Histaminoid response after intradermal and intravenous administration of atracurium, vecuronium and tubocurarine: a comparative study

The object of this study was to investigate the histaminoid responses after intradermal administration of atracurium, vecuronium and tubocurarine and to compare these with the cutaneous and cardiovascular responses to intravenous administration of the above relaxants in the same patients. Positive local cutaneous responses to intradermal injection were most common after tubocurarine (92%) and least common after vecuronium (12%). Tubocurarine produced the greatest fall in systolic pressure 3 min after intravenous administration but there was no difference in this respect between atracurium and vecuronium. In any individual patient the response to intradermal injection of a relaxant was not a reliable predictor of the response to subsequent intravenous administration of the same relaxant. Twenty patients had plasma IgE levels below 12 IU ml-1. This abnormally low titre occurred more frequently in female patients and was associated with an increase in the incidence and degree of histaminoid responses to atracurium and tubocurarine. Low plasma IgE may be associated with a deficiency in surface IgE on mast cells which therefore have an increased sensitivity to drugs that cause direct pharmacological histamine liberation.     

Histaminoid responses to atracurium, vecuronium and tubocurarine

Sixty patients scheduled for elective surgery underwent intradermal testing with 0.1 ml of the following solutions diluted in 0.9% saline: vecuronium and tubocurarine (1 in 1,000), atracurium (1 in 1,000 and 1 in 10,000), thiopentone (1 in 100) and also a 0.9% saline control. Thirty minutes later, an area of erythema of greater than 1.5 cm, or a wheal exceeding 1.0 cm in diameter, was recorded as a positive reaction. The patients then randomly received equipotent doses of atracurium, vecuronium or tubocurarine during a standardized anaesthetic induction. Any cutaneous reaction and the percentage fall in systolic pressure three minutes after administration of the relaxant were recorded. In 51 patients plasma IgE levels were measured. The incidence of positive cutaneous reactions to intradermal and intravenous relaxants was significantly different with each agent (p less than 0.01). The percentage fall in systolic pressure after tubocurarine was significantly different relative to the other two agents (p less than 0.01). This was regarded as reflecting potency in releasing histamine and placed the relaxants in the same order: tubocurarine, atracurium and vecuronium. The response to intradermal administration was no guide to the subsequent response after intravenous administration of the three relaxants. IgE levels below 15 IU X ml-1 occurred significantly more often in females and were associated with a significantly higher incidence of cutaneous reactions after intradermal atracurium (1 in 1,000 and 1 in 10,000) (p less than 0.05 and 0.001 respectively) and tubocurarine (1 in 1,000). With these two agents, generalized flushing after intravenous administration was also more common in this group, relative to the normal/high IgE group.     

Prospective preoperative survey of 300 patients using prick tests with muscle relaxants

It is now well established that the retrospective diagnosis of anaphylaxis to muscle relaxants may be based on skin prick testing. These tests, which use undiluted solutions of muscle relaxants, are as sensitive, specific and reproducible as intradermal tests for the diagnosis of IgE related adverse reactions to muscle relaxants. The rate of muscle relaxant anaphylaxis (1/1 500 to 1/5 000) justifies its prevention based on a possible latent sensitization. A prospective investigation was carried out in 300 surgical patients scheduled for general anaesthesia. Prick tests were carried out using the 6 available muscle relaxants: suxamethonium, gallamine, alcuronium, pancuronium, vecuronium and atracurium. The wheal the drug might produce was compared with that obtained with codeine phosphate (a histamine releasing drug). Thirty-seven patients (13%) were considered to be atopic; 262 (87%) had undergone a previous anaesthesia. Three percent (n = 11) of tests were positive for atracurium. The wheal produced by atracurium was in favour of non-specific histamine release. One test was found positive for suxamethonium. Confirmation of this probable latent sensitization was unfortunately not possible. There were no other positive skin tests. Muscle relaxants were subsequently used in 58 patients (80% vecuronium) without any problem. Skin prick testing should be used on a larger scale to detect latent sensitization. However, predictive skin tests with atracurium should be avoided, as wheal reactions with this drug are probably due to non-specific histamine release.     

