Download Acute Pancreatitis

Acute Pancreatitis
Rajeev Jain, M.D.
December 15, 2003
Normal Anatomy & Physiology
•
neutralize
chyme
•
digestive
enzymes
• hormones
Exocrine Function
common bile
duct
BODY
TAIL
HEAD
pancreatic duct
ampulla
UNCINATE
pancreatic enzymes
Enzyme Secretion
acinus
pancreatic duct
microscopic view
of pancreatic acini
duodenum
Enzyme Secretion
Neural
acetylcholine
VIP
GRP
Hormonal
CCK
gastrin
Secretin (hormonal)
H2O
bicarbonate
Digestive Enzymes in the
Pancreatic Acinar Cell
PROTEOLYTIC
ENZYMES
Trypsinogen
Chymotrypsinogen
Proelastase
Procarboxypeptidase A
Procarboxypeptidase B
AMYOLYTIC ENZYMES
Amylase
LIPOLYTIC ENZYMES
Lipase
Prophospholipase A2
Carboxylesterase lipase
NUCLEASES
Deoxyribonuclease (DNAse)
Ribonuclease (RNAse)
OTHERS
Procolipase
Trypsin inhibitor
Normal Enzyme Activation
enterokinase
trypsinogen
chymotrypsinogen
proelastase
prophospholipase
procarboxypeptidase
duodenal lumen
trypsin
chymotrypsin
elastase
phospholipase
carboxypeptidase
Exocrine Stimulation
•
The more proximal the nutrient infusion…the greater the
pancreatic stimulation (dog studies)
- stomach – maximal stimulation
- duodenum – intermediate stimulation
- jejunum – minimal / negligible stimulation
•
Elemental formulas tend to cause less stimulation than
standard intact formulas
- intact protein > oligopeptides > free amino acids
•
Intravenous nutrients (even lipids) do not appear to
stimulate the pancreas
Protective Measures
•
COMPARTMENTALIZATION - digestive enzymes are
contained within zymogen granules in acinar cells
•
REMOTE ACTIVATION - digestive enzymes are secreted as
inactive proenzymes within the pancreas
•
PROTEASE INHIBITORS – trypsin inhibitor is secreted
along with the proenzymes to suppress any premature
enzyme activation
•
AUTO “SHUT-OFF” – trypsin destroys trypsin in high
concentrations
Acute Pancreatitis
Definition
• Acute inflammatory process involving the
pancreas
• Usually painful and self-limited
• Isolated event or a recurring illness
• Pancreatic function and morphology return
to normal after (or between) attacks
Acute Pancreatitis
Etiology
Idiopathic
10%
Other
10%
EtOH
35%
Gallstones
45%
Acute Pancreatitis
Associated Conditions
• Cholelithiasis
• Ethanol abuse
• Idiopathic
• Medications
• Hyperlipidemia
• ERCP
• Trauma
• Pancreas divisum
• Hereditary
• Hypercalcemia
• Viral infections
- Mumps
- Coxsackievirus
•
•
End-stage renal failure
Penetrating peptic ulcer
Acute Pancreatitis
Causative Drugs
• AIDS therapy: didanosine, pentamidine
• Anti-inflammatory: sulindac, salicylates
• Antimicrobials: metronidazole, sulfonamides, tetracycline,
nitrofurantoin
•
•
•
•
•
Diuretics: furosemide, thiazides
IBD: sulfasalazine, mesalamine
Immunosuppressives: azathioprine, 6-mercaptopurine
Neuropsychiatric: valproic acid
Other: calcium, estrogen, tamoxifen, ACE-I
Adjusted ORs for Pancreatitis
45
42.1
Pancreatitis, ORs
40
35
30
25
20
15
12.4
10
5
2.5
4.8
0
Female
Nl TBili
SOD
Difficult
cannulation
Freeman et al. Gastrointest Endosc. ‘97.
