D.A. Moneret-Vautrin

Skin reactions to intradermal neuromuscular blocking agent injections: a randomized multicenter trial in healthy volunteers.

Background: Numerous reports confirm the performance of intradermal tests for the diagnosis of anaphylaxis during anesthesia; however, there is controversy over their diagnostic value regarding the newer neuromuscular blocking agents (NMBAs). Methods: One hundred eleven healthy volunteers were randomly assigned to receive intradermal injections of two NMBAs, at five increasing concentrations. A concentration was considered as a reactive concentration when it led to a positive reaction in more than 5% of the subjects. These concentrations were compared with the maximal concentration recommended for the diagnosis of sensitization to NMBAs. Results: The maximal nonreactive concentrations were 10−3 m for suxamethonium; 10−4 m for pancuronium, vecuronium, rocuronium, and cisatracurium; and 10−5 m for atracurium and mivacurium. Except for mivacurium, these nonreactive concentrations were close to the maximal concentrations used for the diagnosis of sensitization against NMBAs. For mivacurium, the nonreactive concentrations were higher than the maximal concentration currently recommended in clinical practice. Conclusion: The aminosteroidal NMBAs pancuronium, vecuronium, and rocuronium and the benzylisoquinoline cisatracurium have a similar potency to induce a nonspecific skin reactivity. If the criteria for positivity and the maximal concentrations of the commercially available compounds recommended by French practice guidelines are used, the risk of false-positive results is limited, and only minor modifications of these recommendations could be suggested. A slight reduction in the maximal concentration used for rocuronium from 1:100 to 1:200 and an increase from 1:1,000 to 1:200 for mivacurium can be proposed.

Anaphylaxie aux myorelaxants. Valeur prédictive des intradermoréactions et recherche de l'anaphylaxie croisée

37 patients were studied, all of whom presented with anaphylaxis to a muscle relaxant. The diagnosis was made after simultaneous intradermal testing (IDT), human basophil degranulation tests (HBDT) and Prausnitz-Kustner tests (PK) of passive cutaneous anaphylaxis. Three tests were positive in 6 patients, both IDT and PK in 9, and both IDT and HBDT in 8. In 14 patients, the IDT, repeated twice, were positive both times. A search for crossed anaphylaxis to the other muscle relaxants was carried out in all the patients during a second series of tests, a few months to years after the first one. The drugs tested, at dilutions of the pharmaceutical preparation of 10−3 or more, were : suxamethonium, gallamine, alcuronium, pancuronium, vecuronium, d-tubocurarine. The reliability of IDT in the diagnosis of anaphylaxis is discussed in terms of the small reactive concentration, the reproducibility of the tests, the one HBDT that did become positive later, and in one case the occurrence of shock by crossed anaphylaxis. Skin reactivity seemed to remain constant with time, so allowing the use of IDT as a diagnostic tool, in cases of old anaphylactoid shocks, occurring during general anaesthetics. The frequency of crossed anaphylaxis was assessed to be about 84%. The sensitivity to one or other drugs varied with each patient. Pancuronium and vecuronium appeared to be the least likely drugs to cause crossed anaphylaxis. The predictive use of these tests is discussed. It is also suggested that muscle relaxants with only one quaternary ammonium group should be used, this chemical characteristic probably reducing the risks of sensitization.

Allergy and anaesthesia

The use of anaesthetic agents, drugs and chemicals induce a certain number of anaphylactoid reactions during anaesthesia. The various clinical pictures and their treatment are well-known. There are multiple risk factors and different mechanisms are involved. Numerous diagnostic tests already exist; to these must now be added predictive tests for latent sensitization to muscle relaxants (MR) and latex.

Anaphylactic and anaphylactoid reactions : clinical presentation

ConclusionsThe increasing incidence of anaphylactoid reactions occurring during anesthesia enables good descriptions of clinical reactions. The rapid onset of treatment generally provides a complete recovery, and it may be expected that the incidence of fatal cases will become negligible with the institution of adequate fluid therapy and adrenalin infusion.

Modification de la réactivité cutanée dans l'anaphylaxie aux myorelaxants et hypnotiques après administration d'anti H1, d'anti H2 et de tritoqualine

Inhibition of allergic skin reactivity was studied by the technique of thresholds in 35 patients presenting with an anaphylaxis to muscle relaxants. This method was useful to determine the anti-histamine or anti-anaphylactic effects of differents substances. The best results were obtained with hydroxyzine. Associating it with an anti H2 drug (cimetidine or ranitidine) did not improve these results. Skin reactivity was never entirely abolished. This confirmed that no premedication could avoid the occurrence of an anaphylactic shock, or even reduce its magnitude. However, premedicating before general anaesthesia with anti H1 and anxiolytic drugs must be continued for all high risk patients : the prevention of non-specific histamine release appeared to be much more efficient than that of anaphylaxis.

Non specific interactions in anti-agent IgE-RIA to anaesthetic agents

The sensitivity of usual IgE-RIA for detecting seric anti-neuromuscular blocking drug (NMBD) IgE antibodies is low. Our group and other authors have proposed quaternary ammonium compounds other than NMBD for the preparation of sepharose solid drug phase. These compounds cannot be cyclohexenyl derivatives in order to prevent hydrophobic interactions with seric hydrophobic IgE. Allergic reactions against cyclohexenyl derivatives such as propofol could be linked to a non-specific hydrophobic binding of the drug to hydrophobic seric IgE. Such hydrophobic IgE are seen in 30% of atopic subjects, in 41% of patients with drug allergy and in 100% of those allergic to propofol. The latter had also anti-quaternary ammonium IgE in 5 out of the 8 cases studied. These NMBD antibodies could bind to the quaternary-ammonium ion of the lecithins from Diprivan micelles.

Prolapsus de la valve mitrale : facteur aggravant le choc anaphylactoïde peranesthésique

Initial cardiac failure in anaphylactoid shock is rare, classically related to cardiac anaphylaxis occurring in a highly sensitized patient. However, this anaphylaxis is not always found; the case described here of a histamine shock with ventricular fibrillation after the injection of thiopentone is a good example of this. The severity of the shock may be explained by the presence of a prolapse of the small flap of the mitral valve.Initial cardiac failure in anaphylactoid shock is rare, classically related to cardiac anaphylaxis occurring in a highly sensitized patient. However, this anaphylaxis is not always found; the case described here of a histamine shock with ventricular fibrillation after the injection of thiopentone is a good example of this. The severity of the shock may be explained by the presence of a prolapse of the small flap of the mitral valve.