Limb-sparing treatment for osteosarcoma in dogs

Twenty dogs with spontaneously developing osteosarcoma of the extremities were treated with 1 of 3 multimodality limb-sparing procedures. Excision of the tumor was preceded by intra-arterial (IA) administration of cisplatin (cis-diamminedichloroplatinum) alone directed to the affected extremity, irradiation plus IA administration of cisplatin, or irradiation plus IV administration of cisplatin. All dogs were free of apparent metastatic disease at the time of initial treatment. After diagnosis, dogs administered cisplatin IA had selective angiography performed on arteries supplying the tumor, and 70 mg of cisplatin/m2 of body surface was administered over 2 hours. This protocol was repeated 3 weeks later. Dogs that were irradiated received 25 or 40 Gy in 10 fractions over a 22-day period. The first and last radiation doses were immediately preceded by IA administration of cisplatin. Dogs given IV treatment received 10 mg of cisplatin/m2 2 hours before each radiation fraction was administered. Three weeks after the last treatment, tumors were excised and the limb underwent orthopedic reconstruction, generally using cortical allografting and bone plating. Limb function, allograft healing, local tumor control, and metastatic dissemination were monitored. Limb function was good to excellent in 69% (11/16) of dogs evaluated. Forelimb-sparing procedures were generally associated with better function than were limb-sparing procedures performed on hind limbs. Local tumor control was obtained in 79% (11/14) of dogs thoroughly evaluated, with local recurrences in 3 dogs at 3, 4, and 7 months after treatment. Fifteen dogs developed metastatic disease at a median time of 8 months from the time of diagnosis. Mean and median survival times for all dogs, regardless of cause of death, were 11.7 and 8 months, respectively. Tumor necrosis greater than 80% was statistically associated with lack of recurrence. Of 16 dogs, 5 (31%) developed infections at the surgical site. Multimodality limb-sparing treatment is believed to be a viable alternative for appropriately selected dogs with osteosarcoma. The optimal method of treatment prior to or after tumor excision has not yet been established.     

Effects of etomidate on adrenocortical function in canine surgical patients

Adrenocortical function in canine surgical patients given etomidate at 1 of 2 dosages (1.5 mg/kg of body weight or 3 mg/kg, IV) was evaluated and compared with that of dogs given thiopental (12 mg/kg, IV). The adrenocortical function was evaluated by use of adrenocorticotropic hormone (ACTH) stimulation tests and determination of plasma cortisol concentrations at 0 minute (base line) and 60 minutes after ACTH administration. At 24 hours before administration of either drug (ie, induction of anesthesia), each dog had an increase in plasma cortisol concentration when given ACTH. The ACTH stimulation tests were repeated 2 hours after induction of anesthesia. Dogs given thiopental had base-line plasma cortisol concentrations greater than preinduction base-line values, but did not increase plasma cortisol in response to ACTH stimulation. Postinduction ACTH stimulation tests in dogs given etomidate at either dose indicated base-line and 60-minute plasma cortisol concentrations that were not different from preinduction base-line values. Therefore, adrenocortical function was suppressed 2 and 3 hours after the administration of etomidate in canine surgical patients.     

A Retrospective Study of Aldosterone Secretion in Normal and Adrenopathic Dogs

A retrospective study on stored plasma from normal dogs and dogs with pituitary dependent hyperadrenocorticism (PDH), pituitary dependent hyperadrenocorticism controlled by mitotane (o,p'-DDD),* iatrogenic hyperadrenocorticism, and hypoadrenocorticism was conducted to determine if alterations in aldosterone production exist in these disorders. The plasma aldosterone concentration (PAC) was measured by radioimmunoassay immediately before and 1 hour after adrenocorticotropic hormone (ACTH) administration (0.5 IU/kg, intravenously [IV]). PACs increased significantly when ACTH was administered to normal dogs. Dogs with PDH had a lower baseline PAC, but their PAC increased to levels similar to that of normal dogs after ACTH administration. In dogs with PDH controlled by o,p'-DDD therapy, the response to ACTH was significantly less than that of normal dogs or dogs with untreated PDH. Dogs with iatrogenic hyperadrenocorticism had a lower baseline and post-ACTH PAC than normal dogs. Dogs with hypoadrenocorticism had a normal basal PAC, but showed no significant increase in PAC following ACTH administration. These findings suggest that PACs are significantly altered in a variety of adrenal diseases, and that the ACTH stimulation test may be useful when evaluating aldosterone secretion in adrenopathic disorders. In addition, at therapeutic dosages, o,p'-DDD treatment was associated with a decrease in basal and post-ACTH PACs in dogs with PDH.     

