Consensus clinical scoring for suspected perioperative immediate hypersensitivity reactions.

BACKGROUND: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. METHODS: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. RESULTS: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. CONCLUSION: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.

Management of a surgical patient with a label of penicillin allergy: narrative review and consensus recommendations.

Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.

Epinephrine (adrenaline) preventing recovery from intraoperative anaphylactic shock complicated by systolic anterior motion of the mitral valve with left ventricular outflow tract obstruction on transoesophageal echocardiography.

We describe a case of severe left ventricular outflow tract obstruction (LVOTO) with severe mitral incompetence due to systolic anterior motion of the anterior mitral leaflet (SAM) that was recognised thanks to the immediate availability of transoesophageal echocardiography during the resuscitation of anaphylactic shock. The patient rapidly responded to cessation of the epinephrine (adrenaline) infusion and intravascular volume expansion with intravenous crystalloid. The absence of risk factors for developing SAM/LVOTO serve as a warning to clinicians to consider this diagnosis in all cases of epinephrine non-responsive anaphylactic shock.

Consequences of proceeding with surgery after resuscitation from intra-operative anaphylaxis.

Intra-operative acute hypersensitivity reactions require a decision to be made regarding whether to proceed with or abandon the planned surgical procedure once the patient has stabilised. Using retrospective case controls, we examined all cases (223) of proven acute hypersensitivity reactions from 2005 to 2014 in Western Australia, in which the syndrome was recognised by the treating clinician before or during surgery, to determine whether recovery outcomes were adversely affected by proceeding with the planned procedure. Surgery proceeded in 104 patients (47%) and was abandoned in 119 (53%). The severity of acute hypersensitivity reactions was Société Française d'Anesthésie et de Réanimation grade 1 or 2 in 56 patients (25%), grade 3 in 128 (56%) and grade 4 in 39 (17%). Abandoning surgery was more common in patients with increasing severity of hypersensitivity. The rate of major hypersensitivity-related complications for all patients was zero for grade 1 and 2 reactions, 4.7% for grade 3 and 12.8% for grade 4. There were no deaths. Patients in whom surgery was completed were not observed to have a higher frequency of major hypersensitivity-related complications when compared with cases of similar severity in whom surgery was abandoned. For patients admitted to the intensive care unit, proceeding with surgery was not associated with an increased duration of mechanical ventilation of the lungs. Our results suggest that, once initial resuscitation has been achieved and if resuscitative efforts can be re-instituted if required, continuing with planned surgery in grade 1, 2 and 3 immediate hypersensitivity was not associated with poorer outcomes. After grade 3 reactions, there was a significant incidence of complications attributable to acute hypersensitivity regardless of whether surgery proceeded or was abandoned. Surgery was frequently abandoned in grade 4 immediate hypersensitivity and was associated with a high rate of complications.

Association of juvenile idiopathic arthritis with PTPN22 rs2476601 is specific to females in a Greek population.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by persistent chronic arthritis. Disease risk is believed to be influenced by both genetic and environmental factors. It is well established that the PTPN22 single nucleotide polymorphism (SNP) rs2476601 is associated with JIA susceptibility. It was recently reported in an Australian study that this association is restricted to females and is not observed in males. A significant source of inconsistency amongst the literature on autoimmune disease susceptibility genes stems from an inability to replicate genetic findings across different racial or ethnic groups. We therefore attempted to generate further evidence of the female-specific association of rs2476601 in a homogeneous Greek population. FINDINGS: We genotyped rs2476601 in 128 Caucasian JIA patients (70.3 % female) and 221 healthy controls (28.1 % female) from Northern Greece. Overall, PTPN22 was associated with increased risk of JIA in this Greek sample (OR = 2.3, 95 % CI 1.1 - 5.1, p = 0.038). Sex-stratified analyses showed that, once again, the risk association was restricted to females (Female: OR = 19.9, 95 % CI 1.2 - 342, p = 0.0016; Male: OR = 1.1, 95 % CI 0.3 - 3.1, p = 0.94) supporting the prior findings. CONCLUSIONS: Our data demonstrates that this sex-specific pattern of association is broadly applicable to different populations, and provides further impetus to undertake mechanistic studies to understand the impact of sex on PTPN22 in JIA.

Cefalotin as antimicrobial prophylaxis in patients with known intraoperative anaphylaxis to cefazolin.

