A comparison of ketamine/xylazine and ketamine/xylazine/acepromazine anesthesia in the rabbit

Parenteral anesthetic combinations such as ketamine and xylazine have become the agents of choice for anesthesia in the rabbit, because they are effective, easily administered and inexpensive. A number of recent reports have recommended including acepromazine in this combination, but a critical evaluation of this combination in the rabbit has not been reported. Five adult New Zealand white rabbits were anesthetized intramuscularly with ketamine (35 mg/kg) and xylazine (5 mg/kg) with or without acepromazine (0.75 mg/kg). The study was conducted in a double blind fashion, where each rabbit was administered both combinations at a minimum of 7 day intervals. Physiologic parameters were evaluated including heart rate, respiratory rate, central arterial blood pressure, pedal, palpebral and postural reflex activity. The duration of general anesthesia, estimated by the time elapsed between the loss and return of the palpebral reflex, was greater (means = 99 +/- 20 minutes) when acepromazine was employed in the combination compared to (means = 77 +/- 5 minutes) when ketamine/xylazine were used alone. Mean central arterial blood pressure reached a lower level when acepromazine was utilized (means = 46 +/- 8 mm/Hg) than when it was not (means = 57 +/- 12 mm/Hg.). The addition of acepromazine in a ketamine/xylazine combination resulted in a 28% longer period of anesthesia, a 19% lower mean central arterial blood pressure and a 32% longer recovery of postural reflexes. The ketamine/xylazine/acepromazine combination is a useful regimen for normovolemic animals when anesthetic duration greater than that produced by ketamine/xylazine alone is required.     

Comparison of ketmine with the combination of ketamine and xylazine for effective anesthesia in the rhesus monkey (Macaca mulatta).

The addition of xylazine to ketamine hydrochloride was found to enhance analgesia, anesthesia, and muscle relaxation in rhesus monkeys. At 0.10 ml/kg body weight, this combination provided adequate anesthesia for such procedures as cisternal puncture, lumbar spinal puncture, insertion of urinary catheters, finger amputations, and tattooing. The combination of ketamine and xylazine did depress the heart rate, respiration rate, and body temperature more than the administration of ketamine alone. The period of anesthesia also was prolonged, but the monkeys regained consciousness more rapidly at the end of the anesthetic period.     

Physiologic and electrocardiographic responses of American river otters (Lutra canadensis) during chemical immobilization and inhalation anesthesia

Rectal temperatures and heart rates of American river otters (Lutra canadensis) decreased significantly (P less than 0.05) during chemical immobilization with i.m. ketamine hydrochloride in combination with xylazine hydrochloride and acepromazine and during inhalation anesthesia with isoflurane. Anesthetized otters showed a tendency for apnea during induction and while dorsally recumbent, which was reflected by a respiratory acidosis on arterial blood gases. Declines in rectal temperatures and heart rates were not found to be a function of dosage (mg/kg) of the ketamine combination used except for rectal temperatures of otters in relatively poor body condition (inanition). The electrocardiograms of isoflurane-anesthetized otters were similar to those recorded on immobilized otters with the exception of an r' deflection in the ventricular depolarization complex (RSr'). Electrocardiographic criteria were not found which predicted the degree of right ventricular or generalized cardiac enlargement seen radiographically.     

Anesthesia in the rabbit using a combination of ketamine and promazine

An anesthetic combination of ketamine and promazine (75mg/kg by ketamine content) was tested in 15 male and 15 female adult New Zealand white rabbits. The mean induction time was 9 minutes for both the male and female. Mean duration for anesthesia was 61 minutes for the male and 49 minutes for the female. The mean recovery time was 22 minutes for the male and 33 minutes for the female. The drug combination provided effective anesthesia for a period of 50--60 minutes after a single intramuscular injection.     

