Clinical Usage of Different Doses of Cis-Atracurium in Intracranial Aneurysm Surgery and Its Effect on Motor-Evoked Potentials.

The objective of this work was to investigate the effect of different doses of cis-atracurium on patients undergoing general anesthesia induction (GAI) during intracranial aneurysm surgery (ICAS). In this work, 90 patients who underwent ICAS under the elective motor-evoked potential (MEP) monitoring in the First Affiliated Hospital of Northwest University (Xi'an No. 1 Hospital) from January 2021 to May 2022 were enrolled as the research objects. Randomly, they were rolled into a S1 group (30 cases, 2 times 95% effective dose (ED95) cis-atracurium), a S2 group (30 cases, 3 times ED95 cis-atracurium), and a S3 group (30 cases, 4 times ED95 cis-atracurium). The endotracheal intubation conditions, the train-of-four (TOF) rate (TOFR), body movement, and spontaneous breathing were compared among the three groups of patients. The results showed that the MEP inhibition time of the patients in the S3 group was much longer than that of the S1 and S2 groups, but it showed no significant difference between the S1 group and S2 group (P > 0.05). The good rates of endotracheal intubation conditions in the S2 group (100%) and S3 group (100%) were obviously higher than the rate in the S1 group (43.33%). The TOFRs of patients in S2 and S3 groups at time t2 and t3 were lower obviously to that at time t0, while the TOFRs of patients in S3 group at time t2 and t3 were still lower in contrast to the S2 group (P < 0.05). The mean arterial pressure (MAP) and heart rate (HR) of patients in all groups were lower at t1, t2, and t3 than at t0 (P < 0.05), while the differences among different groups were not remarkable (P > 0.05). Finally, using 3 times ED95 cis-atracurium for GAI could reduce the risk of intraoperative body movement and spontaneous breathing, as well as the residual degree of muscle relaxation, in patients with ICAS, without affecting MEP monitoring, improving endotracheal intubation conditions, and increasing safety during open neurosurgery operations.

Lethal self-administration of propofol and atracurium.

Acute propofol intoxications appear rare and remain primarily related to the acquisition of the material from the hospital. In this study, two cases of suicide following self-administration of a propofol-atracurium combination are presented as well as other propofol-related fatalities, in order to investigate propofol postmortem blood concentrations and circumstances surrounding death. The two case studies involved a 48-years-old male and a 61-year-old female, both anesthesiologists, who were found unresponsive with drugs (propofol, atracurium for both, and cisatracurium for one of them) discovered at the scene. Toxicological analyses were performed using validated chromatographic methods and highlighted the presence of propofol (1.0 µg/ml), laudanosine (0.2 µg/ml), paroxetine (3.4 µg/ml), and ethanol (12 mg/dl) for the first case and propofol (1.9 µg/ml), laudanosine (1.2 µg/ml), and hydroxyzine (0.03 µg/ml) for the second case. In the literature, 14 publications describing 27 cases of propofol-related lethal intoxications were identified. Except for two cases, all these fatalities involved healthcare professionals. Accidental overdose was the most frequently reported manner of death and the reported propofol blood concentrations ranged from 0.026 to 223.8 µg/ml. These cases, in agreement with other reported cases, highlight the concerns related to the misuse of hospital-based medicines, especially by health-care professionals, and so, the need for a much more stringent internal control of such drugs.

MRGPRX2 and Adverse Drug Reactions.

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.

Serious bronchospasm induced by cisatracurium besylate: A case report.

RATIONALE: Cis-atracurium as an intermediate-acting non-depolarizing neuromuscular blocker is widely used clinically with less causing cyclic fluctuations and less histamine release. As the use rate increases, allergic reactions and anaphylactoid reactions caused by cis-atracurium increase. PATIENT CONCERNS: A 23-year-old woman underwent laparoscopic bariatric surgery. Airway spasm occurred after anesthesia induction and the operation was suspended. After adjustment, the anesthesia was performed with the same anesthetic scheme again. After induction, skin flushing and airway resistance increased, then the symptoms were relieved. When the cis-atracurium was given again, the symptoms of airway spasm reappeared immediately, and after communicating with the family, the operation was successfully completed with rocuronium. DIAGNOSES: Serious bronchospasm induced by cisatracurium besylate. INTERVENTIONS: The patient was undergone assisted ventilation with continuous positive airway pressure (CPAP) and aminophylline 250 mg, methylprednisolone 80 mg were given intravenously. OUTCOMES: There was no any obvious discomfort in the patient's self-report during the next day's visit. The patient was discharged 7 days later. No abnormalities were observed during following 4 weeks. LESSONS: Although the anaphylactoid reactions caused by cis-atracurium are rare, the bronchospasm and anaphylactic shock caused by it greatly increase the risk of anesthesia, which should be taken seriously by clinicians. Increased vigilance in diagnosis, and treatment are essential to prevent aggravation and further complication.

