Research Article: Perioperative drug reactions – practical recommendations for allergy testing and patient management

Date Published: June 4, 2018

Publisher: Springer Medizin

Author(s): Wolfgang Pfützner, Knut Brockow.


Allergy testing for perioperative drug reactions poses a particular diagnostic challenge. Neuromuscular blocking agents (NMBA) and antibiotics are among the most common triggers. In principle, however, any drug administered perioperatively is capable of causing a hypersensitivity reaction.

This article is an overview of selected scientific articles and is based on research in PubMed, specialist databases, and guidelines.

Besides patient’s history and laboratory tests (the latter being feasible to only a limited extent), skin tests play a particularly important role. To obtain clinical relevant results, profound knowledge on the best point in time for testing, the drug concentrations to be used, how to perform tests correctly, and the assessment criteria is of special importance.

Final outcomes of the diagnostic procedures should be providing thorough information of the patient about the findings, drugs that should be avoided in the future as well as alternative preparations, and, if necessary, preventive measures to be taken in the event of further surgical interventions.

Partial Text

Perioperative drug reactions (PODR) are defined as hypersensitivity reactions to drugs administered in immediate temporal relation to—i. e., before, during, or after—a surgical procedure. According to various studies, reactions of this kind have an incidence of approximately 1:10,000 procedures, with the number of unknown cases estimated to be much higher. They are generally immediate reactions (onset less than 1 h following administration of the triggering drug); around two thirds are immunoglobulin E (IgE)-mediated and one third is non-allergic in nature. T‑cell-mediated delayed-type reactions are rare. Due to patient history-related limitations (patient’s unawareness of reactions under general anesthesia, anesthetic log often not available or difficult to read), the multitude of different drugs administered, and the limited possibilities to test some preparations (see below), allergy testing in PODR poses a particular challenge.

Skin, cardiovascular, and respiratory symptoms are among those most commonly seen. Skin reactions are described less frequently in this context than in other forms of anaphylaxis. However, skin rashes such as urticaria or flushing may be concealed by surgical drapes. Cardiac symptoms such as hypotension and tachycardia can be misinterpreted as pharmacological side effects and mechanical respiratory difficulties may be attributed to insufficient sedation. Unusual reactions such as myocardial ischemia due to cardiovascular spasms or paradoxical bradycardia are also possible. Delayed reactions are seen hours to days following the surgical procedure in the form of locally indurated plaques at the injection site (e.g., delayed-type reactions to heparins), delayed urticaria and/or angioedema (e. g., as a manifestation of analgesic hypersensitivity to cyclooxygenase inhibitors), as well as delayed-type hypersensitivity rashes (particularly if drug administration is ongoing following the procedure, e. g., continued antibiotic or analgesic administration).

Every effort should be made to evaluate the anesthesia log. Approximately 90% of PODR occur during or shortly after the induction of anesthesia, but only from the anesthesia protocol is one able to determine which drugs were previously administered and in which time sequence. The surgical report can also be helpful by including, e. g., disinfectants, dyes, or materials applied locally during implantation procedures, such as gentamicin, in the diagnostic work-up. Intravenously administered triggers generally elicit clinical reactions within a few minutes, whereas topically or percutaneously administered drugs usually cause reactions with a 1- to 2‑h delay.

Drugs that cause reactions in skin or laboratory tests should be avoided, unless a false-positive test reaction (e. g., to histamine liberators) can be proven by a negative provocation test. Positive skin tests or the detection of specific IgE antibodies to beta-lactams, natural rubber latex, chlorhexidine, and pyrazolone analgesics (in particular metamizole) have high predictive value. Patient history data, test findings, drugs to be avoided, and recommended alternative drugs are documented in an allergy passport, which should be presented to physicians and pharmacists in the future. Recommendations on alternative drugs are particularly important when it comes to drugs with potential cross-reactivity to structurally related preparations; their possible tolerance needs to be determined by means of negative skin tests (e. g., NMBA) or provocation tests (e. g., antibiotics and analgesics). The possibility of an increased risk for PODR to propofol in patients showing IgE-mediated sensitization to potentially cross-reacting food stuff is meanwhile discussed only in relation to children with a previous history of severe anaphylaxis to hen’s egg, but not in relation to adults or individuals allergic to soy and peanut. Similarly, there are no preventive limitations on the perioperative administration of other drugs to patients with mast cell diseases, e. g., mastocytosis, assuming they have no known history of drug hypersensitivity. The administration of morphine is an exception here.




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