Pregnancy Termination in Companion Animals

by C. Scott Bailey, DVM, DACT

Despite much of discussion on the subject, there is still a great disparity in treatment protocols for mismated companion animals in the USA and elsewhere. Numerous treatment protocols are available. Ovariohysterectomy has the advantage of permanently removing the risk of an unwanted pregnancy. Medical treatments have varying side effects depending on the protocol selected, and depend on owner vigilance to prevent future pregnancies. Medical treatment is most often performed in early gestation or mid gestation. Pregnancy termination after fetal ossification (45 days) results in abortion of non-viable or poorly viable fetuses.

            Treatment choices should be guided by an animal’s actual risk of pregnancy. In dogs, a vaginal swab and cytologic evaluation provide 2 key pieces of information: 1) Detection of sperm heads on cytology can confirm exposure to a male, and 2) determination of estrus stage at the time or presentation. In a study involving 16 females with known breeding histories, Whitacre and coworkers demonstrated that sperm could be seen microscopically in 100% of cases within 24 hours of breeding and in 75% of cases within 48 hours of breeding, using a modified sampling technique. Determination of estrus stage is also a key component of determining the risk of pregnancy. Bitches with known or suspected exposure to a male during proestrus are at much lower risk of pregnancy than those exposed during estrus. Cytologic diagnosis of proestrus can be further confirmed with serum progesterone concentrations of <2ng/mL. As cats are induced ovulators, serum progesterone will likely be low in unexposed cats (<2ng/mL) and would rise after coitus in exposed cats.

Prior to any treatment, it is important to carefully consider options for treatment. Animals that are not intended to be breeding animals, do not have high risk-factors for spay-associated disease and which are not in show, should undergo ovariohysterectomy in early diestrus/pregnancy. This will prevent future unwanted pregnancies and may decrease the animals’ risk of several diseases, including pyometra, mammary and ovarian neoplasia. Animals which cannot be spayed may be treated medically with a variety of protocols.

Early pregnancy termination

            Several protocols have been proposed to medically treat bitches as soon as a mismating occurs. This approach is attractive, but may pose a greater risk to the animal and have lower success rates than other protocols. As a result, most reviewers have recommended against these treatment regimens.

            Estrogens have been widely used for this purpose in the past, but potentially severe side-effects should raise concerns. Several reports indicate significant health risks associated with estrogen treatment in dogs and cats, including an increased risk of pyometra, infertility and toxicity.

Pregnancy termination in mid-gestation

            In the dog, pregnancy can be readily diagnosed by palpation approximately 30 days after mating, whereas ultrasonographic examination can confirm pregnancy as early as 15-18 days after the LH surge (~10-20 days after mating). Embryos are easily detectable between day 22 and 25 after LH surge. In the queen, ultrasonographic pregnancy diagnosis can be achieved as soon as 11 days after mating and the embryo becomes visible by 14 or 15 days after mating.

            At this stage, embryonic fluids and tissues are resorbed by the uterus and few clinical signs are expected in response to medical intervention. A bloody discharge may be seen in bitches and queens after approximately 30 days. Abortion (fetal expulsion) occurs after 40-45 days, when fetal ossification is underway.

Prostaglandins

Natural prostaglandins can be used to terminate pregnancy beginning 5 days after ovulation, however prior to 25 days, higher doses are required than later in gestation. Hospitalization and careful monitoring of animals are recommended to control side-effects, which tend to be more severe early and diminish during the course of treatment. Side effects may be minimized by using low doses of prostaglandin, or by starting with a lower dose and gradually increasing it. It should be noted that low doses may not induce permanent luteolysis, resulting in loss of only some pups or fetal death followed by mummification. The synthetic prostaglandin cloprostenol has also resulted in effective pregnancy termination, with few side effects.

Dopamine Agonists

            In both the bitch and queen, prolactin plays a necessary luteotrophic role in pregnancy maintenance. Progesterone can be reduced or eliminated during late pregnancy by administering a dopamine agonist, which inhibits endogenous prolactin secretion.³² However, treatment success for pregnancy termination has been inconsistent in both dogs and cats and dopamine agonists alone are rarely used in companion animals.

Combined Prostaglandin/Dopamine Agonist Regimen

            Extensive work by Verstegen and coworkers, demonstrated that a dual approach to pregnancy termination results in reliable efficacy in mid gestation. Low doses of either natural or synthetic prostaglandins result in luteolysis, while dopamine agonists inhibit prolactin release. In a series of studies, administration of cabergoline and cloprostenol resulted in fetal resorption with minimal discharge or unwanted drug-effects in both dogs and cats. Treatment was continued until ultrasonographic confirmation of fetal demise. The above protocol has several distinct advantages over other protocols described: Both prostaglandins and dopamine agonists are readily available in the USA. The combined luteolytic and antiluteotrophic mechanisms decrease dosages of each drug, substantially reducing side effects. The protocols can be instituted around day 25 and result in resorption prior to fetal ossification, when most animals would abort formed fetuses. The use of orally administered dopamine agonists and long-acting, synthetic prostaglandins eliminates the need for frequent examination and hospitalization.

Conclusions

In conclusion, risk for pregnancy should be determined at the time of mismating and ideally pregnancy should be confirmed prior to treatment in order to avoid unnecessary and potentially harmful medical side effects. Treatment choices should be based on the animal’s stage of gestation and availability and should be tailored to minimize side effects as much as possible. A treatment onset between 25 and 30 days and combination of two drugs, including a prostaglandin and dopamine agonist minimize drug dosage and side effects while inducing fetal resorption rather than abortion.

 

Could it be Addison’s?

Linda E. Luther, DVM

Diplomate ACVIM (SAIM)

Many cases presented for evaluation of vague symptoms end up having hypoadrenocorticism.

Can you spot the classic cases?

Can you spot the not-so-classic cases?

Hypoadrenocorticism, or “Addison’s” disease, results from atrophy of the adrenal cortex, and often presents as a diagnostic challenge. Clinical signs can vary from subtle signs to acute collapse, and the clinical course is often waxing and waning. Untreated collapsed dogs may die, so identifying dogs affected with this disease early is optimal. Types of hypoadrenocorticism include the ‘classic’ glucocorticoid & mineralocorticoid deficient patient, and the more subtle, glucocorticoid deficient patient.

Clinical signs of classic hypoadrenocorticism may include vomiting, diarrhea, lethargy, collapse, bradycardia, abdominal pain, polyuria, polydipsia, or being “just not right”. Physical examination findings are often nonspecific. Laboratory findings in a classic case may include hyponatremia, hyperkalemia, decreased Na/K ratio, azotemia (with or without an inappropriate specific gravity), hypoalbuminemia, hypoglycemia, hypercalcemia, nonregenerative anemia. The lack of a stress leukogram is common; a normal to elevated lymphocyte count, and normal to elevated eosinophil count in a sick dog are frequent, subtle findings.

The not-so-classic case will often present with more subtle clinical signs. They will have normal electrolytes, and will often have a lack of a stress leukogram. They may also have a low normal hematocrit or a non-regenerative anemia, a low to borderline albumin, hypoglycemia and hypercalcemia. These cases are commonly missed. How can you ensure that you spot these? Look at the CBC carefully. Is there a stress leukogram? Look at the albumin level. Is it decreased or in the low normal range? Consider the history. Consider the lack of other obvious disease, and don’t forget to IGNORE the normal electrolytes. If there are enough consistent findings in a dog with vague symptoms, test for hypoadrenocorticism!

Once you suspect hypoadrenocorticism, confirmation historically has been done with an ACTH stimulation test. However, a recent study showed that if a dog had a baseline cortisol level that was greater than 2.0 ug/dL, they were very unlikely to have hypoadrenocorticism. If the baseline cortisol is less than 2.0 ug/dL, hypoadrenocorticism is not ruled out, and an ACTH stimulation test should be done.

But I thought she was in renal failure…

Cases of hypoadrenocorticism can mimic acute renal failure in that clinical signs are similar, and azotemia with an inappropriate urine specific gravity may exist. How does the astute clinician differentiate the two? Questions to ask include: Is there a stress leukogram? Was the resolution of severe azotemia very rapid? Did the patient act like a ‘brand-new dog’ after just a day of fluids?

Let’s compare “Maggie”, a 7-year-old Fs Collie that presented with vomiting and lethargy, to “Bailey”, a 12-yr-old Mn Cocker that presented in lateral recumbancy (see Table 1). Both dogs had severe azotemia with an inappropriate urine specific gravity. “Maggie” lacked a stress leukogram. The electrolyte findings in both dogs were suggestive of hypoadrenocorticism, but this finding is not pathognomonic for the disease. “Maggie” turned out to have hypoadrenocorticism. “Bailey”, did not, and he was diagnosed with renal failure (see Table 3). Because “Maggie” had an abnormal ACTH stimulation test as well as abnormal electrolytes, she had glucocorticoid and mineralocorticoid deficient hypoadrenocorticism.

