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AAGBI/Anaesthesia Research Grant

Prospective, open label, single site pilot study to assess the effects of Spinal Cord Stimulation on autonomic function in patients with failed back surgery syndrome

Dr Sheila Black

Failed Back Surgery Syndrome (FBSS) is a chronic painful condition which results in persistent back and/or leg pain following spinal surgery. It can be treated with pain-relieving medication, physiotherapy and (when appropriate) by spinal cord stimulation (SCS). SCS involves placing stimulating electrodes into the patients' back, near to the nerves which supply the back and leg. The electrical pulses it produces give pain relief over that area. The National Institute of Clinical Excellence recommends SCS as a treatment for FBSS. In our institution, 85% of patients who try the SCS get good pain relief. One of the suggested ways that SCS produces pain relief is via specific types of nerves called autonomic nerves, which also control blood pressure and heart rate. Some patients with chronic pain have increased activity in their autonomic nerves and we speculate that people who display increased autonomic activity will be more likely to benefit from SCS.

We would like to measure resting autonomic activity in patients with FBSS using microneurography, as this has not been demonstrated in this patient group before. We will also compare autonomic nerve activity before and 6 months after SCS implant, to find out if SCS therapy has reduced the autonomic activity.

This is a prospective single-centre open-label pilot study. Ten participants are required. However, due to technical difficulties in performing microneurography, up to 30 participants may need to be recruited in order to achieve 10 successful measurements. Screening for study suitability will be undertaken if they are listed for SCS implantation.

We will measure autonomic activity on 2 occasions: before SCS implant and 6 months after. We will measure heart rate variability, baroreceptor sensitivity and muscle sympathetic nerve activity using microneurography. This involves placing 2 tungsten microelectrodes (similar to acupuncture needles) through the skin; one into the nerve which runs along the outside of the knee joint and another into the skin beside it.

Expected outcomes
We aim to demonstrate the resting autonomic tone in patients with FBSS and demonstrate any change in autonomic activity 6 months after SCS implantation. A change of >=20% reduction in sympathetic activity compared with baseline values will be considered significant. This is a pilot study which will be used to help design a larger study to find out if high or low autonomic activity matches up with the likelihood of getting good pain relief from SCS.

The implication of this study is the potential ability to predict which patients are responders or non-responders of SCS therapy. Microneurography may be useful as a screening tool which might improve clinical outcomes by targeting SCS therapy to those who are likely to benefit most. Patients who do not display high levels of autonomic activity may not benefit from SCS therapy, and therefore should not be referred for this treatment. This will improve patient safety by avoiding the potential risks and complications of SCS implantation which include infection and nerve damage.

Cefoxitin resistance as a marker of AmpC beta-lactamase production: Clinical significance in the Intensive Care Unit

Dr Emma Fitzgerald

Resistance of bacteria to antibiotics is a serious and growing global health threat. It will become increasingly important in the future in those patients who become infected with bacteria that are resistant to conventional antibiotics, leaving their infections effectively untreatable. It is very important that we take great care to minimise the development of antibiotic resistance to try to prevent total resistance becoming a reality.

In patients who are admitted to the Intensive Care Unit (ICU), contracting an infection with certain types of bacteria is associated with a longer stay in ICU, in hospital and also an increased risk of dying. Resistance may not be present when the course of antibiotics is first started but it its development may be a reason why a
patient who is seemingly on the right antibiotic fails to get better.

The bacteria that this study will look at are part of the group of bacteria called coliform bacteria. Bacteria can become resistant to certain antibiotics (e.g. penicillins) in a number of different ways, but one is by producing an enzyme that stops the antibiotic working. One such enzyme is called AmpC beta lactamase. Although coliform bacteria may have the genes that code for this enzyme, not all of them go on and develop resistance.

All bacteria are tested in the laboratory to determine which antibiotics they are sensitive or resistant to. This information guides the choice of antibiotic. In ICU patients, a penicillin based antibiotic called piperacillin-tazobactam (Tazocin) is often used if laboratory testing confirms sensitivity. However, it has been found that if in the laboratory the coliform bacterium is resistant to an antibiotic called cefoxitin, then this is an indicator that this bacterium has the potential to produce the beta lactamase enzyme and potentially develop resistance.