Comparison of the effects of morphine administered by constant-rate intravenous infusion or intermittent intramuscular injection in dogs

OBJECTIVE: To compare physiologic and analgesic effects of morphine when given by IV constant-rate infusion or by IM injection to dogs undergoing laparotomy and to determine pharmacokinetics of morphine in dogs following IV constant-rate infusion. DESIGN: Prospective randomized controlled trial. ANIMALS: 20 dogs. PROCEDURE: Dogs undergoing laparotomy were treated with morphine beginning at the time of anesthetic induction. Morphine was administered by IV infusion (0.12 mg/kg/h [0.05 mg/lb/h] of body weight) or by IM injection (1 mg/kg [0.45 mg/lb]) at induction and extubation and every 4 hours thereafter. Treatments continued for 24 hours after extubation. RESULTS: Blood gas values did not indicate clinically significant respiratory depression in either group, and degree of analgesia (determined as the University of Melbourne Pain Scale score) and incidence of adverse effects (panting, vomiting, defecation, and dysphoria) were not significantly different between groups. Dogs in both groups had significant decreases in mean heart rate, rectal temperature, and serum sodium and potassium concentrations, compared with preoperative values. Mean +/- SEM total body clearance of morphine was 68 +/- 6 ml/min/kg (31 +/- 3 ml/min/lb). Mean steady-state serum morphine concentration in dogs receiving morphine by constant-rate infusion was 30 +/- 2 ng/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that administration of morphine as a constant-rate IV infusion at a dose of 0.12 mg/kg/h induced effects similar to those obtained with administration at a dose of 1 mg/kg, IM, every 4 hours in dogs undergoing laparotomy. Panting was attributed to an opioid-induced resetting of the hypothalamic temperature set point, rather than respiratory depression.     

Evaluation of cisplatin-induced emesis in dogs with malignant neoplasia: 115 cases (1984-1987)

A retrospective review of the records of 115 dogs with 13 types of malignant tumors was performed in an attempt to identify factors that influence the degree of emesis observed within 24 hours after cisplatin therapy. Six groups were established on the basis of dosage of cisplatin and on the route of administration: 10 mg/m2 IV (n = 17), 40 mg/m2 IV (n = 10), 50 mg/m2 IV (n = 19), 60 mg/m2 IV (n = 7), 70 mg/m2 IV (n = 36), and 70 mg/m2 intra-arterially (IA; n = 26). Age, gender, weight, dose of cisplatin, route of administration (IV vs IA), and duration of infusion were evaluated. Increasing doses of cisplatin (P less than 0.01) and the IV route of drug administration (P less than 0.0006) were associated with an increased occurrence of vomiting in response to the first treatment. Anesthesia, performed in dogs that were given cisplatin IA, was a confounding variable that may have reduced the emetic potential of the drug after the dogs were awakened. If the dog vomited in response to the first treatment, there was a greater tendency to vomit after subsequent cisplatin treatments (P = 0.08). Multivariable analysis, after correcting for the effects of age, gender, and weight, indicated that high doses of cisplatin (P less than 0.001) and lower weight of the dog (P less than 0.04) were significantly associated with an increased likelihood of vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma and synovial fluid concentrations of gentamicin in horses after intra-articular administration of buffered and unbuffered gentamicin

