|
Reproduction and Neonatology Margaret V. Root Kustritz, DVM, PhD, DACT Associate Professor, Small Animal Reproduction University of Minnesota College of Veterinary Medicine St. Paul, MN Parturition / Dystocia in the Bitch In the week before parturition is expected to occur, bitches show variable physical and behavioral changes including nesting and lactation. A whelping box or area should be prepared and the bitch acclimated to that area. Commercial whelping boxes are available. Any box used should be easily cleaned, and should be easy for the bitch to step in and out of but high enough to contain the pups. A "pig rail", a protrusion from the side of the box under which puppies can lie to avoid being laid on by the dam, may be desirable. The box should be lined with something easy to remove or clean, such as toweling that can be laundered. Newspaper often is used; this may stain the pups or bitch. In bitches, the fetuses initiate parturition; bitches carrying only one pup or carrying dead pups may not spontaneously enter labor. Serum progesterone concentrations fall abruptly in the last 1-2 days of gestation, causing a transient decline in body temperature to less than 99 degrees F, which may be appreciated by the owner if they are taking the dog's rectal temperature several times daily in the week before expected parturition. Serum progesterone can be measured directly to determine if a bitch is at term. Finally, abdominal radiographs can be used to give some indication of gestational age of the pups. Puppies mineralize from proximal to distal so by the time the distal extremities (bones of the paws, caudal vertebrae) and teeth are easily visible on the pups, they are within days of term. EUTOCIA = NORMAL DELIVERY Labor occurs in three stages. The first is cervical dilation; the bitch is restless and pants, nests, refuses food, and may vomit. No abdominal contractions are visible. This stage may last as long as 12 hours. The second stage is passage of puppies. Puppies may be born either head first with forelimbs extended (cranial presentation) or rear end first with tail and hindlimbs extended (caudal presentation), and may be within the amniotic sac when born. From the first obvious abdominal contractions, a pup should be born within 4 hours. No more than 2 hours should elapse between pups. Abnormalities of second stage labor include prolonged labor with no pups produced; obvious malpresentation of a pup (for example, single limb protruding from the vulva); and passage of abnormal vulvar discharge (frank hemorrhage, purulent fluid, +/- green fluid [indicates placental separation]). Third stage labor is passage of the placentas and usually occurs along with second stage labor, with the bitch passing a puppy and then the placenta 5-15 minutes later. If it does not disturb the bitch unduly, placentas should be removed and the bitch not allowed to eat them. They have no nutritional or hormonal value and may cause gastroenteritis. DYSTOCIA = ABNORMAL DELIVERY If the owner is concerned that dystocia (abnormal delivery) may be occurring, due to prolonged gestation length, apparent abnormality of second stage labor, or other concerns (for example, drop in rectal temperature more than 24 hours previously, bitch acting disoriented), the bitch should be evaluated with a physical examination, digital vaginal examination, and lateral abdominal radiograph to determine physical and mental status of the bitch and to determine number and position of pups present. If there is a concern about fetal viability, abdominal ultrasound should be performed. Consistent fetal heart rate of < 150 beats per minutes is indicative of fetal distress and suggests immediate surgical intervention. Manipulation of puppies for vaginal delivery can be performed in dogs but is difficult due to size considerations. Care should be taken when manipulating puppies since they are extremely fragile. Joints are easily dislocated and degloving injuries are common. I recommend extensive lubrication to minimize trauma to the pup. Gauze may be used to help hold the well lubricated puppies as they are passed. Under no circumstances should instruments be used to grasp and pull puppies through the vaginal canal. The most common medical therapy, recommended only for bitches with no signs of systemic illness that are known to have pups of a size suitable for vaginal delivery, is oxytocin. Historically, veterinarians have used unnecessarily large amounts of oxytocin in bitches. Recent work using tocodynamometers (WhelpWise™, Perinatal Specialties), which monitor changes in intra-abdominal pressure, has demonstrated that administration of 5 IU of oxytocin causes uterine tetany in most bitches, and that doses as small as 0.25 IU may cause effective propulsive uterine contractions. In the absence of such equipment, boluses containing 2-5 IU oxytocin should be given every 20-30 minutes; if there is no response after 3 doses, no more should be given because the receptors of oxytocin on the uterus are filled and no further response is likely, and because oxytocin can cause placental separation and so should not be given without surgical intervention (Cesarean section) always at the ready. Oxytocin increases frequency of uterine contractions. Some bitches respond well to concomitant therapy with calcium, which increases strength of contractions. If it is not obvious whether or not the bitch has responded to oxytocin therapy, take another lateral radiograph and assess for caudal movement of pups. Cesarean section is recommended if the bitch is showing signs of systemic illness, the litter is very large, one or more of the pups is so large as to preclude vaginal delivery, or the bitch has not responded to medical therapy. Anesthetic selection should take into account the ready movement of anesthetic agents across the placenta. Short-acting agents and those that are reversible are desired. The protocol most commonly used at the University of Minnesota Veterinary Medical Center follows:
Puppy resuscitation includes:
Owners may wish to know how best to prevent dystocia at later pregnancies. That question is best answered if the cause of the previous dystocia was identified.
Examination of the Small Animal Pediatric Patient Puppies and kittens are often neglected when they become ill. Financial constraints or lack of a functional relationship between the owner and pediatric patient may preclude the owners contacting veterinarians for assistance. Conversely, lack of experience in care of pediatric patients prohibits many veterinarians from encouraging breeders to present puppies and kittens. HISTORY / PHYSICAL EXAMINATION Historical facts that should be collected include duration of illness and clinical signs, number in the litter affected, any treatments given by the owner, and health and reproductive history of the dam. Ascertain, if possible, whether the puppy or kitten has ingested colostrum. More than 90% of maternal antibodies are passed to the neonate via the colostrum. Neonates should be encouraged to begin nursing within 2 to 3 hours of birth. Maximal absorption of antibodies through the intestine occurs at 8 hours after birth, and decreases significantly by one day of life. Serum IgG concentrations are low at birth, increase rapidly to a peak 18 hours after ingestion of colostrum, and then decline to a nadir at 3 to 4 weeks of age. If the owner is unsure whether a puppy has ingested colostrum, blood can be drawn from the puppy of interest and a littermate that is known to have nursed, and serum alkaline phosphatase (AP) and gamma-glutyl transpeptidase (GGT) concentrations compared between the two. Concentrations remain high for up to 10 days in puppies that have ingested colostrum. If a puppy or kitten has not ingested colostrum, antibodies can be provided by subcutaneous administration of serum from the dam or another immunocompetent animal in the household. In a study of 43 kittens, comparing subcutaneous administration of antibody-rich serum to suckling, it was demonstrated that both techniques significantly increased protective antibody concentrations in kittens, compared to a control group that received no antibodies. Pooled serum from vaccinated adult animals should be used. The empirical dose is 15 ml of serum, given subcutaneously as 5 ml boluses at birth and 12 and 24 hours later. The puppy or kitten should have been weighed at birth, and should be weighed daily thereafter. Low birth weight is correlated with poor viability. Kittens should weigh about 3.5 oz (100 gm) at birth. Puppy birth weight varies by breed; estimates for various breeds are 4.2 oz (120 gm) for Pomeranians, 9 oz (250 gm) for Beagles, 17 oz (490 gm) for Greyhounds, and 22 oz (625 gm) gm for Great Danes. Slight weight loss may occur in the first 24 hours of life. After that, the puppy or kitten should gain weight daily, doubling their birth weight by about one week of age. Rectal temperature varies with age and environment. Puppies and kittens may lose as much as 8.0 degrees F (3.8 degrees C) in the first day of life, even in a normal environment. In the first week of life, brown fat is the main source of thermogenesis; after the first week, the shivering reflex permits some thermoregulation by the pediatric patient itself. Normal rectal temperature is 96.0 +/- 1.5F (35.6 +/- 0.7C) in the first week of life, 98.6 - 100.0F (37.0 - 38.2C) in the second and third weeks of life, and gradually rises to adult levels by the age of seven weeks. In the first 2 to 3 weeks of life, puppies and kittens spend the majority of their time sleeping. They huddle together or near the dam, and will not ordinarily sleep apart from littermates or the dam until 5 to 6 weeks of age. When awake, neonates suckle vigorously. During examination, normal puppies and kittens easily can be encouraged to suckle the examiner's fingers or to root against the examiner's encircled thumb and forefinger. The owner should be encouraged to handle the young animals regularly; careful handling of neonates may help stimulate development and sociability. Caution should be taken to ensure that the dam is not disturbed by handling of her offspring. Assessment of poor muscle tone or observation of decreased activity should prompt veterinary intervention. Pediatric animals that are observed to lie apart from littermates or the dam, that cry excessively, are extremely restless, or that are recumbent should be examined by a veterinarian immediately. Eyelids separate in puppies and kittens from 5 to 14 days of age. Abyssinian kittens may exhibit eyelid separation substantially