Research project outcomes

2013: Therapeutic hypercapnia after cardiac arrest: a pilot feasibility and safety randomised controlled trial
Chief Investigator: A/Professor Glenn Eastwood

Background

The researchers sought to assess the safety and feasibility of targeting slightly higher than normal levels of carbon dioxide in the blood during the early post-resuscitation period for patients admitted to the ICU following cardiac arrest.
They did this because carbon dioxide levels in the blood play a major role in regulating blood flow to the brain. In addition, findings of a large retrospective study of cardiac arrest patients identified patients who experienced higher than normal carbon dioxide levels during the early post-resuscitation period have a greater chance of discharge to home among survivors. However, no trials had tested the safety and feasibility of mild hypercapnia for cardiac arrest patients admitted to the intensive care unit.

The study and findings

Targeting of blood carbon dioxide levels for the purposes of this study was performed while the patient was sedated and receiving breathing support from a breathing machine (ventilator). The concentration of carbon dioxide in the blood was altered by changing the respiratory rate of the patient. Blood samples were routinely taken to ensure blood carbon dioxide levels did not go too high. All other processes of care were at the discretion of their ICU clinicians.

This pilot feasibility and safety study identified a trend to favourable neurological outcome in survivors allocated to slightly higher than normal carbon dioxide at 6 months –  that  is, more patients allocated to higher than normal carbon dioxide targeted therapy were discharged alive from ICU and had spent fewer days in the ICU compared to those allocated to targeted normal. Also, there were proportionally fewer patients who had died in hospital for those allocated to the higher carbon dioxide therapy.

Although our findings did not demonstrate a statistically significant difference,   was not powered (meaning it did not enough a sufficient number of patients) to detect a statistically significant difference in survival for patients allocated to the treatment compared to standard care.

Exciting next steps and a $2.1 million  NHMRC Grant!

The findings of this research justified  further investigation.  In response, the researchers  successfully submitted a proposal to the National Health & Medical Research Council (NHMRC) in 2016 to conduct a definitive phase III multi-centre randomised controlled trial in resuscitated and mechanically ventilated ICU cardiac arrest patients. This $2.1 million  trial will determine whether targeted therapeutic mild hypercapnia (TTMH) during mechanical ventilation improves neurological outcome at 6 months compared to targeted normocapnia (standard care). Supported by compelling preliminary data, the researchers  contend that significant improvements in patient outcomes are achievable with this proposed simple and cost free therapy. To appropriately test this  study hypothesis they  will recruit 1,700 patients, making this the largest trial ever conducted involving cardiac arrest patients admitted to the intensive care unit.  Importantly, if this trial confirms that TTMH is effective, its findings will improve the lives of many Australians, transform clinical practice and yield major economic gains worldwide.

 

2012: The HEAT trial – a randomised placebo-controlled trial of intravenous paracetamol in febrile septic patients.
Chief Investigator: Dr Paul Young

Background

Paracetamol is the world’s most commonly administered medicine and has been around for more than 60 years.. However, there had been some concern among doctors that the common practice of using it to reduce fever in ICU patients might make them worse.

The study and findings

The study involved more than 2,500 doctors and nurses from 23 Intensive Care Units across New Zealand and Australia. This world-first research was funded by the Intensive Care Foundation and the Health Research Council of New Zealand

The study, which was undertaken in partnership with The George Institute for Global Health, found paracetamol is safe for treating patients in intensive care and may even help them recover and leave hospital more quickly. These findings will influence medical practice around the world.

The research, which was published in 2015 in the world’s most prestigious medical journal, The New England Journal of Medicine, found:

  • Paracetamol was safe and well tolerated in ICU patients with fever or infection
  • The medicine reduced body temperature by around a quarter of a degree
  • Paracetamol neither improved nor worsened patient outcomes
  • Patients spent less time in ICU if they were given paracetamol, but patients who died spent more time in ICU before death if given paracetamol

While a brief course of paracetamol did not reduce the overall risk of death, the results of this study will prompt further research looking at whether more prolonged courses of paracetamol can reduce the risk of death in patients requiring Intensive Care.

2012: Structure and Function of the Kidney in Septic Shock. A Prospective Controlled Experimental Study
Chief Investigator: Dr Matthew Maiden

Background
Sepsis is a condition when an infection leads to altered function of the body’s organs.  Most patients with sepsis develop rapid changes in kidney function, but it remains unclear why this occurs.  Previous explanations suggested inadequate blood flow to the kidney, death of kidney cells or small blood clots impairing normal function.  However this is based on scant evidence and extrapolation from other diseases.  Given the frequency of altered kidney function with sepsis and its strong association with mortality, it is vital to understand the mechanisms of this disease.

The Study

This is the first scientific study to examine the structural and functional changes that occur to the kidneys over time as the sepsis evolves.
In essence the study showed that kidney function markedly changes during sepsis, but it still receives plenty of blood flow and there is no evidence of damage, even when examining renal tissue with electron microscopy.  The results of the study have challenged a number of long-held dogmas.  It appears the kidney is acutely “shutting down” and researchers can now embark on studies to determine how this is occurring.

“Pre-clinical studies are essential to understand mechanisms of disease and determine treatment strategies.  This form of medical science is only possible with the financial support of the organisations like the Intensive Care Foundation,” said Dr Maiden.

Publications

Maiden M, Otto S, Brealey J, Chapman M, Nash C, Edwards J, Kuchel T, Bellomo R. Structure and function of the kidney in septic shock – a prospective controlled study. Intensive Care Med Exp 2015;3(Suppl 1):A838.

Maiden MJ, Otto S, Brealey JK, Finnis ME, Chapman MJ, Kuchel TR, Nash CH, Edwards J, Bellomo R. Structure and Function of the in Septic Shock: A Prospective Controlled Experimental Study. Am J Respir Crit Care Med 2016.

2014 study using genetic research reveals cause of lethal infections in children
Chief Investigator: A/Prof Luregn Schlapbach, Paediatric Intensive Care Staff Specialist FCICM, University of Qld and Lady Cilento Children’s Hospital


Background
Sepsis (severe infection) remains one of the leading causes of infant and childhood mortality worldwide. Approximately a third of lethal infections occur in previously apparently healthy children.Fatal bacterial sepsis is an extremely rare disease in previously healthy children. To date the majority of such cases were discharged from ICU without being investigated from a genetic or immunologic point of view. As a result, families, siblings, and survivors were left with no explanation as to what had happened, and concerns about risks for recurrence persisted in many (evidenced by personal communication of participating parents).

