Acute and Chronic Pancreatitis
Prepared and Presented by Jon Manocchio, Pharm D Blanchard Valley Hospital PGY-1 Resident
Objectives
List common causes of acute and chronic pancreatitis Describe the pathophysiology of acute and chronic pancreatitis Differentiate the signs and symptoms of acute from chronic
pancreatitis Discuss the general approach to treatment of acute and chronic
pancreatitis Describe why patients with acute pancreatitis have oral intake
discontinued temporarily Identify when it may be appropriate to prescribe empiric
antibiotics in acute pancreatitis Discuss the use of octreotide in the treatment of acute
pancreatitis Develop a plan for the appropriate administration of pancreatic
enzyme supplementation in patients with chronic pancreatitis
Background
Endocrine Function Iselets of Langerhans Insulin
Glucagon
Somatostatin
Maintenance of blood glucose
Disease caused by dysfunction Diabetes mellitus Type 1
Type 2
Background
Exocrine Function Acinar and Ductal cells Secrete 2.5 L of fluid per day Water
Electrolytes
Pancreatic enzymes
Aid in metabolism
Neutralize gastric acid Appropriate pH for enzyme activity
Pancreatic ducts carry pancreatic juice to the duodenum
Background
Major exocrine enzyme groups Amylolytic Digestion of starches
Lipolytic Breakdown of lipids (cholesterol, TG, etc)
Proteolytic Digest proteins into amino acids
Nucleolytic Breakdown nucleic acids
Other
Case Introduction
Introduction
Define Pancreatitis
Inflammation
Regional involvement
Acute Pancreatitis (AP)
Self-limiting with spontaneous resolution
Progression to chronic pancreatitis
Chronic Pancreatitis (CP)
Long-standing inflammation
Loss of function
“Classic Triad” of progression
Epidemiology
Less than 1% of people will develop AP
Approximately 6/100,000 people will develop CP
Peak incidence age 35-54
85% of cases occur in men
Men: due to alcohol
Women: due to gallstones
Acute Pancreatitis
Etiology
Most common causes
1) Gallstones
2) Alcoholism (elevated TGs)
Other causes
ERCP
End-stage kidney disease
Cigarette smoking
Medications
Risk Factors
Various
Structural
Toxins
Infections
Metabolic
Genetic
Medications
Iatrogenic
Kidney Disease
Trauma
Vascular
Idiopathic
Pathophysiology
Premature activation Trypsinogen to trypsin
Leads to activation of other digestive enzymes
Autodigestion of the pancreas and surrounding areas
Immune response to inflammation
SIRS
Possible infection
Correlation with extremely elevated TG
Presentation and Symptoms
Varies based on severity
Symptoms
Abdominal pain (95%)
Knife-like
Nausea and Vomiting (85%)
Signs
Epigastric tenderness
Laboratory Results
LFT’s (inc) TGs (inc) Amylase (inc) Lipase (inc)
Complications
Local Complications Fluid retention (pleural space) Pancreatic necrosis Infection
15-30% of those with pancreatic necrosis
Abscess
Systemic Complications Cardiovascular Renal Pulmonary (ARDS) Metabolic Hemorrhagic Central Nervous System Long-term complications
Diagnosis
Based on signs and symptoms Abdominal Pain
Increased Amylase
Increased Lipase
Use of CECT
History and patient work-up Presence of gallstones
Alcoholism
Medication Use
Disease Severity DIAGNOSIS
Age > 55 yo
WBC > 16,000/mcL
Glucose > 200mg/dL
LDH > 350 IU/L
AST > 250 IU/L
DEVELOPED (48 HRS)
Hematocrit fall > 10%
BUN rise > 5mg/dL
Ca++ < 8mg/dL
Arterial PO2 < 60 mmHg
Base deficit > 4 mEq/L
Est Fluid Sequestration > 6L
MORTALITY RATES
Number of Criteria Mortality
0-2 1%
3-4 16%
5-6 40%
>7 100%
Ranson Criteria
Goals of Therapy