Neuromuscular Blockade Monitoring in Acute Respiratory Distress Syndrome: Randomized Controlled Trial of Clinical Assessment Alone or With Peripheral Nerve Stimulation.

BACKGROUND: Whether train-of-four (TOF) monitoring is more effective than clinical monitoring to guide neuromuscular blockade (NMB) in patients with acute respiratory distress syndrome (ARDS) is unclear. We compared clinical monitoring alone or with TOF monitoring to guide atracurium dosage adjustment with respect to drug dose and respiratory parameters. METHODS: From 2015 to 2016, we conducted a randomized controlled trial comparing clinical assessments every 2 hours with or without corrugator supercilii TOF monitoring every 4 hours in patients who developed ARDS (Pao2/Fio2 <150 mm Hg) in a cardiothoracic intensive care unit. The primary outcome was the cumulative atracurium dose (mg/kg/h). Secondary outcomes included respiratory parameters during the neuromuscular blockade. RESULTS: A total of 38 patients in the clinical + TOF (C + TOF) group and 39 patients in the clinical (C) group were included in an intention-to-treat (ITT) analysis. The cumulative atracurium dose was higher in the C + TOF group (1.06 [0.75-1.30] vs 0.65 [0.60-0.89] mg/kg/h in the C group; P < .001) compared to C group, as well as the atracurium daily dose (C + TOF - C group mean difference = 0.256 mg/kg/h [95% confidence interval {CI}, 0.099-0.416], P = .026). Driving pressures during neuromuscular blocking agent (NMBA) administration did not differ between groups (P = .653). Intensive care unit (ICU) mortality was 22% in the C group and 27% in the C + TOF group (P = .786). Days on ventilation were 17 (8-26) in the C group and 16 (10-35) in the C + TOF group. CONCLUSIONS: In patients with ARDS, adding TOF to clinical monitoring of neuromuscular blockade did not change ICU mortality or days on mechanical ventilation (MV) but did increase atracurium consumption when compared to clinical assessment alone. TOF monitoring may not be needed in all patients who receive neuromuscular blockade for ARDS.

MRGPRX2 activation in mast cells by neuromuscular blocking agents and other agonists: Modulation by sugammadex.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.

Compared efficacy and tolerance of the neuromuscular blockade induced by brand-name (Nimbex®) and generic (Cisatrex®) of cisatracurium in mechanically ventilated critically ill patients: a crossover double-blind randomized study.

INTRODUCTION: use of generic drugs is common. However, there is still concern among patients and physicians that brand name drugs are more efficient. The aim of the study was to compare efficacy and tolerance between two forms of cisatracurium: brand name versus generic name. METHODS: it´s a crossover, randomized, double-blind physiological trial. Patients admitted for hypoxemic acute respiratory failure with PaO2/FIO2 < 200mmHg despite optimized ventilation and sedation thus requiring non-depolarizing neuromuscular blocking agents (NMBAs), were enrolled. Patients received consecutively, in a random order, cisatracurium brand name (Nimbex®) and generic (Cisatrex®) over two-hour period separated by one-hour washout period. Neuromuscular function was monitored by a calibrated train-of-four (TOF) stimulation device. Paralysis time delay to reach TOF of 2/4, recovery kinetics and tolerance were monitored. The number needed to demonstrate a significant difference in time delays to reach a TOF of 2/4 between the two forms of cisatracurium was estimated at 22 patients. RESULTS: twenty-two patients were included. Eight (36.4%) had acute respiratory distress syndrome; 8(36.4%), acute exacerbation of chronic obstructive pulmonary disease and 3(13.6%), status asthmaticus. Median [IQR] SAPS II at admission, 28.5 [22, 41]. PaO2/FIO2, 121 [81, 156] mmHg. Paralysis time delays were respectively, 80 [50, 112] vs. 87 [65, 115] minutes, in Nimbex® group and Cisatrex® group; (p=0.579). Within the recovery period, the between two-studied drugs´ difference in TOF was at 0.25±0.96; p=0.64. There were no significant hemodynamic differences. CONCLUSION: the present study revealed no significant differences in efficacy nor in tolerance between cisatracurium brand name Nimbex® and generic name Cisatrex® in hypoxemic ventilated patients.

