Three clinical investigations together with a combined editorial and review of the cardiovascular physiology of spinal anaesthesia in normal and preeclamptic pregnancy form the basis of a thesis to be submitted for the degree of Doctor of Medicine at the University of St Andrews. First, the longstanding consensus that spinal anaesthesia could cause severe hypotension in severe preeclampsia was examined using three approaches. The doses of ephedrine required to maintain systolic blood pressure above predetermined limits were first compared in spinal versus epidural anaesthesia. The doses of ephedrine required were then similarly studied during spinal anaesthesia in preeclamptic versus normal control subjects. The principal outcome of these studies, that preeclamptic patients were resistant to hypotension after a spinal anaesthetic, was then further investigated by studying pulse transit time (PTT) changes in normal versus preeclamptic pregnancy. PTT was explored both as beat-to-beat monitor of cardiovascular function and also as an indicator of changes in arterial stiffness. The cardiovascular physiology of obstetric spinal anaesthesia was then reviewed in the light of the three clinical investigations, developments in reproductive vascular biology and the regulation of venous capacitance. It is argued that the theory of a role for vena caval compression as the single cause of spinal anaesthetic induced hypotension in obstetrics should be revised.

Please read the abstract in the dissertation. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Clinical Epidemiology / unrestricted

Thesis (M.Med. ( Anaesthesiology)) --University of Limpopo (Medunsa Campus), 2011 / Introduction: Multiple studies have described a variable incidence of transient hearing loss (hypoacousis) from 0.4% to 40% after subarachnoid block, especially in the low-frequencies range (125 – 500 Hz) (1, 2). The mechanism of transient hypoacousis is attributed to leakage of cerebrospinal fluid, which leads to a decrease in perilymph pressure within the cochlear. Hypothesis: The study hypothesis was based on an assumption that hearing loss is more frequent in young patients who undergo spinal anaesthesia in comparison with elderly patients. Objective: 1) To determine the incidence of hearing loss after spinal anaesthesia in the young versus elderly patients. Materials and Methods: Ninety-eight male patients (ASA 1 - 11) scheduled for cystoscopy under spinal anaesthesia were recruited for the study. Recruitment of patients for the study was age dependent and was divided into two groups: One group (49 patients) had patients aged between 17 and 44 years (Group Y) and the other group had 49 patients aged between 45 and 77 years made up group two (GROUP E). Subarachnoid injection at L3-4 was performed using a standard 22-gauge Quincke spinal needle with patients in the sitting position and 2,5 ml to 3 ml of 0.5% isobaric bupivacaine was administered. Patients were evaluated on the day before spinal anaesthesia by pure tone audiometry at three different frequency sounds viz. 125 – 500 Hz (Low frequency), 500 – 2000 Hz (Speech frequency) and at 2000 – 4000 Hz (High frequency). This assessment was repeated 48 hours after the spinal block was given Statistical Analysis: Analysis was descriptive providing information on the mean (or median) and standard deviation of the variables for each of the two groups. The results of the audiometry were analyzed using repeated measures analysis of variance and transformation to p-value. Differences in outcomes of the study between the two groups were recorded as being statistically significant if p-value is ≤ 0.05. Results: No patient from the two groups developed hearing loss either at low or high frequencies. However, there was a statistically significant improvement in audiometric results (p-value ranging from 0.0001 and 0.063) 48 hours post-surgery in the elderly group as compared with patients in the younger group. Conclusion: The study revealed no hearing loss post-spinal anaesthesia in both groups. It did, however, show that the elderly group have better hearing acuity at all three frequency levels of sound compared to the younger group after spinal anaesthesia

