Anaphylaxis

Background Anaphylactic and anaphylactoid reactions occurring during anesthesia remain a major cause of concern for anesthesiologists. The authors report the results of a 2-yr survey of such reactions observed during anesthesia in France. Methods Between January 1, 1999, and December 31, 2000, 789 patients who experienced immune-mediated (anaphylaxis) or nonimmune-mediated (anaphylactoid) reactions were referred to one of the 40 participating centers. Anaphylaxis was diagnosed on the basis of clinical history, skin tests, and/or specific immunoglobulin E assay. Results Anaphylactic and anaphylactoid reactions were diagnosed in 518 cases (66%) and 271 cases (34%), respectively. The most common causes of anaphylaxis were neuromuscular blocking agents (NMBAs) (n = 306, 58.2%), latex (n = 88, 16.7%), and antibiotics (n = 79, 15.1%). Rocuronium (n = 132, 43.1%) and succinylcholine (n = 69, 22.6%) were the most frequently incriminated NMBAs. Cross-reactivity between NMBAs was observed in 75.1% of cases of anaphylaxis to an NMBA. No difference was observed between anaphylactoid and anaphylactic reactions when the incidences of atopy, asthma, or drug intolerance were compared. However, atopy, asthma, and food allergy were significantly more frequent in the case of latex allergy when compared with NMBA allergy. Clinical manifestations were more severe in anaphylaxis. The positive predictive value of tryptase for the diagnosis of anaphylaxis was 92.6%; the negative predictive value was 54.3%. The diagnostic value of specific NMBA immunoglobulin E assays was confirmed. Conclusions These results further corroborate the need for systematic screening in the case of anaphylactoid reaction during anesthesia and for the constitution of allergoanesthesia centers to provide expert advice to anesthesiologists and allergists.

Anaphylactic and Anaphylactoid Reactions Occurring during Anesthesia in France in 1999–2000

Between January 1, 1997 and December 31, 1998, 467 patients were referred to one of the allergo-anaesthesia centres of the French GERAP (Groupe d'Etudes des Reactions Anaphylactoides Peranesthesiques) network and were diagnosed as having anaphylaxis during anaesthesia. Diagnosis was established on the basis of clinical history, skin tests and/or a specific IgE assay. The most frequent cause of anaphylaxis was a neuromuscular blocking agent (69.2%). Latex was less frequently incriminated (12.1%) than in previous reports. A significant difference was observed between the incidence of anaphylactic reactions observed with each neuromuscular blocking agent and the number of patients who received each drug during anaesthesia in France throughout the study period (P<0.0001). Succinylcholine and rocuronium were most frequently incriminated. Clinical reactions to neuromuscular blocking drugs were more severe than to latex. The diagnostic value of specific IgE assays was confirmed. These results are consistent with changes in the epidemiology of anaphylaxis related to anaesthesia and are an incentive for the further development of allergo-anaesthesia clinical networks.

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Anaphylaxis during anaesthesia. Results of a two‐year survey in France

The details of 826 patients referred to an Anaesthetic Allergy Clinic over a 17-year period are described. 443 were classified as having severe immediate anaphylactic reactions and in the majority of these (263) a muscle relaxant was involved. In Australia, the most common cause of a reaction is alcuronium, which probably reflects usage, although it is the most commonly found to give a positive skin test in relaxant reactors. Suxamethonium and atracurium appear to have an incidence of reactions greater than predicted by market share and pancuronium and vecuronium appear safer both on incidence of reactions and on positive skin tests in reactors. The incidence of reactions is between 1:10,000 and 1:20,000 anaesthetics. Patients who react have greater incidence of allergy, atopy, asthma and previous reactions than non reactors. Previous exposure is usually apparent in reactors to induction agents but not muscle relaxants. Cardiovascular collapse is the most common presenting problem and is the only problem in 10%. Skin changes are the next most common and then bronchospasm which may be transient and is the hardest feature to treat. With an investigation protocol based on history, skin and RIA testing subsequent anaesthesia is usually safe.

