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Local anesthetic allergy

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Local anesthetic allergy

Presented by Sirapassorn Sornphiphatphong, MD

2015

Published in: Health & Medicine
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Local anesthetic allergy

  1. 1. Local anesthetic allergy Reviewed by Sirapassorn Sornphiphatphong, MD.
  2. 2. Overview • Introduction • Adverse reaction to LA • Prevalence of LA allergy • Categories of LA • Types of allergic reactions of LA – Contact dermatitis and Delayed type hypersensitivity – Immediate type hypersensitivity
  3. 3. Local anesthetics (LA) • Discovery of cocaine in 1884 • Multiple forms: gels, ointments, sprays, solutions and injectable forms • Topical, infiltrative, nerve block, epidural, or spinal routes • Dentistry, ophthalmology, minor surgery, endoscopies and obstetrics Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  4. 4. Adverse reactions to LA deShazo RD, et al. JACI 1979
  5. 5. Adverse reactions to LA Bhole MV, et al. British Journal of Anaesthesia, 2012
  6. 6. Categories of LA Joanna Lukawska, et al. Current Allergy & Clinical Immunology, 2009 Vol 22, No. 3
  7. 7. Benzoic acid esters LA • Metabolised by pseudocholinesterase in plasma to para-aminobenzoic acid (PABA) • Reactions thought to be secondary to PABA • Procaine (Novocain) most common • Often cross-react with each other but generally do not cross-react with the amide groups Joanna Lukawska, et al. Current Allergy & Clinical Immunology, 2009 Vol 22, No. 3 Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  8. 8. The amides • Less sensitizing and do not generally cross- react with each other • Not metabolized into the PABA molecule • Metabolised in the liver • Decreased hepatic function are at increased risk of overdosage and toxic reactions Joanna Lukawska, et al. Current Allergy & Clinical Immunology, 2009 Vol 22, No. 3 Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  9. 9. Lidocaine • Prototype for amide local anesthetics • Rapid onset, intermediate duration • Metabolized by the liver and excreted by the kidneys with 10% unchanged and 80% as metabolites Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  10. 10. Mepivacaine • Rapid onset, medium duration • metabolized by the liver • Higher-concentration (4%) causes slight vasoconstriction, longer duration Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  11. 11. Prilocaine • Secondary amide • Metabolized in both liver and kidneys • Methemoglobinemia when using large doses • Avoided in sickle cell anemia, chronic anemia, and hypoxia and in patients taking high doses of acetaminophen Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  12. 12. Articaine • Unique structures including a thiophene ring that enhances its lipid solubility • less systemic toxicity Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  13. 13. Bupivacaine • 4 times more potent than lidocaine, mepivacaine, and prilocaine • Long-term pain control; extraction of impacted third molars, epidural block, or surgical wound sites • Higher cardiotoxicity, caution in patients taking b- blockers or digoxin Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  14. 14. Epinephrine • 1:100,000 • Vasoconstriction • Increased duration, less systemic absorption • Adverse effect: cause palpitations, tachycardia, arrhythmia, hypertension, tremor, headache, and anxiety Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  15. 15. Prevalence of LA allergy • Frequently reported adverse reactions by patients • Extremely rare true immune-mediated reactions estimated <1% of all adverse reactions to LA Fisher MM, et al. Anaesth Intensive Care 1997; 25: 611–614. Gall H, et al. J Allergy Clin Immunol 1996; 97: 933–937. Baluga JC, et al. Allergol Imunopathol 2002; 30(1): 14–19. Gonzalez-Delgado P, et al. J Investig Allergol Clin Immunol 2006 Batinac T, et al. Journal of Dermatology 2013; 40: 522-527
  16. 16. Bhole MV, et al. British Journal of Anaesthesia 108 (6): 903–11 (2012)
  17. 17. Types of allergic reactions of LA • Allergic contact dermatitis and delayed swelling at the site of administration • Immediate reaction: urticaria, anaphylaxis • Other causes that mimic allergic reactions • Multiple drugs used • Other topical agents, such as neomycin • Additives and preservatives; sulfites and parabens
  18. 18. Parabens • Preservatives • Reported reactions to methylparaben in LA • In 1984, FDA mandated its removal from single- dose LA cartridges Macy E, et al. JACI 2002 • Immediate hypersensitivity to pure amide LA agents is extremely rare • Methylparaben was the only established cause for an immediate hypersensitivity reaction during LA identified in a large allergy practice during the past 16 years
