Indian Journal of Allergy, Asthma and Immunology

: 2021  |  Volume : 35  |  Issue : 2  |  Page : 67--71

Clinical profile of drug sensitivity test in patients with a previous history of allergy as part of preanesthetic evaluation

Krishnan Sabhapathy, Shweta Krishnan 
 Allergy Asthma Centre, Krishna Hospital, Kochi, Kerala, India

Correspondence Address:
Dr. Krishnan Sabhapathy
Krishna Hospital, Chittoor Road, Ernakulam, Kochi - 682 011, Kerala


OBJECTIVE: Retrospective study looking at the profile of patients undergoing drug sensitivity tests (DST) and its utility in preventing hypersensitivity in the perioperative period. MATERIALS AND METHODS: Adult patients who had a previous history of drug allergy and or other forms of allergies were enrolled in the study. These were patients referred to our center before procedures requiring anesthesia. DST was done by the Skin prick method and supplemented by intradermal in few patients. Drugs chosen for testing was based on patient's allergic history and referring doctors request, usually anesthetics, antibiotics, and analgesics. RESULTS: Of 110 patients included in study, 84 were female. Eighty-eight had a history of drug allergy, either documented or presumed. Twenty-one had other forms of allergy, of whom 11 had food allergy, eight had allergic rhinitis with or without asthma, and three had allergic dermatitis or urticaria. The DST was positive in 65 patients, negative in 45. Drugs that showed positive reactions were ciprofloxacin in 21 patients, diclofenac in 20, atracurim, and ondansetron in 11, paracetamol, amoxicillin clavulanate, pentazocine in five each. CONCLUSION: DST in preanesthetic evaluation would prevent potential hypersensitivity reaction in the perioperative period. Sixty percent of patients showed sensitivity; ten percent of them had food allergy, allergic rhinitis, skin allergy without a history of drug allergy. Antibiotics and analgesics showed more sensitivity than anesthetics. All patients underwent their anesthetic procedures without any drug hypersensitivity reaction.

How to cite this article:
Sabhapathy K, Krishnan S. Clinical profile of drug sensitivity test in patients with a previous history of allergy as part of preanesthetic evaluation.Indian J Allergy Asthma Immunol 2021;35:67-71

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Sabhapathy K, Krishnan S. Clinical profile of drug sensitivity test in patients with a previous history of allergy as part of preanesthetic evaluation. Indian J Allergy Asthma Immunol [serial online] 2021 [cited 2022 Sep 28 ];35:67-71
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During anesthesia and perioperative period patients are exposed to medications which can produce drug hypersensitivity reactions (DHRs) or anaphylaxis posing difficulties to the surgeon and anesthesiologist. The incidence is one in every 1250–10000 anesthetics.[1] DHRs are the adverse effects of pharmaceutical formulations (including active drugs and excipients) that clinically resemble allergy.[2] DHRs type B adverse drug reactions are dose independent, unpredictable, A-type drug reactions, are dose dependent and predictable.[3] A large number of reactions are presumed to be drug related and allergic in nature, but closer examination often reveals that they are not.[4]

Skin prick tests and intradermal tests are done to demonstrate an immunoglobulin E (IgE)-dependent mechanism,[5] for immediate DHRs, the skin prick test is recommended for initial screening due to its simplicity, rapidity, low cost, and high specificity. Intradermal tests are undertaken when skin prick tests are negative. Compared to skin prick tests, they provide enhanced sensitivity for drug-specific IgE.[6] Their sensitivity and predictive values vary, good for beta-lactam antibiotics, neuromuscular blocking agents, platin salts, and heparins.[7]

 Materials and Methods

Patients were referred to our center for drug sensitivity test (DST) before surgical procedure with the intend to prevent any possible DHRs in the perioperative period by identifying sensitivity to common anesthetics, antibiotics, analgesics, etc., Inclusion criteria

Adult patients who had a previous history of drug allergy and/or other forms of allergy were enrolled in the study. These were patients planned for the surgical procedure, cesarian section, or delivery. The study period was April 2019 to February 2021.

Exclusion criteria

patients whose symptoms suggested Type A drug reaction and not hypersensitivity. Test was conducted at Krishna Hospital Kochi, India, following standard protocols and precautions.

