Download Management of Acute Pancreatitis

Jeddah Gut Club monthly meeting
21/11/2005
Yousef A. Qari
Consultant Gastroenterologist
King A.aziz University Hospital
Acute Pancreatitis
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100,000 hospitalizations annually in the
United States
2000 (2%) directly related deaths from
complications
10% to 15% of deaths occur almost
exclusively as a result of acute necrotizing
pancreatitis
Mortality of acute pancreatitis
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The overall mortality remains approximately
5% to 10%
Rises to >40% if sterile necrosis becomes
superinfected
Etiology of Acute pancreatitis
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Gallstones
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Alcohol
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Endoscopic retrograde cholangiopancreatography (ERCP)
(overall 5% -20%)
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Medications
Trauma
Neoplasms
Anatomic variants
Metabolic problems
– Hypercalcemia
– Hypertriglyceridemta
80% of cases.
10% of patients.
Etiology of Acute pancreatitis
Rare causes of acute pancreatitis
– Annular pancreas
– Autoimmune Pancreatitis
– Hereditary Pancreatitis
– Familial adenomatous polyposis
– Pseudopapillary tumor of the pancreas
Classification of Acute pancreatitis
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Mild
Severe
( interstitial pancreatitis)
(necrotizing pancreatitis)
Majority of cases
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Minimal organ failure
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Uneventful recovery
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Responds well to supportive
therapy
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Approximately 20% of patients
Associated with
– Organ failure
– local complications
 Necrosis
 Infection
 Pseudocyst formation
Requires intensive monitoring and
specific therapies and has a more
guarded prognosis.
Clinical and radiologic scoring systems
1.
2.
3.
4.
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Since 1974
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Ranson's criteria [1]
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1985
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(APACHE II) system [2]
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1994
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CT severity index [3,4]
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New mellinium
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Modified CT index
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MRI severity index
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Contrast enhanced EUS
Ranson JHC et al. Surg Gynecol Obstet 1974; 139:69-81
Knaus WA et al. Crit Care Med 1985; 13:818-829
Balthazar EJ et al Radiology1990; 174:331-336
Balthazar EJ et al , Radiology 1994; 193:297-306
– Multidetector-row
computed tomography
(MDCT)
– MRI with gadolinium
(MRCPs)
The role of imaging in acute pancreatitis
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Confirm the diagnosis
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Identify necrosis
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Determine the presence of complications
– Fluid collections
– Vascular abnormalities
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Assessment of severity
Multidetector-row computed tomography
(MDCT)
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The imaging study of choice
for Acute pancreatitis
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Faster image acquisition
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Improved resolution
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Can be converted into
three-dimensional
reconstructions
CT severity index, by Balthazar in 1994
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Focuses on the presence and degree of:
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Successfully used to predict overall morbidity and mortality
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Limitations
– Pancreatic inflammation (fluid collections)
– Necrosis.
– Does not correlate significantly with
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Development of organ failure
Extrapancreatic parenchymal complications
Peripancreatic vascular complications
– The interobserver agreement is approximating 75%.
CT severity index, by Balthazar in 1994
I - Pancreatic inflammation
Prognostic Indicator
Points
Normal pancreas
0
Focal or diffuse enlargement of the pancreas
1
Intrinsic pancreatic abnormalities with inflammatory changes in
peripancreatic fat
2
Single, ill-defined fluid collection or phlegmon
3
Two or more poorly defined collections or presence of gas in or
adjacent to the pancreas
4
CT severity index, by Balthazar in 1994
II - Pancreatic Necrosis
Prognostic Indicator
Points
None
0
</= 30%
2
> 30-50%
4
> 50%
6
Mild (score, 0-3 points), moderate (4-6 points), or severe (7-10 points).
Modified CT Severity Index by Koenraad
in 2004
I- Pancreatic inflammation
Prognostic Indicator
Points
Normal pancreas
0
Intrinsic pancreatic abnormalities with or without
inflammatory changes in peripancreatic fat
2
Pancreatic or peripancreatic fluid collection or peripancreatic
fat necrosis
4
Koenraad J et al, Am J Roentgenol 183(5):1261-1265, 2004
Modified CT Severity Index by Koenraad
in 2004
II- Pancreatic necrosis
Prognostic Indicator
Points
None
0
</= 30%
2
> 30%
4
Extrapancreatic complications (one or more of pleural
effusion, ascites, vascular complications, parenchymal
complications, or gastrointestinal tract involvement)
2
Mild (0-2 points), moderate (4-6 points), or severe (8-10 points).
