Antagonism of xylazine and ketamine anesthesia by 4-aminopyridine and yohimbine in geldings

Thirty-six fasted, mixed horse breed geldings (6 groups of 6 animals each) were anesthetized with xylazine and ketamine, and when maximally sedated, were given 1 of the following antagonists: saline solution, 4-aminopyridine (4-AP), small-dose yohimbine, large-dose yohimbine, 4-AP plus low-dose yohimbine, or 4-AP plus high-dose yohimbine. Measured data included mean standing time (MST), heart rate, respiratory rate, rectal temperature, and mean total recovery time ( MTRT ). Emergence phenomena were also observed and recorded as smooth, fairly smooth, fairly rough, or rough. Groups given 4-AP alone, small-dose yohimbine alone, or large-dose yohimbine alone produced a significant (P less than 0.05) decrease in MST (9.9 +/- 1.6 minutes, 11.3 +/- 1.7 minutes, and 10.6 +/- 2.3 minutes, respectively) compared with that in the saline control group (24.3 +/- 9.2 minutes). The MTRT were not significantly (P greater than 0.05) different (47.2 +/- 10 minutes, 90.4 +/- 15.1 minutes, and 83.2 +/- 23 minutes, respectively) from control values (66.2 +/- 13.4 minutes). When the antagonists were combined, 4-AP plus small-dose yohimbine and 4-AP plus large-dose yohimbine produced significant (P less than 0.05) decreases (10.3 +/- 2 minutes and 8.3 +/- 2.6 minutes, respectively) in MST compared with that of saline controls. The MTRT was significantly longer in the combined antagonist group (4-AP + small-dose yohimbine--131.8 +/- 28.9 minutes; 4-AP + large-dose yohimbine--131.3 +/- 19.4 minutes) compared with that of control or any antagonist alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Xylazine-pentobarbital anesthesia in dogs and its antagonism by yohimbine

Once a week for 4 weeks, 5 dogs were given IM injections of xylazine (2.2 mg/kg of body weight) followed in 10 minutes by IV injections of pentobarbital (14 mg/kg). The resultant duration of anesthesia, absence of pedal reflex, and time from return of consciousness to ambulation were consistent from week to week. The mean times were 137.3, 111.8, and 56.9 minutes, respectively. A second experiment using 5 other dogs was performed to evaluate the antagonistic effect of yohimbine on the anesthesia induced by the xylazine-pentobarbital combination. When yohimbine (0.1 mg/kg, IV) was administered 10, 60, and 120 minutes after the xylazine-pentobarbital injection (given as in the 1st experiment), it abolished or markedly reduced the duration of anesthesia, absence of pedal reflex, and the time from return of consciousness to ambulation. After being given yohimbine, the dogs had a smooth recovery without postanesthetic excitement. In experiment 3, IM xylazine injections caused bradycardia without changing mean arterial blood pressure. Subsequent IV pentobarbital administration abolished xylazine-induced bradycardia for approximately 20 minutes and decreased arterial blood pressure slightly and gradually. Respiration was markedly depressed for the first 20 minutes of xylazine-pentobarbital anesthesia and gradually decreased during the rest of the 50-minute monitoring period. Yohimbine injection at postpentobarbital dosing minute 50 reversed the resumed xylazine-induced bradycardia and relieved other signs of respiratory depression associated with xylazine-pentobarbital anesthesia. The xylazine-pentobarbital combination was safe and effective for inducing and maintaining up to 2 hours of anesthesia in dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Xylazine-ketamine-induced anesthesia in rats and its antagonism by yohimbine

A combination of xylazine and ketamine was used to anesthetize 60 male rats, and then yohimbine was given to evaluate its reversing effect on xylazine-ketamine-induced anesthesia. In experiment A, xylazine (21 mg/kg of body weight) and ketamine (45 mg/kg) were admixed and administered IM to 12 Sprague-Dawley rats. Anesthesia lasted approximately 70 minutes. The xylazine-ketamine combination also induced polyuria, bradycardia, and bradypnea. When yohimbine (2.1 mg/kg) was given intraperitoneally 20 minutes after the xylazine-ketamine injection, the rats regained consciousness and righting reflexes within approximately 10 minutes. Yohimbine also reversed the bradycardia and bradypnea and appeared to reduce the polyuria induced by the xylazine-ketamine combination. In experiment B, xylazine (15.4 mg/kg) and ketamine (33 mg/kg) were admixed and given IM to 48 Holtzman rats. The combination induced surgical anesthesia for at least 30 minutes, during which a surgical procedure involving grafting a section of the sciatic nerve into the hypothalamus was performed. In rats in which yohimbine (1 mg/kg) was given intraperitoneally 45 to 60 minutes after xylazine-ketamine administration (before natural recovery from the anesthesia), the righting reflex was apparent in less than 10 minutes.     

