Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 4 uppsatser.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine Johannesburg, 2017 / Background: Infections post cardiac surgery can have potentially devastating consequences. Adequate antimicrobial prophylaxis is therefore crucial to limit the occurrence of such complications. Cefazolin is a commonly prescribed prophylactic agent for major cardiac surgery requiring cardiopulmonary bypass (CPB). The effects of CPB on the pharmacokinetic profile of cefazolin are largely unknown. To date there is no published work determining the optimal bolus dosing of cefazolin required to achieve acceptable concentrations intra-operatively during and post CPB. Aim: The aim of this study was to describe the total serum cefazolin levels during elective valve replacement surgery on CPB at CMJAH. Method: A prospective, contextual, descriptive design was used in this study. Cefazolin plasma concentrations were analysed at specific pre-determined time intervals in adults patients scheduled for elective valve replacement surgery. Convenience sampling was used. Results: Sixteen patients were enrolled in the study with equal number of males and females, ranging from 18 years to 59 years of age and with a mean BMI of 28.2 kg/m² (range of 18.1 to 40.2 kg/m²). The mean trough for the unbound concentration of cefazolin was 5.02 μg/ml (range of 2.79 to 10.35 μg/ml). For 5 out of the 16 patients (31.25%) the targeted therapeutic goal of time above MIC (4 μg/ml) of 100% (T > MIC 100%) was not achieved. Seven corresponding pre and post CPB serum samples (A1-A7) were statistically analysed using the paired t-test. The results indicated no statistically significant differences between samples A1-A5 (p = 0.11, 0.34, 0.46, 0.32 and 0.98 respectively). There was a statistically significant difference between the samples A6 and A7 (p = 0.024 and 0.025), however, the clinical significance of these small differences is questionable. Conclusion: Surgical site infections not only result in significant morbidity and mortality but also lead to an increased financial burden to the country’s economy. This study has shown that potentially 31.25% of the patients undergoing cardiac surgery may have an increased risk of acquiring infections due to sub-optimal levels of prophylactic antibiotic during the surgery. In addition, the findings point towards no sequestration of cefazolin in the CPB circuits. / MT2017

No description available.

Diss. (sammanfattning) Umeå : Univ., 2003. / Härtill 4 uppsatser.

Submitted in fulfilment of the Degree of Doctor of Technology: Clinical Technology, Durban University of Technology, 2009. / INTRODUCTION: The role of modified ultrafiltration (MUF) in removing inflammatory mediators, reducing the need for homologous donor blood and decreasing pulmonary vascular resistance after cardiopulmonary bypass (CPB) has already been established. Different types of MUF systems evaluated illustrated that none of the MUF techniques adhered to the normal venous to arterial blood flow dynamics. OBJECTIVES: This experimental study compared a conventional arteriovenous modified ultrafiltration (AVMUF) system to a custom designed venoarterial modified ultrafiltration (VAMUF) system. This technique of VAMUF was designed to mimic the pro-grade flow pattern of the body and cardiopulmonary bypass circuit as compared to the conventional retrograde AVMUF systems. METHODS: Sixty patients that underwent MUF were divided into two groups, the AVMUF (n = 30) and the VAMUF (n=30) groups. Modified ultrafiltration was performed for a mean time of 12 minutes in both groups. In AVMUF blood was removed from the aorta, haemoconcentrated and infused into the right atrium (RA). In VAMUF blood flow was from the RA through a haemoconcentrator and re-infused into the aorta. RESULTS: There was no significant difference in any of the demographic variables, CPB or crossclamping time. Results showed significant difference in the ventilation times, with the VAMUF requiring a shorter ventilation time than the AVMUF group. Intensive care unit (ICU) stay, Hospital stay and discharge days were all significantly lower in the VAMUF group as well. The VAMUF also showed a lower percentage fluid balance than the AVMUF. The systolic and mean blood pressure was significantly higher after VAMUF with a decrease in heart rate, and central venous pressure (CVP). The VAMUF group showed a significantly greater decrease of Creatinine, serum lactacte and uric acid over time with no significant differences in oximetry. CONCLUSION: Results prove that VAMUF is more effective compared to the conventional AVMUF regarding the haemodynamics and clinical parameters of the patient and is more physiological with regards to blood flow dynamics. The VAMUF is, therefore, a more physiological technique than AVMUF.

No description available.

There is significant variation between individual patients in the magnitude and pattern of their systemic response to cardiac surgery. Poor outcomes in these patients have been associated with a dysfunctional host response. This thesis seeks to define such variability at the level of gene expression by sequential analysis of transcription before and after surgery for a low risk group of patients undergoing elective cardiac surgery and cardiopulmonary bypass (CPB) patients using expression microarray profiling. To that aim, we analysed sequential global gene expression patterns in circulating peripheral blood leukocytes. We also investigated the role of DNA sequence variation in modulating the observed changes in gene expression. This approach allowed us to identify important genetic modulators and novel biological pathways and gain new insights into the mechanisms that regulate the host response to surgery.

