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Basics ⬇

Basics

Definition

Pyometra is an acute or chronic suppurative inflammation of the endometrium in ovary-intact bitches which leads to intraluminal accumulation of purulent exudates.

Pathophysiology

  • Incompletely understood and multifactorial in origin.
    • Classic description: Normal cycling bitches-repeated exposure of the endometrium to high concentrations of estrogen during proestrus and estrus followed by high concentrations of progesterone for 2 months during diestrus without pregnancy-leads to development of cystic endometrial hyperplasia (CEH), which predisposes the uterus to a secondary bacterial infection.
    • Strains of Escherchia coli with uropathogenic virulence factors that allow adhesion to the endometrium and establishment of an infection without the presence of CEH enter the uterus during proestrus and estrus and act as a mucosal irritant-stimulating the development of CEH under the influence of progesterone during diestrus.
    • Combination of both disease entities-occurring concurrently.
    • Bacteria-ascend from the vagina through the partially open cervix during proestrus and estrus; uterine secretions provide excellent media for growth; uropathogenic E. coli most common isolate.
    • Regardless of underlying cause-pyometra does not occur without the presence of progesterone (endogeneous or exogeneous source).

Systems Affected

  • Reproductive
  • Hemic/Lymphatic/Immune
  • Hepatobiliary
  • Renal/Urologic

Genetics

  • Genetic predisposition suspected in some ‘lines’ of related bitches.
  • Breed predisposition has been suggested: Bernese mountain dogs, rottweiler, rough-coated collie.

Incidence/Prevalence

Incidence-accurate assessment cannot be made because most dogs and cats in the United States undergo elective ovariohysterectomy.

Signalment

Species

Dog and cat

Mean Age and Range

  • Usually >6 years old; range 4 months to 16 years in dogs.
  • Animals treated with exogenous estrogen or progestagen.
  • Pyometra of the uterine stump in spayed animals-may develop any time after ovariohysterectomy.

Predominant Sex

Female-ovary intact

Signs

Historical Findings

  • Dogs-present within 12 weeks after their last estrus.
  • Cats-present within 4 weeks of last call (estrus).
  • History of treatment with exogenous hormones.

Physical Examination Findings

  • Uterus-with closed cervix palpably enlarged; palpate carefully to avoid rupture; with open cervix, may not be palpably enlarged.
  • Vaginal discharge and systemic illness-depends on patency of cervix.
    • Open cervix-blood-stained, purulent vaginal discharge often only presentation.
    • Closed cervix-systemically ill from endotoxemia and bacteremia: polyuria, polydipsia, lethargy, anorexia, vomiting, abdominal distension, dehydration.
  • May or may not have pyrexia.

Causes

  • Dogs-the unique, repeated exposure of the endometrium to estrogen followed by exposure to progesterone without pregnancy.
  • Cats-may be the result of estrogen at estrus followed by a progestational (pseudopregnancy) phase, caused by induction of ovulation by coitus, mechanical stimulation, hormones (hCG, GnRH), or spontaneous ovulation (incidence of 30% reported).

Risk Factors

  • Middle-aged to older, nulliparous ovary-intact females may be predisposed.
  • Pharmacologic use of estrogen (mismate) shots during midestrus to early diestrus.
  • No correlation with pseudopregnancy in dogs.
  • Use of progestagens in both queens and bitches for estrus prevention.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Pregnancy
  • Other causes of polyuria and polydipsia-diabetes mellitus; hyperadrenocorticism; primary renal disease
  • Severe vaginal disease
  • Metritis and retained fetal memebranes (associated within first days postpartum)
  • Hydrometra (serous intrauterine discharge); mucometra (mucoid intrauterine discharge); hematometra (hemorrhagic intrauterine discharge)

CBC/Biochemistry/Urinalysis

  • Neutrophilia-left shift +/- toxic changes; more severe with closed cervix
  • Mild, normocytic, normochromic, nonregenerative anemia
  • Hyperglobulinemia, hyperproteinemia, hypoalbuminemia, hypercholesterolemia, elevated C-reactive protein
  • Azotemia (elevated BUN and creatinine)
  • ALT and ALP-high with septicemia or severe dehydration
  • Electrolyte disturbances-depend on clinical course
  • Urinalysis-isosthenuria, bacteriuria, glucosuria, and proteinuria can be found. Collect sample by catheterization of urinary bladder or ultrasound-guided cystocentesis to avoid risk of uterine puncture. Midstream urine sample not recommended as contamination with vaginal discharge likely.

Other Laboratory Tests

  • Cytologic examination of vulvar discharge-degenerative polymorphonuclear cells and phagocytized bacteria; may be indistinguishable from the purulent discharge associated with vaginal disease (e.g., vaginitis, vaginal mass, foreign object, and vaginal anatomic anomaly).
  • Bacterial culture and sensitivity test of vulvar discharge-not helpful in confirming diagnosis (bacteria cultured are usually normal vaginal flora); useful in determining appropriate antibiotic use-if sample directly taken from the uterus transcervically or the cranial vagina with the aid of a vaginal speculum (guarded swab from caudal vagina/vestibule bacteria).
  • Serologic testing for Brucella canis-rapid slide agglutination test used as a screen (D-Tec CB®, Zoetis, Corp., (888)-963-8471); sensitive but not specific. If positive, recheck by an agar gel immunodiffusion test (Cornell University Diagnostic Laboratory, (607)253–3900) or bacterial culture of whole blood, lymph node aspirate, or vulvar discharge.
  • Prostaglandin F2 metabolites (PGFM) are elevated in dogs with pyometra compared to those with hydrometra or mucometra.
  • Hormone assay: progesterone concentration >2 ng/mL.

Imaging

Radiography

  • Detect an enlarged and distended uterus (see Web Figure 1).
  • Rule out pregnancy-45 days after ovulation when fetal skeletal ossification is present.

Ultrasonography

  • Uterine horns distended with hypo- to hyperechoic intraluminal fluid, with or without flocculation. Uterine wall often thickened with irregular edges and small hypoechoic areas consistent with cystic change (CEH) (see Web Figure 2) or can be thin if uterus is severely distended as with a closed cervix pyometra.
  • Rule out pregnancy-20–24 days after ovulation.
  • Pyometra-may occur with pregnancy in dogs (rare).

Diagnostic Procedures

  • Vaginoscopy-indicated in dogs with purulent vulvar discharge and no apparent uterine enlargement; allows determination of site of origin of the vulvar discharge; not possible in cats.

Pathologic Findings

  • Endometrium (dogs and cats)-described as cobblestone appearance (see Web Figure 3).
  • Cystic endometrial surface-covered by malodorous, mucopurulent exudate; thickened because of increased endometrial gland size and cystic gland distension.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

  • Inpatient
  • Pyometra-life-threatening condition if the cervix is closed and bitch is systemically ill.

Nursing Care

Supportive care-immediate intravenous fluid administration and broad-spectrum antibiotics.

Client Education

  • Recommend medical treatment only for valuable, young breeding animals that are not azotemic and present systemically well. For all other animals not intended for breeding, ovariohysterectomy is the treatment of choice.
  • Historically, medical treatment of closed-cervix pyometra can be associated with uterine rupture and peritonitis, but with the development of new pharmacologic agents and treatment protocols this is now a rare event.
  • Bitches that are refractory or chronic cases that do not readily respond to medical treatment are candidates for ovariohysterectomy.
  • Warn of possible recurrence of pyometra after medical therapy-important to breed at very next heat and spay when desired number of litters is achieved.

Surgical Considerations

  • Ovariohysterectomy is the preferred treatment in all animals not intended for breeding, older (>4 years) bitches, bitches with evidence of chronic CEH changes, bitches that present systemically unwell and require immediate emergency care and stabilization.The pus-filled uterus, both ovaries and the entire cervix should all be removed.
  • Closed-cervix pyometra-exercise great care in handling the enlarged and friable uterus (see Web Figure 4).
  • Place saline-soaked laparotomy sponges in the abdomen to prevent leakage of purulent material into the peritoneal cavity.
  • Patients should be systemically stabilized prior to anesthesia for surgery (correction of any acid-base derangements, dehydration, hypotension, shock, electrolyte abnormalities, arrythmias and endotoxemia) and started on IV fluids and IV broad-spectrum antibiotics.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

Antibiotics

  • All patients with pyometra
  • Empirical (E. coli most common isolate)-pending results of bacterial culture and sensitivity test
  • Start on broad-spectrum antibiotics prior to receiving culture and sensitivity results-ampicillin (22 mg/kg PO q8h); amoxicillin and clavulonic acid (12.5–25 mg/kg PO q12h) or cefazolin (22 mg/kg IV or IM q8h). Exercise care when using cephalosporins, potentiated sulfonamides and enrofloxacin in dehydrated, potentially septicemic patients with impaired renal or liver function.

Prostaglandins (PGF2)

  • Doses listed below for native compound only (dinoprost tromethamine; Lutalyse®); has both luteolytic and ecobolic actions.
  • New low-dose protocol: start with low doses to minimize side effects and ecobolic effect especially in closed pyometra cases. Once luteolysis has occurred and the cervix is fully open the dose can be gradually increased depending of the individual patient's tolerance to the drug.
  • Side effects: dose dependent and usually not seen with new low dose protocol; tachypnea, vomiting, diarrhea, urination, anxiety; side effects are seen 20 minutes after administration of the drug and last for 15–30 minutes.
  • Animals should be hospitalized for 1 hour after each treatment.
  • Dogs and cats-10 µg/kg SC q6h for 1 day then 25 µg/kg q6h for 1–2 days; then 50 µg/kg q6h for 3–4 days. The queen is more resistant to the luteolytic effects of PGF2 than bitches-often higher doses for longer periods are required.
  • Ovariohysterectomy-performed in patients not responding well to treatment within 5 days and are refractory to prostaglandin treatment (persistent or recurring uterine fluid and vulvar discharge).

Cloprostenol

  • Synthetic form of PGF2
  • Dogs-1 µg/kg SC daily for 7–14 days; greater side effects and prolonged time to resolution compared to the natural form of PGF2

Miscellaneous

Transcervical endoscopic catheterization of open- and/or closed-cervix pyometra-a recently described technique; involves flushing the uterus with warm saline and PGF2; reported resolution within 3–5 days; no uterine rupture or leakage reported but still should be considered a risk-patient selection important.

Contraindications

  • High-dose PGF2 and cloprostenol with closed-cervix pyometra-strong myometrial contractions may cause uterine rupture or force purulent exudate through the oviducts, causing secondary peritonitis.

Precautions

  • PGF2 (dinoprost tromethamine) and cloprostenol-not approved for use in dogs and cats.

Alternative Drug(s)

  • Progesterone receptor antagonist-aglepristone (10 mg/kg SC days 1, 2, and 8) competitively binds to the progesterone receptor with greater affinity than natural progesterone. Minimal side effects. Excellent choice for closed pyometra cases as it dilates the cervix with minimal uterine contractions. Best results achieved when used in combination with prostaglandin-PGF2 is started 24–48h after aglepristone, allowing the cervix to open prior to stimulation of uterine contractions by PGF2; not registered in United States; not suitable for use in bitches with poor liver and/or kidney function.
  • Dopamine agonists-cabergoline (5 µg/kg PO q24h for 7–14 days) or bromocryptine (10–20 µg/kg q8h); both given with food to reduce risk of vomiting; act as prolactin antagonists; best used in combination with PGF2 to potentiate the ecobolic effect-should see cervical opening within 24–48 h.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Antibiotics-continued for at least 14 days after resolution of vulvar discharge and removal of all fluid from the uterine lumen (confirmed by ultrasound).
  • Clinical improvement and a significant increase in vaginal discharge should be noted within 24 hours of commencing PGF2 treatment; vaginal discharge will change from purulent to serosanguineous to serous; a reduction in the uterine lumen should be seen on ultrasound within 3 days after the start of treatment; resolution of clinical signs (no vulvar discharge and no intrauterine fluid visible by ultrasound) should occur within 7 days.
  • Serum progesterone concentrations decline within 48 hours of treatment and should be <2 ng/mL at 5–7 days; CBC and neutrophil count normal after 10–15 days.
  • Follow-up ultrasound of the uterus 4 weeks after discontinuation of treatment to assess uterine health-confirm no intraluminal fluid and determine CEH changes (predictor of future fertility).