  19. 19. Sulfites • Bisulfite or metabisulfite • Antioxidants, stabilize epinephrine • Non–IgE-mediated hypersensitivity reactions, particularly in patients with asthma A case report • 40-year-old woman with severe edema of the face and neck after 2 hr of Neo-lidocaton injection for dental procedure and lasted for 2 days
  20. 20. Case report • Patch testing: positive to Neo-lidocaton at 48, 96 hr and positive patch testing with sodium metabisulfites at 48 and 72 U • No reaction when used lidocaine without metabisulfites Dooms-Goossens A, et al. Contact Dermatitis 1989; 20:124 Neo-Lidocaton contains lidocaine, vasopressin, norepinephrine, p-hydroxybenzoates, 0.2% sodium metabisulfite, sodium chloride, potassium chloride and calcium chloride
  21. 21. Contact dermatitis, delayed local swelling • Within 72 hours • Limited to area in direct contact with agent, at the site of administration • Localized eczematous, pruritic rash, vesicle, blister • Clinical history, patch testing, and possibly challenge
  22. 22. History taking 1. Type of procedure performed 2. Timing of administration of local anesthetic in relation to symptom development 3. Complete review of systems of the reaction 4. Type, amount, and concentration of the local anesthetic used 5. Whether the local anesthetic contained epinephrine 6. Patients’ medical history, particularly kidney, liver, cardiac, and psychiatric history Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  23. 23. Patch testing • Various concentration of LA in patch testing • Lidocaine (in a petroleum vehicle) ranged 5-15% • Finn chambers on Scanpor tape • T.R.U.E. test panel (Allerderm Lab, Phoenix, AZ) includes a "caine mix” contains tetracaine hydrochloride, benzocaine dibucaine hydrochloride, Mackley CL, et al. Arch Dermatol 2003; 139:343 Amado A, et al. Dermatitis 2007; 18:215 Kaufmann JM, et al. J Drugs Dermatol 2002; 1:192 Sanchez-Morillas L, et al. Contact Dermatitis 2005; 53:352
  24. 24. Patch testing
  25. 25. Cross-reactivity • Limited data • Evidence for cross-reactivity within each group of agents • Minimal evidence for cross-reactivity between the two groups Bircher AJ, et al. Contact Dermatitis 1996; 34:387
  26. 26. Sensitisation and cross-reactivity, resulting in delayed-type IV reactions, between ester-LAs are common • Benzocaine, frequently used ester-LAs for topical applications • sun creams and haemorrhoid creams, as well as some topical anaesthetics • PABA, is a common and potent sensitiser Joanna Lukawska, et al. Current Allergy & Clinical Immunology, 2009 Vol 22, No. 3
  27. 27. Case report • 43-yr-old woman • Localized angioedema 24 hr after local anesthesia for dental surgery and after applying sunburn • Contact allergy to ester LA; benzocaine, procaine and tetracaine • Sensitization to lidocaine and cross-reactivity to the other aminoacylamide LA; bupivacaine, mepivacaine, prilocaine but not to articaine • Tolerated to subcutaneous challenge to articaine
  28. 28. Amado A., et al. Dermatitis 2007
  29. 29. Amado A., et al. Dermatitis 2007
  30. 30. Amado A., et al. Dermatitis 2007
  31. 31. Amado A., et al. Dermatitis 2007
  32. 32. Case report • 70-year-old woman with soft-tissue swelling of the cheek 48 hr after dental treatment • Positive patch testing to lidocaine, prilocaine, mepivacaine, and dibucaine Curley RK, et al. Arch Dermatol 1986; 122:924
  33. 33. Immediate type • Pruritus, urticaria, bronchospasm, angioedema of noncontiguous tissues, and anaphylaxis • Within one hour
  34. 34. History taking 1. Type of procedure performed 2. Timing of administration of local anesthetic in relation to symptom development 3. Complete review of systems of the reaction 4. Type, amount, and concentration of the local anesthetic used 5. Whether the local anesthetic contained epinephrine 6. Patients’ medical history, particularly kidney, liver, cardiac, and psychiatric history Volcheck GW, et la. Immunol Allergy Clin N Am 34 (2014) 525–546
  35. 35. Skin prick test, SPT • In the 23 large series, 2487 out of 2978 patients (83.5%) tested using this method • Thirty (1.2%) had positive results • Many authors have used undiluted LA for skin prick tests, although some have preferred to use dilutions Bhole MV, et al. British Journal of Anaesthesia, 2012
  36. 36. Intra-dermal tests, ID test • 2648 of 2978 patients (89%) • Positive in 37 (1.4%) when using 1:10 or greater dilutions of LA • Neat preparations of LA were not commonly used for intra-dermal testing Bhole MV, et al. British Journal of Anaesthesia, 2012