Drugs that were included in the sensitivity test were selected based on the patient's clinical condition [list of drugs shown in [Table 1]] and the referring doctors request.{Table 1}

In those with known drug hypersensitivity those specific medicines were excluded from the testing.

Skin prick test was done using standard dilutions.[8] Skin testing has been reported to be a reliable tool to investigate suspected anaphylactic reactions during anesthesia and to guide the future use of neuromuscular blocking drugs (NMBD) in a study by Soetens et al.[9]

In those cases where skin prick test showed a borderline or inconclusive reaction, intradermal test for those drugs was also done. Patients were counseled before testing. Histamine and normal saline were used as controls. A prick test was considered positive when the diameter of the wheal was at least 3 mm greater than the negative control and at least equal to half of that produced by the positive control test. Intradermal tests are considered positive when the diameter of the wheal was twice or more the diameter of the injection wheal.[6],[10]


A total of 110 patients were included in the study, females 84 and males 26. Sixty-five patients showed positive reactions to one or more drugs on testing. Fourteen of the sixty-five patients showed sensitivity to drugs other than they were earlier allergic to. Twenty-one of positive sixty-five patients did not have a previous history of drug allergy but had other forms of allergy, i. e., 11 had food allergy, eight had allergic rhinitis (with or without asthma) and three had allergic dermatitis or urticaria. Five patients reported a history of allergy to food and medicines. The common food allergens which patients had reported were prawns, seafood, beef, and chicken.

Females (49 out of 65) showed more positive reactions compared to Males.[11] Female patients were those awaiting cesarean section or delivery or other surgical procedures. A significant female predominance has been reported in a study by Light et al.[12] Deaths due to perioperative anaphylaxis occurred in 4.67% of the patients, as reported by Mitsuhata et al.[13]

Various drugs had shown positive skin reactions in our study. The common ones are depicted in [Table 2].{Table 2}

The most common drugs were ciprofloxacin in 21 patients, diclofenac in 20, atracurium in 11, ondansetron in 11, and paracetamol, amoxicillin clavulanate, pentazocine in five patients each. Sensitivity to two or more drugs was noted in twenty patients, commonly diclofenac and ondansetron.

All patients tolerated the procedure well. No severe hypersensitivity or anaphylaxis was noted during the test and the following 24 h. Three had severe itching at the site of testing, which subsided with antihistamine.

For patients who had reported a previous history of drug allergy, the drugs mentioned were paracetamol, penicillin, co-trimoxazole, diclofenac, ibuprofen, less commonly iron infusion, contrast dye.

Of the eleven patients with the previous history of food allergy who underwent the DST, seven showed positive reactions. Atopy has been reported as a risk factor for sensitization to muscle relaxants by Michel et al.[14]

Forty-five patients did not show any sensitivity during DST. Among these were 28 patients who had a history of drug reaction to medications like penicillin, cotrimoxazole. Among the remaining seventeen patients there was history of food allergy in eight, respiratory allergy in six and skin allergy in three patients.

Anesthetic drugs showed a positive reaction in 26 patients, antibiotics in 34, and analgesics (including antipyretics, non-steroidal anti-inflammatory drugs [NSAID]) in 31, as shown in [Table 3].{Table 3}

Drugs which did not reactivity were pantoprazole, neostigmine, glycopyrrolate, midazolam.

The patients who had a previous history of paracetamol allergy showed positive reactions to atracurium, succinyl choline, diclofenac, ondansetron.

Those with previous allergies to diclofenac showed positive reaction to ondansetron, amoxicillin clavulanate, ciprofloxacin. The patients with the history of allergy to penicillin/amoxicillin/amoxicillin clavulanate showed predominant positive reactions to atracurium and ciprofloxacin than to other drugs in the test.

The patients in our study were followed up to 96 h post procedure, with the help of the concerned surgeon, anesthesiologist, and gynecologist. All 110 patients underwent their surgery or cesarian section/delivery with no DHRs. Two of them developed blood transfusion reactions to blood products given 72 h post procedure.