A comparison between the flexor hallucis brevis and adductor pollicis muscles in atracurium-induced neuromuscular blockade using acceleromyography: A prospective observational study.

BACKGROUND: Neuromuscular blockade (NMB) monitoring is essential to avoid residual NMB. While the adductor pollicis is the recommended site for monitoring recovery, it is not always accessible. The flexor hallucis brevis could be an interesting alternative. OBJECTIVE: The aim of our study was to compare NMB onset and recovery at both sites. DESIGN: Prospective observational study. SETTING: Operating rooms at the University Hospital of Poitiers, France. PATIENTS: Sixty patients scheduled for surgery under general anaesthesia with neuromuscular blocking agents were enrolled from January 2016 to September 2017. Data from 56 patients were finally analysed. Among these, 11 patients received pharmacological reversal with neostigmine and atropine before emergence from anaesthesia. INTERVENTION: After atracurium injection, NMB onset and recovery at the adductor pollicis and flexor hallucis brevis were monitored simultaneously. MAIN OUTCOME MEASURES: The time to NMB onset, defined as a train-of-four (TOF) count equal to 0, and the times to NMB recovery: TOF = 1, TOF = 4, T4/T1 ratio = 0.75 and T4/T1 ratio more than 0.90. RESULTS: NMB onset was significantly slower at the flexor hallucis brevis with a mean onset time of 4.4 ±â€Š1.5 versus 3.7 ±â€Š1.2 min at adductor pollicis (P = 0.0001). Recovery to TOF = 1 was significantly slower at flexor hallucis brevis. No difference was found for TOF = 4. The full recovery of NMB (T4/T1 > 0.90) was significantly faster at flexor hallucis brevis with a mean time to recovery of 59.5 ±â€Š9.9 versus 64.5 ±â€Š10.7 min at adductor pollicis (P < 0.0001), a difference of 4.9 min between both sites. This difference was not present after pharmacological reversal with a mean time to recovery of 53.0 ±â€Š12.2 min at flexor hallucis brevis versus 54.0 ±â€Š12.4 min at adductor pollicis (P = 0.28). However, NMB onset and recovery did not follow the same pattern in individual patients. CONCLUSION: Flexor hallucis brevis could be an interesting alternative site for NMB monitoring when the adductor pollicis is not accessible. However, in the absence of pharmacological reversal, monitoring at the hallucis brevis muscle should be used with caution for the detection of residual paralysis. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02825121).

Drug Challenge Tests With General Anesthetics: Predictive Value of Skin Tests.

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

Retrospective evaluation of clinical use of cis-atracurium in horses.

BACKGROUND: To the authors' knowledge, there are no reports describing the use of cis-atracurium in the horse. OBJECTIVE: To describe the onset time and the duration of the neuromuscular blockade (NMB) of three different doses of cis-atracurium in horses and to determine the appropriate dose needed maintain a NMB. STUDY DESIGN: Retrospective study. METHODS: Horses which received cis-atracurium as part of a balanced anaesthetic protocol at the Equine Teaching Hospital of the University of Liège between March 2014 and June 2017 were included in this study. A train-of-four (TOF) stimulation pattern was used to assess the NMB. The cis-atracurium induction dose, the onset and duration of action (when TOF count was under three twitches) of the first bolus, the number of supplementary boluses of cis-atracurium and the total dose of cis-atracurium administered per horse, the total duration of the NMB and the recovery time were recorded and analysed. Also the use of an antidote and any side effects produced by cis-atracurium were recorded. RESULTS: From 37 horses that received cis-atracurium during this period, only 23 had a complete records and were included in the study. Three different doses of cis-atracurium were used to induce NMB: 100 µg/kg (n = 8) 75 µg/kg (n = 3) and 50 µg/kg (n = 12). Cis-atracurium 50 µg/kg failed to induce NMB in 3 horses. The onset of action was not significantly different between the three doses (5 minutes). The duration of the NMB was dose-dependent. The calculated dose of cis-atracurium necessary to maintain a NMB was 2.3 µg/kg/minute based on the sum of the induction dose and the supplementary boluses divided by the duration of the NMB. MAIN LIMITATIONS: A further prospective study is needed to confirm the results. CONCLUSIONS: Cis-atracurium can be an alternative to other NMBA in horses.