earlier (0 to 5 days of age). Corneal cloudiness due to overhydration resolves within 2 to 3 weeks of eyelid separation. Menace and pupillary light responses develop slowly, but should be present by 21 days of age. Shirmer tear testing for adequacy of lacrimation can be performed any time after eyelid separation. The retina and optic disc can be evaluated by about 6 weeks of age. Electroretinography has been described for assessment of optic function; this technique can be used by 5 to 10 weeks of age. The external auditory canals open at about 6 to14 days of age. Immediately after opening, the epithelial cells lining the canals desquamate and the normal mixed flora develops. A thorough otoscopic examination is possible in animals as young as 4 weeks of age. Assessment of hearing in the clinic is difficult. Percussive hearing tests, such as hand clapping out of the animal's field of vision, are inaccurate due to lack of reaction in distracted animals with normal hearing (false negative) and reaction due to pressure changes in deaf animals (false positive). A BAER (brain stem auditory evoked response) test measures electrical potential from the cochlea, cochlear nerve and brain stem in response to auditory stimuli. Functional maturity of hearing, and an accurate BAER test, should be possible by 4 to 6 weeks of age. If the test result is negative, the animal is functionally deaf. Partial deafness is more difficult to assess; changes in ability to detect high and low frequencies vary with age. Assessment of the entire skin and haircoat should be performed. Dermatologic conditions such as flea infestation and dermatophytosis are relatively common in young animals. The umbilicus falls off or is removed by the dam at 2 to 3 days of age. The umbilicus should be examined for evidence of infection. Traumatic inflammation of the appendages may occur if littermates are suckling on each other. Skin turgor is difficult to use as a measure of dehydration but dehydrated pediatric animals exhibit more wrinkling and less turgor of the skin, and deepening of the red color of the ventral abdomen and muzzle. Other signs of dehydration include dryness of the eyes and oral mucous membranes, and visible yellow color of the normally dilute urine. Neurologic examination of pediatric patients is possible at birth, but neurologic function does not mature until 6 to 8 weeks of age. Normal neonatal puppies and kittens can crawl, suckle, vocalize if distressed, and respond to odor, touch and pain. Withdrawal reflexes are present but slow at birth. Flexor dominance is present until about 4 days of age; onset of extensor dominance varies from days 5 to 21. Postural reactions, including non-visual placing, extensor postural thrust, and hemi-walking, are not fully developed until 6 to 8 weeks of age, and generally develop in the forelimbs before the hindlimbs. Palpation of the calvarium should be performed for assessment of closure of the bregmatic fontanelle. Persistence of an open fontanelle is not invariably associated with presence of intracranial disease (Table 1). Ultrasound through the open fontanelle for diagnosis of ventricular enlargement has been described in puppies as young as 3 weeks of age. Assessment of the musculoskeletal system includes evaluation of movement and palpation of the bones and joints. Puppies and kittens can lift their head at birth. They crawl for the first 7 to 14 days of life, and should be able to support weight on their forelimbs by 10 days of age. Locomotion is present by 3 weeks of age, allowing assessment of gait. Muscle tone should be evaluated; decreased muscle tone often precedes other signs of illness. Radiography for assessment of bone and joint abnormalities is difficult in puppies and kittens due to decreased mineralization of bone. Quality of radiographs may be enhanced by decreasing kVp to one-half that for an adult of the same thickness or, in puppies, by using 2 kvP for each 1 cm of soft tissue measured for values up to 80 kVp. The heart may be difficult to auscult in puppies and kittens, due to the small size of the heart and rapid heart rate. Heart rate is 220 beats per minute in the first week of life. Sinus arrhythmia is not described commonly. Bradycardia is associated with hypoxemia in neonates. Cardiac murmurs of grade I-III / VI, most commonly heard at the base of the heart on the left side, are often functional murmurs due to anemia, hypoproteinemia, fever or sepsis. Congenital cardiac abnormalities usually are associated with murmurs of grade III-VI / VI and abnormal peripheral pulses. The tone and grade of the murmur do not change with position of the pup and the murmur persists beyond 4 months of age. Other clinical signs associated with pathologic murmurs include poor growth, lethargy, cough, dyspnea and cyanosis. Electrocardiography can be used to identify arrhythmias and conduction disturbances but accurate assessment of cardiac enlargement by measurement of mean electrical axes is not possible. Echocardiography rarely is performed due to lack of appropriately sized transducers and measurements for pediatric patients. Lung sounds are ausculted easily with a stethoscope with a pediatric head. Respiratory rate is 10-35 breaths per minute in the first week of life and reaches adult levels by 4 weeks of age. Radiographs of the chest may show an apparent mild interstitial pattern in normal puppies. The deciduous teeth are present by 6 weeks of age. Permanent teeth erupt, displacing the deciduous teeth, at 4 to 6 months of age. Abdominal palpation should permit recognition of the left kidney, small intestines, colon and urinary bladder. If the spleen is palpable, splenomegaly is present. Hepatomegaly is present if the liver margin is palpable beyond the ribcage. Abdominal distension often is due to aerophagia due to pain or respiratory disease, maldigestion, or retention of feces or urine. SAMPLE COLLECTION AND LABWORK Venipuncture in pediatric patients can be difficult because the animal may be intractable and the veins are very small and collapse easily. Blood usually is most easily collected from the external jugular vein, although the cephalic vein may be used in larger puppies. The femoral vein is too friable for venipuncture in pediatric patients. The area over the vein should be moistened with water, not alcohol. Puppies or kittens may be restrained either by pulling the forelimbs down over the edge of a table while extending the neck as for larger animals, or by laying the animal on its back, pulling the forelimbs toward the abdomen, extending the neck and introducing the needle toward the thoracic inlet. Appropriate equipment is a 22 or 25 gauge needle attached to a 3 ml syringe. Hemolysis and venous collapse are less likely if the needle is well seated into the vein and the blood is drawn slowly. The recommended minimum data base for assessment of sick pediatric patients is a hematocrit and total protein, blood glucose concentration, blood urea nitrogen, and urine specific gravity and sediment. Contact the laboratory to find the minimum sample size needed. Blood volume in an animal weighing 1 pound (454 gm) is 25 to 40 ml. In-house analyzers need smaller samples and have faster turn-around time than commercial laboratories but may have less rigorous quality control. The blood sample should be placed in a small diameter tube to ensure adequate mixing with any anti-coagulant present and to permit greater depth of serum or plasma to aspirate after centrifugation. Oftentimes, a greater volume of plasma than of serum is obtained from a given sample; green-topped (heparinized) tubes are preferred to red-topped (serum) tubes. Purple-topped (EDTA) tubes should not be used since EDTA alters size and shape of red blood cells (RBC). The plasma sample should be removed from the clot as quickly as possible to prevent an artifactual decrease in glucose due to RBC metabolization and increase in phosphorus due to hemolysis. Urine can be collected by stimulating the genital area for a free catch or by very careful cystocentesis. Another technique is to allow the puppy or kitten to urinate onto a human incontinence pad, remove the urine-soaked inner cotton layer, place it in a syringe and press out the urine with the plunger. COMPLETE BLOOD COUNT (Table 2) Hematocrit is normal at birth but declines in the early weeks of life due to decreased production and shortened RBC lifespan. An increase in polychromasia, nucleated RBCs, Howell-Jolly bodies, and Heinz bodies (kittens) is evident. Hematocrit is normal by 8 weeks of age. A neutrophilia may be seen due to stress during venipuncture. Total white blood cell number may be up to twice that of normal adult reference values in normal pups up to 8 weeks of age. SERUM CHEMISTRY PROFILE (Table 3) Alanine aminotransferase (ALT) concentrations are decreased in young animals. Alkaline phosphatase (AP) concentrations are increased by as much as two times adult concentrations, and remain elevated throughout rapid growth, peaking in kittens at 7 months of age. Total protein (TP) and albumin are decreased in young animals as plasma volume expands faster than hepatic protein synthesis develops; TP is normal by 6 to 9 months of age. Fasting and post-prandial bile acid concentrations are as adult concentrations by 4 weeks of age. Glomerular filtration rate is reduced in puppies and kittens, varying from 20% of adult values at birth to 100% of adult values by several weeks of age. Blood urea nitrogen (BUN) values vary with relation of time of sampling to ingestion of the most recent meal, but BUN is still a more sensitive indicator of renal function than is creatinine in young animals. BUN and creatinine concentrations are high at birth and achieve adult levels by 8 weeks of age. Neonates have maternal blood glucose concentrations at birth, and then have a decrease in blood glucose to about 45 mg/dl in the first 4 to 6 hours of life, with stabilization at about 70 mg/dl by 72 hours of life. Significant hypoglycemia is defined as a blood glucose concentration of < 50 mg/dl. Pathologic hyperglycemia is uncommon in pediatric patients. Juvenile-onset diabetes mellitus has been reported in several breeds of dog and in one cat as young as 6 weeks of age, with blood glucose concentrations of 200 to 700 mg/dl, glucosuria, and clinical signs of disease including weight loss, polyuria, polydipsia, polyphagia, cataracts, and concurrent infections. Serum sodium concentrations may be decreased in the first several days of life but normalize quickly. Calcium and phosphorus concentrations are higher than adult levels unless at least 8 weeks of age. Phosphorus is elevated during rapid bone growth and is normal by 8 to 12 months of age; normalization may take longer in giant breeds. Thyroid hormone values may be elevated in pediatric patients. Serum thyroxine concentrations of 8 to10 ?g/dl were reported in 4 to 5 week-old puppies. URINALYSIS Urine specific gravity is decreased in pediatric patients, at 1.006 to 1.017. Physiologic proteinuria is present in the first days of life as colostral antibodies are absorbed and excreted in the urine. Normoglycemic glucosuria may be present until renal function matures. Parameters described to decrease with age until approximating adult values include creatinine clearance; excretion of sodium, chloride, potassium and phosphorus; protein excretion; and protein:creatinine ratio. Table 1. Published characteristics of dogs with persistent bregmatic fontanelles
