Death adder envenoming causes neurotoxicity not reversed by antivenom - Australian snakebite project (ASP-16)

BACKGROUND: Death adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment. METHODOLOGY/PRINCIPAL FINDINGS: Definite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5-74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5-15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5-168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4-245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom. CONCLUSIONS/SIGNIFICANCE: Death adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The persistent neurological effects despite antivenom, suggests that neurotoxicity is not reversed by antivenom.Christopher I. Johnston, Margaret A. O, Leary, Simon G. A. Brown, Bart J. Currie, Lambros Halkidis, Richard Whitaker, Benjamin Close, Geoffrey K. Isbister, for the ASP investigator

Access block causes emergency department overcrowding and ambulance diversion in Perth, Western Australia

Objective: Access block refers to the situation where patients in the emergency department (ED) requiring inpatient care are unable to gain access to appropriate hospital beds within a reasonable time frame. We systematically evaluated the relationship between access block, ED overcrowding, ambulance diversion, and ED activity. Methods: This was a retrospective analysis of data from the Emergency Department Information System for the three major central metropolitan EDs in Perth, Western Australia, for the calendar years 2001–2. Bivariate analyses were performed in order to study the relationship between a range of emergency department workload variables, including access block (>8 hour total ED stay for admitted patients), ambulance diversion, ED overcrowding, and ED waiting times. Results: We studied 259 580 ED attendances. Total diversion hours increased 74% from 3.39 hours/day in 2001 to 5.90 hours/day in 2002. ED overcrowding (r = 0.96; 95% confidence interval (CI) 0.91 to 0.98), ambulance diversion (r = 0.75; 95% CI 0.49 to 0.88), and ED waiting times for care (r = 0.83; 95% CI 0.65 to 0.93) were strongly correlated with high levels of ED occupancy by access blocked patients. Total attendances, admissions, discharges, and low acuity patient attendances were not associated with ambulance diversion. Conclusion: Reducing access block should be the highest priority in allocating resources to reduce ED overcrowding. This would result in reduced overcrowding, reduced ambulance diversion, and improved ED waiting times. Improving hospital inpatient flow, which would directly reduce access block, is most likely to achieve this

Comparison of two clinical scoring systems for emergency department risk stratification of suspected acute coronary syndrome

Objective: To compare two methods of risk stratification for suspected acute coronary syndrome (ACS) in the ED. Methods: A prospective observational multicentre study was undertaken of patients undergoing evaluation in the ED for possible ACS. We compared the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand (NHF/CSANZ) guideline and the Thrombolysis in Myocardial Infarction (TIMI) risk score for differentiating high- and low-risk patients. Composite outcome was all cause death, myocardial infarction or coronary revascularisation within 30 days. Results: Of 1758 enrolments, 223 (13%) reached the study outcome. Area under the receiver operator characteristic (ROC) curve was 0.79 (95% CI 0.76-0.81) for the NHF/CSANZ group and 0.71 (0.68-0.75) for TIMI score based on initial troponin result (P<0.001), and 0.82 (95% CI 0.80-0.84) and 0.76 (0.73-0.79) respectively when the 8-12h troponin result is included (P=0.001). Thirty day event rates were 33% for NHF/CSANZ high-risk vs 1.5% for combined low/intermediate risk (P<0.001). For TIMI score, 30 day event rates were 23% for a score =2 and 4.8% for TIMI<2 (P<0.001). The NHF/CSANZ guideline identified more patients as low risk compared with the TIMI risk score (61% vs 48%, P<0.001). Conclusions: The NHF/CSANZ guideline is superior to the TIMI risk score for risk stratification of suspected ACS in the ED. © 2011 The Authors. EMA © 2011 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine

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

© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine 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

Poor overall quality of clinical practice guidelines for musculoskeletal pain: a systematic review

