Summary
Local anaesthetics are responsible for 5 to 10% of all reported adverse reactions to anaesthetic drugs. Adverse effects may be classified as: (a) those associated directly with blocking ion channels in cell membranes, such as cardiovascular and CNS toxicity; (b) those due to other effects of drug or vehicle (mainly peripheral nerve complications); (c) allergic reactions (often a mistaken diagnosis); and (d) mechanical or other effects of technique, such as needle trauma or introduction of infection.
Signs and symptoms of CNS toxicity include convulsions, followed by coma and respiratory depression. Convulsions are due to disinhibition of nervous conduction, probably by an action at the γ-aminobutyric acid (GABA) receptor complex, while depressant effects, which predominate at higher doses, are due to blockade of sodium channels. CNS toxicity is potentiated by hypoxia and hypercapnia, so acute management must minimise these.
Cardiovascular toxicity also involves sodium channel blockade, reducing contractility and interfering with conduction. Bupivacaine differs from lidocaine (lignocaine) in the sudden occurrence of dangerous ventricular arrhythmias including fibrillation at subconvulsant doses. Ropivacaine is a newer amide local anaesthetic with toxicity intermediate between these but potency similar to bupivacaine.
Neurotoxic complications leading to prolonged deficit after intraspinal administration are uncommon. Causes are multifactorial, and include pH of and additives to preparations. Allergic reactions account for only 1% of untoward reactions, but anaphylactoid collapse can be life-threatening and requires rapid and effective management.
There is no evidence at present of teratogenic potential of local anaesthetic drugs, and they appear to be safe to use in patients susceptible to malignant hyperthermia.
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References
Adriani J, Zepernick R. Allergic reactions to local anesthetics. Southern Medical Journal 74: 694–699, 1981
Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51: 285–287, 1979
Alexander CM, Berko RS, Gross JB, Kagle DM, Shaw LM. The effect of changes in arterial CO2 tension on plasma lidocaine concentration. Canadian Journal of Anaesthesia 34: 343–5, 1987
Akerman B, Hellberg IB, Trossvik C. Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine (LEA 103). Acta Anaesthesiologica Scandinavica 32: 571–578, 1988
Apfelbaum JL, Shaw LM, Gross JB, Caldwell, CB Spaulding BC. Modification of lidocaine protein binding with CO2. Canadian Anaesthetist’s Society Journal 32: 468–471, 1985
Arthur GR, Feldman HS, Covino BG. Alterations in the pharmacokinetic properties of amide local anaesthetics following local anaesthetic induced convulsions. Acta Anaesthesiologica Scandinavica 32: 522–529, 1988
Assem ES, Punnia-Moorthy A. Allergy to local anaesthetics: an approach to definitive diagnosis. A review with an illustrative study. British Dental Journal 164: 44–47, 1988
Bardoczky GI, Wathieu M, D’Hollander A. Prilocaine-induced methemoglobinemia evidenced by pulse oximetry. Acta Anaesthesiologica Scandinavica 34: 162–164, 1990
Barsa J, Batra M, Fink BR, Sami SM. A comparative in-vivo study of local neurotoxicity of lidocaine, bupivacaine, 2-chloroprocaine and a mixture of 2-chloroprocaine and bupivacaine. Anesthesia and Analgesia 61: 961–967, 1982
Baysinger CL, Schultetus RR. Cocaine abuse during pregnancy: effects on mother and child. Current opinion in Anaesthesiology 3: 418–422, 1990
Bennet CR. in: Monheim’s local anesthesia and pain control in dental practice. 7th ed., p. 225, CV Mosby Co Ltd., St. Louis, 1984
Clarkson CW, Hondeghem L. Mechanism for bupivacaine depression of cardiac conduction: fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology 62: 396–405, 1985
Concepcion M, Arthur GR, Steele SM, Bader AM, Covino BG. A new local anesthetic, ropivacaine. Its epidural effects in humans. Anesthesia and Analgesia 70: 80–85, 1990
Condé-Salazar L, Lliñas MG, Guimaraens D, Romero L. Occupational allergic contact dermatitis from amethocaine. Contact Dermatitis 19: 69–70, 1988
Covino BG, Vassallo HG. Local anesthetics: mechanisms of action and clinical use, 1st ed., Grune and Stratton, New York, 1976
De Jong RH, Robles R, Corbin RW. Cortical actions of lidocaine — synaptic transmission. Anesthesiology 30: 19–23, 1969
De Jongh RH. Local anesthetic seizures. Anesthesiology 30: 5–6, 1969
