Changes in cortisol concentration in response to stress and postoperative pain in client-owned cats and correlation with objective clinical variables

OBJECTIVE: To identify clinical variables that indicate postoperative pain in cats after ovariohysterectomy in a veterinary hospital setting. ANIMALS: 40 cats. PROCEDURE: Cats were anesthetized and ovariohysterectomized by senior veterinary students. Butorphanol (0.1 mg/kg [n = 20] or 0.3 mg/kg [20] of body weight) was administered IM after surgery. Blood samples were obtained before, during, and after the anesthetic period for measurements of PCV and blood glucose and cortisol concentrations. Clinical variables measured included heart rate, systolic blood pressure, respiratory rate, and rectal temperature. Data for these variables were compared with changes in cortisol concentrations and with similar data-which was used as historical control data-obtained from 20 cats in another study (10 that had been ovariohysterectomized but had not received butorphanol and 10 that had only been anesthetized). RESULTS: Surgical durations were longer in this study, and cats had higher cortisol concentrations, compared with historical control cats. Objective clinical variables did not consistently correlate with changes in cortisol concentration. CONCLUSIONS: Cortisol concentration increased in response to surgical stress and pain. This response was greater in cats in which duration of surgery was longer. CLINICAL RELEVANCE: The objective clinical variables evaluated in this study were not consistent indicators of pain in an uncontrolled, clinical situation.     

Comparison of the effects of buprenorphine,oxymorphone hydrochloride,and ketoprofen for postoperative analgesia after onychectomy or onychectomy and sterilization in cats

In this prospective, randomized, blinded study, 68 clinically healthy cats that had onychectomy (n = 20), onychectomy and castration (n = 20), or onychectomy and ovariohysterectomy (n = 28) were randomly assigned to one of four postoperative analgesic treatment groups: buprenorphine (0.01 mg/kg body weight, intramuscularly [IM]), oxymorphone hydrochloride (0.05 mg/kg body weight, IM), ketoprofen (2 mg/kg body weight, IM), and placebo (physiological saline). Sedation scores, visual analog pain scores, cumulative pain scores, serum cortisol concentration, and appetite were used to assess postoperative analgesic effect. Buprenorphine demonstrated the highest efficacy with the lowest cumulative pain scores and serum cortisol levels.     

Changes in the cortisol responses of lambs to tail docking, castration and ACTH injection during the first seven days after birth

Cortisol responses of Dorset and Scottish Blackface lambs were investigated at six ages between birth and seven days. There were four treatments: control handling and blood sampling (n = 52), tail docking (T) (n = 57), castration plus tail docking (CT) (n = 54), and intravenous adrenocorticotrophin (ACTH) injection (n = 60). Most lambs exhibited transient rises in plasma cortisol concentrations after treatment and the results in individuals were expressed as the area under the cortisol curve (integrated response). Postnatal changes in the integrated responses of control, T and CT lambs differed significantly between the two breeds; in Dorsets they increased markedly between four hours and one day and then decreased, whereas in Scottish Blackface lambs there were no significant changes. The cortisol responses of ACTH lambs decreased markedly between four hours and seven days in both breeds. The results shed light on postnatal changes in the activity of the hypothalamic-pituitary-adrenal axis and suggest for both breeds that the average increments in ACTH secretion caused by noxious stimuli increased markedly during the first one to three days after birth. Whether this reflected parallel increases in the levels of distress experienced by the lambs remains to be clarified.     

Effects of multiple intramuscular injections and doses of dexamethasone on plasma cortisol concentrations and adrenal responses to ACTH in horses

Adrenocortical function was assessed in horses given multiple IM doses of dexamethasone to determine the duration of adrenocortical suppression and insufficiency caused by 2 commonly used dosages of dexamethasone (0.044 and 0.088 mg/kg of body weight). Dexamethasone was administered at 5-day intervals for a total of 6 injections. Daily blood samples were collected. The plasma was frozen and later assayed for cortisol. An ACTH response test was determined 2 days before the first injection of dexamethasone and again 8 days after the last dexamethasone injection. Maximum suppression of plasma cortisol was observed in horses given both dosages of dexamethasone (0.044 and 0.088 mg/kg). Plasma cortisol concentrations returned to base-line values in all horses by 4 days after dexamethasone injection. Normal ACTH responses observed after 6 dexamethasone injections given at 5-day intervals indicated that measurable adrenal atrophy did not develop under the conditions of this study.     

