Skip to main content
SpringerLink
Log in

Toxicity and Systemic Effects of Local Anesthetic Agents

  • Chapter
Local Anesthetics

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 81))

Abstract

The primary pharmacological action of local anesthetic agents is the inhibition of the excitation conduction process in peripheral nerves. However, the ability of these agents to stabilize membranes is not limited to peripheral nerves. Any excitable membranes such as exist in heart, brain, neuromuscular junction will be altered by local anesthetic agents if they achieve a sufficient tissue concentration. Regional anesthesia which is properly performed usually does not result in blood levels of local anesthetics which are sufficient to cause systemic effects. However, the accidental intravascular injection or the use of an excessive extravascular amount of local anesthetics can result in blood and tissue levels which will cause profound systemic effects. Most of the systemic effects of local anesthetic agents are considered to be undesirable and toxic in nature. However, some actions have proven to be of therapeutic value. For example, the effect of lidocaine on cardiac membranes is responsible for the efficacy of this agent in the treatment of ventricular dysrhythmias (Rosen et al. 1975). The effect of various local anesthetics on membrane structures in the brain have also proven to be of therapeutic value in the treatment of epilepsy (Bernard and Bohn1965). In general, the primary systemic effects of local anesthetic agents are manifest in the central nervous system and the cardiovascular system.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aberg G, Andersson R (1972) Studies on mechanical actions of mepivacaine (Carbocaine) and its optically active isomers on isolated smooth muscle: role of Ca2+ and cyclic AMp. Acta Pharmacol Toxicol 31:321–336

    Article  CAS  Google Scholar 

  • Aberg G, Dhuner KG (1972) Effects of mepivacaine (Carbocaine) on femoral blood flow in the dog. Acta Pharmacol Toxicol 31:267–272

    Article  CAS  Google Scholar 

  • Adams HJ, Mastri AR, Eichholzer A, Kilpatrick G (1974) Morphologic effects of intrathecal etidocaine and tetracaine on the rabbit spinal cord. Anesth Analg 53:904–908

    Article  PubMed  CAS  Google Scholar 

  • Albright GA (1979) Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51:285–287

    Article  PubMed  CAS  Google Scholar 

  • Aldrete JA, Johnson DA (1970) Evaluation of intracutaneous testing for investigation of allergy to local anesthetic agents. Anesth Analg 49:173–181

    PubMed  CAS  Google Scholar 

  • Aldrete JA, O’Higgins JW (1971) Evaluation of patients with history of allergy to local anesthetic drugs. South Med J 64:1118–1121

    Article  PubMed  CAS  Google Scholar 

  • Barsa JE, Batra M, Fink BR, Sumi SM (1982) Prolonged neural blockade following regional analgesia with 2–chloroprocaine. Anesth Analg 61:961–967

    PubMed  CAS  Google Scholar 

  • Benoit PW, Belt WD (1972) Some effects of local anesthetic agents on skeletal muscle. Exp Neurol 345:264–278

    Article  Google Scholar 

  • Bernhard CG, Bohn E (1965) Local anaesthetics as anticonvulsants. A study on experimental and clinical epilepsy. Almqvist and Wiksell, Stockholm

    Google Scholar 

  • Blair MR (1975) Cardiovascular pharmacology of local anaesthetics. Br J Anaesth 47:247–252

    PubMed  Google Scholar 

  • Block A, Covino BG (1982) Effect of local anesthetic agents on cardiac conduction and contractility. Reg Anesth 6:55–61

    Google Scholar 

  • B. G. Covino, Brown DT, Beamish D, Wildsmith JAW (1981) Allergic reaction to an amide local anaesthetic. Br J Anaesth 53:435–437

    Article  Google Scholar 

  • Covino BG, Vassallo HG (1976) Local anesthetics. Mechanism of action and clinical use.Grune and Stratton, New York

    Google Scholar 

  • Dawkins CJM (1969) An analysis of the complications of extradual and caudal block. Anaesthesia 24:554–563

    Article  PubMed  CAS  Google Scholar 

  • Deguchi T, Narahashi T (1971) Effects of procaine on ionic conductances of end-plate membranes. J Pharmacol Exp Ther 176:423–433

