Chronic pancreatitis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Overview

The goals of chronic pancreatitis management include pain control, management of pancreatic insufficiency by pancreatic enzyme replacement and management of complications. Pain is managed in a stepwise approach of general recommendations, pancreatic enzyme replacement, analgesics and invasive procedures. General recommendations usually include smoking cessation, cessation of alcohol intake, small meals and hydration. Medical therapy includes pancreatic enzyme supplementation, analgesics and antioxidants. Specialized approaches include celiac nerve block, endoscopic therapy, extracorporeal shock wave lithotripsy (ESWL), and radiation. Steatorrhea can be managed by dietary modification, lipase supplementation, vitamin supplementation, and medium chain triglycerides (MCTs). Diabetes is usually managed with a trial of oral hypoglycemic agents followed by insulin therapy.

Chronic pancreatitis management:

The goals of management are:

  • Pain control
  • Management of pancreatic insufficiency by pancreatic enzyme replacement
  • Management of complications[1]

Pain management:

Pain is managed in a stepwise approach of

  • General recommendations
  • Pancreatic enzyme replacement
  • Analgesics
  • Other invasive procedures

General recommendations:

Most of the patients usually improve following the general recommendations with only a few requiring analgesics.

(a) Smoking cessation:
  • Smoking cessation may
    • Delay the progression of chronic pancreatitis
    • Decrease the risk of pancreatic cancer[2]
(b) Cessation of alcohol intake:
  • Alcohol cessation may help in symptomatic improvement particularly in alcohol induced chronic pancreatitis.
  • Alcohol intake is associated with increased mortality in pateints with alcohol induced chronic pancreatitis.[3]
(c) Small meals:
  • Dietary preference in chronic pancreatitis should be small meals with low fat content
  • Medium chain triglyceride (MCTs) supplementation is particularly helpful because;
    • Its antioxidant effects
    •  Minimal increase in plasma CCK levels
    • It may prevent weight loss in patients
(d) Hydration:
  • Keeping the patients well hydrated may help in preventing the development of acute flares pf pancreatitis.

Medical Therapy:

1.Pancreatic Enzyme Supplementation:

  • Pancreatic enzyme supplementation is associated with pain alleviation and may be used when the general recommendations fail.
  • It decreases the release of CCK and thus reduces the stimulation-induced pancreatic pain but mixed results have been observed from various clinical trials.[4][5][6][7][8][9][10][11]
  • It is particularly beneficial in the management of patients with idiopathic chronic pancreatitis.[12][10]

2.Analgesics:

  • Analgesics are usually required when pancreatic enzyme replacement therapy fails to manage pain in chronic pancreatitis.
  • Pain cycle may be disrupted by:
    • Opiates coupled with amitriptyline and an NSAID.[13][14]
    • NPO and short-term hospitalization of the patient.
  • Long-acting agents, such as continuous morphine sulphate or fentanyl patch, are usually recommended for chronic pain management.
  • Adjuvat therapy with Pregabalin is also found to be effective in some clinical trials.[15][16]

3.Antioxidants:

  • Antioxidant therapy has no established effective role in the management of chronic pancreatitis as various studies have shown conflicting results.[17][18][19][20][21]

4.Specialized approaches:

4.1 Celiac nerve block
  • Celiac nerve block is not a proven therapy as [10][22][23][24]
    • It may cause serious complications
    • Recurrence may occur
    • It has limited success in chronic pancreatitis
  • It can be achieved by using alcohol or steroid via
    • Percutaneous approach or
    • Endoscopic approach
4.2 Endoscopic therapy
  • Pain releif can also be acheived by decompression of an obstructed duct via endoscopic approach.[25][26][27][28][29][30]
  • Surgery is more effective when compared to endoscopic therapy.[31]
4.3 Extracorporeal shock wave lithotripsy (ESWL) 
  • Pain can also be relieved by using ESWL.[32]
  • It causes millimetric fragmentation of pancreatic stones.
  • Its role in chronic pancreatitis management is still unclear due to the limited studies done in this area.
4.4 Radiation
  • Radiotherapy is also helpful in pain relief due to its anti-inflammatory properties.[33]

Management of Steatorrhea:

  • In chronic pancreatitis, pancreatic enzyme replacement is usually dependent upon
    • The size and nature of the meal 
    • The residual function of the pancreas
    • The goals of therapy (elimination of steatorrhea, reduction in the abdominal symptoms of maldigestion or acheivement of nutritional goals)
1. Dietary modification
  • The degree of fat intake restriction is usually dependent upon the severity of malabsorption.
  • Medical therapy is considered if steatorrhea persists after dietary restriction.
  • Fat intake of ≤ 20 grams per day is sufficient to prevent steatorrhea.
2. Lipase supplementation
  • The pancreas normally responds with between 700,000 and 1,000,000 lipase units (USP) per meal.[34]
  • 10% of normal pancreatic lipase replacement (70,000 to 100,000 USP) can manage the symptoms of steatorrhea even when all of the pancreatic function has been lost.
  • Usually 30,000 international units (IU) or 90,000 United States Pharmacopeia units (USP) of lipase per meal (5-10%) are sufficient to correct the malabsorption in chronic pancreatitis.
  • 90,000 USP of lipase per meal (5-10%) is sufficient to abolish steatorrhea in chronic pancreatitis.
  • Dosing is usually dependent upon:
    • The individual's weight
    • The degree of pancreatic insufficiency
    • The size and fat content of a meal
  • Creon-24,000 lipase, enteric coated formulations, one to two capsules with meals and one capsule with a snack
  • Viokace Lipase 20,880, non-enteric coated formthree tablets with meals and one to two tablets with a snack
NOTE:
  • Non-enteric supplements may require H2 antagonist or proton pump inhibitor.
  • Non-enteric supplements may be more useful in achlorhydric patients or those with dyssynchronous gastric emptying (eg, Billroth II anatomy).
3. Vitamin supplementation 
  • Patients with severe steatorrhea may require vitamin supplementation.
  • Calcifediol, a naturally occurring analogue of vitamin D (25-hydroxylated form) is more polar and potent than vitamin D2 or D3.
  • It is important to monitor serum cacium levels for the first few week of therapy due to increased risk of developing hypercalcemia.
4. Medium chain triglycerides (MCTs)
  • Medium chain triglycerides are preferred over long chain triglycerides as
    • MCTs do not need the presence of bile for their degradation
    • MCTs may be degraded easily by gastric and pancreatic lipase
    • MCTs can be absorbed directly from the intestinal mucosa
    • MCTs have a weak stimulatory affect on pancreatic secretions

Management of glucose intolerance:

  • Glucose intolerance usually develops in the early course of disease while overt diabetes may develop in the late course of disease.
  • Patients are usually managed with a trial of oral hypoglycemic agents followed by insulin therapy.

References

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