The purpose of this thesis is to review the pharmacology and toxicity of local anaesthetics, particularly highlighting the differences between bupivacaine and ropivacaine and to present an experiment attempting to establish whether ropivacaine is a safer drug, once cardiotoxicity has occurred.

Includes bibliographical references. / The man aim of my studies was to investigate the safety and efficacy of two modes of feedback control of sedation and anaesthesia. A secondary aim was to add to the body of knowledge on the Bispectral Index (BIS). I also wrote a computer program (BISCLAN) that was used in all the studies as a BIS data management tool, and in some studies for manual or automatic control of a propofol infusion. Two studies did not involve feedback control, but were performed to further our understanding of the BIS. For one, I recorded BIS values and the times at which clinical events occurred during 200 general anaesthetics. and studied memory of perioperative events. Broad variation in BIS values at similar levels of anaesthetic depth was found, although there was good separation between the majority of BIS values found during periods of consciousness and unconsciousness. BIS values on awakening were not predictive of memory for subsequent events. For the second study I investigated the effects of the stimuli used lo generate auditory evoked potentials on consciousness levels and the BIS, during sedation and anaesthesia. No effect was found. Three studies of BIS-guided computer control of anaesthesia and sedation were performed. Control performance was assessed in terms of clinical adequacy of anaesthesia and with recognised mathematical criteria. BISCLAN was able to control anaesthesia successfully. Cardiovascular parameters were stable in all patients. With two exceptions, operating conditions were also adequate. Control parameters during sedation and anaesthesia were acceptable and compare favourably with those found in other studies. Two studies of a second mode of feedback control of sedation (patient-maintained sedation) were performed. In both the goal was to determine if system safety was sufficient to prevent volunteers from purposefully inducing loss of consciousness. Sedation scores, propofol concentrations and physiological data were recorded. Secondary data included BIS values, and tests of memory for words. In one study a revised version of a previously developed blood concentration targeted infusion system was used, and in the other an effect-site targeted system. One subject in the second study became over-sedated, but no subjects lost consciousness. There was correlation among BIS values and propofol concentrations, and among BIS and propofol concentrations and the likelihood of memory for words. Several subjects remained conscious during periods when the BIS was < 60.

Background: The maternal haemodynamic responses to vasopressors during spinal anaesthesia for caesarean delivery in patients with severe preeclampsia, have not been accurately described. This study compared the haemodynamic effects of the vasopressors ephedrine and phenylephrine during spinal anaesthesia. Methods: Thirty nine women with treated severe preeclampsia presenting for spinal anaesthesia for caesarean section for a maternal indication, were studied. Baseline maternal haemodynamics were measured in the left lateral position, using minimal invasive cardiac output monitoring (LiDCOrapid). A 300 mL colloid preload was then administered. After standard spinal anaesthesia, 20 patients whose mean arterial pressure decreased to a predetermined target value were randomised to 2 groups of 10, to receive an initial bolus of either 7.5 mg ephedrine or 50 μg phenylephrine, and the haemodynamic responses recorded. The primary outcome was the percentage change in cardiac index. Results: Spinal hypotension in 20 patients was associated with an increase in mean cardiac output from baseline (mean difference 0.7 L/min, p<0.0001). In response to vasopressor, the mean [SD] percentage change in cardiac index was greater, and negative, in patients receiving phenylephrine versus ephedrine (-12 [7.3] vs 2.6 [6] L/min respectively, p=0.0001).] L/min respectively, p=0.0001). Post-vasopressor mean percentage change [SD] in heart rate and systemic vascular resistance (SVR) were higher in patients receiving phenylephrine (-9.1 [3.4] vs 5.3 [12.6], p=0.0027, and 22.3 [7.5] vs -1.9 [10.5] %, p<0.0001 respectively). Conclusions: Phenylephrine effectively reverses spinal anaesthesia-induced haemodynamic changes in severe preeclampsia, if left ventricular function is preserved.

Includes bibliographical references.

