3 research outputs found

    Immune, microvascular and haemodynamic effects of dopexamine in rodent models of laparotomy & endotoxaemia

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    PhDA growing body of evidence suggests that the potential exists to reduce morbidity and high mortality rates associated with major surgery in high-risk patients. Dopexamine is a dopamine analogue with agonist activity at β2-adrenoceptors and dopaminergic receptors that has been used to maintain tissue perfusion in critically ill and high-risk surgical patients with the aim of improving clinical outcomes. Postoperative complications occur more frequently in the presence of poor tissue microvascular flow and oxygenation, and dopexamine has been shown to improve these abnormalities. However, the effect of dopexamine on clinical outcomes is less clear, and the findings of randomized trials have proved inconsistent. These conflicting findings might be explained by dose-related differences in the hemodynamic and immunologic effects of dopexamine. The series of investigations that make up this thesis set out to explore the nature of any such dose-related effects and reveal potent anti-inflammatory effects of dopexamine in the absence of haemodynamic effects.Intensive Care Young Investigator Award and a National Institute of Academic Anaesthesia RCoA/BJA Project Grant

    Acute liver failure following paracetamol overdose.

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    Acute liver failure is a rare syndrome comprising a coagulopathy of liver origin, jaundice and encephalopathy in a patient with no prior history of liver disease. Paracetamol overdose is the leading cause of acute liver failure in the United Kingdom and often presents with extrahepatic organ dysfunction requiring critical care. We present the case of a patient with hyper acute liver failure secondary to paracetamol overdose. Management focused on ensuring the correct diagnosis had been made, administering N-acetyl cysteine, fluid resuscitation and broad spectrum antimicrobials. Early intubation and transfer to a transplant centre were undertaken following development of hepatic encephalopathy. Neuroprotective measures and hypertonic saline were instituted to reduce the risk of intracranial hypertension. High dose haemofiltration was also started to help reduce ammonia levels. Aggressive critical care therapies with specialised input results in good outcomes for patients admitted with paracetamol induced hyper acute liver failure. Liver transplant is reserved for those patients unlikely to survive with medical treatment alone

    The Effect of β-Adrenoceptor Agonists on Leucocyte-Endothelial Adhesion in a Rodent Model of Laparotomy and Endotoxemia.

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    The β-adrenoceptor agonist dopexamine may possess anti-inflammatory actions which could reduce organ injury during endotoxemia and laparotomy. Related effects on leucocyte-endothelial adhesion remain unclear. Thirty anesthetized Wistar rats underwent laparotomy followed by induction of endotoxemia with lipopolysaccharide and peptidoglycan ( = 24) or sham ( = 6). Animals received dopexamine at 0.5 or 1 μg kg min (D0.5 and D1), salbutamol at 0.1 μg kg min, or saline vehicle (Sham and Control) for 5 h. Intravital microscopy was performed in the ileum of the small intestine to assess leucocyteendothelial adhesion, arteriolar diameter, and functional capillary density. Global hemodynamics and biochemical indices of renal and hepatic function were also measured. Endotoxemia was associated with an increase in adherent leucocytes in post-capillary venules, intestinal arteriolar vasoconstriction as well-reduced arterial pressure and relative cardiac index, but functional capillary density in the muscularis was not significantly altered. Dopexamine and salbutamol administration were associated with reduced leucocyte-endothelial adhesion in post-capillary venules compared to control animals. Arteriolar diameter, arterial pressure and relative cardiac index all remained similar between treated animals and controls. Functional capillary density was similar for all groups. Control group creatinine was significantly increased compared to sham and higher dose dopexamine. In a rodent model of laparotomy and endotoxemia, β-agonists were associated with reduced leucocyte-endothelial adhesion in post-capillary venules. This effect may explain some of the anti-inflammatory actions of these agents
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