Interrogation of the Plasma-Catalyst Interface via In Situ/Operando Transmission Infrared Spectroscopy.

Plasma-surface coupling has emerged as a promising approach to perform chemical transformations under mild conditions that are otherwise difficult or impossible thermally. However, a few examples of inexpensive and accessible in situ/operando techniques exist for observing plasma-solid interactions, which has prevented a thorough understanding of underlying surface mechanisms. Here, we provide a simple and adaptable design for a dielectric barrier discharge (DBD) plasma cell capable of interfacing with Fourier transform infrared spectroscopy (FTIR), optical emission spectroscopy (OES), and mass spectrometry (MS) to simultaneously characterize the surface, the plasma phase, and the gas phase, respectively. The system was demonstrated using two example applications: (1) plasma oxidation of primary amine functionalized SBA-15 and (2) catalytic low temperature nitrogen oxidation. The results from application (1) provided direct evidence of a 1% O2/He plasma interacting with the aminosilica surface by selective oxidation of the amino groups to nitro groups without altering the alkyl tether. Application (2) was used to detect the evolution of NOX species bound to both platinum and silica surfaces under plasma stimulation. Together, the experimental results showcase the breadth of possible applications for this device and confirm its potential as an essential tool for conducting research on plasma-surface coupling.

Agreement of a clinical scoring system with allergic anaphylaxis in suspected perioperative hypersensitivity reactions: prospective validation of a new tool.

BACKGROUND: A clinical scoring system to estimate the likelihood that a reaction represents a perioperative immediate hypersensitivity reaction has been devised using a Delphi consensus process. Agreement of this clinical scoring system with the outcome of allergological assessment would allow the use of this tool in post-resuscitation and subsequent management of suspected perioperative immediate hypersensitivity reaction and potentially as a new standard reference for clinical investigations. METHODS: We prospectively scored 301 cases of suspected perioperative immediate hypersensitivity reaction according to the Hypersensitivity Clinical Scoring Scheme. Classification of cases was by allergological workup based on immediate and delayed investigations. The discrimination and calibration of the Hypersensitivity Clinical Scoring Scheme was compared with results from an expert panel of allergologists, skin testing, mast cell tryptase ratios, and specific IgE assays, as was agreement by Cohen's kappa coefficient. RESULTS: The Hypersensitivity Clinical Scoring Scheme predicted cases of allergic perioperative immediate hypersensitivity reaction with comparable discrimination to an expert panel, mast cell tryptase formula, and specific IgE assays in anaphylaxis to neuromuscular blocking drugs. Using a score threshold of 15 or greater to indicate allergic perioperative immediate hypersensitivity reaction, the sensitivity was 88.9%, with a specificity of 79.4%. Prospectively, the Hypersensitivity Clinical Scoring Scheme correctly classified a greater number of subjects than the expert panel and the optimal post hoc binary logistic regression model (86% vs 85% vs 84%), however it was inferior to skin testing. CONCLUSION: The Hypersensitivity Clinical Scoring Scheme predicts allergic perioperative immediate hypersensitivity using features of the acute syndrome. This approach could guide algorithms for the post-resuscitative management of suspected perioperative immediate hypersensitivity, and identify patients requiring drug provocation challenge.

Relationship of perioperative anaphylaxis to neuromuscular blocking agents, obesity, and pholcodine consumption: a case-control study.

BACKGROUND: 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. METHODS: 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. RESULTS: Obesity (odds ratio [OR]=2.96, χ2=11.7, P=0.001), 'definite' pholcodine consumption (OR=14.0, χ2=2.6, P<0.001), and female sex (OR=2.70, χ2=9.61, P=0.002) were statistically significant risk factors for NMBA anaphylaxis on univariate analysis. The risk of NMBA anaphylaxis increased with BMI grade. Confounding analysis indicated that both obesity and pholcodine consumption remained important risk factors after correction for confounding, but that sex did not. The relative rate of rocuronium anaphylaxis was estimated to be 3.0 times that of vecuronium using controls as an estimate of market share, and the risk of NMBA anaphylaxis in patients presenting for bariatric surgery was 8.8 times the expected rate (74.9 vs 8.5 per 100 000 anaesthetic procedures). CONCLUSIONS: 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.

