This thesis examines several intra-operative physiological variables which may indicate the adequacy of global oxygenation in patients undergoing major abdominal surgery. Near infra-red spectroscopy is a non-invasive method to determine tissue oxygenation based on the varying light absorption properties of oxygenated and non-oxygenated substances, such as haemoglobin. This technique was used to assess the changes in oxygen saturation of the thenar muscle (St02) in response to a vascular occlusion test (VOT) of the arm where arteriovenous stasis is achieved using a pneumatic cuff for a pre- determined period of time. Intra-operative St02 monitoring was also undertaken during surgery. Results were obtained from 20 patients who underwent major non-laparoscopic colorectal surgery. The VOT related St02 profile was different between patients who exhibited complications, determined using a modified version of the post-operative morbidity survey (POMS), and those who did not. In addition, a lower median intraoperative St02 was associated with post-operative complications. Microdialysis, an in vivo tissue sampling technique, was used to study the metabolic changes in the lumen of the colon during colorectal surgery. A number of luminal metabolites were related to oxygen delivery index suggesting a link between large bowel metabolism and global oxygenation. Central venous saturation (Scy02) reflects the balance between oxygen delivery and demand with a number of studies supporting its use as a therapeutic haemodynamic target. This variable was measured intra-operatively and examined in relation to oxygen delivery and post-operative outcome. In the 64 patients studied, no relationship between oxygen delivery index and SCV02 was found and intraoperative Scy02 was not associated with post-operative outcome.

The aims of this thesis were: 1. To investigate the changes in reactive oxygen intermediates (ROIs) and that of neutrophil activation during liver transplantation with emphasis on assessing their role on reperfusion injury and outcome of graft function. 2. To ascertain the place of indocyanine green clearance (ICG) test in early prediction and assessment of graft function after liver transplantation. 3. To evaluate the role played by two major vasoactive mediators in the development of the haemodynamic changes which often occur following graft reperfusion in liver transplantation. These are: the endothelins; the most potent biological smooth muscle vasoconstrictors, and guanosine 3', 5'-cyclic mono-phosphate (cGMP); the secondary messenger of nitric oxide (NO) and atrial natriuretic peptide (ANP) which mediates vasorelaxation. This thesis has provided evidence of increasing ROIs activity following reperfusion of liver grafts and the magnitude of changes correlated with the severity of graft dysfunction. It also demonstrated that a significant degree of neutrophil activation occurs following graft reperfusion with evidence of endothelial cell damage as a result of such activity. This thesis has shown that an ICG clearance <200ml/min measured within 24 hrs following liver transplantation predicted graft dysfunction due to reperfusion injury with high specificity and sensitivity. Finally this thesis has demonstrated that the haemodynamic changes following reperfusion of liver graft during transplantation involve predominantly the pulmonary vasculature. It also demonstrates that these changes correlated significantly with a reduction in the levels of cGMP, which suggests a causal relationship. The endothelins levels in blood were raised before transplantation and remained so post-reperfusion, with no evidence of a role to play in the haemodynamic changes during transplantation.

Coagulation studies were performed in a series of 24 patients with asymptomatic abdominal aortic aneurysm. Levels of fibrinogen were high but within the normal range, and there was no evidence of systemic activation of the soluble coagulation or fibrinolytic systems. Coagulation studies were performed in a series of six patients undergoing elective aortic aneurysm repair. It was found that thrombin, fibrinolytic and platelet activation increases during the period of initial dissection in a time dependent manner. After the administration of heparin and the application of the aortic cross clamp, thrombin, fibrinolytic and platelet activation reduced. After reperfusion there was an increase in platelet activation which correlated with the duration of cross-clamping. Coagulation studies were performed in a series of 22 patients presenting with ruptured aortic aneurysm. At time of admission there was marked activation of platelets and thrombin in all patients which increased greatly by the end of operation. Platelet count at the end of operation was significantly lower in patients who died than in survivors. Samples of subcutaneous fat and skeletal muscle were taken at the start of operation in six patients with ruptured aneurysm. Transmission electron microscopy was used to examine the endothelial cells in small vessels in these samples. When compared with samples from six control patients undergoing elective aortic surgery it was found that there were significant ultrastructural differences in the endothelial cells from patients with rupture. A randomised controlled study of fibrin sealant as a topical haemostatic agent at vascular anastomoses was carried out in 57 patients undergoing aortic aneurysm repair, carotid endarterectomy or arterial bypass graft using polytetrafluoroethylene bypass graft. The time taken to achieve haemostasis at the anastomoses was significantly reduced in patients treated with fibrin sealant. The reduction was most marked in patients undergoing carotid endarterectomy.

