Remimazolam anaphylaxis in a patient not allergic to brotizolam: a case report and literature review.

BACKGROUND: Remimazolam is a recently developed, ultrashort-acting benzodiazepine that is used as a general anesthetic. Some cases of remimazolam anaphylaxis have been reported, but its characteristics are not fully understood. We present an interesting case report and review of the literature to better understand remimazolam anaphylaxis. CASE PRESENTATION: A 75-year-old man scheduled for robot-assisted gastrectomy was administered remimazolam for the induction of general anesthesia. After intubation, low end-expiratory CO2, high airway pressure and concurrent circulatory collapse were observed. Bronchoscopy revealed marked tracheal and bronchial edema, which we diagnosed as anaphylaxis. The patient suffered cardiac arrest after bronchoscopy but recovered immediately with intravenous adrenaline administration and chest compressions. We performed skin prick tests for the drugs used during induction except for remimazolam, considering the high risk of systemic adverse reactions to remimazolam. We diagnosed remimazolam anaphylaxis because the skin prick test results for the other drugs used during anesthesia were negative, and these drugs could have been used without allergic reactions during the subsequent surgery. Furthermore, this patient had experienced severe anaphylactic-like reactions when he underwent cardiac surgery a year earlier, in which midazolam had been used, but it was not thought to be the allergen at that time. Based on these findings, cross-reactivity to remimazolam and midazolam was suspected. However, the patient had previously received another benzodiazepine, brotizolam, to which he was not allergic, suggesting that cross-reactivity of remimazolam may vary among benzodiazepines. In this article, we reviewed the 11 cases of remimazolam anaphylaxis that have been described in the literature. CONCLUSIONS: Remimazolam is an ultrashort-acting sedative; however, it can cause life-threatening anaphylaxis. In addition, its cross-reactivity with other benzodiazepines is not fully understood. To increase the safety of this drug, further research and more experience in its use are needed.

Respiratory muscles's thermographic analysis in asthmatic youth with and without bronchospasm induced by eucapnic voluntary hyperpnea.

OBJECTIVE: To compare the thermographic pattern of regions of interest (ROI) of respiratory muscles in young asthmatics with and without bronchospasm induced by eucapnic voluntary hyperpnea (EVH). MATERIALS AND METHODS: Cross-sectional study carried out with 55 young (55% male and 45% females) aged 12.5 ± 3.3 years, divided in nine nonasthmatics, 22 asthmatics without exercise-induced bronchospasm compatible response (EIB-cr) and 24 asthmatics with EIB-cr. The diagnosis of EIB was given to subjects with a fall in forced expiratory volume in the first second (FEV1) ≥ 10% compared to baseline. Thermographic recordings of respiratory muscles were delimited in ROI of the sternocleidomastoid (SCM), pectoral, and rectus abdominis intention area. Thermal captures and FEV1 were taken before and 5, 10, 15 and 30 min after EVH. RESULTS: Twenty-four (52.1%) of asthmatics had EIB-cr. There was a decrease in temperature at 10 min after EVH test in the SCM, pectoral and rectus abdominis ROIs in all groups (both with p < 0.05). There was a decrease in temperature (% basal) in asthmatic with EIB-cr compared to nonasthmatics in the rectus abdominis area (p < 0.05). CONCLUSION: There was a decrease in temperature in the ROIs of different muscle groups, especially in asthmatics. The greater drop in FEV1 observed in individuals with EIB-cr was initially associated with a decrease in skin temperature, with a difference between the nonasthmatics in the abdominal muscle area. It is likely that this decrease in temperature occurred due to a temporary displacement of blood flow to the most used muscle groups, with a decrease in the region of the skin evaluated in the thermography.

Atracurium-Induced Bronchospasm With Flat Capnograph at Induction of General Anaesthesia: A Case Report.

