Theses and Dissertations (Anaesthesiology)

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    Clinical prediction models for risk-adjusted outcomes in South African surgical patients
    (University of Pretoria, 2019) Ker, James A.; Biccard, B.M.; hyla.kluyts@smu.ac.za; Kluyts, Hyla-Louise
    Background National clinical data on perioperative care in South Africa are scarce. There is both an urgent need, and the imminent opportunity, to increase the body of evidence necessary to inform on initiatives to improve safety, affordability and access to surgical- and anaesthesia care in this country. Clinical prediction models are a useful way to present factors that predict a specific endpoint, and the relationships of these factors in influencing the endpoint. Such summarised information is important for perioperative clinicians and teams to understand how their circumstances and their practice influence a patient’s outcome after surgery, and how this influence, and the outcome, compare to teams in different circumstances or institutions. Developing clinical prediction models is an exercise in defining and identifying predictors and endpoints that should form part of a core set of measures for research on perioperative care. It is crucial to validate clinical prediction models in settings other than where it was developed before it is implemented. Prediction models may require updating before it can be generalisable. The aim of this thesis is to report on clinical prediction model development in two surgically heterogeneous South African cohorts: i) a public sector cohort; the South African dataset from the African Surgical Outcomes Study (ASOS); and ii) a private sector cohort, from data gathered for the purpose of model development, in patients presenting for elective non-cardiac surgery in a single private hospital. Methods Data from two cohorts of patients that differ with regards to the sample population, and the healthcare sector, were used to develop two separate clinical prediction models. A clinical prediction model with in-hospital mortality as endpoint was developed in the public sector cohort. A prediction model with healthcare resource use as endpoint was developed from a self-assessment questionnaire in the private sector cohort. Using clinical judgement, predictors for the prediction models were identified from univariate regression analysis and subsequent forward stepwise regression techniques. The prediction models were assessed for performance regarding calibration, discrimination and clinical usefulness, and were internally validated by fitting to a bootstrap sample. The prediction model that was developed from the ASOS South Africa cohort was validated in the cohort of patients participating in the South African Surgical Outcomes Study, which is a temporally separate dataset containing data collected in 2014. The possibility of validating the Surgical Outcomes Risk Tool, an established prediction tool, in the ASOS South Africa cohort, was investigated. There is currently no data available for external validation of the prediction model developed in the private sector cohort. Results During prediction model development, important variables (predictors and endpoints) were identified that should form part of a core dataset. The ASOS South Africa prediction model was developed with postoperative in-hospital mortality, censored at thirty days, as the endpoint. The predictors included in the prediction model were largely related to the risk inherent to the urgency, severity and type of surgical procedure. The private sector prediction model was developed with the cost of hospital admission, excluding fees, as endpoint. The predictors included were the type of surgery and predictors defined from patient-reported information. Although both prediction models performed fairly well with regard to calibration, discrimination and clinical usefulness, the prediction models will require validation in cohorts of patients representing a different South African population. It is expected that the prediction models will require adjustment or updating after external validation. The definitions of predictors will also have to be reconsidered when validating these prediction models in cohorts from other settings. Conclusion During the development of the clinical prediction models, predictor definitions were investigated. Variables (predictors and endpoints) should be defined in such a way as to align with international classification systems, since these are used to ‘code’ variables in electronic health information systems to enable aggregation of data. The advantages of external validation of clinical prediction models, and the subsequent prediction model updating, would be: the opportunity to further refine the definitions of candidate predictors to enable international comparisons; the potential to include health economic measures to inform on the cost-effectiveness of surgery; and the chance to define and include patient-reported measures in the core data set. The result may well be that evidence gathered in this way would assist in developing strategies for optimal delivery of perioperative care to the entire South African population. Doctors, and their patients, will have to voluntarily participate in national multicentre research projects to gather evidence on perioperative care in South Africa. One has to consider the additional burden the collection of perioperative data would entail, and how such ‘citizen scientists’ would be motivated to participate.