Anaphylaxis to intravenous paracetamol containing povidone. A case report and narrative review of excipient allergy related to anaesthesia.

Investigation of intraoperative anaphylaxis includes the exclusion of potential trigger agents the individual was exposed to within a plausible interval preceding the reaction. Occasionally, none of these agents will test positive. In this situation it is important to consider that excipients may be responsible for anaphylaxis, that the dilutions prepared to test the medication may not contain an appropriate concentration of the excipient to induce a positive skin reaction, or if an alternative formulation of the medication is tested, it may not contain the culprit excipient. This case describes a patient, who previously experienced an anaphylactic reaction to Betadine® (Sanofi-Aventis Australia Pty Ltd, North Ryde BC, NSW) experiencing anaphylaxis in the recovery period after general anaesthesia where Betadine was avoided. The recently administered therapeutics were excluded by skin testing, however further investigation determined that a povidone-containing formulation of paracetamol had been administered. Skin testing with povidone-containing paracetamol resulted in a positive reaction in the patient, but not in a volunteer control. Pharmaceutical excipients are added to medications to increase absorption, shelf-life and efficacy. Different brands of the same drug may contain different excipients. When testing for anaphylaxis with such compounds one must be sure the dilution is appropriate for both the parent compound and the excipient to ensure the accuracy of skin-prick and intradermal testing. This case demonstrates the potential for excipients to cause severe allergy and the importance of detailed history pertaining to previous allergic episodes as even the most unlikely of medications can potentially result in anaphylaxis due to excipients.

Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations.

Suspected perioperative allergic reactions are rare but can be life-threatening. The diagnosis is difficult to make in the perioperative setting, but prompt recognition and correct treatment is necessary to ensure a good outcome. A group of 26 international experts in perioperative allergy (anaesthesiologists, allergists, and immunologists) contributed to a modified Delphi consensus process, which covered areas such as differential diagnosis, management during and after anaphylaxis, allergy investigations, and plans for a subsequent anaesthetic. They were asked to rank the appropriateness of statements related to the immediate management of suspected perioperative allergic reactions. Statements were selected to represent areas where there is a lack of consensus in existing guidelines, such as dosing of epinephrine and fluids, the management of impending cardiac arrest, and reactions refractory to standard treatment. The results of the modified Delphi consensus process have been included in the recommendations on the management of suspected perioperative allergic reactions. This paper provides anaesthetists with an overview of relevant knowledge on the immediate and postoperative management of suspected perioperative allergic reactions based on current literature and expert opinion. In addition, it provides practical advice and recommendations in areas where consensus has been lacking in existing guidelines.

The use of drug provocation testing in the investigation of suspected immediate perioperative allergic reactions: current status.

Suspected perioperative allergic reactions are often severe. To avoid potentially life-threatening re-exposure to the culprit drug, establishing a firm diagnosis and identifying the culprit is crucial. Drug provocation tests are considered the gold standard in drug allergy investigation but have not been recommended in the investigation of perioperative allergy, mainly because of the pharmacological effects of drugs such as induction agents and neuromuscular blocking agents. Some specialised centres have reported benefits of provocation testing in perioperative allergy investigation, but the literature on the subject is limited. Here we provide a status update on the use of drug provocation testing in perioperative allergy, including its use in specific drug groups. This review is based on a literature search and experiences of the authors comprising anaesthesiologists and allergists with experience in perioperative allergy investigation. In addition, 19 participating centres in the International Suspected Perioperative Allergic Reaction Group were surveyed on the use of provocation testing in perioperative allergy investigation. A response was received from 13 centres in eight European countries, New Zealand, and the USA. Also, 21 centres from the Australian and New Zealand Anaesthetic Allergy Group were surveyed. Two centres performed provocation routinely and seven centres performed no provocations at all. Nearly half of the centres reported performing provocations with induction agents and neuromuscular blocking agents. Drug provocation testing is being used in perioperative allergy investigation in specialised centres, but collaborations between relevant specialties and multicentre studies are necessary to determine indications and establish common testing protocols.