Effects of physical and chemical restraint on intravenous glucose tolerance test in crested black macaques (Macaca nigra)

The effects of physical and chemical restraint on glucose clearance and insulin secretion were evaluated during intravenous glucose tolerance testing in Macaca nigra. Conscious monkeys placed in plexiglas cylindrical restraining devices (CRD) appeared relaxed, but glucose clearance and insulin secretion were impaired. A combination of midazolam with ketamine, compared to ketamine alone, did not cause detectable changes in the intravenous glucose tolerance tests; midazolam also reduced adverse reactions to ketamine and extended the duration of anesthesia. The cylindrical restraining device can be convenient for examining monkeys, but it is limited by its adverse affects on metabolic and hormonal measurements in intravenous glucose-tolerance tests. Chemical restraint using ketamine with midazolam was more effective than ketamine alone.     

Electrocardiographic changes in rats undergoing thoracic surgery under combined parenteral anesthesia

To compare two protocols of combined parenteral general anesthesia, the authors analyzed electrocardiographic changes in anesthetized rats undergoing left pneumonectomy. One group of rats was anesthetized with a combination of medetomidine and ketamine (group 1, n = 10), and the other was injected with diazepam and ketamine (group 2, n = 10). Investigators obtained two electrocardiograms from each rat, one before surgery (5 min after anesthesia) and one after surgery (60 min after anesthesia). Anesthetic induction was quick for all rats, though four rats in group 2 died before surgery. Mean cardiac frequency and R-wave amplitude were significantly lower in rats in group 1 than in rats in group 2. Rats in group 1 received injections of atipamezole about 60 min after surgery, which reversed the effects of medetomidine; these rats regained voluntary respiratory movement more quickly than did rats in group 2. Two additional rats in group 2 died during postsurgical recovery. These results suggest that for thoracic surgery in rats, medetomidine-ketamine is an appropriate anesthetic combination, may be safer than diazepam-ketamine and yields a shorter recovery time.     

Hyperprolactinemia in monkeys: Induction by an estrogen-progesterone synergy

To evaluate the synergistic effect of estrogens and progesterone on prolactin secretion, rhesus and cynomolgus monkeys in the early follicular phase received estradiol benzoate (100 μg/kg/day, sc) alone for 14 days, then in combination with progesterone (subcutaneous silastic capsule) for an additional 14 days. Blood was drawn daily by femoral venipuncture under ketamine hydrochloride anesthesia (15mg/kg). Similarly, this protocol for exogenous steroid treatment was employed in a monkey having a chronically indwelling (femoral insertion into the vena cava) cannula maintained by a vest and mobile tether apparatus; however, no anesthesia was used to obtain serum specimens. In addition, this assembly was applied to six monkeys to determine the acute effects of ketamine hydrochloride on prolactin secretion. Concentrations of prolactin, estradiol-17β, and progesterone in serum were determined by conventional radioimmunoassays. Under estrogen therapy alone, mean circulating prolactin levels declined from ~15 to < 5 ng/ml; in contrast, the addition of progesterone caused an abrupt serum prolactin elevation, ~8–12 fold. This estradiol-progesterone course led to sustained hyperprolactinemia in the chronically catheterized Monkey, whereas ketamine administration raised serum prolactin only briefly, the elevation lasting less than three hours after injection. These findings establish that an estrogen-progesterone synergy, separate from the transient effects of ketamine, Induced hyperprolactinemia in cycling monkeys having prevailing levels of estrogen and progesterone near those characteristic of late gestation, when sustained prolactin elevations are observed normally.     

Ketamine/xylazine/butorphanol: a new anesthetic combination for rabbits.