    PubMed  CAS  Google Scholar 

  • DeJong RH (1977) Local anesthetics, 2nd ed. Thomas, Springfield

    Google Scholar 

  • DeJong JA, Bonin JD (1980) Deaths from local anesthetic–induced convulsions in mice. Anesth Analg 59:401–405

    CAS  Google Scholar 

  • DeJong JA, Bonin JD (1981) Mixtures of local anesthetics are no more toxic than the parent drugs. Anesthesiology 54:177–181

    Article  CAS  Google Scholar 

  • DeJong RH, Wagman IH, Prince DA (1967) Effect of carbon dioxide on the cortical seizure threshold to lidocaine. Exp Neurol 17:221–232

    Article  CAS  Google Scholar 

  • DeJong RH, Ronfeld RA, DeRosa RA (1982) Cardiovascular effects of convulsant and supraconvulsant doses of amide local anesthetics. Anesth Analg 61:3–9

    Article  CAS  Google Scholar 

  • DeKornfeld TJ, Steinhaus JE (1959) The effect of intravenously administered lidocaine and succinylcholine on the respiratory activity of dogs. Anesth Analg 38:173

    Article  PubMed  CAS  Google Scholar 

  • Demetrescu M, Julien RM (1974) Local anesthesia and experimental epilepsy. Epilepsia 15:235

    Article  PubMed  CAS  Google Scholar 

  • Edde RR, Deutsch S (1977) Cardiac arrest after interscalene brachial plexus block. Anesth Analg 55:446–447

    Google Scholar 

  • Eidelberg E, Neer HM, Miller MK (1965) Anticonvulsant properties of some benzodiazepine derivatives. Neurology (Minneap) 15:223–230

    CAS  Google Scholar 

  • Englesson S (1973) The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. Dissertation, Faculty of medicine, University of Uppsala

    Google Scholar 

  • Englesson S, Eriksson E, Wahlqvist S, Ortengren B (1962) Differences in tolerance to intravenous Xylocaine and Citanest (L67), a new local anesthetic. A double blind study in man. Proc 1st Eur Congr Anesthesiol 2:206–209

    Google Scholar 

  • Essman WB (1966) Anticonvulsive properties of Xylocaine in mice susceptible to audiogenic seizures. Arch Int Pharmacodyn Ther 164:376

    CAS  Google Scholar 

  • Feldman HS, Covino BM, Sage DJ (1982) Direct chronotropic and inotropic effects of local anesthetic agents in isolated guinea pig atria. Reg Anaesth 7:149–156

    CAS  Google Scholar 

  • Foldes FF, Foldes VM, Smith JC, Zsigmond EG (1963) The relation between plasma Cholinesterase and prolonged apnea caused by succinylcholine. Anesthesiology 24:208–216

    Article  PubMed  CAS  Google Scholar 

  • Foldes FF, Davidson GM, Duncalf D, Kuwabara J (1965) The intravenous toxicity of local anesthetic agents in man. Clin Pharmacol Ther 6:328–335

    PubMed  CAS  Google Scholar 

  • Galindo A (1971) Procaine, pentobarbital and halothane: effects on the mammalian myoneural junction. J Pharmacol Exp Ther 177:360–368

    PubMed  CAS  Google Scholar 

  • Gettes LS (1981) Physiology and pharmacology of antiarrhythmic drugs. Hosp Pract 16:89–101

    CAS  Google Scholar 

  • Gissen AJ, Datta S, Lambert D (1984) The chloroprocaine controversy: II. Is chloropro- caine neurotoxic? Reg Anesth 9:135–145

    CAS  Google Scholar 

  • Gordon HR (1968) Fetal bradycardia after paracervical block. Correlation with fetal and maternal blood levels of local anesthetic (mepivacaine). N Engl J Med 279:910–914

    Article  PubMed  CAS  Google Scholar 

  • Hall DR, McGibbon DH, Evans CC, Meadows GA (1972) Gentamicin, tubocuraine, lignocaine and neuromuscular blockade. Br J Anaesth 44:1329–1332

