Xylazine Group Research Articles

Evaluating the effects of three anesthetic regimens on retinal structure and function in the living mouse eye using a customized bimodal OCT/ORG system

Abstract Optical coherence tomography (OCT) is a non-invasive imaging technique that generates cross-sectional images of biological tissues at millimeter-level penetration depth with micron-level resolution. In this study, we developed a custom spectral-domain OCT system equipped with a flash stimulus module for dual-modality imaging of mouse retinal structure and function. The axial resolution of the system reached ∼2.7/2 μm in air/tissue following optimization and calibration. We deployed this system to conduct in vivo OCT structural imaging and optoretinography (ORG) functional assessment of mouse retina to investigate the effects of three anesthesia regimens. Statistical analysis of the results indicates that anesthesia results in a smaller relative intensity of inner/outer segment junction and external limiting membrane and a thickening of the outer segment compared to an awake state. Meanwhile, significant differences were observed in the effects on retinal structure and function between isoflurane and tribromoethanol anesthesia, while differences between isoflurane and esketamine+xylazine groups were small. These findings suggest that the type of anesthetic should be taken into account when comparing imaging results across studies reported in the literature.

Impacts of xylazine on fentanyl demand, body weight, and acute withdrawal in rats: A comparison to lofexidine

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl's behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is not a noted fentanyl adulterant. Here we evaluated xylazine and lofexidine combined with self-administered fentanyl doses in male and female rats and evaluated fentanyl demand, body weight, and acute withdrawal. Consumption of fentanyl alone increased at various unit doses compared to saline. Xylazine but not lofexidine shifted fentanyl consumption downward at a number of unit doses, however, both lofexidine and xylazine suppressed fentanyl demand intensity as compared to a fentanyl alone control group. Further, both fentanyl + lofexidine and fentanyl + xylazine reduced behavioral signs of fentanyl withdrawal immediately following SA, but signs increased by 12 h only in the xylazine co-exposed group. Weight loss occurred throughout fentanyl SA and withdrawal regardless of group, although the xylazine group lost significantly more weight during the first 24 h of withdrawal than the other two groups. Severity of weight loss during the first 24 h of withdrawal was also correlated with severity of somatic signs of fentanyl withdrawal. Together, these results suggest that body weight loss may be an important indicator of withdrawal severity during acute withdrawal from the xylazine/fentanyl combination, warranting further translational evaluation.

A Comparison between ketamine-xylazine and ketamine-midazolam or all of them to induce balance anesthesia in rabbits

The objective of this projectwas to study the induction of smooth anesthesia characterized by good induction (hypnosis), analgesia and good recovery with mild side effects caused by drugs. The effect of using Ketamine with both xylazine and midazolam KXM was investigated in adult rabbitsand compared with the positive control group that was administered with ketamine alone K at 40 mg/kg i.m, and with ketamine - xylazine group KX at 40 and 4 mg/kg i.m respectively, and with ketamine - midazolam group KM also at 40 and 4 mg/kg i.m respectively. Administration of xylazine and midazolam each one alone at 4 and 2 mg/kg I.M induced analgesia in a dose-dependent manner through a significant elevation of the electrical voltage after injection when compared with its value before injection. A minimum doses of a mixture KXM at 20,2 and 2 mg/kg i.m respectively, induced good hypnosis with rapid induction and long duration with recovery periods without significant variations in vital physiological parameters (respiratory rate, heart rate, and rectal temperature) and some biochemical parameters (GPT and GOT and glucose level) comparing with groups K, KX and KM. The outcomes of this work were revealed to the induction of proficient general anesthesia that was described by effective hypnosis with analgesic efficacy throughout the administration a minimum doses of ketamine/xylazine/midazolam combination in rabbits.

