A multisite case report on the clinical use of sevoflurane in dogs.

The purpose of this report was to evaluate the clinical safety and efficacy of sevoflurane as an inhalant anesthetic in dogs. Subjective and objective data from 196 clinical cases utilizing sevoflurane as the maintenance anesthetic was collected at three sites. After preanesthetic evaluation, the attending anesthesiologist assigned the dogs to one of the following six anesthetic protocols: protocol 1, oxymorphone premedication and thiopental induction; protocol 2, oxymorphone/acetylpromazine premedication and thiopental induction; protocol 3, xylazine/butorphanol premedication and thiopental induction; protocol 4, opioid premedication and propofol induction; protocol 5, optional premedication and mask induction with sevoflurane in oxygen; and protocol 6, optional premedication and optional induction. The average quality of induction, maintenance, and recovery was good to excellent in all protocols. The three most common side effects during maintenance and recovery were hypotension, tachypnea, and apnea. Sevoflurane produces anesthesia in dogs comparable to the other inhalation anesthetics currently used (i.e., halothane and isoflurane) for diagnostic or therapeutic procedures.

Recovery from sevoflurane anesthesia: a comparison to isoflurane and propofol anesthesia.

BACKGROUND: Sevoflurane has a lower blood:gas partition coefficient than isoflurane, which may cause a more rapid recovery from anesthesia; it also might cause faster emergence times than for propofol-based anesthesia. We evaluated a database that included recovery endpoints from controlled, randomized, prospective studies sponsored by Abbott Laboratories that compared sevoflurane to isoflurane or propofol when extubation was planned immediately after completion of elective surgery in adult patients. METHODS: Sevoflurane was compared to isoflurane in eight studies (N=2,008) and to propofol in three studies (N=436). Analysis of variance was applied using least squares method mean values to calculate the pooled mean difference in recovery endpoints between primary anesthetics. The effects of patient age and case duration also were determined. RESULTS: Sevoflurane resulted in statistically significant shorter times to emergence (-3.3 min), response to command (-3.1 min), orientation (-4.0 min) and first analgesic (-8.9 min) but not time to eligibility for discharge (-1.7 min) compared to isoflurane (mean difference). Times to recovery endpoints increased with increasing case duration with isoflurane but not with sevoflurane (patients receiving isoflurane took 4-5 min more to emerge and respond to commands and 8.6 min more to achieve orientation during cases longer than 3 hr in duration than those receiving sevoflurane). Patients older than 65 yr had longer times to orientation, but within any age group, orientation was always faster after sevoflurane. There were no differences in recovery times between sevoflurane and propofol. CONCLUSIONS: Recovery from sevoflurane was 3-4 min faster than with isoflurane in all age groups, and the difference was magnified in longer-duration surgical cases (> 3 hr).

Recovery from sevoflurane anesthesia in horses: comparison to isoflurane and effect of postmedication with xylazine.

OBJECTIVE: To compare recovery from sevoflurane or isoflurane anesthesia in horses. STUDY DESIGN: Prospective, randomized cross-over design. ANIMALS: Nine Arabian horses (3 mares, 3 geldings, and 3 stallions) weighing 318 to 409 kg, 4 to 20 years old. METHODS: Horses were anesthetized on three occasions with xylazine (1.1 mg/kg), Diazepam (0.03 mg/kg intravenously [i.v.]), and ketamine (2.2 mg/kg i.v.). After intubation, they were maintained with isoflurane or sevoflurane for 90 minutes. On a third occasion, horses were maintained with sevoflurane and given xylazine (0.1 mg/kg i.v.) when the vaporizer was turned off. Horses were not assisted in recovery and all recoveries were videotaped. Time to extubation, first movement, sternal, and standing were recorded as was the number of attempts required to stand. Recoveries were scored on a 1 to 6 scoring system (1 = best, 6 = worst) by the investigators, and by three evaluators who were blinded to the treatments the horses received. These blinded evaluators assessed the degree of ataxia present at 10 minutes after each horse stood, and recorded the time at which they judged the horse to be ready to leave the recovery stall. RESULTS: Mean times (+/- SD) to extubation, first movement, sternal, and standing were 4.1 (1.7), 6.7 (1.9), 12.6 (4.6), and 17.4 (7.2) minutes with isoflurane; 3.4 (0.8), 6.6 (3.1), 10.3 (3.1), and 13.9 (3.0) minutes with sevoflurane; and 4.0 (1.2), 9.1 (3.3), 13.8 (6.5), and 18.0 (7.1) with sevoflurane followed by xylazine. Horses required a mean number of 4 (2.3), 2 (0.9), and 2 ( 1.6) attempts to stand with isoflurane, sevoflurane, and sevoflurane followed by xylazine respectively. The mean recovery score (SD) for isoflurane was 2.9 (1.2) from investigators and 2.4 (1.1) from blinded evaluators. For sevoflurane, the mean recovery score was 1.7 (0.9) from investigators and 1.9 (1.1) from evaluators, whereas the recoveries from sevoflurane with xylazine treatment were scored as 1.7 (1.2) from investigators and 1.7 (1.0) from blinded evaluators. CONCLUSIONS: Recoveries appeared to vary widely from horse to horse, but were significantly shorter with sevoflurane than isoflurane, although sevoflurane followed by xylazine was no different from isoflurane. Under the conditions of the study, recoveries from sevoflurane and sevoflurane followed by xylazine were of better quality than those from isoflurane. CLINICAL RELEVANCE: Sevoflurane anesthesia in horses may contribute to a shorter, safer recovery from anesthesia.