    Article  PubMed  CAS  Google Scholar 

  • Harrison DC, Sprouse JH, Morrow AG (1963) The antiarrhythmic properties of lidocaine and procaine amide; clinical and physiologic studies of their cardiovascular effects in man. Circulation 28:486–491

    PubMed  CAS  Google Scholar 

  • Hirst GDS, Wood Dr (1971) On the neuromuscular paralysis produced by procaine. Br J Pharmacol 41:94–104

    PubMed  CAS  Google Scholar 

  • Huffman RD, Yim GKW (1969) Effects of diphenylaminoethanol and lidocaine on central inhibition. Int J Neuropharmacol 8:217–225

    Article  PubMed  CAS  Google Scholar 

  • Jorfeldt L, Lofstrom B, Pemow B, Wahren J (1970) The effect of mepivacaine and lidocaine on forearm resistance and capacitance vessels in man. Acta Anaesthesiol Scand 14:183–201

    Article  PubMed  CAS  Google Scholar 

  • Julien RM (1973) Lidocaine in experimental epilepsy. Correlation of anticonvulsant effect with blood concentration. Electroencephalogr Clin Neurophysiol 34:639–645

    Article  PubMed  CAS  Google Scholar 

  • Julien RM, Demetrescu M (1974) A neutral local anesthetic for research in experimental epilepsy. J Life Sci 4:27–30

    CAS  Google Scholar 

  • Kao FF, Jalar UH (1959) The central action of lignocaine and its effect on cardiac output. Br J Pharmacol 14:522–526

    CAS  Google Scholar 

  • Katz RL, Gissen AJ (1969) Effects of intravenous and intraarterial procaine and lidocaine on neuromuscular transmission in man. Acta Anaesthesiol Scand [Suppl] 36:103–113

    Article  CAS  Google Scholar 

  • Kotelko DM, Shnider SM, Dailey PA, Brizgys RV, Levinson G, Shapiro A, Koike M, Rosen MA (1984) Bupivacaine-induced cardiac arrhythmias in sheep. Anesthesiology 60:10–18

    Article  PubMed  CAS  Google Scholar 

  • Kuperman AS, Altura BT, Chezar JA (1968) Action of procaine on calcium efflux from frog nerve and muscle. Nature 217:673

    Article  PubMed  CAS  Google Scholar 

  • Libelius R, Sonesson B, Stamenovic BA, Thesleff S (1970) Denervationlike changes in skeletal muscle after treatment with a local anesthetic (Marcaine). J Anat 106:297–309

    PubMed  CAS  Google Scholar 

  • Lieberman NA, Harris RS, Katz RI, Lipschutz HM, Dolgin M, Fisher VJ (1968) The effects of lidocaine on the electrical and mechanical activity of the heart. Am J Cardiol 22:375–380

    Article  PubMed  CAS  Google Scholar 

  • Liu P, Feldman HS, Covino BM, Giasi R, Covino BG (1982 a) Acute cardiovascular toxicity of procaine, chloroprocaine and tetracaine in anesthetized ventilated dogs. Reg Anaesth 7:14–19

    CAS  Google Scholar 

  • Liu P, Feldman HS, Covino BM, Giasi R, Covino BG (1982) Acute cardiovascular toxicity of intravenous amide local anesthetics in anesthetized ventilated dogs. Anesth Analg 61:317–322

    PubMed  CAS  Google Scholar 

  • Liu PL, Feldman HS, Giasi R, Patterson MK, Covino BG (1983) Comparative CNS toxicity of lidocaine, etidocaine, bupivacaine and tetracaine in awake dogs following rapid IV administration. Anesth Analg 62:375–379

    Article  PubMed  CAS  Google Scholar 

  • Lund PC (1962) Peridural anesthesia: a review of 10,000 administrations. Acta Anaesthesiol Scand 6:143–159

    Article  PubMed  CAS  Google Scholar 

  • Moore DC, Bridenbaugh LD (1966) Spinal (subarachnoid) block: a review of 11,574 cases. JAMA 195:907–912

    Article  PubMed  CAS  Google Scholar 

  • Moore DC, Crawford RD, Scurlock JE (1980) Severe hypoxia and acidosis following local anesthetic–induced convulsions. Anesthesiology 53:259–260