Thanks to the enormous improvements in genetic research in the past years, it is now possible to analyse all genes of a patient within a short time. This so-called genomic approach allows doctors to screen a patient’s entire DNA for mutations that are responsible for diseases. In contrast to previous studies, this new approach allows doctors to discover previously unknown genetic mutations that underlie rare diseases.

The study (2014 Intensive Care Foundation Grant: $15,062)PhotoSchlapbach
Professor Schlapbach and his team began the research working from the assumption that it is very likely that human genes play a key role in determining why certain children are much more vulnerable to severe infections than others. The study was performed in collaboration with leading genomic research groups.

The team investigated families where a previously healthy child developed a very severe infection (sepsis) using the most modern genomic technology (exome sequencing). They sequenced (decoded) all genes of the included patients and their parents. This is the most promising approach to detect the underlying cause.

This pilot study provides proof-of-concept that exome sequencing allows the identification of rare, human genetic variants responsible for fulminant sepsis in children in whom immunodeficiency had not been previously suspected. They were able to diagnose primary immunodeficiency in several cases, with a significant impact on affected families. Given the decreasing cost of exome sequencing, they propose to consider it as a diagnostic procedure for apparently healthy children presenting with unusually severe or fatal sepsis.

Indeed, this study proves that apparently healthy children presenting fulminant life-threatening infections may be suffering from unrecognized immunodeficiencies. Intensivists may thereby be exposed to patients harbouring immunodeficiencies of which they are not aware.

The outcomes of this study hopefully will lead to a change in approach, and optimise diagnosis in children with severe infections.

Thanks to this research, siblings of ICU patients with fulminant sepsis can be tested for underlying immunodeficiencies. In the course of this study, it was possible to rule out a life-threatening immunodeficiency in several young children who tested negative.

The study had special meaning for this family…
“…Whilst nothing will ever be enough, it is exceptionally helpful to have an answer to explain why our child died so suddenly… it meant a lot to know that members of the medical fraternity were equally baffled and cared enough to investigate further…We faced a number of challenging issues during the study, including the possible unknown impact on other family members, (and) future family planning decisions …Following the release of the study results, we arranged for genetic testing of our second child, which in our case provided an indescribable amount of relief as our second child was negative for the primary immunodeficiency …
During the study process it was invaluable to have a responsive point of contact to explain in detail, provide updates and support us as parents. It is good to know that the research that our child participated in could help other children around the world.
The research study was extremely invaluable for our family… Other family members (where relevant) were also able to be tested removing considerable angst from the process of planning and managing their family…”

In the future
Further expansion of research in the field will allow doctors to increase early identification in survivors and family members.

As a result of this study, clinicians and researchers will be encouraged to consider underlying primary immunodeficiencies in children presenting with certain types of life-threatening infections. There is considerable long-term benefit for the involved families, who have received an answer to what has happened, and who were able to test siblings for the immunodeficiency. If further siblings will be diagnosed with the disease, then it will allow for preventative treatment to avoid life-threatening infections.

Professor Schlapbach will use the results of this pilot study to seek larger funding support in 2016 for an extended study on severe sepsis in children.

2012 Research Grant Project Improves Quality of Life Following ICU
Chief Investigator: Dr Jennifer Paratz

Sepsis, a severe inflammatory infection, frequently results in patients landing in intensive care. Sepsis can cause a number of ongoing problems even after the patient has recovered. Patients often complain of muscle weakness, difficulty calculating and thinking, insomnia, anxiety and difficult relationships with carers.

Results of a study funded by a Foundation Grant in 2012 and headed by Dr Jennifer Paratz of Griffith University were recently published in the journal Intensive Care Medicine 2015 and have overturned the established view that it is dangerous to exercise these patients until their infection has been cleared.

The study investigated whether early exercise in patients on admission to intensive care with sepsis improved their quality of life, muscle strength and inflammation. This early treatment consisted of electrical stimulation, passively moving the patient and the patient performing active exercises.

It was found that the early exercise improved the patient’s reports of physical function at six months post hospital discharge. The patients receiving early exercise also had less inflammation in their blood stream in the early stages and less weakness on discharge from intensive care. There were no adverse changes in parameters such as heart rate, oxygenation or blood pressure during exercise.

This Foundation-sponsored study demonstrates that it is safe and effective to institute early exercise in patients with sepsis even while critically ill, and this intervention can prevent a number of ongoing problems.

Promising Research Findings from 2013 Foundation Grant
Glucose malabsorption is common in the critically ill, and frequently compromises clinical outcome and functional recovery.

Mice in labThroughout 2014 Dr Richard Young and his team at the University of Adelaide used a mouse model to test the effectiveness of treatments (approved by the Animal Ethics Committee) to improve glucose absorption.

Their data revealed improved glucose handling and absorption in the mouse model, highlighting the potential clinical benefits of a form of treatment for critically ill patients, potentially reducing mortality.

Their findings were significant and leave the team well positioned to leverage these findings into a large scale multi-centre study across the Australian New Zealand Intensive Care Society Clinical Trials Group.

Research project updates

A randomised controlled study comparing the effect of two different anticoagulation regimens on filter life during Continuous Renal Replacement Therapy (CRRT) – The Heparin Citrate (THC) Study – (2010)
Funded $55,000

Principal Investigators: Dr David Gattas, Ms Dorrilyn Rajbhandari, Dr Celia Bradford and Prof Rinaldo Bellomo

Acute kidney failure is a common and clinically important problem for patients in the intensive care unit (ICU). Continuous renal replacement therapy (CRRT), a type of dialysis treatment, is used to support these patients. CRRT is also a very resource-intensive treatment to use safely and effectively in extremely unwell patients.