Includes bibliographical references. / Patients who undergo a total abdominal hysterectomy (TAH) experience a significant amount of pain postoperatively. Several multimodal pain regimes have been used in the past to manage these women’s pain. Neuraxial anaesthesia is usually not a feasible option in these cases, because of the risks involved. Limited resources with the lack of high care unit beds available when intrathecal opioids are given are also a problem. Effective analgesia includes both improved comfort and decreased opiate side-effects, if morphine requirements can be decreased. After approval from the University of Cape Town Human Research Ethics Committee, the trial was registered with the South African National Clinical Trial Register (DOH-27-0212-3945) and the South African National Human Research Ethics Council. All patients between the ages of 20-65 with an ASA score I-III were included in a prospective double-blind randomised controlled trial after obtaining written informed consent from them the day before their operation. Patients were excluded if they were allergic to any of the trial medication (morphine, bupivacaine), had a history of opioid addiction, coagulation disorders, infection at needle insertion site or were unable to give informed consent. If surgery did not for some reason proceed to a TAH, the patient was also excluded. The patients were visited in the ward the day before their operation to obtain informed consent. All the patients received a patient-controlled analgesia (PCA) pump and this as well as the visual analogue pain scale (VAS) were demonstrated and explained to them. This was done by the same person (principle investigator) for all the patients. Our aim with this double-blind randomised controlled trial was to study the efficacy of ultrasound-guided transversus abdominis plane blocks in patients undergoing total abdominal hysterectomy. We randomly allocated thirty patients to two groups, a transversus abdominis plane block group (n=15) and a placebo group (n=15). The transversus abdominis plane blocks were done with 0.25% bupivacaine. The placebo group received a sham block with normal saline post induction of anaesthesia. All patients received postoperative morphine patient-controlled analgesia. Pain scores and morphine consumption were assessed at 0, 6 and 24 hours postoperatively. Our trial showed a significant between-group difference in morphine requirements (5.2±3.9 vs. 9.7±4.3 mg [p=0.007], and 12.9±8.9 mg vs. 25±12.1 [p=0.006]) for the transversus abdominis plane- compared with placebo group at 6 and 24 hours respectively. There were no significant between-group differences in pain scores. There were no complications associated with any block. Ultrasound-guided transversus abdominis plane block is an effective addition to a multimodal postoperative analgesia regimen for abdominal hysterectomy.

Introduction: Substance abuse has twice the mortality in United States anaesthesia- than non-anaesthesia residents. Since no data exist, the primary objective of this cross-sectional study was to establish the prevalence of substance use in South African anaesthesia practitioners. Secondary objectives were to compare the prevalence in male and female practitioners, and in private- and state practice anaesthetists. Years of experience and level of training were explored as possible risk factors for hazardous or harmful use. Method: Participants completed a self-administered, validated WHO questionnaire, run for ten days surrounding the 2018 South African Society of Anaesthesiologists (SASA) congress. All doctors practicing anaesthesia in South Africa were eligible. Recruitment was via an email link sent to all SASA members, as well as a web-based link at the congress. Results: A total of 1961 SASA members and 113 non-members (anaesthesiologists, registrars and non-specialists) were invited to participate (total 2074). There were 434 responses (response rate 20.9%, margin of error 4.18%); 364 were suitable for analysis. The most commonly lifetime-used substances were alcohol (92.8%), tobacco (42.3%), cannabis (34.7%), and sedatives (34.4%). Questionnaire scores defined low-, medium- and high-risk categories according to substance use during the previous 3 months. Sedative (12.6%) and alcohol (12.1%) users were deemed to be at moderate risk. The prevalence of opioid use was 1.9% (n=7). Prevalence of substance use was similar in male and female practitioners, as well as in those working in private practice or in state hospitals. Conclusion: The prevalence of current use of alcohol and sedatives is of major concern. A significant proportion of respondents were assessed to be at moderate risk of hazardous or harmful substance use. Gender and practice setting have little impact on substance use. Wellness efforts should be aimed at all anaesthesia practitioners in South Africa.

