Case Based Presentation
Severe Acute Pancreatitis,
Or
How I Spent My Christmas
Vacation
S. Mountain
January 8, 2009
The Case

The patient is a 25-year-old obese woman
with a history of non-insulin-dependent
diabetes mellitus (NIDDM) and
hypercholesterolemia who presents to the
emergency department for evaluation of
the acute onset of abdominal pain. The
patient describes the pain, which she says
began 12 hours before her evaluation, as
a constant epigastric cramping associated
with nausea and vomiting.

She denies fever, chills, change in bowel habits,
or alteration in the character of her stool or
urine. The patient's past medical history is
significant for obesity, NIDDM,
hypercholesterolemia, and depression. She is
uncertain of the names of the oral hypoglycemic
and antilipidemic drugs that had been prescribed
to her. She does not use tobacco or alcohol.
There has been no recent travel. Laboratory
studies performed 3 months before her
admission revealed an elevated cholesterol level
of 597 mg/dL, with an HDL level of 42 mg/dL,
and an elevated triglyceride level of 3034 mg/dL.
 The
physical examination is
significant for morbid obesity (weight,
301 lb); temperature, 37°C; blood
pressure, 100/50; pulse, 110/min;
respiratory rate, 16/min; regular heart
rate; clear lungs on auscultation; and
a diffusely tender abdomen without
rebound or guarding. The stool is
guaiac negative.

Laboratory studies:
– White blood cell count 11.6 x 103
– Hemoglobin 13.7 g/dL
– Hematocrit 40.4% (normal: 37%-47%)
– Sodium 135 mmol/L
– Potassium 4 mmol/L
– Chloride 101 mmol/L
– Bicarbonate 11.2 mmol/L
– Blood urea nitrogen 7 mg/dL
– Creatinine 0.7 mg/dL
– Calcium 7.3 mg/dL

Laboratory studies:
–
–
–
–
–
–
–
–
–
–
Glucose 219 mg/dL
Albumin 2.6 g/dL
Amylase 222 U/L
Lipase 5562 U/L (normal: 25-300 U/L)
Aspartate aminotransferase (AST) 48 U/L
Alanine aminotransferase (ALT) 28 U/L
Alkaline phosphatase 88 U/L
Total bilirubin 0.8 mg/dL
Cholesterol 784 mg/dL (normal: 190-260 mg/dL)
Triglycerides 5250 mg/dL (normal: 10-160 mg/dL)

Figure 1. The patient's serum, which is
lipemic, is compared with normal serum.

Figure 2. The abdominal CT scan reveals phlegmonous
changes of the pancreas in the perirenal space,
transverse mesocolon, and small bowel mesentery.

1. What is the diagnosis? Define severe
acute pancreatitis (SAP). Todd
Diagnosis:

Pancreatitis (of the severe acute variety)
– Evidenced by clinical syndrome, laboratory studies
and imaging.

Definition: Pancreatitis associated with other end
organ failure, and/or complications .
–
–
–
–

Necrosis
Abscess
Pseudocyst formation
Radiographic: evidence of previous 3 complications,
rather than degree of inflammatory changes.
Severity of Illness scores (i.e. APACHE II > 8

2. What are the most common etiologies of
SAP in developed countries? How about in
North America (i.e. the USA)? What are some
other causes of pancreatitis? What is the most
likely cause in this patient? Noemie
Acute Pancreatitis
Annual incidence 4.9 to 35 per 100,000
 Mortality of acute pancreatitis 10% and in
severe AP up to 30%
 Two most common causes of AP are
gallstones and alcohol (70%)

Etiologies of severe acute
pancreatitis







Gallstones (35%)
Alcohol (35%)
Trauma
Hypertriglyceridemia
Drugs
Infection
Tumor





Pancreas Divisum
Post ERCP
Hypercalcemia
Idiopathic (10%)
Autoimmune (PAN,
SLE)
Gallstone pancreatitis
Most common cause in most areas of the
world
 Only 3% to 7% of pts with gallstones dvp
pancreatitis
 More common in women vs men
 Dx:

– Ultrasound
– ALT > 3 x normal has a 95% PPV1
– Bili and ALP does not influence dx

30 to 50% recurrence rate without definitive
therapy
1. Am J Gastroenterol. 1994 Oct;89(10):1863-6.
Acute Alcoholic Pancreatitis
Most common dx in US
 ETOH might  the production of digestive
and lysosomal enzymes
 Can present as acute on chronic
pancreatitis  calcifications on CT
 Lipase:amylase ratio > 2

– 91% sensitivity and 76% specificity
What is the most likely cause in
this patient?
chol 15.44, HDL 1.09, trig 34.27
 Hypertriglyceridemia

– Accounts for 1 to 4% of Acute Pancreatitis
– Trig > 11 mmol/L can precipitate attacks
– Acquired causes in adults:
 Alcohol, Obesity, DM, Hypothyroidism, pregnancy, Steroid,
BBB, nephrotic syndrom
– Trig > 11mmol/L  opalescent and milky serum
– Amylase may be falsely low
– Goal is to lower their Trig<2.2mmol/L

3. What is the pathogenesis of SAP?
Neil
Pathogenesis

Premature intrapancreatic activation of
digestive enzymes
– Autodigestion of pancreatic structure
– Ischemia

Inflammatory response
– Cytokine release (IL-6, TNF-alpha, IL-1B)
– Neutrophils
– Platelet Activating Factor (PAF)
Pathogenesis (2)

Increased vascular permeability and
microcirculation impairment
– Constriction of arterioles and stasis of neuts
– Ischemia results in rupture of lysosomes and
release of cytokines
– Increased vascular permeability and NO
release

Infection and necrosis

4. How is pancreatitis diagnosed? What are
the roles and timing of amylase and lipase
elevation, and how do they differ depending
on the underlying etiology? What is the
appropriate role and timing of imaging?
Marios
Diagnosing pancreatitis

Diagnosis is usually made on the basis of:
– Clinical presentation
– Elevated pancreatic enzymes
– Radiologic evidence of inflammation
Pancreatic enzymes

Most common and available are serum
amylase and lipase

Both are released into the circulation as their
production continues in the face of reduced
or absent secretion

Levels do not correlate with severity
Serum Amylase

Rises within 6-12 hours of onset

Elevated for 3 to 5 days in uncomplicated
attacks

May be lower in cases of
hypertriglyceridemia-associated
pancreatitis or in chronic alcoholics
Serum Amylase

Not specific to pancreatic disease:
– Also produced by salivary glands and fallopian
tubes
– Can be absorbed from the gut in intestinal
inflammation/infarction or from the peritoneum in
cases of perforated bowel
– Clearance is reduced in renal failure or with
macroamylasemia (eg from pentaspan)
Serum Lipase

Thought to be more specific than amylase

Can also be elevated in renal failure and in
intestinal inflammation

Appears earlier and stays elevated longer
than serum amylase
Lipase VS Amylase
ROC curves for amylase and
lipase
Enzyme levels over time
(actual figures from the paper)
Role and timing of
imaging in pancreatitis
Abdominal series

Usually part of the initial work-up in ER

Can be normal, or show non-specific
findings such as an ileus and air-fluid
levels

More specific findings include the coloncut-off sign, and a sentinel loop
Colon Cutoff sign
Colon Cutoff Sign
Ultrasonography

No role in the diagnosis or staging of
severe pancreatitis
– Bowel gas often obscures view of pancreas
– Cannot identify necrosis

Should be performed in all patients with
first attacks of pancreatitis to rule-out
gallstones
Contrast-enhanced CT

Unless there is diagnostic uncertainty,
admission CTs are not usually necessary.

Can be performed after 48-72 hours of
conservative management if there is lack of
improvement or worsening of clinical status.

Intravenous contrast is preferred in order to
show areas of necrosis, which will appear as
unenhanced areas (< 50 HU)

5. What are some of the prognostic scoring
systems used to predict severity of
pancreatitis? Please discuss both clinical and
radiographic scoring systems, but focus on
those that are clinically relevant and useful for
an intensivist. Naisan
Clinical Scoring Systems
Scoring systems




Despite traditional measures, including
scoring systems, serum measurements and
radiological evaluation, acute pancreatitis
patients remain challenging to risk stratify
Serum lipase and amylase levels are poorly
correlated with disease severity
CRP is a good discriminator between severe
and mild disease 48 h after the onset of
symptoms. A cut-off level of 150 mg/l is
accepted
a BMI above 30, is a reliable predictor of
severe outcome independently of age
Lab Markers
Predicting Severity


In a meta-analysis of 399 patients
presenting with acute pancreatitis, a
serum haematocrit above 44mg/dl, BMI
above 30 kg/m2, and pleural effusion on
chest X-ray, were the most sensitive
predictors of overall severity in acute
pancreatitis. In the same paper, these
criteria were validated in a prospective
cohort of 238 American patients, as the
‘panc 3 score’
Brown A, James-Stevenson T, Dyson T, et al. The panc 3 score: a rapid and accurate test for predicting severity on
Clinical Scoring

Ranson Criteria distinguish between
mild and severe pancreatitis with about
80% accuracy. The Ranson criteria,
however, require evaluation of 11
parameters over 48 hours.

The APACHE II scale
has advantages in
that it can be
performed on
admission, can be
reevaluated at any
time during the
patient’s
hospitalizaton. It is
cumbersome to use
clinically though
MPM II
Lemeshow S et al. Mortality probability models (MPM II) based on an
international cohort of intensive care patients. JAMA 1993;270:2478-86
Severe Pancreatitis

Severe acute pancreatitis is diagnosed if
3 or more of Ranson’s criteria are
present, if the APACHE II score is 8 or
more, or if one or more of the following
are present: shock, renal insufficiency, and
pulmonary insufficiency
–
Banks PA. Practice guidelines in acute pancreatitis. Am J Gastroenterol 1997;92:377-86.
Practical approach to predicting
severity requiring admission to an ICU:





a BMI above 30, and
left-sided or bilateral effusion on CXR within
24 h of admission,
An APACHE II score of at least 8 at 24 h after
admission, and a CRP above 150 mg/l
or a Ranson score above 3 at 48 h after
admission.
The development of organ failure or
pancreatic necrosis (i.e., SAP by definition)
also warrants immediate transfer to an ICU.
– A. Wilmer / European Journal of Internal Medicine 15 (2004) 274–280
Imaging Criteria
CT Severity Index
--74-year-old man with acute pancreatitis
Mortele, K. J. et al. Am. J. Roentgenol. 2004;183:1261-1265
Copyright © 2006 by the American Roentgen Ray Society
Radiological Scoring

Gurleyik et al found a sensitivity of 85%
and a specificity of 98% in predicting
severe pancreatitis based solely on CT
severity index.
–

Computed tomography severity index, APACHE II score, serumCRP concentration for
predicting the severity of acute pancreatitis. JOP 2005; 6(6):562–7.
severity index less than 3 had a 4%
morbidity rate and no mortality, whereas
patients who had a SI of more than 6 had
a 92% morbidity rate and a 17% mortality
–
Balthazar EJ, Robinson DL, Megibow AJ, et al. Acute pancreatitis: value of CT in establishing
prognosis. Radiology 1990;174(2):331–6.
CT severity index

patients who had a CT severity index
greater than 5 were eight times more
likely to die, 17 times more likely to have
a prolonged hospital course, and 10 times
more likely to require necrosectomy than
patients who had a severity index less
than 5

6. What is the appropriate initial management
approach for a patient with SAP? Yoan
Non ICU pt
– NPO,Fluids
– Analgesia,
– No ATBx
– Abdo U/S: R/O gallstone
– Feed low fat when anorexia gone
Management, ICU patient




Shock, pulmonary failure, renal failure, gastrointestinal bleeding,
multiorgan system failure
Initially NPO
Aggressive fluid resuscitation and monitoring (up to 500cc/hr +
bolus)
ATBX
– Give if infected pancreatic necrosis (CT guided aspiration)
– Do not give for fever only (inflammatory)




Abdo U/S: R/O gallstone-ERCP if gallstone pancreatitis-Cholecystect
in same hospit
NJ feeds initiated early (after initial ressuc- possibly NG)
TPN = 2nd line if feeds not tolerated
CT C+: early if doubt and for baseline, then at 2-5d, then PRN vs
q1week

7. When should the patient with SAP be
monitored in an ICU or step-down unit? Todd
Indications for ICU/stepdown
admission:

Shock (hypovolemic/distributive in setting of SIRS)
– Need for invasive cardiovascular monitoring.
– Hemodynamic support (pressors).
– Massive volume resuscitation, usually “too heavy” for standard
ward care, with resuscitation taking too long for typical busy ER.

Organ failure
– Lung injury
– Renal failure

Specific patient characteristics: elderly, morbid obesity
(BMI > 30), extensive pancreatic necrosis (>30%)

The patient was admitted to the intensive
care unit and was treated with intravenous
fluids, narcotic analgesia, and insulin for
her diabetes. Twenty-four hours after
admission, the patient was noted to be
tachypneic and dyspneic, requiring oxygen
administration.

8. What is the
frequency of
lung injury in
SAP? What is
the proposed
mechanism?
Discuss the
main preventive
and therapeutic
strategies.
Noemie
Lung injury and Acute
Pancreatitis

30% of pts with acute pancreatitis dvp ALI/ARDS
 Responsible for 60% of all deaths in 1st week
 Mechanism:
– Autodigestion of pancreas --> extravasation of
proteolytic enzymes and vasoactive mediators
– Systemic activation of inflammatory cells (Neutrophils)
– Endothelial hyperpermeability and leak
Current Opinion in Critical Care 2002,8:158-163
Lung injury and Acute
Pancreatitis

Prevention and treatment:
– Low tidal volume ventilation
– Inhibition of proinflammatory cascade
 Experimental/Animal models
 Antibodies against neutrophil chemoattractants
 Hypertonic saline
– Attenuates neutrophil activation
– Nutrition
 Enteral feeding shown to have better outcome
(ICAM)
Current Opinion in Critical Care 2002,8:158-163

Forty-eight hours after admission, the
patient was found to have marked
hypocalcemia (calcium, 0.7 mmol/L) and
hypophosphatemia (phosphorus, 0.52
mmol/L), requiring supplementation. On
rounds, you need to make a decision on
nutrition, as the patient has not yet been
fed.

9. What is the etiology of the hypocalcemia
and hypophosphatemia? Neil

What is the etiology of the
hypocalcemia and
hypophosphatemia?
PTH
– Suppressed secretion
– Inactivitated

Cytokines result in intracellular shift of
phosphate

10. What is the optimal mode and timing of
nutritional support for the patient with SAP?
Are there any specific nutritional supplements
that are beneficial in SAP? Are probiotics
useful? Marios
Nutrition in pancreatitis
What is the optimal mode and
timing of nutritional support for
the patient with SAP?
Total infectious complications
Mortality
Nutritional supplements
in SAP
Are probiotics useful?
www.thelancet.com Vol 371 February 23, 2008

On the seventh hospital day, the patient
develops a leukocytosis (white blood cell
count, 13.35 x 103) with 32% bands.
Panculturing is performed. You are
concerned about the possibility of a
secondary pancreatic infection.

11. What is the frequency of infectious
complication in SAP? What is the impact on
prognosis? Naisan
Incidence
20% of patients develop pancreatic necrosis
 15-50% pts that have pancreatic necrosis
develop infected necrosis from translocation of
gut-derived micro-organisms
 The highest risk group is those with 30% or
more necrosis
 infection might occur within the 1st week, but its
incidence tends to peak in the third week

Prognosis
death occurs in 10 to 20% of patients with
infected necrosis.
 Infectious complications account for 80%
of deaths from SAP, as well as the majority
of late complications


12. Should patients with SAP receive
prophylactic antibiotics? What is the evidence?
What about selective decontamination of the
digestive tract (SDD)? Yoan
Question 12
Should patients with SAP receive
prophylactic antibiotics? What is the
evidence? What about selective
decontamination of the digestive tract
(SDD)? Yoan
Nathens et al. Management of the critically ill patient with
severe acute pancreatitis. CCM 2004
Cochrane Data Review/Metaanalysis 2006
Meta Analysis on ATBX in SAP
Am J Gastroenterol 2008
US RCT Multicentric
100pts
 Proved Pancreatic necrosis
 Meropenem/placebo
 No decrease in Ix
 No change in hard outcomes

Dellinger EP, Tellado JM, Soto NE, et al. Early
antibiotic treatment for severe acute
necrotizing pancreatitis: a randomized,
double-blind, placebo controlled study. Ann
Surg 2007; 245:674–683.
We recommend against the routine use of prophylactic
systemic antibacterial or antifungal agents in patients
with necrotizing pancreatitis in light of inconclusive
evidence and divided expert opinion
Nathens et al. Management of the critically ill patient with severe
acute pancreatitis. CCM 2004

We recommend against the routine use of
selective decontamination of the digestive
tract in the management of necrotizing
pancreatitis. Further investigation of this
promising strategy in SAP is warranted
Nathens et al. Management of the critically ill patient with severe
acute pancreatitis. CCM 2004

Cultures all come back negative, and the
empiric antibiotic therapy you initiated is
discontinued. A repeat abdominal CT
scan reveals worsening phlegmonous
changes of the pancreas. The WBC
continues to rise, as do the lipase and
amylase.

