P y o me tra in Smal l A n i m a l s

Ragnvi Hagman, DVM, PhD

KEYWORDS
 Endometritis  Cystic endometrial hyperplasia  Escherichia coli  Endotoxemia
 Aglepristone  Prostaglandin  Cabergoline  Bromocriptine

KEY POINTS
 Pyometra foremost affects middle-aged to older intact bitches and queens, usually within
4 months after estrus.
 Hormonal and bacterial factors are involved in the pathogenesis, and progesterone plays
a key role.
 Cystic endometrial hyperplasia (CEH) is a predisposing factor, but pyometra and CEH can
develop independently.
 Pyometra induces endotoxemia and sepsis, and early diagnosis and treatment increase
the chances of survival.
 Diagnosis is based on clinical signs and findings on physical examination, hematology and
biochemistry laboratory tests, and diagnostic imaging identifying intrauterine fluid.
 Surgical ovariohysterectomy is the safest and most effective treatment, as the source of
infection is removed and recurrence prevented. Medical treatment can be an alternative in
young and otherwise healthy breeding animals with open cervix and without other uterine
or ovarian pathologies.

Video content accompanies this article at http://www.vetsmall.theclinics.com.

INTRODUCTION

Pyometra, literally meaning “pus-filled uterus,” is a common illness in adult intact female
dogs and cats and a less frequent diagnosis in other small animal species.1,2 The dis-
ease is characterized by an acute or chronic suppurative bacterial infection of the uterus
post estrum with accumulation of inflammatory exudate in the uterine lumen and a va-
riety of clinical and pathologic manifestations, locally and systemically.3 The disease de-
velops during the luteal phase, and progesterone plays a key role for the establishment
of infection with ascending opportunistic bacteria. The pathogen most often isolated
from pyometra uteri is Escherichia coli.4–6 A wide range of clinical signs are associated
with the disease, which can be life-threatening in severe cases. It is important to seek

The author has nothing to disclose.

Department of Clinical Sciences, Swedish University of Agricultural Sciences, PO Box 7054,
Uppsala SE-75007, Sweden
E-mail address: [email protected]

Vet Clin Small Anim 48 (2018) 639–661

https://doi.org/10.1016/j.cvsm.2018.03.001 vetsmall.theclinics.com
0195-5616/18/ª 2018 The Author. Published by Elsevier Inc. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
640 Hagman

immediate veterinary care when pyometra is suspected because a patient’s status may
deteriorate rapidly and early intervention increases chances of survival. The diagnosis is
generally straightforward but can be challenging when there is no vaginal discharge and
obscure clinical signs. Surgical ovariohysterectomy (OHE) is the safest and most effi-
cient treatment, but purely medical alternatives may be an option in some cases.

EPIDEMIOLOGY AND RISK FACTORS

Pyometra is an important disease, particularly in countries where elective neutering of

healthy dogs and cats is not generally performed.1,2,7 In Sweden, in average 20% of all
bitches are diagnosed before 10 years of age and more than 50% in certain high-risk
breeds. The disease generally affects middle-aged to older bitches, with a mean age
at diagnosis of 7 years, and has been reported in dogs from 4 months to 18 years of
age. The overall incidence rate is 199 per 10,000 dog-years at risk.7 In cats, pyometra
is not as common, which is believed to depend on less progesterone dominance due
to seasonality and induced ovulation. In queens, 2.2% are diagnosed with the disease
before 13 years of age, with an incidence rate of 17 cats per 10,000 cat-years at risk.2
The mean age at diagnosis is 5.6 years, with an age range of 10 months to 20 years,
and the incidence increases with age and markedly over 7 years of age.2,8–10 A higher
incidence in some dog and cat breeds indicates that they may have a genetic predis-
position.1,2,7,9 Exogenous treatment with steroid hormones, such as progestogens, or
estrogen compounds that increase the response to progesterone, are associated with
increased risk of the disease.11,12 Pregnancy is slightly protective in dogs, an effect
that is also influenced by breed.13 Cystic endometrial hyperplasia (CEH) is believed
to increase the uterine susceptibility for infection.14,15 In cats, little is known about
risk factors and protective factors but previous hormone therapy (ie, exogenous pro-
gesterone) is associated with an increased risk.16

