Cerebral vascular accidents (CVAs) rank as the third leading cause of death in Canada with more than 50,000 of these events occurring annually. The evidence base from which to provide end-of- life care to patients dying from a CVA is currently limited, and there is a dearth of research examining the experiences of nurses charged with the responsibility of caring for these patients. In order to begin to address this gap in the literature, a qualitative study, using van Manen’s interpretive phenomenology was conducted to examine and describe the lived experiences of nurses working on an acute neurosciences unit in a tertiary hospital. Nine nurses were interviewed initially, and two nurses participated in follow-up interviews to confirm the interpretation of the data. This manuscript will discuss the essence of nurses’ lived experience in caring for these patients, as well as implications for education, practice, and future research.

Cerebrospinal fluid (CSF) infusion tests can be used to estimate the dynamic properties of the CSF system. Idiopathic normal pressure hydrocephalus (INPH) is a syndrome signified by a disturbance to the CSF system, where the cause is unknown and the diagnosis is difficult to determine. As an aid in identifying patients with INPH who will improve after shunt surgery, infusion tests are commonly used to determine the outflow conductance (Cout), or outflow resistance (Rout=1/Cout), of the CSF system. The tests are also used to determine shunt function in vivo. The general aim of this thesis was to develop and validate CSF infusion methods, to investigate the dynamics of the CSF system. The methods should be applicable to patients with INPH, to aid in the quest to further improve the diagnosis and management of this syndrome. An existing mathematical model describing the dynamics of the CSF system was further developed. The characteristics of the model were verified and the effect of expanding intracranial air on the intracranial pressure (ICP) was simulated. The simulations supported the recommendation to maintain sea-level pressure during air ambulance transportation of patients with suspected intracranial air. A recently developed infusion apparatus was evaluated, on an experimental model as well as on a patient material. The repetitiveness in estimating Cout was found to be good. A statistically significant difference was found between the repeated Cout estimations in the patient group, indicating that there might have been a small physiological change introduced during the infusion test. A parameter, ∆Cout, was proposed and evaluated. It proved to reflect the reliability of individual Cout investigations in a clinically useful way, as well as to provide easily interpreted information. An adaptive algorithm for assessment of Cout was developed and evaluated on a patient group. The new algorithm was shown to reduce the investigation time, from 60 minutes, by 14.3 ± 5.9 minutes (mean ± SD), p<0.01, without reducing the reliability of the estimated Cout below clinically relevant levels. The relationship between ICP and CSF outflow was studied in a group of patients investigated for INPH. It was found that in the range of moderate increase from baseline pressure, the assumption of a pressure independent Rout was confirmed (p=0.5). However, at larger pressure increments, the relationship had a non-linear tendency (p<0.05). This indicates that the traditional view of a pressure independent Rout might have to be questioned in the region where ICP exceeds baseline pressure too much. Infusion tests can be performed in different ways, where three main categories may be distinguished. The bolus infusion method was compared to the constant pressure and constant flow infusion methods, on an experimental model as well as on a patient material. When physiological pressure fluctuations were added to the model, significant differences were found in the determination of Cout in the range of clinical importance, i.e. low Cout (p<0.05). The finding was supported by the patient investigations, the difference was however not significant. With the application of the new methods developed in this thesis, and the increased knowledge concerning relationships between CSF dynamic parameters, the CSF infusion test was further improved with the ability to increase measurement reliability in a reduced time. This constitutes a good basis to perform a large multi-centre study with the main goal to determine the predictive value of the parameter Cout.

Following a head concussion the intracranial pressure increases due to the impact, which cannot be adequately relieved because of the stiffness of the skull. Popular strategies aimed at decompressing the head consist in the administration of osmotic agents and skull removal. The mechanical properties of bone can be affected by the administration of different solutions. If the malleability of skull is influenced by the osmotic agents that are administered to the patient then the pressure and volume in the intracranial cavity can also be modified following the treatment. In this thesis research, we hypothesize that administered osmotic agents can influence the mechanical properties of the skull, which can also impact the volume the cavity can hold and subsequently the pressure in the head. This premise was tested by modifying existing mathematical models compiled through two general MATLAB codes that allow the computation of a non-symbolic differential-algebraic initial value problem. Three main features were changed in comparison to current models: the skull's influence on the pressure and volume modulation was tested (inputs were obtained from skull tested under different solutions); pulsatile flow was accounted for on the creation and movement of cerebrospinal fluid; and the input on the mechanical behavior of the cranial vessels was accounted for through previously published continuum-mechanics vessel-behavior models. To complete the model, materials and mechanical properties were obtained through laboratory experiments as well as data collection from existing literature. From our bone test we were able to conclude that there are different factors that affect the mechanical properties of bone in various degrees. There is a mild statistical correlation (p-value 0.05) between the mechanical properties of bone obtained from different regions of the skull samples (2-14mm) and the DPBS and hDPBS solutions. Additionally there is a strong statistical difference (p-value 0.05) between the mechanical properties obtained from cross head speed (0.02, 0.002, and 0.004 (mm/s)) and solution variation (DI, DPBS and hDPBS). Finally, we were able to see that there seems to be a correlation between the mechanical properties of bone, the solution treatments and hypertension; although more test need to be developed to affirm this premise since our results are preliminary.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 5 uppsatser.

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 2001. / Typescript. Bibliography: leaves 161-195.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 45-56.

