Articles: neuromuscular-blocking-agents-adverse-effects.
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Ann Fr Anesth Reanim · Jan 1993
Diagnosis of IgE-dependent anaphylaxis to neuromuscular blocking drugs, thiopentone and opioids.
Although allergenic cross-reactivity of neuromuscular blocking drugs (NMBDs) is recognised clinically and has been firmly established at the serological and immunochemical levels, interpretation of in vitro inhibition findings for clinical purposes is not always straightforward. Points to be taken into account when considering serum IgE direct binding and inhibition results and when determining which NMBDs a patient may be sensitive to, include the relationship between in vitro potencies and clinical findings and the nature of the drug solid phase used for testing. It should also be remembered that the stimulating antigenic source for the patients' NMBD-reactive IgE antibodies is almost always unknown. ⋯ In screening sera of patients for IgE antibodies to thiopentone and morphine as well as NMBDs, multiple drug reactivities have been detected in a few subjects. Attention is drawn to defects in the existing thiopentone RIA although it is clear that the test is specific in patients who react to the drug. Addition of the serum tryptase assay to skin tests and IgE RIAs for NMBDs, thiopentone and morphine provides a powerful combination of diagnostic tests for the investigation of anaphylactoid reactions to anaesthetic drugs.
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The discovery of IgE antibodies to neuromuscular blocking drugs, to thiopentone and narcotics, particularly morphine, reinforced earlier beliefs formed from skin test and other clinical findings that many "anaphylactoid" reactions to drugs were true type 1 immediate hypersensitivity reactions. Immunochemical studies established the fine structural specificities of the drug-reactive IgE antibodies and provided an explanation in molecular terms for a number of observed clinical cross-reactions. Subtleties in interpreting relationships between skin tests and IgE radioimmunoassays are pointed out and mechanisms of drug-induced mediator release, persistence of IgE antibodies and the nature of the sensitizing sources are discussed.
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Neuromuscular blocking drugs (NMB) are involved in most of the anaphylactic reactions occurring during anaesthesia. Patients are evaluated usually 6 weeks after the reaction, by skin testing. In order to obtain an earlier diagnosis, we have measured plasma concentrations of histamine, tryptase and NMB-specific IgE antibodies in 14 patients after an anaphylactoid reaction. ⋯ Furthermore, there was no significant difference between the concentrations of NMB-specific IgE antibodies observed at the time of the reaction and 8 weeks later. Thus anaphylaxis to neuromuscular blocking drugs can be demonstrated at the time of the reaction by measuring plasma concentrations of histamine, tryptase and specific IgE. In the event of the patient's death, such measurements may be useful in identifying the likely cause.
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Comparative Study
Clinical evaluation of in vitro leukocyte histamine release in allergy to muscle relaxant drugs.
We have evaluated the in vitro leukocyte histamine release tests for the diagnosis of allergy to muscle relaxant drugs in 40 patients (Group A) and a control group of 44 subjects with negative leukocyte histamine release (Group B). Non-IgE dependent histamine release, expressed as a percentage of the total blood histamine, was 3.94% +/- 0.49 in Group B. The upper limit of positivity was estimated to be 5% (mean + 2 SD). ⋯ Of 20 M2. All of the 10 cases had negative ID tests with M2. Three of these patients subsequently underwent general anesthesia with the muscle relaxant chosen as harmless (M2) without any clinical reaction.
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Intradermal testing and RIA testing for specific IgE antibodies to neuromuscular blocking drugs (NMBDs) were performed in patients referred to an Anaesthetic Allergy Clinic. Six patients were initially investigated four to 29 years after clinical anaphylaxis during anaesthesia and two of these patients and sixteen others were investigated by intradermal testing on two occasions at least four years apart. Seven patients had RIA tests for NMBD-specific IgE antibodies on two occasions at the time of skin testing. ⋯ In one patient all tests became negative and in another the skin test became negative but the positive RIA persisted. Evidence of antibodies to NMBDs persisted in 21 of 22 patients who had had anaphylactic reactions to these drugs during anaesthesia. In the absence of evidence of allergy diminishing with time in the majority of patients it would seem wise to avoid drugs responsible for reactions for the rest of the patient's life.