Pancreas divisum
Hereditary Pancreatitis
• Autosomal dominant with 80% phenotypic
penetrance
• Recurrent acute pancreatitis, chronic pancreatitis,
and 50-fold increased risk of pancreatic cancer
• Mutation in cationic trypsinogen gene (R122H)
• Other genetic defects
- CFTR
- SPINK1
Acute Pancreatitis
Pathogenesis
acinar cell
injury
premature
enzyme activation
failed protective
mechanisms
Acute Pancreatitis
Pathogenesis
premature enzyme activation
autodigestion of pancreatic tissue
local
vascular
insufficiency
local
complications
activation
of white
blood cells
release of
enzymes into
the circulation
distant
organ failure
Acute Pancreatitis
Pathogenesis
SEVERITY
Mild
• STAGE 1: Pancreatic Injury
- Edema
- Inflammation
• STAGE 2: Local Effects
- Retroperitoneal edema
- Ileus
• STAGE 3: Systemic Complications
Severe
- Hypotension/shock
- Metabolic disturbances
- Sepsis/organ failure
Acute Pancreatitis
Clinical Presentation
• Abdominal pain
- Epigastric
- Radiates to the back
- Worse in supine position
• Nausea and vomiting
• Fever
Acute Pancreatitis
Differential Diagnosis
• Choledocholithiasis
• Perforated ulcer
• Mesenteric ischemia
• Intestinal obstruction
• Ectopic pregnancy
Acute Pancreatitis
Diagnosis
• Symptoms
- Abdominal pain
• Laboratory
- Elevated amylase or lipase
• > 3x upper limits of normal
• Radiology
- Abnormal sonogram or CT
Causes of Increased
Pancreatic Enzymes
Amylase
Lipase
↑
Intestinal injury
↑
↑
↑
↑
Tubo-ovarian
disease
↑
Normal
Renal failure
↑
↑
↑
Pancreatitis
Parotitis
Biliary stone
Macroamylasemia
Normal
↑
↑
Normal
Acute Pancreatitis
Diagnosis
• EtOH: history
• Gallstones: abnormal LFTs & sonographic
evidence of cholelithiasis
• Hyperlipidemia: lipemic serum, Tri>1,000
• Hypercalcemia: elevated Ca
• Trauma: history
• Medications: history, temporal association
Acute Pancreatitis
Clinical Manifestations
PANCREATIC
PERIPANCREATIC
Mild: edema, inflammation, fat necrosis
Severe: phlegmon, necrosis, hemorrhage,
infection, abscess, fluid collections
Retroperitoneum, perirenal spaces, mesocolon,
omentum, and mediastinum
Adjacent viscera: ileus, obstruction, perforation
SYSTEMIC
Cardiovascular: hypotension
Pulmonary: pleural effusions, ARDS
Renal: acute tubular necrosis
Hematologic: disseminated intravascular coag.
Metabolic: hypocalcemia, hyperglycemia
Acute Pancreatitis
Time Course
ER presentation
0
12
cytokine release
24
36
48
organ failure
60
hours from pain onset
72
84
96
Predictors of Severity
• Why are they needed?
- appropriate patient triage & therapy
- compare results of studies of the impact of
therapy
• When are they needed?
- optimally, within first 24 hours (damage control
must begin early)
• Which is best?
Severity Scoring Systems
• Ranson and Glasgow Criteria (1974)
- based on clinical & laboratory parameters
- scored in first 24-48 hours of admission
- poor positive predictors (better negative predictors)
• APACHE Scoring System
- can yield a score in first 24 hours
- APACHE II suffers from poor positive predictive value
- APACHE III is better at mortality prediction at > 24
hours
• Computed Tomography Severity Index
- much better diagnostic and predictive tool
- optimally useful at 48-96 hours after symptom onset
Ranson Criteria
Alcoholic Pancreatitis
AT ADMISSION
WITHIN 48 HOURS
1. Age > 55 years
2. WBC > 16,000
3. Glucose > 200
4. LDH > 350 IU/L
5. AST > 250 IU/L
1. HCT drop > 10
2. BUN > 5
3. Arterial PO2 < 60 mm Hg
4. Base deficit > 4 mEq/L
5. Serum Ca < 8
6. Fluid sequestration > 6L
Number
Mortality
<2
3-4
1% 16%
5-6
40%
7-8
100%
Glasgow Criteria
Non-alcoholic Pancreatitis
1.
2.
3.
4.
5.
6.
7.
8.
WBC > 15,000
Glucose > 180
BUN > 16
Arterial PO2 < 60 mm Hg
Ca < 8
Albumin < 3.2
LDH > 600 U/L
AST or ALT > 200 U/L
CT Severity Index
appearance
normal
enlarged
inflamed
1 fluid
collection
2 or more
collections
grade
A
B
C
D
E
score
0
1
2
3
4
necrosis
none
< 33%
33-50%
> 50%
score
0
2
4
6
score
morbidity
mortality
1-2
4%
0%
7-10
92%
17%
Balthazar et al. Radiology 1990.
Severe Acute Pancreatitis
•
Scoring systems
-  3 Ranson criteria
-  8 APACHE II points
-  5 CT points
•
Organ failure
- shock (SBP < 90 mmHg)
- pulmonary edema / ARDS (PaO2 < 60 mmHg)
- renal failure (Cr > 2.0 mg/dl)
•
Local complications
- fluid collections  pseudocysts
- necrosis (mortality 15% if sterile, 30-35% if
infected)
- abscess
Goals of Treatment
•
Limit systemic injury
- support and resuscitation – effective
- decrease pancreatic secretion – ineffective /
harmful?
- inhibit inflammatory mediators – ineffective
- inhibit circulating trypsin – ineffective (too late)
- removing gallstones – mostly ineffective
•
•
Prevent necrosis – how?