Ketamine is often used in combination with tranquilizers to produce surgical anesthesia in rabbits. While generally effective, there is considerable variation in the depth and duration of anesthesia achieved with ketamine combinations. Butorphanol is a mixed agonist-antagonist opioid that is widely used in a variety of other species. In this study, the commonly used ketamine (35 mg/kg)/xylazine (5 mg/kg) combination is compared with ketamine (35 mg/kg)/xylazine (5 mg/kg)/butorphanol (0.1 mg/kg). Rabbits were anesthetized on consecutive weeks with one of the two regimens. Physiologic parameters including heart rate, respiratory rate, blood pressure and arterial blood gases (pH, PO2, PCO2) were measured throughout anesthesia. Loss of palpebral, pedal and righting reflexes were recorded and reflexes were subsequently evaluated. The addition of butorphanol prolonged reflex loss to 140% (X = 68 min +/- 20 SEM) of control for palpebral reflex; 506% (X = 52 min +/- 18 SEM) of control for pedal reflex; and 159% (X = 128 min +/- 21 SEM) of control for righting reflex. Addition of butorphanol to ketamine/xylazine resulted in mild alterations in the physiologic changes traditionally associated with this combination. Butorphanol can be safely added to the ketamine/xylazine combination in rabbits and results in moderate increases in the duration of reflex loss.     

Response of wild subantarctic fur seal (Arctocephalus tropicalis) females to ketamine and tiletamine-zolazepam anesthesia

This study is the first to compare the anesthetic effects of two cyclohexamines on free-ranging subantarctic fur seal (Arctocephalus tropicalis) females. From April to July 1999, 107 females were immobilized for tooth extraction and blood sampling, using either ketamine (Ketalar, n = 58) alone or tiletamine-zolazepam (Zoletil 100, n = 49) mixture. Animals were injected intramuscularly at mean doses of 2.1 mg/kg for ketamine and 1.1 mg/kg for tiletamine-zolazepam mixture. Individual response to both drugs was highly variable. The dosage required to achieve a satisfactory level of anesthesia was smaller for subantarctic fur seals than for most other species of seals and was less for animals in better body condition. Few side effects were observed during the trials, aside from mild tremors caused by ketamine, and respiratory depression or prolonged apnea caused by tiletamine-zolazepam. We recommend use of ketamine, especially by those with little experience in anesthesia of fur seals. However, precautionary measures should be taken, such as using low doses for animals in good body condition and being prepared for anesthetic emergencies to avoid any casualties.     

Azaperone and azaperone-ketamine as a neuroleptic sedative and anesthetic in rats and mice

Azaperone alone and combined with ketamine were evaluated as sedative and anesthetic agents in outbred rats and mice. Using azaperone alone the duration of immobility was 1.9 to 10.8 hours for mice and 0.9 to 2.4 hours for rats. The withdrawal reflex was not eliminated from mice receiving azaperone alone; however, the withdrawal reflex was eliminated from 0.9 to 2.4 hours in rats receiving azaperone. Azaperone produced a tachypnea in rats and male mice while a depressed respiratory rate was observed in female mice. Using azaperone combined with ketamine, the duration of immobilization was 1.1 to 8.8 hours for mice and 1.3 to 6.0 hours for rats. The duration loss of the withdrawal reflex, which was used as an indication of surgical anesthesia, was 0.9 to 1.8 hours for mice and 1.0 to 6.0 hours for rats. An increase in respiratory rate was observed in rats given the combination while mice given the combination showed transient tachypnea followed by bradypnea. Overall, azaperone alone was shown to provide sedation in mice as compared to a dose dependent anesthesia in rats. The azaperone-ketamine combination produced a surgical plane of anesthesia in both rats and mice. Azaperone and the azaperone-ketamine combination appear to be a suitable alternative to sedatives and anesthetics currently used in rats and mice.     