13. What are the indications for surgery in
acute pancreatitis and what is the optimal
timing for intervention? What are the roles for
less invasive approaches, including
percutaneous drainage and laparoscopy? Are
there any specific approaches that need to be
considered with this etiology? Todd
Indications for Surgery in SAP:
Cholecystectomy (stone-associated disease)
 Necrosectomy:

– Infected necrotic tissue (up to 40% of patients with
SAP).
– Possibly in sterile necrotic pancreatitis, in setting of
recalcitrant SIRS/clinical deterioration, or failed
attempts at enteral refeeding after 2-4 weeks.
– Abdominal compartment syndrome in setting of
pancreatitis.
Timing

Key is allowing necrotic pancreas to
demarcate
– Early in abdominal compartment syndrome,
possibly in gallstone-related disease with
cholecystitis.
– Delayed, i.e. >2 weeks, for necrosectomy
(barring uncontrolled SIRS), cholecystectomy.
Other tools

Less invasive options:
– Percutaneous drainage (also useful for
obtaining gram stain/culture to guide surgical
decision and antimicrobial choice).
 May add continuous peritoneal lavage (no planned
re-laparotomy)
– Percutaneous necrosectomy.
– Laparoscopy/Video-assisted retroperitoneal
debridement (VARD).
Endoscopic Retrograde
Cholangiopancreatography

To decompress ducts and drain infected
biliary sludge in patients with
choledocholithiasis.
– This is an early intervention (< 72 hrs) in
setting of obstructive jaundice or biliary
sepsis.
Miscellaneous
Plasma Exchange (PLEX)
 If lipemic plasma is the problem, get rid of
it (at least temporarily)…
 Described in Therapeutic Apheresis 2002
Dec. 6 (6) 454-58.

– 2 patients in Japan with necrotizing
pancreatitis in setting of hypertriglyceridemia.
 Early PLEX--> survival after 60-day hospital course
 Delayed (20 days after onset of illness) --> death
from multiorgan failure and sepsis.

14. Under what circumstances should patients
with gallstone pancreatitis undergo
interventions for clearance of the bile duct?
Noemie
Gallstone AP and interventions for
clearance of the bile duct?

CBD stones cause 35-40% of SAP
 1998 UK guidelines:
– In SAP with u/s proven stone with obstructive
jaundice, urgent ERCP+ES is recommended
– In mild suspected gallstone pancreatitis,
conservative management is recommended. If pt’s
condition fails to improve in 24-48H, ERCP is
indicated
European Journal of Internal Medicine 2004;15:274-280
Studies compared emergency ERCP+ES vs
conservative Tx
 ERCP+ES significantly reduced overall
complication rate (41% vs 31%)
 Trend toward mortality benefit
 Does not influence the course of mild biliary AP

Ann Surg 2006;243: 154-168.
Primary Cholecystectomy vs
early ERCP

One level I trial comparing ERC+ES vs
cholecystectomy for mild biliary AP
– Hospital stay and overall cost for cholecystectomy
group

Three level I trials looking at symptomatic CBD
stones
– suggested less recurrent biliary sx
– Late mortality in ERC group was  in one trial

Recommend that mild biliary AP be treated with
cholecystectomy + intraop cholangio.
Ann Surg 2006;243: 154-168.

15. Is there a role for therapy targeting the
inflammatory response in patients with SAP?
Neil
Is there a role for therapy targeting
the inflammatory response in
patients with SAP?

Octreotide
– Benefit in meta-analysis
– Big RCT = no benefit

Antioxidants vs placebo in SAP
– no difference in organ function

Lexipafant (PAF antagonist)
– No improvement in DBRCT
Siriwardena et al.

The patient's abdominal pain and
laboratory values stabilize and improve
slightly with medical management, and
surgical intervention is withheld. However,
on day 11, the patient’s hemoglobin drops
to 85 from 110 the day before.

16. List at least 4 potential causes of GI
bleeding in SAP. Which are most common;
which are least? Yoan
Jury et al. Review Surg Tx Pancreatitis. MedClinNAm 2008
Cappel et al. Review Pancreatitis MedClinNAm 2008
Left colic artery pseudoaneurysm from pancreatitis presenting as upper gastrointestinal
hemorrhage. Marichal DA, Savage C, Meler JD, Kirsch D, Rees CR. J Vasc Interv Radiol. 2009
Jan;20(1):133-6. Epub 2008 Nov 22.
Acute necrotizing pancreatitis complicated with pancreatic pseudoaneurysm of the superior
mesenteric artery: A case report.
He Q, Liu YQ, Liu Y, Guan YS. World J Gastroenterol. 2008 Apr 28;14(16):2612-4

During the remainder of her hospitalization, the
patient's abdominal pain and laboratory values
continue to improve. She recovers with
conservative medical management and does not
require surgical intervention.On hospital day 20,
the patient is discharged in good condition. She
is followed by her primary care physician and is
compliant with gemfibrozil therapy and continues
without reported recurrent episodes of
pancreatitis for more than 1 year.