While it is believed that unconjugated "small" molecules such as the NMBDs
are able to cross-link IgE molecules at the surface of mast cells and basophils because they are allergenically di- (or multi-) valent (134,135), this, and the capacity to form multi-valent drug-protein complexes in vivo that are immunogenic, may not be the case with the opioid drugs.
Of the 45 patients with a history of a previous adverse reaction, 22 had positive skin tests, one to an opiate and 21 to NMBDs.
Three of 43 patients with multiple allergies had equivocal intradermal tests to histamine releasing NMBDs.
One other patient who was referred because of severe vomiting postoperatively had positive skin tests to NMBDs, which were probably unrelated to the adverse event.
A study in Spain of 424 preoperative patients tested for 30 drugs by prick testing found 20 positive tests; 12 to NMBDs, four to iodine and two each to latex and etomidate (8).