AAGBI/Anaesthesia & BJA/RCoA Small Research Grant
A comparison of minimally and non-invasive cardiac output during abdominal surgery
Dr Daniel Conway
Intravenous Fluid: Getting the Balance Right
An important role of the anaesthetist during major operations is managing fluid balance. Too little fluid causes dehydration, so organs don't get adequate blood flow. Too much intravenous fluid causes swelling of the tissues which slows recovery from surgery. Traditional methods of estimating fluid balance - pulse, blood pressure and urine production are inferior to methods that look at blood flow (cardiac output). This is particularly the case for major surgery, such as bowel cancer operations. Over 170,000 patients each year undergo major surgery in the UK. Sadly, some people can experience complications following their operation when the fluid balance is not right.
Doppler: Improving Patient Outcomes
The oesophageal Doppler cardiac output monitor (ODM) reduces complications following surgery by giving the anaesthetist information about blood flow they need to improve fluid balance. It does this using a soft probe placed in the oesophagus (gullet) via the mouth which then measures blood flow from near the heart using sound waves. ODM is being evaluated by NICE and many hospitals around the world, including our hospital, already use it for major surgery. Research has shown clear benefit for patients when this type of monitor is used by reducing complications and length of stay.
Cheetah: A Non-invasive Alternative?
Unfortunately oesophageal Doppler cannot be used in all cases e.g. head and neck surgery or in awake people after their operation. Therefore there is a need for an alternative blood flow monitor for major surgery that can overcome these problems. Ideally it should be completely non-invasive. The NICOM Cheetah system we are looking at may provide the answer, as we know it accurately estimates blood flow in stable people and those with heart problems. The Cheetah uses electrodes (sticky pads) placed on the front of the chest, very similar to ECG electrodes, which is part of care for all surgery. As yet anaesthetic research has not established whether Cheetah can be used as effectively as the oesophageal Doppler. This research intends to compare the signal received from the Cheetah with ODM. We will assess the usefulness of the new device in estimating fluid balance. There will be no additional treatment made by the researchers, as patients have ODM guided fluid as part of standard care in our hospital. The study is entirely observational, with analysis being performed after surgery.
How this study helps patients: The researchers will use the results of this study to design the next phase of the project. This will be a randomised head-to-head trial of Cheetah versus ODM for major surgery. This larger, more complex trial will tell us if the Cheetah used alone is better, worse or the same as ODM in helping patients withstand surgery. Anaesthetists will then be able to reduce postoperative complications and length of hospital stay for patients having major surgery.
Contribution of non-nociceptive neurons to pain signalling and phenotype
Dr Roman Cregg
Almost all human disease is associated with some form of pain. Almost 1in 5 of the population suffer some form of chronic pain that is poorly treated. This grant addresses the molecular and genetic mechanisms that underpin rare human pain conditions, with the hope that the insights provided will directly translate into new treatments for pain. In 2006 a major breakthrough occurred in pain research, when a sodium channel (Nav1.7) was shown to be essential for human pain perception. People with no functional Nav1.7 are normal but pain free suggesting that this is an ideal new analgesic drug target. I will assess the role of Nav1,7 in a variety of pain conditions in animal models.
Prognostic markers of outcome in infra-inguinal revascularisation: a prospective observational pilot study
Dr Simon James Davies
Background: Over 3000 people each year undergo bypass operations to their lower limbs, and these operations carry significant risks with approximately 1 in 20 of these people dying in hospital, and another 1 in 20 having a heart attack. The number of people having this type of procedure has grown over recent years, and the trend is predicted to continue. Due to this significant increase in the volume of these patients and the associated complications that occur with this surgery utilisation of more resources such as critical care is often needed. Assessment of these patients in order to stratify their risk of both dying and having significant complications aid in improving their care, allow better utilisation of scarce critical care resources, and also allow us to give patients informed consent. A high risk group in major abdominal surgery can be identified through a simple exercise test (cardiopulmonary exercise test) that looks at how the body uses oxygen, and also through a blood test that looks at a hormone secreted by the heart. Vascular surgical patients are at risk for the development of major cardiac complications in the postoperative period but a system for appropriate preoperative risk stratifications has yet to be achieved.
Aims: The aims of the project are to assess the feasibility of exercise testing this group of patients both with cycle and arm exercise, and to identify markers of outcome in this group. Identification of markers that can predict how patients will fair after surgery will allow for informed consent, better resource utilisation, and opportunities to attempt to modify outcomes.
Methodology: This is a prospective observational study designed to test the hypothesis that a combination of cardiopulmonary exercise testing and blood tests provides prognostic value on outcome measures after surgery for lower limb revascularisation. Subjects will have two exercise tests, one arm and one cycle, prior to surgery at their preoperative assessment appointment. From these tests we will measure how much work patients can do, how much oxygen they are able to use, and when the heart is unable to deliver enough oxygen to the cells. In addition they will have blood samples taken prior to the operation (brain naturetic peptide), and on days 1 and 3 (troponin I) after the operation to look at cardiac markers of damage. This data will be used to see if we can predict those patients that have both short and long term complications, and also to see whether the different forms of exercise testing are comparable, or if one type is superior.
Expected outcomes: We expect that through a combination of exercise testing and blood test we will be able to identify patients at increased risk of complications after surgery. We also expected to find that arm exercise will be a more feasible and informative test that cycle exercise.
Implications: Identification of a high risk group would allow appropriate strategies to be implemented to reduce risk, and allow better post-operative resource utilisation. This study will also allow a larger multicentre study to be adequately powered and constructed.
Pulmonary surfactant in adult patients with acute respiratory distress syndrome
Dr Ahilanandan Dushianthan
Acute Respiratory Distress Syndrome (ARDS) is an acute lung injury causing severe problems with getting oxygen into the blood. Patients with ARDS have a high death rate (36-44%). It has been shown that 15% of patients on mechanical ventilators will have ARDS suggesting a major health and economic burden in intensive care setting. Apart from supportive ventilation methods, there are no treatments available that provide a survival advantage. For lungs to work normally they need a substance called surfactant. This substance is secreted by cells lining the air sacks in lungs of healthy adults. Normally surfactant acts as a detergent, which helps prevent the lungs collapsing. It also has a role in protecting the lungs from infection and inflammation. Patients with ARDS have decreased surfactant levels with abnormal composition. These changes in surfactant levels and composition greatly reduce its detergent activity thus promoting lung collapse and impair oxygen transfer from lungs to blood particularly in mechanically ventilated patients. The exact mechanisms of these alterations are not known. It may be because it is not made quickly enough, destroyed more rapidly than normal or simply diluted. Choline is an organic compound, classified as an essential nutrient and grouped within the Vitamin B complex. This is found in the lipids that make up all cell membranes and is an important ingredient that makes up the surfactant. Deuteriated choline chloride (methyl-D9-choline) is a STABLE, NON RADIOACTIVE, NON-TOXIC naturally occurring isotope of choline, that has been used successfully and safely in adult volunteers and neonates to label surfactant and study its metabolism.
Aims:
The aims of this study are:
- To assess rates and mechanisms of surfactant synthesis and breakdown in patients with ARDS in comparison to controls
- To determine the extent to which changes to surfactant synthesis and breakdown may contribute to the disease course in patients with ARDS
- To evaluate whether the results of this study will help predict which patients with ARDS will benefit from being given additional surfactant.
Summary of Study D:
This is a pilot study. 30 ARDS patients and 10 ventilated control patients will be recruited according to the protocol. After assent obtained from patient's relative/next of kin or legal representative, ventilated sedated patients will be infused with a solution of methyl-D9-choline chloride over 3 hours. Blood, lung fluid and urine specimens will be collected before infusion and at 6,12,24,48,72,96 and 120 hours or until extubation. Samples will be processed and frozen for storage and subsequent analysis of incorporation of methyl-D9-choline into surfactant in the lungs and its metabolites in blood and urine. Rates of surfactant synthesis and breakdown will then be compared to clinical condition.
Expected outcomes:
- Establish how changes to surfactant synthesis and breakdown contribute to abnormal surfactant levels and function in ARDS patients
- Determine how these biochemical changes impact on patient outcome.
Implications: This study will improve understanding of surfactant metabolism in patients with ARDS and ventilated non-ARDS controls and will help to guide treatment of future patients with ARDS.
