pancuronium and Drug-Hypersensitivity

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).. 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.. The maximal nonreactive concentrations were 10 m for suxamethonium; 10 m for pancuronium, vecuronium, rocuronium, and cisatracurium; and 10 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.. 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.

Topics: Adolescent; Adult; Androstanols; Atracurium; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Humans; Injections, Intradermal; Isoquinolines; Male; Middle Aged; Mivacurium; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Pancuronium; Reference Values; Rocuronium; Skin; Skin Tests; Succinylcholine; Vecuronium Bromide

Topics: Anaphylaxis; Cross Reactions; Drug Hypersensitivity; Humans; Neuromuscular Blocking Agents; Neuromuscular Nondepolarizing Agents; Pancuronium; Vecuronium Bromide

Adverse drug reactions (ADRs) are known to occur during anaesthesia; in the U.K. such ADRs may be reported through the Yellow Card Scheme (YCS). Our aim was to determine the demographics of ADRs to neuromuscular blocking drugs without formal causality assessment.. A retrospective analysis of ADRs to seven neuromuscular blocking drugs reported via the YCS during a greater than 30-year period was performed. Sex and age were analysed in order to identify at risk groups.. Of 998 reports, 969 included gender. Non-allergic suspected reactions occurred with almost the same frequency as those with an allergic component. The majority occurred in females 676 (70%), and significant sex differences were measured between drugs. Males were more likely to have suffered an ADR to atracurium (p = 0.01) whilst females experienced more ADRs to suxamethonium (p = 0.01). ADRs proved fatal in 81 (9%) of the 950 reports for single drugs. Mortality following suxamethonium was significantly higher in males at 22% compared with 9% females (p < 0.001). More women than men were reported to have allergic reactions, 73% (362/499) compared with 27% (137/499) respectively. The female:male ratio for ADRs was reversed for subjects < 10 years compared with peak ADR reports during the decade from 31-40 years.. Sex differences in mortality exist in this analysis. The unexpected high frequency of non-allergic ADRs suggests that morbidity and mortality from reactions to established drugs is twice that expected from allergic reactions alone. Standards and guidance for the reporting of ADRs warrant urgent development.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Distribution; Aged; Aged, 80 and over; Anaphylaxis; Atracurium; Child; Child, Preschool; Drug Hypersensitivity; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Mortality; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Pancuronium; Pharmacoepidemiology; Risk Assessment; Risk Factors; Sex Distribution; Succinylcholine; United Kingdom; Vecuronium Bromide

Anaphylactic reactions during anesthesia are mainly the result of muscle-relaxant (MR) drugs. Skin tests, serologic detection of specific IgE, and in vitro leukocyte histamine release are used to investigate MR allergy.. We describe a new assay that is based on the detection by flow cytometry of the altered expression of plasma membrane molecules of MR-activated basophils.. For this assay, which we have named the BASIC assay, basophils are incubated in vitro with MR, after which they are fixed and then triple labeled with fluorescein-conjugated anti-CD63, tandem dye R-phycoerythrin-cyanin 5.1 conjugated anti-CD45, and R-phycoerythrin conjugated anti-IgE. The resulting B asophils' A ltered S urface I mmunofluorescence is detected by flow C ytometry (BASIC).. Forty-one patients who had an allergic reaction during general anesthesia and 23 control subjects without such a history were studied. All included subjects' basophils were tested in the BASIC assay with at least 4 MR: suxamethonium, gallamine, vecuronium, and pancuronium. After reaction of the basophils of the MR-allergic patients with MRs, increased surface expression of CD63 and CD45 and decreased expression of IgE were detected. Increased expression of CD63 was observed most frequently and it was stronger than the alteration of the 2 other markers. Cross-reactivity between MRs commonly occurred. MRs diluted 10(-1) activate the basophils of the control subjects, suggesting that at relatively high concentrations MRs are also nonspecific basophil activators.. In the diagnosis of MR allergy, the BASIC assay has a good specificity but a low sensitivity, and it correlates strongly with skin test results. It is currently appraised for the diagnosis of anaphylactic reaction induced by other classes of drugs.