Benzylisoquinolinium neuromuscular blocking agents can precipitate bronchospasm either through allergy/anaphylaxis or isolated stimulation of mast cell histamine release. This report presents a 75-year-old female who attended the day surgery unit for a rigid cystoscopy under general anaesthesia. She had a hyper-reactive airway history of mild historic asthma and sensitivity to aerosols. After administration of atracurium at induction of anaesthesia, ventilation became challenging with no chest rise and a flat CO2 trace. Repeat video laryngoscopy confirmed correct endotracheal tube position. The patient remained cardiovascularly stable with no mucocutaneous signs of anaphylaxis. Administration of high flow oxygen, sevoflurane, salbutamol and magnesium sulfate led to gradual improvement and normalisation of respiratory parameters. Surgery was postponed. This report highlights atracurium as an important trigger of bronchospasm at induction of anaesthesia, and illustrates that in rare cases a flat capnograph does not always indicate a mispositioned airway device. Several aspects of the anaesthetic plan for this patient were suboptimal given her respiratory history, namely, the choice of mode of anaesthesia and choice of neuromuscular blocking agent. These factors are discussed in the context of anaesthetic planning for patients presenting with features suggesting high bronchospastic risk.

Cocaine-Induced Asthma and the "Crack Lung": A Case Report.

Cocaine, the second most used illicit drug, is associated with cardiovascular, pulmonary, and other complications. Lung involvement associated with cocaine use, also known as "crack lung syndrome" (CLS), can elicit new-onset and exacerbate chronic pulmonary conditions. A 28-year-old female with a history of chronic controlled asthma arrived at the Emergency Department (ED), referring to cocaine inhalation, followed by symptoms compatible with an asthmatic crisis, requiring immediate steroid and bronchodilator therapy. Radiological studies and bronchoscopy confirmed CLS diagnosis. Despite treatment with oxygen, bronchodilators, and steroids, the asthmatic crises persisted. However, after 48 hours, we observed a complete regression of the lung infiltrates. This case highlights the importance of clinical suspicion, bronchoscopy findings, and the potential co-occurrence of CLS with asthma exacerbations. While computed tomography (CT) scans can be helpful, they should not be the only tool to diagnose CLS. The successful management of CLS involves the use of bronchodilators, steroids, and oxygen therapy and abstaining from cocaine use. Researchers should conduct further studies to diagnose and treat CLS in conjunction with acute asthma symptoms to assist this patient population better.

Critical Care Management of Severe Asthma Exacerbations.

Severe asthma exacerbations, including near-fatal asthma (NFA), have high morbidity and mortality. Mechanical ventilation of patients with severe asthma is difficult due to the complex pathophysiology resulting from severe bronchospasm and dynamic hyperinflation. Life-threatening complications of traditional ventilation strategies in asthma exacerbations include the development of systemic hypotension from hyperinflation, air trapping, and pneumothoraces. Optimizing pharmacologic techniques and ventilation strategies is crucial to treat the underlying bronchospasm. Despite optimal pharmacologic management and mechanical ventilation, the mortality rate of patients with severe asthma in intensive care units is 8%, suggesting a need for advanced non-pharmacologic therapies, including extracorporeal life support (ECLS). This review focuses on the pathophysiology of acute asthma exacerbations, ventilation management including non-invasive ventilation (NIV) and invasive mechanical ventilation (IMV), the pharmacologic management of acute asthma, and ECLS. This review also explores additional advanced non-pharmacologic techniques and monitoring tools for the safe and effective management of critically ill adult asthmatic patients.

Protective effect of Achyranthes aspera against compound 48/80, histamine and ovalbumin-induced allergic disorders in murine model.