It is not known how clinically significant this is, but if it is, then microbiological testing for it is very important and should be conducted routinely on every one of these samples to minimise antibiotic resistance.

To establish whether presence of cefoxitin resistance leads to higher treatment failure in ICU patients who have a coliform isolated from a sample of secretions taken from their lungs while they are on a ventilator, a "non-bronchoscopic lavage" (NBL) sample.

Blinded retrospective review of microbiological and clinical data collected from all ICU patients in 2013 who had a coliform isolated and who were on appropriate antibiotics according to initial sensitivities.

Statistical analysis will be used to identify any relationship between cefoxitin resistance and whether or not antibiotic treatment is successful. The study will also assess whether this is related to how long a patient is in ICU, in hospital, or their mortality.

Potential Impact
If cefoxitin resistance is associated with a failure of antibiotic therapy, then microbiological testing for it is important and should be conducted routinely on every NBL sample. The result should be considered when choosing the appropriate antibiotic to treat ICU patients to minimise antibiotic resistance, improve treatment success and improve patient outcome.

EPICS: EPidemiology of Critical care after Surgery: version 2

Dr Ramani Moonesinghe
Up to 36,000 people die in hospital after surgery in the UK every year.1 2 We know that standards of care vary between hospitals and countries, and that as a consequence, death rates also vary.1

One intervention which might help prevent complications and death, is admitting those patients who are believed to be "high risk", to a critical care unit (CCU) immediately after the surgery. To this end, two national reports have recommended that high-risk patients are managed on CCU after surgery. 3 4 However, we know from recent studies, that most patients who die after surgery and before leaving hospital, never receive treatment on CCU. 1, 5

We do not understand the reasons for this apparent failure to provide adequate care. It may be that there are not enough CCU beds to meet the demand. It may be that clinicians do not accurately predict which patients might benefit from CCU care. It may also be that some clinicians do not believe CCU care will make any difference to patient outcome. One may sympathise with this view, as there are no randomized controlled trials (RCTs) which have tested the benefits of postoperative critical care.

Thus, the EPICS study has two main aims. The first is to explore the basis for clinical decision-making regarding postoperative CCU admission, and the accuracy of some existing methods of risk prediction. This will enable us to report, for the first time in the UK, whether the reason that so few high-risk surgical patients receive postoperative critical care is because of lack of critical care capacity, or sub-optimal risk prediction and decision-making by clinicians. This could have important implications for resource planning within hospitals, and educational benefit for clinicians, both of which should help to improve the quality of surgical healthcare.

The second aim is to determine if there is any clinical benefit to postoperative critical care admission. Ideally, an RCT would be used to test the benefit of CCU admission. However, in preparation for submitting this grant, we conducted a small survey of experts, which reveals that despite there being some enthusiasm for such an RCT, there are also concerns that such a trial would not be feasible or ethical. Therefore, in order to answer this important question, we propose to conduct an observational study which will use two statistical techniques (propensity score matching [ and instrumental variable analysis [) which are specifically designed to answer questions in non-randomised studies, where there are concerns that would be unethical or infeasible to conduct an RCT.

We will recruit as many hospitals as possible in the UK to take part. We will ask local investigators to collect data on all patients undergoing surgery with a planned overnight stay in hospital, for one week. The data collected will describe patient characteristics (such as their age, medical history and type of surgery). Additionally, we will ask anaesthetists to estimate the risk of postoperative death in each patient they manage; we will also ask them to explain how they arrived at this estimate (e.g. clinical judgment, preoperative exercise testing, or use of a risk scoring system). We will compare the accuracy of these various systems (including clinical judgment) against each other. The anaesthetist will be asked to state if they have referred each patient for CCU admission, and if in fact the patient subsequently received CCU care - thereby exploring whether there are enough CCU beds to meet demand, and if not, to explore the scale of the shortfall.

Several previous studies have used both PSM and IV analysis to determine the effectiveness of interventions in areas where there is professional uncertainty over the ethics and / or feasibility of using an RCT design. The results of EPICS will not only answer the aforementioned important research questions, but also provide data which can be used to establish conclusively whether a large (and potentially very expensive) RCT to test the effectiveness of critical care admission after surgery is feasible or warranted.