Intrathecal adenosine enhances the antinociception of Xylazine in goats

BackgroundThe role of adenosine (AD) in neuromodulation of nociceptive signaling at the level of the spinal cord has been established in both preclinical and clinical models. Recently, the signaling pathway that involves adenosine 5-monophosphate activated protein kinase has been reported to mediate the antinociceptive effects of xylazine (XYL). The objective of this study was to investigate the antinociceptive, cardiorespiratory and hematological effects of intrathecal administration of combined XYL-AD in goats as compared to XYL alone. Six clinically healthy adult goats weighing 25 ± 2 kg were randomly assigned to one of three groups in a cross-over design. Goats were sedated with XYL (0.05 mg/kg, IM) in all groups. Ten min later, 0.9% saline solution [SAL group], XYL (0.05 mg/kg) [XYL group] or a combination of XYL (0.05 mg/kg) and AD (2000 µg) [XYL-AD group] was injected intrathecally. Antinociception scores and both cardiorespiratory and hematological parameters were measured before XYL sedation and intrathecal injection (baseline), and at 5, 10, 15, 30, 60, 90, 120 and 150 min thereafter.ResultsThe XYL-AD group showed significantly earlier onset of antinociception [5 (5–7) min] than XYL [13 (12–14.25] min (P = 0.031). The duration of complete antinociception in goats that received XYL-AD was significantly longer (P = 0.031) than that received XYL alone [65 (58.75–66.25) and 47.5 (43.75–51.25) min, respectively]. In both XYL and XYL-AD groups, heart rate (HR), arterial blood pressure (SAP, MAP and DAP) were significantly decreased (P < 0.05) compared to the baseline. Compared to the SAL group, a statistically significant reduction in HR from 10 to 150 min (P < 0.05) was detected in the XYL group contrary to the XYL-AD group. Differences in the hematological parameters among different groups were insignificant.ConclusionsAD injected intrathecally interacts synergistically with XYL to promote antinociception in goats. This discovery supports the use of AD in combination with XYL in clinical trials.

A new anesthetic protocol to medullary nerve roots access in rats.

ABSTRACTPurpose:To describe a new anesthetic protocol medullary and nerve roots access and in Rattus norvegicus.Methods:Seventy female Wistar rats (n=70) were used. The animals were randomly divided into two laminectomy groups: cervical (n=40) and thoracic (n=30). In cervical group, a right posterior hemilaminectomy was performed to access the nerve roots. In thoracic group, a laminectomy of the eighth thoracic vertebra was accomplished. Thirty-five rats (20 cervical and 15 thoracic) were submitted to old anesthetic protocol (ketamine 70 mg/kg plus xylazine 10 mg/kg); and the 35 other animals (20 cervical and 15 thoracic) were submitted to a new anesthetic protocol (ketamine 60 mg/kg,xylazine 8 mg/kg and fentanyl 0.03 mg/kg).Results:The time to complete induction was 4.15 ±1.20 minin ketamine, xylazine and fentanyl group, and it was 4.09 ±1.47 min in the ketamine and xylazine group. There was no correlation in the time required to perform the cervical laminectomy in the old anesthetic protocol. In all groups, the animals submitted to the old anesthetic protocol had a higher level of pain on the first and third postoperative days than the animals submitted to the new anesthetic protocol.Conclusions:The new anesthetic protocol reduces the surgical time, allows better maintenance of the anesthetic plan, and brings more satisfactory postoperative recovery.

Acepromazina e/ou xilazina na sedação de suínos

Avaliou-se a tranquilização da acepromazina e o sinergismo decorrente da associação da mesma com a xilazina. Utilizou-se sete suínos, SRD, hígidos, machos, com 60 a 70 dias e pesando em média 18,3 ± 2,7 kg. Compostos de dois grupos: grupo A - acepromazina 1%, 0,1 mg/kg, via intramuscular; e grupo AX - xilazina 2%, 0,3 mg/kg, associada à acepromazina 1%, 0,1 mg/kg, na mesma seringa. Avaliaram-se: frequência cardíaca; pressão arterial sistólica; frequência respiratória; saturação de oxihemoglobina; temperatura corpórea e eletrocardiograma. A sedação: sedação ausente, discreta ou intensa. O relaxamento muscular: ausente, moderado ou excelente. Mensuração dos parâmetros: 0 e aos 15, 30, 45, 60, 75, 90, 105 e 120 minutos após. A FC foi maior no GA. Não ocorreu diferença significativa na f. A SpO2 não variou entre grupos nem entre momentos. A TC reduziu significativamente no GAX. A PAS não variou em ambos os grupos. No ECG observaram-se: alternância na amplitude da onda R. No período de latência e na duração de sedação não ocorreu diferença significativa entre grupos. No relaxamento muscular, no GAX foi maior em M75. Ambos os protocolos são seguros e promovem sedação em suínos, havendo um sinergismo quando da utilização de acepromazina associada à xilazina.

