Early Parenteral Nutrition Vs. Standard Care In The Critically Ill Patient: A Level I Randomised Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$1,852,333.00
Summary
Nutritional support is accepted as a standard of care for the hospitalised patient however there is little agreement as to how it should be provided to the critically ill patient. Despite the fact that studies consistently link malnutrition to worse outcomes, the provision of nutritional support to the critically ill patient is highly variable. Although there is general agreement that it is best to feed critically ill patients via the gastrointestinal tract (stomach tube feeding), there is no ge ....Nutritional support is accepted as a standard of care for the hospitalised patient however there is little agreement as to how it should be provided to the critically ill patient. Despite the fact that studies consistently link malnutrition to worse outcomes, the provision of nutritional support to the critically ill patient is highly variable. Although there is general agreement that it is best to feed critically ill patients via the gastrointestinal tract (stomach tube feeding), there is no general agreement as to when intravenous artificial nutrition should be begun if a patient cannot tolerate a feeding tube. A recent systematic review of all available clinical trials suggests that if a critically ill patient cannot be fed by a stomach tube for at least 24 hours, they may benefit from intravenous artificial nutrition. This is not what currently happens under standard care. The purpose of this multi-centre randomised controlled trial is to determine if early intravenous nutrition saves lives. Because of the cost, and possible risk of increased infections, a study of this type is required before early intravenous nutrition could become a routine therapy in Australia. Informed consent to participate in the study will be obtained from next of kin, or directly from the patient themselves. The study will be managed at the Royal North Shore Hospital, University of Sydney and will include 26 collaborating ANZ hospitals over 18 months.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.
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
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
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
Do PACAP-containing Neurons In The Hypothalamus Regulate Reproductive Hormone Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$182,559.00
Summary
This project investigates the role of a brain chemical called PACAP which is found in a part of the brain called the hypothalamus which regulates the reproductive system. The hypothalamus does this by controlling the secretion of several pituitary gland hormones, LH and prolactin, which in turn stimulate normal function of the ovaries or testes. Abnormal secretion of these hormones is seen in conditions such as anorexia nervosa, bulimia, stress, critical illness, aging and many others with the r ....This project investigates the role of a brain chemical called PACAP which is found in a part of the brain called the hypothalamus which regulates the reproductive system. The hypothalamus does this by controlling the secretion of several pituitary gland hormones, LH and prolactin, which in turn stimulate normal function of the ovaries or testes. Abnormal secretion of these hormones is seen in conditions such as anorexia nervosa, bulimia, stress, critical illness, aging and many others with the result that patients have low levels of steroids in their blood and inactive gonads, changes which in themselves lead to other health problems. Because these hormones are essential for normal reproduction, it is possible that PACAP may play an important role in regulating this process, both under normal conditions and in disease. It is hoped that this research will lead to a more detailed understanding of how the endocrine system is controlled in humans and to new methods for the manipulation of the reproductive axis, under normal and disease conditions.Read moreRead less
Nephro-protective Effects Of L-amino Acids In Critically Ill Patients: A Multi-centre Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$863,209.00
Summary
More than 60,000 Australians become critically ill each year with up to one third of these patients developing Acute Kidney Injury during their illness. Acute Kidney Injury leads to longer recovery times, may require lifelong dialysis and results in a significantly increased chance of dying as a result of the original critical illness. The purpose of this clinical trial is to determine if a simple and cheap amino acid infusion can reduce the onset of Acute Kidney Injury during critical illness.