Therapy for “Maggie” started with intravenous fluid therapy. The hyperkalemia was treated with the fluids, as well as intravenous sodium bicarbonate therapy (1 mEq/kg, slow IV). Glucocorticoids were given, initially using dexamethasone sodium phosphate (0.1-2 mg/kg IV). Chronic glucocorticoid therapy with physiologic dose of prednisone (0.1-0.2 mg/kg/day, doubled when she was stressed) was initiated. She was also given mineralocorticoid therapy using Percorten®-V (Desoxycorticosterone pivalate or DOCP, 2.2 mg/kg IM or SQ q. 25 initially). Florinef ® (fludrocortisone acetate, 0.01-0.02 mg/kg/day initially), which also has glucocorticoid effects, could have been used instead of Percorten®.

Could he be an Addisonian?

Some Addisonian dogs have very subtle symptoms. “Max” is a 7-yr-old Mn Labrador retriever that presented for a blood panel to monitor carprofen therapy that was chronically administered to treat degenerative joint disease (see Table 2).

“Max’s” blood panel revealed significant anemia. Upon further questioning, the owner thought that he had been quieter lately. He really was not all that sick though. Besides the anemia, the blood work showed a lack of a stress leukogram, his electrolytes were normal, and there was no azotemia. An ACTH stimulation test was done (see Table 3), and “Max” indeed was an Addisonian! Since “Max” had normal electrolytes, he had glucocorticoid deficient hypoadrenocorticism, and he was not mineralocorticoid deficient. Chronic glucocorticoid therapy with a physiologic dose of prednisone (0.1-0.2 mg/kg/day, doubled when he was stressed), was started. Mineralocorticoid therapy was not indicated in this dog. Some glucocorticoid deficient cases eventually develop mineralocorticoid deficiency, thus periodic monitoring of electrolytes was indicated.

In summary, hypoadrenocorticism can be a challenging disease to diagnose. Suspicion of the disease in dogs with vague symptoms is recommended, even in dogs that have normal electrolytes.

Disclaimer: Please verify all drug dosages before administering.

References:

Scott-Moncrieff JCR. Hypoadrenocorticism. In Ettinger SJ, Feldman EC (eds.) Textbook of Veterinary Internal Medicine, 7th ed. Saunders Elsevier, St. Louis, 2010, 1847-1857.

Lennon EM, Boyce TE, Hutchins RG et al. Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005). J Am Vet Med Assoc 2007;231:413-416.

Thompson AL, Scott-Moncrieff JC, Anderson JD. Comparison of classic hypoadrenocorticism with glucocorticoid-deficient hypoadrenocorticism in dogs: 46 cases (1985-2005). J Am Vet Med Assoc 2007;230:1190-1194.

Table 1.	“Maggie”	“Bailey”	Normal values
White blood cells, #/μL	12,880	28,290	5,500-16,900
Neutrophils, #/μL	7,670	24,750	2,000-12,000
Lymphocytes, #/μL	2,710	490	500-4,900
Monocytes, #/μL	1,550	2,370	300-2,000
Eosinophils, #/μL	890	520	100-1,490
Platelets, # x 103/μL	299	431	175-500
BUN, mg/dL	130	130	7-27
Creatinine, mg/dL	7.7	7.7	0.5-1.8
Calcium, mg/dL	13.8	5.5	7.9-12
Phosphorus, mg/dL	14.6	16.1	2.5-6.8
Na, mmol/L	136	145	144-160
K, mmol/L	9.0	9.0	3.5-5.8
Cl, mmol/L	103	111	109-122
Na/K	15.1	16.1	< 27
Urine specific gravity	1.015	1.015

Table 2.	“Max”	Normal values
Hematocrit, %	23.6	37-55
White blood cells, #/μL	2,500	5,500-16,900
Neutrophils, #/μL	1,840	2,000-12,000
Lymphocytes, #/μL	340	500-4,900
Monocytes, #/μL	110	300-2,000
Eosinophils, #/μL	190	100-1,490
Platelets, # x 103/μL	325	175-500
BUN, mg/dL	35	7-27
Creatinine, mg/dL	1.3	0.5-1.8
Albumin, mg/dL	1.2	2.3-4
Na, mmol/L	152	144-160
K, mmol/L	5.5	3.5-5.8
Cl, mmol/L	123	109-122
Na/K	27.6	< 27

Table 3.	“Maggie”	“Bailey”	“Max”	Normal values
Pre-ACTH cortisol, ug/dL	< 0.5	8.0	< 0.5	> 2.0
Post-ACTH cortisol, ug/dL	< 0.5	N/A	< 0.5	> 8.0
* Note that “Bailey’s” baseline cortisol adequately ruled out hypoadrenocorticism. “Maggie” and “max” had baseline cortisol values < 2.0 ug/dL, thus an ACTH stimulation was needed to rule in the disease.

Cool Recent Abstracts

SMALL ANIMAL

Intracranial Arachnoid Cysts in Dogs

from Compendium by Curtis W. Dewey - Veterinary Answers Consultant, Peter V. Scrivani, Ursula Krotscheck, Sofia Cerda-Gonzalez, Kerry Smith Bailey, Dominic J. Marino

Intracranial arachnoid cyst (IAC) is an infrequently reported developmental disorder seen primarily in small-breed dogs. It usually occurs in the caudal fossa, in the region of the quadrigeminal cistern. Although still considered uncommon, IAC is being recognized more frequently in veterinary medicine, coinciding with the increased availability of magnetic resonance imaging. In this article, clinical information from previously reported cases of canine IAC is combined with additional case information from our hospitals. Similar to IAC in people, it is thought that canine IAC is often an incidental finding. When IAC is responsible for neurologic disease in dogs, generalized seizures and cerebellovestibular dysfunction are the most common clinical presentations. Medical therapy of IAC focuses on management of increased intracranial pressure and seizures, if the latter are part of the clinical complaints. Surgical therapy of IAC involves either cyst fenestration or shunting the excess fluid to the peritoneal cavity.


Peripheral Nucleated Red Blood Cells as a Prognostic Indicator in Heatstroke in Dogs

from JVIM by I. Aroch, G. Segev, E. Loeb, Y. Bruchim

Heatstroke in dogs is often fatal and is associated with a high prevalence of secondary complications. Peripheral nucleated red blood cells (NRBC) occur in dogs with heatstroke, but their association with complications and the outcome is unclear. Peripheral NRBC are common in dogs with heatstroke and have prognostic significance. Forty client-owned dogs with naturally occurring heatstroke. Prospective, observational study. Dogs were followed from presentation to discharge or death. Serum biochemistry and coagulation tests were performed at presentation. CBC and evaluation of peripheral blood smears were performed at presentation and every 12 hours. The relative and the absolute NRBC numbers were calculated. Presence of NRBC was observed in 36/40 (90%) of the dogs at presentation. Median relative and absolute NRBC were 24 cells/100 leukocytes (range 0[ndash]124) and 1.48 × 103/[mu]L (range 0.0[ndash]19.6 × 103/[mu]L), respectively. Both were significantly higher in nonsurvivors (22) versus survivors (18) and in dogs with secondary renal failure and DIC versus those without these complications. Receiver operator curve analysis of relative NRBC at presentation as a predictor of death had an area under curve of 0.92. A cut-off point of 18 NRBC/100 leukocytes corresponded to a sensitivity and specificity of 91 and 88% for death. Relative and absolute numbers of peripheral NRBC are clinically useful, correlate with the secondary complications, and are sensitive and specific markers of death in dogs with heatstroke, although they should never be used as a sole prognostic indicator nor should they replace clinical assessment.


Relationships between Low Serum Cobalamin Concentrations and Methlymalonic Acidemia in Cats