DHRs are a serious cause of concern for anesthesiologists and surgeons in the perioperative period. The nature of the reaction is such it could vary from mild itching to anaphylactic shock. Laguna et al. had suggested it would be advisable for hospitals to have a consensus protocol of action for diagnosis and treatment of these reactions.[15] The incidence of perioperative reactions in a Spanish study was 1:381; of these, 48% were mild, involving only the skin, whereas 52% were anaphylaxis.[15] The mortality following such anaphylaxis was noted to be between 3% and 10% in one study by Mertes et al.[16]

Our study was to determine which drugs were more likely to cause hypersensitivity in patients with a previous history of any form of allergy (not only drug allergy) and were posted for a surgical procedure requiring anesthesia, so as to prevent an adverse event. Pre-existing allergy to anesthetic medications is not forthcoming unless patients had such documentation during a previous anesthetic procedure unlike antibiotics and NSAID where a test dose before the injection would have been done or hyper sensitivity reaction would have been documented. Among the drugs which can potentially cause anaphylaxis in the perioperative period NMBD, antibiotics, latex, and chlorhexidine have been frequently reported.[17] In our study, we noted positive skin reactions predominantly for antibiotics followed by NSAID and NMBD. Antibiotics were reported to be the most common cause of perioperative anaphylaxis in the United States, while NMBAs are the leading cause in most European studies.[18],[19]

Food allergies have not been recognized as a risk factor with the exception of patients allergic to tropical fruit (especially avocado, banana, and kiwi) because of the cross-allergy with latex. In our study 11 of 110 patients showed positive reactions; drugs implicated were NMBA atracurium and succinylcholine.

Among NMBA to which patients in our study showed positive reactions, atracurium was the most common, followed by succinylcholine. Reactions caused by antibiotics have increased, reflecting the increasing prevalence of allergy to these drugs and their increased use in perioperative antibiotic prophylaxis. This was reflected in our study as well; ciprofloxacin, amoxicillin clavulanate, showed more sensitivity than anesthetic drugs.

The patients who showed positive reactions on testing were grouped into three [Table 4]. Group A, where the patients were aware of the drugs they were previously allergic to (which were commonly antibiotics, NSAID), but the referring doctor requested the DST for anesthetic medications, ondansetron, pantoprazole, etc., The group B patients were those who had a history of drug allergy but were not documented. Here, the test done was for the commonly used anesthetic, antibiotics, antiemtics, analgesics, as shown in [Table 1]. Group C these were patients who had a past history of food allergy, allergic rhinitis with or without asthma, allergic dermatitis, urticaria in the absence of past history of drug allergy. Four patients gave a past history of food allergy along with drug allergy.{Table 4}

Sixty-five of the 110 patients positive reactions to one or more drugs during the DST. The common medications to which positive skin reactions noted were analgesics, antipyretics, antibiotics followed by anesthetic medications. Those who had a past of being allergic to penicillin showed a positive reaction to predominantly anesthetic medications followed by ondansetron and diclofenac which are used in the postoperative period. Those who had history of diclofenac showed positive reactions to ciprofloxacin, Ofloxacin. In more than 60% of patients belonging to Group A and B, we could identify positive reactions; in those belonging Group B, we could identify positive drug reactions to more than 50% of patients. Patients in Group C who had a previous history of food allergy to prawns and seafood showed positive reactions to atracurium and succinyl choline.

We analyzed those 40% of patients (45/110) who showed negative reactions during DST; 11% of them had inadvertently reported the known side effects of medications as “allergy” to the doctor who had referred the case for testing. In the remaining 29% of patients no drug could be identified; here, the treating doctor is required to use lesser medications and with caution.

Thus, we could identify the positive drug reactions in 60% of the patients who underwent the DST.

The estimated sensitivity of skin tests for muscle relaxants is approximately 94%–97% but for other substances, it varies. It is optimal for synthetic gelatins but poor for barbiturates, opioids, and benzodiazepines. In this clinical scenario, the surgeon and anesthesiologist could choose an alternative drug.

In our study, among the 110 patients referred for drug allergy testing, none of them reported drug allergy reactions in the perioperative period. This correlates well with the study by Miller et al. of 70 patients showed that assessment with skin testing in a specialty clinic resulted in 67 patients undergoing repeat anesthesia without adverse events.[20] Thus, we emphasize the need for DST before anesthetic procedures in patients with the history of drug allergy, food allergy, allergic rhinitis, asthma, and skin allergies.


Drug sensitivity testing in preanesthetic evaluation helps in identifying drugs that could potentially cause hypersensitivity reaction in patients who either had a history of drug allergy but were not aware of the offending medication and or who had food allergy, allergic rhinitis without a prior history of drug allergy. Antibiotics and NSAID groups of drugs showed sensitivity during testing, followed by anesthetics. All patients referred to testing underwent the procedure without any adverse drug reactions.


