Letters to the Editor: Letters & Announcements
It is a great honor being criticized by such an expert in the area of allergy in anesthesia. I understand the reactions of major Australian and French specialists in this area to our results published recently in Anesthesia & Analgesia (1). Indeed, our results demonstrate that with our present level of understanding, the current practice in skin testing is invalid, and we cannot formally rely on prick tests to confirm allergy to neuromuscular blocking agents (NMBAs).
I am not sure that the results of our French study are conflicting but rather complete the interesting study performed by Levy et al. (2), which has clearly demonstrated that intradermal 10−5 M of most NMBAs promoted degranulation-free skin reactions, suggesting that “intradermal nonreactive” NMBA concentration is equal or smaller than 10−6 M. We have shown that a 100-fold increase of this “intradermal nonreactive concentration” corresponded to prick nonreactive concentration. Our observation is coherent with the hypothesis that skin response to NMBAs is mainly the result of a direct effect upon cutaneous vasculature.
I agree that the results of our French study contrast with those obtained by Professor Fischer. However, both studies are not comparable in either their design or the studied population. We have performed a randomized controlled prick testing study in young healthy anesthesia-naive adult volunteers comparing bioequivalence of rocuronium and vecuronium in terms of skin sensitivity. The Australian study compared prick and intradermal testing in patients suspected to be allergic to vecuronium after an anesthetic reaction (3). Although not comparable in terms of methodology and populations, I believe that operator factors cannot explain the frequent incidence of positive prick tests to undiluted rocuronium and vecuronium we demonstrated. In order to limit this risk factor, our study was performed in the dermatology department of the most important French CRO, a single specialized physician administered all 300 prick tests, wheal and flare measurements were performed by an independent technician, and source data have been revisited by two investigators without any major discordance. We have built and performed a methodologically strong study, and our results question the reliability of prick testing with undiluted solution of steroid-derived relaxants for the diagnosis of allergy.
I am not an expert in epidemiology or evidence-based medicine, but I believe that any diagnostic test, like skin testing, should be evaluated in term of specificity and sensitivity before being exported to clinical practice. In other words, a large cohort of healthy volunteers from several countries and of different skin colors should be tested in order to determine skin sensitivity to NMBAs. Unfortunately, in the absence of major studies for better applications of skin testing and validation of other diagnostic approaches of allergy to anesthetic agents, it is not clear that we are making the correct diagnosis of allergy to rocuronium and vecuronium using prick responses to undiluted stock solutions. I believe that a rate of 40–50% false positive is unacceptable for a diagnostic test, but a 10% incidence of false positive would have been also probably not acceptable. Under these circumstances, unexplained reactions during anesthesia question whether these steroid-derived relaxants are the principal cause of anaphylaxis during anesthesia.
Gilles Dhonneur, MD
Thoracic Cardiac and Vascular Surgical Intensive Care Unit
Henri Mondor University Hospital of Creteil
1. Dhonneur G, Combes X, Chassard D, Merle JC. Skin sensitivity to rocuronium and vecuronium: a randomized prick-testing study in healthy volunteers. Anesth Analg 2004;98:986–9.
2. Levy JH, Gottge M, Szlam F, et al. Weal and flare responses to intradermal rocuronium and cisatracurium in humans. Br J Anaesth 2000;85:844–93.
3. Fischer MM, Bowey CJ. Intradermal versus prick resting in the diagnosis of anaesthetic anaphylactic reactions. Brit J Anaesth 1997;79:59–63.