Pyometra

• Disease of the luteal phase (metestrus - diestrus).
• Cause: hormonally-mediated cystic endometrial hyperplasia associated with bacterial hemo-purulent metritis.
• Signs: polydipsia/polyuria, vomiting, hemorrhagic-purulent vulvar discharge.
• Diagnosis: signs, history, imaging (especially ultrasonography), exploratory laparotomy.
• Treatment: ovariohysterectomy or conservative therapy with antibiotics and ecbolics if breeding potential is to be preserved.
• Prognosis: good - if prompt treatment before animal systemically ill.
  Print off the owner factsheet Pyometra ('pyo' or womb infection) Pyometra ('pyo' or womb infection) to give to your client.

• Polydipsia/polyuria.
• Anorexia.
• Depression.

• Vulvar discharge.
• Vomiting.

• Endotexemia.
• Shock.
• Collapse.

• >6 years old.

• Usually occurs 4-8 weeks after estrus, or after exogenous administration of estrogens or progestins.

• 5-6 estrous cycles → cyclic progesterone concentrations → marked proliferation and increased secretory function of the endometrium → cystic endometrial hyperplasia → pyometra.
• Secondary bacterial infection of the material in the endometrial glands (embryotroph). 60-90% are due to E. coli Escherichia coli, Proteusspp Proteus spp and Klebsiellaspp Klebsiella pneumoniae. B-hemolytic streptococci are also important Streptococcus spp.

• Older bitch (more than 6 years old); it may occur in young bitches following their first or second reproductive cycles.
• 5-80 days after the end of estrus. >80% of bitches affected with closed pyometra still have a functional corpus luteum.

Specific

• Use of estrogen for prevention of pregnancy (mismating).
• Prolonged use of progestagens for the prevention or suppression of estrus.

• 5-6 estrous cycles → progesterone-primed uterus → cystic endometrial hyperplasia → pyometra.

• Renal disease: several aspects of the renal changes associated with pyometra are incompletely understood. In most dogs with E.coli pyometra, renal dysfunction is transient and it involves the nephron both at the glomerular and proximal tubular level. The renal dysfunction may be characterized by:

Prerenal uremia

• Dehydration, shock and toxemia → poor renal perfusion → Ab-Ag complexes deposited on the basement membrane → glomerular disease → persistent proteinuria Proteinuria.
• Bacterial toxins or immune complexes interfere with resorption → tubular disease → impaired ability to concentrate urine → polyuria → dehydration and electrolyte loss.
• Concurrent renal disease is commonly found in older dogs.

Acid base balance

• Metabolic acidosis Acid base imbalance is more common but metabolic alkalosis may develop through prolonged vomiting.

Electrolytes

• Vomiting, uterine loss and renal dysfunction → Na/K loss.

Bone marrow

• Toxic suppression of the bone marrow → depressed RBC and platelet numbers Hematology: red blood cell count Hematology: platelet count → normocytic, normochromic anemia and thrombocytopenia.

White cells

• Neutrophilia with a left shift. WBC 20,000 cu/mm - higher in closed pyometra Hematology: leukocyte (WBC) Hematology: neutrophil.

• 9-10 estrous cycles.
• Metestrus (5-80 days after estrus).

• Polydipsia/polyuria.
• Vomiting.
• Vulvar discharge.
• Depression.

• Middle-aged to old entire bitch.
• Recent estrus (5-80 days).
• Polydipsia/polyuria.

• Vomiting.
• Anorexia.
• Abdominal distension.

• Vulvar discharge.

• Abdominal enlargement.
  Palpation of the distended uterus may be possible.

• May see toxic neutrophils  , on smear of discharge.

• WBC: neutrophilia Hematology: band neutrophil, band cell with a left shift (20,000 cu/mm). Leukopenia possible due to overwhelming infection or sequestration of neutrophils in uterus.
• RBC: mild or moderate normocytic normochromic anemia.
• Platelets: thrombocytopenia.

• Highly effective diagnostic modality shows enlarged uterine horns filled with fluid of marked echogenicity .

• Plain lateral radiographs Radiography: abdomen of the posterior abdomen.
• Attempt to identify the coiled viscus of the fluid-filled uterus .
• A wooden or plastic "spoon" or flat surface can be used to apply pressure to the caudal abdomen. This will displace intestines out of the way and can be useful in the diagnosis of open, small pyometras.
  Particularly useful where the laboratory findings are equivocal.
  Contrast radiography is rarely necessary.

• Non-specific changes:
• Electrolyte abnormalities.
• Increased liver enzymes associated with toxemia.
• TP: total proteins Blood biochemistry: total protein , are increased.
• Hyperglobulinemia Blood biochemistry: gamma globulin.
• Urea Blood biochemistry: urea , and creatinine Blood biochemistry: creatinine increased.
• Hypoglycemia Blood biochemistry: glucose.

• Urine - proteinuria Urinalysis: protein.
• Active urine sediment Urinalysis: centrifuge sediment.
• Isosthenuria Urinalysis: specific gravity.
  Do not perform cystocentesis if pyometra suspected.

• May have perineal staining from discharge.
• Uterine distension is typical, occasionally asymmetrically.
• Uterine wall thickened.
• Culture uterine contents via swab through sterile incision.
• Uterine mucosa may be necrotic, hemorrhagic, hyperplastic.
• Examine ovaries for cysts and corpora lutea.

• Extra-uterine lesions might include bone marrow depression, extramedullary hemopoiesis, occasionally immune-complex glomerulonephritis.

• Check for mechanical obstruction of the cervix.

• Uterine wall typically hyperplastic, with marked suppurative inflammation from secondary bacterial infection.
• Numerous plasma cells in stroma around cystic glands.

• Fix bone marrow (femur, rib), spleen, liver to check for bone marrow suppression and extramedullary hemopoiesis.
• Fix kidney to check for secondary glomerulonephritis.

• Pregnancy, especially if radiographs are taken <35 days from the last day of estrus.
• Hydrometra; mucometra.
• Uterine tumors Uterus: neoplasia.

Polydipsia/polyuria

• Renal dysfunction Kidney: chronic kidney disease (CKD).
• Hyperadrenocorticism Hyperadrenocorticism.
• Liver disease Liver: chronic disease - overview.
• Diabetes mellitus Diabetes mellitus.
• Diabetes insipidus Diabetes insipidus.

• Vaginal Vaginal neoplasia /uterine tumors.
• Vaginitis Vaginitis.

• Fluid replacement Fluid therapy: for electrolyte abnormality, for dehydration and to maintain renal function.
• Electrolyte replacement and acid/base correction.
• Broad spectrum antimicrobials Therapeutics: antimicrobial drug.
  Platelet-rich plasma or whole blood may be indicated pre-operatively.

• Ovariohysterectomy Ovariohysterectomy.
  Dehydration, electrolyte and acid/base imbalances, should be corrected pre-operatively.

• Salvage of the reproductive capacity of the bitch may be possible by inducing luteolysis and myometrial contractions to effect uterine drainage.
• Usually requested by the owners of valuable breeding bitches.
  Not recommended! Pyometra likely to reoccur. Can rupture → death.
• Medical management should only be attempted:
  • Where no signs of systemic illness exist.
  • Where owners understand the risks of failure and the need for rapid ovariohysterectomy if treatment is unsuccessful.
  • With appropriate antibiotic therapy.
  • With appropriate follow-up with diagnostic imaging, especially abdominal ultrasonography.

Prostaglandins

• PGF2-alpha (Dinoprost Dinoprost trimethamine ).
• Side effects associated with prostaglandin administration may be reduced by starting treatment with low doses and progressively increasing them during the treatment period. Example:
  • 25 ug/kg TID day 1; then 50 ug/kg TID day 2; 100 ug/kg until the end of treatment (5-7 days) depending on the rate of uterine evacuation as assessed by serial ultrasonography during the treatment period.
  • The synthetic prostaglandin analogue cloprostenol may be used at a dose of 2.5 ug/kg BID or TID for 5-7 days; side effects may be reduced by using doses of 1 ug/kg.
    At higher doses fatalities have been reported.
• PGE1 (Misoprostol Misoprostol ) - there are no published reports of safety and efficacy of PGE treatment in dogs with pyometra.
• Prostaglandins cause luteolysis and rapid uterine contractions but seldom expulsion of the pus.
  Doses of more than 125 ug (0.125 mg)/kg are more likely to produce the side effects of vomiting and diarrhea but usually decrease after second - third dose.
  Reports of the success rate are variable but some bitches may be salvaged. They should be bred at the next heat to prevent recurrence of the pyometra.
• Short term side effects: panting, salivation, vomiting, defecation, urination and tenesmus.

Dopamine agonists (cabergoline)

• Cabergoline Cabergoline : 5 ug/kg SID for 7 days:
  • Dopamine agonists are recommended in cases where the patency of the cervix is questionable; it will induce luteolysis but not uterine contractions. Once the cervix is confirmed open, then treatment with ecbolics (prostaglandins) may be initiated.
  • The combination of dopamine-agonist (cabergoline) and prostaglandin induces a more rapid luteolysis than each drug used alone.

Progesterone-receptor antagonist RU-534 aglepristone (Alizine®)

• Aglepristone blocks all biological effects of endogenous progesterone by competitively binding to progesterone receptors. It mimics luteolysis and causes cervical relaxation. Aglepristone has been used successfully in combination with cloprostenol to treat open and closed pyometras. Dose: 10 mg/kg/day; two injections 24 h apart.
  Dopamine agonists are recommended.

• Drainage of the uterus via hysterotomy for surgical drainage of uterine contents followed by uterine lavage using transcervical catheterization have been recently successfully described in 8 bitches that become pregnant in the subsequent cycles.
  Repeated transcervical catheterization for uterine lavages requires specialized training and skillful use of semi-rigid ureteroscopes or cystoscopes. The success rate is variable and the procedure represents considerable risk.

• Prostaglandins should be continued until the neutrophil count is normal, the vaginal cytology is normal and the pyometra is no longer visible on ultrasound.

• Good if early surgical intervention.
• Prognosis seriously affected if animal systemically ill.
• Renal dysfunction is mostly transient and it should resolve once the pyometra condition is successfully treated following surgical or medical treatment.

• Resolution of signs following ovariohysterectomy.
• May need post-operative support for toxemia, but can usually be released from hospital in 2-3 days.

• Delayed treatment - animal systemically ill.
• Ruptured uterus → peritonitis carries poor prognosis.
• Failure to stabilize patient prior to surgery.

Refereed papers

• Recent references from PubMed and VetMedResource.
• Verstegen J, Dhaliwal G, Verstegen-Onclin K (2008) Mucometra, cystic endometrial hyperplasia, and pyometra in the bitch: advances in treatment and assessment of future reproductive success. Theriogenology 70 (3), 364-374 PubMed.