Projeto de aplicação de cuidados anestésicos na monitorização de situações clínicas de hipoperfusão orgânica

Apesar dos avanços na sua abordagem terapêutica, a hemorragia severa continua a ser a principal causa de morbilidade e mortalidade em animais vítimas de trauma ou sujeitos a intervenção cirúrgica. O aparecimento de lesões decorrentes, ou da morte consequente, deve-se ao deficit de volume de fluidos intravasculares e subsequente desenvolvimento do estado hipovolémico. Em termos fisiológicos, a consequência mais devastadora desta condição é a diminuição, absoluta ou relativa, da pré-carga cardíaca, resultando num baixo débito cardíaco, perfusão tecidular inadequada e diminuição do aporte de oxigénio aos tecidos, o qual compromete, inequivocamente, a função celular. O controlo da hipovolémia passa pela resolução da hemorragia e pela correção do deficit de volume intravascular causado e envolve, obrigatoriamente, o recurso à administração de fluidos intravenosos. A escolha do tipo de fluido mais adequado para a terapia intravenosa, em cada ocorrência, é uma tarefa que exige reflexão e ponderação. A seleção dos fluidos apropriados é da responsabilidade do médico veterinário, sendo, no entanto, fundamental que o enfermeiro veterinário detenha conhecimentos básicos sobre as diferenças entre os fluidos disponíveis para a fluidoterapia. O objetivo deste projeto é determinar qual o tipo de fluido mais adequado para ajudar a preservar a integridade e funcionalidade hepática, em situações de hipoperfusão, e assim ajudar a padronizar a sua escolha no momento da decisão pela fluidoterapia. Para atingir este objetivo recorreu-se ao modelo suíno, a fim de recrear a situação de hipoperfusão e posteriormente avaliar os efeitos de dois fluidos diferentes administrados na reposição volémica, o lactato de Ringer e hidroxietilamido 130/0,4. Os animais foram sujeitos a uma hemorragia controlada, após a qual foi reposta a volémia com os respetivos fluidos. Após esta reposição volémica os animais foram eutanaziados e foram obtidas amostras de vários órgãos, incluindo fígado, objeto do presente estudo, alvo de diversas técnicas histopatológicas, nomeadamente o estudo histopatológico de rotina, através de hematoxilina e eosina, e diversos métodos para deteção de eventos apoptóticos, incluindo citocromo c, TUNEL e M30.Após a avaliação exaustiva dos resultados obtidos através das técnicas realizadas, foi possível concluir que o lactato de Ringer confere uma maior proteção contra a lesão de reperfusão, quando comparado com o hidroxietilamido 130/0,4.

Computed Tomography Perfusion Can Guide Endovascular Therapy in Bilateral Carotid Artery Dissection

Carotid artery dissection (CAD) is a major cause of stroke in those under age 45, accounting for around 20% of ischaemic events[1,2]. In the absence of known connective tissue disorders, most dissections are traumatic[2]. First-line management is comprised of antiplatelet or anticoagulation therapy, but many traumatic dissections progress despite this and carry the risk of long-term complications from embolism or stenosis[3]. We report a case of traumatic bilateral carotid dissection leading to progressive neurological symptoms and hypoperfusion on computed tomography perfusion (CTP), despite escalation in anticoagulation, which led to emergency carotid stenting.

