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Original Article
Perioperative allergic reactions: Experience in a Flemish referral centre
J. Antunes1, A.-M. Kochuyt, J.L. Ceuppens
Corresponding author
jan.ceuppens@uzleuven.be

Corresponding author.
Clinical Department of Allergy and Clinical Immunology, University Hospital Gasthuisberg, KU Leuven, Belgium
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Basal &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>90&#41; and acute phase tryptase levels &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>59&#41;&#46; Tryptase levels were measured with an immunoassay&#46; Results did not follow a Gaussian distribution &#40;D&#8217;Agostino and Pearson omnibus normality test&#41;&#46; Significance was calculated after logarithmic scale conversion&#44; by using paired <span class="elsevierStyleItalic">t</span>-test &#40;basal versus acute phase levels in both IgE and non-IgE-reactions&#41; and unpaired <span class="elsevierStyleItalic">t</span>-test &#40;basal and acute phase levels in IgE-mediated reactions versus non-IgE-reactions&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Complications during general anaesthesia have multiple causes&#44; among which allergic reactions are rare&#46; However&#44; as they are a potential cause of perioperative morbidity and mortality&#44; all possible allergic reactions should be carefully investigated&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;5</span></a> Data on the incidence of perioperative anaphylaxis have already been published in France&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;10</span></a> Australia&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Scandinavia<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#8211;14</span></a> and England&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> The anaphylaxis rate varies between reports but it is overall estimated to be 1 per 10&#44;000&#8211;20&#44;000 anaesthetic procedures&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;10&#44;17</span></a> Thirty to 60&#37; of cases are due to IgE-mediated reactions with a 3&#46;5&#8211;10&#37; mortality rate&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> The most commonly involved agents are NMBA &#40;50&#8211;90&#37;&#41;&#44; latex &#40;4&#8211;30&#37;&#41; and antibiotics &#40;5&#8211;20&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11&#44;13</span></a> In other reports latex and antibiotics were identified as the main culprits&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;19</span></a> Dyes&#44; hypnotic agents&#44; local anaesthetics&#44; opioids&#44; colloids&#44; aprotinin&#44; protamine&#44; chlorhexidine&#44; and contrast agents are less frequently involved&#46; With some of these agents &#40;e&#46;g&#46; non-steroidal anti-inflammatory agents&#44; opioids and contrast agents&#41;&#44; non-immune mechanisms are more likely to be involved than IgE-mediated reactions&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#8211;20</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Diagnosis of perioperative allergic reactions is not always straightforward and the level of certainty in this area is still limited since provocation tests&#44; which are the gold standard in drug allergy diagnosis&#44; are contraindicated or impossible with many anaesthetics&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;21&#44;22</span></a> Skin tests remain the gold standard for the detection of type I reactions&#46; Some authors question the accuracy of these tests and point out the occurrence of false-positive results with intradermal testing due to non-specific histamine release by some agents with inappropriately higher concentrations &#40;e&#46;g&#46; NMBA and opioids&#41; or due to cross-reactions with other agents&#44; such as cough medication&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#8211;26</span></a> For this reason&#44; although recommendations regarding skin tests procedures have been published&#44; validation is still lacking&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;21&#8211;23</span></a> Laboratory tests include baseline and acute episode serum tryptase levels&#44; specific IgE assays and cellular assays &#40;e&#46;g&#46; histamine release assay&#44; basophil activation test and cellular antigen stimulation test&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;21&#44;22</span></a> Although such in vitro tools have been proposed in clinical practice&#44; they are not available in many centres&#46; Specific IgE assays have been developed for some drugs &#40;e&#46;g&#46; suxamethonium&#44; some beta-lactam antibiotics&#44; thiopental&#44; propofol&#44; chlorhexidine and aprotinin&#41;&#44; but they seem to be less sensitive than skin tests&#46; Basophil activation test has been proposed for the indirect detection of specific-IgE antibodies&#44; particularly when skin tests are difficult to interpret&#44; but they also require further investigation&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;21&#44;22</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We carried out a 5-year retrospective study of the clinical data of