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    Cardiopulmonary effects of anaesthesia maintained by propofol infusion versus isoflurane inhalation in cheetah (Acinonyx jubatus)
    (University of Pretoria, 2017) Zeiler, Gareth Edward; Tordiffe, Adrian Stephen Wolferstan; roxannebuck88@gmail.com; Buck, Roxanne Kate
    Objective To compare the cardiopulmonary function of cheetahs (Acinonyx jubatus) undergoing propofol total intravenous anaesthesia (TIVA) to isoflurane maintenance in order to evaluate their feasibility for field use. Study design Prospective clinical study Animals 24 adult cheetahs Materials and Methods Cheetahs were immobilised with tiletamine-zolazepam (1.2 mg kg-1) and medetomidine (40 ?g kg-1) intramuscular by darting. A maintenance protocol of propofol TIVA (Group-P) or isoflurane inhalation (Group-I) was randomly assigned to each cheetah. Anaesthesia was maintained for at least 60 minutes. Cheetah breathed spontaneously throughout anaesthesia. Oxygen was supplemented at 3 L minute-1. Cardiopulmonary parameters were recorded at five minute intervals and three arterial blood gas samples analysed. Following maintenance, atipamezole was administered intramuscular (200 ?g kg-1) and recovery observed. Data is reported as mean ±SD; variables over time were compared using a linear mixed model (fixed: time, treatment; random: cheetah). Results Lack of response to manipulations was maintained in all cases (end-tidal isoflurane 1.1 ± 0.1%, propofol infusion rate maintained at 0.1 mg kg-1 minute-1). The heart rate and respiratory rate were 82 ± 10 beats minute-1 and 14 ± 4 breaths minute-1, respectively for both groups overall. The end-tidal carbon dioxide tension increased slowly (to 44.0 ± 5.0 mmHg at the end of maintenance) with no differences between groups. All cheetahs were initially markedly hypertensive (mean arterial pressure (MAP) 163.3 ± 17 mmHg); MAP normalised for Group-I (125 ± 30 mmHg) but remained high for Group-P (161.0 ± 17 mmHg) (p < 0.001). The arterial carbon dioxide tension (48.9 ± 14.6 mmHg) never differed between groups. Recovery time was 10.8 ± 5.0 and 51.9 ± 23.5 minutes for Group-I and Group-P, respectively. Conclusions and clinical relevance Both protocols provided acceptable cardiopulmonary values. Propofol may be an alternative to isoflurane for field use, but the prolonged recovery requires investigation.
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    Ondersoek na die invloed van die narkosetegniek (Ketamien plus Midasolam teenoor Sufentaniel) op breinskade tydens hartoperasies by die mens (Afrikaans)
    (University of Pretoria, 2003) Hugo, Johan M.; Bartel, Peter R.; Vermaak, William J.H.; Smith, Francois Jacobus
    Introduction The neuropsychological deterioration after cardiac surgery involving cardiopulmonary bypass (CPB), is ascribed to brain ischaemia caused by, amongst others, hypotension, cerebral hyperthermia, cerebral embolism, interaction between pharmacological methods and hypothermia during ischaemia, and the directly neurotoxic of anaesthetic drugs. AimTo investigate the effect of the anaesthetic techniques midazolam plus ketamine (MK) or sufentanil (S) on the quantitative EEG (QEEG), reaction time (RT), serum neuron specific enolase (NSE), and serum S-100b protein after cardiac surgery involving CPB in humans. Patients and methodsThe sample consisted of a total of 42 patients scheduled for elective coronary artery bypass (CABG) or valve replacement (VR). All patients were not available for all the postoperative tests. Patients were allocated randomly to group MK or S. Anaesthetic technique: S or MK. Isoflurane was administered when necessary. CPB technique: 30°C, membrane oxygenation, a 40 mm filter in the arterial cannula and a-stat-blood gas management, blood pressure of 50 to 70 mm Hg and a haematocrit > 22%. Patients were weaned from CPB when nasopharyngeal temperature reached a maximum of 37,5°C. QEEG and RT was performed 1 to 2 days preoperatively and 5 to 6 days postoperatively.Serum-NSE and -S-100b protein were measured preoperatively, 2 minutes after going on CPB, after rewarming to 37°C, just before the end of CPB and 2, 4, 10, 20, 30, and 48 hours after CPB. ResultsQEEG: The most noticable finding was an increase in slow wave activity (relative q and s). The QEEG outcome was better after CABG than after VR (p < 0,001), but not different between MK and S (p = 0,5000). Dq% was better with MK than S (p = 0,0120). Dq% (p = 0,0010), Da/q% (p = 0,0090) and DPS% (p = 0,0025) was better after CABG than VR. Reaction time: There was a significant deterioration in 5/18 (27,78%) of MK and 12/18 (66,67%) of S (p = 0,0220). The change in accuracy in sequential reation time 1 (p = 0,0100), and sequential reation time 2 (p = 0,0970) and the cumulative accuracy was better with MK than S(p = 0,0020). Chemical markers: Over groups 14,8% of patients had a poor NSE and 61,9% a poor S-100b outcome. Within groups a poor NSE outcome was found in 14,8% of MK and 14,8% of S (p = 1,0000), and 4,8% of CABG but 23,8% of VR (p = 0,1840). Within groups as adverse S-100b outcome was found in 42,9% of MK but 81,0% van S (p = 0,0250; Fisher's exact test), and 66,7% of CABG and 57,1% of KV (p = 0,7510. According to area under the curve of corrected NSE, CABG had a better outcome than VR (p = 0,0040). According to both maximum S-100b level and the area under the curve of S-100b, an interaction occurred between the anaesthetic technique and the procedure, with VR doing better with MK while CABG did significantly better with S (p = 0,0180 en 0,0040 respectively). Conclusion, shortcomings, significance and contribution This study has shown that, in as far as brain damage is concerned, the outcome was probably better with MK than with S, and CABG better than VR. An interaction was found between the anaesthetic technique and the type of operation.
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    Is the absorption of anaesthetic agents non linear?