ETIOLOGY AND PATHOGENESIS

The complex pathogenesis of pyometra is not yet completely understood but involves
both hormonal and bacterial factors. Although most studies have been done in dogs, the
development is believed similar in cats. The uterine environment during the luteal phase
is suitable for pregnancy but also for microbial growth. Progesterone stimulates growth
and proliferation of endometrial glands, increased secretion, cervical closure, and sup-
pression of myometrial contractions.14 The local leukocyte response and uterine resis-
tance to bacterial infection also become decreased.17–19 Circulating concentrations of
estrogen and progesterone are not usually abnormally elevated in pyometra, and
increased numbers and sensitivity of hormone receptors are believed to initiate an
amplified response.20,21 Simultaneous corpora lutea and follicular cysts are more often
found in bitches with pyometra, supporting a synergistic hormonal effect.22
Progesterone-mediated pathologic proliferation and growth of endometrial glands
and formation of cysts (ie, cystic endometrial hyperplasia [CEH]) is believed to predis-
pose for pyometra but the 2 disorders can develop independently (Fig. 1).23 Sterile
fluid may accumulate in the uterine lumen, with or without CEH, which is defined as
hydrometra or mucometra or, more rarely, hemometra, depending on the type of fluid
and its mucin content. Clinical signs are generally subclinical or mild when there is no
bacterial infection of the uterus.3,24,25
E coli is the predominant pathogen isolated from pyometra uteri, but other species
may also occur (Table 1).4,26–29 More than 1 bacterial species can be involved, and
cultures are sometimes negative.28,29 Emphysematous pyometra is caused by gas-
producing bacteria.30 A healthy uterus eliminates bacteria that have entered during
 Pyometra in Small Animals 641

Fig. 1. Images of histologic examination findings in uterine tissues examples from dogs with
CEH/pyometra. (A) CEH; (B) larger magnification of (A); (C) CEH–endometritis; (D) pyometra;
(E) larger magnification of (D); (F) pyometra–atrophic endometrium.

cervical opening, but the clearance capacity varies depending on the estrus cycle
stage. Experimental E coli infection during the luteal phase more often leads to
CEH/pyometra compared with in other estrus cycle stages.31 The infection is most
likely ascending because the same strains are present in the gastrointestinal tract,
but hematogenic spread could possibly also occur.6,32,33 E coli are natural inhabitants

Table 1
Bacterial species isolated from the uterus in bitches and queens with pyometra

Proportion in Proportion in
Organism Bitches (%) Queens (%)
Escherichia coli 65–90 71
Staphylococcus spp 2–15 8
Streptococcus spp 4–23 19
Pseudomonas spp 1–8 —
Proteus spp 1–4 —
Enterobacter spp 1–3 —
Nocardia spp 1 0
Pasteurella spp 1–2 <1
Klebsiella spp 2–14 <1
Mixed culture 4–16 —
No growth 10–26 20
Mycoplasma spp, Enterococcus spp, <1 <1
Clostridium perfringens, Corynebacterium
spp, Citrobacter spp, Moraxella spp,
Edwardsiella spp, and others

Data from Refs.4,5,8–10,28,30,47,52–54,93

642 Hagman

of the vaginal flora34 and have an increased ability to adhere to specific receptors in a
progesterone-stimulated endometrium.5 Certain serotypes of E coli are more common
and often exhibit the same virulence traits as isolates from urinary tract infections.35–37
The same bacterial clone can frequently be isolated from the uterus and the urinary
bladder in pyometra.5,6,33
Bacteria and bacterial products are potent inducers of local and systemic inflamma-
tion. Endotoxin, lipopolysaccharide components of Gram-negative bacteria, such as
E coli, are released into the circulation during bacterial disintegration and induces fe-
ver, lethargy, tachycardia, and tachypnea.38 Higher endotoxin concentrations may
cause fatal shock, disseminated intravascular coagulation, and generalized organ fail-
ure.39,40 Pyometra has been associated with endotoxemia40,41 and bacteremia,42 and
disseminated infection may affect various organs.43,44 Approximately 60% of bitches
and 86% of queens with pyometra suffer from sepsis (ie, life-threatening organ
dysfunction caused by a dysregulated host response to an infectious process).45,46
The illness is considered a medical emergency and it is important to seek immediate
veterinary care because a patient’s health status may deteriorate rapidly.

CLINICAL PRESENTATION

Typically, middle-aged to older animals are presented up to 2 months to 4 months af-

ter estrus with a history of various signs associated with the genital tract and systemic
illness (Table 2). A continuous or intermittent mucopurulent to hemorrhagic vaginal
discharge is often present but can be absent if the cervix is closed.47 The systemic
illness is often more severe if the cervix is closed, and the uterus may become severely

Table 2
History data and clinical signs in bitches with pyometra

Case History and Clinical Signs In Percentage (%)

Vaginal dischargea 57–88
Lethargy/depressiona 63–100
Inappetence/anorexiaa 42–87
Polydipsiaa 28–89
Polyuriaa 34–73
Vomiting 13–38
Diarrhea 0–27
Abnormal mucous membranes 16–76
Dehydration 15–94
Palpable enlarged uterus 19–40
Pain on abdominal palpation 23–80
Lameness 16
Distended abdomen 5
Fever 32–50
Hypothermia 3–10
Tachycardia 23–28
Tachypnea 32–40
Systemic inflammatory response syndrome 57–61
a
Usually in greater than 50% of the bitches.
Data from Refs.24,25,48,49,53,93,107
 Pyometra in Small Animals 643

distended.48 Classic systemic signs are anorexia, depression/lethargy, polydipsia,

polyuria, tachycardia, tachypnea, weak pulse quality, and abnormal visible mucous
membranes. Fever, dehydration, vomiting, abdominal pain on palpation, anorexia,
gait abnormalities, and diarrhea are present in approximately 15% to 30% of bitches
with the disease.47,49 The most common clinical signs in queens are vaginal discharge,
lethargy, and gastrointestinal disturbances, such as anorexia, vomiting, and diarrhea
(Fig. 2).8,10 Vaginal discharge may absent or concealed by fastidious cleaning habits in
up to 40% of affected queens.9 Weight loss, dehydration, polydipsia/polyuria, tachy-
cardia, tachypnea, abdominal pain on palpation, abnormal mucous membranes (pale,
hyperemic, or toxic), and unkept appearance are other findings associated with feline
pyometra.

DIAGNOSIS

The disease is easy to recognize in classic cases but can be more challenging when
there is no vaginal discharge (ie, closed cervix), and the history and clinical picture are
obscure. Pyometra should be a differential diagnosis in bitches and queens admitted
with signs of illness after estrus, but the disease can occur at any time during the
estrus cycle. The preliminary diagnosis is based on history and findings on physical
and gynecologic examinations, hematology and blood biochemistry analyses, and
ultrasonography and/or radiography of the abdomen. Bacteriologic culturing of the
vaginal discharge is not helpful for the diagnosis because the same microbes are pre-
sent in the vagina in healthy animals.50 Careful abdominal palpation, to avoid rupture
of a fragile uterus, may identify an enlarged uterus. Diagnostic imaging is valuable for
determining the uterine size and to rule out other causes of uterine enlargement
(Fig. 3A–G). Radiography frequently identifies a large tubular structure in the caudo-
ventral abdomen. Ultrasonography has the advantage of detecting intrauterine fluid,
even when the uterine diameter is within the normal range, and of revealing additional
pathologic changes of the uterine tissue and ovaries, such as ovarian cysts or CEH,
which may affect the outcome of medical treatment negatively (Fig. 4, Video 1).
More advanced diagnostic imaging techniques are seldom necessary. Differential di-
agnoses include mucometra, hydrometra, and hemometra that may have similar clin-
ical presentation and ultrasonography findings.51 Vaginal cytology usually shows
severe leukocyte degeneration, neutrophils and some macrophages, plasmacytes,
and lymphocytes but bacterial phagocytosis is not always visible.52 Vaginoscopy is

Fig. 2. Purulent vaginal discharge in a queen with open cervix pyometra.

644 Hagman

Fig. 3. (A) Uterine enlargement in a cat; diagnosis: pyometra. Tubular structures of soft
tissue/fluid opacity (arrows). (B) Uterine enlargement in a dog; diagnosis: CEH. Tubular
structures of soft tissue/fluid opacity (arrows). (C) Ultrasound images of CEH in a dog.
Thickening of the uterine wall with multiple anechoic cystic structures, no intraluminal
fluid. Uterine diameter was 2 cm. Cervix located between double-headed arrow. (D)
CEH and pyometra—thickening of the uterine wall with multiple anechoic cystic struc-
tures; the intraluminal fluid was purulent. Both images in (D) are of the same uterus.
The uterine diameter was 2 cm. (E) CEH in a rabbit. (F) Atrophic wall pyometra: enlarged
uterus with a thin wall and echogenic intraluminal fluid. (G) Uterus or small intestines of
the same diameter (radiograph to the left). Uterus between white double-headed ar-
rows, CEH. Small intestine with typical layered appearance between black double-headed
arrows.
 Pyometra in Small Animals 645

Fig. 4. Canine uterus with CEH and purulent appearance of the fluid in some cysts.

helpful for determining the origin of a vaginal discharge and to exclude other pathol-
ogies but is usually not performed in the emergent clinical setting. The diagnosis pyo-
metra is verified by postoperative macroscopic and histologic examination of the
uterus and ovaries, and microbiological examination of the uterine content.

CLINICOPATHOLOGIC TESTING—LABORATORY PARAMETERS

Hematology and biochemistry parameter abnormalities are generally investigated,49,53

with additional tests performed depending on the health status (Table 3). Leukocytosis,
with neutrophilia and left shift, and monocytosis are characteristic findings in pyometra
together with normocytic, normochromic regenerative anemia. Renal dysfunction is
common, to which endotoxemia, glomerular dysfunction, renal tubular damage and
decreased response to antidiuretic hormone contribute.54,55 Concomitant cystitis
and proteinuria usually resolve after treatment of the pyometra, but severe proteinuria
that remains may predispose for renal failure.54 Circulating inflammatory mediators
and acute phase proteins are generally increased.56 A hypercoagulable state is usually
present.57

TREATMENT ALTERNATIVES

Surgical treatment, OHE, is safest and most effective because the source of infection
and bacterial products are removed and recurrence prevented.53 Laparoscopically
assisted techniques have been developed but are not commonly used and only in
mild cases.58 Medical management (solely pharmacologic) may be possible in young
and otherwise healthy breeding animals or in a patient for which anesthesia and sur-
gery is hazardous. In patients with serious illness or when complications, such as peri-
tonitis or organ dysfunctions, are present or the cervix is closed, medical treatment is
not recommended and surgery is the treatment of choice. Candidates for medical
treatment need to be carefully selected for best prognosis for recovery and subse-
quent fertility.59 Microbiological culturing and sensitivity testing are prerequisites for
optimal selection of antimicrobial therapy, for which samples are obtained from the
cranial vagina or postoperatively from the uterus.

SURGICAL TREATMENT

Prior to surgery, the patient is stabilized with adequate intravenous fluid therapy to
correct hypotension, hypoperfusion, shock, dehydration, acid-base balance and
646 Hagman

Table 3
Laboratory findings in bitches with pyometra

Abnormality In No. of Bitches (%)

Leukopenia 4
Leukocytosis 61
Neutropenia 4
Neutrophilia 55
Monocytopenia 3
Monocytosis 60
Anemia 55
Band neutrophils 40
Band neutrophils >3% 83
Trombocytopenia 37
Toxic changes present 9
Increased ALAT 22
Hypoalbuminemia 33
Decreased ALP 49
Increased ALP 37
Increased AST 64
Cholesterolemia 74
Hypernatremia 29
Hypochloremia 2
Hypochloremia 33
Azotemia 5
BUN decreased 10
BUN increased 5
Bile acids increased 21
Hypoglycemia 6
Hyperglycemia 4
Hypokalemia 4
Hypercalcemia 6
Hypokalemia 25
Hyperlactatemia 10
Urine enzymes increased 42
Bacteruria 25

Abbreviations: ALAT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate transam-
inase; BUN, blood urea nitrogen.
Data from Refs.24,49,54

electrolyte abnormalities, coagulation disturbances, and organ dysfunctions.60 Moni-

toring and intervention in critically ill patients following parameters according to the
“rule of 20” is recommended.61 In moderately severely and severely ill patients, or if
sepsis or serious complications are identified, intravenous broad-spectrum bacteri-
cidal antimicrobials are administered to prevent systemic effects of bacteremia and
sepsis.62 The initial choice of antimicrobial drug should be effective against the
most common pathogen E coli and adjusted after culture and sensitivity results to a
narrow-spectrum alternative.62 The drug should not be nephrotoxic, and the dose,
 Pyometra in Small Animals 647

route, and frequency of administration adjusted to ascertain optimal effect. In 1 study,

90% of E coli pyometra isolates were sensitive to ampicillin.4 The frequency of antimi-
crobial resistance, however, may differ by geographic location, which needs to be
considered, and national regulations concerning restriction of antimicrobial usage in
pets should be followed.27,32 In life-threatening peritonitis, severe sepsis, or septic
shock, a combination of antimicrobials is usually recommended for covering a wider
range of pathogens.62 If the health status is close to normal or only mildly depressed
and without complications or concurrent diseases, OHE is curative for pyometra per
se, and antimicrobials not included in the perioperative supportive treatment.
Removal of the infection is key, and surgery should not be unnecessarily delayed
due to the risk of endotoxemia and sepsis when the uterus remains in situ. Anes-
thesia and perioperative management are focused on maintaining hemodynamic
function, gastrointestinal function and protection, pain management, cellular oxygen-
ation, nutrition, and nursing care.63 Certain drugs may alleviate the inflammatory
response.64 A standard OHE is performed with some modifications.16,65 The uterus
may be large, friable, and prone to rupture, and it is important to handle the tissues
carefully (Figs. 5–9). The abdominal cavity should be protected from accidental
leakage of pus via uterine laceration or the fallopian tubes/ovarian bursa opening
by packing off the uterus with moistened laparotomy swabs (see Fig. 9). Vessels
in the broad ligament are usually ligated. Purulent material is completely removed
from the remaining cervical tissue stump, which is not oversewn. Urine for bacterial
culturing can be obtained by cystocentesis when the bladder is exposed. The
abdomen is routinely closed but if contaminated with pus this should be removed
and the abdomen rinsed with several liters of warmed physiologic saline solution
and a closed suction (or open) drainage considered.63,65 Samples for bacterial
culturing are acquired before abdominal closure if needed. For verification of the
diagnosis, macroscopic and histopathologic examination of the uterus and ovaries
is performed.
Intensive postoperative monitoring is essential, and in uncomplicated cases 1 day
to 2 days of postoperative hospitalization is usually sufficient. The need for continued
supportive care and antimicrobial therapy is evaluated several times daily on a case-
by-case basis.49 Antimicrobial therapy is discontinued as soon as possible. The over-
all health status and most laboratory abnormalities improve rapidly after surgery and
often normalize within 2 weeks.56,66

Fig. 5. Canine pyometra uterus.

648 Hagman

Fig. 6. Canine pyometra uterus.

Considering the seriousness of pyometra, the prognosis for survival is good and
mortality rates relatively low, 3% to 20%.1,9,49,67 If more severe systemic illness or
complications, such as uterine rupture, peritonitis, or septic shock, develop, however,
mortality rates can be considerably higher.9,62,68 In queens with pyometra and uterine

Fig. 7. Feline pyometra uterus.

 Pyometra in Small Animals 649

Fig. 8. Canine pyometra uterus.

rupture, a mortality rate of 57% has been reported.8 Complications develop in approx-
imately 20% of pyometra patients, the most common peritonitis, in 12%.9,43,44,49,69
Other reported complications include uveitis, urinary tract infection, intracranial throm-
boemboli, bacterial osteomyelitis, pericarditis, myocarditis, septic arthritis, incisional
swelling, dehiscence, urethral trauma, recurrent estrus, uterine stump pyometra, fistu-
lous tracts, and urinary incontinence.43,44,54

MEDICAL (NONSURGICAL) TREATMENT

For purely medical management, careful patient selection is central to ensure the best
possible outcome (ie, resolution of clinical illness and maintained fertility). Suitable can-
didates are young and otherwise healthy breeding bitches and queens with open cervix
and that have no ovarian cysts. It is important that the patients are stable and not crit-
ically ill, because it may take up to 48 hours until treatment effect for some drugs
used.70 Contraindications include systemic illness, fever or hypothermia, intrauterine
fetal remains, organ dysfunctions, or complications, such as peritonitis or sepsis.
Adverse drug effects may occur, and endotoxemia and sepsis can quickly transform
a clinically stable pyometra to an emergency. Hospitalization is, therefore,

Fig. 9. Canine pyometra uterus with rupture and leakage of pus showing at the tip of the
clamp.
650 Hagman

recommended to allow close monitoring, supportive treatments, and rapid interven-

tion. Clinical signs, reduction, and clearing of the vaginal discharge, the uterine size,
and laboratory abnormalities gradually normalize in 1 week to 3 weeks.71 OHE may
be necessary without delay if complications arise or the general health status deterio-
rates and in refractory cases. Antimicrobials alone for treatment of pyometra may
reduce the disease and prevent its progression but does not result in uterine healing.
The strategies of medical treatment are to minimize effects of progesterone by pre-
venting its production and/or action, eliminate the uterine infection, promote relaxation
of the cervix and expulsion of the intraluminal pus, and facilitate uterine healing.
Commonly used drugs are natural prostaglandin F2a (PGF2a) or its synthetic analog
cloprostenol, dopamine agonists (cabergoline and bromocriptine), or progesterone-
receptor blockers (aglepristone)72 (Tables 4 and 5). The available protocols include sys-
temic antimicrobial therapy, often recommended for 2 weeks or more.73 The shortest
effective duration of adjunctive antimicrobial therapy, however, has not been deter-
mined, and 5 days and 6 days were sufficient in 2 studies using aglepristone.70,74 The
antimicrobial drug and administration protocol should be based on bacterial culturing,
sensitivity tests, and pharmacokinetics/pharmacodynamics for achieving optimal effect.
Additional supportive treatment, including intravenous fluids and electrolyte supple-
mentation, is provided depending on physical examinations and laboratory tests results.
PGF2a is luteolytic and uterotonic and stimulates smooth musculature. Side effects,
such as hypothermia, frequent defecation, diarrhea, salivation, vomiting, restlessness,
shivering, and depression, are common and dose dependent and may last for approxi-
mately 1 hour after administration.75 PGF2a should be administrated far from feeding to
reduce the risk of vomiting. Treatment with metoclopramide or walking the bitch for
15 minutes to 20 minutes after administration has been suggested to lessen nausea
and vomiting.72,76 Serious adverse effects of the drug (PGF2a), such as death, shock,
and ventricular tachycardia, have been reported and the therapeutic window is narrow,
which is why dosage calculations should be done meticulously. It is therefore very impor-
tant to chose the lowest possible effective dose and hospitalize patients during treatment
for monitoring and immediate intervention if severe side-effects develop. Brachycephalic
breeds may be predisposed to bronchospasm, making PGF2a contraindicated.73,76
Owner consent, with information of potential risks, is necessary to obtain prior to extra-
label drug usage. Several protocols are still considered experimental, because efficiency
and optimal dosages have not yet been established. For natural PGF2a, ie, dinoprost tro-
methamine, subcutaneous administration of 0.1 mg/kg every 12 hours to 24 hours until
resolution is the dose generally recommended in bitches and queens. Despite at the
lower end of the recommended range and administered once daily, this dose is associ-
ated with many undesired side effects (the recommended range includes higher doses,
following evaluation of the effect of a lower dose), which is why other lower dose alterna-
tives and drug combinations are becoming more commonly used.75,77 Other authors
suggest starting by giving 10 mg/kg subcutaneously 5 times on the first day, gradually
increasing the dose to 25 mg/kg 5 times on the second day, and reaching 50 mg/kg by
day 3. Doses of 50 mg/kg were then given 3 times to 5 times daily from day 3 and onward
over the treatment period, a regime resulting in side effects in 15% of treated bitches.72 A
dose of 100 mg/kg natural PGF2a administered subcutaneously once daily for 7 days
resulted in recovery in 7 bitches, but many side-effects were observed and lower doses
are preferable.78 Natural PGF2a, 20 mg/kg, was given intramuscularly 3 times daily on up
to 8 consecutive days in 1 study, and 30 mg/kg was given subcutaneously twice daily for
8 days in another study, resulting in resolution of the illness in 70% of 10 bitches and in
100% of 7 bitches, respectively, and no side effects.79,80 More recent low dose proto-
cols, recommend subcutaneous administration of natural PGF2a at a dose of 10-50mg/
Table 4
Examples of studies of medical treatment protocols for open cervix pyometra in dogs

