A Randomised, Placebo-controlled Trial Of Erythropoietin In ICU Patients With Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$1,950,735.00
Summary
Patients who suffer a moderate or severe head injury (traumatic brain injury) have a 50% chance of having a long term neurological disability or death. Erythropoietin is a medication which encourages red blood cell formation but its other beneficial effects are likely to improve outcomes after traumatic brain injury. This study will examine the safety and effects of erythropoietin on long term neurological function in patients who have suffered a traumatic brain injury.
Oesophageal, Gastric And Small Intestinal Motility In Critical Illness
Funder
National Health and Medical Research Council
Funding Amount
$494,250.00
Summary
A major concern in critically ill patients is the provision of adequate nutrition to facilitate recovery from devastating insults. Abnormal contractions of the oesophagus, stomach and small intestine occur commonly in critically ill patients. These may prevent effective feeding of patients at a time when they are especially vulnerable to malnutrition and also result in major complications such as pneumonia, septicaemia and gastrointestinal haemorrhage. The applicants, with the support of the NH ....A major concern in critically ill patients is the provision of adequate nutrition to facilitate recovery from devastating insults. Abnormal contractions of the oesophagus, stomach and small intestine occur commonly in critically ill patients. These may prevent effective feeding of patients at a time when they are especially vulnerable to malnutrition and also result in major complications such as pneumonia, septicaemia and gastrointestinal haemorrhage. The applicants, with the support of the NH and MRC, have had a longstanding interest in motility disorders of the gut and have made important contributions to knowledge about both the causes and treatments of the disturbances that occur in the oesophaus, stomach and small intestine. In the previous grant (207753) these studies have provided the most comprehensive studies to date of the motor abnormalities associated with gut dysfunction in critical illness which have important implications for treatment. The applicants now seek to continue their work by investigating the mechanisms underlying these motor abnormalities and the impact of therapeutic strategies designed to enhance delivery of nutrition to critically ill patients.Read moreRead less
Impact Of Gastrointestinal Dysmotility On Enteral Nutrition In The Critically Ill
Funder
National Health and Medical Research Council
Funding Amount
$533,792.00
Summary
Critically ill patients require nutrition for optimum recovery. Ideally, this is provided via the gut, but oesophageal reflux, slow gastric emptying and small intestinal dysfunction frequently prevent adequate delivery of nutrients to these patients, exposing them to complications such as pneumonia and gastrointestinal bleeding. The work performed by the applicants will improve the ability of doctors in the Intensive Care Unit to feed patients and prevent the development of such complications.
Does Increased Non-Linear Behavior Caused By Dynamic Variables Increase Ventilatory-Induced Lung Injury (VILI)?
Funder
National Health and Medical Research Council
Funding Amount
$109,625.00
Summary
Acute lung injury (ALI) is precipitated by a variety of different insults, either directly to the lung or elsewhere to the body. Approximately 50% of the patients die. ALI is characterized by an increase in the leakiness of the barrier that normally separates the blood from the airspaces. The fluid which consequently floods the airspaces not only makes it difficult for patients to adequately obtain oxygen, but also dramatically increases the work of breathing by changing the surface forces withi ....Acute lung injury (ALI) is precipitated by a variety of different insults, either directly to the lung or elsewhere to the body. Approximately 50% of the patients die. ALI is characterized by an increase in the leakiness of the barrier that normally separates the blood from the airspaces. The fluid which consequently floods the airspaces not only makes it difficult for patients to adequately obtain oxygen, but also dramatically increases the work of breathing by changing the surface forces within the lungs. As a result, the patients must be mechanically ventilated. However, the very act of using a positive pressure to inflate the lungs often creates further damage, either through repeated opening and closing of collapse tissue or through its over distension. Ventilatory-induced lung injury (VILI), in itself is estimated to contribute to ~30% of the mortality. The best way shown to minimize VILI is through the use of small programmed breaths so as not to overinflate the lungs while still allowing adequate gas exchanges, superimposed upon a background pressure, in order to pre-inflate the lungs and prevent them from repeatedly collapsing. A remaining problem is that just as a rubber band changes its elasticity as it is stretched, so too the lung changes its mechanical properties during distension. Moreover, the lung is considerably more complex since different regions have different elasticities, which change differentially as air flows in and out of them. Airflow in turn depends on regional differences in the location, size, and number of conducting airways. Indeed, we have recently shown for the first time that dynamic changes in lung mechanics may contribute to VILI in patients, despite the use of safe ventilation modalities. This application proposes to examine the extent to which dynamic changes in lung mechanic contribute to VILI in an animal model, as a prelude to more costly, large scale clinical trials aimed at improving mortality.Read moreRead less
Multicentre, Open Label, Randomised, Controlled Trial Of Severe ARF Management With An Augmented Vs Normal CRRT Regimen
Funder
National Health and Medical Research Council
Funding Amount
$1,879,125.00
Summary