Plasma hormone concentrations after administration of dexamethasone during the middle of the luteal phase in cows

The effect of glucocorticoids on gonadal steroid and gonadotropic hormone concentrations and subsequent follicular activity in cows undergoing normal estrous cycles was evaluated by administration of dexamethasone (DXM) during the middle of the luteal phase. Seven cows were given physiologic saline solution twice daily from day 13 to day 17 of the estrous cycle (control experiment). During the next estrous cycle, cows were administered DXM (2 mg, IM) twice daily on days 13 through 17. Plasma specimens obtained twice daily throughout the control and DXM-treatment cycles were assayed for progesterone and estradiol concentrations. The appearance of estrus after DXM treatment was delayed until days 23 to 25 in 3 cows and was not seen by day 35 in the other 4 cows, compared with mean (+/- SD) cycle length of 22.4 +/- 3.2 in cows during the control experiment. Progesterone concentration remained significantly (P less than 0.01) high on days 19 to 23, whereas estradiol values failed to increase (P less than 0.05) on days 19 and 20 after treatment with DXM. Blood samples were obtained at 15-minute intervals for 12 hours to compare (by analysis of covariance) the effect of DXM treatment on plasma hormone concentrations on day 15 of each cycle with those of day 10. Compared with values during the control experiment, a significant (P less than 0.05) decrease was observed in the size of the pulses of luteinizing hormone (LH) and estradiol, although the number of pulses of each hormone per 12 hours was not affected when cows were given DXM. Baseline concentrations of LH and estradiol were not altered by type of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of phenylbutazone and anabolic steroids on adrenal and thyroid gland function tests in healthy horses

Adrenal and/or thyroid gland function tests were evaluated in horses at various times during short-term therapy with phenylbutazone, stanozolol, and boldenone undecylenate. There were no significant treatment or time effects on mean basal plasma cortisol concentrations in horses during treatment with the following: phenylbutazone, given twice daily (4 to 5 mg/kg, IV) for 5 days; stanozolol, given twice weekly (0.55 mg/kg, IM) for 12 days; boldenone undecylenate, given twice weekly (1.1 mg/kg, IM) for 12 days; or nothing. There was no significant effect of phenylbutazone treatment on the changes in plasma cortisol concentration during the combined dexamethasone-suppression adrenocorticotropic hormone (ACTH)-stimulation test. Plasma cortisol concentration was significantly decreased from base line at 3 hours after dexamethasone administration and was significantly increased from base line at 2 hours after ACTH in all horses (P less than 0.05). Likewise, the stimulation of basal plasma cortisol concentrations at 2 hours after administration of ACTH (P less than 0.05) was not affected by treatment with stanozolol or boldenone undecylenate. There were no significant treatment effects on mean basal plasma concentrations of thyroxine (T4) or triiodothyronine (T3) among horses during the following treatments: stanozolol, given twice weekly (0.55 mg/kg, IM) for 12 days; boldenone undecylenate, given twice weekly (1.1 mg/kg, IM) for 12 days; or nothing. There was a significant time effect on overall mean basal plasma T4 and T3 concentrations (P less than 0.05): plasma T4 was lower on day 8 than on days 1, 10, and 12; plasma T3 was higher on day 8 than on days 4 and 12.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma endogenous ACTH concentrations and plasma cortisol responses to synthetic ACTH and dexamethasone sodium phosphate in healthy cats