Single- and multiple-dose pharmacokinetics of clarithromycin, a new macrolide antimicrobial.

The pharmacokinetics of clarithromycin and its active 14(R)-hydroxy metabolite were evaluated after single and multiple oral doses of 250 and 500 mg of clarithromycin. Multiple-dose regimens used 12-hour dosing intervals for 7 doses. Plasma and urine concentrations were measured using high-performance liquid chromatography. Appearance of clarithromycin and its metabolite in plasma were rapid, as reflected by mean times to maximum plasma concentration ranging from 1.8 to 2.6 and 1.8 to 2.9 hours, respectively. The rises in clarithromycin peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) were disproportionate to increase in dose, suggesting nonlinearity in parent compound pharmacokinetics. Clarithromycin terminal disposition half-life (t1/2) also exhibited dose dependency, ranging from harmonic means of 2.7 to 4.8 hours. In contrast, based on Cmax AUC, and predicted/observed accumulation ratios, nonlinearity in metabolite pharmacokinetics was not observed. Plasma accumulation of metabolite occurred to a much lesser degree than that of the parent compound despite a substantially longer t1/2 for the metabolite (metabolite accumulation ratios based on AUC dose 7/AUC dose 1:250-mg regimen = 1.03 +/- 0.33, 500-mg regimen = 0.81 +/- 0.29, parent accumulation ratios: 250-mg regimen = 1.64 +/- 0.47, 500-mg regimen = 1.65 +/- 0.69). This would suggest that formation of this metabolite is capacity-limited and that this may in part account for the nonlinearity observed in clarithromycin pharmacokinetics. Urinary excretion constituted a relatively important route of elimination of clarithromycin, with renal clearance accounting for 17 to 31% of apparent total body clearance.

The relationship between buspirone bioavailability and dose in healthy subjects.

Dose dependency of the pharmacokinetics of buspirone, a new anxiolytic agent, was tested in 24 healthy volunteers. Each subject received 10, 20, and 40 mg doses according to a randomized, three-way crossover design with a 7-day interval between treatments. Buspirone AUC values at 10, 20, and 40 mg doses were in the ratio of 1:1.7:3.5 while Cmax values had a ratio of 1:1.9:3.7. The dose normalized (10 mg basis) AUC and Cmax values, Tmax values, and half-lives were not significantly different (p greater than 0.05) among the doses. Buspirone half-life did not change as a function of dose (mg kg-1). It was concluded that buspirone exhibits linear pharmacokinetics following doses in the therapeutic range.

Comparative bioavailability of trazodone formulations using stable isotope methodology.

The bioavailability of trazodone, a new antidepressant, from 50 mg dividose (A) or film-sealed (B) tablets relative to an oral solution was determined in six healthy male subjects using 50 mg of D4-trazodone as a stable isotope labelled standard. Concentrations of trazodone and D4-trazodone were measured by GCMS. The pharmacokinetics of trazodone and D4-trazodone were identical indicating no isotope effect. For formulation A, B and solution, the relative (trazodone/D4-trazodone) Cmax values were 0.84 +/- 0.09, 0.90 +/- 0.05 and 1.05 +/- 0.04. The relative bioequivalence of the dosage formed with a power of 85% (power by conventional ANOVA was 54%). Among subjects % relative standard deviations (RSD) for the D4-trazodone AUC values, a measure of intra-subject variability, were 6 to 38% while the % RSDs by period, a measure of inter-subject variability, were 26 to 55%.

Alterations of plasma high-density lipoprotein cholesterol levels associated with consumption of selected medications. The Lipid Research Clinics Program Prevalence Study.

From the 10 North American study populations of the Lipid Research Clinics Program, mean levels of plasma high-density (HDL) cholesterol were contrasted between users of eight categories of prescribed medications and a control group of nonusers of those categories matched for age, sex, study population and ponderosity. Women taking propranolol had a mean HDL cholesterol level 12 mg/dl lower than nonusers (p < 0.05). Men taking phenytoin had a mean HDL cholesterol level more than 18 mg/dl higher than nonusers (p < 0.05). Men taking benzodiazepine derivatives had a mean HDL cholesterol level 3.3 mg/dl lower than nonusers (p < 0.05). No significant differences were found between users and nonusers of thiazide diuretics, chlorthalidone, barbiturates, sympathomimetics or antihistamines.

Altered plasma lipid and lipoprotein levels associated with oral contraceptive and oestrogen use. Report from the Medications Working Group of the Lipid Research Clinics Program.

In a study of women attending ten North American Lipid Research Clinics plasma total cholesterol, triglyceride, low density (L.D.L.), very low density (V.L.D.L.), and high density (H.D.L.) lipoprotein levels in those taking oral contraceptives (O.C.) and in those taking oestrogens for menopausal symptoms were compared with those in women not taking gonadal hormones, after adjustment for age, educational attainment, and body-mass index, O.C. and oestrogen users were leaner than non-users. Compared with controls, O.C. users showed increased cholesterol, triglyceride, and L.D.L.-cholesterol and V.L.D.L.-cholesterol levels, but H.D.L.-cholesterol levels were similar. Cholesterol, triglyceride, and H.D.L.-cholesterol and V.L.D.L.-cholesterol levels were positively associated with the quantity of the oestrogen component of the O.C. preparations. Compared with non-users, menopausal oestrogen users had slightly lower cholesterol and triglyceride levels, significant decreases in L.D.L.-cholesterol and V.L.D.L.-cholesterol, and a significant increase in H.D.L.-cholesterol.