Sudden serious kidney failure is a major problem that frequently occurs in patients who are in Intensive Care. For these patients, their chances of survival are significantly decreased. In Australia sudden serious kidney failure is usually treated with continuous kidney support by a kidney machine. A recent study found that by using greater than normal levels of kidney support, that is , running larger volumes of fluid through the kidney machine, patients in Intensive Care Units (ICU's) may be l ....Sudden serious kidney failure is a major problem that frequently occurs in patients who are in Intensive Care. For these patients, their chances of survival are significantly decreased. In Australia sudden serious kidney failure is usually treated with continuous kidney support by a kidney machine. A recent study found that by using greater than normal levels of kidney support, that is , running larger volumes of fluid through the kidney machine, patients in Intensive Care Units (ICU's) may be less likely to die from their sudden serious kidney failure. Despite these positive findings, this high level of kidney support is not commonly used in Australian ICU's. Clearly though, if greater than normal levels of kidney support do increase the chances that individuals will live, then patients should be receiving this treatment. The Australia and New Zealand Intensive Care Society, in conjunction with The George Institute for International Health, propose to conduct a new study involving 1500 patients from ICU's throughout Australia, who require continuous kidney support due to sudden serious kidney failure. These patients will be randomly assigned so that half receive the normally used levels of kidney support and the other half receive kidney support at greater than normal levels. Patients will then be followed for three months to compare the proportions of patients who die in each group. All other outcomes and serious side effects will be closely monitored throughout the study. The results will be available to the public within four years of starting the study, and these are likely to influence the treatment of patients admitted to ICU's with sudden serious kidney failure, not only in Australia but also worldwide.Read moreRead less
The Australasian Resuscitation In Sepsis Evaluation - Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$2,424,807.00
Summary
Patients with severe infections often present to Emergency Departments and early treatment with particular fluids, blood transfusions and stimulants, may improve survival rates. To determine whether early treatment is safe and effective in reducing deaths, the Australian and New Zealand Intensive Care Society Clinical Trials Group, in conjunction with the Australasian College of Emergency Medicine, plan to perform a large trial of early goal directed therapy in patients with severe infections.
Management Of Burn Injury: Fluid Dynamics And Antibiotic Pharmacokinetics
Funder
National Health and Medical Research Council
Funding Amount
$342,375.00
Summary
It is well known that major burns, as well as being relatively common injuries, are notoriously difficult to manage. Patients exhibit significant variability due to a combination of anatomic, physiologic, hormonal and immunologic alterations occurring both at the wound site and, more importantly, in other body compartments and vital organ systems. Skin burn injury results in the release of multiple inflammatory mediators in addition to significant fluid loss. The distribution of inflammatory med ....It is well known that major burns, as well as being relatively common injuries, are notoriously difficult to manage. Patients exhibit significant variability due to a combination of anatomic, physiologic, hormonal and immunologic alterations occurring both at the wound site and, more importantly, in other body compartments and vital organ systems. Skin burn injury results in the release of multiple inflammatory mediators in addition to significant fluid loss. The distribution of inflammatory mediators and wound bacteria to central organs can cause complex physiological changes that may lead to multiple organ failure, with serious infections occurring in around 50% of patients with serious burns. Antibiotic distribution kinetics, such as bioavailability, clearance, volume of distribution, elimination half-life and unbound fraction in plasma can be significantly altered in burn patients. Without detailed knowledge of changes and relationships between factors such as wound pH, tissue oxygenation, protein concentrations of fluid leaked from the local wound microvasculature, tissue binding, oedema and changes in burned and non-burned tissue induced by resuscitation therapies, the optimisation of both local and systemic infection contriol therapies can hardly be expected to advance. This project aims to determine how changes the physiology of burn patients, in particular in the burn wound environment, affect antibiotic penetration and distribution into tissues. We also believe that these changes will vary between patients and are aiming to determine whether certain parameters can be used to give an indication of the best antibiotic dosing regimens for individual patients.Read moreRead less
A Phase II Randomised Controlled Trial Of Atorvastatin Therapy In Intensive Care Patients With Severe Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$622,148.00
Summary
Infections are common in patients in the intensive care unit and produce inflammation that may spread throughout the body. Despite improved therapies, when infections cause failure of the body's vital organs, up to 40% of patients may die. The medication atorvastatin and other statins have been used for many years to treat and prevent conditions such as heart attack and stroke. They act primarily by reducing cholesterol production. In addition, they also modify inflammation and the immune system ....Infections are common in patients in the intensive care unit and produce inflammation that may spread throughout the body. Despite improved therapies, when infections cause failure of the body's vital organs, up to 40% of patients may die. The medication atorvastatin and other statins have been used for many years to treat and prevent conditions such as heart attack and stroke. They act primarily by reducing cholesterol production. In addition, they also modify inflammation and the immune system which may make them a useful treatment for patients with established infections. Although the statin drugs are usually safe, rare side effects may affect muscle and the liver. Because of concerns about increased risk of side effects it is currently recommended that statins should be stopped when patients become unwell. However, a number of studies have suggested that patients on statins for heart disease are less likely to develop infections and that their infections are less likely to be severe or result in death. Other studies have suggested that stopping statins in patients that present with infections (as suggested by current guidelines), may worsen infection outcomes. However, these studies have not been detailed enough to exclude all factors affecting outcome, such as patient age, severity of the infection, and the presence of other diseases. We plan to perform a study to assess the effect of atorvastatin on the outcome of infections in the intensive care unit. We will study 250 patients presenting with severe infections. We will randomly assign patients to receive either atorvastatin or placebo and monitor the effect on signs of inflammation and levels of life support. Outcomes and side effects will be carefully monitored. The study will help us decide whether to perform a larger study to determine if atorvastatin can reduce the risk of dying from serious infections.Read moreRead less
A Randomised Controlled Trial Of Normoglycaemia Versus Conventional Glycaemic Control In Intensive Care Unit Patients.