    Article  PubMed  CAS  Google Scholar 

  • Morishima HO, Pedersen H, Finster M, Sakuma K, Bruce SL, Gutsche BB, Stark RI, Covino BG (1981) Toxicity of lidocaine in adult, newborn and fetal sheep. Anesthesiology 55:56–61

    Article  Google Scholar 

  • Morishima HO, Pederson H, Finster M, Feldman HS, Covino BG (1983 a) Etidocaine toxicity in the adult, newborn and fetal sheep. Anesthesiology 58:342–346

    Article  PubMed  CAS  Google Scholar 

  • Morishima HO, Pederson H, Finster M, Tsuji A, Hiraoka H, Feldman HS, Arthur RA, Covino BG (1983 b) Is bupivacaine more cardiotoxic than lidocaine? Anesthesiology 59:A409

    Google Scholar 

  • Munson ES, Gutnick MJ, Wagman IH (1970) Local anesthetic druginduced seizures in rhesus monkeys. Anesth Analg 49:486–494

    Article  Google Scholar 

  • Munson ES, Tucker WK, Ausinsch B, Malagodi H (1975) Etidocaine, bupivacaine, and lidocaine seizures thresholds in monkeys. Anesthesiology 42:471–478

    Article  PubMed  CAS  Google Scholar 

  • Nishimura N, Morioka T, Sato S, Kuba T (1965) Effects local anesthetic agents on the peripheral vascular system Anesth Analg 44:135

    Article  PubMed  CAS  Google Scholar 

  • Pizzalato D, Renegar OJ (1959) Histopathologic effects of long exposure to local anesthetics on peripheral nerves. Anesth Analg 38:138–141

    Google Scholar 

  • Prentiss JE (1979) Cardiac arrest following caudal anesthesia. Anesthesiology 50:51–53

    Article  PubMed  CAS  Google Scholar 

  • Ravindran RS, Bond VK, Tasch MD, Gupta CD, Luerssen TG (1980) Prolonged neural blockade following regional analgesia with 2–chloroprocaine. Anesth Analg 59:447–451

    PubMed  CAS  Google Scholar 

  • Ravindran RS, Turner MS, Muller I (1982) Neurological effects of subarachnoid administration of 2–chloroprocaine-CE, bupivacaine and low pH normal saline in dogs. Anesth Analg 61:279–283

    PubMed  CAS  Google Scholar 

  • Reisner LS, Hochman BN, Plumer MH (1980) Persistent neurologic deficit and adhesive arachnoiditis following intrathecal 2–chloroprocaine injection. Anesth Analg 59:452–454

    Article  PubMed  CAS  Google Scholar 

  • Rosen MR, Wit AL, Hoffman BF (1975) Electrophysiology and pharmacology of cardiac arrhythmias: V. Cardiac antiarrhythmic effects of lidocaine. Am Heart J 89:526–536

    Article  PubMed  CAS  Google Scholar 

  • Rosen MA, Baysinger CL, Shnider SM, Dailey DA, Norton M, Levinson G, Curtis JD, Collins W, Davis RL (1982) Evaluation of neurotoxicity of local anesthetics following subarachnoid injection. Anesthesiology 57:A196

    Article  Google Scholar 

  • Sage D, Feldman HS, Arthur GA, Covino BG (1983) Cardiovascular effects of lidocaine and bupivacaine in the awake dog. Anesthesiology 59:A210

    Google Scholar 

  • Sage DJ, Feldman HS, Arthur GR, Datta S, Ferretti AM, Norway SM, Covino BG (1984) Influence of lidocaine and bupivacaine on isolated guinea pig atria in the presence of acidosis and hypoxia. Anesth Analg 63:1–7

    Article  PubMed  CAS  Google Scholar 

  • Scott DB (1975) Evaluation of the toxicity of local anaesthetic agents on man. Br J Anaesth 47:56–61

    Article  PubMed  CAS  Google Scholar 

  • Scott DB (1981) Toxicity caused by local anaesthetic drugs. Br J Anaesth 53:553–554

    Article  PubMed  CAS  Google Scholar 

  • Seo N, Oshima E, Steven J, Mori K (1982) The tetraphasic action of lidocaine on CNS electrical activity and behavior in cats. Anesthesiology 57:451–457