The incidence and clinical features of anaphylactic reactions during anaesthesia in Australia

Anaphylactic reactions to anaesthetic and associated agents used during the perioperative period have been reported with increasing frequency in most developed countries. Any drug administered in the perioperative period can potentially produce life-threatening immune-mediated anaphylaxis. Most published reports on the incidence of anaphylaxis come from France, Australia, the UK and New Zealand. These reflect an active policy of systematic clinical and/or laboratory investigation of suspected immune-mediated reactions. The estimated incidence of anaphylaxis ranges from 1:10,000 to 1:20,000. Muscle relaxants (69.1%) and latex (12.1%) were the most frequently involved drugs according to the most recent French epidemiological survey. Clinical symptoms do not afford an easy distinction between immune-mediated anaphylactic reactions and anaphylactoid reactions resulting from direct non-specific histamine release. Moreover, when restricted to a single clinical symptom, anaphylaxis can easily be misdiagnosed. Pre- and postoperative investigation must be performed to confirm the nature of the reaction, the responsibility of the suspected drugs and to provide precise recommendations for future anaesthetic procedures. These include plasma histamine, tryptase and specific IgE concentration determination at the time of the reaction and at skin tests 6 weeks later. In addition, since no specific treatment has been shown reliably to prevent the occurrence of anaphylaxis, allergy assessment must be performed in all high-risk patients. Treatment of anaphylaxis is aimed at interrupting contact with the responsible antigen, inhibiting mediator production and release, and modulating the effects of released mediators. It must be initiated as quickly as possible and relies on widely accepted principles. Finally, the need for proper epidemiological studies and the relative complexity of allergy investigation should be underscored. They represent an incentive for further development of allergo-anaesthesiology clinical networks to provide expert advice for anaesthetists and allergologists.

Allergic reactions occurring during anaesthesia

Sixty one patients who had suffered intra-operative anaphylactoid reactions were studied. Intradermal testing identified the causative agent in 84% of cases and, in 75% of these, muscle relaxants were responsible. Predisposing factors in patients sensitive to muscle relaxants were: female sex, previous allergy and atopy. The incidence of previous exposure was considerably higher than that reported in the literature. Pancuronium is suggested to be the least likely currently available agent to provoke a major anaphylactoid reaction.

Anaphylactoid reactions during anaesthesia. Seven years' experience of intradermal testing

Morphine and tubocurarine may release histamine by direct mast cell degranulation which may result in systemic effects such as cutaneous flushing, local wheal and flare formation and hypotension. This randomised, double-blind study examined whether preoperative combined oral terfenadine (60 mg) and ranitidine (150 mg) attenuates the reduction in blood pressure and cutaneous flushing after the administration of tubocurarine and morphine in 60 patients undergoing elective gynaecological surgery. In addition, investigation was made of whether tubocurarine and morphine cause a significant decrease in gastric pH in comparison to the nonhistamine-releasing agents fentanyl and vecuronium. Patients were randomly assigned to one of three groups receiving either pre-operative terfenadine and ranitidine and intra-operative tubocurarine and morphine (group A); pre-operative placebo and intra-operative tubocurarine and morphine (group B); pre-operative placebo and intra-operative fentanyl and vecuronium (group C). Compared to group B, group A had less hypotension and tachycardia but no significant decrease in cutaneous flushing immediately following morphine and tubocurarine (p > 0.05). There were no significant differences in haemodynamic changes between the groups A and C. In those patients not pretreated with terfenadine and ranitidine (groups B and C), gastric pH decreased between 5 and 10 min following bolus administration of morphine and tubocurarine (group B), whereas patients receiving fentanyl and vecuronium (group C) had an increase in gastric pH. This suggests that histamine release following administration of morphine and tubocurarine is sufficient to increase gastric acidity.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of the H1 and H2 receptor antagonists, terfenadine and ranitidine on the hypotensive and gastric pH effects of the histamine releasing drugs, morphine and tubocurarine.

The hypothesis that benzodiazepine night sedation causes acute tolerance to benzodiazepine sedation given the following morning was examined in six volunteers in a double blind, randomised, crossover study. Before each of three study days, subjects received midazolam 15 mg or flunitrazepam 2 mg or placebo as oral night sedation. They were then given intravenous midazolam 5 mg the following morning and the resulting sedative effects examined, using an observers sedation scale and a psychomotor test battery (critical flicker fusion frequency, digit-symbol substitution, reflex time, tapping test and a visual analogue sedation scale). Although a consistent pattern emerged with the greatest degree of sedation following the placebo night sedation and the least degree of sedation following the midazolam, with flunitrazepam intermediate, no statistically significant differences were present between the three treatment groups. The results indicate that single use of benzodiazepine night sedation is not an important influence on benzodiazepine requirements for intravenous sedation.

https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2044.1991.tb09849.x

D. C. Galletly

Papers

Anaphylactoid reactions during anaesthesia. Seven years' experience of intradermal testing

The influence of the H1 and H2 receptor antagonists, terfenadine and ranitidine on the hypotensive and gastric pH effects of the histamine releasing drugs, morphine and tubocurarine.

Acute tolerance from benzodiazepine night sedation.