Predictive value of intradermal tests using muscle-relaxing drugs

A retrospective postal inquiry was carried out to find out a possible relation between the results of intradermal tests carried out for a previous anaesthetic and the course of a second anaesthetic performed afterwards. This study included 350 patients who have had an intradermal test to vecuronium, alcuronium, suxamethonium, gallamine, pancuronium, thiopentone, fentanyl and droperidol between March 1984 and November 1986. Eighty-nine did not reply (25.4%), 183 (52.3%) did not undergo new general anaesthetic since the skin tests, whilst 78 (22.3%) did. The inquiry was then sent to the 73 anaesthetists corresponding to the last group of patients. The 51 complete answers included 62 anaesthetics. Twenty-four patients had negative intradermal tests before the new anaesthetic, the other 27 having had a test positive to at least one muscle relaxant. Of these latter, 16 were given a muscle relaxant during their general anaesthetic, selected among those resulting in a negative intradermal test. Thirteen had undergone skin testing because of an anaphylactic reaction during induction. No new anaphylactic reaction was observed. Three anaesthetists only were not aware of the results of the intradermal tests at the time of the new anaesthetic. These data tend to demonstrate that a muscle relaxant could be injected in a patient who has had a previous anaphylactic reaction with positive intradermal tests, provided that the drug chosen for the new anaesthetic does not give a positive intradermal reaction.     

The use of atracurium besylate for laparoscopy

An anaesthetic technique is described for laparoscopy using an intravenous induction, atracurium 0.2 mg/kg for muscle relaxation and intermittent positive pressure ventilation of the lungs with nitrous oxide and oxygen. It was found to be a suitable and simple technique. Recovery of spontaneous ventilation was achieved without the use of reversal agents in all 40 patients. A 15% incidence of cutaneous histaminoid reactions was noted. This is no higher than reported in other studies of atracurium, and further clinical trials are awaited.     

Epidemiology of anesthetic anaphylactoid reactions. Fourth multicenter survey (July 1994-December 1996)]

Since 1984 an epidemiological survey of anaphylactoid reactions occurring during anaesthesia has been obtained in France with regular repeated inquiries by the Perioperative Anaphylactoid Reactions Study Group (Gerap). The members of this group collected during the study period cases of patients having suffered from an anaphylactoid reaction and subsequently tested in their allergoanaesthetic outpatient clinic. The three previous surveys published in the Annales fran?aises d'anesthésie et de réanimation in 1990, 1993 (in English) and 1996 included 1,240, 1,585 and 1,730 patients respectively. The current survey concerned 1,648 patients, tested by the GERAP (38 diagnostic centres) from July 1994 to December 1996. The diagnostic tests for IgE anaphylaxis were cutaneous tests (prick tests and intradermal tests), which minimal dilutions for specific positive skin test were previously determined by comparison with control subjects. The cutaneous tests were performed by all the centres. These tests were associated, in 29 centres, with the detection of specific IgEs against quaternary ammonium compound and inhibition test, and detection of IgEs against propofol, thiopental and latex. Moreover, leukocyte histamine release test was performed in seven centres. The mechanism of the reaction was: anaphylaxis in 692 patients (characteristic clinical symptoms and positive allergological tests), anaphylactoid reactions in 611 patients (characteristic clinical symptoms and negative allergological tests), and other causes in 345 patients (unusual clinical symptoms and negative allergological tests). An immune mechanism was found in 53% of the reactions, with characteristic clinical symptoms occurring during anaesthesia. The 692 cases of anaphylaxis were due to 734 substances (double anaphylaxis in 42 patients): muscle relaxants (61.6%), latex (16.6%), antibiotics (8.3%), hypnotics (5.1%), colloids (3.1%), opioids (2.7%) and others (2.6%) among which aprotinin (four cases) ethylene oxide (five cases) local anaesthetics (two cases). The muscle relaxants implicated in anaphylactic reactions included: vecuronium (n = 130), atracurium (n = 107), suxamethonium (n = 106), pancuronium (n = 41), rocuronium (n = 41), mivacurium (n = 18), and gallamine (n = 9). These results reflected French anaesthetic practice, except for suxamethonium (5% of the French market share of curares). In 70% of the patients who were allergic to one muscle relaxant, cross-sensitivity was found with the other relaxants. The comparison with the three previous surveys confirms that the mechanism of about half of the anaphylatoid reactions occurring during anaesthesia is of immune origin, due to specific IgE antibodies. Muscle relaxants remain the most common cause of anaphylaxis, followed by latex whose incidence seems to decrease, whereas the incidence of anaphylaxis to antibiotics increases. Incidence of reactions to suxamethonium decreased, corresponding however to one quarter of all muscle relaxant anaphylaxis, similar with vecuronium and atracurium. For this survey, more clinical information was obtained in 583 patients, allowing the following conclusions: reactions were always more severe in case of anaphylaxis than nonspecific histamine release; reactions occurred more frequently in females (F/M = 2.5); 17% of patients allergic to a muscle relaxant were never anaesthetized beforehand; a history of reactions during previous anaesthetics was a risk factor for a reaction during subsequent anaesthetics; neither drug allergy nor atopy (except for latex allergy) were a predisposing factor for reactions with anaesthetic agents. Considering that in 1996, 8 million anaesthetics were administered in France, of which 2.5 million included the use of muscle relaxants, the overall incidence for anaphylactic reactions, all agents included, was evaluated as 1 in 13,000 anaesthetics, while the incidence of anaphylaxis to muscle relaxants was 1 in 6,500 anaesthetics.     