BACKGROUND: Achyranthes aspera L. (family Amaranthaceae) is a plant species valued in Ayurveda for the treatment of respiratory ailments. Scientific validation of its antiallergic potential was aimed. METHODS AND RESULTS: Three extracts of A. aspera [aqueous (AaAq), hydroalcoholic (AaHA), ethanolic (AaEt)] were evaluated for their potency against C48/80-induced anaphylaxis in mice at 200 mg/kg BW oral dose. The effective dose of the most potent extract was determined through its effect on C48/80-induced anaphylaxis, and was further analyzed through its effect on mast cell degranulation, histamine-induced bronchospasm and ovalbumin (OVA)-induced asthma in a murine model. Among the three extracts, AaAq was found to be most potent at 200 mg/kg BW. AaAq 400 (400 mg/kg BW) was found to be the most effective dose in terms of inhibition of mortality and histamine level. AaAq 400 prevented the peritoneal and mesenteric mast cells from undergoing morphological changes due to degranulation induced by C48/80. Further, AaAq 400 delayed pre-convulsive time in histamine-induced bronchospasm. In the OVA-induced asthma model, AaAq 400 inhibited the level of inflammatory cell count in blood, bronchoalveolar lavage fluid and peritoneal fluid of mice. The Th2 cytokines (IL-4, IL-5, IL-13), TGF-ß and OVA-specific IgE were also reduced as evaluated by ELISA. Also, significant reduction in IL-5 (an eosinophilia indicator) transcript abundance and lung inflammatory score was observed. AaAq was safe up to 4000 mg/kg BW. CONCLUSIONS: Thus AaAq 400 possesses significant antiallergic potential and acts via attenuation of C48/80-induced anaphylaxis and inhibition of mast cell degranulation. It reduces pre-convulsive dyspnea in histamine-induced bronchospasm and Th2 cytokines in asthmatic mice.

Exercise-Induced Asthma: Managing Respiratory Issues in Athletes.

Asthma is a complex respiratory condition characterized by chronic airway inflammation and variable expiratory airflow limitation, affecting millions globally. Among athletes, particularly those competing at elite levels, the prevalence of respiratory conditions is notably heightened, varying between 20% and 70% across specific sports. Exercise-induced bronchoconstriction (EIB) is a common issue among athletes, impacting their performance and well-being. The prevalence rates vary based on the sport, training environment, and genetics. Exercise is a known trigger for asthma, but paradoxically, it can also improve pulmonary function and alleviate EIB severity. However, athletes' asthma phenotypes differ, leading to varied responses to medications and challenges in management. The unique aspects in athletes include heightened airway sensitivity, allergen, pollutant exposure, and temperature variations. This review addresses EIB in athletes, focusing on pathogenesis, diagnosis, and treatment. The pathogenesis of EIB involves complex interactions between physiological and environmental factors. Airway dehydration and cooling are key mechanisms, leading to osmotic and thermal theories. Airway inflammation and hyper-responsiveness are common factors. Elite athletes often exhibit distinct inflammatory responses and heightened airway sensitivity, influenced by sport type, training, and environment. Swimming and certain sports pose higher EIB risks, with chlorine exposure in pools being a notable factor. Immune responses, lung function changes, and individual variations contribute to EIB in athletes. Diagnosing EIB in athletes requires objective testing, as baseline lung function tests can yield normal results. Both EIB with asthma (EIBA) and without asthma (EIBwA) must be considered. Exercise and indirect bronchoprovocation tests provide reliable diagnoses. In athletes, exercise tests offer effectiveness in diagnosing EIB. Spirometry and bronchodilation tests are standard approaches, but the diagnostic emphasis is shifting toward provocation tests. Despite its challenges, achieving an optimal diagnosis of EIA constitutes the cornerstone for effective management, leading to improved performance, reduced risk of complications, and enhanced quality of life. The management of EIB in athletes aligns with the general principles for symptom control, prevention, and reducing complications. Non-pharmacological approaches, including trigger avoidance and warming up, are essential. Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy in athletes. Short-acting beta agonists (SABA) are discouraged as sole treatments. Leukotriene receptor antagonists (LTRA) and mast cell stabilizing agents (MCSA) are potential options. Optimal management improves the athletes' quality of life and allows them to pursue competitive sports effectively.

