Received: 6 January 2021Accepted: 19 January 2021

DOI: 10.1111/jvim.16053

C O N S E N S U S S T A T E M E NT

Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide the veterinary community with up-
to-date information on the pathophysiology, diagnosis, and treatment of clinically important animal diseases. The ACVIM Board of
Regents oversees selection of relevant topics, identification of panel members with the expertise to draft the statements, and
other aspects of assuring the integrity of the process. The statements are derived from evidence-based medicine whenever
possible and the panel offers interpretive comments when such evidence is inade- quate or contradictory. A draft is prepared
by the panel, followed by solicitation of input by the ACVIM membership which may be incorporated into the statement. It is
then submitted to the Journal of Veterinary Internal Medicine, where it is edited prior to publication. The authors are solely
responsi- ble for the content of the statements.

ACVIM consensus statement on pancreatitis in cats

Marnin A. | Joerg M. Steiner2 | P. Jane Armstrong3 |

Forman1
Melinda S. | Lorrie Gaschen5 | Steve L. Hill6 | Caroline S. |
Camus4 Mansfield7
Katja Steiger8

1
Cornell University Veterinary Specialists,
Stamford, Connecticut Abstract
2
Gastrointestinal Laboratory, College of Background: Pancreatitis in cats, although commonly diagnosed, still
Veterinary Medicine and Biomedical
Sciences, Texas A&M University, College presents many diagnostic and management challenges.
Station, Texas Objective: To summarize the current literature as it relates to etiology,
3
College of Veterinary Medicine,
pathogenesis, diagnosis, and management of pancreatitis in cats and
University of Minnesota, St Paul,
Minnesota to arrive at clinically relevant suggestions for veterinary clinicians that
4
Department of Pathology, College of are based on evidence, and where such evi- dence is lacking, based on
Veterinary Medicine, University of
consensus of experts in the field.
Georgia, Athens, Georgia
5
Department of Veterinary Clinical Animals: None.
Sciences, School of Veterinary Medicine, Methods: A panel of 8 experts in the field (5 internists, 1 radiologist, 1
Louisiana State University, Louisiana
clinical pathol- ogist, and 1 anatomic pathologist), with support from a
6
Flagstaff Veterinary Internal
Medicine Consulting, Flagstaff, librarian, was formed to assess and summarize evidence in the peer
Arizona reviewed literature and complement it with consensus clinical
7
Melbourne Veterinary School,
recommendations.
University of Melbourne, Victoria,
Australia Results: There was little literature on the etiology and pathogenesis of
8
Institute of Pathology, School of spontaneous pancreatitis in cats, but there was much in the literature
Medicine, Technical University of
Munich, Munich, Germany
about the disease in humans, along with some experimental evidence
in cats and nonfeline species. Most evidence was in the area of
Correspondence
Joerg M. Steiner, Gastrointestinal Laboratory,
diagnosis of pancreatitis in cats, which was summarized carefully. In
College of Veterinary Medicine and contrast, there was little evidence on the management of pancreatitis
Biomedical Sciences, Texas A&M
University, College Station, TX.
Email: [email protected]

Marnin A. Forman and Joerg M. Steiner are co-chairs, listed in alphabetical order.
P. Jane Armstrong, Melinda S. Camus, Lorrie Gaschen, Steve L. Hill, Caroline S. Mansfield, and Katja Steiger are panel members, listed in alphabetical order.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution
and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary
Internal Medicine.

J Vet Intern Med. 2021;35:703–723. 703

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704 FORMAN ET AL.

both forms of pancreatitis can be managed successfully in many cats,

management measures are far less clearly defined for chronic
pancreatitis.

KE Y W O R DS
cat, diagnosis, etiology, gastroenterology, management, pancreas, pancreatitis,

1 | INTRODUCTION although morbidity may be impacted by concurrent dis-

eases. In contrast, clinically severe pancreatitis is
Pancreatitis historically has been considered rare in cats, characterized by extensive pancreatic necrosis, multiple
but cur- rent evidence suggests that this disease is quite organ involvement or even fail- ure, and in some cases a
common, similar to the situation in both humans and dogs. 1 poor prognosis.7
In a study of 115 cats undergoing necropsy at the
University of California Davis, the overall histopathologic
prevalence of pancreatitis was 66.1%, with 50.4% of cats
having evidence of chronic pancreatitis alone, 6.1% having
evidence of acute pancreatitis alone, and 9.6% having evi-
dence of both acute and chronic pancreatitis. Also, 45% of
the apparently healthy cats had evidence of pancreatitis. 1
This finding raises the question as to whether there is a
population of cats with subclinical pancreatitis or whether
the current histopathologic defi- nition of pancreatitis leads
to overdiagnosis and needs clarification. In contrast to
these histopathological data, clinical pancreatitis is
diagnosed much less frequently in cats, but the consensus
panel agrees that the frequency of a diagnosis of
pancreatitis has increased steadily over the last 2 decades,
mainly because of an increased level of awareness and
availability of noninvasive and minimally invasive diagnostic
tests. Management of pancreatitis in cats remains
challenging and definitive treatments are currently
unavailable.

2 | DEFINITION

Although in humans the definition and classification of

pancreatitis have been standardized by integrating different
medical disciplines, the classification of pancreatitis in cats
lacks standardization.2,3 In general, acute pancreatitis is
characterized by inflammation that is completely reversible
after removal of the inciting cause, whereas chronic
pancreatitis results in irreversible histopathologic
changes.1,4 The differences between acute and chronic
pancreatitis are mainly histopathologic, and not necessarily
clinical.5 Thus, it may be impossi- ble clinically to distinguish
an exacerbation of chronic pancreatitis from an episode of
acute pancreatitis.4,6
Both acute and chronic pancreatitis can be mild or
severe, but chronic cases are more commonly mild and
acute cases more com- monly severe. Clinically, mild
pancreatitis is associated with few sys- temic complications,
minimal pancreatic necrosis, and generally a low mortality,
 Pancreatitis can be accompanied by uncommon
pancreatic complications, the terminology of which
historically has been confus- ing in cats. In humans, the
current consensus statement defines acute peripancreatic
fluid accumulations, acute necrotic collections or, late after
the onset of acute pancreatitis, pseudocysts or walled-off
necrosis; each may be sterile or infected with bacteria. 2
These fluid accumulations have been described previously as
phlegmons or abscesses in cats.2,7

3 | ETIOLOGY

Pancreatitis has no age, sex, or breed predisposition. 1

Additionally, associations with body condition score,
dietary indiscretion, or drug history have not yet been
established in cats.
Although pancreatitis has been observed in cats with
various infections, including certain parasites (eg,
Toxoplasma gondii, Eurytrema procyonis, Amphimerus
pseudofelineus) and viruses (eg, coro- navirus, parvovirus,
herpesvirus, calicivirus), these infections represent rare
causes of pancreatitis in cats.6,8-10 Intraoperative
manipulation of the pancreas and pancreatic biopsy have
been suggested as risk factors for the development of
pancreatitis, but hypotension associated with anesthesia
may be more important than pancreatic manipulation.1
Although pancreatic injury is possible with manipulation, an
increased risk for the development of pancreatitis has not
been noted in studies involving pancreatic sampling.11,12
Neoplasia involving the pancreas has been associated with
pancreatitis, but is not diagnosed commonly in cats.13
Pancreatic trauma after road accidents or falling from high
build- ings, potentially resulting in pancreatic ischemia, has
been established as a cause.14 Two cases of pancreatitis in
cats after topical use of fenthion, an organophosphate
cholinesterase inhibitor, have been reported.15 Many other
pharmaceutical compounds, such as potassium bromide or
phenobarbital, have been implicated in causing pancreatitis
in humans and dogs, but have not been reported to cause
pancreatitis in cats.16,17 Hypercalcemia and snake bites have
been reported to rarely cause acute pancreatitis in other
species and in experimental models in cats.18-20
Autoimmune pancreatitis (AIP) occurs uncommonly in
people. It can be categorized as type 1 when the pancreas
is involved in a mul- tisystemic fibro-inflammatory disease
(also known as immunoglobulin 4 [IgG-4]-associated
systemic disease) and as type 2, which has been
associated with chronic enteropathy.21 The presence of
IgG4-staining cells in the pancreas and incidence of
circulating antibodies against the pancreas have not been
established in cats, but response to immu- nosuppressive
therapy with chronic pancreatitis may suggest an immune-
mediated etiology in some cats.
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FORMAN ET AL. 705

FIG U R E 1 Mechanisms that protect the pancreas from premature activation of zymogens (panel A). Events that can lead to
acute pancreatitis due to premature activation of trypsinogen (panel B)

