-
self-limited and subsides spontaneously, usually within 3 to
7 days after
treatment is instituted (85-90%). Conventional measures
include :
-
analgesics for pain
-
intravenous fluids and colloids to maintain normal
intravascular volume
-
no oral alimentation
-
nasogastric
suction
to decrease gastrin release from the stomach and prevent
gastric contents
from entering the duodenum. Recent controlled trials,
however, have shown
that nasogastric suction offers no clear-cut advantages in
the treatment
of mild to moderately severe acute pancreatitis. Its use,
therefore, must
be considered elective rather than mandatory
-
total
parenteral
nutrition (TPN)
: the patient with mild to moderate pancreatitis usually
requires treatment
with intravenous fluids, fasting, and possibly nasogastric
suction for
2 to 4 days. A clear liquid diet is frequently started on
the 3d to6th
day, and a regular diet by the 5th to 7th day. The decision
to reintroduce
oral intake is usually based on the following criteria: (1)
a decrease
in or resolution of abdominal pain; (2) the patient is
hungry; and (3)
organ dysfunction, if present, has improved. Elevation of
serum amylase/lipase
or persistent inflammatory changes seen on CT scans should
not discourage
feeding a hungry asymptomatic patient. In this regard,
persistence of inflammatory
changes on CT scans or persistent elevations in serum
amylase/lipase may
not normalize for weeks to months. The use of parenteral
nutrition makes
it possible to give nutritional support to patients with
severe, acute,
or protracted pancreatitis who are unable to eat normally.
Several studies
have demonstrated that enteral feeding via a nasojejunal
tube infused distal
to the ligament of Treitz is associated with a decreased
rate of complications,
including infection, when compared to total parenteral
nutrition.
-
the patient with unremitting fulminant pancreatitis usually
requires inordinate
amounts of fluid and close attention to complications such
as cardiovascular
collapse, respiratory insufficiency, and pancreatic
infection. The latter
should be managed by a combination of radiologic and
surgical means. While
earlier uncontrolled studies suggested that peritoneal
lavage through a
percutaneous dialysis catheter was helpful in severe
pancreatitis, subsequent
studies indicate that this treatment does not influence the
outcome of
such attacks. Aggressive surgical pancreatic debridement (necrosectomy)
should be undertaken soon after confirmation of the presence
of infected
necrosis, and multiple operations may be required. Since the
mortality
rate from sterile acute necrotizing pancreatitis is
approximately 10%,
laparotomy with adequate drainage and removal of necrotic
tissue should
be considered if conventional therapy does not halt the
patient's deterioration.
Patients with severe gallstone-induced pancreatitis may
improve dramatically
if papillotomy is carried out within the first 36 to 72 h of
the attack.
Studies indicate that only those patients with gallstone
pancreatitis who
are in the very severe group should be considered for urgent
ERCP
-
prophylactic antibiotics in necrotizing acute
pancreatitis => significant
reduction in sepsis by 21% and mortality by 12%. The current
recommendation
is the use of a systemic antibiotic such as imipenem-cilastatin
,
500 mg thrice daily for 2 weeks. In addition, because
secondary infection
of necrotic pancreatic tissue (abscess, pseudocyst or
obstructed biliary
passages, ascending cholangitis complicating choledocholithiasis)
contributes to many of the late deaths from pancreatitis,
appropriate antibiotic
therapy of established infections is quite important.
-
intraabdominal Candida
spp.
infection during acute necrotizing pancreatitis is
increasing in frequency
and is associated with an increased mortality rate. In one
representatitve
trial, intraabdominal Candida infection was found in
13 of 37 cases
and was associated with a mortality rate 4-fold greater than
that associated
with intraabdominal bacterial infection alone. Given the
impact of Candida
infection on the mortality rate in acute necrotizing
pancreatitis and the
apparent benefit of prophylactic chemotherapy, these data
suggest earlier
use of fungicides.
-
several other drugs have been evaluated by prospective
controlled trials
and found ineffective in the treatment of acute
pancreatitis. The list,
by no means complete, includes glucagon, H2
antagonist
,
serine
protease inhibitors
such as aprotinin, glucocorticoids, calcitonin, nonsteroidal
anti-inflammatory
drugs (NSAIDs), and lexiplafant, a PAFR
antagonist. A recent meta-analysis of somatostatin,
ocreotide, and
the antiprotease gabexate mesilate in therapy of acute
pancreatitis suggested
(1) a reduced mortality rate but no change in complications
with octreotide,
and (2) no effect on the mortality rate but reduced
pancreatic damage with
gabexate
-
it has been demonstrated that CCK-stimulated pancreatic
secretion is almost
abolished in 4 different experimental models of acute
pancreatitis. This
finding probably explains why drugs to block pancreatic
secretion (somatostatin,
somatostatin analogue octreotide, and CCKA
antagonists) in acute pancreatitis have failed to have
any therapeutic
benefit. For this and other reasons, anticholinergic drugs
are not indicated
in acute pancreatitis. In addition to nasogastric suction
and anticholinergic
drugs, other therapies designed to "rest the pancreas" by
inhibiting pancreatic
secretion have not changed the course of the disease.
Although antibiotics
have been used in the treatment of acute pancreatitis,
randomized, prospective
trials have shown no benefit from their use in acute
pancreatitis of mild
to moderate severity.
-
IS-741, a novel diamino-pyridine derivative
anti-inflammatory agentref
-
the treatment for patients with
hypertriglyceridemia-associated pancreatitis
includes (1) weight loss to ideal weight, (2) a
lipid-restricted diet,
(3) exercise, (4) avoidance of alcohol and of drugs that can
elevate serum
triglycerides (i.e., estrogens, vitamin
A
,
thiazide
diuretics
,
and b-blockers
),
and (5) control of diabetes.
-
persistent biliary obstruction worsens the outcome and
increases the severity
of acute pancreatitis and predisposes the patient to
bacterial cholangitis.
ERCP is used with endoscopic sphincterotomy to extract
impacted gallstones
and to drain infected bile in severe acute pancreatitisref1,
ref2,
ref3,
ref4.
Although ERCP has risks, including bleeding after
sphincterotomy and causing
acute pancreatitis, complications are uncommon when the
procedure is performed
by experienced endoscopists. 3 randomized trials involving a
total of 511
patients with gallstone pancreatitis compared conservative
management with
ERCP and endoscopic sphincterotomy within 24 to 72 hours
after admission.
The studies showed a significantly lower risk of
pancreatitis-associated
complications in the ERCP group (odds ratio, 0.27; 95%
confidence interval,
0.14 to 0.53)ref
-
hospitalization : patients who present with persistent or
severe pain,
vomiting, dehydration, or signs of impending severe acute
pancreatitis
(to be discussed later) should be hospitalized. Clinical
trials have failed
to show the efficacy of medications proposed to alter the
course of acute
pancreatitis, including an inhibitor of platelet-activating
factor (lexipafantref),
somatostatin
and its analogues, and protease inhibitorsref;
treatment is primarily supportive. Patients should receive
nothing by mouth
and receive intravenous pain medication and aggressive
hydration to treat
or prevent hemoconcentration (e.g., a bolus of fluids to
achieve hemodynamic
stability, followed by 250 to 500 ml of crystalloid
solutions per hour
in an average-sized patient without substantial kidney or
heart disease).
Fluid balance should be maintained and pulse oximetry should
be considered,
especially when narcotic analgesics are used
-
predicting severe acute pancreatitis : the severity of acute
pancreatitis
is defined by the presence or absence of organ failure,
local complications,
or bothref1,
ref2,
ref3,
ref4,
ref5.
It is critical to identify patients who are at high risk for
severe disease,
since they require close monitoring and possible
intervention. Recognized
markers of the risk of severe acute pancreatitis include
specific laboratory
values that measure the systemic inflammatory response (such
as C-reactive
protein), scoring systems that assess inflammation or organ
failure (such
as Ranson's score), and findings on imaging studiesref1,
ref2
(Table 2). The Acute Physiology and Chronic Health
Evaluation score (based
on initial values of 12 routine physiological measurements,
age, and previous
health status) is among the best predictors of severity on
admission, whereas
elevated C-reactive protein levels are equally useful when
measured 24
to 48 hours after the onset of symptomsref.
Severity scores are useful in predicting both complications
and death (Table
3).
Scoring Methods for the Prediction of Severe Acute
Pancreatitis.
Value of Various Scoring Systems and Inflammatory Markers in
the Prediction
of Severe Acute Pancreatitis.
Relationship between Severity Scores and Outcomes in Acute
Pancreatitis.
Other markers that are not included in standard scoring
systems should
also be considered. Obesity (a body-mass index of > 30)
is associated with
an increase in the risk of a severe clinical course by a
factor of 2 to
3ref.
A hematocrit above 44% is a clear risk factor for pancreatic
necrosisref,
although it is a poor predictor of the severity of disease.
Preliminary
evidence suggests that genetic factors, such as
polymorphisms in the chemokine
monocyte chemotactic protein 1 (MCP-1) generef,
may also predict severity, although such genetic testing is
not currently
used in practice. Several clinical findings — including
thirst, poor urine
output, progressive tachycardia, tachypnea, hypoxemia,
agitation, confusion,
a rising hematocrit level, and a lack of improvement in
symptoms within
the first 48 hours — are warning signs of impending severe
disease. If
such symptoms develop, admission to an intensive care unit
should be considered.
Intensive care may also be warranted in patients at risk for
rapid deterioration
in their condition, including those over the age of 55 yearsref,
those who need ongoing volume resuscitation or invasive
monitoring of fluid
status (e.g., central venous pressure monitoring), or those
with renal
failure or respiratory compromiseref
-
pancreatic-fluid collections, pseudocysts, and necrosis : up
to 57% of
patients who are hospitalized with acute pancreatitis will
have fluid collections,
with 39% having two areas involved and 33% having 3 or moreref.
Fluid collections are initially ill definedref,
evolve over time, and are usually managed conservatively. If
the fluid
collections continue to enlarge, cause pain, become infected
(as suggested
by the presence of unexplained fever, leukocytosis, or gas
in the fluid
collection), or compress adjacent organs, then medical,
endoscopic, or
surgical intervention may be neededref1,
ref2.
Fluid collections with very high levels of pancreatic
enzymes are usually
associated with pancreatic-duct disruptions and may
eventually form pseudocysts
(usually over a period of several weeks), ascites, or
pleural effusionsref.
Asymptomatic pseudocysts can be managed conservatively,
whereas symptomatic
pseudocysts can often be drained endoscopicallyref.
ERCP may help to define the anatomy of the pancreatic duct
and identify
any duct disruptions to guide further interventionref1,
ref2
-
pancreatic necrosis, occurring as diffuse or focal areas of
nonviable pancreatic
parenchymaref,
is an important complication that can develop during the
first few days
of pancreatitis; the condition is associated with late
complications and
death if the necrotic tissue becomes infected. The
development of necrosis
is associated with pancreatic inflammation, hypovolemia, and
hypotension
from the shunting of blood from other organs, vascular
spasm, and hemoconcentrationref.
Pancreatic necrosis can be demonstrated by a loss of tissue
perfusion on
contrast-enhanced CTref.
Infection of necrotic tissue is suspected when there is
fever, leukocytosis,
and a failure to improve or unexpected deterioration —
usually after the
first week of illness. Visualization of gas bubbles within
the necrotic
tissue on CT is evidence of infection. The diagnosis of
infected necrosis
is usually made by fine-needle aspiration of the necrotic
area guided by
either CT or ultrasonography, with Gram's staining and
culture of the aspirateref.
-
lack of improvement : if the condition of a patient
whose pancreatitis
is predicted to be mild fails to improve within 2-3 days,
then contrast-enhanced
CT ("pancreas protocol") should be considered to identify
fluid collections,
pancreatic necrosis, or other complications that may require
intervention.
Antibiotic therapy and nutritional support also warrant
consideration in
patients whose condition fails to improve promptly or in
whom complications
develop.
-
use of antibiotics : the proper role of antibiotics
in acute pancreatitis
remains controversial. No antibiotics are indicated in mild
cases. However,
infectious complications are an important concern in severe
cases, especially
cases of pancreatic necrosis. A potential role for
prophylactic antibiotics
in severe pancreatitis was initially given support by a
randomized trial
demonstrating that the administration of imipenem reduced
infectious complications,
including central-line sepsis, pulmonary infection, urinary
tract infection,
and infected pancreatic necrosisref.37
Subsequent
trials yielded mixed, but generally confirmatory, resultsref.
However, a recent randomized trial failed to demonstrate
differences in
outcome among patients treated with ciprofloxacin plus
metronidazole, as
compared with placebo, leading some experts to recommend
against the routine
use of prophylactic antibioticsref.
Some centers use antifungal therapy as well as antibacterial
therapy, but
this practice has not been validated by randomized trials
-
nutritional support : ensuring adequate nutrition is
important in
patients with severe or complicated pancreatitis, but the
optimal means
of doing so remains controversialref.
2 small trials involving a total of 70 patients showed a
nonsignificant
reduction in adverse outcomes with enteral feeding through
nasoenteric
feeding tubes, as compared with total parenteral nutritionref.
More recent meta-analyses of 6 randomized trials involving a
total of 263
patients demonstrated improved outcomes with enteral
nutritionref1,
ref2,
including decreased rates of infectionref1,
ref2
and surgical interventionref,
a reduced length of hospital stayref,
and reduced costs (20% of the costs associated with total
parenteral nutrition)ref.
Enteral feeding is usually well tolerated in patients with
ileusref.
However, total parenteral nutrition may be necessary for
patients who cannot
obtain sufficient calories through enteral nutrition or in
whom enteral
access cannot be maintainedref.
-
surgical intervention is indicated in patients with
infected pancreatic
necrosis. In most cases, the diagnosis is confirmed by
fine-needle aspiration
before surgical intervention, but because false negative
results can occur
(reported sensitivity, 88%)ref,
surgery also warrants consideration when there is a high
index of suspicion
of infected necrosis even if infection is not documented.
Surgery within
the first few days after the onset of severe acute
pancreatitis is associated
with rates of death up to 65%ref.
Furthermore, there is no clear demarcation between viable
and nonviable
tissue early in the course of acute pancreatitisref.
Observational data support delaying surgical débridement of
necrotic
tissue for at least two weeks if possible while the
patient's medical condition
is optimized and viable pancreatic tissue becomes evidentref.
This approach appears to improve survival and maximize organ
preservationref.
-
discharge planning : whenever possible, the cause of
pancreatitis
should be determined and plans to prevent recurrence should
be devised
before the patient is discharged from the hospital. In
patients with acute
pancreatitis caused by gallstones, cholecystectomy should be
considered
before discharge in those with mild cases or within a few
months in those
with more severe or complicated cases to allow inflammatory
processes or
fluid collections to organize or resolveref.
ERCP with sphincterotomy is an alternative in patients who
are not surgical
candidates or in whom surgery must be delayedref.
If the cause is hypertriglyceridemia, then dietary measures,
cessation
of alcohol intake, weight reduction, and possibly, treatment
with the administration
of gemfibrozil or fenofibrate should be initiatedref.
The identification of hypercalcemia requires attention to
the underlying
cause, such as hyperparathyroidism or cancer. Medications
associated with
acute pancreatitis should be discontinuedref.
Recurrent pancreatitis — in the absence of biliary disease,
alcoholism,
and toxic or metabolic causes — suggests other causes, such
as strictures,
pancreas divisum, duct-obstructing masses, autoimmune
pancreatitis, and
genetic susceptibility (Morinville V, Whitcomb DC. Recurrent
acute and
chronic pancreatitis: complex disorders with a genetic
basis. Gastroenterol
Hepatol 2005;1:195-205). Systematic approaches to idiopathic
and recurrent
acute pancreatitis have been reviewed elsewhereref1,
ref2.
Patients can be discharged when their pain is controlled
with oral analgesics
and they are able to eat and drink. Oral feeding can be
started when abdominal
tenderness diminishes and the patient becomes hungry.
Clinical experience
provides support for a recommendation that patients eat
small, low-fat
meals of carbohydrates and proteins, with a gradual increase
in quantity
over a period of 3-6 days as toleratedref.
Patients who are unable to eat because of persistent pain or
gastric compression
from a pseudocyst have been successfully treated as
outpatients with nasoenteric
feeding tubes, surgical jejunal tubes, or total parenteral
nutrition.
The prophylactic use of antibiotics in patients with
pancreatic necrosis
is supported by the guidelines of the International
Association of Pancreatology
for the surgical management of acute pancreatitisref
and the Japanese Society of Abdominal Emergency Medicine53
but is discouraged
by an expert panel of the American Thoracic Society and
other organizationsref.
No consensus was reached by the United Kingdom Working Party
on Acute Pancreatitisref.
The last 3 organizationsref1,
ref2,
ref3
favor the use of enteral nutrition over total parenteral
nutrition in patients
with severe acute pancreatitis whenever possible.
Early intervention for gallstone pancreatitis with bile-duct
obstruction
with the use of ERCP with endoscopic sphincterotomy is
consistently recommended.