Chronic pancreatitis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute intermittent episodic pain

1st line – alcohol and cigarette smoking cessation plus dietary intervention

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1st line –

alcohol and cigarette smoking cessation plus dietary intervention

Alcohol and smoking cessation should be a cornerstone of any treatment programme for patients with chronic pancreatitis, despite low quality of evidence for alcohol cessation.[44][45][85][146][147][148][149]

One randomised controlled trial indicated that repeat counselling at 6 monthly intervals is associated with fewer recurrent attacks of alcohol-related pancreatitis.[150]

Performing elective interventional procedures on patients who are actively using alcohol should be considered cautiously. Patients requiring urgent or emergent procedures for complications of chronic pancreatitis should be considered separately.[85]

Smoking is a risk factor for developing acute and chronic pancreatitis, increases the risk of progressing from acute to chronic pancreatitis, and accelerates the progression and onset of complications (pancreatic calcifications, pancreatic cancer).[85]

Malabsorption of fat and protein, in addition to fat-soluble vitamin deficiencies (A, D, E, and K), can lead to malnutrition.[96][152][153] Up to 63% of patients with chronic pancreatitis have fat-soluble vitamin deficiencies.[96][154]

Malnourished patients should be advised to eat high-protein, high-energy food in five to six small meals per day.[153]

Early intervention with dietitian input providing balanced dietary advice has been shown to be as effective at reducing malnutrition as providing supplements, and should be considered for all patients diagnosed with chronic pancreatitis.[152][155]

Plus – analgesia

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Plus –

analgesia

Treatment recommended for ALL patients in selected patient group

Acute, intermittent episodes of pain require conservative management. In addition to lifestyle changes, pain can be managed initially with simple analgesia (e.g., paracetamol and ibuprofen) with the addition of a weak opioid (e.g., tramadol) if necessary.[83][164]

Patients with chronic pancreatitis may require rapidly increasing doses of strong opioids risking tolerance and hyperalgesic adverse effects.[83] Although opioid analgesics may be necessary while developing a pain management programme, a major goal is to reduce pain with opioid-sparing adjunctive agents in order to avoid two major opioid complications: dependence and gastrointestinal adverse effects.

Primary options

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

ibuprofen: 400-800 mg orally every 6-8 hours when required, maximum 2400 mg/day

tramadol: 50-100 mg orally (immediate-release) every 4-6 hours when required, maximum 400 mg/day; 100 mg orally twice daily or 150 mg once daily initially (extended-release), increase when required, maximum 400 mg/day

Secondary options

oxycodone: 5-30 mg orally (immediate-release) every 6 hours when required

morphine sulfate: 10 mg orally (immediate-release)/intravenously every 3-4 hours when required

ONGOING

persistent pain management

1st line – alcohol and cigarette smoking cessation

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1st line –

alcohol and cigarette smoking cessation

One randomised controlled trial indicated that repeat counselling at 6 monthly intervals is associated with fewer recurrent attacks of alcohol-related pancreatitis.[150]

Consider – analgesia

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Consider –

analgesia

Additional treatment recommended for SOME patients in selected patient group

A stepwise approach to analgesia is recommended (i.e., simple analgesics, tramadol, low-dose tricyclic antidepressants such as nortriptyline, and gabapentinoids such gabapentin and pregabalin).[83]

Patients with chronic pancreatitis may require rapidly increasing doses of strong opioids, risking tolerance and hyperalgesic adverse effects.[83] Although opioid analgesics may be necessary while developing a pain management programme, a major goal is to reduce pain with opioid-sparing adjunctive agents in order to avoid two major opioid complications: dependence and gastrointestinal adverse effects.[83]

Nortriptyline combined with gabapentin has been shown to improve neuropathic pain, and is a suggested adjunct treatment for patients with chronic pancreatitis.[83][165] Low-to-moderate quality evidence indicates that pregabalin (a gabapentinoid effective in treating centralised neuropathic pain of other causes) reduces abdominal pain of chronic pancreatitis compared with placebo.[166][167][224]

Care should be taken when prescribing to avoid polypharmacy.[83]

Primary options

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

ibuprofen: 400-800 mg orally every 6-8 hours when required, maximum 2400 mg/day

Secondary options

morphine sulfate: 5-20 mg orally (immediate-release)/subcutaneous/intramuscular every 4 hours when required; 2.5 to 5 mg intravenously every 4 hours when required

pregabalin: consult specialist for guidance on dose

gabapentin: consult specialist for guidance on dose

nortriptyline: consult specialist for guidance on dose

Consider – pancreatic enzyme replacement therapy

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Consider –

pancreatic enzyme replacement therapy

Additional treatment recommended for SOME patients in selected patient group

Pancreatic enzyme replacement therapy is recommended for patients with chronic pancreatitis and exocrine pancreatic insufficiency to improve the complications of malnutrition, but not to treat pain alone.[85]

A reduction in steatorrhoea and associated gastrointestinal symptoms; improvement in fat-soluble vitamin levels; and improvement in weight, muscle mass, and muscle function are the indicators of successful pancreatic enzyme replacement therapy.[84]

Both timing and dosing of pancreatic enzymes influence the effectiveness of treatment.[136] The American Gastroenterological Association recommends taking pancreatic enzyme supplements during a meal.[84] An initial dose of at least 40,000 USP units of lipase is recommended in adults during each meal; a dose of at least 20,000 USP units is recommended with snacks.[84] Subsequent doses can be adjusted on the basis of meal size and fat content.[84]

Some patients may need gastric acid suppression with a proton-pump inhibitor or H2 antagonist to improve absorption.[83] Pancreatic enzyme products that are not enteric-coated require administration with a proton-pump inhibitor.

Options for patients who remain symptomatic include increasing the dose and switching from immediate-release (non-enteric-coated) enzymes to enteric-coated microspheres.[160][161][162]

Primary options

pancreatin: 500-2500 lipase units/kg/dose orally with each meal, adjust dose according to symptoms and fat content of diet, maximum 10,000 lipase units/kg/day

Consider – dietary modifications plus enteral feeding

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Consider –

dietary modifications plus enteral feeding

Additional treatment recommended for SOME patients in selected patient group

A low-fat diet may contribute to development of fat-soluble vitamin deficiencies and is an unnecessary intervention for treatment of steatorrhoea.[153] About 80% of patients with chronic pancreatitis can be managed with normal diet (30% fat content) and pancreatic enzyme replacement therapy, with 10% to 15% requiring nutritional supplementation and 5% requiring enteral tube feeding.[83][156]

Malnourished patients should be advised to eat high-protein, high-energy food in five to six small meals per day.[153]

Dietary modifications (e.g., a low-fat diet) and enteral feeding may reduce pain, conceivably by minimising enteral cholecystokinin release and reducing pancreatic stimulation. According to normal digestive physiology, an elemental diet fed orally or by enteral tube reduces exocrine pancreatic secretion by 50% and reduces secretion to basal levels (true 'pancreatic rest') when enteral feeding is delivered 40 cm to 60 cm past the ligament of Treitz.[157]

A significant number of patients who received long-term jejunal feeding via endoscopically placed feeding tubes experienced pain relief and weight gain, and enteral feeding in hospitals using nasojejunal tubes has been reported to decrease pain and limit malnutrition.[156][158]

Consider – antioxidants

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Consider –

antioxidants

Additional treatment recommended for SOME patients in selected patient group

Antioxidant therapy may be considered for the management of pain associated with chronic pancreatitis.[85]

One randomised controlled trial indicated that a five-component antioxidant cocktail (containing selenium, beta-carotene, vitamin C, vitamin E, and methionine) may reduce the frequency of pain by 1.5 days per month in patients with chronic pancreatitis.[168] This modest effect may be limited to a subset of patients, specifically those with deficiencies of antioxidants and/or antioxidant-scavenging enzymes and with increases in markers of oxidative stress. A subsequent RCT performed in patients without these characteristics reported that the same five-component antioxidant cocktail had no impact on any outcome measured other than increasing antioxidant levels.[169]

Systematic reviews have concluded that antioxidants can reduce pain in patients with chronic pancreatitis, particularly in those age 42 years or older and with chronic pancreatitis associated with alcohol.[170][171]

Antioxidant levels should be measured and, if abnormal, antioxidant supplementation should be provided.[168]

Consider – coeliac plexus block

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Consider –

coeliac plexus block

Additional treatment recommended for SOME patients in selected patient group

Coeliac plexus block (CPB) with a corticosteroid and local anaesthetic may be offered for the management of debilitating abdominal pain due to chronic pancreatitis, particularly for pain refractory to other treatments.[85] This salvage therapy is recommended by the American College of Gastroenterology (conditional recommendation, very low quality of evidence), but the American Gastroenterological Association advises against routine use of CPBs because of uncertain outcomes and procedural risks.[85][172] A single treatment can potentially provide pain reduction or relief for 3-6 months, may reduce or eliminate the need for oral analgesia, and can be performed quickly and repeated as needed.[85]

Randomised controlled trials and meta-analyses have addressed the potential benefit of CPBs in chronic pancreatitis.[173][174][175][176] Endoscopic ultrasound (EUS)-guided CPB may be superior to a percutaneous technique with fluoroscopic guidance.[177]

Common side effects of a CPB include diarrhoea and postural hypotension.[178] Paraplegia has rarely been reported in posterior-approach CPB, and in EUS coeliac plexus neurolysis.[179][180]

with pseudocysts

Consider – endoscopic or surgical pseudocyst decompression

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Consider –

endoscopic or surgical pseudocyst decompression

Additional treatment recommended for SOME patients in selected patient group

Decompression of pseudocysts is indicated for persistent pain, cyst enlargement, or complications of the pseudocyst.

In addition to lifestyle changes and analgesia, endoscopic treatment to dilate strictures, remove stones, or drain pseudocysts can improve pain.[83]

Endoscopic decompressive procedures include endoscopic retrograde cholangio-pancreatography (ERCP) with pancreatic sphincterotomy, stone clearance, stricture dilation, and pancreatic duct stenting.[85] For benign biliary strictures due to chronic pancreatitis, the American Gastroenterological Association recommends ERCP with stent insertion and prefers fully covered self-expanding metal stents over multiple plastic stents.[172] The American College of Gastroenterology recommends malignancy should be excluded prior to offering long-term endoscopic treatment and favours treatment with multiple plastic stents over fully covered self-expanding metal stents when the gallbladder is in situ, to avoid occluding the cystic duct and increasing the risk of acute cholecystitis.[182]

Endoscopic drainage procedures may be performed as first-line (through ERCP and/or EUS) in patients with a symptomatic obstructed pancreatic duct.[85]

Endoscopic drainage is successful in 80% to 89% of patients, and recurrence rates range from 4% to 18% after 2 years.[183][184] Results from one Cochrane review favoured endoscopic drainage over surgical drainage in mixed populations of patients (acute and chronic pancreatitis).[185] The endoscopic (EUS) approach resulted in a higher short-term quality of life, although a higher rate of additional procedures.[185] Coupling EUS-guided drainage to nasobiliary drainage may further improve outcomes.

Surgery should be performed when medical and endoscopic options have failed.[82][85] The American Gastroenterological Association recommends surgery over endoscopic treatment for the long-term treatment of patients with painful obstructive chronic pancreatitis.[172]

Surgical drainage fails in around 7% to 10% of patients.[186][187][188]

All pseudocyst drainage procedures have complication rates ranging from 8% to 34% due to infection, bleeding, perforation, leaking, and fistulation.[110][186][187][188]

with biliary complications

Consider – endoscopic or surgical biliary decompression

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Consider –

endoscopic or surgical biliary decompression

Additional treatment recommended for SOME patients in selected patient group

Biliary decompression should be considered if twofold elevation in alkaline phosphatase persists for longer than 1 month, and after excluding other causes of cholestasis (e.g., parenchymal disease, abscess).[201]

Endoscopic drainage procedures may be performed first-line (through ERCP and/or EUS) in patients with a symptomatic obstructed pancreatic duct.[85]

Endoscopic therapy involves biliary sphincterotomy with placement of multiple simultaneous plastic stents rather than single stents.[189][190][191] Placement of a single covered self-expandable metallic stent, however, has a comparable biliary stricture success rate to that seen with multiple plastic stents.[192][193] Endoscopic approaches require repeated therapy sessions and place patients at risk for stent-related complications, particularly cholangitis.

A major endoscopic complication is recurrent obstruction.

with intractable pain and main pancreatic duct dilation (>5 to 7 mm)

Consider – endoscopic or surgical pancreatic ductal decompression

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Consider –

endoscopic or surgical pancreatic ductal decompression

Additional treatment recommended for SOME patients in selected patient group

Endoscopic drainage procedures may be performed first-line (through ERCP and/or EUS) in patients with a symptomatic obstructed pancreatic duct.[85]

Pancreatic ductal decompression can be considered in patients with intractable pain and main pancreatic duct dilation (>5 to 7 mm) with and without pancreatic duct stones, to provide pain relief. Endoscopic management is not first line and should be considered only after failure of other measures.[194] [ ] However, the choice of surgical versus endoscopic therapeutic options may be influenced by patient comorbidities and considerations that long-term pain can also recur in surgical groups.[47]

Surgical decompression has better immediate and long-term results than endoscopic techniques.[194][225][226][227] [ ] This is possibly because surgery addresses other hypothesised aetiologies of pain by denervating pancreatic sensory nerves and reducing pancreatic tissue pressure, an endpoint that may predict the magnitude of pain resolution.[228] Pain relief is immediate with surgery but delayed with endoscopic decompression.[194][226][227]