During CRRT, blood is circulated outside the body and then ‘cleaned’ by passing it through a complex series of tiny membranes held inside a filter). Unfortunately, this process also stimulates the blood to clot inside the filter. This clotting is preventable by also treating patients with blood thinners (anticoagulants). If the filter becomes clotted with blood, the entire apparatus attached to the CRRT machine must be replaced. This process interrupts CRRT for the patient, may result in blood loss, and consumes precious time and resources. Anticoagulants, on the other hand, pose a risk of bleeding elsewhere and they must therefore be used very carefully so that this risk is low but the CRRT treatment is still able to run smoothly.

This clinical trial will compare two different ways of anti-coagulating the CRRT filter to see which method is better at making the filter run smoothly without clotting. The two anticoagulants that we will use are citrate and heparin. Both will be delivered to the filter and blocked by other medications (calcium and protamine) so that the blood inside the filter is “thinned” but the blood inside the patient is not. The trial has the potential to improve the quality and safety of delivering CRRT to patients, decrease blood loss and conserve substantial ICU resources all at the same time.

Development of a new hyperosmolar solution for use in neurotrauma (2010)
Funded $20,000

Principal Investigators: A/Prof Hayden White, Prof Bala Venkatesh, Dr Teong Chuah

Traumatic brain injury (TBI) is one of the most common causes of morbidity and death in young people. Currently, much of the management is based on empirical evidence and small studies. A mainstay of treatment for brain swelling which accompanies TBI is to administer fluids which help to shrink the brain. The 2 commonest fluids used are mannitol (sugar based solution) and hypertonic saline (sodium chloride solution). These solutions work by drawing fluid out of the brain tissue, thus shrinking the brain and decreasing pressure. Both have significant side effects and neither provides nutrients to the brain tissue.

We intend to use a novel solution containing hypertonic saline and ketone bodies (fatty acids) as a means of treating TBI. Initially however, we need information about the metabolic effects of this sodium ketone solution. The purpose of this study is to investigate these effects before we can advance to human studies. Sodium ketone (NaBHB) solutions of varying concentrations will be administered to rats. The results of this experiment will provide new information regarding the time course and magnitude of changes in blood and CSF levels of ketones, glucose and acid/base. Once the metabolic effects have been confirmed, a head injury study will be designed. This will pave the way for a similar study in humans and if the results are confirmed in humans, may lead to the development of a new treatment for TBI.

MRI determination of renal blood flow during acute renal failure (2010)
Funded $15,000

Principal Investigators: Prof Rinaldo Bellomo, Dr J Prowle

Acute kidney injury (AKI) occurs in more than 30% of ICU patients and is severe (requires dialysis) in 5%. Its treatment with dialysis is invasive and costly. More than 50% of such patients die. Despite the importance of AKI, we have limited understanding of what causes it to happen. Traditionally, doctors have believed that decreased blood flow to the kidneys is responsible for it. However, this is doubtful. Experimental animals with severe infection can develop AKI despite very high kidney blood flow. Small studies in humans have suggested the same. However, the major problem with being able to know if decreased blood flow is really the cause of AKI in ICU is that measuring it safely and accurately has been very difficult and dangerous.

Recently, however, magnetic resonance technology has been developed that makes such measurement possible safely and accurately. This is called “cine phase-contrast MR scanning”. In our hospital, we have developed a combination of unique local expertise in AKI and cine phase-contrast MR imaging with a new software, which now makes such measurements possible. In this study we plan to measure kidney blood flow in critically ill patients with AKI and normal volunteers. This will give us new insights into the causes of kidney failure. With these results, we will then later go on to test potential treatments for AKI in the future using such monitoring of blood flow to guide them. This approach is going to represent a major change in patient monitoring and treatment and will be a “first in the world” investigation.

Pilot RCT of continuous beta-lactam infusion compared with intermittent dosing in critically ill patients (2010)
Funded $20,000

Principal Investigators: Prof Jeffrey Lipman, A/Prof Steve Webb, Dr Joel Dulhunty, Prof John Myburgh, Prof Rinaldo Bellomo, Prof David Paterson, Dr Jason Roberts, A/Prof Charles Gomersall

Beta-lactam antibiotics are commonly used to treat life-threatening infections in critically ill patients. As a class of antibiotics, beta-lactams are known as “time-dependent” antibiotics because they have their greatest effect when the antibiotic concentration in the blood remains above a critical level (dependent on the organism being treated) for the duration of the course. Continuousinfusion of beta-lactams has been shown to more consistently achieve these time-dependent pharmacodynamic endpoints than the standard practice of bolus dosing. However, the relatively small and often poorly designed randomised controlled trials to date have not shown improved clinical outcomes, such as resolution of infection or lower mortality. Better evidence is required from well-designed trials with adequate numbers of patients.

The purpose of this pilot randomised controlled trial of beta-lactam antibiotics delivered by continuous infusion compared to the standard bolus dosing regimen typically employed in critically ill patients. This pilot trial will be carried out by a multi-centre collaborative team which includes intensive care specialists, an infectious diseases physician and a clinical pharmacist with international recognition research into antibiotic therapy for severe and serious infections in critically ill patients.

PCT guided antibiotic decision making in ICU (2010)
Funded $109,000

Principal Investigators: A/Prof Yahya Shehabi, Dr Ian Seppelt, Dr Kanaka Sundaram Rachakonda, Dr Martin Sterba

Procalcitonin, a substance produced in the body, can be detected in the blood of people with an infection. Procalcitonin may be detected in the early stages of an infection, and levels increase when an infection becomes severe. It cannot be detected in a healthy person’s blood. Recently research studies have looked at using blood levels of procalcitonin to guide doctors in prescribing antibiotic treatment for patients with infections, and compared this with the normal way antibiotics are prescribed. The results have shown that patients who had their treatment guided by procalcitonin levels, were less likely to be prescribed ‘unnecessary’ antibiotics, and received antibiotics for a shorter time without it affecting their outcome. There have been no large research studies in Australia that evaluate using Procalcitonin levels to guide antibiotic treatment in intensive care.