Detomidine and xylazine, at different doses, in donkeys (Equus asinus)

The effects of detomidine and xylazine in northeasters donkeys were compared. Six animals participated, randomly, of all experimental groups: xylazine 10%, 0.8 mg/kg (xylazine group 0.8 - GX0.8), 1.0 mg/kg (GX1.0) and 1, 2 mg/kg (GX1.2); and detomidine 1%, 0.02 mg/kg (Detomidine group 0.02 - GD0.02), 0.04 mg/kg (GD0.04) and 0.06 mg/kg (GD0.06) intravenous. Heart rate (HR) and respiratory rate (RR), rectal temperature (RT), mean arterial pressure (MAP), blood glucose, sedation, analgesia, ataxia, arrhythmias and urination were monitored. Duration of sedation was greater in the groups in which detomidine was administered. The muzzle-soil distance significantly reduced in all groups five minutes after the sedative administration, remaining smaller for a longer time in the GD0.06. Ataxia in GX1.0 was greater than in GX0.08 and GX1,2, being equivalent to GD0,04 and GD0,06. Analgesia lasted 30 minutes in GD0.06 and 10 minutes in the others. There was reduction of HR in GD0.02 and GD0.04 and atrioventricular block. There was a reduction in TR in GX1,2, GD0.02, GD0,04 and GD0,06. RR decreased in all groups. MAP increased in GD0.02, GD0.04 and GD0.06 five, 20, 30 and 10 minutes after administration of detomidine, respectively. Hyperglycaemia occurred for 120 minutes in all animals receiving detomidine. The frequency of micturition was higher in GD0.06 (2.2 ± 0.8) than in GX0.8 (0.8 ± 0.4). In northern Brazil, detomidine and xylazine promote short duration analgesia and cardiorespiratory alterations, but detomidine causes a greater sedative, hypertensive and hypothermic effect.

Comparison of anesthetic effects of isoflurane used alone or combined with xylazine on induced cerebral ischemia

Intraluminal suture method of middle cerebral artery occlusion (MCAo) has been extensively used in ischemic stroke study. Although the MCAo model has several advantages in comparing different stroke model, it has time‐consuming demands and requires high level of surgical skill. Low mortality and reproducible infarct size in MCAo model are affected by surgical technique, environmental variation and prolonged duration of surgery. The purpose of this study was to determine the effect of anesthetics during prolonged experimental surgery on reproducible stroke model. Animals were subjected to MCAo using intraluminal suture method and provide with isoflurane anesthesia or combined xylazine sedation (20 mg/kg). Animals were randomly divided into three groups: no anesthesia groups (control), inhaled anesthetics groups (isoflurane), inhaled anesthetics combined sedative group (isoflurane + xylazine). Inhaled anesthetics group was provided isoflurane during MCAo surgery (20 min), post‐occlusion period (60 min) and reperfusion (5–10 min), thus total duration of inhaled anesthesia was about 90 min. Inhaled anesthetics combined sedative groups was provided isoflurane during MCAo surgery (20 min) and reperfusion (5–10) min. Xylazine (20 mg/kg) was administered 5 min prior to MCAo and 30 min after MCAo by intramuscular injection. That total duration of inhaled anesthesia was about 30 min. Inhaled anesthetics group that anesthetized during all the post‐occlusion period demonstrated a poor prognosis and high mortality rate compared with control and inhaled anesthetics combined xylazine group. Although the stable respiration signal was shown without abnormal thorax movement, brain infarct size and neurologic deficits revealed no difference between groups. Our results indicated that a modified method of inhalation anesthesia combined xylazine sedation could improve the reproducibility of stroke model and reduce the risk of mortality.Support or Funding InformationFunding: NRF‐2013R1A2A2A01067169, NRF‐2017R1A2A2A01067169, KRIBB‐KGM4611714This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hematological and splenic Doppler ultrasonographic changes in dogs sedated with acepromazine or xylazine