Relieve abdominal pain
Relieve nausea
Replace fluids
Correct electrolyte, glucose, and lipid imbalances
Minimize systemic complications
Prevent infection (when appropriate)
NPO
Treatment
Supportive Care Abdominal pain Hydromorphone 0.5mg IV q3h PRN Meperidine Morphine
Nausea Ondansetron 4mg IV q6h PRN Promethazine 12.5-25mg IM/PO q4-6h PRN
Nutrition Begin oral feeding when bowel sounds are
present and pain has been resolved Utilize enteral feeding if oral feeding is expected
to be held for > 7 days
Treatment
Supportive Care IV fluids Plays a major role in improving prognosis 0.9% NS run continuously
Correct electrolyte deficiencies Calcium, Potassium, and Magnesium
Correct hyperglycemia Insulin
Necrotizing Pancreatitis may require antibiotics Not recommended to use as prophylaxis If infectious Imipenem/cilastatin 500mg IV q8h Ciprofloxacin or levofloxacin + metronidazole
Treatment
Limit Systemic Complications
Medications that fail to show benefit
Proton Pump Inhibitors
H2 Antagonists
Corticosteroids
Protease Inhibitors (aprotinin)
Prophylactic antibiotics
Somatostatin or Octreotide
Supportive Care
Monitoring
Hydration status
Electrolytes
Calcium, Potassium, Magnesium
Pain control
Nutritional status
Severe acute pancreatitis
Many different monitoring parameters
Prognosis
Course of disease Transient disorder Self-limiting and subsides in 3-5 days Mortality increases with unfavorable signs
Severe necrotizing disease 10% mortality rate 30-40% mortality rate with infected necrosis
Mortality During the first few days SIRS Multi-organ failure
Thereafter Infected necrosis, pan. abscess, and sepsis
Chronic Pancreatitis
Etiology
Most common cause Chronic alcohol consumption (alcoholism)
70-80% of cases Idiopathic
20% of cases Rare causes
10% of cases
Genetics Three genes
Catatonic trypsinogen (PRSS1) Serine protease inhibitor Kazal type 1 (SPINK1) Cystic fibrosis transmembrane conductance
regulator (CFTR)
Risk Factors
M-ANNHEIM Multiple risk factors
Alcohol
Nicotine
Nutritional factors
Heredity factors
Efferent duct factors
Immunologic factors
Miscellaneous and rare factors
Pathophysiology
Exact mechanism is unknown
Proposed theories
Oxidative stress
Toxic metabolite
Ductal obstruction
Periductal necrosis
Presentation and Symptoms
“Classic Triad” Chronic abdominal pain Steatorrhea Diabetes mellitus
Signs Malnutrition Abdominal mass Possible jaundice
Laboratory Results May only be abnormal during an acute attack Glucose (inc) CBC
Diagnosis
Based on signs and symptoms
Presence of the “Classic Triad”
Imaging studies
Gold standard: ERCP
Also EUS
History and patient work-up
Presence of gallstones
Alcoholism
Medication Use
Acute pancreatitis seldom indicates progression to chronic pancreatitis
Goals of Therapy
Relieve abdominal pain
Treatment of associated complications Steatorrhea
Malabsorption
Diabetes Mellitus
Loss of endocrine function
Improve quality of life
Treating secondary disorders Depression
Malnutrition
Treatment
Lifestyle modifications
Abstain from alcohol
Smoking cessation
Eat small, frequent meals
Reduce dietary fat intake
0.5g/kg/day
Treatment
Specific Regimens Abdominal Pain Non-opioid analgesics APAP 500mg QID maximum (with alcohol)
NSAIDS normal dosing patterns
Tramadol 50-100mg q4-6h
Non-opioid analgesics + pancreatic enzymes
Opioid analgesics Codeine 30-60mg PO q6h
Hydrocodone 5-10mg PO q4-6h
Hydromorphone 0.5-1mg PO q4-6h
Treatment
Specific Regimens Malabsorption Begin when steatorrhea is present and
weight loss occurs