Patients in this study will be randomly placed into one of two groups. One group will have their antibiotic treatment guided by their doctor based on their Procalcitonin levels, and the other group will have their antibiotic treatment guided by the treating doctor in the usual way. The purpose of this study is to investigate if Procalcitonin guided therapy improves the accuracy and suitability of antibiotic treatment in patients with presumed infection. Procalcitonin therapy may lead to a potential reduction in hospital acquired infections, including antibiotic resistant infections such as ‘golden staph’,resulting in a reduced length of stay in ICU and hospital. This will be investigated by comparing the two groups.

The efficacy, cost-effectiveness and environmental impact of Selective Decontamination of the Digestive tract in critically ill patients treated in Intensive Care unit – The SuDDICU study (2010)
Funded $40,000

Principal Investigators: Dr Ian Seppelt, Prof John Myburgh, Prof Simon Finfer, Prof Jeffrey Lipman, Prof David Paterson, Prof Brian Cuthbertson, Dr Jillian Francis, Dr Parisa Glass

Infections acquired in hospital are a major cause of illness and death for patients, and markedly increase health care costs. Intensive care patients are particularly susceptible to these infections and do badly if they acquire them. Simple interventions such as hand washing can reduce the frequency of these infections but are not enough alone to prevent them from occurring.

Selective Decontamination of the Digestive tract (SDD) is one lintervention which may reduce infection rates and deaths from these hospital acquired infections is. SDD involves the application of antibiotic pastes to the mouth, throat and stomach and a short course of antibiotics into a vein. The evidence supporting the use of SDD is strong with 28 randomised controlled studies in the medical literature. However, intensive care staff have been reluctant to use SDD, due to fears that perceived overuse of antibiotics will lead to infection with organisms such as MRSA and Clostridia Difficile, as well as concerns that Australia and New Zealand are a very different environment to the European countries where these studies were done.

The proposed research is designed to understand why SDD has not been fully implemented into Intensive Care practice in Australian and New Zealand. It may be that a definitive study is needed to determine the role of SDD in Australian practice, where infections with multi-resistant organisms are more common. But since there are so many factors that may affect clinicians’ decisions about whether to use this controversial therapy, we believe we need to first understand the reasons why clinicians have not implemented SDD to date. This study will define the barriers to implementation of this potentially live saving treatment and to identify what further information is required before a definitive large clinical trial can be undertaken.

Patient comfort and safety practices in ICU (2010)
Funded $10,000

Principal Investigators: Prof Doug Elliott, Prof L Aitken, Prof T Bucknall, Dr Ian Seppelt, Dr Steve Webb, Ms L Weisbrodt, Prof S McKinley

A Point Prevalence study is an important and systematic way of understanding what the current practice is for specific aspects of patient care across many health care organisations. For intensive care unit (ICU) patients, this snapshot of practice provides important information in planning and implementing new ways to manage this group of patients. The ANZICS Clinical Trials Group (CTG) in partnership with the George Institute of International Health has established a systematic Point Prevalence Program, where a number of point prevalence studies can be conducted simultaneously on two specified days each year.

The aim of this study is to determine the prevalence of specific practices related to sedation, analgesia and delirium for patients managed in ICUs across Australia and New Zealand. A range of options currently exist for the assessment and management of ICU patients in relation to sedation, analgesia and delirium. Determining the similarities and variations in practice across our two countries for these three common clinical activities will be an important element in understanding the practice base in relation to the research evidence. Findings will be used to provide baseline information for planning further intervention studies to improve the delivery of care and patient outcomes.

Compliance with Processes of Care in the Intensive Care Unit (2009)
Part funded for $15,000

Principal Investigators: Prof Doug Elliott, Prof L Aitken, Prof T Bucknall, Dr Ian Seppelt, Dr Steve Webb, Ms L Weisbrodt, Prof S McKinley

A Point Prevalence study is an important and systematic way of understanding what the current practice is for specific aspects of patient care across many health care organisations. For intensive care unit (ICU) patients, this snapshot of practice provides important information in planning and implementing new ways to manage this group of patients. The ANZICS Clinical Trials Group (CTG) in partnership with the George Institute of International Health has established a systematic Point Prevalence Program, where a number of point prevalence studies can be conducted simultaneously on two specified days each year.

The aim of this study is to determine the prevalence of specific practices related to sedation, analgesia and delirium for patients managed in ICUs across Australia and New Zealand. A range of options currently exist for the assessment and management of ICU patients in relation to sedation, analgesia and delirium. Determining the similarities and variations in practice across our two countries for these three common clinical activities will be an important element in understanding the practice base in relation to the research evidence. Findings will be used to provide baseline information for planning further intervention studies to improve the delivery of care and patient outcomes.

Economic Evaluation of Resuscitation in Sepsis (2009)
Partial funding of $100,000 – $50,000 in 2009 & $50,000 in 2010

Principal Investigators: Professor Rinaldo Bellomo, Ms Alisa Higgins, A/Prof A Harris, Dr Anthony Delaney, Dr Sandra L Peake, Dr Alistair Nichol

This research project will determine the cost effectiveness of a treatment known as “Early Goal Directed Therapy” compared to standard treatment for patients with severe sepsis. When a person has severe sepsis they have a severe infection and their body reacts to the infection, affecting important organs in the body such as the heart and lungs.

Standard treatment for sever sepsis in Australia involves treatment with fluids given into the vein and medications to support the blood pressure and keep the heart working properly.

Early goal directed therapy (EGDT) is the name given to a new way of giving these standard treatments by following a strict protocol. A study performed at one hospital in the United States has shown that this strict protocol works better than standard treatment. A large study of EGDT compared to standard treatment for severe sepsis (the ARISE study) will start in Australian and New Zealand hospitals in late 2008 to see if EGDT is better than standard treatment.

Intensive Care Treatment is expensive and consumes a significant portion of hospital resources. This study will collect this information on a group of patients enrolled in the ARISE study to determine the costs of EGDT and standard treatment. These costs will be combined with measures of effectiveness such as survival to determine how much it costs for each additional survivor with EGDT, and how much it costs for each life year gained with EGDT.

Last updated November 2008

The RELEVENT Study (2009)
Partial funding $8,000

Chief Investigators: Professor D J (Jamie) Cooper, Dr Andrew Westbrook, D Alistair Nichol, Dr Stuart M Lyon

Patients who are admitted to the intensive care unit with traumatic brain injury (TBI) are at a significant risk of developing blood clots in their legs because 1) they are immobile, 2) their blood clots more quickly (part of the stress response to TBI) and 3) they tend not to be prescribed anti-clotting medication as they are at risk of further bleeding in their brain. About 30% of blood clots in the lower leg extend into the thigh and if untreated half of these will travel to the lung. Of those clots that travel to the lung 25% cause death. There is no current Australian or international data concerning the rate of blood clots in the legs in TBI. We plan to assess all patients with TBI on admission to the intensive care unit for blood clots by performing an ultrasound of their legs and repeating this twice weekly until discharge.

We also plan to determine each participant’s propensity to develop clots: this shall be done by performing a blood test (1 teaspoon) called a thromboelastogram and these tests shall be done whenever a patient has an ultrasound.

The results of the study will provide currently unknown data regarding the rate of lower limb blood clots in this at risk population. This in turn will help in the design of a future clinical trial comparing different clot prevention strategies in these patients.

Last updated November 2008

Mapping ICU Liaison Nurse Services in Australia (2009)
Partial funding $8,000

Principal Investigators: Suzanne Eliott, Ms. Andrea Doric, A/Prof David Ernest, Prof Wendy Chaboyer

The Intensive Care Unit (ICU) Liaison Nurse (LN) assists in managing patients with complex care needs in hospitals and facilitates the smooth transition of patients admitted to and discharged from the ICU. A recent Victorian survey illustrated the diverse nature of ICU LN services with substantial variations in ICU LN services.

To date, there has been little uniformity in the roles or functions undertaken by these specialist nurses, which has made evaluation of the role difficult. In order to develop a clearer understanding of the role, the aim of this study is to document this diversity in practices of the ICU LN workforce. An electronic survey of all public and private hospitals within Australia and New Zealand will be undertaken.

The survey instrument includes demographic and clinical characteristics as well as questions about the LN service. Donabedian’s structure, process outcome framework was used in survey development. Structural questions relate to staffing levels, hours of service and other resources. Process elements include the types of services provided, key responsibilities and extended practices undertaken. Outcomes focus on the and key performances indicators used as markers of the quality of the ICU LN service. A preliminary study using the proposed survey has been completed in Victoria.

The results of this project will identify the scope of practice of this specialist group of nurses. It will highlight the extent to which the service contributes to improved patient care and will provide an essential framework for the future development and evaluation of the ICU LN role.

Last updated November 2008

An Audit of the Time and Costs involved in the Ethical and Governance Review Process of a Mulit-Centre Clinical Trial in Australia and New Zealand – TAME Study (Time and Money Evaluation) – (2009)
Partial funding $3,000

Principal Investigators: Belinda Howe, Dorrilyn Rajbhandari, Ms Patricia Williams

Traditionally, the ethical review process has involved large, multi-centred studies being submitted for ethics approval locally at each individual site. This process has engendered criticism from sponsors, industry and researchers in regards to the issues of time delays, high financial cost and duplication of effort.

To address these issues a single ethical review process has recently been introduced in New South Wales and a national system will follow. New Zealand introduced a regional ethics approval process in 2004 due to similar issues. The single ethical review system, as introduced in NSW and New Zealand, has yet to demonstrate any savings on cost or reduction in time taken to complete the ethical and essential document review process.

This study seeks to explore and compare the issues of the time taken to gain site approval, financial cost and research staff time required to prepare and support the ethical review process for a multi-centre clinical trial in Australia and New Zealand. The sites utilizing a single ethical review system will be compared to other sites, which submit to locally.

The study results have the potential to highlight the performance of the new single ethical review system compared to the traditional ethical review process. It will determine, in a real situation, if the new system is meeting its expectations and if any shortcomings are apparent. This comparison may display the advantages of the single ethical review process and expedite its national implementation or may highlight deficiencies which need to be addressed before national implementation.

Last updated November 2008

Impact of the Intensive Care Discharge Process on Patient Outcomes (2009)
Partial funding $50,000

Principal Investigators: A/Prof. John Santamaria, Dr David Pilcher, Dr Graeme J Duke, Prof D James Cooper

The aim of our study is to identify the factors associated with mortality after discharge from intensive care and then develop methods to reduce preventable deaths.

Over 5,000 patients discharged from ICU in Australasia each year will die before hospital discharge and a similar number will be readmitted to ICU. International and local studies have suggested that survival is not only linked to the severity of illness but also to processes of care surrounding discharge from ICU. For example, patients discharged after hours and those requiring re-admission to ICU have less chance of leaving hospital alive. The care on wards and emergency services within the hospital may also contribute to outcomes. Unfortunately, most of these studies used information within intensive care databases which contain little or no information about the condition of patients around the time of ICU discharge.

Our study has been designed to examine a range of factors at ICU discharge including the nature of disease, the severity of illness, whether the patient has untreatable conditions, the nature of handover of information to ward staff, and the presence of emergency or follow-up ICU teams who continue to manage patients in general wards. We will follow a large number of patients (about 10,000) after discharge from ICU. However this could be achieved within 2-3 months of study onset.

With the information obtained, we hope later to implement evidenced-based solutions to ensure that more ICU patients leave hospital alive and in a shorter duration of time.

Last updated November 2008

The effect of varying arterial carbon dioxide concentrations (PaCo2) within the normocapnic range on brain tissue oxygenation and microdialysis markers of cell injury in severe traumatic brain injury (2009)
Partial funding $10,000

Principal Investigators: Professor David James Cooper, Prof Jeffrey Rosenfeld, Dr Ruwan Wijemunige

Each year, close to 5000 people in Australia suffer a severe traumatic brain injury (TBI). The traumatized brain is very vulnerable to further injury in the first few days after the injury, and studies have showed that despite current best practice, approximately 50% of patients with severe TBI suffer a secondary injury during their stay in ICU. These secondary injuries occur due to two main reasons. The first reason is our inability to continually monitor the function of the brain leaving the unconscious patient vulnerable to “silent” injuries occurring to the brain despite being in intensive care. The second reason is the difficulty in optimizing the metabolic requirements of the brain (such as oxygen and blood).

One of the factors that affects the metabolism of the brain is the level of carbon dioxide in the blood. High levels of carbon dioxide in the blood lead to brain swelling and decreased blood supply to the brain tissue. Therefore, patients with TBI had their carbon dioxide levels kept very low to decrease brain swelling. However, 10 years ago it was demonstrated that low carbon dioxide levels lead to constriction of the blood vessels in the brain and therefore cause long term damage to the brain.

Now patients’ carbon dioxide levels are kept in a range that is neither high nor low. However it is unclear whether there is an optimum level of carbon dioxide in the blood which maximizes the blood supply to the brain.

This study involves using technology to directly measure brain metabolism in 30 patients with severe TBI as there carbon dioxide level varies within this “normal” range. This will help us determine if there is an optimum carbon dioxide level for each patient and whether this optimal level changes as the medical condition of the patient changes. This will also help us develop experience in directly monitoring brain metabolism (which is currently not done routinely) and tailoring treatment for each patient based on the individual characteristics of their brain.

Last updated November 2008

The ANZICS Clinical Trials Group Point Prevalence Program (2009)
Partial funding of $86,400 over two years

Principal Investigators: Dr Ian Seppelt, Prof John Myburgh, Prof DJ (Jamie) Cooper, Prof Simon R Finfer, Ms Rhiannon Elliott

When commencing any research program the researchers need information about current practice, before they can make any intelligent attempt at designing research that might improve on current practice. Colloquially, this means asking ‘what do we do now?’ [perhaps also ‘what do we think we do now?’] before moving on to ‘what should we do next?’

A Point Prevalence study is a systematic snapshot of current practice. It is an observational study, without any intervention, and involves collecting data on topics of interest, in patients in multiple Intensive Care Units, on a specific day or days. It provides no information on outcomes, but provides very important information on how common a problem is, and what is currently being done to manage that problem. The ANZICS Clinical Trials Group has done many point prevalence studies in the past which have provided crucial information, but each of these has been a stand alone study designed anew each time.

The Clinical Trials Group in partnership with the George Institute of International Health wishes to establish a systematic Point Prevalence Program, where multiple point prevalence studies will be done simultaneously, on two specified days each year. The mechanics of running a point prevalence study will be streamlined for researchers, while duplication of effort is avoided.

As a piece of research infrastructure the program will also foster junior researchers and encourage Intensive Care Units which have not previously participated in intensive care research, and will provide data necessary for the design of many future research projects.

Last updated November 2008

Haemodynamic Effects of Paracetamol (2009)
Partial funding $15,000

Principal Investigators: Dr Ian Seppelt, Prof John Myburgh, Prof DJ (Jamie) Cooper, Prof Simon R Finfer, Ms Rhiannon Elliott

When commencing any research program the researchers need information about current practice, before they can make any intelligent attempt at designing research that might improve on current practice. Colloquially, this means asking ‘what do we do now?’ [perhaps also ‘what do we think we do now?’] before moving on to ‘what should we do next?’

A Point Prevalence study is a systematic snapshot of current practice. It is an observational study, without any intervention, and involves collecting data on topics of interest, in patients in multiple Intensive Care Units, on a specific day or days. It provides no information on outcomes, but provides very important information on how common a problem is, and what is currently being done to manage that problem. The ANZICS Clinical Trials Group has done many point prevalence studies in the past which have provided crucial information, but each of these has been a stand alone study designed anew each time.

The Clinical Trials Group in partnership with the George Institute of International Health wishes to establish a systematic Point Prevalence Program, where multiple point prevalence studies will be done simultaneously, on two specified days each year. The mechanics of running a point prevalence study will be streamlined for researchers, while duplication of effort is avoided.

As a piece of research infrastructure the program will also foster junior researchers and encourage Intensive Care Units which have not previously participated in intensive care research, and will provide data necessary for the design of many future research projects.

Last updated November 2008

Bicarbonate in cardiac surgery (2008)
Fully funded for $53,315

Principal Investigators: Prof Rinaldo Bellomo, Dr Frank van Haren, Dr Shay McGuinness

Background
Injury to the kidney with loss of function is common after cardiac surgery, especially in patients with previous kidney disease, old age, diabetes and others with the need for complex open heart surgery.  It is associated with increased ICU and hospital length of stay and an increased risk of death.  No reliable treatment has yet been found to reduce the incidence and severity of this secondary kidney injury.

Although the mechanisms involved in kidney injury after cardiac surgery are not fully understood, some evidence suggests that release of free haemoglobin from red blood cells may be a contributing factor. Experimental studies suggest kidney toxicity and free haemoglobin can by reduced by giving intravenous bicarbonate.  Recently, a multiple blind, controlled, randomised pilot study of 100 patients demonstrated that intravenous administration of bicarbonate decreased kidney injury to these patients.

The Study
Based on the pilot results, this study plans to enrol 470 high risk patients having open heart surgery in four hospitals to further evaluate the role of intravenous bicarbonate in reducing acute kidney injury following cardiac surgery. If the results of the pilot are confirmed, given the low cost of the intervention and the importance of the complication, bicarbonate infusion may be tested in a much larger trial.  Identifying an effective treatment has important implications for the treatment for more than a million patients every year world wide.

Outcome
A positive outcome from this project will provide strong evidence that bicarbonate protects the kidney during cardiac surgery.

Last updated October 2008

Heparin in severe sepsis: IL-6 as a marker of efficiency (2008)
Fully funded for $6,134

Principal Investigators: Dr Alistair Nichol, Dr Megan Robertson, Prof Jamie Cooper, Dr Jeffrey John Presneill, Dr Steven Webb

Background
In Australia and New Zealand, around five thousand patients are admitted to intensive care every year with severe infection (sepsis). Despite aggressive treatment, around 35% of these patients do not survive.

Most patients admitted to ICU receive heparin injections to prevent the formation of blood clots in their leg veins from decreased physical activity. The clots are dangerous as they can travel to the lungs and cause death. As technology has advanced, more purified forms of heparin have replaced the traditionally used unfractionated heparin (low and ultra low molecular weight heparins) because of reported increased effectiveness in preventing blood clots.

Recent studies have suggested that unfractionated heparin may have beneficial therapeutic effects in infection in addition to its action to prevent blood clots. These immune-active effects are related to molecular size and therefore may be lost with the current trend to use purified heparin forms.