The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after IV (2.2 mg/kg of body weight), intra-articular (IA; 150 mg), and simultaneous IV and IA administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered IA and simultaneously IV and IA. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 micrograms/ml) after IV administration was significantly (P less than 0.05) greater than that (0.69 microgram/ml) after IA administration of gentamicin and that (0.55 microgram/ml) after administration of gentamicin buffered with sodium bicarbonate. Gentamicin concentration greater than a therapeutic concentration was not attained in the plasma after IA administration of buffered or unbuffered gentamicin. The peak mean synovial fluid concentration (1,828 micrograms/ml) after IA administration of unbuffered gentamicin was significantly (P less than 0.05) greater than that (2.53 micrograms/ml) after IV administration and significantly (P less than 0.05) less than that (5,720 micrograms/ml) after simultaneous IV and IA administration. The peak mean synovial fluid concentration after IA administration of buffered gentamicin, with and without simultaneous IV administration (2,128 and 2,680 micrograms/ml, respectively), was not significantly different than that after IA treatment with unbuffered gentamicin. Mean synovial fluid concentration did not differ significantly between groups after IA administration of gentamicin in any combination at postinjection hours 8, 12, and 24, but remained significantly (P less than 0.05) greater than that at the same times after IV administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiopulmonary and anesthetic effects of ketamine and its enantiomers in dogs

Dogs were used to determine cardiopulmonary and chemical restraining effects of racemic ketamine and its enantiomers. Levorotatory ketamine induced the shortest duration of unconsciousness and recumbency when compared with effects of dextrorotatory and racemic ketamine. Administration of racemic ketamine or either of its enantiomers (30 mg/kg of body weight, IV) to dogs recovering from isoflurane anesthesia induced transient, but significant (P less than 0.05), decreases in arterial blood pressure, left ventricular contractility, cardiac output, and total peripheral vascular resistance. Arterial blood pressure and left ventricular contractility significantly (P less than 0.05) increased at later times after ketamine administration. Arterial pH and the PO2 values decreased after IV administration of racemic ketamine or its enantiomers. Significant differences in cardiopulmonary variables were not observed between groups given ketamine or its enantiomers.     

Adrenal response to adrenocorticotropic hormone in dogs before and after surgical attenuation of a single congenital portosystemic shunt

BACKGROUND: Dogs with single congenital portosystemic shunts (CPSS) often develop postoperative hypoglycemia and prolonged anesthetic recovery. These abnormalities could be attributable to inadequate adrenal response. However, adequacy of adrenal response after CPSS surgery is unexplored. HYPOTHESIS: Dogs with CPSS have inadequate postoperative adrenal response. ANIMALS: Eight nonoperated, 8 ovariohysterectomy (OHE), and 16 CPSS dogs. METHODS: Consecutive day ACTH stimulation tests were performed on nonoperated healthy dogs, healthy dogs before and after OHE, and CPSS dogs before and after surgery. Adequate response was defined as >50% or >30 ng/mL increase in cortisol after ACTH administration. Blood glucose (BG) was monitored before and after surgery. Prolonged anesthetic recovery and refractory hypoglycemia episodes were recorded. RESULTS: Results of consecutive day ACTH stimulation tests did not vary in normal dogs. Results of preoperative ACTH stimulation tests of CPSS and OHE dogs were not significantly different. Dogs with CPSS had higher postoperative baseline cortisol concentrations (median, 329 ng/mL) than OHE dogs (median, 153 ng/mL). Postoperative cortisol increase after ACTH in CPSS was < or =50% in 10/16 and < or =30 ng/mL in 6/16. After surgery, BG was < or =60 mg/dL in 7/16 CPSS dogs. Cortisol concentrations were not correlated with BG. Two CPSS dogs had refractory hypoglycemia and 4 had delayed recovery; all improved with dexamethasone administration (0.1-0.2 mg/kg/IV). CONCLUSIONS AND CLINICAL IMPORTANCE: Contrary to previous reports, baseline cortisol concentrations in CPSS and healthy dogs are similar. Many CPSS dogs have postoperative hypercortisolemia. Response to ACTH does not correlate with postoperative hypoglycemia or prolonged anesthetic recovery.     

Evaluation of Single-Agent Mitoxantrone as Chemotherapy for Relapsing Canine Lymphoma

Many chemotherapeutic regimens will induce remission in dogs with lymphoma, but almost all dogs suffer relapse. Mitoxantrone was selected for evaluation as single-agent chemotherapy for relapsing canine lymphoma based on its use in humans undergoing salvage chemotherapy for non-Hodgkin's lymphoma and its tumoricidal effect against canine lymphoma. Dogs entered into study had multicentric lymphoma, and all had been treated solely with a standard combination chemotherapy protocol. At 1st relapse, all dogs were again staged and underwent lymph node biopsy. Mitoxantrone was administered IV at 6 mg/m² every 21 days. Dogs were evaluated for lymphadenopathy before each dose of mitoxantrone. Fifteen dogs were entered into study. The average age (±SEM) of the dogs studied was 7.7 ± 0.91 years, and most dogs were large (mean ± SEM weight, 24.44 ± 2.15 kg). Twelve dogs (80%) had B-cell lymphoma, and 3 had T-cell lymphoma. Dogs were staged IV (n = 12) or V (n = 3). The median duration of chemotherapy before entry into the study was 98 days. Overall median duration of response after mitoxantrone chemotherapy was 21 days. Complete responses were attained in 7 of 15 dogs (47%) with a median response duration of 84 days. Nine of 15 (60%) dogs attained a complete remission with additional chemotherapy after failing mitoxantrone chemotherapy. Mild toxicities were observed after mitoxantrone administration. No adverse reactions were observed during mitoxantrone infusions. The results of this study demonstrate that mitoxantrone, as a single agent, has limited value for dogs with lymphoma at 1st relapse after conventional multidrug chemotherapy.     

Finasteride-induced prostatic involution by apoptosis in dogs with benign prostatic hypertrophy

OBJECTIVE: To determine the effect of finasteride on programmed cell death (apoptosis) of prostatic cells during prostatic involution in dogs with benign prostatic hypertrophy (BPH). ANIMALS: 9 dogs with BPH. PROCEDURE: Dogs were randomly assigned to treatment or control groups. Treatment dogs (n = 5) were administered finasteride (0.1 to 0.5 mg/kg, PO, q 24 h) for 16 weeks, whereas the 4 control dogs were administered an inert compound. Prostatic cells from the prostatic fluid portion of the ejaculate of treatment and control dogs were obtained before and 1, 2, 3, 4, 8, and 16 weeks after initiation of treatment. Cells were concentrated by use of centrifugation. Prostatic cells were examined for indications of apoptosis by use of a terminal deoxyribonucleotidyl transferase-mediated deoxyuracil triphosphate nick-end labeling technique. After receiving the inert compound for 16 weeks, the 4 control dogs were administered finasteride for 16 weeks, and evaluations were repeated. RESULTS: Percentage of apoptotic prostatic cells in ejaculated prostatic fluid of treatment dogs increased significantly (from 9% before treatment to 33, 31, 26, and 27% after 1, 2, 3, and 8 weeks of treatment, respectively). There was no significant change in percentage of apoptotic prostatic cells in the ejaculated prostatic fluid of control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Finasteride-induced prostatic involution appears to be via apoptosis in dogs with BPH. Finasteride treatment of dogs with BPH causes prostatic involution by apoptosis rather than necrosis.     

Evaluation of plasma aldosterone concentrations before and after ACTH administration in clinically normal dogs and in dogs with various diseases

Plasma aldosterone concentrations were measured in response to adrenocorticotropic hormone (ACTH) gel administration in clinically normal dogs, in dogs with hypoadrenocorticism, and in dogs (with electrolyte abnormalities) that did not have hypoadrenocorticism. Baseline plasma aldosterone concentrations were determined from specimens obtained every 10 minutes for 3 hours from 2 dogs and every 30 minutes for 7.5 hours from 2 other dogs. During the evaluation period, plasma aldosterone concentrations varied by at least 50% in each dog. A randomized crossover design was used to compare changes in plasma aldosterone concentrations after administration of ACTH gel and physiologic NaCl solution. Dogs had significantly (P = 0.002) higher plasma aldosterone concentrations after administration of ACTH gel than after administration of NaCl solution. Plasma cortisol concentrations increased as expected after ACTH gel administration. Analysis of cortisol and aldosterone concentrations in the same specimens obtained at 7 sample collection times did not reveal significant linear correlation, and scatterplots did not indicate a nonlinear association. In addition, plasma aldosterone concentrations were determined in response to ACTH administration alone and to ACTH combined with a high dose of dexamethasone (0.1 mg/kg, IV). The plasma aldosterone response to ACTH alone was not significantly different from the response to ACTH combined with dexamethasone. For both tests, plasma aldosterone concentrations at 60 and 120 minutes after ACTH administration were significantly (P less than 0.0005 and P = 0.0001, respectively, increased, compared with base-line values. Six dogs with adrenocortical hypofunction, as determined by plasma cortisol concentrations before and after ACTH administration, had plasma aldosterone concentrations that were diminished or did not increase after ACTH administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of pamidronate to reverse vitamin D3-induced toxicosis in dogs.

OBJECTIVES: To determine whether pamidronate disodium can reduce vitamin D3-induced hypercalcemia in dogs and whether combination treatment with calcitonin is more effective than treatment with pamidronate alone. ANIMALS: 20 clinically normal male Beagles. PROCEDURE: All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were assigned randomly to 4 groups of 5 dogs each. Dogs were given 0.9% NaCl solution IV (group 1), calcitonin SC and 0.9% NaCl solution IV (group 2), pamidronate and 0.9% NaCl solution IV (group 3), or a combination of all 3 agents (group 4). Dogs were observed for 28 days, and serial blood and urine samples were collected for determination of serum biochemical, electrolyte, and 25(OH)D3 values, CBC, and urine mineral excretion. Samples of kidney, stomach, lung, aorta, liver, duodenum, and brain were evaluated by light microscopy and quantitative mineral analysis. RESULTS: Two dogs in group 1 were euthanatized 4 days after CCF administration because of severe clinical signs of disease. Dogs in group 3 lost less weight and had significantly lower serum phosphorus, total and ionized calcium, and urinary zinc concentrations, compared with dogs in group 1. On day 4, serum urea nitrogen concentration was significantly lower in dogs of groups 3 and 4, compared with dogs in group 1. Mild to moderate mineralization of kidneys and stomach were observed in the 2 group-1 dogs euthanatized on day 4. CONCLUSIONS: Pamidronate administration effectively prevents CCF-induced hypercalcemia and mineralization of soft tissues. CLINICAL RELEVANCE: Pamidronate is a potentially useful antidote against CCF toxicosis in dogs.     

Serum concentrations of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates in healthy dogs following stimulation with two doses of cosyntropin

OBJECTIVE: To compare the effects of 2 doses of cosyntropin (5 microg/kg vs 250 microg, IV) on serum concentrations of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates and determine the optimal sample collection time after adrenal stimulation with cosyntropin. ANIMALS: 10 healthy, privately owned, neutered dogs. PROCEDURE:Dogs were randomly assigned to initially receive cosyntropin at 5 microg/kg or as a total dose of 250 microg, IV. Dogs received the alternate dose 1 to 2 weeks later. Serum was obtained from blood samples collected before (0 minutes) and 30, 60, 90, and 120 minutes after cosyntropin administration. RESULTS:Maximum stimulation of cortisol, androstenedione, progesterone, and 17-hydroxyprogesterone production was achieved at 60 minutes following IV administration of cosyntropin at 5 microg/kg or as a total dose of 250 microg. Serum estradiol concentration did not increase in response to either cosyntropin dose. For all hormones, no significant difference in serum hormone concentrations was found among sample collection times of 0, 30, 60, and 90 minutes when comparing the 2 doses of cosyntropin. CONCLUSIONS AND CLINICAL RELEVANCE: Cosyntropin, when administered at 5 microg/kg, IV, effectively stimulated maximum production of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates at 1 hour after administration.     

Oral bioavailability of etoposide after administration of a single dose to tumor-bearing dogs

OBJECTIVE: To characterize oral bioavailability and pharmacokinetic disposition of etoposide when the IV formulation was administered orally to dogs. ANIMALS: 8 tumor-bearing dogs. PROCEDURES: An open-label, single-dose, 2-way crossover study was conducted. Dogs were randomly assigned to initially receive a single dose of etoposide (50 mg/m2) IV or PO. A second dose was administered via the alternate route 3 to 7 days later. Medications were administered before IV administration of etoposide to prevent hypersensitivity reactions. Oral administration of etoposide was prepared by reconstituting the parenteral formulation with 0.9% NaCl solution and further diluting the reconstituted mixture 1:1 with a sweetening agent. Plasma samples were obtained after both treatments. Etoposide concentrations were measured with a high-performance liquid chromatography assay, and plasma etoposide concentration-time profiles were analyzed by use of noncompartmental methods. RESULTS: 4 dogs had hypersensitivity reactions during IV administration of etoposide. No adverse effects were detected after oral administration. Plasma etoposide concentrations were undetectable in 2 dogs after oral administration. Oral administration of etoposide resulted in significantly lower values for the maximum plasma concentration and the area under the plasma etoposide concentration-versus-time curve, compared with results for IV administration. Oral bioavailability of etoposide was low (median, 13.4%) and highly variable among dogs (range, 5.7% to 57.3%). CONCLUSIONS AND CLINICAL RELEVANCE-Vehicle-related toxicosis can limit the IV administration of etoposide in dogs. The parenteral formulation of etoposide can be safely administered orally to dogs, but routine use was not supported because of low and variable oral bioavailability in this study.     