ObjectiveTo evaluate the onset and duration of hematological changes and the use of Doppler ultrasound (spleen) in dogs sedated with acepromazine or xylazine. Study designClinical study. AnimalsA total of 24 mixed breed dogs aged 1–4 years and weighing 15–25 kg. MethodsDogs were randomly distributed into two groups: acepromazine group (AG) which were administered acepromazine (0.05 mg kg−1) intramuscularly and xylazine group (XG) administered xylazine (0.5 mg kg−1) intramuscularly. Sonographic evaluations (morphologic and hemodynamic splenic vascularization) and hematologic tests were performed before drug administration (baseline) and 5, 15, 30, 60, 120, 240, 360, 480 and 720 minutes after drug administration. ResultsA significant reduction occurred in erythrogram variables in AG at 15–720 minutes corresponding with a significant enlargement of the spleen. In XG, a significant reduction was observed in the erythrogram variables at 30–60 minutes without a significant enlargement of the spleen. Hilar diameter did not change over time in either group. Flow alterations were found only in the splenic artery in AG, with a decreased final diastolic velocity observed at 60–120 minutes. ConclusionsAdministration of acepromazine resulted in decreased red blood cell count, hemoglobin, packed cell volume and an increased diameter of the spleen. Xylazine administration resulted in similar hematologic changes but of smaller magnitude and duration and without splenic changes. The absence of significant changes in the Doppler flow parameters of the splenic artery and vein and the hilar diameter suggests that the splenomegaly that was observed in AG was not due to splenic vasodilation. No splenic sequestration occurred after xylazine administration. Clinical relevanceThe results indicate that acepromazine decreases the erythrocyte concentrations by splenic erythrocyte sequestration and concomitant splenomegaly. Xylazine can cause slight hematologic changes, but without splenic changes.

The effects of anesthetic regimen in 90% hepatectomy in rats

To evaluate the influence of the anesthetic regimen on anesthetic recovery, survival, and blood glucose levels following a 90% partial hepatectomy in rats. Thirty adult male Wistar rats were divided into two groups according to their anesthetic regimens: intraperitoneal ketamine and xylazine or inhaled isoflurane. In order to prevent hypoglycemia, glucose was administered intraperitoneally and glucose (20%) was added to the drinking water. Anesthetic recovery time was longer in the ketamine and xylazine group. The survival rate after 72 hours was lower (log rank=0.0001) in the ketamine and xylazine group (0.0%) than in the isoflurane group (26.7%). The blood glucose after six hours was lower (p=0.017) in the ketamine and xylazine group (63 ± 31.7 mg/dL) than in the isoflurane group (98 ± 21.2 mg/dL). The prolonged anesthesia recovery time associated with ketamine and xylazine decreased the survival rate and blood glucose levels after 90% hepatectomy. Isoflurane anesthesia reduced the recovery time and incidence of hypoglycemia and increased the survival rate in the early hours, providing a therapeutic window that is suitable for experimental studies.

Effect of acepromazine or xylazine on tear production as measured by Schirmer tear test in normal cats

To evaluate the effect of acepromazine or xylazine on Schirmer tear test 1 results in clinically normal cats. Sixteen healthy cross-breed cats. The animals were randomly divided into two groups of eight cats each. The first group was sedated with acepromazine alone (0.2 mg/kg) and the second group received only xylazine (2 mg/kg). All cats had Schirmer tear test (STT) readings taken prior to sedation and at 15 and 25 min postsedation. Sedation with acepromazine or xylazine in cats with normal pre-sedation STT 1 values caused a statistically significant decrease in mean values of tear production in both groups. In acepromazine group the mean +/- SEM STT at T(15) and T(25) were 4.31 +/- 0.98 (P < 0.001) and 5.18 +/- 1.07 (P = 0.002). The post-treatment mean +/- SEM values in xylazine group were 2.18 +/- 0.97 (P < 0.001) and 2.62 +/- 1.17 (P = 0.001) at 15 and 25 min respectively. Comparison between T(15) and T(25) in acepromazine group (P = 0.49) and xylazine group (P = 0.56) revealed no significant differences. These observations indicate that both acepromazine or xylazine significantly reduced tear production in clinically normal cats. In cats, clinicians should measure STT values prior to utilizing acepromazine or xylazine as sedatives in order to accurately assess the results. Moreover, sterile ocular lubricant or tear replacement should be used as a corneal protectant during sedation with these drugs.