右美托咪定联合氯胺酮与咪达唑仑麻醉诱导用于困难气道插管中的价值分析

目的:探讨右美托咪定联合氯胺酮与咪达唑仑麻醉诱导在困难气道插管中的应用价值。方法:选取2016年1月至2018年10月我院收治的80例困难气道患者进行回顾性研究,根据插管顺序将受试者分为对照组和研究组两组,每组40例。对照组患者给予氯胺酮与咪达唑仑进行麻醉诱导,研究组患者在对照组的基础上联合右美托咪定进行麻醉诱导。比较两组麻醉前(T1)、纤支镜经过会厌时(T2)、声门时(T3)、插管即刻(T4)、插管后60 s(T5)、插管后180 s(T6)、插管后300 s(T7)时的平均动脉压(mean arterial pressure,MAP)、心率(Heart rate,HR)、血氧饱和度(Blood oxygen saturation,SpO_2)及Ramsay评分变化,并监测T1、T4及T6时间点去甲肾上腺素(Norepinephrine,NE)、肾上腺素(epinephrine,E)及皮质醇(Cortisol,Cor)水平及不良反应的发生情况。结果:两组不同时间点Sp O_2比较无统计学差异(P0.05),但研究组患者在T3-T7时间点的MAP、HR显著低于对照组,Ramsay评分显著高于对照组(P0.05)。两组患者T1时的NE、E及Cor水平比较无统计学差异(P0.05),但研究组T4及T6时NE、E及Cor水平均显著低于对照组(P0.05)。研究组患者呛咳、恶心、躁动及呼吸抑制的发生率均显著低于对照组(P0.05)。结论:与氯胺酮联合咪达唑仑相比,右美托咪定联合氯胺酮与咪达唑仑对心血管系统影响小,安全性更高,患者应激反应较低,在困难气道插管麻醉诱导中具有较高的应用价值。     

Comparison of psychic emergence reactions after (+/-)-ketamine and (+)-ketamine in mice

Ketamine is a racemic mixture containing equal parts of (+)-ketamine and (-)-ketamine. The ketamine enantiomorphs are different in anesthesia and psychic emergence reactions after anesthesia. Therefore, (+)-ketamine was compared with racemic ketamine in a number of randomized studies in volunteers and patients. However, their relations remain controversial. In the present studies, the psychic emergence reactions after injection of (+/-)-ketamine and (+)-ketamine were compared in mice. At equimolar doses, the (+)-isomers elicited episodes of hypnosis nearly 1.4-fold more potent than those of the racemic ketamine. After the administration of equihypnotic doses of (+)-ketamine and (+/-)-ketamine, the posthypnotic stimulation of locomotor activity, stereotype behavior and 5-HT-induced head-twitch response by the (+)-enantiomorph was significantly less intense than that of racemic ketamine. In receptor binding test, (+)-ketamine showed a higher affinity for NMDA receptor than that of (+/-)-ketamine, while (+)-ketamine and (+/-)-ketamine showed no affinity for dopamine D2 and serotonin 5-HT2 receptor. These results suggest that the (+)-ketamine has fewer posthypnotic side effects than (+/-)-ketamine when (+)-ketamine and (+/-)-ketamine were administered at equihypnotic dosages and that dopamine D2 and serotonin 5-HT2 receptor were not involved in the effects of (+)-ketamine and (+/-)-ketamine.     

Influence of restraint and ketamine anesthesia on adrenal steroids, progesterone, and gonadotropins in rhesus monkeys

Changes in gonadotropins, progesterone, cortisol, DHA, and DHAS were monitored in 10 female rhesus monkeys (Days 20-23 of the menstrual cycle) subjected to cage restraint with or without ketamine anesthesia for successive venipunctures. All animals were bled without sedation for 2 hr at 30-min intervals. Then 4 of the animals were anesthetized with ketamine-HCl and bleedings in all animals were continued for an additional 2.5 hr. FSH and progesterone were not appreciably affected by either restraint technique. LH declined steadily for the duration of the bleedings (P less than 0.05). Serum levels of cortisol and the adrenal androgens increased twofold (P less than 0.05). Anesthesia with ketamine had no effect on any of the six variables when compared with saline controls. Cortisol and dehydroepiandrosterone (DHA) levels tended to plateau (P less than 0.01) after 2 hr in both treated and control groups. In contrast, dehydroepiandrosterone sulfate (DHAS) levels increased continuously throughout the entire study period. These data indicate that ketamine anesthesia does not alter endocrine responses to venipuncture when administered following cage restraint of conscious animals. These findings further confirm the difficulties in obtaining estimates of basal levels of hormones which are responsive to stress and suggest that the first sample may provide the best estimate.     

