RF Anaesthesia Studies


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Summary -

COSMOS (Characterising the impact of Oxidative Stress & Mitochondrial function on Outcomes following major Surgery) is an observational study looking into the how our bodies react to the process of surgery.

We will investigate the metabolic responses during surgery. In particular, we are studying mitochondrial function, the energy house of our cells, using muscle biopsies from the perioperative period and measuring mitochondrial metabolism with a technique called high resolution respirometry. We will also measure oxidative stress, from perioperative blood samples, where we will assess the degree of molecular damage caused by the release of reactive oxygen species.

Other elements of the study include a pre-operative cardiopulmonary exercise test, along with data collection from the intra-operative phase and post-operative recovery. This will help us to develop a further understanding of why some patients make a better recovery after surgery than others.

Principal Investigator - Dr Daniel Martin

Team - Dr Jia Liu Stevens (Lead Investigator), Dr Gavin Jell, Helder Filipe, Christine Eastgate, Margaret O’Neil, David Bruce


COLT trial

A feasibility study of Cardiac Output optimisation following Liver Transplantation

Patients with liver cirrhosis undergoing liver transplantation have a hyperdynamic circulation which persists into the early postoperative period making accurate assessment of fluid requirements challenging. Goal-directed fluid therapy (GDFT) has been shown to reduce morbidity and mortality in a number of surgery settings. The impact of GDFT in patients undergoing liver transplantation is unknown. A feasibility trial was designed to determine patient and clinician support for recruitment into a randomised controlled trial of GDFT following liver transplantation, adherence to a GDFT protocol, participant withdrawal, and to determine appropriate endpoints for a subsequent larger trial to evaluate the efficacy of GDFT in patients undergoing liver transplantation.

Chief Investigator - Prof Brian Davidson 

Principal Investigator - Dr Daniel Martin, Dr Nick Schofield


This study was funded by the NIHR PB-PB-0214-33043


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Short Term Outcomes with Intrathecal Opioid and Patient Controlled Analgesia versus Thoracic Epidural Analgesia for Hepatic Resection: A Randomised Controlled Trial

Thoracic epidural analgesia (TEA) forms the mainstay of most multimodal analgesia packages in Enhanced Recovery Programmes (ERP) for hepatic resection (HR) surgery. Postoperatively TEA has been shown to provide superior analgesia and improved respiratory function in major intra-abdominal surgery. TEA however, is accompanied by a significant failure rate. The use of TEA in HR can result in postoperative hypotension and excessive fluid administration, leading to increased “top up” blood transfusions, delayed mobilisation and increased length of stay (LOS).  Due to the absence of large scale trials there is a state of clinical equipoise as to whether alternative forms of analgesia can provide better outcomes for HR.

Intrathecal morphine (ITM) and PCA has been shown to be an effective alternative to TEA in HR and may offer advantages in the context of an ERP. To date there have been no randomised controlled trial (RCT) looking at outcomes beyond pain scores between these two analgesic options.

This RCT aims to compare the outcomes of TEA with those of single shot ITM plus PCA for HR. The primary outcome is time until medically fit for discharge (tMFD). Secondary outcomes are total LOS, pain scores, fluid and blood transfusion requirements, time to mobilisation, postoperative morbidity scores (POMS), morbidity and 30 day mortality; and quality of recovery (QoR) and quality of life (QoL) scores.

Chief Investigator - Dr Lasitha Abeysundara, Dr Ciara Donohue, Dr Ben Clevenger

This study was funded by a grant from the NIAA/AAGBI



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the Hypotension Probability Indicator in Clinical Practice

Increasing evidence supports the association between intra-operative hypotension and poor post-operative outcomes, especially acute kidney and myocardial injury. At present there are no tools to robustly aid in prediction of hypotension. Edwards Lifesciences have developed the Hypotension Probability Indicator (HPI) algorithm as a means to predict hypotension up to five minutes prior to its onset. If effective, this tool would permit earlier intervention to avoid or ameliorate the severity of hypotension and potentially improve perioperative outcomes. This study is the first independent validation of the HPI algorithm in complex surgery.