Doyle KA, Goepferd SJ. An allergy to local anesthetics? The consequences of a misdiagnosis. Journal of Dentistry for Children 56: 103–106, 1989
Dundee JW, Fee JPH, McDonald JR, Clarke RSJ. Frequency of allergy and atopy in an anaesthetic patient population. British Journal of Anaesthesia 50: 793–798, 1978
Engberg G, Danielson K, Henneberg S, Nilsson A. Plasma concentrations of prilocaine and lidocaine and methaemoglobin formation in infants after epicutaneous application of a 5% lidocaine-prilocaine (EMLA). Acta Anaesthesiologica Scandinavica 31: 624–628, 1987
Englesson S. The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. Acta Anaesthesiologica Scandinavica 18: 79–87, 1974
Englesson S, Grevsten S. The influence of acid-base changes on central nervous system toxicity of local anaesthetics II. Acta Anaesthesiologica Scandinavica 18: 88–103, 1974
Feldman HS, Arthur GR, Covino BG. Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog. Anesthesia and Analgesia 69: 794–801, 1989
Finucane BT. Ropivacaine — a worthy replacement for bupivacaine? Canadian Journal of Anaesthesia 37: 722–725, 1990
Fisher MMcD. The diagnosis of acute anaphylactoid reactions to anaesthetic drugs. Anaesthesia and Intensive Care 9: 235–241, 1981
Fisher MMcD. Intradermal testing after anaphylactoid reactions to anaesthetic drugs: practical aspects of performance and interpretation. Anaesthesia and Intensive Care 12: 115–120, 1984
Fisher MMcD. Clinical observations on the pathophysiology and treatment of anaphylactic cardiovascular collapse. Anaesthesia and Intensive Care 14: 17–21, 1986
Fisher MMcD, Outhred A, Bowey CJ. Can clinical anaphylaxis to anaesthetic drugs be predicted from allergic history? British Journal of Anaesthesia 59: 690–692, 1987
Friedman JM. Teratogen update: anesthetic agents. Teratology 37: 69–77, 1988
Gissen AJ. Toxicity of local anesthetics in obstetrics II: chloroprocaine — research and clinical aspects. Clinics in Anaesthesiology 4: 101–108, 1986
Gronert GA, Mott J, Lee J. Aetiology of malignant hyperthermia. British Journal of Anaesthesia 60: 253–267, 1988
Hadeed AJ, Siegel SR. Maternal cocaine use during pregnancy: effect on the newborn infant. Pediatrics 84: 205–210, 1989
Hamilton RC. Apnoea after retrobulbar block. Anaesthesia 44: 862–863, 1989
Jakobson B, Nilsson A. Methaemoglobinaemia associated with a prilocaine-lignocaine cream and trimethoprim-sulphamethoxazole: a case report. Acta Anaesthesiologica Scandinavica 29: 453–455, 1985
Kane RE. Neurological deficits following epidural or spinal anesthesia. Anesthesia and Analgesia 60: 150–161, 1981
Kemp DR, Choong LS. Malignant hyperthermia and the conscious patient. Australian and New Zealand Journal of Surgery 58: 423–427, 1988
Katz JA, Bridenbaugh PO, Knarr DC, Helton SH, Denson DD. Pharmacodynamics and pharmacokinetics of epidural ropivacaine in humans. Anesthesia and Analgesia 70: 16–21, 1990
Korevaar WC, Burney RG, Moore PA. Convulsions during stellate ganglion block: a case report. Anesthesia and Analgesia 58: 329, 1979
Lange RA, Cigarroa RG, Yancy Jr CW, Willard JE, Popma JJ, et al. Cocaine-induced coronary-artery vasoconstriction. New England Journal of Medicine 321: 1557–62, 1989
Kotelko DM, Shnider SM, Dailey PA, Brizgys RV, Levinson G, et al. Bupivacaine-induced cardiac arrhythmias in sheep. Anesthesiology 60: 10–18, 1984
Mesulam MM. Lidocaine toxicity and the limbic system. American Journal of Psychiatry 144: 1623–1624, 1987
Minasian A, Yagiela JA. The use of amide local anesthetics in patients susceptible to malignant hyperthermia. Oral Surgery Oral Medicine and Oral Pathology 66: 405–415, 1988
Modica PA, Templehof R, White PF. Pro- and anticonvulsant effects of anesthetics. Anesthesia and Analgesia 70: 303–315, 433–444, 1990
Moller R, Covino B. Cardiac electrophysiological effects of lidocaine and bupivacaine. Anesthesia and Analgesia 67: 107–114, 1988
Moller R, Covino BG. Cardiac electrophysiologic properties of bupivacaine and lidocaine compared with those of ropivacaine, a new amide local anesthetic. Anesthesiology 72: 322–329, 1990
Moore DC, Bonica JJ. Convulsions and ventricular tachycardia from bupivacaine with epinephrine: successful resuscitation — congratulations. Anesthesia and Analgesia 64: 843–847, 1985
Moore DC, Thompson GE, Crawford RE. Long acting local anaesthetic drugs and convulsions with hypoxia and acidosis. Anesthesiology 56: 230–232, 1982
