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21.

Objective

To characterise, as a clinical study, the pharmacokinetics and pharmacodynamics and describe the hypnotic effect of the neurosteroid alfaxalone (3α-hydroxy-5 α-pregnane-11, 20-dione) formulated with 2-hydroxypropyl-β-cyclodextrin in male and female rats.

Study design

Prospective, experimental laboratory study.

Animals

A total of 12 (six male and six female) adult, aged-matched Sprague Dawley rats.

Methods

Surgery and instrumentation was performed under isoflurane anaesthesia in an oxygen/nitrous oxide mixture (1:2) and local anaesthetic infiltration. All animals received a loading dose (1.67 mg kg?1 minute?1) for 2.5 minutes followed by a constant rate infusion (0.75 mg kg?1 minute?1) for 120 minutes of alfaxalone. Isoflurane and nitrous oxide was discontinued 2.5 minutes after the alfaxalone infusion started. Cardiorespiratory variables (heart rate, respiratory rate, arterial blood pressure and end tidal carbon dioxide tension) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Carotid artery blood samples were collected at strategic time points for blood gas analysis, haematology, biochemistry, and plasma concentrations of alfaxalone. Plasma samples were assayed using liquid chromatography-mass spectrometry.

Results

There were significant differences between the sexes for plasma clearance (p = 0.0008), half-life (p = 0.0268) and mean residence time (p = 0.027). Mean arterial blood pressure was significantly higher in the male rats (p = 0.0255).

Conclusions and clinical relevance

This study confirms that alfaxalone solubilised in 2-hydroxypropyl-β-cyclodextrin provides excellent total intravenous anaesthesia in rats. Sex-based differences in pharmacokinetics and pharmacodynamics were demonstrated and must be considered when designing biomedical research models using alfaxalone.  相似文献   
22.

Objective

To characterise the minimum dose of intramuscular alfaxalone required to facilitate intubation for mechanical ventilation, and to investigate the impact of cranial versus caudal injection on anaesthetic depth.

Study design

Randomised crossover study.

Animals

Six healthy juvenile ball pythons (Python regius).

Methods

Three dosages (10, 20 and 30 mg kg–1) of alfaxalone were administered to each python in a caudal location with a minimum 2 weeks washout. Induction and recovery were monitored by assessing muscle tone, righting reflex, response to a noxious stimulus and the ability to intubate. A subsequent experiment assessed the influence of injection site by comparing administration of 20 mg kg–1 alfaxalone in a cranial location (1 cm cranial to the heart) with the caudal site. Respiration rate was monitored throughout, and when intubation was possible, snakes were mechanically ventilated.

Results

Regardless of dose and injection site, maximum effect was reached within 10.0 ± 2.7 minutes. When administered at the caudal injection site, intubation was only successful after a dosage of 30 mg kg-1, which is higher than in previous reports for other reptiles. However, intubation was possible in all cases after 7.2 ± 1.6 minutes upon cranial administration of 20 mg kg–1, and anaesthetic duration was significantly lengthened (p < 0.001). Both 30 mg kg–1 at the caudal site and 20 mg kg–1 at the cranial site led to apnoea approximately 10 minutes post-injection, at which time the snakes were intubated and mechanically ventilated.