The Study
A pilot study to investigate whether unfractionated heparin is beneficial for patients with severe sepsis is currently underway. This additional grant supports the Intensive Care Foundation’s grant last year and allows the researchers to measure sensitive blood markers of the inflammatory response to sepsis to confirm whether unfractionated heparin use is of additional benefit.

If unfractionated heparin is shown to be beneficial to these patients, this would be a simple, cheap and widely applicable additional treatment for severe infection that could save lives world wide, both in first and third world countries.

Outcome
Due to inadequate recruitment this project was stopped early. The findings from this project have encouraged a rethink of the best strategy to determine if Heparin is a useful treatment in patients with severe sepsis.

The project investigators are currently working on a new distinct design of a trial that will be feasible, safe and will determine if Heparin is a useful treatment in severe sepsis.

While this project will not proceed in its current form, it is hoped that these findings will lead to a world class trial which will determine the efficacy of Heparin. This larger trial will inform clinical practice.

Last updated October 2008

Optimal ventilation (PHARLAP) in acute lung injury (2008)
Fully funded for $30,699

Principal Investigators:  Prof.  D .  James (Jamie) Cooper, Dr Alistair Nichol, Dr Andrew Davies, A/Prof David Tuxen, Ms Carol Hodgson

Background
This randomised, controlled trial will compare a new mechanical ventilation strategy called Permissive Hypercapnia and Alveolar Recruitment with Limited Airway Pressures (PHARLAP) with current best practice ventilation in patients with an inflammatory response following acute lung injury.

Acute lung injury and the more severe acute respiratory distress syndrome are inflammatory conditions of the lungs which result in a mortality of 30 to 40%.  Patients with acute lung injury are at high risk for ventilator-associated lung injury which in turn contributes to the high mortality.  In ventilator associated lung injury, the lungs have been demonstrated to act like an ‘engine’ of inflammation, increasing blood levels of chemical mediators which cause inflammation and even failure in other organs in the body or death.

Reducing the size of each breath delivered by the ventilator and an occasional sustained deep breath have been used to try to prevent the damaging effects of lung injury on patients.  These protective strategies frequently result in higher than normal levels of carbon dioxide, a gas produced by normal tissue and organs which we exhale.  These higher levels of carbon dioxide than normal may actually be protective to the body.

The PHARLAP ventilation strategies, which have all been individually shown to benefit patients, when packaged together could potentially provide superior protection and benefit.

The Study
Beginning in February 2008, PHARLAP is a mechanical ventilation trial which aims to determine the ideal method of assisting respiration in critically ill patients with acute lung injury.

To date the study has recruited 14 of the anticipated 30 patients required. On completion of the study, blood sample taken from these patients will be analysed to see if the new method of ventilation reduces the inflammatory response.

Outcome
It is hoped that this study will provide the key evidence required proceeding to a future larger trial in Australia and New Zealand which will show that PHARLAP ventilation improves survival.

Last updated October 2008

Nutritional therapy of severe acute pancreatitis (2008)
Funded for $24,600

Principal Investigators: Dr Andrew Davies, Mrs Suzanne S Morrison, Dr James (Jamie) Cooper, Ms Merrilyn Banks

Background
Pancreatitis is an inflammatory disease of the pancreas which ranges in severity from mild to lethal.  At least six hundred patients a year are admitted to ICUs in Australasia with pancreatitis.  These patients often have a long and complicated hospitalisation and usually need to stay in ICU twice as long as other patients.  At least one in thirteen will die from this condition.

It was previously thought that resting the digestive system by fasting was the best treatment for these patients. Nutrition was typically provided directly into the blood stream via an intravenous drip until the patient improved. Studies have shown that providing nutrition into the digestive system is better than via intravenous methods as it reduces complications, length of stay and possibly even organ failure.  This has now led to the view that nutrition is now a therapy which should be an important component of the management strategy of patients with acute pancreatitis.

We currently do not know how nutrition is provided for the treatment of patients with pancreatitis in Australasia.

The Study
This study will provide a baseline of current standard treatment of patients with severe acute pancreatitis in Australia and New Zealand and allow for world comparison. It will also provide information to plan a future interventional trial to investigate how nutrition should be provided to these patients.

Outcome
The six month recruitment period for this project has finished. The data is currently being collected and entered into the database. A data analysis plan has been formulated. The data cleaning and subsequent analysis will proceed in due course.

The objectives of this study are to:

  • Describe the clinical and epidemiological features of severe acute pancreatitis within Australasia
  • Describe current nutritional management in Australasia of patients with severe acute pancreatitis
  • Measure patient outcomes, including all-cause in-hospital mortality, duration of mechanical ventilation, duration of intensive care (ICU) stay, and duration of hospital stay
  • Benchmark Australasian nutritional management practices against local and international guidelines
  • Assess the feasibility of a multicentre, randomized, controlled trial to investigate nasogastric feeding vs. nasojejunal feeding in patients with severe acute pancreatitis

It is envisaged that by achieving these aims this study will demonstrate the need to improve nutritional management of patients with severe acute pancreatitis within Australasia. The data obtained will allow clinicians to benchmark their sites performance with regard to international guidelines; and it is hoped this will facilitate the decrease in complication rates and improve patient outcomes.

Last updated October 2008

Reducing CSF sampling frequency to minimise ventriculitis (2008)
Part funded for $30,000

Principal Investigators: A/Prof Gavin Leslie, A/Prof GJ Dobb, Ms TA Williams, Prof PV van Heerden, Ms BL Roberts

Background
Increased pressure in the skull following a severe head injury or other non traumatic brain injuries can cause further damage to the brain.  This pressure can be reduced by draining excess fluid out of the skull through a catheter.  Because of the invasive nature of this treatment there is an increased risk of infection (ventriculitis).  Up to 45% of intensive care patients with these drainage catheters have been reported to get ventriculitis, which can become life-threatening.

Antibiotic treatment needs to commence as soon as the infection starts to give any chance of successful treatment. Samples of the fluid (cerebro-spinal fluid) are routinely taken from the drainage system to test for infection. However there is no consensus on how often this should be done as sampling itself may present an infection risk.

