The problem of hypersensitivity to local anesthetics


ABSTRACT. The problem of the development of adverse reactions as a result of the use of diagnostic and medicinal products (drugs) in medicine is becoming increasingly important. Patients more often note reactions to local anesthetics (LA) – 43.2 %, antibiotics – 18.8 %, nonsteroidal anti-inflammatory drugs – 9.7 %, other drugs – 28.4 %. LA include two chemical groups: esters of benzoic acid (Ester-type anesthetics), which are potentially allergens, and amides (Amide-type anesthetics), which have virtually no allergenic potential. Based on the history for doctor is often difficult to assess the risk of allergic reactions, so if in the past the patient had a side effect of LA, then these drugs should be skin and provocative tests, having obtained the informed consent of the subject to conduct them. Skin prick tests are used for initial diagnosis in patients with suspected LA allergy. If the results of the pre-test and intradermal test are negative, a subcutaneous challenge test with LA is performed. Skin testing for suspected hypersensitivity (НS) of the delayed type begins with application (patch) tests and only with a negative result using an intradermal test with LA. Laboratory methods for diagnosing НS to LA are used much less often than skin and provocative tests, because for many drugs the appropriate methods have not been developed, as well as because it is a time-consuming and expensive method of diagnosis. Therapeutic tactics in the event of НS to LA include providing patients with emergency care in the development of anaphylaxis and treatment of other clinical manifestations of HS reactions in accordance with existing international and domestic protocols. Epinephrine, oxygen therapy, colloid/crystalloid infusions, antihistamines, systemic and topical corticosteroids, protease inhibitors, inhaled β2-agonists, leukotriene receptor antagonists, etc. are most commonly used for this purpose.

Keywords: hypersensitivity, local anesthetics, diagnosis, treatment.


Дранник Г. Н. Клиническая иммунология и аллергология. – К., 2010. – 482 с.

Зайков С. В., Дмитриева Э. Н. Проблема лекарственной аллергии в анестезиологии. Раціональна фармакотерапія. 2009; 3 (12): 22-27.

Жукова Д. Г., Феденко Е. С., Юдин А. А. Определение оптимальных концентраций и доз лекарственных средств для диагностики реакций гиперчувствительности в периоперационном периоде. Рос. аллергологич. журн. 2015; 1: 27-33.

Кайдашев И. П. Гиперчувствительность к лекарственным препаратам. Руководство для врачей. – К., 2016. – 288 с.

Кайдашев И. П. Как диагностировать непереносимость антибиотиков? Астма та алергія. 2016; 1: 56-59.

Клиническая аллергология: рук-во для практических врачей. Под ред. Р. М. Хаитова. – М.: МЕДпресс-информ, 2002. – 624 с.

Кобзев Д.Ю., Удовиченко Е.Н., Перфилова И.А., Гамова И.В., Астафьева Н. Г. Лекарственная гиперчувствительность при оперативных вмешательствах. Лечащий врач. 2004; 11.

Лекарственная аллергия: методические рекомендации для врачей. Под ред. Р. М. Хаитова. – М., 2012. – 73 с.

Пухлик Б. М., Анісімов М. В., Римарчук О. М. Медикаментозна алергія в стоматологічній практиці. Недооцінена небезпека. Медичні перспективи. 2009; XIY (2): 4-7.

Пухлик Б. М., Викторов А. П., Зайков С. В. Лекарственная аллергия и побочные эффекты лекарственных средств в аллергологии. – Львів: Медицина світу, 2008. – 107 с.

Степанова Е. В. Современные аспекты диагностики и лечения лекарственной аллергии. Лечащий врач. 2004; 9.

Уніфікований клінічний протокол екстреної, первинної, вторинної (спеціалізованої) та третинної (високоспеціалізованої) медичної допомоги. Адаптована клінічна настанова, заснована на доказах «Медикаментозна алергія, включаючи анафілаксію». Наказ МОЗ України № 916 від 30.12.2015.

Хаитов Р. М., Ильина Н. И., Латышева Т. В. и др. Рациональная фармакотерапия аллергических заболеваний: рук. для практикующих врачей. – М.: Литтерра, 2007. – 504 с.

Aberer W., Bircher A., Romano A. et al. The ENDA and the EAACI Interest Group on Drug Hypersensitivity. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy. 2003; 58: 854-863.

Agache I., Ryan D., Rodriguez M. et al. Allergy management in primary care across European countries – actual status. Allergy. 2013; 68 (7): 836-843.

