Key Points
-
The amine local anaesthetics have varying potency: toxicity ratios and maximal safe doses should be adhered to.
-
Although rare, LAST accounts for a high proportion of mortalities in the dental office, with LAST-induced cardiac arrest particularly resistant to standard resuscitation methods.
-
We encourage all facilities that use amide local anaesthetics to have a 'rescue kit' and guidelines readily available.
Abstract
The accidental overdose of local anaesthetics may prove fatal. The commonly used amide local anaesthetics have varying adverse effects on the myocardium and beyond a certain dose all are capable of causing death. Local anaesthetics are the most frequently used drugs in dentistry and although uncommon, local anaesthetic systemic toxicity (LAST) accounts for a high proportion of mortalities in the dental office, with local anaesthetic-induced cardiac arrest particularly resistant to standard resuscitation methods. Over the last decade there has been convincing evidence of using intravenous lipid emulsions as a rescue in local anaesthetic – cardiotoxicity and anaesthetic organisations over the globe have developed guidelines on the use of this drug. Despite this, however, awareness among practitioners appears to be lacking. All who use local anaesthetics in their practice should have an appreciation of patients at high risk of toxicity, early symptoms and signs of toxicity, preventative measures when using these drugs and the initial management of systemic toxicity with intravenous lipid emulsion. In this review we intend to discuss the pharmacology and pathophysiology of local anaesthetic toxicity, and the rationale for intravenous lipid emulsion therapy.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Halsted W S . Practical comments on the use and abuse of cocaine: suggested by its invariably successful employment in more than a thousand minor surgical operations. NY Med J 1885; 42: 294–295.
Nizharadze N, Mamaladze M, Chipashvili N, Vadachkoria D . Articaine - the best choice of local anesthetic in contemporary dentistry. Georgian Med News 2011; 190: 15–23.
Ritchie J M, B. Ritchie B, Greengard P . The active structure of local anesthetics. J Pharmacol Exp Ther 1965; 150: 152–159.
Tsuchiya H, Ueno T, Mizogami M, Takakura K . Local anesthetics structure-dependently interact with anionic phospholipid membranes to modify the fluidity. Chem Biol Interact 2010; 183: 19–24.
Tsuchiya H, Ueno T, Mizogami M . Stereostructure-based differences in the interactions of cardiotoxic local anesthetics with cholesterol-containing biomimetic membranes. Bioorg Med Chem 2011; 19: 3410–3415.
Valenzuela C, Delpón E, Franqueza L, Gay P, Snyders D J, Dunwiddie T V . Effects of ropivacaine on a potassium channel (hKv1.5) cloned from human ventricle. Anesthesiology 1997; 86: 718–728.
Auroy Y, Benhamou D, Barques L et al. Major complications of regional anaesthesia in France: the SOS Regional Anesthesia Hotline Service. Anesthesiology 2002; 97: 1274–1280.
Mehra P, Caiazzo A, Maloney P . Lidocaine toxicity. Anesth Prog 1998; 45: 38–41.
Virts B E . Local anesthesia toxicity review. Pediatr Dent 1999; 21: 375.
Zenouz A, Ebrahimi H, Mahdipour M, Pourshahidi S, Amini P, Vatankhah M . The incidence of intravascular needle entrance during inferior alveolar nerve block injection. J Dent Res Dent Clin Dent Prospects 2008 2: 38–41
Heavner J E . Cardiac toxicity of local anaesthetics in the intact isolated heart model: a review. Reg Anesth Pain Med 2002; 27: 545–555.
Weinberg G, Lin B, Zheng S et al. Partitioning effect in lipid resuscitation: further evidence for the lipid sink. Crit Care Med 2010; 38: 2268–2269.
Rosen M A, Jone R M, Yano Y, Budinger T F . Bupivacaine-induced cardiotoxicity in hypoxic and acidotic sheep. Anesth Analg 1985; 64: 1089–1096.
Foxall G, McCahon R, Lamb J, Hardman J G, Bedforth N M . Levobupivacaine-induced seizures and cardiovascular collapse treated with Intralipid. Anaesthesia 2007; 62: 516–518.