Peri-operative cardiac arrest due to suspected anaphylaxis as reported to the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project (NAP7) of the Royal College of Anaesthetists studied peri-operative cardiac arrest. Among 59 cases reported as possible anaphylaxis, 33 (56%) were judged to be so by the review panel with high or moderate confidence. Causes in excluded cases included: isolated severe hypotension; bronchospasm; and oesophageal intubation. Severe bronchospasm leading to cardiac arrest was uncommon, but notably in one case led to a reported flat capnograph. In the baseline survey, anaesthetists estimated anaphylaxis as the cause of 10% of cases of peri-operative cardiac arrests and to be among the four most common causes. In a year-long registry of peri-operative cardiac arrest, suspected anaphylaxis was the seventh most common cause accounting for 4% of reports. Initial management was most often with low-dose intravenous adrenaline, and this was without complications. Both the NAP7 baseline survey and case registry provided evidence of reluctance to starting chest compressions when systolic blood pressure had fallen to below 50 mmHg and occasionally even when it was unrecordable. All 33 patients were resuscitated successfully but one patient later died. The one death occurred in a relatively young patient in whom chest compressions were delayed. Overall, peri-operative anaphylaxis leading to cardiac arrest occurred with a similar frequency and patterns of presentation, location, initial rhythm and suspected triggers in NAP7 as in the 6th National Audit Project (NAP6). Outcomes in NAP7 were generally better than for equivalent cases in NAP6.

Life-threatening bronchospasm induced by an angiotensin-converting enzyme inhibitor in a chronically ventilated patient: Diagnostic pitfalls and literature review.

Cough- and asthma-like symptoms are common adverse reactions to angiotensin-converting enzyme inhibitors (ACEi). However, attributing these symptoms to the use of ACEi might be masked by clinical confounders. We report a 68-year-old female residing in a long-term acute-care facility for patients requiring prolonged invasive mechanical ventilation treated for years with ACEi. Daily reversible bouts of life-threatening severe bronchospasm gradually developed over 6 weeks and abruptly resolved following the cessation of ACEi treatment. The late appearance of bronchospasm and the unique clinical setup of chronic invasive ventilation in a patient with smoking-related chronic obstructive lung disease are among the principal confounders that delay the identification of the causative association between ACEi and respiratory compromise. Chronic positive pressure ventilation may also conceal small airway reactivity and obstruction, similar to auto-positive end-expiratory pressure (auto-PEEP). Conceivably, angiotensin receptor blockers should be preferred over ACEi in such patients.

Salbutamol transport and deposition in healthy cat airways under different breathing conditions and particle sizes.

Salbutamol is a bronchodilatator commonly used for the treatment of feline inflammatory lower airway disease, including asthma or acute bronchospasm. As in humans, a pressurized metered dose inhaler (pMDI) is used in conjunction with a spacer and a spherical mask to facilitate salbutamol administration. However, efficacy of inhalation therapy is influenced by different factors including the non-cooperative character of cats. In this study, the goal was to use computational fluid dynamics (CFD) to analyze the impact of breathing patterns and salbutamol particle size on overall drug transport and deposition using a specific spherical mask and spacer designed for cats. A model incorporating three-dimensional cat airway geometry, a commercially available spherical mask, and a 10 cm spacer, was used for CFD analysis. Two peak inspiratory flows were tested: 30 mL/s and 126 mL/s. Simulations were performed with 30s breathing different inspiratory and expiratory times, respiratory frequencies and peaks. Droplet spray transport and deposition were simulated with different particle sizes typical of the drug delivery therapies (1, 5, 10, and 15 µm). The percentage of particle deposition into the device and upper airways decreased with increasing particle diameter during both flows imposed in this cat model. During increased mean ventilatory rate (MVR) conditions, most of the salbutamol was lost in the upper airways. And during decreased MVR conditions, most of the particles remained in suspension (still in hold-up) between the mask and the carina, indicating the need for more than 30 s to be transported. In both flows the percentage of particles traveling to the lung was low at 1.5%-2.3%. In conclusion, in contrast to what has been described in the human literature, the results from this feline model suggest that the percentage of particles deposited on the upper airway decreases with increasing particle diameter.

