Trials in Emergency for Advancing Management of Sepsis: TEAM SEPSIS

Severe infection (sepsis) takes the lives of over 2000 Queenslanders every year. Despite this toll and intense global research, few advances and innovations have improved sepsis management for decades. The TEAM SEPSIS project comprises three studies to improve the diagnosis and treatment of patients with sepsis in the Emergency Department (ED).

ICARUS-MD is a randomised controlled trial assigning patients to receive or not receive albumin in addition to standard sepsis care. Albumin will be commenced in the early phase of emergency treatment and continued each day for ten days. Albumin has the potential to improve outcomes if started early in the ED - ICARUS-MD may provide much needed evidence.

ARTEMIS is an observational study in a subset of ICARUS-MD patients with blood samples taken across several time points to determine the effect of albumin on the function of the critical lining of small blood vessels – the endothelial glycocalyx.

BETTER aims to improve the investigation of septic patients in ED by validating a novel test for bacteraemia in patients at highest risk for this condition. The study will use patients from the ICARUS-MD cohort as well as other emergency patients with low white cell count and suspected infection. Earlier diagnosis of bacteraemia enables directed therapy, improves patient outcomes, and conserves our most powerful antibiotics for patients who need them.

This programme of collaborative research involving ED and infectious diseases clinicians promises to advance knowledge of the best approach to diagnosis and treatment for emergency patients at highest risk from sepsis.

SONIC: Study of Neck Injuries in Children. A PREDICT study

Currently in Australia, children with suspected neck injuries undergo neck scans such as x-rays, computed tomography (CT) or magnetic resonance imaging (MRI). However these scans may carry risks from radiation exposure, and are often associated with discomfort and distress for young patients and the need for sedation.

Considerable emergency department time and costs are also associated with these scans and it is unclear when it can be safely avoided. Rules and tools can help doctors decide when scans are necessary. The SONIC study aims to look at whether existing rules for adults are also appropriate for use in children, and to develop and test a specific tool to help doctors decide which children need a neck x-ray or scan. The study will involve a large number of children across multiple hospitals in Australia and New Zealand. The research is expected to help researchers learn more about looking after children with neck injuries and hopefully allow us to safely limit the number of scans that need to be done.

The SONIC study is also supported by the Commonwealth of Australia through a MRFF Grant ID1199748 administered by the Murdoch Children’s Research Institute.

Coronary Artery Disease in Aboriginal and Torres Strait Islander People

Aboriginal and Torres Strait Islander people die from heart attacks at younger ages than non-indigenous Australians. The factors that increase risk of death from heart attack in young Aboriginal and Torres Strait Islander people are unknown.

Most patients who present to an Emergency Department (ED) with chest pain do not have a heart problem but all are assessed for their risk of having a life-threatening cause, such as heart attack. The level of risk determines which tests are performed so that a final diagnosis can be obtained as quickly as possible. Due to the lack of knowledge about risk factors in the Aboriginal and Torres Strait Islander population there is uncertainty about how best to use chest pain risk assessments in indigenous patients.

In this study, we will determine the rate of coronary artery disease (a hardening of arteries and the underlying cause of heart attacks) in Aboriginal and Torres Strait Islander people who present to the ED with chest pain. We will also compare the characteristics of patients who do and do not have heart attacks to identify potential risk factors for heart attack in this population.

The findings from this study will: 1) allow ED doctors to determine a baseline level of risk of heart attack for the Aboriginal and Torres Strait Islander patient population, and 2) provide preliminary information necessary for the design of large-scale research studies with the goal of determining specific risk factors for heart attack in Aboriginal and Torres Strait Islander people.

Better ways of pain management in adults with hip fractures

Hip fractures are extremely painful yet medications which are usually used to manage the pain can have significant complications, particularly in frail individuals. Numbing medications injected into the groin on the side of the hip fracture have been shown to decrease pain, confusion and chest infections in patients with hip fracture awaiting an operation.

It is usual for most patients presenting to emergency departments with a hip fracture to get a single injection of numbing medication. What isn’t known is whether multiple regular doses of numbing medications injected regularly via a plastic tube in the groin are more effective than a single injection in managing the pain of hip fractures.
The purpose of this study is to show multiple regular doses of numbing medications are better than a single injection. This will be achieved by examining the difference in the amount of pain, the quantity of pain medications, and the degree of confusion between the patients getting multiple doses and those getting a single injection.

This study will be the first of its kind to be done in an emergency department and is also unique in that it will involve patients with dementia who make up more than a third of patients with hip fracture and are usually excluded from studies. The study is expected to help manage the pain of the 1.6 million hip fracture patients worldwide and give emergency doctors an additional option of managing hip fracture pain.

Using bedside ultrasound to diagnose forearm fractures in children

This is a multicentre, open-labelled diagnostic randomised controlled trial to comparing the use of portable ultrasound and x-ray imaging to diagnose a buckle fracture in children. The trial will determine if there are differences in functional outcomes, patient and care-giver preferences, and health system benefits.

Children frequently present to the emergency department with forearm injuries and often have an x-ray to assess if there is a fracture. Due to the soft and plastic nature of the bones in young children, injuries can cause their bones to bend, known as a buckle fracture. Bedside ultrasound is a test that emergency practitioners can use to rapidly diagnose a fracture at the time of examination, without exposing children to ionising radiation. Ultrasound in this setting is well tolerated, only requiring light touch and gentle manipulation of the forearm and has similar accuracy when compared with x-rays for diagnosing children’s forearm fractures.

