Screening for mast cell tryptase and serum IgE antibodies in 18 patients with anaphylactic shock during general anaesthesia.

BACKGROUND: In the perioperative setting multiple agents can cause anaphylaxis. Often the reactions are dramatic, and due to their lifethreatening potential it is crucial that the responsible agent is identified in order to avoid future adverse reactions. The aim of the present study was to measure the concentration of serum mast cell tryptase (MCT), to investigate the prevalence of serum IgE antibodies against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex and to perform skin prick tests (SPTs) in 18 patients experiencing an anaphylactic reaction during induction of general anaesthesia. METHODS: Serum samples from 18 patients with an anaphylactic reaction during general anaesthesia were analyzed for MCT and specific IgE against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex. Skin prick tests were performed in 11 out of 18 patients. RESULTS: Ten patients had elevated MCT levels and specific IgE against ammonium ion, morphine and (with the exception of patient nos 3, 9 and 10) suxamethonium. Seven of these patients had positive SPTs to suxamethonium. One of the patients tested positive to latex in addition to suxamethonium. Two patients showed elevated MCT, while specific IgE against the drugs tested was not detected. Three patients tested positive to ammonium ion, morphine and suxamethonium, but negative to MCT. Three patients tested negative to both MCT and specific IgE. CONCLUSIONS: Fifteen out of 18 sera tested positive for MCT and/or specific IgE against neuromuscular blocking drugs (NMBDs). Ten of the 18 patients experienced an IgE-mediated anaphylactic reaction to NMBDs during anaesthesia, verified by detection of specific IgE and elevated levels of MCT.

Participación de receptores histaminérgicos involucrados en la permeabilidad vascular / Participation of histaminergic receptors involved in vascular permeability

La permeabilidad vascular puede ser modificada por la liberación de histamina endógena como resultado de la presencia de ciertos tiobarbitúricos (tiopental) en el organismo. Esta modificación en la permeabilidad es mediada por la activación del receptor histaminérgico H1, pero es incierta la participación del receptor H2. En este trabajo se evalúa la participación de receptores H1 y H2 durante los cambios de permeabilidad vascular inducidos por histamina, a través de la determinación de concentraciones séricas de albúmina, proteínas totales y globulinas, que indirectamente lo indican. Se formaron 5 grupos de organismos; un control y 4 experimentales denominados grupo A, B, C y D. A los organismos del grupo A se les aplicó histamina IV, 10 µg/Kg de peso, y finalmente al grupo D se le inyectó simultáneamente 0.16 mg/Kg de peso; al grupo C se le inyectó ranitidina IV, 0.13 mg/Kg de peso, y finalmente al grupo D se le inyectó simultáneamente 0.16 mg/Kg de peso y 0.13 mg/Kg de peso de astemizol y ranitidina IV, respectivamente. El grupo A mostró un decremento significativo en las concentraciones de albúmina, proteínas totales y globulinas. En los grupos B, C y D se observó una disminución en la concentración de proteínas totales y globulinas, pero no de albúmina. Estos resultados muestran que los receptores H1 y H2 están involucrados en el aumento de permeabilidad vascular a la albúmina, pero tal vez exista un proceso de permeabilidad diferencial en el cual el paso de globulinas desde la luz vascular hasta el intersticio esté regulado por otro mecanismo

Evaluation of mast cell activation (tryptase) in two patients suffering from drug-induced hypotensoid reactions.

Tryptase is predominantly found in mast cells, where it resides in secretory granules, and is released with other mediators during mast cell degranulation. By using a newly developed commercial assay for measurements of tryptase levels we have investigated two cases of suspected drug-induced anaphylaxis. Each patient had a similar clinical presentation, consisting of hypotension and cyanosis after administration of thiopentone and suxamethonium. One of the patients showed a highly elevated serum level of tryptase reaching 26 micrograms/l 30 min after the initial reaction. In addition, slightly elevated levels of specific IgE antibodies to thiopentone were detected. The other patient with similar symptoms showed no increase in the level of tryptase, nor any specific IgE to thiopentone or suxamethonium. These data indicate the patient I suffered from true anaphylaxis, whereas the reaction of patient II occurred by a different mechanism.

The molecular basis of IgE antibody binding to thiopentone. Binding of IgE from thiopentone-allergic and non-allergic subjects.