Conclusions and clinical relevance

Alfaxalone provided rapid, smooth induction when administered intramuscularly to pythons, and may serve as a useful induction agent prior to provision of volatile anaesthetics. The same dosage injected in the cranial site led to deeper anaesthesia than when injected caudally, suggesting that shunting to the liver and first-pass metabolism of alfaxalone occur when injected caudally, via the renal portal system.  相似文献   
23.
24.
ObjectiveTo compare the propofol infusion rate and cardiopulmonary effects during total intravenous anesthesia with propofol alone and propofol combined with methadone, fentanyl or nalbuphine in domestic chickens undergoing ulna osteotomy.Study designProspective, randomized, experiment trial.AnimalsA total of 59 healthy Hissex Brown chickens weighing 1.5 ± 0.2 kg.MethodsAnesthesia was induced with propofol (9 mg kg–1) administered intravenously (IV) and maintained with propofol (1.2 mg kg–1 minute–1) for 30 minutes. Birds were intubated and supplemented with 100% oxygen through a nonrebreathing circuit under spontaneous ventilation. Thereafter, each animal was randomly assigned to one of four groups: group P, no treatment; group PM, methadone (6 mg kg–1) intramuscularly (IM); group PN, nalbuphine IM (12.5 mg kg–1); and group PF, fentanyl IV (30 μg kg–1 loading dose, 30 μg kg–1 hour–1 constant rate infusion). During the osteotomy surgery, the propofol infusion rate was adjusted to avoid movement of birds and provide adequate anesthesia. Pulse rate, invasive blood pressure, respiratory frequency, end-tidal carbon dioxide partial pressure (Pe′CO2) and hemoglobin oxygen saturation (SpO2) were recorded.ResultsData were available from 58 chickens. The mean ± standard deviation propofol infusion rate (mg kg–1 minute–1) for the duration of anesthesia was: group P, 0.81 ± 0.15; group PM, 0.66 ± 0.11; group PN, 0.60 ± 0.14; and group PF, 0.80 ± 0.07. Significant differences were P versus PM (p = 0.042), P versus PN (p = 0.002) and PF versus PN (p = 0.004). Pulse rate, blood pressure and SpO2 remained acceptable for anesthetized birds with minor differences among groups. Values of Pe′CO2 >60 mmHg (8 kPa) were observed in all groups.Conclusions and clinical relevanceMethadone and nalbuphine, but not fentanyl, decreased the propofol infusion rate required for anesthesia maintenance, but resulted in no obvious benefit in physiological variables.  相似文献   
25.
采用醋酸纤维薄膜电泳法和氚—胸腺嘧啶核苷掺入法(~3H—Thymidine,~3H—TdR)分别检测了铁剂对仔猪体液免疫和细胞免疫的效应.结果显示,注射过安泰促长素(Antai GrowthPromotor,AGP)的32日龄仔猪,其平均血清丙种免疫球蛋白(r-Immunoglobulin,r-Ig)和淋巴细胞转化能力均明显高于对照组仔猪(P<0.01).另一种国产铁剂牲血素(shengxiesu)也显示有同样的作用.这提示注铁后,随着仔猪血红蛋白的提高,其免疫功能亦获得提高.注铁后22日龄与32日龄仔猪的血清r-Ig水平差异不显著(P>0.05),但32日龄时的淋巴细胞转化能力明显地高于22日龄的(P<0.05).本试验在国内首次应用~3H-TdR掺入法进行仔猪贫血的研究,并提供了一些资料.  相似文献   
26.
ObjectiveTo assess agreement between infrared (IR) analysers and a refractometer for measurements of isoflurane, sevoflurane and desflurane concentrations and to demonstrate the effect of customized calibration of IR analysers.Study designIn vitro experiment.SubjectsSix IR anaesthetic monitors (Datex-Ohmeda) and a single portable refractometer (Riken).MethodsBoth devices were calibrated following the manufacturer’s recommendations. Gas samples were collected at common gas outlets of anaesthesia machines. A range of agent concentrations was produced by stepwise changes in dial settings: isoflurane (0–5% in 0.5% increments), sevoflurane (0–8% in 1% increments), or desflurane (0–18% in 2% increments). Oxygen flow was 2 L minute?1. The orders of testing IR analysers, agents and dial settings were randomized. Duplicate measurements were performed at each setting. The entire procedure was repeated 24 hours later. Bland–Altman analysis was performed. Measurements on day-1 were used to yield calibration equations (IR measurements as dependent and refractometry measurements as independent variables), which were used to modify the IR measurements on day-2.ResultsBias ± limits of agreement for isoflurane, sevoflurane and desflurane were 0.2 ± 0.3, 0.1 ± 0.4 and 0.7 ± 0.9 volume%, respectively. There were significant linear relationships between differences and means for all agents. The IR analysers became less accurate at higher gas concentrations. After customized calibration, the bias became almost zero and the limits of agreement became narrower.Conclusions and clinical relevanceIf similar IR analysers are used in research studies, they need to be calibrated against a reference method using the agent in question at multiple calibration points overlapping the range of interest.  相似文献   
27.
ObjectiveTo investigate an infusion of propofol for anesthesia in comparison to tiletamine-zolazepam anesthesia, evaluating physiological variables and recovery in squirrel monkeys.Study designProspective non-blinded randomized study.AnimalsEight healthy squirrel monkeys (Saimiri sciureus), aged 3 years and weighing 0.340–0.695 kg.MethodsPremedication was intramuscular midazolam (0.5 mg) and meperidine (4 mg). Anesthesia was induced with intravenous (IV) propofol (4 mg kg?1 minute?1) and maintained with propofol starting at 0.4 mg kg?1 minute?1 (PRO, n = 4) or IV tiletamine-zolazepam (5 mg kg?1) and maintained with supplementary doses of TZ (TZ, n = 4). Cardiopulmonary variables were measured continuously. Arterial blood gases and lactate concentration were measured at the end of anesthesia. Quality and times of recovery were determined. Repeatedly measured data for significant differences were tested between groups with t-test and within groups by anova.ResultsMedian time for induction of anesthesia in PRO was 180 seconds. Mean maintenance infusion rate of propofol was 0.43 ± 0.05 mg kg?1 minute?1, varying during the 1 hour period. One monkey died after administration of TZ; others required 1, 4, or 8 supplemental doses. Cardiopulmonary variables were similar between groups, but hypotension was recorded. Recovery times to ventral recumbency in PRO (32 ± 17 minutes) and TZ (84 ± 11 minutes) and normal ambulation in PRO (58 ± 22 minutes) and TZ (358 ± 109minutes) were significantly different (p < 0.05). Recovery quality was superior in PRO, with less ataxia and fewer unsuccessful attempts to stand. Lactate concentration was not different between treatments.Conclusions and clinical relevanceCardiopulmonary variables were similar between protocols, aside from the higher incidence of hypotension in PRO, indicating that further studies with a larger number of animals are required. Compared to tiletamine-zolazepam, propofol anesthesia provided faster and superior anesthetic recovery in these animals.  相似文献   
28.
Objective To compare hemodynamic variables during, and recovery quality following, anesthesia for feline blood donation using intramuscular ketamine–midazolam–butorphanol (KMB) versus inhaled sevoflurane in oxygen (SEV). Study design Prospective blinded, randomized, crossover study. Animals Twenty healthy, client‐owned, mixed breed cats, aged 4–8 years, weighing 5.2–6.4 kg. Methods Cats were anesthetized with KMB for one donation and SEV for another. Heart rate (HR), respiratory rate (fR), pulse quality, mucous membrane color, capillary refill time, arterial hemoglobin saturation with oxygen (SpO2), and noninvasive arterial blood pressure (Doppler) were assessed by a blinded observer every 1 minute during collection. A nonblinded anesthesiologist delivered drugs and responded to hemodynamic changes. Each donation consisted of 55 mL of whole blood drawn via jugular puncture over 5–22 minutes. Donors received 60 mL subcutaneous lactated Ringer’s solution before recovery. Donors were monitored for a minimum of 4 hours post‐donation, before returning home. Owners, unaware of anesthetic protocol, completed a questionnaire regarding their cat’s behavior during the 24 hours following donation. Results Both protocols provided adequate restraint but were complicated by significant hypotension, requiring intervention in 16 (84%) SEV cats, and eight (42%) KMB cats. KMB cats experienced post‐procedure hyperthermia, with body temperatures >103.5°F. All animals responded to symptomatic therapy within 2 hours. Owners noted a significantly faster return to normal behavior at home following SEV. Conclusion All cats experienced hypotension, with many animals requiring intervention. There was no significant difference between protocols in incidence and severity of hypotension. The primary post‐procedure complication was hyperthermia with KMB. Clinical relevance As a result of the potential for hypotension during blood donation, intravenous (IV) access and blood pressure monitoring are recommended for all anesthetized donor cats, regardless of the anesthetic protocol. Post‐procedure hyperthermia is a risk with KMB, so temperature monitoring is recommended. Return to normal behavior is faster with SEV.  相似文献   
29.
复方蒲公英注射液的研制   总被引:2,自引:0,他引:2  
以蒲公英、金银花、黄芩、连翘、丹参5味药为基础,研制开发了复方蒲公英注射液,并对其质量、安全性和疗效进行了研究。对注射液的质量控制及稳定性的研究表明注射液符合各项要求,并且颜色、澄明度和pH值对光、热稳定。注射液的安全性研究表明该制剂安全、有效、刺激性小,在经口毒性试验中,小鼠无一死亡,腹腔注射的LD50为51.20mL/kg,95%可信限为44.19~59.24mL/kg。在复方蒲公英注射液的药效学试验中,表明本注射液有良好的抗炎作用,在药敏试验中,本注射液对金黄色葡萄球菌有一定的抑制作用,最小抑菌浓度为1/40,对于奶牛临床型乳房炎有较好的疗效(治愈率为48.39%,有效率为77%);而对于奶牛的隐性乳房炎则有良好的治疗和预防效果,对照组在第8天检测时,自我痊愈率为12.5%,新感染率为16.7%,复方蒲公英注射液组治愈率为70.96%,新感染率为0。  相似文献   
30.
概述了用亲水性或疏水性缓释材料制备的溶液型长效注射剂、用氢化蓖麻油或乙基纤维素等疏水性缓释材料制备的类似于胶体状态的长效注射剂和长效混悬注射剂等几种含阿维菌素类药物(AVMs)的长效注射剂.其中长效混悬注射剂包括AVMs以微粒状态或以载药微粒状态悬浮于制剂中的水悬或油悬注射剂;侧重概述了用AVMs/明胶微球制备的一种具有脉冲式释药的长效注射剂和用AVMs/氢化蓖麻油固体分散体制备的长效注射剂.同时对制剂的组成特点、缓释原理和缓释效果都作了综述和分析.  相似文献   
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