This is the first trial of its kind to assess whether an x-ray is unnecessary when there is either a buckle fracture or no fracture seen on a portable ultrasound machine. This is important as they can be treated at the time of review without any further delay, which will avoid these children being exposed to ionising radiation. Children will be randomised to receive either an ultrasound or x-ray for their forearm injury. Both groups will be followed up to see whether there are any differences in their recovery and to determine any complications. We will also determine the time and cost implications of this new approach, which could enable families to go home earlier and could be more cost-effective, with less x-rays being ordered.

Early resuscitation in paediatric sepsis

Sepsis is a leading cause of death and disability in children, globally accounting for more than one million childhood deaths per year. Recommended sepsis treatment currently consists of intravenous antibiotics and aggressive fluid boluses followed by inotropes and consideration for intravenous steroids. However, the evidence for interventions other than antibiotics is limited and aggressive fluid administration may be associated with harm. Therefore, fluid-sparing algorithms using early inotropes to treat shock have been proposed. Another strategy to hasten shock resolution consists in intravenous steroids, alone or in combination with thiamine and vitamin C, postulated to support metabolic dysfunction in recent studies.

In this project, the research team is conducting a randomised controlled pilot trial in children presenting with septic shock. They are assessing the feasibility of a fluid-sparing algorithm using early inotropes and early intravenous administration of Vitamin C, Thiamine and Hydrocortisone and the impact on survival free of organ dysfunction.

Fluid resuscitation in emergency patients with sepsis and hypotension (ARISE Fluids)

The question of fluid volume in resuscitation has been identified as the top priority in sepsis research by emergency physicians in the United Kingdom, Australia and New Zealand. Guidelines and sepsis pathways recommend an initial intravenous (IV) fluid bolus of 30ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this strategy. Both observational data as well as randomised studies suggest there may be harm associated with injudicious use of fluids in sepsis. Since there is equipoise regarding a more liberal or restricted fluid volume resuscitation as first line treatment for sepsis-related hypotension, we conducted the pilot multicentre REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH) trial comparing a restricted fluid protocol with early initiation of vasopressor support against standard guideline care.

The data from REFRESH will inform feasibility of a large, multicentre phase III study. However, further ground work is essential for the optimal design of a Phase III trial that will provide valuable information on feasibility (road test recruitment rate and screening processes) as well as refinement of the protocol (sample size estimation, processes of care, prevalence of the population of interest, real world clinical practice regarding fluid use).

In this ARISE Fluids study, we aim to provide more insight into current practice by conducting a bi-national multi-site prospective observational study of fluid administration in (suspected) sepsis and hypotension in the Emergency Departments of Australia and New Zealand hospitals. Sites have been selected on the basis of having expressed interest in participating in a phase III trial.

STOPAsthmaQLD

Grass pollen is the major outdoor allergen globally and grass pollen exposure has an important measurable and manageable impact on the medical burden of asthma. We propose investigating the role of allergy status on triggers for asthma in patients visiting hospital emergency departments in two regions of south east Queensland over a two year period, coinciding with NHMRC and ARC funded environmental health research led by collaborator CI Davies.

Data on weather and pollen exposure will be integrated with direct assessment of specific IgE profiles and respiratory viral triggers of asthma. Patients, including children over 12 years, presenting with primary diagnosis of asthma to a major urban hospital in a subtropical region and rural hospitals in the temperate regions of the Darling Downs will be recruited with informed consent.

Outcomes of this study are expected to inform need for utilising local current pollen exposure information to manage emergency department demand surges and underpin better management of pollen allergies outside of hospital by allergy physician and general practice.

International mass gathering impact on Gold Coast Hospitals’ emergency departments

Queensland is known for its ability to attract mass gathering events of international significance, such as the 2018 Commonwealth Games, 2023 FIFA Women’s World Cup and the 2032 Olympic Games. Such events have the potential to impact the normal operational capacity of our emergency health services.

The objective of this study is to describe the impact of the 2018 Commonwealth Games on the emergency departments in the Gold Coast region. This research has two key aims, which align with two discrete but related studies:

Study 1 Aim: To describe and determine whether changes in patient, health service, and economic outcomes occur before, during and after the Commonwealth Games.
Study 2 Aim: To explore healthcare staff experience of planning, preparedness and lessons learnt from the Commonwealth Games.

Evaluation of the Geriatric Emergency Department Intervention (GEDI) implementation

Advances in health have led to populations living longer with more chronic disease and frailty. Frail older people presenting to emergency departments (EDs) have special needs that are often overlooked. In response, the innovative Geriatric Emergency Department Intervention (GEDI) was developed by clinicians at Nambour Hospital, Queensland.

GEDI is a unique nurse-led, physician-championed model of service delivery which facilitates advanced assessment tailored to the individual, nurse-initiated specialist referral, fast-tracking of care through the ED and appropriate safe discharge planning for persons aged 70 and over, including those from residential aged care facilities. A successful trial in one ED was awarded the 2016 Queensland Premier’s Award for Excellence. The evaluative research we conducted found that when older adults presented to ED during the times the GEDI team was working they were more likely to be discharged, if admitted they spent, on average, 24 hours less in hospital and the costs of their care were reduced by up to 30%.

The staffing for a trial of GEDI in two further Queensland EDs will be funded by the Queensland Health Improvement Unit. This EMF-funded evaluation project employs the principles of implementation science to evaluate the introduction of GEDI into these EDs to determine whether the knowledge learned from the trial can be translated to other sites and to determine the best strategies for future implementations of GEDI across Queensland and interstate. If implementation is found to be successful future roll out of GEDI will improve patient outcomes and reduce costs in Queensland and across the country.