Vet Times The website for the veterinary profession https://www.vettimes.co.uk Female reproductive emergencies approaches to pyometra treatment Author : Daniel Forster Categories : Vets Date : May 2, 2011 Daniel Forster describes the background to this common condition, and outlines both surgical and medical therapy methodologies BITCHES and queens are prone to a variety of different reproductive problems the majority of which are confined to the entire animal. One of the most common reproductive problems is detailed in this article. Pyometra We all know the basics behind the classic pyometra complex and its habit of presenting itself towards the end of an already manic work day often on a Friday. In fact, they are so common that, as veterinary surgeons, we often have them in and out of the hospital within 24 hours after a bout on fluids and a swift ovariohysterectomy to treat the condition. However, they are not always straightforward. The disease can be complicated by factors associated with the patient itself and by circumstances surrounding the patient s owners (such as financial issues, which may be a reflection of why the bitch has not already been spayed). Cystic endometrial hyperplasia pyometra is arguably the most serious condition of the bitch s reproductive system and is likely to be the most common. Despite this, its pathogenesis is not completely understood. Traditionally, it has been regarded that a pyometra represents the end stage of a uterus, which has developed cystic hyperplastic changes over time, following a series of 1 / 6
oestrus cycles. More recently, however, pyometra and cystic endometrial hyperplasia (CEH) have been regarded as separate diseases, although it is recognised that CEH often precedes a pyometra. Pyometra is considered by many to reflect an opportunistic ascending bacterial infection during the phase of oestrus when the cervix is open. The disease manifests itself later, following hormonal effects led by the production of progesterone by a functional corpus luteum. The animal is in dioestrus during this period, and the effects of progesterone include increased growth of and uterine secretions from endometrial glands, decreased myometrial contractility and closure of the cervix. Clearly, this creates an ideal environment for multiplication of any pathogens that entered the uterus during oestrus. Progesterone also has an immunosuppressive effect by inhibiting the leukocyte response, which probably encourages development of the disease. It is also possible that oestrogens play a part, as the cell receptors for progesterone are oestrogendependent. Escherichia coli is the most commonly isolated pathogen in this condition, although Staphylococcus, Streptococcus, Proteus and Pasteurella species among others have also been isolated. As outlined above, the infection phase begins during oestrus under the influence of progesterone. The resulting response by the immune system is to direct white blood cells to the infection site, resulting in a pus-filled organ ( Figure 1 ). The release of endotoxins from bacterial cell walls of invading pathogens into the bloodstream may then follow, with further consequences. Clinical signs are usually seen around eight weeks post-oestrus in the bitch and four weeks in the queen. Any middle-aged to older entire bitch that is unwell postseason (particularly within the first two months) should be checked for a pyometra before any further investigation or treatment. Typically, animals present dull, inappetent, vomiting and polydipsic, although clinical signs are variable. A vaginal discharge may or may not be present, depending on whether the cervix is open. The discharge typically contains degenerating leukocytes. There is usually pyrexia initially, but the temperature may revert to normal as the condition progresses. The majority of the symptoms are likely to be related to systemic toxaemia. Polydipsia often develops due to interference with the normal resorptive function of renal tubule cells. Glomerulonephritis can develop due to circulating antigen: antibody immune complexes. The enlarged uterus may be palpable and the abdomen may also be distended ( Figure 2 ). 2 / 6
Physiologically, queens should only develop a pyometra ( Figures and 3b) after a mating where progesterone levels are increased, since they are induced ovulators. The condition has, however, been reported in cats that have not been mated, suggesting they have been stimulated to ovulate in another fashion. Queens receiving progestogen treatment for skin disorders also have an increased incidence of pyometra. Diagnosis A history of recent oestrus in an entire bitch that is presenting with the above symptoms is enough to arouse suspicion of a pyometra. Further investigation to confirm the condition and rule out other problems is important though. An ultrasound scan is the fastest and least invasive method of confirming the uterine infection. Typically, there will be variable sized loops, usually with anechoic fluid, but sometimes floccular. The possibility of hydrometra or mucometra should also be considered. Radiography can also be used if the uterus is visible on a lateral radiograph, it is likely to be enlarged. Intestines may be displaced and a soft tissue opacity will be evident ventrally. It should be noted that a gravid uterus will appear enlarged and fluid-filled at four to six weeks the foetal skeletons will not be visible until later ( Figure 4 ). Ultrasound can distinguish the enlarged pregnant uterus from a pyometra. Haematology typically demonstrates a neutrophilia with left shift, consistent with an active infection. However some animals will have a normal white blood cell count (particularly those with open pyometras). Anaemia associated with chronic inflammation may also be present (due to suppression of erythropoiesis). Biochemistry may indicate azotaemia, which can be associated with dehydration and hypovolaemia (prerenal), or could be associated with pre-existing renal failure. There may be elevations in liver enzymes, especially in older patients, such as elevated alanine aminotransferase (ALT) and alkaline phosphatase (AKLP). Other bitches will have raised liver enzymes, secondary to toxaemia-induced hepatocellular damage or dehydration. Urine samples can help to clarify the changes in urea and creatinine as pre-renal or renal. Some patients may be hypoglycaemic due to sepsis and the systemic inflammatory response depleting glycogen stores, thereby increasing peripheral glucose use and decreasing gluconeogenesis. In contrast, blood glucose levels can also be elevated secondary to progesterone induced growth hormone production. Production of endotoxins (typically associated with E coli i nfection) may be responsible for polyuria and polydipsia. Damage to the renal tubule cells and glomerulus caused by immune complex deposition in renal tissue causes a lack of response of the kidneys to anti-diuretic hormone, thus 3 / 6
inducing polydipsia and polyuria. Treatment Stabilisation prior to surgery is essential. Placing an intravenous (IV) catheter to allow appropriate IV fluids to correct underlying hypovolaemia and starting IV antibiosis are the first steps. Broadspectrum antibiotics are a good choice initially, such as amoxicillin clavulanate or equivalent. Once the hypovolaemia has been corrected, an ovariohysterectomy can be performed. Use of postoperative antibiotics is up to the veterinary surgeon. It is recommended particularly where there is contamination/ sepsis during surgery. A large incision is useful during surgery to allow exposure of the infected organ without any tears and subsequent abdominal contamination. The uterus may be friable and vessels will be engorged, so extra care should be taken during clamping and ligation. Medical therapy is a possibility for breeding bitches, where there is reason for avoiding surgery, or in very old bitches, which are high-risk surgery candidates. These individuals should be selected with care, and the owner should be made aware that surgery may still be required, and of the high risk of recurrence if medical therapy is effective. Many drugs are not licensed for treating pyometra in bitches. Options for medical therapy include using prostaglandins (such as cloprostenol), progesterone antagonists (such as aglepristone), dopamine receptor agonists (such as cabergoline) and antibiotics. It is a good idea to admit bitches during medical treatment to watch for side effects (particularly from using prostaglandins), which may include salivation, panting, abdominal pain, mydriasis, anxiety, diarrhoea and vomiting. Use of prostaglandins at too high a dose can result in ataxia, collapse, hypovolaemic shock, respiratory distress and death. The effect of the prostaglandins is two-fold. They cause luteolysis and uterine contraction, and, therefore, should only be used in bitches with an open cervix pyometra. The luteolysis is rapid and progesterone levels will usually fall to within normal limits after two to three days (normal limits are regarded as less than 2ng/ml or less than 7nmol/L). Response to therapy can be assessed by measuring blood progesterone levels in combination with ultrasound measurement of uterine lumen width. Some studies have indicated that natural prostaglandins have fewer systemic effects than synthetic prostaglandins. The principle behind the use of dopamine receptor agonists (such as cabergoline) is their action as prolactin antagonists. They have a long-lasting inhibitory effect on prolactin secretion. This is thought to help contribute to luteal regression, since prolactin is luteotropic, and various studies have been done to investigate their use in combination with prostaglandins. 4 / 6
Aglepristone is a synthetic steroid with antiprogestagenic activity, which works by binding to progesterone receptors with three times the affinity of progesterone. In pyometra treatment, this can aid in opening the cervix to help evacuate the uterine contents, which can be particularly useful in treating closed pyometra. Studies have been conducted using a combination treatment of cloprostenol (prostaglandin F2? analogue), potentiated sulphonamide antibiotics and cabergoline (dopamine receptor agonist), with reasonable success rates (England, 2007). Further studies looking at the effects of aglepristone in treating pyometra have been conducted. Use of aglepristone on its own and in combination with cloprostenol have been trialled with varying results. In 17/17 bitches with a closed pyometra treated with aglepristone, all bitches cervices opened within 48 hours of the drug being administered. The study found that bitches treated with cloprostenol as well had a significantly better recovery rate (Fieni, 2006). Studies of medical therapy for cats with pyometra have also been conducted. A 2009 study published in the Journal of Feline Medicine and Surgery investigated follow-up examinations after medical treatment of pyometra in cats with the progesteroneantagonist aglepristone. Ten cats were used in the study and treated with aglepristone at a dose of 10mg/kg bodyweight subcutaneously on days one, two, seven and 14 (if not cured). In addition, trimethoprim/sulphadoxine was also administered at a dose of 15mg/kg bodyweight subcutaneously once a day for seven days. Nine out of the 10 cats responded well to treatment. No recurrence was observed in a follow-up period of two years. No side effects were observed (Nak, 2009). The authors suggest that aglepristone treatment is a promising approach for the medical treatment of pyometra in cats. The author refers readers to relevant papers for more information on medical treatment protocols for pyometra, and reiterates that these treatment protocols involve using medicines that may not be licensed for use in cats and dogs, or for the treatment of pyometra. Stump pyometra Stump pyometras are typically recognised in spayed bitches with ovarian remnant syndrome, although they can also occur in spayed bitches receiving exogenous progesterones. During surgery, the abdominal cavity should be searched for any remaining ovarian tissue, and if found it should be removed, along with the infected stump. Blood tests for circulating hormones may prove useful in the diagnostic work-up. To download published Veterinary Times articles, visit www.vetsonline.com 5 / 6
Powered by TCPDF (www.tcpdf.org) References Castex G et al (2003). A study of two protocols combining aglepristone and cloprostenol to treat open cervix pyometra in the bitch, Journal of Theriogenology 60: 901-908. England G C W, Freeman S L and Russo M (2007). Treatment of spontaneous pyometra in 22 bitches with a combination of cabergoline and cloprostenol, Veterinary Record 160: 293-296. Fieni F (2006). Clinical evaluation of the use of aglepristone, with or without cloprostenol, to treat cystic endometrial hyperplasia-pyometra complex in bitches, Journal of Theriogenology 66: 1,550-1,556. Fransson B A and Ragle C A (2003). Canine pyometra: an update on pathogenesis and treatment, Compendium on Continuing Education for the Practising Veterinarian 25: 602-612. Harvey M (1998). Conditions of the non-pregnant female. In Sampson G et al (eds) BSAVA Manual of Small Animal Reproduction and Neonatology, BSAVA Publishing: 46-49. Hedlund C S (2002). Surgery of the reproductive and genital systems. In Fossum T W et al (eds), Small Animal Surgery, Mosby: 639-644. Nak D and Nak Y (2009). Follow-up examinations after medical treatment of pyometra in cats with the progesterone antagonist aglepristone, Journal of Feline Medicine and Surgery 11: 499-502. Thomas P G A (2003). Reproductive disorders. In Schaer M (ed), Clinical Medicine of the Dog and Cat, Manson: 460-461. ABSTRACT Pyometra complex is a common reproductive disorder of entire bitches and queens that requires emergency treatment. Diagnosis is based on history, and clinical tests including diagnostic imaging, haematology and biochemistry bloods. Treatment entails stabilisation with fluids, followed by a surgical ovariohysterectomy. More recently, medical treatment protocols based on using hormonal medications and antibiotics have been researched, with variable success rates. Recovery is good when a surgical route is taken. Readers are advised some medicines in this article are not licensed for use in cats, dogs or for pyometra treatment. Key words: pyometra, progesterone, ovariohysterectomy, antibiotics. 6 / 6