Yohimbine/flumazenil antagonism of hemodynamic alterations induced by a combination of midazolam, xylazine, and butorphanol in dogs.

Reversal of hemodynamic alterations induced by midazolam maleate (1.0 mg/kg of body weight), xylazine hydrochloride (0.44 mg/kg), and butorphanol tartrate (0.1 mg/kg) with yohimbine (0.1 mg/kg) and flumazenil (0.25 mg/kg) was evaluated in 5 dogs. The dogs were anesthetized with isoflurane for instrumentation. With return to consciousness, baseline values were recorded, and the midazolam/xylazine/butorphanol mixture with glycopyrrolate was administered IV. Hemodynamic data were recorded for 60 minutes, and then a reversal mixture of yohimbine and flumazenil was administered IV. All variables were measured 1 minute from beginning of the reversal injection. Mean arterial pressure, pulmonary arterial pressure, systemic vascular resistance, and right ventricular stroke work index increased significantly (P < 0.05) above baseline at 60 minutes. Cardiac index and central venous pressure significantly decreased below baseline at 60 minutes. After reversal, mean arterial pressure and central venous pressure significantly decreased from baseline, whereas cardiac index, pulmonary arterial pressure, and right ventricular stroke work index increased significantly above baseline. Heart rate, cardiac index, and right ventricular stroke work index increased significantly above the 60-minute value after reversal. Mean arterial pressure and systemic vascular resistance decreased significantly (P < 0.05) below the 60-minute value after reversal. The hemodynamic alterations accompanying midazolam/xylazine/butorphanol sedation-anesthesia may be rapidly reversed with a combination of yohimbine and flumazenil.     

Continuous intravenous anesthesia in dogs using a combination of xylazine, ketamine and guaifenesin]

The tested anaesthesia through a permanent infusion of a xylazine, ketamine and guaifenezine (XKG) mixture was used in ten experimental dogs without clinical signs of a disease and in fifty two patients during different surgical interventions. After joint i.m. atropine (0.05 mg/kg) and xylazine (2 mg/kg) premedication, anaesthesia in dogs was induced by an i.v. administration of 1% ketamine at a dose of 2 mg/kg, and the XKG was infused instantly after the previous treatment. The mixture contained 2.0 ml of 5% ketamine and 1.25 ml of 2% xylazine added to 100 ml of 5% guaifenezine. The infusion was applied at a rate of 3.3 ml/kg for the first five minutes and then it was maintained at constant values of 2.2 ml/kg during the whole surgical intervention (Tab. I). The induction and course of anaesthesia, and waking up and recovery from anaesthesia were evaluated in all dogs, and the trias values were also followed. These additional parameters were followed in the test group: breathing volumes, ECG values and acid-base balance parameters were determined from the collected blood samples. The observation of measurable parameters (Figs. 1 to 5) and ECG analysis did not demonstrate any large departures from the starting values, and the changes in the acid-base balance (Tab. II) suggest the partly compensated respiratory acidosis. On the basis of our results, we can recommend this tested method for general anaesthesia particularly of dogs of larger breeds and for longer-lasting operations. This method is suitable to be used first of all in the veterinary establishments where inhalation anaesthesia is not practicable.     

The reversal of xylazine/ketamine immobilisation of fallow deer with yohimbine

Fallow deer were immobilised using a combination of xylazine and ketamine. Adult males (n = 10) and adult females (n = 10) received 4 mg/kg of each drug intramuscularly. Juveniles (n = 11) received 2 mg/kg of each drug, intravenously. Times to recumbency were as follows: adult males 4.9 +/- 2.9 min, adult females 4.1 +/- 1.9 min, juveniles 2.3 +/- 1.1 min. After 30 min each deer received 0.2 mg/kg of yohimbine, or an equal volume of sterile diluent intravenously. Yohimbine substantially reduced the recovery times of treated deer. Adults males were releasable 7.2 +/- 4.3 min after yohimbine administration, whereas control males were not releasable until 165 +/- 18 min. Treated adult females were releasable after 6.6 +/- 4.3 min, while control females were not releasable until 84 +/- 29 min. Juveniles were releasable 2.1 +/- 0.8 min after administration of yohimbine but control juveniles were not releasable until 62 +/- 16 min. Xylazine/ketamine administration produced statistically significant changes in packed cell volume, total plasma protein, albumin, sodium, glucose, creatine phosphokinase and inorganic phosphate values after 30 min. Yohimbine administration had no effect on these changes.     

