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Definition

Allergic or anaphylactic reactions are mediated by immunoglobulin E (IgE) and may occur following administration of any drug. When severe, termed anaphylaxis, they can lead to shock and death if not recognized and treated promptly.

Risk factors

 Type of local anaesthetic

 Previous exposure to the drug

Pathogenesis

Type 1 hypersensitivity reactions occur due to previous sensitization and formation of IgE antibodies. Re‐exposure to the drug will cause mast cell and basophil degranulation with liberation of histamine, leukotrienes and prostaglandins, leading to an anaphylactic reaction. These reactions normally occur very quickly following administration of the drug, usually within 10 minutes, although delayed reactions can also occur and they may progress slowly or rapidly.

The ester‐type local anesthetics (e.g. procaine) cause more allergic reactions than the amide‐type local anesthetics (e.g. lidocaine, mepivacaine) due to a metabolite that is produced during ester hydrolysis named p‐aminobenzoic acid (PABA). However, some preservatives used in formulations of amide‐type local anesthetics, such as methylparaben or sodium metabisulfite, are metabolized to PABA [66] and therefore they could also cause allergic reactions.

There are reports of horses’ deaths due to acute anaphylactic reactions to some drugs (e.g. trimethoprim sulphadiazine, phenylbutazone, water‐soluble benzylpenicillin salts), but to the best of the author's knowledge, the occurrence of allergic reactions induced by local anesthetics in horses has not been reported.

Prevention

Skin testing is used in humans with suspected hypersensitivity to a local anesthetic that require loco‐regional anesthesia, again to determine whether they are truly allergic and to which drug/s. However, these tests are rarely positive [67]. Another option is to do an in vitro leukocyte migration test, but this test has a high rate of false positives and false negatives [68]. If these tests are not possible, an antihistamine drug (e.g. diphenhydramine, chlorphenamine) could be administered before the suspect drug or alternative drugs/therapies may be considered (e.g. general anesthesia). Cross‐reactivity between ester‐type local anesthetics occurs in humans, but is not common between amides or between esters and amides [67].

Diagnosis

The clinical signs of an allergic reaction may be mild, normally including urticaria with presence of wheals and/or facial edema, which may be self‐limiting and resolve without any specific treatment [69]. However, an allergic reaction could also be severe and life‐threatening with acute bronchoconstriction, hypotension, arrhythmias, laryngospasm and pulmonary edema, which if not treated promptly, will lead to the death of the horse. When allergic reactions develop during general anesthesia, the apparent severity of clinical signs may be attenuated; however, anesthesia does not preclude the development of these reactions [70].

When these reactions occur, especial attention should be paid to the cardio‐respiratory status of the horse and if a life‐threatening reaction is developing, treatment should be instituted immediately. If an allergic reaction occurs during general anesthesia, even if it is apparently mild, the recovery from anesthesia should be closely monitored for signs of respiratory obstruction, as laryngospasm could occur after extubation [69].

Treatment

Treatment might not be necessary for mild reactions. If the urticarial reaction is very significant, a glucocorticoid ± an antihistamine drug may be administered. If the reaction is severe causing bronchoconstriction, laryngospasm, pulmonary edema and/or cardiovascular collapse, immediate tracheal intubation, oxygen supplementation and administration of epinephrine (adrenaline) are lifesaving. In these instances, the administration of fluids and glucocorticoids (e.g. methylprednisolone) may also be necessary. In humans, a systematic review of the literature failed to find any evidence supporting or refuting the usefulness of glucocorticoids for the treatment of anaphylaxis [71].

Expected outcome

When reactions are mild the outcome is generally good even without any treatment [69]. Acute anaphylactic reactions may lead to the death of the horse if not treated promptly.