Physiologic effects of electroacupuncture combined with intramuscular administration of xylazine to provide analgesia in goats

To investigate physiologic effects of electroacupuncture (EA) combined with xylazine administration in goats. 48 healthy crossbred goats. Goats were randomly allotted to 8 groups of 3 (nonpregnant and nonlactating) female goats and 3 male goats each. The 8 treatment groups were as follows: 1 EA group, 3 xylazine (0.1, 0.2, and 0.4 mg/kg, IM) groups, 3 EA plus xylazine (0.1, 0.2, and 0.4 mg/kg, IM) groups, and 1 control group. Electroacupuncture was performed for 90 minutes. Xylazine was administered 20 minutes after EA was performed. Pain threshold, heart rate, mean arterial pressure (MAP), respiration rate, and rectal temperature were observed at 0, 5, 25, 45, 65, and 85 minutes after xylazine administration. Xylazine administered at 0.4 mg/kg increased the pain threshold and reduced MAP. Xylazine administered at 0.1, 0.2, or 0.4 mg/kg reduced heart rate, respiration rate, and temperature. Electroacupuncture increased the pain threshold but had no effect on heart rate, MAP, respiratory rate, or rectal temperature. Pain threshold in goats that underwent EA plus xylazine administration was higher than in goats that received EA or xylazine alone. Electroacupuncture combined with xylazine at 0.1 mg/kg did not affect heart rate, MAP, respiratory rate, or rectal temperature. Pain threshold in goats that underwent EA plus xylazine administration at 0.1 mg/kg was higher than in goats given xylazine at 0.4 mg/kg alone. Electroacupuncture combined with xylazine, even at 0.1 mg/kg, provided analgesia without significantly affecting cardiorespiratory parameters or rectal temperature in goats.

Cardiopulmonary effects of dorsal recumbency and high-volume caudal epidural anaesthesia with lidocaine or xylazine in calves

The objective of this study was to investigate the cardiopulmonary effects of dorsal recumbency and high-volume caudal epidural anaesthesia induced by xylazine or lidocaine in calves. Twenty-eight German Holstein-Friesian calves (57.7 ± 5.8 kg bodyweight) were randomly allocated to four equal (n=7) groups for one of the following treatments, each injected into the caudal epidural space: (1) no treatment (control); (2) sterile saline (0.4 mL/kg); (3) lidocaine (2%), or (4) xylazine (0.1mg/kg), with the latter two treatments diluted with sterile saline to a final volume of 0.4 mL/kg. Cardiac output was measured by thermodilution and cardiopulmonary function parameters were determined at preset time intervals over an observation period of 335 min. After baseline measurements in the standing animals, the calves received the epidural injection and were positioned in dorsal recumbency for 95 min. In the control group, dorsal recumbency caused a significant (P < 0.05) decrease in cardiac index (CI) (baseline 210 ± 12 mL/kg/min, minimum value 174 ± 11 mL/kg/min), without significant change in blood-gas values. Calves treated with lidocaine or saline did not differ from the control group in any of the parameters measured. The epidural injection of xylazine caused a more pronounced decrease in CI (baseline 209 ± 12 mL/kg/min, minimum value 127 ± 11 mL/kg/min), compared to the control group. At the same time, the heart rate was significantly (P < 0.05) decreased (baseline 113 ± 7 beats per min, minimum value 86 ± 4 beats per min). Furthermore, a significant (P < 0.05) increase in the oxygen extraction ratio was observed in the xylazine group (baseline 39 ± 7%, maximum value 47 ± 7%). In all groups, cardiorespiratory parameters remained within physiological limits. Changes in cardiopulmonary function induced by dorsal recumbency and high-volume caudal epidural anaesthesia with lidocaine or xylazine were well tolerated in healthy calves.

Uso de morfina, xilazina e meloxicam para o controle da dor pós-operatória em cadelas submetidas à ovariossalpingo-histerectomia

