Hadzic's Peripheral Nerve Blocks and Anatomy for Ultrasound-Guided Regional Anesthesia, 2nd

9. Toxicity of Local Anesthetics

Steven Dewaele, and Alan C. Santos


Systemic toxicity of local anesthetics can occur after administration of an excessive dose, with rapid absorption, or because of an accidental intravenous injection. The management of local anesthetic toxicity can be challenging, and in the case of cardiac toxicity, prolonged resuscitation efforts may be necessary.1,2 Therefore, understanding the circumstances that can lead to systemic toxicity of local anesthetics and being prepared for treatment is essential to optimize the patient outcome.

Systemic toxicity is typically manifested as central nervous system (CNS) toxicity (tinnitus, disorientation, and ultimately, seizures) or cardiovascular toxicity (hypotension, dysrhythmias, and cardiac arrest).3The dose capable of causing CNS symptoms is typically lower than the dose and concentration result in cardiovascular toxicity. This is because the CNS is more susceptible to local anesthetic toxicity than the cardiovascular system. However, bupivacaine toxicity may not adhere to this sequence, and cardiac toxicity may precede the neurologic symptoms.4 Although less common, cardiovascular toxicity is more serious and more difficult to treat than CNS toxicity.

Other reported, but much less common, adverse effects of certain local anesthetics include allergic reactions,5 methemoglobinemia,6 and bronchospasm.7 Direct neural8 and local tissue toxicity9 have been reported also; however, discussion about these topics is beyond the scope of this chapter.

Signs and Symptoms of Systemic Local Anesthetic Toxicity

The earliest signs of systemic toxicity are usually caused by blockade of inhibitory pathways in the cerebral cortex.10 This allows for disinhibition of facilitator neurons resulting in excitatory cell preponderance and unopposed (generally enhanced) excitatory nerve activity. As a result, initial subjective symptoms of CNS toxicity include signs of excitation, such as lightheadedness and dizziness, difficulty focusing, tinnitus, confusion, and circumoral numbnesss.11,12 Likewise, the objective signs of local anesthetic toxicity are excitatory, for example, shivering, myoclonia, tremors, and sudden muscular contractions.13 As the local anesthetic level rises, tonic-clonic convulsions occur. Symptoms of CNS excitation typically are followed by signs of CNS depression: Seizure activity ceases rapidly and ultimately is succeeded by respiratory depression and respiratory arrest. In the concomitant presence of other CNS depressant drugs (e.g., premedication), CNS depression can develop without the preceding excitatory phase.

The CNS toxicity is directly correlated with local anesthetic potency.14–17 However, there is an inverse relationship between the toxicity of local anesthetics and the rate at which the agents are injected: Increasing speed of injection will decrease the blood-level threshold for symptoms to appear.

All local anesthetics can induce cardiac dysrhythmias,18,19 and all, except cocaine, are myocardium depressants.20–25 Local anesthetic–induced arrhythmias can manifest as conduction delays (from prolonged PR interval to complete heart block, sinus arrest, and asystole) to ventricular dysrhythmias (from simple ventricular ectopy to torsades de pointes and fibrillation). The negative inotropic action of local anesthetics is exerted in a dose-dependent fashion and consists of depressed myocardial contractility and a decrease in cardiac output. Dysrhythmias due to local anesthetic overdose may be recalcitrant to traditional therapies; the reduced myocardial contractility and low output state further complicate the treatment.

The sequence of cardiovascular events is ordinarily as follows: Low blood levels of local anesthetic usually generate a small increase in cardiac output, blood pressure, and heart rate, which is most likely due to a boost in sympathetic activity and direct vasoconstriction. As the blood level of local anesthetic rises, hypotension ensues as a result of peripheral vasodilation due to relaxation of the vascular smooth muscles. Further rise of local anesthetic blood levels leads to severe hypotension, resulting from the combination of reduced peripheral vascular resistance, reduced cardiac output, and/or malignant arrhythmias. Eventually, extreme hemodynamic instability may lead to cardiac arrest.

