Frances B. Kinnear

REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial

BackgroundGuidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified.Methods/designThe REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of < 100 mmHg, persisting after a 1000-ml fluid bolus with isotonic crystalloid. Participants will be randomised to either a second 1000-ml fluid bolus (standard care) or maintenance rate fluid only, with the early commencement of a vasopressor infusion to maintain a mean arterial pressure of > 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support ‘free days’ to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups.DiscussionThis is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a large, international, multicentre trial with sufficient power to assess clinical outcomes. The embedded biomarker study aims to provide mechanistic plausibility for a larger trial by defining the effects of fluid volume on markers of systemic inflammation and the vascular endothelium.Trial registrationAustralia and New Zealand Clinical Trials Registry, ID: ACTRN12616000006448. Registered on 12 January 2016.

RESPECT-ED: Rates of pulmonary emboli (PE) and sub-segmental PE with modern computed tomographic pulmonary angiograms in emergency departments: A multi-center observational study finds significant yield variation, uncorrelated with use or small PE rates

Introduction Overuse of CT Pulmonary Angiograms (CTPA) for diagnosing pulmonary embolism (PE), particularly in Emergency Departments (ED), is considered problematic. Marked variations in positive CTPA rates are reported, with American 4–10% yields driving most concerns. Higher resolution CTPA may increase sub-segmental PE (SSPE) diagnoses, which may be up to 40% false positive. Excessive use and false positives could increase harm vs. benefit. These issues have not been systematically examined outside America. Aims To describe current yield variation and CTPA utilisation in Australasian ED, exploring potential factors correlated with variation. Methods A retrospective multi-centre review of consecutive ED-ordered CTPA using standard radiology reports. ED CTPA report data were inputted onto preformatted data-sheets. The primary outcome was site level yield, analysed both intra-site and against a nominated 15.3% yield. Factors potentially associated with yield were assessed for correlation. Results Fourteen radiology departments (15 ED) provided 7077 CTPA data (94% ≥64-slice CT); PE were reported in 1028 (yield 14.6% (95%CI 13.8–15.4%; range 9.3–25.3%; site variation p <0.0001) with four sites significantly below and one above the 15.3% target. Admissions, CTPA usage, PE diagnosis rates and size of PE were uncorrelated with yield. Large PE (≥lobar) were 55% (CI: 52.1–58.2%) and SSPE 8.8% (CI: 7.1–10.5%) of positive scans. CTPA usage (0.2–1.5% adult attendances) was correlated (p<0.006) with PE diagnosis but not SSPE: large PE proportions. Discussion/ Conclusions We found significant intra-site CTPA yield variation within Australasia. Yield was not clearly correlated with CTPA usage or increased small PE rates. Both SSPE and large PE rates were similar to higher yield historical cohorts. CTPA use was considerably below USA 2.5–3% rates. Higher CTPA utilisation was positively correlated with PE diagnoses, but without evidence of increased proportions of small PE. This suggests that increased diagnoses seem to be of clinically relevant sized PE.

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax

Introduction Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP. Methods and analysis This multicentre, prospective, randomised, open label, parallel group, non-inferiority study will randomise 342 participants with a first large PSP to conservative or interventional management. To maintain allocation concealment, randomisation will be performed in real time by computer and stratified by study site. Conservative management will involve a period of observation prior to discharge, with intervention for worsening symptoms or physiological instability. Interventional treatment will involve insertion of a small bore drain. If drainage continues after 1 hour, the patient will be admitted. If drainage stops, the drain will be clamped for 4 hours. The patient will be discharged if the lung remains inflated. Otherwise, the patient will be admitted. The primary end point is the proportion of participants with complete lung re-expansion by 8 weeks. Secondary end points are as follows: days in hospital, persistent air leak, predefined complications and adverse events, time to resolution of symptoms, and pneumothorax recurrence during a follow-up period of at least 1 year. The study has 95% power to detect an absolute non-inferiority margin of 9%, assuming 99% successful expansion at 8 weeks in the invasive treatment arm. The primary analysis will be by intention to treat. Ethics and dissemination Local ethics approval has been obtained for all sites. Study findings will be disseminated by publication in a high-impact international journal and presentation at major international Emergency Medicine and Respiratory meetings. Trial registration number ACTRN12611000184976; Pre-results.

