Serum mast cell tryptase measurements: Sensitivity and specificity for a diagnosis of anaphylaxis in emergency department patients with shock or hypoxaemia.

OBJECTIVE: Clinical diagnosis of anaphylaxis is principally based on symptoms and signs. However, particularly for patients with atypical symptoms, laboratory confirmation of anaphylaxis would be useful. This study investigated the utility of mast cell tryptase, an available clinical biomarker, for differentiating anaphylaxis from other causes of critical illness, which can also involve mast cell activation. METHODS: Tryptase was measured (ImmunoCAP) in serum from patients with anaphylaxis and non-anaphylactic critical illness (controls) at ED arrival, and after 1-2, 3-4 and 12-24 h. Differences in both peak and delta (difference between highest and lowest) tryptase concentrations between groups were investigated using linear regression models, and diagnostic ability was analysed using Receiver Operating Characteristic curve analysis. RESULTS: Peak tryptase was fourfold (95% CI: 2.9, 5.5) higher in anaphylaxis patients (n = 67) than controls (n = 120) (P < 0.001). Delta-tryptase was 5.1-fold (95% CI: 2.9, 8.9) higher in anaphylaxis than controls (P < 0.001). Optimal test characteristics (sensitivity: 72% [95% CI: 59, 82] and specificity: 72% [95%CI: 63, 80]) were observed when peak tryptase concentrations were >11.4 ng/mL and/or delta-tryptase ≥2.0 ng/mL. For hypotensive patients, peak tryptase >11.4 ng/mL had improved test characteristics (sensitivity: 85% [95% CI: 65, 96] and specificity: 92% [95% CI: 85, 97]); the use of delta-tryptase reduced test specificity. CONCLUSION: While peak and delta tryptase concentrations were higher in anaphylaxis than other forms of critical illness, the test lacks sufficient sensitivity and specificity. Therefore, mast cell tryptase values alone cannot be used to establish the diagnosis of anaphylaxis in the ED. In particular, tryptase has limited utility for differentiating anaphylactic from non-anaphylactic shock.

The Australian Snakebite Project, 2005-2015 (ASP-20).

OBJECTIVE: To describe the epidemiology, treatment and adverse events after snakebite in Australia. DESIGN: Prospective, multicentre study of data on patients with snakebites recruited to the Australian Snakebite Project (2005-2015) and data from the National Coronial Information System. Setting, participants: Patients presenting to Australian hospitals with suspected or confirmed snakebites from July 2005 to June 2015 and consenting to participation. MAIN OUTCOME MEASURES: Demographic data, circumstances of bites, clinical effects of envenoming, results of laboratory investigations and snake venom detection kit (SVDK) testing, antivenom treatment and adverse reactions, time to discharge, deaths. RESULTS: 1548 patients with suspected snakebites were enrolled, including 835 envenomed patients (median, 87 per year), for 718 of which the snake type was definitively established, most frequently brown snakes (41%), tiger snakes (17%) and red-bellied black snakes (16%). Clinical effects included venom-induced consumption coagulopathy (73%), myotoxicity (17%), and acute kidney injury (12%); severe complications included cardiac arrest (25 cases; 2.9%) and major haemorrhage (13 cases; 1.6%). There were 23 deaths (median, two per year), attributed to brown (17), tiger (four) and unknown (two) snakes; ten followed out-of-hospital cardiac arrests and six followed intracranial haemorrhages. Of 597 SVDK test results for envenomed patients with confirmed snake type, 29 (4.9%) were incorrect; 133 of 364 SVDK test results for non-envenomed patients (36%) were false positives. 755 patients received antivenom, including 49 non-envenomed patients; 178 (24%), including ten non-envenomed patients, had systemic hypersensitivity reactions, of which 45 (6%) were severe (hypotension, hypoxaemia). Median total antivenom dose declined from four vials to one, but median time to first antivenom was unchanged (4.3 hours; IQR, 2.7-6.3 hours). CONCLUSIONS: Snake envenoming is uncommon in Australia, but is often severe. SVDKs were unreliable for determining snake type. The median antivenom dose has declined without harming patients. Improved early diagnostic strategies are needed to reduce the frequently long delays before antivenom administration.