Creon 6,000, Creon 12,000, Creon 24,000 Varies based on lipase content
Administer with or just after a meal
May be used with a PPI or H2A to allow for greater availability (gastric pH prevents release)
Diabetes Insulin remains the gold standard
Monitoring
Pain Control
Constipation
Weight
Stool frequency
Blood glucose
Prognosis
Life expectancy 10 year survival rate
70%
20 year survival rate
45%
Morality Cardiovascular disease
Infection
Malignancy
Pancreatic Cancer 15 times more likely with alcoholic pancreatitis
Case Conclusion
Conclusion
Pancreatitis can be an acute or a chronic disease
Limiting alcohol intake greatly reduces the chances of developing pancreatitis
The exact pathophysiological causes of each is ambiguous
A person with acute pancreatitis will not necessarily develop chronic pancreatitis
The gold standard for treatment is supportive care as well as pain management
Other treatment modalities have vague evidence with limited success
Patients should be monitored frequently to identify any recurrent exacerbations or complications associated with each disease state
Questions?
References 1) Banks PA and Freeman ML. Practice Guidelines in Acute Pancreatitis. Am
J Gastroenterol. 2006; 101: 2379-2400.
2) Bolesta S, Montgomer PA, “Chapter 46. Pancreatitis” (Chapter). DiPiro JT, et al: Pharmacotherapy: A Pathophysiologic Approach, 8e: http://www.accesspharmacy.com.polar.onu.edu
3) Fauci AS, et al, “Chapter 313. Acute and Chronic Pancreatitis” (Chapter).
Fauci et al: Harrison’s Principles of Internal Medicine, 17e: http://www.accesspharmacy.com.onu.edu
4) Giuliano CA, et al. Pancreatic Enzyme Products: Digesting the Changes.
Ann Pharmacother. 2011; 45: 658-65. 5) McPhee SJ et al, “Differential Diagnosis and Diagnostic Algorithms”
(Chapter). Nicoll D, McPhee SJ, Pignone M: Pocket Guide to Diagnostic Tests, 5e: http://www.accesspharmacy.com.polar.onu.edu
Previous Test Questions
Clinically, which opioid analgesic is most often used in the inpatient setting to control the pain associated with pancreatitis? Morphine
Hydromorphone
Meperidine
Oxycodone
Fentanyl
Previous Test Questions
Which statement adequately describes the use of antibiotics with pancreatitis?
Antibiotics should always be used as prophylaxis
Antibiotics should be used during pancreatitis only when a culture and sensitivity is available
Antibiotic therapy should only be initiated after pain is completely controlled
Antibiotics should only be initiated if infection is suspected, as in the development of sepsis
Antibiotics are contraindicated for use at anytime during pancreatitis
Previous Test Questions
A 73yom presents to the ED complaining of epigastric pain and nausea for the past 10 days. His history is significant for CP, HTN, DM, and alcoholism. Lab results are wnl except for glucose (187), potassium (3.2) and sCr (1.6). Home medications were unable to be obtained. Based on this information, which of the following options would be an appropriate to initiate?
Begin 0.9%NS @150 mL/hr
Begin hydromorphone 0.5mg IV q3-4h
Begin imipenem/cilastatin 500mg IV q8h
A and B
A, B, and C
Previous Test Questions
Which enzyme is responsible for converting trypsinogen to trypsin?
Enterokinase
CCK
Secretin
Amylase
VIP
Previous Test Questions
Which of the following is NOT associated with the “Classic Triad” of chronic pancreatitis?
Epigastric Pain
Diarrhea
Steatorrhea
Diabetes mellitus
None of the above, all of these are associated with the “Classic Triad”