Chief Investigator - Dr Daniel Martin

Principal Investigator - Dr Jeremy Fabes, Dr Michael Spiro 

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Coagulation after Orthotopic Liver transplantation

In end stage liver disease, haemostasis is “re-balanced”, and despite the prolonged PT/INR, thrombin generation is normal or even increased but with a markedly decreased reserve. Liver transplantation (LT) introduces stress to this fragile haemostatic balance, and both excessive bleeding and thrombosis are potential risks in the perioperative period. To date, there have been very limited studies on coagulation profiles following LT, but it appears that there may be an underestimated intrinsic hypercoagulable state following transplantation, associated with low anticoagulant levels and high factor VIII, together with fibrinolysis suppression. To complicate matters marginal grafts may have delayed synthetic function and coagulation might not improve immediately after transplantation with consequent risk of bleeding.

We aim to conduct a comprehensive study of coagulation changes in the early postoperative period following LT. This observational study will evaluate the changes to haemostasis in 30 patients at seven specific time points, beginning immediately after induction of anaesthesia and concluding on the 10th postoperative day and correlate with bleeding and thrombotic complications. An in-depth understanding of postoperative coagulation will enable tailored administration of clotting products where necessary and inform anticoagulation protocols, resulting in a reduction in bleeding and thromboembolic complications following surgery.

Research team - Dr Julia Benham Hermetz, Dr Clare Morkane, Dr Don Milliken, Dr Alexa Stachan, Dr Nick Schofield

This study is funded by an NIAA/NIHR grant



Short and Long term post-operative Health Related Quality of Life  of Vascular Patients undergoing Complex Aortic Surgery using an automated SMS Patient Reported Outcome Measures Tool

Complex aortic endovascular procedures (FEVAR/TEVAR) are performed in high-risk patients with often multiple comorbidities. The long term functional outcomes of endovascular techniques are not known but are the topic of current on-going investigation.

Patient Reported Outcome Measures (PROMS) are now routinely used in several types of elective surgical procedures. They are valued by patients, clinicians, and policy-makers as they provide valuable information supplementing clinical outcomes, help to inform disease management practices, therapeutic choices, reimbursement decisions, and health policy. They can be administered in a number of ways but there is evidence of text message (SMS) PROMS tools being used in chronic disease conditions to do such work. As mobile phone use is almost ubiquitous and increasingly used by the older population (such as those with aortic disease), using this technology to collect PROMS specific to the complex aortic patient allows clinically important information to be captured in real-time and at a clinically relevant time allowing for continuous feedback and improvement.

The Royal Free Perioperative Research Group propose a service improvement project that specifically tracks complex aortic patients’ perceptions of their post-operative functional improvement, quality of life, and satisfaction with treatment. This study will take place at the Royal Free Hospital, London and include adult patients scheduled to have fenestrated and /or thoracic endovascular aortic aneurysm repairs (FEVAR or TEVAR). The patients will be recruited before their operation and followed up by automated SMS over 52 weeks at pre-determined time points; weeks 6, 12, 26 and 52 following elective major complex aortic surgery.

Research Team - Dr Julia Benham Hermetz

This study is funded by the Royal Free Charity

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The use of intravenous lidocaine infusion for intractable ischaemic limb pain unresponsive to conventional therapy in adult vascular patients: a pilot study

Critical limb ischaemia is characterized by rest pain, ulceration and gangrene caused by proven arterial occlusion.  Ultimately this can lead to amputation of the affected limb. The pain is notoriously difficult to manage and is often neuropathic in nature. Patients commonly describe tingling, throbbing, sharp shooting pains and pins and needles. Conventional therapies include the use of strong opioid analgesia, in association with adjuvant therapies, such as gabapentinoids and ketamine.

In normal pain transduction, primary afferents carry nerve impulses from the area of the stimulus to the dorsal horn in the spinal cord. The primary afferent synapses in the dorsal horn releasing neurotransmitters, specifically glutamate, into the synaptic cleft, which binds to AMPA receptors in the post-synaptic membrane. This causes nerve propagation towards the appropriate centres of the brain, resulting in a painful sensation. 