Foram realizados estudos empregando-se analgésicos por via epidural e subcutânea em cadelas de diferentes raças e idades, submetidas à castração mediante celiotomia. Vinte animais foram tranquilizados e anestesiados com tiletamina-zolazepam, e aleatoriamente distribuídos em quatro grupos (n=5), de acordo com o fármaco e a via de administração. Os do grupo morfina (GM) foram submetidos à anestesia epidural no espaço lombossacro, com morfina (0,1mg/kg) associada ao cloreto de sódio a 0,9%. Aos do grupo xilazina (GX), foram administrados xilazina (0,2mg/kg) e cloreto de sódio a 0,9%. Os do grupo meloxicam (GME) receberam 0,2mg/kg do anti-inflamatório meloxicam associado ao cloreto de sódio a 0,9%, injetado pela via subcutânea. Os do grupo-controle (CG) receberam apenas cloreto de sódio a 0,9%. O volume final para as injeções epidurais foi padronizado para 0,3mL/kg. A mensuração inicial da concentração de cortisol plasmático, do ritmo cardíaco, da frequência respiratória e os parâmetros comportamentais foram registrados imediatamente antes do procedimento cirúrgico (M1). Registros adicionais foram apresentados às 2, 6, 12 e 24 horas após o procedimento cirúrgico (M2, M3, M4 e M5, respectivamente). As variáveis comportamentais foram avaliadas por meio de sinais clínicos e seus respectivos escores. Em GX foram observadas depressão respiratória, bradicardia e concentração de cortisol mais alta do que o registrado no GM. A analgesia obtida pelo meloxicam foi considerada ineficiente. É possível concluir que a morfina, via epidural, promoveu menor incidência de efeitos colaterais e melhor analgesia e bem-estar animal.

Effect of bupivacaine on epidural analgesia produced by xylazine or medetomidine in buffaloes (Bubalus bubalis)

ObjectiveTo evaluate and compare the effect of epidural bupivacaine on analgesia produced by epidural xylazine or medetomidine in buffaloes. Study designProspective, blinded study. AnimalsTen male buffalo calves (6-8 months of age; body weight 70-90 kg) were used on two occasions to conduct a total of 20 investigations. MethodsCaudal extradural analgesia was produced in four buffalo calves each by the injection of either xylazine (0.05 mg kg−1), medetomidine (15 μg kg−1) or 0.5% bupivacaine (0.125 mg kg−1), or combinations of xylazine and bupivacaine (0.05 and 0.125 mg kg−1), or medetomidine and bupivacaine (15 μg kg−1 and 0.125 mg kg−1) at the first intercoccygeal extradural space. Analgesia was tested using deep pinprick stimuli. ResultsExtradural administration of xylazine or medetomidine resulted in complete analgesia of the tail, perineum, inguinal region and the upper parts of the hind limbs, which was faster in onset and longer in duration in the medetomidine group than in the xylazine group. Addition of bupivacaine increased the intensity of the analgesia produced by xylazine, but not that produced by medetomidine. All the drugs caused mild to moderate ataxia, but signs of sedation were apparent only in animals which received xylazine or medetomidine. The extradural injections of all the drugs caused significant decrease in heart rate (p = 0.024), respiratory rate (p = 0.026) and rectal temperature (p = 0.036) from the respective baseline values, but the differences between the groups were not significant. ConclusionsMedetomidine produced a longer duration of analgesia than that produced by xylazine. Bupivacaine prolonged the analgesia produced by xylazine, but the analgesia produced by the combination of medetomidine and bupivacaine was not superior to that produced by medetomidine alone. Clinical relevanceBupivacaine may be used to prolong the extradural analgesia produced by xylazine, but not that produced by medetomidine in buffaloes.

Comparative study of epidural xylazine or clonidine in horses

ObjectiveTo evaluate the cardiorespiratory and behavioural effects of epidural xylazine (XYL) or clonidine (CLO) in horses. Study designBlinded, randomized experimental study. AnimalsTwelve healthy Arabian yearling horses weighing 117–204 kg were randomly allocated into two groups: XYL (n = 6) and CLO (n = 6). MethodsAn epidural catheter was inserted and a facial arterial catheter was placed and the next day the horses were restrained in stocks. Baseline values for heart (HR) and respiratory (RR) rates, arterial pressure and behavioural responses were evaluated before (T0) and 10, 20, 30, 45, 60, 90 and 120 minutes after epidural injection (T10–T120). The horses received 0.2 mg kg−1 of XYL or 5 μg kg−1 CLO; adjusted to (3.4 + (body weight in kg × 0.013) mL with saline. Data were analysed by the Kolmogorov–Smirnov test, one-way anova with repeated measures, and one-way anova followed by a Student–Newman–Keuls test or Fisher's exact test, as necessary. Significance was set at p ≤ 0.05. ResultsSedation and ataxia were seen at T10, persisting until T120 in four and three horses, respectively, in XYL and all horses in CLO respectively. Two XYL and one CLO horses became recumbent at T45 and T25 respectively. Penile prolapse occurred in four of five males at T30 and T45, in the XYL and CLO groups, respectively, resolving by T120. Tail relaxation was present from T10 to T120 in all horses in XYL and in four horses in CLO. Head drop was observed from T20 to T60 and from T10 to T120 in XYL and CLO respectively. Respiratory rate decreased significantly only at T45 in the CLO group. Heart rate and arterial blood pressure remained stable. Conclusions and clinical relevanceEpidural CLO and XYL produce similar cardiorespiratory and behavioural changes but neither would be safe to use clinically at the doses used in this study.