The pathophysiology of CADASIL: studies in a Scottish cohort

Since identification that mutations in NOTCH3 are responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the early 1990s, there has been extensive characterisation of the clinical and radiological features of the disease. However therapeutic interventions remain elusive, partly due to a limited understanding of the vascular pathophysiology and how it leads to the development of strokes, cognitive decline and disability. The apparent rarity and heterogenous natural history of CADASIL potentially make conducting any longitudinal or therapeutic trials difficult. The role of disease biomarkers is therefore of some interest. This thesis focuses on vascular function in CADASIL and how it may relate to clinical and radiological markers of disease. Establishing the prevalence of CADASIL in the West of Scotland was important to assess the impact of the disease, and how feasible a trial would be. A mutation prevalence of 10.7 per 100,000 was demonstrated, suggesting significant under diagnosis of the disease across much of Scotland. Cerebral hypoperfusion is thought to be important in CADASIL, and it has been shown that vascular abnormalities precede the development of brain pathology in mouse models. Investigation of vascular function in patients, both in the brain and systemically, requires less invasive measures. Arterial spin labelling magnetic resonance imaging (MRI) and transcranial Doppler ultrasound (TCD) can both be used to obtain non-invasive and quantifiable indices of vascular function. Monitoring patients with MRI whilst they receive different concentrations of inspired oxygen and carbon dioxide can provide information on brain function, and I reviewed the practicalities of this technique in order to guide the design of the studies in this thesis. 22 CADASIL patients were recruited to a longitudinal study. Testing included peripheral vascular assessment, assessment of disability, neurological dysfunction, mood and cognition. A CO2 reactivity challenge during both TCD and arterial spin labelling MRI, and detailed MRI sequences were obtained. I was able to demonstrate that vasoreactivity was associated with the number of lacunes and brain atrophy, as were carotid intima-media thickness, vessel stiffness, and age. Patients with greater disability, higher depressive symptoms and poorer processing speed showed a tendency to worse cerebral vasoreactivity but numbers were small. This observation suggests vasoreactivity may have potential as a therapeutic target, or a biomarker. I then wished to establish if arterial spin labelling MRI was useful for assessing change in cerebral blood flow in CADASIL patients. Cortical grey matter showed the highest blood flow, mean (SD), 55 (10) ml/100g/min and blood flow was significantly lower within hyperintensities (19 (4) ml/100g/min; p <0.001). Over one year, blood flow in both grey matter (mean -7 (10) %; p = 0.028) and deep white matter (-8 (13) %; p = 0.036) declined significantly. Cerebrovascular reactivity did not change over one year. I then investigated whether baseline vascular markers were able to predict change in radiological or neuropsychological measures of disease. Changes in brain volume, lacunes, microbleeds and normalised subcortical hyperintensity volume (increase of 0.8%) were shown over one year. Baseline vascular parameters were not able to predict these changes, or those in neuropsychological testing. NOTCH3 is found throughout the body and a systemic vasculopathy has been seen particularly affecting resistance vessels. Gluteal biopsies were obtained from 20 CADASIL patients, and ex vivo myography investigated the response to vasoactive agents. Evidence of impairment in both vasodilation and vasoconstriction was shown. The addition of antioxidants improved endothelium-dependent relaxation, indicating a role for oxidative stress in CADASIL pathology. Myography measures were not related to in vivo measures in the sub-group of patients who had taken part in both studies. The small vessels affected in CADASIL are unable to be imaged by conventional MR imaging so I aimed to establish which vessels might be responsible for lacunes with use of a microangiographic template overlaid onto brain images registered to a standard brain template. This showed most lacunes are small and associated with tertiary arterioles. On the basis of this thesis, it is concluded that vascular dysfunction plays an important role in the pathophysiology of CADASIL, and further assessment of vascular measures in longitudinal studies is needed. Arterial spin labelling MRI should be used as it is a reliable, non-invasive modality that can measure change over one year. Furthermore conventional cardiovascular risk factor prevention should be undertaken in CADASIL patients to delay the deleterious effects of the disease.

Asymptomatic intradialytic hypotension: the need for pre-emptive intervention

Intradialytic hypotension (IDH) remains the most common severe side effect of hemodialysis despite numerous technological advancements. Recent evidence emphasises the significance of asymptomatic hypotensive episodes, as well as the hypoperfusive consequences of both relative blood pressure drops and repetitive, symptomatic events. This article reviews the physiological importance of rapid blood pressure decrease during hemodialysis, and highlights the pathological consequences of repeated asymptomatic and symptomatic hypoperfusive episodes. In proposing a view concerned with asymptomatic IDH, a practicalpre-emptive intervention is offered to improve the long-term outcomes of patients on hemodialysis. Ongoing monitoring of individual patient's mean arterial pressure (MAP) throughout the dialysis treatment can facilitate the identification of an asymptomatic hypotensive episode. A brief pause in ultrafiltration enables vascular refill and subsequent increase in MAP, allowing resumption of safe fluid removal. Such enhanced assessment results in a reduction off patient risk, allowing safe and optimal fluid removal.