Activation of spinal N-methyl-D-aspartate (NMDA) receptors stimulates cyclooxygenase and nitric oxide pathways. Compounds that block the activity of these NMDA receptor systems reduce pain hypersensitivity. However, their usefulness is limited by the side effects they produce. One way of reducing side effects is by combining drugs that produce the same overt effect by different mechanisms, which hopefully increase the net effect. In these series of studies, drugs that interact with NMDA receptor systems and their combinations were screened in vitro to identify spinal antinociceptive synergistic combinations that could be assessed in vivo. Based on developmental changes in thresholds, conduction velocities and blocking actions of the local anaesthetic lignocaine in neonatal rat L4/L5 dorsal root potentials, it was decided to use spinal cord in vitro preparation from 5- to 7-day-old rat pups. In single drug studies, the NMDA receptor channel blocker ketamine (1-50 µM) and the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (200-600 µM), but not the NSAID salicylate (1000 µM) and the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 1-100 µM), reduced spinal NMDA receptor-mediated transmission. Ketamine also depressed non-NMDA receptor-mediated transmission. Using isobolographic and composite additive line analyses, fixed-ratio combinations of ketamine and ketoprofen, ketamine and L-NAME, and ketopofen and L-NAME synergistically depressed NMDA receptor-mediated transmission. The two former combinations had a subadditive effect on non-NMDA receptor-mediated transmission, and the latter had no significant effect. These studies identified that all combinations synergistically reduced both nociceptive transmission and potential side effects. In free-moving sheep implanted with indwelling cervical intrathecal catheters, 100 µ1 subdural administration of ketamine (25-400 µM) and ketoprofen (200-3200 µM) alone and in a fixed-ratio combination (873.95-3350.78 µM, 0.045:0.955) did not raise nociceptive thresholds as assessed by mechanical stimulation of one foreleg. Subdural administration of NMDA (2 mM) decreased mechanical nociceptive thresholds, and this was prevented by the highest concentrations of ketamine and ketoprofen alone and in combination. These findings demonstrated that NMDA receptor channel blockers and NSAIDs alone or in combination had no direct hypoalgesic effects when given onto the spinal cord of sheep, but they prevented NMDA-induced pain hypersensitivity. Simultaneous blockade of NMDA receptor systems could have important clinical implications.

Survey on maternal satisfaction in receiving spinal anesthesia for Cesarean section / A quantitative descriptive and cross-sectional study was conducted. The purpose of the study was to evaluate the maternal satisfaction after the experience of spinal anaesthesia for Caesarean section in one public hospital of Gauteng Province in South Africa. Data were collected by administering a questionnaire which included the demographic profile and satisfaction score in terms of perioperative elements to 82 women in their postoperative period. Analysis of data was performed by The Statistical Package for the Social Sciences (SPSS) version 13 and Excel 2010 was used for tabular and graphical illustrations. The findings revealed that the majority of women studied were black (95,1%), not married (73,2%) and unemployed (64,6%). The levels of maternal satisfaction in terms of intraoperative, postoperative and other perioperative elements were high, at 94,4%, 90,3% and 85,4% respectively. The lowest percentage (76,8%) was found for the maternal satisfaction about the preoperative explanation. The overall level of maternal satisfaction in this study was 86,7%. The majority of women (82,9%) would opt for spinal anaesthesia in future, while 6,1% would not accept it and 11,0% were not sure if they would opt for it or not. / Health Studies / M.A. (Public Health)

Survey on maternal satisfaction in receiving spinal anesthesia for Cesarean section / A quantitative descriptive and cross-sectional study was conducted. The purpose of the study was to evaluate the maternal satisfaction after the experience of spinal anaesthesia for Caesarean section in one public hospital of Gauteng Province in South Africa. Data were collected by administering a questionnaire which included the demographic profile and satisfaction score in terms of perioperative elements to 82 women in their postoperative period. Analysis of data was performed by The Statistical Package for the Social Sciences (SPSS) version 13 and Excel 2010 was used for tabular and graphical illustrations. The findings revealed that the majority of women studied were black (95,1%), not married (73,2%) and unemployed (64,6%). The levels of maternal satisfaction in terms of intraoperative, postoperative and other perioperative elements were high, at 94,4%, 90,3% and 85,4% respectively. The lowest percentage (76,8%) was found for the maternal satisfaction about the preoperative explanation. The overall level of maternal satisfaction in this study was 86,7%. The majority of women (82,9%) would opt for spinal anaesthesia in future, while 6,1% would not accept it and 11,0% were not sure if they would opt for it or not. / Health Studies / M. A. (Public Health)