High Caudal Epidural Anaesthesia with Local Anaesthetics or α2‐Agonists in Calves

The objective of this study was to examine the efficacy of a caudal epidural anaesthesia using lidocaine or xylazine in a high volume for analgesia of the flank, navel and hamstring tendon. Fourteen calves weighing 57.7 +/- 5.1 kg and 37.9 +/- 9.3 (mean +/- SEM) days old were randomly divided into two groups of seven calves each. Calves belonging to the lidocaine group were given a 2% lidocaine solution in the sacrococcygeal vertebral space epidurally at a volume of 0.4 ml/kg (8 mg/kg) body weight (BW). Animals of the xylazine group were administered an epidural anaesthesia with xylazine at a dose of 0.1 mg/kg BW, diluted with a 0.9% saline solution to a corresponding final volume of 0.4 ml/kg BW. Heart rate and respiratory rate were measured and the degree and duration of analgesia was determined by the response to a skin prick with a hypodermic needle over a period of 350 min after epidural injection. After epidural anaesthesia with lidocaine the mean heart rate increased during dorsal recumbency, whereas after xylazine both heart rate and respiratory rate decreased significantly (P < 0.05). The epidural injection of xylazine compared with lidocaine caused longer (P < 0.05) analgesia at the hamstring tendon (mean +/- SEM, 120.7 +/- 29.7 min versus 93.6 +/- 3.5 min) and at the flank (100.7 +/- 24.4 min versus 78.3 +/- 11.1 min). There were no differences in the intensity of analgesia between groups. After xylazine application analgesia at the navel was achieved for 95.0 +/- 14.1 min whereas after lidocaine injection sufficient analgesia at the navel was found in just two of seven calves for 55 and 95 min respectively. Based on above experiences, a second study was performed, in which a combination of xylazine and local anaesthetics was used and the injection volume was increased to prove the efficacy of caudal epidural anaesthesia in 15 calves (26.3 +/- 26.7 days; 57.1 +/- 19.5 kg) submitted to the clinic for regular umbilical surgery. In these cases the xylazine (0.1 mg/kg BW) was diluted with 2% lidocaine (n = 7) or 2% procaine (n = 8) to a corresponding final volume of 0.5-0.6 ml/kg BW. In all cases complete anaesthesia of the surgical area was achieved and no adverse effects were observed. Overall the high volume caudal epidural anaesthesia represents an effective, safe, cheap and easy to perform alternative for anaesthesia of the navel, flank and hamstring tendon in calves without major side effects.

Multiple Centrally Acting Antidotes Protect against Severe Organophosphate Toxicity

Accumulation of acetylcholine in the central nervous system is believed to account for the rapid lethality of organophosphate pesticides and chemical nerve agents. Diazepam is known to supplement atropine therapy, but its specific mechanism of action is uncertain. To test four centrally acting agents for early antidotal efficacy in severe dichlorvos poisoning in the murine model. The up-and-down method was used to dose four candidate antidotes: diazepam, xylazine, morphine, and ketamine. Antidotes were administered subcutaneously to unsedated adult Sprague-Dawley rats who were pretreated with 3 mg/kg intraperitoneal glycopyrrolate. All animals received 20 mg/kg of dichlorvos subcutaneously 5 minutes later. A blinded observer adjudicated the outcomes of 10-minute mortality and survival time. All animals pretreated with either no antidote (8/8 deaths) or glycopyrrolate alone (8/8) died within 10 minutes of dichlorvos injection. Pretreatment with diazepam (3/9 deaths), or xylazine (3/9), decreased lethality substantially (Fisher p = 0.007; median effective doses, 0.12 mg/kg and 3.0 mg/kg, respectively). Intermediate doses of morphine (3.1 to 5.5 mg/kg) resulted in survival, but higher doses did not, presumably because of excessive respiratory depression (7/11 deaths; p = 0.09). Ketamine (7/8 deaths) was ineffective as an antidote. Survival times also were prolonged in the diazepam and xylazine groups (log-rank p < 0.001) and, to a lesser degree, the morphine group (p = 0.07). Doses of diazepam, xylazine, and morphine below those used for deep sedation protect against severe dichlorvos poisoning, implying that several distinct central mechanisms are each sufficient to avert lethality. These findings suggest new possibilities for prophylaxis or therapy.