Lidocaine is an amide local anaesthetic agent, which acts to block the sodium channels on the neurones. When given intravenously (iv) it is thought to prevent spontaneous firing of these damaged neurons and so demonstrates analgesic, antihypertensive and anti-inflammatory properties. There is also evidence to suggest that iv lidocaine reduces central sensitization and NMDA receptor activation. Our aim with this study is to demonstrate a role for lignocaine in the management of the critically ischaemic limb in the inpatient setting.

Research team - Dr Mo Haque, Dr Alexa Strachan

This study is funded by a Departmental Research Grant from the AAGBI



The SAFER study - SAphenous vs. FEmoRal pressures in liver transplantation

During liver transplant the blood that normally flows from the gut through the liver is rerouted so that it can return to the heart while the liver is removed and replaced. It is important during surgery that the anaesthetist is able to measure how well blood is returning to the heart in order to maintain the patient's blood pressure. If there are problems with the blood return then the surgeon must be informed to correct the issue.

Usually a central line is placed in the femoral vein to compare the blood pressure here, below the liver, to that in the heart, above the liver. One of the potential complications of inserting a large cannula in this area is the risk of bleeding that can be hard to stop. There is a greater risk of this in patients with liver disease having a liver transplant which may have problems with their blood clotting.

The aim of this study is to find out whether the insertion of a smaller cannula in the foot of a patient having a liver transplant can provide the same information as central femoral line. These have much lower rates of complication and the bleeding caused is easy to stop if it does occur. If this study shows that the cannula in the foot is as effective then we will be able to stop inserting central femoral lines and so reduce the risk of bleeding in future patients having a liver transplant.

Research team - Dr Julia Benham Hermetz, Dr Don Milliken

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Cohort Study using TEG 6 Viscoelastic Testing

Sepsis-induced DIC has a unique pathophysiology with profound inhibition of native fibrinolysis and high incidence of multi-organ dysfunction. This coagulopathic component of sepsis is currently poorly described, especially it’s temporal evolution, and lacks validated criteria or scoring systems to aid diagnosis and management. Understanding this constituent of the natural history of sepsis may open up new therapeutic strategies to improve outcome mirroring those seen in the management of the underlying infective aetiology and shock. Early and accurate detection of evolving hypocoagulability will permit management to ameliorate organ dysfunction and prevent the evolution of established DIC with attendant improvements in patient outcome.

Characterising the evolution of coagulopathy in a homogeneous cohort of septic patients with lower respiratory tract infection will permit identification of common themes and trends. This information will permit risk stratification, identify potential novel interventions and therapeutic strategies and contribute to the management of severe sepsis.

This study is funded by an Investigator Initiated Trial Grant from Haemonetics.


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Delirium and Population Health Informatics Cohort (DELPHIC) Study


Background: Delirium is a syndrome of severe brain dysfunction caused by acute illness. It affects at least 1 in 8 hospitalised patients. Several studies show that delirium is linked with both high risk of new dementia, and worsening of existing dementia. This is extremely important because it suggests that targeting delirium may be a beneficial intervention in dementia prevention. Yet our understanding of the delirium-dementia relationship remains poor. Major gaps include: (i) Which delirium features (e.g. duration, severity, subtypes, causes) are associated with worse cognitive outcomes.

Aim: This study will track cognitive function before, during and after hospitalisation in delirium cases and controls.

Methods: Participants will undergo baseline cognitive assessments including the modified Telephone Interview for Cognitive Status (TICS-m). Hospitalised participants will be assessed for delirium (diagnosis, duration, severity, subtype, associated clinical data) each day participants are admitted. A cohort of patients undergoing high risk surgery will also be studied to look for possible mechanisms of the causes of delirium.

Outcomes: DELPHIC will be the first prospective population study relating delirium and its features to risk of incident dementia and worsening of prevalent dementia.

Research team - Dr David Walker, Dr Bence Hajdu, Dr Julia Benham Hermetz, Dr Alex Leigh