Intracranial monitoring after severe traumatic brain injury offers the possibility for early detection and amelioration of physiological insults. In this thesis, I explore cerebral insults due raised intracranial pressure, decreased cerebral perfusion pressure and impaired cerebral pressure reactivity after traumatic brain injury. In chapter 2, the importance of intracranial pressure, cerebral perfusion pressure and pressure reactivity in regulating the cerebral circulation is elucidated along with a summary of the existing evidence supporting intracranial monitoring in traumatic brain injury. In chapter 4, intracranial pressure, cerebral perfusion pressure, and pressure reactivity insults are demonstrated to be common, prognostically important, and responsive to long-term changes in management policies. Further, while these insults often occur independently, coexisting insults portend worse prognosis. In chapter 5, I examine possible imaging antecedents of raised intracranial pressure and demonstrate that initial subarachnoid haemorrhage is associated with the subsequent development of elevated intracranial pressure. In addition, elevated glucose during the intensive care stay is associated with worse pressure reactivity. Cortical blood flow and brain tissue oxygenation are demonstrated to be sensitive to increases in intracranial pressure in chapter 6. In chapter 7, a method is proposed to estimate the cerebral perfusion pressure limits of reactivity in real-time, which may allow for more nuanced intensive care treatment. Finally, I explore a recently developed visualisation technique for intracranial physiological insults and apply it to the cerebral perfusion pressure limits of reactivity. Taken together, this thesis outlines the scope, risk factors and consequences of intracranial insults after severe traumatic brain injury. Novel signal processing applications are presented that may serve to facilitate a physiological, personalised and precision approach to patient therapy.

Introdução: Dados sobre a relação entre a farmacocinética do fluconazol (FCZ) e anfotericina B (AMB) no líquido cefalorraquidiano (LCR) e a hipertensão intracraniana (HIC) não se encontram disponíveis na literatura. Objetivos: Avaliar a influência da pressão intracraniana na concentração dos antifúngicos AMB e FCZ no LCR de pacientes com meningite criptococócica internados no Hospital de Clínicas de Porto Alegre (HCPA), no período de 1 ano. Métodos: Foram estudados 15 pacientes com meningite criptococócica durante os primeiros 14 dias de tratamento com AmB (1 mg/kg/dia) e FCZ (800 mg/dia). As amostras de LCR foram obtidas por meio de punções lombares de rotina realizadas nos dias 1, 7 e 14 da terapia antifúngica, respectivamente. Os valores das pressões intracranianas de abertura foram obtidos no momento de cada punção lombar. Os níveis de AmB e FCZ no LCR foram medidos pela metodologia de cromatografia líquida de alta performance (HPLC). A concentração inibitória mínima (CIM) para AmB, FCZ, voriconazol (VRZ) e flucitosina (5-FC) de cada isolado de Cryptococcus sp. foi realizada de acordo com o as normas descritas no documento M27-A3, do CLSI, publicado em 2008. Resultados: Entre os 15 pacientes incluídos no estudo, C. gattii foi isolado do LCR de 2 pacientes e C. neoformans foi isolado do LCR de 13 pacientes apresentaram. A condição de imunossupressão encontrada foi a AIDS, seguida de transplante de órgão sólido. Nove pacientes apresentaram cultura negativa de LCR no 14º dia de terapia antifúngica. Os níveis de AmB no LCR foram indetectáveis para a maioria das amostras de LCR durante os 14 dias de terapia antifúngica. Os níveis de FCZ no LCR aumentaram progressivamente do dia 1 ao dia 14 de terapia. Seis pacientes apresentaram HIC no dia 1, com variação da pressão de abertura entre 100 mmH2O e 650 mmH2O no respectivo dia. A pressão intracraniana não interferiu nas concentrações de FCZ no LCR. Não observamos correlação entre a HIC e as concentrações de AMB e FCZ no LCR de acordo com a correlação de Spearman (Spearman p= 0.122). Conclusão: São necessários mais estudos para avaliar o papel da HIC na eficácia terapêutica de diferentes agentes antifúngicos em pacientes com meningite criptococócica. / Introduction: Data considering the relationship between pharmacokinetics of fluconazole (FCZ) and amphotericin B (BPA) in cerebrospinal fluid (CSF) and intracranial hypertension (IH) are not available in the literature. Objectives: To evaluate the influence of intracranial pressure on the concentration of the antifungals AMB and FCZ in the CSF of patients with cryptococcal meningitis admitted at the Hospital de Clínicas de Porto Alegre (HCPA), within a period of one year. Methods: Fifteen patients with cryptococcal meningitis were studied during the first 14 days of treatment with AmB (1 mg / kg / day) and FCZ (800 mg / day). CSF samples were obtained by means of routine lumbar punctures performed on days 1, 7 and 14 of antifungal therapy, respectively. The values of intracranial opening pressures were obtained at the time of each lumbar puncture. The levels of AmB and FCZ in the CSF were measured by high performance liquid chromatography (HPLC) methodology. The minimum inhibitory concentration (MIC) for AmB, FCZ, voriconazole (VRZ) and flucytosine (5-FC) of each isolate of Cryptococcus sp. was performed according to CLSI guideline M27-A3, published in 2008. Results: Among the 15 patients included in the study, C. gattii was isolated from the CSF of 2 patients and C. neoformans was isolated from the CSF of 13 patients presented. The immunosuppressive condition found was AIDS, followed by solid organ transplantation. Nine patients presented negative CSF culture on the 14th day of antifungal therapy. AmB levels in the CSF were undetectable for most of the CSF samples during the 14 days of antifungal therapy. CSF FCZ levels increased progressively from day 1 to day 14 of therapy. Six patients presented IH on day 1, with variation of the opening pressure between 100 mmH2O and 650 mmH2O on the respective day. Intracranial pressure did not interfere with CSF on FCZ concentrations. We did not observe a correlation between IH and the concentrations of AMB and FCZ in the CSF according to the Spearman correlation (Spearman p = 0.122). Conclusion: Further studies are needed to evaluate the role of IH in the therapeutic efficacy of different antifungal agents in patients with cryptococcal meningitis.