Acid–base status plays an important role in the setting of local anesthetic toxicity.26 Acidosis and hypercarbia amplify the CNS effects of local anesthetic overdose and exacerbate cardiotoxicity. Hypercarbia enhances cerebral blood flow; consequently, more local anesthetic is made accessible to the cerebral circulation. Diffusion of carbon dioxide across the nerve membrane can cause intracellular acidosis, and as such, it is promoting the conversion of the local anesthetic into the cationic, or active, form. Because it is impossible for the cationic form to travel across the nerve membrane, ionic trapping occurs, worsening the CNS toxicity of the local anesthetic. Hypercarbia and/or acidosis also reduce the binding of local anesthetics by plasma proteins,27 and as a result, the fraction of free drug readily available for diffusion expands.


Prevention of toxicity is key to safer practice, and it starts with making sure that the work environment is optimized for performing regional anesthesia.28 The logistics for treating an emergency, including equipment for airway management and treating cardiac arrest, must be readily available and functioning.

A judicious selection of the type, dose, and concentration of the local anesthetic, and the regional anesthesia technique, is important. As a rule, the optimal dose and concentration is the lowest one that achieves the aimed for effect. The effects of pretreatment with a benzodiazepine is often debated but almost routinely used in our practice. Benzodiazepines lower the probability of seizures29–32 but can mask early signs of toxicity.33 A sedated patient is theoretically less able to keep the physician updated on the subjective symptoms of light toxicity, and severe toxicity can establish itself without a recognizable toxic prodrome. This concern remains only theoretical; many symptoms of limited, mild CNS toxicity can be prevented by routine premedication with benzodiazepines in addition to making the PNB procedure more pleasant to patients.

Therefore, the presence of premedication or general anesthesia is not perceived to increase the risk of local anesthetic toxicity. Considerable research has been invested into the subject of the ideal test for detecting intravenous injection and to what constitutes the ideal test dose. Epinephrine (5–15 μg) is still widely in use as a marker of intravascular injection. End points with an acceptable sensitivity are defined by an increase in heart rate >10 bpm, increase in systolic blood pressure by >15 mm Hg,34 or a 25% decrease in lead II T-wave amplitude.35 However, elderly patients are less responsive to beta stimulation36 as are those on beta-blocking agents. Low cardiac output can prolong drug circulation and delay the clinical effect of the beta mimetic, and therefore, the sensitivity of the test. Accordingly, the interpretation of the test result is not always as straightforward as one would wish. The significant proportion of false negative test results warrants a reevaluation of the routine use of this test as a sole determinant to detect inadvertent intravenous injection.

Regardless of whether epinephrine is used as a marker of an intravascular injection, it is of utmost importance to use slow, incremental injections of local anesthetic, with frequent aspirations (every 3–5 mL) between injections while monitoring the patient for signs of toxicity.37 A slow rate of injection of divided doses at distinct intervals can decrease the possibility of summating intravascular injections. With a rapid injection the seizures may occur at higher blood level because there is no time for distribution of the drug as compared to a slow infusion where the seizure occurs at a lower drug level because of the distribution. It is prudent to decrease the local anesthetic dosage in elderly or debilitated patients and in any patient with diminished cardiac output. However, there are no firm recommendations on the degree of dose reduction.


Early recognition of the toxicity and early discontinuation of the administration is of crucial importance.38 The administration of local anesthetics should be stopped immediately. The airway should be maintained at all times, and supplemental oxygen is provided while ensuring that the monitoring equipment is functional and properly applied. Neurologic parameters and cardiovascular status should be assessed until the patient is completely asymptomatic and stable.39

Administration of a benzodiazepine to offset or ameliorate excitatory neurological symptoms or a potential tonic-clonic seizure is indicated.40 Early treatment of convulsions is particularly meaningful because convulsions can result in metabolic acidosis, thus aggravating the toxicity. Seizures should be controlled at all times. Based on the recent data in animal studies,41–43 as well as mounting case reports,44–53starting an infusion of lipid emulsion (intralipid), especially in those cases where symptoms of cardiac toxicity are present, should be contemplated early.54 Importantly, there is a mounting consensus that infusion of intralipids may be initiated early, to also prevent, rather then treat cardiac arrest. If available, arrangements for transfer to an operating room where cardiopulmonary bypass can be instituted should also be contemplated in situations where the response to early treatment is not favorable.55–58

