxic drug, on macromolecular synthesis in muscle. Biochem Pharmacol 1978;27:1753–1757.PubMedCrossRefGoogle Scholar
  84. 84.
    Zink W, Graf BM. Local anesthetic myotoxicity. Reg Anesth Pain Med 2004;29: 333–340.PubMedGoogle Scholar
  85. 85.
    Foster AH, Carlson BM. Myotoxicity of local anesthetics and regeneration of the damaged muscle fibers. Anesth Analg 1980;59:727–736.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • David L. Brown
    • 1
  1. 1.Department of Anesthesiology and Pain MedicineM. D. Anderson Cancer CenterHoustonUSA

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