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.     

Cardiorespiratory responses and plasma cortisol concentrations in dogs treated with medetomidine before undergoing ovariohysterectomy

OBJECTIVE: To evaluate effects of medetomidine on anesthetic dose requirements, cardiorespiratory variables, plasma cortisol concentrations, and behavioral pain scores in dogs undergoing ovariohysterectomy. DESIGN: Randomized, prospective study. ANIMALS: 12 healthy Walker-type hound dogs. PROCEDURE: Dogs received medetomidine (40 micrograms/kg [18.2 micrograms/lb] of body weight, i.m.; n = 6) or saline (0.9% NaCl) solution (1 ml, i.m.; 6) prior to anesthesia induction with thiopental; thiopental dose needed for endotracheal intubation was compared between groups. Ovariohysterectomy was performed during halothane anesthesia. Blood samples were obtained at various times before drug administration until 300 minutes after extubation. Various physiologic measurements and end-tidal halothane concentrations were recorded. RESULTS: In medetomidine-treated dogs, heart rate was significantly lower than in controls, and blood pressure did not change significantly from baseline. Plasma cortisol concentrations did not increase significantly until 60 minutes after extubation in medetomidine-treated dogs, whereas values in control dogs were increased from time of surgery until the end of the recording period. Control dogs had higher pain scores than treated dogs from extubation until the end of the recording period. CONCLUSION AND CLINICAL RELEVANCE: Administration of medetomidine reduced dose requirements for thiopental and halothane and provided postoperative analgesia up to 90 minutes after extubation. Dogs undergoing ovariohysterectomy by use of thiopental induction and halothane anesthesia benefit from analgesia induced by medetomidine administered prior to anesthesia induction. Additional analgesia is appropriate 60 minutes after extubation.     

Effect of alternate-day prednisolone administration on hypophyseal-adrenocortical activity in dogs.

OBJECTIVE: To evaluate effect of alternate-day oral administration of prednisolone on endogenous plasma ACTH concentration and adrenocortical response to exogenous ACTH in dogs. ANIMALS: 12 Beagles. PROCEDURE: Dogs were allotted to 2 groups (group 1, 8 dogs treated with 1 mg of prednisolone/kg of body weight; group 2, 4 dogs given excipient only). During a 30-day period, blood samples were collected for determination of plasma ACTH and cortisol concentrations before, during, and after treatment with prednisolone. From day 7 to 23, prednisolone or excipient was given on alternate days. Sample collection (48-hour period with 6-hour intervals) was performed on days 1, 7, 15, 21, and 28; on other days, sample collection was performed at 24-hour intervals. Pre- and post-ACTH plasma cortisol concentrations were determined on days 3, 9, 17, 23, and 30. RESULTS: A significant difference was detected between treatment and time for group 1. Plasma ACTH concentrations significantly decreased for 18 to 24 hours after prednisolone treatment in group-1 dogs. At 24 to 48 hours, ACTH concentrations were numerically higher but not significantly different in group-1 dogs. Post-ACTH plasma cortisol concentration significantly decreased after 1 dose of prednisolone and became more profound during the treatment period. However, post-ACTH cortisol concentration returned to the reference range 1 week after prednisolone administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Single oral administration of 1 mg of prednisolone/kg significantly suppressed plasma ACTH concentration in dogs for 18 to 24 hours after treatment. Alternate-day treatment did not prevent suppression, as documented by the response to ACTH.     

Comparison of two low-dose dexamethasone suppression protocols as screening and discrimination tests in dogs with hyperadrenocorticism

Two low-dose dexamethasone suppression test protocols were evaluated in 18 dogs with hyperadrenocorticism (14 dogs with pituitary-dependent hyperadrenocorticism [PDH] and 4 dogs with adrenocortical tumor) and in 5 healthy control dogs. Blood was obtained immediately before and 2, 4, 6, and 8 hours after IV administration of either 0.01 mg of dexamethasone sodium phosphate/kg of body weight or 0.015 mg of dexamethasone polyethylene glycol/kg. At 8 hours after dexamethasone administration, 18 of 18 (100%) dogs with hyperadrenocorticism given the sodium phosphate preparation and 16 of 18 (89%) affected dogs given the polyethylene glycol preparation failed to have suppression of plasma cortisol concentration (less than 1.4 micrograms/dl). Plasma cortisol concentration was suppressed to less than 1.4 micrograms/dl at 2, 4, and/or 6 hours after administration of either dexamethasone preparation in 5 of 14 dogs with PDH and to less than 50% of baseline cortisol concentration in 10 of 14 dogs with PDH. Suppression, as identified by these 2 criteria, was not observed at 2, 4, 6, or 8 hours after administration of either dexamethasone preparation in dogs with adrenocortical tumor. For both protocols, the 8-hour plasma cortisol concentration was suppressed to less than 1.4 micrograms/dl and to less than 50% of baseline in the 5 control dogs. Both protocols were comparable for use as screening tests in establishing a diagnosis of hyperadrenocorticism. Suppression of plasma cortisol concentration to less than 50% of baseline (or less than 1.4 micrograms/dl) during the test was consistent with diagnosis of PDH. Failure to have such suppression, however, was observed in dogs with PDH as well as in those with adrenocortical tumor.     