Hemodynamic response to anesthesia in pregnant and nonpregnant ICR mice

Mean arterial blood pressure (BP) and heart rate (HR) during and after recovery from anesthesia in pregnant and nonpregnant ICR mice were evaluated. Mice were evaluated during mechanical ventilation, from 15 to 60 min after induction of anesthesia. The anesthetic protocols were pentobarbital (80 mg/kg, given intraperitoneally [i.p.]); two low doses of ketamine and xylazine (90 mg/kg, 7.5 mg/kg, respectively, i.p., with a second dose given 20 min after the initial dose); and a single high dose of ketamine and xylazine (150 mg/kg, 12.5 mg/kg, respectively, i.p.). The BP was measured in the right carotid artery, using a fluid-filled catheter connected to a chamber containing a solid-state pressure transducer. Mechanical ventilation was performed via tracheotomy, using a normalized minute ventilation of 3.5 ml*min-1*g-1 for nonpregnant mice and 3.0 ml*min-1*g-1 for pregnant mice. Mean BP was lower and HR was higher in pregnant than in nonpregnant mice for each anesthetic protocol. Pentobarbital induced significantly greater tachycardia and hypotension than did the other protocols. The average BP and HR were similar between two low doses and a single high dose of ketamine and xylazine. During spontaneous breathing from 30 to 180 min after recovery from anesthesia by use of a single low dose, ketamine and xylazine induced similar HR profiles, but mean BP in pregnant mice recovered earlier than did that in nonpregnant mice. These results suggest that ketamine and xylazine induced adequate anesthesia for superficial surgical procedures in pregnant and nonpregnant mice while inducing small changes in HR and BP, and pregnancy resulted in a different hemodynamic reaction in response to ketamine and xylazine. These data will be useful for the design and interpretation of physiologic protocols using pregnant and nonpregnant genetically targeted mice.     

Differential effects of chloral hydrate- and ketamine/xylazine-induced anesthesia by the s.c. route

The proper use of anesthetics in animal experimentation has been intensively studied. In this study we compared the use of chloral hydrate (500 mg kg(-1)) and ketamine (167 mg kg(-1)) combined with xylazine (33 mg kg(-1)) by the s.c. route in male Wistar rats. Chloral hydrate and ketamine/xylazine produced a depth of anesthesia and analgesia sufficient for surgical procedures. The decrease of systolic and diastolic blood pressure was of a higher magnitude in rats anesthetized with chloral hydrate than with ketamine/xylazine. The initial microvascular diameter and blood flow velocity did not differ between both agents. On the other hand, ketamine/xylazine reduced the heart rate more intensively than chloral hydrate. Both anesthetics promoted an increase in arterial pCO(2) and a decrease in pH levels compared to unanesthetized animals. The blood glucose levels were of a higher magnitude in rats after ketamine/xylazine anesthesia than after chloral hydrate. In mesenteric arterioles studied in vivo, ketamine/xylazine anesthesia reduced the constrictive effect of noradrenaline and the dilator effect of bradykinin. However, both anesthetics did not modify the vasodilator effect promoted by acetylcholine. Based on our data, we concluded that both anesthetics alter metabolic and hemodynamic parameters, however the use of chloral hydrate in studies of microvascular reactivity in vivo is more appropriate since ketamine/xylazine reduces the responses to vasoactive agents and increases blood glucose levels.     

Anesthesia for prairie dogs

The combination of 20 mg xylazine/kg of body weight and 100-150 mg ketamine/kg of body weight provided satisfactory levels of anesthesia in 63 prairie dogs, and the combination was tolerated well with a mortality rate of 3.2%.     