  37. 37. Subcutaneous challenge • 2560 of the total 2978 patients (86%) had subcutaneous challenges • Positive challenge tests in 19 patients (0.74%) • In most cases, this procedure has been used to demonstrate tolerance to an alternative agent rather than confirm allergy Bhole MV, et al. British Journal of Anaesthesia, 2012
  38. 38. Drug provocative test Joanna Lukawska, et al. Current Allergy & Clinical Immunology, 2009 Vol 22, No. 3
  39. 39. Skin testing and challenge deShazo RD, et al. JACI 1979
  40. 40. SPT, ID 1. SPT and IDT (concentrations not defined), if negative, a single subcutaneous challenge (as opposed to incremental); if positive, then skin test and challenge to an unrelated local anesthetic 2. If negative SPT → IDT with (1:100) 0.04 mL, if negative → 1 mL subcutaneous challenge. if positive skin test, retest with pure local anesthetic solution without methylparaben or other preservative Volcheck GW, et la. Immunol Allergy Clin N Am, 2014 Bhole MV, et al. Br J Anaesth 2012 Harboe T, et al. Acta Anaesthesiol Scand 2010;54:536–42
  41. 41. SPT, ID 3. If negative SPT→ IDT with 1:100 dilution, if negative → subcutaneous challenge with (1:10) 0.1 mL, then undiluted 0.1 mL, then undiluted 1.0 mL Volcheck GW, et la. Immunol Allergy Clin N Am, 2014 Macy E. Ann Allergy Asthma Immunol 2003;91:319–20
  42. 42. NPV of SPT • The negative predictive value of the skin test was 97% Brad McClimon, et al. Allergy Asthma Proc, 2011 Specjalski K, et al. Int Arch Allergy Immunol 2013;162:86–88
  43. 43. Skin testing and challenge Chandler MJ, et al. JACI 1987:79:883-6
  44. 44. Drug provocative test • No cases of immediate-type hypersensitivity by skin test or test-dose challenge • We suggest that intradermal testing be abandoned in favor of prick testing followed by incremental subcutaneous provocative dose testing • “The patient has received 3 ml of the local anesthetic without an adverse reaction and appears to be at no greater risk for a repeat reaction than the general population” Chandler MJ, et al. JACI 1987:79:883-6
  45. 45. Drug provocative test • Injecting 0.1 mL, 0.5 and 1 ml of undiluted local anesthetic solution subcutaneously into the upper arm at a different location at 15 min interval • A positive subcutaneous challenge was defined as a wheal 3 mm greater than negative control Brad McClimon, et al. Allergy Asthma Proc, 2011
  46. 46. Drug provocative test • Poland, 2006 to July 2012 • 154 patients • SPT – 1%lidocaine, 0.5%bupivacaine, mepivacaine and articaine • The next step, ICT with LA diluted (1: 10), positive in the case of a wheal of ≥ 5 mm in diameter Specjalski K, et al. Int Arch Allergy Immunol 2013;162:86–88
  47. 47. Drug provocative test • The drug was injected in the lateral side of an arm every 30 min in increasing doses: 0.1 ml of diluted drug (1: 10), 0.1 ml of undiluted drug and 1 ml of undiluted drug Specjalski K, et al. Int Arch Allergy Immunol 2013;162:86–88
  48. 48. Cross-reactivity • 39-year-old man, in Spain • Itching, generalized urticaria with facial angioedema 15 min after mepivacaine administration • SPT: strong positive reaction to mepivacaine, lidocaine, and ropivacaine, but negative reactions to bupivacaine and levobupivacaine • Double-blind placebo-controlled subcutaneous challenge with bupivacaine and levobupivacaine was well tolerated González-Delgado P, et al. J Investig Allergol Clin Immunol 2006
  49. 49. 1%, 2% lidocaine • with 1:80,000 epinephrine injection solution • No-methylparaben formulation
  50. 50. 2% Mepivacaine • With adrenaline • 1.8, 2.2 ml • Contains sulfites • 3% is SULFITE FREE • without vaso- constrictor • No-methylparaben 3% Mepivacaine
  51. 51. 4% articaine • No-methylparaben • With 1:100,000 epinephrine injection solution • Contains sodium metabisulfite
  52. 52. Citanest (Prilocaine) • 1%prilocaien • Contains Paraben
  53. 53. Conclusions: Facts • Adverse reactions to LAs are often related to epinephrine, psychogenic factors, other drugs • Toxic effect of LA may occasionally be misdiagnosed as LA allergy • Risk of adverse drug reaction to LA may be increased in patients with deranged liver function or pseudocholinesterase dysfunction Joanna Lukawska, et al. Current Allergy & Clinical Immunology, 2009 Vol 22, No. 3
  54. 54. Conclusions • Rare IgE-mediated hypersensitivity to LAs • Sensitisation and cross-reactivity, resulting in delayed-type IV reactions, between ester-LAs are common • Patch testing is a reliable method of diagnosis of delayed-type IV hypersensitivity reactions

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