Malignant arrhythmias and asystole are managed using standard cardiopulmonary resuscitation protocols,59,60 acknowledging that a prolonged effort may be needed to increase the chance of resuscitation. The rationale of this approach is to maintain the circulation until the local anesthetic is redistributed or metabolized below the level associated with cardiovascular toxicity, at which time spontaneous circulation should resume. Because the contractile depression is a core factor underlying severe cardiotoxicity, it would be intuitive to believe that the use of sympathomimetics should be helpful. Nonetheless, epinephrine can induce dysrhythmia or it can exacerbate the ongoing arrhythmia associated with local anesthetic overdose.61,62 Consequently, in the setting of local anesthetic toxicity, vasopressin may be more appropriate to maintain the blood pressure, support coronary perfusion, and facilitate local anesthetic metabolism.63 The appropriateness of phosphodiesterase inhibitors administration is not corroborated by published research results. Although these inhibitors can promote hemodynamics, there is no evidence of a better outcome. As potent vasodilators, phosphodiesterase inhibitors do no support blood pressure,64 and they have been associated with ventricular arrhythmias.65

The current advanced cardiac life support algorithm emphasizes amiodarone as the mainstay drug for treatment of arrhythmias.66,67 Also, for ventricular arrhythmias prompted by local anesthetic overdose, current data favor amiodarone. Published studies of using lidocaine to treat arrhythmias reveal conflicting results, but it is logical to think that treating local anesthetic–induced arrhythmias with just another local anesthetic antiarrhythmic is likely to add to the cardiotoxicity. The use of bretylium is no longer endorsed. Occurrence of Torsades des Pointes with bupivacaine toxicity may require overdrive pacing if that rhythm predominates.

Calcium channel blockers and phenytoin are contraindicated because their coadministration with local anesthetics may increase the risk of mortality.68,69 Recovery from local anesthetic–induced cardiac arrest can take enduring resuscitation efforts for more than an hour. Propofol is not an adequate alternative for treatment with intralipid, although judicious administration to control seizures when used in small divided doses is appropriate.70,71Administration of the lipid emulsion has become an important addition to the treatment of severe local anesthetic toxicity.72 Because it is still an innovative therapy, future laboratory and clinical experiences are needed for a better understanding of the mechanisms and further refinement of the treatment protocols.73

Allergic Reactions

The amino-esters, such as chloroprocaine, are all derivatives of the allergen paraaminobenzoic acid (PABA). Accordingly, the local anesthetics belonging to the ester group may cause positive skin reactions, ranging from toxic eruptions in situ to generalized rash or urticaria.74 Previous study results indicate an incidence of 30%, but no subject developed anaphylaxis. However, true allergic reactions to the local anesthetics of the amino-amide group are extremely rare. By and large, preparations of amide anesthetics do not cause allergic reactions, unless they contain the preservative methylparaben, which is in its chemical structure virtually the same as PABA.75 For patients who reported an allergy to amino-amides, one can safely use a preservative-free amide anesthetic unless a well-documented allergology reports point to an unambiguous allergy. Anaphylaxis due to local anesthetics remains a rare event, even within the ester group. It should be considered if the patient starts wheezing or develops respiratory distress instantly following injection. However, many symptoms can be explained by a variety of other causes including anxiety, hyperventilation, toxic effects of the drug, vasovagal reactions, reactions to epinephrine, or contamination with latex.

Management of local anesthetic triggered allergic reactions does not differ from the treatment algorithms for other more common allergic reactions. Intravenous lidocaine can result in paradoxical airway narrowing and bronchospasm in patients with asthma. The mechanism of this reaction is not well understood. Apparently, it is not explained by an exacerbation of the asthmatic condition itself or by some anaphylactoid cascade activated by lidocaine or its preservatives.