all patients with probable perioperative hypersensitivity reaction referred to our University Allergy Centre from 2007 to 2011&#46; Our aim was to compare the causes of perioperative allergic reactions to that in other countries&#44; to evaluate cross-reactivity among NMBA and to analyze the diagnostic relevance of tryptase levels in the discrimination between IgE and non-IgE-mediated hypersensitivity reactions&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Materials and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">All patients with perioperative reaction possibly due to IgE-mediated allergy during or immediately after general anaesthesia were included &#40;i&#46;e&#46; dermal signs&#44; such as generalized erythema&#44; urticaria or angioedema&#59; respiratory disturbances&#44; such as cough&#44; bronchospasm&#44; increased airway resistance or difficulty with ventilation&#59; cardiovascular signs&#44; such as hypotension&#44; tachycardia&#44; bradycardia&#44; arrhythmia and cardiac or respiratory arrest&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> The diagnostic workup included medical history &#40;age&#44; sex&#44; number of previous interventions&#44; history of other allergic diseases&#41;&#44; serum tryptase &#40;Uni-CAP Tryptase&#44; Phadia&#44; Sweden&#41; during the adverse reaction &#40;&#60;2<span class="elsevierStyleHsp" style=""></span>h&#41; and at a later time point &#40;several days&#47;weeks after&#41;&#44; and specific-IgE assays for latex&#44; penicillin&#44; amoxicillin and ethylene oxide &#40;Immuno-CAP System&#44; Phadia&#44; Sweden&#41;&#46; Data on the clinical characteristics and timing of the reaction as well as drugs administered during surgery were obtained from anaesthetic record charts&#46; An elevated tryptase level was defined as &#62;11&#46;4<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#44; according to the reference value provided by the company&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">All patients underwent skin tests with the drugs and&#47;or substances administered during the perioperative period and suspected of being involved in the reaction&#44; including latex &#40;commercial extracts for skin prick testing from ALK and Stallergenes&#41;&#46; Skin tests were performed according to standardized diagnostic procedures&#44; at least 4&#8211;6 weeks after the initial episode&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In case of a positive reaction to the NMBA used for the anaesthesia&#44; skin tests were also performed with other available NMBA&#44; in an attempt to find an alternative drug for future procedures&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnosis of an IgE-mediated reaction was suspected on the basis of the skin test and&#47;or IgE assay results consistent with the type of reaction and the anaesthetic protocol&#46; Statistical analysis was performed with GraphPad Prism 5 for Windows &#40;GraphPad Software&#44; Inc&#46;&#41;&#46; Fisher&#39;s exact test was used as the measure of contingency&#46; D&#8217;Agostino and Pearson omnibus normality test was used for serum tryptase data&#46; After logarithmic scale conversion&#44; paired and unpaired <span class="elsevierStyleItalic">t</span>-test were used ad hoc&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">A total of 119 patients were included&#44; with female preponderance &#40;61&#46;3&#37;&#41; and with ages ranging from 15 to 81 years &#40;mean age of 49&#46;8 years&#41;&#46; All patients had undergone general anaesthesia with NMBA&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Identification of IgE-mediated allergic reactions</span><p id="par0045" class="elsevierStylePara elsevierViewall">A diagnosis of IgE-mediated reaction was established by skin tests and&#47;or ImmunoCap in 76 cases &#40;63&#46;9&#37;&#41;&#46; The remaining 43 cases &#40;36&#46;1&#37;&#41; were considered as non-IgE-mediated reactions &#40;possibly non-immune as well&#41; and classified accordingly as &#8220;unidentified cases&#8221; &#40;see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Gender differences were not statistically associated with either the reaction mechanism or the causative agent&#46; A statistically significant association was found between atopy and IgE-mediated reactions &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#46; As for the clinical manifestations in patients with allergic reactions&#44; dermal symptoms &#40;erythema&#44; urticaria or angioedema&#41; were reported in 81&#46;6&#37;&#44; followed by cardiovascular symptoms in 72&#46;4&#37; &#40;hypotension&#44; tachycardia or bradycardia&#44; arrhythmia or cardiac arrest&#41; and respiratory symptoms in 34&#46;2&#37; &#40;cough&#44; bronchospasm&#44; increased airway resistance or difficulty inflating&#41;&#46; Isolated dermal symptoms occurred in 15&#46;8&#37; of cases&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The most frequent cause of perioperative allergic reactions was NMBA &#40;61&#46;9&#37;&#41;&#44; followed by antibiotics &#40;14&#46;5&#37;&#41;&#44; latex &#40;9&#46;2&#37;&#41; and chlorhexidine &#40;5&#46;2&#37;&#41;&#46; Among patients with NMBA