Acute Pancreatitis
Content
Acute Pancreatitis
Definition
A disorder of the exocrine pancreas, and is associated with acinar cell injury with local and systemic inflammatory responses. The inflammation
may range from mild oedema to peri-pancreatic necrosis.
Epidemiology
Acute pancreatitis is a potentially lethal disease that is increasing in incidence. Its mortality has improved as a result of a better understanding of
the natural history of the disease and improvement of critical care. Incidence varies from 4.5 to 79.8 per 100,000 per year in different countries.
This variation is due to different diagnostic criteria, geographical factors, and changes over time. A 10-fold increase in its incidence from 1960 to
1980, with a mortality rate from 1% to 9%, was noted. Approximately 210,000 patients are admitted to hospitals each year with acute
pancreatitis, with approximately 20% meeting criteria for severe pancreatitis alone in the US. The mortality rate is influenced by the severity of
the disease, and several prognostic factors have been investigated and described. In contrast to the milder form of the disea se, which has a
mortality rate of 1%, the mortality associated with severe acute pancreatitis is 10% with sterile and 25% with infected pancreatic
necrosis. Gallstone pancreatitis is more common in white women >60 years of age, especially among patients with microlithiasis. Alcoholic
pancreatitis is seen more frequently in men.
Aetiology
Several aetiological factors have been described for acute pancreatitis, but in 10% to 20% of cases an aetiological factor cannot be identified.
These cases are then considered idiopathic. The presence of microlithiasis or biliary sludge accounts for 80% of idiopathic pancreatitis. In the US,
gallstones followed by alcohol intake are responsible for 80% to 90% of cases of acute pancreatitis. The most common cause worldwide is
alcohol consumption.
Other causes include:
Hypertriglyceridaemia
Hypercalcaemia
Pancreatic malignancy
Post-endoscopic retrograde cholangiopancreatography (ERCP) (2% to 3%)
Trauma
Infections (mumps, mycoplasma, Epstein-Barr virus, Ascaris lumbricoides, HIV-related co-infections)
Drugs (sulphonamides, azathioprine, thiazides, furosemide, oestrogens, valproic acid)
Autoimmune conditions (collagen vascular diseases)
Pancreas divisum
Sphincter of Oddi dysfunction
Heredity.
Pathophysiology
The exact mechanism by which pancreatitis occurs is unknown. Several pathophysiological processes have been described that ultimately lead to
intra-pancreatic zymogen activation and auto-digestion with destruction of the acinar cell. Pancreatic ductal obstruction and hypersecretion have
been mentioned as factors that contribute to the initiation of the inflammatory process.
Intra-acinar activation of trypsinogen still plays a central role in the pathogenesis of acute pancreatitis, resulting in activation of proteases that
ultimately causes cell damage. Some investigations have led to newer hypotheses, including ischaemia/reperfusion injury and enzymatic colocalisation. [
Ethanol-induced pancreatitis has different pathophysiological mechanisms. Studies have described that ethanol is a direct toxic insult to the acinar
cell, causing inflammation and membrane destruction. Other mechanisms include sphincter of Oddi dysfunction, induction of
hypertriglyceridaemia, or formation of free oxygen radicals. Some studies have demonstrated that ethanol causes an increase in ductal pressures
secondary to protein deposition within the pancreatic duct, favouring retrograde flow and intra-pancreatic enzymatic activation.
Classification
Balthazar classification
This is a classification based on the extent of pancreatic inflammation and the presence or absence of fluid collections or gas suggestive of
necrosis on CT with IV contrast.
A: Normal
B: Focal or diffuse gland enlargement; small intra-pancreatic fluid collection
C: Any of the above plus peri-pancreatic inflammatory changes and <30% gland necrosis
D: Any of the above plus single extra-pancreatic fluid collection and 30% to 50% gland necrosis
E: Any of the above plus extensive extra-pancreatic fluid collection, pancreatic abscess, and >50% gland necrosis.
General pathological classification
Surgical textbooks often distinguish between oedematous and haemorrhagic pancreatitis, based on pathological/histological features:
Oedematous pancreatitis: pancreatic parenchyma and surrounding retroperitoneal structures are engorged with interstitial fluid and
infiltration of inflammatory cells
Haemorrhagic pancreatitis: bleeding into the parenchyma and surrounding retroperitoneal structures with extensive pancreatic
necrosis.
Secondary prevention
The most important aspect of prevention is patient education. Eating a balanced, low-fat diet, maintaining adequate triacylglyceride control, and
decreasing the amount of alcohol intake are a few dietary and behavioural measures that may decrease the incidence of acute pancreatitis.
Effectively, addressing gallstone disease by any means available (such as cholecystectomy, endoscopic retrograde cholangiopancreatography
[ERCP], ursodeoxycholic acid), may decrease the ductal obstruction risk and hence the risk of pancreatitis. Other risk factors may be controlled
through patient education and medicine dose adjustments. Probiotics, antioxidants and immune nutrition have no role in the pr evention of acute
pancreatitis. Several studies have addressed the use of pharmacological treatment (somatostatin, gabexate, glycerine trinitrate, nafamostat
mesylate), adequate patient selection, and stent placements during ERCP to prevent pancreatic injury. The use of somatostatin has been linked to
a better protection against ERCP-induced pancreatitis than gabexate in some studies, but two meta-analyses yielded different conclusions. Stents
are an option for endoscopists with experience in the field, but the manipulation to obtain biliary access (rather than patient characteristics or
endoscopist experience) is the main factor in the development of ERCP-induced pancreatitis.
The use of a guidewire bile duct cannulation technique during ERCP has been shown to decrease the incidence of post-ERCP pancreatitis in
comparison with the standard contrast injection cannulation.
Those with idiopathic chronic pancreatitis, recurrent acute pancreatitis, or a family history of pancreatitis should be considered for genetic testing,
especially in the setting of pancreatic cancer. The clinical relevance and the therapeutic consequences of the gene mutations l eading to
pancreatitis are still controversial, and genetic testing is recommended when a patient with idiopathic pancreatitis is u nder 25 years of age at
diagnosis or when one or more family members have either pancreatitis or pancreatic cancer. Genetic analysis of asymptomatic family members
should only be offered after adequate genetic counselling, and antenatal diagnosis is not recommended.
Diagnostic tests
1st tests to order
Test
Result
serum amylase
Normal range: 35 to 118 units/L. Amylase levels should be checked in every patient with severe abdominal pain. It has a
sensitivity of 75% to 92% and a specificity of 20% to 60% with a positive predictive value approaching 100%.The sensitivity
of the test is limited by hypertriglyceridaemia and alcoholism, and the specificity by inflammatory intra-abdominal processes
and parotid and submandibular salivary gland inflammation. Levels start rising over the first 2 to 12 hours, peak at 48 hours,
and return to normal within 3 to 5 days. Tends to be higher in patients with gallstone pancreatitis than in alcoholic pancreatitis.
3 times the upper limit of
the normal range
can be elevated if
serum lipase
Lipase is more sensitive (50% to 99%) and specific (86% to 100%) than amylase; however, the utility is limited in acute
amylase normal
pancreatitis due to discrepancies in measurement method, patient selection, and cut-off points. Hence, the determination of
lipase is not necessary in a patient with a clinical diagnosis of acute pancreatitis and 3 times the normal value of serum amylase.
Its use can be helpful in patients with a clinical presentation suggestive of pancreatitis and normal amylase. Due to additional
cost and lack of benefit in the majority of patients, utilising serum lipase in conjunction with serum amylase is considered
inappropriate. Levels start rising 4 to 8 hours after the onset of pain, peak at 24 hours, and last for 8 to 14 days. Patient s with
alcoholic pancreatitis have higher levels of lipase than those with gallstone pancreatitis.
ratio of serum lipase:amylase
Low sensitivity. Favours alcoholic pancreatitis.
>5
urinary amylase
>5000 international
units/24 hours
AST/ALT
if >3 times the upper
normal limit, predicts
gallstone disease as
aetiology in 95% of cases
Low sensitivity and specificity for pancreatitis.
FBC and differential
Mild leukocytosis with left shift and elevated haematocrit as a result of dehydration or low haematocrit as a result of
haemorrhage can be seen. The development of haemoconcentration has been associated to predict the risk of developing
necrotising pancreatitis.
leukocytosis
haematocrit
Indicator of severity and prognosis.
if >44% on admission, is
a predictor of pancreatic
necrosis
arterial blood gas
It is important to monitor the arterial oxygenation, since patients may be hypoxaemic, requiring supplemental oxygen. During
the initial management, consider arterial blood gases every 12 hours for the first 3 days to assess both oxygenation and acidbase status.
hypoxaemia and
disturbances in acid-base
balance
abdominal plain film
Abnormal in two-thirds of patients.
may find a sentinel loop
(isolated dilatation of a
segment of gut) adjacent
to the pancreas, gas
distending the right colon
that abruptly stops in the
mid- or left transverse
colon (cut-off sign), or
calcifications
CXR
may show atelectasis and
pleural effusion
(especially in the left
side)
ultrasound
Sensitivity in detecting pancreatitis is 62% to 95%. Is non-invasive, easy to perform at the bedside, and inexpensive. Limited by
obesity, bowel gas, and is operator-dependent. Useful when biliary causes are suspected. The use of endoscopic ultrasound
allows tissue diagnosis and has replaced endoscopic retrograde cholangiopancreatography (ERCP).
may show pancreatic
inflammation, peripancreatic stranding,
calcifications, or fluid
collections
Tests to consider
Test
Result
C-reactive protein (CRP)
Indicator of severity. Useful after first 36 to 48 hours.
if >200 units/L, is
associated with
pancreatic necrosis
abdominal CT scan
CT scan with IV contrast is the most sensitive and specific study for confirming diagnosis of pancreatitis. Has a sensitivity of
90% and specificity of 100%. It is used when clinical and biochemical findings are equivocal, Ranson score of >3 or APACHE
II score of >8 to detect and stage complications, and when patients have persisting organ failure, show signs of sepsis, or
present with clinical deterioration or do not improve after 48 to 72 hours of treatment. Signs of complicated pancreatitis ar e
usually seen 3 days after the onset of abdominal pain.
findings may include
diffuse or segmental
enlargement of the
pancreas with irregular
contour and obliteration
of the peri-pancreatic fat,
necrosis, or pseudocysts
magnetic resonance cholangiopancreatography (MRCP)
MRCP is superior to CT scanning for staging acute pancreatitis and detecting complications. It also has the advantage of not
requiring IV contrast.
findings may include
stones, diffuse or
segmental enlargement
of the pancreas with
irregular contour and
obliteration of the peripancreatic fat, necrosis,
or pseudocysts
endoscopic retrograde cholangiopancreatography (ERCP)
ERCP has a limited use as a diagnostic tool in acute attacks of acute pancreatitis and has been mostly replaced by ultrasound
and MRCP. Indications are preoperative evaluation to verify duct condition in patients with traumatic pancreatitis, in patients
with severe pancreatitis and suspected biliary obstruction (allows sphincterotomy, stone removal, stent placement, tissue
diagnosis) that do not improve after 24 hours of conservative management, and as work-up for idiopathic pancreatitis. Studies
have shown a reduction of morbidity and mortality in patients with early ERCP (<24 hours) and biliary disease.
identifies stones and
allows their retrieval
during the same
intervention; can identify
duct filling defects and
strictures
fine needle aspiration
If sepsis is suspected in patients with pancreatic necrosis, a percutaneous needle aspiration can be performed to rule out
bacterial colonisation.
identification of
causative organism if
bacterial colonisation
Emerging tests
Test
Result
elevated
urinary trypsinogen-2
Sensitivity of 94% and specificity of 95%. Now considered a better serological screening test than
amylase.
serum IL-6
Sensitivity of 81% to 88% and specificity of 75% to 85% for prediction of severe acute
pancreatitis.
serum IL-8
Sensitivity of 65% to 70% and specificity of 69% to 91% for prediction of severe acute
elevated
elevated
pancreatitis.