Role Of FoxO Proteins In The Regulation Of Skeletal Muscle Anabolism, Catabolism And Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$503,426.00
Summary
Loss of muscle tissue or muscle wasting is a hallmark of many common health problems including diabetes, cancer, Cushing's syndrome, sepsis, HIV-Aids and renal failure. In the past 2-3 years important progress has been made in understanding the molecular regulation of both catabolism (muscle wasting) and anabolism (muscle growth) within mammalian skeletal muscles. It has been known for some time that a certain family of transcription factors, known as FoxO proteins, activate catabolic pathways. ....Loss of muscle tissue or muscle wasting is a hallmark of many common health problems including diabetes, cancer, Cushing's syndrome, sepsis, HIV-Aids and renal failure. In the past 2-3 years important progress has been made in understanding the molecular regulation of both catabolism (muscle wasting) and anabolism (muscle growth) within mammalian skeletal muscles. It has been known for some time that a certain family of transcription factors, known as FoxO proteins, activate catabolic pathways. However, recently, we have shown that FoxO proteins also cause muscle wasting by blocking anabolic pathways. Our new data heighten the importance of targeting FoxO proteins are therapeutics for human diseases where muscle tissue wasting occurs. This proposal will investigate methods that will allow for blocking the action of FoxO proteins in the hope that muscle wasting can be prevented.Read moreRead less
Testing A Home Based Rehabilitation Program For Survivors Of A Critical Illness: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$447,602.00
Summary
The aim of this study is to evaluate whether a home-based, individually tailored physical rehabilitation program can improve the physical and psychological recovery for survivors of a critical illness. Surviving a critical illness results in physical de-conditioning and emotional sequelae. Many observational studies have demonstrated a delayed recovery, often beyond a six-month period. At present there is a lack of specific service provision for the recovering intensive care patient, and prelimi ....The aim of this study is to evaluate whether a home-based, individually tailored physical rehabilitation program can improve the physical and psychological recovery for survivors of a critical illness. Surviving a critical illness results in physical de-conditioning and emotional sequelae. Many observational studies have demonstrated a delayed recovery, often beyond a six-month period. At present there is a lack of specific service provision for the recovering intensive care patient, and preliminary work by us indicates a need for an outreach follow-up service for ICU survivors that does not require individuals to attend an outpatient clinic. The 8-week program includes prescribed training of lower limb exercises, walking, and upper limb exercises, with the goal of improved physical strength and endurance at study end-point of 26 weeks. The standardised leg and arm exercises will be adjusted according to participant progress, using a specifically designed rehabilitation manual. Physical function, endurance and psychological well-being between the usual care and this program will be compared. Importantly, the project addresses outcomes that are clinically meaningful for the patients. It is designed to evaluate whether physical rehabilitation for people recovering from a critical illness improves physical and psychological recovery, which contribute to how people function and they feel. There appears to be little research in this area, so the innovative aspects of the study are an important consideration. The project addresses one of the National Research Priorities using an exercise-based rehabilitation program. It also provides an important innovation: successful implementation and positive findings from this home-based rehabilitation program will provide a model of care that existing primary care or community services can adopt so that all survivors of a critical illness will have the opportunity to improve their physical and psychological recovery.Read moreRead less
Functional Modulation Of Ovine And Human Somatotropes By In Vitro Application Of Leptin
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Obesity is a common disorder in developed countries and a prevalent condition which is often stigmatized. Actuarial data indicate that life expectancy is reduced when body-mass index (body mass in kg-square of the height in metres) is 20% or more above the ideal (obesity is >28% above ideal). Growth hormone (GH) from pituitary gland is the major anabolic hormone to increase muscle and reduce fat. A significant reduction in GH is found in obesity. Indeed, visceral fat mass is primary negative ....Obesity is a common disorder in developed countries and a prevalent condition which is often stigmatized. Actuarial data indicate that life expectancy is reduced when body-mass index (body mass in kg-square of the height in metres) is 20% or more above the ideal (obesity is >28% above ideal). Growth hormone (GH) from pituitary gland is the major anabolic hormone to increase muscle and reduce fat. A significant reduction in GH is found in obesity. Indeed, visceral fat mass is primary negative statistical determinant of GH secretion in middle age men and women. It is clear that the reduction in GH is due to a low sensitivity of GH cells to GH-releasing hormone (GHRH) from brain. It is therefore necessary to understand the change of pituitary GH cells in obesity. A recently identified, fat cell secreted, polypeptide (leptin) is demonstrated to reduce food intake and increase energy expenditure. Receptors for leptin have been found in pituitary gland, mainly in GH secreting cells. In our preliminary experiments, leptin reduces GH secretion by decreasing GHRH receptor synthesis. Meanwhile, this leptin treatment increased the receptors for GH-releasing peptide (GHRP), a synthetic peptide stimulating GH secretion. We aim to investigate the effect of leptin on cultured ovine and human GH cells by studying important cell functions including hormone and receptors synthesis, intracellular signaling molecules, membrane ion channels and cellular secreting machinery. The results will clarify the mechanism underlying GH deficiency in obese patients. We will also test the effect of synthetic GHRP in combination with leptin in vitro. The relationship between GHRP and leptin on the functional modification of GH cells will also be studied. It is likely to see that GHRP reduces the inhibitory effect of leptin on GH cells. This may end up an effective therapeutical use of GHRP (oral available) in the treatment of obesity.Read moreRead less