A unique side effect of some local anesthetics is methemoglobinemia.76,77 It has been associated with the topical, epidural, and intravenous administration of prilocaine. Hepatic metabolism of prilocaine produces orthotoluidine, which converts hemoglobin into methemoglobin. The doses needed to effectuate diminished oxygen saturation levels that are clinically significant, however, are typically above what is used in the clinical practice of regional anesthesia. Regardless, because of this theoretical possibility, in some countries, the use of prilocaine in regional anesthesia is banned. The condition of methemoglobinemia caused by prilocaine is spontaneously self-limiting and reversible. Reversal can be accelerated with the administration of methylene blue intravenously (1 mg/kg).



• Always maintain a high degree of suspicion.

• Monitor electrocardiogram, blood pressure, and arterial oxygen saturation.

• When feasible, communicate with the patient.

• Be conservative with local anesthetic (LA) dose in patients with advanced age, poor cardiac function, conduction abnormalities, or abnormally low plasma protein concentration.

• Gently aspirate every 3–5 mL.

• Inject slowly (<20 mL/min), and avoid forceful high-pressure injections.

• Use a pharmacologic marker (e.g., epinephrine 5 μg/mL of LA) with high-volume blocks.

• Monitor the patient after high-dose blocks for 30 minutes.

• Be prepared: A plan for managing systemic local anesthetic toxicity should be established in facilities where local anesthetics are used.

• Current recommendations are to have 20% lipid emulsion stocked close to sites where local anesthetics are used.

• Consider infusing lipid emulsion early to help prevent cardiac toxicity.

Detection of Systemic LA Toxicity

• Maintain a high degree of suspicion.

• The single most important step in treating local anesthetic toxicity is to consider its diagnosis.

• CNS symptoms are often subtle or absent.

• Cardiovascular signs (e.g., hypertension, hypotension, tachycardia, or bradycardia) may be the first signs of local anesthetic toxicity.

• CNS excitation (agitation, confusion, twitching, seizure), depression (drowsiness, obtundation, coma, or apnea), or nonspecific neurologic symptoms (metallic taste, circumoral paresthesias, diplopia, tinnitus, dizziness) are typical of LA toxicity.

• Ventricular ectopy, multiform ventricular tachycardia, and ventricular fibrillation are hallmarks of cardiac toxicity of LA.

• Progressive hypotension and bradycardia, leading to asystole, are the hallmark of severe cardiovascular toxicity.

Treatment of Systemic LA Toxicity

• Get help and call for 20% lipid emulsion.

• Perform airway management. Hyperventilate with 100% oxygen.

• Abolish the seizures.

• Perform cardiopulmonary resuscitation

• Epinephrine–controversial; may have to use higher doses then recommended in ACLS.

• Consider using vasopressin to support circulation

• Alert the nearest facility having cardiopulmonary bypass capability.

• Perform lipid emulsion treatment (for a 70-kg adult patient):

Image Bolus 1.5 mL/kg intravenously over 1 minute (about 100 mL)

Image Continuous infusion 0.25 mL/kg per minute (about 500 mL over 30 minutes)

Image Repeat bolus every 5 minutes for persistent cardiovascular collapse.

Image Double the infusion rate if blood pressure returns but remains low.

Image Continue infusion for a minimum of 30 minutes.




1. Weinberg GL. Current concepts in resuscitation of patients with local anesthetic cardiac toxicity. Reg Anesth Pain Med. 2002;27:568-575.

2. Long WB, Rosenblum S, Grady IP. Successful resuscitation of bupivacaine-induced cardiac arrest using cardiopulmonary bypass. Anesth Analg. 1989;69:403-406.

3. Feldman HS. Toxicity of local anesthetic agents. In: Rice SA, Fish KJ, eds. Anesthetic Toxicity. New York, NY: Raven Press; 1994.

4. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology. 1979;51(4):285-287.

5. Boren E, Teuber S, Naguwa S, Gershwin M. A critical review of local anesthetic sensitivity. Clin Rev Allergy Immunol. 2007;32(1):119-127.

6. Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anest Analg. 2009;108(3):837-845.

7. Burches B, Warner D. Bronchospasm after intravenous lidocaine. Anesth Analg. 2008;107(4):1260-1262.

8. Kalichman MW. Physiologic mechanisms by which local anesthetics may cause injury to nerve and spinal cord. Reg Anesth. 1993;18(6 Suppl):448-452.