Correlation of Scoring Indexes With
Patient Outcome
Variables
The length of the hospital
Statistically significant correlation
CT severity index
(Balthazer)1994
Only with mild severity
groups
Modified index
(Koenraad)2004
With all severity groups
The need for surgical or
percutaneous interventions
Yes
Yes
The presence of infection
Yes
Yes
No
Yes
Development of organ failure
Koenraad J et al, Am J Roentgenol 183(5):1261-1265, 2004
Comparison between currently accepted
and modified CT severity indexes
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74-year-old man with acute
pancreatitis. Axial contrastenhanced CT scan shows:
– One fluid collection in
anterior pararenal space
– Minimal necrosis (< 30%).
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On currently accepted CT
severity index score was 5
(moderate pancreatitis)
On modified CT severity
index score was 8 (severe
pancreatitis)
MRCP-severity index
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Based on the existing
Balthazar CTSI
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Advantage:
– Non-nephrotoxic contrast
agent gadolinium
– Ability to generate
cholangiopancreatography
image
– Detection of pancreatic duct
disruption with the use of
secretin
Arvanitakis M, et al.. Gastroenterology 2004; 126:715—723.
MRCP-severity index
Correlated with
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Serum level of C-reactive protein at 48 hours
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Duration of hospitalization
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Ranson score
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Morbidity from local and systemic complications.
Arvanitakis M, et al.. Gastroenterology 2004; 126:715—723.
Acute Pancreatitis -- Prediction of Severity
using serum proteomic patterns
Patterns of low-molecular-mass biomarkers
Reveal an underlying, organ-specific pathology.
Sensitive and specific way to determine which patients
are likely to develop multisystem failure
Papachristou GI et al. Gastroenterology. 2004;126(suppl 2):A-29.
Acute Pancreatitis -- Prediction of Severity
using early hematocrit values
Retrospective evaluation of 230 patients
They found that
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Absence of hemoconcentration at admission (defined as a
hematocrit value of 43 or less)
Drop in 24-hour hematocrit level had a negative predictive
value of 94.7% for the subsequent development of necrosis.
Gardner TB et al. Am J Gastroenterol. 2004;99:S48.
Characterization of ICU patients using a model based
on the presence or absence of organ dysfunctions
and/or infection
Evidence of organ failure
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–
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–
–
–
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–
–
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Respiratory failure
PaO2 of less than 60 mm Hg
Ventilatory support.
Cardiovascular system failure
Systolic BP of < 90 mm Hg
signs of peripheral hypoperfusion
need for vasopressor or inotropic agents
Renal failure
serum creatinine level > 300 µmol/L
urine output < 500 mL/24 hr or < 180 mL/8 hr
need for hemo- or peritoneal dialysis.
Fagon JY et al .Intensive Care Med 1993; 19:137-144
Characterization of ICU patients using a model based
on the presence or absence of organ dysfunctions
and/or infection
Evidence of organ failure
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Central nervous system failure
– Glasgow Coma Scale score greater than 6 in the absence of sedation
– Sudden onset of confusion or psychosis.
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Hepatic failure
– Serum bilirubin levels greater than 100 µmol/L
– Alkaline phosphatase levels >3× the normal range.
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Hematologic system failure
– Hematocrit level < 20%,
– WBC < 2,000/mm3,
– Platelet count of < 40,000/mm3.
Fagon JY et al .Intensive Care Med 1993; 19:137-144
Principles for managing patients with
acute pancreatitis
Assessing the severity remains the key
element in the initial assessment of patients.
Principles for managing patients with
acute pancreatitis
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Supportive care with close attention to volume status and
electrolyte balance
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Fasting of the patient
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Pain management using narcotic agents.
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Predicting the severity of an attack and triaging of patients to
intensive care units or a regular floor
Bassi C, Cochrane Database of Systematic Reviews. 2003;(4):CD002941
Principles for managing patients with
acute pancreatitis (Cont‘d)
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Early detection of complications
Prophylactic broad-spectrum antibiotics for patients with
predicted severe pancreatitis
Identification of patients who may benefit from ERCP
(when severe pancreatitis is complicated by progressive jaundice or cholangitis)
Adequate nutritional support
Bassi C, Cochrane Database of Systematic Reviews. 2003;(4):CD002941
Increased risk of post ERCP Pancreatitis
Patient factors
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Sphincter of Oddi dysfunction
Younger age
Female sex
History of prior post-ERCP pancreatitis
Procedure factors
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Low endoscopist experience
Small common bile duct diameter
Pancreatic sphincterotomy
Difficult biliary cannulation
Precut sphincterotomy
Multiple cannulations
Sphincter of Oddi manometry
Increased risk of post ERCP Pancreatitis
(1 – 10%)
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1-2% after ERCP
1-4% after biliary endoscopic sphincterotomy (ES)
4-8% after pancreatic ES
13-35% after minor papilla ES
Prevention of post-ERCP pancreatitis
Not useful
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Corticosteroids
Antibiotics
Anticholinergics
Interleukin-10
Lexipafant
Lidocaine sprayed on the ampulla of Vater
Volume expansion with 10% Dextran-40
Prevention of post-ERCP pancreatitis
Potentially useful: Require further studies
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Somatostatin
Nitroglycerine
Diclofenac
intravenous secretin
High-dose allopurinol
Gabexate
Prevention of post-ERCP pancreatitis
Most useful
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Proper technique and patient selection
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Pancreatic duct stenting in high risk patients
Prevention of post-ERCP pancreatitis
Somatostatin
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Inhibition of exocrine secretion of the pancreas,
which plays an important role in the pathogenesis
of acute pancreatitis.
