Resolution of Organ Injury in Acute Pancreatitis - RESORP
Resolution of Organ Injury in Acute Pancreatitis - RESORP
Acute pancreatitis (AP) is inflammation of the pancreas usually triggered by gallstones or
 drinking excessive alcohol. 80% of people who have an episode of AP will recover without
 complications. However, 20% will require treatment in high dependency or intensive care for
 multiple organ dysfunction (AP-MODS). It is known that this negatively affects recovery and
 can have a lasting effect on health although it is incompletely understood what causes this.

 Aim: To recruit 500 patients with acute pancreatitis. Participants will be assessed at
 recruitment and and again at 3 and 36 months. Recovery of organ function will be serially
 measured and the presence of novel factors important in recovery assessed.
Acute pancreatitis (AP) is a common and devastating disease with an annual incidence of 22-30
 per 100,000 in the UK. The incidence is increasing. AP is most commonly triggered by
 gallstones or alcohol excess and has a range of outcomes, from complete resolution to death,
 with an overall mortality in Scotland of 5.2%. AP is characterised by acute inflammation of
 the pancreas, which initiates a cascade of inflammatory events throughout the body that can
 lead to multiple organ dysfunction syndrome (MODS) in approximately 25% of AP patients.
 Mortality in AP is greatest in those patients who develop MODS, with death rates reported to
 be up to 28%.

 The development of persistent organ failure characterises severe AP (SAP) as defined in the
 revised Atlanta classification, and is strongly predictive of a fatal outcome. A significant
 proportion of research has focussed on reducing mortality and morbidity in the first week. As
 a consequence, it remains to be seen whether the patterns of early organ dysfunction are
 reflected in the causes of long-term mortality and morbidity.

 Recently published data from a retrospective analysis of patients admitted to the Royal
 Infirmary of Edinburgh with acute pancreatitis has shown that the early development of MODS
 is associated with an increased mortality rate up to 10 years after the index presentation.
 This strongly suggests that MODS in acute pancreatitis (AP-MODS) has a persistent and
 deleterious impact on patients' physiological status, though the exact nature of this
 pathology remains to be characterised. Recent data has indicated that the severity of the
 first attack of AP significantly influences the risk of progression to chronic pancreatitis,
 and therefore subsequent long-term morbidity.

 This observational clinical cohort study aims to characterise the nature and extent of the
 pathophysiological impact of SAP on organ function over the first 3 years following the index
 event and the long-term deleterious effect of SAP. This will be achieved by prospectively
 evaluating the pathophysiological consequences of an episode of AP by measuring organ system
 function in patients recruited during a hospital admission with AP. We will obtain an
 in-depth assessment of patients' health at presentation, and at 3 months and 36 months after
 the first episode of AP using markers of organ function and/or disease in the peripheral
 blood. In a nested cohort within the main study cohort, we will conduct cardiorespiratory
 evaluation tests (including exercise testing), specialised blood tests of the immune system,
 tests for precision medicine, and imaging to assess structure and function of key organ
 systems.

 The results of this study will inform the design of future interventions designed to improve
 the long-term prognosis of patients.
Inclusion Criteria:

 All patients treated at Royal Infirmary Edinburgh with a clinical or radiological diagnosis
 of acute pancreatitis will be recruited where possible.

 For the potential clinical diagnosis of acute pancreatitis an appropriate clinical history
 based on compatible clinical features, will be required (i.e. abdominal pain, nausea and/or
 vomiting), supported by the finding of elevated serum amylase greater than 3x the upper
 limit of the reference range for the laboratory (currently 300 U/L).

 For the radiological diagnosis, if applicable, computerised tomography (CT) and/or
 ultrasound scan (USS) evidence of acute pancreatitis will be accepted.

 Exclusion Criteria:

 The following exclusion criteria will be adhered to:

 i. Patients under the age of 16 years will be excluded from the present study. ii.
 Prisoners will be excluded from the present study. iii. Patients lacking the capacity to
 consent will be excluded but can be included if they regain capacity.

 Additional exclusions will apply only to those patients being considered for the nested
 cohort study:

 iv. Patients not able to undergo MRI scanning for technical reasons will be excluded (e.g.
 those with cochlear implants, implanted pacemaker) v. Patients with a known allergy to
 salbutamol