[2 cases of anaphylactic shock caused by probable sensitization to a solvent of flunitrazepam].
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Biomedical subjects
Publications and source records attributed to S Widmer.
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A radio-immunoassay (RIA) was used to screen for specific IgE to myorelaxants. Alcuronium was coupled to epoxy-activated Sepharose. Sixteen patients with anaphylaxis to alcuronium (n = 2), gallamine (n = 2) or suxamethonium (n = 12) were studied. The diagnosis was established by intradermal tests (ID), passive cutaneous anaphylaxis tests and human basophil degranulation tests. The amount of non specific label retained by Sepharose-ethanolamine (with sera of patients) and Sepharose-alcuronium (with sera of 11 control subjects) was estimated. The RIA was positive 10/16 (8/14 patients having reacted to a muscle relaxant other than alcuronium). The RIA seemed to be useful in the diagnosis of anaphylaxis to muscle relaxants. Drug-reactive antibodies were specific of the quaternary ammonium radical, which was the common allergenic determinant of all molecules of muscle relaxants. This test accounted for in vitro cross-reactivity, but had no predictive value for the clinical risk of crossed-anaphylaxis. This risk was best assessed by ID; it was positive in three cases. Although it was not possible to compare ID and RIA, the interpretation of which was different, both tests should be recommended for the detection of sensitivity to muscle relaxants.
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.
A homogeneous series of 103 cases of shock due to muscle relaxants has been used to identify the risk factors in anaphylactoid shocks due to either true anaphylaxis or to non-specific histamine release. Clinical atopy (asthma) and sub-clinical atopy as shown up by skin tests with mites and pollens, as well as a history of IgE-dependent drug allergy, were present with a significantly greater frequency in the history of patients presenting with anaphylaxis. Abnormal histamine release and reactivity to histamine, as assessed by skin tests with 48/80 and histamine, were often found in those patients who presented with non-specific histamine release induced by muscle relaxants. Whatever the mechanism for the shock, the frequency of spasmophilia was increased. A history of non-immunological intolerance to acetyl salicylic acid and other non-steroid anti-inflammatory drugs was more often found than in the reference drugs was more often found than in the reference population. However, 25% of the patients studied did not have any of these risk factors. Several possibilities of preventing anaphylactoid reactions are given, if one or more of these risk factors are found in the history: a better choice of anaesthetic drugs, in the light of previous anaesthetic protocols, the relief of anxiety by appropriate premedication, antihistamine premedication and the prevention of bronchospasm.
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-Küstner 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 producibility 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.
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 different 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.
The histamine releasing potential of atracurium was assessed by testing skin reactivity in ten patients who had previously suffered from a preanaesthetic anaphylactoid accident, but in whom the diagnosis of anaphylaxis had not been confirmed. Atracurium was injected intradermally in increasing concentrations so as to determine the reactivity level, comparing it in the same patient with that due to d-tubocurarine and alcuronium given in the same way. Skin tests with histamine and 48/80 were also carried out at the same time. When a positive reaction was obtained with atracurium, the injection was repeated 4 h after, the patient having taken 50 mg hydroxyzine p.o. The results showed that the skin reactivity level with d-tubocurarine was obtained with 1 in 100 dilution and with atracurium 1 in 10, with nine patients out of ten reacting positively. Alcuronium is the least histamine releasing drug, as it gave rise to a positive reaction in only two patients at a dilution of 1 in 10. Histamine release due to atracurium was greatly reduced by giving hydroxyzine. The allergizing potential was also studied in six other patients who had a tone anaphylaxis to a muscle relaxant and in whom crossed anaphylaxis was being tested for. All the commercial muscle relaxants together with atracurium were tested, even though none of the patients had ever received this last. Anaphylaxis was confirmed when the intradermal reaction was positive with a dilution of 1 in 1,000 and beyond. These tests showed that five patients out of the six had a crossed anaphylaxis, and one of these five was sensitive to all four muscle relaxants (atracurium included).(ABSTRACT TRUNCATED AT 250 WORDS)
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The cross-reactivity between muscle relaxants (MRs) is a risk for inducing anaphylaxis in sensitized patients. The preventive use of monovalent haptens (MHs) was studied in 21 cases. Inhibition of the skin reactivity by mixing MRs and MHs was observed, as was the inhibition of leucocyte histamine release to MRs, up to 3 h after infusion of MHs. These results argue for the use of such a protocol, if surgery requires the use of a MR in patients at risk for anaphylaxis.
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