Topics: Adult; Aged; Anaphylaxis; Basophils; Drug Hypersensitivity; Female; Flow Cytometry; Humans; Male; Middle Aged; Muscle Relaxants, Central; Pancuronium; Reproducibility of Results; Skin Tests; Vecuronium Bromide

Two women experienced anaphylactoid reactions after induction of general anaesthesia. Prick tests, intradermal tests (IDT), human basophil degranulation tests (HBDT) and a quaternary ammonium sepharose radioimmunoassay were undertaken several weeks later and repeated together with a leucocyte histamine release (LHR) test after 4 months. Anaphylaxis to suxamethonium was documented by four tests in patient 1 and to pancuronium by four tests in patient 2. Anaphylaxis to thiopentone was shown with IDT, HBDT and LHR in both women. It was concluded that simultaneous anaphylaxis to thiopentone and a neuromuscular blocker had occurred in these patients.

Topics: Adult; Anaphylaxis; Anesthesia, General; Basophil Degranulation Test; Drug Hypersensitivity; Female; Histamine Release; Humans; Intradermal Tests; Leukocytes; Pancuronium; Succinylcholine; Thiopental

A case of anaphylactic shock to pancuronium bromide is described in which a type I immunological reaction occurred. A 33-yr-old male anaesthetist, with no family or personal history of allergy, collapsed soon after induction of anaesthesia. The drugs used included fentanyl, droperidol, thiopentone and pancuronium. Diffuse erythema occurred, with probable cardiac arrest. The patient was treated with cardiac massage, sympathomimetics and cortisone, and made a complete recovery. Examination (skin tests, passive transfer according to Prausnitz and Küstner, in vitro lymphocyte transformation test, total IgE assay) revealed that the allergic reaction was to pancuronium bromide.

Topics: Adult; Anaphylaxis; Drug Hypersensitivity; Humans; Immunologic Tests; Male; Pancuronium; Resuscitation; Skin Tests

Topics: Drug Hypersensitivity; Humans; Pancuronium; Skin Tests; Vecuronium Bromide

Anaphylaxis to muscle relaxants appears to be a very useful model to study the IgE-dependent mechanisms of mediator release in humans. The serum IgE binding sites of the drugs appeared to be the ammonium ion determinants. In patients allergic to suxamethonium, one of the most frequently used muscle relaxants for general anesthesia, significant histamine release could be obtained in each case with simple diammonium salts. The length of the chain linking the ammonium groups appears to play an important role. In fact, when the length was less than or equal to 4 A, no significant histamine release could be obtained, whereas the optimal length for histamine release appeared to be greater than or equal to 6 A. Furthermore, muscle relaxants with a rigid backbone between the ammonium determinants (such as pancuronium) are less active than flexible molecules (such as suxamethonium) in initiating mediator release. This study suggests that small divalent molecules can induce anaphylactic shock in sensitized patients and that the length and the flexibility of the chain bearing the haptenic determinants appear to be important factors in the elicitation of mediator release.

Topics: Drug Hypersensitivity; Epitopes; Histamine Release; Humans; Leukocytes; Muscle Relaxants, Central; Pancuronium; Quaternary Ammonium Compounds; Radioallergosorbent Test; Succinylcholine

Twenty-one patients, who had previously experienced an anaphylactic reaction to suxamethonium during general anaesthesia, were selected for this study. Initially, skin tests with muscle relaxants were carried out in the twenty-one patients, detection of specific anti-choline IgE in nineteen, and leucocyte histamine release in seventeen. These three tests were then repeated between 1 year and 4 years after the initial evaluation. In the majority of patients, sensitization to the muscle relaxants persisted for more than 1 year after the anaphylactic reaction. Only three patients out of twenty-one (4%) had negative skin tests when retested 1-4 years later. A reduction in leucocyte histamine release was noticed in one of the seventeen retested patients (6%). Modifications of anti-choline IgE were observed in five of nineteen patients (26%). The persistence of sensitization to suxamethonium may result from repeated stimulation by occasional contacts with quaternary ammonium compounds. This study demonstrates the reliability of skin tests, leucocyte histamine release and detection of anti-choline IgE to diagnose allergic reactions to suxamethonium, even when they are performed a long time after the initial anaphylactic reaction.

