SMS 201-995 in the Management of Portal Hypertension

McKee, Ruth Fraser (1988) SMS 201-995 in the Management of Portal Hypertension. MD thesis, University of Glasgow.

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Bleeding from oesophageal varices is one of the most serious emergencies seen in medical practice. Control of the bleeding is the first priority but neither of the two treatments commonly used today, oesophageal tamponade or intravenous vasopressin, is ideal. Oesophageal tamponade can give control of bleeding in more than 90% of cases (1) but may cause aspiration pneumonia or respiratory arrest and certainly causes considerable discomfort to the patient. Vasopressin is hardly less unpleasant and carries the risk of myocardial infarction and cardiac arrest (2,3). Therefore a new drug for the temporary control of bleeding from oesophageal varices would be useful. There is evidence that naturally occurring somatostatin is at least as effective as vasopressin in this regard and has no major side-effects (4, 5) but its short half-life and instability in solution are disadvantageous. SMS 201-995 is a new long-acting analogue of somatostatin with a plasma half-life of 45 minutes and which is stable in solution (6). Little work has been done using this analogue and in particular it has not been assessed in a clinical trial of treatment of bleeding varices. This thesis sets out to examine the effects of SMS 201-995 in patients with portal hypertension and in two rat models of portal hypertension. The literature on portal hypertension is reviewed with particular reference to the management of bleeding oesophageal varices. Chapter 2 consists of a retrospective study of oesophageal tamponade in the management of variceal bleeding, assessing its efficacy in bleeding control as well as the complications encountered. In Chapters 3 to 7, three studies using SMS 201-995 are reported. The acute effects of SMS 201-995 on portal and systemic haemodynamics were measured in stable cirrhotic patients and this is described in Chapter 3. Cardiac output and systemic vascular resistance were measured using the thermodilution method and portal pressure was assessed by measuring the wedged and free hepatic venous pressures. Thereafter work proceeded in two areas simultaneously. Chapters 4 to 6 describe studies of the effects of SMS 201-995 in normal rats and in two rat models of portal hypertension. A rat model of extra-hepatic portal hypertension, using partial portal vein ligation, and a rat model of cirrhosis, induced by carbon tetrachloride, had been established and characterised previously in the University Department of Surgery, Glasgow Royal Infirmary (7). These models were used to study the effects of SMS 201-995 on systemic haemodynamics, portal pressure and portasystemic shunting. A radioactive microsphere method was used to measure blood flow and portasystemic shunting. Running concurrently with this animal study a controlled clinical trial was undertaken to compare the efficacy of SMS 201-995 with that of oesophageal tamponade in active variceal bleeding. This trial is described in Chapter 7. The efficacy of both treatments with regard to control of bleeding was studied along with their complications and side-effects , in 40 episodes of variceal bleeding. In Chapter 8 conclusions are drawn from the results of these studies and the work is placed in the context of other recent work in therapy for portal hypertension. A number of questions are raised by this work and several avenues for further investigation are suggested.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Medicine, Pharmacology
Date of Award: 1988
Depositing User: Enlighten Team
Unique ID: glathesis:1988-77777
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53

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