Use of noninvasive dental dolorimetry to evaluate analgesic effects of intravenous and intrathecal administration of morphine in anesthetized dogs

OBJECTIVE: To determine whether changes in amplitude of the reflex-evoked muscle action potential (REMP) elicited by noninvasive dental dolorimetry (electrical stimulation of the tooth pulp) in anesthetized dogs may be used to objectively evaluate the effectiveness of IV and intrathecal (IT) administration of morphine. ANIMALS: 6 male Beagles that were 2 to 6 years old. PROCEDURE: Dogs were used in a crossover design with at least a 5-day washout period between treatments. Each dog received morphine, saline (0.9% NaCl) solution, and oxytocin via the IV and IT routes of administration; however, only results for morphine and saline treatments were reported here. Dogs were anesthetized and prepared for noninvasive dental dolorimetry. After IV or IT administration, electrical stimulation was applied to a tooth, and REMPs of the digastricus muscle were recorded at 5-minute intervals for 60 minutes. To determine differences in REMP amplitude between treatments, a linear regression line was fitted for each dog-treatment combination. RESULTS: The IV administration of morphine significantly inhibited REMP amplitude, compared with IV administration of saline solution. Intrathecal administration of morphine significantly inhibited REMP amplitude, compared with IT administration of saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Noninvasive dental dolorimetry in anesthetized dogs has promise as a technique for use in evaluating the analgesic potential of drugs administered IV and IT through evaluation of their effect on REMP amplitude recorded for the digastricus muscle.     

Determination of synovial fluid and serum concentrations, and morphologic effects of intraarticular ceftiofur sodium in horses

OBJECTIVES: To determine the serum and synovial fluid concentrations of ceftiofur sodium after intraarticular (IA) and intravenous (IV) administration and to evaluate the morphologic changes after intraarticular ceftiofur sodium administration. STUDY DESIGN: Strip plot design for the ceftiofur sodium serum and synovial fluid concentrations and a split plot design for the cytologic and histopathologic evaluation. ANIMALS: Six healthy adult horses without lameness. METHODS: Stage 1: Ceftiofur sodium (2.2 mg/kg) was administered IV. Stage 2: 150 mg (3 mL) of ceftiofur sodium (pHavg 6.57) was administered IA into 1 antebrachiocarpal joint. The ceftiofur sodium was reconstituted with sterile sodium chloride solution (pH 6.35). The contralateral joint was injected with 3 mL of 0.9% sterile sodium chloride solution (pH 6.35). Serum and synovial fluid samples were obtained from each horse during each stage. For a given stage, each type of sample (serum or synovial fluid) was collected once before injection and 12 times after injection over a 24-hour period. All horses were killed at 24 hours, and microscopic evaluation of the cartilage and synovium was performed. Serum and synovial fluid concentrations of ceftiofur sodium were measured by using a microbiologic assay, and pharmacokinetic variables were calculated. Synovial fluid was collected from the active joints treated during stage 2 at preinjection and postinjection hours (PIH) 0 (taken immediately after injection of either the ceftiofur sodium or sodium chloride), 12, and 24, and evaluated for differential cellular counts, pH, total protein concentration, and mucin precipitate quality. RESULTS: Concentrations of ceftiofur in synovial fluid after IA administration were significantly higher (P = .0001) than synovial fluid concentrations obtained after IV administration. Mean peak synovial fluid concentrations of ceftiofur after IA and IV administration were 5825.08 microg/mL at PIH .25 and 7.31 microg/mL at PIH 4, respectively. Mean synovial fluid ceftiofur concentrations at PIH 24 after IA and IV administration were 4.94 microg/mL and .12 microg/mL, respectively. Cytologic characteristics of synovial fluid after IA administration did not differ from cytologic characteristics after IA saline solution administration. White blood cell counts after IA ceftiofur administration were < or =3,400 cells/ML. The mean synovial pH of ceftiofur treated and control joints was 7.32 (range, 7.08-7.5) and 7.37 (range, 7.31-7.42), respectively. Grossly, there were minimal changes in synovium or cartilage, and no microscopic differences were detected (P = .5147) between ceftiofur-treated joints and saline-treated joints. The synovial half-life of ceftiofur sodium after IA administration joint was 5.1 hours. CONCLUSIONS: Synovial concentrations after intraarticular administration of 150 mg of ceftiofur sodium remained elevated above minimal inhibitory concentration (MIC90) over 24 hours. After 2.2 mg/kg IV, the synovial fluid ceftiofur concentration remained above MIC no longer than 8 hours. CLINICAL RELEVANCE: Ceftiofur sodium may be an acceptable broad spectrum antimicrobial to administer IA in septic arthritic equine joints.     

