Anaphylactoid reactions to neuromuscular blockers: major role of IgE antibodies and possible contribution of IgE-independent mechanisms.
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Anaphylaxis↗
Biomedical subjects
E S Assem
Publications and source records attributed to E S Assem.
Highlights of controversial issues in anaesthetic reactions.
This chapter will first briefly deal with some of the controversial issues surrounding allergic reactions to anaesthetics. Other points which appear to be of fundamental importance and which need further investigation will also be mentioned. Readers are referred to other chapters for further information on some of the issues.
Anaphylaxis↗
Effect of picumast on histamine release from rat cardiac and peritoneal mast cells.
Compound 48/80-induced histamine release (HR) from the isolated perfused rat heart was markedly and significantly inhibited by picumast (PIC), possibly by acting as a calmodulin antagonist (CMA) or membrane stabilizer. Trifluoperazine (TFP, another CMA in clinical use) had a similar effect. However, an action as CMA being the basis of inhibition of HR could not be confirmed in another 'allergy' model, namely HR from rat peritoneal mast cells (RPMC). PIC, TFP and two other CMA, W7 and N-(4-aminobutyl)-5-chloro-1-naphthalenesulfonamide) failed consistently to inhibit 48/80-induced HR from RPMC, and when used on their own at high concentration these compounds caused HR. PIC and TFP also potentiated the heat-induced haemolysis of rat erythrocytes, i.e. lacked membrane stabilizing effect in this model.
Animals↗
Characteristics of deoxycholic acid-induced histamine release from mast cells of guinea-pig rectocolonic mucosa and rat peritoneal cavity.
Deoxycholic acid (DA) caused a dose-related release of histamine (HR) from mast cells of rat peritoneum (RPMC) and mucosal cells of guinea pig rectocolon (RCMC). In both cell populations, DA-induced HR was: (1) accompared by a parallel release of lactate dehydrogenase (LDH), (2) not affected by metabolic inhibitors, (3) dependent on time of incubation, temperature and pH, and affected by Ca++ concentration in RPMC but not in RCMC. DA-induced HR from RCMC may be involved in certain functional disorders of the colon.
Animals↗
In vivo and in vitro tests in anaphylactic reactions to anaesthetic agents.
The majority of patients with anaphylactoid reactions (AR) under general anaesthesia showed histamine release from basophil leucocytes (HRL) by neuromuscular blockers in vitro (none in normals) and high levels of serum IgE antibody (detected by the 'new' paper radioallergosorbent test, RAST; little or none in normals) which reacted with the quaternary ammonium group of choline, and less frequently of alcuronium, strongly suggesting that IgE antibody, HRL and AR are related. Skin tests on their own are of limited value.
Anaphylaxis↗
Ischaemia and mediator release: interrelationship in antigen-challenged sensitized guinea-pig kidney.
Renal vasoconstriction and ischaemia that follow in vitro antigen challenge of isolated perfused kidney of sensitized guinea-pig appears to be a self-perpetuating process, starting with a primary peak of release of vasoconstrictor mediators and followed by secondary peaks (particularly of arachidonic acid metabolites) which are probably initiated by ischaemia/reperfusion damage.
Animals↗
Inhibition of histamine release from human lung and rat peritoneal mast cells by cyclosporin-A.
Cyclosporin A (CS-A) partly inhibited IgE-mediated histamine release from human lung tissue in vitro (chopped and collagenase-dispersed preparations). Inhibition started at concentrations within the clinical blood level of the drug, but the IC50 was much higher (10-50 microM; 50% inhibition reached only in some experiments). CS-A also inhibited histamine release from rat peritoneal mast cells (RPMC) induced by antigen, concanavalin-A (Con-A), compound 48/80 and ionophore A23187. The IC50 values were 0.3, 23.0, and 33.0 microM for Con-A, A23187 and ovalbumin respectively. Inhibition of 48/80-induced release did not reach 50%. By comparison with human basophils the human lung and RPMC were less sensitive to the inhibitory action of CS-A. The IgE-mediated Schultz-Dale reaction in human lung strips was slightly and inconsistently inhibited by CS-A, but IgG1-mediated reaction in guinea-pig lung strips was potentiated by the drug.
Animals↗
A modified radioimmunoassay for the detection of histamine release in vivo and in vitro in man.
Histamine (Hi) release in vitro or in vivo in man was measured by variants of a radioimmunoassay (RIA) procedure. Hi released from isolated basophils was converted enzymically to N-tau-methylhistamine (NMH) which was then measured by a very sensitive RIA. This modified RIA was compared with the standard spectrofluorometric assay and was found to have additional advantages in certain applications. RIA of NMH in plasma was found to be of value in acute medical conditions of obscure aetiology.
Adult↗
Anaphylactic anaesthetic reactions. The value of paper radioallergosorbent tests for IgE antibodies to muscle relaxants and thiopentone.