BACKGROUND: The most common trigger for intraoperative anaphylaxis in Western Australia for the period 2014-5 was an antibiotic used for surgical prophylaxis, cefazolin. In these patients who subsequently present for surgery, alternative cephalosporins are forbidden by current guidelines because of concerns regarding an increased risk of anaphylaxis. However, consideration of the structure-activity relationships relevant to anaphylaxis suggests that cefalotin is a safe alternative because of structural dissimilarities, although there are no pubished clinical data relevant to the perioperative setting. METHODS: Patients diagnosed with intraoperative anaphylaxis to cefazolin at the Western Australian Anaesthetic Allergy Clinic were tested with intradermal cefalotin and, if negative, subsequently challenged i.v. If tolerated, cefalotin was recommended for subsequent surgery, and subjects were followed up to determine the safety of subsequent intraoperative doses. RESULTS: Twenty-one subjects diagnosed with immediate hypersensitivity to cephazolin, including 19 subjects with confirmed anaphylaxis, participated. None tested positive to intradermal cefalotin, and all received a graded i.v. challenge to cefalotin without developing signs or symptoms of anaphylaxis. Three subjects subsequently received intraoperative cefalotin 12-139 days later without adverse events. CONCLUSIONS: A negative intradermal cefalotin skin test has a good negative predictive value in patients who have previously suffered anaphylaxis to cefazolin, allowing the rational and desirable use of this alternative cephalosporin for future surgery and the avoidance of less desirable antimicrobial agents.

The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females.

A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22 rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes. We performed main effect and sex-stratified association analyses to determine whether a sex-specific association exists in JIA. As expected, rs2476601 was associated with JIA in our discovery (413 cases and 690 controls) and replication (1008 cases and 9284 controls) samples. Discovery sample sex-stratified analyses demonstrated an association specifically in females (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.52-3.63, P=0.00011) but not males (OR=0.91, 95% CI=0.52-1.60, P=0.75). This was similarly observed in the replication sample. There was evidence for genotype-by-sex interaction (Pinteraction=0.009). The association between rs2476601 and JIA appears restricted to females, partly accounting for the predominance of females with this disease.

Efficacy of sugammadex in rocuronium-induced or antibiotic-induced anaphylaxis. A case-control study.

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

Intraoperative anaphylaxis to sugammadex and a protocol for intradermal skin testing.

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

Survival from perioperative anaphylaxis in Western Australia 2000-2009.

BACKGROUND: The mortality from perioperative anaphylaxis has recently been quoted in a range between 3 and 9%. However, it was our impression in Western Australia that we had had no deaths from perioperative anaphylaxis for over a decade. As we have comprehensive processes in place to investigate both perioperative anaphylaxis and anaesthesia-related deaths, we undertook this study to determine our actual perioperative anaphylaxis mortality rate. METHODS: We obtained the number of deaths related to perioperative anaphylaxis for the decade 2000-2009 from the database of the West Australian Anaesthetic Mortality Committee; in Western Australia it is a legal requirement to report all deaths that occur within 48 h of an anaesthetic, and all deaths due to a complication of an anaesthetic. We obtained the number of cases of perioperative anaphylaxis for the same period from the database of the West Australian Anaesthetic Drug Reaction Clinic. RESULTS: From 2000 to 2009, there were 45 anaesthesia-related deaths in Western Australia, but none of these involved anaphylaxis. Over this period, there were 264 cases classified by the West Australian Anaesthetic Drug Reaction Clinic as anaphylaxis. The 95% confidence interval for the observed 0/264 mortality rate is 0-1.4%. There were about three million anaesthetics administered in Western Australia over the decade, giving a perioperative anaphylaxis rate of ~1:11,000. CONCLUSIONS: Our incidence of perioperative anaphylaxis was within expectations, but our mortality rate was lower than recently quoted figures. It is likely that the current true perioperative anaphylaxis mortality rate is within the range 0-1.4%.

Anaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011.

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

The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model.

The availability of sugammadex as a selective encapsulating agent for rocuronium has led to speculation that it may be useful in mitigating rocuronium-induced anaphylaxis. Off-label use of sugammadex for this indication has already been documented in case reports although there are theoretical objections to the likelihood of an allergen-binding agent's being able to attenuate the immunological cascade of anaphylaxis. Using a cutaneous model of anaphylaxis in rocuronium-sensitised patients, we were unable to demonstrate that sugammadex was effective in attenuating the type-1 hypersensitivity reaction after it has been triggered by rocuronium, but we were able to demonstrate that these patients are anergic to sugammadex-bound rocuronium. These findings demonstrate that a cyclodextrin can bind an allergen and exclude it from interacting with the immune system, and may potentially lead to novel applications in other allergic diseases. However, there is no evidence that sugammadex should be used for the treatment of rocuronium-induced anaphylaxis, and clinical management should follow established protocols.

Anaesthesia trainees' exposure to airway management in an Australian tertiary adult teaching hospital.