    (University of Pretoria, 2005-09-22) Hugo, Johan M.; upetd@up.ac.za; Steyn, Johan Daniel
    Knowledge of the absorption of inhalation anaesthetic agents is essential if one is to safely administer them. Despite many years of research in linear science, no model has been described that can reliably predict inhalation agent uptake. To date no published investigation has looked for non¬linearity in the absorption process. The aim if this research project was to determine if the absorption of anaesthetic agents is non-linear, using isoflurane and enflurane as examples. To detect non-linearity, four conditions must be met:
    • Sensitivity to initial conditions,
    • Fractal Dimension of the attract or,
    • Invariant probability distribution of the attractor, and
    • Detection of an underlying dynamical process.
    Ten measured time series for both isoflurane and enflurane absorption were measured. These were then compared with ten noise signals, with similar standard deviations, means and number of points in the series. Calculated Lyapunov exponents tested sensitivity to initial conditions. The dimension of the attractor was calculated using the following statistics, each giving an approximation of the fractal dimension. Approximate entropy, information entropy, correlation dimension and fractal dimension (box counting method). The Invariant probability distribution of the attractor was tested for using non-linear forecasting. Detection of an underlying dynamical process was determined by the method of surrogate data. Each of the four conditions required have been met with statistical significance ( p< 0.05) and acceptable statistical power (>0.8). It is therefore concluded that the absorption of both isoflurane and enflurane are non-linear processes. The implications and implementations in anaesthesia practice are discussed.
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    The effect of music after hip or knee replacement on morphine consumption
    (University of Pretoria, 2010-08-23) Smith, Francois Jacobus; dwaynemohr@gmail.com; Mohr, Dwayne
    Introduction Alternative medicine has been employed in the treatment of several diseases. Listening to music after minor surgery has been beneficial regarding pain control. Aim The aim of this study was to determine the effect of music on intravenous patient-controlled (PCA) morphine consumption after hip or knee replacement. Methods This was an open label, randomized controlled trial. Forty (twenty per group) consecutive patients scheduled for arthroplasty were included. A standardized anaesthetic technique was used, consisting of propofol, sufentanil, rocuronium, and isoflurane. Postoperatively patients were allocated to one of two groups: Group M listened to music during the first 24 postoperative hours, while Group C did not listen to music. The PCA dose consisted of morphine 1.5 mg and droperidol 83.3 ìg with a lockout time on seven minutes. Rescue doses of morphine 15 ìg/kg intravenously every one-minute until the patient was pain free was administered by a nurse according to a visual descriptive pain score. Both groups received paracetamol 1 g intravenously six hourly. After 24 hours the total (PCA plus rescue) morphine dose was recorded. Morphine consumption in groups was analysed using the one-sided Student two-sample t test. The significance level was 0.05 and the power 0.95. Results Neither the PCA usage (p = 0.4138) nor the rescue doses of morphine (p = 0.9163) differed significantly between the groups. Conclusion Although a statistical difference could not be shown in this study, music during the postoperative period does offer a pleasant distraction from this overall undesirable experience. AFRIKAANS : Inleiding Alternatiewe medisyne word dikwels gebruik vir die hantering van verskeie siektetoestande. Daar is al aangetoon dat deur na musiek te luister voordelig is na geringer chirurgie ten opsigte van pynbeheer. Doel Die studie het ten doel gehad om die effek van musiek na heup- of knievervanging op intraveneuse pasiënt- beheerde morfienverbruik (PBA) te bepaal. Metodes Hierdie was ʼn enkel-blinde gerandomiseerde gekontroleerde studie. Veertig (twintig per groep) agtereenvolgende pasiënte geskeduleer vir gewrigsvervanging is by die studie ingesluit. ʼn Standaard narkosetegniek is gebruik, bestaande uit propofol, sufentaniel, rokuronium en isofluraan. Die pasiënte is postoperatief aan een van twee groepe toegedeel: Groep M het gedurende die eerste postoperatiewe 24 uur na musiek geluister terwyl Groep K nie na musiek geluister het nie. Die PBA-dosis het bestaan uit morfien 1.5 mg en droperidol 83.3 μg met ‘n uitsluitingstyd van sewe minute. Addisionele dosisse morfien is toegelaat. Dit is intraveneus deur die verpleegkundige volgens ʼn verbaal beskrewe pynskaal toegedien en het bestaan uit 15 μg/kg IV elke een minuut totdat die pasiënt volgens haar oordeel pynvry was. Beide groepe het ook sesuurliks parasetamol 1 g intraveneus ontvang. Vier en twintig uur na die operasie is die totale morfienverbruik (PBA plus bykomende dosisse) aangeteken. Die morfienverbruik in groepe is geanaliseer met behulp van die eenkantige tweesteekproef-t-toets. Die beduidenheidspeil was 0.05 en die onderskeidingsvermoë 0.90. Resultate Daar was tussen groepe geen beduidende verskil ten opsigte van die PBA (p = 0.4138) en die bykomende dosisse (p = 0.9613) morfien nie. Gevolgtrekking Alhoewel daar geen statisties beduidende verskil tussen groepe aangetoon is nie, bied musiek gedurende die postoperatiewe fase ʼn aangename afleiding van die andersins onaangename ondervinding. Copyright