Coronary Artery Bypass Grafting (CABG) is an effective and invasive cardiac surgery to salvage blocked coronary artery. Cardiopulmonary bypass (CPB) is usually applied to support circulation during temporary cardiac arrest. Studies have demonstrated that cardiac injury, inflammation, and oxidative stress could be induced during CABG with CPB. We conducted two studies to investigate the release of cardiac biochemical markers and inflammatory response as well as to compare the effect of different coating biomaterial of CPB on the induction of inflammation and oxidative stress during CPB. We investigated the release patterns and the serum levels of cardiac markers as well as inflammatory markers in patients undergoing elective CABG at different time points after initiation of CPB. In this study, we demonstrated that cardiac markers such as creatine kinase isoenzyme MB (CK-MB), and cardiac troponin I (cTnI) and inflammatory markers such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were highly elevated after CPB. Moreover, we confirmed that cTnI is still a better biochemical marker for cardiac injury than others following CABG with CPB. Other nonspecific but highly sensitive markers such as lactate dehydrogenase (LDH), lactate, TNF-alpha, IL-6, and hsCRP could be potential surrogate markers for evaluation of cardiac injury following CPB. Based on these findings, we conducted a further investigation to demonstrate our hypothesis that different biocompatible materials used in CPB may affect the inflammation and oxidative stress differently. Biocompatible materials are thinly coated on CPB tubes to provide similar environment like endothelial cells during cardiac surgery. There are several biocompatible materials available in the market. Each of them has unique characteristics. Inflammatory response is one of the bodys fundamental defense mechanisms against foreign invaders. However, inappropriate or excessive response can lead to harmful, potentially life-threatening consequences due to severe inflammatory tissue destruction. CPB-induced inflammatory response can be one of the factors, which can affect surgical outcomes. Depending on the presence of different biocompatible materials in CPB circuits, the degree of immunoreactions can be varied. In this study, we analyzed hsCRP, an acute phase protein, and tau protein, a marker of neurocognitive deficiency. Furthermore we analyzed inflammatory cytokines including TNF-alpha, IL-6, IL-10, and interferon-gamma (IFN-gamma) to evaluate the levels of inflammation. Serum levels of oxidized nitric oxide as a marker of oxidative stress were also assessed. We demonstrated that different biocompatible material has different impacts on inflammation and oxidative stress. In the aspect of anti-inflammation, heparin-coated biocompatible material is better than others whereas surface-modifying additives biocompatible material is worse than others. Overall, different coating biomaterial of CPB results in various inflammatory response. In terms of oxidative stress, we did not observe significant difference between different biomaterial-coated CPB.

Coronary Artery Bypass Grafting (CABG) is an effective and invasive cardiac surgery to salvage blocked coronary artery. Cardiopulmonary bypass (CPB) is usually applied to support circulation during temporary cardiac arrest. Studies have demonstrated that cardiac injury, inflammation, and oxidative stress could be induced during CABG with CPB. We conducted two studies to investigate the release of cardiac biochemical markers and inflammatory response as well as to compare the effect of different coating biomaterial of CPB on the induction of inflammation and oxidative stress during CPB. We investigated the release patterns and the serum levels of cardiac markers as well as inflammatory markers in patients undergoing elective CABG at different time points after initiation of CPB. In this study, we demonstrated that cardiac markers such as creatine kinase isoenzyme MB (CK-MB), and cardiac troponin I (cTnI) and inflammatory markers such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were highly elevated after CPB. Moreover, we confirmed that cTnI is still a better biochemical marker for cardiac injury than others following CABG with CPB. Other nonspecific but highly sensitive markers such as lactate dehydrogenase (LDH), lactate, TNF-alpha, IL-6, and hsCRP could be potential surrogate markers for evaluation of cardiac injury following CPB. Based on these findings, we conducted a further investigation to demonstrate our hypothesis that different biocompatible materials used in CPB may affect the inflammation and oxidative stress differently. Biocompatible materials are thinly coated on CPB tubes to provide similar environment like endothelial cells during cardiac surgery. There are several biocompatible materials available in the market. Each of them has unique characteristics. Inflammatory response is one of the bodys fundamental defense mechanisms against foreign invaders. However, inappropriate or excessive response can lead to harmful, potentially life-threatening consequences due to severe inflammatory tissue destruction. CPB-induced inflammatory response can be one of the factors, which can affect surgical outcomes. Depending on the presence of different biocompatible materials in CPB circuits, the degree of immunoreactions can be varied. In this study, we analyzed hsCRP, an acute phase protein, and tau protein, a marker of neurocognitive deficiency. Furthermore we analyzed inflammatory cytokines including TNF-alpha, IL-6, IL-10, and interferon-gamma (IFN-gamma) to evaluate the levels of inflammation. Serum levels of oxidized nitric oxide as a marker of oxidative stress were also assessed. We demonstrated that different biocompatible material has different impacts on inflammation and oxidative stress. In the aspect of anti-inflammation, heparin-coated biocompatible material is better than others whereas surface-modifying additives biocompatible material is worse than others. Overall, different coating biomaterial of CPB results in various inflammatory response. In terms of oxidative stress, we did not observe significant difference between different biomaterial-coated CPB.

Thesis (Ph.D.)--University of Western Australia, 2003.