Table 2. Complete blood count (CBC) values for puppies (P) and kittens (K)1,2,4,21
* WBC # = white blood cell number, Neuts = neutrophils, Lymphs = lymphocytes, Monos = monocytes, Eos = eosinophils, Basos = basophils Table 3. Serum chemistry profile values in puppies (P) and kittens (K)1-4,22
* ALT = alanine aminotransferase, AP = alkaline phosphatase, BUN = blood urea nitrogen COMMON DISORDERS OF THE SMALL ANIMAL NEONATE INTRODUCTION Mortality of puppies and kittens is high, even in well managed colonies. The rate of stillbirths averages 12.9% with a range of 4.7 to 22.1% in cats. Greatest incidence of mortality occurs within the first week of life and averages 27.3% in kittens and 26.0% in puppies. Overall mortality by weaning at 8 to 12 weeks of age averages 23.2% in kittens and 18.7% in puppies. Neonatal mortality in puppies is associated with age of the dam. The number of pups weaned per litter decreases and puppy mortality increases with increasing age of the dam. In cats, increased kitten mortality has been associated with obesity of the queen, increasing parity of the queen, and litter sizes of one or 7 kittens. Mortality is increased in Persians, Manx, and Himalayans compared to short-haired cat breeds. It is recommended that all dead puppies and kittens be submitted for necropsy. If a large number of animals is affected, sacrifice of a failing animal may be indicated. Dead animals should be stored in the refrigerator, not frozen, to prevent artifactual changes in tissue. Although necropsy is expensive and is reported to identify cause of death in only about 1/3 of submissions, diagnosis of a specific condition may enhance the veterinarian's ability to treat the remaining littermates or control a colony-wide problem. Trauma and maternal neglect are common causes of neonatal loss. The rate of puppy deaths from trauma was 37% in one colony described. Cannibalism is not uncommon in cat colonies; 25 of 107 live-born kittens (23%) were cannibalized within 3 days of life in one colony. Anecdotal reports suggest that hypocalcemia may cause bitches to savage pups. Other traumatic insults to neonates include dystocia, suckling by littermates, and overzealous cleaning by the dam. Maternal neglect may occur in high-strung dams or if the neonate is sick or chilled. If a bitch or queen repeatedly rejects a neonate, even after re-warming and physical examination to rule-out overt abnormalities, it may be best to remove that animal for hand-raising. Behavior that suggests illness of a pediatric patient includes separation from the dam, indicating either fever or culling by the dam, crying for more than 20 minutes at a time, and decreased activity. On physical examination, decreased muscle tone, pale to cyanotic mucous membranes, lack of normal bowel sounds, panting or labored breathing, rough hair coat, and diarrhea may be evident. For continuing examination of puppies and kittens, it may be beneficial to have a quantitative measure of vitality. In human medicine, babies are given an APGAR score, which is an objective measure allowing physicians and nurses to monitor for improvement or decline of that patient. An APGAR scale for puppies and kittens has been devised (Table 1); no research has been done documenting its use relative to clinical management of pediatric small animal patients. Table 1. APGAR scale for neonatal dogs and cats
Interpretation:
For puppies and kittens that present having very recently died or that arrest during examination, the followings steps should be taken:
LOW BIRTH WEIGHT / POOR GROWTH RATE The puppy or kitten should have been weighed at birth, and should be weighed daily thereafter. Kittens should weigh about 3.5 oz (100 gm) at birth. Puppy birth weight varies by breed; estimates for various breeds are 4.2 oz (120 gm) for Pomeranians, 9 oz (250 gm) for Beagles, 17 oz (490 gm) for Greyhounds, and 22 oz (625 gm) gm for Great Danes. Low birth weight is correlated with poor survivability in puppies and kittens. Birth weight is not influenced by sex of the neonate, and is more likely an indicator of inadequate intrauterine nutrition or congenital abnormalities than of prematurity. In one cat colony, 60% of 192 kittens with low birth weight died by weaning, while only 32% of normal weight kittens died by weaning. Fifty-four percent of stillborn kittens and 73% of kittens that died by 3 days of age had low birth weight in that colony. This suggests that a guarded prognosis should be given to neonates with lower than average weight at birth. Slight weight loss may occur in the first 24 hours of life. Puppies that lose greater than 10% of birth weight in the first day of life have a poor prognosis. After that, the puppy or kitten should gain weight daily, doubling their birth weight by 7 to 10 days of age. Kittens should gain 1.8 to 3.5 oz (50 to 100 gm) weekly. Puppies should gain 0.05 to 0.1 oz (1 to 2 gm) per pound (2 to 4 gm/kg) of anticipated adult weight daily, about a 10% increase per day. Pediatric animals with poor growth rate should be assessed for adequacy of nursing. Ensure that they are not being excluded from nursing by competition with stronger littermates, that the nipples are not hyperkeratotic, that mastitis is not present, and that there are no congenital abnormalities in the patient precluding effective suckling, such as cleft palate. During and after weaning, the animal should be fed a high quality, energy-dense food. Animals with slow growth and poor body condition may suffer from disorders such as a portosystemic shunt, renal failure, megaesophagus, exocrine pancreatic insufficiency, or cardiac disease. Animals with slow growth and normal body condition may suffer from disorders such as hypothyroidism, diabetes mellitus, or adrenal disease. ANOXIA Length of the anoxic episode is not associated with outcome in neonates. Anoxia is associated with bradycardia and hypoventilation in very young animals, and often is accompanied by hypothermia and a subsequent lower oxygen demand. HYPOTHERMIA Rectal temperature varies with age and environment. Puppies and kittens may lose as much as 8.0F (3.8C) in the first day of life, even in a normal environment. In the first week of life, brown fat is the main source of thermogenesis; after the first week, the shivering reflex permits some thermoregulation by the pediatric patient itself. Normal rectal temperature is 96.0 +/- 1.5F (35.6 +/- 0.7C) in the first week of life, 98.6 - 100.0F (37.0 - 38.2C) in the second and third weeks of life, and gradually rises to adult levels by the age of seven weeks. Re-warming of hypothermic puppies and kittens should be gradual, taking 30 minutes to 2 hours. The neonate should be turned and rectal temperature monitored frequently. Do not warm to a rectal temperature greater than 101F (36.3C) so as not to cause dehydration. Re-warming can be accomplished with careful use of surface heat, such as circulating hot water pads and hot water bottles, warmed inspired air or warmed fluids administered intravenously or intraosseously. Body temperature of less than 94-95F (34.5 - 35.0C) is associated with failure to suckle and ileus, visceral paralysis. Do not give milk products orally until body temperature is returned to normal since hypothermic animals are incapable of digesting milk and predisposed to aspiration if the stomach is distended. Calories can be provided by parenteral or oral administration of glucose-rich solutions, which do not require normal peristalsis for absorption. DEHYDRATION / FLUID THERAPY Dehydration is more difficult to assess in pediatric patients than in adult animals. Skin turgor may be used as a measure of dehydration; dehydrated pediatric animals exhibit more wrinkling and less turgor of the skin, and deepening of the red color of the ventral abdomen and muzzle. Other signs of dehydration include dryness of the eyes and oral mucous membranes, and visible yellow color of the normally dilute urine. Pediatric animals require more water relative to body mass compared to adults and suffer relatively greater surface losses, with a fluid requirement of about 200 ml/kg day. Pediatric animals have decreased cardiac capacity and underdeveloped renal function, and so cannot tolerate large volume replacement. Fluids can be administered via intraperitoneal (IP), subcutaneous (SQ), intravenous (IV), or intraosseous (IO) routes. Absorption of fluids from the IP space is slow, especially in hypovolemic animals, and fluids must be administered with strict aseptic technique. Similarly, SQ administration of fluids is made difficult by the limited amount of fluid that can be provided in the SQ space, and sporadic absorption, even in only moderately dehydrated animals. Isotonic fluids without glucose should be given SQ so as to prevent sloughing of skin over the injection site. Intravenous catheters for bolus or continuous infusion of fluids are best placed in the external jugular vein. Twenty-three to 25 ga catheters can be placed in the cephalic vein but the small size of the veins and short legs of pediatric animals make cephalic placement and maintenance of fluid flow difficult. One recommended protocol for IV rehydration in pediatric patients is 4 to 10 ml/kg/hr of 0.45% saline with or without 5% dextrose. Intraosseous administration of fluids is an alternative to IV therapy in animals in which placement of an IV catheter is impossible or would take an excessive amount of time. An 18 to 22 ga spinal needle is passed through the soft cortical bone at the trochanteric fossa of the femur or greater tubercle of the humerus. The needle is inserted parallel to the long axis of the bone into the intramedullary canal. Fluid flow rates of up to 11 ml/minute can