Effects of doxapram HCl on laryngeal function of normal dogs and dogs with naturally occurring laryngeal paralysis

OBJECTIVES: To compare the effects of IV doxapram on glottic size and arytenoid motion in normal dogs and in dogs with laryngeal paralysis. STUDY DESIGN: Prospective experimental and clinical trials. ANIMALS: Six healthy dogs weighing 24.5 +/- 3.9 kg and six dogs weighing 27.4 +/- 11.5 kg suspected of having laryngeal paralysis. METHODS: Dogs were pre-medicated with acepromazine and butorphanol, and a light plane of anesthesia was induced with isoflurane by mask. Videoendoscopic examination of laryngeal function was recorded before (baseline) and after IV doxapram administration. Normalized glottal gap area (NGGA) at maximal inspiration and expiration, and percentage change in height, width, area, and NGGA were calculated with measurements from digitized images of the glottal gap. RESULTS: Active arytenoid motion was present in all normal dogs at baseline. After doxapram administration, depth of respiration appeared greater, but arytenoid motion, as measured by percentage change in NGGA, and in area and width, did not significantly increase in normal dogs. No arytenoid motion was detected in dogs with laryngeal paralysis at baseline; however, rima glottidis NGGA of dogs with laryngeal paralysis was greater at inspiration and expiration than normal dogs. After doxapram administration, dogs with laryngeal paralysis developed paradoxical arytenoid motion and significant, negative percentage change in area (-61%) and NGGA (-145%) because of inward collapse of the arytenoids during inspiration. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of doxapram during laryngeal examination is useful for differentiating normal dogs from dogs with laryngeal paralysis. Dogs with laryngeal paralysis may suffer extreme glottic constriction with vigorous respirations, and may require intubation during examination.     

Cisplatin and doxorubicin toxicosis in dogs with osteosarcoma

Toxicosis associated with doxorubicin and cisplatin administration starting either 2 or 10 days after limb amputation for osteosarcoma was examined retrospectively in dogs. The purpose was to determine whether dosage and timing of chemotherapy affected rates of toxicosis after administration of the 1st treatment. Records of 100 dogs with appendicular osteosarcoma without evidence of metastases or concurrent disease were examined. Dogs received chemotherapy with doxorubicin and cisplatin every 3 weeks for 3 treatments starting 2 days (n = 51) or 10 days (n = 49) after amputation. The dosage of cisplatin was 60 mg/m2 and was given with 6-hour saline diuresis and butorphanol. Doxorubicin was given at 12.5-25 mg/ml during fluid administration. Hematologic data were collected before and weekly after treatment. Client interviews were conducted to assess gastrointestinal toxicosis during the interval between treatments. The reported toxicoses were graded on a scale of 0 to 4. Dogs receiving 25 mg/m2 of doxorubicin experienced greater rates of grade 4 toxicity (67%; n = 6) than dogs in groups receiving 12.5-20 mg/m2 of doxorubicin (< or = 25%; n = 94, P = .03). Dogs in the Day 2 group experienced greater rates (35%) of grade 4 toxicity than dogs in the Day 10 group (12%, P = .007). We concluded that chemotherapy administered 2 days after surgery produced an unacceptable level of toxicoses. except at greatly reduced dosages, and that even with a delay of treatment, 25 mg/m2 of doxorubicin, when given in combination with cisplatin at 60 mg/m2, was too toxic for routine use.     