The Effects of Postoperative Residual Neuromuscular Blockade on Hospital Costs and Intensive Care Unit Admission: A Population-Based Cohort Study.

BACKGROUND: Postoperative residual neuromuscular blockade continues to be a frequent occurrence with a reported incidence rate of up to 64%. However, the effect of postoperative residual neuromuscular blockade on health care utilization remains unclear. We conducted a retrospective cohort study to investigate the effects of postoperative residual neuromuscular blockade on hospital costs (primary outcome), intensive care unit admission rate, and hospital length of stay (secondary outcomes). METHODS: We performed a prespecified secondary analysis of data obtained in 2233 adult patients undergoing surgery under general anesthesia. Postoperative residual neuromuscular blockade was defined as a train-of-four ratio <0.9 in the postanesthesia care unit (PACU). Our confounder model adjusted for a variety of patient, surgical, and anesthesia-related factors. We fitted truncated negative binomial regression models for hospital cost and hospital length of stay analyses and a logistic regression model for our intensive care unit admission analysis. RESULTS: Overall, 457 (20.5%) patients in our cohort had residual neuromuscular blockade on admission to the PACU. Postoperative residual neuromuscular blockade was not independently associated with increased hospital costs (adjusted incidence rate ratio, 1.04, CI, 0.98-1.11; P = .22). There were significantly higher odds of intensive care unit admission in those with postoperative residual neuromuscular blockade compared to those without (adjusted odds ratio, 3.03, CI, 1.33-6.87; P < .01). Further, we found a trend toward increased hospital length of stay in patients with postoperative residual neuromuscular blockade (adjusted incidence rate ratio, 1.09; P = .06). Sensitivity analysis using the same model in the day of surgery admissions and ambulatory surgery confirmed our findings. CONCLUSIONS: Postoperative residual neuromuscular blockade at PACU admission was not significantly associated with increased hospital costs, but was associated with higher rates of intensive care unit admission. These findings support the view that clinicians should continue to work to reduce the rate of postoperative residual neuromuscular blockade.

Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome.

BACKGROUND: The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear. METHODS: We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days. RESULTS: The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months. CONCLUSIONS: Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).

Intraoperative Use of Nondepolarizing Neuromuscular Blocking Agents During Cardiac Surgery and Postoperative Pulmonary Complications: A Prospective Randomized Trial.

OBJECTIVE: Nondepolarizing neuromuscular blocking agents (NMBAs) are associated with perioperative complications in noncardiac surgery; however, little is known about their effect on cardiac surgery. This study assessed the effect of neuromuscular blockade (NMB) on the incidence of postoperative pulmonary complications (PPCs) after cardiac surgery and operating conditions. DESIGN: Prospective, randomized clinical trial with blinded outcomes assessment. SETTING: University hospital, single institution. PARTICIPANTS: Adult patients having cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: One hundred patients were randomized to receive succinylcholine (group SUX) for intubation with no further NMB administered or cisatracurium (group CIS) for intubation and maintenance NMB. The primary outcome was a composite incidence of PPCs in the 72 hours after elective cardiac surgery. PPCs included failure to extubate within 24 hours, need for reintubation, pneumonia, aspiration, unanticipated need for noninvasive respiratory support, acute respiratory distress, and mortality from respiratory arrest. The secondary outcome was the adequacy of operating conditions as assessed by blinded surgeon survey (including a rating of surgical conditions on a Likert scale from 1 = poor to 5 = excellent), anesthesiologist report, and patient questionnaire. MEASUREMENTS AND MAIN RESULTS: The composite incidence of PPCs did not differ between groups (8 of 50 patients in both groups; 16%). Mean surgeon rating of surgical conditions was lower in the SUX group (4.65 ± 0.85 v 4.96 ± 0.20, p = 0.02). CONCLUSION: Although avoiding nondepolarizing NMBA is feasible, doing so worsened operating conditions and did not reduce the incidence of postoperative pulmonary complications.