Plasma cortisol responses of 19 healthy cats to synthetic ACTH and dexamethasone sodium phosphate (DSP) were evaluated. After administration of 0.125 mg (n = 5) or 0.25 mg (n = 6) of synthetic ACTH, IM, mean plasma cortisol concentrations increased significantly (P less than 0.05) at 15 minutes, reached a peak at 30 minutes, and decreased progressively to base-line values by 120 minutes. There was no significant difference (P greater than 0.05) between responses resulting from the 2 dosage rates. After administration of 1 mg of DSP/kg of body weight, IV (n = 7), mean plasma cortisol concentrations decreased at postadministration hour (PAH) 1, and were significantly lower than control cortisol concentrations at PAH 4, 6, 8, 10, and 12 (P less than 0.01). Administration of 0.1 mg of DSP/kg, IV (n = 8) or 0.01 mg of DSP/kg, IV (n = 14) induced results that were similar, but less consistent than those after the 1 mg of DSP/kg dosage. Mean plasma cortisol concentrations returned to base-line values by PAH 24. There was not a significant difference between the 3 doses (P greater than 0.05) at most times. Measurement of endogenous ACTH in 16 healthy cats revealed plasma ACTH of less than 20 to 61 pg/ml. Seemingly, administration of synthetic ACTH consistently induced a significant (P less than 0.05) adrenocortical response in healthy cats. On the basis of time-response studies, post-ACTH stimulation cortisol samples should be collected at 30 minutes after ACTH administration to ensure detection of peak adrenocortical response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and body fluid and endometrial concentrations of cefoxitin in mares

Four healthy adult mares were each given a single injection of sodium cefoxitin (20 mg/kg of body weight, IV), and serum cefoxitin concentrations were measured serially during a 6-hour period. The mean elimination rate constant was 1.08/hour and the elimination half-life was 0.82 hour. The apparent volume of distribution (at steady state) and the clearance of the drug were estimated at 0.12 L/kg and 259 ml/hr/kg, respectively. Each mare and 2 additional mares were then given 4 consecutive IM injections of sodium cefoxitin (400 mg/ml) at a dosage of 20 mg/kg. Cefoxitin concentrations in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium were measured serially. After IM administration, the highest mean serum concentration was 23.1 micrograms/ml 30 minutes after the 2nd injection. The highest mean synovial concentration was 11.4 micrograms/ml 1 hour after the 4th injection. The highest mean peritoneal concentration was 10.4 micrograms/ml 2 hours after the 4th injection. The highest mean endometrial concentration was 4.5 micrograms/g 4 hours after the 4th injection. Mean urine concentrations reached 11,645 micrograms/ml. Cefoxitin did not readily penetrate the CSF. Bioavailability of cefoxitin given IM was 65% to 89% (mean +/- SEM = 77% +/- 5.9%). One of the 6 mares developed acute laminitis during the IM experiment.     

Cortisol secretion after adrenocorticotrophin (ACTH) and Dexamethasone tests in healthy female and male dogs

Background

For the conclusive diagnosis of Cushing''s Syndrome, a stimulating ACTH test or a low suppressive Dexamethasone test is used. Reports in other species than the dog indicate that plasma cortisol concentration after ACTH administration is affected by gender. We investigated the effect of gender on the cortisol response to ACTH and Dexamethasone tests in dogs.

Methods

Seven healthy adult Cocker Spaniels (4 females and 3 males) were assigned to a two by two factorial design: 4 dogs (2 females and 2 males) received IV Dexamethasone 0.01 mg/kg, while the other 3 dogs received an IV saline solution (control group). Two weeks later the treatments were reversed. After one month, ACTH was given IV (250 μg/animal) to 4 dogs (2 female and 2 males) while the rest was treated with saline solution (control group). Cortisol concentrations were determined by a direct solid-phase radioimmunoassay and cholesterol and triglycerides by commercial kits.