Prevention/Avoidance

  • Animals not intended for breeding should be spayed.
  • Breeding females should be spayed as soon as the desired number of litters has been obtained.
  • Females should be bred when they are young (<4 years) and subsequently have the desired number of litters as soon as possible-a pregnant uterus reduces the risk of developing pyometra and maximizes uterine health of the bitch.
  • Breed during the estrus immediately following treatment-the gravid uterus is less susceptible to reinfection; a bitch with underlying cystic endometrial hyperplasia has limited breeding life (best to get the desired number of pups as soon as possible); ultrasound examination 28 days after the LH surge for early detection of recurring pyometra allows surgical management before the bitch becomes systemically ill.
  • Breeding management at the subsequent heat is important to maximize the chance of pregnancy-use of high-quality semen, timed insemination with extenders containing antibiotics, or timed natural mating with young proven stud dog.
  • Antibiotic therapy at subsequent heat-vaginal cytology monitoring: presence of neutrophils during estrus indication to start broad-spectrum antibiotic (amoxicillin or amoxicillin and clavulonic acid) until early ultrasound (for 4 weeks after the LH surge).
  • Medical treatment can result in a shortened interestrus interval which can be associated with decreased fertility-lengthen interestrus interval with an androgen-receptor agonist such as mibolerone to allow sufficient time for the uterus to remodel/recover; start mibolerone 1 month after the end of treatment and continue for 2–3 months to ensure a minimum interval of 6 months from the last heat.

Possible Complications

  • Bitch may enter estrus sooner after treatment than anticipated if medical treatment induces premature luteolysis (see “Prevention/Avoidance”).
  • Recurrence of pyometra at subsequent heats.

Expected Course and Prognosis

  • Prognosis for survival is good with both medical and surgical treatment if uterine rupture does not occur; 4% mortality rate reported in bitches and 8% in queens.
  • Recurrence rate of pyometra is dependent on age, parity, and pre-existing uterine pathology.
  • Variable pregnancy rates reported after treatment for pyometra (50–90%).

Miscellaneous ⬆

Miscellaneous

Associated Conditions

  • Pyometra of the uterine stump in spayed animals-may develop any time after ovariohysterectomy; may be associated with the presence of an ovarian remnant.

Pregnancy/Fertility/Breeding

  • Any of the drugs used for the treatment of pyometra are also abortificants-always rule out pregnancy before administration to valuable breeding animals.
  • See “Prevention/Avoidance” and “Expected Course and Prognosis” for futurebreeding/fertility after treatment of a pyometra and ways to reduce incidence of pyometra.

Abbreviations

  • ALP = alkaline phosphatase
  • ALT = alanine aminotransferase
  • CEH = cystic endometrial hyperplasia
  • PGF2 = prostaglandin F2
  • WBC = white blood cell

Suggested Reading

Gibson A, Dean R, Yates D, Stavisky J. A retrospective study of pyometra at five RSPCA hospitals in the UK: 1728 cases from 2006 to 2011. Vet Rec 2013, 173(16):396–396.

Hagman R, Lagerstedt AS, Hedhammar Å, Egenvall A. A breed-matched case-control study of potential risk-factors for canine pyometra. Theriogenology 2011, 75(7):1251–1257.

Krekeler N, Marenda MS, Browning GF, Holden KM, Charles JA, Wright PJ. The role of Type 1, P and S fimbriae in binding of Escherichia coli to the canine endometrium. Vet Microbiol 2013, 164(3):399–404.

Schlafer DH, Gifford AT. Cystic endometrial hyperplasia, pseudo-placentational endometrial hyperplasia, and other cystic conditions of the canine and feline uterus. Theriogenology 2008, 70(3):49–358.

Verstegen J, Dhaliwal G, Verstegen-Onclin K. Mucometra, cystic endometrial hyperplasia, and pyometra in the bitch: Advances in treatment and assessment of future reproductive success. Theriogenology 2008, 70:364–374.

Authors Fiona Hollinshead and Natali Krekeler

Consulting Editor Sara K. Lyle

Acknowledgment The authors and editors acknowledge the prior contribution of Margaret V. Root Kustritz.

Client Education Handout Available Online