However, the choice of surgical versus endoscopic therapeutic options may be influenced by patient comorbidities and considerations that long-term pain can also recur in surgical groups.[47]

with intractable pain and pancreatic duct calcifications

Consider – extracorporeal shock wave lithotripsy (ESWL)

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Consider –

extracorporeal shock wave lithotripsy (ESWL)

Additional treatment recommended for SOME patients in selected patient group

ESWL can be offered to patients with pancreatic duct calcifications with a minimal diameter of 2-5 mm.[82] One meta-analysis found that 53% of patients with chronic calcific pancreatitis (pancreatic duct stones greater than 5 mm and/or failed conservative management) who underwent ESWL were pain free at follow-up; quality of life improved in 88% patients.[181]

ESWL is used mostly in Europe, although it is available in a few specialised centres in the US.[82]

with intractable pain and small duct disease

Consider – surgical interventional procedures

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Consider –

surgical interventional procedures

Additional treatment recommended for SOME patients in selected patient group

Resection using pancreaticoduodenectomy (PD; Whipple procedure) is recommended if disease is present in the head of the pancreas, particularly with pancreatic head enlargement, and other options are exhausted.[47][205] PD may be performed as a pylorus-preserving PD.

One Cochrane review found that duodenum-preserving pancreatic head resection procedures (with or without drainage of the pancreatic duct) are as effective as PD at pain relief, reducing morbidity, and reducing the incidence of postoperative endocrine insufficiency.[206] Length of hospital stay may be shorter following duodenal-preserving pancreatic head resection procedures, but adverse events, quality of life, and mortality are not significantly different between PD and duodenum-preserving pancreatic head resection.[206] [ ]

The outcomes of different duodenum-preserving surgeries are similar; effects upon quality of life and pain control persist after 16 years of follow-up.[46][207][208][209]

Controversy exists about offering total pancreatectomy combined with islet cell autotransplantation for treatment of pain in early chronic pancreatitis.[210][211]

Islet cell transplantation reduces insulin dependence in some patients.[212] Remnant pancreatitis may account for persistent but reduced pain in some patients.[205] Total pancreatectomy with islet autotransplant is only recommended for highly selected patients with refractory chronic pain in whom all other symptom control measures have failed.[205]

It is hypothesised that denervation of pancreatic sensory nerves may improve pain.[213] Denervation has been accomplished using an open surgical approach and using thoracoscopic surgery.[213][214]

One systematic review reported that thoracoscopic splanchnicectomy reduces pain and improves quality of life for patients with chronic pancreatitis.[215] Two prospective studies with long-term follow-up suggest that pain relief with thoracoscopic splanchnicectomy is of short duration, with only about 50% of patients reporting pain relief after 2 years.[216][217]

Pre-operative opioid use is independently predictive of pain relief.[218]

with intractable pain and distal pancreatic disease ± pancreatic head enlargement

Consider – distal pancreatectomy

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Consider –

distal pancreatectomy

Additional treatment recommended for SOME patients in selected patient group

Indicated for pseudocysts and fibrosis limited to the tail. It is an uncommon indication for relieving pain, because the pancreatic head is considered the predominant pacemaker for pain.[47][205]

Distal pancreatectomy in patients with disease limited to the tail is associated with a complication rate of 20% to 40% and low morbidity (15% to 46%) and mortality (0% to 3%).[219][220][221] Surgery performed for pain and localised fibrosis is associated with a high recurrence rate of pain.[222]

Due to the generalised nature of the disease, persistent or recurrent symptoms may occur, requiring 20% to undergo completion pancreatectomy.[223] Unsuspected pancreatic carcinoma causing post-obstructive chronic pancreatitis may be an underlying pathology (particularly for strictures >10 mm).[204][222]

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Chronic pancreatitis

Treatment algorithm

acute intermittent episodic pain

alcohol and cigarette smoking cessation plus dietary intervention

analgesia

Primary options

Secondary options

persistent pain management

alcohol and cigarette smoking cessation

analgesia

Primary options

Secondary options

pancreatic enzyme replacement therapy

Primary options

dietary modifications plus enteral feeding

antioxidants

coeliac plexus block

endoscopic or surgical pseudocyst decompression

endoscopic or surgical biliary decompression

endoscopic or surgical pancreatic ductal decompression

extracorporeal shock wave lithotripsy (ESWL)

surgical interventional procedures

distal pancreatectomy