Local Anesthetic Systemic Toxicity: A Historical Perspective

The most feared complication associated with the administration of local anesthetics is the profound and potentially lethal effect that these agents can have on cardiac conduction and function. This review traces the evolution of local anesthetic systemic toxicity beginning with the early deaths associated with the introduction of cocaine into clinical practice. The development of bupivacaine is discussed, with particular emphasis on the delayed recognition and acceptance of its inherent cardiotoxicity. Finally, the origins of lipid resuscitation are reviewed with respect to their theoretical foundation, as well as the confluence of events and experimental investigations that delivered this therapy into clinical practice.

[1]  J. Butterworth.  Models and Mechanisms of Local Anesthetic Cardiac Toxicity: A Review , 2009, Regional Anesthesia & Pain Medicine.

[2]  M. Harvey,et al.  Intralipid infusion ameliorates propranolol-induced hypotension in rabbits , 2008, Journal of Medical Toxicology.

[3]  J. Dilger,et al.  Simulation education in anesthesia training: a case report of successful resuscitation of bupivacaine-induced cardiac arrest linked to recent simulation training. , 2008, Anesthesia and analgesia.

[4]  S. Stehr,et al.  Reversal of central nervous system and cardiac toxicity after local anesthetic intoxication by lipid emulsion injection. , 2008, Anesthesia and analgesia.

[5]  J. Warren,et al.  Intravenous lipid infusion in the successful resuscitation of local anesthetic-induced cardiovascular collapse after supraclavicular brachial plexus block. , 2008, Anesthesia and analgesia.

[6]  J. Mazoit,et al.  Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child. , 2008, Anesthesia and analgesia.

[7]  G. Weinberg,et al.  Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine. , 2008, Annals of emergency medicine.

[8]  A. Spence.  Lipid reversal of central nervous system symptoms of bupivacaine toxicity. , 2007, Anesthesiology.

[9]  I. Hahn,et al.  Hemodynamic effects of intravenous fat emulsion in an animal model of severe verapamil toxicity resuscitated with atropine, calcium, and saline. , 2007, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[10]  M. Harvey,et al.  Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity. , 2007, Annals of emergency medicine.

[11]  S. Stehr,et al.  Successful resuscitation of a patient with ropivacaine‐induced asystole after axillary plexus block using lipid infusion * , 2006, Anaesthesia.

[12]  J. Eisenkraft,et al.  Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. , 2006, Anesthesiology.

[13]  J. Krieglstein,et al.  Influence of emulsified fat on chlorpromazine availability in rabbit blood , 1974, Experientia.

[14]  C. Errando,et al.  Cardiac arrest after interscalene brachial plexus block , 2004, Acta anaesthesiologica Scandinavica.

[15]  D. Feinstein,et al.  Lipid Emulsion Infusion Rescues Dogs From Bupivacaine-Induced Cardiac Toxicity , 2003, Regional Anesthesia & Pain Medicine.

[16]  G. Edelman,et al.  Bupivacaine Inhibits Acylcarnitine Exchange in Cardiac Mitochondria , 2000, Anesthesiology.

[17]  G. Weinberg,et al.  Pretreatment or Resuscitation with a Lipid Infusion Shifts the Dose‐Response to Bupivacaine‐induced Asystole in Rats , 1998, Anesthesiology.

[18]  B. Burton,et al.  Malignant ventricular dysrhythmias in a patient with isovaleric acidemia receiving general and local anesthesia for suction lipectomy. , 1997, Journal of clinical anesthesia.

[19]  G. Marx.  Bupivacaine cardiotoxicity--concentration or dose? , 1986, Anesthesiology.

[20]  K. Saternus,et al.  [Cocaine poisoning]. , 1986, Archiv fur Kriminologie.

[21]  M. Rosen,et al.  Bupivacaine‐Induced Cardiotoxicity in Hypoxic and Acidotic Sheep , 1985, Anesthesia and analgesia.

[22]  B. Covino,et al.  The Cardiovascular Effects of Convulsant Doses of Lidocaine and Bupivacaine in the Conscious Dog , 1985, Regional Anesthesia & Pain Medicine.

[23]  M. Finster,et al.  Bupivacaine Toxicity in Pregnant and Nonpregnant Ewes , 1985, Anesthesiology.

[24]  L. Hondeghem,et al.  Mechanism for Bupivacaine Depression of Cardiac Conduction: Fast Block of Sodium Channels during the Action Potential with Slow Recovery from Block during Diastole , 1985, Anesthesiology.

[25]  M. Rosen,et al.  Bupivacaine‐induced Cardiac Arrhythmias in Sheep , 1984, Anesthesiology.

[26]  L. Strunin,et al.  Trial by media: the bupivacaine story , 1984, Canadian Anaesthetists' Society journal.

[27]  Adverse reactions with bupivacaine. , 1983, FDA drug bulletin.

[28]  B. Covino,et al.  Acute Cardiovascular Toxicity of Intravenous Amide Local Anesthetics in Anesthetized Ventilated Dogs , 1982, Anesthesia and analgesia.

[29]  D. Moore,et al.  Long-acting local anesthetic drugs and convulsions with hypoxia and acidosis. , 1982, Anesthesiology.

[30]  R. H. de Jong,et al.  Cardiovascular Effectsv of Convulsant and Supraconvulsant Doses of Amide Local Anesthetics , 1982, Anesthesia and analgesia.

[31]  D. Scott.  Toxicity caused by local anaesthetic drugs. , 1981, British journal of anaesthesia.

[32]  A. J. Gandolfi,et al.  HEPATORENAL INDICES AMONG GENERAL ANESTHETICS IN OBESITY , 1980 .

[33]  D. Moore,et al.  Severe hypoxia and acidosis following local anesthetic-induced convulsions. , 1980, Anesthesiology.

[34]  J. Prentiss.  Cardiac arrest following caudal anesthesia. , 1979, Anesthesiology.

[35]  G A Albright,et al.  Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. , 1979, Anesthesiology.

[36]  J. Cwik,et al.  Bupivacaine—A New Long‐Acting Local Anesthetic Agent: A Preliminary Clinical and Laboratory Report , 1970, Anesthesia and analgesia.

[37]  G. Tucker,et al.  Bupivacaine hydrochloride: laboratory and clinical studies. , 1970, Anesthesiology.

[38]  K. Martin,et al.  [Hazards of paracervical block in obstetrics. A survey of 107 hospitals for women with a total of 32, 652 cases]. , 1969, Geburtshilfe und Frauenheilkunde.

[39]  R. Brattsand,et al.  Some Pharmacological and Toxicological Properties of a New Long‐Acting Local Analgesic, Lac‐43 (Marcaine®), in Comparison With Mepivacaine and Tetracaine , 1966, Acta anaesthesiologica Scandinavica. Supplementum.

[40]  I. Nyirjesy,et al.  HAZARDS OF THE USE OF PARACERVICAL BLOCK ANESTHESIA IN OBSTETRICS. , 1963, American journal of obstetrics and gynecology.

[41]  R. L. Russell,et al.  ALLEVIATION OF BARBITURATE DEPRESSION BY FAT EMULSION , 1962 .

[42]  R. L. Russell,et al.  Alleviation of barbiturate depression. , 1962, Anesthesia and analgesia.