• Charles Miranda

Student thesis: Doctor of Medicine


TITLE: Novel approaches to the diagnosis and management of severe acute pancreatitis.INTRODUCTION: Severe Acute Pancreatitis (SAP) is the rapid onset ofinflammation within the pancreatic organ. Unlike the milder form of this illness,SAP is associated with a high mortality and morbidity. No significant reduction inthe outcomes of this disease has been made since the implementation of organsupportive management over two decades ago. This is due to difficulties indistinguishing between the milder form of the disease in the early period of theonset of symptoms when clinical intervention is most likely to preventcomplications and death. Clinical equipoise exists in the management of one ofthese complications, namely Abdominal Compartment Syndrome (ACS) as theconventional management of surgery runs contrary to published evidence showingearly abdominal surgery deteriorates clinical outcomes.AIMS: Validation of the potential use of the Early Warning Score (EWS) as apredictor of SAP. Evaluation of the evidence for recombinant human protein C(Xigris ) in the early treatment of SAP. Determination of the safety profile of Xigris when given early in SAP. To determine if surgical management of ACS in SAP is of significant benefit compared to conventional management alone.‚ÄÉMETHODS: Four studies were performed: A prospective observational studyassessing the median EWS of patients admitted with acute pancreatitis; asystematic review of published evidence reporting the use of Xigris in SAP; aprospective cohort study using a 24 hour infusion of Xigris early in patientsdiagnosed with SAP and a pilot randomized controlled trial of targeteddecompression in patients with ACS complicating SAP.RESULTS: The highest EWS values for 130 patients with acute pancreatitis within the first 3 days of admission were not shown to have significant sensitivity and specificity in predicting an unfavourable outcome. A review of the published literature between from January 1985 to January 2011 supported the further investigation of Xigris as a treatment for SAP. No significant adverse events or differences in outcomes were evident in 19 patients who received a 24-hour infusion of Xigris early in SAP compared to matched historical controls. 22 patients were screened for the development of ACS. No patient developed ACS and consequently no randomization to either treatment arm was possible.CONCLUSION: With the recent advent of an updated classification system for theseverity of acute pancreatitis, further prospective evaluation of the use of EWS inclinical practice is warranted. The results of the Phase 1 clinical trial of Xigris didnot reveal significant safety issues that might preclude the further investigation ofXigris as a specific therapy early in the onset of SAP. The absence of ACS inpatients with SAP lends support to a theory that ACS may be anepiphenomenon in the course of SAP.
Date of Award1 Aug 2017
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorAjith Siriwardena (Supervisor) & Colin Sibley (Supervisor)


  • Abdominal compartment syndrome
  • Xigris
  • Pancreatitis
  • Early warning score
  • Activated protein C

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