Approaches to treatment of major peptic ulcer haemorrhage

Kubba, Adam K. (1996) Approaches to treatment of major peptic ulcer haemorrhage. MD thesis, University of Glasgow.

Abstract

In 200 BC Hippocrates wrote that "those diseases which medicines cannot cure, the knife cures, those which the knife cannot cure, cautery cures and those which cautery cannot cure are reckoned to be wholly incurable". This dictum applies well to the management of peptic ulcer haemorrhage. In my period of research at the Western General, I aimed to address some aspects of these three corners of management. I-Cautery: Endoscopic injection therapy with dilute adrenaline stops bleeding and prevent rebleeding from peptic ulcers. No treatment is perfect, 15-25% of patients rebleed and require urgent surgery. My work has examined clinical and experimental approaches of improving endoscopic injection treatment. i) Major peptic ulcer haemorrhage is the consequence of arterial erosion and the focus of therapy is to cause thrombosis of the arterial defect, Whilst adrenaline probably stops bleeding by causing vasoconstriction , a more permanent approach is to inject thrombin into the bleeding ulcer. Therefore, 140 patients with significant peptic ulcer haemorrhage were randomised to endoscopic injection with adrenaline (70 patients, group 1) or to adrenaline plus human thrombin (70 patients, group 2). Fourteen (20%) group 1 patients and three (4.5%) group 2 patients rebled (p<0.005). The 30 day mortality was 10% in group 1 patients and nil in group 2 patients (p<0.013). Combination of adrenaline plus human thrombin injection appears safe and may represent best treatment for bleeding peptic ulcers. ii) The mechanisms by which endoscopic therapy stops bleeding are unclear , and to explore this, experiments were performed in a validated animal model in which bleeding mucosal ulcers were treated by a range of injection materials. Active ulcer haemorrhage was arrested by an adrenaline/thrombin combination whilst other agents including sclerosants , hypertonic solution and alcohol were only moderately effective. Arterial thrombosis was not effected by any regime, although the thrombin/adrenaline combination caused local submucosal thrombosis of small vessels which probably act as a haemostatic plug. iii) Whilst the immediate outcome of patients treated endoscopically for ulcer bleeding is well documented, late prognosis is unclear. 121 patients treated endoscopically for severe peptic ulcer haemorrhage were followed for a median period of 36 months, and outcome was compared with that of age and sex matched controls. Kaplan-Mieir plots showed reduced survival in ulcer patients (p<0.01). 30 patients (26%) died during the follow up period, deaths were largely restricted to patients who had co-morbid diseases. n-Medicines Acid reducing agents are extensively used in patients with ulcer haemorrhage but there is no evidence that they have any effect on morbidity or mortality . This leaves those who fail endoscopic therapy and are not fit for surgery at a great risk of death. Octreotide has been used to stop variceal bleeding largely by reducing splanchnic blood flow and it was reasoned that this action may be of value in reducing arterial blood loss from peptic ulcer haemorrhage. Gastroduodenal mucosal blood flow was measured in experimental animals using a Laser Doppler Flowmeter. Intravenous octreotide infusion markedly reduced gastro-duodenal mucosal blood flow in a dose dependent manner, without causing any systemic haemodynamic disturbance. These findings suggest that this agent may be helpful in the management of bleeding from gastroduodenal ulcer disease and gastritis and trials of octreotide in peptic ulcer haemorrhage are in progress. (Abstract shortened by ProQuest.).

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Keywords: Medicine
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: Palmer, Dr. Kevin
• Date of Award: 1996
• Depositing User: Enlighten Team
• Unique ID: glathesis:1996-71827
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 17 May 2019 09:31
• Last Modified: 01 Jul 2022 10:57
• Thesis DOI: 10.5525/gla.thesis.71827
• URI: https://theses.gla.ac.uk/id/eprint/71827