Topics: Alcuronium; Anaphylaxis; Antibody Specificity; Choline; Desensitization, Immunologic; Drug Hypersensitivity; Female; Gallamine Triethiodide; Histamine Release; Humans; Immunoglobulin E; Intradermal Tests; Leukocytes; Male; Pancuronium; Succinylcholine; Time Factors

Topics: Anesthesia, General; Drug Hypersensitivity; Humans; Hypertension; Male; Middle Aged; Pancuronium

Topics: Adult; Drug Hypersensitivity; Humans; Male; Neuromuscular Blocking Agents; Pancuronium; Vecuronium Bromide

Using an ordinal measure of cutaneous sensitivity to intradermal injections of atracurium and vecuronium, 40 nonreacting subjects were compared with a group of 24 patients previously suffering life-threatening anaphylactoid reactions to other muscle relaxants. Enhanced cutaneous sensitivity to vecuronium was found in three, and to atracurium in two of the previously reacting group. With the exception of those showing abnormal reactivity, no significant difference was found in the distribution of cutaneous sensitivity in the control and reacting group. A concentration of vecuronium 8.75 times that of atracurium was required to produce an equivalent intradermal wheal response.

Topics: Anaphylaxis; Atracurium; Drug Hypersensitivity; Humans; Intradermal Tests; Isoquinolines; Neuromuscular Blocking Agents; Pancuronium; Skin Tests; Vecuronium Bromide

An inhibition assay was used to determine quantitatively the allergenic cross-reactivity of some myoneural blocking drugs not yet released for use in Australia, in the sera of patients who had experienced anaphylactic reactions to neuromuscular blocking drugs. Two of the compounds, metocurine and atracurium were highly cross-reactive with the currently used myoneural blockers; fazadinium was weakly cross-reactive and vecuronium intermediate in potency between these two extremes. From these results, we predict that anaphylactic reactions to these compounds, and particularly to metocurine and atracurium, will occur in some patients allergic to the currently used neuromuscular blocking agents.

Topics: Anaphylaxis; Antibodies; Atracurium; Cross Reactions; Drug Hypersensitivity; Humans; Immunoglobulin E; Isoquinolines; Neuromuscular Blocking Agents; Pancuronium; Pyridinium Compounds; Tubocurarine; Vecuronium Bromide

Topics: Adult; Drug Hypersensitivity; Female; Humans; Neurofibromatosis 1; Pancuronium

A detailed review of drug-induced bronchospasm is presented. Four types of reactions are described. Furthermore, pathogenesis, clinical picture, treatment and prophylaxis of the "Aspirin-induced asthma" are demonstrated.

Topics: Adrenal Cortex Hormones; Aspirin; Asthma; Bronchi; Bronchial Spasm; Drug Hypersensitivity; Female; Humans; Male; Pancuronium; Peptide Hydrolases; Proteins; Tartrazine; Thiopental

Topics: Alfaxalone Alfadolone Mixture; Anaphylaxis; Anesthetics; Drug Hypersensitivity; Histamine Release; Humans; Methohexital; Pancuronium; Propanidid; Succinylcholine; Thiopental

Topics: Anesthetics; Bronchial Spasm; Drug Combinations; Drug Hypersensitivity; Humans; Hydroxysteroids; Molecular Conformation; Pancuronium; Pregnanediones; Protein Binding

Topics: Aged; Anesthetics; Drug Combinations; Drug Hypersensitivity; Humans; Hydroxysteroids; Male; Middle Aged; Pancuronium; Pregnanediones

Topics: Anesthetics; Bronchial Spasm; Drug Hypersensitivity; Humans; Ketones; Pancuronium; Pregnanes; Skin Tests