Drug N Protocol and Dosage Outcome and Side Effects Reference

Aglepristone 24 Aglepristone 10 mg/kg SC q 24 h on day 2, 7 and 14 Recovery in 100%; recurrence after up to 54 months Jurka et al,84 2010
12%; fertility in 12% of 17 bitches mated
Aglepristone 28 Aglepristone 10 mg/kg SC q 24 h on days 1, 2, 7, 15, Recovery in 75% (resolution of clinical signs); Ros et al,85 2014
and 23, 29 if not cured recurrence: 48% after up to 6 y; fertility in 69% of
13 mated bitches
Aglepristone 52 Aglepristone 10 mg/kg SC q 24 h on days 1, 2, and 7 Recovery in 92%; recurrence: 10% after 3 months, Trasch et al,83 2003
19% in 37 bitches followed up to 1 y; fertility in
83% (5/6 mated bitches)
Aglepristone 13 Aglepristone 10 mg/kg SC q 24 h on days 1, 2, 7, and Recovery in 46% Gurbulak et al,82 2005
14
Aglepristone 20 Aglepristone 10 mg/kg SC q 24 h on days 1, 2, and 8 Recovery in 60% Fieni,70 2006
and if not cured on day 15
Aglepristone 32 Aglepristone 10 mg/kg SC q 24 h on days 1, 2, and 8 Recovery in 84%; no side effect of cloprostenol in Fieni,70 2006

Pyometra in Small Animals

1 cloprostenol and if not cured on days 14 and 28 1 cloprostenol: 45% of the bitches; in 56% some side effects were
1 mg/kg SC q 24 h on days 3–7 noted: loss of appetite, lethargy, vomiting,
nausea; 19% recurrence; in closed cervix
pyometra cases: recovery in 76.5%, in open cervix
pyometra recovery in 74.3%; 1 euthanasia due to
declining health, 1 death; Follow-up time: 90 d
and up to 2 y in 23 bitches; fertility in 80%
(4/5 mated bitches)

(continued on next page)

651
 652
Hagman
Table 4
(continued )
Drug N Protocol and Dosage Outcome and Side Effects Reference
Aglepristone 73 Traditional protocol: aglepristone 10 mg/kg SC q Recovery with traditional protocol in 88%; Contri et al,74 2015
24 h on days 1, 2, and 7 (26 bitches) recurrence: 17%; fertility in 86%
Modified protocol: aglepristone 10 mg/kg SC q 24 h Resolution of clinical signs of pyometra with modified
on days 1, 3, 6, and 9 (47 bitches) protocol, in 100%; recurrence: 0%; fertility in 78%
Follow-up after 2 y
Aglepristone 15 Aglepristone 10 mg/kg SC q 24 h on days 1, 3, 8, and Recovery in 100%, recurrence: 20% by the next Gobello et al,91 2003
1 cloprostenol 15 (if not cured) 1 cloprostenol: estrus cycle (in all 15 bitches); fertility in 100%
a. 1 mg/kg SC q 24 h on days 3 and 8 (N 5 8) (1 bitch mated); no side effects reported
b. 1 mg/kg, SC q 24 h on days 3, 5, 8 10, 12, and 15
(N 5 7)
Cabergoline 29 Cabergoline 5 mg/kg PO q 24 h Recovery in 83% by day 14, recurrence: 21%; fertility Corrada et al,81 2006
1 cloprostenol 1 cloprostenol 1 mg/kg SC q 24 h for 7–14 d in 1/2 mated bitches. Mild side effects noted.
Cabergoline 22 Cabergoline 5 mg/kg PO q 24 h Recovery in 90.5% by day 13; recurrence: 20%; England et al,71 2007
1 cloprostenol 1 cloprostenol 5 mg/kg every third day SC for 7–13 d fertility in 64% of 11 bitches mated; side effects:
retching, vomiting, mild abdominal straining,
diarrhea, and panting up to 60 min after
administration

All protocols combined with and systemic antimicrobial therapy. See the original reference for the most accurate information and more details.
Abbreviations: N, number of bitches; PO, per os; PG, prostaglandin; recovery, resolution of pyometra; SC, subcutaneous.
 Pyometra in Small Animals 653

Table 5
Selected studies of medical treatment protocols for open cervix pyometra in cats

Drug N Protocol and Dosage Outcome and Side Effects Reference

PGF2a (natural) 21 0.1 mg/kg SC q 12–24 h for Resolution of signs of Davidson et al,8
3–5 d (6 queens); pyometra and return to 1992
0.25 mg/kg was used in cyclicity in 95%;
15 queens but was not treatment was repeated
more effective in 1 queen; fertility in
81%; no difference
between the 2 different
dosages (ie, the lower
dosage recommended);
transient side effects
observed in 76%:
vocalization, panting,
restlessness, grooming,
tenesmus, salivation,
diarrhea, kneading,
mydriasis, emesis,
urination, and lordosis
lasting up to 60 min.
Recurrence of pyometra
in 14% (3 cats)
Prostaglandin 5 5 mg/kg SC q 24 h for 3 Resolution of signs of Garcia Mitacek
F2a (synthetic consecutive days pyometra in 100%; et al,92 2014
analog no recurrence after 1 y;
cloprostenol) fertility in 40%;
transient side effects:
diarrhea, vomiting,
vocalization
Progesterone 10 10 mg/kg SC q 24 h on Resolution of signs of Nak et al,87
receptor days 1, 2, and 7 and on pyometra in 90%; no 2009
blocker day 14 (if not cured) recurrence after 2-y
(aglepristone) follow-up; no side
effects observed

See the original reference for the most accurate information and more details.
Abbreviations: IM, intramuscular administration; q, every; N, number of cats; PO, oral adminis-
tration; SC, subcutaneous administration.

kg every 4-6 hours.73 The synthetic PGF2a analog cloprostenol is administered at a

notably lower dose than for natural PGF2a,78 and accurate calculations are crucial to
avoid serious side-effects or fatalities. For cloprostenol, subcutaneous administration
of 1 mg/kg to 3 mg/kg every 12 hours to 24 hours to resolution/effect is the recommended
dose for bitches and queens.75 Subcutaneous administration of low-dose cloprostenol,
1 mg/kg, once daily was effective in 100% of 7 bitches in 1 study but with a high recur-
rence rate, 85%, and subsequent fertility rate of 14%.78
The dopamine agonists cabergoline and bromocriptine are effectively luteolytic from
day 25 after estrus because of their antiprolactin effects and have been used together
with PGF2a for augmented treatment of pyometra.71,72 Cabergoline usually causes less
vomiting than bromocriptine, which is an advantage.72,73,76 Cabergoline combined with
a low dose of cloprostenol led to resolution of the illness in 90.5% of 22 treated bitches
with pyometra in 1 study.71 In another study using cabergoline and cloprostenol, 83% of
29 bitches recovered from the illness.81 This combination was also shown the most
effective compared with only low-dose cloprostenol or natural PGF2a.78 For treatment
654 Hagman

of pyometra in cats, no clinical studies have been published on cabergoline and bromo-
criptine, but similar doses and regimes as for dogs have been suggested.16
The progesterone blocker aglepristone is commonly used in Europe for treatment of
pyometra (see Tables 4 and 5) but is not currently approved for use in North America.
Aglepristone binds to progesterone receptors effectively and competitively and
without stimulating any of the hormone’s effects. Side effects are usually rare and
not severe, and cervical relaxation induced within 48 hours.70,74,82–85 According to
the recommended protocol, 10 mg/kg aglepristone is administered subcutaneously
once daily on days 1, 2, and 7 or 8 and on days 14 and 28 if not cured. This protocol
results in success rates of 46% to 100%, recurrence rates 0% to 48% and subsequent
fertility rates of 69% to 85%.86 Aglepristone was administered more frequently (on
days 1, 3, 6, and 9) in a modified protocol, which resulted in resolution of the illness
in all 47 treated bitches and with no reported recurrence for up to 2 years.74 Treatment
with aglepristone resulted in resolution of pyometra in 9 of 10 queens, with no recur-
rence reported after 2 years and no side effects observed (see Table 5).87
Local treatment methods of pyometra have been shown effective but are not yet
commonly used in clinical practice in bitches and have not been reported in cats.88 Intra-
vaginal infusion of prostaglandins and antimicrobials yielded successful result in 15 of 17
treated bitches, without side effects or recurrence after 12 months.89 Aglepristone in
combination with intrauterine antimicrobials was successful in 9 of 11 bitches.82 Intra-
uterine drainage through transcervical catheters may facilitate recovery in refractory
cases.88 Surgical drainage and intrauterine lavage resulted in fertility in 100% of 8 treated
bitches.90 Whether prostaglandin E2, administered intravaginally or orally, gives a cervi-
cal relaxation that is beneficial in medical treatment protocols remains to be studied.73,76

PROGNOSIS AFTER MEDICAL TREATMENT

The prognosis for survival and fertility is considered guarded to good. Breeding on the
subsequent estrus cycle is consistently recommended after medical treatment, to avoid
recurrence. The mean reported long-term success (resolution of clinical illness) of med-
ical treatment is approximately 86% (range 46%–100%) in dogs67,70,71,74,78,81–83,85,91
and in cats 95% (range 90%–100%)8,87,92 (see Tables 4 and 5). The prognosis for
fertility after medical treatment is generally considered good, with a mean fertility rate
of 70% (range 14%–100%) reported in dogs and of 60% in cats. The mean recurrence
rate reported in dogs is 29% (range 0%–85%), and 0% to 14% in cats. Fertility rates
after aglepristone treatment are higher in younger (<5 years) bitches and those that
have no other uterine or ovarian pathology.84,85

PREDICTIVE MARKERS

Of clinical and laboratory parameters investigated, leukopenia has been associated

with both presence of peritonitis and increased postoperative hospitalization in surgi-
cally treated bitches with pyometra.49 Concentrations of the acute-phase proteins,
C-reactive protein and serum amyloid A, are increased in sepsis.69,93 Concentrations
of C-reactive protein and PGF2a have been linked with length of postoperative hospi-
talization.25,69 Acute-phase proteins concentrations decrease gradually during post-
operative recovery, and maintained or increased concentrations may indicate
complications.56 Persistent proteinuria and urinary protein-creatinine indicate renal
disease that requires special attention.54 Central venous oxygen saturation and
base-deficit and lactate levels were valuable for determining outcome in bitches
with pyometra and sepsis.94 Band neutrophil concentrations, lymphopenia and mono-
cytosis, blood urea nitrogen greater than 30 mg/dL, and creatinine concentrations
 Pyometra in Small Animals 655

greater than 1.5 mg/dL have been associated with death.95 Certain inflammatory vari-
ables may be clinically useful for prognostication if cageside tests become available.96
In queens, white blood cell counts, neutrophils, band neutrophils, monocytes, and the
percentage band neutrophils were positively, and albumin concentrations negatively,
associated with postoperative hospitalization.10

DIFFERENTIATION OF PYOMETRA AND MUCOMETRA OR HYDROMETRA

Fluid in the uterine lumen is present in both pyometra and mucometra/hydrometra, and
their clinical manifestations can be similar. In pyometra, however, life-threatening com-
plications may develop because of the bacterial infection, and differentiation of these
disorders is thus important to optimize treatments. Ultrasonographic examination of
the uterus illustrating the fluid echogenicity and hemodynamic parameters may be
helpful in some cases but is not diagnostic.51 The health status is more depressed
and lethargy and gastrointestinal disturbances more frequently observed in pyometra.
More than 3 clinical signs of illness and a more pronounced inflammatory response are
also indicative of pyometra as opposed to mucometra/hydrometra.24,25

PREVENTION

To diagnose and treat CEH and pyometra early is favorable, and noninvasive diagnostic
methods are warranted.97,98 Elective OHE has the advantage of being performed in a
healthy animal and preventing pyometra and other uterine diseases. Because there
are many negative side effects of spaying, all pros and cons of such intervention, need
to be thoroughly evaluated in each individual.99 If breeding on the first estrus after med-
ical treatment is not possible, close monitoring is advisable to rule out abnormalities that
may emerge during the luteal phase. Progesterone receptor blockers or prostaglandins
may prevent the development of pyometra in high-risk patients.97 Some investigators
recommend postponing the subsequent estrus after medical treatment of pyometra,
to promote uterine healing.72

STUMP PYOMETRA

A stump pyometra is when pyometra develops in residual uterine tissue in incompletely

spayed bitches and queens, most often because of hormone-producing ovarian rem-
nants.100 The clinical presentation is similar, except for a history of previous spay. Ultra-
sonography usually shows areas of local fluid accumulation at the tissue stump, but it
may be difficult to localize the ovarian remnant tissue unless follicles are present
(Fig. 10). Incomplete resection is the leading cause, but ectopic or revascularized

Fig. 10. Stump pyometra due to ovarian remnant.

656 Hagman

ovarian tissue separated from the ovary during surgery have also been proposed.100
Treatment includes surgical resection of remaining uterine and ovarian tissue, in combi-
nation with supportive treatments and antimicrobials, if indicated.
Pyometra has been described in many other small animals, such as rabbits
(see Fig. 3), rodents, guinea pigs, hamsters, gerbils, ferrets, and chipmunks.101–104
The causative microbes often differ from isolates in dogs and cats with the disease.
Ultrasonography and cytology are helpful to confirm a presumptive diagnosis based
on clinical signs and physical examination, and the preferred treatment is OHE.
Aglepristone combined with antibiotics has been used successfully for medical treat-
ment in a golden hamster and a guinea pig.105,106

ACKNOWLEDGMENTS

The author is very grateful for the following experts’ contributions: Dr Fredrik
Södersten, DVM, PhD, Swedish University of Agricultural Sciences, performed histo-
pathology examinations and provided the images in Fig. 1. Dr George Mantziaras,
DVM, PhD, VetRepro, Athens, Greece, provided the ultrasonography Video 1 supple-
mentary files and the stump pyometra ultrasonography image for Fig. 10. Associate
Professor, Kerstin Hansson, DVM, PhD, Diplomate ECVDI, Swedish University of Agri-
cultural Sciences and the University Animal Hospital, Swedish University of Agricul-
tural Sciences provided the diagnostic imaging and text in Fig. 3.

SUPPLEMENTARY DATA

Supplementary data related to this article can be found online at https://doi.org/10.

1016/j.cvsm.2018.03.001.

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