Subsequent general anaesthesia in patients with a history of previous anaphylactoid/anaphylactic reaction to muscle relaxant

Of 151 patients with a possible anaphylactoid/anaphylactic reaction to a muscle relaxant investigated over a 20-year period, follow-up for any subsequent general anaesthesia was complete in 145 (96%). One hundred and twenty-two anaesthetics in 72 patients were documented. There were no anaesthetic-related deaths. No subsequent reactions were seen if muscle relaxants were not used in the subsequent anaesthetic, nor were they in patients with severe reactions if the original intradermal test had been equivocal or negative. In the patients with a severe reaction and a positive intradermal test to one or more muscle relaxants, six out of 40 later anaesthetics using muscle relaxants were associated with clinical problems, three being probable anaphylactic reactions, whilst three were minor. Intradermal testing should be performed prior to surgery in this group of patients for the muscle relaxant(s) planned, or an anaesthetic technique which avoids relaxants should be used. This review should encourage other centres to undertake similar follow-up.     

Bradycardia in patients receiving atracurium or vecuronium in conditions of low vagal stimulation

Four groups of 20 patients each received either vecuronium or atracurium together with either glycopyrronium or saline, and underwent anaesthesia free of vagolytic drugs, and surgery devoid of vagal activity. Determinations of plasma histamine concentrations were made to examine the possible correlation between these levels and changes in heart rate and blood pressure as well as a possible relationship with skin reactions after the administration of the relaxants. Patients who received vecuronium without the anticholinergic drug, glycopyrronium, showed a greater tendency towards bradycardia (though not statistically significant) than those given atracurium. More cutaneous reactions were observed with patients who received atracurium than in those with vecuronium, but there was no correlation with plasma histamine concentrations of either relaxant group. There was no correlation either between histamine concentrations and heart rate or blood pressure associated with atracurium. The incidence of bradycardia with either relaxant is low if the anaesthetic technique and the surgery are devoid of vagal activity.     