from JVIM by C. G. Ruaux, J. M. Steiner, D. A. Williams

Serum cobalamin concentrations below reference range are a common consequence of gastrointestinal disease in cats. Serum cobalamin [le] 100 ng/L is associated with methylmalonic acidemia. To determine the prevalence of cobalamin deficiency, defined by elevated serum methylmalonic acid (MMA), in cats with serum cobalamin [le] 290 ng/L, and the optimum serum cobalamin concentration to predict cobalamin deficiency in cats. Residual serum samples (n = 206) from cats with serum cobalamin [le] 290 ng/L. Retrospective, observational study. Serum cobalamin and folate were measured with automated assays. Serum MMA was determined by gas chromatography-mass spectrometry. Cobalamin deficiency was defined as serum MMA > 867 nmol/L. Sensitivity and specificity of serum cobalamin concentrations [le]290 ng/L for detecting MMA > 867 nmol/L were analyzed using a receiver-operator characteristic curve. There was a negative correlation between serum cobalamin and MMA concentrations (Spearman's r=[minus]0.74, P < 0.0001). The prevalence of MMA [ge] 867 nmol/L in cats with serum cobalamin [le] 290 ng/L was 68.4%. Serum cobalamin [le] 160 ng/L had a 74% sensitivity and 80% specificity for detecting MMA > 867 nmol/L. No significant difference in serum folate concentrations was detected between affected and unaffected cats. Elevated MMA concentrations, suggesting cobalamin deficiency, are common in cats with serum cobalamin [le] 290 ng/L. Cobalamin deficiency is clinically significant, and supplementation with parenteral cobalamin is recommended for cats with gastrointestinal disease and low serum cobalamin concentrations.

For more on MMA in human beings, click here.


Small Mammals
Single- and multiple-dose pharmacokinetics of marbofloxacin after oral administration to rabbits

From AJVR by James W. Carpenter, MS, DVM; Christal G. Pollock, DVM (VETERINARY ANSWERS CONSULTANT); David E. Koch, MS; Robert P. Hunter, PhD

Objective—To determine the pharmacokinetics of marbofloxacin after oral administration every 24 hours to rabbits during a 10-day period.

Animals—8 healthy 9-month-old female New Zealand White rabbits.

Procedures—Marbofloxacin (5 mg/kg) was administered orally every 24 hours to 8 rabbits for 10 days. The first day of administration was designated as day 1. Blood samples were obtained at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours on days 1 and 10 of marbofloxacin administration. Plasma marbofloxacin concentrations were quantitated by use of a validated liquid chromatography–mass spectrometry assay. Pharmacokinetic analysis of marbofloxacin was analyzed via noncompartmental methods.

Results—After oral administration, mean ± SD area under the curve was 10.50 ± 2.00 μg·h/mL and 10.90 ± 2.45 μg·h/mL, maximum plasma concentration was 1.73 ± 0.35 μg/mL and 2.56 ± 0.71 μg/mL, and harmonic mean terminal half-life was 8.0 hours and 3.9 hours for days 0 and 10, respectively.

Conclusions and Clinical Relevance—Marbofloxacin administered orally every 24 hours for 10 days appeared to be absorbed well and tolerated by rabbits. Administration of marbofloxacin at a dosage of 5 mg/kg, PO, every 24 hours is recommended for rabbits to control infections attributable to susceptible bacteria.


EQUINE
Risk Factors for Equine Postoperative Ileus and Effectiveness of Prophylactic Lidocaine

from JVIM by S. Torfs, C. Delesalle, J. Dewulf, L. Devisscher, P. Deprez
Postoperative ileus (POI) is a frequent and often fatal complication of colic surgery. Reliably effective treatments are not available. To determine risk factors and protective factors associated with POI, and to assess the effect of lidocaine IV on short-term survival. One hundred and twenty-six horses that underwent small intestinal colic surgery and that survived for at least 24 hours postoperatively. Retrospective cross-sectional study. The association of 31 pre-, intra-, and postoperative variables with POI and the association of lidocaine treatment with short-term survival were investigated. Associations were evaluated with univariable logistic regression models, followed by multivariable analysis. Significant associations of high heart rate (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.03[ndash]1.08), the presence of more than 8 L of reflux at admission (OR = 3.02, 95% CI 1.13[ndash]8.02) and the performance of a small intestinal resection (OR = 2.46, 95% CI 1.15[ndash]5.27) with an increased probability of POI were demonstrated. Prophylactic lidocaine treatment was significantly associated with a reduced incidence of POI (OR = 0.25, 95% CI 0.11[ndash]0.56). Lidocaine treatment was also significantly associated with enhanced short-term survival (OR = 0.30, 95% CI 0.09[ndash]0.98). The variables associated with an increased risk of POI can be useful in identifying horses at risk of POI and in providing a more accurate prognosis. The results are supportive for lidocaine IV as an effective prokinetic treatment after small intestinal colic surgery.