allergy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>47&#41;&#44; the most common culprit agent was rocuronium &#40;48&#46;9&#37;&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">All patient with latex allergy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41; had positive skin prick tests and positive specific-IgE assays &#40;Immuno-CAP&#41;&#44; 7&#46;98<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;73<span class="elsevierStyleHsp" style=""></span>kU&#47;L&#46; Latex allergy was statistically associated with a history of asthma and&#47;or allergic rhinitis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;005 and relative risk&#44; RR of 3&#46;17&#44; 95&#37; CI&#41;&#46; After careful retrospective assessment of their medical history&#44; 3 patients &#40;42&#46;9&#37;&#41; reported previous symptoms of fruit allergy or intolerance to materials containing latex before surgery&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Antibiotic allergy was diagnosed in 11 patients&#44; in all but one &#40;i&#46;e&#46; rifampicin&#41; due to cephalosporins &#40;i&#46;e&#46; cefazoline&#41;&#46; Diagnosis was established by skin prick testing and intradermal testing&#46; None of these patients reported history of drug allergy&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Most patients &#40;77&#46;6&#37;&#41; with perioperative allergic reactions had undergone 1 or 2 surgical interventions under general anaesthesia in the past&#46; Nine patients reported adverse reactions during prior surgeries &#40;9&#47;59&#41;&#46; Urticaria was the most common previous perioperative reaction reported by patients&#46; Allergy to NMBA was diagnosed in 11 patients with no previous surgeries and no known previous exposures to NMBA &#40;23&#46;4&#37;&#41; &#40;see <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Allergic reactions most frequently occurred during the induction&#47;preparation phase &#40;72&#46;4&#37;&#41;&#46; Fifteen patients reacted during the maintenance phase and 6 during the recovery phase&#46; Among NMBA allergic patients&#44; most reactions occurred during the induction&#47;preparation phase &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001 and RR of 2&#46;21&#41; while IgE-mediated reactions to latex occurred mainly in the maintenance and recovery phases &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0152 and RR of 6&#46;55&#41;&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Tryptase levels</span><p id="par0080" class="elsevierStylePara elsevierViewall">Tryptase levels during the acute phase were obtained in 59 patients&#46; Among them&#44; 36 patients had experienced an IgE-mediated reaction &#40;61&#46;0&#37;&#41; and 23 patients had a non-IgE-mediated reaction &#40;39&#46;0&#37;&#41;&#46; Mean acute phase tryptase values were significantly higher in patients with IgE-mediated reactions &#40;59&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;0<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L versus 11&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0004&#41;&#46; No significant difference was found between basal tryptase levels of patients with IgE and non-IgE-mediated reactions&#46; Among patients with non-IgE-mediated reactions&#44; tryptase levels during the acute phase were above the upper limit &#40;&#62;11&#46;4<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#41; in 7 cases &#40;30&#46;4&#37;&#41;&#46; On the other hand&#44; among patients with IgE-mediated reactions&#44; tryptase levels were found to be increased in 29 cases&#44; but to be within the normal range in 7 &#40;19&#46;4&#37;&#41;&#46; All patients with tryptase levels above 25<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L had IgE-mediated perioperative reactions &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Non-irritant dilutions and cross-reactivity among NMBA</span><p id="par0085" class="elsevierStylePara elsevierViewall">Skin testing with inappropriately high concentrations can induce irritative reactions &#40;i&#46;e&#46; false-positive results&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Although none of our patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>119&#41; had been exposed to vecuronium&#44; we found a high rate of positive reactions on intradermal testing with 1&#58;10 dilution&#46; Among patients without NMBA allergy and without previous exposition to vecuronium &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41;&#44; intradermal test with 1&#58;10 dilution induced a positive reaction in 22 cases &#40;84&#46;6&#37;&#41;&#46; With 1&#58;100 or higher dilution&#44; only 3 out of these 26 patients were positive&#46; Mivacurium was tested in 14 patients not previously exposed to this drug and non-allergic to any other NMBA&#46; Among them&#44; 3 had a positive reaction with 1&#58;1000 or 1&#58;10&#44;000 dilutions&#46; With 1&#58;100 dilution&#44; 11&#47;14 &#40;85&#46;7&#37;&#41; had a positive reaction&#46; This high rate of false positive reactions with 1&#58;100 dilution is in accordance with other literature data and we did not consider this concentration in our analysis&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In