The patient-important outcomes of cardiac and non-cardiac surgery are well-recognized but poorly understood. The causes of major morbidity and mortality in patients undergoing non-cardiac are not known. This is not the case in cardiac surgery, which is provided to a homogenous patient population that has been well-described through clinical registries. Recent improvements to the care of cardiac surgical patients have led to dramatic decreases in major morbidity and mortality. However, neurocognitive and functional impairments after cardiac surgery remain the most feared by patients and least understood by clinicians. This thesis comprises 6 chapters that inform these knowledge gaps and establish the basis upon which future research will be based. Chapter 1 is an introduction providing the rationale for conducting each of the included studies. Chapter 2 reports the VISION Mortality study, which explores the relationship between major complications and death within 30-days of undergoing inpatient, noncardiac surgery. Chapter 3 reports a study validating the use of the Standardized Assessment of Global activities in the Elderly (SAGE) scale in patients undergoing cardiac surgery. Chapter 4 presents a pilot observational study that establishes the feasibility of conducting a large, prospective cohort study to determine the relationship between decreases in cerebral saturation during cardiac surgery and postoperative functional decline. Chapter 5 presents a pilot study conducted to inform the feasibility of a large, randomized cluster crossover trial examining whether an institutional policy of restricted benzodiazepine administration during cardiac surgery (compared to liberal administration) would reduce delirium after cardiac surgery. Chapter 6 discusses the conclusions, limitations, and implications of the research presented in this PhD thesis. / Thesis / Candidate in Philosophy

Aortic homograft valves are the preferred choice of replacement valve in aortic valve replacement procedures. The major drawback to their use is their availability. This project addressed two of the methods by which availability can be increased by assessing mechanical properties of the valves. Most pre-operative methods that assess homograft valve post-operative functional ability use biochemical or histological protocols. Rarely is their mechanical ability to sustain the pressure across them tested. Uniaxial tensile tests were performed on radial and circumferential leaflet sections from human and porcine aortic and pulmonary valves. The pulmonary valve has very similar anatomy to the aortic valve, although it is thinner and there is less pressure across it in vivo. When a patients own pulmonary valve is used to replace their aortic (their pulmonary valve is replaced with an aortic homograft), good post-operative results are achieved. The aim of this study was to see if pulmonary homografts would be able to sustain aortic pressures. It is concluded that pulmonary leaflet specimens have comparable mechanical characteristics to aortic and should therefore be suitable for aortic valve replacement. This would double the number of valves available for surgeons to use during valve replacements. Porcine aortic specimens were found to be stiffer and fail at higher stresses than the other valve types. The results from the porcine pulmonary specimen properties indicated that bioprosthetic valve manufacturers can consider their use in bioprosthetic valve manufacture as they are more than able to cope with human aortic valve pressures. Some storage methods have been assigned short duration or 'sell-by' dates, with no evidence that the mechanical integrity of the tissues has been significantly compromised. Currently retrospective studies are used to assess whether the treatments are detrimental to the tissues; the post-operative durability being taken as the indicator! If the storage times can be extended then the number of valves available to surgeons would increase. Four treatments of valves used for storage were tested over three months and their effect on leaflet specimen tensile properties determined. Glutaraldehyde had a significant effect on the tensile properties of the specimens and this suggests that alternative methods should be used to treat bioprosthetic valves, which are fixed in it. Treatment with antibiotics produced losses in stiffness of the tissues at three months, but these were within physiological limits. Therefore valves stored in this manner can be stored as long as three months at least with no effect on valve function in vivo. Cryopreservation with glycerol over three months produced less changes in specimen properties which again should not affect valve function in vivo. Cryopreservation with dimethyl sulphoxide (DMSO) caused the least difference in specimen properties compared to fresh tissues. It is therefore recommended as the first choice in valve treatments for storage. It is suggested that all new valve storage treatments be assessed for their mechanical effects on the tissues routinely. Preliminary work on a non-destructive intact valve test device using polarised light is introduced. This has potential for use in pre-operative assessment of valve mechanical integrity.