Morishima HO, Pedersen H, Finster M, Sakuma K, Bruce SL, et al. Toxicity of lidocaine in adult, newborn, and fetal sheep. Anesthesiology 55: 57–61, 1981
Morishima HO, Pedersen H, Finster M, Hiraoka H, Tsuji A, et al. Bupivacaine toxicity in pregnant and nonpregnant ewes. Anesthesiology 63: 134–139, 1985
Myers RR, Kalichman MW, Reisner LS, Powell HC. Neurotoxicity of local anesthetics: altered perineurial permeability, edema, and nerve fiber injury. Anesthesiology 64: 29–35, 1986
Nancarrow C, Rutten A, Runciman W, Mather LE, Carapetis RJ, et al. Myocardial and cerebral drug concentrations and the mechanisms of death after fatal intravenous doses of lidocaine, bupivacaine, and ropivacaine in the sheep. Anesthesia and Analgesia 69: 276–283, 1989
Nath S, Håggmark S, Johannson G, Reiz S. Intracoronary injection of bupivacaine and lidocaine, an experimental study of cardiac rhythm, myocardial function and regional coronary artery blood, flow in anaesthetised pigs. Proceedings of the Swedish Society of Anaesthetists Research Meeting, Uppsala, 1985
Nilsson A, Engberg G, Henneberg S, Danielson K, De Verdier CH. Inverse relationship between age-dependent erythrocyte activity of methaemoglobin reductase and prilocaine-induced, methaemoglobinaemia during infancy. British Journal of Anaesthesia 64: 72–76, 1990
Pollack CV, Swindle GM. Use of diphenhydramine for local anesthesia in ‘caine’-sensitive patients. Journal of Emergency Medicine 7: 611–614, 1989
Ready LB, Plumer MH, Haschke RH, Austin E, Sumi M. Neurotoxicity of intrathecal local anesthetics in rabbits. Anesthesiology 63: 364–370, 1985
Reiz S, Nath SW. Cardiotoxicity of local anaesthetic agents. British Journal of Anaesthesia 58: 736–746, 1986
Reiz S, Nath SW. Cardiotoxicity of LEA 103 — a new amide local anesthetic agent. Acta Anaesthesiologica Scandinavica 33: 93–98, 1989
Reynolds F. Local anaesthetic drugs. Clinics in Anaesthesiology 2: 577–604, 1984
Reynolds F. Adverse effects of local anaesthetics. British Journal of Anaesthesia 59: 78–95, 1987
Rieder HU, Frei FJ, Zbinden AM, Thomson DA. Pulse oximetry in methaemoglobinaemia: failure to detect low oxygen saturation. Anaesthesia 44: 326–327, 1989
Rigler ML, Drasner K, Krejcie TC, Yelich SJ, Scholnick FT, et al. Cauda equina syndrome after continuous spinal anesthesia. Anesthesia and Analgesia 72: 275–281, 1991
Rutten AJ, Nancarrow C, Mather L, Ilsey AH, Runciman WB, et al. Hemodynamic and central nervous system effects of intravenous bolus doses of lidocaine, bupivacaine and ropivacaine in sheep. Anesthesia and Analgesia 69: 291–299, 1989
Saklad M, Dwyer CS, Kronenberg S, Neves E, Sorkin M. Intraspinal segmental anesthesia: a preliminary report. Anesthesiology 8: 270–287, 1947
Saravay SM, Marke J, Steinberg MD, Rabiner CJ. ‘Doom anxiety’ and delirium in lidocaine toxicity. American Journal of Psychiatry 144: 159–163, 1987
Scott DB. Toxic effects of local anaesthetic agents on the central nervous system. British Journal of Anaesthesia 58: 732–735, 1986
Scott DB, Lee A, Fagan D, Bowler GM, Bloomfield P, et al Acute toxicity of ropivacaine compared with that of bupivacaine. Anesthesia and Analgesia 69: 563–569, 1989
Stoelting RK, Creasser CW, Martz RC. Effect of cocaine administration on halothane MAC in dogs. Anesthesia and Analgesia 54: 422–424, 1975
Stone WE, Javid MJ. Anticonvulsive and convulsive effects of lidocaine: comparison with those of phenytoin, and implications for mechanism of action concepts. Neurological Research 10: 161–168, 1988
Taverner D, Baine WAC. Intravenous lignocaine as anticonvulsant. Lancet 2: 1145–1147, 1958
Watkins J. Second report from an anaesthetic reactions advisory service. Anaesthesia 44: 157–159, 1989
Wang BC, Hillman DE, Spielholz NI, Turndorf H. Chronic neurological deficits and Nesacaine-CE. Anesthesia and Analgesia 63: 445–447, 1984
Weiss LD, Generalovich T, Heller MB, Paris PM, Stewart RD, et al Methemoglobin levels following intravenous lidocaine administration. Annals of Emergency Medicine 16: 323–325, 1987
Wildsmith JAW. Peripheral nerve and local anaesthetic drugs. British Journal of Anaesthesia 58: 692–700, 1986
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McCaughey, W. Adverse Effects of Local Anaesthetics. Drug-Safety 7, 178–189 (1992). https://doi.org/10.2165/00002018-199207030-00003
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DOI: https://doi.org/10.2165/00002018-199207030-00003