Changes

May 2021 — reviewed. A literature search was conducted in April 2021 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has been updated in line with current evidence in the literature including the National Institute for Health and Care Excellence (NICE) guideline Pancreatitis (NICE, 2020). No major changes to recommendations have been made. A new section on the Follow up of confirmed acute pancreatitis has been added to the Scenario on Management.

Update

Goals

To support primary healthcare professionals to:

• Be aware of when to suspect acute pancreatitis and make a provisional diagnosis.
• Arrange urgent hospital admission for all people with suspected acute pancreatitis.
• Arrange appropriate clinical management of people with acute pancreatitis following hospital discharge.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

NICE quality standards

No NICE quality standards were found during the review of this topic.

What is it?

• Acute pancreatitis is an acute inflammatory process of the pancreas with varying involvement of local tissues or more remote organ systems [Johnson, 2005; Banks, 2012; Johnson, 2014; Goodchild, 2019; Leppaniemi, 2019].
  • Mild acute pancreatitis is characterized by the absence of local or systemic complications or organ failure. It usually has an uneventful recovery and resolves in the first week. This is the most common form of acute pancreatitis.
  • Moderately severe acute pancreatitis is characterized by local complications and/or transient organ failure which resolves within 48 hours.
  • Severe acute pancreatitis is characterized by persistent single or multiorgan failure for more than 48 hours.
  • It is not possible to classify the severity of acute pancreatitis based on the clinical findings at presentation [Olson, 2019].
• Recurrent acute pancreatitis describes acute pancreatitis which occurs on more than one occasion, with full recovery between episodes [Whitcomb, 2019].

What are the risk factors and causes?

• Acute pancreatitis is most commonly caused by gallstones or alcohol misuse, which account for around 75% of cases [Johnson, 2005] [Goodchild, 2019] [NICE, 2020].
  • Gallstones
    • The commonest cause of acute pancreatitis in the UK, accounting for about 50% of cases [Johnson, 2014; O'Reilly, 2016].
    • Obstruction of the pancreatic duct initiates the activation of pancreatic enzymes, which cause auto-digestion of pancreatic tissue, stimulating a local inflammatory response [Leppaniemi, 2019; NICE, 2020]. See the CKS topic on Gallstones for more information.
  • Alcohol
    • This is the second commonest cause of acute pancreatitis in the UK, accounting for about 25% of cases [Johnson, 2014; O'Reilly, 2016].
    • The mechanism of pancreatic injury is poorly understood, and may include alcohol acting as a direct toxin to the pancreatic cells causing inflammation and cell destruction, or increased ductal pressures caused by protein deposition causing retrograde flow and intra-pancreatic enzymatic activation [Goodchild, 2019; Leppaniemi, 2019; NICE, 2020]. See the CKS topic on Alcohol - problem drinking for more information.
• Other risk factors for acute pancreatitis include [Johnson, 2014] [Goodchild, 2019] [Zheng, 2021]: 
  • Post-endoscopic procedures such as endoscopic retrograde cholangiopancreatography (ERCP) due to pancreatic duct or sphincter of Oddi disruption [Johnson, 2005; Olson, 2019].
  • Blunt abdominal trauma may lead to pancreatitis duct disruption [Olson, 2019].
  • Surgery near the pancreas such as biliary tract procedures, gastric surgery, and splenectomy [Leppaniemi, 2019].
  • Metabolic conditions such as hypertriglyceridaemia and hypercalcaemia [Johnson, 2005; Leppaniemi, 2019; Whitcomb, 2019; NICE, 2020]. See the CKS topics on Hypercholesterolaemia - familial and Hypercalcaemia for more information.
  • Infections such as mumps, coxsackie B4 virus, and Mycoplasma pneumonia infection [Johnson, 2005]. See the CKS topic on Mumps for more information.
  • Drugs such as thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, statins, fenofibrate, azathioprine, tetracyclines, oestrogens, corticosteroids, valproic acid, and dipeptidyl peptidase-4 (DPP-4) inhibitors [MHRA, 2014; Goodchild, 2019; Olson, 2019; Whitcomb, 2019].
  • Chronic pancreatitis [O'Reilly, 2016]. See the CKS topic on Pancreatitis - chronic for more information.
  • Microlithiasis (small gallstones and biliary sludge) [O'Reilly, 2016].
  • Anatomical or functional disorders such as pancreas divisum, ampullary stenosis, and/or sphincter of Oddi dysfunction [Johnson, 2005; Whitcomb, 2019; NICE, 2020].
  • Autoimmune conditions such as systemic lupus erythematosus and Sjögren's syndrome [Olson, 2019; NICE, 2020].
  • Pancreatic adenocarcinoma, cholangiocarcinoma, or peri-ampullary tumours [Leppaniemi, 2019; Olson, 2019; Whitcomb, 2019; NICE, 2020]. See the CKS topic on Gastrointestinal tract (upper) cancers - recognition and referral for more information.
• About 10% of episodes of acute pancreatitis are idiopathic, with no identified underlying cause [Johnson, 2014].