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Cardiac surgery is traditionally a heavy user of blood and blood products. Until recently, the benefits of transfusion have been largely assumed and the risks relatively ignored. This has prompted us to examine new ways of minimising patient exposure to donor red blood cells (RBC's). At the present time, most clinical guidelines for RBC transfusion are based mainly upon haemoglobin concentration ([Hb]). As [Hb] may be artificially depressed by the haemodiluting effect of the heavy clear fluid load associated with cardiac surgery, transfusing based upon [Hb] alone may overestimate the requirement for RBC's. Where such haemodilution is present, systemic oxygenation may be maintained through a viscosity mediated patho-physiological response. The work reported in this thesis attempts to explore the relative contribution of both red cell volume (RCV) and plasma volume (PV) to the anaemia encountered following cardiac surgery while also examining factors that may be associated with a low post-operative RCV. In addition, we have explored on a theoretical basis what [Hb] would represent a critical level of systemic oxygen delivery (DO2Crit). Taken together, this has allowed us to develop an RCV based transfusion guideline aimed at reducing the incidence of unnecessary (and potentially counter-productive) RBC transfusion. As RBC's may be associated with pulmonary endothelial damage, we have also studied the impact of the RCV guideline developed on post-operative acute lung injury (ALI). Finally, in a separate study, the merits of a simple activated clotting time (ACT) based system of anti-coagulation management for cardiopulmonary bypass (CPB) versus that of an individualised heparin management system (HMS) are described.

Thesis advisor: Dorothy A. Jones / Cardiac surgery is frequently performed as a surgical intervention within the United States; but there is little known about how the older adult (70 years of age or greater) experiences cardiac surgery and recovery over time. This qualitative research study utilized narrative methodology to interview 13 older adults to inform understanding of the older adult's cardiac surgical experience. The purpose of this study was to describe the story of the older adult both coming to surgery (preoperative period) and during the transitional time of the acute recovery period following cardiac surgery (up to 8 weeks after cardiac surgery). The primary research question asked was "What stories do older adults tell of their experience of cardiac surgery from the preoperative period through the first 2 months postoperatively?" Using narrative analysis of participant discourse, consisting of both structural (re-storying of narrative content) and thematic analysis of interview content, there emerged an overarching story of older adult experience of cardiac surgery which can be described thematically as: Moving toward healing: engaged in and appreciating life while conscious of time passing amidst the primacy and struggle of the symptom experience. Knowledge gained from this study can help to broaden the understanding of the experience and the trajectory of older adult recovery after cardiac surgery, and also serves to inform nursing education and practice models, nursing interventions, instrument development and innovative models of care designed to support the perioperative care of older adults. / Thesis (PhD) — Boston College, 2015. / Submitted to: Boston College. Connell School of Nursing. / Discipline: Nursing.

La chirurgie cardiaque implique le plus souvent le recours à la circulation extracorporelle (CEC) en per-opératoire. Echanges gazeux et perfusion sont ainsi assurés pour les organes à l’exception du cœur, qui malgré la cardioplégie, peut présenter des signes de souffrance résultant d’une protection myocardique incomplète et génératrice d’ischémie. Les complications post-opératoires les plus souvent rencontrées sont d’une part le syndrome de réaction inflammatoire systémique (SIRS) souvent précédé d’une vasoplégie per-CEC et d’autre part la fibrillation auriculaire (FA), trouble du rythme le plus fréquemment rencontré. Les mécanismes impliqués sont multifactoriels mais l’ischémie-reperfusion myocardique engendrée par la CEC semble jouer un rôle prépondérant. Au niveau moléculaire, un acteur clé de ces désordres pourrait être l’adénosine, un nucléoside purique ubiquitaire issu de la déphosphorylation de l’ATP et libéré par nombre de cellules en cas de stress oxydatif et d’inflammation. Marqueur biologique très précoce d’hypoxie et d’ischémie globale, l’adénosine contrôle les systèmes cardiovasculaire et immunitaire par l’intermédiaire de quatre types de récepteurs avec notamment un effet vasodilatateur via le récepteur A2A et un effet pro-arythmique documenté par plusieurs études fondamentales et cliniques.Les objectifs de notre travail ont été dans un premier temps de montrer l’implication de l’adénosine dans la survenue de complications hémodynamiques et rythmiques en post-opératoire de chirurgie cardiaque sous CEC, puis dans un second temps d’évaluer l‘intérêt de la caféine, un antagoniste non spécifique des récepteurs de l’adénosine, dans la prévention de la FA. / Cardiac surgery often requires peri-operative cardiopulmonary bypass (CB). . Gas exchanges and perfusion are provided for the organs excepting the heart, which despite cardioplegia, can display stress signs resulting from an insufficient myocardial protection that generates ischemia. Most common post-surgery complications are the systemic inflammatory response syndrome (SIRS) often preceded by vasoplegia and auricular fibrillation (AF), most common rhythm disorder. Mechanisms involved are multifactorial but the CB-induced myocardial re-perfusion ischemia seems to play a major role. At a molecular level, adenosine could be a key actor, a ubiquitous glycoside derived from the dephosphorylation of ATP and released by numerous cells in case of oxidative stressor inflammation. Very early marker of hypoxemia and general ischemia, adenosine controls both cardiovascular and immune systems through 4 types of receptors most particularly with a vasodilator effect through the A2A receptor and a pro-arrhythmic effect documented by several fundamental and clinical studies.The objectives of our work were to demonstrate the involvement of adenosine in the appearance of hemodynamic and rhythmic complications in post cardiac surgery under CB and then to assess the interest of caffeine, a nonspecific antagonist of adenosine receptors, in the prevention of AF.