be achieved with gravity, and the fluid is readily absorbed. Catheter maintenance is as for IV placement. INFECTIOUS DISEASES Severity of clinical signs with infectious disease is dependent on nutrition, thermoregulation, concurrent parasitism and developmental or hereditary defects of the immune system, and acquisition of passive immunity. PUPPIES HERPESVIRUS Herpesvirus is an opportunistic virus that most readily infects bitches in late gestation, causing stillbirths and abortion, or puppies during passage through the birth canal or in the first 3 weeks of life, causing acute neonatal viremia. Puppies exhibit abdominal pain and constant crying and die within 24-48 hours of onset of signs. Diagnosis usually is made at necropsy, during which hemorrhagic necrotizing changes are seen as petechiation of the kidneys, liver, and intestinal mucosa. Excessive pleural and abdominal fluid may be present, and inclusion bodies may be identified in hepatocytes. Treatment generally is unrewarding. The optimal temperature for incubation of the virus in tissue culture is 95.0 to 98.6F (35.0 to 37.0C); replication may be inhibited in infected puppies by maintaining body temperature above 101.0 to 102.2F (36.3 to 37.0C). INFECTIOUS CANINE HEPATITIS Puppies may be infected with this adenovirus in utero or during passage through the birth canal. This disease usually is diagnosed at necropsy; characteristic intranuclear inclusion bodies are present in hepatocytes. Infectious canine hepatitis is rare due to vaccination. CANINE DISTEMPER This disease also is uncommon due to vaccination. It usually is diagnosed at necropsy in puppies; thymic atrophy, bronchopneumonia, and characteristic intranuclear inclusion bodies are seen. KITTENS UPPER RESPIRATORY INFECTION A complex of respiratory diseases occurs in cats caused by viruses, such as rhinotracheitis and calicivirus, bacteria including Bordetella bronchiseptica and Chlamydia psittaci and, rarely, fungal organisms. Queens often are asymptomatic until stressed by queening, at which time organisms are shed and the less immunocompetent kittens infected. Clinical signs vary from mild conjunctivitis and serous oculonasal discharge to sneezing, tenacious oculonasal discharge, self-trauma due to pawing at the face, and respiratory distress. The condition usually is self-limiting and resolves in 10 to 14 days. Antibiotic therapy may hasten resolution of clinical signs. Appropriate vaccination within the colony is important for control. Calicivirus infection may be associated with mononuclear cell infiltration of joints, causing a lameness that usually is self-resolving; this is sometimes termed "limping kitten syndrome". PANLEUKOPENIA Kittens infected with feline distemper parvovirus in utero develop cerebellar hypoplasia. Those infected as neonates exhibit acute onset of vomiting and diarrhea, fever, rapid dehydration, leukopenia and death. The disease is uncommon due to vaccination. FELINE LEUKEMIA Feline leukemia virus can be transmitted to susceptible kittens while nursing or by any other close contact with infected animals. Infected kittens undergo lymphoid depletion with thymic atrophy. Clinically, they exhibit failure to thrive and secondary sepsis. FELINE INFECTIOUS PERITONITIS Feline infectious peritonitis (FIP) is rarely described as a cause of mortality in very young kittens. Diagnosis via serology is difficult due to cross-reaction with the relatively non-pathogenic enteric coronavirus (FECV). Animals infected with FECV, including kittens, shed virus before becoming viremic, lessening the value of serologic testing as a means to decrease introduction of infected animals into the cattery. BARTONELLA Bartonella henselae is the causative organism in cat scratch disease, a zoonotic disease most commonly passed to humans from cats less than one year of age. Infected kittens may be asymptomatic or may show lymphadenopathy, fever, lethargy and anorexia. SEPTICEMIA Septicemia, also called neonatal sepsis, is system-wide infection with one or more bacterial organisms. Entry occurs most commonly via the umbilicus. Other possible points of entry include the gastrointestinal tract, peritoneal cavity, respiratory tract, skin lacerations, and urinary tract. Causative organisms usually can be cultured from the dam's vaginal secretions. The animal may be predisposed to septicemia by inadequate ingestion of colostrum or concurrent disease of the neonate or dam. Gram-negative organisms are most commonly involved, with E. coli the most prevalent isolate. The subtype of E. coli identified usually is the same as that isolated from vulvar discharge of the dam and feces of animals in the facility. Other possible causative organisms include species of Staphylococcus, Streptococcus, Klebsiella, Pseudomonas, Pasteurella, Enterobacter, Enterococcus, Clostridium, Bacteroides, Fusobacterium, Brucella, and Salmonella. Clinical signs vary with the organ(s) affected. Reported syndromes include gastroenteritis with foamy vomitus, liquid diarrhea, reddening of the anus, rapid dehydration and death, pyelonephritis with abdominal pain, fever, dehydration and hematuria, omphalitis, conjunctivitis, pneumonia with respiratory distress and cyanosis, and non-specific weakness, vocalization and dehydration. Acute respiratory distress syndrome, characterized by life-threatening non-cardiogenic pulmonary edema, may occur secondary to septicemia, as may sloughing of the extremities, perhaps due to concurrent disseminated intravascular coagulation (DIC), tissue hypoxemia or vasculitis. Putative diagnosis is based on clinical signs, presence of normocytic normochromic anemia, thrombocytopenia, and mild to moderate neutrophilia with a left shift on complete blood count, and hypoglycemia on serum chemistry profile. Hypoglycemia may develop due to impaired glycogenolysis and gluconeogenesis, decreased liver perfusion due to congestion of major organs, and increased use of glucose by bacteria and leukocytes. Definitive diagnosis requires blood culture. Blood cultures can be performed by diluting 1 ml of whole blood with 5-10 ml enrichment broth, and examining the broth culture 6 to 18 hours later. Urine culture may be positive in some septicemic animals. Septicemia is commonly diagnosed at necropsy. Treatment of septicemia requires fluid therapy to counter dehydration and hypoglycemia (balanced electrolyte solution with 5% dextrose and KCl supplement if serum potassium concentrations are less than 2.5 mEq/L), oxygen therapy for management of tissue hypoxemia, and appropriate antibiotic therapy. Penicillins and cephalosporins are appropriate empirical choices pending culture and sensitivity results. CONGENITAL DEFECTS Congenital defects, those present at birth, may be hereditary, developmental, or due to exposure of the dam to teratogenic substances. The fetuses are most susceptible to noxious influences in the first third of pregnancy, during organogenesis. The congenital defect most commonly reported in a survey of 51 kittens was cleft palate. A survey of 1679 pups aged 8-16 weeks identified cryptorchidism, patellar luxation, cardiac abnormalities with murmurs, cleft palate, and umbilical and inguinal hernias as the most common congenital defects. Excellent reviews of congenital and hereditary defects in puppies and kittens exist. Examples of hereditary defects are cryptorchidism and patellar luxation. If a given defect occurs in more than one litter from a given dam or sire, or frequency of the defect increases with inbreeding, a hereditary basis should be suspected and the animals involved removed from the breeding program. Gross anatomic abnormalities are visible at necropsy. Microanatomic and biochemical abnormalities may be identified by special testing available at the University of Pennsylvania. Developmental abnormalities may occur in offspring from dams with metabolic disease. For example, women with diabetes mellitus are three times more likely to have babies with defects of the heart and neural tube than women from the general population. Chromosomal aberrations have varying effects on development; autosomal abnormalities generally are incompatible with life, while sex chromosome anomalies more commonly produce offspring with abnormalities of the reproductive tract and genitalia. Developmental defects may or may not cause secondary disease. Effects of drugs during pregnancy in dogs and cats often are extrapolated from work in other species (Table 2). Teratogens present during the first 26 days after conception often cause cephalic, ocular, otic, and/or cardiac abnormalities while those present in the transition period immediately following day 26 are more likely to cause palate, cerebellar, and/or urogenital defects. Defects of the central nervous system, cardiovascular system, and respiratory tract, depending on degree, often are incompatible with life. Queens infected with or, presumably, vaccinated with modified live virus vaccine for panleukopenia may give birth to kittens with cerebellar hypoplasia. Table 2. Teratogenic drugs
PROBLEMS OF SPECIFIC SYSTEMS EYES / EARS Ophthalmia neonatorum is conjunctivitis and infection behind closed eyelids in kittens and puppies less than 10 to 14 days of age. It is common in catteries with endemic herpesvirus (rhinotracheitis) infection. Treatment is gentle separation of the eyelids and application of topical ophthalmic ointment. Cataracts may develop in puppies and kittens fed either commercial or home-made milk replacers. These small focal cataracts usually resolve spontaneously after weaning. Upper respiratory infections also may cause ocular disease. Chlamydia psittaci often causes only mild ocular disease in kittens in the United States. Recommended therapy is daily treatment with tetracycline ophthalmic ointment for 2 weeks. The kittens should be monitored carefully for adverse reactions. If a negative reaction occurs, the eyes should be flushed with saline, chloramphenicol ophthalmic ointment substituted, and white blood cell number monitored for decline. SKIN Fleas are a common external parasite of young animals. Severe flea infestation can cause anemia, with clinical signs including pale mucous membranes, lethargy, tachycardia, and collapse and death. Fleas also can transmit tapeworms. The preferred treatment for fleas in animals less than 2 months of age is thorough bathing and grooming with a flea comb. Dipping and/or systemic treatment is not recommended for animals less than 3 months of age. Dermatophytosis is relatively common, especially in catteries. Microsporum caninum is the most common isolate. The kittens exhibit progressive crusty alopecia and may or may not be pruritic. The organism lives in dead skin and in the hair shafts of infected animals. It is difficult to eradicate from the environment and is zoonotic. If griseofulvin is used for treatment, kittens may exhibit side-effects of anorexia, vomiting, diarrhea, anemia and leukopenia, and ataxia. Griseofulvin is slowly metabolized in kittens and may be hepatotoxic. NERVOUS SYSTEM Neurological disorders may be congenital, such as hydrocephalus and cerebellar ataxia, or acquired, such as traumatic injury to the spinal column, lead toxicity, or parasitism. Bilirubin encephalopathy (kernicterus) is a rare cause of brain damage in kittens, due to high concentrations of unconjugated bilirubin in serum. GASTROINTESTINAL TRACT "Toxic milk syndrome" is a term often used to describe increased vocalization and abdominal distension in 3 to 14 day old puppies or kittens. This is more likely to be due to hypothermia with secondary ileus or to overfeeding than to abnormalities of the dam's milk. Diarrhea often occurs secondary to overfeeding of neonates or disruption of the normal gastrointestinal environment with changes in diet or antimicrobial therapy. Primary bacterial diarrhea also has been reported. Diarrhea may be difficult to diagnose in young animals with zealous dams and may be first observed as lack of weight gain and dehydration. Treatment is supportive care with fluid therapy and assessment of the feeding schedule. Intestinal parasites are common in young animals, especially those born in warm climates or in closely managed facilities. In puppies, roundworms (Toxocara canis) and hookworms (Ancyclostoma caninum) are very common. Roundworms can pass transplacentally in late gestation. Within infected puppies, the larvae may migrate to the lungs and liver, causing a non-productive cough and poor weight gain. Hookworms are passed via the dam's milk and can cause significant blood loss in infected pups within 8 days of infection although oocysts are not shed in the feces until about 14 days after infection. Treatment of puppies 2 weeks of age or older is with pyrantel pamoate (5 to 10 mg/kg per os once daily for 2 to 3 weeks). Prevention involves treatment of the bitch with fenbendazole (50 mg/kg per os once daily) from the fortieth day of gestation to 14 days post-partum. Kittens also can be infected with roundworms; treatment is with pyrantel pamoate, as described previously. Use of piperazine is not recommended in kittens. Coccidiosis can occur in either puppies or kittens. Infection usually is asymptomatic and self-limiting. If diarrhea occurs, treatment may be instituted with sulfadimethoxine (30 mg/kg once daily or 15 mg/kg twice daily in puppies, 30 mg/kg once daily in kittens weighing at least 1 kg) until signs regress. Similarly, infection with Giardia sp. usually is asymptomatic and self-limiting. If necessary, puppies and kittens can be treated with either metronidazole (30 mg/kg per os once daily for 7 to 10 days or 25 mg/kg per os twice daily for 5 days, then 10 mg/kg twice daily) or fenbendazole (50 mg/kg per os once daily for 3 to 7 days). Pentatrichomonas hominis is a trichomonad parasite, reported to cause diarrhea in some affected kittens.Hemobartonella felis may be an incidental finding on complete blood counts in kittens, or may be a cause of red blood cell destruction, anemia, and icterus. It can be treated with doxycycline (10 mg/kg once daily) and decreasing doses of prednisone. Toxoplasma gondii is an uncommon cause of a syndrome in kittens characterized by neurological signs, fever, respiratory disease, anemia, lymphadenopathy, and death within 3 to 12 days. Mode of transmission is undefined, but congenital infection seems likely since the disease has been definitively diagnosed in kittens as young as 2 weeks of age. Treatment is with triple sulfonamides, pyrimethamine, and folic acid; efficacy is questionable. Infected kittens, their feces and their bedding should be isolated and all contaminated materials destroyed. Toxoplasma oocysts are resistant to commonly used disinfectants. A zoonotic potential exists; pregnant women should not handle infected cats or contaminated materials. MUSCULOSKELETAL - "SWIMMERS" Swimmer puppies and kittens have dorsoventral compression and lateral widening of the thoracic cavity. Cause is unknown; hereditary and environmental factors (such as slippery flooring) may be involved. Treatment is taping of the limbs in an adducted position and/or provision of a non-slip surface or an uneven surface, such as egg carton foam. Nandrolone laurate (10 mg) may be administered twice with a 2 week interval, presumably to promote growth of muscle and joint-associated connective tissue. FADING PUPPIES AND KITTENS Causes of fading in puppies and kittens depends on definition of the term. Taken at its most broad, fading puppies and kittens are those that are either born weak and fail to thrive, or are vigorous and weaken, dying by about one week of age. The causes are many and include (1) septicemia, (2) inadequate environment, (3) low birth weight, (4) congenital abnormalities, (5) maternal neglect or trauma, (6) lack of ingestion of colostrum or inadequate milk, and (7) neonatal isoerythrolysis (described in cats only). In most cases, more than one of these factors probably is causative, with primary factors such as hypothermia, deficient colostrum ingestion and immunodeficiency predisposing the animal to secondary infection with subsequent hypoglycemia and dehydration leading to cardiopulmonary failure. Hypothesized causes of fading in puppies and kittens include poor thymic development with abnormal development or maturation of T cells, undefined hereditary factors causing increased neonatal mortality in inbred animals, thyroid dysfunction which may respond to treatment with 3 to 5 ?g L-thyroxine per os once daily, and abnormalities of surfactant causing inability of the neonate to breathe and suckle normally. Treatment of fading puppy and kitten syndrome is dependent on identification of the underlying cause. There is a report of successful treatment of puppies with a non-specific inimmunostimulant. NEONATAL ISOERYTHROLYSIS Neonatal isoerythrolysis is an acute disease of kittens in the first days of life. Cats have naturally occurring antibodies blood types they are lacking; development does not require previous pregnancy or transfusion. There are two main feline blood types, A and B. Homologous A/A or heterozygous A/B cats are type A. Homozygous B/B cats are type B. The rare AB blood type occurs with presence of a third allele that is codominant with B. Type A cats have weak anti-B antibodies while type B cats have strong anti-A antibodies. Kittens with blood type A born to type B queens become acutely ill after ingestion of colostrum and absorption of her anti-A antibodies. Clinical signs in the kittens include anemia, icterus, tail tip necrosis due to hemagglutination in peripheral capillaries and localized thrombus formation, weakness, tachypnea, tachycardia, hemoglobinuria, and sudden death. Severity of signs may vary within the litter, presumably due to variability in antibody uptake. The mortality rate is high in affected kittens, even with prompt intervention. The kittens should be removed from the dam and transfused if necessary. The dam is a good blood donor since she has no antibodies to her own red blood cells. Prevention involves avoiding incompatible matings (type B queens to type A toms). Estimation of proportion of incompatible matings by breed is 0.25% for domestic short-haired cats, and as high as 14-25% for Persians and Abyssinians. The type B blood type is most prevalent in the Devon and Cornish Rex and British Shorthair breeds (Table 3). Blood-typing can be performed in-house (DMS Laboratories, Flemington NJ, 1-800-567-4367) or by commercial laboratories. Table 3. Frequency of type A and B blood in cats in the United States
Contraception in Male and Female Dogs and Cats /
Pregnancy Termination in Bitches Reproductive physiology of the female The ovaries contain thousands of follicles, each of which contains an egg or ovum. As each estrous cycle begins, a cohort of follicles is selected to begin development. Development is promoted by release of hormones from the hypothalamus (gonadotropin releasing hormone [GnRH]) and pituitary (follicle stimulating hormone [FSH] and luteinizing hormone [LH]). As the follicle develops, it secretes estrogen, which causes the physical and behavioral signs of early heat, or proestrus. Estrogen levels fall about 9 days after the onset of proestrus; at this time, the bitch will stand to be bred (standing heat or estrus) and a surge of LH is released, causing ovulation. The eggs are released from the follicles into the uterine tube, where fertilization occurs. The egg ovulated into the oviduct is surrounded by a thick capsule, the zona pellucida, and by a layer of cells from the follicle. Spermatozoa introduced into the reproductive tract of the bitch undergo capacitation, a process involving the acrosome reaction on the head of the spermatozoon and achievement of hypermotility. Capacitated spermatozoa digest the layer of cells surrounding the egg and invade the zona pellucida. As soon as one spermatozoon gets to the inner layer of the zona pellucida, entry of other spermatozoa is blocked by an electrochemical reaction so only one spermatozoon fertilizes each egg. Cell division begins immediately. The developing embryo moves into the uterus within days but does not implant in the uterine wall and develop a placenta until 16 to 18 days after the LH surge. Reproductive physiology of the male Testes of male dogs should be descended into the scrotum by 8 weeks of age and must be descended by 6 months of age for the dog to be considered normal. The testes contain spermatogonia, which will divide to form spermatozoa under the influence of the hormone testosterone. Testosterone secretion is stimulated by GnRH and LH release from the hypothalamus and pituitary, respectively. Spermatozoa are manufactured in the testis but are neither motile nor capable of fertilization until after they pass through the epididymis. Spermatozoa ejaculated at the time of semen collection come from the epididymis. Reproduction control Sterilization = any procedure that makes an individual incapable of reproduction Ovariectomy (surgical removal of the ovaries), ovariohysterectomy (surgical removal of the ovaries and uterus) and tubal ligation (tying off the uterine tubes) are the techniques described. Tubal ligation is not commonly used for contraception of bitches anywhere in the world. Ovariectomy is commonly used in Europe and appears to offer the same benefits and concerns as does ovariohysterectomy (OHE or spay). Ovariectomy is reported to be less time-consuming and less invasive then OHE. In one study of 264 dogs, 126 of which had undergone ovariectomy and 138 of which had undergone OHE, no significant differences were reported in incidence of urogenital problems during a follow-up period of 8 to 11 years after surgery. Urinary incontinence was a reported finding in both groups; difference in incidence between the groups was not statistically significant. In the United States, OHE still is the most common surgical sterilization method. Benefits of OHE include absence of estrous cycling, absence of future ovarian and uterine disease and decreased incidence of mammary neoplasia in bitches and queens. For the latter, greatest benefit occurs when animals are spayed before their first estrus but recent research from Belgium suggests some benefit in bitches even as old as 9 years of age at the time of OHE. Laparoscopic OHE has been described and is associated with longer procedure time but decreased pain after surgery. Flank OHE also has been described; this technique requires dissection through muscle planes to access the abdomen and is difficulty in barrel-shaped or obese dogs. Regrowth of hair in the flank may yield coat in that area with unusual color or consistency. Concerns of OHE in general include subsequent obesity and estrogen-responsive urinary incontinence. Females gonadectomized before 3 months of age may be at increased risk of development of urinary incontinence, compared to those gonadectomized at greater than 3 months of age. Size also is a risk factor for development of urinary incontinence, with bitches weighing greater than 20 kg reportedly at higher risk. Bitches that have undergone OHE also may be at increased risk of developing neoplasia, with spayed bitches reported to be at 4X greater risk of developing hemangiosarcoma and 2X greater risk of developing osteosarcoma than intact bitches. In male dogs and cats, castration (surgical removal of both testes) and vasectomy (tying off the spermatic cord) are reported sterilization techniques. Castration is the most common surgical sterilization method. Benefits include absence of future testicular disease, decreased incidence of prostate diseases and decrease in gender-specific behaviors (roaming, mounting, urine marking). Concerns include obesity and a possible predisposition to prostatic neoplasia in castrated male dogs. Contraception = the prevention of conception Pharmacologic - Drug therapy affects normal hormone secretion, decreasing estrous cycling. Examples include: a) Progesterone - Megestrol acetate (Ovaban™). This is the only approved estrus-suppressing drug for dogs in the United States. Ovaban can be given either during anestrus (0.25 mg/lb once daily per os x 30 days), to prolong time until the next proestrus begins, or within the first 3 days of proestrus (1.0 mg/lb once daily per os x 8 days), at which point the bitch will go out of heat in 5 to 6 days and will not ovulate at that cycle. If used properly, Ovaban should not cause uterine disease or impact fertility in bitches. Possible side-effects of treatment with any form of progesterone in dogs include weight gain, predisposition to mammary neoplasia and uterine disease and induction of diabetes mellitus. These same side-effects are seen in queens with administration of progesterone, as is mammary hypertrophy. Current research describes use of progesterone within silastic implants, reported to suppress estrus for up to 2 years in bitches with no side-effects. b) Estrogen - Estrogen compounds can be used to induce azoospermia (lack of spermatozoa in the ejaculate) in dogs. However, toxic effects of estrogen include induction of squamous metaplasia in the prostate and pancytopenia. I do not recommend the use of estrogens in male dogs. c) Androgens - The only androgen approved for use in female dogs (Cheque™) is no longer available from the manufacturer. This compound never was approved for use in breeding bitches. Other androgens described for estrus suppression are forms of testosterone, which is effective in a dose-dependent manner and has been reported to be only 66% effective at suppressing estrus in Beagle bitches. Possible side-effects include vaginitis, hypertrophy of the clitoris and liver disease. Androgens cannot safely be used for estrus suppression in queens, in which they are hepatotoxic and thyrotoxic. d) GnRH agonists - These drugs mimic the action of GnRH, causing release of FSH and LH. Initially this will cause estrus but continued treatment with the drug will shut down the system, with no further estrous cycling. These drugs have been demonstrated to prevent estrus in bitches for up to 27 months and have not been associated with decreased fertility. Similarly, in males initially administration of these drugs will cause increased release of LH and testosterone but will eventually shut down the system, decreasing testosterone secretion and spermatogenesis. GnRH agonists have been demonstrated to suppress fertility for up to 27 months in dogs with subsequent return to normal fertility. These drugs are not approved for use in dogs or cats in the United States. In queens, GnRH can be used to induce ovulation (GnRH; 25 mcg/cat IM). Luteinized follicles will be maintained an average of 40 to 50 days, giving the owner a respite from estrous cycling in the queen. Ovulation induction by physical means also has been described but in the author's experience is less effective than is pharmacologic induction of ovulation. Immunologic - Immunologic approaches to contraception work by vaccinating the animal against one of the tissues or hormones described above. When an animal is vaccinated against a tissue, for example, it will create antibodies against that tissue that will either destroy the tissue or prevent its normal function. There is no commercially available contraceptive vaccine for dogs or cats at this time. Because of variable efficacy and likely lack of return on the significant investment required for FDA product approval, contraceptive vaccines are not expected to be available for at least 8 to 10 years. Compounds that are being investigated include: a) Zona pellucida - Vaccinated animals may or may not continue to cycle and time until re-vaccination is required varies much between individuals. This technique may or may not be reversible; ovarian pathology described after immunization of bitches against porcine zona pellucida proteins include ovarian atrophy and polycystic disease. b) GnRH - This is a compound against which animals do not develop antibodies readily. Immune response in tested animals has been poor, however, at this time this vaccine may be the best candidate for commercial availability in the near future. Sclerosing agents - Sclerosing agents are drugs or compounds that are injected into the testes or epididymes to cause localized inflammation and destroy or scar testicular or epididymal tissue, preventing formation and movement of spermatozoa. Many compounds have been investigated. In 2002, the FDA approved one compound, Neutersol™, for use in puppies aged 3 to 10 months with testicular width between 10 and 27 mm. The compound (zinc gluconate with arginine) is injected directly into each testis, with dose dependent on testicular width. Sedation may be required but most dogs are reported to tolerate the injection well. Immediate side effects include transient swelling of the testes or scrotum and vomiting. Neutersol™ cannot be used in cryptorchid dogs and should not be used in dogs with scrotal irritation or malformation of the testes or epididymes. In a field study of 224 dogs treated with Neutersol™, 223 were considered to be completely sterilized by 6 to 12 months after injection, based on inability to collect normal semen from these males. Testosterone secretion was decreased but not to as great an extent as with castration. Studies are ongoing for evaluation of safety of the product, efficacy as a contraceptive or sterilant and effect of decreased testosterone concentrations on prostate disease and behavior. PREGNANCY TERMINATION The canine follicle consists of a single ovum surrounded by granulosa cells and theca cells. Gonadotropin releasing hormone (GnRH) released from the hypothalamus stimulates release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary. FSH stimulates follicular growth and release of estradiol from the follicle. Estradiol stimulates production of LH receptors and feeds back to the pituitary to decrease production of FSH and stimulate an LH surge. The LH surge induces ovulation, defined as rupture of the follicle with release of the ovum into the uterine tube. The ruptured follicle fills with blood and as the granulosa and thecal cells increase in number and accumulate cholesterol, the blood is absorbed and two population of luteal cells form to make up the corpus luteum (CL). The CL secretes progesterone; in the dog, the CL is the only source of progesterone during gestation. Progesterone must be present for pregnancy to be maintained. Bitches ovulate a primary oocyte that must undergo 2 cell divisions before becoming a fertilizable secondary oocyte. The ova are fertilized in the uterine tube several days after ovulation. The zygotes remain in the uterine tube for 8-12 days, and then move into the uterus where implantation occurs 17-18 days post-fertilization. Several different methods for pregnancy termination are described in the veterinary literature. Please note that no drug is approved for use in the dog for pregnancy termination in the United States and that some of these drugs are not yet available in the United States. The following list is by no means complete. OVARIOHYSTERECTOMY (OHE, spay)