Anderson I. A. Allergic reaction to drug and biologic agents. JAMA. 1992; 268: 2848-2857.

Arbous M. S. et al. Mortality associated with anaesthesia: a qualitative analysis to identify risk factors. Anaesthesia. 2004; 59 (10): 1141-1153.

Atanaskovic-Markovic M., Caubet J. Management of drug hypersensitivity in the pediatric population. Expert Rev. Clin. Pharmacol. 2016: 1-9.

Axon A. D. Anaphylaxis and anaesthesia – all clear now? British Journal of Anaesthesia. 2004; 93 (4): 501-504.

Becker D. E., Reed K. L. Essentials of local anesthetic pharmacology. Anesth. Prog. 2006 Fall; 53 (3): 98-109.

Becker D. E., Reed K. L., Becker D. E. et al. Similar articles. Local anesthetics: review of pharmacological considerations. Anesth. Prog. 2012 Summer; 59 (2): 90-101.

Beeler A., Pichler W. In vitro tests of T‑cell-mediated drug hypersensitivity. Drug Hypersensitivity. Basel, Karger, 2007: 380-390. doi: 10.1111/j.1398-9995.2007.01516.x.

Bercum Y., Ben-Zvi A., Levy Y. et al. Evaluation of adverse reactions to local anesthetics: experience with 236 patients. Ann. Allergy Asthma Immunol. 2003; 91: 342-345.

Bhole M. V., Manson A. L., Seneviratne S. L., Misbah S. A. IgE‑mediated allergy to local anaesthetics: separating fact from perception: a UK perspective. Br. J. Anaesth. 2012 Jun; 108 (6): 903-11. doi: 10.1093/bja/aes162.

Bousquet P.-J., Demoly P. et al. Position paper. Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GA2 LEN platform. The Galenda project. Allergy. 2009; 64: 194-203.

Brockow K., Garvey L., Aberer W. et al. ENDA/EAACI Drug Allergy Interest Group. Skin test concentrations for systemically administered drugs – an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2013; 68 (6): 702-12. doi: 10.1111/all.12142. Epub 2013 Apr 25.

Brockow K., Romano A., Aberer W. et al. Skin testing in patients with hypersensitivity reactions to iodinated contrast media – a European multicenter study. Allergy. 2009; 64 (2): 234-241. doi: 10.1111/j.1398-9995.2008.01832.x.

BSACI guidelines for the management of drug allergy. Clinical and Experimental Allergy. 2008; 39: 43-61.

Chandler M., Grammer L., Patterson R. Provocative challenge with local anesthetics in patients with a prior history of reaction. J. Allergy Clin. Immunol. 1987; 79: 883-886.

De Moly P., Adkinson F., Brockow K. et al. International consensus on drug allergy. Allergy. 2014; 69: 420-437.

Dewachter P., Mouton-Faivre C. Patients who experience a perioperative anaphylactic reaction should not be skin-tested too early. Can. J. Anaesth. 2007 Sep; 54 (9): 768-769.

Drug allergy: diagnosis and management of drug allergy in adults, children and young people. NICE (National Institute of Health and Care Excellence) Clinical Guideline 183. Sep 2014: 1-167.

Ebo D., Leysen J., Mayorga C. et al. The in vitro diagnosis of drug allergy: status and perspectives. Allergy. 2011; 66 (10): 1275-1286. doi: 10.1111/j.1398-9995.2011.02661.x.

Eggleston S. T., Lush L. W. Understanding allergic reactions to local anesthetic. Ann. Pharmacother. 1996; 30: 851-857.

European Academy of Allergology Asthma and Immunology (EAACI). Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Available at:

Ewan P., Dugue P., Mirakian R., Dixon T., Harper J., Nasser S. BSACI guidelines for the investigation of suspected anaphylaxis during general anaesthesia. Clin. Exp. Allergy. 2010 Jan; 40 (1): 15-31.

Fisher M., Graham R. Adverse responses to local anaesthetics. Anaesth. Intensive Care. 1984; 12: 325-327.

Gall H., Kaufmann R., Kalveram C. Adverse reactions to local anesthetics: analysis of 197 cases. J. Allergy Clin. Immunol. 1996; 97 (4): 933-937.

Incaudo G., Schatz M., Poatterson R. et al. Administration of local anesthetics to patients with a history of prior adverse reactions. 1978; 61: 339-345.

Jacobsen R., Borch J., Bindshev-Jensen C. Hypersensitivity to local anesthetics. Allergy. 2005; 60: 262-264.