In patients with history of food allergy, there was no documented skin prick report for those allergens.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Mertes PM, Tajima K, Regnier-Kimmoun MA, Lambert M, Iohom G, Guéant-Rodriguez RM, et al. Perioperative anaphylaxis. Med Clin North Am 2010;94:761-89.
2Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004;113:832-6.
3WHO. International drug monitoring: the role of national centres. Report of a WHO meeting. World Health Organ Tech Rep Ser 1972;498:1-25.
4Messaad D, Sahla H, Benahmed S, Godard P, Bousquet J, Demoly P. Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction. Ann Intern Med 2004;140:1001-6.
5Bircher AJ. Symptoms and danger signs in acute drug hypersensitivity. Toxicology 2005;209:201-7.
6Brockow K, Romano A, Blanca M, Ring J, Pichler W, Demoly P. General considerations for skin test procedures in the diagnosis of drug hypersensitivity. Allergy 2002;57:45-51.
7Brockow K, Garvey LH, Aberer W, Atanaskovic-Markovic M, Barbaud A, Bilo MB, et al. Skin test concentrations for systemically administered drugs – An ENDA/EAACI Drug Allergy Interest Group position paper. Allergy 2013;68:702-12.
8Scolaro RJ, Crilly HM, Maycock EJ, McAleer PT, Nicholls KA, Rose MA, et al. Australian and New Zealand Anaesthetic Allergy Group perioperative anaphylaxis investigation guidelines. Anaesth Intensive Care 2017;45:543-55.
9Soetens FM, Smolders FJ, Meeuwis HC, Van der Donck AG, Van der Aa PH, De Vel MA, et al. Intradermal skin testing in the investigation of suspected anaphylactic reactions during anaesthesia – A retrospective survey. Acta Anaesthesiol Belg 2003;54:59-63.
10Torres MJ, Adkinson NF Jr., Caubet JC, Khan DA, Kidon MI, Mendelson L, et al. Controversies in drug allergy: Beta-lactam hypersensitivity testing. J Allergy Clin Immunol Pract 2019;7:40-5.
11Berroa F, Lafuente A, Javaloyes G, Cabrera-Freitag P, de la Borbolla JM, Moncada R, et al. The incidence of perioperative hypersensitivity reactions: A single-center, prospective, cohort study. Anesth Analg 2015;121:117-23.
12Light KP, Lovell AT, Butt H, Fauvel NJ, Holdcroft A. Adverse effects of neuromuscular blocking agents based on yellow card reporting in the U.K.: Are there differences between males and females? Pharmacoepidemiol Drug Saf 2006;15:151-60.
13Mitsuhata H, Matsumoto S, Hasegawa J. The epidemiology and clinical features of anaphylactic and anaphylactoid reactions in the perioperative period in Japan. Masui 1992;41:1664-9.
14Michel MP, Pascal D, Rodolphe S. Perioperative Allergic Reactions. World Allergy Organization. Available from: [Last accessed on 2017 Oct 14; Last updated on 2019 Mar 20].
15Laguna JJ, Archilla J, Doña I, Corominas M, Gastaminza G, Mayorga C, et al. Practical guidelines for perioperative hypersensitivity reactions. J Investig Allergol Clin Immunol 2018;28:216-32.
16Mertes PM, Laxenaire MC, Alla F; Groupe d'Etudes des Réactions Anaphylactoïdes Peranesthésiques. Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000. Anesthesiology 2003;99:536-45.
17Mertes PM, Volcheck GW. Anaphylaxis to neuromuscular-blocking drugs: All neuromuscular-blocking drugs are not the same. Anaesthesiology 2015;122:5-7.
18Gurrieri C, Weingarten TN, Martin DP, Babovic N, Narr BJ, Sprung J, et al. Allergic reactions during anesthesia at a large United States referral center. Anesth Analg 2011;113:1202-12.
19Harboe T, Guttormsen AB, Irgens A, Dybendal T, Florvaag E. Anaphylaxis during anesthesia in Norway: A 6-year single-center follow-up study. Anesthesiology 2005;102:897-903.
20Miller J, Clough SB, Pollard RC, Misbah SA. Outcome of repeat anaesthesia after investigation for perioperative anaphylaxis. Br J Anaesth 2018;120:1195-201.