Pancreatitis in cats has been associated with several

the pathogenesis of pancreatitis in both humans and
concurrent diseases, including diabetes mellitus, chronic
cats (Figures 1-3). The pancreas has several safeguards in
enteropathies, hepatic lipidosis, cholangitis, nephritis, and
place to protect against activation of zymogens of digestive
immune-mediated hemolytic ane- mia.22-26 Whether these
enzymes (ie, inactive preforms of digestive enzymes)
conditions cause, or are risk factors for, pan- creatitis has
within acinar cells (Figure 1A).28-31
not been determined.23,24,27 In summary, > 95% of cases of
Hypotheses for the spontaneous development of
pancreatitis in cats are considered to be idiopathic, and a
pancreatitis (Figure 1B) include autoactivation of cationic
specific cause cannot be identified.
trypsinogen (more likely when pH ≥5.0)29,30; activation of
zymogens by thrombin during bacte- rial toxemia, ischemia,
or hypoxia29; colocalization of lysosomal prote- ases and
4 | PATHOPHYSIOLOGY
zymogen granules (because of an apical block of zymogen
granule secretion)29; activation of trypsinogen by cathepsin
Premature activation of pancreatic digestive enzymes
B29-32; and, enterokinase entering the portal circulation after
within aci- nar cells, leading to activation of other
a meal in con- junction with biliary-pancreatic reflux, which
zymogens and resulting in pancreatic autodigestion, is
may cause zymogen activation.29
assumed to play an important role in
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ET
FORMAN

FIG U R E 3The pathophysiological mechanisms relevant for chronic pancreatitis that occur independently of trypsin
Local and systemic inflammation ensues in acute pancreatitis, which is independent of trypsin

activation and acute pancreatitis

ongoing stimulation of the NFκB
FIG U R
7
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FORMAN ET AL. 707

Over the past 3 decades, studies have concluded that tion (ie, platelet-derived growth factor, transforming growth
trypsinogen activation within the pancreas is the initiating factor β,
tumor necrosis factor α, and interleukins [IL]-1, IL-6, and IL-
event for acute pancreati- tis.33,34 However, there is no
10), or
consensus on how this inciting event unfolds. Recent recurrent oxidative stress, periacinar fibrosis develops. 55 Also,
hypotheses postulate that abnormalities in calcium sig- naling lipo- polysaccharides can activate PSCs by activation of toll-
lead to the colocalization of lysosomes and zymogen granules like receptor-4, suggesting a potential role of endotoxemia in
and trypsinogen activation, causing acinar cell death and the pathogenesis of pancreatic fibrosis.56 Additionally,
early activation of metabolites accumulate within the pancreas because of
the nuclear factor kappa B (NFκB) pathway.35-37 However, the decreased blood flow and potentially acidosis and low-grade
local and
ongoing activation of trypsinogen to trypsin. 57 Ductal
systemic inflammation that ensues in acute pancreatitis is
independent obstruction may develop as part of this process, further
of trypsin activation, but dependent on ongoing stimulation exacerbating the low-grade inflammation and fibrosis. This
of the NFκB may occur because of
pathway.38,39 The events that follow include an influx of
neutrophils, increased vascular permeability, and loss of apical
paracellular barriers. All of these events worsen acinar cell,
organ, vascular, and systemic injury.40 The extent of systemic
inflammation in an individual cat depends on the degree of
compensatory anti-inflammatory responses that are present.41
This proposed cascade of systemic inflammatory and
compensatory anti- inflammatory pathways during acute
pancreatitis has been described extensively in experimental
rodent models and people, but it is unknown whether this
cascade also occurs in cats.42-48
Hypoperfusion and thrombosis also may serve as
triggers for the development of peripancreatic necrosis. 40
Additionally, high concen- trations of bile acids or trypsin
within the pancreatic circulation may contribute to the
development of necrosis, although this has been identified
only in a feline pancreatitis model. 49 Overall, most experi-
mental models of pancreatitis fail to replicate the events
that occur in vivo in cats. However, it has been shown that
cats do have increased pancreatic permeability in response
to infusion of some substances, such as ethanol, but not
sterile bile.50,51 Experimentally, infusion of infected bile into
the pancreatic duct induced severe pan- creatitis, but when
bacteria suspended in saline were infused, only mild
pancreatitis developed.50,51 The unique anatomy of the cat,
with shared entry of the common bile duct and the
pancreatic duct into the duodenum, may explain the
association between acute cholangitis or bacterial
cholecystitis and pancreatitis.
When chronic pancreatitis occurs independently of acute
pancre-
atitis, trypsin activation is not considered the inciting
event.52 Studies suggest that cholecystokinin and oxidative
stress synergistically sensi- tize pancreatic acinar cells to
injury and necrosis, independent of tryp- sin activation.53
This occurs via calcium ion signaling and collapse of the
mitochondrial membrane potential.
In people, an acute initial insult, which may lead to
subclinical dis- ease, exposes the pancreas to oxidative
stress that causes activation of pancreatic stellate cells
(PSC).54 These PSCs are the source of fibro- sis and, if
exposed to continued stimulation by low-grade inflamma-
TABL E 1 Incidence of clinical signs and physical Abdominal radiography is neither sensitive nor specific for
examination findings reported in cats with the diagno- sis of pancreatitis in cats.64 The left lobe of the
pancreatitis11,15,59-63
pancreas occasionally
Clinical sign Incidence %

Lethargy 51-100
Partial/complete anorexia 62-97
Vomiting 35-52
Weight loss 30-47
Diarrhea 11-38
Dyspnea 6-20
Physical examination finding Incidence %

Dehydration 37-92
Hypothermia 39-68
Icterus 6-37
Apparent abdominal pain 10-30
Hyperthermia/fever 7-26
Abdominal mass/cranial abdominal 4-23
organomegaly

precipitation of protein and calcium in the duct after a

decrease in bicarbonate secretion, as well as decreased
fluid volume of pancreatic secretions.56 In feline
experimental models, chronic pancreatitis may result from
simple obstruction of the pancreatic duct, but this is
unlikely to be the primary pathogenesis in naturally
occurring dis- ease.50,51 Damage to the ductal epithelium
independent of ductal obstruction has been shown
experimentally to be essential for devel- opment of
chronic pancreatic inflammation in cats.58
Primary inflammation in neighboring abdominal
organs, such as the biliary system or the intestines, also
may cause inflammatory changes within the pancreas by
upregulation of inflammatory media- tors, their receptors,
or both.56

5 | CLINICAL SIGNS

Clinical signs and physical examination findings

associated with both acute and chronic pancreatitis in cats
are nonspecific (see Table 1). The presenting signs in each
case help to categorize the severity of the disease.
Interestingly, in contrast to people, where abdominal pain
is considered a hallmark finding of the disease, cats with
pancreatitis infrequently are reported to have abdominal
discomfort. However, the panel feels that this discrepancy
is most likely because of under- recognition of abdominal
pain in cats. Additional clinical signs may be caused by
concurrent diseases.59

6 | DIAGNOSTIC IMAGING

6.1 | Radiography
 708 FORMAN ET AL.

can be identified on ventrodorsal radiographs in cats with

echogenicity to the liver. The left lobe of the pancreas is
pancreatitis. Radiographic signs of severe pancreatitis in
located between the caudal curvature of the stomach and
cats can include loss of peritoneal detail in the cranial
the cranial border of the transverse colon and is more
abdomen or a mass effect. Although both can be assessed
readily visible than the right lobe.70 The pancreatic duct
by radiography, neither finding is specific for pancreatitis.65
usually is identified as a small hypoechoic tubular structure
Endoscopic retrograde cholangiopancreatography has
centrally located within the left lobe of the pancreas. The
been reported in healthy cats as a contrast fluoroscopic
right pancreatic lobe is small and can be difficult to identify.
technique to assess the biliary tract and the exocrine
It is best located by tracing the pancreatic body to the right
pancreas, but is technically challeng- ing, requiring special
of the portal vein and searching medial to the duodenum.
equipment and expertise, and is not yet established as a
The thickness of the left lobe ranges from 5-9 mm,
diagnostic test in cats.66
whereas the right lobe is 3-6 mm.70 In cats <10 years of
age, the mean duct diame- ter has been reported as 0.8 ±
0.25 mm and in cats >10 years of age as 1.2 ± 0.4 mm
6.2 | Ultrasonography
(ranging from 0.5 to 2.5 mm) in diameter.70,71
Sonographic findings in acute pancreatitis in cats
Ultrasonography remains the most routine diagnostic
(Figure 4) may be equivocal or may include pancreatic
imaging modal- ity for cats suspected of having pancreatitis
enlargement, a hyperechoic surrounding mesentery, and
and should be considered part of the minimum database in
focal abdominal effusion.65 The duode- num can be
these cats. Furthermore, cats with gastrointestinal signs
distended or corrugated. The sensitivity of these findings for
may have comorbidities of the intestines, liver, and
diagnosing acute pancreatitis in cats has been reported to
gallbladder, which also can be assessed using this
range between 11% and 67%, and sensitivity is considered
modality.67
to be severity- dependent and operator-dependent.65
Although high frequency transducers (>7.5 MHz), either
Pancreatic ultrasonography has developed over the last 3
curved or linear array, allow good visualization of the feline
decades and thus results of the various papers reporting on
pancreas, pancre- atic duct, surrounding mesentery, and
sensitivity may not be directly comparable.
vasculature, some limitations remain. These include
Ultrasonographic features of chronic pancreatitis (Figure
ultrasonographer experience and lack of speci- ficity to
5) are not well established in cats.59,72 Findings may include
differentiate normal pancreas from acute or chronic
a hyperechoic or mixed echoic pancreas, a dilated common
pancrea- titis and to differentiate hyperplasia from
bile duct, enlarged pan- creas, and irregular pancreatic
neoplasia when nodules or masses are detected.68
margins.72 Because of overlap between these features and
After clipping the ventral abdomen, swabbing with
those of acute pancreatitis, ultrasonography is a poor
alcohol, and applying ultrasound gel, the examination
diagnostic tool for assessing chronicity.59
begins by identifying the portal vein at the porta hepatis,
Pancreatic nodular hyperplasia can be an incidental
where the blood vessels and the com- mon bile duct exit the
finding in older cats.68 Compatible findings include
liver. The portal vein then is traced caudally to the caudal
parenchymal nodules up to
border of the stomach where the pancreatic body can be
1 cm in diameter, in addition to pancreatic enlargement.
seen ventral to the portal vein. 69 The normal pancreas is
Overlap exists among ultrasonographic findings in cats with
isoechoic or hypoechoic compared to the surrounding
pancreatitis, benign nodules, and malignant ones.
mesentery and is similar in
Morphologic tissue evaluation is necessary to differentiate
among them.70
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FIG U R E 4 Sagittal plane abdominal ultrasound image of
FIG UR E 5 Sagittal plane abdominal ultrasound image using
the left pancreatic limb in a cat with acute pancreatitis an
performed with an 8.5 MHz curved array transducer of the left pancreatic limb
8.5 MHz curved array transducer. The left limb of the of a cat with chronic pancreatitis. The pancreas is mildly
pancreas is enlarged (1.65 cm), diffusely hypoechoic, and enlarged at 1.5 cm (X-X). The pancreatic parenchyma is
surrounded by a halo of hyperechoic mesentery diffusely heterogenous and has a mottled echotexture. The
surrounding mesentery is unremarkable
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FORMAN ET AL. 709

