Suspected Pulmonary Embolism Exclusion with D-dimers in Emergency Departments (SPEED-ED)

Pulmonary embolism (PE) refers to blood clots in the lung. They can cause sudden death, collapse, chest pain, shortness of breath yet sometimes they cause no symptoms at all and are discovered incidentally. As they can be severe, they have become regarded as a not-to-miss diagnosis. As they can present with a variety of symptoms, emergency clinicians consider the possibility of PE on a frequent basis.

When considering whether a patient has a PE, the clinician may confirm or exclude the diagnosis directly with definitive chest scans. However, these scans are time consuming, costly and have other side effects including exposure to radiation and to chemical contrast agents. When patients are assessed to be less likely of having a PE, it is often possible to safely exclude PE by applying a set of clinical decision rules or doing a blood test called a D-dimer. If the level of D-dimer is below a certain threshold, then PE can be excluded.

We aim to safely exclude PE without scans where possible. Evidence has been building that employing a higher D-dimer threshold is reasonable, yet uptake of this newer approach is limited. We hope to demonstrate that a higher threshold can work in Australia without compromising safety. This will be a large study that answers this question and if shown to be the case, then patient care can be improved while using less resources in busy emergency departments.

A randomised controlled trial of plasmalyte versus normal saline as resuscitation and maintenance fluid therapy for patients presenting with diabetic ketoacidosis (BEST-DKA) BalancEd fluids vs Saline Trial in Diabetic KetoAcidosis

We propose to conduct a multi-centre blinded cluster cross over randomised clinical trial (RCT) of plasmalyte (PL), a balanced salt solution versus normal saline (NS) in patients admitted to an Intensive Care Unit (ICU) with diabetic ketoacidosis (DKA), a life-threatening complication of diabetes mellitus. DKA results in elevated acid levels in the blood leading to severe dehydration and electrolyte imbalance.

ICU admission rates for patients with DKA in Australia has risen annually. In 2019 and 2020, there were 2751 and 2812 admissions to ICUs respectively. Almost all patients present through the Emergency Departments and in regional hospitals, they are often admitted to the ICU.

NS is often used as the first line fluid for dehydration, but NS use frequently results in persistent acidosis. We have shown in a pilot trial, conducted in 7 Queensland regional Emergency departments and ICUs, that the use of a balanced salt solution such as PL resulted in a more rapid resolution of acidosis with trends to shorter length of ICU and hospital stay as compared to NS. The efficacy of PL in DKA needs evaluation in a large clinical trial.

We plan to study 480 patients from Australia of whom a third will be expected to be enrolled in Queensland. Patients will be randomised to receive either NS or PL and the primary end point is hospital length of stay. This proposed trial will answer a fundamental clinical question and will inform policy and practice in Australia and New Zealand and around the world.

SPASMS: Study of Paediatric Appendicitis Scores and Management Strategies

Abdominal pain is one of the commonest reasons for children to attend the emergency department (ED), and acute appendicitis is the most common cause of abdominal pain requiring surgery. There are various clinical prediction scores that have been developed to help doctors diagnose appendicitis; however, most scores were developed overseas and are not routinely used in Australian EDs. The aim of this project is to review different published scores and compare them with overall clinician impression in diagnosing acute appendicitis in children presenting to ED.

The project will include all patients presenting to the ED with abdominal pain that are having investigations for possible appendicitis. The treating doctor will be asked to complete a case report form detailing patient history, examination findings, investigation results, as well as their overall clinical impression of the patient’s likelihood of having the diagnosis of appendicitis. Data collected will be analysed by project researchers to determine which scores are the most helpful for clinicians in diagnosing acute appendicitis in children presenting to Australian EDs, with the expectation that this will improve future care provided to children with abdominal pain.

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.