- is probably a phase of chronic pancreatitis.
D I A B M I M
Varies by region
- 21-50 per 100,000 is typical
Peaks in 4th-6th decades.
Smaller in areas with low alcohol consumption.
High fat diet.
D I A B M I M
The pancreas is protected from autodigestion by:
- secreting inactive forms of enzymes; not active until passed into
- (duodenal enterokinase converts trypsinogen to trypsin; this
activates other pancreatic proenzymes)
- ducts lined with membrane
- production of an anti-trypsin
- dilution and rapid propulsion of juices into the duodenum.
These protective mechanisms are overcome in pancreatitis.
--> injury to acinar cells.
--> intracellular activation of trypsinogen to trypsin
- likely mediated by cathepsin B (lysosomal hydrolase)
--> a positive feedback cycle of worsening disease can ensue.
--> inflammatory response couples to extrapancreatic
inflammation-mediated organ effects.
Pancreas divisum (bifid pancreas; failure to unite)
--> duct obstruction
- incidence ~10%, but probably a rare cause.
Sphincter of Oddi malformations.
Abnormal cationic trypsinogen
--> intracellular activation of trypsinogen.
- begin young, and develop chronic disease and often cancer.
- eg mumps; ?toxicity
Parasites may obstruct the ducts.
Autoimmune (eg biliary, Sjogrens); SLE.
--> & vasculitis
- direct Ig in lymphoplasmacytic autoimmune pancreatitis
Affecting the ampulla.
- & other periampullary pathologies.
--> main duct obstruction & hypertension activating
proenzymes, probably, rather than reflux
- stones usually pass spontaneously.
--> interferes with pancreas microcirculation.
--> accelerates conversion of trypsinogen to trypsin
--> facilitates enzyme activation.
--> ?vitamin / mineral deficit
Alcohol consumption (25%)
--> directly toxic, causes free radicals, hypersecretion (with
plugs & duct obstruction) and hyperlipidaemia
- may also lead to sphincter spasm
- diet of alcoholics likely contributary.
--> potent pancreatic secretogogue.
--> disrupts parenchyma / ducts
Ischaemia of pancreas
-->free radicals, endothelial injury
- azathioprine, steroids, diuretics, estrogens, frusemide,
metronidazole, tetracycline, thiazide, triprim, valproate.
--> alters secretions / are toxic to pancreas.
- paracetamol, methyl-dopa, isoniazid, procainamide, statins.
--> ductal disruption / enzyme extravasation.
Idiopathic by exclusion.
Around 10% in most series.
- often pts have sludge / microcholelithiasis & cholecystectomy
- others have Sphincter malfuction, treatable by sphincterotomy.
- others may have subclinical CF gene mutation.
D I A B M I M
Autodigestion causes inflammatory reaction.
Severity depends on the degree of pancreatic damage.
Fluid may accumulate locally, retroperitoneally, or
Gradient from mild localised interstitial oedema to confluent
- vascular disruption, intraparenchymal haemorrhage at the severe
Divided into 2 types
- usually become prominent in management beyond the first week.
Revised Atlanta Classification
1. Acute fluid collection
Occurs early in or near pancreas, ~30-50%.
- lack a wall, regress spontaneously in >50%.
- those that do not may form pseudocysts
- most do not need treatment and remain sterile.
2. Acute necrotic collection
First 4 weeks - collection containing variable amounts of fluid and
Typically includes fat necrosis
- some may resolve as fibrous tissue, others form pseudocysts
Fluid collection in peripancreatic tissues with a defined wall
- usually after 4 weeks.
4. Walled-off necrosis
Mature, encapsulated collection of pancreatic necrosis, well defined
Usually maturation after >4 weeks of necrotising pancreatitis.
5. Infected necrosis
Suspected by clinical course and gas within collection.
FNA if necessary but most can be managed without.
Other Local Problems
Some or all of pancreas may be necrosed.
- associated with peri-pancreatic fat necrosis.
Oedema may cause obstruction to bile flow and obstructive jaundice.
- or obstruction of small bowel.
A major peripancreatic vessel may form a pseudoaneurism, usually
after pseudocyst infiltration.
Recurrent bleeding with associated infection is common
- fatal hemorrhage may ensue
- haemosuccus pancreaticus
is bleeding through into the pancreatic duct
--> presents as transpapillary upper-Gi bleeding.
Splenic vein thrombosis
Not unusual in severe pancreatitis, due to proximity.
May lead to sinistral (Left) varices and bleeding.
Necrosis of the pancreas and surrounding fat may lead to deposition
of calcium (stearification)
--> precipitous falls in serum calcium levels.
