Anaphylaxis to intravenous gelatin-based solutions: a case series examining clinical features and severity.

The proportion of patients receiving intravenous gelatin-based colloids has increased in the last decade due to safety concerns about starch-based products. Recent research suggests hypersensitivity reactions to intravenous gelatin-based solutions occur at similar rates per administration as non-depolarising neuromuscular blocking agents such as rocuronium (6.2/100,000 administrations). There are scant published data on clinical features, diagnosis and time course of these reactions. We undertook a review of cases reported and tested at one of the UK's largest drug allergy clinics. All patients seen in the drug allergy clinic at Imperial College Healthcare NHS Trust (London, UK) with a confirmed diagnosis of anaphylaxis to gelatin-based solutions between May 2013 and May 2018 were included. We retrospectively reviewed clinical histories, skin test results and severity of reactions in this cohort of patients. Twelve patients with anaphylaxis to gelatin-based solutions were identified (eight women, mean (SD) age 58 (17) years). Eleven reactions were severe or life-threatening with three progressing to cardiac arrest. Presentation was commonly delayed; only three patients suffered reactions within 5 min of the solution being administered with a further six presenting 10-70 min later. Where measured, tryptase was elevated in all patients (median (IQR [range]) 14.7 (8.2-23.8 [6.5-83.4]) ng.ml-1 ). Reactions to gelatin-based solutions are usually severe and can present with latency uncommon with other intravenous anaesthetic triggers. The use of gelatin-based solutions in the peri-operative setting should be re-assessed given the risk of severe allergy.

Specialist perioperative allergy clinic services in the UK 2018: Results from the Royal College of Anaesthetists Sixth National Audit Project (NAP6) investigation of perioperative anaphylaxis.

BACKGROUND: The Royal College of Anaesthetists 6th National Audit Project examined Grade 3-5 perioperative anaphylaxis for 1 year in the UK. OBJECTIVE: To describe the causes and investigation of anaphylaxis in the NAP6 cohort, in relation to published guidance and previous baseline survey results. METHODS: We used a secure registry to gather details of Grade 3-5 perioperative anaphylaxis. Anonymous reports were aggregated for analysis and reviewed in detail. Panel consensus diagnosis, reaction grade, review of investigations and clinic assessment are reported and compared to the prior NAP6 baseline clinic survey. RESULTS: A total of 266 cases met inclusion criteria between November 2015 and 2016, detailing reactions and investigations. One hundred and ninety-two of 266 (72%) had anaphylaxis with a trigger identified, of which 140/192 (75%) met NAP6 criteria for IgE-mediated allergic anaphylaxis, 13% lacking evidence of positive IgE tests were labelled "non-allergic anaphylaxis". 3% were non-IgE-mediated anaphylaxis. Adherence to guidance was similar to the baseline survey for waiting time for clinic assessment. However, lack of testing for chlorhexidine and latex, non-harmonized testing practices and poor coverage of all possible culprits was confirmed. Challenge testing may be underused and many have unacceptably delayed assessments, even in urgent cases. Communication or information provision for patients was insufficient, especially for avoidance advice and communication of test results. Insufficient detail regarding skin test methods was available to draw conclusions regarding techniques. CONCLUSION AND CLINICAL RELEVANCE: Current clinical assessment in the UK is effective but harmonization of approach to testing, access to services and MHRA reporting is needed. Expert anaesthetist involvement should increase to optimize diagnostic yield and advice for future anaesthesia. Dynamic tryptase evaluation improves detection of tryptase release where peak tryptase is <14 µg/L and should be adopted. Standardized clinic reports containing appropriate details of tests, conclusions, avoidance, cross-reactivity and suitable alternatives are required to ensure effective, safe future management options.

Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6).

