The REFRESH study is a multicentre, open-label, randomised, phase II clinical feasibility trial. This 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.
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.READ MORE
Acutely agitated patients are commonly seen in the emergency department (ED). As these patients may cause harm to themselves or others, a large proportion need to be managed with injectable sedative medications such as benzodiazepines (eg midazlolam) and/ or antipsychotics (e.g droperidol).
Unfortunately, these medications may precipitate life threatening events (e.g hypoventilation). Safety data related to the use of these medications for the management of acute agitation in the ED setting are scant. Acute agitation in the ED setting is usually caused by mental health issues or substance abuse, again little is known about which sedative medications are best suited for different groups of acutely agitated patients.
The aim of this study is to determine the nature and incidence of adverse events associated with parenteral sedation medication administered to acutely agitated patients in the ED and to determine the risk factors for these adverse events. It is a multicentre national observational study, aiming to recruit 2000 patients over the age of 18, over a 2 year period. It is hoped that the evidence this study generates will define the risk of AE in this population and may guide clinicians in future treatment choices in sedating this challenging group of patients, hopefully reducing future AE.READ MORE