9. Sadove S, Kolodny S. Local anesthetic agents in combination with vasoconstrictors part I, epinephrine. Acta Anaesth Scand. 1961;5(1):13-19.

10. Scott DB. Toxic effects of local anaesthetic agents on the central nervous system. Br J Anaesth. 1986;58:732-735.

11. Scott DB. Evaluation of the toxicity of local anaesthetic agents in man. Br J Anaesth. 1975;47:56-61.

12. Mather LE, Tucker GT, Murphy TM, Stanton-Hicks MD, Bonica JJ. Cardiovascular and subjective central nervous system effects of long-acting local anaesthetics in man. Anaesth Intensive Care. 1979;7:215-221.

13. Scott DB. Evaluation of clinical tolerance of local anaesthetic agents. Br J Anaesth. 1975;47 Suppl:328-331.

14. Rutten AJ, Nancarrow C, Mather LE, et al. Hemodynamic and central nervous system effects of intravenous bolus doses of lidocaine, bupivacaine, and ropivacaine in sheep. Anesth Analg. 1989;69:291-299.

15. Huang YF, Pryor ME, Mather LE, et al. Cardiovascular and central nervous system effects of bupivacaine and levobupivacaine in sheep. Anesth Analg. 1998;86:797-804.

16. 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.

17. Liu P, Feldman H, Giasi R, Patterson M, Covino B. Comparative CNS toxicity of lidocaine, etidocaine, bupivacaine, and tetracaine in awake dogs following rapid administration. Anesth Analg. 1983;62:375-379.

18. Reiz S, Nath S. Cardiotoxicity of local anaesthetic agents. Br J Anaesth. 1986;58:736-746.

19. Hogan Q. Local anesthetic toxicity: an update. Reg Anesth. 1996;21(6S):43-50.

20. Feldman HS, Covino BM, Sage DJ. Direct chronotropic and inotropic effects of local anesthetic agents in isolated guinea pig atria. Reg Anesth. 1982;7:149-156.

21. Lynch C. Depression of myocardial contractility in vitro by bupivacaine, etidocaine, and lidocaine. Anesth Analg. 1986;65:551-559.

22. Block A, Covino B. Effect of local anesthetic agents on cardiac conduction and contractility. Reg Anesth. 1982;6:55-61.

23. Stewart D, Rogers W, Mahaffrey J, Witherspoon S, Woods E. Effect of local anesthetics on the cardiovascular system in the dog. Anesthesiology. 1963;24:620-624.

24. Tanz RD, Heskett T, Loehning RW, Fairfax CA. Comparative cardiotoxicity of bupivacaine and lidocaine in the isolated perfused mammalian heart. Anesth Analg. 1984;63:549-556.

25. Pitkanen M, Feldman HS, Authur GR, Covino BG. Chronotropic and inotropic effects of ropivacaine, bupivacaine, and lidocaine in the spontaneously beating and electrically paced isolated, perfused rabbit heart. Reg Anesth Pain Med. 1992;17:183-192.

26. Englesson S. The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. I. An experimental study in cats. Acta Anaesth Scand. 1974;18:79-87.

27. Burney R, DiFazio C, Foster J. Effects of pH on protein binding of lidocaine. Anesth Analg. 1978; 57:478-480.

28. Mulroy M. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Reg Anesth Pain Med. 2002;27(6):556-561.

29. de Jong RH, Heavner JE. Diazepam prevents local anesthetic seizures. Anesthesiology. 1971;34:523-531.

30. de Jong RH, Heavner JE. Diazepam prevents and aborts lidocaine convulsions in monkeys. Anesthesiology. 1974;41:226-230.

31. de Jong RH, Bonin JD. Benzodiazepines protect mice from local anesthetic convulsions and deaths. Anesth Analg. 1981;60:385-389.

32. Ausinsch B, Malagodi MH, Munson ES. Diazepam in the prophylaxis of lignocaine seizures. Br J Anaesth. 1976;48:309-313.