patients with NMBA allergy it is important to propose an alternative agent for eventual surgeries in the future&#46; Therefore&#44; besides the culprit NMBA we also tested these patients with an alternative NMBA&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">For the skin test assessment of cross-reactivity between NMBA&#44; only the patients with proven NMBA allergy were considered &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>47&#41; &#40;see <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; and the highest concentrations for intradermal testing were 1&#58;100 for cisatracurium&#44; vecuronium and rocuronium&#44; 1&#58;1000 for mivacurium and suxamethonium&#46; Vecuronium was tested as an alternative agent in 42 patients&#46; A positive reaction was found in 20 patients and most of them &#40;75&#46;0&#37;&#41; had experienced a perioperative reaction with rocuronium&#46; Mivacurium was tested as an alternative drug in 26 patients and 12 were positive&#46; On the contrary&#44; rocuronium and cisatracurium showed low cross-reactivity risk on skin testing &#40;22&#46;3&#37; and 13&#46;9&#37; respectively&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">Similarly to what has been previously reported in the literature&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;16</span></a> NMBA were the leading cause of perioperative allergic reactions &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>47&#44; 61&#46;9&#37;&#41; in our series&#46; Antibiotics represent the third cause in most reports&#46; Our data shift antibiotic allergy to the second place &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#44; 14&#46;5&#37;&#41;&#46; Cephalosporins &#40;cefazoline in particular&#41; were involved in all but one of these cases&#46; This high prevalence could possibly be due to their widespread use in the context of general anaesthesia in Belgium&#44; although we have no exact data on this issue&#46; The impact of each causative agent on perioperative allergy will eventually change with time and can be different in other geographical areas&#44; as it is influenced by the variable pattern of usage&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;13&#44;27</span></a> In the past&#44; suxamethonium was the most frequently reported cause of perioperative allergic reactions but it is now a rare cause of allergy as it is seldom used&#46; Recent data instead suggest an increasing incidence of allergy to atracurium&#44; rocuronium and cisatracurium&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;28</span></a> Our results also indicate a high incidence of allergy to rocuronium &#40;48&#46;9&#37; of all NMBA allergic patients&#41;&#46; This apparent increase might rather be due to an increased rocuronium market share&#44; biased reporting of adverse effects of new drugs or possibly by false positive results on skin tests&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;27&#8211;29</span></a> It should be mentioned that we have no data on the market share of NMBA in Belgium&#46; Mertes et al&#46; classified suxamethonium and rocuronium as drugs with a high risk of sensitization&#44; pancuronium and vecuronium as having medium risk and atracurium and cisatracurium as having a low risk&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> These conclusions could be reached by relating the occurrence of allergic reactions to the frequency of use for anaesthesia&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Cross-reaction occurs commonly among NMBA &#40;60&#8211;70&#37; of the patients&#41; and demands special attention regarding the selection of an alternative drug&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;28&#44;29</span></a> It is recommended to perform skin tests with several commercially available NMBA in order to increase the probability of finding a safe alternative&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> According to Mertes et al&#46; vecuronium has the highest risk of cross-reaction &#40;87&#46;5&#37;&#41; followed by rocuronium &#40;80&#46;6&#37;&#41;&#44; atracurium &#40;76&#46;8&#37;&#41; and suxamethonium &#40;54&#46;3&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In another study&#44; rocuronium was the least cross-reactive&#44; with negative skin-tests in one-third of the patients with NMBA allergy&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> We also found vecuronium &#40;at the 1&#58;100 or 1&#58;1000 dilution&#41; to have the highest cross-reactivity rate assessed by skin testing &#40;47&#46;6&#37;&#41;&#46; On the contrary&#44; rocuronium and cisatracurium showed low cross-reactivity risk &#40;22&#46;3&#37; and 13&#46;9&#37;&#44; respectively&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Although skin tests were performed with &#8216;non-irritant&#8217; concentrations according to international protocols&#44; a significant number of patients reacted to vecuronium at the 1&#58;10 dilution&#46; These were probably irritative reactions &#40;i&#46;e&#46; false-positive results&#41; as none of these patients received vecuronium during present or past surgeries and none reacted to any NMBA other than vecuronium&#46; This