Differential diagnosis
Condition
Peptic ulcer disease
Perforated viscus
Differentiating signs/symptoms Differentiating tests
Oesophageal spasm
Intestinal obstruction
Abdominal aorta
aneurysm
Longstanding
epigastric pain, which
does not generally
radiate to the back;
reflux; heartburn; and
anorexia. Identifiable
causes such as nonsteroidal antiinflammatory drug
(NSAID)
use, Helicobacter
pylori, ZollingerEllison's syndrome
may be present.
Will present with
acute abdomen,
peritoneal signs,
tachycardia, and
sepsis. Generally the
abdomen is rigid and
tender in all 4
quadrants, with
guarding.
Dysphagia,
odynophagia, weight
loss, history of
retrosternal pain.
Physical examination
may be normal.
History of abdominal
surgeries (especially
colon resection,
caesarean sections,
and aortic
procedures).
May improve with proton pump inhibitors, lifestyle modifications, and H pylori treatment.
Normal lipase and amylase.
Tonometry may show evidence of reflux.
Laboratory evaluation will show normal values of amylase and lipase.
Endoscopic evaluation will be diagnostic after visualising erosions, erythema, or ulcers,
and allows biopsies to be performed.
Normal lipase. May have elevated amylase (usually less marked than that seen in acute
pancreatitis).
Plain x-rays show sub-diaphragmatic air.
A swallow study may demonstrate a contracted and abnormal-appearing oesophagus with
increased pressures on oesophageal manometry.
Normal lipase and amylase.
Acute abdominal series will show ground glass appearance, air-fluid levels, distended
bowel loops, absence of distal gas, pneumatosis.
An abdomen/pelvic CT scan may be more diagnostic, and will show point of transition and
potentially identify aetiology (such as volvulus, hernias, intussusception, masses).
Hernias in the
physical examination.
Presents with
abdominal distension
(depends on the level
of obstruction),
tympanism, decreased
bowel sounds,
anorexia, emesis
(quality depends on
location of
obstruction),
obstipation, or
constipation.
Cardiovascular risk
factors:
hyperlipidaemia,
tobacco, diabetes
High index of suspicion is necessary to make a rapid diagnosis and improve outcomes. In
stable patients, where history and physical examination are equivocal, a CT angiography
may be useful as a rapid way to make diagnosis.
mellitus,
homocystinaemia.
Cholangitis
Choledocholithiasis
Cholecystitis
Viral gastroenteritis
If too unstable for radiographic evaluation, patients usually go directly to surgery.
Acute tearing-like
abdominal pain,
pulsating abdominal
mass, hypotension,
and mottled lower
extremities with
decreased pulses and
abdominal distension.
Charcot's triad
(jaundice, right upper
quadrant pain, and
fever) present in 70%
of patients, altered
mental status, and
hypotension indicate
biliary sepsis, usually
caused by gramnegative bacteria.
Several clinical findings are present more frequently in cholangitis, such as fever (95%),
right upper quadrant pain (90%), and jaundice (80%).
Normal lipase and amylase.
Blood cultures are usually positive, especially during episodes of chills, with Escherichia
coli andKlebsiella as the most common micro-organisms isolated from infected bile.
Patient may have a
history of gallstones,
peri-ampullary
neoplasms, or biliary
manipulation such as
endoscopic retrograde
cholangiopancreatogr
aphy (ERCP).
Severe right upper
quadrant pain of
sudden onset,
jaundice, acholia,
choluria, and hx of
cholelithiasis. May
occlude the common
bile duct and cause
pancreatitis.
Pain is generally
triggered after a fatty
meal and localised in
the right upper
quadrant. More
common in
overweight females
between 40 and 50
years of age.
Normal lipase and amylase.
Ultrasound will show gallstones, stones within the common bile duct with extra-hepatic
and/or intra-hepatic duct dilatation.
Chemistry will show biochemical obstruction, with increased levels of total and direct
bilirubin, alkaline phosphatase, gamma-GT, and a slight increase in ALT/AST but normal
levels of pancreatic enzymes (especially lipase).
Normal lipase and amylase.
A right upper quadrant ultrasound will show thickened gallbladder wall, stones with
acoustic shadows, biliary sludge, peri-cholecystic fluid, and sonographic Murphy's sign,
and allows evaluation of the duct system. Can suggest pancreatic head inflammation. May
show mild leukocytosis and a very mild elevation of liver enzymes.
A hepatobiliary iminodiacetic acid (HIDA) scan is diagnostic when there is no filling of the
gallbladder or with delayed emptying of the radiotracer.
Anorexia, nausea, and
vomiting may be
present. May show a
positive Murphy's
sign and low-grade
fever.
Generalised nonspecific abdominal
pain, anorexia,
nausea, emesis,
diarrhoea, and
dehydration.
Is usually a self-
Normal lipase and amylase.
Important to obtain serum electrolytes and an FBC.
Hypokalaemia and alkalosis may be seen secondary to diarrhoea, vomiting, and
dehydration.
Stool examination for microscopy, culture, osmolality, ova, parasites, Clostridium
limiting viral infection
but if fever is
documented, bacterial
and invasive
organisms should be
suspected.
Hepatitis
Mesenteric ischaemia
Myocardial infarction
difficile toxin, and white blood cells may help in identifying the causative factor.
Consider in travellers
and
immunosuppressed
patients.
Consider osmotic and
secretory diarrhoea
from hx.
Jaundice, right upper
quadrant pain,
anorexia, and general
malaise. Choluria and
acholia may be seen.
Normal lipase and amylase.
Elevated liver function tests are characteristic. AST/ALT in the range of the 1000 units/L is
not rare. Serological titres can make diagnosis of aetiological cause.
Radiographic studies not important for its diagnosis.
Examination:
tenderness to
palpation over the
right upper quadrant
and enlarged liver.
Patients are usually
older, may have a
history of atrial
fibrillation and risk
factors for peripheral
vascular disease.
High index of suspicion of diagnosis is necessary. Angiography and CT scan may be useful
in diagnosis as well as lactic acid levels.
Normal lipase. May have elevated amylase (usually less marked than that seen in acute
pancreatitis).
Hypercoagulable
states may lead to
bowel necrosis. Pain
is usually out of
proportion to the
finding of the physical
examination.
Pain is usually
retrosternal with
radiation to jaw, neck,
and left upper
extremity. Associated
with shortness of
breath, nausea,
vomiting, and
diaphoresis.
Cardiovascular risk
factors in the history.
Elevated cardiac enzymes (creatine kinase or creatine phosphokinase, troponins), ECG
changes, and clinical scenario make the diagnosis.
Normal lipase and amylase.
Cardiac catheterisation, perfusion scans, and echocardiograms are useful during the workup of cardiac ischaemia.
Step-by-step diagnostic approach
The diagnosis of pancreatitis is always one of exclusion, so it must be included with any complaint of severe abdominal pain. History and
examination can be indicative of acute pancreatitis; however, the keys for diagnosis are elevated levels of amylase and lipase, which need to be at
least 3 times their normal value.
History
A detailed history is imperative to narrow the large number of differentials of abdominal pain. Metabolic, nutritional, and procedural aetiologies
of pancreatitis should be considered during history-taking. A detailed family history is important to rule out collagen vascular diseases, cancer, or
hereditary pancreatitis. Any medicine and indications for their use should be reviewed, since many medications can have pancreatic injury as an
adverse effect. Age and sex are important demographic variables, since the 2 most common causes of acute pancreatitis differ. Gallstone
pancreatitis is seen most commonly in patients with gallbladder disease - the 5 "Fs": fat, forty, female, fertile, and family history. Alcoholic
pancreatitis is seen more frequently in men, generally younger than those with gallstone pancreatitis. Patients usually manifest after an average of
4 to 8 years of alcohol intake, and bingeing behaviour increases the risk of acute pancreatitis.
Patients may present with agitation and confusion, and in severe distress. They may give a history of anorexia, nausea, and vomiting with poor
oral intake. The most common symptom is severe mid-epigastric pain that radiates to the back (band distribution), worsens with movement, and
is alleviated when assuming the fetal position (bent over, with spine, hips, and knees flexed). Gallstone pancreatitis may be more acute in onset
than alcoholic pancreatitis, which may be preceded with a few days of mild epigastric discomfort.
Physical examination
Signs of hypovolaemia (decreased skin turgor, dry mucous membranes, hypotension) are usually found. Patients may appear diaphoretic,
tachycardic, and tachypnoeic. Fever may indicate a complicated pancreatitis or may simply represent cytokine release as part of the inflammatory
process. Decreased breath sounds may be detected if there is a pleural effusion (more common on the left side); this is seen in up to 50% of
patients with acute pancreatitis. The abdominal examination may reveal a tender and distended abdomen with diminished bowel sounds (if an
ileus has developed) and voluntary guarding to palpation of the upper abdomen. There may be a mild rigidity without re-bound tenderness.
Clinical signs of hypocalcaemia are rare but may be evident, such as facial muscle spasm when facial nerve is tapped (Chvostek's sign) and
carpopedal spasm when blood pressure cuff is applied (Trousseau's sign). Complicated haemorrhagic pancreatitis may exhibit ecchymotic
discoloration of several areas, including the peri-umbilical skin (Cullen's sign), over both flanks (Grey-Turner's sign) or over the inguinal
ligament (Fox's sign), and may be seen as soon as presentation or 24 to 48 hours after the onset.
Laboratory work-up
Any patient with an acute abdomen should have an FBC with differential and a blood chemistry including renal, liver, and pancreatic function
tests. Mild leukocytosis with left shift and elevated haematocrit as a result of dehydration or low haematocrit as a result of haemorrhage can be
seen. The development of haemoconcentration is associated with an increased risk of developing necrotising pancreatitis. As a result of
dehydration there may be some degree of pre-renal azotaemia, manifested by elevated creatinine and urea. In the absence of choledocholithiasis,
liver function tests are usually normal, but a slight increase in alkaline phosphatase and bilirubin may be seen. The key for diagnosis is elevated
levels of amylase or lipase; amylase levels more than 3 times the normal value are highly specific for acute pancreatitis. The degree of pancreatic
inflammation is not directly correlated with the amylase or lipase absolute value. Due to additional cost and lack of benefit in the majority of
patients, utilising serum lipase as a first test in conjunction with serum amylase is considered inappropriate. Measuring lipase can be helpful in
patients with a clinical presentation suggestive of pancreatitis in whom the amylase levels were normal.
It is important to monitor arterial oxygenation, since patients may be hypoxaemic, requiring supplemental oxygen. During initial management,
arterial blood gases should be considered every 12 hours for the first 3 days to assess both oxygenation and acid-base status.
C-reactive protein (CRP) is performed subsequently and is an indicator of severity; useful after the first 36 to 48 hours. [
If sepsis is suspected in patients with pancreatic necrosis, a percutaneous needle aspiration can be performed to rule out ba cterial colonisation.
Imaging
Radiographic studies are not used for diagnosis of acute pancreatitis, but may determine possible causative factors and exclu de other diagnoses.