Berde C B . Toxicity of local anesthetics in infants and children. J Pediatr 1993. 122:14–20.
De Negri P, Ivani G, Tirri T, Del Piano A C . New local anaesthetics for pediatric anaesthesia. Curr Opin Anaesthesiol 2005; 18: 289–292.
Albright G A . Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anaesthesiology 1979; 51: 285–287.
Bruelle P, LeFrant J Y, de La Coussaye J E et al. Comparative electrophysiologic and hemodynamic effects of several amide local anesthetic drugs in anesthetised dogs. Anesth Analg 1996; 82: 648–656.
Maughan D W . Kinetics and energetics of the crossbridge cycle. Heart Fail Rev 2005; 10: 175–185.
Newton D J, McLeod G A, Khan F, Belch J J . Vasoactive characteristics of bupivacaine and levobupivacaine with and without adjuvant adrenaline in peripheral human skin. Br J Anaesth 2005; 94: 662–667.
Weinberg G L, Palmer J W, VadeBoncouer T R, Zuechner M B, Edelman G, Hoppel C L . Bupivacaine inhibits acylcarnitine exchange in cardiac mitochondria. Anesthesiology 2000; 92: 523–528.
Royse C F, Royse A G . The myocardial and vascular effects of bupivacaine, levobupivacaine, and ropivacaine using pressure volume loops. Anesth Analg 2005; 101: 679–687.
Weinberg G L, VadeBoncouer T R, Ramaraju G A, Garcia-Amaro M F, Cwik M J . Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology 1998; 88: 1071–1075.
Weinberg G L, Ripper R, Feinstein D L, Hoffman W . Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med 2003; 28: 198–202.
Rosenblatt M A, Abel M, Fischer G W, Itzkovich C J, Eisenkraft J B . Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology 2006; 105: 217–218.
Ludot H, Tharin J Y, Belouadah M, Marzoit J X, Malinovsky J M . Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child. Anesth Analg 2008; 106: 1572–1574.
Litz R J, Roessel T, Heller A R, Stehr S N . Reversal of central nervous system and cardiac toxicity after local anesthetic intoxication by lipid emulsion injection. Anesth Analg 2008; 106: 1575–1577.
Warren J A, Thoma R B, Georgescu A, Shaj S J . Intravenous lipid infusion in the successful resuscitation of local anesthetic-induced cardiovascular collapse after supraclavicular brachial plexus block. Anesth Analg 2008; 106: 1578–1580.
Cave G ., Harvey M, Graudins A . Intravenous lipid emulsion as antidote: a summary of published human experience. Emerg Med Australas 2011; 23: 123–141.
Dix S K, Rosner G F, Nayar M, et al. Intractable cardiac arrest due to lidocaine toxicity successfully resuscitated with lipid emulsion. Crit Care Med 2011; 39: 872–874.
AAGBI. Management of severe local anaesthetic toxicity. AAGBI Safety Guideline 2010; online article available at http://www.aagbi.org/sites/default/files/la_toxicity_2010_0.pdf
Gabrielli A, O'Connor M F, Maccioli G A . Anesthesia advanced circulatory life support. The American Society of Critical Care Anesthesiologists and The American Society of Anesthesiologists, Committee on Critical Care Medicine, 2008.
Neal J M, Bernards C M, Butterworth J F 4th et al. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med 2010; 35: 152–161.
Weinberg G L, Ripper R, Murphy P et al. Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart. Reg Anesth Pain Med 2006; 31: 296–303.
Silveira L, Hirabara H M, Alberici L C et al. Effect of lipid infusion on metabolism and force of rat skeletal muscles during intense contractions. Cell Physiol Biochem 2007; 20: 213–26.
Coat M, Pennec J P, Guillouet M, Arvieux C C, Gueret G . [Haemodynamic effects of intralipid after local anaesthetics intoxication may be due to a direct effect of fatty acids on myocardial voltage-dependent calcium channels]. Ann Fr Anesth Reanim 2010; 29: 661.