Direct anti-inflammatory and cytoprotective
effects.
Uhl W, Buchler MW, Malfertheiner P et al. Gut. 1999;45:97-104.
Cavallini G et al, Dig Liver Dis. 2001;33:192-201.
Prevention of post-ERCP pancreatitis
Diclofenac
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Diclofenac is a potent inhibitor of phospholipase A2,
which regulates inflammatory mediators, including
prostaglandins, leukotrienes, and platelet activating
factor.
100 mg rectal diclofenac given immediately after
ERCP reduces the incidence of acute pancreatitis
in patients at higher risk for post-ERCP pancreatitis
Murray B, et al. Gastroenterology 2003, 124:1786-1791.
Prevention of post-ERCP pancreatitis
Nitroglycerine
Transdermal glyceryl trinitrate patch placed a half
hour before the procedure and continued for 24
hours led to a reduction in post-ERCP pancreatitis
Moretó M, Zaballa M, Casado I, et al.: Gastrointest Endosc 2003, 57:1-7.
Pancreatic stenting in patients "at-risk“
of post-ERCP pancreatitis
Problems
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Inability to place a pancreatic duct stent
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Ampullary trauma
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Pancreatic duct changes
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Need to repeat endoscopy to retrieve stents
Fazel A et al. Gastrointest Endosc 2003, 57:291-294.
Pancreatic stenting in patients "at-risk“
of post-ERCP pancreatitis
Effective ??
5 randomized controlled trials
Great reduction in the risk of post-ERCP pancreatitis
Three-Fr gauge soft, unflanged, single pigtail pancreatic stents
Advantages and disadvantages of performing ERCP to
seal and stent a pancreatic duct disruption in patients
with acute pancreatitis.
Pros
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Pancreatic ductal disruption or leak
is a common event in severe
pancreatitis(37%)
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Predicts a prolonged hospital stay.
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Treatment with a combination of
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Endoscopic stenting of the
pancreatic duct
Percutaneous drains
Surgery as necessary
Safe, will promote healing of the
leak, and will improve patient
outcome.
Advantages and disadvantages of performing ERCP to
seal and stent a pancreatic duct disruption in patients
with acute pancreatitis.
Pros
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Pancreatic ductal disruption or leak
is a common event in severe
pancreatitis(37%)
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Predicts a prolonged hospital stay.
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Treatment with a combination of
–
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–
Against
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Lack of controlled data
A subgroup of patients,
– Pancreatic ascites
– Peripancreatic fluid collections
Endoscopic stenting of the
pancreatic duct
Percutaneous drains
Surgery as necessary
Safe, will promote healing of the
leak, and will improve patient
outcome.
May benefit from an ERCP usually
after the first 2 weeks
Antibiotic therapy for prophylaxis against
infection of pancreatic necrosis in acute
pancreatitis
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The mortality risk rises to >40% if sterile necrosis
becomes superinfected
Window of opportunity of 1 – 2 weeks
Strong evidence that intravenous antibiotic for 10
to 14 days decreased the risk of superinfection of
necrotic tissue and mortality
Indications for surgical intervention
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No universally valid answer
Persistence of organ failure and/or systemic
inflammatory signs after 72 h of maximal supporting
intensive care therapy is an indication for operative
treatment.