The purpose of this study was to estimate the exposure of trainees to airway management techniques in an Australian tertiary adult teaching hospital. Anaesthesia records for all patients over a 20-week period were reviewed and the following data were obtained: the presence of a trainee, the type of airway used, the grade of the laryngoscopic view and the use of non-standard laryngoscopy for intubation. Data was recorded contemporaneously and analysed retrospectively. The data was then extrapolated to give a yearly estimate of airway procedures per trainee. There were 28 full-time trainees in the department over the study period. The estimated mean number of standard intubations performed per trainee per year was 157.4, with 2.9% being grade 3 or 4 laryngoscopies. The estimated mean annual numbers for other airway techniques were: 1.2 fibreoptic intubations, 0.5 mask-only anaesthetics and 3.7 endobronchial double-lumen tubes. Our results suggest that trainees' exposure to airway management techniques is not extensive. As there is no previous study to determine experience gained by trainees, we are unable to establish whether there has been a decrease in experience, however we believe this is likely. Although competency is difficult to assess, it may be that this data has implications for training, unsupervised practice and rostering. Experience in certain airway skills may need to be supplemented using techniques such as simulation.

Proton radiography of a laser-driven implosion.

Protons accelerated by a picosecond laser pulse have been used to radiograph a 500 microm diameter capsule, imploded with 300 J of laser light in 6 symmetrically incident beams of wavelength 1.054 microm and pulse length 1 ns. Point projection proton backlighting was used to characterize the density gradients at discrete times through the implosion. Asymmetries were diagnosed both during the early and stagnation stages of the implosion. Comparison with analytic scattering theory and simple Monte Carlo simulations were consistent with a 3+/-1 g/cm3 core with diameter 85+/-10 microm. Scaling simulations show that protons>50 MeV are required to diagnose asymmetry in ignition scale conditions.

The organisation of federal Veterinary Services in Canada: the Canadian Food Inspection Agency.

The organisational design of a national Veterinary Service is critical to the overall quality and integrity of its animal health and veterinary public health infrastructure. It is well recognised that the diversity of political, economic and social situations which exist in and between countries dictates that no one model of organisational structure can be applied to all circumstances. In Canada, a re-organisation of the approach of the federal government to food inspection in 1997 resulted in the transfer of the veterinary administration to a newly created agency called the Canadian Food Inspection Agency (CFIA). The authors provide a short background on the impetus for the creation of the CFIA and an overview of its organisational structure and responsibilities in animal and veterinary public health and food safety. Also included are the logic models that were developed for the federal Veterinary Services as part of their quality and performance management framework. Integrating all federally mandated food inspection systems under the CFIA has had concrete benefits in clarifying roles and responsibilities, reducing overlap and duplication of programme functions, improving service delivery and facilitating federal-provincial collaboration. Moreover, the strength of the organisation lies in the ability of the Canadian Veterinary Services to adhere to the fundamental principles of quality which are recommended by the OIE (World organisation for animal health) for the evaluation of Veterinary Services. No single organisational structure can guarantee a highly effective or competent Veterinary Service. Common challenges exist that may or may not be addressed in whole or in part by the organisational structure. The challenges highlighted in this paper provide further thoughts on the management of shared jurisdiction, meeting public health objectives, balancing science and political accountability, and defining the role and jurisdiction of veterinarians.

Herbal medicines: current trends in anesthesiology practice--a hospital survey.

STUDY OBJECTIVES: To develop a simple survey to determine the patient population actively utilizing dietary supplements and/or herbs, during the preoperative period. DESIGN: Prospective study, with survey instrument. SETTING: University medical center. PATIENTS: 1,017 patients presenting for preanesthetic evaluation prior to outpatient surgery. INTERVENTIONS: After undergoing preanesthetic evaluation, patients were asked to complete a survey listing which of the nine most popular nutraceuticals currently available on the market they were using. MEASUREMENTS AND MAIN RESULTS: A total of 1017 surveys were submitted over a period of five months, with 32% being poorly completed and thus discarded. Of the remaining 755 valid surveys, 482 patients used at least one nutraceutical agent. 90% of these patients were using vitamins, 43% garlic extracts, 32% Gingko Biloba, 30% St. John's Wort, 18% Ma Huang, 12% Ecchinaceae, 10% Aloe, 8% Cascare, 3% licorice. CONCLUSION: A significant population of patients scheduled for an elective surgical procedure are self-administering nutraceutical agents. Some of these agents have the potential to cause serious drug interactions and hemodynamic instability during surgery. Hence, it may be important to identify patients self-administering these medications, during the preoperative period.

Estimation of the under-reporting rate for the surveillance of Escherichia coli O157:H7 cases in Ontario, Canada.

Two models estimating the proportion of Escherichia coli O157:H7 cases not reported in the Ontario notifiable diseases surveillance system are described. The first model is a linear series of adjustments in which the total number of reported cases is corrected by successive underreporting coefficients. The structure of the second model is based on a relative difference in the proportion of E. coli O157:H7 cases which are hospitalized between the surveillance database and the underlying population. Based on this analysis, the rate of under-reporting of symptomatic cases of E. coli O157:H7 infection in Ontario ranges from 78 to 88% corresponding to a ratio of 1 reported case for approximately 4-8 symptomatic cases missed by the surveillance system. This study highlights the need to increase awareness among public health workers of the potential biases that may exist in the interpretation of routine surveillance data.