Weinberg G L . Intravenous lipid emulsion: why wait to save a life? Emerg Med Australas 2011; 23: 113–115.
Markowitz S, Neal J M . Immediate lipid emulsion therapy in the successful treatment of bupivacaine systemic toxicity. Reg Anesth Pain Med 2009; 34: 276.
Charbonneau H, Marcou T A, Mazoit J X, Zetlaoui P J, Benhamou D . Early use of lipid emulsion to treat incipient mepivacaine intoxication. Reg Anesth Pain Med 2009; 34: 277–278.
Sonsino D H ., Fischler M . Immediate intravenous lipid infusion in the successful resuscitation of ropivacaine-induced cardiac arrest after infraclavicular brachial plexus block. Reg Anesth Pain Med 2009; 34: 276–277.
Bern S, Weinberg G . Local anaesthetic toxicity and lipid resuscitation in pregnancy. Curr Opin Anaesthesiol 2011; 24: 262–267.
Hiller D B, Gregoria G D, Ripper R et al. Epinephrine impairs lipid resuscitation from bupivacaine overdose: a threshold effect. Anesthesiology 2009; 111: 498–505.
Rosenberg P H, Veering B T, Urmey W F . Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med 2004; 29: 564–575.
Branco F P, Ranali J, Ambrosano G M, Volpato M C . A double-blind comparison of 0.5% bupivacaine with 1:200,000 epinephrine and 0.5% levobupivacaine with 1:200,000 adrenaline for the inferior alveolar nerve block. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 101: 442–447.
Lee Y Y, Kee W D N, Fong S Y, Liu J T C, Gin T . The median effective dose of bupivacaine, levobupivacaine, and ropivacaine after intrathecal injection in lower limb surgery. Anesth Analg 2009; 109: 1331–1334.
Weinberg G L . Lipid Rescue. Available from: http://www.lipidrescue.org/.
Dorf E, Kuntz A F, Kelsey J, Holstege C P . Lidocaine-induced altered mental status and seizure after haematoma block. J Emerg Med 2006; 31: 251–253.
Marra, D E, Yip D, Fincher E F, Moy R L . Systemic toxicity from topically applied lidocaine in conjunction with fractional photothermolysis. Arch Dermatol 2006; 142: 1024–1026.
Donald M J, Derbyshire S . Lignocaine toxicity; a complication of local anaesthesia administered in the community. Emerg Med J 2004; 21: 249–250.
Smith M., Wolfram W, Rose R . Toxicity – seizures in an infant caused by (or related to) oral viscous lidocaine use. J Emerg Med 1992; 10: 587–590.
Martinez M A, Ballesteros S, Segura L J, Garcia M . Reporting a fatality during tumescent liposuction. Forensic Sci Int 2008; 178: e11–e16.
Klein J A, Kassarjdian N . Lidocaine toxicity with tumescent liposuction. A case report of probable drug interactions. Dermatol Surg 1997; 23: 1169–1174.
Seigne R . Lignocaine toxicity--a surgical surprise. Anaesthesia 1997; 52: 91.
Rao R B, Ely S F, Hoffman R S . Deaths related to liposuction. N Engl J Med 1999; 340: 1471–1475.
Collins J . Awareness of local anaesthetic toxicity issues among hospital staff. Anaesthesia 2010; 65: 960–961.
Author information
Authors and Affiliations
Corresponding author
Additional information
Refereed paper
Rights and permissions
About this article
Cite this article
Ciechanowicz, S., Patil, V. Intravenous lipid emulsion – rescued at LAST. Br Dent J 212, 237–241 (2012). https://doi.org/10.1038/sj.bdj.2012.187
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.bdj.2012.187
This article is cited by
-
The effect of intravenous lipid emulsion (ILE) on the pharmacokinetic/toxicokinetic dispositions of ivermectin and carprofen in rabbits
Naunyn-Schmiedeberg's Archives of Pharmacology (2024)
-
General medicine and surgery for dental practitioners: part 3. Management of specific medical emergencies in dental practice
British Dental Journal (2014)