Le risque histaminique et anaphylactique de l''atracurium

The histamine releasing potential of atracurium was assessed by testing skin reactivity in ten patients who had previously suffered from a preanaesthetic anaphylactoid accident, but in whom the diagnosis of anaphylaxis had not been confirmed. Atracurium was injected intradermally in increasing concentrations so as to determine the reactivity level, comparing it in the same patient with that due to d-tubocurarine and alcuronium given in the same way. Skin tests with histamine and 48/80 were also carried out at the same time. When a positive reaction was obtained with atracurium, the injection was repeated 4 h after, the patient having taken 50 mg hydroxyzine p.o. The results showed that the skin reactivity level with d-tubocurarine was obtained with 1 in 100 dilution and with atracurium 1 in 10, with nine patients out of ten reacting positively. Alcuronium is the least histamine releasing drug, as it gave rise to a positive reaction in only two patients at a dilution of 1 in 10. Histamine release due to atracurium was greatly reduced by giving hydroxyzine. The allergizing potential was also studied in six other patients who had a tone anaphylaxis to a muscle relaxant and in whom crossed anaphylaxis was being tested for. All the commercial muscle relaxants together with atracurium were tested, even though none of the patients had ever received this last. Anaphylaxis was confirmed when the intradermal reaction was positive with a dilution of 1 in 1,000 and beyond. These tests showed that five patients out of the six had a crossed anaphylaxis, and one of these five was sensitive to all four muscle relaxants (atracurium included).(ABSTRACT TRUNCATED AT 250 WORDS)     

Intradermal skin testing in the investigation of suspected anaphylactic reactions during anaesthesia--a retrospective survey

An anaphylactic reaction is a rare, but severe anaesthetic complication. In this retrospective survey we report on patients with a severe suspected anaphylactic reaction during anaesthesia and the investigation with intradermal skin testing of these suspected anaphylactic reactions. In the patients with an anaphylactic reaction to neuromuscular blocking drugs, the subsequent anaesthetic history was examined. Sixty-five patients suffered a suspected anaphylactic reaction between 1976 and 2001. In 47 patients skin testing was performed and 43 of these patients had positive skin tests: neuromuscular blockings drugs and succinylcholine more specifically, were the most frequently incriminated drugs. After the anaphylactic reaction 19 patients had surgery on 26 occasions with the use of a skin-test-negative neuromuscular blocking drug; no problems occurred. Skin testing proved to be a reliable tool to investigate suspected anaphylactic reactions during anaesthesia and to guide the future use of neuromuscular blocking drugs.     

Rocuronium and cisatracurium-positive skin tests in non-allergic volunteers: determination of drug concentration thresholds using a dilution titration technique

BACKGROUND: Muscle relaxants are believed to be responsible for 2/3 of the cases of anaphylactic reactions during anesthesia. This assumption is based mainly on positive skin tests obtained in individuals that have experienced anesthesia-related anaphylaxis. A positive skin test is supposed to be associated with mast cell degranulation of vasoactive amines. In the present study we tested the frequency of positive skin tests with two commonly used muscle relaxants, rocuronium and cisatracurium, in a selected group of volunteers with low potential for allergic reactions. METHODS: Thirty healthy volunteers without known allergy or previous exposure to muscle relaxants were studied. Low potential for allergic reactions was determined prior to inclusion in the study, using various allergy tests. Each individual was tested with intradermal and skin prick tests, and molar drug concentration thresholds for positive skin reactions were determined using a dilution titration technique. The presence or absence of mast cell degranulation was tested by electron microscopic investigation of skin biopsies obtained from positive and negative skin reactions. RESULTS: None of the volunteers had a positive skin prick test. More than 90% of the volunteers had a positive intradermal test with both rocuronium and cisatracurium. The highest molar drug concentration that was not associated with a positive intradermal test was 10(-6) M (rocuronium) and 10(-7) M (cisatracurium), equivalent to vial dilution 1 : 1000 for both drugs. In none of the volunteers was mast cell degranulation detected. CONCLUSION: Non-mast-cell-mediated positive intradermal skin reactions are frequently occurring with rocuronium and cisatracurium, even at vial dilution 1 : 1000. A clinically applicable test technique is needed that is able to separate positive skin tests associated with mast cell degranulation from non-mast-cell-mediated reactions.     