BACKGROUND: Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. METHODS: The 6th National Audit Project (NAP6) on perioperative anaphylaxis collected and reviewed 266 reports of Grades 3-5 anaphylaxis over 1 yr from all NHS hospitals in the UK. RESULTS: The estimated incidence was ≈1:10 000 anaesthetics. Case exclusion because of reporting delays or incomplete data means true incidence might be ≈70% higher. The distribution of 199 identified culprit agents included antibiotics (94), neuromuscular blocking agents (65), chlorhexidine (18), and Patent Blue dye (9). Teicoplanin comprised 12% of antibiotic exposures, but caused 38% of antibiotic-induced anaphylaxis. Eighteen patients reacted to an antibiotic test dose. Succinylcholine-induced anaphylaxis, mainly presenting with bronchospasm, was two-fold more likely than other neuromuscular blocking agents. Atracurium-induced anaphylaxis mainly presented with hypotension. Non-depolarising neuromuscular blocking agents had similar incidences to each other. There were no reports of local anaesthetic or latex-induced anaphylaxis. The commonest presenting features were hypotension (46%), bronchospasm (18%), tachycardia (9.8%), oxygen desaturation (4.7%), bradycardia (3%), and reduced/absent capnography trace (2.3%). All patients were hypotensive during the episode. Onset was rapid for neuromuscular blocking agents and antibiotics, but delayed with chlorhexidine and Patent Blue dye. There were 10 deaths and 40 cardiac arrests. Pulseless electrical activity was the usual type of cardiac arrest, often with bradycardia. Poor outcomes were associated with increased ASA, obesity, beta blocker, and angiotensin-converting enzyme inhibitor medication. Seventy per cent of cases were reported to the hospital incident reporting system, and only 24% to Medicines and Healthcare products Regulatory Agency via the Yellow Card Scheme. CONCLUSIONS: The overall incidence of perioperative anaphylaxis was estimated to be 1 in 10 000 anaesthetics.

Cross-sectional study of perioperative drug and allergen exposure in UK practice in 2016: the 6th National Audit Project (NAP6) Allergen Survey.

BACKGROUND: Details of the current UK drug and allergen exposure were needed for interpretation of reports of perioperative anaphylaxis to the 6th National Audit Project (NAP6). METHODS: We performed a cross-sectional survey of 356 NHS hospitals determining anaesthetic drug usage in October 2016. All cases cared for by an anaesthetist were included. RESULTS: Responses were received from 342 (96%) hospitals. Within-hospital return rates were 96%. We collected 15 942 forms, equating to an annual caseload of 3.1 million, including 2.4 million general anaesthetics. Propofol was used in 74% of all cases and 90% of general anaesthetics. Maintenance included a volatile agent in 95% and propofol in 8.7%. Neuromuscular blocking agents were used in 47% of general anaesthetics. Analgesics were used in 88% of cases: opioids, 82%; paracetamol, 56%; and non-steroidal anti-inflammatory drugs, 28%. Antibiotics were administered in 57% of cases, including 2.5 million annual perioperative administrations; gentamicin, co-amoxiclav, and cefuroxime were most commonly used. Local anaesthetics were used in 74% cases and 70% of general anaesthetics. Anti-emetics were used in 73% of cases: during general anaesthesia, ondansetron in 78% and dexamethasone in 60%. Blood products were used in ≈3% of cases, gelatin <2%, starch very rarely, and tranexamic acid in ≈6%. Chlorhexidine and povidone-iodine exposures were 74% and 40% of cases, and 21% reported a latex-free environment. Exposures to bone cement, blue dyes, and radiographic contrast dye were each reported in 2-3% of cases. CONCLUSIONS: This survey provides insights into allergen exposures in perioperative care, which is important as denominator data for the NAP6 registry.

Anaesthesia, surgery, and life-threatening allergic reactions: management and outcomes in the 6th National Audit Project (NAP6).