Analgesic effect of pre-operative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy

The analgesic, bleeding, and renal effects of dogs pre‐medicated with etodolac with and without butorphanol were evaluated. Twenty‐four 1‐year‐old healthy dogs, weighing 19 ± 3 kg (mean ± SD) were randomly assigned to four treatment groups (n = 6): control (C), etodolac (E), butorphanol (B), and etodolac with butorphanol (EB). Etodolac (12–14 mg kg^?1 PO) was given 1 hour before propofol induction and isoflurane maintenance anesthesia. Butorphanol (0.4 mg kg^?1 IV) was given immediately following endotracheal intubation. Control dogs received only propofol (8 mg kg^?1 to effect) and isoflurane anesthesia. All dogs were mechanically ventilated to maintain Pe ′CO₂ between 35 and 45 mm Hg (4.7–6.0 kPa). Lactated Ringer's solution was given at 10 mL kg^?1 hour^?1 during anesthesia. Plasma cortisol concentrations were assessed 1 day prior to surgery (baseline), immediately prior to anesthesia induction, and every 30 minutes until 5 hours following extubation, and 1 day after surgery. Total duration of anesthesia was 50 minutes and total surgery duration was 30 minutes. Isoflurane concentration area under the curve (AUC) over time during the anesthesia was compared among treatment groups. Buccal mucosal bleeding time (BMBT) was assessed 1 day before E administration and during surgery. Urine GGT to urine creatinine ratio, BUN, and plasma creatinine were taken daily from 1 day before to 3 days after surgery. Behavioral pain scores (numerical rating scale) were assessed by two observers blinded to the treatment during the 5‐hour recovery period at 30 minute intervals until 3 hours, and again at 5 hours after extubation. All data were analyzed using anova . Multiple comparisons were performed if the anova was significant. Alpha value was set at 0.05. Plasma cortisol concentrations significantly increased from time of extubation in all the treatment groups. They did not return to the baseline until 5, 2.5, 1.5, and 1.5 hours after extubation in the C, B, E, and EB groups, respectively. Isoflurane AUC was not significantly different among treatment groups. Dogs treated with EB had significantly less behavioral pain than all other groups throughout the 5‐hour recovery period. No significant difference was found between treatment groups or within treatment groups over time in BMBT, or any renal variables. This study demonstrated that (i) pre‐operative administration of E provides profound analgesia during the post‐operative period without renal or bleeding side‐effects in dogs undergoing OHE; and (ii) a combination of butorphanol–etodolac provides the best analgesic effect during the post‐operative period based on the behavioral pain score.     

Duration of pituitary and adrenocortical suppression after long-term administration of anti-inflammatory doses of prednisone in dogs.

Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P less than 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P less than 0.05) reduced and reserve function was markedly (P less than 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.     

Effects of exercise-induced stress and dexamethasone on plasma hormone and glucose concentrations and sedation in dogs treated with dexmedetomidine

