Title: Jeddah Gut Club monthly meeting
1Jeddah Gut Club monthly meeting
Management of Acute Pancreatitis
21/11/2005
- Yousef A. Qari
- Consultant Gastroenterologist
- King A.aziz University Hospital
2Acute Pancreatitis
- 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
3Mortality of acute pancreatitis
- The overall mortality remains approximately 5 to
10 - Rises to gt40 if sterile necrosis becomes
superinfected -
4Etiology of Acute pancreatitis
- Gallstones
-
80 of cases. - Alcohol
- Endoscopic retrograde cholangiopancreatography
(ERCP) (overall 5 -20) - Medications
- Trauma
- Neoplasms 10 of
patients. - Anatomic variants
- Metabolic problems
- Hypercalcemia
- Hypertriglyceridemta
-
5Etiology of Acute pancreatitis
- Rare causes of acute pancreatitis
- Annular pancreas
- Autoimmune Pancreatitis
- Hereditary Pancreatitis
- Familial adenomatous polyposis
- Pseudopapillary tumor of the pancreas
6 Classification of Acute pancreatitis
- Mild
-
- ( interstitial pancreatitis)
- Majority of cases
- Minimal organ failure
-
- Uneventful recovery
- Responds well to supportive therapy
-
- Severe
- (necrotizing pancreatitis)
- 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.
7Clinical and radiologic scoring systems
- Since 1974
- 1985
- 1994
- New mellinium
- Ranson's criteria 1
- (APACHE II) system 2
- CT severity index 3,4
- Modified CT index
- Multidetector-row computed tomography (MDCT)
- MRI severity index
- MRI with gadolinium (MRCPs)
- Contrast enhanced EUS
- Ranson JHC et al. Surg Gynecol Obstet 1974
13969-81 - Knaus WA et al. Crit Care Med 1985 13818-829
- Balthazar EJ et al Radiology1990 174331-336
- Balthazar EJ et al , Radiology 1994 193297-306
8The role of imaging in acute pancreatitis
- Confirm the diagnosis
- Identify necrosis
- Determine the presence of complications
- Fluid collections
- Vascular abnormalities
- Assessment of severity
9Multidetector-row computed tomography (MDCT)
- The imaging study of choice for Acute
pancreatitis -
- Faster image acquisition
- Improved resolution
- Can be converted into three-dimensional
reconstructions
10CT severity index, by Balthazar in 1994
- Focuses on the presence and degree of
- Pancreatic inflammation (fluid collections)
- Necrosis.
- Successfully used to predict overall morbidity
and mortality -
- Limitations
- Does not correlate significantly with
- Development of organ failure
- Extrapancreatic parenchymal complications
- Peripancreatic vascular complications
- The interobserver agreement is approximating 75.
11CT severity index, by Balthazar in 1994
I - Pancreatic inflammation 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
12CT severity index, by Balthazar in 1994
II - Pancreatic Necrosis II - Pancreatic Necrosis
Prognostic Indicator Points
None 0
lt/ 30 2
gt 30-50 4
gt 50 6
Mild (score, 0-3 points), moderate (4-6 points),
or severe (7-10 points).
13Modified CT Severity Index by Koenraad in 2004
I- Pancreatic inflammation 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
14Modified CT Severity Index by Koenraad in 2004
II- Pancreatic necrosis II- Pancreatic necrosis
Prognostic Indicator Points
None 0
lt/ 30 2
gt 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).
15Correlation of Scoring Indexes With Patient
Outcome
Variables Statistically significant correlation Statistically significant correlation
Variables CT severity index (Balthazer)1994 Modified index (Koenraad)2004
The length of the hospital Only with mild severity groups With all severity groups
The need for surgical or percutaneous interventions Yes Yes
The presence of infection Yes Yes
Development of organ failure No Yes
Koenraad J et al, Am J Roentgenol
183(5)1261-1265, 2004
16Comparison between currently accepted and
modified CT severity indexes
- 74-year-old man with acute pancreatitis. Axial
contrast-enhanced CT scan shows - One fluid collection in anterior pararenal space
- Minimal necrosis (lt 30).
-
- On currently accepted CT severity index score was
5 (moderate pancreatitis) - On modified CT severity index score was 8 (severe
pancreatitis)
17MRCP-severity index
- Based on the existing Balthazar CTSI
- 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
126715723.
18MRCP-severity index
- Correlated with
- Serum level of C-reactive protein at 48 hours
- Duration of hospitalization
- Ranson score
- Morbidity from local and systemic complications.
Arvanitakis M, et al.. Gastroenterology 2004
126715723.
19Acute 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.
2004126(suppl 2)A-29.
20Acute Pancreatitis -- Prediction of Severity
using early hematocrit values
- Retrospective evaluation of 230 patients
-
- They found that
-
- 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.
200499S48.
21Characterization of ICU patients using a model
based on the presence or absence of organ
dysfunctions and/or infection
- Evidence of organ failure
-
- Respiratory failure
- PaO2 of less than 60 mm Hg
- Ventilatory support.
-
- Cardiovascular system failure
- Systolic BP of lt 90 mm Hg
- signs of peripheral hypoperfusion
- need for vasopressor or inotropic agents
- Renal failure
- serum creatinine level gt 300 µmol/L
- urine output lt 500 mL/24 hr or lt 180 mL/8 hr
- need for hemo- or peritoneal dialysis.
-
Fagon JY et al .Intensive Care Med 1993
19137-144
22Characterization of ICU patients using a model
based on the presence or absence of organ
dysfunctions and/or infection
- Evidence of organ failure
- Central nervous system failure
- Glasgow Coma Scale score greater than 6 in the
absence of sedation - Sudden onset of confusion or psychosis.
-
- Hepatic failure
- Serum bilirubin levels greater than 100 µmol/L
- Alkaline phosphatase levels gt3 the normal range.
-
- Hematologic system failure
- Hematocrit level lt 20,
- WBC lt 2,000/mm3,
- Platelet count of lt 40,000/mm3.
Fagon JY et al .Intensive Care Med 1993
19137-144
23Principles for managing patients with acute
pancreatitis
-
- Assessing the severity remains the key element
in the initial assessment of patients.
24Principles for managing patients with acute
pancreatitis
- Supportive care with close attention to volume
status and electrolyte balance - Fasting of the patient
- Pain management using narcotic agents.
-
- 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
25Principles for managing patients with acute
pancreatitis (Contd)
- 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
26Increased risk of post ERCP Pancreatitis
- Patient factors
- Sphincter of Oddi dysfunction
- Younger age
- Female sex
- History of prior post-ERCP pancreatitis
- Procedure factors
- Low endoscopist experience
- Small common bile duct diameter
- Pancreatic sphincterotomy
- Difficult biliary cannulation
- Precut sphincterotomy
- Multiple cannulations
- Sphincter of Oddi manometry
27Increased risk of post ERCP Pancreatitis
- (1 10)
- 1-2 after ERCP
- 1-4 after biliary endoscopic sphincterotomy
(ES) - 4-8 after pancreatic ES
- 13-35 after minor papilla ES
28Prevention of post-ERCP pancreatitis
- Not useful
- Corticosteroids
- Antibiotics
- Anticholinergics
- Interleukin-10
- Lexipafant
- Lidocaine sprayed on the ampulla of Vater
- Volume expansion with 10 Dextran-40
29Prevention of post-ERCP pancreatitis
- Potentially useful Require further studies
- Somatostatin
- Nitroglycerine
- Diclofenac
- intravenous secretin
- High-dose allopurinol
- Gabexate
30Prevention of post-ERCP pancreatitis
- Most useful
- Proper technique and patient selection
- Pancreatic duct stenting in high risk patients
31Prevention of post-ERCP pancreatitis
- Somatostatin
- 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.
19994597-104.
Cavallini G et al, Dig Liver Dis.
200133192-201.
32 Prevention of post-ERCP pancreatitis
- Diclofenac
- 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,
1241786-1791.
33 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, 571-7.
34Pancreatic stenting in patients "at-risk of
post-ERCP pancreatitis
- Problems
- Inability to place a pancreatic duct stent
- Ampullary trauma
- Pancreatic duct changes
- Need to repeat endoscopy to retrieve stents
Fazel A et al. Gastrointest Endosc 2003,
57291-294.
35Pancreatic 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
36Advantages and disadvantages of performing ERCP
to seal and stent a pancreatic duct disruption in
patients with acute pancreatitis.
- Pros
- Pancreatic ductal disruption or leak is a common
event in severe pancreatitis(37) - Predicts a prolonged hospital stay.
-
- Treatment with a combination of
- Endoscopic stenting of the pancreatic duct
- Percutaneous drains
- Surgery as necessary
-
- Safe, will promote healing of the leak, and
will improve patient outcome.
37Advantages and disadvantages of performing ERCP
to seal and stent a pancreatic duct disruption in
patients with acute pancreatitis.
- Pros
- Pancreatic ductal disruption or leak is a common
event in severe pancreatitis(37) - Predicts a prolonged hospital stay.
-
- Treatment with a combination of
- Endoscopic stenting of the pancreatic duct
- Percutaneous drains
- Surgery as necessary
-
- Safe, will promote healing of the leak, and
will improve patient outcome.
- Against
- Lack of controlled data
-
- A subgroup of patients,
- Pancreatic ascites
- Peripancreatic fluid collections
-
-
- May benefit from an ERCP usually after the
first 2 weeks
38Antibiotic therapy for prophylaxis against
infection of pancreatic necrosis in acute
pancreatitis
- The mortality risk rises to gt40 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
39Indications for surgical intervention
- 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.
40The timing of pancreatic debridement
- Controversial issue
-
- Demarcation of pancreatic necrosis (2-3 w) is a
precondition for sufficient debridement - Necrosectomy, performed later than three weeks
after the onset of disease higher rate
of successful debridement of pancreatic necrosis
41(No Transcript)
42Idiopathic Recurrent Acute Pancreatitis
- 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
43Idiopathic Recurrent Acute Pancreatitis
- 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
44Idiopathic Recurrent Acute Pancreatitis
- 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.
45Management of Idiopathic Recurrent Acute
Pancreatitis
- 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
46Comparison between currently accepted and
modified CT severity indexes
- 266 patients acute pancreatitis during a 1-year
period - 66 underwent contrast-enhanced MDCT within 1 week
of the onset of symptoms. - Parameters
- The length of the hospital stay (in days)
- The need for surgical intervention
- The need for percutaneous intervention
(aspiration and drainage) - Evidence of infection in any organ system
(positive results on a Gram stain or culture or
the combination of a fever gt100F and an elevated
WBC gt 15,000/mm3) -
- Evidence of organ failure
Koenraad J et al, Am J Roentgenol
183(5)1261-1265, 2004
47- 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-?B also
occurs early in experimental pancreatitis.. - expression of interleukin-6, tumor necrosis
factor-a, 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.
48(No Transcript)
49Conclusion
- 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-?B. - 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
50Balthazar Computed Tomography Severity Index
(CTSI)
- Graded the severity of pancreatitis on the basis
of - Degree of pancreatic inflammation
- Degree of pancreatic necrosis.
-
- Correlated with
- Morbidity
- Mortality
- Not correlated with
- organ failure
- peripancreatic complications
Balthazar EJ .et al Radiology 1990 174331336.