How common is it?

The incidence of acute pancreatitis is increasing over time.

• A 12-year follow-up study of Welsh hospital admissions using linked in-patient, mortality, and primary care data (n = 10,589 episodes) found the overall incidence of acute pancreatitis was 30 per 100,000 population, with an average annual increase in incidence of 2.7% per year [Roberts, 2013].
• A UK population-based cohort study of primary care data (n = 19,182 patients) found the age-standardized incidence of pancreatitis increased from 14.8 to 31.2 in 100,000 males and from 14.5 to 28.3 in 100,000 females over a 13-year period (1990–2013) [Hazra, 2014].
• In the UK, most hospitals serving a population of 300,000–400,000 people will admit approximately 100 people with acute pancreatitis per year [Johnson, 2014].
• A systematic review of 10 population-based cohort studies of acute pancreatitis reported a global incidence estimate of 33.74 cases per 100,000 person-years, and there was no difference in incidence between men and women [Xiao, 2016].

What is the prognosis?

The prognosis of acute pancreatitis is based on the underlying cause, and the mortality rate is influenced by the severity of the disease [Goodchild, 2019].

• The World Society of Emergency Surgery (WSES) guidelines state that 80–85% of people with acute pancreatitis will have mild self-limiting disease, with a mortality rate of 1–3%. In contrast, about 20% will have moderate or severe disease, with a mortality rate of 13–35%. People with severe acute pancreatitis and infected necrosis have the highest risk of death [Leppaniemi, 2019].
• A US 10-year prospective tertiary centre study (n = 400) of mixed patients with mild (52%), moderate (23.5%), and severe (24.5%) acute pancreatitis found the overall case fatality rate was 5%, and all deaths occurred in the severe group [Koutroumpakis, 2017].
• A systematic review of 10 population-based cohort studies found the pooled mortality from an episode of acute pancreatitis was 1.16 per 100,000 person-years [Xiao, 2016].
• A UK population-based cohort study of primary care data (n = 19,182 patients) found the overall case-fatality rate was 4.3% at 90 days and 7.9% at 1 year after a diagnosis of acute or chronic pancreatitis [Hazra, 2014].
• A Dutch multicentre prospective study of hospital patients (n = 639) with severe acute pancreatitis (necrotizing pancreatitis) found the overall hospital mortality rate was 15% [van Santvoort, 2011].
• A systematic review of 14 cohort studies (n = 8492 adults) found that following a first episode of acute pancreatitis, 21% of people developed recurrent acute pancreatitis, and 10% of people (predominantly males) developed chronic pancreatitis [Sankaran, 2015]. See the CKS topic on Pancreatitis - chronic for more information.

What are the complications?

Local and/or systemic complications may develop in people with moderately severe or severe acute pancreatitis.

• Local complications include:
  • Pancreatic necrosis (necrotizing pancreatitis) with or without infection [Crockett, 2018; Leppaniemi, 2019; Zheng, 2021].
    • Inflammatory mediators released in acute pancreatitis induce thrombosis and haemorrhage, leading to pancreatic necrosis.
    • The necrotic area is initially sterile, but infection of pancreatic and peripancreatic necrosis may occur in 20–40% of cases of acute severe pancreatitis.
    • Infected pancreatic necrosis is responsible for 80% of deaths from acute pancreatitis.
  • Pseudocyst [Johnson, 2005; Johnson, 2014; Zheng, 2021].
    • Ischaemia and inflammation of the pancreas causes disruption of the pancreatic ducts, leading to localized, thick-walled collections of pancreatic fluid within and surrounding the pancreas, known as pseudocysts, usually occurring at least 4 weeks after the onset of acute pancreatitis.
    • Pseudocysts can be complicated by infection, rupture, or haemorrhage. 
  • Pancreatic abscess [Johnson, 2005].
    • Pancreatic abscess is a collection of pus within the abdomen that sometimes contains gas. It follows an infection of peri-pancreatic fluid collections and usually takes 2–4 weeks to evolve.
  • Fistulae [Goodchild, 2019; Leppaniemi, 2019].
    • Pancreatic fistulae are caused by disruption of the pancreatic ducts. They can track from the pancreatic ducts to the abdominal cavity (causing ascites), pleural cavity (causing pleural effusion), or pericardial cavity (causing pericardial effusion).
    • Internal fistulae may communicate with the small bowel, large bowel, or biliary system, or they may track to the skin as external fistulae (most commonly after surgical intervention).
  • Vascular [Banks, 2012; Goodchild, 2019].
    • Pre-hepatic portal hypertension, usually involving the splenic vein and causing subsequent segmental portal hypertension.
    • Erosion of a pancreatic, splenic, or peri-pancreatic artery or vein with haemorrhage.
• Systemic complications include [Banks, 2012] [Johnson, 2014] [NICE, 2020]:
  • Multi-organ failure.
  • Sepsis. See the CKS topic on Sepsis for more information.
  • Acute kidney injury. See the CKS topic on Acute kidney injury for more information.
  • Acute respiratory distress syndrome.
  • Disseminated intravascular coagulation.