A CXR may show pleural effusion and basal atelectasis, and a sentinel loop (isolated dilatation of a segment of gut) may be seen in a KUB. Plain
abdominal x-ray may reveal a sentinel loop adjacent to the pancreas, gas distending the right colon that abruptly stops in the mid- or left
transverse colon (cut-off sign), or calcifications.
Magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), trans-abdominal ultrasound,
and endoscopic ultrasound are usually indicated in patients with elevated liver function tests suggestive of bile duct obstruction, to exclude
strictures, neoplasms, or stones.
Ultrasound is considered to be the preferred initial study in suspected gallstone pancreatitis as it is inexpensive, easy to perform at the bedside,
and allows examination of the gallbladder and bile duct system. Its sensitivity in detecting pancreatitis is 62% to 95%. It is limited by obesity and
bowel gas, and is operator-dependent. The use of endoscopic ultrasound allows tissue diagnosis and has replaced ERCP.
The advantage of the ERCP is that it has the added benefit of treating certain aetiological conditions (e.g., by stone removal, stent placement, or
sphincterotomy), but it has been largely superseded as a diagnostic modality by MRCP and ultrasound.
MRCP is generally used in patients with renal insufficiency, in whom the use of CT with IV contrast is discouraged. It is superior to CT scanning
for staging acute pancreatitis and detecting complications.
Patients who show signs of systemic inflammatory response or sepsis, or who do not improve, should have a CT scan to rule out peri-pancreatic
collections, necrosis, and abscess. Areas of non-perfusion indicate infected pancreatic necrosis.
Emerging tests
Urinary trypsinogen-2 is now considered a better serological screening test than amylase but is not yet used clinically; sensitivity of 94% and
specificity of 95%.Interleukins IL-6 and IL-8 are inflammatory mediators that have been recently described as predictive serum markers for
development of severe acute pancreatitis.
Treatment Options
Patient Group
Tx Line
all patients
1st
Treatment
initial resuscitation
IV hydration with crystalloids is essential, and an effort to keep urinary output above 30 mL/hour is
necessary to avoid potential kidney damage.
Pain control is important when pain is present, and the most commonly used pharmacological drugs
are the opioids. Pethidine, fentanyl, or morphine can be used, either for breakthrough pain or as
patient-controlled analgesia. Monitor respiratory and CNS depression. Meperidine is considered
superior to morphine because it does not increase sphincter of Oddi pressures.
Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), can be used in patients with intact renal
function.
Ondansetron is the most commonly used antiemetic.
Primary Options
crystalloids : 20-40 mL/kg intravenously
and
pethidine : 25-100 mg subcutaneously/intramuscularly every 4 hours when required
and
ondansetron : 2-4 mg intravenously every 4-6 hours when required
Secondary Options
crystalloids : 20-40 mL/kg intravenously
-- AND -morphine sulphate : 1-5 mg intravenously every 4 hours when required
or
fentanyl : 50-100 micrograms intravenously, followed by 50 micrograms every 1-2 hours when
required
or
ketorolac : 10 mg intravenously/intramuscularly initially, followed by 10-30 mg every 4-6 hours when
required for 2 days, maximum 90 mg/day
-- AND -ondansetron : 2-4 mg intravenously every 4-6 hours when required
plus
nutritional support
Initially patients should be kept nothing by mouth. Oral intake is re-started when there is notable
clinical improvement, nausea and abdominal pain has resolved, and amylase levels have dropped to
normal. Premature resumption of diet may result in exacerbation of the disease. In patients who are
expected to have a prolonged nothing by mouth status, a trans-pyloric nasojejunostomy feeding tube
should be placed, allowing enteral nutrition without stimulating the pancreas.
adjunct
The regimen should provide 25 to 35 kcal/kg/day energy, 1.2 to 1.5 g/kg/day protein, 3 to 6 g/kg/day
carbohydrates, and 2 g/kg/day lipids.
Parenteral nutrition should be reserved for patients who do not tolerate enteral feeding or in whom an
adequate infusion can not be reached within 2 to 4 days.
calcium replacement therapy
In severe cases of pancreatitis, hypocalcaemia should be identified and treated accordingly. Calcium
should be titrated to normal serum ionic calcium levels. Calcium chloride is used less frequently, since
it must be given by a central line.
Primary Options
calcium gluconate : 2-15 g/day intravenously given as infusion or in divided doses, or see local
protocol for dosing guidelines; 500-1000 mg orally four times daily
More
adjunct
magnesium replacement therapy
Magnesium should be replaced if low levels are identified, commonly seen in alcoholic patients. Renal
function (creatinine) should be checked before magnesium administration. It may need daily
replacement.
Primary Options
magnesium sulphate : 1-2 g intravenously every 6 hours on first day, followed by 60 mg/kg/day as an
infusion, or see local specialist protocol for dosing guidelines
adjunct
insulin
adjunct
Blood glucose control and insulin administration to keep glucose <8.33 mmol/L (<150 mg/dL) has
been associated with reductions in morbidity and mortality in critically ill patients. In less severe cases,
regular insulin sliding scales can be used.
See local specialist protocol for dosing guidelines.
antibiotic therapy
Decontamination of the gut, where antibiotics are given to decrease the intra-luminal bacterial count,
has not been proven effective in decreasing the incidence of pancreatic sepsis, but a meta-analysis of 8
randomised controlled trials found reduction in mortality of patients with severe acute pancreatitis
when prophylactic IV antibiotics with pancreatic penetrance were administered.
It is important, however, to limit the use of antibiotics for this subset of patients to avoid fungal
superinfection.
Imipenem is the antibiotic most studied because of its pancreatic penetration.
In patients with necrotising pancreatitis, antibiotic use should be restricted to patients in whom there
are signs, symptoms, and laboratory tests indicating that infection is present (fever, leukocytosis, organ
failure, and positive cultures).
There is no consensus in the literature to date of how long patients need to be on antibiotics. However,
clinical improvement, with resolution of organ failure and improvement of systemic markers of
inflammation, can be considered as reasonable indicators that antimicrobials can be stopped.
Primary Options
cilastatin+imipenem : 500-1000 mg intravenously every 6 hours
More
Secondary Options
ceftriaxone : 1-2 g intravenously every 12 hours
OR
ampicillin : 500 mg intravenously every 6 hours
OR
ciprofloxacin : 400 mg intravenously every 12 hours
with gallstones: surgical candidates
adjunct
cholecystectomy
In patients in whom the diagnosis of acute gallstone pancreatitis is obtained by ultrasound, a
cholecystectomy with common bile duct exploration (either surgical or postoperatively with
endoscopic retrograde cholangiopancreatography [ERCP]) should be performed during the same
hospitalisation for the acute attack, soon after the attack resolves. A longer delay, even a few weeks, is
associated with a high recurrence (80%).
When a laparotomy is performed for diagnosis and mild to moderate pancreatitis is found,
cholecystectomy with intra-operative cholangiogram should be performed but the pancreas should be
left alone. For severe pancreatitis, the lesser sac should be opened and the pancreas fully inspected.
Some surgeons place drains and irrigating catheter around the pancreas.
with gallstones: non-surgical
candidates
adjunct
endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy
with alcohol-induced disease
plus
In patients who are not candidates for surgery because of comorbidities with a high ASA index, sepsis,
or severe disease, ERCP must be considered.
The use of ERCP and sphincterotomy, performed within 72 hours after the onset of the disease, has
been shown to decrease the incidence of concomitant biliary sepsis and systemic complications in
severe but not in mild forms of pancreatitis. Contradictory results have been obtained for mortality
rates.
A meta-analysis of 4 randomised controlled trials of endoscopic sphincterotomy in patients with severe
acute pancreatitis showed that sphincterotomy reduced complications and mortality. The role of ERCP
in patients without biliary obstruction or cholangitis is unknown. Cholecystectomy has to be
considered after discharge.
benzodiazepines
Patients with alcohol-induced pancreatitis may need alcohol-withdrawal prophylaxis. Lorazepam is
generally used in this group of patients.
Primary Options
lorazepam : 1-2 mg orally/intravenously/intramuscularly every 6-8 hours
plus
vitamin and mineral replacement
The objective of replacement of thiamine in chronic alcoholism is to replenish the stores in patients.
The treatment has to be continued until the patient can return to eating a well-balanced meal during
hospitalisation.
Other water-soluble vitamins that are supplemented during hospital or emergency department course
include folic acid and cyanocobalamin. Cyanocobalamin can be given orally except in states when
absorption is impaired.
Primary Options
thiamine : 100 mg orally/intravenously/intramuscularly once daily
and
folic acid : 1 mg orally/intramuscularly once daily
and
cyanocobalamin : 1000 micrograms intramuscularly/orally once daily for 1-2 weeks, followed by 1000
micrograms once every 1-3 months
with infected pancreatic necrosis
plus
necrosectomy
If sepsis is considered, a percutaneous needle aspiration can be performed to rule out bacterial
colonisation. Necrosectomy involves resection of the necrotic pancreatic tissue and placement of
irrigating drains within the debrided spaces, allowing postoperative lavage. The only criteria for
debridement are multi-organ failure (with or without infection) with CT evidence of necrotic tissue.
Outcomes are better if surgery is delayed until the necrosis has organised, usually about 4 weeks after
the onset of abdominal pain. Allowing organisation of the inflammation makes the dissection through
planes easier.
Treatment approach
The main goal of initial treatment is to prevent complications of severe pancreatitis by reducing pancreatic secretory stimuli and correction of
fluid and electrolyte abnormalities. Initially, the patients should be fluid resuscitated and kept nothing by mouth with bowel rest when nausea,
vomiting, and abdominal pain are an issue.
At diagnosis supportive care continues until pain is resolved and diet re-started. The majority of patients will improve within 3 to 7 days of
conservative management. Patients with organ failure or with poor prognostic signs (Glasgow score >3, APACHE score >8, and Ra nson score
>3) should be admitted to the intensive care unit.
Initial resuscitation
Resuscitation with IV fluids, analgesics, and antiemetics are the initial treatments even before diagnosis is made.
IV hydration with crystalloids is essential, and an effort to keep urinary output above 30 mL/hour is necessary to avoid potential kidney damage.
The patient should be catheterised to monitor urinary output in severe cases of acute pancreatitis. The adequacy of fluid replacement is the single
most important aspect of the medical management. In haemorrhagic pancreatitis, blood transfusion may be necessary.
Pain control is important when pain is present, and the most commonly used pharmacological drugs are opioids. Pethidine, fentanyl, or morphine
can be used, either for breakthrough pain or as patient-controlled analgesia (PCA). Ketorolac, a non-steroidal anti-inflammatory drug (NSAID),
can be used in patients with intact renal function.
It is important to monitor the arterial oxygenation, since patients may be hypoxaemic, requiring supplemental oxygen. During the initial
management, consider arterial blood gases every 12 hours for the first 3 days to assess both oxygenation and acid-base status.
Severe pancreatitis
In severe cases of pancreatitis, hypocalcaemia should be identified and treated accordingly. Treatment of this electrolyte imbalance is important,
since hypocalcaemia may lead to cardiac dysrhythmias. Magnesium should be replaced if low levels are identified, commonly seen in alcoholic
patients.
Blood glucose control and insulin administration to keep glucose <8.33 mmol/L (<150 mg/dL) has been associated with reductions in morbidity
and mortality in critically ill patients. Insulin sliding scales, insulin drips, or long-acting insulin should be used in patients with hyperglycaemia
that is difficult to treat.
The use of antibiotics is not a routine practice, and controversial results have been obtained in recent studies. However, some studies have shown
some benefit in cases of severe necrotising pancreatitis. The main indication for necrosectomy is infection in severe necrotising pancreatitis.
Nutrition
A period of nothing by mouth is required initially, especially during the first 24 to 48 hours after the onset of pancreatitis (the phase of
resuscitation and control of nausea and pain). This reduces exocrine stimulation by cholecystokinin and secretin, and reduces the risk of
aspiration if a dynamic ileus is present. Oral intake is re-started when there is notable clinical improvement, nausea and abdominal pain has
resolved, and amylase levels have dropped to normal. Premature resumption of diet may result in exacerbation of the disease. In patients who are
expected to have a prolonged nothing by mouth status, a trans-pyloric nasojejunostomy feeding tube should be placed beyond the ampulla of
Vater. This allows enteral nutrition without stimulating the pancreas. Parenteral nutrition should be reserved for patients who do not tolerate
enteral feeding or in whom an adequate infusion cannot be reached within 2 to 4 days. When compared with parenteral nutrition, enteral feeds are
associated with better outcomes, less mortality, and better blood glucose control. They also protect the gut barrier by preventing intestinal
atrophy, leading to less sepsis and fewer infectious complications. The recommended nutrient requirements in severe acute pancreatitis are as
follows: energy 25 to 35 kcal/kg/day, protein 1.2 to 1.5 g/kg/day, carbohydrates 3 to 6 g/kg/day, and lipids 2 g/kg/day.
Alcohol-induced pancreatitis
Patients with alcohol-induced pancreatitis may need alcohol-withdrawal prophylaxis. Lorazepam, thiamine, folic acid, and multi-vitamins are
generally used in this group of patients.
Gallstone pancreatitis
In patients in whom the diagnosis of acute gallstone pancreatitis is obtained by ultrasound, imaging of the common bile duct is required. If the
presence of stones in the common bile duct is confirmed, a cholecystectomy with common bile duct exploration (either surgical or
postoperatively with endoscopic retrograde cholangiopancreatography [ERCP]) should be performed during the same hospitalisation in mild to
moderate disease soon after the attack resolves. A longer delay, even of a few weeks, is associated with a high recurrence (80%).
If the pancreatitis is severe, some allow a few months for the inflammation to completely resolve before performing a cholecystectomy.
In patients who are not candidates for surgery because of comorbidities with a high American Association of Anesthesiology (ASA) index,
sepsis, or severe disease, ERCP must be considered. Urgent ERCP is indicated in patients with biliary sepsis and obstructive jaundice that show
no improvement in 48 hours after the onset of the attack. ERCP is a diagnostic and therapeutic intervention. It allows defining of the biliary
system anatomy, to remove stones causing jaundice, sepsis, and pancreatitis, as well as placement of stents for strictures or pancreatic duct leaks
(secondary to pancreatitis or trauma), and permits facilitation of biliary drainage by performing of sphincterotomy.
Pancreatitis found on laparotomy
When a laparotomy is performed for diagnosis and mild to moderate pancreatitis is found, cholecystectomy with intra -operative cholangiogram
should be performed but the pancreas should be left alone. For severe pancreatitis, the lesser sac should be opened and the pancreas fully
inspected. Some surgeons place drains and irrigating catheter around the pancreas.
Step by step
Monitoring
Long-term monitoring is not necessary. Patients usually resolve after their acute attack. If they modify their risk factors, another episode may not
recur later in life. Lipids should be monitored in those with hypertriglyceridaemia.
Patient Instructions
Before discharge from hospital after an acute attack of acute pancreatitis, patients should be advised to modify lifestyle risk factors. For example,
alcoholic patients need to stop drinking, especially bingeing behaviour, modify diet in order to control hypertriglyceridaemia, and use lipidlowering medicines such as statins or niacin. Patients taking medicines (e.g., furosemide, didanosine, oestrogens) should be educated about the
adverse effects and how to recognise an acute attack of pancreatitis.
Patients should be advised to eat small, low-fat meals of carbohydrates and proteins, with a gradual increase in quantity over a period of 3 to 6
days as tolerated.
Complications
Complicationhide all
Timeframe Likelihood
acute renal failure
short term
high
short term
medium
see our comprehensive coverage of Acute renal failure
Seen in patients with severe acute pancreatitis. May be caused by circulating toxins or rhabdomyolysis. Hypovolaemia
and inflammatory mediators. Acute renal failure is a complication with poor outcome.
necrotising pancreatitis
Secondary to inadequate fluid resuscitation, vasoactive and toxic substances (phospholipases, endotoxins, activated
trypsin, complement activation, thromboxane, and elastase).
pancreatic abscess
short term
Occurs when the peri-pancreatic fluid collections become colonised and infected. Invariably fatal if not treated surgically.
Follows secondary bacterial contamination of necrotic pancreatic tissue and haemorrhagic exudates. It is unknown
whether prophylactic antibiotics given early in the course of the disease decrease the incidence of abscess. Generally
low
patients present 2 to 4 weeks after the onset of pancreatitis, with fever, and clinically worsen.
CT is diagnostic, showing a ring-enhancing fluid collection with gas. Its treatment is drainage (surgical versus
percutaneous) and antibiotics to cover E. coli, Bacteroides, Staphylococcus, Klebsiella, Proteus, and Candida albicans.
pancreatic insufficiency
Recurrent attacks may lead to exocrine pancreatic insufficiency more commonly than endocrine failure.
long term
low
chronic pancreatitis
Recurrent attacks of acute pancreatitis may lead to chronic scarring, and, if the aetiological factor is not treated, may
present with the classic characteristics of chronic pancreatitis: glucose intolerance, pancreatic insufficiency, and
calcifications.
long term
low
portal vein/splenic thrombosis
Ongoing pancreatic inflammation may cause irritation and inflammation of the portal vein and/or splenic vein, leading to
portal hypertension. Suspect splenic vein thrombosis in patients with recurrent pancreatitis, splenomegaly, and bleeding
from gastric varices.
long term
low
enteric fistulas
Resulting from inflammation surrounding the pancreas and adjacent duodenum or transverse colon.
long term
low
intestinal obstruction
Ileus may be frequently seen in pancreatitis, a result of dehydration, electrolyte abnormalities, or adjacent bowel
inflammation. Intestinal obstruction can be seen later in the course of the disease, when a pseudocyst or abscess causes a
mechanical compression of the bowel (generally duodenum or transverse colon). [
long term
low
multiorgan failure
The gut mucosa plays a central role in the development of multi-organ failure. Several descriptions about how the gut
modulates the inflammatory response by priming neutrophils and secreting cytokines can be found in the literature.
variable
medium
pancreatic ascites
variable
Consists of accumulated pancreatic fluid in the peritoneal cavity. It is due to chronic leakage of a pseudocyst, but some
cases may be due to duct disruption. Clinically manifested by weight loss and unresponsiveness of the ascites to diuretics.
Initial treatment involves hyper-alimentation and somatostatin. If no improvement is obtained in 2 to 3 weeks, endoscopic
retrograde cholangiopancreatography (ERCP) and surgery should be considered.
medium
pancreatic effusion
Secondary to pancreatic fistula draining into the chest. The diagnosis is based on thoracentesis with fluid rich in amylase
and a CT scan/retrograde pancreatogram that shows the fistula. Its treatment consists of drainage with a chest tube,
somatostatin, and total parenteral nutrition. If fistula persists, operative intervention with fistula resection or distal
pancreatectomy should be performed.
variable
medium
infected pancreatic necrosis
Infection is responsible for 80% of deaths. Gram-negative bacteria (Esterichia
coli, Pseudomonas, Klebsiella,Proteus, Enterobacter) are more common than gram-positive micro-organisms. Previous
studies describe a mortality rate of 50% to 80% in the absence of operative treatment and 10% to 40% among patients
who receive debridement.
variable
medium
acute lung injury/ARDS
variable
medium
variable
low
variable
low
variable
low
see our comprehensive coverage of Acute respiratory distress syndrome
The production and excretion of inflammatory mediators (such as cytokines, prostaglandins, and thromboxanes) during
pancreatitis may damage the alveolocapillary membrane, leading to destruction of pneumocytes and decrease in the
amount of surfactant. This leads to airway destruction, increase in superficial tension, and inadequate oxygenation.
Patients usually present with hypoxaemia, requiring higher levels of supplemental oxygen, with bilateral interstitial
infiltrates, PaO2:FiO2 ratio <300, and a normal pulmonary capillary wedge pressure. Patients may require mechanical
ventilation during the course of their disease.
disseminated intravascular coagulation
see our comprehensive coverage of Disseminated intravascular coagulation
Severe acute pancreatitis, especially if associated with necrosis, has been linked to liberation of cytokines and systemic
inflammatory response, with activation of the complement, coagulation, and fibrinolytic cascades, leading to a state of
coagulopathy and disseminated intravascular coagulation with elevated levels of split fibrin products and d-dimer with
low fibrinogen.
sepsis
see our comprehensive coverage of Sepsis
The gut mucosa plays a central role in the development of sepsis. Several descriptions about how the gut modulates the
inflammatory response by priming neutrophils and secreting cytokines can be found in the literature. Gram-negative
bacteria are the main cause of sepsis in patients with acute pancreatitis, and the gut mucosa is considered as the source of
such organisms. Therefore, it is important to maintain integrity of the anatomical barrier by providing enteral nutrition.
pseudocyst
Pseudocysts are encapsulated collections of fluid with high enzyme concentrations. The walls are formed by
inflammatory fibrosis of the peritoneal, mesenteric, and serosal membranes, which limits the spread of the pancreatic
fluid. Pseudocysts have no epithelial lining. Pseudocyst diagnosis should be suspected when a patient fails to respond
after 1 week of treatment or symptoms recur. Pain is the most common finding, followed by a palpable mass. CT scan is
the diagnostic study of choice. Pseudocysts can be complicated with infection, rupture (in 5%), and haemorrhage. The
principal indications for treatment are to improve symptoms and to prevent complications.
Expectant management is important in the first 6 to 12 weeks of existence of cysts that have arisen during an acute attack
of acute pancreatitis. The chance of spontaneous resolution is 40%. Thereafter, for cysts >5 cm in size, treatment is
usually recommended over conservative management.
Treatment options include excision of the cyst, external drainage (surgical or percutaneous), or internal drainage
(preferred method of treatment), which can be either a cystojejunostomy Roux-en-Y, cystogastrostomy, or
cystoduodenostomy.
gastrointestinal bleeding
variable
low
variable
low
see our comprehensive coverage of Assessment of upper GI bleed
From adjacent inflamed stomach or duodenum, ruptured pseudocyst, or peptic ulcer.
intra-peritoneal bleeding
From coeliac or splenic artery rupture or acute splenic vein thrombosis.
Prognosis
The majority of patients with acute pancreatitis will improve within 3 to 7 days of conservative management. The cause of pancreatitis should be
identified, and a plan to prevent recurrence should be initiated before the patient is discharged from hospital. In gallstone pancreatitis, a
cholecystectomy should be considered before discharge in mild cases and a few months after the discharge date in patients wit h severe symptoms.
In patients who are not candidates for surgery, endoscopic retrograde cholangiopancreatography (ERCP) must be considered.
Long-term prognosis is based on the aetiological factor and patient compliance to lifestyle modifications. Acute pancreatitis generally resolves
and leaves pancreatic function intact. May progress to chronic pancreatitis in the event of recurrent alcoholic intake, pancreas divisum, or cystic
fibrosis. The most commonly used prognostic scores are APACHE II, Ranson, Glasgow, Balthazar, and Atlanta.
Definition
A disorder of the exocrine pancreas, and is associated with acinar cell injury with local and systemic inflammatory responses. The inflammation
may range from mild oedema to peri-pancreatic necrosis.
Epidemiology
Acute pancreatitis is a potentially lethal disease that is increasing in incidence. Its mortality has improved as a result of a better understanding of
the natural history of the disease and improvement of critical care. Incidence varies from 4.5 to 79.8 per 100,000 per year in different countries.
This variation is due to different diagnostic criteria, geographical factors, and changes over time. A 10-fold increase in its incidence from 1960 to
1980, with a mortality rate from 1% to 9%, was noted. Approximately 210,000 patients are admitted to hospitals each year with acute
pancreatitis, with approximately 20% meeting criteria for severe pancreatitis alone in the US. The mortality rate is influenced by the severity of
the disease, and several prognostic factors have been investigated and described. In contrast to the milder form of the disea se, which has a
mortality rate of 1%, the mortality associated with severe acute pancreatitis is 10% with sterile and 25% with infected pancreatic
necrosis. Gallstone pancreatitis is more common in white women >60 years of age, especially among patients with microlithiasis. Alcoholic
pancreatitis is seen more frequently in men.
Aetiology
Several aetiological factors have been described for acute pancreatitis, but in 10% to 20% of cases an aetiological factor cannot be identified.
These cases are then considered idiopathic. The presence of microlithiasis or biliary sludge accounts for 80% of idiopathic pancreatitis. In the US,
gallstones followed by alcohol intake are responsible for 80% to 90% of cases of acute pancreatitis. The most common cause worldwide is
alcohol consumption.
Other causes include:
Hypertriglyceridaemia
Hypercalcaemia
Pancreatic malignancy
Post-endoscopic retrograde cholangiopancreatography (ERCP) (2% to 3%)
Trauma
Infections (mumps, mycoplasma, Epstein-Barr virus, Ascaris lumbricoides, HIV-related co-infections)
Drugs (sulphonamides, azathioprine, thiazides, furosemide, oestrogens, valproic acid)
Autoimmune conditions (collagen vascular diseases)
Pancreas divisum
Sphincter of Oddi dysfunction
Heredity.
Pathophysiology
The exact mechanism by which pancreatitis occurs is unknown. Several pathophysiological processes have been described that ultimately lead to
intra-pancreatic zymogen activation and auto-digestion with destruction of the acinar cell. Pancreatic ductal obstruction and hypersecretion have
been mentioned as factors that contribute to the initiation of the inflammatory process.
Intra-acinar activation of trypsinogen still plays a central role in the pathogenesis of acute pancreatitis, resulting in activation of proteases that
ultimately causes cell damage. Some investigations have led to newer hypotheses, including ischaemia/reperfusion injury and enzymatic colocalisation. [
Ethanol-induced pancreatitis has different pathophysiological mechanisms. Studies have described that ethanol is a direct toxic insult to the acinar
cell, causing inflammation and membrane destruction. Other mechanisms include sphincter of Oddi dysfunction, induction of
hypertriglyceridaemia, or formation of free oxygen radicals. Some studies have demonstrated that ethanol causes an increase in ductal pressures
secondary to protein deposition within the pancreatic duct, favouring retrograde flow and intra-pancreatic enzymatic activation.
Classification
Balthazar classification
This is a classification based on the extent of pancreatic inflammation and the presence or absence of fluid collections or gas suggestive of
necrosis on CT with IV contrast.
A: Normal
B: Focal or diffuse gland enlargement; small intra-pancreatic fluid collection
C: Any of the above plus peri-pancreatic inflammatory changes and <30% gland necrosis
D: Any of the above plus single extra-pancreatic fluid collection and 30% to 50% gland necrosis
E: Any of the above plus extensive extra-pancreatic fluid collection, pancreatic abscess, and >50% gland necrosis.
General pathological classification
Surgical textbooks often distinguish between oedematous and haemorrhagic pancreatitis, based on pathological/histological features:
Oedematous pancreatitis: pancreatic parenchyma and surrounding retroperitoneal structures are engorged with interstitial fluid and
infiltration of inflammatory cells
Haemorrhagic pancreatitis: bleeding into the parenchyma and surrounding retroperitoneal structures with extensive pancreatic
necrosis.
Secondary prevention
The most important aspect of prevention is patient education. Eating a balanced, low-fat diet, maintaining adequate triacylglyceride control, and
decreasing the amount of alcohol intake are a few dietary and behavioural measures that may decrease the incidence of acute pancreatitis.
Effectively, addressing gallstone disease by any means available (such as cholecystectomy, endoscopic retrograde cholangiopancreatography
[ERCP], ursodeoxycholic acid), may decrease the ductal obstruction risk and hence the risk of pancreatitis. Other risk factors may be controlled
through patient education and medicine dose adjustments. Probiotics, antioxidants and immune nutrition have no role in the pr evention of acute
pancreatitis. Several studies have addressed the use of pharmacological treatment (somatostatin, gabexate, glycerine trinitrate, nafamostat
mesylate), adequate patient selection, and stent placements during ERCP to prevent pancreatic injury. The use of somatostatin has been linked to
a better protection against ERCP-induced pancreatitis than gabexate in some studies, but two meta-analyses yielded different conclusions. Stents
are an option for endoscopists with experience in the field, but the manipulation to obtain biliary access (rather than patient characteristics or
endoscopist experience) is the main factor in the development of ERCP-induced pancreatitis.
The use of a guidewire bile duct cannulation technique during ERCP has been shown to decrease the incidence of post-ERCP pancreatitis in
comparison with the standard contrast injection cannulation.
Those with idiopathic chronic pancreatitis, recurrent acute pancreatitis, or a family history of pancreatitis should be considered for genetic testing,
especially in the setting of pancreatic cancer. The clinical relevance and the therapeutic consequences of the gene mutations l eading to
pancreatitis are still controversial, and genetic testing is recommended when a patient with idiopathic pancreatitis is u nder 25 years of age at
diagnosis or when one or more family members have either pancreatitis or pancreatic cancer. Genetic analysis of asymptomatic family members
should only be offered after adequate genetic counselling, and antenatal diagnosis is not recommended.
Diagnostic tests
1st tests to order
Test
Result
serum amylase
Normal range: 35 to 118 units/L. Amylase levels should be checked in every patient with severe abdominal pain. It has a
sensitivity of 75% to 92% and a specificity of 20% to 60% with a positive predictive value approaching 100%.The sensitivity
of the test is limited by hypertriglyceridaemia and alcoholism, and the specificity by inflammatory intra-abdominal processes
and parotid and submandibular salivary gland inflammation. Levels start rising over the first 2 to 12 hours, peak at 48 hours,
and return to normal within 3 to 5 days. Tends to be higher in patients with gallstone pancreatitis than in alcoholic pancreatitis.
3 times the upper limit of
the normal range
can be elevated if
serum lipase
Lipase is more sensitive (50% to 99%) and specific (86% to 100%) than amylase; however, the utility is limited in acute
amylase normal
pancreatitis due to discrepancies in measurement method, patient selection, and cut-off points. Hence, the determination of
lipase is not necessary in a patient with a clinical diagnosis of acute pancreatitis and 3 times the normal value of serum amylase.
Its use can be helpful in patients with a clinical presentation suggestive of pancreatitis and normal amylase. Due to additional
cost and lack of benefit in the majority of patients, utilising serum lipase in conjunction with serum amylase is considered
inappropriate. Levels start rising 4 to 8 hours after the onset of pain, peak at 24 hours, and last for 8 to 14 days. Patient s with
alcoholic pancreatitis have higher levels of lipase than those with gallstone pancreatitis.
ratio of serum lipase:amylase
Low sensitivity. Favours alcoholic pancreatitis.
>5
urinary amylase
>5000 international
units/24 hours
AST/ALT
if >3 times the upper
normal limit, predicts
gallstone disease as
aetiology in 95% of cases
Low sensitivity and specificity for pancreatitis.
FBC and differential
Mild leukocytosis with left shift and elevated haematocrit as a result of dehydration or low haematocrit as a result of
haemorrhage can be seen. The development of haemoconcentration has been associated to predict the risk of developing
necrotising pancreatitis.
leukocytosis
haematocrit
Indicator of severity and prognosis.
if >44% on admission, is
a predictor of pancreatic
necrosis
arterial blood gas
It is important to monitor the arterial oxygenation, since patients may be hypoxaemic, requiring supplemental oxygen. During
the initial management, consider arterial blood gases every 12 hours for the first 3 days to assess both oxygenation and acidbase status.
hypoxaemia and
disturbances in acid-base
balance
abdominal plain film
Abnormal in two-thirds of patients.
may find a sentinel loop
(isolated dilatation of a
segment of gut) adjacent
to the pancreas, gas
distending the right colon
that abruptly stops in the
mid- or left transverse
colon (cut-off sign), or
calcifications
CXR
may show atelectasis and
pleural effusion
(especially in the left
side)
ultrasound
Sensitivity in detecting pancreatitis is 62% to 95%. Is non-invasive, easy to perform at the bedside, and inexpensive. Limited by
obesity, bowel gas, and is operator-dependent. Useful when biliary causes are suspected. The use of endoscopic ultrasound
allows tissue diagnosis and has replaced endoscopic retrograde cholangiopancreatography (ERCP).
may show pancreatic
inflammation, peripancreatic stranding,
calcifications, or fluid
collections
Tests to consider
Test
Result
C-reactive protein (CRP)
Indicator of severity. Useful after first 36 to 48 hours.
if >200 units/L, is
associated with
pancreatic necrosis
abdominal CT scan
CT scan with IV contrast is the most sensitive and specific study for confirming diagnosis of pancreatitis. Has a sensitivity of
90% and specificity of 100%. It is used when clinical and biochemical findings are equivocal, Ranson score of >3 or APACHE
II score of >8 to detect and stage complications, and when patients have persisting organ failure, show signs of sepsis, or
present with clinical deterioration or do not improve after 48 to 72 hours of treatment. Signs of complicated pancreatitis ar e
usually seen 3 days after the onset of abdominal pain.
findings may include
diffuse or segmental
enlargement of the
pancreas with irregular
contour and obliteration
of the peri-pancreatic fat,
necrosis, or pseudocysts
magnetic resonance cholangiopancreatography (MRCP)
MRCP is superior to CT scanning for staging acute pancreatitis and detecting complications. It also has the advantage of not
requiring IV contrast.
findings may include
stones, diffuse or
segmental enlargement
of the pancreas with
irregular contour and
obliteration of the peripancreatic fat, necrosis,
or pseudocysts
endoscopic retrograde cholangiopancreatography (ERCP)
ERCP has a limited use as a diagnostic tool in acute attacks of acute pancreatitis and has been mostly replaced by ultrasound
and MRCP. Indications are preoperative evaluation to verify duct condition in patients with traumatic pancreatitis, in patients
with severe pancreatitis and suspected biliary obstruction (allows sphincterotomy, stone removal, stent placement, tissue
diagnosis) that do not improve after 24 hours of conservative management, and as work-up for idiopathic pancreatitis. Studies
have shown a reduction of morbidity and mortality in patients with early ERCP (<24 hours) and biliary disease.
identifies stones and
allows their retrieval
during the same
intervention; can identify
duct filling defects and
strictures
fine needle aspiration
If sepsis is suspected in patients with pancreatic necrosis, a percutaneous needle aspiration can be performed to rule out
bacterial colonisation.
identification of
causative organism if
bacterial colonisation
Emerging tests
Test
Result
elevated
urinary trypsinogen-2
Sensitivity of 94% and specificity of 95%. Now considered a better serological screening test than
amylase.
serum IL-6
Sensitivity of 81% to 88% and specificity of 75% to 85% for prediction of severe acute
pancreatitis.
serum IL-8
Sensitivity of 65% to 70% and specificity of 69% to 91% for prediction of severe acute
elevated
elevated
pancreatitis.
Differential diagnosis
Condition
Peptic ulcer disease
Perforated viscus
Differentiating signs/symptoms Differentiating tests
Oesophageal spasm
Intestinal obstruction
Abdominal aorta
aneurysm
Longstanding
epigastric pain, which
does not generally
radiate to the back;
reflux; heartburn; and
anorexia. Identifiable
causes such as nonsteroidal antiinflammatory drug
(NSAID)
use, Helicobacter
pylori, ZollingerEllison's syndrome
may be present.
Will present with
acute abdomen,
peritoneal signs,
tachycardia, and
sepsis. Generally the
abdomen is rigid and
tender in all 4
quadrants, with
guarding.
Dysphagia,
odynophagia, weight
loss, history of
retrosternal pain.
Physical examination
may be normal.
History of abdominal
surgeries (especially
colon resection,
caesarean sections,
and aortic
procedures).
May improve with proton pump inhibitors, lifestyle modifications, and H pylori treatment.
Normal lipase and amylase.
Tonometry may show evidence of reflux.
Laboratory evaluation will show normal values of amylase and lipase.
Endoscopic evaluation will be diagnostic after visualising erosions, erythema, or ulcers,
and allows biopsies to be performed.
Normal lipase. May have elevated amylase (usually less marked than that seen in acute
pancreatitis).
Plain x-rays show sub-diaphragmatic air.
A swallow study may demonstrate a contracted and abnormal-appearing oesophagus with
increased pressures on oesophageal manometry.
Normal lipase and amylase.
Acute abdominal series will show ground glass appearance, air-fluid levels, distended
bowel loops, absence of distal gas, pneumatosis.
An abdomen/pelvic CT scan may be more diagnostic, and will show point of transition and
potentially identify aetiology (such as volvulus, hernias, intussusception, masses).
Hernias in the
physical examination.
Presents with
abdominal distension
(depends on the level
of obstruction),
tympanism, decreased
bowel sounds,
anorexia, emesis
(quality depends on
location of
obstruction),
obstipation, or
constipation.
Cardiovascular risk
factors:
hyperlipidaemia,
tobacco, diabetes
High index of suspicion is necessary to make a rapid diagnosis and improve outcomes. In
stable patients, where history and physical examination are equivocal, a CT angiography
may be useful as a rapid way to make diagnosis.
mellitus,
homocystinaemia.
Cholangitis
Choledocholithiasis
Cholecystitis
Viral gastroenteritis
If too unstable for radiographic evaluation, patients usually go directly to surgery.
Acute tearing-like
abdominal pain,
pulsating abdominal
mass, hypotension,
and mottled lower
extremities with
decreased pulses and
abdominal distension.
Charcot's triad
(jaundice, right upper
quadrant pain, and
fever) present in 70%
of patients, altered
mental status, and
hypotension indicate
biliary sepsis, usually
caused by gramnegative bacteria.
Several clinical findings are present more frequently in cholangitis, such as fever (95%),
right upper quadrant pain (90%), and jaundice (80%).
Normal lipase and amylase.
Blood cultures are usually positive, especially during episodes of chills, with Escherichia
coli andKlebsiella as the most common micro-organisms isolated from infected bile.
Patient may have a
history of gallstones,
peri-ampullary
neoplasms, or biliary
manipulation such as
endoscopic retrograde
cholangiopancreatogr
aphy (ERCP).
Severe right upper
quadrant pain of
sudden onset,
jaundice, acholia,
choluria, and hx of
cholelithiasis. May
occlude the common
bile duct and cause
pancreatitis.
Pain is generally
triggered after a fatty
meal and localised in
the right upper
quadrant. More
common in
overweight females
between 40 and 50
years of age.
Normal lipase and amylase.
Ultrasound will show gallstones, stones within the common bile duct with extra-hepatic
and/or intra-hepatic duct dilatation.
Chemistry will show biochemical obstruction, with increased levels of total and direct
bilirubin, alkaline phosphatase, gamma-GT, and a slight increase in ALT/AST but normal
levels of pancreatic enzymes (especially lipase).
Normal lipase and amylase.
A right upper quadrant ultrasound will show thickened gallbladder wall, stones with
acoustic shadows, biliary sludge, peri-cholecystic fluid, and sonographic Murphy's sign,
and allows evaluation of the duct system. Can suggest pancreatic head inflammation. May
show mild leukocytosis and a very mild elevation of liver enzymes.
A hepatobiliary iminodiacetic acid (HIDA) scan is diagnostic when there is no filling of the
gallbladder or with delayed emptying of the radiotracer.
Anorexia, nausea, and
vomiting may be
present. May show a
positive Murphy's
sign and low-grade
fever.
Generalised nonspecific abdominal
pain, anorexia,
nausea, emesis,
diarrhoea, and
dehydration.
Is usually a self-
Normal lipase and amylase.
Important to obtain serum electrolytes and an FBC.
Hypokalaemia and alkalosis may be seen secondary to diarrhoea, vomiting, and
dehydration.
Stool examination for microscopy, culture, osmolality, ova, parasites, Clostridium
limiting viral infection
but if fever is
documented, bacterial
and invasive
organisms should be
suspected.
Hepatitis
Mesenteric ischaemia
Myocardial infarction
difficile toxin, and white blood cells may help in identifying the causative factor.
Consider in travellers
and
immunosuppressed
patients.
Consider osmotic and
secretory diarrhoea
from hx.
Jaundice, right upper
quadrant pain,
anorexia, and general
malaise. Choluria and
acholia may be seen.
Normal lipase and amylase.
Elevated liver function tests are characteristic. AST/ALT in the range of the 1000 units/L is
not rare. Serological titres can make diagnosis of aetiological cause.
Radiographic studies not important for its diagnosis.
Examination:
tenderness to
palpation over the
right upper quadrant
and enlarged liver.
Patients are usually
older, may have a
history of atrial
fibrillation and risk
factors for peripheral
vascular disease.
High index of suspicion of diagnosis is necessary. Angiography and CT scan may be useful
in diagnosis as well as lactic acid levels.
Normal lipase. May have elevated amylase (usually less marked than that seen in acute
pancreatitis).
Hypercoagulable
states may lead to
bowel necrosis. Pain
is usually out of
proportion to the
finding of the physical
examination.
Pain is usually
retrosternal with
radiation to jaw, neck,
and left upper
extremity. Associated
with shortness of
breath, nausea,
vomiting, and
diaphoresis.
Cardiovascular risk
factors in the history.
Elevated cardiac enzymes (creatine kinase or creatine phosphokinase, troponins), ECG
changes, and clinical scenario make the diagnosis.
Normal lipase and amylase.
Cardiac catheterisation, perfusion scans, and echocardiograms are useful during the workup of cardiac ischaemia.
Step-by-step diagnostic approach
The diagnosis of pancreatitis is always one of exclusion, so it must be included with any complaint of severe abdominal pain. History and
examination can be indicative of acute pancreatitis; however, the keys for diagnosis are elevated levels of amylase and lipase, which need to be at
least 3 times their normal value.
History
A detailed history is imperative to narrow the large number of differentials of abdominal pain. Metabolic, nutritional, and procedural aetiologies
of pancreatitis should be considered during history-taking. A detailed family history is important to rule out collagen vascular diseases, cancer, or
hereditary pancreatitis. Any medicine and indications for their use should be reviewed, since many medications can have pancreatic injury as an
adverse effect. Age and sex are important demographic variables, since the 2 most common causes of acute pancreatitis differ. Gallstone
pancreatitis is seen most commonly in patients with gallbladder disease - the 5 "Fs": fat, forty, female, fertile, and family history. Alcoholic
pancreatitis is seen more frequently in men, generally younger than those with gallstone pancreatitis. Patients usually manifest after an average of
4 to 8 years of alcohol intake, and bingeing behaviour increases the risk of acute pancreatitis.
Patients may present with agitation and confusion, and in severe distress. They may give a history of anorexia, nausea, and vomiting with poor
oral intake. The most common symptom is severe mid-epigastric pain that radiates to the back (band distribution), worsens with movement, and
is alleviated when assuming the fetal position (bent over, with spine, hips, and knees flexed). Gallstone pancreatitis may be more acute in onset
than alcoholic pancreatitis, which may be preceded with a few days of mild epigastric discomfort.
Physical examination
Signs of hypovolaemia (decreased skin turgor, dry mucous membranes, hypotension) are usually found. Patients may appear diaphoretic,
tachycardic, and tachypnoeic. Fever may indicate a complicated pancreatitis or may simply represent cytokine release as part of the inflammatory
process. Decreased breath sounds may be detected if there is a pleural effusion (more common on the left side); this is seen in up to 50% of
patients with acute pancreatitis. The abdominal examination may reveal a tender and distended abdomen with diminished bowel sounds (if an
ileus has developed) and voluntary guarding to palpation of the upper abdomen. There may be a mild rigidity without re-bound tenderness.
Clinical signs of hypocalcaemia are rare but may be evident, such as facial muscle spasm when facial nerve is tapped (Chvostek's sign) and
carpopedal spasm when blood pressure cuff is applied (Trousseau's sign). Complicated haemorrhagic pancreatitis may exhibit ecchymotic
discoloration of several areas, including the peri-umbilical skin (Cullen's sign), over both flanks (Grey-Turner's sign) or over the inguinal
ligament (Fox's sign), and may be seen as soon as presentation or 24 to 48 hours after the onset.
Laboratory work-up
Any patient with an acute abdomen should have an FBC with differential and a blood chemistry including renal, liver, and pancreatic function
tests. Mild leukocytosis with left shift and elevated haematocrit as a result of dehydration or low haematocrit as a result of haemorrhage can be
seen. The development of haemoconcentration is associated with an increased risk of developing necrotising pancreatitis. As a result of
dehydration there may be some degree of pre-renal azotaemia, manifested by elevated creatinine and urea. In the absence of choledocholithiasis,
liver function tests are usually normal, but a slight increase in alkaline phosphatase and bilirubin may be seen. The key for diagnosis is elevated
levels of amylase or lipase; amylase levels more than 3 times the normal value are highly specific for acute pancreatitis. The degree of pancreatic
inflammation is not directly correlated with the amylase or lipase absolute value. Due to additional cost and lack of benefit in the majority of
patients, utilising serum lipase as a first test in conjunction with serum amylase is considered inappropriate. Measuring lipase can be helpful in
patients with a clinical presentation suggestive of pancreatitis in whom the amylase levels were normal.
It is important to monitor arterial oxygenation, since patients may be hypoxaemic, requiring supplemental oxygen. During initial management,
arterial blood gases should be considered every 12 hours for the first 3 days to assess both oxygenation and acid-base status.
C-reactive protein (CRP) is performed subsequently and is an indicator of severity; useful after the first 36 to 48 hours. [
If sepsis is suspected in patients with pancreatic necrosis, a percutaneous needle aspiration can be performed to rule out ba cterial colonisation.
Imaging
Radiographic studies are not used for diagnosis of acute pancreatitis, but may determine possible causative factors and exclu de other diagnoses.
A CXR may show pleural effusion and basal atelectasis, and a sentinel loop (isolated dilatation of a segment of gut) may be seen in a KUB. Plain
abdominal x-ray may reveal a sentinel loop adjacent to the pancreas, gas distending the right colon that abruptly stops in the mid- or left
transverse colon (cut-off sign), or calcifications.
Magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), trans-abdominal ultrasound,
and endoscopic ultrasound are usually indicated in patients with elevated liver function tests suggestive of bile duct obstruction, to exclude
strictures, neoplasms, or stones.
Ultrasound is considered to be the preferred initial study in suspected gallstone pancreatitis as it is inexpensive, easy to perform at the bedside,
and allows examination of the gallbladder and bile duct system. Its sensitivity in detecting pancreatitis is 62% to 95%. It is limited by obesity and
bowel gas, and is operator-dependent. The use of endoscopic ultrasound allows tissue diagnosis and has replaced ERCP.
The advantage of the ERCP is that it has the added benefit of treating certain aetiological conditions (e.g., by stone removal, stent placement, or
sphincterotomy), but it has been largely superseded as a diagnostic modality by MRCP and ultrasound.
MRCP is generally used in patients with renal insufficiency, in whom the use of CT with IV contrast is discouraged. It is superior to CT scanning
for staging acute pancreatitis and detecting complications.
Patients who show signs of systemic inflammatory response or sepsis, or who do not improve, should have a CT scan to rule out peri-pancreatic
collections, necrosis, and abscess. Areas of non-perfusion indicate infected pancreatic necrosis.
Emerging tests
Urinary trypsinogen-2 is now considered a better serological screening test than amylase but is not yet used clinically; sensitivity of 94% and
specificity of 95%.Interleukins IL-6 and IL-8 are inflammatory mediators that have been recently described as predictive serum markers for
development of severe acute pancreatitis.
Treatment Options
Patient Group
Tx Line
all patients
1st
Treatment
initial resuscitation
IV hydration with crystalloids is essential, and an effort to keep urinary output above 30 mL/hour is
necessary to avoid potential kidney damage.
Pain control is important when pain is present, and the most commonly used pharmacological drugs
are the opioids. Pethidine, fentanyl, or morphine can be used, either for breakthrough pain or as
patient-controlled analgesia. Monitor respiratory and CNS depression. Meperidine is considered
superior to morphine because it does not increase sphincter of Oddi pressures.
Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), can be used in patients with intact renal
function.
Ondansetron is the most commonly used antiemetic.
Primary Options
crystalloids : 20-40 mL/kg intravenously
and
pethidine : 25-100 mg subcutaneously/intramuscularly every 4 hours when required
and
ondansetron : 2-4 mg intravenously every 4-6 hours when required
Secondary Options
crystalloids : 20-40 mL/kg intravenously
-- AND -morphine sulphate : 1-5 mg intravenously every 4 hours when required
or
fentanyl : 50-100 micrograms intravenously, followed by 50 micrograms every 1-2 hours when
required
or
ketorolac : 10 mg intravenously/intramuscularly initially, followed by 10-30 mg every 4-6 hours when
required for 2 days, maximum 90 mg/day
-- AND -ondansetron : 2-4 mg intravenously every 4-6 hours when required
plus
nutritional support
Initially patients should be kept nothing by mouth. Oral intake is re-started when there is notable
clinical improvement, nausea and abdominal pain has resolved, and amylase levels have dropped to
normal. Premature resumption of diet may result in exacerbation of the disease. In patients who are
expected to have a prolonged nothing by mouth status, a trans-pyloric nasojejunostomy feeding tube
should be placed, allowing enteral nutrition without stimulating the pancreas.
adjunct
The regimen should provide 25 to 35 kcal/kg/day energy, 1.2 to 1.5 g/kg/day protein, 3 to 6 g/kg/day
carbohydrates, and 2 g/kg/day lipids.
Parenteral nutrition should be reserved for patients who do not tolerate enteral feeding or in whom an
adequate infusion can not be reached within 2 to 4 days.
calcium replacement therapy
In severe cases of pancreatitis, hypocalcaemia should be identified and treated accordingly. Calcium
should be titrated to normal serum ionic calcium levels. Calcium chloride is used less frequently, since
it must be given by a central line.
Primary Options
calcium gluconate : 2-15 g/day intravenously given as infusion or in divided doses, or see local
protocol for dosing guidelines; 500-1000 mg orally four times daily
More
adjunct
magnesium replacement therapy
Magnesium should be replaced if low levels are identified, commonly seen in alcoholic patients. Renal
function (creatinine) should be checked before magnesium administration. It may need daily
replacement.
Primary Options
magnesium sulphate : 1-2 g intravenously every 6 hours on first day, followed by 60 mg/kg/day as an
infusion, or see local specialist protocol for dosing guidelines
adjunct
insulin
adjunct
Blood glucose control and insulin administration to keep glucose <8.33 mmol/L (<150 mg/dL) has
been associated with reductions in morbidity and mortality in critically ill patients. In less severe cases,
regular insulin sliding scales can be used.
See local specialist protocol for dosing guidelines.
antibiotic therapy
Decontamination of the gut, where antibiotics are given to decrease the intra-luminal bacterial count,
has not been proven effective in decreasing the incidence of pancreatic sepsis, but a meta-analysis of 8
randomised controlled trials found reduction in mortality of patients with severe acute pancreatitis
when prophylactic IV antibiotics with pancreatic penetrance were administered.
It is important, however, to limit the use of antibiotics for this subset of patients to avoid fungal
superinfection.
Imipenem is the antibiotic most studied because of its pancreatic penetration.
In patients with necrotising pancreatitis, antibiotic use should be restricted to patients in whom there
are signs, symptoms, and laboratory tests indicating that infection is present (fever, leukocytosis, organ
failure, and positive cultures).
There is no consensus in the literature to date of how long patients need to be on antibiotics. However,
clinical improvement, with resolution of organ failure and improvement of systemic markers of
inflammation, can be considered as reasonable indicators that antimicrobials can be stopped.
Primary Options
cilastatin+imipenem : 500-1000 mg intravenously every 6 hours
More
Secondary Options
ceftriaxone : 1-2 g intravenously every 12 hours
OR
ampicillin : 500 mg intravenously every 6 hours
OR
ciprofloxacin : 400 mg intravenously every 12 hours
with gallstones: surgical candidates
adjunct
cholecystectomy
In patients in whom the diagnosis of acute gallstone pancreatitis is obtained by ultrasound, a
cholecystectomy with common bile duct exploration (either surgical or postoperatively with
endoscopic retrograde cholangiopancreatography [ERCP]) should be performed during the same
hospitalisation for the acute attack, soon after the attack resolves. A longer delay, even a few weeks, is
associated with a high recurrence (80%).
When a laparotomy is performed for diagnosis and mild to moderate pancreatitis is found,
cholecystectomy with intra-operative cholangiogram should be performed but the pancreas should be
left alone. For severe pancreatitis, the lesser sac should be opened and the pancreas fully inspected.
Some surgeons place drains and irrigating catheter around the pancreas.
with gallstones: non-surgical
candidates
adjunct
endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy
with alcohol-induced disease
plus
In patients who are not candidates for surgery because of comorbidities with a high ASA index, sepsis,
or severe disease, ERCP must be considered.
The use of ERCP and sphincterotomy, performed within 72 hours after the onset of the disease, has
been shown to decrease the incidence of concomitant biliary sepsis and systemic complications in
severe but not in mild forms of pancreatitis. Contradictory results have been obtained for mortality
rates.
A meta-analysis of 4 randomised controlled trials of endoscopic sphincterotomy in patients with severe
acute pancreatitis showed that sphincterotomy reduced complications and mortality. The role of ERCP
in patients without biliary obstruction or cholangitis is unknown. Cholecystectomy has to be
considered after discharge.
benzodiazepines
Patients with alcohol-induced pancreatitis may need alcohol-withdrawal prophylaxis. Lorazepam is
generally used in this group of patients.
Primary Options
lorazepam : 1-2 mg orally/intravenously/intramuscularly every 6-8 hours
plus
vitamin and mineral replacement
The objective of replacement of thiamine in chronic alcoholism is to replenish the stores in patients.
The treatment has to be continued until the patient can return to eating a well-balanced meal during
hospitalisation.
Other water-soluble vitamins that are supplemented during hospital or emergency department course
include folic acid and cyanocobalamin. Cyanocobalamin can be given orally except in states when
absorption is impaired.
Primary Options
thiamine : 100 mg orally/intravenously/intramuscularly once daily
and
folic acid : 1 mg orally/intramuscularly once daily
and
cyanocobalamin : 1000 micrograms intramuscularly/orally once daily for 1-2 weeks, followed by 1000
micrograms once every 1-3 months
with infected pancreatic necrosis
plus
necrosectomy
If sepsis is considered, a percutaneous needle aspiration can be performed to rule out bacterial
colonisation. Necrosectomy involves resection of the necrotic pancreatic tissue and placement of
irrigating drains within the debrided spaces, allowing postoperative lavage. The only criteria for
debridement are multi-organ failure (with or without infection) with CT evidence of necrotic tissue.
Outcomes are better if surgery is delayed until the necrosis has organised, usually about 4 weeks after
the onset of abdominal pain. Allowing organisation of the inflammation makes the dissection through
planes easier.
Treatment approach
The main goal of initial treatment is to prevent complications of severe pancreatitis by reducing pancreatic secretory stimuli and correction of
fluid and electrolyte abnormalities. Initially, the patients should be fluid resuscitated and kept nothing by mouth with bowel rest when nausea,
vomiting, and abdominal pain are an issue.
At diagnosis supportive care continues until pain is resolved and diet re-started. The majority of patients will improve within 3 to 7 days of
conservative management. Patients with organ failure or with poor prognostic signs (Glasgow score >3, APACHE score >8, and Ra nson score
>3) should be admitted to the intensive care unit.
Initial resuscitation
Resuscitation with IV fluids, analgesics, and antiemetics are the initial treatments even before diagnosis is made.
IV hydration with crystalloids is essential, and an effort to keep urinary output above 30 mL/hour is necessary to avoid potential kidney damage.
The patient should be catheterised to monitor urinary output in severe cases of acute pancreatitis. The adequacy of fluid replacement is the single
most important aspect of the medical management. In haemorrhagic pancreatitis, blood transfusion may be necessary.
Pain control is important when pain is present, and the most commonly used pharmacological drugs are opioids. Pethidine, fentanyl, or morphine
can be used, either for breakthrough pain or as patient-controlled analgesia (PCA). Ketorolac, a non-steroidal anti-inflammatory drug (NSAID),
can be used in patients with intact renal function.
It is important to monitor the arterial oxygenation, since patients may be hypoxaemic, requiring supplemental oxygen. During the initial
management, consider arterial blood gases every 12 hours for the first 3 days to assess both oxygenation and acid-base status.
Severe pancreatitis
In severe cases of pancreatitis, hypocalcaemia should be identified and treated accordingly. Treatment of this electrolyte imbalance is important,
since hypocalcaemia may lead to cardiac dysrhythmias. Magnesium should be replaced if low levels are identified, commonly seen in alcoholic
patients.
Blood glucose control and insulin administration to keep glucose <8.33 mmol/L (<150 mg/dL) has been associated with reductions in morbidity
and mortality in critically ill patients. Insulin sliding scales, insulin drips, or long-acting insulin should be used in patients with hyperglycaemia
that is difficult to treat.
The use of antibiotics is not a routine practice, and controversial results have been obtained in recent studies. However, some studies have shown
some benefit in cases of severe necrotising pancreatitis. The main indication for necrosectomy is infection in severe necrotising pancreatitis.