Comparison of perioperative analgesic protocols for dogs undergoing tibial plateau leveling osteotomy

OBJECTIVE: To compare effects of 3 commonly used perioperative analgesic protocols (epidural injection, intra-articular injection, and intravenous [IV] injection) for management of postoperative pain in dogs after tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: Fifty-six healthy dogs with naturally occurring cranial cruciate ligament rupture. METHODS: Dogs were premedicated with IV hydromorphone and acepromazine and were randomly assigned to receive either E (preoperative epidural injection with morphine and bupivacaine), IA (pre- and postoperative intra-articular injections of bupivacaine), or C (neither epidural morphine and bupivacaine, nor intra-articular bupivacaine). All dogs were administered hydromorphone (0.05 mg/kg IV) at extubation and as needed to maintain comfort postoperatively. Patients were observed and monitored continuously for 24 hours and discomfort was assessed using visual analog pain scores (VASs), multifactorial pain scores (MPSs), and response to a pressure nociceptive threshold (PNT) measuring device. Time to 1st dose and the total doses of hydromorphone required to achieve adequate comfort for each dog were recorded. RESULTS: No differences in measured indices of postoperative pain were observed between dogs of each treatment group; VAS (P=.190), MPS (P=.371), and PNT (P=.160). Time to 1st analgesic intervention was longer for Group E compared with Group C (P=.005) and longer for Group IA compared with Group C (P=.032). Although time to 1st intervention between Groups E and IA were longer for Group E, differences were not significant. To provide an adequate level of comfort, more analgesic interventions were administered to dogs in Group C compared with dogs in group E (P=.015). On average, more hydromorphone was administered to Group C compared with Group IA (P=.072) and to Group IA compared with Group E (P=.168), but statistical significance was not reached for these data. CONCLUSIONS: In this study population, significant differences were seen in time to 1st hydromorphone dose between Groups E and IA compared with Group C. As well, more supplemental analgesia was administered to Group C compared with Group E to maintain the same level of postoperative comfort. Although differences between Groups E and IA tended to favor the epidural group, differences were minimal and not statistically significant. CLINICAL RELEVANCE: Our results suggest that regardless of analgesic protocol, measured indices of pain in dogs after TPLO can be minimized if dogs are continuously observed and appropriately supplemented with parenteral opioids. However, the frequency of postoperative opioid dosing can be minimized and may be a factor when contemplating supplementary use of epidural or intra-articular injections as part of a balanced analgesic approach.     

Effect of pre-anesthetic meperidine on gastro-esophageal reflux in anesthetized dogs

Meperidine has been shown to decrease lower esophageal sphincter tone in monkeys and people, to have little effect in cats, and to physically increase it in dogs. We hypothesized that administration of meperidine to dogs before anesthesia would decrease the probability of GER during the subsequent anesthetic. In this randomized, prospective clinical trial we aimed to determine the incidence of GER in dogs undergoing elective orthopedic surgery and receiving either meperidine or morphine prior to anesthesia. Dogs were admitted to the study, if they were healthy, with no history of vomiting or dysphagia. Dogs were fasted overnight. Dogs were received either morphine (0.66 mg kg^–1 IM) or meperidine (8.8 mg kg^–1 IM) with acepromazine. Anesthesia in all dogs included thiopental and isoflurane in oxygen. To measure esophageal pH a sensor-tipped catheter was placed with the tip 5–7 cm cranial to the lower esophageal sphincter, and connected to a computer for continual data collection. Dogs were observed for vomiting after pre-medication, and the pH of any fluid running from the mouth or nose during anesthesia was measured. Gastro-esophageal reflux was defined as a decrease in esophageal pH below 4 or an increase above 7.5 for greater than 15 seconds. One-way anova was used to test significance of differences between groups in parametric variables. Fisher's Exact test was used to test significance of differences in incidence between groups. In dogs receiving meperidine the incidence of vomiting was 0, and of GER was 31% (4/13), compared to 60% (6/10) and 60% (6/10), respectively in dogs receiving morphine. In this preliminary study, the administration of pre-anesthetic meperidine was associated with a 29% reduction in the absolute risk of GER compared to morphine.