Intradermal compared with prick testing in the diagnosis of anaesthetic allergy

We have tested the hypothesis that intradermal testing is a more effective method for determining the drug responsible for anaesthetic anaphylactic reactions than prick testing in 212 consecutive patients, aged more than 10 yr, referred to an anaesthetic allergy clinic over a 4-yr period. The study was a prospective, non-randomized design. Intradermal testing was conducted using a previously described method and diluted drugs, and prick testing using undiluted drugs (with the exception of opioid analgesics which were diluted 1:10). The tests were performed on individual patients' forearms on the same occasion. Patients were followed-up to determine the results of subsequent anaesthesia and the difference between tests was analysed using kappa and tau statistics. There was 93% agreement overall between the paired tests. Which test detected the drug responsible was dependent on diagnostic criteria for positivity. The differences between the tests were not statistically significant. Using both tests improved predictability by 67% (tau = 0.67, P < 0.001). We conclude that in the absence of data to support one test being superior, other factors influence the choice of test. Prick testing was cheaper, and the reduction in pain and trauma with prick testing makes it more suitable for children. However, there are no data available on the safety of subsequent anaesthesia based on the results of prick testing alone, and reliability with time has not been assessed. Intradermal testing may be easier for the infrequent user. Skin testing is valuable in the investigation of anaesthetic anaphylaxis whichever test is chosen. When there is doubt both tests should be performed.      

Marqueurs biologiques précoces des réactions anaphylactoïdes peranesthésiques

Three markers of in vivo histamine release, i.e. plasma histamine and tryptase, and urinary methylhistamine, were assessed using sensitive radioimmunoassays in 18 patients who had experienced an adverse reaction to an anaesthetic agent. Controls were obtained from 35 patients following a general anaesthetic, which included a muscle relaxant, and who remained free from any adverse reaction. A first blood sample was obtained from all 18 patients a mean 25 ± 26 min after the reaction, and a second one in thirteen a mean 120 ± 65 min after the reaction. Ten patients had had a life-threatening reaction. Plasma histamine levels were increased in all these cases, and tryptase concentrations in 9 out of 10. Urinary methylhistamine rarely reached pathological levels (4 out of 10). Skin tests were positive in the four tested patients. Plasma histamine concentration was still high in 8 cases thirty minutes after the reaction, and remained increased for more than 2 h in two patients. Among the other eight patients with a moderate reaction, 3 had high histamine levels, with normal or weakly increased tryptase concentrations, and normal urinary methylhistamine. Two of these patients had positive skin tests. There were no abnormal findings in any of the investigations carried out in the other five patients, except for a slightly positive skin test to atracurium in one patient. Plasma histamine had a higher sensitivy than tryptase levels. Methylhistamine concentrations were only rarely of interest. There were no false positives with the three investigated markers. For life-threatening reactions, we suggest that plasma histamine and tryptase levels be measured during the first 10 to 20 minutes, and again 30 to 120 min, after the reaction. For moderate reactions, high figures for these markers are of interest, but normal values may be associated with slightly positive skin tests. Skin testing is therefore imperative in all cases.     

Substances responsables des chocs anaphylactiques peranesthésiques. Troisième enquête multicentrique française (1992–1994)