Funder
National Health and Medical Research Council
Funding Amount
$1,773,507.00
Summary
The concentration of sugar in the blood is often increased in patients in intensive care and patients with increased blood sugar levels are more likely to die. A recent study performed in a Belgian intensive care unit found that using high doses of insulin to lower blood sugars levels to normal increased the number of patients who survived. The chance of surviving to leave hospital was increased from 89% to 93%. Whilst the result is very encouraging, Intensive Care Specialists in Australia are u ....The concentration of sugar in the blood is often increased in patients in intensive care and patients with increased blood sugar levels are more likely to die. A recent study performed in a Belgian intensive care unit found that using high doses of insulin to lower blood sugars levels to normal increased the number of patients who survived. The chance of surviving to leave hospital was increased from 89% to 93%. Whilst the result is very encouraging, Intensive Care Specialists in Australia are unsure if the treatment would work in their patients because of differences in the types of patients found in intensive care units in Australia, and because of other treatment given to the patients in the Belgian study. In particular the doctors in the Belgian unit studied only patients who had had operations and gave large amounts of intravenous sugar to their patients. This is not normally done in Australian Intensive Care Units and the safety of giving high dose insulin to patients not receiving large amounts of intravenous sugar is not known. This is of particular interest as reducing blood glucose to abnormally low levels can cause serious side effects and even result in permanent brain damage. The Australian and New Zealand Intensive Care Society proposes to conduct a new study involving 4,000 patients from intensive care units in Australia and New Zealand and will study all patients regardless of whether or not they have had an operation. These patients will be randomly assigned to receive insulin to control blood sugar levels to normal or to slightly above normal levels as has been tradition in intensive care units around the world. Outcome and serious side effects will be closely monitored. The results will be available within three years of starting the study, and these are likely to influence the treatment of the majority of patients admitted to intensive care units both in Australia and worldwide.Read moreRead less
Upper Gastrointestinal Motor And Absorptive Function In Critically Ill Patients
Funder
National Health and Medical Research Council
Funding Amount
$260,760.00
Summary
A major concern in critically ill patients is the provision of adequate nutrition to facilitate recovery from devastating metabolic insults. Abnormal contractions of the oesophagus, stomach and small intestine appear to be common in critically ill patients. These may prevent effective feeding of patients at a time when they are especially vulnerable to malnutrition and also result in major complications such as pneumonia, septicaemia and gastrointestinal haemorrhage. However little is known abou ....A major concern in critically ill patients is the provision of adequate nutrition to facilitate recovery from devastating metabolic insults. Abnormal contractions of the oesophagus, stomach and small intestine appear to be common in critically ill patients. These may prevent effective feeding of patients at a time when they are especially vulnerable to malnutrition and also result in major complications such as pneumonia, septicaemia and gastrointestinal haemorrhage. However little is known about the reasons underlying these dysfunctions. The applicants, with ongoing support from the NH and MRC have had a longstanding interest in motility disorders of the gut and have made important contributions to knowledge about both the causes and treatments of these conditions. These contributions have been underpinned by pioneering the development of new methodologies to examine gut function. In collaboration with the intensive care specialists in Adelaide, we now seek to apply this knowledge to evaluate gut function in patients in the Intensive Care Unit. The proposed studies will provide the most comprehensive studies to date of the gut function in critically ill patients and have important implications for treatment.Read moreRead less