Abdominal ultrasound examination also can be used to patient for comorbidities or complications.86
collect cytological samples. Ultrasound-guided fine-needle Hematologic findings in cats with pancreatitis vary. In
aspiration of the feline pancreas frequently is performed cats with acute pancreatitis, indicators of erythrocyte mass
using a 20G or 22G hypoder- mic or spinal needle and is safe (eg, red blood cell number, hematocrit or packed cell volume)
in cats, including those with pancreati- tis.73 An optimal may be increased second- ary to dehydration from fluid loss
technique has not been determined. One study found a as a result of decreased intake, vomiting, diarrhea, or some
67% cell recovery rate of diagnostic samples (24/73 combination of these. An inflammatory leukogram,
samples were nondiagnostic).73 To optimize sample characterized by neutrophilia with a left shift or
distribution for micro- scopic evaluation, samples obtained
by fine-needle aspiration should be smeared gently and
quickly, as would be done with peripheral blood.74
Pancreatic acinar cells deteriorate quickly, because of
release of digestive enzymes, making rapid cell
preservation imperative. 75

6.3 | Advanced imaging modalities

Contrast-enhanced Doppler ultrasonography of the

pancreas has not gained wide use in cats for the diagnosis
of pancreatitis.76,77
Recent studies have established the multiphase
contrast enhanced computed tomography (CT) features of
the normal and abnormal feline pancreas.78-81 The pancreas
in healthy cats enhances homogenously on arterial, portal,
and delayed phase scans. The pan- creas is
hypoattenuating or isoattenuating to the liver and spleen on
precontrast scans.82 Mean widths of the left limb, body, and
right limb determined by CT are similar to those of the
same regions obtained by ultrasonography.71,80,83
On magnetic resonance imaging (MRI), the normal
pancreas in cats is T1 hyperintense and T2 isointense to
hypointense.84,85 Mag- netic resonance imaging features of
suspected pancreatitis in 10 cats included T1 hypointensity
and T2 hyperintensity of the parenchyma, enlargement of
the pancreas, pancreatic duct dilatation, and contrast
enhancement.85 Nine cats had enlargement of the pancreas
>10 mm in thickness, 5 cats had pancreatic duct diameters
>2.5 mm, whereas 2 had peripancreatic hyperintensity.
None of these advanced imaging modalities have yet
been established as a routine diagnostic tool for
pancreatitis in cats.

7 | CLINICAL PATHOLOGY

7.1 | General clinical pathology

A complete blood count (CBC), routine serum or plasma

biochemistry profile, and urinalysis are part of the minimum
database obtained for evaluation of any sick patient.
Although these tests are not specific for the diagnosis of
either acute or chronic pancreatitis in cats, they are helpful
in eliminating other differential diagnoses and assessing the
neutropenia may be present, particularly with acute source of other enzymes is not limited to pancreatic acinar
pancreatitis. In severe cases, evidence for cells. Thus, an ideal marker for pancreatitis would be one
hypocoagulability with disseminated intra- vascular that is synthesized only by acinar cells and not cleared
coagulation may be present, as evidenced by prolonged immediately from the vascular space. Pancreatic lipase
clotting times, often occurring concurrently with fulfills these criteria, but to be useful as a biomarker, the
thrombocytopenia and increased fibrin degradation molecule must be measured using an assay specific for
products (FDPs), D-Dimers, or both.86 pancreatic lipase, which can be problematic.
Changes on the routine serum or plasma biochemical
profile also are variable and unpredictable. Hepatic
enzyme activities (eg, alanine amino transferase [ALT],
aspartate transaminase [AST]) and total bili- rubin
concentrations may be increased because of concurrent
inflam- mation of the biliary tree, extrahepatic biliary
obstruction, hepatic lipidosis, or some combination of
these.86
Serum creatinine, blood urea nitrogen (BUN), and
symmetric dimethylarginine (SDMA) concentrations may
be increased as a result of dehydration. In cats with
severe acute pancreatitis, azotemia and low urine specific
gravity may result from acute kidney injury, second- ary
to hypoxemia, impaired renal microcirculation, or
hypovolemia. 87
Azotemia has been linked to progression of
the disease.63 Hypoglyce- mia and hyperglycemia can be
seen with acute necrotizing and suppu- rative pancreatitis,
and hypoglycemia has been associated with poor
outcome.15,63
In other species, pancreatitis is associated with
hyperlipidemia, consisting of increased serum triglyceride
or cholesterol concentra- tions, or both.88-90 In cats
however, hypertriglyceridemia is rare and no association
of hypertriglyceridemia with pancreatitis has been
reported. 86,88,91
Changes in serum electrolyte
concentrations are vari- able, particularly depending on
the hydration status of the patient, but hypokalemia,
hypochloremia, hyponatremia, and hypocalcemia are the
most common electrolyte abnormalities in cats with
severe acute pancreatitis.86

7.2 | Lipase

Pancreatic acinar cells synthesize and secrete a wide

variety of diges- tive enzymes (eg, amylase, lipase, DNAse,
and RNAse) and inactive preforms of digestive enzymes
(zymogens; eg, trypsinogen, chymo- trypsinogen,
proelastase, prophospholipase), which are all released into
the small intestine via the pancreatic duct.92 However,
small amounts of these enzymes and zymogens reach the
vascular space. In principle, when the pancreas undergoes
inflammation or damage, zymogen granules leak from the
acinar cells into the interstitial space, ultimately reaching
the vascular space.
Measurement of any pancreatic enzyme or zymogen
theoretically could be used as a diagnostic marker for
acinar cell damage and pan- creatitis. However, some
enzymes are very small or are scavenged by inhibitors or
both, and are rapidly cleared from the bloodstream. The
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710 FORMAN ET AL.

Many lipases exist in the body, some of which occur in reported lower diagnostic accuracy in cats with pancreatitis
large quanti- ties, such as pancreatic lipase or gastric lipase. than did other studies, the reason for this discrepancy is
Various substrates are utilized for lipase activity assays, unclear.72 It remains to be further studied whether, as in
including 1,2-diglycerides, triolein, and 1,2-o-dilauryl-rac- dogs, inflammatory diseases of other organs (eg, chronic
glycero glutaric acid-(60 -methylresorufin) ester enteropathy, peritonitis) may be associated with pancreatic
(DGGR; eg, PSL by Antech Laboratories, Fountain Valley, inflammation and an increase in serum PLI concentration in
CA), but, despite choosing favorable conditions for cats.101
measurement of pancreatic lipase, none have shown to be Several commercial assays are available for the measurement
of
specific for the measurement of pancre- atic lipase to date.93
fPLI concentration. Although none have been analytically
Shortly after DGGR was introduced for the mea- surement validated in
of serum lipase activity in humans, studies showed that
DGGR-based assays not only measure pancreatic lipase, but
also hepatic and lipoprotein lipase, pancreatic lipase-related
protein 2 (PLRP2), vari- ous esterases, and even
hemoglobin.93 Although not demonstrated in cats per se, it
has been shown that PLRP2 is synthesized in many extra-
pancreatic tissues in dogs, such as gastric mucosa and renal
parenchyma (ahead of print, S. Lim, Texas A&M
University).94 Also, stimulation of hepatic and lipoprotein
lipase release by heparin administration in cats leads to an
increase in serum lipase activity as measured by DGGR.94
Theoretically, the lack of specificity of DGGR-based lipase
assays can be overcome by changing cutoff values for the
diagnosis of pancreatitis, but doing so causes a decrease in
sensitivity.
Few reports are available concerning the use of serum
lipase activity for the diagnosis of pancreatitis in cats. In an
older study that employed 1,2-diglyceride as a substrate,
none of 12 cats with severe acute pancreatitis had serum
lipase activity outside the reference interval and serum
lipase activities did not differ significantly among healthy
cats, cats with severe acute pancreatitis, and cats with
extra- pancreatic diseases.95 In another study, the
correlation of a DGGR- based lipase assay with Spec fPL
(Idexx Laboratories, Westbrook, ME; see below)
concentration was evaluated in 161 cats and Cohen's kappa
coefficient was reported to be 0.7, indicating discordance.72
Another means of measuring lipase is to measure serum
pancre- atic lipase immunoreactivity (fPLI). A commercial
ELISA for the mea- surement of fPLI, Spec fPL, is available.
Fewer articles have been published concerning measurement
of PLI as a diagnostic test for pan- creatitis in cats than for
dogs. However, most of the data suggest that the
measurement of fPLI is highly specific for the measurement
of pancreatic lipase and also is sensitive for the diagnosis of
pancreati- tis.72,96-98 However, it should be noted that
sensitivity is higher for severe cases than for mild cases. 99
One retrospective study reported a positive predictive value
of 90% and a negative predictive value of 76% for Spec fPL
in 275 sick cats.100 The authors suggested that a positive
Spec fPL result indicated pancreatitis as a probable diagnosis,
but that the test cannot be used to rule out pancreatitis. 100
However, cases in this study were not further categorized
based on severity or acute vs. chronic disease.100 One study
the primary literature, the Spec fPL has been analytically pan- creatic atrophy ultimately have a decreased serum
validated in a panel member's laboratory and has been used fTLI, indicating exocrine pancreatic insufficiency. Also,
for several clinical stud- ies published in the primary increased serum fTLI concen- trations previously have been
literature.96,98,102 Another commercial fPLI assay by associated with acute pancreatitis in cats.106 However, this
Laboklin (Bad Kissingen, Germany) failed analytical test is nonspecific and increased serum fTLI concentrations
validation. 100,103
also have been associated with chronic enteropathy and
At least 2 patient-side assays are available for the gastrointestinal lymphoma, and may occur in cats with a
immunologic measurement of pancreatic lipase. The SNAP decreased glomerular filtration rate86,105 Thus, the utility of
fPL (Idexx Laboratories, fTLI for the diagnosis of pancreatitis in cats is limited.
Westbrook, ME) is a semiquantitative test that has been
shown to correlate well with the Spec fPL and reports
results as either “normal”
or “abnormal.”96 Cats with a “normal” result are unlikely to
have pan-
creatitis, whereas those with an “abnormal” result might have
pancre- atitis or a Spec fPL in the equivocal range. Another
patient-side assay,
the VCheck fPL (Bionote, Hwaseong, Korea), is available in
parts of Asia. Although this species-specific assay has not yet
been assessed in the primary literature, the VCheck cPL for
use in dogs failed analytical validation.104
Agreement between DGGR-lipase (cutoff, 26 U/L) and
Spec fPL (cutoff, >5.3 μg/L) has been reported to have a κ
of 0.681 and 0.70,2 which is considered good when
comparing results of subjective diag-
nostic modalities, but less so for objective ones. There also
is poor agreement between the ultrasonographic
diagnosis of pancreatitis
and DGGR-lipase (cutoff, 26 U/L) or Spec fPL (cutoff,
>5.4 μg/L),
with κ = 0.22 and κ = 0.26, respectively.2 The highest
agreement of
both types of increased serum lipase results was with
hypoechoic or mixed echogenic pancreatomegaly.2
Another study reported poor agreement between
pancreatic histology and DGGR assay results
(cutoff, >26 U/L) or Spec fPL assay (cutoff, >3.5 μg/L), with
κ = 0.06
and κ = 0.10, respectively.3 However, this study
postulated that mild infiltration of the pancreas with
inflammatory cells should be consid-
ered normal.3,72

7.3 | Additional laboratory tests

Historically, increases in serum amylase activity have been

associated with acute pancreatitis in some cats. However,
because of both, poor diagnostic sensitivity and lack of
tissue specificity, enzymatic activity of amylase has
minimal utility as a biomarker for pancreatitis in
86,94,105
cats.
Trypsin-like immunoreactivity (TLI) measures trypsinogen,
trypsin, and likely some trypsin that has been bound by
protease inhibitors and is measured using a species-specific
immunoassay. Studies indi- cate variable results in cats with
pancreatitis, with sensitivity ranging from 30-86%.105,106
Because trypsinogen is produced by pancreatic acinar
cells, some cats with chronic pancreatitis and subsequent
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FORMAN ET AL. 711

Trypsinogen activation peptide (TAP) is a byproduct of

trypsino- gen activation that normally is excreted in the FIG U R E 6 Pancreatic aspirate from a cat. Modified Wright's
stain. 50× magnification. There is a cluster of acinar cells
urine. In health, this N- terminal peptide is present in very
(arrow) surrounded by erythrocytes and many
low concentrations in both urine and serum.105 In cats with
nondegenerate neutrophils (arrowheads), consistent with
acute pancreatitis, TAP is formed at a higher rate because suppurative pancreatic inflammation
of rapid cleavage of trypsinogen by cathepsin B or through
autoactivation.107 Although initially considered to be a
promising biomarker for the detection of pancreatitis,
inconsistent performance characteristics and lack of
commercial availability limit the utility of this analyte. 107

7.4 | Cytology

Cytology allows for close examination of a focal area of

aspiration, but individual aspirates may not be
representative of the tissue as a whole. With acute
pancreatitis, pancreatic aspirates often are highly cellular.
They are characterized by inflammatory cells,
predominantly neutrophils, that show variable degrees of
degeneration with fewer foamy macrophages on a
background of amorphous, necrotic debris, which
occasionally contains refractile crystalline material
(Figure 6).74,108 The inflammatory cells often are closely
associated with pancreatic acinar cells, with fewer ductal
epithelial cells.74 In the presence of inflammation, acinar cells
may appear dysplastic, with evi- dence for cytomegaly,
karyomegaly, prominent nucleoli, and increased cytoplasmic
basophilia.74 It is extremely difficult to distinguish cyto-
logically between primary pancreatitis with dysplastic
epithelial cells and an inflamed pancreatic carcinoma. 74,108-
110
However, pancreatic neoplasia is rare in cats and is
considered much less likely.13
With chronic pancreatitis, pancreatic aspirates often
are poorly
cellular, because of the presence of fibrosis, which
occasionally forms 1 or more mass-like lesions.110
Mesenchymal cells, including reactive fibroblasts, typically
exfoliate poorly. Variable numbers of mixed inflammatory
cells often are present, including lymphocytes and plasma
cells with occasional neutrophils.
 However, in both acute and chronic pancreatitis, the
absence of inflammatory cells should not preclude a 8.1 | Gross lesions of the pancreas
clinical diagnosis of pancrea- titis, because inflammatory
infiltration can be highly localized, espe- cially with When performing a laparotomy, gross lesions may not
chronic disease.74,108-110 always be apparent in cats with pancreatitis, but findings
Particularly with acute pancreatitis, a focal fluid suggestive of pancre- atic inflammation should be noted
accumulation may occur adjacent to the pancreas. and communicated to the patholo- gist.15,65 These are, in
Microscopic evaluation of this fluid after aspiration can be cases of acute pancreatitis, peripancreatic fat
done by cytology or by histology after preparation of a cell
block.111 Laboratory analysis of the fluid typically discloses
a high protein concentration with variable cellularity,
resulting in a classification of high-protein transudate
(modified tran- sudate) or exudate. The background of the
fluid often contains blood, mineral, and free lipid.
Nucleated cells primarily are variably degener- ate
neutrophils and activated macrophages, which often
contain crisp, distinct lipid vacuoles, hemosiderin, or both,
indicative of fat saponifi- cation and prior hemorrhage,
respectively.108

8 | PATHOLOGY

For collection of pancreatic biopsy specimens in cats,

surgical or lapa- roscopic biopsy procedures have been
shown to have a low risk for complications.112 Detailed
descriptions of these procedure have been published.113
Histologic analysis of pancreatic biopsy specimens has
been widely considered the gold standard for antemortem
diagnosis of pancreatitis in cats,1,59 although limitations exist
because of variable localization, consid- erable differences in
description of the lesions, and definition of severity.1 When
evaluating tissue biopsy specimens from cats with suspected
pan- creatitis, the accuracy of histologic diagnosis can be
limited by the multifocal distribution of lesions in cats with
both acute and chronic pan- creatitis.1,15,65 In 1 study, only
half of the cats diagnosed with pancreatitis had lesions
identified in all 3 regions of the pancreas.1 Thus, multiple
biop- sies are recommended, and pancreatitis should not be
excluded based on negative biopsy results alone.8 If only 1
biopsy can be performed, biopsy of the left lobe is
preferred.1 No available study correlates microscopic
findings with clinical disease classification or severity. Mild
histologic changes must be interpreted with caution
because it is not possible to determine which lesions are
relevant clinically.114 Pancreatic biopsy speci- mens, not to
exceed 1 cm3 to ensure proper fixation, should be placed
immediately into 10% neutral buffered formalin at a ratio of
10:1 (fixative to tissue) and stored at room temperature
until submission.115
Pancreatic histomorphology can be affected by the
sensitivity of
the pancreas to hypoxemia, whether induced by
hypotension during anesthesia or impairment of
pancreatic blood flow after manipulation of other organs
during surgery.116
 712 FORMAN ET AL.

necrosis, focal peritonitis, or pancreatic hemorrhage, edema,

pancreatitis in cats.1 The extent of concurrent acute and
and con- gestion or, in cases with severe pancreatic
chronic inflammatory changes of the pancreas is debated.
necrosis, fibrin strands that pass from the pancreatic
The histopathol- ogy report should specify whether
surface to the omentum, mesentery, or vis- ceral surfaces
pancreatitis is acute, acute on chronic (chronic active), or
of the liver.117 Gross lesions of chronic pancreatitis often are
solely chronic. This distinction likely is clinically relevant
more subtle, but in severe cases, the pancreas may be
because of the potential long-term sequelae of chronic
small with a firm, gray, multinodular appearance, 117 or with
disease, such as exocrine pancreatic insufficiency and dia-
a dull granular capsular surface.118 Adhesions to the small
betes mellitus.5
intestine also may be present.116

8.2 | Histologic classification and

interpretation

Although the relevance of histologic classification of

pancreatitis in cats, especially with respect to clinical findings
and prognosis, remains unclear,5 some histologic standards
for the classification of pancreatic inflammatory disease in
cats are provided.
In general, interpretation of pancreatic biopsy
specimens should include evaluation of inflammatory cell
infiltrates as well as their spatial distribution (ie, intralobular
vs. interlobular) and the presence of edema, necrosis,
FIG UR E 7 Histopathologic image of acute pancreatitis
fibrosis, amyloid, cystic acinar degen- eration, or acinar in a cat showing fat necrosis (star) and focal suppurative
atrophy.1 The consensus panel agreed that these histologic infiltration (arrow) with early focal acinar-to-ductal
findings should be reported following a previously publi- metaplasia (arrowhead). Scale
shed scoring system, which has been slightly modified by bar = 100 μm
the consensus panel (Table 2).1 This system can be used for
routine diagnostic pathology and may advance the
understanding of

TA BL E 2 Semiquantitative histopathology scoring system for pancreatitis in cats

Acute pancreatitis Chronic pancreatitis

Acute suppurativeAcute necrotizing

pancreatitispancreatitis

Lesion Edema and Inflammation, Fibrosis Cystic

fat lymphocyti degeneration
Inflammat necrosis c/
ion, mononuclea
neutrophil r
ic
Score 0 None None No or only isolated lymphocytes None None
or erratic small
nests of
lymphocytes
Score Mild infiltration Mild Mild mononuclear infiltrate Mild thickening of septa or ≤3 cysts
1
(<25% of (<25% of the (<25% of the parenchyma multifocal areas of mild
the parenchym affected) interstitial fibrosis
parenchym a (<15% of the
a affected) parenchyma affected)
affected)
Score Moderate Moderate Moderate mononuclear Moderate thickening of 4-5 cysts
2 infiltrati (25%-50% of infiltrate (25%-50% of the most septa
on the parenchyma (15%-30% of the
(25%-50% of the parenchyma affected) parenchyma
 parenchyma affected) affected)

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affected)
Score Severe Severe Severe mononuclear Severe thickening of all ≥6 cysts
3 infiltration (>50% of infiltration (>50% of the septa, dissecting the
(>50% of the the parenchyma lobules
parenchyma parenchyma affected) (>30% of the parenchyma
affected) affected affected)
Disease Total score: 1-2 mild AP, 3-4 moderate AP, Total score: 1-3 mild CP, 4-6 moderate CP, 7-9
severe CP index 5-6 severe AP

Source: Modified from DeCock et al1

Abbreviations: AP, acute pancreatitis; CP, chronic pancreatitis.
 19391676, 2021, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16053 by Cochrane Colombia, Wiley Online Library on [25/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons
FORMAN ET AL. 713

8.2.1 | Acute pancreatitis cholangitis, chronic enteropathy) play an important part in

successful management. In humans, no proven disease-
In general, pancreatic biopsy in cats with suspected specific pharmacologic treatment changes the natural
moderate or severe acute pancreatitis is infrequently progression of acute pancreatitis, although new therapeutic
performed (Figure 7). Thus, the majority of knowledge of targets and pharmacologic agents are on the horizon.123 For
histologic changes in cats with acute pancreatitis is from example, recently, a leukocyte function-associated antigen 1
necropsy material.1,15,49,119 (LFA-1) antagonist was approved for the treatment of acute
One study divided acute pancreatitis in cats into 2
forms: acute necrotizing pancreatitis with substantial
necrosis and acute suppura- tive pancreatitis where
necrosis is not a feature.15 This approach cor- responds to
the classification of acute pancreatitis in humans with a
mild interstitial form with little or no necrosis and a severe
necrotizing form.120 Additional studies are needed to
determine if these 2 mor- phologies are truly distinct in
cats.

8.2.2 | Chronic pancreatitis

Chronic pancreatitis in cats is characterized histologically

by lympho- cytic or lymphoplasmacytic inflammation,
fibrosis, and acinar atrophy (Figure 8).1,117 Retention cysts
(ie, microscopic intraparenchymal cysts) may be visible
and, although the most frequent type of pancrea- titis in
cats is mild,1,116 fibrosis can be extensive throughout the
interlobular septa and extend into the lobules in severe
cases.117 Extensive periductal fibrosis also may be present,
leading to localized stenosis and cyst formation, with
squamous metaplasia of the ductal epithelium.117 Acinar-to-
ductal metaplasia also can be present. Pan- creatic
neoplasia also can be associated with chronic pancreatitis. 13
Morphologically, chronic pancreatitis in cats resembles the
most fre- quent type of chronic pancreatitis in humans,
which is alcohol-induced chronic pancreatitis.121

9 | MANAGEMENT OF
ACUTE PANCREATITIS

Whenever possible, the inciting cause of acute pancreatitis

should be removed or treated. However, doing so may be
difficult, because most cases of pancreatitis are idiopathic
in cats. Management is predomi- nantly supportive and
symptomatic (see Supplementary Tables 1, 2, and 3 for a
formulary).11,62,116,122 Most management recommenda- tions
are extrapolated from management recommendations for
humans and dogs, expert opinion, or experimentally
induced models 8,19,41,49,116,123-129
of pancreatitis in cats.
Management of complications (eg, hepatic lipidosis,
cholestasis, acute kidney injury, pneumonia, shock,
myocarditis, disseminated intravascular coagulation,
multiorgan failure) and diagnosis and treat- ment of
comorbidities (eg, diabetes mellitus, diabetic ketoacidosis,
 hypovolemia.63 Dehydration, inappetence, vomiting, and
diarrhea can lead to hypoperfusion, resulting in metabolic
acidosis and prerenal azotemia, which can be

FIG UR E 8 Histopathologic image of chronic

pancreatitis in a cat, showing moderate lymphocytic
infiltration (star), interlobular and intralobular fibrosis
(arrows), and acinar-to-ductal metaplasia (arrowheads).
Scale bar = 100 μm

pancreatitis in dogs in Japan (personal communication,

Joerg Steiner 2020). Management goals for acute
pancreatitis are focused on fluid therapy, pain
management, control of vomiting and apparent nausea,
and nutritional support.

9.1 | Treatment of inciting cause

Several diseases and risk factors have been associated with

pancreati- tis, some of which allow specific treatment.
Some infectious agents that cause systemic disease,
which may include pancreatitis, such as Toxoplasma gondii
or others that rarely may cause pancreatitis, such as
Amphimerus pseudofelineus or Erytrema procyonis
infestation, are amendable to treatment.9,10,130 However,
because such cases are rare, generally there is no need to
test for these organisms.
A careful drug history should be taken, and those drugs
implicated in causing pancreatitis in cats or other species
should be avoided if possible.

9.2 | Fluid therapy

Intravenous crystalloid fluid is administered to correct

dehydration and electrolyte imbalances. In addition to the
adverse effects of hypo- volemia, the pancreas also is
susceptible to altered blood flow as a result of increased
vascular permeability (because of inflammation and acinar
cell injury) and microthrombi formation (because of hyp-
ercoagulability).131 Establishing normovolemia using early
IV fluid therapy may limit tissue damage by improving
pancreatic perfusion and oxygen delivery. In humans,
early aggressive hydration with lac- tated Ringer's solution
hastens clinical improvement in patients with acute
pancreatitis.124,125 The duration of clinical signs before
presen- tation to the hospital is directly proportional to the
odds of death, which is attributed, at least in part, to
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714 FORMAN ET AL.

corrected by fluid therapy. Concurrent hypoglycemia, composite pain scale (MCPS) has been validated to assess
diabetic ketoacidosis, and kidney disease may further postoperative pain in cats,143,144 but validated pain scoring
contribute to metabolic acidosis. Further study is needed to systems specifically for use in cats with pancreatitis are
determine the ideal fluid choice for the treatment of acute needed.
pancreatitis in cats, but lactated Ringer's or a similar Although abdominal pain is less frequently reported in
solution (eg, acetated Ringer's) often is the first choice. cats with acute pancreatitis as compared to humans or dogs,
Fluid therapy must be monitored closely to avoid it probably is underestimated.11 Opioids should be used as
overhydration. the primary analgesics for cats with acute pancreatitis.
Buprenorphine is adequate for most cats, whereas
methadone or fentanyl are good analgesic choices for
9.3 | Antiemetics and gastrointestinal
prokinetics

Vomiting and apparent nausea often are noted in cats with

pancreati- tis, but less frequently than in dogs. Antiemetics
are important to min- imize fluid and electrolyte losses and
to decrease the potential for regurgitation and secondary
esophagitis. Adequately managing nausea and vomiting likely
allows for earlier tolerance of either voluntary per os (PO)
intake or tube feeding.
The most commonly used antiemetic in cats is
maropitant citrate, a neurokinin1 receptor (NK1R)
antagonist, which acts both centrally and peripherally by
inhibiting the binding of substance P to the NK1R located in
the vomiting center, chemoreceptor trigger zone, and the
gastrointestinal tract.132-134 Both injectable and orally-
administered maropitant is used commonly to treat
vomiting in cats.133 Maropitant may have additional
benefits, such as visceral analgesia and anti- inflammatory
activity.134,135 Ondansetron is a 5-hydroxytryptamine3 (5HT3)
receptor antagonist that inhibits serotonin-induced
stimulation of vagal afferent activity and also can be used
as primary or additive antiemetic. Because maropitant and
5HT3 antagonists work by differ- ent mechanisms, these
drugs can be used in combination if needed.
In cats with functional gastroparesis or ileus, prokinetic
treatment
can be effective at improving motility. Metoclopramide has
question- able central antiemetic effects in cats, but when
administered as a constant rate infusion (CRI),
metoclopramide increases gastric empty- ing and decreases
gastric atony.136-139 One study suggested a contra- indication
to the use of metoclopramide because of dopamine
antagonism in cats with pancreatitis, but no clinical studies
have con- firmed such a contraindication. 127 Compounded
cisapride is an effec- tive PO prokinetic in cats and is the
treatment of choice for delayed gastric emptying.140,141
Erythromycin also has been shown to have a gastric
prokinetic effect in cats.136

9.4 | Pain management

Pain is difficult to evaluate in cats. 142 The Universidade

Estadual Paulista (UNESP)-Botucatu multidimensional
cats with more severe pain. Experimental evidence suggests acute pancreatitis, enteral nutrition may be provided by the
that mar- opitant citrate also may provide visceral gastric or jejunal route if PO feeding is not tolerated.157,161
analgesia. 134
Orally adminis- tered buprenorphine or Limited information about the optimal nutritional
management of
maropitant can be used for analgesia in outpatients.
acute pancreatitis is available for cats.162 Evidence in studies
Additionally, tramadol, gabapentin, or a combination of
of humans with pancreatitis and the results of experimental
these 2 drugs can be considered as PO analgesic
and clinical studies in animals support the use of enteral
options.146-150
nutrition.155,157,158,160-170 Because

9.5 | Appetite stimulants

Most cats with acute pancreatitis are inappetent, which

can contrib- ute to malnutrition and impaired
gastrointestinal barrier and immune function. Therefore,
restoring food intake is an important factor in recovery.
With mild to moderate pancreatitis, appetite stimulants
often are an effective way to restore voluntary food intake.
The most commonly prescribed appetite stimulants in cats
are mirtazapine and capromorelin. Mirtazapine has been
evaluated in inappetent cats, but can have adverse effects
(eg, vocalization, agitation, vomiting, abnor- mal gait or
ataxia, tremors, hypersalivation, tachypnea, tachycardia,
lethargy) with more adverse effects noted at higher
dosages.151 An additional benefit of mirtazapine may be its
antiemetic activity.152 Mirtazapine transdermal ointment
can be used in cats and generally is well-tolerated and
efficacious.153 The safety and efficacy of capromorelin PO
solution as an appetite stimulant have been reported in
healthy cats.154 Also, capromorelin recently has been
approved for use in cats with chronic kidney disease (CKD) in
the United States and can be considered as an appetite
stimulant for cats with pancreatitis.

9.6 | Nutrition

Nutritional support plays a central role in the management

of acute pancreatitis in humans. Lack of enteral nutrition
may lead to impaired gastrointestinal motility, intestinal
villous atrophy, compromised intes- tinal blood flow,
altered barrier function, and disruption of the normal
intestinal microbiota.155,156 Thus, in patients with severe
acute pan- creatitis, early enteral nutrition is viewed as an
active therapeutic intervention that minimizes infected
pancreatic necrosis and decreases the incidence of
multiple organ failure, thus improving out- come.157,158 In
contrast, prolonged fasting or parenteral nutrition is no
longer recommended unless enteral nutrition cannot be
achieved. Early enteral nutrition was evaluated in a
prospective randomized trial of humans with severe acute
pancreatitis, and compared nasojejunal and nasogastric
routes of feeding. It was determined that enteral nutrition
was tolerated by both routes with no difference in
outcome measures.159 The International Consensus
Guidelines Committee sup- ports the use of nasogastric
tube feeding in humans with acute pan- creatitis within 24
hours after hospital admission.160 In patients with severe
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FORMAN ET AL. 715

most cats with pancreatitis have been inappetent for a

placed under local anesthesia, avoiding the need for
variable period of time, any withholding of food may be
general anesthe- sia, and are a good choice for short-term
detrimental and is not rec- ommended. Additionally, some
nutritional support of hospi- talized or severely debilitated
cats, when inappetent or prevented from eating, will develop
cats. With nasoesophageal tubes, feeding is limited to a
hepatic lipidosis, which will substantially increase mortality.22
liquid diet. Placement of esophagostomy tubes requires
In cats with acute pancreatitis, PO feeding or enteral nutri-
general anesthesia and more technical expertise, but is an
tion via tube feeding should be initiated early. Cats with
excellent option when long-term feeding is anticipated.
mild to moder- ate acute pancreatitis often begin to eat with
Esophagostomy tubes allow for feeding of canned diets as a
appropriate supportive and symptomatic care, whereas
gruel.
severe cases with complications often will require a feeding
For cats in which enteral feeding is not an option
tube for appropriate alimentation. Additionally, a feed- ing
because of unmanageable vomiting, short-term
tube can be used for hydration, administration of PO
alimentation can be provided by partial or total parenteral
medications, and for gastric decompression, when indicated.
nutrition. However, survival rates for cats receiving partial
The dietary needs for cats with acute pancreatitis have not
parenteral nutrition exclusively are lower than in cats
been determined. Cats have high dietary protein
receiving supplemental enteral nutrition.175
requirements, making them susceptible to protein-energy
malnutrition and lean muscle mass loss during starvation.171,172
Also, cats have a higher tolerance for dietary fat than do 9.7 | Other treatments for cats with
dogs. Additionally, decreased dietary arginine and acute pancreatitis
methionine may limit the synthesis of hepatic lipoproteins
and phospholipids, which may contribute to the In addition to supportive and symptomatic care, cats with
development of hepatic lipidosis.173 Highly digestible diets, severe nec- rotizing pancreatitis and complications or
often labeled concurrent disorders require intensive care. Indicators of
as “gastrointestinal diets,” are recommended. Severely ill cats severe pancreatitis include marked dehy- dration (ie, 8%-
are prone 10%), persistent clinical signs despite medical manage- ment,
to food aversion and it may be prudent to delay the use of
hypotension, hypoglycemia, ionized hypocalcemia, or some
the long-term diet of choice until the cat has improved and is
combination of these. Severe complications may include
being fed at home.
systemic inflammatory response syndrome, cardiovascular
Placement of an enteral feeding tube is indicated for
shock, disseminated intravascular coagulation, pulmonary
cats that fail to respond to appetite stimulants within 48
thromboembolism, or multiorgan failure.8,176
hours or those that have a history of more prolonged
anorexia before presentation. Nasoesophageal tubes
(Figure 9A) or esophagostomy tubes (Figure 9B) are the
9.7.1 | Advanced fluid therapy
most commonly placed tubes in cats with acute
pancreatitis. Nasogastric tubes also are appropriate for Fluid, electrolyte, and acid-base imbalances must be
short-term use in hospitalized cats and allow for gastric assessed and corrected as early as possible. In addition to
suctioning when indicated.162 However, nasogastric correction of dehydration and maintenance fluid support
suctioning in humans with pancreatitis has been reported to with crystalloids, colloid therapy is beneficial when
lead to worsening gastric distension, gastro-esophageal indicated to maintain and support colloid osmotic
reflux, pain, and nausea and the efficacy of gastric
suctioning has not yet been evaluated in cats with
pancreatitis.173,174 Gastrostomy tubes or jejunostomy tubes
placed endoscopically or surgically are less com- monly
utilized. Nasoesophageal tubes are cost-effective and
easily
FIG U R E 9 Nasoesophageal
(A) and esophagostomy (B) tubes
are the most practical tubes for
alimentary support of cats with
acute pancreatitis
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716 FORMAN ET AL.

pressure and to prevent fluid imbalance and edema Antibiotics are not recommended for noncomplicated cases
formation. Fresh frozen plasma (FFP) provides colloid of pancreatitis. Reports of bacterial complications, such as
support by supplementing albu- min and is therapeutic for pancreatic abscessation, are rare.11 Broad-spectrum antibiotics
correction of coagulopathies secondary to disseminated should be reserved for cats with acute pancreatitis in which
intravascular coagulation. Studies in dogs suggest that pancreatic infection is suspected or confirmed (eg,
when α2-macroglobulin, a scavenger protein for activated pancreatic abscess, infected necrotic tissue), infection has
proteases in ascended the common pancreatic or bile duct, or CBC
serum, is depleted, death ensues rapidly.126 Fresh whole findings are suggestive of sepsis.11,122,181 Bacterial infections
blood and
can occur with con- current disorders, including cholangitis
FFP contain α2-macroglobulin. However, in clinical trials in
and aspiration pneumonia.
humans177,178 and in a retrospective study in dogs179 with
acute pan- creatitis, a survival benefit of plasma
administration was not demon-
strated. Also, FFP is not recommended in current consensus
statements on the treatment of acute pancreatitis in
humans.180 Although some questions remain about the
potential beneficial effects of plasma, it is an expensive
treatment that probably should be reserved for cats with
coagulopathy.
Synthetic colloids (eg, hydroxyethyl starch, dextran)
and hyper- tonic saline are cost-effective alternatives to
FFP. However, they pro- vide only colloidal support, rather
than supplementation of coagulation factors. None of these
products have been evaluated in cats with pancreatitis, and
they generally are reserved for animals with severe disease
and hypotension, refractory to the administration of
crystalloids. In cats receiving aggressive fluid support, it is
important to avoid volume overload by monitoring
respiratory rate and effort, performing pulmonary
auscultation, and measuring central venous pressure.
Cats that are hypotensive despite crystalloid and colloid
fluid therapy may require vasopressor support. Dopamine is
a vasopressor that also may increase pancreatic blood flow
and decrease microvas- cular permeability. However, its
effect on pancreatic perfusion is tran- sient, and dopamine
may induce vomiting. In 1 study, progression of
experimental pancreatitis in cats could be prevented by use
of low- dose dopamine therapy, but only when given within
12 hours of induction of pancreatitis.127 Although this time
limit hampers the clini- cal utility of dopamine in cats with
spontaneous pancreatitis, dopa- mine may be beneficial in
cats with pancreatitis that must undergo anesthesia. In
persistently hypotensive cats, additional vasopressors to
consider include norepinephrine, vasopressin, and
epinephrine.

9.7.2 | Antibiotics

In humans, antibiotics are not recommended in

management of acute pancreatitis unless an infection is
strongly suspected or has been con- firmed.180 In veterinary
medicine, acute pancreatitis is considered to be a sterile
process, based, in most instances, on inability to detect
microbial growth using routine bacterial culture media.
Fluorescence in situ hybridization has identified bacteria in Doppler echocardiog- raphy often permit rapid diagnosis to
the pan- creas of 35% of cats with moderate to severe guide treatment. Thoracocentesis with pleural fluid analysis
pancreatitis. 182
The localization and type of intrapancreatic is indicated in cats with pleural effusion. Although the
bacteria suggest translocation of enteric bacteria as a finding of simultaneous pleural and peritoneal effusions has
likely source.182 However, to date no evidence supports the been reported to indicate a poor to grave prognosis, such is
presence of bacterial DNA in pancreatic tissue as having not the consensus panel's experience in cats with
clinical relevance, and thus the consensus panel does not pancreatitis.190 Differentiation of pleural effusion secondary
suggest use of antibiotics in cats with pancreatitis unless to
strong clinical indications are present. Additionally,
antibiotic usage may be associated with adverse effects
and development of multidrug resistance.

9.7.3 | Corticosteroids

Corticosteroids are not used routinely for the treatment of

acute pan- creatitis in humans, dogs, or cats. Historically,
there has been a reluc- tance to use corticosteroids for the
treatment of pancreatitis, because of concerns that
glucocorticoids may be a risk factor for the develop- ment
of pancreatitis. However, a definitive relationship between
glu- cocorticoids and acute pancreatitis has not been
established in humans, and several studies indicate that they
do not cause pancreati- tis in dogs.183-185 Corticosteroids
have broad anti-inflammatory effects, and research
suggests they play a key role in enhancing apo- ptosis and
increasing production of pancreatitis-associated protein,
which exerts a protective effect against pancreatic
inflammation.186 Glucocorticoids also may treat critical
illness-related corticosteroid insufficiency, which is
reported in humans with acute pancreatitis.187 Recent
studies evaluating glucocorticoids for the treatment of
acute pancreatitis in humans and dogs have shown
improved out- comes.188,189 However, no studies have
evaluated the use of gluco- corticoids in cats with acute
pancreatitis, and thus there is insufficient evidence to
recommend their routine use.
Similar to antibiotics, corticosteroids are beneficial in
the treat-
ment of certain concurrent disorders, including chronic
inflammatory enteropathy and sterile cholangitis, and
should be considered if these comorbidities are present.
However, corticosteroids also are associ- ated with
important adverse effects for which cats with pancreatitis
are already at risk (eg, diabetes mellitus).

9.7.4 | Management of respiratory

complications

Tachypnea and labored breathing are common

complications of severe pancreatitis in cats, and may be
caused by pleural effusion or pulmonary edema secondary
to acute lung injury or both, acute respi- ratory distress
syndrome, volume overload, congestive heart failure,
aspiration pneumonia, pulmonary thromboembolism, pain,
or some combination of these. Thoracic radiographs and
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FORMAN ET AL. 717

congestive heart failure from that caused by pancreatitis is to moderate acute pancreatitis generally have a good
critically important for accurate modification of fluid prognosis with appropriate man- agement, whereas cats with
therapy and initiation of diuretic treatment. In cats with severe acute pancreatitis, especially when complications or
aspiration pneumonia, antibiotics and oxygen treatment (if comorbidities are present, have a guarded to grave
hypoxemia is present) are indicated. prognosis. Low plasma ionized calcium concentrations in cats
with acute pancreatitis have been associated with poor
outcome. 60,197

9.7.5 | Pancreatic surgery

In humans with acute pancreatitis, the most common

indication for invasive procedures, infected necrosis, now
usually is treated using minimally invasive approaches (eg,
percutaneous, endoscopic, laparo- scopic, or retroperitoneal),
and traditional open resection of necrotic tissue usually is
avoided because of risk of major complications or death.161
Surgical management rarely is indicated in cats with acute
pancreatitis, and clear indications to perform surgery have
not been determined. In cats with severe acute pancreatitis
and concomitant extrahepatic biliary obstruction or
pancreatic abscess, surgical inter- vention may be
beneficial.191 However, most clinicians are conserva- tive
when considering pancreatic surgery, because most cats
with severe pancreatitis are poor surgical candidates, and a
benefit of sur- gery, including in cats with extrahepatic bile
duct obstruction, has not been proven.191

9.7.6 | Other therapeutic strategies

Many other therapeutic strategies, including trypsin

inhibitors (eg, aprotinin), platelet-activating factor
inhibitors, antacids (eg, proton pump inhibitors),
antisecretory agents (eg, anticholinergics, calcitonin,
glucagon, somatostatin), selenium and other antioxidants,
and perito- neal lavage have been evaluated in
experimental studies or in human patients with pancreatitis,
but are not efficacious. None of these ther- apeutic
strategies have been evaluated in cats with pancreatitis,
and their routine use is not recommended. Hyperbaric
oxygen therapy (HBOT) is recommended by some
veterinary specialists for the man- agement of pancreatitis,
but no studies are available in veterinary patients and only
a few experimental studies in rodents and a case report in a
human patient are available.192-195 Also, HBOT has not been
included in current treatment guidelines for humans with
pan- creatitis.196 Until clinical studies are performed in cats,
routine use of this modality in cats cannot be
recommended.