Paediatric high-flow nasal cannula therapy in children with bronchiolitis: A retrospective safety and efficacy study in a non-tertiary environment

The objective was to examine the safety and efficacy of high‐flow nasal cannula (HFNC) therapy for children with bronchiolitis in a non‐tertiary paediatric setting.

Correction: RESPECT-ED: Rates of Pulmonary Emboli (PE) and sub-segmental PE with modern computed tomographic pulmonary angiograms in emergency departments: A multi-center observational study finds significant yield variation, uncorrelated with use or small PE rates (PLoS ONE (2016) 11:12 (e0166483) DOI: 10.1371/journal.pone.0166483)

[This corrects the article DOI: 10.1371/journal.pone.0166483.].

Applying the Ottawa subarachnoid haemorrhage rule on a cohort of emergency department patients with headache

Objective The Ottawa subarachnoid haemorrhage (SAH) rule suggests that alert patients older than 15 years with a severe nontraumatic headache reaching maximum intensity within 1 h and absence of high-risk variables effectively have a SAH ruled out. We aimed to determine the proportion of emergency department (ED) patients with any headache fulfilling the entry criteria for the Ottawa SAH rule. Patients and methods The Ottawa SAH rule was applied retrospectively in a substudy of a prospective snapshot of 34 EDs in Queensland, Australia, carried out over 4 weeks in September 2014. Patient aged 18 years and older with a nontraumatic headache of any potential cause were included. Clinical data and results of investigations were collected. Results Data were available for 644 (76%) patients. A total of 149 (23.1%, 95% confidence interval: 20.0–26.5%) fulfilled and 495 (76.9%, 95% confidence interval: 73.5–80.0%) did not fulfil the entry criteria. In patients who fulfilled the entry criteria, 30 (<5% overall) did not have any high-risk variables for SAH. In patients who fulfilled the entry criteria and had at least 1 high-risk feature, almost half (46%) received a computed tomographic brain. No SAH were missed. Conclusion In this descriptive observational study, the majority of ED patients presenting with a headache did not fulfil the entry criteria for the Ottawa SAH rule. Less than 5% of the patients in this cohort could have SAH excluded on the basis of the rule. More definitive studies are needed to determine an accepted benchmark for the proportion of patients receiving further work-up (computed tomographic brain) after fulfilling the entry criteria for the Ottawa SAH rule.

Evaluation of a multiple-encounter in situ simulation for orientation of staff to a new paediatric emergency service: a single-group pretest/post-test study

Aim To assess the utility of a multiple-encounter in-situ (MEIS) simulation as an orientation tool for multidisciplinary staff prior to opening a new paediatric emergency service. Methods A single-group pretest/post-test study was conducted. During the MEIS simulation, multidisciplinary staff with participant or observer roles managed eight children (mannequins) who attended triage with their parent/guardians (clinical facilitators) for a range of emergency presentations (structured scenarios designed to represent the expected range of presentations plus test various clinical pathways/systems). Participants were debriefed to explore clinical, systems and crisis-resource management issues. Participants also completed a pre-intervention and post-intervention questionnaire comprising statements about role confidence and orientation adequacy. Pre-test and post-test results were analysed using t-test and Wilcoxon signed rank test. Results Eighty-nine staff participated in the MEIS simulation, with the majority completing the pre-simulation and post-simulation questionnaire. There was a significant improvement in post-intervention versus pre-intervention Likert scores for role confidence and orientation adequacy (p=0.001 and <0.001, respectively); effect sizes suggested the greatest impact was on orientation adequacy. Nearly all scenarios resulted in significant increases in participants’ confidence levels. Conclusions The MEIS simulation was of utility in orientation of staff, at least with respect to self-reported role confidence and orientation adequacy. Its effectiveness in practice or compared with other orientation techniques was not assessed, but it did identify several flaws in planned systems allowing remediation prior to opening.