In Bitches diagnosed with Pyometra , is Medical Therapy using Antibiosis Alone as Effective as Combining Ovariohysterectomy with Antibiosis in Reducing Morbidity and Mortality ?

Clinical bottom line Ovariohysterectomy combined with antibiosis is more effective in achieving clinical cure than systemic antibiosis alone. Systemic antibiosis may be associated with recrudescence of the pyometra and the evidence base is weaker for this approach


Limitations:
• Small population studied • No long term follow-up on the animals.
• No control group used.

Clinical bottom line
Ovariohysterectomy combined with antibiosis is more effective in achieving clinical cure than systemic antibiosis alone.Systemic antibiosis may be associated with recrudescence of the pyometra and the evidence base is weaker for this approach.

Sample size: N=13
Intervention details: Bitches undergoing treatment for pyometra had blood samples taken immediately before and 7days after ovariohysterectomy

Study design: Case controlled study
Outcome studied: Whether haematological parameters and immune function normalised after ovariohysterectomy.

Main findings: (relevant to PICO question):
• Haematological parameters and immune function normalised within 7days of ovariohysterectomy.• Further immunostimulation was not necessary.

Limitations:
• All animals underwent same procedure; could not clarify whether was immunostimulation or if derragements were secondary to systemic inflammation.• No population justification noted.

Sample size: N=8
Intervention details: Dogs with confirmed pyometra were given supportive fluid therapies and antibiosis (Gentamicin and potentiated amoxicillin).They then underwent trans-cervical uterine lavage using 5% povidone-iodine in saline solution, combined with direct visualisation of the uterus.

Study design: Case control study
Outcome studied: Whether surgical lavage of the uterus produced more reliable and faster outcomes.

Main findings: (relevant to PICO question):
• E. coli was the most common organism isolated.
• Vaginal discharge was scant following the procedure, becoming absent by day4 in all except 1 dog, which resolved after 12days.• All dogs subsequently returned to cyclicity and conceived.

Limitations:
• No set exclusion criteria; any dog presenting with pyometra was accepted.• No case controls used.
• Treatment is not licensed and small population means further studies needed before this method could be justified routinely.• Likely expensive as a treatment; benefit over medical therapy uncertain.

Limitations:
• No statistics used in this study.

Study design: Descriptive case series
Outcome studied: Resolution of the clinical signs of open pyometra.

Main findings: (relevant to PICO question):
• All dogs achieved clinical cure in this study, with no recurrence during a one year period.• Within 5-7 days then palpable uterine diameter reduced significantly.• No vulval discharge was observed after 12 days.• 4 out of 22 dogs conceived after subsequent mating.
• The authors concluded that this treatment regime can be adopted with great success.

Limitations:
• The study is not clear with regards to the population numbers; it says 22 initially and then 14 and does not clarify this point.

Main findings: (relevant to PICO question):
• All dogs achieved clinical cure in this study; 3 dogs after 4 days treatment and a further 2 dogs after 6 days of treatment.
• No dogs experienced recurrence of the pyometra.
• The authors recommend that ovariohysterectomy be the choice treatment.• The authors discussed that this medical management was effective only in the "earlier" stages of pyometra.

Limitations:
• This is a case series, so whilst treatment was successful there is no control group to compare the findings too.total pages: 11 • 1 dog required a second port to exteriorise uterus.

Limitations:
• Case series; not a prospective clinical trial so no comparison of different techniques.• No statistics were used in this descriptive study.• Only 7 dogs form the case series, 1 of which required conversion to an open approach so less frequent complications may not have been encountered.• Wide range of follow-up means not all complications may have been noticed.• Use of concurrent antibiosis not recorded.

Wheaton et al (1989)
Population: Entire female dogs diagnosed with pyometra who were managed surgically with ovariohysterectomy

Sample size: N=73
Intervention details: Medical records were analysed for all dogs diagnosed with pyometra and treated surgically between January 1976 and April 1987.The diagnosis was confirmed surgically.Some dogs had the diagnosis further confirmed histologically but these observations were not included.

Study design: Retrospective descriptive study based on case records
Outcome studied: To discuss the outcome of dogs with pyometra when managed surgically with ovariohysterectomy.It also aims to discuss three particular complications associated with such management.

Main findings: (relevant to PICO question):
• Mean age of affected dogs was 7.9 years.• 6/8 dogs aged <3years had received estradiol cyprionate or megestrol acetate within 6 months of presentation, and one 10yr old bitch.• The mean time since the last observed season was 8 weeks.
• The most common bacteria isolated was E. coli (66% cases).
• 3 dogs developed post-operative complications related to embolization of septic foci.All dogs survived, but one dog suffered intermittent recurrence of clinical signs which were antibiotic responsive over the next 3 years.• 4 dogs (5%) died either during surgery or in the immediate post-operative period.• Age did not appear to affect outcome in this study.

Limitations:
• Retrospective case study; no control groups.
• Diagnosis confirmed based on visual assessment only; early cases or cases with less gross pathological change may have been inadvertently excluded.• No statistical analysis was performed in any of these groups and so associations cannot be clarified.• Long term follow up data is lacking.
• The paper does not specify that all complications are mentioned; overall data on complication rates is difficult to state here.

Appraisal, application and reflection
Overall, there seemed to be much better quality evidence to support the use of ovariohysterectomy compared to antibiosis alone.That said however, there were no studies which directly compared the two methods.Whilst potentially very useful, such studies would need careful case selection and safeguards given the potential for a detrimental clinical effect.Once available however, a review of the new evidence alongside existing evidence would allow a more definitive comparison of the two protocols to be made.The quality of the current published papers reviewed also means that a bias towards ovariohysterectomy may have been made owing to the increased level of detail that the ovariohysterectomy protocols contained, and the fact that such papers were written more recently.
In the studies themselves, inclusion criteria were often well defined; exclusion criteria were rarely defined though.A substantial number of papers were rejected for review because they focused on different protocols, such as comparing the efficacy of dopamine agonists versus an anti-progestin.Such protocols will be evaluated separately.Unfortunately, several other papers were rejected as they were single case reports.Such reports were not deemed sufficient evidence to support the use of certain treatment protocols.
Whilst systemic antibiosis was advocated in all studies reviewed, there were no studies in which antibiosis alone was evaluated and compared to a control group.It would also be interesting to see studies in which ovariohysterectomy was utilized in non-septic patients and no antibiosis used, which may prove beneficial from the perspective of antibiotic resistance.Ovariohysterectomy appeared to yield good results clinically, with the large majority of cases achieving resolution of the clinical signs.Statistical analysis was not commonly utilized in the studies evaluated here; primarily because they tended to be case series rather than controlled clinical trials.No studies seemed to include a phrase justifying their sample size either; with many clinical studies involving relatively small study populations.Study recruitment issues may have been factors here.
However, many of the studies did agree on anamnestic factors such as age of presentation.The most frequently isolated organisms were similar where culture and sensitivity was performed (with E. coli being most frequently isolated).

Methodology Section Search Strategy
Databases searched and dates covered: The following search terms were applied to the PubMed database, accessed via the NCBI website

Jitpean et al (2014) Population: Bitches diagnosed with pyometra Sample size: N= 356 Intervention details: Bitches presenting to a Swedish hospital with pyometra between 2006-07 Study design: Retrospective case controlled clinical audit Outcome studied: Complications arising from therapy for pyometra Main findings: (relevant to PICO question):
• No figures are directly quoted; the outcomes of surgery here are very vague and that paper better describes the pathological changes (gross and histological) associated with canine pyometra.•There is no control group to compare the findings too.

4 total pages: 11 Limitations:•
Cases were not controlled at the time of admission; therefore therapeutic protocol not necessarily standardised between animals.•Included animals not receiving surgery in certain statistical calculations; artificially lowers scores.• Most animals received ovariohysterectomy; cannot reliably compare outcomes to medical therapy.
Population: Female entire dogs with open pyometra Sample size: N=22 or N=14 unclear

•
It is a case series study; no control group and no statistics are performed.•Unknown number of dogs received systemic fluid therapy, antibiosis and anti-emetic therapy.• There is a very limited literature review in this paper, with a textbook being referenced too.
Population: Dogs diagnosed with pyometraSample size: N= 5Intervention details: All dogs received intramuscular injection of ceftriaxone sodium and tazobactum sodium for 4-6 days.Vitamin B injections and meloxicam was also used for supportive treatment.Veterinary Evidence ISSN: 2396-9776 Vol 1, Issue 1 DOI: http://dx.doi.org/10.18849/ve.v1i1.16next review date: 18 Jan 2018 p a g e | 5 total pages: 11 Study design: Case series Outcome studied: Clinical resolution of the pyometra.
• Being a case series, no statistical analysis of the results was performed.•Only5dogs took part in this study, therefore the significance of the findings should be interpreted with caution.•Thepaper mentions a lack of recurrence of pyometra, but follow up times are not quoted.•Medications given were mentioned in the study but other supportive measures, such as the need for intravenous fluid therapy, was not mentioned.•Dosages of other medications used was not mentioned.•Long term follow up is not available.

8 total pages: 11 Exclusion / Inclusion Criteria Exclusion
and the CAB abstracts database (1973-2015) accessed on the OVID platform Search terms: (dog OR dogs OR canine OR bitch OR bitches) AND (antibio* OR amoxicillin OR sulphona* OR sulfona* OR genta OR ceftriaxone) AND (ovariohysterect* OR ovariehysterect* OR hysterect* OR spey OR spay* OR neuter*) AND (pyometra) AND (treat* OR manag*) : Articles not available in English, single case reports, book chapters and conference proceedings, articles which were not relevant to the PICO.Inclusion: Articles available in English which were relevant to the PICO.Articles had to involve more than one animal and had to describe the protocol used Veterinary Evidence ISSN: 2396-9776 Vol 1, Issue 1 DOI: http://dx.doi.org/10.18849/ve.v1i1.16next review date: 18 Jan 2018 p a g e |