Kano Y. , Hirahara K., Mitsuyama Y. et al. Utility of the lymphocyte transformation test in the diagnosis of drug sensitivity: dependence on its timing and the type of drug eruption. Allergy. 2007; 62 (12): 1439-1444. doi: 10.1111/j.1398-9995.2007.01553.x.

Lammintausta K., Kortekangas-Savolainen O. The usefulness of skin test to prove drug hypersensitivity. Br. J. Dermatol. 2005; 152 (5): 968-974. doi: 10.1111/j.1365-2133.2005.06429.x.

Laxenaire M. C. et al. Anaphylaxis during anaesthesia. Results of two-year survey in France. Anaesthesia. 2004; 59 (10): 549-558.

Lieberman Р., Nicklas R., Oppenheimer J. et al. The diagnosis and management of anaphylaxis practice parameter: 2010 Update. J. Allergy Clin. Immunol. 2010; 126 (3): 477-480. doi: 10.1016/j.jaci.2010.06.022.

Lobera T., Audicana M., Pozo M. et al. Study of hypersensitivity reactions and anaphylaxis during anesthesia in Spain. J. Investig. Allergol. Clin. Immunol. 2008; 18 (5): 350-356.

Macias E., Ruiz A., Moreno E. et al. Usefulness of interdermal test and patch test in the diagnosis of nonimmediate reactions to metamizol. Allergy. 2007; 62 (12): 1462-1464. doi: 10.1111/j.1398-9995.2007.01487.x.

Macy E., Schatz M., Zeiger R. Immediate hypersensitivity to methylparaben causing false-positive results of local anesthetic skin testing or provocative dose testing. Perm. J. 2002 Fall; 6 (4): 17-21.

McClimon B., Rank M., Li J. The predictive value of skin testing in the diagnosis of local anesthetic. Allergy Asthma Proc. 2011 Mar 1; 32: 95-98.

Mertes P., Malinovsky J., Jouffroy L. et al. The ENDA and the EAACI Interest Group on Drug Allergy. Reducing the risk of anaphylaxis during anesthesia: 2011 updated guidelines for clinical practice. J. Investig. Allergol. Clin. Immunol. 2011; 21 (6): 442-453.

Michalska-Krzanowska G. Anaphylactic reactions during anaesthesia and the perioperative period. Anaesthesiol. Intensive Ther. 2012 Aug 8; 44 (2): 104-111.

Michalska-Krzanowska G. Tryptase in diagnosing adverse suspected anaphylactic reaction. Adv. Clin. Exp. Med. 2012 May-Jun; 21 (3): 403-8.

Mirakian R., Ewan P., Durham S. et al. BSACI guidelines for the management of drug allergy. Clin. Exp. Allergy. 2009 Jan; 39 (1): 43-61. doi: 10.1111/j.1365-2222.2008.03155.x.

Mertes P., Lambert M., Gueant-Rodriguez R. et al. Perioperative anaphylaxis. Immunol. Allergy Clin. North Am. 2009 Aug; 29 (3): 429-451.

Mertes P., Tajima K., Regnier-Kimmoun M. et al. Perioperative anaphylaxis. Med. Clin. North Am. 2010 Jul; 94 (4): 761-789.

Monneret G., Benoit Y., Debard A., Bienvenu J. Monitoring of basophil activation using CD63 and CCR3 in allergy to muscle relaxant drugs. Clin. Immunol. 2002; 102: 192-9.

Morais-Almeida M., Gaspar A., Marinho S., Rosado-Pinto J. Allergy to local anesthetics of the amide group with tolerance to procaine. J. Allergy. 2003 Aug; 58 (8): 827-8.

Morgan P. W. et al. Giving long-persistent starch as volume replacement саn cause pruritus after cardiac surgery. Anaesthesia. 2004; 59 (10): 696-699.

Muraro A., Lemanske R., Castells M. et al. Precision medicine in allergic disease – food allergy, drug allergy, and anaphylaxis – PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology. Allergy. 2017; 72: 1006-1021.

Muraro A., Roberts G., Clark A. et al. The management of anaphylaxis in childhood: position paper of the European academy of allergology and clinical immunology. Allergy. 2007; 62: 857-871.

Nettis E., Napoli G., Ferrannini A., Tursi A. The incremental challenge test in the diagnosis of adverse reactions to local anesthetics. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod. 2001 Apr; 91 (4): 402-5.

