Predisposing Factors and History

Endometritis and metritis are inflammatory conditions of the uterus. Endometritis is more superficial and involves only the uterine lining, and metritis is deeper inflammation and extends to the myometrium. Both are significant diseases in mares because of frequent postpartum contamination of the uterus, the general susceptibility of the uterus to infection, the potential life-threatening complications of uterine infections, and the negative implications for future fertility.^1–3 Poor perineal conformation may predispose to ascending placentitis, or postpartum uterine contamination.^2,4 Susceptible mares may be predisposed to puerperal complications because of poor anatomic barriers, subsequent increased contamination with bacteria and debris, and impaired uterine contractility. A preexisting maternal infection resulting in uterine or placental disease may manifest as puerperal endometritis-metritis. Uterine inertia resulting from dystocia, uterine torsion, hydrops, abnormalities of the allantoic or amniotic fluids,^1,5–7 or endocrine imbalance may predispose a mare to puerperal infection.⁸ Dystocia resulting in maternal trauma or requiring forced extraction or fetotomy may lead to contamination of the uterus with bacteria. Trauma to the uterus, cervix, vagina, or vulva during parturition may create favorable conditions for microbial overgrowth.³⁸ Unsanitary foaling practices, poor environmental conditions, and retention of a dead fetus, particularly after dystocia or attempted abortion of twins, may predispose to disease. Retained fetal membranes may occur as a primary condition or as a sequel to other abnormalities of parturition.

Diagnosis

The most common clinical signs associated with maternal endometritis-metritis during the puerperal period are an abnormal vulvovaginal discharge and fever. In severe cases, mares are toxemic and endotoxemic and they may exhibit any or all of the following clinical signs: inappetence, depression, fever, tachycardia, tachypnea, injected mucous membranes, ileus, vulvovaginal discharge, and an increase in the height and force of digital pulses. A physical examination should include an evaluation of the horse for signs of laminitis. Abdominocentesis may be indicated in cases in which signs of colic or abdominal pain, peritonitis, severe perimetritis, or uterine rupture and laceration are suspected. A complete blood count may reveal hemoconcentration, elevated white blood cell numbers, and an increase in fibrinogen. The differential white blood cell count often shows neutrophilia or neutropenia with a left shift and toxic changes. Serum chemistry may reveal an increase in muscle enzymes due to recumbency and prerenal azotemia due to dehydration or renal injury due to circulating endotoxins. Urinalysis, especially if done on a free catch specimen, will routinely reveal blood and increased protein due to contamination by the vaginal discharge. An examination of the reproductive tract should be complete and should include visual and digital examination of the perineum, vagina, cervix, uterus, broad ligaments, and ovaries using a combination of vaginoscopy, transrectal palpation, and ultrasonography. The perineum should be examined for bruises and lacerations. A vaginal examination may disclose any of the following: vaginal or cervical trauma including bruises, hematomas, and lacerations (particularly on the dorsal aspect); fluid pooled in the cranial vagina; vaginal hyperemia; wide dilatation of the cervix, which exposes the endometrium; the presence of retained fetal membranes; and a voluminous, watery, and fetid discharge that originates from the uterus. A subinvoluted uterus, which is overly large and soft and extends beyond reach, without palpable rugae, may be identified by transrectal palpation. Ultrasonography of the uterus allows the examiner the opportunity to evaluate the uterus and broad ligaments for hematoma formation; to evaluate the tips of the horns for rupture, inversion, or membrane retention; to determine the character and amount of free intrauterine fluid; and to evaluate the uterus for evidence of retained fetal membranes. Transrectal ultrasonography may be used to confirm the presence of partially or fully retained fetal membranes by observing a dense echogenic core in the uterus, which indicates debris or retained fetal membranes, or free floating pieces or edges of membranes. Hysteroscopy, if required to identify retained fetal membranes, may be used to directly visualize the uterine wall and is best performed after distending the uterus with fluid because it is difficult to achieve full insufflation with air or carbon dioxide in the postpartum uterus.

Examination of the fetal membranes may provide clues as to the cause of the disorder. If available, the entire placenta should be examined; however, membranes that protrude from the vagina should not be overlooked. Both surfaces of the membranes should be examined. Delivered fetal membranes should be examined for completeness and the site of rupture determined. If torn, the completeness of delivery may be assessed by reconstructing the placenta using the large vessels on the allantoic surface as guides. These fetal vessels branch from the umbilicus and encircle both horns of the placenta. A large avillous area on the chorionic surface may indicate placental separation and possibly the presence of a twin. The presence of a large demarcated region, typically green to brown in color, extending from the cervical star inward, is typical of an ascending cervical infection, while the presence of a diffuse or focal thick exudate on the chorionic surface of the uterine body or horns and clumping of the microvilli may suggest a hematogenous infection. Adenomatous hyperplasia, which grossly appears as raised round or oval firm nodules on the allantoic surface, has been associated with bacterial and fungal infection in mares.⁹ Smears from an endometrial swab, exudate, or imprints from the tissue can be dried and stained.^10,11 Microscopic examination may yield clues to the nature of the disease process. A Gram stain of the exudate can be performed to determine the type of organism involved. A potassium hydroxide digestion, or periodic acid–Schiff stain with a nigrosin counterstain may be used to identify fungal elements, and a Wright-Giemsa stain is used to identify bacteria, yeast, and inflammatory cells such as macrophages and neutrophils.^11,12 Samples of the discharge should be submitted for culture and sensitivity. Fresh samples are typically more representative of the problem, as secondary opportunistic organisms frequently invade as part of the process of autolysis, may overgrow the primary pathogen, or result in a mixed culture that is difficult to interpret. Fetoplacental infection accounts for the largest proportion of fetal and neonatal losses.^13,14

Etiology

Bacterial organisms that cause endometritis-metritis during the puerperal period include Streptococcus equi zooepidemicus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Crossiella equi (nocardioform actinomycete), Leptospira spp., Brucella abortus, Salmonella abortus equi, and Listeria monocytogenes. Most authors report Streptococcus to be the most common isolate. Gram-negative organisms are commonly isolated from cases of toxic endometritis-metritis. Mixed infections are common and anaerobic bacteria may be involved in some infections. Anaerobes require special sample culture devices for growth. The most common fungal isolate is Aspergillus, followed by mucoraceous fungi.^11–14 A positive postpartum uterine culture does not always indicate a clinically significant problem because potentially pathogenic microorganisms are commonly recovered from apparently healthy mares owing to normal contamination of the uterus during stage II and III of labor.⁸ Culture results need to be interpreted in light of the clinical findings.

Pathogenesis

The pathogenesis of postpartum uterine infections involves inoculation with organisms through the cervix, by hematogenous spread, or by iatrogenic introduction. Fungal organisms commonly ascend through the cervix. An inflammatory process ensues and results in exudation. Under favorable growing conditions provided by dead or devitalized tissues, or in mares with impaired uterine contractility, the organisms replicate quickly and cause further inflammation with subsequent release of toxins. These toxins, if absorbed into the maternal circulation, create specific responses such as fever. Release of organisms into the circulation of the dam may occur and produce septicemia. Complications of endotoxemia and septicemia include systemic illness that may lead to death of the dam or neonate, lactation failure, impaired fertility, and laminitis.

Treatment

Treatment of endometritis and metritis in mild cases includes systemic antimicrobial therapy and multiple injections of oxytocin to encourage uterine involution. In more advanced cases, the mare’s condition should first be stabilized with fluid therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), and systemic antibiotic therapy. The perineum should be thoroughly cleansed and a large catheter or tube introduced through the cervix into the uterus or through the interior of the retained fetal membranes. The uterus is lavaged with saline or dilute tamed iodine solution (<1%) to remove intrauterine fluid and debris until the effluent is clear. Uterine lavage is followed by administration of oxytocin (10–40 units) to effect. Multiple small doses of oxytocin (10–20 units) may be used between lavages to help remove debris and encourage uterine involution. Uterine lavage may be repeated several times a day as long as signs of uterine disease are present. Transrectal palpation and serial complete blood counts may be used to determine the progress of the uterine therapy. Nonsteroidal anti-inflammatory drugs are indicated in cases in which a risk of laminitis is present, when signs of laminitis are present (sawhorse stance, reluctance to move, high resting heart rate that increases with locomotion, bounding digital pulses, hot hooves, extreme solar sensitivity to a hoof tester, and reluctance to lift a leg), or in cases in which endotoxemia or septicemia is present. Currently, phenylbutazone, ketoprofen, vedaprofen, or flunixin meglumine are used to treat signs of laminitis or endotoxemia-septicemia. Vasodilators such as acepromazine may be used to encourage circulation to the hooves. Bilateral palmar digital nerve blocks may be required to encourage some horses to move or to allow their hooves to be trimmed. Special hoof care for laminitic horses is advised and may involve trimming, using shoes or pads to reduce weight borne by the sole and the dorsal hoof wall, and pads to cushion the solar surface and lend frog support. Commercially available pads, shoes, and devices (Thera-Flex pads,^*Lilly pads,^† Farley boot^‡) that can be taped on, glued on, or held in place with straps, or a horseshoe may be recommended. Radiography may be used to obtain additional prognostic information concerning laminitis. Any ventral rotation of the coffin bone relative to the dorsal hoof wall is considered undesirable, and rotation of greater than 5.5 degrees is associated with a grave prognosis. Free fluid and gas may be seen on radiographs to intervene between the coffin bone and the hoof wall in acute cases with deep abscesses in the sole.¹⁵ The clinical signs observed in a particular animal may not relate well to radiographic signs; thus, each case should be treated on an individual basis. Dorsal hoof wall resections and heart bar shoes have been used with mixed success. Tenotomy of the deep flexor tendon has recently been recommended as a treatment for severe, intractable laminitis. Recovery from a severe case of acute laminitis that involves rotation of the coffin bone is prolonged, and athletic function may not be regained. The slow-growing nature of the hoof results in a convalescent period that may exceed 1 year. Regular hoof care is required to prevent pathologic changes seen in hooves of chronically laminitic cases. Lactation failure may be treated by the administration of domperidone (1.1 mg/kg PO once or twice a day). An increase in milk production is expected within 24 hours.