1. Breeding was witnessed-----------------------2 1'.Breeding was not witnessed-----------------------3 2. Breeding occurred fewer than 25 days ago-----------------------3 2'.Breeding occurred more than 25 days ago-----------------------4 3.Only 2/3 of dogs presumed to be bred accidentally actually become pregnant. Collection of a vaginal cytology specimen to look for spermatozoa is not definitive proof that the bitch was not bred; of course, if spermatozoa are visualized on a vaginal swab, that is definitive proof that she was bred. Without a strong suspicion of likely pregnancy, it usually is best to bide one's time until pregnancy diagnostics can be performed before making a decision about treatment. 4.The dog is verified to be pregnant-----------------------5 4'.The dog is verified not to be pregnant-----------------------6 5.Pregnancy termination with any of the compounds effective at or after mid-gestation can be used. It is recommended that pregnancy termination be performed at as close to mid-gestation as possible. At about 30-40 days of pregnancy, all tissues will be resorbed. From 40-50 days, tissues and fluid may be passed through the vulva. After about 50 days, recognizable puppies may be passed as pregnancy termination progresses. After about 55 days, live pups may be passed. 6.No treatment is necessary. Diagnosis and Management of Prostate Disease in the Dog The prostate is the only accessory sex gland of the male dog. It is a retroperitoneal organ with only the craniodorsal surface covered by peritoneum. It is bounded by the rectum dorsally and the symphysis pubis ventrally. The prostate completely encircles the urethra at the bladder neck. It is surrounded by a fibromuscular capsule and divided into two lobes by a median raphe which is palpable on the dorsal surface per rectum. Its position is pelvic until it becomes enlarged with advancing age or disease, at which time it may pull the bladder cranially and be palpable abdominally. Histologically, the glandular epithelial cell population differs with distance from the urethra, from low cuboidal to tall columnar. These glandular cells are divided into indistinct lobules by bands of smooth muscle. Blood is supplied by branches of the prostatic artery and drained by the prostatic and urethral veins. Lymph drainage is to the iliac lymph nodes. The hypogastric and pelvic nerves provide sympathetic and parasympathetic innervation, respectively. Prostate growth and secretion is androgen-dependent. Castration leads to decreased prostate volume and atrophy of glandular and stromal elements, with decreased ability to take up and metabolize androgens. The principle androgen regulating prostatic growth is 5alpha-dihydrotestosterone (DHT), which is formed from testosterone by the enzyme 5alpha reductase. Locally manifested growth factors may also act as modulators of epithelial cell growth and function. The prostate gland secretes seminal plasma under the control of hormonal factors and stimulation by the parasympathetic nervous system. Expulsion of prostatic fluid into the urethra is stimulated by the sympathetic nervous system. Prostatic fluid makes up the first and third fractions of the canine ejaculate and acts to thin and increase volume of the ejaculate, and possibly aid sperm transport. Prostatic fluid is secreted constitutively, and is normally expelled into the prostatic urethra, from where it drains into the urinary bladder and along the penile urethra. Prostatic disease is fairly common in the dog, with a reported incidence of 2.5%. The normal prostate gland grows until the dog reaches 4 years of age, at which time growth plateaus and prostatic function, as assessed by ejaculate volume, peaks before abruptly declining. Incidence of all types of prostatic disease increases with advancing age, with a mean reported age of 8.9 years before onset of clinical signs. Prostatic diseases reported in the dog include benign prostatic hypertrophy/hyperplasia (BPH), acute and chronic bacterial prostatitis, prostatic abscesses, prostatic retention (true) cysts and paraprostatic cysts, and prostatic neoplasia. Diagnosis of all prostatic diseases requires (1) assessment of prostate size by rectal palpation, contrast radiography and/or ultrasonography, (2) evaluation of prostatic fluid, collected by ejaculation or prostatic massage, for inflammatory changes and presence of bacteria, and (3) possible prostatic aspirate or biopsy. Diagnosis by use of cytology has been demonstrated to agree with histopathology results in 75-80% of cases. In man, measurement of a secretory protein, prostate specific antigen (PSA), can be used in diagnosis and assessment of efficacy of treatment of prostatic diseases. A related but distinct protein, canine specific arginine esterase (CSAE) has been identified in the dog. While this protein makes up 90% of secretory proteins found in canine seminal plasma and is almost exclusively expressed in the prostate, concentrations in serum and seminal fluid have not been demonstrated to differ significantly between normal dogs and dogs with different prostate diseases, limiting our ability to use serologic tests to verify or assess progression of canine prostatic disease. BENIGN PROSTATIC HYPERTROPHY/HYPERPLASIA (BPH) Benign prostatic hypertrophy/hyperplasia (BPH) is a condition commonly seen in aged men. The dog is the only domestic species known to exhibit this disorder. In men, it is characterized by hyperplasia of stromal cells within periurethral tissues. In the dog, both hypertrophy (increased cell size) and hyperplasia (increased cell number) occur, with diffuse glandular proliferation and overall increase in volume and weight of the prostate. BPH is a natural consequence of aging; in one study, 50% of dogs examined had histologic evidence of BPH by 4-5 years of age. Both estrogens and androgens must be present for significant hypertrophy/hyperplasia to occur. Estrogens may act by increasing the number of androgen receptors in prostatic tissue, or by forming metabolites with free radical activity which damage the prostate, altering its response to DHT. Prostates affected with BPH apparently also have increased ability to metabolize androgens; a high correlation exists between size of the prostate and ability to form DHT from testosterone. Local growth factors and catecholamines may also have a role in mediating growth and contractility of the gland. Small cysts containing bloody or serosanguinous fluid may form, and as the gland develops increased vascularity, there is an increased tendency for prostatic bleeding. In man, pollakiuria (increased frequency of passage of small amounts of urine) is the most common presenting sign of disease, presumably due to the periurethral location of hyperplasia and increased contractility of the gland. In the dog, signs are referable to increased size of the gland and subsequent pressure on the rectum and surrounding structures. Bloody to serosanguinous urethral discharge unrelated to urination, hematuria, tenesmus, hemospermia, and infertility may be seen. Systemic signs of disease are uncommon. BPH only is seen in intact animals. The hypertrophied/hyperplastic prostate is symmetrically enlarged and non-painful when palpated per rectum. Radiographically, the gland is enlarged and may displace the bladder cranially and the rectum dorsally. Mean normal area is not as large nor the gland as asymmetrical as in neoplasia or cystic prostatic disease. The prostate is enlarged if it encompasses greater than 70% of the distance from the cranial aspect of the pubic bone to the sacral promontory on a lateral projection radiograph. Ultrasonographically, the homogeneous parenchyma is normal to slightly hyperechoic. Prostatic fluid cytology is non-inflammatory and cultures are non-significant (< 100,000 bacteria/ml). Prostatic biopsy rarely is necessary to confirm the diagnosis. Treatment 1) Castration Bilateral orchiectomy is the treatment of choice. No medical therapy has yet been shown to be as effective as castration in decreasing prostatic size and causing resolution of clinical signs long-term. However, castration causes permanent infertility, and so may be inappropriate as a first-choice treatment in valuable breeding animals. 2) Estrogens Oral and injectable estrogen preparations have been shown to decrease prostatic size and signs of BPH. Estrogen prohibits pituitary LH release by negative feedback, with subsequent decline in serum testosterone concentrations. However, estrogens also induce squamous metaplasia of the gland and secretory stasis, which predispose the gland to ascending infection. In one study, complete degeneration of testicular germ cells was noted 40 days after administration of estrogen. Estrogens also may cause fatal bone marrow suppression in susceptible animals. An anti-estrogen compound, tamoxifen, has been shown to have some effect on decreasing prostatic size in BPH, but does not inhibit androgen-induced stromal proliferation. Estrogens cannot be recommended as a routinely successful treatment for BPH at this time. 3) Progestins Megestrol acetate (Ovaban™, Schering; 0.5 mg/kg/day po x 4-8 weeks) and medroxyprogesterone acetate (3-4 mg/kg SQ) have been shown to decrease serum testosterone concentrations, and possibly competitively inhibit binding of DHT to intracellular receptors, inhibit 5alpha reductase activity, and decrease prostatic androgen receptor number. Prostate size was decreased and clinical signs resolved within 4-7 weeks of therapy. No changes were noted in total sperm number, libido, or testicular size and consistency after treatment. Signs recurred 10-24 months after treatment with a single dose of medroxyprogesterone acetate. Progestins are not approved for use in male dogs in the United States. 4) 5alpha reductase inhibitors Several types of 5alpha reductase inhibitors, which act by suppressing conversion of testosterone to DHT, are described in the literature. Chlormadinone acetate and others described cause a decrease in prostatic size and resolution of clinical signs, but may cause reduced fertility. Finasteride (Proscar™, Merck) is, to date, the drug of this class best evaluated, and apparently most effective in treatment of canine BPH. At doses of 0.1-0.5 mg/kg/day (one 5 mg tablet daily for dogs up to 50 kg in body weight) finasteride causes atrophy of both the glandular and stromal compartments of the prostate with a subsequent decrease in prostatic weight and volume. This decrease is due to apoptosis (programmed cell death), not necrotic change. Prostatic size decreases significantly by 4 weeks of treatment, and reaches maximal atrophy, a 33-50% reduction in pre-treatment volume, by 6 weeks of treatment. Treatment with finasteride has not been demonstrated to cause changes in testicular weight or histomorphology, or daily sperm production. Semen volume will decrease in treated male dogs but semen quality is not negatively affected. Finasteride has not been evaluated for teratogenicity, and it is not recommended that men attempt to father children while on the drug. Finasteride is not approved for use in male dogs in the United States. 