33. Liguori G, Chimento GF, Borow L, Figgie M. Possible bupivacaine toxicity after intraarticular injection for postarthroscopic analgesia of the knee: implications of the surgical procedure. Anesth Analg. 2002; 94:1010-1013.

34. Kahn RL, Quinn TJ. Blood pressure, not heart rate, as a marker of intravascular injection of epinephrine in an epidural test dose. Reg Anesth. 1991;16:292-295.

35. Tanaka M, Nishikawa T. A comparative study of hemodynamic and T-wave criteria for detecting intravascular injection of the test dose (epinephrine) in sevoflurane-anesthetized adults. Anesth Analg. 1999;89:32-36.

36. Schoenwald PK, Whalley DG, Schluchter MD, Gottlieb A, Ryckman JV, Bedocs NM. The hemodynamic responses to an intravenous test dose in vascular surgical patients. Anesth Analg. 1995;80:864-868.

37. Weinberg G. Current concepts in resuscitation of patients with local anesthetic cardiac toxicity. Reg Anesth Pain Med. 2002;27(6):568-575.

38. 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.

39. Association of Anaesthetists of Great Britain and Ireland. Guidelines for the Management of Severe Local Anaesthetic Toxicity. London, UK: AAGBI, 2007.

40. Crews JC, Rothman TE. Seizure after levobupivacaine for interscalene brachial plexus block. Anesth Analg. 2003; 96:1188-1190.

41. Weinberg G, VadeBoncouer T, Ramaraju G, Garcia- Amaro M, Cwik M. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anaesthesiology.1998;88:1071-1075.

42. Weinberg G, Ripper R, Feinstein D, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine induced cardiac toxicity. Reg Anesth Pain Med. 2003; 8:198-202.

43. Weinberg G, Di Gregorio G, Ripper R, et al. Resuscitation with lipid versus epinephrine in a rat model of bupivacaine overdose. Anesthesiology. 2008;108:907-913.

44. Rosenblatt M, Abel M, Fischer G, Itzkovich C, Eisenkraft J. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine related cardiac arrest. Anaesthesiology. 2006;105:217-218.

45. Litz R, Popp M, Stehr S, Koch T. Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion. Anaesthesia. 2006;61:800-801.

46. McCutchen T, Gerancher J. Early Intralipid may have prevented bupivacaine associated cardiac arrest. Reg Anaesth Pain Med. 2008;33:178-180.

47. Foxall G, McCahon R, Lamb J, Hardman J, Bedforth N. Levobupivacaine-induced seizures and cardiovascular collapse treated with Intralipid. Anaesthesia. 2007;62:516–518.

48. Whiteside J. Reversal of local anaesthetic induced CNS toxicity with lipid emulsion. Anaesthesia. 2008;63:203–204.

49. Spence A. Lipid reversal of central nervous system symptoms of bupivacaine toxicity. Anaesthesiology. 2007;107:516–517.

50. Litz R, Roessel T, Heller A, Stehr S. Reversal of central nervous system and cardiac toxicity following local anaesthetic intoxication by lipid emulsion injection. Anesth Analg. 2008;106:1575–1577.

51. Zimmer C, Piepenbrink K, Riest G, Peters J. Cardiotoxic and neurotoxic effects after accidental intravascular bupivacaine administration. Therapy with lidocaine propofol and lipid emulsion. Anaesthesist.2007;56(5):449-453.

52. Ludot H, Tharin JY, Belouadah M, Mazoit JX, Malinovsky JM. Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child. Anesth Analg. 2008;106(5):1572-1574.

53. Warren JA, Thoma RB, Georgescu A, Shah SJ. Intravenous lipid infusion in the successful resuscitation of local anesthetic-induced cardiovascular collapse after supraclavicular brachial plexus block. Anesth Analg. 2008;106(5):1578-1580.

54. Picard J, Meek T. Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob. Anaesthesia. 2006;61:107–109.

55. Tsai MH, Tseng CK, Wong KC. Successful resuscitation of a bupivacaine-induced cardiac arrest using cardiopulmonary bypass and mitral valve replacement. J Cardiothorac Anesth. 1987;1:454-456.