2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines.

The World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis provide a unique global perspective on this increasingly common, potentially life-threatening disease. Recommendations made in the original WAO Anaphylaxis Guidelines remain clinically valid and relevant, and are a widely accessed and frequently cited resource. In this 2015 update of the evidence supporting recommendations in the Guidelines, new information based on anaphylaxis publications from January 2014 through mid- 2015 is summarized. Advances in epidemiology, diagnosis, and management in healthcare and community settings are highlighted. Additionally, new information about patient factors that increase the risk of severe and/or fatal anaphylaxis and patient co-factors that amplify anaphylactic episodes is presented and new information about anaphylaxis triggers and confirmation of triggers to facilitate specific trigger avoidance and immunomodulation is reviewed. The update includes tables summarizing important advances in anaphylaxis research.

Influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel Australian hospitals in 2013: the Influenza Complications Alert Network.

The National Influenza Program aims to reduce serious morbidity and mortality from influenza by providing public funding for vaccination to at-risk groups. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 14 sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with confirmed influenza, estimates vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2013 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals, with influenza confirmed by nucleic acid testing. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 5 April to 31 October 2012, 631 patients were admitted with confirmed influenza at the 14 FluCAN sentinel hospitals. Of these, 31% were more than 65 years of age, 9.5% were Indigenous Australians, 4.3% were pregnant and 77% had chronic co-morbidities. Influenza B was detected in 30% of patients. Vaccination coverage was estimated at 81% in patients more than 65 years of age but only 49% in patients aged less than 65 years with chronic comorbidities. Vaccination effectiveness against hospitalisation with influenza was estimated at 50% (95% confidence interval: 33%, 63%, P<0.001). We detected a significant number of hospital admissions with confirmed influenza in a national observational study. Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. Our results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza in the 2013 season.

Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock.

BACKGROUND: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may cause death. Adrenaline is recommended as the initial treatment of choice for anaphylaxis. OBJECTIVES: To assess the benefits and harms of adrenaline (epinephrine) in the treatment of anaphylaxis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to March 2007), EMBASE (1966 to March 2007), CINAHL (1982 to March 2007), BIOSIS (to March 2007), ISI Web of Knowledge (to March 2007) and LILACS (to March 2007). We also searched websites listing ongoing trials: http://clinicaltrials.gov/, http://www.controlledtrials.com and http://www.actr.org.au/; and contacted pharmaceutical companies and international experts in anaphylaxis in an attempt to locate unpublished material. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing adrenaline with no intervention, placebo or other adrenergic agonists were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed articles for inclusion. MAIN RESULTS: We found no studies that satisfied the inclusion criteria. AUTHORS' CONCLUSIONS: Based on this review, we are unable to make any new recommendations on the use of adrenaline for the treatment of anaphylaxis. Although there is a need for randomized, double-blind, placebo-controlled clinical trials of high methodological quality in order to define the true extent of benefits from the administration of adrenaline in anaphylaxis, such trials are unlikely to be performed in individuals with anaphylaxis. Indeed, they might be unethical because prompt treatment with adrenaline is deemed to be critically important for survival in anaphylaxis. Also, such studies would be difficult to conduct because anaphylactic episodes usually occur without warning, often in a non-medical setting, and differ in severity both among individuals and from one episode to another in the same individual. Consequently, obtaining baseline measurements and frequent timed measurements might be difficult, or impossible, to obtain. In the absence of appropriate trials, we recommend, albeit on the basis of less than optimal evidence, that adrenaline administration by intramuscular (i.m.) injection should still be regarded as first-line treatment for the management of anaphylaxis.