Effects of atracurium besylate on corneal endothelium of chickens: in vitro study / Avaliação dos efeitos do besilato de atracúrio no endotélio corneano de galinhas: estudo in vitro

The aim of this study was to investigate the acute effects of atracurium besylate on cellular damage in corneal endothelium of chickens. Twenty healthy chicken eyes were assigned to the following groups: Group 1 (G1), experimental group (n=10); and Group 2 (G2), control (n=10). Excised corneoscleral buttons were immediately placed on glass microscopy slides with endothelial region faced up. Corneal endothelium of eyes in G1 were covered with AB (0.2mL, 10mg/mL) for 3 min and then rinsed with balanced salt solution (BSS), while the corneal endothelium of eyes in G2 were covered with BBS for 3 min. Corneas from both groups were stained with alizarin red/trypan blue and visualized by light microscopy. Ten random photographs were taken from each cornea. The area of cellular damage was measured by software in all samples and cell loss of each group was averaged and compared. Endothelial area of denudation and Descemet's membrane exposure were higher in G1 than G2. In conclusion, atracurium besylate induced an acute damage on corneal endothelium of chickens.(AU)'

Objetivou-se avaliar os efeitos agudos do besilato de atracúrio sobre o endotélio corneano de galinhas. Vinte olhos saudáveis de galinhas foram aleatoriamente separados em dois grupos com 10 olhos cada, sendo G1 o grupo controle e G2 o grupo tratamento. Imediatamente após a excisão dos botões corneoesclerais estes foram colocados em lâminas de microscopia de vidro com o lado endotelial voltado para cima. No Grupo 1, o endotélio corneano foi recoberto com 0,2ml de besilato de atracúrio (10mg/ml) durante 3 minutos e depois lavado com solução salina balanceada. No Grupo 2, o endotélio corneano foi recoberto apenas com solução salina balanceada durante 3 min. As córneas de ambos os grupos foram coradas com vermelho de alizarina e azul de tripano e visualizadas com microscópio óptico. Foram obtidas dez fotografias aleatórias de cada amostra. As imagens foram analisadas e com auxílio de um software as áreas com ausência de células endoteliais calculadas. A perda celular endotelial foi significativamente maior no grupo tratamento comparativamente ao grupo controle. Com base nos resultados apresentados foi possível concluir que o besilato de atracúrio induziu dano agudo nas células do endotélio da córnea de galinhas.(AU)

Fatal Anaphylaxis to Atracurium: A Case Report.

A 52-year-old patient was scheduled for a cystoscopy. Anesthesia was induced by intravenous injection of fentanyl and propofol. After administration of atracurium, he became bradycardic and suffered a cardiac arrest. Despite prolonged cardiopulmonary resuscitation, the patient could not be revived. Electrolytes and hemoglobin levels were normal, and a transthoracic echocardiogram showed no signs of pericardial effusions or of any left ventricular contraction. The postmortem found no pathology. However, mast cell tryptase was raised significantly, indicating fatal anaphylaxis. Having presented no classic clinical signs, this case is a reminder that rapid cardiovascular collapse can be the sole clinical feature of anaphylaxis.

MRGPRX2-mediated mast cell response to drugs used in perioperative procedures and anaesthesia.

The study of anaphylactoid reactions during perioperative procedures and anaesthesia represents a diagnostic challenge for allergists, as many drugs are administered simultaneously, and approximately half of them trigger allergic reactions without a verifiable IgE-mediated mechanism. Recently, mast cell receptor MRGPRX2 has been identified as a cause of pseudo-allergic drug reactions. In this study, we analyse the ability of certain drugs used during perioperative procedures and anaesthesia to induce MRGPRX2-dependent degranulation in human mast cells and sera from patients who experienced an anaphylactoid reaction during the perioperative procedure. Using a ß-hexosaminidase release assay, several drugs were seen to cause mast cell degranulation in vitro in comparison with unstimulated cells, but only morphine, vancomycin and cisatracurium specifically triggered this receptor, as assessed by the release of ß-hexosaminidase in the control versus the MRGPRX2-silenced cells. The same outcome was seen when measuring degranulation based on the percentage of CD63 expression at identical doses. Unlike that of the healthy controls, the sera of patients who had experienced an anaphylactoid reaction induced mast-cell degranulation. The degranulation ability of these sera decreased when MRGPRX2 was silenced. In conclusion, MRGPRX2 is a candidate for consideration in non-IgE-mediated allergic reactions to some perioperative drugs, reinforcing its role in mast cell responses and their pathophysiology.