Right place, no trace: A case report of postintubation bronchospasm.

Evidence suggests obesity correlates with airway hyperreactivity, which can result in severe bronchospasm. This report presents a 31-year-old female with a high body mass index who presented for a laparoscopic hysterectomy and bilateral salpingo-oophorectomy. She had no past medical or atopic history. After induction of anaesthesia and intubation, O2 saturation fell with no CO2 trace, breathing sounds or chest rise. Despite confirming endotracheal tube position by video laryngoscopy, the CO2 trace remained flat and mechanical ventilation was difficult with high airway pressures. Blood pressure was stable with no mucocutaneous signs of anaphylaxis. Administration of 100% O2, bronchodilators and steroids improved ventilation and oxygenation with a return of a CO2 trace. The operation was postponed. Prior to her subsequent surgery, the patient was premedicated with inhaled steroids and long-acting beta agonist with an uneventful induction and intubation. Giving a rising obese population, this case report aims to educate anaesthetists and anaesthetic practitioners as to the presentation, risk factors, mechanisms and management of uncommon, life-threatening postintubation bronchospasm.

Another case of preventable death from asthma.

INTRODUCTION: Asthma prevalence is 262 million globally, with more than 1,000 deaths each day, most of them preventable. We were performing a longitudinal study, in Brazil, with the objective to following up patients who had a severe asthma attack and attended an emergency room (ATTACK Study). Here we present a case of a 28-year-old woman presenting what was considered moderate asthma, enrolled in ATTACK, who subsequently died of asthma. CASE STUDY: The patient was initially evaluated at an emergency room (ER) with uncontrolled asthma and no regular treatment. She had an asthma diagnosis just before this visit to the ER, despite presenting symptoms of asthma since childhood. She was subsequently evaluated by a specialist, who prescribed a treatment with regular inhaled corticosteroid and an inhaled bronchodilator, if necessary. The patient was systematically monitored by telephone for six months. RESULTS: The patient did not adhere to the treatment, in spite of repeated warnings, and 6 months later had an asthma attack resulting in her death. CONCLUSION: It is important to prioritize asthma in primary health care, including building capacity health care professionals for early diagnosis, asthma management, and to educate patients with asthma patients for the identification of worsening and signs of severity, to manage the exacerbations according to a written asthma plan. This may reduce the number of premature and preventable asthma deaths.

Perioperative Care of the Pediatric Patient and an Algorithm for the Treatment of Intraoperative Bronchospasm.

Asthma remains a common comorbid condition in patients presenting for anesthetic care. As a chronic inflammatory disease of the airway, asthma is known to increase the risk of intraoperative bronchospasm. As the incidence and severity of asthma and other chronic respiratory conditions that alter airway reactivity is increasing, a greater number of patients at risk for perioperative bronchospasm are presenting for anesthetic care. As bronchospasm remains one of the more common intraoperative adverse events, recognizing and mitigating preoperative risk factors and having a pre-determined treatment algorithm for acute events are essential to ensuring effective resolution of this intraoperative emergency. The following article reviews the perioperative care of pediatric patients with asthma, discusses modifiable risk factors for intraoperative bronchospasm, and outlines the differential diagnosis of intraoperative wheezing. Additionally, a treatment algorithm for intraoperative bronchospasm is suggested.

Inhaled Short-Acting Beta Agonist Treatment-Associated Supraventricular Tachycardia in Children: Still a Matter of Concern in Pediatric Emergency Departments?

Inhaled selective short-acting ß-2 agonists (SABA), such as salbutamol, are the rescue treatment of choice for the relief of symptoms of acute asthma exacerbations: one of the leading causes of pediatric emergency department admission and hospitalization. Cardiovascular events, including supraventricular arrhythmias, are the most frequent side effects reported with inhaled SABA in children with asthma and are the main reason for a continuing debate about their safety, despite their widespread use. Although supraventricular tachycardia (SVT) is the most common potentially serious dysrhythmia in children, the incidence and risk factor of SVT after SABA administration is currently unknown. We here reported three cases and conducted a review of the literature in an attempt to gain insight into this issue.