Results and Discussion

No effect of treatment was observed in metabolite concentrations, but females presented higher cholesterol concentrations. ACTH-treated dogs showed an increase in cortisol levels in the first hour after sampling until 3 hours post injection. Cortisol concentrations in Dexamethasone-treated dogs decreased one hour post injection and remained low for 3 hours, thereafter cortisol concentrations increased. The increase in cortisol levels from one to two hours post ACTH injection was significantly higher in females than males. In Dexamethasone-treated males cortisol levels decreased one hour post injection up to 3 hours; in females the decrease was more pronounced and prolonged, up to 5 hours post injection.

Conclusion

We have demonstrated that cortisol response to ACTH and Dexamethasone treatment in dogs differs according to sex.     

Effects of cortisol on pregnancy rate and corpus luteum function in heifers: an in vivo study

To determine whether glucocorticoids affect the function of the bovine corpus luteum (CL) during the estrous cycle and early pregnancy, we examined the effects of exogenous cortisol or reduced endogenous cortisol on the secretion of progesterone (P4) and on pregnancy rate. In preliminary experiments, doses of cortisol and metyrapone (an inhibitor of cortisol synthesis) were established (n=33). Cortisol in effective doses of 10 mg blocked tumor necrosis factor-induced prostaglandin F(2α) secretion as measured by its metabolite (PGFM) concentrations in the blood. Metyrapone in effective doses of 500 mg increased the P4 concentration. Thus, both reagents were then intravaginally applied in the chosen doses daily from Day 15 to 18 after estrus (Day 0) in noninseminated heifers (n=18) or after artificial insemination (n=36). Pregnancy was confirmed by transrectal ultrasonography between Days 28-30 after insemination. Plasma concentrations of P4 were lower in cortisol-treated heifers than in control heifers on Days 17 and 18 of the estrous cycle (P<0.05). However, the interestrus intervals were not different between control and cortisol-treated animals (P>0.05). Moreover, metyrapone increased P4 and prolonged the CL lifespan in comparison to control animals (P<0.05). Interestingly, in inseminated heifers, cortisol increased the pregnancy rate (75%) compared with control animals (58%), whereas metyrapone reduced the pregnancy rate to 16.7% (P<0.05). The overall results suggest that cortisol, depending on the physiological status of heifers (pregnant vs. nonpregnant), modulates CL function by influencing P4 secretion. Cortisol may have a positive influence on CL function during early pregnancy, leading to support of embryo implantation and resulting in higher rates of pregnancy in heifers.     

Pharmacokinetics and body fluid and endometrial concentrations of cephapirin in mares

Six healthy adult horse mares were each given a single injection of sodium cephapirin (20 mg/kg of body weight, IV), and serum cephapirin concentrations were measured serially over a 6-hour period. The mean elimination rate constant was 0.78 hour-1 and the elimination half-life was 0.92 hours. The apparent volume of distribution (at steady state) and the clearance of the drug were estimated at 0.17 L/kg and 598 ml/hour/kg, respectively. Each mare was then given 4 consecutive IM injections of sodium cephapirin (400 mg/ml) at a dosage level of 20 mg/kg. Cephapirin concentrations in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium were measured serially. After IM administration, the highest mean serum concentration was 14.8 micrograms/ml 25 minutes after the 4th injection. The highest mean synovial and peritoneal concentrations were 4.6 micrograms/ml and 5.0 micrograms/ml, respectively, 2 hours after the 4th injection. The highest mean endometrial concentration was 2.2 micrograms/g 4 hours after the 4th injection. Mean urine concentrations reached 7,421 micrograms/ml. Cephapirin did not readily penetrate the CSF. When cephapirin was given IM at the same dose, but in a less concentrated solution (250 mg/ml), serum concentrations peaked at 25.0 micrograms/ml 20 minutes after injection, but the area under the serum concentration-time curve was not significantly different (P greater than 0.05). The bioavailability of the drug was greater than or equal to 95% after IM injection.     