The timing of pancreatic debridement
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Controversial issue
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Demarcation of pancreatic necrosis (2-3 w) is a
precondition for sufficient debridement
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Necrosectomy, performed later than three weeks
after the onset of disease
higher rate of
successful debridement of pancreatic necrosis
Idiopathic Recurrent Acute Pancreatitis
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Laboratory analysis
CFTR gene analysis
sweat chloride test
trypsin gene studies
duodenal aspiration for microcrystals
measurement of CA 19-9 and CEA
ERCP reveals a diagnosis in about 70% of patients with IRAP after a
negative initial evaluation
the procedure is not justified after the first episode of pancreatitis,[
bile is aspirated for microcrystals
SOM is performed when SOD is suspected,
minor papilla is cannulated when pancreas divisum is suspected.[75]
Idiopathic Recurrent Acute Pancreatitis
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EUS is increasingly used to evaluate patients with IRAP
EUS has equal or superior sensitivity to other commonly used
tests in the diagnosis of microlithiasis and sludge.[
SOD is detected using secretin-stimulated EUS by
demonstrating persistent dilatation of the pancreatic duct
following secretin administration
EUS has reasonable sensitivity and specificity in detecting
structural lesions such as pancreas divisum] and an
anomalous pancreatobiliary junction.[
Occult ampullary and pancreatic tumors may also be
discovered.[
Finally, EUS can detect the presence of chronic pancreatitis in
patients initially presenting with IRAP.[57,58]
Idiopathic Recurrent Acute Pancreatitis
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The primary value of MRCP for IRAP is in identifying
anatomic abnormalities such as pancreas divisum, a
choledochocele, anomalous pancreatobiliary
junction, or annular pancreas
MRCP may also detect
neoplasia
chronic pancreatitis
microlithiasis
its value for diagnosing these disorders has been
minimally evaluated.
Management of Idiopathic Recurrent
Acute Pancreatitis
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Therapeutic options are limited
A number of "nonvalidated" therapies therefore exist for TIRAP
Smooth muscle relaxers
calcium-channel blockers
nitrates, have been of limited utility in patients with SOD
Pancreatic enzymes inhibitors
antioxidants, such as
beta carotene,
methionine,
vitamin C, and vitamin E, may be beneficial by inhibiting the release of oxygen-derived
free radicals.[87]
pancreatic duct stents or endoscopic sphincterotomy (biliary or pancreatic) in patients
with TIRAP.[40,88] There is only 1 prospective, randomized trial to have evaluated the
use of pancreatic duct stents for this indication.[89] Patients randomized to stent
placement suffered fewer episodes of pancreatitis during the nearly 3-year follow-up.
However, such therapy cannot be widely supported outside of a research protocol until
more data are available.
empiric laparoscopic cholecystectomy
Empiric administration of ursodeoxycholic acid and a low-fat diet
Comparison between currently accepted and
modified CT severity indexes
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266 patients acute pancreatitis during a 1-year period
66 underwent contrast-enhanced MDCT within 1 week of the onset of symptoms.
Parameters
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The length of the hospital stay (in days)
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The need for surgical intervention
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The need for percutaneous intervention (aspiration and drainage)
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Evidence of infection in any organ system (positive results on a Gram stain or
culture or the combination of a fever >100°F and an elevated WBC >
15,000/mm3)
Evidence of organ failure
Koenraad J et al, Am J Roentgenol 183(5):1261-1265, 2004
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The calcium-dependent intra-acinar cell activation of pancreatic digestive
zymogens, particularly proteases, is an early event in the initiation of acute
pancreatitis.
Activation of transcription factor NF-κB also occurs early in experimental
pancreatitis..
expression of interleukin-6, tumor necrosis factor-α, and inducible nitric oxide
synthase
neurally mediated inflammation has an important role in acute pancreatitis.
Neurogenic inflammation is mediated by peripheral release of chemical
transmitters, including substance P
inhibiting cyclo-oxygenase-2 by either pharmacologic inhibition or gene
deletion reduced pancreatitis severity and lung injury
Leukotrienes play a role in inflammation, ischemia, and reperfusion. Use of a
peptide leukotriene receptor antagonist to improve experimental acute
pancreatitis has been described. Translation of this research into prevention of
ERCP-induced pancreatitis is noted in this review.
Conclusion
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increased understanding of early cellular events and the regulation of early
and late inflammatory mediators.
The importance of neuronal mediators has been demonstrated and deserves
further study.
Arachidonic acid metabolites are important mediators of local inflammation
and lung injury in experimental models. This has been translated into the use
of diclofenac in prevention of post-ERCP pancreatitis.
Local delivery of inflammatory inhibitors via the pancreatic duct should be
explored for the prevention of ERCP-induced pancreatitis, as should
combination therapy that blocks Ca2+ mobilization, pH changes, and early
transcription factors such as NF-κB.
Although progress continues in understanding of experimental pancreatitis
and successfully attenuating the disease in the laboratory, there has been
difficulty in translating this research into therapy for clinical acute pancreatitis.
Better understanding of inflammatory cytokines, chemokines, and neurogenic
mediators in experimental pancreatitis promises therapies to reduce
pancreatic necrosis and lung injury in clinical pancreatitis
Balthazar Computed Tomography Severity Index
(CTSI)
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Graded the severity of pancreatitis on the basis of
– Degree of pancreatic inflammation
– Degree of pancreatic necrosis.
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Correlated with
– Morbidity
– Mortality
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Not correlated with
– organ failure
– peripancreatic complications
Balthazar EJ .et al Radiology 1990; 174:331—336. •