raises questions on validation of skin test procedures&#46; We therefore conclude that 1&#58;10 dilution of vecuronium induces a high rate of false-positive reactions and higher dilution factors &#40;i&#46;e&#46; 1&#58;100 or more&#41; should be used&#46; Low concentrations however may compromise the sensitivity of the diagnostic procedure&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Among patients who received mivacurium during surgery &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41;&#44; 11 had positive reaction with the prick test or with intradermal test at 1&#58;1000 or 1&#58;10&#44;000 dilutions and were accordingly considered allergic to mivacurium&#46; The other 15 patients reacted with 1&#58;100 dilution &#40;intradermal test&#41; and in 2 of these cases another cause for the perioperative reaction was found &#40;antibiotics&#41;&#46; In view of the false positive reactions with this dilution as already pointed out by Mertes et al&#46;&#44; we could not ascertain the diagnosis of mivacurium allergy in these 13 subjects&#44; and considered them as negative&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Whether or not these patients were allergic to mivacurium remains uncertain&#46; Therefore&#44; more research is still required in order to avoid diagnostic errors&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Seven of our patients had latex allergy&#46; Atopy&#44; female gender&#44; professional exposure&#44; repeated surgeries or procedures involving natural rubber latex products&#44; especially in the first year of life&#44; constitute important risk factors for latex allergy&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Our data indicate that risk factors for latex allergy could have been identified in 3&#47;7 patients by a more careful history &#40;latex-fruit syndrome in 1 patient and adverse symptoms with latex products in 2 patients&#41;&#44; drawing attention to the need for a specific preoperative screening instead of a standard preanaesthetic questionnaire&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;10</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Most patients with IgE-mediated reactions had previous exposure to anaesthetic drugs&#46; Reactions occurred upon first contact in 17 patients &#40;22&#46;4&#37;&#41;&#44; a rate higher than seen in France &#40;12&#46;3&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Most cases &#40;64&#46;7&#37;&#41; were attributed to NMBA hypersensitivity&#46; According to literature&#44; allergic reactions to NMBA can occur on the first exposure in 15&#8211;50&#37; of cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;13</span></a> Sensitization to quaternary amine epitopes&#44; the major allergenic determinants in NMBA&#44; might be the result of cross-reaction pathways&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Sex hormones have been suggested to have immunomodulatory properties&#44; skewing the immune response towards a Th2 profile and may&#44; therefore&#44; play a role in drug sensitization&#46; This could explain the higher prevalence of IgE-mediated perioperative anaphylaxis in female patients&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The timing of reaction is&#44; to some extent dependent on the culprit agent and the route of exposure&#46; Antibiotics are often given intravenously at induction&#44; commonly within a minute of induction agents and a rapid onset of symptoms is usually reported&#46; The same applies to NMBA&#46; With latex&#44; the allergens are absorbed through the peritoneum&#44; respiratory mucosa or skin and symptoms tend to develop more slowly&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In line with previous reports&#44; we found significant differences in time of onset of symptoms&#44; with NMBA allergy causing symptoms during the induction&#47;preparation phase and latex allergy being responsible for later phase reactions&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Concerning clinical features&#44; dermal symptoms are the most commonly reported but may be absent in about one-third of patients&#44; particularly in cases of rapidly progressive anaphylaxis&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;19</span></a> We found 22&#46;4&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>17&#41; patients with IgE-mediated reaction with no skin involvement&#46; Therefore&#44; the absence of dermal symptoms should not preclude an allergic mechanism&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Serum tryptase elevation can occur in both IgE-mediated and non-IgE-mediated reactions and does not help to identify the specific cause&#46; In a study of 712 patients with perioperative allergic reactions&#44; the positive predictive value of tryptase for the diagnosis of perioperative anaphylaxis &#40;IgE-mediated mechanism&#41; was 95&#46;3&#37; and the negative predictive value was 49&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> According to our results&#44; mean tryptase values during acute reactions were significantly higher in patients with IgE-mediated reactions&#46; At a cut-off value of 25<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L