OBJECTIVE: To compare the effects of pretreatment with dexamethasone, physical stress (exercise), or both on sedation and plasma hormone and glucose concentrations in dogs treated with dexmedetomidine (DEX). ANIMALS: 6 healthy purpose-bred Beagles. PROCEDURE: Dogs received 4 treatments each in a randomized order prior to i.v. administration of DEX (5 fLg/kg). Pretreatments were as follows: (1) i.v. administration of saline (0.9% NaCI) solution and no exercise (control group); (2) IV administration of dexamethasone (0.05 mg/kg) and no exercise (DM group); (3) i.v. administration of saline solution and exercise (EX group; 15 minutes of trotting on a treadmill at a speed of 2 m/s); and (4) i.v. administration of dexamethasone and exercise (DM+EX group). RESULTS: Following DEX administration, all dogs had similar times to recumbency and sedation index values, irrespective of pretreatment with values, irrespective of pretreatment with dexam-d ethasone or exercise. Plasma catecholamine concentrations decreased after DEX administration. Compared with control group dogs, plasma cortisol concentrations were higher in EX-group dogs prior to DEX administration and lower in DM- and DM+EX-group dogs following DEX administration. Administration of DEX decreased plasma cortisol concentration in EX-group dogs only. Plasma glucose concentration was not influenced by exercise or dexamethasone administration was lower than baseline concentrations at 30 minutes after DEX administration and returned to baseline values by 90 minutes. Heart and respiratory rates and rectal temperature increased during exercise. After DEX administration, these values decreased below baseline values. The decrease in heart rate was of shorter duration in dogs that underwent pretreatment with dexamethasone, exercise, or both than in control group dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Pretreatment with dexamethasone, moderate physical stress (exercise), or both did not influence sedation or cause adverse effects in healthy dogs treated with DEX.     

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)     

Plasma pharmacokinetics and tissue fluid concentrations of meropenem after intravenous and subcutaneous administration in dogs

OBJECTIVE: To estimate pharmacokinetic variables and measure tissue fluid concentrations of meropenem after IV and SC administration in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURE: Dogs were administered a single dose of meropenem (20 mg/kg) IV and SC in a crossover design. To characterize the distribution of meropenem in dogs and to evaluate a unique tissue fluid collection method, an in vivo ultrafiltration device was used to collect interstitial fluid. Plasma, tissue fluid, and urine samples were analyzed by use of high-performance liquid chromatography. Protein binding was determined by use of an ultrafiltration device. RESULTS: Plasma data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean +/- SD values for half-life, volume of distribution, and clearance after IV administration for plasma samples were 0.67 +/- 0.07 hours, 0.372 +/- 0.053 L/kg, and 6.53 +/- 1.51 mL/min/kg, respectively, and half-life for tissue fluid samples was 1.15 +/- 0.57 hours. Half-life after SC administration was 0.98 +/- 0.21 and 1.31 +/- 0.54 hours for plasma and tissue fluid, respectively. Protein binding was 11.87%, and bioavailability after SC administration was 84%. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of our data revealed that tissue fluid and plasma (unbound fraction) concentrations were similar. Because of the kinetic similarity of meropenem in the extravascular and vascular spaces, tissue fluid concentrations can be predicted from plasma concentrations. We concluded that a dosage of 8 mg/kg, SC, every 12 hours would achieve adequate tissue fluid and urine concentrations for susceptible bacteria with a minimum inhibitory concentration of 0.12 microg/mL.     

Adrenocortical suppression in the dog given a single intramuscular dose of prednisone or triamcinolone acetonide

Adrenocortical function was assessed in dogs given a single intramuscular dose of either prednisone or triamcinolone acetonide (TCA; or saline solution to controls) to determine the duration of adrenocortical suppression caused by 2 commonly used glucocorticoids. The glucocorticoids were administered at recommended therapeutic doses; therefore, dogs given prednisone received a greater amount of glucocorticoid activity than did in dogs given TCA. Basal and ACTH-stimulated plasma cortisol concentrations, as determined by radioimmunoassay, were obtained once a week. Total intravascular eosinophil concentration and skin responses to intradermally injected histamine phosphate were quantitated. Dogs given TCA showed suppressed basal and ACTH-stimulated plasma cortisol concentrations 1 week after injection; the latter change persisted 2 weeks after injection. Adrenocortical function in 1 of 4 dogs given TCA remained suppressed for 4 weeks. In contrast, prednisone did not significantly alter adrenocortical function. Although intravascular eosinophil concentrations did not vary among groups, skin responses to intradermally injected histamine phosphate were reduced 6 days after prednisone and TCA were given.     

Effects of a program of human interaction and alterations in diet composition on activity of the hypothalamic-pituitary-adrenal axis in dogs housed in a public animal shelter