Prevent infection
- antibiotics (imipenem and ciprofloxacin) –
probably effective in necrotic pancreatitis
- prevent colonic bacterial translocation
- removing gallstones – variably effective
Treatment of Mild
Pancreatitis
•
•
Pancreatic rest
•
Refeeding (usually 3 to 7 days)
- bowel sounds present
- patient is hungry
- nearly pain-free (off IV narcotics)
- amylase & lipase not very useful here
Supportive care
- fluid resuscitation – watch BP and urine
output
- pain control
- NG tubes and H2 blockers or PPIs are
usually not helpful
Treatment of Severe
Pancreatitis
• Pancreatic rest & supportive care
-
fluid resuscitation* – may require 5-10 liters/day
careful pulmonary & renal monitoring – ICU
maintain hematocrit of 26-30%
pain control – PCA pump
correct electrolyte derangements (K+, Ca++, Mg++)
• Rule-out necrosis
- contrasted CT scan at 48-72 hours
- prophylactic antibiotics if present
- surgical debridement if infected
• Nutritional support
- may be NPO for weeks
- TPN vs. enteral support (TEN)
Role of ERCP
• Gallstone pancreatitis
- Cholangitis
- Obstructive jaundice
• Recurrent acute pancreatitis
- Structural abnormalities
- Neoplasm
- Bile sampling for microlithiasis
• Sphincterotomy in patients not suitable for
cholecystectomy
Nutrition in Acute
Pancreatitis
•
Metabolic stress
- catabolism & hypermetabolism seen in 2/3 of
patients
- similar to septic state (volume depletion may
be a major early factor in the above
derangements)
•
Altered substrate metabolism
- increased cortisol & catecholamines
- increased glucagon to insulin ratio
- insulin resistance
•
Micronutrient alterations
- calcium, magnesium, potassium, etc
Systemic Changes in Acute
Pancreatitis
• Hyperdynamic
- Increased cardiac output
- Decreased systemic vascular resistance
- Increased oxygen consumption
• Hypermetabolism
- Increased resting energy expenditure
• Catabolism
- Increased proteolysis of skeletal muscle
Reduced Oral Intake in
Acute Pancreatitis
• Abdominal pain with food aversion
• Nausea and vomiting
• Gastric atony
• Ileus
• Partial duodenal obstruction
Factors Differentiating Mild from
Severe Pancreatitis
Mild
Severe
Pancreatitis
Pancreatitis
80%
20%
No
Yes
80%
0%
Morbidity
8%
38%
Mortality
3%
27%
Parameter
Admissions
Pancreatic
necrosis
Oral diet within 5
days
TPN in Acute Pancreatitis
•
•
•
•
delay until volume repleted & electrolytes corrected
check triglycerides first – goal <400
lipids are OK to use (possible exception of sepsis)
monitor glucose levels carefully
- can see insulin insufficiency and resistance
- may need to limit calories at first
- separate insulin drip may be needed
TPN in Acute Pancreatitis
•
Benefit or harm?
- early uncontrolled studies suggested benefit
- two retrospective studies (70’s & 80’s) showed
no benefit with TPN in pancreatitis
- 1987 – randomized study of early TPN vs. IVF
alone showed more sepsis, longer stays, & no
fewer complications with TPN
•
When to use TPN?
- jejunal access is unavailable
- ileus prevents enteral feeding
- patients in whom TEN clearly exacerbates
pancreatitis
Enteral Nutrition in Acute
Pancreatitis
•
studies
- late 80’s – patients who received jejunal feeding tubes
at the time of surgery, did well with early
post-op enteral support
- 1991 – randomized study of early TPN vs. early TEN
post-op showed no short-term difference
- 1997 – early TPN vs. early TEN (Peptamen) via
nasojejunal tube in 32 patients showed no difference
except 4x less cost & less hyperglycemia
- 1997 – similar study showed fewer complications and
lower cost without change in length of stay
- 1998 – similar study showed more sepsis and organ
failure in the TPN group
Summary of Prospective RCTs
Enteral vs Parenteral Nutrition for Acute
Pancreatitis
McClave et al.
Kalfarenztos et al. Windsor et al.
1997
1997
1998
No of patients
32
38
34
Etiology
EtOH 19/32
--
Biliary 23/34
19%
100%
38%
Semi-elemental
Semi-elemental
Polymeric
Cost
5x less
3x less
--
Outcome
No difference
Fewer comp
Less SIRS
Severe
pancreatitis
Enteral
formula
Total Enteral Nutrition in
Severe Pancreatitis
• may start as early as possible
- when emesis has resolved
- ileus is not present
• nasojejunal route preferred over
nasoduodenal
• likely decreases risk of infectious
complications by reducing
transmigration of colonic bacteria
Conclusions
• Acute pancreatitis is a self-limited disease in
which most cases are mild.
• Gallstones and alcohol are the leading causes of
acute pancreatitis.
• In mild pancreatitis, nutritional support is usually
not required
• In severe pancreatitis, nutritional support will
likely be required with the enteral route preferred
over TPN because of both safety and cost.