    Article  PubMed  CAS  Google Scholar 

  • Skou JC (1954) Local anaesthetics. II. The toxic potencies of some local anaesthetics and of butyl alcohol, determined on peripheral nerves. Acta Pharmacol Toxicol 10: 292–296

    Article  CAS  Google Scholar 

  • Sorel L, Lejeune R (1955) Modifications de l’EEG du Lapin sons l’action de divers succedanes de la cocaine injectes par voie intraveineuse. Arch Int Pharmacodyn Ther 102:314–334

    PubMed  CAS  Google Scholar 

  • Stewart DM, Rogers WP, Mahaffey JE, Witherspoon S, Woods EF (1963) Effect of local anesthetics on the cardiovascular system in the dog. Anesthesiology 24:620–624

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto T, Schaal SF, Dunn NM, Wallace AG (1969) Electrophysiological effects of lidocaine in awake dogs. J Pharmacol Exp Ther 166:146–150

    PubMed  CAS  Google Scholar 

  • Tanaka K, Yamasaki M (1966) Blocking of cortical inhibitory synapses by intravenous lidocaine. Nature 209:207–208

    Article  PubMed  CAS  Google Scholar 

  • Telivuo L (1967) Effects of intra-arterial mepivacaine and bupivacaine on neuromuscular transmission in man. Acta Anaesthesiol Scand 11:327–332

    Article  PubMed  CAS  Google Scholar 

  • Wagman IH, deJong RH, Prince DA (1968) Effects of lidocaine on spontaneous cortical and subcortical electrical activity: Production of seizure discharges. Arch Neurol 18:277–290

    PubMed  CAS  Google Scholar 

  • Wang BC, Hillman DE, Spiedholz NI, Turndorf H (1984) Chronic neurological deficits and Nesacaine-CE - An effect of the anesthetic, 2–chloroprocaine, or the antioxidant, sodium bisulfite. Anesth Analg 63:445–447

    Article  PubMed  CAS  Google Scholar 

  • Wanna HT, Geigis SD (1978) Procaine, lidocaine, and ketamine inhibit histamine-induced contracture of guinea pig tracheal muscle in vitro. Anesth Analg 57:25–27

    Article  PubMed  CAS  Google Scholar 

  • Warnick JE, Kee RD, Yim GKW (1971) The effects of lidocaine on inhibition in the cerebral cortex. Anesthesiology 34:327–332

    Article  PubMed  CAS  Google Scholar 

  • Weiss EB, Patwardhan AV (1977) The response to lidocaine in bronchial asthma. Chest 72:429–438

    PubMed  CAS  Google Scholar 

  • Weiss EB, Anderson WH, O’Brien KP (1975) The effect of a local anesthetic, lidocaine, on guinea pig trachealis muscle in vitro. Am Rev Resp Dis 112:393–400

    PubMed  CAS  Google Scholar 

  • Weiss EB, Hargraves WA, Viswanath S (1978) The inhibitory action of lidocaine in anaphylaxis. Am Resp Dis 117:859–869

    CAS  Google Scholar 

  • Wollenberger A, Krayer O (1948) Experimental heart failure caused by central nervous system depressants and local anesthetics. J Pharmacol Exp Ther 94:439–443

    PubMed  CAS  Google Scholar 

  • Zener JC, Harrison DC (1974) Serum enzyme values following intramuscular administration of lidocaine. Arch Intern Med 134:48–49

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. B. G. Covino
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Anesthesia Research Laboratories, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    Gary R. Strichartz Ph. D. (Associate Professor) (Associate Professor)

  2. Department of Pharmacology, Harvard Medical School, Boston, MA, 02115, USA

    Gary R. Strichartz Ph. D. (Associate Professor) (Associate Professor)

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Covino, B.G. (1987). Toxicity and Systemic Effects of Local Anesthetic Agents. In: Strichartz, G.R. (eds) Local Anesthetics. Handbook of Experimental Pharmacology, vol 81. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71110-7_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-71110-7_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-71112-1

  • Online ISBN: 978-3-642-71110-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation