Prognostic markers in female dogs with pyometra: a retrospective study of 331 casesABSTRACT
Pyometra is one of the most frequently observed gynecological diseases in elderly female dogs, with an estimated prevalence of 13.2% of reproductive disorders. The aim of this retrospective study was to assess the evolution of clinical and laboratory parameters during the first three days of hospitalization, seeking to identify the value of these variables as prognostic markers. A total of 331 female dogs with pyometra were included, being divided into groups of surviving and non-surviving animals with diagnoses of sepsis, severe sepsis and septic shock. In the statistical analysis, the Chi-square test or Fisher's exact test were performed, and the comparison between groups was performed using the Mann-Whitney test; p<0.05. The prevalence was higher in animals of mixed breed (28%), the age had a mean ± standard deviation of 12 ± 4 years. The most prevalent comorbidities were breast tumor (18.1%) followed by renal dysfunction (10.5%). The most frequent complication was peritonitis (7.2%). The presence of renal dysfunction, closed cervix, the use of vasoactive and abnormal capillary refill time (CRT) are prognostic markers, as well as the values of laboratory tests such as: myelocytes, band neutrophils, segmented neutrophils, lymphocytes, urea and creatinine.
Keywords:
canine; prognostic factors; reproductive disorders; survival rate; uterine infection
RESUMO
A piometra é uma das doenças ginecológicas mais frequentemente observadas em cadelas idosas, com prevalência estimada de 13,2% de distúrbios reprodutivos. O objetivo deste estudo retrospectivo foi avaliar a evolução dos parâmetros clínicos e laboratoriais durante os três primeiros dias de internação, buscando identificar o valor dessas variáveis como marcadores prognósticos. Foram incluídas 331 cadelas portadoras de piometra, sendo divididas em grupos de animais sobreviventes e não sobreviventes com diagnósticos de sepse, sepse grave e choque séptico. Na análise estatística, foi realizado o teste qui-quadrado ou o teste exato de Fisher, e a comparação entre os grupos foi realizada pelo teste de Mann-Whitney; p<0,05. A prevalência foi maior em animais sem raça definida (28%), e a idade apresentou média ± desvio-padrão de 12 ± 4 anos. As comorbidades mais prevalentes foram tumor de mama (18,1%) seguido de disfunção renal (10,5%). A complicação mais frequente foi peritonite (7,2%). A presença de disfunção renal, colo uterino fechado, o uso de vasoativos e o tempo de enchimento capilar (TPC) anormal são marcadores prognósticos, assim como os valores de exames laboratoriais como: mielócitos, bastonetes, segmentados, linfócitos, ureia e creatinina.
Palavras-chave:
cães; fatores prognósticos; distúrbios reprodutivos; taxa de sobrevivência; infecção uterina
INTRODUCTION
Pyometra is a disease that typically occurs during the diestrus phase of adult female dogs. It is characterized by the accumulation of purulent, infectious discharge in the uterus (Hagman, 2018; Ahn et al., 2021). However, it may also affect younger females under six years of age, particularly those exposed to exogenous estrogens or progesterone. The estimated prevalence of pyometra is 13.2% among reproductive disorders (Beadu-Lange et al., 2021). Compared to other breeds, including mixed-breed dogs, certain breeds such as Collies, Rottweilers, Cavalier King Charles Spaniels, Golden Retrievers, Bernese Mountain Dogs, Cocker Spaniels, Great Danes, and Leonbergers show a higher risk of developing the disease (Egenvall et al., 2001; Jitpean et al., 2012). This breed predisposition may be attributed to genetic factors, including mutations in genes such as ABCC4, which encodes prostaglandin transporters in Golden Retrievers (Arendt et al., 2021; Hagman, 2022).
There is limited information available on the morbidity and mortality factors associated with pyometra, contributing to gaps in our understanding of its progression and outcomes (Beadu-Lange et al., 2021). During infection, endotoxins are released into circulation, triggering systemic effects such as lethargy, inappetence, diarrhea, vomiting, depression, polyuria, and polydipsia. These signs are typically more severe in cases of closed-cervix pyometra, as the absence of vaginal discharge often delays diagnosis. Affected animals frequently develop systemic inflammatory response syndrome (SIRS), which may progress to dehydration, hypotension, hypothermia, toxemia, sepsis, severe sepsis, or septic shock (Hagman, 2018, 2022).
Hematological and biochemical abnormalities are commonly observed and vary depending on the severity of infection and the animal’s clinical status (Hagman, 2018). Anemia is present in approximately 93% of pyometra cases (Paudel et al., 2023), with many studies reporting normocytic, normochromic, non-regenerative anemia as a frequent finding (Evangelista et al., 2010; Paes et al., 2014; Hagman, 2022). Another hallmark of pyometra is an inflammatory leukogram, which may include marked leukocytosis, neutrophilia with a left shift, toxic neutrophil changes, monocytosis, and lymphopenia (Evangelista et al., 2010; Paes et al., 2014; Jitpean et al., 2017; Sant’Anna et al., 2019; Hagman, 2022, 2023).
This retrospective study aimed to assess changes in clinical and laboratory parameters over the first three days of hospitalization in female dogs with pyometra, to evaluate their potential as prognostic indicators.
MATERIALS AND METHODS
It is a retrospective study conducted at the Veterinary Hospital of the Federal University of Minas Gerais (UFMG), located in the city of Belo Horizonte, Brazil. Data was obtained through a review of electronic medical records of patients admitted with a diagnosis of pyometra. An initial search of the hospital’s electronic records system, covering the period from May 30, 2015, to January 1, 2021, identified 1,161 medical records. After reviewing these records for data consistency, 675 were confirmed as eligible cases involving ovariohysterectomy (OH) surgery. Following the application of inclusion criteria, 331 medical records were selected for final analysis.
Among the 331 cases of pyometra, patients were subclassified according to clinical status: sepsis, severe sepsis, or septic shock. Each patient was also categorized based on outcome as either a survivor (discharged alive) or non-survivor (died during hospitalization). Inclusion in the sepsis group required confirmation of an infectious focus along with at least two of the following criteria: rectal temperature < 38.1ºC or > 39.2ºC, heart rate > 120 beats per minute, respiratory rate > 20 breaths per minute, and leukocyte count (×10³) < 6 or > 16 (Silverstein and Sanotoro-Beer, 2013; Cortellini et al., 2024). Patients with renal dysfunction (urea > 56 mg/dL and creatinine > 1.5mg/dL) were classified under the severe sepsis group. Animals requiring vasoactive drugs to maintain a systolic blood pressure (SBP) > 90 mmHg or a mean arterial pressure (MAP) > 65 mmHg despite fluid resuscitation were assigned to the septic shock group.
Data analysis was based on two time points: M0 (at admission) and M48 (48 hours after ovariohysterectomy). Associations between qualitative variables were assessed using the Chi-square test of independence or Fisher's exact test when expected cell counts were below 5. The Mann-Whitney U test was used to compare qualitative and quantitative variables. To evaluate changes over time within individual animals, the Wilcoxon signed-rank test for paired data was applied. A p-value < 0.05 was considered statistically significant. All statistical analyses were performed using R software (version 3.6.1; R Core Team, 2019).
ETHICAL ASPECTS
This study was approved to the Animal Use Ethics Committee of the Federal University of Minas Gerais (UFMG) and was approved under protocol number 71/2021.
RESULTS
The prevalence of pyometra in the studied population was 49% (n = 331/675). The mortality rate among these cases was 11.8%, with most deaths occurring in animals diagnosed with septic shock. The remaining 344 records (51%) were excluded due to the presence of mucus or hematometra, insufficient data to confirm a diagnosis of pyometra, multiple comorbidities, or a history of more than one surgical procedure.
Among the affected animals, the prevalence of sepsis, severe sepsis, and septic shock was 69.5% (n = 230), 22% (n = 73), and 8.5% (n = 28), respectively. Over the 5.5-year study period, pyometra was most frequently observed in mixed-breed female dogs (28%), followed by Poodles (11.8%). A total of 60.2% of affected animals belonged to various pure breeds, including Labrador Retrievers (6.6%), Pinschers (6%), Yorkshire Terriers (5.5%), Golden Retrievers (4.8%), Rottweilers and Shih Tzus (4.5% each), Lhasa Apsos (3.6%), Basset Hounds and Chow Chows (2.4% each), and Schnauzers, Pit Bulls, and German Shepherds (1.8% each). Other breeds accounted for 14.5% of cases. The age of affected dogs ranged from 5 to 25 years (mean: 12 ± 4 years).
The most common comorbidities identified were mammary tumors (18.1%), followed by renal dysfunction (10.5%). A statistically significant difference was observed between survivors and non-survivors in the presence of renal dysfunction. Specifically, 23.1% of non-survivors had renal dysfunction, compared to 10% of survivors-an outcome that contrasts with previous findings in the literature.
Peritonitis was the most frequently observed complication, affecting 7.2% of cases. At the time of clinical evaluation, 70.7% of dogs had open-cervix pyometra, while 29.3% presented with a closed cervix. Regarding the use of vasoactive agents, only 3.4% of surviving animals required them during treatment. However, a statistically significant difference was found between survivors and non-survivors in the need for vasoactive support. Hospitalization duration also differed significantly between the two groups. Non-survivors had a mean hospital stay of 3 ± 2 days, while survivors remained hospitalized for an average of 4 ± 3 days. Similarly, capillary refill time (CRT) was significantly different: non-survivors had a CRT of 3 ± 0.6 seconds, compared to 2 ± 0.4 seconds in survivors.
Significant differences in laboratory values between survivors and non-survivors were observed only at M48 (48 hours after surgery). Specifically, segmented neutrophil counts differed significantly (Mann-Whitney, p < 0.001), indicating prognostic relevance. A similar difference was observed in band neutrophil counts at M48 (Mann-Whitney, p = 0.013). Table 1 shows that animals discharged from the hospital had a higher number of band neutrophils compared to those that died, supporting its use as a potential prognostic marker.
A significant difference in myelocyte counts between surviving and non-surviving animals was observed only at M48 (Mann-Whitney, p = 0.045) (Table 1). Significant differences in lymphocyte counts were also found at M48 (Mann-Whitney, p < 0.001). Additionally, urea concentrations differed significantly between the two groups at both M0 (Mann-Whitney, p < 0.001) and M48 (Mann-Whitney, p < 0.001). Similarly, creatinine levels showed significant differences at M0 (Mann-Whitney, p = 0.002) and M48 (Mann-Whitney, p = 0.001) (Table 1).
Mean values and respective standard deviations for the number of segmented neutrophil (μL), band neutrophil (μL), myelocyte (μL), lymphocyte (μL), urea (mg/dL), creatinine (mg/dL), of surviving and non-surviving animals diagnosed with pyometra, at time M0 (admission) and M48 (48 hours after ovariohisterectomy - OH)
DISCUSSION
In the present study, the rates of animals diagnosed with sepsis, severe sepsis, and septic shock were 69.5%, 22%, and 8.5%, respectively. These results are similar to the study by Jitpean et al. (2017), in which 61% of the animals were classified as having sepsis. In the study by Conti-Patara et al. (2012), it was observed that 54% and 44% of animals had severe sepsis and septic shock, respectively. This differs from the present study, which showed a lower frequency of both conditions. The reduction in the number of female dogs with pyometra developing severe sepsis or septic shock may be related to increased contact and care from the owners, due to the more frequent presence of the dogs inside the homes (Willems et al., 2016). The presence of owners with dogs can be beneficial, as they can more easily detect any apparent symptoms, leading to veterinary assistance and early treatment (Willems et al., 2016). The mortality rate of pyometra is relatively low, ranging from 3% to 20% (Egenvall et al., 2001; Jitpean et al., 2017). In the study conducted by Jitpean et al. (2014), a mortality rate of 10% was observed in animals with pyometra, similar to that of the present study.
The highest occurrence of pyometra was observed in mixed-breed females and poodles. Although this was noted, it is not possible to conclude that there is a breed predisposition, as the frequency of these breeds is higher in the hospital’s routine. A similar observation was made by Mamão (2010), whose evaluations were also performed at the same location as the present study, where mostly mixed-breed female dogs (35%) and poodles (30%) were observed. The study by Paudel et al. (2023) showed a high prevalence of pyometra in large-breed animals, especially mixed-breeds, with an average diagnosis age of 5.82 ± 3.07 years, and the results were partly similar to those of the present study.
Evangelista (2009) also observed a higher incidence of mixed-breed dogs with pyometra (60%), linking it to the higher occurrence of these animals in the hospital routine. Similarly, in the study by Conti-Patara et al. (2012), a prevalence of 40% mixed-breed and 23.3% poodle female dogs was observed. However, according to Egenvall et al. (2001) and Jitpean et al. (2012), the risk of developing pyometra is higher in Collies, Rottweilers, Cavalier King Charles Spaniels, Golden Retrievers, Bernese Mountain Dogs, Cocker Spaniels, Great Danes, and Leonbergers compared to all other breeds, including mixed-breed dogs.
Pyometra is a condition of high incidence in elderly female dogs (8-10 years) (Stone, 2007; Beadu-Lange et al., 2021; Hagman, 2022). Most of the animals included in this study were considered elderly based on their size and age, demonstrating a higher incidence of pyometra in older female dogs, as described in the literature.
The comorbidities with the highest relative frequency were mammary tumors and renal dysfunction. According to Hagman et al. (2011), the risk of developing pyometra did not change in dogs with mammary tumors, even though reproductive hormones are involved in the pathogenesis of both diseases. Although renal dysfunction was the second most common comorbidity, it was observed at a rate approximately four times lower than that reported in the literature. This discrepancy may be due to the diagnosis being based solely on the presence of azotemia. Renal injury in pyometra culminates in glomerular injury, progressing to tubular involvement and loss of renal function, which can be detected early by the presence of proteinuria, and later by the appearance of azotemia (Figueiredo et al., 2017; Sant’Anna et al., 2019; Ribeiro, 2019).
In addition, differences were observed between survivors and non-survivors regarding the presence of renal dysfunction, with a high percentage of both survivors and non-survivors not exhibiting renal dysfunction. This can be explained by the fact that the diagnosis may have been compromised due to the retrospective nature of the study, with patients primarily being monitored based only on the presence or absence of azotemia. Renal dysfunction can often be silent and is frequently masked by other concomitant conditions, which may divert the clinician's attention from the urinary system. Such diagnostic failures are concerning because they can lead to serious consequences. Therefore, without follow-up through laboratory analysis of early markers, such as proteinuria or urinary gamma-glutamyl transferase (GGT), renal dysfunction may be overlooked, potentially leading to chronic kidney disease or sudden death (Santos et al., 2013; Sant’Anna et al., 2019).
Peritonitis was the most common complication in this study. In a study conducted by Jitpean et al. (2014), peritonitis was observed in 12.4% of the animals, making it the most frequent complication in the group of animals studied. Female dogs undergoing ovariohysterectomy (OH) solely due to pyometra are hospitalized for 1 to 2 days. However, a prolonged postoperative period (defined as ≥ 3 days) is seen in cases of specific complications such as peritonitis, which can lead to sepsis, severe sepsis, and progression to septic shock. In these cases, the animal requires additional veterinary care and monitoring (Jitpean et al., 2014).
Regarding the cervix, most of the females included in the study had open pyometra at the time of clinical evaluation. An open cervix is more common in animals with pyometra compared to a closed cervix (Jitpean et al., 2014, 2017), a finding also observed in the present study. In the most severe cases of sepsis, severe sepsis, and septic shock, non-survivors had a higher relative frequency of a closed cervix. These results corroborate the literature, which suggests that pyometra in dogs without vaginal discharge is more severe than in dogs with an open cervix (Smith et al., 2008).
The use of vasoactive drugs was significantly higher in the group of animals that died, suggesting that cardiovascular dysfunction leads to greater severity in animals with septic shock. Septic shock is initially classified as distributive due to peripheral vasodilation, and its progression results in the overlap of all other types of shock. It accurately describes how pyometra, a uterine infection, can trigger a severe systemic inflammatory response that leads to distributive shock (Glickman et al., 2009). You correctly highlighted that this type of shock occurs due to widespread vasodilation caused by the release of inflammatory mediators such as cytokines (TNF-α, IL-1, IL-6), prostaglandins, and nitric oxide (Glickman et al., 2009). These mediators promote vasodilation and increase vascular permeability, resulting in the loss of vessel tone, decreased peripheral vascular resistance, and reduced blood pressure, which compromises the perfusion of vital organs (Glickman et al., 2009). Hypovolemic and cardiogenic shock, caused by decreased efficiency of the cardiac pump in response to the release of cardiodepressant substances into the circulation, contribute to hypotension (Cândido et al., 2012).
Regarding the length of hospitalization, there were significant differences between the surviving and non-surviving animals. Non-surviving animals had a lower mean number of days hospitalized compared to survivors in this study, because animals that died often arrived in critical condition due to severe cases of septic shock, severe sepsis, or sepsis, which reduced the number of days of hospitalization in this group. The prolonged hospitalization (≥ 4 days) of the surviving animals may be related to the fact that the main complication identified in the study was peritonitis. According to Jitpean et al. (2014), prolonged postoperative hospitalization (≥ 3 days) occurs in cases of specific complications, such as peritonitis, requiring additional veterinary care and monitoring.
CRT values differed between surviving and non-surviving animals and are used to evaluate peripheral perfusion in dogs, being considered adequate when mucosal colors return to normal within 2 seconds after local digital compression. Increased CRT occurs in cases of dehydration, reduced cardiac output, and vasoconstriction, as seen in sepsis, severe sepsis, or septic shock (Cândido et al., 2012; Salomão et al., 2014). In studies conducted by Hernández et al. (2014, 2019), it was observed that CRT was an early marker in a group of septic shock patients when compared to lactate, and was also associated with increased survival. This finding corroborates the results of this study, as a significant difference was found between surviving animals (normal CRT) and non-surviving animals (abnormal CRT).
Significant differences regarding the number of segmented neutrophils were observed only at M48, and the mean values of segmented neutrophils were higher than the reference value at all assessed times, corroborating a response to the infectious process (Trall, 2007). Most of the total leukocytes in the animals of this study were represented by segmented neutrophils, allowing for the classification of neutrophilic leukocytosis. In a study conducted by Anh et al. (2021) comparing pyometra and healthy female dogs, the concentrations of leukocytes, neutrophils, and monocytes were higher in the affected group. In the study by Paudel et al. (2023), female dogs with closed pyometra showed increases in leukocyte and lymphocyte concentrations, along with neutropenia.
Detection of significant differences in the number of segmented neutrophils at time M48 can be considered a prognostic marker. This difference is shown in Table 1, where animals that were discharged from the hospital had a higher number of segmented neutrophils than those that died. This change suggests a good bone marrow capacity to produce defense cells in response to infection. Therefore, the reduction in segmented neutrophils in non-surviving animals may indicate bone marrow depletion in the face of infection (Emanuelli, 2012; Hagman, 2018).
Significant differences were also observed in relation to band neutrophils at M48. The mean values of band neutrophils were above the reference range at all assessed times, but did not exceed the values of segmented neutrophils, indicating the presence of a regenerative left shift.
Increased bone marrow release of immature neutrophils into circulation occurs when there is an increased functional demand for neutrophils in the tissues. The presence of band neutrophils above the normal range for the species constitutes a left shift. The extent of the left shift indicates the severity of the disease; however, the magnitude of the cell count reflects the bone marrow’s ability to meet the demand. According to Stone (2007), absolute neutrophilia (usually above 25,000 cells/mm³) associated with varying degrees of cellular immaturity characterizes a left shift (> 300 band neutrophils/μL) and is a common white blood cell count (WBC) finding in animals with pyometra due to infection.
The number of banded neutrophils decreased when compared to previous time points. This finding corroborates the study by Evangelista et al. (2009), which compared laboratory changes before and after surgery, observing a reduction in the mean value of band neutrophils after ovariohysterectomy (OH), following the removal of the infectious focus.
