rocuronium and Drug-Hypersensitivity

Many adverse reactions to therapeutic drugs appear to be allergic in nature, and are thought to be triggered by patient-specific Immunoglobulin E (IgE) antibodies that recognize the drug molecules and form complexes with them that activate mast cells. However, in recent years another mechanism has been proposed, in which some drugs closely associated with allergic-type events can bypass the antibody-mediated pathway and trigger mast cell degranulation directly by activating a mast cell-specific receptor called Mas-related G protein-coupled receptor X2 (MRGPRX2). This would result in symptoms similar to IgE-mediated events, but would not require immune priming. This review will cover the frequency, severity, and dose-responsiveness of allergic-type events for several drugs shown to have MRGPRX2 agonist activity. Surprisingly, the analysis shows that mild-to-moderate events are far more common than currently appreciated. A comparison with plasma drug levels suggests that MRGPRX2 mediates many of these mild-to-moderate events. For some of these drugs, then, MRGPRX2 activation may be considered a regular and predictable feature after administration of high doses.

Topics: Anaphylaxis; Animals; Atracurium; Cell Degranulation; Drug Hypersensitivity; Humans; Immunoglobulin E; Mast Cells; Morphine; Nerve Tissue Proteins; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Rocuronium; Vancomycin

Cyclodextrins, oligosaccharides linked in a circular arrangement around a central cavity, are used extensively in the pharmaceutical industry to improve drug delivery. Their usefulness depends on their capacity to form a drug inclusion, or host-guest, complex within the cavity. In an attempt to improve the delivery of the widely used neuromuscular blocking drug (NMBD) rocuronium, a rocuronium inclusion complex was formed with a chemically modified γ-cyclodextrin. The high binding affinity and specificity of the modified carrier (named sugammadex) for rocuronium (and other aminosteroid NMBDs) led to its use in anaesthesia as an innovative and useful agent for rapid reversal of rocuronium-induced neuromuscular block by sequestering the drug as an inclusion complex. This, in turn, led to the suggestion that sugammadex might be useful to remove the NMBD from the circulation of patients experiencing rocuronium-induced anaphylaxis, a suggestion subsequently supported in case reports where traditional treatment had failed. Successful resuscitations suggested that sugammadex might be a valuable new treatment for such intractable cases but, given the inappropriateness of clinical trials, confirmation or refutation will have to await the slow accumulation of results of individual case reports. Important questions related to antibody accessibility of drug allergenic structures on the rocuronium-sugammadex inclusion complex, and the competition between sugammadex and IgE antibodies (both free and cell bound) for rocuronium, also remain and can be investigated in vitro. The sugammadex findings indicate that the use of carrier molecules such as the cyclodextrins to improve drug delivery will sometimes give rise to changed immunologic and allergenic behaviour of some drugs and this will have to be taken into account in preclinical drug safety assessments of drug-carrier complexes. The possibility of encapsulating and removing other allergenic drugs, e.g., penicillins and cephalosporins, in cases of difficult-to-reverse anaphylaxis to these drugs is discussed.

Topics: Anaphylaxis; Androstanols; Cyclodextrins; Drug Hypersensitivity; Drug Interactions; gamma-Cyclodextrins; Humans; Neuromuscular Nondepolarizing Agents; Perioperative Period; Rocuronium; Sugammadex

Topics: Anaphylaxis; Androstanols; Anesthesia; Anesthetics, Local; Anti-Bacterial Agents; Arginine Vasopressin; Drug Hypersensitivity; Homeostasis; Humans; Immunoglobulin E; Latex Hypersensitivity; Neuromuscular Blocking Agents; Risk Factors; Rocuronium; Skin Tests

We report a grade III allergic hypersensitivity reaction occurring in a 72-year-old patient immediately after anaesthesia induction. Anaphylaxis to cisatracurium was diagnosed on clinical symptoms, biological tests and positivity of the cutaneous tests to this neuromuscular blocking agent. Five days after this allergological assessment, rocuronium, a muscle relaxant for which skin tests appeared negative was used during surgery without adverse effects. The authors underline the value of a detailed allergological assessment to identify the pathophysiologic mechanism, the culprit drug and to propose a safer alternate drug that might be used.

Topics: Adenocarcinoma; Aged; Anaphylaxis; Androstanols; Atracurium; Bronchial Spasm; Drug Hypersensitivity; Humans; Intraoperative Complications; Male; Neuromuscular Nondepolarizing Agents; Rectal Neoplasms; Rocuronium; Sigmoid Neoplasms; Skin Tests

Numerous reports confirm the performance of intradermal tests for the diagnosis of anaphylaxis during anesthesia; however, there is controversy over their diagnostic value regarding the newer neuromuscular blocking agents (NMBAs).. One hundred eleven healthy volunteers were randomly assigned to receive intradermal injections of two NMBAs, at five increasing concentrations. A concentration was considered as a reactive concentration when it led to a positive reaction in more than 5% of the subjects. These concentrations were compared with the maximal concentration recommended for the diagnosis of sensitization to NMBAs.. The maximal nonreactive concentrations were 10 m for suxamethonium; 10 m for pancuronium, vecuronium, rocuronium, and cisatracurium; and 10 m for atracurium and mivacurium. Except for mivacurium, these nonreactive concentrations were close to the maximal concentrations used for the diagnosis of sensitization against NMBAs. For mivacurium, the nonreactive concentrations were higher than the maximal concentration currently recommended in clinical practice.. The aminosteroidal NMBAs pancuronium, vecuronium, and rocuronium and the benzylisoquinoline cisatracurium have a similar potency to induce a nonspecific skin reactivity. If the criteria for positivity and the maximal concentrations of the commercially available compounds recommended by French practice guidelines are used, the risk of false-positive results is limited, and only minor modifications of these recommendations could be suggested. A slight reduction in the maximal concentration used for rocuronium from 1:100 to 1:200 and an increase from 1:1,000 to 1:200 for mivacurium can be proposed.

Topics: Adolescent; Adult; Androstanols; Atracurium; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Humans; Injections, Intradermal; Isoquinolines; Male; Middle Aged; Mivacurium; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Pancuronium; Reference Values; Rocuronium; Skin; Skin Tests; Succinylcholine; Vecuronium Bromide

Diagnosis of allergy from neuromuscular blocking agents is not always straightforward. The objectives of the current study were to investigate the value of quantification of immunoglobulin E (IgE) by ImmunoCAP (Phadia AB, Uppsala, Sweden) in the diagnosis of rocuronium allergy and to study whether IgE inhibition tests can predict clinical cross-reactivity between neuromuscular blocking agents.. Twenty-five rocuronium-allergic patients and 30 control individuals exposed to rocuronium during uneventful anesthesia were included. Thirty-two sera (total IgE > 1,500 kU/l) were analyzed for potential interference of elevated total IgE titers. Results were compared with quantification of IgE for suxamethonium, morphine, and pholcodine. Cross-reactivity between drugs was assessed by IgE inhibition and skin tests.. Sensitivity of IgE for rocuronium, suxamethonium, morphine, and pholcodine was 68, 60, 88, and 86%, respectively. Specificity was 100% for suxamethonium, morphine, and pholcodine IgE and 93% for rocuronium IgE. ROC analysis between patients and control individuals changed the threshold to 0.13 kUa/l for rocuronium, 0.11 kUa/l for suxamethonium, 0.36 kUa/l for morphine, and 0.43 kUa/l for pholcodine. Corresponding sensitivity was 92, 72, 88, and 86%, respectively. Specificity was unaltered. Interference of elevated total IgE with quantification of IgE was demonstrated by the analysis in sera with a total IgE greater than 1,500 kU/l. IgE inhibition did not predict clinical relevant cross-reactivity.. The rocuronium ImmunoCAP constitutes a reliable technique to diagnose rocuronium allergy, provided an assay-specific decision threshold is applied. IgE assays based on compounds bearing ammonium epitopes are confirmed to represent reliable tools to diagnose rocuronium allergy. High total IgE titers were observed to affect specificity of the assays.

Topics: Analgesics; Androstanols; Antibodies, Anti-Idiotypic; Antibody Specificity; Codeine; Cross Reactions; Drug Hypersensitivity; Humans; Immunoglobulin E; Morphine; Morpholines; Narcotics; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Reference Values; ROC Curve; Rocuronium; Sensitivity and Specificity; Skin Tests; Succinylcholine

Prick tests are frequently used for the authentication of neuromuscular blocking drugs (NMBDs) as causative drugs for anaphylactic reactions during anesthesia. Unfortunately, the actual threshold concentration for skin testing remains debatable for most NMBDs. We studied the flare and wheal responses to prick tests with rocuronium and vecuronium. Thirty healthy, nonatopic, anesthesia-naive male and female volunteers (14 men and 16 women) from 18 to 40 yr of age were assigned randomly to receive a total of 10 prick tests-4 ascending dilutions (1:1000, 1:100, 1:10, and 1) of rocuronium and vecuronium and 2 controls-on both forearms. An assessor blinded to the assignment monitored systemic and skin responses to NMBDs and measured wheal and flare surfaces immediately after and 15 min after prick tests. None of the volunteers experienced any immediate systemic or cutaneous responses to rocuronium or vecuronium. Although a dilution of 1:1000 of both NMBDs failed to promote any skin response at 15 min, 50% and 40% of the subjects had a positive skin reaction to undiluted rocuronium and vecuronium, respectively. We demonstrated a sex effect related to smaller threshold concentration-induced cutaneous reactions in female volunteers to both muscle relaxants. Our observation questions the reliability of prick testing with undiluted solutions of rocuronium and vecuronium for the diagnosis of allergy.. Building concentration-skin response curves to prick tests with rocuronium and vecuronium in healthy, nonatopic, anesthesia-naive male and female volunteers demonstrated that the nonreactive concentration for both muscle relaxants is the 1:1000 dilution of the stock solutions. Our observation calls into question the past practice of prick-testing skin for sensitivity to neuromuscular blocking drugs by using undiluted solutions.

Topics: Adolescent; Adult; Anaphylaxis; Androstanols; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Humans; Male; Neuromuscular Nondepolarizing Agents; Rocuronium; Sex Characteristics; Skin Tests; Vecuronium Bromide

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Androstanols; Atracurium; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Histamine Release; Humans; Indicator Dilution Techniques; Male; Mast Cells; Microscopy, Electron; Middle Aged; Neuromuscular Nondepolarizing Agents; Regression Analysis; Risk Assessment; Rocuronium; Skin; Skin Tests

The cross-reactivity of rocuronium with other neuromuscular blocking agents (NMBAs) was studied in 31 patients known to be allergic to a muscle relaxant. Tests for diagnosing cross-reactivity were skin tests (prick tests and intradermal tests: IDTs), detection by RAST assay of IgEs against the quaternary ammonium group (QAS-RIA: quaternary ammonium sepharose radio-immuno-assay), QAS-RIA inhibition test to detect IgE specificity, and leucocyte histamine release test (LHRT). Skin tests were performed with rocuronium, suxamethonium, gallamine, vecuronium, pancuronium, atracurium. The threshold for cross-reactivity was 10(-1) with all the NMBAs except for atracurium (10(-2)). The inhibition test and LHRT were performed with rocuronium and the NMBA responsible for the shock. Ten volunteers made up the control group for prick tests, QAS-RIA, LHRT. Cross-reactivity was found in 30 patients out of 31. Rocuronium did not cross-react in 10 patients out of 31. They had negative cutaneous tests and negative LHRTs. In one of the five patients allergic to all the NMBAs available, rocuronium was the only one which did not cross-react. In those 10 patients, rocuronium may be safely used for subsequent anaesthesia. In terms of allergy, rocuronium appeared to be very close to the other steroidal NMBAs.

Topics: Adult; Aged; Androstanols; Antibody Specificity; Cross Reactions; Drug Hypersensitivity; Female; Histamine Release; Humans; In Vitro Techniques; Leukocytes; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Passive Cutaneous Anaphylaxis; Radioimmunoassay; Rocuronium; Skin Tests

The optimal timing of diagnostic testing for perioperative hypersensitivity (POH) remains unknown. It has been recommended that investigation is best carried out at least 4 to 6 weeks after the event. On the other hand, guidelines discourage the use of in vitro tests later than 3 years after the index reaction.. This retrospective study aimed to assess the reliability of early and late skin tests (STs). It also attempted to verify whether discouraging late ex vivo and in vitro tests is substantiated.. For the first aim, patients were stratified over three epochs: an early timing group, with investigations performed within 6 weeks; a recommended timing group, with tests performed between 6 weeks and 6 months; and a late timing group, tested later than 6 months after the event. For the second study purpose, we studied the reliability of specific IgE quantification and basophil activation test rocuronium within 6 weeks and after 3 years in patients who experienced an ST-proven POH to rocuronium.. A total of 677 patients were included. Based on a positive ST result, a causative agent was found in 74.2% of the early timing group, 62.6% of the recommended timing group, and 50% of the late timing group. A positive specific IgE for rocuronium or morphine was found in 80% of patients tested within 6 weeks, 63% of patients tested between 6 weeks and 3 years, and 50% of patients tested more than 3 years after the event. A positive basophil activation test was found in 83.3%, 51%, and 20%, respectively, of patients.. Our data confirm that evaluation of drug allergy for suspected POH can be performed before 6 weeks after the event, and there is no maximal upper time limit disclosing ex vivo and in vitro testing.

Topics: Anaphylaxis; Drug Hypersensitivity; Humans; Immunoglobulin E; Reproducibility of Results; Retrospective Studies; Rocuronium; Skin Tests

Mas-related G protein-coupled receptor-X2 (MRGPRX2) expressed on mast cells (MCs) contributes to hypersensitivity reactions to cationic US-Food and Drug Administration (FDA) approved drugs such as the neuromuscular blocking agent, rocuronium. In addition, activation of MRGPRX2 by the neuropeptide substance P (SP) and the pro-adrenomedullin peptide (PAMP-12) is associated with a variety of cutaneous conditions such as neurogenic inflammation, pain, atopic dermatitis, urticaria, and itch. Thus, small molecules aimed at blocking MRGPRX2 constitute potential options for modulating IgE-independent MC-mediated disorders. Two inverse MRGPRX2 agonists, named C9 and C9-6, have recently been identified, which inhibit basal G protein activation and agonist-induced calcium mobilization in transfected HEK293 cells. Substance P serves as a balanced agonist for MRGPRX2 whereby it activates both G protein-mediated degranulation and β-arrestin-mediated receptor internalization. The purpose of this study was to determine if C9 blocks MRGPRX2's G protein and β-arrestin-mediated signaling and to determine its specificity. We found that C9, but not its inactive analog C7, inhibited degranulation in RBL-2H3 cells stably expressing MRGPRX2 in response to SP, PAMP-12 and rocuronium with an IC

Topics: Adrenomedullin; Anaphylatoxins; Animals; beta-Arrestins; beta-N-Acetylhexosaminidases; Calcium; Cell Degranulation; Drug Hypersensitivity; HEK293 Cells; Humans; Immunoglobulin E; Mast Cells; Mice; Nerve Tissue Proteins; Neuropeptides; Pertussis Toxin; Receptors, G-Protein-Coupled; Receptors, IgE; Receptors, Neuropeptide; Rocuronium; Substance P

Hypersensitivity reactions are an important aspect of perioperative care and are a crucial interdisciplinary issue in anaesthesiological practice, as well as allergological and laboratory diagnostics. This phenomenon was observed as early as the 1980s and 1990s in Western European countries, and knowledge on this subject has grown significantly over time. Although hypersensitivity reactions are not frequent events (the incidence of perioperative hypersensitivity reactions ranges from 1:386 to 1:13 000 procedures, with higher frequency - 1 per 6500 general anaesthesias with neuromuscular blocking agents administrations), their courses are unfortunately serious and life-threatening. It should also be noted that there is no information regarding the occurrence of perioperative hypersensitivity reactions in many countries. Hence, global assessment of the problem is underestimated. The primary source of actual knowledge comes from epidemiological studies, which indicate an increasing frequency of hypersensitivity reaction occurrence and changes in aetiological factors. The first report from France (1984 to 1989) described two main causes - neuromuscular blocking agents and hypnotic agents. The following years confirmed an increase in perioperative hypersensitivity reactions associated with latex and antibiotics. The most recent data from the National Audit Project 6 indicated increased participation of antibiotics, chlorhexidine, and contrast agents. The results of epidemiological analyses are the basis of medical management guidelines and practice modification. Thanks to the activity of many organisations monitoring the intensity and nature of perioperative hypersensitivity reactions, guidelines for diagnostics and management have been developed. This article presents the results of numerous studies, including the first and the most recent, from various geographical regions. The clinical significance, pathogenesis mechanisms are also discussed. This publication also presents important directions for further scientific and epidemiological research on perioperative hypersensitivity reactions.Key messagesThe incidence of perioperative hypersensitivity reactions ranges from 1:386 to 1:13 000 procedures, with higher frequency - 1 per 6500 general anaesthesias with neuromuscular blocking agents administrations.Reactions may occur during the first episode of anaesthesia, most frequently in the induction of general anaesthesia, and much less frequently during postope

Topics: Anaphylaxis; Anesthesia, General; Contrast Media; Drug Hypersensitivity; Humans; Neuromuscular Nondepolarizing Agents; Patient Safety; Perioperative Care; Rocuronium

Topics: Adolescent; Adult; Aged; Drug Hypersensitivity; Female; Humans; Immunoglobulin E; Male; Middle Aged; Nerve Tissue Proteins; Neuromuscular Nondepolarizing Agents; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Retrospective Studies; Rocuronium; Skin Tests; Young Adult

Neuromuscular blocking agents (NMBAs) like atracurium and rocuronium as well as fluoroquinolones (FQs) cause mast cell-mediated anaphylaxis by activating Mas-related G protein-coupled receptor X2 (MRGPRX2), but many questions remain unanswered. Here, we address three of them, namely whether primary human mast cells show similar activation by these drugs as murine mast cells and mast cell lines, how sugammadex protects from atracurium-induced MRGPRX2-mediated mast cell activation, and why some but not all patients treated with rocuronium develop anaphylaxis. We used peripheral blood-derived cultured mast cells from healthy donors and patients, assessed mast cell activation and degranulation by quantifying intracellular calcium and CD63 expression, respectively, and made use of MRGPRX2-silencing,

Topics: Anaphylaxis; Anti-Bacterial Agents; Atracurium; Calcium Signaling; Cell Degranulation; Cells, Cultured; Ciprofloxacin; Drug Hypersensitivity; Humans; Immunoglobulin E; Levofloxacin; Mast Cells; Nerve Tissue Proteins; Neuromuscular Nondepolarizing Agents; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Rocuronium; Time Factors

Topics: Basophils; Drug Hypersensitivity; Humans; Immunoglobulin E; Neuromuscular Nondepolarizing Agents; Reproducibility of Results; Retrospective Studies; Rocuronium; Skin Tests

Topics: Anaphylaxis; Drug Hypersensitivity; GTP-Binding Proteins; Humans; Receptors, G-Protein-Coupled; Rocuronium

The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests.. Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018.. We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery.. After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Anesthetics, General; Anesthetics, Intravenous; Atracurium; Drug Hypersensitivity; Female; Fentanyl; Humans; Male; Middle Aged; Neuromuscular Blocking Agents; Perioperative Period; Predictive Value of Tests; Propofol; Remifentanil; Rocuronium; Skin Tests; Sugammadex; Young Adult

The objective of the study is to describe an emergency procedure for left ventricle venting during veno-arterial extracorporeal life support for refractory cardiac arrest. Veno-arterial extracorporeal membrane oxygenation is widely used in refractory cardiac arrest but is characterized by an increase in left ventricle afterload, which may impair cardiac contractility improvement. Different left ventricle venting techniques are available. We report the use of a surgical approach with sternotomy for left ventricle venting in a 21-year-old patient who was placed under veno-arterial extracorporeal membrane oxygenation for refractory cardiac arrest with severe pulmonary edema, respiratory failure, and left ventricle stasis. A 21-year-old woman was admitted for laparoscopic sleeve gastrectomy. In the recovery room, she developed a refractory circulatory shock. Transthoracic echocardiography revealed a dilated cardiomyopathy with severe left ventricle systolic dysfunction (left ventricle ejection fraction at 20%). Coronary angiogram was normal. On day 2, she underwent laparotomy for sepsis and she presented cardiac arrest secondary to ventricular tachycardia. We proceeded to peripheral veno-arterial extracorporeal membrane oxygenation as the cardiac arrest was refractory. A miniaturized veno-arterial extracorporeal membrane oxygenation system was implanted into the right femoral vessels onsite .The low flow duration was 40 minutes. Veno-arterial extracorporeal membrane oxygenation blood flow was set to 3 L min

Topics: Anesthesia Recovery Period; Drug Hypersensitivity; Extracorporeal Membrane Oxygenation; Female; Gastrectomy; Heart Arrest; Humans; Laparoscopy; Myocarditis; Neuromuscular Nondepolarizing Agents; Recovery of Function; Rocuronium; Sternotomy; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Young Adult

The neuromuscular blocking agent (NMBA) rocuronium is a relevant cause of perioperative hypersensitivity (POH) with a significant risk of diagnostic error. Recently, it has been suggested to reclassify hypersensitivity to NMBA as type A reactions resulting from off-target occupation of the nonimmune MRGPRX2 receptor.. To investigate whether basophil activation experiments can benefit diagnosis and add to the insights in the pathomechanisms of rocuronium hypersensitivity.. A total of 140 patients with a suspected POH to rocuronium in whom peak tryptase was available had complete diagnostic workup for all potential culprits including triple confirmatory testing with skin tests, basophil activation test (BAT), and quantification of specific IgE (sIgE) antibodies to rocuronium and morphine. To further analyze the clinical relevance of sIgE antibodies, quantitative basophil inhibition experiments were performed by coincubation of the cells with rocuronium and morphine, an opiate known to harbor a substituted ammonium structure.. Diagnosis of rocuronium hypersensitivity was established in 72 of 140 patients (51.4%), of whom 65 (90.3%) demonstrated mast cell activation. Of the 72 patients, 64 displayed a positive skin test, 8 (11.1%) had their diagnosis documented only by BAT. Coincubation of morphine and rocuronium induced a dose-dependent inhibition of BAT with rocuronium that was restricted to 4 of 6 patients with IgE reactivity to rocuronium and/or morphine.. BAT can benefit diagnosis of rocuronium hypersensitivity. As basophils barely express MRGPRX2 and BAT rocuronium can be inhibited by morphine, we believe that hypersensitivity to rocuronium still mainly results from IgE/high-affinity receptor for sIgE (FcεRI)-dependent effector cell activation. However, it cannot be excluded that in a few patients rocuronium hypersensitivity results from off-target occupation of the MRGPRX2 receptor.

Topics: Adult; Aged; Basophil Degranulation Test; Drug Hypersensitivity; Female; Humans; Immunoglobulin E; Male; Mast Cells; Middle Aged; Nerve Tissue Proteins; Neuromuscular Nondepolarizing Agents; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Rocuronium; Skin Tests; Young Adult

Topics: Abdominal Pain; Adolescent; Anaphylaxis; Anesthesia, Dental; Drug Hypersensitivity; Ephedrine; Epinephrine; Female; Humans; Molar, Third; Pain, Postoperative; Postoperative Period; Rocuronium; Severity of Illness Index; Sugammadex; Tooth Extraction

Topics: Anesthesia, General; Appendectomy; Appendicitis; Drug Hypersensitivity; Epinephrine; Erythema Nodosum; Female; Heart Arrest; Humans; Immunoglobulin E; Mast Cells; Mastocytosis, Systemic; Middle Aged; Neuromuscular Blocking Agents; Rocuronium; Sugammadex

To evaluate the incidence of hypersensitivity and anaphylaxis after administration of sugammadex.. Retrospective analysis.. Sugammadex clinical development program and post-marketing experience.. Surgical patients and healthy volunteers who received sugammadex or placebo/comparator with anesthesia and/or neuromuscular blockade (NMB).. Sugammadex administered as 2.0 mg/kg at reappearance of the second twitch, 4.0 mg/kg at 1-2 post-tetanic count, or 16.0 mg/kg at 3 min after rocuronium 1.2 mg/kg.. Three analytical methods were used: 1) automated MedDRA queries; 2) searches of adverse events (AEs) consistent with treatment-related hypersensitivity reactions as diagnosed by the investigator; and 3) a retrospective adjudication of AEs suggestive of hypersensitivity by a blinded, independent adjudication committee (AC). In addition, a search of all post-marketing reports of events of hypersensitivity was performed, and events were retrospectively adjudicated by an independent AC. Anaphylaxis was determined according to Sampson Criterion 1.. The pooled dataset included 3519 unique subjects who received sugammadex and 544 who received placebo. The automated MedDRA query method showed no apparent increase in hypersensitivity or anaphylaxis with sugammadex as compared to placebo or neostigmine. Similarly, there was a low overall incidence of AEs of treatment-related hypersensitivity (<1%), with no differences between sugammadex and placebo or neostigmine. Finally, the retrospective adjudication of AEs suggestive of hypersensitivity showed a low incidence of hypersensitivity (0.56% and 0.21% for sugammadex 2 mg/kg and 4 mg/kg, respectively), with an incidence similar to subjects who received placebo (0.55%). There were no confirmed cases of anaphylaxis in the pooled studies. During post-marketing use, spontaneous reports of anaphylaxis occurred with approximately 0.01% of sugammadex doses.. Subjects who received sugammadex with general anesthesia and/or NMB had a low overall incidence of hypersensitivity, with no apparent increase in hypersensitivity or anaphylaxis with sugammadex as compared to placebo or neostigmine.

Topics: Adult; Aged; Anaphylaxis; Anesthesia Recovery Period; Anesthesia, General; Cholinesterase Inhibitors; Drug Hypersensitivity; Female; Humans; Incidence; Male; Middle Aged; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Placebos; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Retrospective Studies; Rocuronium; Sugammadex

Topics: Drug Hypersensitivity; Humans; Neuromuscular Blockade; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Postoperative Care; Rocuronium; Sugammadex

The danger of anaphylaxis, a rare but life threatening complication of general anesthesia (GA) can be summarized in two: 1. General Anesthesia masks the typical early signs of allergy which can be seen in an awake patient. 2. Anaphylaxis during GA manifests mostly as circulatory/ventilatory failures which can be interpreted as adverse effects of anesthetics or surgery and this can lead to critical delay of effective therapy. A 19-year-old female admitted for posterior spinal fusion and instrumentation (the 5th surgery in patient's life) desaturated seconds after intubation. Cardiopulmonary resuscitation (CPR) was started and the absence of cutaneous signs along with a loud holosystolic murmur were questioned. The patient was promptly resuscitated and allergy to rocuronium was confirmed by intradermal tests 6weeks later. Factors influencing decision making and potential etiology of the newly heard holosystolic murmur during anaphylaxis are discussed.

Topics: Adult; Anaphylaxis; Androstanols; Anesthesia, General; Anesthetics, Intravenous; Cardiopulmonary Resuscitation; Clinical Decision-Making; Drug Hypersensitivity; Female; Fentanyl; Humans; Hypotension; Intradermal Tests; Neuromuscular Nondepolarizing Agents; Propofol; Rocuronium; Scoliosis; Shock; Spinal Fusion; Systolic Murmurs; Vasoconstrictor Agents; Young Adult

We present 3 cases of pseudoallergic (anaphylactoid) reactions to perioperatively administered rocuronium, which rapidly resolved after sugammadex injection. Allergological workup showed no evidence for immediate-type hypersensitivity to the drugs used for anesthesia, including rocuronium. However, rocuronium induced an irritative reaction in skin tests in all 3 patients and in 3 healthy individuals. This reaction was specifically suppressed by adding sugammadex at a 1:1 molecular proportion to rocuronium before the skin tests. This observation suggests that the patients suffered from a pseudoallergic reaction, and indicates that sugammadex might act via the inhibition of non-IgE mediated MRGPRX2 (Mas-related G-protein-coupled receptor member X2)-triggered mast cell degranulation induced by rocuronium.

Topics: Adult; Aged; Androstanols; Drug Hypersensitivity; Female; gamma-Cyclodextrins; Humans; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Phenotype; Rocuronium; Skin Tests; Sugammadex

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Anaphylaxis; Androstanols; Causality; Child; Delayed Emergence from Anesthesia; Drug Hypersensitivity; Epinephrine; Female; gamma-Cyclodextrins; Humans; Immunoglobulin E; Intraoperative Complications; Male; Middle Aged; Rocuronium; Skin Tests; Sugammadex; Young Adult

Sugammadex has a unique mechanism of action and is widely used because of its safety and efficacy. A few recent reports have described allergic reactions to clinical doses of sugammadex. We hereby describe another series of cases of possible anaphylaxis to sugammadex.. We present three suspected cases of sugammadex-induced anaphylactic shock, including a 13-year-old boy who underwent laparoscopic appendectomy, a 75-year-old woman who underwent left knee arthroplasty, and a 34-year-old man who underwent left pansinectomy for sinobronchitis. All three patients received general anesthesia with rocuronium and their tracheas were intubated. Shortly after injection of sugammadex for reversal of rocuronium, all of them experienced a decrease in blood pressure along with mucocutaneous erythema. In the most severe case, reintubation after extubation was required due to difficulty in manual ventilation. All patients recovered with anti-allergic therapy. On later investigation, all three patients had a positive skin reaction to sugammadex.. Our results suggest that physicians using sugammadex should be aware of the possibility of sugammadex-induced anaphylaxis.

Topics: Adolescent; Adult; Aged; Anaphylaxis; Androstanols; Appendectomy; Arthroplasty, Replacement, Knee; Drug Hypersensitivity; Female; gamma-Cyclodextrins; Humans; Male; Neuromuscular Nondepolarizing Agents; Paranasal Sinuses; Rocuronium; Sugammadex

Topics: Adult; Anaphylaxis; Androstanols; Drug Hypersensitivity; Epinephrine; gamma-Cyclodextrins; Hemodynamics; Humans; Male; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Treatment Outcome; Vasoconstrictor Agents

During the perioperative period, anaphylactic reactions rarely occur. Neuromuscular blocking agents (NMBAs) are responsible for 60-70% of perioperative anaphylactic reactions. This case, we report a case of rocuronium-induced anaphylaxis in a 3-year-old girl with no previous exposure to NMBAs. This case cautions and informs practitioners that an IgE-mediated anaphylactic reaction with rocuronium is possible even in young children with no previous exposure to NMBAs.

Topics: Anaphylaxis; Androstanols; Child, Preschool; Drug Hypersensitivity; Female; Humans; Immunoglobulin E; Neuromuscular Nondepolarizing Agents; Rocuronium

The availability of sugammadex as a selective encapsulating agent for rocuronium has led to speculation that it may be useful in mitigating rocuronium-induced anaphylaxis. Off-label use of sugammadex for this indication has already been documented in case reports although there are theoretical objections to the likelihood of an allergen-binding agent's being able to attenuate the immunological cascade of anaphylaxis. Using a cutaneous model of anaphylaxis in rocuronium-sensitised patients, we were unable to demonstrate that sugammadex was effective in attenuating the type-1 hypersensitivity reaction after it has been triggered by rocuronium, but we were able to demonstrate that these patients are anergic to sugammadex-bound rocuronium. These findings demonstrate that a cyclodextrin can bind an allergen and exclude it from interacting with the immune system, and may potentially lead to novel applications in other allergic diseases. However, there is no evidence that sugammadex should be used for the treatment of rocuronium-induced anaphylaxis, and clinical management should follow established protocols.

Topics: Anaphylaxis; Androstanols; Drug Hypersensitivity; gamma-Cyclodextrins; Humans; Immunoglobulin E; Neuromuscular Nondepolarizing Agents; Off-Label Use; Rocuronium; Skin Tests; Sugammadex

Topics: Anaphylaxis; Androstanols; Catecholamines; Drug Evaluation; Drug Hypersensitivity; Drug Resistance; gamma-Cyclodextrins; Humans; Immunoglobulin E; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Research Design; Rocuronium; Sugammadex

Neuromuscular blocking agents have been implicated in 60-70% of anaphylactic events associated with anaesthesia. We report two cases of probable hypersensitivity reaction to sugammadex and an additional suspected but less supported case of possible immune-mediated reaction or other adverse reaction. The patients were given a bolus of sugammadex 100 mg immediately before extubation. In all three patients, a possible allergic reaction was suspected within 4 min of sugammadex administration, but with different degrees of severity. Skin testing was positive in two of these patients. Hypersensitivity to sugammadex unaccompanied by cardiovascular or respiratory symptoms might be missed during the course of anaesthesia. Careful monitoring for possible allergic responses is required in patients who have received sugammadex.

Topics: Adult; Aged, 80 and over; Androstanols; Anesthesia, General; Drug Hypersensitivity; Female; gamma-Cyclodextrins; Humans; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests; Sugammadex

We report here an intellectually compromised 7-year-old boy with cerebral palsy who developed a hypersensitivity reaction several minutes after the administration of sugammadex for subsequent extubation. He developed signs of upper airway stenosis and decreased oxygen saturation, as well as wheals on his neck, chest, and both upper extremities. He was successfully treated with immediate administration of adrenaline and hydrocortisone. A hypersensitivity reaction to sugammadex was suspected on the basis of the patient's clinical course.

Topics: Androstanols; Child; Drug Hypersensitivity; gamma-Cyclodextrins; Humans; Male; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

We report the anesthetic management of a patient with catatonic schizophrenia and pseudocholinesterase deficiency, using the nondepolarizing neuromuscular blocking drug, rocuronium, reversed by its specific reversal agent, sugammadex, for a series of electroconvulsive therapy sessions. Rocuronium and sugammadex were used every 48 hours for 8 consecutive times and proved to be an effective and safe combination in a situation where succinylcholine was contraindicated.

Topics: Adult; Androstanols; Apnea; Butyrylcholinesterase; Cholinesterases; Drug Hypersensitivity; Drug Interactions; Electroconvulsive Therapy; gamma-Cyclodextrins; Humans; Male; Metabolism, Inborn Errors; Neuromuscular Nondepolarizing Agents; Rocuronium; Schizophrenia, Catatonic; Sugammadex

We describe the case of a fit 17-year-old man who developed a severe allergic reaction to a low clinical dose of sugammadex (3.2 mg kg(-1) , 200 mg intravenously), 1 min after its administration. This was manifest by an intense erythema over the anterior part of the thorax, severe lip and palpebral oedema and bilateral wheeze. On later investigation, the patient had a positive skin prick test to sugammadex (5-mm diameter response, with a negative saline control and positive histamine control of 5 mm) and no response to any other drug tested. Other diagnostic tests supported a diagnosis of allergic reaction to sugammadex.

Topics: Adolescent; Anaphylaxis; Androstanols; Drug Administration Schedule; Drug Hypersensitivity; gamma-Cyclodextrins; Humans; Male; Neuromuscular Nondepolarizing Agents; Postoperative Complications; Rocuronium; Sugammadex

Allergy to rocuronium can be life-threatening. Correct diagnosis is a prerequisite because of serious consequences of diagnostic error.. To assess skin testing, quantification of specific IgE (sIgE) and flow-assisted activation of basophils [basophil activation test (BAT)] in the diagnosis of rocuronium allergy.. This study comprises 104 curarized patients with a history of profound hypotension and severe bronchospasm immediately after induction of anaesthesia. All patients had skin tests, quantification of sIgE and BAT to rocuronium, together with investigations for all relevant compounds administered during anaesthesia that could have evoked the reaction. Diagnosis of rocuronium allergy was considered definite when the patient demonstrated a positive outcome for at least two of the three aforementioned tests.. The positive predictive value for skin testing, BAT and sIgE was 98% (CI 95%: 92-99%), 97% (CI 95%: 88-100%) and 83% (CI 95%: 74-89%), respectively. The negative predictive value for skin testing, BAT and sIgE was 96% (CI 95%: 86-99%), 75% (CI 95%: 67-75%) and 72% (CI 95%: 58-83%), respectively. Cross-reactivity with vecuronium was documented in 69% of the patients.. Skin testing merits the status of primary diagnostic investigation to document rocuronium allergy and cannot be substituted by quantification of sIgE or BAT. SIgE can offer a diagnostic advantage in cases where skin tests yield negative results. However, additional tests (e.g. BAT) are of capital importance in patients with negative skin tests and positive sIgE results to help in interpreting the clinical significance of a positive sIgE result. Optimal assessment of cross-reactivity between rocuronium and vecuronium implies both skin testing and BAT.

Topics: Adolescent; Adult; Aged; Androstanols; Basophils; Drug Hypersensitivity; Female; Humans; Hypersensitivity; Immunoglobulin E; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Predictive Value of Tests; Prospective Studies; Rocuronium; Skin Tests; Vecuronium Bromide; Young Adult

Topics: Adult; Androstanols; Drug Hypersensitivity; Electroconvulsive Therapy; Female; gamma-Cyclodextrins; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Succinylcholine; Sugammadex

During the induction of anesthesia for strabismus correction, a six-year-old boy suffered anaphylaxis with hypotension. Midazolam, propofol, sufentanil, rocuronium, dexamethasone and ibuprofen had been administered. The boy's history failed to reveal any drug allergies. Intracutaneous testings with drugs used for anesthesia and other muscle relaxants verified a positive reaction to rocuronium as well as to cisatracurium, mivacurium, vecuronium and atracurium. There was no reaction to suxamethonium.

Topics: Anaphylaxis; Androstanols; Child; Drug Eruptions; Drug Hypersensitivity; Humans; Male; Perioperative Care; Rocuronium

Topics: Aged; Amides; Analgesia, Epidural; Analgesics, Non-Narcotic; Androstanols; Anesthesia, General; Anesthetics, Dissociative; Contraindications; Drug Hypersensitivity; Fentanyl; Humans; Ketamine; Male; Methyl Ethers; Neuromuscular Nondepolarizing Agents; Pain, Postoperative; Preanesthetic Medication; Propofol; Rocuronium; Ropivacaine; Sevoflurane; Skin Tests; Spinal Fusion; Succinylcholine

Diagnosis of anaphylaxis from neuromuscular blocking agents (NMBA) is not always straightforward.. To assess flow cytometric analysis of activated basophils (BAT) as a diagnostic instrument in anaphylaxis from rocuronium. To investigate whether the technique might help to identify cross-reactive and safe alternative compounds.. For validation of the BAT, 14 patients with perioperative anaphylaxis demonstrating a positive skin test (ST) for rocuronium and eight individuals that tolerated rocuronium and a negative ST for this drug were enrolled. To confirm specificity of the BAT, five patients that tolerated atracurium or cisatracurium with a negative ST for rocuronium were tested. Basophil activation with rocuronium, vecuronium, atracurium, cisatracurium and suxamethonium was analysed flow cytometrically by labelling with anti-CD123/anti-HLADR/anti-CD63.. Sensitivity of BAT for rocuronium was 91.7% and specificity 100%. However, in two patients the BAT was lost as a diagnostic tool, as their cells were nonresponsive to positive control stimulation and allergen. Seven from the 12 responsive patients also demonstrated a clear basophilic activation for vecuronium. Moreover, according to ST and/or BAT cross-reactivity between rocuronium and vecuronium was suspected in 10/14 patients. Except one patient, all patients had negative BAT and ST investigations for atracurium and cisatracurium. Currently, five patients tolerated administration of cisatracurium. All control individuals demonstrated negative ST and BAT for all tested NMBA.. The BAT constitutes a reliable instrument to diagnose anaphylaxis from rocuronium. The technique also allows quick and simultaneous testing of different potential cross-reactive NMBA and to tailor a safe alternative.

Topics: Anaphylaxis; Androstanols; Basophils; Cross Reactions; Diagnosis, Differential; Drug Hypersensitivity; Female; Flow Cytometry; Humans; Male; Neuromuscular Nondepolarizing Agents; Predictive Value of Tests; Rocuronium

Topics: Androstanols; Drug Hypersensitivity; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests; Vecuronium Bromide

Published reports from France and Norway suggest a frequent incidence of anaphylaxis to rocuronium and have raised concerns about its safety. We hypothesized that the Food and Drug Administration Adverse Event Reporting System could be used to confirm whether there has been an unusual incidence of anaphylactic events for rocuronium in the United States (U.S.) and whether the reporting patterns differ within and outside of the U.S.. We queried the Food and Drug Administration Adverse Event Reporting System for 1999 through the first quarter of 2002 for all adverse events for the drugs rocuronium and vecuronium and then searched on the terms considered to represent possible anaphylaxis using proprietary software. We compared the frequency of these terms in data both for rocuronium and vecuronium. We then assessed the occurrence of reports of anaphylaxis-related terms in reports from the U.S. compared with reports originating outside of the U.S.. For rocuronium, the database contained 311 reports, 166 domestic and 145 from foreign sources. Fifty percent of the foreign reports contained an anaphylaxis term versus 20% of the domestic reports (P < 0.001). For vecuronium, the comparable figures were 17% and 19% (not significant) and the total number of reports was 243. The incidence of the reports containing anaphylaxis terms did not differ between vecuronium and rocuronium in the U.S. but were significantly different for foreign reports (P < 0.001). These data confirm that U.S. anesthesia providers have not observed a significant difference in anaphylactic reactions between the two commonly used intermediate-acting muscle relaxants and suggest that frequency of reports of anaphylaxis may be significantly influenced by the area from which the reports originate.

Topics: Adverse Drug Reaction Reporting Systems; Anaphylaxis; Androstanols; Databases, Factual; Drug Hypersensitivity; Drug Utilization; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; United States; United States Food and Drug Administration; Vecuronium Bromide

Topics: Anaphylaxis; Androstanols; Drug Hypersensitivity; False Positive Reactions; Humans; Neuromuscular Blocking Agents; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests; Vecuronium Bromide

Topics: Adult; Anaphylaxis; Androstanols; Anesthesia; Drug Hypersensitivity; Fluid Shifts; Humans; Intraoperative Complications; Male; Neuromuscular Nondepolarizing Agents; Rocuronium

We report two cases of severe anaphylactic reactions to rocuronium. Diagnosis was confirmed by skin tests and specific IgE assay. Cross-reactivity to all neuromuscular blocking agents was investigated by intradermal tests and leucocyte histamine release test. Intradermal tests and leukocyte histamine release were negative for cisatracurium. The two patients had undergone a subsequent general anaesthesia using cisatracurium and did not present any adverse reaction.

Topics: Aged; Anaphylaxis; Androstanols; Anesthesia, General; Atracurium; Cross Reactions; Drug Hypersensitivity; Histamine Release; Humans; Immunoglobulin E; Leukocytes; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests

Topics: Adult; Androstanols; Anesthetics, Inhalation; Basophils; Drug Hypersensitivity; Female; Flow Cytometry; Histamine Release; Humans; Immunoglobulin E; Middle Aged; Neuromuscular Depolarizing Agents; Rocuronium; Succinylcholine

Anaphylaxis during induction of anaesthesia is a dreaded complication with a mortality rate of 3-6%, most frequently associated with the use of muscle relaxants. Current knowledge on this matter is reviewed in relation to the presentation of 3 cases of anaphylaxis and bronchospasm associated with the use of the recently released nondepolarizing muscle relaxant rocuronium. Bronchospasm may be the sole sign of a serious drug reaction, triggered by precipitation of insoluble thiopental crystals when mixed with a muscle relaxant in the intravenous (iv) line. It is recommended that these drugs are administered via different injection ports. The hypotension requires immediate treatment with oxygen, epinephrine and large amounts of iv fluids. Epinephrine infusion may be needed for hours. It is recommended that serum tryptase is measured approximately 2 h after debut of the serious drug reaction. Allergy testing should be performed for all the drugs the patient was exposed to, 4-8 weeks after the incident, and due to cross-reactivity, including all available muscle relaxants. Doctors are urged to inform their patients, and systematically register adverse drug reactions.

Topics: Adult; Anaphylaxis; Androstanols; Anesthesia, Inhalation; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests

To report a case of anaphylaxis to rocuronium and the sensitivities to multiple neuromuscular blocking drugs in a patient with no previous exposure to this group of drugs. We describe the current recommendations for both intraoperative and postoperative testing of these patients.. A 36-yr-old man was admitted for repair of a ruptured Achilles tendon. Following induction of general anesthesia with fentanyl and propofol, 60 mg of rocuronium were given to facilitate tracheal intubation. He immediately became profoundly hypotensive with impalpable pulses, and blood pressure could not be recorded. Airway pressure increased markedly, and hand ventilation of the lungs became very difficult. His airway was secured and he was successfully resuscitated with 3 mg epinephrine and three litres crystalloid and colloid intravenous fluid therapy. His recovery in the intensive care unit was uneventful and the operation was performed four days later under spinal anesthesia. Subsequent skin prick testing, performed six weeks later, demonstrated strong positive weal and flare reactions to rocuronium, vecuronium and pancuronium, and some cross-reactivity with the benzylisoquinolinium group of muscle relaxants.. Muscle relaxants are responsible for 61.6% of cases of anaphylaxis during general anesthesia. Cross-reactivity is common, as this group of drugs share a quaternary ammonium group. It is mandatory that patients be tested for both the agent responsible and cross-reactivity following an anaphylactic response. We suggest a protocol for investigation of suspected anaphylaxis.

Topics: Achilles Tendon; Adult; Anaphylaxis; Androstanols; Anesthesia; Drug Hypersensitivity; Humans; Male; Neuromuscular Blocking Agents; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests

The technique of Flow Cytometry for activation of basophils (TAB), expressed as the marker CD63, is at present one of the pathways of research applied to drug allergy. In this work are reported the results of TAB of Pneumoallergens and Hymenoptera venoms. TAB can define better than total IgE the atopy of the subject: in effect the fluorescence of the basophils is emphasized in comparison with non-atopic subjects. This hypothesis has been confirmed by a study of three groups of subjects. With regard to drug allergy, it is important to study patients in whom the observations have been documented very objectively by clinical history and positive skin tests to the drug, compared with a negative reference to the same drug. So, TAB has been shown to be very useful in diagnosis of allergy to certain drugs, such as the Myorelaxants.

Topics: Allergens; Anaphylaxis; Androstanols; Animals; Antigens, CD; Basophils; Bee Venoms; Dogs; Drug Hypersensitivity; Dust; Flow Cytometry; Histamine Release; Hypersensitivity, Immediate; Immunoglobulin E; Mites; Neuromuscular Nondepolarizing Agents; Platelet Membrane Glycoproteins; Pollen; Rocuronium; Skin Tests; Tetraspanin 30; Wasp Venoms

Topics: Abdominal Pain; Adolescent; Anaphylaxis; Androstanols; Antibodies; Bronchial Spasm; Chymases; Drug Hypersensitivity; Edema; Female; Follow-Up Studies; Humans; Immunoglobulin E; Inflammation Mediators; Laparoscopy; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Serine Endopeptidases; Skin Tests; Tryptases; Urticaria

Immuno-biological diagnosis of allergies lo medicines can be carried out using a Flow Cytometer and by activating cells such as basophils and lymphocytes with membrane markers. A description is given of two cases of patients allergic to a myorelaxant: Rocuronium, who showed a correlation between the clinical history, skin tests and a positive basophil activation test, when compared to six negative controls.

Topics: Anaphylaxis; Androstanols; Basophil Degranulation Test; Basophils; Drug Hypersensitivity; Flow Cytometry; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests