Acute pancreatitis: problems in adherence to guidelines.

Abstract

Although evidence-based guidelines on managing acute pancreatitis are available, many physicians are not following them. The authors identify and discuss several problems in adherence to guidelines on testing, imaging, and treatment.

Full text

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Tyler STevenS, MD
Digestive Disease Institute,
Cleveland Clinic
Acute pancreatitis:
Problems in adherence to guidelines
AbstrAct
■■
Although evidence-based guidelines on managing acute
pancreatitis are available, many physicians are not fol-
lowing them. The authors identify and discuss several
problems in adherence to guidelines on testing, imaging,
and treatment.
KEY POINts
■■
Serum amylase and lipase levels are often needlessly
measured every day.
Often, severity assessments are not performed regularly
or acted on.
Often, not enough fluid is replaced, or fluid status is not
adequately monitored.
In many severe cases, enteral or parenteral feeding is not
started soon enough.
Computed tomography is not done in many patients
with severe acute pancreatitis, or it is performed too
soon.
In many cases of suspected infected necrosis, fine-needle
aspiration is not done.
Broad-spectrum antibiotics are often used inappropriate-
ly in patients with mild acute pancreatitis and in patients
with sterile necrotizing pancreatitis who are clinically
stable and have no signs of sepsis.
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 12 DECEMBER 2009 697
S
how to manage acute pancreatitis, based on
evidence from high-quality randomized trials
and nonrandomized studies as well as on ex-
pert opinion.1–3 Information is limited on how
well physicians in the United States comply
with these guidelines, but compliance is sub-
optimal in other developed countries, accord-
ing to several studies,4–8 and we suspect that
many US physicians are not following the
guidelines either.
Acute pancreatitis is a frequent inpatient
diagnosis that internists, gastroenterologists,
and surgeons all confront. The most common
causes are gallstones and heavy alcohol intake.
Its management is typically straightforward:
intravenous fluids, analgesia, and nothing by
mouth. However, treatment of severe cases
can be quite complex, particularly if multiple
organ systems are involved or if there are local
complications.
The primary aim of this article is to raise
awareness of recognized deviations from es-
tablished recommendations that may lead to
adverse patient outcomes.
everal major gastroenterological and sur-
gical societies have issued guidelines on
Measuring enZYMe LeVeLs daiLY
adds COsT BuT LiTTLe BeneFiT

■
Problem: Serum amylase and lipase levels
are often needlessly measured every day.
Measuring the serum amylase and lipase lev-
els is useful in diagnosing acute pancreatitis, which
requires two of the following three features1:
Characteristic abdominal pain•?
Levels of serum amylase or serum lipase, or •?
both, that are three or more times the up-
per limit of normal
rEVIEW
doi:10.3949/ccjm.76a.09060
ManSour a. ParSi, MD
Digestive Disease Institute,
Cleveland Clinic
r. MaTThew walSh, MD
The Rich Family Distinguished Chair
in Digestive Diseases, Department of
Hepatic-Pancreatic-Biliary and Transplant
Surgery, Digestive Disease Institute,
Cleveland Clinic
EDUCATIONAL OBJECTIVE: Readers will recognize and adhere to established guidelines
CREDIT
CME

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CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 12 DECEMBER 2009
AcutE PANcrEAtItIs
Findings of acute pancreatitis on computed
tomography (CT).
However, the magnitude or duration of
the serum enzyme elevation does not correlate
with the severity of the attack. Further, we
have noticed that physicians at our hospital
often order daily serum amylase and lipase lev-
els in patients admitted with acute pancreati-
tis.
The American College of Gastroenterol-
ogy (ACG) guidelines1 state that daily moni-
toring of amylase and lipase has limited value
in managing acute pancreatitis. Rechecking
these concentrations may be reasonable if pain
fails to resolve or worsens during a prolonged
hospitalization, as this may suggest a recurrent
attack of acute pancreatitis or a developing
pseudocyst. But in most cases of acute pancre-
atitis, daily serum enzyme measurements add
cost but little benefit.
•?

reguLar assessMenT is iMPOrTanT
■
Problem: Often, severity assessments are not
performed regularly or acted on.
Most cases of acute pancreatitis are mild,
with rapid recovery and excellent prognosis.
However, 15% to 20% are severe and may
result in a prolonged hospitalization, system-
ic inflammatory response syndrome (SIRS),
multiorgan system failure, and death.
In severe acute pancreatitis, as pancreatic
enzymes and inflammatory cytokines damage
the blood vessels, a vast amount of fluid leaks
out into the interstitial (“third”) space. This
fluid extravasation leads to decreased effective
circulating volume, local pancreatic necrosis,
hemodynamic instability, and end-organ fail-
ure.
It is important to recognize severe acute
pancreatitis early because the patient needs to
be transferred to a step-down unit or intensive
care unit to receive optimal fluid resuscitation
and supportive care for organ dysfunction. Af-
ter 48 to 72 hours, a prediction of severe acute
pancreatitis should also prompt the physician
to order CT to detect pancreatic necrosis, and
also to initiate nutritional support.
Assessment of severity begins in the emer-
gency room or on admission to the hospital.
Older age, obesity, organ failure, and pulmo-
nary infiltrates or pleural effusions are initial
indicators of poor prognosis. Signs of SIRS
(high or low core body temperature, tachycar-
dia, tachypnea, low or high peripheral white
blood cell count) or organ failure (eg, elevated
serum creatinine) are present on admission in
21% of patients with acute pancreatitis.9
Hemoconcentration is a marker of de-
creased effective circulating volume in severe
acute pancreatitis. A hematocrit higher than
44% at admission or that rises in the first 24
to 48 hours of admission predicts necrosis.10,11
However, a more robust marker of organ fail-
ure may be the blood urea nitrogen level.12
Clinical scoring systems
Several clinical scoring systems have been
studied for assessing severity.

The Ranson score is based on 11 clinical
factors, 5 checked at admission and 6 checked
at 48 hours (Table 1). Patients are at higher
risk of death or “serious illness” (needing 7 or
more days of intensive care) if they have 3 or
more of these factors.13 In a meta-analysis of
12 studies, a Ranson score of 3 or higher had a
sensitivity of 75% and a specificity of 77% for
predicting severe acute pancreatitis.14
Limitations of the Ranson score are that
the serum
enzyme level
does not
correlate with
the severity
of the attack
TaBLe 1
the ranson score for assessing
acute pancreatitis
On admission
Age > 55 years
White blood cell count > 16,000/mL
Lactate dehydrogenase > 350 IU/L
Aspartate aminotransferase > 250 IU/L
Glucose > 200 mg/dL
at 48 hours
Hematocrit decrease > 10%
Blood urea nitrogen increase > 5 mg/dL
Calcium < 8 mg/dL
Partial pressure of oxygen, arterial < 60 mm Hg
Base deficit > 4 mg/dL
Fluid sequestration > 6 L
The presence of three or more factors predicts a higher risk
of death or serious illness.
BASED ON INFORMATION IN RANSON JH, RIFkIND kM, ROSES DF,
FINk SD, ENg k, SpENCER FC. pROgNOSTIC SIgNS AND THE ROLE OF
OpERATIVE MANAgEMENT IN ACUTE pANCREATITIS.
SURg gyNECOL OBSTET 1974; 139:69–81.

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CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 12 DECEMBER 2009 699
stEVENs ANd cOllEAguEs
it can only be completed after 48 hours, all
the data points are not always obtained, and
it cannot be repeated on a daily basis. Owing
to these limitations and its less-than-optimal
predictive value, the Ranson score has fallen
into disuse.

The APACHE II (Acute Physiology and
Chronic Health Evaluation II) score is more
versatile. It is based on multiple clinical and
laboratory values, and it correlates very well
with the risk of death in acute pancreati-
tis. Death rates are less than 4% when the
APACHE II score is less than 8, and 11% to
18% when it is 8 or higher.1 The trajectory of
the APACHE II score in the first 48 hours is
also an accurate prognostic indicator.
Previous limitations of the APACHE II
score were that it was complicated and time-
consuming to calculate and required arte-
rial blood gas measurements. Easy-to-use on-
line calculators are now available (eg, www.
globalrph.com/apacheii.htm), and the venous
bicarbonate level and the oxygen saturation
can be substituted for the arterial pH and oxy-
gen partial pressure.

BISAP, a new five-point scoring system,15
was recently prospectively
“BISAP” is an acronym for the five markers it
is based on, each of which has been shown to
predict severe illness in acute pancreatitis:
Blood urea nitrogen level > 25 mg/dL•?
Impaired mental status•?
SIRS•?
Age > 60 years•?
Pleural effusion.•?
The presence of three or more of these fac-
tors correlates with higher risk of death, organ
failure, and pancreatic necrosis.12
Compared with APACHE II, BISAP has
similar accuracy and is easier to calculate.
Also, BISAP was specifically developed for
acute pancreatitis, whereas APACHE II is a
generic score for all critically ill patients.

The Atlanta criteria16 define severe acute
pancreatitis as one or more of the following:
A Ranson score of 3 or higher during the •?
first 48 hours
An APACHE II score of 8 or higher at any •?
time
Failure of one or more organs•?
One or more local complications (eg, ne-•?
crosis, pseudocysts, abscesses).
validated.12
recommendation:
assess severity at least daily
A severity assessment should be performed at
admission and at least every day thereafter.
Clinical guidelines recognize the importance
of severity assessment but vary in their specific
recommendations.
The ACG advises calculating the
APACHE II score within 3 days of admission
and measuring the hematocrit at admission, at
12 hours, and at 24 hours. The level of evi-
dence is III, ie, “from published well-designed
trials without randomization, single group
prepost, cohort, time series, or matched case
controlled studies”.1
The American Gastroenterological Asso-
ciation (AGA) provides a more generalized
recommendation, that “clinical judgment”
should take into account the presence of risk
factors (eg, age, obesity), presence or absence
of SIRS, routine laboratory values (eg, hema-
tocrit, serum creatinine), and APACHE II
score when assessing severity and making de-
cisions.2
In a German survey, only 32% of gastro-
enterologists used the APACHE II score for
assessing risk in acute pancreatitis, in spite
of national guidelines emphasizing its impor-
tance.7 Also, not all patients with severe acute
pancreatitis are transferred to a step-down
unit or intensive care unit as recommended.
In a British study,4 only 8 (17%) of 46 patients
with predicted severe acute pancreatitis were
transferred, and 8 of the 38 patients who were
not transferred died.
FLuid MusT Be aggressiVeLY
rePLaCed and MOniTOred

■
Problem: Often, not enough fluid is replaced,
or fluid status is not adequately monitored.
Fluid must be aggressively replaced to bal-
ance the massive third-space fluid losses that
occur in the early inflammatory phase of acute
pancreatitis. Intravascular volume depletion
can develop rapidly and result in tachycardia,
hypotension, and renal failure. It may also im-
pair the blood flow to the pancreas and worsen
necrosis.
Animal studies show that aggressive fluid
replacement supports the pancreatic microcir-
culation and prevents necrosis.17 It may also
there is
massive fluid
sequestration
in severe acute
pancreatitis

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CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 12 DECEMBER 2009
AcutE PANcrEAtItIs
support the intestinal microcirculation and
gut barrier, preventing bacterial transloca-
tion.
In humans, no controlled trials have been
done to test the efficacy of aggressive fluid
resuscitation in acute pancreatitis. However,
the notion that intravascular fluid loss con-
tributes to poor outcomes is inferred from hu-
man studies showing more necrosis and deaths
in patients with hemoconcentration. In one
study, patients who received inadequate fluid
replacement (evidenced by a rise in hemato-
crit at 24 hours) were more likely to develop
necrotizing pancreatitis.18
recommendation:
early, aggressive fluid replacement
Experts have suggested initially infusing 500
to 1,000 mL of fluid per hour in those who are
volume-depleted, initially infusing 250 to 350
mL per hour in those who are not volume-
depleted, and adjusting the fluid rate every 1
to 4 hours on the basis of clinical variables.19
The sufficiency of fluid replacement should be
carefully monitored by vital signs, urine out-
put, and serum hematocrit.
On the other hand, overly aggressive fluid
resuscitation can be detrimental in patients at
risk of volume overload or pulmonary edema.
Fluid replacement should be tempered in el-
derly patients and those with cardiac or renal
comorbidities, and may require monitoring of
central venous pressure.
The ACG and AGA guidelines both rec-
ognize the need for early aggressive volume
replacement in acute pancreatitis (level of
evidence III), but they do not specify the ex-
act amounts and rates. Young and healthy pa-
tients should receive a rapid bolus of isotonic
saline or Ringer’s lactate solution followed
by an infusion at a high initial maintenance
rate.
Few studies have been done to assess physi-
cians’ compliance with recommendations for
aggressive volume replacement. In an Italian
multicenter study, patients with mild or severe
acute pancreatitis received an average of only
2.5 L of fluid per day (about 100 mL/hour).20
Gardner et al21 recently summarized the avail-
able evidence for fluid support in acute pan-
creatitis.
nuTriTiOnaL suPPOrT
■
Problem: In many severe cases, enteral or par-
enteral feeding is not started soon enough.
Nutritional support entails enteral or par-
enteral feeding when an oral diet is contrain-
dicated. Enteral feeding is usually via a na-
sojejunal tube, which may need to be placed
under endoscopic or radiographic guidance.
Neither parenteral nor nasojejunal feeding
stimulates pancreatic secretion, and both are
safe in acute pancreatitis.
Severe acute pancreatitis is an intensely
catabolic state characterized by increased
energy expenditure, protein breakdown, and
substrate utilization. Patients may not be
able to resume an oral diet for weeks or even
months, particularly if local complications
develop. Early nutritional support has been
shown to improve outcomes in severe acute
pancreatitis.22 Therefore, nutritional support
should be started as soon as possible in severe
acute pancreatitis based on initial clinical and
radiographic indicators of severity, optimally
within the first 2 or 3 days.
Enteral nutrition is preferred to parenteral
nutrition in pancreatitis: it is less expensive
and does not pose a risk of catheter-related in-
fection or thrombosis or hepatic complications.
Also, there is experimental evidence that en-
teral nutrition may preserve the gut barrier,
decreasing mucosal permeability and bacterial
translocation.
A number of small randomized trials com-
pared enteral and parenteral nutrition in acute
pancreatitis, but they yielded mixed results. A
meta-analysis of six trials showed a lower rate
of infectious complications with enteral than
with parenteral nutrition. 23 However, no sig-
nificant difference was found in the rates of
death or noninfectious complications.
recommendation:
enteral feeding, when possible
Nutritional support is unnecessary in most
cases of mild acute pancreatitis. Pancreatic
inflammation typically resolves within a few
days, allowing patients to resume eating. Oc-
casionally, patients in whom pain resolves
slowly and who fast for more than 5 to 7 days
need nutritional support to prevent protein-
calorie malnutrition.
Assessment
of severity
begins in the
emergency
room or
on hospital
admission

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CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 12 DECEMBER 2009 701
stEVENs ANd cOllEAguEs

gest that, whenever possible, enteral rather
than parenteral feeding should be given to
those who require nutritional support. The
level of evidence is II (“strong evidence from
at least one published properly designed ran-
domized controlled trial of appropriate size
and in an appropriate clinical setting”).
However, not all physicians recognize the
benefit of enteral feeding. In a cohort of Ger-
man gastroenterologists, only 73% favored
enteral over parenteral feeding in acute pan-
creatitis.7
The ACG guidelines1 and most others sug-
COMPuTed TOMOgraPHY
■
Problem: CT is not done in many patients
with severe acute pancreatitis, or it is done
too soon during the admission.
Dual-phase, contrast-enhanced, pancreat-
ic-protocol CT provides a sensitive structural
evaluation of the pancreas and is useful to
diagnose necrotizing pancreatitis. Pancreatic
necrosis is correlated with a severe clinical
course, the development of single or multior-
gan dysfunction, and death.
Necrosis is diagnosed when more than 30%
of the pancreas does not enhance (ie, perfuse)
after intravenous contrast is given. The Bal-
thazar-Ranson CT severity index includes the
degree of pancreatic enlargement and inflam-
mation, presence and number of fluid collec-
tions, and degree of necrosis (Table 2).24
recommendation: CT in severe cases
Not every patient with acute pancreatitis
needs to undergo CT. Most mild cases do not
require routine CT, since necrosis and other
local complications are infrequent in this
group.
Also, CT is often ordered too soon during
the hospitalization. Indicators of severity on
CT are not usually evident until 2 to 3 days
after admission.25 CT should be considered
about 3 days after the onset of symptoms rath-
er than immediately upon admission.
On the other hand, CT at the time of ad-
mission may be warranted to rule out other
life-threatening causes of abdominal pain and
hyperamylasemia (eg, bowel obstruction, vis-
cus perforation). CT may also be useful in the
late phase of acute pancreatitis (weeks after
admission) to diagnose or monitor complica-
tions (eg, pseudocysts, abscesses, splenic vein
thrombosis, splenic artery pseudoaneurysms).
Magnetic resonance imaging with gadolinium
contrast is a reasonable alternative to CT for
detecting pancreatic necrosis and other local
complications.
In patients who have severe acute pancre-
atitis and compromised renal function (serum
creatinine > 1.5 mg/dL), CT can be performed
without contrast to assess severity based on a
limited Balthazar score (ie, without a necrosis
score). Studies in rats suggest that iodinated
contrast may decrease pancreatic microcir-
culation and worsen or precipitate necrosis,26
although published human studies do not sup-
port this contention.27,28
Guidelines uniformly recommend CT for
patients with severe acute pancreatitis (the
ACG guideline gives it a level of evidence of
III), but this recommendation is not always
followed. A study from Australia showed that
CT was done in only 27% to 67% of patients
with severe acute pancreatitis.5 In a British
study, only 8 of 46 patients with clinically
predicted severe pancreatitis underwent CT
within the first 10 days of admission.4
severe
acute
pancreatitis
is an intensely
catabolic state
TaBLe 2
the balthazar-ranson severity
index for acute pancreatitis
Findings On COMPuTed TOMOgraPHYsCOre*
Normal
Focal or diffuse enlargement of the pancreas
Intrinsic pancreatic abnormalities associated with haziness
and streaky densities representing inflammatory changes in
the peripancreatic fat
Single, ill-defined fluid collection
Two or more fluid collections
No necrosis
1/3 necrosis
1/2 necrosis
> 1/2 necrosis
0
1
2
3
4
0
2
4
6
*Almost all patients with a total score of 7 or higher develop complications, and
17% of them die.
BASED ON INFORMATION IN BALTHAzAR EJ, ROBINSON DL, MEgIBOw AJ, RANSON JH. ACUTE
pANCREATITIS: VALUE OF CT IN ESTABLISHINg pROgNOSIS. RADIOLOgy 1990; 174:331–336.