Between 30 - 50% of patients undergoing surgery suffer from post-operative nausea and vomiting which may be associated with pulmonary aspiration, and fluid and electrolyte imbalance. This thesis has explored the upper gastrointestinal motor associated with nausea and vomiting in peri-operative patients. Specific objectives were: 1. Evaluation of motor disturbances in the upper gastrointestinal tract associated with emesis in the first 24 hours following surgery; 2. Development of a novel computerised method for recognition and measurement motor abnormalities associated with emesis; 3. Investigation of intragastric pH changes associated with bile shifts and bile vomiting; 4. Evaluation of the effects of specific antiemetic therapy and laparoscopic surgery on upper gastrointestinal dysmotility following cholecystectomy; and 5. Investigation of the contribution of opiate analgesia to symptoms and motor disturbances associated with post-operative vomiting. In a human model of emesis, we have shown the presence of small bowel phasic bursts which migrate in a retrograde fashion. These retrograde phasic bursts are significantly associated with vomiting episodes. Such motor abnormalities can be measured by a novel computer programme during prolonged ambulatory recordings. During the post-operative period gastric pH rises, possibly as a consequence of enterogastric flow of bile and subsequently falls when vomiting occurs. The potent 5HT3 receptor antagonist antiemetic, ondansetron, ameliorates post-operative nausea and vomiting symptoms and is associated with a reduction in retrograde activity in the small bowel. Morphine, when given to healthy volunteers, induced similar motor patterns to those observed during post-operative emesis. Emesis in volunteers was also associated with retrograde small bowel phasic activity. This motor response to opiates may contribute to post-operative nausea and vomiting.

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In surgical procedures for femoral shaft fracture treatment, current techniques for locking the distal end of intramedullary nails, using two screws, rely heavily on the use of two-dimensional X-ray images to guide three-dimensional bone drilling processes. Therefore, a large number of X-ray images are required, as the surgeon uses his/her skills and experience to locate the distal hole axes on the intramedullary nail. The long-term effects of X-ray radiation and their relation to different types of cancer still remain uncertain. Therefore, there is a need to develop a surgical technique that can limit the use of X-rays during the distal locking procedure. A Robotic-Assisted Orthopaedic Surgery System has been developed at Loughborough University named Loughborough Orthopaedic Assistant System (LOAS) to assist orthopaedic surgeons during distal-locking of intramedullary nails. It uses a calibration frame and a C-arm X-ray unit. The system simplifies the current approach as it uses only two near-orthogonal X-ray images to determine the drilling trajectory of the distal-locking holes, thereby considerably reducing irradiation to both the surgeon and patient. The LOAS differs from existing computer-assisted orthopaedic surgery systems, as it eliminates the need for optical tracking equipment which tends to clutter the operating theatre environment and requires care in maintaining the line of sight. Additionally use of optical tracking equipment makes such systems an expensive method for surgical guidance in distal-locking of intramedullary nails. This study is specifically concerned with the improvements of the existing system.

This thesis is concerned with the measurement of changes in the circulation during the period of surgery. A loss of albumin from the circulation is to be expected from observations and experiments made in the postoperative period. In this thesis a sensitive measurement technique is described which allows extravasation of albumin to be studied in patients undergoing elective surgery. Radio-isotope labelled albumin and radio-isotope labelled red cells are injected; the ratio between the two is not affected by blood loss or infusion and the ratio is therefore used as a measure of albumin extravasation. To measure the relative loss of albumin from the circulation the isotopes were administered some days prior to surgery to allow distribution and equilibration of the albumin. To measure the rate of loss of albumin (capillary permeability) the isotopes were administered at the time of surgery. The results indicate that major surgery under general anaesthesia is accompanied by a loss of albumin from the circulation, an increased capillary permeability to albumin and a fall in plasma volume that is greater than can be explained on the basis of blood loss and greater than would be expected on the basis of the reduction in red cell volume. The results suggest that patients who receive only glucose and salt solutions intravenously during major surgery will usually suffer a contraction in their blood volumes unless unacceptably large volumes of fluid are infused.