The Study
This study aims to assess whether decreasing the frequency of routine testing for ventriculitis to 3rd daily can reduce the incidence of the infection without compromising surveillance.

Outcome
It is hoped that by reducing the number of times fluid is sampled from around the brain in patients with an Extra Ventricular Drain (EVD) in place there will be a reduction in the inflammation and infection rate, which will reduce costs to patients and the community for sampling equipment and antibiotic use, length of stay and potential serious brain injury following the infection of CSF.

Last updated October 2008

Western Australia Outcome Obtained by Linkage (2008)
Fully funded for $103,280

Principal Investigators: Clinical Associate Professor Steve Webb, Prof Judith C Finn, Dr David Blythe, Dr Mary Pinder, Clinical Associate Professor Geoffrey J Dobb, Associate Professor Ian G Jacobs, Prof Lyle J Palmer,

Background
Large population based research studies, such as the Framingham Study in the United States, have played a pivotal role in improving medical knowledge. Intensive care represents a vital component of the health system serving to save the lives of patients with many different forms of life-threatening critical illness. About 125 000 Australians are treated in an ICU each year at a cost of about 1 billion dollars. Despite the importance of intensive care there have been no large population based research studies of ICU patients- either in Australia and New Zealand or elsewhere in the world.

The Study
Such a study would have the potential to substantially improve the understanding of all aspects of critical illness. Western Australia possesses unique advantages for the conduct of this type of research study. However, these studies are expensive and require complex planning.

Outcome
The purpose of this grant is to conduct a pilot study to determine the feasibility of conducting a large population based research study that would aim to recruit all ICU patients in WA on an indefinite basis. The purpose of this feasibility project is to provide a demonstration of large scale accurate data collection and to evaluate rates of recruitment in a single ICU in WA. This data is essential for the planning and funding of the proposed large population based research study.

Last updated October 2008

Aminophylline in Severe Bronchiolitis (2007)

Chief Investigator: Barry Wilkins

Background
Bronchiolitis is a common infection of the bronchioles, the tiny airways that lead to the lungs.The airways swell and fill with mucus making it difficult to breathe, especially for young children. Yearly around 300 children with severe bronchiolitis are admitted to Paediatric Intensive Care Units in Australia and New Zealand. These children experience significant breathing difficulty and around 60 percent are ill enough to need help with breathing through a breathing machine (mechanical ventilation).The normal treatment is to support their breathing and give nutrition and fluids until recovery.

The Study
This research project aims to see if aminophylline, commonly used to treat asthma, chronic bronchitis, emphysema and other lung diseases – can be also used as a treatment for children with bronchiolitis. The researchers will compare the duration of mechanical ventilation, length of stay in Intensive Care and other variables of two groups of children.One group will receive the standard treatment for bronchiolitis and the other group of children will receive standard treatment and aminophylline.

This study had recruited only a small proportion of the required number of patients when glass ampoules of saline (needed for the control group) were removed from the market, so the trial had to be suspended. The project will be starting again in August 2008 as arrangements have been made to have the ampoules especially made for the trial.

Outcome
Benefits of the trail to date have only been indirect with the main one being that it is one of the first controlled trials conducted by the ANZICS Paediatric Study Group.

If it is proven that aminophylline reduces the proportion and duration of patients being ventilated, there could be a saving of 40 hours of intensive care per patient, saving $1-2 million of health service resources per year Australia and New Zealand wide.  This study is due to commence.

Last updated October 2008

The Australasian Resuscitation is Sepsis Evaluation (ARISE) (2007)

Chief Investigator: Sandra Peake

Background
Each year approximately 13,000 people in Australia and New Zealand develop sepsis. Sadly, many of them will end up critically ill in ICU and approximately 4,000 each year don’t survive. The effective management of sepsis remains one of the most important areas of intensive care research.

A study conducted in one hospital in the USA has suggested that delivering targeted interventions based on a specific protocol to manage severe sepsis very early during the patient’s hospital admission may significantly reduce the number of people who die from the condition. However, it is not known whether this type of protocol-driven care would have the same effect, and be appropriate for use, in Australian and New Zealand.

The Study
The ARISE Study is an observational study designed to provide essential information about the current management of severe sepsis in Emergency Departments (EDs) across Australia and New Zealand. The information collected during the ARISE Study will help the investigators and the ANZICS Clinical Trials Group design a large trial to examine the best way to treat people with sepsis in the ED before they require admission to ICU.

This is an ANZICS Clinical Trials Group endorsed study.

Outcome
The ARISE Study was conducted between October 2006 – January 2007. A total of 288 patients were studied during this time across 32 different hospitals giving a thorough overview of sepsis treatment practices in Australasia. Results have been collated and a large trial investigating protocol-driven management of severe sepsis has been designed based on the results of this important study.

Last updated September 2007

Heparin in Severe Sepsis (2007)

Chief Investigator: Megan Robertson

Background
In Australia and New Zealand, around 5000 patients are admitted to Intensive Care every year with severe infection (sepsis).Despite aggressive treatment, around 35% of these patients do not survive, making severe sepsis the most common non-cardiac cause of death in intensive care patients.Even surviving patients often suffer a period of multiple organ failure.

Most patients admitted to ICU receive heparin injections to prevent the formation of blood clots in their leg veins which can travel to the lungs.As technology has advanced, more purified forms of heparin (low and ultra low molecular weight heparins) have replaced the traditionally used unfractionated heparin because of reported increased effectiveness in preventing blood clots.

Recent studies have suggested that unfractionated heparin may have beneficial therapeutic effects in infection in addition to its action to prevent blood clots. These immune-active effects are related to molecular size and therefore may be lost with the current trend to use purified heparin forms.

The Study
This research will be a pilot study to assess the feasibility of conducting a large multicentre trial to investigate whether unfractionated heparin is beneficial to patients with severe sepsis. If unfractionated heparin is shown to be beneficial to these patients, this would be a simple, cheap and widely applicable additional treatment for severe infection that could save lives world wide, both in first and third world countries.

This is an ANZICS Clinical Trials Group endorsed study.

Outcome
The Heparin in Severe Sepsis Pilot Study is due to commence in September 2007

Last updated September 2007