Nyfeler B., Pichler W. The lymphocyte transformation test in for the diagnosis of drug allergy: sensitivity and specificity. Clin. Exp. Allergy. 1997; 27: 175-181. doi: 10.1111/j.1365-2222.1997.tb00690.x.

Phillips J. F., Yates A. B., Deshazo R. D. Approach to patients with suspected hypersensitivity to local anesthetics. Am. J. Med. Sci. 2007 Sep; 334 (3): 190-6.

Pichler W., Tilch J. The lymphocyte transformation test in for the diagnosis of drug hypersensitivity. Allergy. 2004; 59 (8): 809-820. doi: 10.1111/j.1398-9995.2004.00547.x.

Porebski G., Gschwend-Zawodniak A., Pichler W. In vitro diagnosis of T‑cell-mediated drug allergy. Clin. Exp Allergy. 2011; 41 (4): 461-470. doi: 10.1111/j.1365-2222.2011.03701.x.

Posadas S., Pichler W. Delayed drug hypersensitivity reactions – new concepts. Clin. Exp. Allergy. 2007; 37: 989-999.

Schatz M. Adverse reactions to local anesthetics. Immunol. Allergy Clin. North Amer. 1992; 12: 585-609.

Scherer K., Brockow K., Aberer W. et al. Desensitization in delayed drug hypersensitivity reactions – an EAACI position paper of the Allergy Interest Group. Allergy. 2013; 68 (7): 844-852.

Simons E., Ardusso L., Dimov V. et al. World Allergy Organization Anaphylaxis Guidelines: 2013 update of the evidence base. Int. Arch. Allergy Immunol. 2013; 162: 193-204.

Sindel L. J., De Shazo R. D. Accidents resulting from local anesthetic. True or false allergy? Clin. Rev. Allergy. 1991; 9: 379-395.

Soto-Aguilar M.C., de Shazo R. D., Danson E. S. Approach to the patient with suspected local anestethic sensitivity. Immunol and Allergy Clinic of North America. 1998; 18: 851-865.

Speca S. J., Boynes S. G., Cuddy M. A. Allergic reactions to local anesthetic formulations. Dent. Clin. North Am. 2020; 54: 655-664.

Thong B., Mirakian R., Castells M. et al. A World Allergy Organization international survey on diagnostic procedures and therapies in drug allergy / hypersensitivity. WAO Journal. 2011; 4: 257-270. doi: 10.1097/WOX.0b013e31823dc02c.

Thyssen J., Menne T., Elberling J., Plaschke P., Johansen J. Hypersensitivity to local anaesthetics – update and proposal of evaluation algorithm. Contact Dermatitis. 2008; 589: 69-78.

Tomoyasu Y., Hayashi T., Sakaguchi M. Allergic reactions to local anesthetics in dental patients: analysis of intracutaneous and challenge tests. The Open Dentistry Journal. 2011; 5: 146-149. DOI: 10.2174/1874210601105010146. PMID: 21915228. PMCID: PMC3170934.

Venemalm L., Degerbeck F., Smith W. IgE‑mediated reaction to mepivacaine. J. Allergy Clin. Immunol. 2008 Apr; 121 (4): 1058-9. doi: 10.1016/j.jaci.2007.12.1154.

How to Cite
Zaikov, S. V., Kaidashev, I. P., & Gumeniuk, G. L. (2020). The problem of hypersensitivity to local anesthetics. Infusion & Chemotherapy, (3), 43-51.

Author Biographies

S. V. Zaikov, National Medical Academy of Postgraduate Education named after P. L. Shupyk, Kyiv, Ukraine

Zaikov Sergii Viktorovych
Professor of the Department of Phthisiology and Pulmonology, National Medical Academy of Postgraduate Education named after P. L. Shupyk.
MD, professor.
10, M. Amosova st., Kyiv, 03038, Ukraine.

I. P. Kaidashev, Ukrainian Medical Stomatological Academy, Poltava, Ukraine

Kaidashev Igor Petrovych
Professor of the Department of Internal Medicine № 3 with Phthisiology
MD, professor.
23, Shevchenko st., Poltava, 36011, Ukraine

G. L. Gumeniuk, National Institute of Phthisiology and Pulmonology named after F. G. Yanovsky NAMS of Ukraine, Kyiv

Gumeniuk Galyna Lvivna
Professor of the Department of Phthisiology and Pulmonology, National Medical Academy of Postgraduate Education named after P. L. Shupyk.
10, M. Amosova st., Kyiv, 03038, Ukraine.