Background: The purpose of this study is to determine whether precursor events are associated with a post-operative composite outcome in a low-medium risk cardiac surgical population. These precursor events may be promising targets for strategies aimed at quality improvement. Methods: This study was a case control design where the outcome of major adverse events (MACE) was assessed in patients exposed to four intra-operative precursor events. Cases and controls were matched 1:1 using propensity score matching, Univariate comparison of ?1 precursor event in the matched groups was performed. Results: The primary outcome of ?1 precursor event occurred significantly more frequently in the MACE patient group vs the non-MACE patients group (33% vs. 24%; p=0.015). The individual events of bleeding and difficulty weaning from CPB were significantly higher in the MACE group whereas incomplete revascularization/repair and repair/regrafting were not. Conclusion: Quality improvement techniques aimed at mitigating the consequences of precursor events may improve surgical outcomes for these patients.

INTRODUCTION: The Modified Blalock Taussig (BT) shunt is the most common palliative procedure in neonatal cardiac repair to secure pulmonary blood flow (3-6) despite high mortality and morbidity rates of 4-14% (3,5) and 9-18% (4,5) respectively. The high risk of thrombosis and stenosis associated with the polytetrafluoroethylene (PTFE) material that is currently used for BT shunts significantly contributes to these high mortality and morbidity rates. Thrombosis and stenosis occur in 3-12% of patients (1,5), primarily due to the lack of endothelium of the synthetic PTFE graft. This study hypothesizes that a preserved autologous umbilical vein could be a feasible replacement for the PTFE graft. Experiments were performed to examine and optimize preservation methods of umbilical veins for use as BT shunts. METHODS: Umbilical cords (n=45) were collected from healthy neonates and umbilical vein segments were preserved in either static (n=145) or flow conditions (n=84) for 7 days or 14 days in varying media. Samples of each vein were collected at time of harvest (Day 0) and at the end of culture and compared by burst pressure, histopathology, platelet adhesion and scanning electron microscopy (SEM). RESULTS: Burst pressure strength of veins from Day 0 to up to two weeks of preservation did not significantly differ (431 ± 229 mmHg vs 438 ± 244 mmHg). Overall histology demonstrated an improved morphology in endothelial and medial layers of the segments preserved in flow culture with UW + 5% HPL for 7 days. Platelet adhesion testing demonstrated significantly less platelet attachment in flow samples compared to static, indicating less endothelial injury. SEM showed greater cellular flow-alignment and consistency of the endothelium in flow samples. CONCLUSION: Flow culture utilizing UW plus 5% HPL adequately preserves morphology and function of the endothelium. Preserved autologous umbilical veins stand as a viable option to replace the current PTFE graft used for BT shunts due to the presence of an endothelium.

Clostridium difficile ist einer der führenden Nosokomialkeime in Bezug auf postoperative Diarrhoe. Die Inzidenz ist steigend und der Verlauf bei fulminanter Infektion häufig fatal. Es besteht der Anspruch der Vermeidung schwerer Verläufe und der horizontalen Verbreitung des Erregers. Ziel der Arbeit war, für den prä-, intra- und postoperativen Zeitraum Risikofaktoren zu identifizieren, welche Einfluss auf Ausprägung und Schwere der Infektion hatten. Die vorliegende klinische Studie umfasst 2.823 Patienten mit Diarrhoe nach kardiochirurgischem Eingriff, darunter 1.256 Patienten mit Clostridium-difficile-Nachweis, welche im Herzzentrum Leipzig von April 1999 bis April 2011 operativ versorgt worden sind. Die Datenanalyse erfolgte retrospektiv an zuvor festgelegten Parametern, die mittels statistischer Verfahren analysiert wurden. Besonderes Augenmerk wurde auf die Entwicklung gastrointestinaler Komplikationen und die Mortalität gelegt. Risikofaktoren für eine fulminante CDI waren u.a. männliches Geschlecht, kardiopulmonale Komorbiditäten, Diabetes mellitus Typ II, Verwendung von Assist-Systemen, perioperative Transfusionstherapie, sowie lange Operationszeiten und ein verlängerter Aufenthalt auf Intensivstation. Das Überleben bei fulminanter Infektion war mit einer Sterblichkeit von 63,4% bei einer 30-Tages-Mortalität von 21,6% deutlich schlechter als das der Vergleichsgruppen. Die Identifikation der perioperativen Risikofaktoren soll eine individualisierte Stratifizierung und damit die optimale Überwachung von Hochrisikopatienten für einen frühen Therapiebeginn und im besten Falle eine Prävention möglich machen.