The three currently available paper radioallergosorbent tests ('suxamethonium', alcuronium and thiopentone) were evaluated. 'Suxamethonium' radioallergosorbent test (which employs choline conjugated to paper discs) proved to be reliable in the detection of allergy to neuromuscular blockers, which were confirmed as the most common cause of anaphylactic reaction during general anaesthesia. Thiopentone radioallergosorbent test may also be useful, and is recommended in conjunction with 'suxamethonium' radioallergosorbent test in the preliminary investigation of reactions. Patients with positive 'suxamethonium' radioallergosorbent test usually require further testing, including alcuronium radioallergosorbent test, skin testing with a wide range of drug concentrations or leucocyte histamine release test.
Adolescent↗
Naturally occurring IgG-antibody-like substance reacting with quaternary ammonium group and neuromuscular blockers: a common finding in humans and other species?
IgG antibodies reacting with the quaternary ammonium group of choline and alcuronium appeared to be present in the sera of humans, guinea pigs, and rats. The antibodies, particularly those 'against' alcuronium, were detected in every serum by paper immunosorbent test(s). This finding, if substantiated, would be of fundamental importance in view of the wide distribution of choline derivatives within the body and in the environment. It may also be relevant to the histamine-releasing activity of neuromuscular blockers and compounds possessing the quaternary ammonium group.
Alcuronium↗
Urine methylhistamine concentrations before and after chloroquine in healthy black subjects.
Urine concentrations of methylhistamine were measured in 11 subjects who experienced itching with chloroquine ('itchers') and in 14 who did not itch ('non-itchers'). In each group, urine methylhistamine concentrations were significantly greater at 12, 24 and 36 h after ingestion of 1 g chloroquine phosphate than before. There was no significant difference between itchers and non-itchers as regards urine methylhistamine concentrations at any time-point. Furthermore, there was no correlation between urine methylhistamine concentration and degree of pruritus in itchers. The findings suggest that histamine may be released by chloroquine, but it is unlikely to be the main cause of chloroquine-induced pruritus.
Adult↗
The cardiac and renal effects of the complement fragment C5a des Arg are partly mediated by the release of histamine and arachidonic acid metabolites.
This report suggests that the release of various inflammatory mediators such as histamine, LTC4, D4 and E4, and TXA2 measured as the stable metabolite TXB2 are partly responsible for the various cardiac and renal effects of the complement fragment C5a des Arg anaphylatoxin, in addition to its direct vasoconstrictor activity.
Animals↗
Anaphylactic reactions affecting the human heart.
We have investigated a large number of patients, most of whom suffered from severe systemic anaphylactic or anaphylactoid reactions during the induction of anaesthesia; the term 'anaphylactoid' was restricted to patients who had no history of prior exposure. Cardiac dysrhythmia (including severe bradydysrhythmia), which was documented by electrocardiography, was one of the principal manifestations, and in one case there was evidence of myocardial ischemia as well.
Anaphylaxis↗
Suxamethonium-induced histamine release from the heart of naïve and suxamethonium-sensitized guinea-pigs: evidence suggesting spontaneous sensitization in naïve animals, and relevance to anaphylactoid reactions in man.
A guinea-pig model for anaphylactic and anaphylactoid reactions to suxamethonium was evaluated. 'Sensitization' to that drug was demonstrated both by cardiac anaphylaxis in the Langendorff preparation, and by serum antibody studies. Spontaneous sensitization to cross-reacting chemicals in a proportion of control animals is strongly suggested, somewhat akin to spontaneous sensitization in patients with anaphylactoid reactions to neuromuscular blockers on first exposure, and in whom IgE antibodies are detected.
Anaphylaxis↗
Role of thromboxane A2, leukotriene C4 and histamine in the antigen-induced vasoconstriction in perfused, sensitized guinea-pig kidney.
The existence of a role for TXA2, histamine, and possibly LTC4 in the antigen-induced renal vasoconstriction in isolated, perfused kidney of sensitized guinea-pigs is demonstrated.
Animals↗
Anaphylaxis due to suxamethonium in a 7-year-old child: a 14-year follow-up with allergy testing.
In 1973 a 7-year-old girl had anaphylactic reactions after two general anaesthetics. In-vitro testing with the leucocyte challenge histamine release test showed a strong response to suxamethonium, and other tests indirectly suggested an allergic mechanism. The conclusion was that this was an allergy to suxamethonium. Further blood was sent for testing against a range of neuromuscular blockers, but the patient was 'lost' until she re-appeared 14 years later as an antenatal patient. In-vitro testing was repeated against suxamethonium and all the available neuromuscular blockers after delivery. The radio-allergosorbent test for allergen-specific IgE antibodies was performed on newly collected serum and that which had been stored for 13-14 years. Skin testing was also performed. The results remain positive and suggest a degree of allergy to all the neuromuscular blockers with the possible exception of vecuronium. The radio-allergosorbent test was negative in the patient's baby.
Anaphylaxis↗