The analgesic effects of intrathecal xylazine and detomidine in sheep and their antagonism with systemic atipamezole

ObjectiveTo evaluate the analgesic and adverse side effects of intrathecal (IT) xylazine (XYL) and detomidine (DET) and the subsequent effects of two doses of intravenous (IV) atipamezole (ATI). Study designProspective, randomized, cross-over. AnimalsFive adult healthy female sheep with mean body mass of 55 ± 2.3 kg. Material and methodsEach sheep underwent four treatments: 1) 50 μg kg−1 XYL IT and 5 μg kg−1 ATI IV, 2) 50 μg kg−1 XYL IT and 2.5 μg kg−1 ATI IV, 3) 10 μg kg−1 DET IT and 5 μg kg−1 ATI IV, 4) 10 μg kg−1 DET IT and 2.5 μg kg−1 ATI IV. Pain threshold (TH) was tested by applying pulsed and stepwise incremental direct current to the skin overlying the pastern. The current at the point of foot lift was recorded as the TH. Heart rate (HR), mean arterial pressure, arterial oxygen (PO2) and carbon dioxide (PCO2) tensions were monitored. Outcomes were derived as differences between baseline assessment and measurements after treatment. Two-way anova was used to analyse drug effects, treatment differences between groups were examined with an F-test or Wilcoxon's rank sum test in case of non-parametric data distribution. p was set at 0.05. ResultsBoth drugs increased the pain TH, caused small increases in PCO2, and small decreases in HR, the latter was only significant for XYL recipients. Xylazine produced a significantly higher TH, more rapidly and for longer than DET. Atipamezole only significantly affected PaCO2 in the XYL group 2. The pain TH was not affected in either group after IV ATI. ConclusionsAt the doses used, IT XYL, and to a lesser extent DET, induced pastern analgesia. Atipamezole 5 μg kg−1 IV antagonized some side effects without affecting analgesia. Clinical relevanceIntrathecal XYL may be useful as an analgesic in sheep. Its safety is increased because IV ATI antagonizes side effects, but not analgesia.

Importance of anesthesia for the genesis of neurogenic pulmonary edema in spinal cord injury

There are reports describing both provocation and inhibition of neurogenic pulmonary edema by anesthetic drugs. Therefore, we compared the effect of two types of anesthesia on the formation of neurogenic pulmonary edema in rats with balloon-induced acute spinal cord injury. Animals with sham procedure (group 1) were anesthesized by intraperitoneal sodium pentobarbital. In the experimental groups, rats were submitted to acute spinal cord lesion by insufflations of a balloon in the epidural space at T8 for 1 min (group 3 under i.p. sodium pentobarbital and group 2 under i.p. xylazine–ketamine anesthesia). In rats with pentobarbital anesthesia, systolic blood pressure doubled the baseline value during compression, whereas this effect was less pronounced in the ketamine–xylazine group. The pulmonary index (100 × wet lung weight/body weight) was 0.395 (±0.018) in sham-operated rats, rose to 0.499 (±0.060) in group 2, and was maximum under pentobarbital anesthesia (0.639 ± 0.14; p = 0.0018). Histologic examination of the spinal cord showed parenchymal ruptures and acute hemorrhage. Comparison of the pulmonary index with histologic slides of lung parenchyma revealed that relevant intra-alveolar edema occurred only for index values above 0.55. On electron microscopy, endothelial alterations, and damage of the alveolar lining cells were found. Our study indicates that neurogenic pulmonary edema caused by spinal cord injury is less pronounced in rats under xylazine–ketamine anesthesia, when compared with pentobarbital.