Comparative epidemiology of suspected perioperative hypersensitivity reactions.

Suspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.

Molecular mechanisms and pathophysiology of perioperative hypersensitivity and anaphylaxis: a narrative review.

Perioperative hypersensitivity reactions (POH) constitute a clinical and diagnostic challenge, a consequence of heterogeneous clinical presentations, and multiple underlying pathomechanisms. POH do not necessarily involve an allergen-specific immune response with cross-linking of specific immunoglobulin E (sIgE) antibodies on mast cells and basophils. POH can also result from alternative specific and non-specific effector cell activation/degranulation such as complement-derived anaphylatoxins and off-target occupancy of mast cell, basophil, or both surface receptors. Moreover, POH and anaphylaxis can occur independent from mast cell and basophil degranulation. The manifestations of POH primarily affect the cardiovascular, respiratory, and integumentary systems. POH present within the context of surgical or procedural pathology and the effects of surgical and anaesthetic techniques on pre-existing physiological reserve. The majority of cases of appropriately-treated intraoperative anaphylaxis can be considered a compensated cardiovascular anaphylaxis. With increasing severity of anaphylaxis, maldistribution and hypovolaemia lead to reduced venous return and circulatory failure. Treatment with a combination of epinephrine and i.v. fluid is critical for successful resuscitation, although the excessive use of epinephrine without adequate volume expansion may be deleterious. Neural control of the airways is important in the pathophysiology of bronchospasm. Anticholinergic drug premedication is beneficial in patients with hyperreactive airways. Pulmonary oedema can result from a combination of pulmonary capillary hypertension, incompetence of the alveolocapillary membrane, or both. Angioedema can be distinguished mechanistically into histaminergic and non-histaminergic (e.g. bradykinin-mediated). An understanding of the molecular mechanisms and pathophysiology of POH are essential for the immediate management and subsequent investigation of these cases.

The First Case Report of Anaphylaxis Caused by the Inclusion Complex of Rocuronium and Sugammadex.

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.

Exploring the link between pholcodine exposure and neuromuscular blocking agent anaphylaxis.

Neuromuscular blocking agents (NMBAs) are the most commonly implicated drugs in IgE-mediated anaphylaxis during anaesthesia that can lead to perioperative morbidity and mortality. The rate of NMBA anaphylaxis shows marked geographical variation in patients who have had no known prior exposure to NMBAs, suggesting that there may be external or environmental factors that contribute to the underlying aetiology and pathophysiology of reactions. Substituted ammonium ions are shared among NMBAs and are therefore thought to be the main allergenic determinant of this class of drugs. Substituted ammonium ions are found in a wide variety of chemical structures, including prescription medications, over-the-counter medications and common household chemicals, such as the quaternary ammonium disinfectants. Epidemiological studies have shown parallels in the consumption of pholcodine, a nonprescription antitussive drug which contains a tertiary ammonium ion, and the incidence of NMBA anaphylaxis. This link has prompted the withdrawal of pholcodine in some countries, with an ensuing fall in the observed rate of NMBA anaphylaxis. While such observations are compelling in their suggestion of a relationship between pholcodine exposure and NMBA hypersensitivity, important questions remain regarding the mechanisms by which pholcodine is able to sensitize against NMBAs and whether there are other, as yet unidentified, agents that can elicit similar hypersensitivity reactions. This review aims to explore the evidence linking pholcodine exposure to NMBA hypersensitivity and discuss the implications for our understanding of the pathophysiology of these reactions.