instead of 11&#46;4<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#44; serum tryptase is highly suggestive of an IgE-mediated reaction&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Regarding the limitations of our work&#44; the data on atopy were based exclusively on a history of eczema&#44; asthma and&#47;or rhinitis&#46; This constitutes a relevant limitation for the analysis of atopy as a risk factor for perioperative allergy&#46; The data on timing of reaction and clinical manifestations were not available in all cases due to inappropriate reports in anaesthetic charts&#46; Tryptase data &#40;i&#46;e&#46; acute phase or basal assessment&#41; were not available for some patients&#44; and blood samples during the acute reaction were taken in the first 6<span class="elsevierStyleHsp" style=""></span>h but not necessarily all at the same time point in relation to the acute reaction&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Globally&#44; these results support an active policy of risk reduction&#44; with control of unnecessary exposure to potentially sensitizing compounds &#40;i&#46;e&#46; quaternary amine epitopes&#41; and a systematic search for eventual risk factors before anaesthesia &#40;e&#46;g&#46; latex allergy and latex-fruit syndrome&#41;&#46; Further&#44; it is crucial to raise awareness among anaesthesiologists and surgeons for identifying patients with history of allergic perioperative reactions and to perform a proper evaluation before eventual reexposure&#46; Intradermal tests should be performed and interpreted only by experienced physicians and the assessment of non-irritative concentrations&#44; in particular for NMBA&#44; should receive more attention in the future research&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Brief summary statement</span><p id="par0165" class="elsevierStylePara elsevierViewall">In a retrospective analysis of 119 patients with perioperative hypersensitivity reactions&#44; an IgE-mediated allergy was diagnosed in 64&#37; of cases&#46; Neuromuscular blocking agents remain the agents most likely to cause an IgE-mediated reaction&#46; Antibiotics were more frequently involved than latex and some rare causes were also identified&#46; The authors raise a number of concerns about validity and sensitivity of drug skin testing&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Ethical disclosures</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patients&#8217; data protection</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Right to privacy and informed consent</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Protection of human subjects and animals in research</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Financial support</span><p id="par0185" class="elsevierStylePara elsevierViewall">Grant from the <span class="elsevierStyleGrantSponsor" id="gs0005">Study Center for Allergy Projects &#40;SCAP&#41;</span>&#44; Harlem&#44; The Netherlands&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare&#46;</p></span></span>"
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              "identificador" => "sec0020"
              "titulo" => "Identification of IgE-mediated allergic reactions"
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          "titulo" => "Tryptase levels"
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              "titulo" => "Non-irritant dilutions and cross-reactivity among NMBA"
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              "titulo" => "Patients&#8217; data protection"
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              "titulo" => "Right to privacy and informed consent"
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              "titulo" => "Protection of human subjects and animals in research"
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          "palabras" => array:5 [
            0 => "Anaesthesia"
            1 => "Drug allergy"
            2 => "Latex"
            3 => "Neuromuscular blocking agents"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The incidence of perioperative anaphylactic reactions is overall estimated to be 1 per 10&#44;000&#8211;20&#44;000 anaesthetic procedures&#46; We performed a retrospective analysis of patients referred to a University Allergy Centre in Belgium with the suspicion of an allergic reaction during or shortly after general anaesthesia&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Our aim was to assess the causes of perioperative allergic reactions&#44; to evaluate cross-reactivity among neuromuscular blocking agents &#40;NMBA&#41; and to analyze the diagnostic relevance of tryptase levels in the discrimination between IgE and non-IgE-mediated reactions&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 119 patients&#44; referred from 2007 to 2011 were included&#46; The diagnostic protocol consisted in case history&#44; serum tryptase measurements&#44; immunoassays and skin tests&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A diagnosis of IgE-mediated reaction was established in 76 cases &#40;63&#46;9&#37;&#41;&#46; The most common agents were NMBA &#40;61&#46;8&#37;&#41;&#44; antibiotics &#40;14&#46;5&#37;&#41;&#44; latex &#40;9&#46;2&#37;&#41; and chlorhexidine &#40;5&#46;2&#37;&#41;&#46; Rocuronium was the most frequently causative NMBA &#40;48&#46;9&#37;&#41;&#46; Vecuronium cross-reactivity was established by skin testing in 47&#46;6&#37; of cases&#46; Cisatracurium was the NMBA most frequently tolerated &#40;cross-reaction in 13&#46;9&#37;&#41;&#46; In 23&#46;4&#37; of NMBA allergic patients&#44; the reaction occurred on the first exposure&#46; Most IgE-mediated reactions occurred during the induction phase &#40;72&#46;4&#37;&#41;&#46; Latex-induced reactions occurred mainly during maintenance and recovery phases &#40;71&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; Mean tryptase values were significantly higher in patients with IgE-mediated reactions &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; than in those with no identified cause&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">NMBA&#44; antibiotics&#44; latex and chlorhexidine were the main culprits of IgE-mediated perioperative reactions&#46; Uncertainties remain concerning the specificity and sensitivity of skin testing&#46; Tryptase assays can be useful in the discrimination of IgE and non-IgE-mediated reactions&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Present address&#58; Department of Immunoallergy&#44; Dona Estef&#226;nia Hospital&#44; Centro Hospitalar de Lisboa Central&#44; Lisbon&#44; Portugal&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Meetings at which the work has been presented&#58; XXX Congress of the European Academy of Allergy and Clinical Immunology&#46; Geneva&#44; 16&#8211;20 July 2012&#46;</p>"
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&#8805;1 previous surgery &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Adverse reaction during previous surgeries &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antibiotics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;72&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;14&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chlorhexidine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;50&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Latex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;42&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;57&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;50&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NMBA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;23&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;76&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Others&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;42&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;22&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59 &#40;77&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;11&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab522870.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Previous surgeries in patients with IgE-mediated perioperative reactions &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>76&#41;&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Causal agent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&#46; of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Skin test positivity for other NMBA agents<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Cisatracurium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Mivacurium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Rocuronium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Vecuronium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atracurium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#58;3 &#40;66&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#58;3 &#40;66&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#58;3 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#58;3 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cisatracurium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#58;4 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#58;6 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#58;6 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mivacurium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#58;10 &#40;20&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#58;11 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#58;9 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rocuronium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#58;21 &#40;4&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#58;17 &#40;23&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#58;22 &#40;68&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suxamethonium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#58;2 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#58;2 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#58;2 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#58;2 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#58;36 &#40;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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Original language: English
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos