rocuronium and Anaphylaxis

Allergic reactions are generalized hypersensitivity processes triggered by different antigenic stimuli, resulting in the end effect of mast cell degranulation and adverse physiologic effects. During the perioperative period, the most commonly identified agents include antibiotics, neuromuscular blocking agents (rocuronium and succinylcholine), chlorhexidine, and iodinated dyes for radiologic imaging. Sugammadex is a novel agent for the reversal of neuromuscular blockade achieved with rocuronium or vecuronium. Its unique mechanism of action, whereby it encapsulates and forms a one-to-one complex with rocuronium, has led to its anecdotal use as an adjunct in the treatment of anaphylactic and anaphylactoid reactions following rocuronium. The current manuscript discusses the potential use of sugammadex in the treatment of allergic reactions following the administration of rocuronium, reviews previous anecdotal reports of its use in these scenarios, and provides recommendations for future care.

Topics: Anaphylaxis; Androstanols; Animals; gamma-Cyclodextrins; Humans; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

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

Skin tests are the gold standard for detecting the culprit drug of anaphylaxis, and should ideally be performed after an interval of 4-6 weeks after the reaction to avoid false-negative results. However, when re-operation cannot be delayed and early allergy tests are necessary, special attention is required during subsequent anesthesia, because early skin tests tend to produce false-negative results. This report presents a case of rocuronium-induced anaphylaxis in which early skin tests showed negative results for all the drugs tested. The second anesthesia was safely performed by avoiding all the drugs used for the first anesthesia. Ultimately, skin tests and basophil activation tests (BATs) performed after re-operation demonstrated rocuronium as the drug responsible for anaphylaxis. We recommend performing BATs in addition to skin tests to improve the accuracy of diagnosis of anaphylaxis. In this report, we also discuss interpretation of the results of early skin tests and subsequent selection of drugs for anesthesia. After postponement of surgery due to anaphylaxis, we are often required to perform allergy tests at an early stage if re-operation cannot be delayed. In such cases, skin test results alone should not be used to guide subsequent anesthesia management to avoid recurrent anaphylaxis.

Topics: Adult; Aged; Anaphylaxis; Anesthesia, General; Anesthesiology; Female; Humans; Male; Middle Aged; Rocuronium; Skin Tests

Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common cause of anaphylaxis during anesthesia is reportedly neuromuscular blocking agents. Of the many muscle relaxants that are clinically available, rocuronium is becoming popular in many countries. Recent studies have demonstrated that succinylcholine (but also rocuronium use) is associated with a relatively high rate of IgE-mediated anaphylaxis compared with other muscle relaxant agents. Sugammadex is widely used for reversal of the effects of steroidal neuromuscular blocking agents, such as rocuronium and vecuronium. Confirmed cases of allergic reactions to clinical doses of sugammadex have also been recently reported. Given these circumstances, the number of cases of hypersensitivity to either sugammadex or rocuronium is likely to increase. Thus, anesthesiologists should be familiar with the epidemiology, mechanisms, and clinical presentations of anaphylaxis induced by these drugs. In this review, we focus on the diagnosis and treatment of anaphylaxis to sugammadex and neuromuscular blocking agents. Moreover, we discuss recent studies in this field, including the diagnostic utility of flow cytometry and improvement of rocuronium-induced anaphylaxis with the use of sugammadex.

Topics: Anaphylaxis; Androstanols; Anesthesia; gamma-Cyclodextrins; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Succinylcholine; Sugammadex; Vecuronium Bromide

Rocuronium, a non-depolarizing neuromuscular blocking drug has a rapid onset of action, a comparatively low potency and, with a more favourable side effects profile than succinylcholine, it has become a popular alternative to that drug for rapid sequence inductions in anaesthesia. The rocuronium-binding cyclodextrin derivative sugammadex, prepared by per-6 substitution of the primary hydroxyls of γ-cyclodextrin with thiol ether-linked propionic acid side chains to extend the hydrophobic cavity to accommodate rocuronium, is used to reverse neuromuscular blockade by encapsulating the drug as an inclusion complex and removing it from the neuromuscular junction to the plasma. It has recently been suggested that sugammadex might also be of value in the management of rocuronium-induced anaphylaxis and this has been potentially supported by recent case reports. However, before sugammadex can be recommended for this purpose, it is important to establish whether or not the allergenic substituted ammonium groups at each end of the rocuronium molecule in the inclusion complex are masked within the cavity or left exposed for interaction with rocuronium-reactive IgE antibodies in the sera of rocuronium-allergic patients. Detailed experimental strategies and experimental protocols to investigate the allergenic potential of the sugammadex-rocuronium inclusion complex are presented and a possible explanation of the apparently rapid and successful reversal of anaphylaxis by administration of sugammadex is advanced and discussed.

Topics: Allergens; Anaphylaxis; Androstanols; Animals; Drug Carriers; gamma-Cyclodextrins; Humans; Immunoglobulin E; Models, Molecular; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

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

Few randomized studies have assessed recovery from rocuronium- or vecuronium-induced moderate or deep neuromuscular blockade with sugammadex in pediatric participants.. To assess sugammadex for reversal of neuromuscular blockade in pediatric participants.. This was a randomized, phase IV, active comparator-controlled, double-blind study. Participants aged 2 to <17 years, under moderate or deep neuromuscular blockade, were administered sugammadex (2 or 4 mg/kg) or neostigmine (50 µg/kg; for moderate neuromuscular blockade only). Predefined adverse events of clinical interest, including clinically relevant bradycardia, hypersensitivity, and anaphylaxis, were monitored. The primary efficacy endpoint was time to recovery to a train-of-four ratio of ≥0.9 in participants receiving sugammadex 2 mg/kg versus neostigmine for reversal of moderate neuromuscular blockade, analyzed by analysis of variance adjusted for neuromuscular blocking agent and age.. Of 288 randomized participants, 272 completed the study and 276 were included in the analyses. Clinically relevant bradycardia was experienced by 2.0%, 1.6%, and 5.9% of participants in the sugammadex 2 mg/kg, sugammadex 4 mg/kg, and neostigmine groups, respectively. No hypersensitivity or anaphylaxis events were observed. Recovery to a train-of-four ratio of ≥0.9 with sugammadex 2 mg/kg was faster than neostigmine (1.6 min, 95% CI 1.3 to 2.0 vs. 7.5 min, 95% CI 5.6 to 10.0; p < .0001) and was comparable to sugammadex 4 mg/kg (2.0 min, 95% CI 1.8 to 2.3).. Pediatric participants recovered from rocuronium- or vecuronium-induced moderate neuromuscular blockade significantly faster with sugammadex 2 mg/kg than with neostigmine. Time to reversal of deep neuromuscular blockade with sugammadex 4 mg/kg was consistent with that of moderate neuromuscular blockade reversal. No meaningful differences in clinically relevant bradycardia, hypersensitivity, or anaphylaxis were seen with sugammadex vs neostigmine. These results support the use of sugammadex for reversal of moderate and deep rocuronium- and vecuronium-induced neuromuscular blockade in patients aged 2 to <17 years.. NCT03351608/EudraCT 2017-000692-92.

Topics: Anaphylaxis; Anesthetics; Bradycardia; Child; Humans; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Vecuronium Bromide

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

Topics: Anaphylaxis; Androstanols; Atracurium; Humans; Neuromuscular Blocking Agents; Rocuronium

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

Although anaphylaxis during anaesthesia is a rare event, neuromuscular blocking drugs are responsible for 62% of anaesthesia-related anaphylaxis. However, sugammadex, a modified gamma-cyclodextrin, can encapsulate rocuronium molecules and cause the rapid reversal of the neuromuscular blockade. A 68-year-old man who presented for a radical prostatectomy was induced with IV fentanyl/propofol/rocuronium. He had not received rocuronium previously but had received cisatracurium. Shortly after anaesthesia, the patient's heart rate abruptly increased, and systolic blood pressure (SBP) dropped to 40 mm Hg. Despite cardiopulmonary resuscitation and intensive management, his haemodynamic stability did not improve until he received IV sugammadex, 200 mg. Intradermal skin tests showed he was positive for cisatracurium, rocuronium and succinylcholine. The patient was suspected to have cross-reactivity of rocuronium with cisatracurium. This case highlights the potential benefit of sugammadex as an adjunct to conventional measures during rocuronium-induced anaphylaxis.

Topics: Aged; Anaphylaxis; Androstanols; Humans; Male; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

The causes of anaphylaxis in a general hospital may differ from those occurring in a community setting. Underlying diseases in admitted patients and vague presenting symptoms can make the diagnosis of anaphylaxis difficult. Serum tryptase measurements may provide valuable evidence for diagnosing anaphylaxis in admitted patients.. This study was designed as a retrospective study of 53 patients with an anaphylaxis episode at a Korean tertiary care general hospital. Tryptase levels were measured at baseline and different time points from the onset of anaphylaxis.. Drugs (42 cases; 79.2%) and foods (10 cases; 18.9%) were the most common causes of anaphylaxis. In drug-induced anaphylaxis, antibiotics (24.5%), anticancer medications, which included monoclonal antibodies (22.6%), and contrast agents (11.3%) were the most frequent causes. The muscle relaxant eperisone (5.7%), neuromuscular blocking agent rocuronium (5.7%), and its antagonist sugammadex (3.8%) were other frequent triggering agents. Wheat-dependent exercise-induced anaphylaxis was the most common entity in food-induced anaphylaxis. Tryptase concentrations were higher in patients with higher grades of anaphylaxis, as well as in accidental anaphylaxis, compared to meticulously provoked anaphylaxis. Overall diagnostic sensitivity was higher for tryptase algorithm criteria (≥[1.2×baseline+2] µg/L: 71.4%) than for abnormal tryptase level criteria (≥11.4 µg/L: 52.8%).. The triggers of anaphylaxis in a Korean tertiary care hospital were diverse, including beta-lactam antibiotics, anticancer medications, contrast medias, eperisone, nonsteroidal anti-inflammatory drugs, rocuronium, sugammadex, and wheat. Tryptase measurements provided valuable evidence for diagnosis, and the sensitivity of algorithm criteria was superior to that of the abnormal value criteria.

Topics: Anaphylaxis; Anti-Bacterial Agents; Hospitals, General; Humans; Republic of Korea; Retrospective Studies; Rocuronium; Sugammadex; Tertiary Healthcare; Tryptases

Topics: Anaphylaxis; Humans; Rocuronium; Sugammadex

Topics: Anaphylaxis; Androstanols; Humans; Rocuronium; Sugammadex

We present the first case of a patient with severe aortic stenosis who developed anaphylactic shock and was successfully treated with adrenaline and landiolol, a highly selective β1-receptor blocker, to prevent disruption of the myocardial oxygen supply-demand balance caused by tachycardia.. An 86-year-old woman was scheduled for simultaneous anterior-posterior fixation for a burst fracture of the 12th thoracic vertebra; 200 mg sugammadex, a neuromuscular blocking agent antagonist, was administered postoperatively, and she was extubated without complications. However, 6 min after extubation, her blood pressure decreased abruptly to 55/29 mm Hg, and her heart rate increased to 78 bpm. Then, we intervened with fluid loading, an increased dose of noradrenaline, and phenylephrine administration. However, her blood pressure did not increase.. A general observation revealed urticaria on the lower leg; thus, we suspected anaphylactic shock due to sugammadex administration.. We carefully administered 2 doses of 0.05 mg adrenaline and simultaneously administered landiolol at 60 μg/kg/min to suppress adrenaline-induced tachycardia. Adrenaline administration resulted in a rapid increase in blood pressure to 103/66 mm Hg and a maximum heart rate of 100 bpm, suppressing excessive tachycardia.. The patient's general condition was stable after the intervention, and circulatory agonists could be discontinued the following day. She was discharged from the intensive care unit on the fourth postoperative day.. Landiolol may help control the heart rate of patients with aortic stenosis and anaphylactic shock. The combined use of landiolol and adrenaline may improve patient outcomes; however, their efficacy and risks must be evaluated by studying additional cases.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Aged, 80 and over; Anaphylaxis; Aortic Valve Stenosis; Echocardiography; Epinephrine; Female; Humans; Morpholines; Postoperative Complications; Rocuronium; Spinal Fractures; Sugammadex; Urea

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

Sugammadex is a modified cyclodextrin that is being increasingly used in anesthetic practice worldwide for the reversal of the aminosteroid neuromuscular blockers rocuronium and vecuronium. Its safety profile, however, is incompletely understood. One such aspect is the incidence of anaphylactic reactions that occur after its administration. While several case reports exist in the literature, there is a paucity of information on the actual incidence of anaphylactic reactions.. A single-center retrospective chart review identified patients who experienced anaphylaxis to sugammadex in the institutional electronic medical record system. These charts were then reviewed to determine whether the etiology of anaphylaxis was sugammadex administration.. Two patients experienced anaphylaxis to sugammadex, which occurred in a single institution cohort of 19,821 patients who received 23,446 total doses. This rate is markedly lower than the 1/300 that the manufacturer's package insert states and also lower than the 1/2500 that the only other large cohort study performed has reported.. The incidence of anaphylaxis to sugammadex in this cohort of patients was 2 of 19,821 patients, who received a total of 23,446 doses.

Topics: Aged, 80 and over; Anaphylaxis; Cohort Studies; Female; Humans; Incidence; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Retrospective Studies; Rocuronium; Sugammadex

We present the case of a 3-month-old infant with severe, persistent bronchoconstriction following administration of rocuronium. This observation raises awareness of a rare but potentially life-threatening reaction to neuromuscular blocking agents.

Topics: Anaphylaxis; Bronchoconstriction; Dose-Response Relationship, Drug; Female; Humans; Infant; Neuromuscular Nondepolarizing Agents; Rocuronium; Severity of Illness Index

Neuromuscular-blocking agents (NMBAs) can cause both IgE-dependent and IgE-independent anaphylactic reactions, with activation of the mast cell receptor MRGPRX2 being important to the latter. Sugammadex, a reversal agent for certain aminosteroid NMBAs, has been proposed as an antidote for these anaphylactic events with conflicting outcomes.. We further characterize the involvement of MRGPRX2 in NMBA-induced mast cell activation and determine how this is influenced by sugammadex. We then apply these in vitro results to infer the possible utility of sugammadex in the acute management of non-IgE-dependent anaphylaxis.. The LAD2 human mast cell line and a MRGPRX2 knock-down derivative were used to validate the involvement of MRGPRX2 and to test the effect of sugammadex on mast cell activation by NMBAs and other MRGPRX2 agonists.. All MRGPRX2 agonists tested were shown to induce MRGPRX2-dependent LAD2 mast cell calcium mobilization and cytokine release and all, apart from rocuronium, induced degranulation. Co-treatment of mast cells with sugammadex and some MRGPRX2 agonists significantly reduced cell activation, but if sugammadex was administered a few minutes following stimulation, degranulation was not attenuated. However, addition of sugammadex up to 180 min following LAD2 MRGPRX2 stimulation, significantly reduced CCL2 mRNA and protein induction.. We show that sugammadex, known to reverse muscle blockade by certain NMBAs, is also able to reduce MRGPRX2 activation by NMBAs and other, but not all, MRGPRX2 agonists. As sugammadex was ineffective in attenuating mast cell degranulation when added rapidly post MRGPRX2 activation, this suggests against the agent having efficacy in controlling acute symptoms of anaphylaxis to NMBAs caused by MRGPRX2 activation. Interestingly, however, sugammadex did impair MRGPRX2-induced CCL2 release, suggesting that it may have some benefit in perhaps dampening less well-defined adverse effects of MRGPRX2-dependent anaphylaxis associated with the more slowly elaborated mast cell mediators.

Topics: Anaphylaxis; Antidotes; Atracurium; Cell Line; Chemokine CCL2; Gene Knockdown Techniques; Humans; In Vitro Techniques; Mast Cells; Nerve Tissue Proteins; Neuromuscular Blocking Agents; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; RNA, Messenger; Rocuronium; Sugammadex

Topics: Anaphylaxis; Humans; Incidence; Rocuronium; Smoke; Sugammadex

The observation that patients presenting for bariatric surgery had a high incidence of neuromuscular blocking agent (NMBA) anaphylaxis prompted this restricted case-control study to test the hypothesis that obesity is a risk factor for NMBA anaphylaxis, independent of differences in pholcodine consumption.. We compared 145 patients diagnosed with intraoperative NMBA anaphylaxis in Western Australia between 2012 and 2020 with 61 patients with cefazolin anaphylaxis with respect to BMI grade, history of pholcodine consumption, sex, age, comorbid disease, and NMBA type and dose. Confounding was assessed by stratification and binomial logistic regression.. Obesity (odds ratio [OR]=2.96, χ. Obesity is a risk factor for NMBA anaphylaxis, the risk increasing with BMI grade. Pholcodine consumption is also a risk factor, and this is consistent with the pholcodine hypothesis. Rocuronium use is associated with an increased risk of anaphylaxis compared with vecuronium in this population.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anaphylaxis; Bariatric Surgery; Case-Control Studies; Cefazolin; Codeine; Female; Humans; Incidence; Male; Middle Aged; Morpholines; Neuromuscular Blocking Agents; Obesity; Prospective Studies; Risk Factors; Rocuronium; Young Adult

Perioperative hypersensitivity (POH) to the neuromuscular blocking drug (NMBD) rocuronium was previously thought to be IgE and mast cell (MC)-mediated. However, the recent seminal observation that rocuronium induces degranulation in murine peritoneal MCs (PMCs) via Mas-related G protein-coupled receptor B2 (MrgprB2) led to the idea that POH to this drug involves the activation of MRGPRX2 (human ortholog of MrgprB2). Furthermore, based on the demonstration that a patient with POH to rocuronium displayed three missense mutations (M196I, L226P and L237P) in MRGPRX2's transmembrane domains, it was proposed that this hypersensitivity reaction resulted from aberrant activation of this receptor. We found that rocuronium at 20 µg/mL caused degranulation in mouse PMCs via MrgprB2 but required at least 500 µg/mL to induce degranulation in human MCs via MRGPRX2. Furthermore, RBL-2H3 cells transiently expressing M196I, L226P and L237P variants did not display enhanced degranulation in response to rocuronium when compared to the wild-type receptor. These findings provide the first demonstration that rocuronium induces degranulation in human MCs via MRGPRX2. Furthermore, the important differences between MrgprB2 and MRGPRX2 and the inability of rocuronium to induce enhanced response in cells expressing MRGPRX2 variants suggest that the mechanism of its POH is more complex than previously thought.

Topics: Anaphylaxis; Animals; Cell Degranulation; Cell Line; Female; HEK293 Cells; Humans; Male; Mast Cells; Mice; Mice, Inbred C57BL; Mutation, Missense; Nerve Tissue Proteins; Neuromuscular Nondepolarizing Agents; Protein Domains; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Rocuronium; Skin

Differentiating between anaphylaxis and hypotension during general anaesthesia is difficult, especially when patients present with only hypotension and without any of the other classical features of anaphylaxis. We report the successful management of an anaphylactic reaction to rocuronium that presented as isolated hypotension in a 45-year-old Indonesian man presented with lacerations on the scalp and right pinna caused by an assault to the head after the induction of general anaesthesia, refractory to fluids and high doses of vasopressors. This case highlights that a possible indicator of anaphylaxis can be the presence of isolated hypotension during.

Topics: Anaphylaxis; Anesthesia, General; Humans; Hypotension; Indonesia; Male; Middle Aged; Rocuronium

There are a few reports in the literature about the successful use of sugammadex in the treatment of hypersensitivity reactions caused by rocuronium; however, the pathophysiological mechanism is still unknown. This study aims to investigate the changes caused by rocuronium in the lung and the effect of sugammadex on these changes with biochemical, light microscopic and immunohistochemical parameters on a rat model.. For the study, 28-male Sprague-Dawley rats were randomly divided, seven of each, into four groups. Group C (control) received only 0. 9 % NaCl without any drug. Group R received rocuronium alone 1mg/kg. Group S received sugammadex alone 96 mg/kg. Group RS received rocuronium 1mg/kg and sugammadex 96 mg/kg. After 24 h later, the animals were sacrificed and their tissues were removed. Biochemical (IgE/CRP), light microscopic and immunohistochemical findings were recorded.. Immunoglobulin E and CRP levels, peribronchial, alveolar septal lymphocytic infiltration, thickening of the alveolar membranes and bleeding sites in Group R were significantly higher than all the other groups. In Group RS, while these parameters were significantly lower than that of Group R and Group S, it was significantly higher than that of Group C. Total mast cells and tryptase-positive mast cells counts were significantly higher in Group R than in all other groups. In Group RS, these parameters were statistically lower than that of Group R and Group S, but higher than that of Group C.. This study shows that allergic inflammatory changes due to rocuronium in the lungs of rats are reduced with sugammadex. These results support cases of anaphylaxis due to rocuronium which improved with sugammadex.

Topics: Anaphylaxis; Animals; C-Reactive Protein; Disease Models, Animal; Hemorrhage; Hypersensitivity; Immunoglobulin E; Inflammation; Lung; Lymphocytes; Male; Mast Cells; Neuromuscular Nondepolarizing Agents; Pulmonary Alveoli; Random Allocation; Rats; Rats, Sprague-Dawley; Rocuronium; Sugammadex; Tryptases

Topics: Anaphylaxis; Humans; Mast Cells; Receptors, G-Protein-Coupled; Rocuronium

Topics: Anaphylaxis; Anesthesia, General; Humans; Rocuronium

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

In sugammadex-induced anaphylaxis, sugammadex and/or sugammadex-rocuronium complex have possible allergenic epitope.. We report a case of sugammadex-induced anaphylaxis during general anesthesia in a 60-year-old male undergoing orthopedic hand surgery, manifesting as profound hypotension and urticaria. The timing of onset was closely associated with sugammadex administration. The patient recovered after extensive therapy including fluid, epinephrine, other vasopressors, steroid, and antihistamine administration. By intradermal skin test which was done at four weeks after anaphylaxis, we confirmed positive reactions to both sugammadex and sugammadex-rocuronium complex.. This is a rare case of sugammadex-induced anaphylaxis that both sugammadex and sugammadex-rocuronium complex were confirmed as allergenic epitopes.

Topics: Anaphylaxis; Drug Combinations; Humans; Intraoperative Complications; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

Topics: Anaphylaxis; gamma-Cyclodextrins; Humans; Rocuronium; Skin Tests; Sugammadex

Topics: Anaphylaxis; Anesthesia; Bronchial Spasm; Desflurane; Humans; Rocuronium; Sugammadex

Topics: Allergens; Anaphylaxis; Humans; Immunoglobulin E; Rocuronium; Sugammadex

Anaphylaxis is a life-threatening hypersensitivity reaction that can quickly progress to circulatory collapse, even in the presence of timely epinephrine administration. This report describes a case of rocuronium anaphylaxis which progressed to circulatory arrest despite intravenous epinephrine and crystalloid resuscitation. Transesophageal echocardiography performed during cardiopulmonary resuscitation enabled rapid identification of the cause of shock and redirected management to prioritize further fluid administration, leading to return of spontaneous circulation with a good outcome. The etiology of shock in anaphylaxis can be variable, and transesophageal echocardiography can rapidly identify the likely mechanism and guide treatment without interrupting ongoing resuscitative efforts.

Topics: Anaphylaxis; Cardiopulmonary Resuscitation; Echocardiography, Transesophageal; Heart Arrest; Humans; Rocuronium

Topics: Adrenergic alpha-Agonists; Adult; Anaphylaxis; Glucocorticoids; Humans; Intraoperative Complications; Male; Methylprednisolone; Mutation; Nerve Tissue Proteins; Neuromuscular Nondepolarizing Agents; Norepinephrine; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Rocuronium

It is recommended that a skin test be performed 4-6 weeks after anaphylaxis. However, there is little evidence about the timing of the skin test when there is a need to identify the cause within 4-6 weeks.. A 57-year-old woman was scheduled to undergo surgery via a sphenoidal approach to remove a pituitary macroadenoma. Immediately after the administration of rocuronium, pulse rate increased to 120 beats/min and blood pressure dropped to 77/36 mmHg. At the same time, generalized urticaria and tongue edema were observed. Epinephrine was administered and the surgery was postponed. Reoperation was planned two weeks after the event. Four days after the anaphylactic episode, rocuronium was confirmed to be the cause by the skin prick test. Cisatracurium, which showed a negative reaction, was selected as an alternative agent for future procedures. Two weeks later, the patient underwent reoperation without any adverse events.. The early skin test can be performed if there is a need even earlier than 4-6 weeks after anaphylaxis.

Topics: Adenoma; Anaphylaxis; Anesthesia; Anesthesia, General; Female; Humans; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests; Surgical Procedures, Operative

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

While anaphylaxis can occur at any time during general anesthesia, 90% of cases occur at induction of anesthesia. As several drugs are administered simultaneously at this time, it is difficult to identify the causative agent. However, it has been found that rocuronium is the most common drug associated with perioperative anaphylaxis. We treated 2 cases of patients who were administered sugammadex for anaphylactic symptoms thought to be caused by rocuronium, after which the anaphylactic symptoms disappeared. One of the most important aspects of treating anaphylactic shock is improving hemodynamics. If signs indicating circulatory collapse are observed, epinephrine should be administered immediately. However, because rocuronium was suspected of being the causative agent, and taking the patients' clinical course over time into consideration, sugammadex was initially administered. As a result, symptoms improved. Therefore, we believe that the administration of sugammadex may be effective for treating anaphylaxis caused by rocuronium and also help in identifying the causative agent.

Topics: Anaphylaxis; Androstanols; gamma-Cyclodextrins; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

Topics: Allergens; Anaphylaxis; Androstanols; Coronary Vasospasm; gamma-Cyclodextrins; Humans; Rocuronium; Sugammadex

Sugammadex is a reversal agent for non-depolarizing neuromuscular blockers and widely used worldwide on account of its rapid and effective reversal from neuromuscular blockade, despite its advantages, multiple cases of sugammadex-induced anaphylactic shock have been reported.. A 42-year-old man developed anaphylactic shock in the postanesthesia care unit. Initially, sugammadex was suspected as the causative agent, but an intradermal skin test revealed negative results. A further skin test was performed with sugammadex-rocuronium complex that yielded positive results.. Anesthesiologists and healthcare providers should be aware of the possibility of anaphylaxis from the sugammadex-rocuronium complex, as well as from sugammadex or rocuronium alone.

Topics: Adult; Anaphylaxis; Humans; Male; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Shock; Sugammadex

The curative role of sugammadex has been challenged in several observations of rocuronium-induced anaphylaxis because sugammadex may not completely encapsulate the molecule of rocuronium. In such conditions, rocuronium remains able to cause immunoglobulin E cross-linkage and the anaphylaxis mechanism can continue. We describe a case of rocuronium-induced anaphylaxis in which clinical improvement followed sugammadex administration. Intradermic skin tests confirmed rocuronium immunoglobulin E-mediated anaphylaxis but also showed intradermal injection of mixing in equal molecular ratio of sugammadex with rocuronium preventing rocuronium anaphylactic skin reaction. This observation demonstrates the efficacy of sugammadex to prevent rocuronium interaction with the skin immune system.

Topics: Aged; Anaphylaxis; Female; Humans; Immunoglobulin E; Rocuronium; Sugammadex; Treatment Outcome

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: Anaphylaxis; Anesthesia; Anesthetics, Inhalation; Bronchial Spasm; Desflurane; Humans; Isoflurane; Rocuronium; Sugammadex

In recent years, extracorporeal membrane oxygenation has become increasingly common in the treatment of in-hospital cardiac arrest in non-cardiac surgery patients. This includes cardiac arrest secondary to perioperative anaphylactic shock refractory to standard advanced life support protocols, which is a rare but catastrophic event associated with significant mortality. Neuromuscular blocking drugs are most commonly implicated in perioperative anaphylaxis, with rocuronium playing a major role. In this article, we report two cases of young and otherwise fit and well patients who experienced a perioperative arrest secondary to rocuronium anaphylaxis before elective surgery; both patients did not respond to conventional advanced life support, but survived neurologically intact after institution of urgent veno-arterial extracorporeal membrane oxygenation.

Topics: Adult; Anaphylaxis; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Neuromuscular Nondepolarizing Agents; Perioperative Period; Rocuronium

Topics: Aged; Anaphylaxis; Cardiopulmonary Resuscitation; Fracture Fixation, Internal; Heart Arrest; Humans; Male; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

Topics: Anaphylaxis; Androstanols; Cesarean Section; Female; gamma-Cyclodextrins; Humans; Pregnancy; Rocuronium; Sugammadex

Topics: Anaphylaxis; Androstanols; Cesarean Section; Female; Humans; Pregnancy; 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: Anaphylaxis; Anesthesia, General; Coronary Vasospasm; Gastrectomy; Humans; Kounis Syndrome; Male; Middle Aged; Rocuronium; Skin Tests; Stomach Neoplasms; Sugammadex

We experienced rocuronium-induced anaphylaxis in a 62-year-old man who was scheduled for laparoscopic ileocecal excision for cecal cancer under general anes- thesia. The patient did not have a preoperative history and examinations suggestive of heart disease, or pre- disposing factors for myocardial infarction. Just after induction of anesthesia, we noticed abnormally low blood pressure and ST segment elevation on his elec- trocardiogram. The surgery was postponed and percu- taneous coronary intervention was performed to treat coronary artery stenosis. Re-operation was planned 73-days after the first operation. The patient suffered cardiac arrest just after induction of general anesthesia At the same time, we noticed systemic erythema all over his body, which led to the diagnosis of anaphy- laxis. Cardiopulmonary resuscitation was performed and the surgery was postponed once again. Cardiovas- cular agents, including adrenaline, noradrenaline, atro- pine and amiodarone, improved his hemodynamics. In addition, steroids and anti-histamines were also admin- istered to treat anaphylaxis. We advised him to undergo skin tests to determine the causative agent of anaphylaxis, but he declined. Instead, a basophil activa- tion test was performed, which showed a positive reac- tion to rocuronium. Therefore, we planned general anesthesia without using muscle relaxants such as rocuronium for the third attempt at surgery. The sur- gery was performed safely with this protocol. It is likely that his symptoms in the first general anesthesia were caused by Kounis syndrome. We conclude that the basophil activation test seems to be valuable in determining the causative agent of anaphylaxis, partic- ularly when a patient does not agree to undergo skin tests.

Topics: Anaphylaxis; Anesthesia, General; Appendiceal Neoplasms; Basophils; Humans; Kounis Syndrome; Male; Middle Aged; Rocuronium

An anaphylactic reaction during a cesarean section occurs rarely, and rocuronium is thought to be one of the common agents causing perioperative anaphylaxis. Here we report an anaphylactic shock after cesarean section that is suggested to be induced by the rocuronium-sugammadex complex. A 36-year-old primigravida underwent an elective cesarean section under general anesthesia due to placenta previa. While the operation was completed uneventfully, she developed anaphylactic shock following sugammadex administration. She was successfully managed with rapid treatments. Serum tryptase level was significantly elevated. Although sugammadex was first suspected to be the causative agent, the result of intradermal skin tests with sugammadex were negative. Surprisingly, a subsequent intradermal test with undiluted rocuronium caused the patient to fall into a state of shock. Furthermore, a later skin-prick test with pre-mixed rocuronium-sugammadex complex also revealed a strong positive reaction, and a test with only rocuronium showed negative. We finally concluded that the rocuronium-sugammadex complex is the causative agent in this case. To the best of our knowledge, this is the first report suggesting anaphylaxis caused by the rocuronium-sugammadex complex. This case highlights the importance of appropriate examinations to determinate the pathogenesis of anaphylaxis in order to establish risk reduction strategies.

Topics: Adult; Anaphylaxis; Androstanols; Anesthesia, General; Cesarean Section; Female; gamma-Cyclodextrins; Humans; Neuromuscular Nondepolarizing Agents; Pregnancy; Rocuronium; Sugammadex

Fatal anaphylaxis is uncommon but not rare. Extrapolated mortality rates are 0.52% of total anaphylaxis patients Bock et al. (Jan. 2001) [1]. Nevertheless, compared with the incidence of the other cardiac arrest events, the incidence of cardiac arrest due to anaphylaxis is relatively small. As a result, the effect using targeted temperature management after anaphylaxis is not clearly understood. We report the case of a 63-year-old man who developed cardiac arrest after ingestion of two pieces of peach. He was resuscitated and his circulation returned spontaneously after approximately 11min of cardiopulmonary resuscitation, but he was unresponsive and had fixed dilated pupils. We initiated therapeutic hypothermia on the basis of protocol for 24h. The patient was gradually and successfully cooled and rewarmed. The patient opened his eyes spontaneously on day 5, obeyed commands on day 6, and was discharged on day 18. At the time of discharge, he had no neurologic deficiencies or other complications.

Topics: Anaphylaxis; Androstanols; Fentanyl; Food Hypersensitivity; Heart Arrest; Humans; Hypothermia, Induced; Male; Midazolam; Middle Aged; Neuromuscular Nondepolarizing Agents; Prunus persica; Rewarming; Rocuronium; Treatment Outcome

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

A 49-year-old woman was scheduled for endoscopic cholecystectomy under general anesthesia in another hospital. The anesthesia was performed by a surgeon, but the operation was cancelled because of anaphylac- tic shock, and the surgeon performed emergency treatment Afterward, the surgeon declined operation, and she could not receive medical treatment. She visited our hospital for complete examination and 'operation. Drug-induced lymphocyte stimulation test (DLST) and standard perioperative test results were almost normal, and we could not find the cause of anaphylaxis preoperatively. After induction of anesthesia, the erythema ap- peared with hypotension and tachycardia. She was responsive to symptomatic treatment such as transfu- sion, antihistamine agent and streroid administration. After the recovery from the shock state, the operation proceeded without complications and she recovered from anesthesia uneventfully. She had no major post- operative complication.

Topics: Anaphylaxis; Anesthesia, General; Female; Humans; Middle Aged; Rocuronium

We experienced a case of 82-years-old-man who developed anaphylactic shock immediately after admin- istration of sugammadex. He was scheduled for ventral hernia surgery. Anesthesia was induced by propofol, rocuronium and remifentanil, and maintained with des- flurane, remifentanil and intermittent rocuronium. Intraoperative course was stable. After the operation, sugammadex was administered. After 3 minutes, hypo- tension with tachycardia developed. We administered ephedrine, but it was not effective. Then, wheal with redness also appeared over the trunk and limbs. We considered anaphylactic shock caused by sugammadex, and immediately administered adrenaline and cortico- steroid. In addition rapid volume load of crystalloid solution 500 ml was given. His hemodynamics recov- ered, and wheal with redness also disappeared gradu- ally. His respiratory state was stable and he was extubated. After administration of methylpredniso- lone, he was transferred to the surgical ward and showed no troubles thereafter. Anaphylaxis caused by sugammadex is a rare event However, considering the high frequency of sugamma- dex use in Japan, we should always keep the possibil- ity of anaphylactic shock caused by sugammadex in mind during daily general anesthetic management.

Topics: Aged, 80 and over; Anaphylaxis; Epinephrine; Hemodynamics; Humans; Japan; Male; Propofol; Remifentanil; Rocuronium; Sugammadex

Intraoperative anaphylaxis to neuromuscular blocking agents (NMBAs) is a rare event that is unpredictable and potentially life threatening. Most of the previous reports on such intraoperative anaphylaxis used market share surveys or self-reported data to estimate the incidence.. To determine the incidences of intraoperative anaphylaxis to NMBAs using electronic medical records.. A retrospective observational study.. Two tertiary hospitals in South Korea.. This study involved patients exposed to NMBAs during anaesthesia between 1 January 2005 and 31 May 2014. Nineteen episodes were deemed to be intraoperative anaphylaxis to NMBAs.. We calculated the incidences of intraoperative anaphylaxis to NMBAs. Exposure to the agents was determined from intraoperative records maintained in an electronic medical recording system. An anaphylactic reaction was determined from both clinical signs and the results of skin tests.. Over 9 years, 729 429 patients were exposed to NMBA, the most frequently used being rocuronium [425 047 (58.3%)] and vecuronium [274 801 (37.7%)]. The overall incidence of intraoperative anaphylaxis was 2.6 per 100 000 (19 cases), and was higher with rocuronium (16 cases, 3.8 per 100 000) than with vecuronium (two cases, 0.7 cases per 100 000), P = 0.014. Comparing the first 3 years with the last 6 years, the incidence of intraoperative rocuronium anaphylaxis appeared to increase 1.4-fold (P = 0.006).. Among commonly used NMBAs, rocuronium appears to have the highest incidence of anaphylaxis. Our findings suggest that future prospective investigation for NMBA-induced anaphylaxis should use internationally agreed skin test protocols.

Topics: Adolescent; Adult; Aged; Anaphylaxis; Androstanols; Electronic Health Records; Female; Humans; Incidence; Intraoperative Care; Male; Middle Aged; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Republic of Korea; Retrospective Studies; Risk Factors; Rocuronium; Skin Tests; Tertiary Care Centers; Time Factors; Vecuronium Bromide

Topics: Anaphylaxis; Androstanols; Female; gamma-Cyclodextrins; Humans; Middle Aged; Rocuronium; Skin Tests; Sugammadex

We report here a case of rocuronium-induced anaphylactic shock in a 41-year-old woman. She was scheduled for partial hepatectomy due to liver metastasis of a pheochromocytoma. Anesthesia was induced with propofol, remifentanil, and rocuronium. Bag-mask ventilation was difficult, and her blood pressure fell to around 40 mmHg just after induction. Subsequently, her trachea was intubated and adrenaline was injected. However, due to the subsequent persistence of severe hypotension and hypoxia, cardiopulmonary resuscitation was necessary. Suspecting the development of pulmonary embolism or anaphylaxis, we performed transesophageal echography; however, no evidence of right heart dilatation was observed, indicating a low possibility of pulmonary embolism. Although her general condition was stabilized, surgery was canceled. Blood tests showed high serum histamine and tryptase levels, suggesting an Ig-E mediated allergic reaction. A skin test performed five weeks after anesthesia suggested that she had suffered from rocuronium-induced anaphylaxis. A skin test also showed cross-reactivity between rocuronium and vecuronium. Therefore, we did not use any neuromuscular agent for the subsequent surgery, which was completed uneventfully. Determining the drug responsible for anaphylaxis helps to prevent recurrence of anaphylaxis.

Topics: Adult; Anaphylaxis; Androstanols; Anesthesia, General; Female; Humans; Neoplasm Recurrence, Local; Neuromuscular Blocking Agents; Piperidines; Propofol; Pulmonary Embolism; Remifentanil; Rocuronium; Skin Tests; Tryptases

We present a case of early skin and challenge testing in a patient following severe anaphylaxis to rocuronium. The patient presented for semi-elective laparoscopic cholecystectomy and developed anaphylaxis with severe cardiovascular collapse after induction of anaesthesia. Surgery was cancelled but was considered necessary before the recommended four to six weeks for formal allergy testing. Limited skin and challenge testing was performed to rocuronium and cisatracurium while the patient was in the intensive care unit to identify a safe neuromuscular blocking drug for subsequent early surgery. The subsequent surgery, 48 hours after the initial reaction, was uneventful. The case highlights the difficulties when anaesthetising patients with recent anaphylaxis who have not yet had formal allergy testing and presents a potential management strategy involving early skin testing.

Topics: Adolescent; Anaphylaxis; Androstanols; Atracurium; Cholecystectomy, Laparoscopic; Female; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests

Rocuronium is the agent most frequently involved in perioperative anaphylaxis, and sugammadex has also been known to induce anaphylactic reactions. We describe a case of successive anaphylactic episodes that seemed to be induced by clinical doses of rocuronium and sugammadex. The patient was a 19-year-old woman who had a medical history of asthma, but no history of surgery. She had been injured in a fall, and several surgeries were scheduled for multiple bone fractures. At the first surgery under general anesthesia, she developed anaphylaxis 5 min after sugammadex administration. A second general anesthesia for treatment of calcaneal fracture was induced uneventfully without neuromuscular blockade after 10 days. A third general anesthesia was scheduled to reinforce the spinal column 12 days after the first surgery. She developed anaphylaxis 8 min after rocuronium administration. The level of plasma histamine was elevated, but serum tryptase level remained normal. This surgery was canceled and rescheduled without use of a neuromuscular blockade. Skin tests were performed in a later investigation. The patient showed positive results on intradermal tests for sugammadex and rocuronium, supporting a diagnosis of allergic reactions to both drugs. Clinicians must be aware that anaphylactic reactions can be induced by both sugammadex and rocuronium.

Topics: Adult; Anaphylaxis; Androstanols; Female; gamma-Cyclodextrins; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Surgical Procedures, Operative; Young Adult

Topics: Adult; Anaphylaxis; Androstanols; gamma-Cyclodextrins; Humans; Male; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

We report our experience of a patient with a history of anaphylactic shock suspected to be caused by rocuronium who was scheduled to undergo hepatic tumor resection. The patient was a 17-year-old female (height : 166 cm, weight : 46 kg). During general anesthesia at another hospital several years ago, she had an anaphylactic shock, and rocuronium was suspected to be the offending drug. To collect information and search for the cause, skin tests were performed for rocuronium, vecuronium and suxamethonium. She was positive for rocuronium, and negative for other drugs. At anesthesia induction, we administered vecuronium and confirmed no development of anaphylaxis before commencement of surgery. In the perioperative period, she had no symptoms that indicated anaphylaxis. Since there is potential high cross-reactivity among muscle relaxants, it is important to perform a test for alternative drugs when a muscle relaxant may be a cause of anaphylaxis. Selection and administration of an alternative drug should be carefully performed, even when a skin test is negative for the alternative drug.

Topics: Adolescent; Anaphylaxis; Androstanols; Anesthesia, General; Female; Humans; Liver Neoplasms; Perioperative Period; Rocuronium; Skin Tests; Treatment Outcome; Vecuronium Bromide

A 50-year-old man developed a severe anaphylactic reaction shortly after the administration of sugammadex at the end of an uneventful laparoscopic appendectomy. Subsequent skin testing was negative to all agents to which the patient was exposed including sugammadex. Because of the temporal relationship to the administration of sugammadex, further skin testing was performed with premixed sugammadex and rocuronium that produced a markedly positive response. This is the first case report of anergy to the individual components but sensitivity to the inclusion complex of rocuronium and sugammadex. Written informed consent was obtained from the patient for skin testing, photography, laser perfusion imaging, and publication of this case report.

Topics: Anaphylaxis; Androstanols; Drug Therapy, Combination; gamma-Cyclodextrins; Humans; Male; Middle Aged; Neuromuscular Depolarizing Agents; Rocuronium; Sugammadex

Topics: Anaphylaxis; Androstanols; Atracurium; Female; Humans; Male; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Succinylcholine

Intraoperative anaphylaxis is a rare but serious occurrence, often triggered by neuromuscular-blocking drugs (NMBDs). Previous reports suggest that the rates of anaphylaxis may be greater for rocuronium than for other NMBDs, but imprecise surrogate metrics for new patient exposures to NMBDs complicate interpretation.. This was a retrospective, observational cohort study of intraoperative anaphylaxis to NMBDs at two hospitals between 2006 and 2012. Expert anesthetic and immunologist collaborators investigated all referred cases of intraoperative anaphylaxis where NMBDs were administered and identified those where a NMBD was considered responsible. New patient exposures for each NMBD were extracted from electronic anesthetic records compiled during the same period. Anaphylaxis rates were calculated for each NMBD using diagnosed anaphylaxis cases as the numerator and the number of new patient exposures as the denominator.. Twenty-one patients were diagnosed with anaphylaxis to an NMBD. The incidence of anaphylaxis was 1 in 22,451 new patient exposures for atracurium, 1 in 2,080 for succinylcholine, and 1 in 2,499 for rocuronium (P < 0.001).. In Auckland, the rate of anaphylaxis to succinylcholine and rocuronium is approximately 10-fold higher than to atracurium. Previous estimates of NMBD anaphylaxis rates are potentially confounded by inaccurate proxies of new patient exposures. This is the first study to report anaphylaxis rates using a hard denominator of new patient exposures obtained directly from anesthetic records.

Topics: Adult; Aged; Aged, 80 and over; Anaphylaxis; Androstanols; Atracurium; Causality; Cohort Studies; Female; Humans; Incidence; Intraoperative Complications; Male; Middle Aged; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; New Zealand; Retrospective Studies; Rocuronium; Succinylcholine

We report 13 cases of presumed rocuronium-induced anaphylaxis in which sugammadex was administered with the intention of reversing the immunological reaction. Of these 13 cases, eight (62%) were later confirmed to be type-1 hypersensitivity reactions to rocuronium, three (23%) were triggered by an antibiotic and two (15%) were non-immunologically mediated. Response to treatment was scored by the treating anaesthetist, and compared with haemodynamic and inotrope measurements from the resuscitation and anaesthetic records. Haemodynamic improvement was seen in only six (46%) cases, three of which were associated with a non-rocuronium trigger. Of the three cases in which the treating anaesthetist thought that sugammadex had been beneficial, one was not caused by rocuronium, one had no improvement in blood pressure and one required 8.5 times as much adrenaline in boluses after, compared with the period before, sugammadex administration. These data suggest that sugammadex does not modify the clinical course of a suspected hypersensitivity reaction.

Topics: Anaphylaxis; Androstanols; Anti-Bacterial Agents; Case-Control Studies; gamma-Cyclodextrins; Hemodynamics; Humans; Neuromuscular Nondepolarizing Agents; Retrospective Studies; Rocuronium; Sugammadex; Treatment Outcome

Anaphylaxis is an acute and fatal systemic allergic reaction to an allergen, and it could be an unpredictable and life-threatening cause during anesthesia. The main purpose of this paper is to report a case of anaphylactic shock during the anesthesia induction and to review the prophylaxis and treatment of anaphylactic reactions and anaphylactoid reactions during the anesthesia period. A 63-year-old man, with a mass on his adrenal, was scheduled to a laparoscopic adrenal tumor excision. During the anesthesia induction period, after administrated sulfentanil, propofol and rocuronium, the blood pressure was decreased and the heart rate was increased. Then, the patient had rash on his whole body and developed an anaphylactic shock. After being treated with the anti-allergic agents and norepinephrine, the rash disappeared and the vital sign become stable. The patient felt nothing uncomfortable during the two weeks'follow-up. Anaphylactic reactions and anaphylactoid reactions are not rare during the anesthesia period. The most common inducements are muscle relaxant, latex and antibiotics. Anaphylactic reactions in the perioperative period are often serious and potentially life-threatening conditions, involving multiple organ systems in which the clinical manifestations are the consequence of the release of preformed mediators from mast cells and basophils. Before anesthesia, we should acquire the allergic history. During the anesthesia period, the vital sign and the skin should be observed carefully.

Topics: Adrenal Gland Neoplasms; Anaphylaxis; Androstanols; Anesthesia; Humans; Male; Middle Aged; Perioperative Period; Rocuronium; Skin

Sugammadex is a selective binding agent for aminosteroid neuromuscular blockers whose use is increasing in anaesthetic practice. We present three cases of severe anaphylaxis coincident with sugammadex administration. Subsequent intradermal testing confirmed sugammadex as the triggering agent, with all patients having positive skin responses to a 1:100 dilution of the standard 100 mg/ml solution and two out of three having a positive response to a 1:1000 dilution. As all patients were administered sugammadex to reverse neuromuscular blockade with rocuronium, we considered that sugammadex-rocuronium complexes were a potential unique allergen. In the two patients who were additionally tested with a rocuronium-sugammadex (3.6:1 molecular ratio) mixture, the wheal-and-flare response was significantly attenuated.

Topics: Adolescent; Adult; Anaphylaxis; Androstanols; Clinical Protocols; Female; gamma-Cyclodextrins; Humans; Intradermal Tests; Intraoperative Complications; Neuromuscular Blockade; Rocuronium; 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

Topics: Anaphylaxis; Androstanols; Female; gamma-Cyclodextrins; Humans; Rocuronium; Sugammadex

Topics: Aged; Anaphylaxis; Androstanols; Female; gamma-Cyclodextrins; Humans; Intubation, Intratracheal; Neuromuscular Nondepolarizing Agents; Oxygen; Rocuronium; Sugammadex; Time Factors; Treatment Outcome

To report rapid recovery from grade IV rocuronium-induced anaphylaxis with a large dose of sugammadex administered early after the onset of symptoms.. A 22-yr-old female without relevant medical history developed an anaphylactic reaction within three minutes of rocuronium injection at induction of anesthesia for a routine cholecystectomy. During the first six minutes, she was unresponsive to usual treatment and her condition evolved to a grade IV anaphylaxis reaction despite a cumulated dose of epinephrine 0.7 mg. Sugammadex 14 mg·kg(-1), injected six minutes after rocuronium, resulted in total resolution of all manifestations of anaphylaxis within three minutes. The patient was discharged from hospital the next day. Allergy investigations confirmed rocuronium as the cause of anaphylaxis.. Very early administration of a large dose of sugammadex may be an effective treatment for rocuronium-induced anaphylaxis.

Topics: Anaphylaxis; Androstanols; Cholecystectomy; Epinephrine; Female; gamma-Cyclodextrins; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Time Factors; Treatment Outcome; 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

Topics: Aged; Anaphylaxis; Androstanols; Female; Heart Arrest; Humans; Neuromuscular Nondepolarizing Agents; Postoperative Complications; Recovery Room; Rocuronium

We report a case of a 19-year-old male with rocuronium-induced anaphylactic shock. He was scheduled for endoscopic sinus surgery for chronic sinusitis under general anesthesia. Induction of anesthesia was done with fentanyl, propofol and sevoflurane. Just after administration of rocuronium, he developed tachycardia with extended exanthema on the face, anterior chest wall and abdomen. He was difficult to ventilate manually with mask and then intubated without difficulty. The carotid arterial pulse was not palpable and adrenaline was given intermittently to maintain blood pressure. Although the systolic blood pressure increased to 80 mmHg, hemodynamics was unstable with adrenaline. Sugammadex was then given and the blood pressure became stable without adrenaline. Exanthema also disappeared gradually. He was then transferred to ICU and extubated without any sequela. The plasma beta-tryptase increased to 46 microg x l(-1) during the shock state and returned to 14.1 microg x l(-1) 8 hrs after the event. The blood hemoglobin level also increased to 21.3 g x dl(-1) during the shock state and returned to 17.2 g x dl(-1) during the recovery phase. The laboratory data showed a marked increase in vascular permeability caused by rocuronium-induced anaphylactic shock.

Topics: Anaphylaxis; Androstanols; Capillary Permeability; gamma-Cyclodextrins; Humans; Male; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Young Adult

Neuromuscular blocking drugs (NMBDs) are the most common cause of intraoperative anaphylaxis in Western Australia. Differences in the rates of anaphylaxis between individual agents have been surmised in the past, but not proven, and are an important consideration if agents are otherwise equivalent.. We estimated a rate of anaphylaxis to NMBDs by analysing cases of NMBD anaphylaxis referred to the only specialized diagnostic centre in Western Australia over a 10 yr period. Exposure was approximated by analysing a 5 yr period of NMBD ampoule sales data. Agents were also ranked according to the prevalence of cross-reactivity in patients with previous NMBD anaphylaxis.. Rocuronium was responsible for 56% of cases of NMBD anaphylaxis, succinylcholine 21%, and vecuronium 11%. There was no difference in the severity of reactions for different NMBDs. Rocuronium had a higher rate of IgE-mediated anaphylaxis compared with vecuronium (8.0 vs 2.8 per 100,000 exposures; P=0.0013). The prevalence of cross-reactivity after NMBD anaphylaxis suggested that succinylcholine also has a high risk of triggering anaphylaxis. Cisatracurium had the lowest prevalence of cross-reactivity in patients with known anaphylaxis to rocuronium or vecuronium.. Rocuronium has a higher rate of IgE-mediated anaphylaxis compared with vecuronium, a result that is statistically significant and clinically important. Cisatracurium had the lowest rate of cross-reactivity in patients who had previously suffered anaphylaxis to rocuronium or vecuronium.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anaphylaxis; Androstanols; Child; Child, Preschool; Cross Reactions; Female; Humans; Incidence; Male; Middle Aged; Neuromuscular Blocking Agents; Rocuronium; Time Factors; Vecuronium Bromide; Western Australia

Sugammadex, a new reversal agent for rocuronium, encapsulates the rocuronium molecule and results in rapid reversal of rocuronium-induced neuromuscular blockade. A case in which sugammadex was used to treat an anaphylactic reaction that occurred after rocuronium is presented. The binding/encapsulation of rocuronium by sugammadex may selectively eliminate the antigenic quaternary ammonium activity of circulating rocuronium, and prevent the propagation of rocuronium-induced anaphylaxis.

Topics: Anaphylaxis; Androstanols; Female; gamma-Cyclodextrins; Humans; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

Recently, three case reports have suggested the possible efficacy of sugammadex in anaphylactic shock refractory to conventional treatment induced by rocuronium. We report a new case of severe anaphylactic reaction to rocuronium treated with sugammadex. After 18 minutes of conventional treatment because of persistent cardiocirculatory failure and bronchospasm, a bolus of 2000 mg (18 mg/kg) of sugammadex was injected. This was associated with rapid correction of arterial hypotension and bronchoconstriction. The underlying pathophysiological mechanisms that explain the potential beneficial effect of sugammadex in this context are unknown but it is important to know that refractory anaphylactic shock to rocuronium can be potentially corrected with sugammadex.

Topics: Anaphylaxis; Androstanols; Female; gamma-Cyclodextrins; Hemodynamics; Humans; Middle Aged; Neuromuscular Nondepolarizing Agents; Pulmonary Ventilation; Recovery of Function; Rocuronium; Sugammadex; Time Factors

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

Topics: Anaphylaxis; Androstanols; Female; gamma-Cyclodextrins; Humans; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

Anaphylaxis during anesthesia is a rare event that may occur in up to 1:20,000 cases and approximately 60% to 70% of these cases are secondary to the use of muscle relaxants, particularly succinylcholine and rocuronium. The aim of this report is to describe the treatment of a case of rocuronium-induced anaphylaxis with inadequate response to traditional therapy, and the case resolution after using sugammadex.. A female patient, 62 years old, 72kg, was referred to the surgical center for treatment of epidural hematoma following an accident at home. She was monitored with pulse oximetry, cardioscope, and blood pressure meter for non-invasive blood pressure (BP) measurement. The baseline data were: BP 138/80 mm Hg, heart rate (HR) 80 bpm, and oxygen saturation (SaO(2)) 100% on room air. Anesthesia was induced with propofol 70 mg, fentanyl 200mg, and rocuronium 45 mg. After tracheal intubation, anaphylaxis non-responsive to conventional treatment was diagnosed. We chose the use of sugammadex 700 mg intravenously as an adjuvant agent. The patient had reversal of the anaphylactic reactions with improvement of hemodynamic profile and was operated and conducted to the intensive care unit.. In this case, sugammadex was used to reverse the hemodynamic picture caused by rocuronium-induced anaphylaxis. However, it was not possible to identify the exact mechanism for the reversal.

Topics: Anaphylaxis; Androstanols; Female; gamma-Cyclodextrins; Humans; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

A 17-year-old man was scheduled for ventriculo-peritoneal shunt under general anesthesia. Anesthesia was induced by propofol, rocuronium and pentazocine, and maintained with sevoflurane and nitrous oxide. The operation was finished in 1 hour and 4 minutes without trouble. After the operation, sugammadex was administered. After about 2 minutes, the redness and the wheal appeared in the body trunk, and SpO2 dropped to The appearance of rapid symptom immediately after administration of sugammadex indicated that anaphylactic reaction had occurred. We administered adrenaline. After the administration of adrenaline several times, cutaneous findings became improved and SpO2 was stabilized. We started continuous infusion of adrenaline, and the patient was moved to the intensive care unit (ICU). Twelve hours after entering the ICU, the patient was extubated. He showed no troubles thereafter, and left hospital. After introduction of sugammadex to clinical use, 7 cases of anaphylactic reaction to sugammadex were reported. We must know that anaphylactic reaction can be induced by sugammadex.

Topics: Adolescent; Anaphylaxis; Androstanols; Anesthesia, General; Epinephrine; gamma-Cyclodextrins; Humans; Male; Neuromuscular Nondepolarizing Agents; Postoperative Care; Rocuronium; Sugammadex; Treatment Outcome; Ventriculoperitoneal Shunt

We audited patients with anaphylaxis to muscle relaxants during anaesthesia referred to the Department of Anaesthesia at the Royal Adelaide Hospital between the start of 2000 and the end of 2009. Of the 220 patients tested during this period, 43 had a positive intradermal test to the muscle relaxant given during their anaesthetic. The majority of these were to rocuronium and suxamethonium. Where rocuronium was the index agent, 65% of patients cross-reacted with another relaxant and 29% of patients with suxamethonium as their index agent demonstrated cross-reaction with another relaxant.

Topics: Adult; Aged; Aged, 80 and over; Anaphylaxis; Androstanols; Cross Reactions; Female; Humans; Intradermal Tests; Male; Medical Audit; Middle Aged; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Rocuronium; Succinylcholine

Topics: Adult; Anaphylaxis; Androstanols; Anesthesia; Blood Pressure; Colostomy; Dose-Response Relationship, Drug; Epinephrine; Female; gamma-Cyclodextrins; Humans; Hypotension; Intraoperative Complications; Neuromuscular Nondepolarizing Agents; Obesity, Morbid; Rocuronium; Spinal Dysraphism; Sugammadex; Vasoconstrictor Agents

We present a case of anaphylaxis to suxamethonium and/or vecuronium in a patient who had previously suffered an anaphylactic reaction, presumably to rocuronium. The patient had not been referred for formal allergy testing after the first anaphylactic reaction. Subsequent formal allergy testing revealed sensitivities to suxamethonium, rocuronium and vecuronium. Her next anaesthetic, using cisatracurium, was uneventful. It is recommended that all patients with suspected perioperative anaphylaxis are referred for testing. This is the responsibility of the anaesthetist. Particular caution should be used with suspected neuromuscular blocking drug allergy as cross-reactivity is common and not predictable by drug structure.

Topics: Aged; Anaphylaxis; Androstanols; Atracurium; Cross Reactions; Female; Humans; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests; Succinylcholine; Vecuronium Bromide

Anaphylaxis during anaesthesia is a rare event that in ∼60-70% of cases is secondary to neuromuscular blocking agents. It has been suggested previously that the recent introduction of sugammadex may provide a novel therapeutic approach to the management of rocuronium-induced anaphylaxis. We describe the case of a 33-yr-old female who suffered a severe anaphylactic reaction to rocuronium, presenting with cardiovascular collapse on induction of anaesthesia. After 19 min of traditional management, she was given a bolus of sugammadex 500 mg. This was associated with an improvement in the adverse haemodynamic state. The underlying reasons for this are unclear, but sugammadex may potentially be a useful adjunct in the management of rocuronium-induced anaphylaxis.

Topics: Adult; Anaphylaxis; Androstanols; Female; gamma-Cyclodextrins; Hemodynamics; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; 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

The significance of IgE antibodies to neuromuscular blocking agent (NMBA)-induced anaphylactic reactions during anaesthesia is unclear. We investigated the relevance of IgE to rocuronium using an in vitro technique.. Serum samples from 61 patients with anaphylactic reactions during anaesthesia were investigated. On the basis of clinical history, allergy to NMBA was considered likely in 48 patients, further assessed using intradermal skin tests for several commonly used NMBAs, including rocuronium, vecuronium, and succinylcholine. To determine the presence of rocuronium IgE in human serum, a rocuronium-human serum albumin (rocHSA) conjugate was coupled to a solid phase and a radioallergosorbent test performed. The biological effects of patient serum NMBA-IgE on histamine release were investigated using in vitro sensitized basophils from healthy blood donors.. IgE to rocuronium was found in 23 of 48 serum samples (48%) with NMBA allergy, although only two of these were able to sensitize basophils to release histamine in response to rocHSA. IgE-responsiveness in the basophil test was only observed with conjugated rocHSA and not with unconjugated rocuronium or the other NMBAs evaluated. However, unconjugated rocuronium inhibited the histamine release induced by rocHSA. Correlation between skin-test reactivity to rocuronium and IgE to rocHSA was low (P>0.1). In contrast, striking correlation between IgE to rocuronium and skin-test reactivity to succinylcholine was found (P<0.001).. Our results indicate that NMBA-related anaphylaxis requires not only IgE NMBA reactivity, but also altered cellular reactivity in the patient. The latter may be demonstrable by testing basophils from the patient, a skin test with (steroidal) NMBA, or both.

Topics: Adult; Aged; Anaphylaxis; Androstanols; Anesthesia, General; Antibody Specificity; Basophil Degranulation Test; Female; Histamine Release; Humans; Immunoglobulin E; Intraoperative Complications; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Radioallergosorbent Test; Rocuronium; Skin Tests

Topics: Anaphylaxis; Androstanols; Basophils; Cells, Cultured; Dose-Response Relationship, Drug; gamma-Cyclodextrins; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

Topics: Anaphylaxis; Androstanols; Female; gamma-Cyclodextrins; Humans; Intraoperative Complications; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

Topics: Anaphylaxis; Androstanols; Cholecystectomy, Laparoscopic; Female; gamma-Cyclodextrins; Humans; Intraoperative Complications; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium; 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: Anaphylaxis; Androstanols; gamma-Cyclodextrins; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

We experienced two cases of anaphylaxis during anesthesia using rocuronium in two months. In both cases, we carried out intradermal test and positive reaction occurred with rocuronium. In both cases, the second anesthesia without neuromuscular blockade was uneventful. Though it is difficult to diagnose anaphylaxis, we should suspect anaphylaxis when cardiovascular collapse, bronchospasm and/or dermal symptoms occur after induction of anesthesia.

Topics: Adult; Anaphylaxis; Androstanols; Anesthesia, General; Humans; Male; Middle Aged; Rocuronium

Topics: Acetaminophen; Anaphylaxis; Androstanols; Anesthesia, General; Anti-Inflammatory Agents, Non-Steroidal; Contraindications; Female; Histamine Antagonists; Histamine Release; Humans; Hysterectomy; Intraoperative Complications; Mast Cells; Mastocytosis, Systemic; Middle Aged; Preanesthetic Medication; Rocuronium; Tonsillectomy

Topics: Anaphylaxis; Androstanols; Coronary Artery Bypass; Cosmetics; Humans; Male; Middle Aged; Models, Anatomic; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Rocuronium; Succinylcholine

To report the use of vasopressin to treat a patient who, after failing to respond to volume expansion and epinephrine administration, experienced an anaphylactic reaction to rocuronium.. A 17-yr-old female was scheduled to undergo transnasal, transsphenoidal resection of a pituitary tumour. Shortly after induction of general anesthesia, for which rocuronium 50 mg iv was administered to facilitate tracheal intubation, the patient developed severe hypotension and diffuse erythema. This severe,allergic response was refractory to the administration of intravenous fluids, epinephrine, and phenylephrine. However, arginine vasopressin, administered intravenously as a bolus of two units, followed by an infusion of 2 U.hr(-1), rapidly corrected the hemodynamic instability. Her recovery from this episode was uneventful, but surgery was cancelled. Skin testing, performed six weeks later, was positive for rocuronium and negative for cisatracurium and latex, as well as all other medications administered. Eight weeks later, the surgical procedure was performed, uneventfully, using cisatracurium as the muscle relaxant.. Vasopressin may be effective in the resuscitation of anesthetized patients, with hemodynamic instability associated with anaphylaxis resistant to epinephrine and alpha-agonists.

Topics: Adolescent; Anaphylaxis; Androstanols; Female; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Treatment Outcome; Vasoconstrictor Agents; Vasopressins

Topics: Anaphylaxis; Androstanols; Aprotinin; Female; Hemostatics; Humans; Intraoperative Complications; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Neuromuscular Nondepolarizing Agents; Rocuronium; Skin Tests

Topics: Adrenergic Agonists; Anaphylaxis; Androstanols; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Angelman Syndrome; Anti-Allergic Agents; Anti-Inflammatory Agents; Blood Pressure; Cardiopulmonary Resuscitation; Child; Diphenhydramine; Epinephrine; Female; Heart Arrest; Humans; Male; Methyl Ethers; Methylprednisolone; Midazolam; Monitoring, Physiologic; Neuromuscular Nondepolarizing Agents; Nitrous Oxide; Rocuronium; Sevoflurane; Tachycardia, Sinus; Vagus Nerve

Topics: Adverse Drug Reaction Reporting Systems; Anaphylaxis; Androstanols; Anesthesia; Drug-Related Side Effects and Adverse Reactions; Humans; Rocuronium; United States; Vecuronium Bromide

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

Muscle relaxant drugs are the most frequent cause of anaphylactic and anaphylactoid reactions during anaesthesia. We report a case of a life-threatening anaphylactic reaction during induction of anaesthesia with severe bronchospasm as the first clinical symptom. Mechanical ventilation was nearly impossible. The patient required a multimodal antiallergic therapy and a high-dose catecholamine therapy for stabilization. Rocuronium was identified as the allergic agent using intradermal testing.

Topics: Anaphylaxis; Androstanols; Anesthesia; Bronchial Spasm; Catecholamines; Humans; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Respiration, Artificial; Rocuronium; Skin; Skin Tests

Topics: Adrenergic beta-Agonists; Adult; Anaphylaxis; Androstanols; Anesthesia, General; Arrhythmias, Cardiac; Dobutamine; Electrocardiography; Female; Gynecologic Surgical Procedures; Humans; Hypotension; Neuromuscular Nondepolarizing Agents; Rocuronium; Stroke; Uterine Cervical Neoplasms

Topics: Anaphylaxis; Androstanols; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium

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: Aged; Anaphylaxis; Androstanols; Bronchodilator Agents; Dacryocystorhinostomy; Electrocardiography; Epinephrine; Humans; Hydrocortisone; Intraoperative Complications; Male; Myocardial Infarction; Neuromuscular Nondepolarizing Agents; Nitroglycerin; Oxygen Inhalation Therapy; Premedication; Rocuronium

Topics: Anaphylaxis; Androstanols; Female; Humans; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium

Topics: Anaphylaxis; Androstanols; Female; Hernia, Ventral; Humans; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium

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; Anaphylaxis; Androstanols; Female; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Succinylcholine

A 56-year-old patient was scheduled for coronary artery bypass surgery, because of a severe coronary artery disease. Soon after induction of anaesthesia, he rapidly developed a cardiovascular collapse with bronchospasm and rash. Specific immunoglobulin E and tryptase measurements supported the diagnosis of grade III anaphylactic shock due to rocuronium bromide. A few days later, a general anaesthesia was administered without muscle relaxant and was uneventful.

Topics: Anaphylaxis; Androstanols; Coronary Artery Bypass; Hematologic Tests; Humans; Immunoglobulin E; Intraoperative Complications; Middle Aged; Neuromuscular Nondepolarizing Agents; Preanesthetic Medication; Rocuronium; Serine Endopeptidases; Tryptases

Reports about anaphylactic and anaphylactoid reactions to rocuronium have increased recently. We report two new cases of documented grade III anaphylaxis, leading to death in one patient. The first case occurred in an 81-year-old ASA II woman scheduled for emergency abdominal surgery. Severe hypotension and tachycardia were observed after rocuronium, without bronchospasm. Neosynephrine allowed rapid resuscitation, and the patient recovered fully. The second patient was a 64-year-old ASA II man scheduled for abdominal surgery. Severe haemodynamic instability and bronchospasm occurred after rocuronium. Despite immediate life support, the postoperative period was complicated by persistent low systolic pressure, acute respiratory distress syndrome, acute renal failure, disseminated intravascular coagulation and pancreatitis, leading to the death of the patient.

Topics: Aged; Aged, 80 and over; Anaphylaxis; Androstanols; Fatal Outcome; Female; Humans; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium

Topics: Anaphylaxis; Androstanols; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium

Patients suspected of anaphylaxis during anaesthesia have been referred to the senior author's clinic since 1974 for investigation. Since release of rocuronium on to the worldwide market, concern has been expressed about its propensity to cause anaphylaxis. We identified 24 patients who met clinical and laboratory (intradermal, mast cell tryptase and morphine radioimmunoassay) criteria for anaphylaxis to rocuronium. The incidence of rocuronium allergy in New South Wales, Australia has risen in parallel with sales, while there has been an associated fall in reactions to other neuromuscular blocking drugs. Data from intradermal testing suggested that rocuronium is intermediate in its propensity to cause allergy in known relaxant reactors compared with low-risk agents (e.g. pancuronium, vecuronium) and higher-risk agents (e.g. alcuronium, succinylcholine).

Topics: Anaphylaxis; Androstanols; Cross Reactions; Female; Humans; Intradermal Tests; Male; Neuromuscular Blocking Agents; Neuromuscular Nondepolarizing Agents; Risk Assessment; Rocuronium

Topics: Anaphylaxis; Androstanols; Anesthesia; Anti-Infective Agents, Local; Chlorhexidine; Denmark; Humans; Neuromuscular Nondepolarizing Agents; Norway; Rocuronium

Drug induced anaphylaxis is frequently attributed to the use of muscle relaxants during anaesthesia. Recently The Norwegian Medicines Agency recommended that rocuronium bromide (Esmeron) be withdrawn from routine practice due to frequent reports of anaphylaxis. Over a period of two and a half years approximately 150,000 patients received rocuronium as part of their anaesthesia. In this period the Norwegian drug authorities received 29 reports of anaphylaxis or anaphylactoid reactions in patients treated with rocuronium. This is in stark contrast to the situation in other Nordic countries where a total of only seven cases of anaphylaxis in approximately 800,000 patients treated with rocuronium had been recorded by December 2000. This situation highlights the many potential problems of the surveillance of adverse drug reactions: reporting bias may lead to an over-estimate of the risk of one drug compared to another, and the possibility of under-reporting of adverse events (due to a weak reporting culture) further limit the validity of such comparisons. The surveillance of adverse drug reactions also represents a statistical challenge. While adverse event reports may help us to estimate the anaphylaxis rate we need to appreciate the uncertainty of such estimates. Adverse reactions are rare, random, and mostly independent events, resulting from the successive exposure of patients to a low risk intervention. The frequency distribution of adverse events will therefore conform to that of a Poisson process. The resulting Poisson distribution may inform us about the variability of adverse event data. An understanding of these methodological problems and statistical challenges will allow anaesthesiologists to make informed decisions concerning the use of muscle relaxants and other drugs associated with severe adverse reactions.

Topics: Adverse Drug Reaction Reporting Systems; Anaphylaxis; Androstanols; Anesthesia; Cluster Analysis; Humans; Incidence; Models, Statistical; Neuromuscular Nondepolarizing Agents; Norway; Poisson Distribution; Risk; Rocuronium; Statistics as Topic

Topics: Anaphylaxis; Androstanols; Humans; Neuromuscular Nondepolarizing Agents; Retrospective Studies; Rocuronium

We describe three histaminoid reactions occurring on induction of anaesthesia. The patients were all resuscitated successfully and subsequent skin testing suggested sensitivity to rocuronium. In this hospital, the incidence of such reactions is of the order of 1 in 3000. This may be coincidental but suggests that there should be close monitoring of the incidence of reactions to rocuronium. Review of the cases suggests that current guidelines on management are not always followed.

Topics: Adult; Anaphylaxis; Androstanols; Female; Humans; Intraoperative Complications; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium

Topics: Aged; Anaphylaxis; Androstanols; Female; Heart Arrest; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium

Topics: Anaphylaxis; Androstanols; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium

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

Topics: Anaphylaxis; Androstanols; Humans; Immunoglobulin E; Neuromuscular Nondepolarizing Agents; Predictive Value of Tests; Rocuronium; Skin Tests

Topics: Alcuronium; Anaphylaxis; Androstanols; Female; Humans; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Rocuronium

The authors report four cases of severe anaphylactic reactions (grade III or IV) to rocuronium bromide. In three of them, it was the first contact with a muscle relaxant. In three patients the reaction was mediated by IgE anti-bodies. A cross-reactivity with other muscle relaxants was existing in two cases (suxamethonium, vecuronium and atracurium in one patient, suxamethonium, vecuronium and pancuronium in the other.

Topics: Adult; Anaphylaxis; Androstanols; Antibodies; Atracurium; Cross Reactions; Female; Humans; Immunoglobulin E; Male; Middle Aged; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Pancuronium; Rocuronium; Skin Tests; Succinylcholine; Vecuronium Bromide

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