Stability of neuromuscular blocking drugs used for skin testing

Abstract

For most clinicians dealing with the management of anaphylaxis induced by neuromuscular blocking drugs (NMBDs), diagnosis and prevention of subsequent reactions usually rest on a detailed history and appropriate skin tests that are cheap, generally reliable, easy to perform with the free drugs, and do not require special equipment. 1 An aspect of skin testing with NMBDs that has been somewhat neglected is the stability of the dilutions employed for testing, the subject of the recent communication to the journal by Gonzalez-Estrada et al. 2 In their letter, the authors carelessly state, "A previous manuscript has recommended storing diluted NMBAs up to 3 months at 4°C" and incorrectly attribute this recommendation to the text book of Baldo and Pham. 3 In fact, in considering skin testing as one of the diagnostic procedures for the diagnosis of suspected anaphylaxis to NMBDs, we concluded: "Information on the shelf life of diluted NMBD preparations is lacking, an indication that solutions for skin testing should be freshly prepared at the time of testing and rejected upon completion but, except for atracurium, cisatracurium, mivacurium and rocuronium, each of which should be freshly diluted, storage of test solutions for up to 3 months at 4°C has been suggested by some." [Emphasis added]. In fact, the source of the recommendation is the published guidelines for clinical practice for reducing the risk of anaphylaxis during anaesthesia implemented in France under the auspices of the Société Française d'Anesthésie et de Réanimation according to the French National Agency of Evaluation of Medicine. This published recommendation for storage of NMBD test solutions has been repeated a number of times in the literature. 4 Apart from manufacturers' recommendations on storage and shelf life of NMBDs in solution (generally, restriction of storage to 24 hours at 2-8°C once the container is opened; see for example references 5 and 6) and a number of detailed studies on the stability of succinylcholine, 7,8 the study by Gonzalez-Estrada et al 2 provides some welcome quantitative measurements of potencies of NMBD solutions at dilutions beyond those routinely administered to induce neuromuscular block. Given the variables and uncertainties inherent in exposure times to light (pancuronium, vecuronium, atracurium, cisatracurium and mivacurium should be protected from light) and different temperatures, the employment of different diluents and containers, adsorption of drugs to contacted materials, and the frequent absence of aseptic methods in the preparation of test solutions, the demonstration of decreased drug stability at high dilutions further supports the need for an always prudent approach in the testing and storage of NMBD skin test solutions. Add to that the rare occurrence of NMBD-induced anaphylaxis and long intervals between cases, NMBD skin test solution dilutions should not be stored for extended periods even in a refrigerator. As a general rule it is recommended that, for all NMBDs, skin test solution dilutions are fre...