Background: Open AAA repair is a major, high risk surgery and is associated with significant morbidity and mortality. Current literature quotes an overall mortality of ruptured AAA at 85-90%, including those who do not reach the operating theatre. Mortality of elective AAA repairs is 4-8%. Many patients presenting with abdominal aortic aneurysms are elderly and have pre-existing medical conditions, therefore putting them at high risk for numerous post-operative complications, such as acute kidney injury, pulmonary and cardiac complications. These complications lead to potentially increased ICU and hospital stays. Objectives: To the author's knowledge, an audit into the morbidity and mortality at Groote Schuur Hospital has not yet been formally performed. Such a retrospective audit will be useful in establishing where this hospital stands in terms of mortality, as compared with published data from international centres. In terms of morbidity, this research focused on the development of acute kidney injury following AAA repair. Methods: The study design was an observational retrospective file audit, of both emergency and elective open abdominal aortic aneurysm repairs. 90 case reports of operations performed between October 2006 and December 2014 were analysed. The primary outcome measure was the incidence and causes of perioperative (30-day) mortality. The secondary outcome measure was the incidence of acute kidney injury and renal replacement therapy (RRT). We further analysed whether cross-clamp time and anatomical classification of the aneurysm had any effect on the subsequent need for RRT, utilising the Mann-Whitney test. Results: Of the 90 patients, 76.7% were male (n=69). The study population had a mean age of 64.9 years. Overall perioperative (30-day) mortality of both emergency and elective cases was 15 out of 90 cases (16.6%); the mortality for emergency cases was 12 out 31 (38.7%), as compared to 3/59 (5.1%). Seventeen patients (18.9%) developed KDIGO stage 3 AKI, and RRT was instituted in 12 cases (13.3% of all patients); seven patients survived, and no patients were dialysis-dependent on hospital discharge. AKI was not significantly associated with abdominal aortic cross-clamp time (46 minutes vs. 38 minutes, p=0.9021), but was significantly associated with anatomical classification of the aneurysm (supra-/juxtarenal vs. infrarenal, p=0.037). Conclusions: In comparison with research from international centres, this study population was predominantly male, with a similar age profile to that quoted. The bulk of the perioperative mortality was from emergency AAA repairs, with the mortality associated with elective open AAA surgical repair being within the ranges quoted in international literature. Of the patients who received RRT, there was a mortality of 41.6%. There were many limitations in this study, as the population analysed was extremely heterogeneous, owing to the small sample size. There is great potential for further research, especially into the outcomes of open versus endovascular repairs of AAAs.

Includes bibliographical references (leaves 55-59). / Experimentation involving small animals has, over the years, been of major importance in the development of our current understanding of nerve - muscle physiology. This dissertation describes the development of an in vivo model of the rat nerve interface at the Faculty of Health Sciences at the University of Cape Town. Such a model was not previously available to the faculty. The development was the result of collaboration between the Departments of Anaesthesia and Human Biology.

Bibliography: leaves 148-172.

Background: Postoperative critical care support is required for emergency and elective cases having either major surgery, with poor physiological states or significant comorbidities, and for support following unexpected surgical or anaesthetic complications. Research suggests that as many as 48% of all critical care unit (CCU) admissions occur postoperatively, yet limited literature is available regarding the support role that onsite critical care availability provides for surgery. Research into this area is therefore necessary to understand the impact of accessible critical care support, especially in hospitals at regional and district level. Objectives: The objective of this research is to contribute to the literature on perioperative critical care by presenting data quantifying and describing the patients requiring postoperative critical care at New Somerset Hospital (NSH) - a regional hospital in Cape Town, in the Western Province of South Africa. Further to this, the research aims to identify cases that would not have proceeded here if the option of on-site postoperative critical care did not exist. Methods: Data was collected using a prospective survey spanning a six-month period from June 2015 to November 2015. The data represented two sets of patients: 1) every case done, documenting whether they would have proceeded at NSH without the presence of a critical care unit; 2) each admission to a critical care service directly from theatre, describing their indications for admission and their postoperative critical care pathway, interventions and outcomes. Results: A total of 3247 complete cases were included in the analysis. Of the total sample of cases assessed, 66 (2%) were supported by critical care at NSH, of which roughly half (31 cases) would not have proceeded at NSH without availability of a critical care bed. Of these patients, 7 did not have a bed reserved preoperatively, and were not admitted, highlighting an important subgroup of patients: those not admitted to a CCU, but yet received surgery at NSH solely due to the potential of postoperative critical care support there. New admissions amounted to 48 (1.5%) of all cases of which 43 were emergencies, and 14 were unplanned. 45% of admissions required monitoring or epidural care only, for which High Care would have been sufficient, while 55% received cardiorespiratory support. Conclusion: These results confirm that at NSH, an on-site CCU allows for cases to proceed that would otherwise have been transferred elsewhere. Of note, obstetrics accounted for 3 of the unplanned admissions, confirming that a level 2 obstetric service requires critical care support despite treating otherwise low risk patients. This data indicates that critical care plays a beneficial role in supporting a regional theatre service. 6 Further research is required in this field to determine whether these results can be generalised to other regional hospitals. This survey should help as baseline data, especially for studies to better assess quality and outcomes against national and international metrics.