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. OBJECTIVES: Undertake a systematic critical appraisal of contemporary clinical practice guidelines (CPGs) for common musculoskeletal (MSK) pain conditions: spinal (lumbar, thoracic and cervical), hip/knee (including osteoarthritis) and shoulder.DESIGN: Systematic review of CPGs (PROSPERO number: CRD42016051653).Included CPGs were written in English, developed within the last 5?years, focused on adults and described development processes. Excluded CPGs were for: traumatic MSK pain, single modalities (eg, surgery), traditional healing/medicine, specific disease processes (eg, inflammatory arthropathies) or those that required payment.DATA SOURCES AND METHOD OF APPRAISAL: Four scientific databases (MEDLINE, Embase, CINAHL and Physiotherapy Evidence Database) and four guideline repositories. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument was used for critical appraisal.RESULTS: 4664 records were identified, and 34 CPGs were included. Most were for osteoarthritis (n=12) or low back pain (n=11), most commonly from the USA (n=12). The mean overall AGREE II score was 45% (SD=19.7). Lowest mean domain scores were for applicability (26%, SD=19.5) and editorial independence (33%, SD=27.5). The highest score was for scope and purpose (72%, SD=14.3). Only 8 of 34 CPGS were high quality: for osteoarthritis (n=4), low back pain (n=2), neck (n=1) and shoulder pain (n=1)

A randomised controlled trial of intramuscular vs. intravenous antivenom for latrodectism - the RAVE study

Background: Widow spider-bite causes latrodectism and is associated with significant morbidity worldwide. Antivenom is given by both the intravenous (IV) and intramuscular (IM) routes and it is unclear which is more effective. Aim: To compare the effectiveness of IV vs. IM redback spider antivenom. Design: Randomized controlled trial. Methods: Patients with latrodectism were given either IV or IM antivenom according to a randomized double-dummy, double-blind protocol. The first antivenom treatment was followed by another identical treatment after two hours if required. The primary outcome was a clinically significant reduction in pain two hours after the last treatment. A fully Bayesian analysis was used to estimate the probability of the desired treatment effect, predetermined as an absolute difference of 20%. Results: We randomly allocated 126 patients to receive antivenom IV (64) and IM (62). After antivenom treatment pain improved in 40/64(62%) in the IV group vs. 33/62(53%) in the IM group (+9%; 95% Credible Interval [CrI]: –8% to +26%). The probability of a difference greater than zero (IV superior) was 85% but the probability of a difference >20% was only 10%. In 55 patients with systemic effects, these improved in 58% after IV antivenom vs. 65% after IM antivenom ( 8%; 95% CrI: –32% to +17%). Twenty-four hours after antivenom pain had improved in 84% in the IV group vs. 71% in the IM group (+13%; 95% CrI: –2% to +27%). A meta-analysis including data from a previous trial found no difference in the primary outcome between IV and IM administration. Discussion: The difference between IV and IM routes of administration of widow spider antivenom is, at best, small and does not justify routinely choosing one route over the other. Furthermore, antivenom may provide no benefit over placebo

Consensus guidelines for the investigation and management of encephalitis in adults and children in Australia and New Zealand.

Encephalitis is a complex neurological syndrome caused by inflammation of the brain parenchyma. The management of encephalitis is challenging because: the differential diagnosis of encephalopathy is broad; there is often rapid disease progression; it often requires intensive supportive management; and there are many aetiologic agents for which there is no definitive treatment. Patients with possible meningoencephalitis are often encountered in the emergency care environment where clinicians must consider differential diagnoses, perform appropriate investigations and initiate empiric antimicrobials. For patients who require admission to hospital and in whom encephalitis is likely, a staged approach to investigation and management is preferred with the potential involvement of multiple medical specialties. Key considerations in the investigation and management of patients with encephalitis addressed in this guideline include: Which first-line investigations should be performed?; Which aetiologies should be considered possible based on clinical features, risk factors and radiological features?; What tests should be arranged in order to diagnose the common causes of encephalitis?; When to consider empiric antimicrobials and immune modulatory therapies?; and What is the role of brain biopsy