5) Miscellaneous treatments These include DHT receptor blockers, ketoconazole, nutritional supplements (Prostsafe™, Whitewing Laboratories; UrozincJ™, Prostahelp Inc.), smooth muscle relaxants (doxasin mesylate, Cardura™, Pfizer), catecholamine receptor blockers, gossypol, electrovaporization, transurethral collagenase injection, transurethral light treatment after photosensitization, transurethral high-intensity focused ultrasound, MRI-guided thermal coagulation of prostatic tissue, and rotoresect, mechanical ablation plus high-frequency tissue coagulation. PROSTATITIS / PROSTATIC ABSCESS Prostatitis is bacterial infection of the prostate, usually due to ascending infection by a member of the normal urethral flora. Prostatitis often develops as a secondary disorder. A primary disorder such as BPH, squamous metaplasia, or neoplasia predisposes the gland to infection by altering defense mechanisms which normally prevent retrograde movement of bacteria, such as urine flow during micturition, a urethral high-pressure zone, bactericidal effects of prostatic fluid and local IgA production, and offering media for bacterial growth, such as serosanguinous fluid retained within a cystic prostate. Organisms most commonly isolated are E. coli, Mycoplasma sp., Staphylococcus sp., Streptococcus sp., Klebsiella and Proteus. Brucella canis also has been isolated from canine prostatitis. In 70% of cases of bacterial prostatitis, a single causative organism is isolated. Presenting clinical signs vary with course of the disease. Acutely infected animals are painful, febrile and lethargic, and may exhibit hematuria or locomotor difficulties, or present for infertility or unwillingness to breed. In chronically infected dogs, fewer systemic signs are seen. Dogs with prostatic abscessation may be nearly asymptomatic or present with signs of sepsis due to fulminating infection and peritonitis. All dogs with prostatitis are likely to show evidence of urinary tract infection (UTI); all intact male dogs with recurrent UTI should be assumed to have prostatic involvement. Prostatitis is more likely to be seen in intact than in neutered dogs. The infected prostate gland may or may not be enlarged. Asymmetrical prostatomegaly may be severe if a prostatic abscess is present. Radiographically, prostatomegaly and mineralization may be evident. Chronic prostatitis appears as diffusely increased echogenicity of the prostatic parenchyma by ultrasound. Abscesses are visible ultrasonographically as hypo- to anechoic lesions with distant enhancement, and cannot be differentiated from cysts or hematomas. Positive culture and inflammatory cytology of prostatic fluid, collected by ejaculation or prostatic massage, are more definitive diagnostic tests. Inflammatory cytology of prostatic fluid and pure growth of greater than 100,000 bacteria/ml of a single organism have been shown to have 87% and 68-80% correlation with histopathology of the infected prostate, respectively. As UTI is a common concomitant disease process which may hinder ability to diagnose prostate disease, some authors recommend evaluation of urine, collected by antepubic cystocentesis, and urethral cytology and culture specimens concurrently with prostatic fluid. Blood leukocyte count has not been demonstrated to reflect infection within the prostate. Changes in pH of prostatic fluid are also non-diagnostic for canine prostatitis. Prostatic biopsy is another definitive test for canine prostatitis. However, biopsy or fine-needle aspirate of the prostate in the presence of infection may lead to seeding of bacteria along the needle tract with subsequent peritonitis. Treatment 1) Castration Infection will be more readily cleared from the prostate of castrated dogs than intact dogs. Castration may also promote resolution of disorders underlying prostatitis, for example BPH. 2) Antibiotic therapy Antibiotic choice should be based on culture and sensitivity results whenever possible. In acute prostatitis, the blood/prostate barrier is disrupted, allowing most antibiotics to readily diffuse into prostatic tissue. In chronic prostatitis or abscessation, antibiotics that can penetrate the intact blood/prostate barrier must be used. Characteristics of a suitable antibiotic include high lipid solubility, low protein binding and pKa complementary to the pH of the prostatic fluid, allowing ionization and subsequent trapping of the antibiotic within the prostate. Acidic prostatic fluid (pH < 7.2) will ionize antibiotics with a high pKa, and basic prostatic fluid (pH > 7.4) will ionize antibiotics with a low pKa. Examples of antibiotics with poor movement into prostatic tissue due to low lipid solubility include tetracyclines, aminoglycosides, cephalosporins and ampicillin. Examples of antibiotics that readily penetrate the prostatic capsule include chloramphenicol, trimethroprim-sulfa and enrofloxacin. Chloramphenicol has high protein binding and so must be used at the high end of the dose range. Owners should be cautioned of the human health hazards of this drug. Trimethoprim-sulfa may cause secondary signs of anemia and keratoconjunctivitis sicca if given long-term. Concurrent administration of 5 mg/day folic acid may ameliorate these problems. Enrofloxacin (Baytril™, Bayer) has a low molecular weight favoring tissue penetration, is a zwitterion with 2 pKa's and is highly lipid soluble. It achieves serum and intraprostatic concentrations well above the minimum inhibitory concentration of most pathogens when administered at a dose of 5 mg/kg BID. Pharmacokinetics of other fluoroquinolone antibiotics in canine prostate disease have not been studied in detail but they are assumed to have good tissue penetration. Antibiotic therapy should be continued for at least 3-4 weeks. Prostatic fluid should be cultured 1-2 weeks after completion of treatment, and again 2-4 weeks later to ensure clearance of infection. Chronically infected dogs may benefit from long-term treatment with a 50%-reduced dose of antibiotic given once daily, or castration. Abscess resolution Antibiotic therapy should be instituted as described above. Safe retrieval of a sample for culture and sensitivity may be difficult in a large, solitary abscess. Empirical treatment with a highly diffusible antibiotic, like enrofloxacin, may be required. Abscesses may resolve with medical treatment to decrease prostatic size, such as finasteride. Oftentimes, marsupialization or placement of Penrose drains is necessary. Morbidity is high in dogs requiring surgical drainage of abscesses, with reported complications including incontinence, chronic draining stomas, peritonitis, septic shock and death. New surgical techniques have been described which appear to show decreased morbidity. PROSTATIC RETENTION (TRUE) CYSTS / PARAPROSTATIC CYSTS Numerous small cysts may be seen as a component of BPH and are treated accordingly. Retention (true) cysts are thin walled structures within the prostatic parenchyma containing non-purulent fluid. Etiology is unknown; some hypotheses are that cysts are either prostatic ducts that have become obstructed and dilated secondary to squamous metaplasia from exposure to endogenous or exogenous estrogens, or calcified fibrous walls of resolving prostatic hematomas. Paraprostatic cysts are most commonly seen craniolateral or caudal to the bladder and prostate in older, large breed dogs. They are thin walled structures outside the prostatic parenchyma that often contain malodorous fluid containing fibronecrotic debris. Etiology is again unknown; these may be vestiges of the Mullerian ducts. With either retention cysts or paraprostatic cysts, the dogs may present with anorexia, weakness, abdominal distension and other gastrointestinal signs, and urinary tract signs such as hematuria or dysuria. Radiographically, these dogs have apparent prostatomegaly. Contrast radiography may be required to differentiate a paraprostatic cyst from true prostatomegaly. Mineralization may be present in the wall of paraprostatic cysts. Ultrasound may also be used to differentiate retention cysts from paraprostatic cysts. Infusion of saline into the urinary bladder through a urethral catheter may be helpful in defining structures. Both retention cysts and paraprostatic cysts are best treated by surgical removal. Surgical drainage may be attempted but infection is a common complication. Percutaneous drainage with visualization of the procedure by ultrasound has been successfully used as a treatment. Castration may aid in resolution of retention cysts. Effect of castration on resolution of paraprostatic cysts is unknown. PROSTATIC NEOPLASIA Reported incidence of prostatic neoplasia in one survey of veterinary teaching hospital admissions was 0.2%. Although metastatic prostatic neoplasia (for example, transitional cell carcinoma) and possible benign prostatic neoplasia have been reported, primary prostatic adenocarcinoma is the most common prostatic neoplasm. It is a locally invasive tumor that readily metastasizes to the iliac lymph nodes, lungs and lumbar vertebrae. It is most common in aged dogs; one report documented a mean age at diagnosis of 10 years. One study described the Bouvier des Flandres as a breed at increased risk. The tumor does not appear to be androgen-dependent. Age at castration therefore has no sparing effect on its incidence. In fact, some studies suggest that castration is a risk factor for development of prostatic neoplasia, with the lack of androgens associated not with initiation of tumor growth but with tumor progression. Prostatic neoplasia may be seen in intact or castrated animals, and is the only prostatic disease reported in castrated animals. Dogs with neoplasia are likely to present with systemic signs as the tumor has often metastasized by the time of diagnosis. Signs seen include pain, hindlimb weakness, tenesmus, weight loss, stranguria and urethral bleeding. The prostate is palpably enlarged and may be asymmetrical and firm. Survey radiographs demonstrate prostatomegaly and possibly mineralization. Contrast radiographs show destruction or distortion of the prostatic urethra. Ultrasonographically, capsular disruption, focal or multifocal mineralization and parenchymal asymmetry are evident. Treatment is palliative. Prostatectomy, chemotherapy and radiation therapy may be attempted. Hormonal therapy, as used in man, is unlikely to be effective in the dog. CONCLUSION Castration is the treatment of choice for most dogs with prostatic disease. Medical treatment in general is best used for valuable breeding animals. Because the dog is a model for human prostate disease, new treatment modalities are likely to emerge in the future. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