Loss of fluid from circulating volume may cause shock.
Cardio, Pulmonary, Renal, Haematologic, Metabolic, Neurologic, GI
systems vulnerable in severe attack.
Mortality has remained about 10-15% for 20 years.
- early deaths due to MODS
- later usually due to infective complications.
(Revised Atlanta Classification)
Two out of:
1. Abdo pain consistent with acute pancreatitis
2. Serum lipase or amylase >3x upper limit of normal
3. Characteristic findings of acute pancreatitis on CT (or other
Acute abdominal pain.
- usually rapid onset, maximum within minutes.
- may have been slight attacks prior to main attack.
- may be sudden dramatic onset with fainting.
- may be localised to either UQ & loins
- or generalised later in course.
Radiates to middle of the back (50%).
- classically sit forward for relief.
Vomiting, may be profuse
- often nausea or retching without much material brought up.
- never feculent.
Fever is variable.
- often normal / cold at first
- rises with inflammation, commonly reaching 38-39 in severe attacks
(nb this is not infection)
Features of those above.
Shock commonly seem in severe cases.
- tachypnoea common
- tachycardia usual
- varying features of shock
Slight cyanotic appearance in severe attacks
If severe & bleeding, flank ecchymosis (Grey-Turner sign)
- or periumbilical ecchymosis (Cullen's sign).
- neither pathognomonic
- usually late
Jaundice may accompany biliary cause.
- or result from severe illness or obstruction from inflammation.
Subcut fat necrosis can cause tender red nodules on legs.
Epigastric tenderness is usual.
- rigidity possible / inconstant; often lax abdo wall.
- percussion, rebound tenderness & guarding possible.
Tender mass may be palpable.
Distension with ileus; rarely ascites.
Percuss / Auscultate
Pleural effusion in 10-20%.
Pulmonary oedema possible.
Decreased BS basally common due to splinting / atelectasis.
(Revised Atlanta Classification)
Depends on organ failure, acute or persistent (>48h), and local
or systemic complications
- organ failure based on 3 systems: resp, cardiac, renal
Mild = absence or organ failure or local / systemic
Moderate = transient organ failure or local or systemic
complications in absence of persistent organ failure
Severe = persistent organ failure
- set in motion by activation of cytokine cascades resulting in
- when SIRS is present in early phases, anticipate and treat as
1. Post op abdo pain, fever, unexplained shock.
2. Diabetic coma and shock.
3. Clinically suggestive of MI with abdo distension.
Commonly mistaken for perf DU
- general abdominal rigidity usually occurs earlier in perf DU
- cf 'epigastric peritonism' in pancreatitis usually.
- liver dullness loss / free air helps.
- history of onset / order of symptoms help (less vomiting and pain
early in appdx)
D I A B M I M
Amylase elevated, often 5-10x normal.
Short lived 24 hr peak.
- N range 30-110 U/L
- rise in 2-12hrs, normalise in 3-6 days (Sabiston)
- persisting elevation suggests complication.
- not a predictor of severity.
Specificity ~90%; also raised in cholecystitis, bowel obstruction,
perforated ulcer, bowel infarction, renal failure, salivary disease.
- however levels 4x normal are indicative (B&L).
Sensitivity ~90%, may be normal in the most severe cases.
Other enzymes / mediators
Eg lipase, trysinogen, elastase can be measured
- urinary measurement of activation peptides may help define
severity of attacks.
- similarly IL1, IL6, TNF-a, and especially CRP may be measure for
severity (see below).
- usually 2-5x higher than N in pancreatitis (N range 30-210 U/L)
- May be preferable to amylase, as more specific
- may still be slightly high in renal disease, PUD, occasionally
- also slightly more sensitive (FN rate with amylase is 10% or so).
- and remains elevated longer than amylase (5-7d); rises in 4-8h
- haematocrit a good marker of severity and need for rehydration.
Hypochloraemic metabolic alkalosis may follow vomiting.
Take blood cultures if cholangitis suspected.
Deranged coags, thrombocytopaenia, high fibrin degredation products,
and low fibrinogen if DIC developing.
Elevated bili x2 or AST x3 has a PPV of 95% for gallstones as cause.
Ascertain Modified Glasgow or Ranson for predicting
- severe if 3 or more in both
- no one system shown better than any other.
- 80% have a mild attack, mortality ~1%, little morbidity.
- 10% have a severe attack.
- mortality is 10-25% in a severe attack; now reducing in good
- traditionally 50% in infected necrosis; now reducing in good
Glasgow Scale (Imrie et al)
Age > 55
Glucose > 10 (not diabetic)
Urea > 16 (no response to IV fluids)
PaO2 <60 (8kPa)
Ranson's (New York)
- Hill: "Ranson score not frequently used as relates to
American population with alcohol as dominant aetiology".
Urea rise >5%
- criticised as difficult to calculate fluid sequestration.
CRP: severe if:
- >210 in first 4 days
- or >120 at end of first week.
- good predictive value & simple.
Score of 8+ is severe.
A score that worsens over first 48hrs despite treatment (and simply
score at 48hrs) is particularly accurate. (Sabiston)
Rises with severity.
AXR may show a sentinel loop
- local ileus
- loss of psoas shadow (fluid)
- gastric dilation
- pancreas poorly seen in 25-50%.
- importantly, ?gallstones, dilation of CBD.
CXR - ?ARDs.
- frequent basal atelectasis.
- gold standard for necrosis & collections
- IV contrast and helical CT (2-3 mm slices) can detect even subtle
- timing is controversial
- one study suggested early CT with contrast worsened
outcome but verification has failed
- early CT will not alter treatment
- recommended if diagnosis is uncertain or pt deteriating or
sometimes if severe disease
MRI - if CT surprisingly normal or renal disease (has same
sensitivity and specificity)
- MRCP can be considered in duct obstruction / disease
Balthazar Score for CT
A = Normal
B = focal or diffuse enlargement, including irregularities of
contour and inhomogeneous attenuation
C = Pancreatic gland abnormalities in grade B+ peri-pancreatic fluid
D = Grade C+ fluid collection
E = Grade C and 2+ fluid collections and/or gas in/around pancreas.
Diagnosis at laparotomy indicates poor practice
- fat necrosis of omentum
- blood-stained peritoneal fluid
CT can show cysts or bubbles suggesting infection.
- or guide FNA for infection confirmation.
- taking one sample site enough: do not need multiple passes.
D I A B M I M
Ascertain Severity (above).
Focus is on maximizing tissue oxygen perfusion and pain control.
Careful monitoring for end-organ effects.
With modern management in specialist centres, death from severe
acute panc has dropped to 5-10%
Generally NBM / sips of fluid
- no evidence for this, but may prevent pain or ileus problems.
- many will allows pts improving with mild disease to eat a bland
IV fluids to achieve adequate resuscitation, monitor urine output.
- ideally want >50ml/hr.
- ensure accurate balance will be kept.
- some say pethidine
- theoretically morphine can induce sphincter spasm, worsening
- no evidence for this however.
No antibiotics unless evidence of infection
No therapeutic treatments
CT scanning unnecessary unless deteriorates.
*Be aware may progress in severity*
NG only useful if ileus or for feeding
Enteral feeding is supported by the literature
- enhances epithelial barrier function, reduces sepsis and perhaps
- every attempt should be made to access the tract and feed
enterally in severe disease.
- inadequate evidence to support conservative or aggressive fluid
- usual parameters: urine output, HR etc, are unreliable.
- replace until it is adequate as per ABGs.
--> do an ABG early and treat as per subsequent ABGs to show
restoration of bicarb and base deficit (most reliable indicators of
- need invasive monitoring:
- CVP to guide fluids, especially when lung injury present and art
- maintain pO2: O2, CPAP, intubation etc.
- may be low, and if symptomatic, aggressively treat.
ERCP if reqd (see below)
- peritoneal dialysis to eliminate proinflammatory factors
(multicentre prospective RCT)
- any attempt to reduce GI / pancreatic secretion eg H2-blockers,
PPIs, somatostatin, atropine, calcitonin, glucagon.
- anti-inflammatories, eg steroids, PGs, indomethacin.
- agents inhibiting proteolytic enzymes eg aprotonin.
Should I use prophylactic antibiotics?
Ongoing area of controversy
Infected necrosis is a severe complication, responsible for second
spike in deaths beyond 10d
- updated meta-analysis in BJS 2006 (Mazaki et al) collated evidence
from 6 RCTs
- IV cefuroxime 1.5g tds or imipenim 500mg tds have been trialled,
or norfloxacin 200mg bd + metronidazole 500mg bd.
--> no evidence for reduction in infected necrosis, death,
non-pancreatic infections, need for surgical intervention.
--> p=0.04 for reduction in hospital stay (around 5d)
--> risk of promoting resistant organism infection is convincing,
risk of C diff significant, fungi
- weaknesses: poor quality studies with variable treatment and
pooling of first-phase deaths
Bottom line: do not
use routinely on current imperfect data.
- may choose to do in high risk patients, but add in a systemic
Mortality high in operated patients
To be avoided unless evidence of infected pancreatic necrosis or
Debriding necrosis, or draining abscesses / pseudocysts may become
- if culture from CT biopsy +ve, or gas seen on CT (see below)
Gallstones and timing of ERCP /
Awaits full clarification
- there are risks (contrast, introducing infection up duct) and
benefits (clearing blocked duct)
RCTs on early ERCP in serious cases have conflicting results
- but meta-anlysis showed benefit (for complication prevention, not
Bottom line: ERCP rserved for pts in whom biliary obstruction
clearly identified and conservative measures are failing to
- and then should be done within 48h.
All pts with acute cholangitis should be decompressed.
The GB should be removed as soon as the pt is well enough
- and preferably prior to discharge from hospital.
- recurrence rate within 6weeks is up to 30-40%; 90d recurrence 50%
- those with ductal stone problems may betreated with ERCP and
sphincterotomy alone if v. high risk candidates and discussed risks
Time when inflammation settling, pain resolved, then conversion rate
and CBD injury minimised.
US / MRCP +/- ERCP prior to surgery is useful.
If severe pancreatitis, may need to wait several months before
cholecystectomy can be pursued and all inflammation and
If pregnant and mild disease, best time is second trimester
- keep pressures <10mmHg and use MRCP rather than CT.
Usually resolve spontaneously.
Re-image at intervals until clear sign of regression.
Drainage of fluid collections or abscesses, if they persist or cause
Sterile necrotic material should not be drained.
Onset of infected necrosis greatly worsens prognosis
- demonstrated by CT with areas of Hounsfield <30
But debridement of sterile necrosis increases morbidity and
- as does early debridement
Major surgical debridement is possibly indicated if infected
necrosis is confirmed.
- infection usually occurs within 3-4 weeks of the attack
- if infected material retrieved, may need debridement
... growing practice of delaying debridement of infected necrosis as
long as possible
- may be best to wait for demarcation of necrosis and
compartmentalization of infection.
- may take 3-4 weeks
Optimize physiological parameters, treat sepsis
And consider risk balance of aggressive intervention vs delay to
How to diagnose infected necrosis?
SIRS is not specific
Procalcitonin very promising.
CT-guided FNA with microbial culture of necrotic tissue is
- imaging may show clues with gas, septated collections
- important to work with radiologists to minimize contrast dosing
Surgical strategies for infected necrosis
- guided by clinical condition.
- timing is a specialist decision that depends on patient factors,
disease factors and surgical factors.
- e.g. immune compromise, virulence, physiological status,
- approach depends on location, surgeon, course, patient.
2. Open Surgery
- if done early, expect major difficulty with adherent haemorrhagic
tissues; may need damage control; best avoided
- if done late, can 'scoop' out infected demarcated necrotic
- access pancreas, coagulate bleeding friable tissues,
- less enthusiasm for high-volume lavage.
3. Endoscopic necrosectomy
- very specialised strategy; via stomach
- access via gastrotomy, lavage / scooping and suction; avoid harm
- may leave as a cyst gastrostomy
- CT planning; remove tissue by a combination of blunt graspers,
irrigation and suction.
Place NG, stop enteral feeding, administer somatostatin
- aim to reduce pancreatic fluid secretion.
50-60% respond with resolution of ascites in 2-3 weeks.
Place a transpapillarly stent, as above may seal site of leakage.
Surgically treated by resection of tail, or Roux-en-Y drainage.
- reserved for those not responding to endoscopic treatment.
General term encompassing infected pancreatic necrosis, infected
pseudocysts, to other abscesses
Perc drainage may help with diagnosis then cure (resolves abscess in
Often require a multimodal approach
- source control with drainage, antibiotics, resuscitation and
supportive care, ABs.
Bacteruaial cultures are often polymyrobial with gut and clostridia;
generally use e.g. meropenem.
Avoid draining sterile collections.
May require surgery if does not settle, e.g. as per infected
- minimally invasive strategies preferred with a step-up approach as
Transpapillary stent management similarly used for
For false aneurysms, therapeutic angiography ideal
- subsequent distal pancreatectomy may be more ideal for tail
Pancreaticoenteric fistulas may need surgical intervention if
Splenic vein thrombosis may lead to varices; splenectomy may be
- less than 10% of such varices bleed, so splenectomy unusual.
D I A B M I M
Mazaki T et al. Meta-analysis of prophylactic antibiotic use in
acute necrotising pancreatitis. BJS 2006.
Hill J. Surgical Emergencies.