Thiopentone-specific IgE antibodies from the sera of subjects who experienced a life-threatening anaphylactic reaction to the drug and IgE antibodies that cross-react with thiopentone via substituted ammonium groups in either cyclic or acyclic form, were studied by direct binding immunoassays and quantitative hapten inhibition methods. Findings provided an explanation for the apparent 'non-specific' nature of some IgE antibody reactions with thiopentone and reinforce the conclusion that the thiopentone IgE immunoassay is a valuable aid in the diagnosis of immediate allergic reactions to the drug.

Drugs as allergens: the molecular basis of IgE binding to thiopentone.

Using an immunoassay developed for the detection of thiopentone-reactive IgE antibodies, the combining site specificities of such antibodies found in sera of patients who experienced life-threatening anaphylactic reactions to the drug were studied. The antibody combining sites from one patient were complementary to the region of the thiopentone molecule containing a thio group at position 2 of the barbiturate ring. The allergenic determinant recognized by IgE antibodies from another patient encompassed a secondary pentyl group and an ethyl group attached to position 5 on the other side of the barbiturate ring. Thus, it is already clear that there is more than one allergenic determinant on the thiopentone molecule with the capacity to provoke IgE formation and drug-induced allergic reactions.

Detection of thiopentone-reactive IgE antibodies following anaphylactoid reactions during anaesthesia.

A radioimmunoassay was developed to detect IgE antibodies to the anaesthetic induction agent thiopentone. Significant levels of thiopentone-reactive IgE antibodies were found in the sera of two patients who had experienced life-threatening anaphylactoid reactions following administration of the drug. Inhibition experiments revealed that cross-reactivity occurs between the drug-reactive IgE antibodies and four barbiturate analogues pentobarbitone, phenobarbitone, barbitone and methohexital. The assay should supplement skin testing for the detection of patients with potentially lethal sensitivity to thiopentone.

Anaphylaxis due to thiopental sodium anesthesia.

Anaphylaxis due to an anesthetic is one type of cardiovascular emergency that can occur during general anesthesia. Anaphylactic reactions to muscle relaxants have been documented. Barbiturates, used as sedatives, are well known to produce cutaneous reactions, but anaphylaxis after their ingestion seems to be rare. Generalized allergic reactions to thiopental sodium during anesthesia are mentioned in the product monograph for Penthothal sodium, and rare case reports of anaphylactic reactions to infused thiopental have appeared, generally in the anesthesiology literature. Documentation of the immunologic responses to thiopental sodium has been limited to the demonstration of an allergic reaction to thiopental by skin testing in some cases. This report describes a woman who, after having tolerated thiopental sodium and other general anesthetics, became sensitive to this agent and had a severe acute reaction at the time of induction of general anesthesia.

Pulmonary metastases, a potential biologic consequence of anesthetic-induced immunosuppression by thiopental.

This set of experiments was devised to determine the effects of the commonly employed anesthetic induction agent, thiopental, on the incidence of pulmonary metastases in a murine fibrosarcoma system. A correlation was made with cell-mediated immune responses in vivo and in vitro. In two separate experiments, thiopental-treated mice had a significantly increased incidence of pulmonary metastases. This was correlated with an impaired delayed hypersensitivity reaction to the de novo antigen. 2,4-dinitrochlorobenzene (DNCB) and a suppressed mixed leukocyte culture (MLC) reaction. However, if animals were sensitized with DNCB 5 days prior to receiving pentothal, no impairment of DNCB reactivity was noted. This suggests strongly that the observed defect is in the afferent arm of the immune response. Thiopental suppresses cell-mediated immune responses in this system, and the observed biologic consequence is an increase in pulmonary metastases.

[Anaphylactic shock to pentothal induction]. / Un choc anaphylactique au pentothal à l'induction

In a patient who had been anaesthetised twice with penthiobarbitone, who had contracted a localised then a generalised eczema, collapse appeared during a third anaesthetic induction, 30 minutes after the injection of penthiobarbitone which was revealed by Shelley's test to be the most positive product.

[2 cases of anaphylactic-type reaction related to anesthesia]. / Deux cas de réactions de type anaphylactique en rapport avec l'anesthésie

Two cases of anaphylactic shock during anaesthesia are presented, in which the etiology is confirmed by the lymphoblastic transformation test. In one case, the responsability was due to Pentothal, in the other to the combination of Pentothal-succinylcholine.