BACKGROUND: Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. There is little published information on management and outcomes of perioperative anaphylaxis in the UK. METHODS: The 6th National Audit Project of the Royal College of Anaesthetists (NAP6) collected and reviewed 266 reports of Grade 3-5 anaphylaxis from all UK NHS hospitals over 1 yr. Quality of management was assessed against published guidelines. RESULTS: Appropriately senior anaesthetists resuscitated all patients. Immediate management was 'good' in 46% and 'poor' in 15%. Recognition and treatment of anaphylaxis were prompt in 97% and 83% of cases, respectively. Epinephrine was administered i.v. in 76%, i.m. in 14%, both in 6%, and not at all in 11% of cases. A catecholamine infusion was administered in half of cases. Cardiac arrests (40 cases; 15%) were promptly treated but cardiac compressions were omitted in half of patients with unrecordable BP. The surgical procedure was abandoned in most cases, including 10% where surgery was urgent. Of 54% admitted to critical care, 70% were level 3, with most requiring catecholamine infusions. Ten (3.8%) patents (mostly elderly with cardiovascular disease) died from anaphylaxis. Corticosteroids and antihistamines were generally administered early. We found no clear evidence of harm or benefit from chlorphenamine. Two patients received vasopressin and one glucagon. Fluid administration was inadequate in 19% of cases. Treatment included sugammadex in 19 cases, including one when rocuronium had not been administered. Adverse sequelae (psychological, cognitive, or physical) were reported in one-third of cases. CONCLUSIONS: Management of perioperative anaphylaxis could be improved, especially with respect to administration of epinephrine, cardiac compressions, and i.v. fluid. Sequelae were common.

An observational national study of anaesthetic workload and seniority across the working week and weekend in the UK in 2016: the 6th National Audit Project (NAP6) Activity Survey.

BACKGROUND: UK national anaesthetic activity was studied in 2013 but weekend working was not examined. Understanding changes since 2013 in workload and manpower distribution, including weekends, would be of value in workforce planning. METHODS: We performed an observational survey of NHS hospitals' anaesthetic practice in October 2016 as part of the 6th National Audit Project of the Royal College of Anaesthetists (NAP6). All cases cared for by an anaesthetist during the study period were included. Patient characteristics and details of anaesthetic conduct were collected by local anaesthetists. RESULTS: Responses were received from 342/356 (96%) hospitals. In total, 15 942 cases were reported, equating to an annual anaesthetic workload of ≈3.13 million cases. Approximately 95% (9888/10 452) of elective and 72% (3184/4392) of emergency work was performed on weekdays and 89% (14 145/15 942) of activity was led by senior (consultant or career grade) anaesthetists and 1.1% (180/15942) by those with <2 yr anaesthetic experience. During weekends case urgency increased, the proportion of healthy patients reduced and case mix changed. Cases led by senior anaesthetists fell to 80% (947/1177) on Saturday and 66% (342/791) on Sunday. Senior involvement in obstetric anaesthetic activity was 69% (628/911) during the week and 45% (182/402) at weekends, compared with 93% (791/847) in emergency orthopaedic procedures during the week and 89% (285/321) at weekends. Since 2013, the proportion of obese patients, elective weekend working, and depth of anaesthesia monitoring has increased [12% (1464/12 213) vs 2.8%], but neuromuscular monitoring has not [37% (2032/5532) vs 38% of paralysed cases]. CONCLUSIONS: Senior clinicians deliver most UK anaesthesia care, including at weekends. Our findings are important for any planned workforce reorganisation to rationalise 7-day working.

Anaesthesia, surgery, and life-threatening allergic reactions: protocol and methods of the 6th National Audit Project (NAP6) of the Royal College of Anaesthetists.

BACKGROUND: Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. METHODS: The Sixth National Audit Project (NAP6) of the Royal College of Anaesthetists examined the incidence, predisposing factors, management, and impact of life-threatening perioperative anaphylaxis in the UK. NAP6 included: a national survey of anaesthetists' experiences and perceptions; a national survey of allergy clinics; a registry collecting detailed reports of all Grade 3-5 perioperative anaphylaxis cases for 1 yr; and a national survey of anaesthetic workload and perioperative allergen exposure. NHS and independent sector (IS) hospitals were approached to participate. Cases were reviewed by a multi-disciplinary expert panel (anaesthetists, intensivists, allergists, immunologists, patient representatives, and stakeholders) using a structured process designed to minimise bias. Clinical management and investigation were compared with published guidelines. This paper describes detailed study methods and reports on project engagement by NHS and IS hospitals. The methodology includes a new classification of perioperative anaphylaxis and a new structured method for classifying suspected anaphylactic events including the degree of certainty with which a causal trigger agent can be attributed. RESULTS: NHS engagement was complete (100% of hospitals). Independent sector engagement was limited (13% of approached hospitals). We received >500 reports of Grade 3-5 perioperative anaphylaxis, with 266 suitable for analysis. We identified 199 definite or probable culprit agents in 192 cases. CONCLUSIONS: The methods of NAP6 were robust in identifying causative agents of anaphylaxis, and support the accompanying analytical papers.

BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007).

This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa.

Management of allergy to penicillins and other beta-lactams.

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and non-immediate allergic reactions to penicillins and other beta-lactams. The guideline is intended for UK specialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, all BSACI members were consulted using a Web-based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta-lactams, molecular structure, formulations available in the UK and a description of known beta-lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross-reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta-lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included.

T cells producing the anti-inflammatory cytokine IL-10 regulate allergen-specific Th2 responses in human airways.

BACKGROUND: Murine models suggest a critical functional role for the anti-inflammatory cytokine IL-10 in local regulation of allergic airways inflammation. There is little corresponding information on human airway cells. This study aimed to investigate whether local IL-10 production regulates responses by respiratory mucosal leucocytes isolated from nasal polyps. MATERIALS AND METHODS: Nasal polyp tissue was harvested from 24 patients sensitised to aeroallergens with chronic rhinitis and polyposis undergoing routine polypectomy. Cells were isolated by matrix proteolysis. Cytokine production by polyp cells was determined by cytometric bead array (CBA) and intracellular cytokine analysis. Surface marker expression by polyp cells was determined by flow cytometry. RESULTS: Allergen stimulation significantly enhanced production of IL-10, but not IL-5 or IFN-γ by nasal polyp cell suspensions. Under the same conditions, neutralisation of IL-10 significantly increased allergen-specific IL-5 and IFN-γ production by nasal polyp cells. Cell depletion experiments showed that T cells themselves were primarily responsible for IL-10 production or for inducing its production by other cells. Intracellular cytokine staining confirmed production of IL-10 in the absence of IL-2 production by T cells in response to allergen. CONCLUSION: T cells within the human respiratory mucosa produce IL-10, which is capable of inhibiting pro-inflammatory Th2 and Th1 cytokine production in an antigen-specific fashion.

Corrigendum to 'Allergy and anaesthesia: managing the risk' [BJA Education 20 (2020) 298-304].

[This corrects the article DOI: 10.1016/j.bjae.2020.04.005.].

BSACI guidelines for the management of allergic and non-allergic rhinitis.

This guidance for the management of patients with allergic and non-allergic rhinitis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and paediatricians practicing in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are clinical classification of rhinitis, aetiology, diagnosis, investigations and management including subcutaneous and sublingual immunotherapy. There are also special sections for children, co-morbid associations and pregnancy. Finally, we have made recommendations for potential areas of future research.

Improvements in an oral aspirin challenge protocol for the diagnosis of aspirin hypersensitivity.

Oral aspirin challenge (OAC) is used to confirm aspirin hypersensitivity (AHs) but there is no consensus on a standardized protocol. As a prior clinical history of adverse reactions to aspirin is poorly predictive of a positive result from formal aspirin challenge, many patients have an OAC performed. We retrospectively identified and prospectively validated how a 1-day OAC protocol could be modified, and patient selection improved, to deliver a safe and more efficient service. In a retrospective audit of 45 OACs using a 2 h dose interval, all reactions occurred within 90 min of the threshold dose. Forty OACs were then performed using a 90-min dose interval. This reduced the mean duration of a positive and negative OAC from 6 to 5 h and from 8 to 6 h, respectively. Histories of multiple manifestations of AHs were found in 91.6% (11) of those with asthma, 87.5% (7) with angiooedema, 70.6% (12) with rhinosinusitis, 63.6% (7) with chronic non-vasculitic urticaria and all with anaphylaxis, who developed a positive OAC. None of those with anaphylaxis, 8.3% (1) with asthma and 12.5% (1) with angiooedema, with a positive OAC, had a history of a single manifestation of AHs. The efficiency of an OAC service can safely be improved by reduction of the dose interval from 2 to 1 (1/2) h, and more targeted patient selection, as the likelihood of a positive OAC increases among patients with a history of asthma, angiooedoema or anaphylaxis with multiple manifestations of AHs.