56. Long WB, Rosenblum S, Grady IP. Successful resuscitation of bupivacaine-induced cardiac arrest using cardiopulmonary bypass. Anesth Analg. 1989;69:403-406.

57. Freedman MD, Gal J, Freed CR. Extracorporeal pump assistance—novel treatment for acute lidocaine poisoning. Eur J Clin Pharmacol. 1982;22:129-135.

58. Soltesz EG, van Pelt F, Byrne JG. Emergent cardiopulmonary bypass for bupivacaine cardiotoxicity. J Cardiothorac Anesth. 2003;17:357-358.

59. Chazalon P, Tourtier JP, Villevieille T, et al. Ropivacaine-induced cardiac arrest after peripheral nerve block: successful resuscitation. Anesthesiology. 2003;99:1449–1451.

60. Huet O, Eyrolle LJ, Mazoit JX, Ozier YM. Cardiac arrest and plasma concentration after injection of ropivacaine for posterior lumbar plexus blockade. Anesthesiology. 2003;99:1451–1453.

61. Heavner JE, Pitkanen MT, Shi B, Rosenberg PH. Resuscitation from bupivacaine-induced asystole in rats: comparison of different cardioactive drugs. Anesth Analg. 1995;80:1134-1139.

62. Bernards CM, Carpenter RL, Kenter ME, Brown DL, Rupp SM, Thompson GE. Effect of epinephrine on central nervous system and cardiovascular system toxicity of bupivacaine in pigs. Anesthesiology. 1989;71:711-717.

63. Krismer AC, Hogan QH, Wenzel V, et al. The efficacy of epinephrine or vasopressin for resuscitation during epidural anesthesia. Anesth Analg. 2001;93:734-742.

64. Arnold JM. The role of phosphodiesterase inhibitors in heart failure. Pharmacol Ther. 1993;57:161-161.

65. DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med. 1989;320:677-683.

66. Nolan JP, Deakin CD, Soar J, Böttiger BW, Smith G. European Resuscitation Council Guidelines for Resuscitation 2005 Section 4. Adult advanced life support. Resuscitation. 2005;67S1:S39-S86.

67. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: Part 7.3: Management of Symptomatic Bradycardia and Tachycardia. Circulation.2005;112:IV-67-IV-77.

68. Tallman RD Jr, Rosenblatt RM, Weaver JM, Wang YL. Verapamil increases the toxicity of local anesthetics. J Clin Pharmacol. 1988;28:317-321.

69. Simon L, Kariya N, Pelle-Lancien E, Mazoit JX. Bupivacaine-induced QRS prolongation is enhanced by lidocaine and by phenytoin in rabbit hearts. Anesth Analg. 2002; 94:203-207.

70. Heavner JE, Arthur J, Zou J, McDaniel K, Tyman-Szram B, Rosenberg PH. Comparison of propofol with thiopentone for treatment of bupivacaine-induced seizures in rats. Br J Anaesth. 1993;71:715-719.

71. Momota Y, Artru AA, Powers KM, Mautz DS, Ueda Y. Posttreatment with propofol terminates lidocaine induced epileptiform electroencephalogram activity in rabbits: effects on cerebrospinal fluid dynamics. Anesth Analg.1998;87:900-906.

72. Weinberg GL. Lipid infusion therapy: translation to clinical practice. Anesth Analg. 2008;106(5):1340-1342.

73. Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review. Acad Emerg Med. 2009;16(9):815-824.

74. Aldrete JA, Johnson DA. Evaluation of intracutaneous testing for investigation of allergy to local anesthetic agents. Anesth Analg. 1970;49:173-183.

75. Cashman AL, Warshaw EM. Parabens: a review of epidemiology, structure, allergenicity, and hormonal properties. Dermatitis. 2005;16(2):57-66.

76. Lund PC, Cwik JC. Propitocaine (Citanest) and methemoglobinemia. Anesthesiology. 1965; 26:569-571.

77. Scott DB, Owen JA, Richmond J. Methemoglobinemia due to prilocaine. Lancet. 1964;284:728-729.

If you find an error or have any questions, please email us at admin@doctorlib.info. Thank you!