When should I suspect a diagnosis of acute pancreatitis?

• Suspect a diagnosis of acute pancreatitis in any person who presents with:
  • Acute sudden-onset upper or generalized abdominal pain, which may be associated with:
    • Nausea and/or vomiting.
    • A history or clinical features of gallstones, alcohol misuse, or other risk factors. See the CKS topics on Gallstones and Alcohol - problem drinking for more information.

How should I assess a person with suspected acute pancreatitis?

If a person has a diagnosis of suspected acute pancreatitis following initial assessment:

• Ask about:
  • The characteristics of abdominal pain.
    • This is typically severe pain of sudden onset which becomes constant, is located in the epigastric region, right and/or left upper quadrant, and may radiate to the back or flanks.
    • It may worsen with movement and can be alleviated by leaning forwards or assuming the fetal (knee-chest) position.
    • It may be generalized with peritonism if peritonitis is present.
    • If caused by gallstones, pain may be described as sudden and knife-like, and may be worse after food.
    • If alcohol-related, pain may be of less abrupt onset and poorly localized.
    • Note: the degree of abdominal pain at presentation does not necessarily reflect the severity of an episode of acute pancreatitis.
  • Additional symptoms, such as nausea, anorexia, and vomiting.
  • Any known risk factors, including alcohol intake, gallstones, hypertriglyceridaemia, and drugs.
  • Any previous episodes of acute pancreatitis.
  • Any family history suggesting hereditary pancreatitis or a familial cancer syndrome.
• Examine the person for:
  • Signs of shock — such as tachycardia, tachypnoea, and hypotension.
  • Fever — may be associated with an initial inflammatory response or a complication such as pancreatitis necrosis or sepsis. See the CKS topic on Sepsis for more information.
  • Abdominal tenderness — may be signs of generalized peritonitis, rebound tenderness, and guarding if severe episode.
  • Abdominal distension — common, caused by leakage of fluid into the retroperitoneum. May be exacerbated by loops of bowel filled with gas, and fluid from small bowel ileus.
  • Ecchymoses (bluish discolouration) around the umbilicus (Cullen's sign), the flanks (Grey-Turner's sign), or over the inguinal ligament (Fox's sign) — sometimes associated with complicated haemorrhagic pancreatitis (rare).

What else might it be?

Conditions which can present similarly to acute pancreatitis include:

• Perforated peptic ulcer. See the CKS topic on Dyspepsia - proven peptic ulcer for more information.
• Bowel obstruction.
• Ischaemic bowel.
• Ruptured abdominal aortic aneurysm (may cause retroperitoneal haemorrhage).
• Ruptured ectopic pregnancy (may cause retroperitoneal haemorrhage). See the CKS topic on Ectopic pregnancy for more information.
• Myocardial infarction. See the CKS topic on Chest pain for more information.
• Biliary colic, acute cholecystitis, or cholangitis. See the CKS topics on Gallstones and Cholecystitis - acute for more information.
• Gastroenteritis. See the CKS topic on Gastroenteritis for more information.
• Viral hepatitis. See the CKS topics on Hepatitis A, Hepatitis B, and Hepatitis C for more information.
• Appendicitis. See the CKS topic on Appendicitis for more information. 

Scenario: Management of acute pancreatitis

From age 18 years onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of acute pancreatitis.

Search dates

April 2016 - April 2021

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• Exp Pancreatitis/
• *Pancreatic Diseases / epidemiology*
• Acute pancreatitis.kw,ti,ab.

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
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Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

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Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.