A significant difference was observed between the surviving and non-surviving groups at M48, which can be considered a prognostic factor. Animals that were discharged had higher band neutrophil values. This change suggests a good bone marrow capacity to produce defense cells in response to infection.
Significant differences regarding the number of myelocytes were observed only at M48. In the present study, an increase in the number of myelocytes was observed in the group of animals that did not survive when M0 was compared to M48, demonstrating a left shift, reflecting a high demand for neutrophils in the tissues, with younger stages such as myelocytes being released to address the infection (Stockham and Scott, 2011). In the surviving animals, a decrease in the mean values of myelocytes was observed, likely due to the surgical removal of the uterus, the site of neutrophil migration (Hedlund, 2005). Another important finding in this study was the detection of a significant difference between the surviving and non-surviving groups at M48, which suggests a prognostic marker regarding the number of myelocytes.
Significant differences were observed between surviving and non-surviving females in relation to the lymphocyte variable at M48. The mean lymphocyte values were within the reference range, but a slight lymphopenia was noted in the non-surviving animals at M48. Lymphopenia may be associated with severe bacterial infections, such as pyometra. The reduction in the number of lymphocytes is directly proportional to the severity of the health deterioration in female dogs (Faldyna et al., 2001).
The values of urea concentration showed significant differences between M0 and M48, as well as in relation to the survival of the females. A reduction in urea values was observed in the present study, with concentrations normalizing in the surviving group. However, in the non-surviving group, the mean values remained approximately twice the maximum reference. The mean creatinine values in the surviving group decreased and remained within the reference range for the species, while in the non-surviving group, the mean values increased during the second evaluation, which may have contributed to these animals’ death.
Renal dysfunction can occur in animals with pyometra (Gasser et al., 2020). The increase in urea and creatinine in animals with pyometra can be attributed to prerenal azotemia, resulting from decreased renal perfusion due to dehydration. Typically, after surgical treatment and fluid therapy, azotemia resolves in these patients. However, azotemia unresponsive to volume replacement suggests acute tubular necrosis because of sepsis, severe sepsis, and septic shock, which indicates a poor prognosis (Julkowitz, 2005). Another important finding in this study was the significant difference between the surviving and non-surviving groups, suggesting that the presence of azotemia can serve as a valuable prognostic marker in pyometra patients.
CONCLUSION
Based on the results evaluated, the information presented in this study pertains to manifestations observed during the first three days of hospitalization in female dogs with pyometra. It can be concluded that the presence of renal dysfunction, closed cervix, use of vasoactive agents, abnormal CRT, as well as the quantification of band neutrophils, segmented neutrophils, myelocytes, lymphocytes, and levels of urea and creatinine, can serve as prognostic markers in female dogs with pyometra.
REFERENCES
- AHN, S.; BAE, H.; KIM, J.; KIM, S. et al. Comparison of clinical and inflammatory parameters in dogs with pyometra before and after ovariohysterectomy. Can. J. Vet. Res., v.85, p.271-278, 2021.
- ARENDT, M.; AMBROSEN, A.; FALL, T.; MARCIN KIERCZAK, M. et al. The ABCC4 gene is associated with pyometra in golden retriever dogs. Sci. Rep., v.11, p.16647, 2021.
- BEAUDU-LANGE, C.; LARRAT, S.; LANGE, E.; LECOQ, K. et al. Prevalence of reproductive disorders including mammary tumors and associated mortality in female dogs. Vet. Sci., v.8, p.184, 2021.
- CÂNDIDO, T.D.; TEIXEIRA NETO, F.J.; MARUCIO, R.L.; FRAZÍLIO, F.O. Diagnóstico e tratamento de choque séptico em cães. Medvep, v.10, p.128-132, 2012.
- CONTI-PATARA, A.; CALDEIRA, J.A.; MATTOS-JUNIOR, E.; CARVALHO, H.S. et al. Changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization at admission to ICU and the relation to outcome. J. Vet. Emerg. Crit. Care, v.22, p.409-418, 2012.
- CORTELLINI, S.; DECLUE, A.E.; GIUNTI, M.; GOGGS, R. et al. Defining sepsis in small animals. J. Vet. Emerg. Crit. Care, v.34, p.97-109, 2024.
- EGENVALL, A.; HAGMAN, R.; BONNETT, B.N.; HEDHAMMAR, A. et al. Breed risk of pyometra in insured dogs in Sweden. J. Vet. Intern. Med., v.15, p.530-538, 2001.
- EMANUELLI, M.P.; MARTINS, D.B.; WOLKMER, P.; ANTONIAZZI, A.Q. et al. Complete blood count, total plasma protein, neutrophil oxidative metabolism, and lipid peroxidation in female dogs with pyometra associated with Escherichia coli. Comp. Clin. Pathol., v.21, p.309-313, 2012.
- EVANGELISTA, L.S.M. Alterações clínicas e laboratoriais em cadelas com piometra antes e após ovariosalpingohisterectomia. 2009. 45f. Dissertação (Mestrado em Ciência Animal) - Universidade Federal do Piauí, Teresina, PI.
- EVANGELISTA, L.S.M.; QUESSADA, A.M.; ALVES, R.P.A.; LOPES, R.R.F.B. et al. Função renal em cadelas com piometra antes e após ovariosalpingohisterectomia. Acta Vet. Bras., v.4, p.153-161, 2010.
- FALDYNA, M.; LAZNICKA, A.; TOMAN, M. Immunosuppression in bitches with pyometra. J. Small Anim. Pract., v.42, p.5-10, 2001.
- FIGUEIREDO, M.S.; MALM, C.; MAMÃO, L.D.; OLIVEIRA, J. et al. Renal injury in female dogs with pyometra. Cienc. Rural, v.47, p.1-7, 2017.
- GASSER, B.; USCATEGUI, R.A.R.; MARONEZI, M.C.; PAVAN, L. et al. Clinical and ultrasound variables for early diagnosis of septic acute kidney injury in bitches with pyometra. Sci. Rep., v.10, p.8994, 2020.
- GLICKMAN, L.T.; GLICKMAN, N.W.; GLICKMAN, N.W. Canine pyometra: Pathogenesis, diagnosis, and management. Vet. Clin. North Am. Small Anim. Pract., v.39, p.747-762, 2009.
- HAGMAN, R. Pyometra in small animals 2.0. Vet. Clin. North Am. Small Anim. Pract., v.52, p.631-657, 2022.
- HAGMAN, R. Pyometra in small animals 3.0. Vet. Clin. North Am. Small Anim. Pract., v.53, p.1223-1254, 2023.
- HAGMAN, R. Pyometra in small animals. Vet. Clin. North Am. Small Anim. Pract., v.48, p.639-661, 2018.
- HAGMAN, R.; LAGERSTEDT, A.S.; HEDHAMMAR, A.; EGENVALL, A. A breed-matched case-control study of potential risk-factors for canine pyometra. Theriogenology, v.75, p.1251-1257, 2011.
- HEDLUND, C.S. Cirurgia dos sistemas reprodutivo e genital. In: SLATTER, D. (Ed.). Cirurgia de pequenos animais. Rio de Janeiro: Elsevier, 2005. p.702-774.
- HERNÁNDEZ, G.; LUENGO, C.; BRUHN, A.; KATTAN, E. et al. When to stop septic shock resuscitation: clues 567 from a dynamic perfusion monitoring. Ann. Intensiv. Care, v.4, p.30, 2014.
- HERNÁNDEZ, G.; OSPINA-TASCÓN, G.A.; DAMIANI, L.P.; ESTENSSORO, E. et al. Effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on 28-day mortality among patients with septic shock the Andromeda-Shock Randomized Clinical Trial. JAMA, v.321, p.654-664, 2019.
- JITPEAN, S.; AMBROSEN, A.; EMANUELSON, U.; HAGMAN, R. Closed cervix is associated with more severe illness in dogs with pyometra. BMC Vet. Res., v.13, p.11, 2017.
- JITPEAN, S.; HAGMAN, R.; STRÖM HOLST, B.; HÖGLUND, O.V. et al. Breed variations in the incidence of pyometra and mammary tumors in Swedish dogs. Reproduction, v.6, p.347-450, 2012.
- JITPEAN, S.; STRÖM-HOLST, B.; EMANUELSON, U.; HÖGLUND, O.V. et al. Outcome of pyometra in female dogs and predictors of peritonitis and prolonged postoperative hospitalization in surgically treated cases. BMC Vet. Res., v.10, p.1-12, 2014.
- JUTKOWITZ, L.A. Reproductive emergencies. Vet. Clin. North Am. Small Anim. Pract., v.35, p.414-420, 2005.
- MAMÃO, L.D. Avaliação clínica, laboratorial e hemogasométrica de cadelas com piometra. 2010. 118f. Dissertação (Mestrado em Ciência Animal) - Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, MG.
- PAES, P.R.O.; ANDRADE, M.G.M.G.; LEME, F.O.P.; VELOSO, L.B. et al. Desvio para a esquerda associado a compartimento medular de reserva dos neutrófilos não esgotado em cadelas portadoras de piometra. Arq. Bras. Med. Vet. Zootec., v.66, p.1611-1614, 2014.
- PAUDEL, M.; KAFLE, S.; GOMPO, T.R.; KHATRI, K.B. et al. Microbiological and hematological aspects of canine pyometra and associated risk factors. Heliyon, v.9, p.e22368, 2023.
- RIBEIRO, L.S. Injúria renal aguda em cadelas com piometra: a importância do diagnóstico precoce. 2019. 53f. Dissertação (Mestrado em Ciência Animal), Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Goiás.
- SALOMÃO, R.; PETRONILHO, F.E.; RITTER, C. Fisiopatologia da sepse. In: AZEVEDO, L.C.P.; MACHADO, F.R. (Eds.). Sepse. São Paulo: Atheneu, 2014. p.13-20.
- SANT’ANNA, M.C.; MARTINS, G.F.; FLAIBAN, K.K.M.C.; TRAUTWEIN, L.G.C. et al. Protein-to-creatinine urinary in the early diagnosis of renal injury in canine pyometra. Pesqui. Vet. Bras., v.39, p.186-91, 2019.
- SANTOS, R.V.; MERLINI, N.B.; SOUZA, L.P.; MACHADO, V.M.V. et al. Ultrassonografia Doppler na avaliação renal de cadelas diagnosticadas com piometra antes e após tratamento com ovariosalpingohisterectomia. Pesqui. Vet. Bras., v.33, p.635-642, 2013.
- SILVERSTEIN, D.; SANOTORO-BEER, K. Síndrome da resposta inflamatória sistêmica (SRIS). In: RABELO, R.C. (Ed.). Emergências de pequenos animais: condutas clínicas e cirúrgicas no paciente grave. Rio de Janeiro: Elsevier, 2013. p.316-321.
- SMITH, Y.C.; RASMUSSEN, S.B.; GRANDE, K.K.; CONRAN, R.M. et al. Hemolysin of uropathogenic Escherichia coli evokes extensive shedding of the uroepithelium and hemorrhage in bladder tissue within the first 24 hours after intraurethral inoculation of mice. Infec. Immun., v. 6, p.2978-2990, 2008.
- STOCKHAM, S.L.; SCOTT, M.A. Fundamentos de patologia clínica veterinária. Rio de Janeiro: Guanabara Koogan, 2011. 744p.
- STONE, E.A. Ovário e útero. In: SLATTER, D. (Ed.). Manual de cirurgia de pequenos animais. Nova York: Elsevier, 2007. p.1487-1502.
- TRALL, M.A. Hematologia nas espécies domésticas comuns. In: ______. (Ed.) Hematologia e bioquímica clínica veterinária. São Paulo: Roca, 2007. p.63-188.
- WILLEMS, A.; PAEPE, D.; MARYNISSEN, S.; SMETS, P. et al. Results of screening of apparently healthy senior and geriatric dogs. J. Vet. Internal. Med., v.31, p.1-12, 2016.
The data generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