Nutrition
A period of nothing by mouth is required initially, especially during the first 24 to 48 hours after the onset of pancreatitis (the phase of
resuscitation and control of nausea and pain). This reduces exocrine stimulation by cholecystokinin and secretin, and reduces the risk of
aspiration if a dynamic ileus is present. Oral intake is re-started when there is notable clinical improvement, nausea and abdominal pain has
resolved, and amylase levels have dropped to normal. Premature resumption of diet may result in exacerbation of the disease. In patients who are
expected to have a prolonged nothing by mouth status, a trans-pyloric nasojejunostomy feeding tube should be placed beyond the ampulla of
Vater. This allows enteral nutrition without stimulating the pancreas. Parenteral nutrition should be reserved for patients who do not tolerate
enteral feeding or in whom an adequate infusion cannot be reached within 2 to 4 days. When compared with parenteral nutrition, enteral feeds are
associated with better outcomes, less mortality, and better blood glucose control. They also protect the gut barrier by preventing intestinal
atrophy, leading to less sepsis and fewer infectious complications. The recommended nutrient requirements in severe acute pancreatitis are as
follows: energy 25 to 35 kcal/kg/day, protein 1.2 to 1.5 g/kg/day, carbohydrates 3 to 6 g/kg/day, and lipids 2 g/kg/day.
Alcohol-induced pancreatitis
Patients with alcohol-induced pancreatitis may need alcohol-withdrawal prophylaxis. Lorazepam, thiamine, folic acid, and multi-vitamins are
generally used in this group of patients.
Gallstone pancreatitis
In patients in whom the diagnosis of acute gallstone pancreatitis is obtained by ultrasound, imaging of the common bile duct is required. If the
presence of stones in the common bile duct is confirmed, a cholecystectomy with common bile duct exploration (either surgical or
postoperatively with endoscopic retrograde cholangiopancreatography [ERCP]) should be performed during the same hospitalisation in mild to
moderate disease soon after the attack resolves. A longer delay, even of a few weeks, is associated with a high recurrence (80%).
If the pancreatitis is severe, some allow a few months for the inflammation to completely resolve before performing a cholecystectomy.
In patients who are not candidates for surgery because of comorbidities with a high American Association of Anesthesiology (ASA) index,
sepsis, or severe disease, ERCP must be considered. Urgent ERCP is indicated in patients with biliary sepsis and obstructive jaundice that show
no improvement in 48 hours after the onset of the attack. ERCP is a diagnostic and therapeutic intervention. It allows defining of the biliary
system anatomy, to remove stones causing jaundice, sepsis, and pancreatitis, as well as placement of stents for strictures or pancreatic duct leaks
(secondary to pancreatitis or trauma), and permits facilitation of biliary drainage by performing of sphincterotomy.
Pancreatitis found on laparotomy
When a laparotomy is performed for diagnosis and mild to moderate pancreatitis is found, cholecystectomy with intra -operative cholangiogram
should be performed but the pancreas should be left alone. For severe pancreatitis, the lesser sac should be opened and the pancreas fully
inspected. Some surgeons place drains and irrigating catheter around the pancreas.
Step by step
Monitoring
Long-term monitoring is not necessary. Patients usually resolve after their acute attack. If they modify their risk factors, another episode may not
recur later in life. Lipids should be monitored in those with hypertriglyceridaemia.
Patient Instructions
Before discharge from hospital after an acute attack of acute pancreatitis, patients should be advised to modify lifestyle risk factors. For example,
alcoholic patients need to stop drinking, especially bingeing behaviour, modify diet in order to control hypertriglyceridaemia, and use lipidlowering medicines such as statins or niacin. Patients taking medicines (e.g., furosemide, didanosine, oestrogens) should be educated about the
adverse effects and how to recognise an acute attack of pancreatitis.
Patients should be advised to eat small, low-fat meals of carbohydrates and proteins, with a gradual increase in quantity over a period of 3 to 6
days as tolerated.
Complications
Complicationhide all
Timeframe Likelihood
acute renal failure
short term
high
short term
medium
see our comprehensive coverage of Acute renal failure
Seen in patients with severe acute pancreatitis. May be caused by circulating toxins or rhabdomyolysis. Hypovolaemia
and inflammatory mediators. Acute renal failure is a complication with poor outcome.
necrotising pancreatitis
Secondary to inadequate fluid resuscitation, vasoactive and toxic substances (phospholipases, endotoxins, activated
trypsin, complement activation, thromboxane, and elastase).
pancreatic abscess
short term
Occurs when the peri-pancreatic fluid collections become colonised and infected. Invariably fatal if not treated surgically.
Follows secondary bacterial contamination of necrotic pancreatic tissue and haemorrhagic exudates. It is unknown
whether prophylactic antibiotics given early in the course of the disease decrease the incidence of abscess. Generally
low
patients present 2 to 4 weeks after the onset of pancreatitis, with fever, and clinically worsen.
CT is diagnostic, showing a ring-enhancing fluid collection with gas. Its treatment is drainage (surgical versus
percutaneous) and antibiotics to cover E. coli, Bacteroides, Staphylococcus, Klebsiella, Proteus, and Candida albicans.
pancreatic insufficiency
Recurrent attacks may lead to exocrine pancreatic insufficiency more commonly than endocrine failure.
long term
low
chronic pancreatitis
Recurrent attacks of acute pancreatitis may lead to chronic scarring, and, if the aetiological factor is not treated, may
present with the classic characteristics of chronic pancreatitis: glucose intolerance, pancreatic insufficiency, and
calcifications.
long term
low
portal vein/splenic thrombosis
Ongoing pancreatic inflammation may cause irritation and inflammation of the portal vein and/or splenic vein, leading to
portal hypertension. Suspect splenic vein thrombosis in patients with recurrent pancreatitis, splenomegaly, and bleeding
from gastric varices.
long term
low
enteric fistulas
Resulting from inflammation surrounding the pancreas and adjacent duodenum or transverse colon.
long term
low
intestinal obstruction
Ileus may be frequently seen in pancreatitis, a result of dehydration, electrolyte abnormalities, or adjacent bowel
inflammation. Intestinal obstruction can be seen later in the course of the disease, when a pseudocyst or abscess causes a
mechanical compression of the bowel (generally duodenum or transverse colon). [
long term
low
multiorgan failure
The gut mucosa plays a central role in the development of multi-organ failure. Several descriptions about how the gut
modulates the inflammatory response by priming neutrophils and secreting cytokines can be found in the literature.
variable
medium
pancreatic ascites
variable
Consists of accumulated pancreatic fluid in the peritoneal cavity. It is due to chronic leakage of a pseudocyst, but some
cases may be due to duct disruption. Clinically manifested by weight loss and unresponsiveness of the ascites to diuretics.
Initial treatment involves hyper-alimentation and somatostatin. If no improvement is obtained in 2 to 3 weeks, endoscopic
retrograde cholangiopancreatography (ERCP) and surgery should be considered.
medium
pancreatic effusion
Secondary to pancreatic fistula draining into the chest. The diagnosis is based on thoracentesis with fluid rich in amylase
and a CT scan/retrograde pancreatogram that shows the fistula. Its treatment consists of drainage with a chest tube,
somatostatin, and total parenteral nutrition. If fistula persists, operative intervention with fistula resection or distal
pancreatectomy should be performed.
variable
medium
infected pancreatic necrosis
Infection is responsible for 80% of deaths. Gram-negative bacteria (Esterichia
coli, Pseudomonas, Klebsiella,Proteus, Enterobacter) are more common than gram-positive micro-organisms. Previous
studies describe a mortality rate of 50% to 80% in the absence of operative treatment and 10% to 40% among patients
who receive debridement.
variable
medium
acute lung injury/ARDS
variable
medium
variable
low
variable
low
variable
low
see our comprehensive coverage of Acute respiratory distress syndrome
The production and excretion of inflammatory mediators (such as cytokines, prostaglandins, and thromboxanes) during
pancreatitis may damage the alveolocapillary membrane, leading to destruction of pneumocytes and decrease in the
amount of surfactant. This leads to airway destruction, increase in superficial tension, and inadequate oxygenation.
Patients usually present with hypoxaemia, requiring higher levels of supplemental oxygen, with bilateral interstitial
infiltrates, PaO2:FiO2 ratio <300, and a normal pulmonary capillary wedge pressure. Patients may require mechanical
ventilation during the course of their disease.
disseminated intravascular coagulation
see our comprehensive coverage of Disseminated intravascular coagulation
Severe acute pancreatitis, especially if associated with necrosis, has been linked to liberation of cytokines and systemic
inflammatory response, with activation of the complement, coagulation, and fibrinolytic cascades, leading to a state of
coagulopathy and disseminated intravascular coagulation with elevated levels of split fibrin products and d-dimer with
low fibrinogen.
sepsis
see our comprehensive coverage of Sepsis
The gut mucosa plays a central role in the development of sepsis. Several descriptions about how the gut modulates the
inflammatory response by priming neutrophils and secreting cytokines can be found in the literature. Gram-negative
bacteria are the main cause of sepsis in patients with acute pancreatitis, and the gut mucosa is considered as the source of
such organisms. Therefore, it is important to maintain integrity of the anatomical barrier by providing enteral nutrition.
pseudocyst
Pseudocysts are encapsulated collections of fluid with high enzyme concentrations. The walls are formed by
inflammatory fibrosis of the peritoneal, mesenteric, and serosal membranes, which limits the spread of the pancreatic
fluid. Pseudocysts have no epithelial lining. Pseudocyst diagnosis should be suspected when a patient fails to respond
after 1 week of treatment or symptoms recur. Pain is the most common finding, followed by a palpable mass. CT scan is
the diagnostic study of choice. Pseudocysts can be complicated with infection, rupture (in 5%), and haemorrhage. The
principal indications for treatment are to improve symptoms and to prevent complications.
Expectant management is important in the first 6 to 12 weeks of existence of cysts that have arisen during an acute attack
of acute pancreatitis. The chance of spontaneous resolution is 40%. Thereafter, for cysts >5 cm in size, treatment is
usually recommended over conservative management.
Treatment options include excision of the cyst, external drainage (surgical or percutaneous), or internal drainage
(preferred method of treatment), which can be either a cystojejunostomy Roux-en-Y, cystogastrostomy, or
cystoduodenostomy.
gastrointestinal bleeding
variable
low
variable
low
see our comprehensive coverage of Assessment of upper GI bleed
From adjacent inflamed stomach or duodenum, ruptured pseudocyst, or peptic ulcer.
intra-peritoneal bleeding
From coeliac or splenic artery rupture or acute splenic vein thrombosis.
Prognosis
The majority of patients with acute pancreatitis will improve within 3 to 7 days of conservative management. The cause of pancreatitis should be
identified, and a plan to prevent recurrence should be initiated before the patient is discharged from hospital. In gallstone pancreatitis, a
cholecystectomy should be considered before discharge in mild cases and a few months after the discharge date in patients wit h severe symptoms.
In patients who are not candidates for surgery, endoscopic retrograde cholangiopancreatography (ERCP) must be considered.
Long-term prognosis is based on the aetiological factor and patient compliance to lifestyle modifications. Acute pancreatitis generally resolves
and leaves pancreatic function intact. May progress to chronic pancreatitis in the event of recurrent alcoholic intake, pancreas divisum, or cystic
fibrosis. The most commonly used prognostic scores are APACHE II, Ranson, Glasgow, Balthazar, and Atlanta.
