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
The appropriate dosing of antibiotics for patient admitted to ICU after a traumatic injury is poorly defined and based on intuition rather than evidence. Doctors need to predict which patients may develop very high antibiotic clearances and dose accordingly so that potentially life-threatening infections do not occur. Given these patients are unknown, this research seeks to identify such patients and recommend which antibiotic and which dose is appropriate to ensure adequate treatment.
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