OBJECTIVE: To determine whether a program of human interaction or alterations in diet composition would alter activity of the hypothalamic-pituitary-adrenal (HPA) axis in dogs housed in an animal shelter. DESIGN: Prospective study. ANIMALS: 40 dogs. PROCEDURE: Dogs were (n = 20) or were not (20) enrolled in a program of regular supplemental human interaction (20 min/d, 5 d/wk, for 8 weeks) involving stroking, massaging, and behavioral training. In addition, half the dogs in each group were fed a typical maintenance-type diet, and the other half were fed a premium diet. Plasma cortisol and ACTH concentrations were measured during weeks 0, 2, 4, and 8 and before and after exposure to a battery of novel situations during weeks 0 and 8. RESULTS: Plasma cortisol concentration was significantly decreased by week 2, but plasma ACTH concentration was not significantly decreased until week 8 and then only in dogs fed the premium diet. Following exposure to novel situations, plasma cortisol and ACTH concentrations were significantly increased. However, during week 8, dogs enrolled in the program of human interaction had significantly lower increases in cortisol concentration than did dogs not enrolled in the program. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that both a program of human interaction and alterations in diet composition have moderating effects on activity of the HPA axis in dogs housed in an animal shelter and that activity of the HPA axis may be increased for a longer period during shelter housing than measurement of plasma cortisol concentration alone would suggest.     

Effects of preoperative administration of ketoprofen on anesthetic requirements and signs of postoperative pain in dogs undergoing elective ovariohysterectomy

OBJECTIVE: To determine the effects of preoperative administration of ketoprofen on anesthetic requirements and signs of postoperative pain in dogs undergoing elective ovariohysterectomy. DESIGN: Randomized, controlled clinical trial. ANIMALS: 22 clinically normal client-owned dogs. PROCEDURE: 60 minutes before induction of anesthesia, 11 dogs were given ketoprofen (2 mg/kg [0.9 mg/lb], i.m.), and the other 11 were given saline (0.9% NaCl) solution. Dogs were premedicated with glycopyrrolate, acepromazine, and butorphanol and anesthetized with thiopental; anesthesia was maintained with isoflurane. Ovariohysterectomy was performed by an experienced surgeon, and butorphanol was given 15 minutes before completion of the procedure. Objective behavioral scores and numerical pain scores at rest and with movement were recorded every 2 hours for 12 hours after surgery and then every 4 hours for an additional 12 hours. RESULTS: Preoperative administration of ketoprofen did not reduce the dose of thiopental required to induce anesthesia or the end-tidal concentration of isoflurane required to maintain anesthesia. Activity levels and median objective behavioral scores were significantly higher 4 and 6 hours after surgery in dogs given ketoprofen than in dogs given saline solution. However, mean numerical pain scores in dogs given ketoprofen were not significantly different from scores for dogs given saline solution at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that preoperative administration of ketoprofen does not reduce anesthetic requirements in dogs undergoing elective ovariohysterectomy but may reduce signs of pain after surgery. Results also suggest that the objective behavioral score may be a more sensitive measure of acute postoperative pain than traditional numerical pain scores.     

Comparison of the effects of etomidate and its fluoro analogue, R 8110, on plasma Cortisol, 11β-deoxycortisol, 17α-hydroxyprogesterone and testosterone concentrations in dogs

R 8110, an imidazole derivative, was shown to be clinically superior to etomidate for induction and maintenance of anaesthesia in dogs. The present study compared the effects of intravenous (i.v.) R 8110, etomidate and Ringer solution on cortisol biosynthesis by the adrenal gland in seven male labradors. A tetracosactide challenge was carried out 30 min after the i.v. injection of 3 mg/kg of both drugs and after i.v. Ringer solution (1 ml/kg). Etomidate and R 8110 both suppressed the cortisol response to tetracosactide almost completely and increased the plasma 11 beta-deoxycortisol levels more than 20 fold. Maximal 11 beta-deoxycortisol values were reached 120 min after R 8110, and not less than 300 min after etomidate. Plasma 17 alpha-hydroxyprogesterone and testosterone concentrations did not differ between placebo and R 8110 treatment, but they decreased after etomidate. These results indicate that the effects of R 8110 on steroid biosynthesis in dogs are less pronounced than those of etomidate and are largely limited to a temporary inhibition of the 11 beta-hydroxylase in the adrenal gland.     

Comparison of the immunoreactive plasma corticotropin and cortisol responses to two synthetic corticotropin preparations (tetracosactrin and cosyntropin) in healthy cats.

Plasma cortisol and immunoreactive (IR)-ACTH responses to 125 micrograms of tetracosactrin and cosyntropin--the formulation of synthetic ACTH available in Europe and the United States, respectively--were compared in 10 clinically normal cats. After administration of tetracosactrin or cosyntropin, mean plasma cortisol concentration reached a peak and plateaued between 60 and 120 minutes, then gradually decreased to values not significantly different from baseline concentration by 5 hours. Mean plasma IR-ACTH concentration reached a maximal value at 15 minutes after administration of tetracosactrin or cosyntropin and was still higher than baseline concentration at 6 hours. Difference between mean plasma cortisol and IR-ACTH concentrations for the tetracosactrin or cosyntropin trials was not significant at any of the sample collection times. Individual cats had some variation in the time of peak cortisol response after administration of either ACTH preparation. About half the cats had peak cortisol concentration at 60 to 90 minutes, whereas the remainder had the peak response at 2 to 4 hours. In general, however, peak cortisol concentration in the cats with delayed response was not much higher than the cortisol concentration at 60 to 90 minutes. Overall, these results indicate that tetracosactrin or cosyntropin induce a comparable, if not identical, pattern of adrenocortical responses when administered to healthy cats.     

Plasma cortisol concentrations in dogs given cortisone or placebo by mouth

Fasted normal dogs (n=8) were given fixed doses of cortisone acetate orally as 5 mg and 25 mg tablets; plasma cortisol concentrations were determined, and C_max, t_max and area under the curve of plasma cortisol concentration plotted against time from zero to 12 hours were compared for the two preparations. In addition, these variables were compared when 25 mg tablets were administered with and without food. No significant difference in cortisol availability was noted for the two preparations and feeding did not apparently affect cortisone absorption. The findings in two hypoadrenocorticoid dogs were similar. Plasma cortisol concentrations in placebo-treated dogs similarly sampled showed minor fluctuations and were generally within accepted reference limits for normal dogs.     

Pharmacokinetic variables of mivacurium chloride after intravenous administration in dogs.

OBJECTIVE: To determine pharmacokinetic variables of mivacurium chloride after IV administration in dogs. ANIMALS: 5 healthy Labrador Retrievers. PROCEDURE: Anesthesia was induced with thiopental and maintained with halothane in oxygen. Dogs were ventilated mechanically to an end-tidal P(CO)2 value between 35 and 40 mm Hg. Heart rate, direct blood pressure, and arterial pH were recorded throughout the experiment. Core temperature, end-tidal P(CO)2, and halothane concentration were kept constant throughout the experiment. Paired blood samples for determination of plasma cholinesterase activity were collected prior to administration of a bolus of mivacurium (0.05 mg/kg of body weight), which was administered IV during a 2-second period. Arterial blood samples were obtained for determination of plasma mivacurium concentration 0, 1, 3, 5, 10, 30, 60, 120, 150, and 180 minutes after administration of mivacurium. Blood was collected into tubes containing EDTA and 0.25% echothiophate. Mivacurium concentration was determined, using reversed-phase high-performance liquid chromatography. RESULTS: For the trans-trans isomer, mean +/- SEM volume of distribution was 0.18+/-0.024 L/kg, median half-life was 34.9 minutes (range, 26.7 to 53.5 minutes), and clearance was 12+/-2 ml/min/kg. For the cis-trans isomer, values were 0.31+/-0.05 L/kg, 43.4 minutes (range, 31.5 to 69.3 minutes), and 15+/-2 ml/min/kg, respectively. Values for the cis-cis isomer were not calculated, because it was not detectable in plasma 60 minutes after mivacurium administration in all 5 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The transtrans and cis-trans isomers of mivacurium have a long half-life and slow clearance in healthy dogs anesthetized with halothane.     

Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism

The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (+/- SD) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 +/- 1.6 micrograms/dl), lowest in 15 control dogs (1.3 +/- 0.5 micrograms/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH; 3.4 +/- 1.2 micrograms/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P less than 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with PDH; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P less than 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 +/- 0.2 microgram/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later. Twenty dogs with hyperadrenocorticism (11 with PDH, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with PDH failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P less than 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (ACTH).(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of a low-dose synthetic adrenocorticotropic hormone stimulation test in clinically normal dogs and dogs with naturally developing hyperadrenocorticism.

OBJECTIVE: To determine whether low doses of synthetic ACTH could induce a maximal cortisol response in clinically normal dogs and to compare a low-dose ACTH stimulation protocol to a standard high-dose ACTH stimulation protocol in dogs with hyperadrenocorticism. DESIGN: Cohort study. ANIMALS: 6 clinically normal dogs and 7 dogs with hyperadrenocorticism. PROCEDURE: Each clinically normal dog was given 1 of 3 doses of cosyntropin (1, 5, or 10 micrograms/kg [0.45, 2.3, or 4.5 micrograms/lb] of body weight, i.v.) in random order at 2-week intervals. Samples for determination of plasma cortisol and ACTH concentrations were obtained before and 30, 60, 90, and 120 minutes after ACTH administration. Each dog with hyperadrenocorticism was given 2 doses of cosyntropin (5 micrograms/kg or 250 micrograms/dog) in random order at 2-week intervals. In these dogs, samples for determination of plasma cortisol concentrations were obtained before and 60 minutes after ACTH administration. RESULTS: In the clinically normal dogs, peak cortisol concentration and area under the plasma cortisol response curve did not differ significantly among the 3 doses. However, mean plasma cortisol concentration in dogs given 1 microgram/kg peaked at 60 minutes, whereas dogs given doses of 5 or 10 micrograms/kg had peak cortisol values at 90 minutes. In dogs with hyperadrenocorticism, significant differences were not detected between cortisol concentrations after administration of the low or high dose of cosyntropin. CLINICAL IMPLICATIONS: Administration of cosyntropin at a rate of 5 micrograms/kg resulted in maximal stimulation of the adrenal cortex in clinically normal dogs and dogs with hyperadrenocorticism.     

Efficacy and cost-effectiveness of transdermal fentanyl patches for the relief of post-operative pain in dogs after anterior cruciate ligament and pelvic limb repair

OBJECTIVES: To determine whether transdermal fentanyl patches provided cost-effective post-operative analgesia in dogs with pelvic limb injuries. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: Twenty-four dogs undergoing repair of ruptured cranial cruciate ligaments or pelvic limb fractures. METHODS: Dogs were randomly assigned to one of two groups: those receiving transdermal fentanyl patches (group F) and those receiving injectable morphine for control of post-operative pain (group M). Patients in both treatment groups were monitored for adequacy of analgesia and alterations in physiological variables. Plasma fentanyl concentrations were measured in Group F. Rescue morphine was given if a dog was deemed uncomfortable. The time of first rescue morphine, the total amount, and number of doses of morphine administered over 72 hours was quantified and compared for each group. RESULTS: There was no significant treatment effect on any of the parameters, except for serum cortisol concentration, which was significantly lower overall in group F (p = 0.01). Pain scores peaked at 6 hours post-extubation and were higher than baseline from 2 to 20 hours post-extubation. Cortisol concentrations were the highest at time 0 (extubation) and were significantly higher than baseline until 2 hours post-extubation. Pain scores correlated with fentanyl plasma concentrations (p = 0.0001 and p = 0.01, respectively), but the correlation was low (r = 0.26 and r = 0.16, respectively). No correlation was found between serum cortisol concentrations and pain scores in either group. Fentanyl cost and total cost for pain management were considerably higher for group F. CONCLUSIONS: Fentanyl patches did not provide better analgesia or a reduced requirement for rescue opioid compared with intramuscular morphine. CLINICAL RELEVANCE: When considering overall costs to the client for comparable analgesic intervention, fentanyl patches increased rather than decreased cost during the first 24 hours post-operatively.     

Effects of single intravenous doses of dexamethasone on baseline plasma cortisol concentrations and responses to synthetic ACTH in healthy dogs

The duration of adrenocortical suppression resulting from a single IV dose of dexamethasone or dexamethasone sodium phosphate was determined in dogs. At 0800 hours, 5 groups of dogs (n = 4/group) were treated with 0.01 or 0.1 mg of either agent/kg of body weight or saline solution (controls). Plasma cortisol concentrations were significantly (P less than 0.01) depressed in dogs given either dose of dexamethasone or dexamethasone sodium phosphate by posttreatment hour (PTH) 2 and concentrations remained suppressed for at least 16 hours. However, by PTH 24, plasma cortisol concentrations in all dogs, except those given 0.1 mg of dexamethasone/kg, returned to control values. Adrenocortical suppression was evident in dogs given 0.1 mg of dexamethasone/kg for up to 32 hours. The effect of dexamethasone pretreatment on the adrenocortical response to ACTH was studied in the same dogs 2 weeks later. Two groups of dogs (n = 10/group) were tested with 1 microgram of synthetic ACTH/kg given at 1000 hours or 1400 hours. One week later, half of the dogs in each group were given 0.01 mg of dexamethasone/kg at 0600 hours, whereas the remaining dogs were given 0.1 mg of dexamethasone/kg. The ACTH response test was then repeated so that the interval between dexamethasone treatment and ACTH injection was 4 hours (ACTH given at 1000 hours) or 8 hours (ACTH given at 1400 hours). Base-line plasma cortisol concentrations were reduced in all dogs given dexamethasone 4 or 8 hours previously.(ABSTRACT TRUNCATED AT 250 WORDS)