The antagonism of ketamine/xylazine anesthesia ("Hellabrunn mixture") in wild zoo ruminants

The ability of the antagonists tolazoline, yohimbine and the combination of yohimbine with 4-aminopyridine to reverse the effects of the xylazine-component of the "Hellabrunn mixture" (125 mg/ml xylazine and 100 mg/ml ketamine) on nondomestic zoo ruminants is discussed. Arousal time, recovery time and changes in the parameter of circulatory and respiratory functions after antagonization are shown. Tolazoline is able to antagonize the xylazine effect completely within a short time. Using a dosage of 3-5 mg/kg there is a marked negative effect on the cardio-vascular system. Yohimbine in the used dosage of 0.25-0.3 mg/kg in non-domestic ruminants did not approve in its effects. Combining yohimbine (0.25-0.3 mg) with 4-aminopyridine (0.5 mg/kg) recovery time is about 30 minutes. The negative effect on the cardio-vascular system is less pronounced compared with tolazoline.     

Reversal of thiopental-induced anesthesia by 4-aminopyridine, yohimbine, and doxapram in dogs pretreated with xylazine or acepromazine

Groups of atropinized dogs (6 dogs/group) were sedated, using xylazine HCl (2.2 mg/kg of body weight, IM) or acepromazine maleate (0.25 mg/kg, IM), and were anesthetized to loss of pedal reflexes, using thiopental, IV. The dogs were given 1 of the following test antagonists, IV: saline solution (2 ml; control group), 4-aminopyridine (4-AP; 0.5 mg/kg), yohimbine (0.4 mg/kg), doxapram (5.0 mg/kg), or dual combinations of the latter 3 substances in the same doses as used for each agent. In xylazine-treated dogs, the mean dosage of thiopental required to induce anesthesia was 4.8 mg/kg. Control mean arousal time (MAT) and walk time (MWT) were 37.1 minutes and 53.8 minutes, respectively. These values were decreased to less than 2 minutes and less than 3 minutes, respectively, by yohimbine, 4-AP + yohimbine, and doxapram + yohimbine. With doxapram and with 4-AP + doxapram, MAT was less than 2 minutes and MWT was less than 8 minutes. In acepromazine-treated dogs, the mean dosage of thiopental required for anesthesia was 15.0 mg/kg. Control MAT and MWT were 20.7 minutes and 36.5 minutes, respectively. These values were decreased to 8.1 minutes and 18.1 minutes, respectively, by doxapram, and to 3.5 minutes and 19.9 minutes, respectively, by doxapram + yohimbine. Doxapram, 4-AP + doxapram, and doxapram + yohimbine caused periodic extensor rigidity before and during arousal. This rigidity was accompanied by opisthotonos in 2 dogs of the doxapram + yohimbine group and may have been mild tonic seizures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of ketamine, xylazine, and diazepam anesthesia with retrobulbar block for phacoemulsification in dogs

Objective  The study was undertaken to evaluate the use of ketamine, xylazine, and diazepam along with a local retrobulbar nerve block for routine phacoemulsification in the dog.
Animals  Ten clinically healthy mixed-breed dogs of either sex, weighing between 10 and 15 kg.
Procedures  Ten mixed-breed dogs were selected for unilateral cataract removal by phacoemulsification. Standard preoperative preparations for cataract surgery were followed. Pre-anesthetic medication consisted of atropine sulfate (0.02 mg/kg, SC). Anesthesia was induced by xylazine HCl (1.0 mg/kg, IM) followed by ketamine (5.0 mg/kg, IM). Anesthesia was maintained subsequently with IV ketamine and diazepam to effect and depth of anesthesia was assessed clinically by pedal reflex and jaw reflex. After induction of anesthesia, a retrobulbar nerve block was performed using 2 mL of 2% lignocaine. Eye position was graded after retrobulbar block and IOP was examined preoperative, post-anesthetic, 6 h postoperative and 24 h after surgery. Phacoemulsification was performed using the phaco-chop technique and an intraocular lens was placed. Anesthetic recovery and postoperative recovery following surgery was recorded.
Result  The exposure of the globe in all the dogs was adequate; the desired central fixation of the eye was obtained and surgery could be performed uneventfully. The mean IOP recorded after induction of anesthesia was 15.75 ± 0.82, which was not significantly ( P  > 0.01) different from pre-anesthetic values (14.85 ± 0.85).
Conclusion  Phacoemulsification was successfully performed with this anesthetic regimen without encountering major intraoperative or anesthetic complications.     

Evaluation of xylazine and ketamine for total intravenous anesthesia in horses

OBJECTIVE: To evaluate the use of xylazine and ketamine for total i.v. anesthesia in horses. ANIMALS: 8 horses. PROCEDURE: Anesthetic induction was performed on 4 occasions in each horse with xylazine (0.75 mg/kg, i.v.), guaifenesin (75 mg/kg, i.v.), and ketamine (2 mg/kg, i.v.). Intravenous infusions of xylazine and ketamine were then started by use of 1 of 6 treatments as follows for which 35, 90, 120, and 150 represent infusion dosages (microg/kg/min) and X and K represent xylazine and ketamine, respectively: X35 + K90 with 100% inspired oxygen (O2), X35 + K120-(O2), X35 + K150-(O2), X70 + K90-(O2), K150-(O2), and X35 + K120 with a 21% fraction of inspired oxygen (ie, air). Cardiopulmonary measurements were performed. Response to a noxious electrical stimulus was observed at 20, 40, and 60 minutes after induction. Times to achieve sternal recumbency and standing were recorded. Quality of sedation, induction, and recovery to sternal recumbency and standing were subjectively evaluated. RESULTS: Heart rate and cardiac index were higher and total peripheral resistance lower in K150-(O2) and X35 + K120-air groups. The mean arterial pressure was highest in the X35 + K120-air group and lowest in the K150-(O2) group (125 +/- 6 vs 85 +/- 8 at 20 minutes, respectively). Mean Pa(O2) was lowest in the X35 + K120-air group. Times to sternal recumbency and standing were shortest for horses receiving K150-(O2) (23 +/- 6 minutes and 33 +/- 8 minutes, respectively) and longest for those receiving X70 + K90-(O2) (58 +/- 28 minutes and 69 +/- 27 minutes, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Infusions of xylazine and ketamine may be used with oxygen supplementation to maintain 60 minutes of anesthesia in healthy adult horses.     

Comparison of yohimbine, 4-aminopyridine and doxapram antagonism of xylazine sedation in deer (Cervus elaphus)

Trials were conducted to test the ability of yohimbine, 4-aminopyridine and doxapram given by intravenous injection to antagonise xylazine sedation in red deer (Cervus elaphus). Yohimbine produced the best and most consistent result. The mean time taken for 34 animals to stand spontaneously after receiving yohimbine (0.2 to 0.25 mg/kg) was 2 minutes 25 seconds and this occurred, on average, 33 minutes after the initial doze of xylazine. Control deer took 67 and 104 minutes on average to stand after receiving intravenous (0.64-0.96 mg/kg) and intramuscular (1.0-1.5 mg/kg) injections of xylazine respectively. Two deer which received an overdose of xylazine (4 mg/kg) recovered 3 and 9 minutes respectively after receiving yohimbine. Two deer given a high intravenous dose of yohimbine (1.0 mg/kg) became mildly nervous and anxious, but returned to normal within an hour. 4-aminopyridine (0.3 mg/kg) alone produced some arousal from xylazine sedation (0.6-1.0 mg/kg) but was inconsistent. In combination with yohimbine (0.125 mg/kg) it produced rapid recovery in two deer but caused convulsions in two other deer. Doxapram (1 mg/kg) produced respiratory stimulation and some arousal from xylazine sedation (0.6-1.0 mg/kg) in the majority of deer but the effect was transitory. Animals relapsed into moderate sedation and recumbency within 10 minutes and required vigorous stimulation to arouse them again. Yohimbine, administered by intravenous injection at a dose rate of 0.2 to 0.25 mg/kg, appears to be a safe and reliable drug for the reversal of xylazine sedation in deer.     

Tiletamine-zolazepam, ketamine, and xylazine anesthesia of captive cheetah (Acinonyx jubatus).

Thirty-two anesthetic episodes used a combination of tiletamine-zolezepam (50 mg/ml each), ketamine (80 mg/ml), and xylazine (20 mg/ml) at various dosages for routine diagnostic and minor surgical procedures in 13 captive cheetahs (Acinonyx jubatus). The mean dosage (0.023 +/- 0.003 ml/kg) provided rapid induction with a single i.m. injection along with safe predictable working time, good muscle relaxation, and analgesia. Yohimbine administration subsequently accelerated smooth and rapid recovery.     

Observations on some cardiopulmonary effects of midazolam, xylazine and a midazolam/ketamine combination in the goat

Xylazine, midazolam and a midazolam/ketamine combination were administered to 6 goats in a randomised 3-way block design. All goats received all treatments with at least a 7-day interval between treatments. Statistically significant (P < 0.05) changes were observed in some of the measured cardiopulmonary variables for xylazine and midazolam/ ketamine. Xylazine administration resulted in statistically significant decreases in minute volume, arterial partial pressure of oxygen, heart rate and mean arterial blood pressure. The increase in arterial partial pressure of carbon dioxide was not statistically significant. For the midazolam/ketamine combination, the decrease in tidal volume was statistically significant, but not the decrease in minute volume and increase in arterial partial pressure of carbon dioxide. The decrease in the arterial partial pressure of oxygen was also statistically significant. The mean arterial blood pressure for the combination was statistically significantly higher compared to xylazine. The changes in cardiopulmonary variables after midazolam administration were not statistically significant, such as tidal and minute volume, arterial partial pressure of oxygen and carbon dioxide. However, clinically significant effects such as hypoventilation and hypoxia were observed after its administration. The change in mean arterial blood pressure was minimal.     

Epidural anesthesia in Egyptian water buffalo (Bubalus bubalis): a comparison of lidocaine,xylazine and a combination of lidocaine and xylazine

Objective

To evaluate and compare the analgesic effects of a combination of lidocaine and xylazine to lidocaine or xylazine administered alone for epidural anesthesia in Egyptian water buffalo (Bubalus bubalis).

Use of xylazine and ketamine in the induction of halothane anesthesia in dogs]

Our experience of the administration of xylazine and ketamine for an induction of halothane inhalation anaesthesia in dogs is described in this paper. After this procedure had been evaluated in 10 test dogs, the xylazine-ketamine induction was used for different surgical interventions in 160 patients. After joint i.m. atropine (0.05 mg/kg) and xylazine (1.5-2 mg/kg) pre-medication general anaesthesia of the dogs was induced by an i.v. administration of 1% ketamine (2 mg/kg). After intubation and anaesthetizer connection halothane vapours had to be applied for 2 to 8 minutes at a 2.5% to 3.5% concentration to induce the tolerance stage of anaesthesia. Then the anaesthesia level was maintained by an application of halothane vapours at a 0.5 to 1.5% concentration (Tab. I). In addition to an evaluation of the anaesthesia proper, breathing-rate, inspiratory and expiratory volumes, internal body temperature were recorded, ECG was made and venous blood samples were taken to evaluate acid-base balance changes. The processing of the obtained data (Figs. 1 to 5, Tab. II) revealed a transient breathing attenuation after the xylazine-ketamine induction and partly compensated respiratory acidosis. On the basis of our results this tested method can replace the traditional thiopental induction associated with the risks of cardiopulmonary depression, or even blood circulation stoppage.     

Prolongation of anesthesia with xylazine, ketamine, and guaifenesin in horses: 64 cases (1986-1989)

On 74 occasions, 54 horses and 6 foals were anesthetized with xylazine and ketamine or xylazine, guaifenesin, and ketamine, with or without butorphanol. On 64 occasions, anesthesia was prolonged for up to 70 minutes (34 +/- 15 min) by administration of 1 to 9 supplemental IV injections of xylazine and ketamine at approximately a third the initial dosage. All horses except 5 were positioned in lateral recumbency, and oxygen was insufflated. In adult horses, the time from induction of anesthesia to the first supplemental xylazine and ketamine injection was 13 +/- 4 minutes and the time between supplemental injections was 12.1 +/- 3.7 minutes. These results were consistent with predicted plasma ketamine concentration calculated from previously published pharmacokinetic data for ketamine in horses. Respiratory and heart rates and coccygeal artery pressure remained consistent for the duration of anesthesia. The average interval between the last injection of ketamine and assumption of sternal position was approximately 30 minutes, and was the same regardless of the number of supplemental injections. The time to standing was significantly longer (P less than 0.05) in horses given 2 supplemental injections, compared with those not given any or only given 1, but was not longer in horses given 3 supplemental injections. Recovery was considered unsatisfactory in 5 horses, but did not appear to be related to prolongation of anesthesia.