Since 1989, the epidemiological survey of anaphylactoid reactions occurring during anaesthesia is obtained in France with repeated inquiries by the Perioperative Anaphylactic Reactions Study Group. The members of this group collect during the study period the cases of patients having suffered from an anaphylactoid reaction and tested in their allergo-anaesthetic outpatient clinic, their characteristics (age, gender), the results of the allergological tests (mechanism, agents responsible for the reactions). The two previous surveys published in the Annales françaises d'anesthésie et de réanimation in 1990 and 1993 included 1,240 and 1,585 patients respectively. The current survey concerned 1,750 patients tested in 27 diagnostic centres, from January 1992 to June 1994.The reactions occurred at all ages, predominantly between 10 and 50 years, the sex-ratio (F/M) was 2.4. Allergological tests carried out to diagnose an immune mechanism for the shock were cutaneous tests in all centres (prick-tests in 21 centres, intradermal tests in 27 centres) using the same dilutions for the tested agents and the same threshold for positivity. Specific IgE antibodies against muscle relaxants, thiopentone and propofol, were measured by radio immunoassays in 20 centres. The leucocyte histamine release test was used in 10 centres. The immune origin of the shock — IgE dependent anaphylaxis — was diagnosed in 1,000 patients (57.8%) and due to 1,030 agents: muscle relaxants (59.2%), latex (19%), hypnotics (5.9%), benzodiazepines (2.1%), opioids (3.5%), plasma substitutes (5.0%), antibiotics (3.1%) and other drugs given during anaesthesia such as aprotinine and protamine (2.2%). Suxamethonium was responsible for 39.3% of muscle relaxant anaphylaxis, vecuronium for 36%, atracurium for 14.5%, pancuronium for 4.8%, gallamine for 3.1% and alcuronium for 2.3%. The latter has been withdrawn from the French market in 1993. These differences in the incidence of reactions are correlated with the clinical use of muscle relaxants in France for vecuronium and atracurium, however not for suxamethonium, responsible for 39% of the reactions but representing only 5% of the muscle relaxants sold in France.The comparison with the two previous surveys confirms that the mechanism of more than half of the anaphylactoid reactions occurring during anaesthesia is of immune origin, due to specific IgE antibodies. It is therefore essential to systematically carry out an allergologic assessment several weeks after the reaction, in order to discard for the subsequent anaestheticts the agent (s) responsible for anaphylaxis. If the muscle relaxants remain the first drugs involved in shock occurring at induction, there is a significant increase in latex shock, as demonstrated by the three epidemiological surveys (0.5%, 12.5 and now 19%). The incidence of other anaesthetic agents, antibiotics and plasma substitutes remains unchanged.     

Recovery of neuromuscular function and postoperative morbidity following blockade by atracurium, alcuronium and vecuronium

Recovery of neuromuscular function and postoperative morbidity were studied in 51 fit female patients who had nonemergency gynaecological laparoscopy as inpatients. They were allocated randomly to one of three groups to receive either atracurium 0.31 mg/kg, alcuronium 0.25 mg/kg, or vecuronium 0.06 mg/kg as part of an otherwise standard anaesthetic technique. There were neither differences in intubation conditions nor in the occurrence of postoperative diplopia whichever muscle relaxant was used. Deficits in grip strength and expiratory force were seen at one hour after reversal with atropine 1.2 mg and neostigmine 2.5 mg in all patients, deficits which persisted for 3 hours in those who received alcuronium. The recovery of inspiratory force was slower and less complete at up to 3 hours in those who received alcuronium and there was a high incidence of minor postoperative morbidity at up to 24 hours in each of the three groups. The only statistical difference in symptomatic morbidity was an increase in muscle weakness in those who received alcuronium compared with atracurium at 3 hours after laparoscopy. Only 25%, 20% and 31% of the patients who received atracurium, alcuronium and vecuronium respectively said that they would have liked to be day stay patients.     

Life-threatening anaphylactoid reactions to muscle relaxants

Sixty-seven patients who had life-threatening reactions to muscle relaxant drugs diagnosed by intradermal testing or challenge were studied. Six patients reacted on two occasions; four reacted to different relaxants. There was a significantly greater ratio of female-to-male patients who reacted than in a nonreacting population. Patients who reacted to muscle relaxants had an incidence of allergy, atopy, asthma, and previous reactions to anesthesia that was significantly greater than nonreacting patients, but not greater than patients who had reacted to induction agents. Eighty-five percent of patients who reacted to muscle relaxants had never previously been exposed to the drug, whereas 60% of patients reacting adversely to induction agents had been previously exposed to induction agents. The reactions were not related to additives or preservatives. In spite of a lack of previous exposure, type I hypersensitivity appears the most likely mechanism responsible for life-threatening reactions to muscle relaxants.     

