title: Rocuronium and cisatracurium-positive skin tests in non-allergic volunteers: determination of drug concentration thresholds using a dilution titration technique.
abstract: BACKGROUND
  Muscle relaxants are believed to be responsible for 2/3 of the cases of anaphylactic reactions during anesthesia. This assumption is based mainly on positive skin tests obtained in individuals that have experienced anesthesia-related anaphylaxis. A positive skin test is supposed to be associated with mast cell degranulation of vasoactive amines. In the present study we tested the frequency of positive skin tests with two commonly used muscle relaxants, rocuronium and cisatracurium, in a selected group of volunteers with low potential for allergic reactions.
  
  
  METHODS
  Thirty healthy volunteers without known allergy or previous exposure to muscle relaxants were studied. Low potential for allergic reactions was determined prior to inclusion in the study, using various allergy tests. Each individual was tested with intradermal and skin prick tests, and molar drug concentration thresholds for positive skin reactions were determined using a dilution titration technique. The presence or absence of mast cell degranulation was tested by electron microscopic investigation of skin biopsies obtained from positive and negative skin reactions.
  
  
  RESULTS
  None of the volunteers had a positive skin prick test. More than 90% of the volunteers had a positive intradermal test with both rocuronium and cisatracurium. The highest molar drug concentration that was not associated with a positive intradermal test was 10(-6) M (rocuronium) and 10(-7) M (cisatracurium), equivalent to vial dilution 1 : 1000 for both drugs. In none of the volunteers was mast cell degranulation detected.
  
  
  CONCLUSIONS
  Non-mast-cell-mediated positive intradermal skin reactions are frequently occurring with rocuronium and cisatracurium, even at vial dilution 1 : 1000. A clinically applicable test technique is needed that is able to separate positive skin tests associated with mast cell degranulation from non-mast-cell-mediated reactions.
authors.affiliation: Department of Anesthesia, Ullevaal University Hospital, Oslo, Norway.
authors.forename: C M
authors.initials: CM
authors.lastname: Berg
authors.forename: T
authors.initials: T
authors.lastname: Heier
authors.forename: V
authors.initials: V
authors.lastname: Wilhelmsen
authors.forename: E
authors.initials: E
authors.lastname: Florvaag
mesh_terms: D000293:Adolescent; D000328:Adult; D000732:Androstanols / Q000009:adverse effects* / Q000493:pharmacokinetics; D001279:Atracurium / Q000009:adverse effects* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000175:diagnosis*; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007201:Indicator Dilution Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000648:ultrastructure; D008854:Microscopy, Electron; D008875:Middle Aged; D003473:Neuromuscular Nondepolarizing Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D012044:Regression Analysis; D018570:Risk Assessment; D000077123:Rocuronium; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012882:Skin Tests / Q000379:methods*
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; D000077123:Rocuronium