Suitability of oxygen concentrators for use with the Diamedica Portable Anaesthesia system (DPA 01)
Dr Roger Eltringham
Background:
More than two billion people worldwide do not have access to safe surgery, most of them in developing countries. The applicants have been responsible for a robust anaesthetic machine that is now in use in 35 countries worldwide, mostly in Africa but also in parts of Asia. A portable anaesthetic machine has recently been introduced which weighs just 10 kg and fits into a container the size of a small suitcase. It is ideal for use in remote rural hospitals and clinics, as well as in disaster situations and by the armed forces. To increase its performance we want to be able to recommend a suitable oxygen concentrator to accompany it that will function in the extreme conditions encountered in many parts of the developing world. Oxygen concentrators generate oxygen from the air and are an extremely safe, inexpensive and convenient alternative to cylinders of oxygen or piped oxygen supply. Oxygen concentrators are especially useful for hospitals in low income countries where a reliable oxygen supply is essential for emergency medicine, resuscitation, anaesthesia and treatment of serious illnesses.
Aims:
The aim is to compare the performance of various oxygen concentrators in order to recommend a reliable model to accompany the Diamedica portable anaesthesia machine (DPA 01).The equipment must be robust enough to withstand hostile conditions such as high humidity, extreme temperatures, unreliable power supply, etc. Much medical equipment is not fit for purpose in such challenging conditions, so it quickly breaks down or fails to work at all. This is clearly a terrible waste of resources and can endanger patients' lives.
Methods: The oxygen concentrators will be tested at the independent UKAS accredited commercial testing house in Bideford. These tests will include running the machines in extreme conditions, such as high temperatures and humidity, and at high oxygen output over extended periods of time. They will also be checked for safety, such as protection against electric shock and sound levels. We will compare test results with the manufacturer's specifications and the international standards (ISO 8359), to ensure the machines are performing safely and efficiently.
Expected outcomes:
The outcome of this study will be to identify which oxygen concentrators are the best for use with the Diamedica portable anaesthetic machine in extreme conditions. The tests may also reveal models that fail to perform adequately and which do not meet international standards. The result will be a definitive list of the preferred low-cost concentrators suitable for use in harsh conditions.
Implications:
We want to publish the results in a widely read medical journal. Our findings will provide guidance to those selecting oxygen concentrators for use in developing countries, such as aid agencies, and help them to make the best choice. Choosing the right equipment for the job will help to save lives and money.
Preliminary assessment of frailty in cardiac surgery (definition, prevalence and impact on neutrophil activation
Dr Nandor Marczin
Background: Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalisation and mortality. However, it is becoming recognised that frailty is a distinct clinical syndrome with a characteristic biological basis. Frailty appears to be a dynamic progression from robustness to functional decline affecting multiple systems. During this process, total physiological reserves decrease and become less likely to be sufficient for the maintenance and repair of the ageing body. It is becoming increasingly recognised that older patients particularly those who are frail suffer more postoperative complications following major general and specialised heart surgery than younger and fitter patients. However, there are various operational definitions of frailty that impact on estimated prevalence and on the reported relationship between frailty and health outcomes, In addition, the biological reasons underlying the higher risk of frail patients are not known with certainty. Nevertheless, recent concepts suggest that part of the immune system is overactive in older and frail patients leading to a chronic inflammatory state.
Aims: The principle aim of the current pilot study is to better define frailty in the setting of cardiac surgery and to establish the early postoperative clinical course of these patients. We also wish to utilise this framework to begin exploring biological mechanisms that potentially contribute to the increased postoperative risks of these frail patients.
Methodology: This is a pilot observational study in patients presented for heart surgery who are older than 65 years. We will define frailty by three independent means based on patients self-assessment using up to 36 criteria and clinical investigation. We will then define the fraction of patients who are fit and those who are frail and the group in between. These definitions are widely used in medicine of the elderly. We will then assess if complications occur more frequently in the frail groups. We will also explore the status of the immune cells focusing on a particular cell type called neutrophils in these patient groups and their activation state after surgery. We will investigate both cellular activation and the release of their principle mediators into the blood.
Expected outcomes: We anticipate high prevalence of frailty in the patient population and increased complication rates after heart surgery. We also anticipate that immune cells will be activated in the frail patients even before surgery and to a higher degree with mediator release and increased plasma concentrations of these mediators after surgery when compared to the robust patient population.
Implications: This investigation will provide novel insights into the true prevalence of frailty in the heart surgical population and regarding fundamental immunological mechanisms related to ageing and frailty in the surgical settings. Such insights may lead to novel diagnostic, monitoring and therapeutic strategies in the future. The data obtained in this pilot will aid the optimal design including prediction of necessary sample size and power of future studies addressing these important issues.