10 | PROGNOSIS OF
ACUTE PANCREATITIS

The mortality rate in cats with acute pancreatitis ranges

from 9% to 41%, based on 4 studies. 60,63,102,162 Cats with mild
Hypoglycemia and azotemia also are poor prognostic renal diets, low-carbohydrate diets) is helpful in managing
indicators.63 Mortality in humans with acute pancreatitis cats with this condition. In contrast, high fat diets may be
is reported to be 5%- 15%, but it has decreased over helpful in providing adequate caloric intake with a small
time and overall mortality of people with acute food volume. Overall, it is recommended that each cat's
pancreatitis is approximately 2% with state-of-the-art diet be assessed and
stan- dard of care. 161,198

11 | MANAGEMENT OF
CHRONIC PANCREATITIS

Little research is available on the treatment of chronic

pancreatitis in cats, and most recommendations are
based on case reports or per- sonal opinion rather than
peer-reviewed literature. Chronic pancreati- tis in cats
often occurs concurrently with other diseases,23 and
diagnosis and treatment of these conditions usually takes
clinical pri- ority. Targeted management of chronic
pancreatitis often is not required. However, if chronic
pancreatitis occurs as an isolated condi- tion or appears to
be a complicating factor that worsens the prognosis of
comorbidities, particularly diabetes mellitus, then targeted
manage- ment is indicated (see Supplementary Tables 1,
2, and 3 for a formulary).

11.1 | Analgesia

Visceral pain is mediated by cytokines, substance P,

neurokinin A, and calcitonin gene peptide, and thus
traditional analgesics may not be effective in cats with
chronic pancreatitis.199 During overt bouts of disease,
transmucosal buprenorphine can be administered. For
long- term treatment, gabapentin or tramadol may be
better choices.200 Maropitant, often selected for control of
vomiting, also may provide visceral analgesia in cats.201
Supplementation of pancreatic enzymes has been
suggested in humans with pancreatitis to potentially
decrease pain associated with feeding, but doing so is no
longer rec- ommended unless subclinical exocrine
pancreatic insufficiency is pre- sent. 202
Development of
feline-specific monoclonal antibodies targeting pain
mediators is a promising area of research that may
transform pain management in cats with pancreatitis.203

11.2 | Nutritional support

Enteral nutritional support or dietary modification may

be required for treatment of underlying or concurrent
diseases, but rarely is required to manage chronic
pancreatitis as a primary condition. Although scientific
evidence that dietary fat is deleterious in cats with
pancreatitis is not available and the majority of the
consensus panel did not have any concerns about
dietary fat content in cats with chronic pancreatitis,
some panel members felt that avoiding high fat diets (eg,
 19391676, 2021, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16053 by Cochrane Colombia, Wiley Online Library on [25/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons
718 FORMAN ET AL.

altered if the diet is thought to have contributed to decreased, dis- continuation of treatment should be
pancreatitis or a comorbidity. considered. In cats that show a clinical response,
continuation of treatment is indicated. Unmasking latent
toxoplasmosis may be a concern with long-term use of
11.3 | Antiemetics and appetite stimulants high-

During bouts of vomiting or when inappetence is

attributable to nau- sea, antiemetic treatment using
maropitant or a 5HT3 antagonist should be considered.
Appetite stimulants, such as mirtazapine, may be useful to
help maintain voluntary food intake.

11.4 | Antimicrobial treatment

Bacterial infection is not implicated in chronic pancreatitis

and antimi- crobials are not indicated unless required to
treat concurrent condi- tions or infectious complications.

11.5 | Other supportive treatment

Cobalamin supplementation is indicated when

hypocobalaminemia is documented. It may be considered
when anorexia or concurrent gas- trointestinal disease is
present.

11.6 | Anti-inflammatory and

immunosuppressive therapy

Inflammation and subsequent fibrosis are important

pathologic aspects of chronic pancreatitis in cats and may
lead to subsequent deficiencies of the exocrine or endocrine
functions of the pancreas. Prednisolone is a commonly used
anti-inflammatory and immunosup- pressive drug that is
potentially antifibrotic and has minimal adverse effects in
cats when used at low doses. The adverse effect of most
concern is enhanced peripheral insulin resistance, and the
risk of dia- betes mellitus.
Although some panel members felt that prednisolone
should only be used in cats that are not hyperglycemic and
only at anti- inflammatory dosages (ie, 0.5-1.0 mg/kg PO
q24h on a tapering schedule), other panel members felt that
immunosuppressive dosages of prednisolone (eg, 2.0 mg/kg
q12h for 5 days and then 1.0 mg/kg q12h for 6 weeks with
a decreasing dosing schedule after that time) with close
monitoring (ie, clinical re-evaluation and measurement of
fPLI after 2-3 weeks) could have a beneficial effect. If
hyperglycemia develops, or is pre-existing, some panel
members recommend the use of cyclosporine (5 mg/kg q24h
for 6 weeks) with close monitoring (ie, clinical re-evaluation
and measurement fPLI after 2-3 weeks).204,205 In cats treated
with either prednisolone or cyclosporine in which clinical
signs have not improved and pancreatic lipase has not
dose cyclosporine.206 Toxoplasmosis may be of a greater basis. Dr. Steiner also serves as a paid con- sultant and
concern in geographic locations where cats frequently speaker for Idexx Laboratories, Westbrook, ME, the
hunt in the wild or con- sume raw meat and has been manufacturer of the Spec fPL and SNAP fPL assays and
reported in renal transplant cats and a cat treated for for ISK,
atopy.207-209
Other immunosuppressive medications, such as
chlorambucil, also may be beneficial, but have not been
studied in cats with chronic pancreatitis.

11.7 | Monitoring

If serum fPLI is increased at the time of diagnosis, it can be

used to monitor response, along with clinical variables.
However, the sensitiv- ity of serum fPLI is lower in cats
with mild disease than in those with severe disease and,
like any other diagnostic test, this laboratory test should
not be used in isolation to assess clinical remission.

12 | CONCLUSION

In conclusion, although both acute and, especially, chronic

pancreatitis are considered to occur commonly in cats,
diagnosis remains challeng- ing. Most of what is known
regarding the etiology and pathogenesis of pancreatitis in
cats is extrapolated from spontaneous disease in other
species or from experimental animal models, including
cats. Accurate diagnosis of pancreatitis in cats requires the
integration of history and clinical findings, diagnostic
imaging, laboratory data, and potentially cytology or
histopathology. Depending on the clinical find- ings in an
individual cat, additional diagnostic tests to rule out other
differential diagnoses may be needed.
Management of acute pancreatitis involves treatment
of potential causes, fluid therapy, analgesics, antiemetics,
nutritional support, and other symptomatic and supportive
care as needed. Management of chronic pancreatitis
involves the treatment of potential causes, diag- nosis and
management of concurrent conditions, analgesics, anti-
emetics, and potentially anti-inflammatory and
immunosuppressive treatment.

ACKNOWLEDGMENT
No funding was received for this study. We acknowledge
the help of Mr. Brian Collins, Outreach Librarian at the
School of Veterinary Med- icine, Louisiana State University
for his help with literature research and building the
reference database for the consensus statement using
ACVIM guidelines. We also thank Kate Patterson at
MediPics and Prose in Fairlight, New South Wales, Australia
for creating Figures 1-3.

CONFLICT OF INTEREST DECLARATION

Dr. J. Steiner serves as the director of the Gastrointestinal
Laboratory at Texas A&M University, which offers
measurement of fPLI concen- tration on a fee-for-service
 19391676, 2021, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16053 by Cochrane Colombia, Wiley Online Library on [25/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons
FORMAN ET AL. 719

Osaka, Japan, the manufacturer of fuzapladib. None of these immunoreactivity concentrations and abdominal
organiza- tions influenced the outcome of this consensus ultrasonographic findings in cats with trauma resulting
from high-rise syndrome. J Am Vet Med Assoc.
statement. None of the other authors declare any conflict of
2013;242:1238-1243.
interest. 15. Hill RC, Winkle TJ. Acute necrotizing pancreatitis and acute
suppu- rative pancreatitis in the cat. J Vet Intern Med.
OFF- LABEL ANTIMICROBIAL DECLARATION 1993;7:25-33.
16. Badalov N, Baradarian R, Iswara K, Li J, Steinberg W,
Authors declare no-off label use of antimicrobials.
Tenner S. Drug-induced acute pancreatitis: an evidence-
based review. Clin Gastroenterol Hepatol. 2007;5:648-661.
INSTITUTIONAL ANIMAL CARE AND USE
COMMITTEE (IACUC) OR OTHER APPROVAL
DECLARATION
Authors declare no IACUC or other approval was needed.

HUMAN ETHICS APPROVAL DECLARATION

Authors declare human ethics approval was not needed for
this study.

ORCID
Joerg M. Steiner https://orcid.org/0000-0003-3336-2086

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SUPPORTING INFORMATION
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How to cite this article: Forman MA, Steiner JM,

Armstrong PJ, et al. ACVIM consensus statement
on pancreatitis in cats. J Vet Intern Med.