Allergische Reaktionen im Rahmen von Anästhesieverfahren: Untersuchungen zur Relevanz der Hauttestungen mit Muskelrelaxantien und der Bestimmung der Mastzelltryptase im Serum

Anaphylaxis is a major challenge for allergological diagnostics. The question to be answered is what role skin tests and in-vitro diagnostics play for a meaningful diagnosis concerning muscle relaxants as elicitors of allergic reactions, which are considered the most common cause of perioperative drug-induced anaphylaxis and whether mast cell tryptase is a specific anaphylaxis marker. The study group consisted of 42 patients who underwent elective surgery under general anaesthesia at the Department of Dermatology and Allergology at the University Hospital in Marburg. Their ages varied between 24-73 years. Initially, a detailed allergy history was taken one day prior to the operation. On the following day, two tryptase values were determined during the surgical procedure, one 30 minutes and one 120 minutes after induction of anaesthesia. On the following day, basal tryptase level was determined, in addition both the total IgE concentration as well as different values of specific IgE antibodies were measured: Furthermore skin prick and intradermal tests of different concentrations of the four muscle relaxants rocuronium, cis-atracurium, succinylcholine and mivacurium as well as prick tests with the atopy determining allergens grass, birch, cat and house dust mite were performed. In selected patients with positive skin tests for muscle relaxants, basophil activation tests (BATs) were conducted with rocuronium, atracurium, succinylcholin and mivacurium. The gender ratio was balanced in the subject collective. 47.6% of the patients received one of the above-mentioned muscle relaxants intraoperatively. 40.5% could be classified as atopic via sensitisation to the above-mentioned atopy allergens, and 25.6% of the subjects showed elevated total IgE values >100U/ml. All patients tolerated the anesthesia very well with no evidence of anaphylaxis (angioedema, flush, urticaria or drop in oxygen saturation). The duration of the operation was between 75-300 minutes. 21% of subjects showed hypotension <90mmHg, but this was not due to anaphylaxis. At skin testing, all prick tests with muscle relaxants were negative. In the intradermal tests, positive reactions measured by a wheal size > 2x the injected depot were observed in 70.6% for rocuronium, 20.6.% for succinylcholine, 73.5% for cis-atracurium and 97.1% for mivacurium. Considering a wheal size of ≥ 8 mm as positive, 41.2% reacted to rocuronium, 8.8% to succinylcholine, 47.1% to cis-atracurium and 61.8% to mivacurium. The specific IgE for rocuronium and succinylcholine did not show elevated values in any of the subjects. The six BAT tests performed with different muscle relaxants were also all negative. Serum mast cell tryptase levels varied between 1.0 and 16.7 µg/l; the median of basal tryptase concentrations was 2.81 µg/l, the median measured 30 min after induction of anesthesia was 2.98 µg/l and 3.09 µg/l determined after 120 minutes. With the currently recommended formula assessing if the tryptase level is increased as a potential sign of anaphylaxis (1.2 x basal value + 2 µg/l), no significantly increased delta values could be found between the basal and perioperative tryptase measurements. Furthermore, no correlations were observed between absolute tryptase levels and intraoperative measurements of blood pressure, duration of anaesthesia or the applied different muscle relaxants. With regard to basal tryptase, the Mann Whitney U-test showed no significant difference between men and women. With a p-value of 0.067, there was a trend in the association of age and the level of basal tryptase. The major finding of the study was that skin tests with muscle relaxants are unreliable with regard to the unequivocal detection of IgE-mediated sensitisations, which would confirm an allergy against the muscle relaxants. The BAT alone has too little significance to decide on the presence of a drug allergy, therefore it should only be used as a complementary diagnostic to the other tests. In addition, this study showed that tryptase levels do not change significantly during a surgical procedure under general anaesthesia. Thus, an increase in tryptase delta during a surgical procedure under general anaesthesia would be of great significance with regard to a possible perioperative anaphylaxis. No association was demonstrated between atopic patients in the patient population and positive skin tests for the four muscle relaxants or tryptase levels.