A comparison of four methods of analgesia in cats following ovariohysterectomy

OBJECTIVE: To evaluate the effectiveness of preoperative administration of oral carprofen, subcutaneous ketoprofen, and local nerve block with bupivacaine in preventing postoperative pain-associated behavior in cats after ovariohysterectomy. ANIMALS: Fifty-two female intact cats. Materials and methods Cats received butorphanol (0.44 mg kg(-1) IM), carprofen (2.2 mg kg(-1) PO), ketoprofen (2.2 mg kg(-1) SQ), or bupivacaine infiltration block (1.1 mg kg(-1) SQ) before surgery. Cortisol and drug concentrations and visual analog scale (VAS) and interactive visual analog scale (IVAS) pain-associated behavior scores were measured 2 hours before and 0, 1, 2, 4, 8, 12, and 24 hours after ovariohysterectomy. RESULTS: Cats receiving butorphanol had significantly increased IVAS scores 2 hours after surgery compared with baseline measurements. Cats receiving carprofen, ketoprofen, and bupivacaine had significant increases from baseline in VAS and IVAS scores 1 and 2 hours after surgery. VAS and IVAS scores for cats receiving bupivacaine were significantly greater 1 and 2 hours after surgery than for cats that received butorphanol. Cats receiving carprofen had significant increases in cortisol 1 hour after surgery and significant decreases 24 hours after surgery compared with baseline measurements. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative carprofen and ketoprofen have effects on pain-associated behavior similar to butorphanol in cats undergoing ovariohysterectomy. Cats receiving bupivacaine blocks may require additional analgesics immediately after surgery.     

Comparison of intravenous and intramuscular routes of administering cosyntropin for corticotropin stimulation testing in cats.

Plasma cortisol and immunoreactive (IR)-ACTH responses to 125 micrograms of synthetic ACTH (cosyntropin) administered IV or IM were compared in 10 clinically normal cats. After IM administration of cosyntropin, mean plasma cortisol concentration increased significantly (P less than 0.05) within 15 minutes, reached maximal concentration at 45 minutes, and decreased to values not significantly different from baseline concentration by 2 hours. After IV administration of cosyntropin, mean plasma cortisol concentration also increased significantly (P less than 0.05) at 15 minutes, but in contrast to IM administration, the maximal cortisol response took longer (75 minutes) and cortisol concentration remained significantly (P less than 0.05) higher than baseline cortisol concentration for 4 hours. Mean peak cortisol concentration (298 nmol/L) after IV administration of cosyntropin was significantly (P less than 0.05) higher than the peak value (248 nmol/L) after IM administration. All individual peak plasma cortisol concentrations and areas under the plasma cortisol response curve were significantly (P less than 0.05) higher after IV administration of cosyntropin than after IM administration. Mean plasma IR-ACTH concentration returned to values not statistically different from baseline by 60 minutes after IM administration of cosyntropin, whereas IR-ACTH concentration still was higher than baseline concentration 6 hours after IV administration. Peak plasma IR-ACTH concentration and area under the plasma IR-ACTH response curve also were significantly (P less than 0.05) higher after IV administration of cosyntropin. Results of the study confirmed that IV administration of cosyntropin induces significantly (P less than 0.05) greater and more prolonged adrenocortical stimulation than does IM administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Acute haemolysis associated with etomidate-propylene glycol infusion in dogs

Acute haemolysis occurred in medetomidine-atropine premedicated dogs (n=6) after infusion of etomidate in 35% propylene glycol (etomidate-PG). Free plasma haemoglobin concentration was 12.0 +3.5 μg/dl at baseline. After premedication (medetomidine 15 μg/kg, IM; atropine 0.044 mg/kg, IM) values were 14 ± 5.2 and 20 ± 4.8 mg/dl, at 5 and 10 minutes, respectively. Plasma haemoglobin values increased significantly (p±0.05; 121 +24.2 mg/dl) 5 minutes after etomidate-PG loading dose (0.5 mg/kg) and infusion (50μg/kg/min) and remained significantly elevated (127 ± 12.7 to 310.6 ± 69.3 mg/dl) throughout the 60-minute infusion period. Acute haemolysis was also observed in dogs (n=3) that received etomidate-PG infusion alone (2 mg/kg loading dose followed by 110 μg/ kg/ min constant infusion). In addition, fresh dog blood (n=3) was incubated alone or with either 0.9% saline or etomidate-PG in test tubes for 5 minutes and free plasma haemoglobin concentration measured. Free plasma haemoglobin concentrations were 18.3 ± 6.8, 11.7 +4.5 and 1712.0 ± 309.6 mg/dl for blood alone, saline-blood and etomidate-PG-blood, respectively. It was concluded that etomidate-PG caused acute haemolysis in dogs both in vivo and in vitro. The clinical significance of this amount of haemolysis is not clear at this time and thus, requires further study.     