Reversal of ketamine/xylazine anesthesia in the rabbit with yohimbine

Ketamine and xylazine used in combination have been shown to be effective, easily administered, cost efficient agents for surgical anesthesia in the rabbit. The effect of xylazine on the central nervous system has been shown to be mediated through alpha-2 adrenergic receptors. Yohimbine, an alpha-2 adrenergic antagonist has been shown to reverse xylazine induced depression and partially antagonize ketamine in other species. We evaluated the antagonistic effect of yohimbine on ketamine/xylazine anesthesia in the rabbit. Six New Zealand White rabbits were anesthetized with intramuscular ketamine (50 mg/kg) and xylazine (10 mg/kg) to establish baseline parameters including respiratory rate, heart rate, and palpebral, pedal and postural reflex activity. Fourteen days later each rabbit was subjected to the same anesthetic regimen followed 30 minutes later by the intravenous administration of yohimbine (0.2 mg/kg). The duration of anesthesia estimated by the time elapsed between the loss and return of the palpebral reflex was reduced in the yohimbine treated trial (means = 29.7 +/- 1.9 minutes) compared to the control trial (means = 67.0 +/- 13.5 minutes). The palpebral reflex returned within 5 minutes following yohimbine treatment. Our results indicated that yohimbine is an effective antagonist of ketamine/xylazine anesthesia in the rabbit. Yohimbine decreases anesthetic duration after intravenous administration and also may aid in the control of undesirable anesthetic effects and overdosage.     

两种用于小型猪胰肾联合移植实验麻醉方法的比较

目的比较静脉复合吸入全麻和静脉全麻两种方法用于小型猪胰肾联合移植实验中的麻醉效果,探讨简单、安全、易行的麻醉方法。方法A、B两组健康贵州小香猪,每组6只,基础麻醉后气管插管,A组：持续吸入异氟醚维持麻醉,根据手术要求间断注入万可松和芬太尼;B组：持续注入氯胺酮,间断静脉注射万可松和芬太尼维持麻醉。观察麻醉持续时间,镇痛和肌松药量,术后拔管和完全清醒时间,监测麻醉过程中血压、心率、脉搏氧的变化。结果A组术中麻醉效果好,血压、心率和脉搏氧稳定,与B组有显著差异（P〈0.05）;B组麻醉效果较差,肌松用药量明显增多,术后完全清醒时间长于A组（P〈0.05）。结论气管插管后静吸复合的麻醉方法是用于贵州小型猪实验安全、合适的麻醉方法。     

Plasma-free amino acid concentrations during ketamine anesthesia in the rhesus monkey: a short methodological study

The effect of ketamine anesthesia on the pattern of free amino acids in plasma was investigated in four healthy non-pregnant rhesus monkeys. Blood samples were collected at intervals during a period of 150 min both with and without anesthesia. Repeated measures analysis of variance, with time and ketamine/control as trial factors, was used. In only four amino acids were any changes with time or with ketamine treatment observed, the rest remaining unchanged. Ketamine anesthesia seemed to reduce the concentrations of several amino acids, but the findings were not conclusive.     

丙泊酚与咪哒唑仑复合氯胺酮用于小儿心导管术麻醉效果研究

目的:探讨丙泊酚与咪哒唑仑复合氯胺酮用于小儿心导管术麻醉的优缺点与安全性。方法:将2008年7月~2012年7月入住我院的100例行心导管术的先心病患儿按照抽签法随机地均分为A、B组,A组采用6 mg/(kg·h)丙泊酚+3 mg/(kg·h)氯胺酮维持,B组采用0.15 mg/(kg·h)咪达唑仑+3 mg/(kg·h)氯胺酮维持,比较两组麻醉效果、HR、SPO2、MAP、体动次数、停药唤醒时间及不良反应发生率。结果:对照组麻醉优良率为80.00%,小于观察组(100.00%)(P0.05);两组术前MAP、HR差异无统计学意义(P0.05),但股动脉穿刺时二者差异具有统计学意义(P0.05),两组术中SPO2差异无统计学意义(P0.05),两组体动次数、停药唤醒时间相比,具有统计学差异(P0.05,P0.01);对照组不良反应发生率为24.00%,明显大于观察组(10.00%),两组相比,差异具有显著的统计学意义(P0.01)。结论:咪哒唑仑复合氯胺酮用于小儿心导管术麻醉效果显著,安全性高,值得在临床上加以推广并应用。