Allergy of anaesthetizing agents in Spain

We have investigated the incidence of requests for allergy testing in 5005 patients attending an anaesthetic assessment clinic. Diagnosis of allergy to anaesthetic drugs was established using cutaneous tests. Allergy tests were requested in 151 (3.0%) patients, proving positive in 43 (0.86%). No allergic reactions were observed during subsequent anaesthesia.      

Anaphylactoid skin reactions after intravenous regional anaesthesia using 0.5% prilocaine with or without preservative — a double-blind study

Methylparaben, the preservative of various local anaesthetic solutions, is a potential allergen.
In a double-blind study, 0.5% prilocaine with (Citanest, n=100) or without (n=100) methylparaben were compared for the occurrence of skin reactions after intravenous regional anaesthesia of the arm in surgical patients. Skin reactions were registered after the deflation of the tourniquet cuff, and intradermal tests were performed with 0.5% prilocaine, 0.1% methylparaben and saline in all patients. Seventeen patients in the Citanest group and four patients in the methylparaben-free prilocaine group developed erythematous skin reactions in the exposed arm after deflation of the tourniquet cuff ( P <0.05, between the groups). The skin symptoms disappeared within an hour and were always restricted to the region which had been anaesthetised. None of the affected patients had positive intradermal tests.
The observed skin reactions are probably non-IgE-mediated anaphylactoid reactions in which the presence of methylparaben in the local anaesthetic solution plays a major role.     

Early biological markers of anaphylactoid reactions occurring during anesthesia]

Three markers of in vivo histamine release, i.e. plasma histamine and tryptase, and urinary methylhistamine, were assessed using sensitive radioimmunoassays in 18 patients who had experienced an adverse reaction to an anaesthetic agent. Controls were obtained from 35 patients following a general anaesthetic, which included a muscle relaxant, and who remained free from any adverse reaction. A first blood sample was obtained from all 18 patients a mean 25 +/- 26 min after the reaction, and a second one in thirteen a mean 120 +/- 65 min after the reaction. Ten patients had had a life-threatening reaction. Plasma histamine levels were increased in all these cases, and tryptase concentrations in 9 out of 10. Urinary methylhistamine rarely reached pathological levels (4 out of 10). Skin tests were positive in the four tested patients. Plasma histamine concentration was still high in 8 cases thirty minutes after the reaction, and remained increased for more than 2 h in two patients. Among the other eight patients with a moderate reaction, 3 had high histamine levels, with normal or weakly increased tryptase concentrations, and normal urinary methylhistamine. Two of these patients had positive skin tests. There were no abnormal findings in any of the investigations carried out in the other five patients, except for a slightly positive skin test to atracurium in one patient. Plasma histamine had a higher sensitivity than tryptase levels. Methylhistamine concentrations were only rarely of interest. There were no false positives with the three investigated markers.(ABSTRACT TRUNCATED AT 250 WORDS)     

The investigation of bronchospasm during induction of anaesthesia

Background: The aim of this study was to ascertain whether anaesthetic induction-related anaphylactic bronchospasm could be distinguished from other types of bronchospasm by clinical features and response to treatment. Such features could then be used to identify a group of patients in whom skin testing is indicated.
Methods: We retrospectively studied data from 183 patients referred to an anaesthetic allergy clinic because of bronchospasm during induction. For the analysis, the patients were divided into two groups depending on whether there was evidence suggesting immunological anaphylaxis.
Results: When the patients in whom intradermal tests were positive were compared with those in whom intradermal tests were negative, the skin test-positive patients had significantly more severe reactions, and they were more commonly associated with other clinical signs. Mast cell tryptase (MCT) was an excellent discriminator between reactions likely to be allergic and those unlikely to be allergic.
Conclusions: Anaphylactic bronchospasm related to induction of anaesthesia is more likely to be severe than bronchospasm due to non-immune causes. An allergic cause is more likely if there are associated features of anaphylaxis (skin changes, hypotension, angioedema) or elevated MCT. Patients with any of these features should undergo immuno-allergolical investigation.