Inhaled volatile anesthetic gas for severe bronchospasm in the emergency department.

Bronchospasm is caused by reversible constriction of the smooth muscles of the bronchial tree. This causes obstruction of the lower airways, which is commonly seen at the emergency department (ED) in patients with acute exacerbation of asthma or chronic obstructive pulmonary disease. Ventilation may be difficult in mechanically intubated patients with severe bronchospasm due to airflow limitation, air trapping, and high airway resistance. The beneficial effects of volatile inhaled anesthetic gas had been reported due to its bronchodilation properties. In this case series, we would like to share our experience delivering inhaled volatile anesthetic gas via a conserving device for three patients with refractory bronchospasm at the ED. Inhaled anesthetic gas is safe, feasible and should be considered as an alternative rescue therapy for ventilated patients with severe lower airway obstruction.

The usefulness of a nasopharyngeal multiplex polymerase chain reaction system to screen pediatric patients with preoperative fever.

BACKGROUND: When children have a preoperative fever, anesthesiologists must help determine whether to postpone or proceed with surgery, as fever may be a sign of upper respiratory tract infection (URTI). Such infections are a known risk factor for perioperative respiratory adverse events (PRAEs), which are still one of the prime causes of anesthetic mortality and morbidity in pediatric patients. Since the COVID-19 pandemic, preoperative assessments have become drastically more complex as hospitals strive to balance practicality and safety. In our facility, if pediatric patients presented with preoperative fever, we used the FilmArray® Respiratory Panel 2.1 to determine whether to postpone or proceed with surgery. METHODS: This is a single-center retrospective observational study evaluating the efficacy of the FilmArray® Respiratory Panel 2.1 as a preoperative screening test. This study included pediatric patients scheduled for elective surgeries between March 2021 and February 2022. FilmArray was used if a patient had a preoperative fever (determined by axillary temperature, ≥38°C for <1-year-old, ≥37.5°C for ≥1-year-old) between hospital admission and before surgery. We excluded patients if they had apparent symptoms of URTI. RESULTS: In the FilmArray positive group, 11 of 25 (44%) cases developed subsequent symptoms after surgery was canceled. No patients in the negative group developed symptoms. The proportion of the development of subsequent symptoms between the FilmArray positive and negative groups was statistically significant (p < .001, odds ratio: 29.6, 95% confidence interval: [3.80-1356.01]). CONCLUSIONS: Our retrospective observational study revealed that 44% of the FilmArray positive group subsequently developed symptoms, and no PRAEs were observed in the FilmArray negative group. We suggest that FilmArray could be useful as a screening test for pediatric patients with preoperative fever.

The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma.

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

Can physical exercise assist in controlling and reducing the severity of exercise-induced bronchospasm in children and adolescents? A systematic review.

OBJECTIVE: The aim of this study was to analyze whether physical exercise can contribute to improving the control and severity of exercise-induced bronchospasm (EIB) in children and adolescents. METHOD: This is a systematic review that used PubMed/Medline and Scopus databases as a search source, and using descriptors indexed to DeCS/Mesh. The articles were analyzed in three stages in the selection process. Methodological quality was assessed using the TESTEX scale. RESULT AND DISCUSSION: A total of 5867 articles were filtered in the initial search; however, only eight of these were included after the eligibility criteria. All presented improvements in cardiorespiratory fitness. Only two followed the international EIB diagnostic guidelines. Of these, only one described a reduction in FEV1 and considered that this improvement may influence the EIB response in children and adolescent athletes with a non-asthmatic sample. CONCLUSION: The studies analyzed in this review did not enable drawing a conclusion regarding the influence of physical exercise on EIB in asthmatics. The lack of clinical trials on EIB and physical exercise, as well as the difficulty in methodological standardization for EIB diagnosis evidence the lack of scientific knowledge in this area, serving as a stimulus for researchers to find more consolidated answers.