AAGBI/Anaesthesia Small Research Grant
The successful applicants for the AAGBI/Anaesthesia Small Research Grant were:
Principal Applicant
Dr Neil Crooks
Critical Care Research Fellow, Heart of England NHS Foundation Trust
Title
PECaN-ED (Probiotic E. coli Nissle 1917 - Efficacy & Dosing) - Evaluation of the efficacy and dosing of probiotic Escherichia coli Nissle 1917 in ventilated intensive care patients
Amount
£13,210
Scientific Abstract
Ventilator-associated pneumonia(VAP) is the most common ICU-acquired infection. VAP complicates management in up to 30% of patients ventilated for >=48 hours and has been shown to double risk of death. Although VAP may be reduced with ventilator care bundles,efforts are hampered by the emergence of multiresistant Gram-negative bacteria(GNB). GNB are now the predominant cause of ICU infection leading to significant morbidity, mortality, prolonged stay and increased costs.
Colonisation of the oropharynx and stomach with nosocomial pathogens is more common in ventilated patients. Colonisation of the stomach is believed to occur due to poor gut motility and increased gastric pH. This allows overgrowth of GNB in the duodenum which reflux into the stomach and are aspirated into the lungs increasing the risk of VAP.
A meta-analysis of five RCTs(n=689) using Lactobacillus spp demonstrated a reduction(OR 0.61) in VAP with the administration of probiotics. Although benefit has been demonstrated with Lactobacillus, we hope that by using Eschericheria coli Nissle we can ultimately reduce VAP by exploiting its superiority at inhibiting colonisation by other Enterobacteriaceae plus its immunomodulatory effects. In our proof of concept study we aim to demonstrate successful gastric colonisation with E.coli Nissle, prevention of gastric colonisation by pathogenic GNB and to establish the optimum dose.
Principal Applicant
Dr Raghavendran Krishnaiyan
Honorary Lecturer and Specialty Registrar in Anaesthesia, Critical Care and Pain, Leicester Royal Infirmary
Title
Prognostic value of SSEPs in Hypoxic Brain Injury with Therapeutic Induced Mild Hypothermia at Different time intervals
Amount
£14,995
Scientific Abstract
Cardiac arrest (with subsequent resuscitation), triggers a cascade of events from various cellular and molecular processes within the brain resulting in ischaemic/anoxic neuronal injury. The neurological sequelae are varied and significant. Therapeutic hypothermia improves neurological outcome when given early. However there is no benefit if the patient has already suffered severe brain damage and there is no reliable method to predict who would benefit from therapeutic hypothermia.
Somatosensory evoked potentials (SSEPs) have become a reliable tool to predict neurological recovery when performed 24-72 hours after resuscitation from cardiac arrest (i.e. after completing therapeutic hypothermia treatment). We propose to perform a pilot study to assess whether early SSEPs can predict neurological outcome before starting therapeutic hypothermia treatment.
We will study patients eligible for therapeutic hypothermia following resuscitation for cardiac arrest, as per our Trust protocol. After obtaining 'deferred assent' SSEP measurements and neurological assessment data will be recorded within 8 hours (early) of cardiac arrest and repeated at 24 -48 hours and 72 hours (late) post cardiac arrest. This data will be analysed to assess the reliability and reproducibility of early SSEPs compared to the well-established late SSEP measurements.
Principal Applicant
Dr Gary Minto and Dr Richard Struthers
Consultant Anaesthetists, Derriford Hospital, Plymouth Hospitals NHS Trust
Title
A pilot study into the non-invasive measurement of oxygen delivery and consumption after elective major upper abdominal surgery
Amount
£7,825
Scientific Abstract
We propose to assess agreement between 2 methods to measure resting oxygen consumption (VO2), cardiac output (CO) and oxygen delivery (DO2) after surgery. In 20 patients we will compare a system using Indirect Calorimetry, Pulse Cooximetry and Pulse wave transit time ("Non invasive") to standard invasive measures these values at six intervals in the first 24 hours following open liver resection for colorectal cancer metastasis.
Research from the 1980s described increased VO2 in patients after major surgery and suggested that failure to adequately meet this demand resulted in severe complications including death. This hypothesis generated complementary streams of research into manipulation of the cardiovascular system to ensure DO2 (Goal Directed Fluid Therapy "GDT") and pre-operative testing (for example cardiopulmonary exercise testing "CPET") of patients` functional capacity to increase DO2.
Major advances in perioperative care have reduced the stress response after surgery. Recent studies suggest that previous assumptions do not hold - less fit patients do well and GDT has less impact. Previous studies used invasive measurements to calculate VO2 & DO2. These methods are inconsistent with modern care.
We propose to establish whether non-invasive methods can replicate the findings from earlier work. A crucial initial step is to validate these technologies.
Final Report from Dr G Minto & Dr R Struthers (77 KB)
Principal Applicant
Dr Kyle Pattinson
MRC Clinician Scientist Fellow, University of Oxford
Title
The effect of chronic opioid therapy on respiratory control during sleep
Amount
£14,940
Scientific Abstract
In this proposal we seek pilot funding to investigate neural mechanisms underlying opioid disturbance of respiration during sleep. Patients who are prescribed long-term opioid analgesics are at increased risk of respiratory depression and death, which usually occur during sleep.
Opioids disturb sleep by decreasing the duration of rapid eye motion (REM) sleep, and increasing the duration of non-REM sleep. It is during non-REM sleep that that the incidence of opioid-related breathing disturbances is highest. Many brain areas implicated in control of non-REM sleep are also implicated in the control of respiration and express high densities of opioid receptors. These areas include the brainstem periaqueductal grey matter, thalamus, insula and anterior cingulate cortex.
We hypothesise that chronic opioid therapy causes sleep-disordered breathing by interfering with shared non-REM sleep and respiratory control mechanisms. By combining polysomnography, respiratory physiology and neuroimaging we shall investigate how opioids, sleep and pain interact in patients with chronic back pain, a highly-prevalent condition, on long-term high-dose opioid.
This work will help with the appraisal and design of novel strategies and compounds that mitigate against opioid-induced respiratory depression (e.g. safer opioids or specific drugs to antagonise respiratory side-effects), thus improving safety and efficacy of opioid analgesia.
Final report from Dr K Pattinson.pdf (614 KB)
Principal Applicant
Surg Cdr Jane Risdall
Consultant in Anaesthetics & Intensive Care, Royal Navy
Title
Blast Brain Injury: Use of genetic probes to identify key cell types involved in the cerebral inflammatory response to blast exposure
Amount
£6,945
Scientific Abstract
Blast brain injury has risen to prominence in recent military conflicts. It represents a specific form of primary brain injury, with sufficiently different physical attributes (and possible biological consequences) to be classified separately.
We have demonstrated that inflammation follows an isolated blast exposure to the head in an anaesthetised rat model. Cytometric bead and qPCR arrays have shown significant increases in the chemokines responsible for monocyte recruitment and the expression of the chemokine genes involved in monocyte and T-cell recruitment.
Further targeted analysis, using qRT-PCR arrays, is required to ascertain which cell types act as the principle drivers of this inflammatory response and where they are located in the cerebral tissue. Knowledge of anatomical location and whether inflammation is driven by intrinsic (astrocytes/microglia) or extrinsic (circulating granulocytes) cell types will guide future translational research.
Using branched DNA technology we will probe histological samples for the expression of mRNA modified by blast exposure. From our genetic expression array data we have selected the genes governing MCP-1 and MCP-5 expression as central to the inflammatory response and will use in-situ RNA hybridisation to probe cerebral tissue sections for these genes with a view to identifying the cell types involved.
Please see the NIAA's position statement on the use of animals in medical research.
Final report from Surg Cdr J Risdall (72 KB)
Principal Applicant
Dr Robert Sanders
Senior Clinical Research Associate, Imperial College London
Title
The impact of blood pressure thresholds on perioperative mortality in non-cardiac surgery in a United Kingdom database
Amount
£14,320
Scientific Abstract
There are limited data to inform the perioperative care of hypertensive patients, including blood pressure values that are associated with increased perioperative mortality or optimal preoperative medication for reducing perioperative risk. Meta-analysis provided largely inconclusive evidence for an increase in perioperative risk, though our recent study of has suggested that hypertension is an independent predictor of perioperative mortality in total
hip or knee replacement (n=414,985). However it is unclear whether higher blood pressure values are associated with incremental increases in mortality. Nor are the perioperative risks associated with first line antihypertensive agents (Angiotensin Converting Enzyme inhibitors, Angiotensin Receptor Blockers, and Calcium Channel Blockers) clear. We will
investigate these issues using a primary care database that incorporates pharmaceutical information to determine the impact of blood pressures and chronic cardiovascular medication on 30- and 90- day perioperative mortality. Blood pressure will be analyzed both as a threshold variable (according to hypertension guidelines) and as a continuous variable (using a restricted cubic spline function). We will analyze data from a large population undergoing non-cardiac surgery and also analyze three specific surgical cohorts separately: abdominal aortic aneurysm repair, total hip or knee replacement, or hysterectomy surgery.
First Year Report from Dr R Sanders (54 KB)
Interim report from Dr R Sanders 2012 R2.pdf (57 KB)
Principal Applicant
Dr Neeraj Saxena
Locum Consultant, Anaesthetics, Royal Glamorgan Hospital
Title
Understanding the mechanisms of sedation: Effects of GABAergic and non GABAergic sedatives on magnetoencephalographic visual gamma responses
Amount
£15,000
Scientific Abstract
Despite advances in anaesthetic pharmacology, the mechanisms of anaesthetic action remain relatively poorly understood. Gamma-Aminobutyric Acid (GABA), the most common inhibitory neurotransmitter, has been implicated in neurophysiological processes such as sleep and sedation, and pathologies like epilepsy and schizophrenia. Gamma oscillations (30-80 Hz range) are implicated in functions including memory, attention and consciousness and are generated by a significant contribution from GABAergic inhibitory neurons. In our recent work, with mild propofol induced sedation, we demonstrated an increase in stimulus-induced gamma amplitude, suppression and a simultaneous amplitude reduction of the pattern onset evoked response, in response to a simple visual task using magnetoencephalographic (MEG) recordings. This suggests a possible local hypersynchronous GABAergic mechanism disrupting the long range cortico-cotical connections responsible for maintaining consciousness. We propose to compare the cortical oscillatory effects of mild sedation induced with propofol (GABAergic sedative with cortical and subcortical effects) and dexmedetomidine (non-GABAergic sedative with mainly subcortical effect) using MEG. This could also provide further insight into the development of cognitive dysfunction (POCD) in postoperative and intensive care patients, with the use of GABAergic compounds. A better understanding of this in vivo alteration of task induced gamma oscillatory activity would help develop a potential biomarker for GABAergic activity in humans and for conditions such as POCD.
First year progress report from Dr N Saxena (189 KB)
Interim report from Dr N Saxena.pdf (190 KB)