A comparison between pre-operative carprofen and a long-acting sufentanil formulation for analgesia after ovariohysterectomy in dogs

OBJECTIVE: To assess the analgesic efficacy and adverse effects of a novel, long-acting sufentanil preparation in dogs undergoing ovariohysterectomy (OHE). STUDY DESIGN: Blinded, positively controlled, randomized field trial with four parallel treatment groups. ANIMALS: Eighty client owned dogs undergoing elective OHE randomly allocated into four treatment groups (each n = 20). MATERIALS AND METHODS: Three groups received intramuscular (IM) sufentanil (at 10, 15 and 25 microg kg(-1), respectively) and the control group received subcutaneous (SC) carprofen 4 mg kg(-1) SC plus acepromazine 0.05 mg kg(-1) IM as pre-anaesthetic medication. OHE was performed under thiopental/halothane anaesthesia. Visual Analogue Scale (VAS) scores for pain and sedation were awarded and mechanical nociceptive thresholds were measured at the wound and hock before surgery and up to 24 hours after tracheal extubation. Serum cortisol was measured before surgery, during surgery and up to 24 hours after tracheal extubation. Animals with inadequate post-operative analgesia were given rescue medication. RESULTS: In the carprofen group, VAS pain scores were significantly higher, wound tenderness was greater and requirement for rescue analgesia was more than in the sufentanil-treated groups. Sufentanil produced dose dependent analgesia and sedation. All treatment groups showed similar patterns of change for cortisol concentrations. Use of the sufentanil preparation was associated with a relatively high incidence of adverse events. CONCLUSIONS: The long-acting preparation of sufentanil provided excellent post-operative analgesia that was significantly better than that provided by carprofen. However, use of this formulation, in the anaesthetic technique used in the study, resulted in a relatively high incidence of adverse effects. CLINICAL RELEVANCE: Full mu (MOP) opioid agonists provide significantly better post-operative analgesia than nonsteroidal anti-inflammatory drugs after moderately painful surgery. However, the widely recognized adverse effects of opioids may preclude the use of these agents.     

Amikacin sulfate in mares: pharmacokinetics and body fluid and endometrial concentrations after repeated intramuscular administration

Six mares were given 5 IM injections (at 12-hour intervals between doses) of amikacin sulfate at a dosage of 7 mg/kg of body weight. Serum amikacin concentrations were measured serially throughout the study; synovial, peritoneal, endometrial, and urine concentrations were determined after the last injection. Amikacin concentrations of the CSF were measured serially in 3 of the 6 mares; 1 of the 3 mares had septic meningitis. Mean serum amikacin concentrations peaked at 1 to 2 hours after IM injection. The highest mean serum concentration was 19.2 micrograms/ml (1.5 hours after the 5th injection). The highest mean synovial concentration was 10.8 micrograms/ml at 2 hours after the 5th injection; the highest mean peritoneal concentration was 16.2 micrograms/ml at 3 hours after the 5th injection. The mean endometrial amikacin concentration was 2.5 micrograms/g (1.5 hours after the 5th injection). Amikacin reached a CSF concentration of 0.97 micrograms/ml in the mare with meningitis, but amikacin was not detected in CSF of healthy mares. Urine concentrations reached 1,458 micrograms/ml. Pharmacokinetic values were estimated after the 1st injection (elimination rate constant = 0.31/hour; half-life = 2.3 hours; apparent volume of distribution = 0.26 L/kg), and after the 5th injection (elimination rate constant = 0.28/hour; half-life = 2.6 hours; apparent volume of distribution = 0.30 L/kg); significant differences were not observed.     

Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations

The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single IV and IM doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml. The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After IV administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of greater than 10 micrograms/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t1/2 alpha, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t1/2 beta, harmonic mean = 3.14 hours). Mean +/- SD clearance after IV administration was 2.51 +/- 0.96 ml/kg/min. After IM administration, the harmonic mean for the elimination phase (t1/2 beta) was prolonged at 5.20 hours. Bioavailability after IM dosing gave a mean +/- SD (n = 5) of 76.0 +/- 28.0%. Adult, lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first IV, remainder IM) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 microgram/ml at 2 hours after each dosing and 0.5 micrograms/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrine responses of healthy parrots to ACTH and thyroid stimulating hormone

Effects of exogenous ACTH on plasma corticosterone and cortisol concentrations and the effects of thyroid stimulating hormone (TSH) on plasma triiodothyronine (T3) and thyroxine (T4) were determined in the following 3 species of parrots: red-lored Amazon (group 1), blue-fronted Amazon (group 2), and African gray (group 3). Each bird was given ACTH (0.125 mg/bird) IM, except for 3 to 4 birds in each group, which were given saline solution (controls). Blood samples were collected before and 90 minutes after ACTH stimulation. In group 1 (n = 12), mean plasma corticosterone concentrations increased significantly (P less than 0.001) from 1.06 microgram/dl (before ACTH) to 4.89 micrograms/dl (after ACTH); mean corticosterone concentrations increased in the control birds from 1.06 microgram/dl to 1.84 microgram/dl; and mean cortisol concentrations increased only slightly from 0.228 microgram/dl to 0.266 microgram/dl. In group 2 (n = 12), mean corticosterone concentrations increased significantly (P less than 0.001) from 2.09 micrograms/dl to 10.58 micrograms/dl; control mean corticosterone concentrations decreased slightly from 2.09 micrograms/dl to 1.77 microgram/dl; and mean cortisol concentrations increased from less than or equal to 0.16 microgram/dl to 0.266 microgram/dl. In group 3 (n = 12), mean plasma corticosterone concentrations increased significantly (P less than or equal to 0.001) from 2.33 micrograms/dl to 4.67 micrograms/dl; mean control plasma corticosterone concentrations decreased from 2.33 micrograms/dl to 1.68 microgram/dl; and plasma corticol concentrations were not detectable. Each bird was given TSH, IM (1 U/bird). Blood samples were collected before and 6 hours after TSH administration. Saline solution was not administered as controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of epidural and systemic tramadol for analgesia following ovariohysterectomy

The objective of the study was to compare epidural and systemic tramadol for postoperative analgesia in bitches undergoing ovariohysterectomy. Twenty animals, randomly divided into two groups, received either epidural (EPI) or intramuscular (IM) tramadol (2 mg/kg) 30 min before anesthetic induction. Analgesia, sedation, cardiorespiratory parameters, end-tidal isoflurane, blood catecholamines and cortisol, and arterial blood gases were measured at different time points up to 24 hr after agent administration. There were no differences between the two groups regarding cardiorespiratory parameters, end-tidal isoflurane, and pain scores. Two dogs in the IM and one in the EPI group required supplemental analgesia. Cortisol was increased (P<0.05) at 120 min (3.59 μg/dL and 3.27μg/dL in the IM and EPI groups, respectively) and 240 min (2.45 μg/dL and 2.54μg/dL in the IM and EPI groups, respectively) compared to baseline. Norepinephrine was also increased (P<0.05) at 120 min in both groups compared to baseline values. Epinephrine values were higher (P<0.05) in the IM group compared with the EPI group at 50 min, 120 min, and 1,440 min after tramadol administration. Epidural tramadol is a safe analgesic, but does not appear to have improved analgesic effects compared with IM administration.