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1.
ObjectiveTo evaluate perioperative stress-related hormones in isoflurane-anesthetized horses administered infusions of dexmedetomidine alone or with butorphanol or remifentanil, compared with ketamine–morphine.Study designRandomized, prospective, nonblinded clinical study.AnimalsA total of 51 horses undergoing elective surgical procedures.MethodsHorses were premedicated with xylazine, anesthesia induced with ketamine–diazepam and maintained with isoflurane and one of four intravenous infusions. Partial intravenous anesthesia (PIVA) was achieved with dexmedetomidine (1.0 μg kg–1 hour–1; group D; 12 horses); dexmedetomidine (1.0 μg kg–1 hour–1) and butorphanol bolus (0.05 mg kg–1; group DB; 13 horses); dexmedetomidine (1.0 μg kg–1 hour–1) and remifentanil (3.0 μg kg–1 hour–1; group DR; 13 horses); or ketamine (0.6 mg kg–1 hour–1) and morphine (0.15 mg kg–1, 0.1 mg kg–1 hour–1; group KM; 13 horses). Infusions were started postinduction; butorphanol bolus was administered 10 minutes before starting surgery. Blood was collected before drugs were administered (baseline), 10 minutes after ketamine–diazepam, every 30 minutes during surgery and 1 hour after standing. Mean arterial pressure (MAP), pulse rate, end-tidal isoflurane concentration, cortisol, nonesterified fatty acids (NEFA), glucose and insulin concentrations were compared using linear mixed models. Significance was assumed when p < 0.05.ResultsWithin D, cortisol was lower at 120–180 minutes from starting surgery compared with baseline. Cortisol was higher in KM than in D at 60 minutes from starting surgery. Within all groups, glucose was higher postinduction (except DR) and 60 minutes from starting surgery, and insulin was lower during anesthesia and higher after standing compared with baseline. After standing, NEFA were higher in KM than in DB. In KM, MAP increased at 40–60 minutes from starting surgery compared with 30 minutes postinduction.Conclusions and clinical relevanceDexmedetomidine suppressed cortisol release more than dexmedetomidine–opioid and ketamine–morphine infusions. Ketamine–morphine PIVA might increase catecholamine activity.  相似文献   

2.
ObjectiveTo determine the thermal and mechanical antinociceptive effects of two different subanesthetic constant rate infusions of racemic ketamine in cats.Study designProspective, randomized, blinded, experimental study.AnimalsEight healthy adult domestic shorthair cats (two intact females and six neutered males).MethodsThe thorax and the lower thoracic limbs of each cat were shaved for thermal (TT) and mechanical threshold (MT) testing and a cephalic catheter was placed. Three intravenous treatments of equivalent volume were given as loading dose (LD) followed by an infusion for 2 hours: (K5) 0.5 mg kg?1 ketamine followed by 5 μg kg?1 minute?1 ketamine infusion, (K23) 0.5 mg kg?1 ketamine followed by 23 μg kg?1 minute?1 ketamine infusion or (S) 0.9% saline solution. Effects on behavior, sedation scores, MT and TT were obtained prior to drug treatment and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.25, 2.5 2.75, 3 hours then every 0.5 hours for 7 hours and 10, 12, 14 and 26 hours after loading dose administration.ResultsKetamine induced mild sedation for the period of the infusion, no adverse behavioral effects were observed. Thermal threshold was significantly higher than baseline (K5: 44.5 ± 0.7 °C; K23: 44.5 ± 0.5 °C) at 15 minutes in the K5 group (46.8 ± 3.5 °C) and at 45 minutes in the K23 group (47.1 ± 4.1 °C). In the K23 group TT was significantly increased compared to S and K5 at 45 minutes. In K5 at 15 minutes MT (9.6 ± 4.0 N) was different to baseline (6.1 ± 0.8 N) and to the S group (5.9 ± 2.3 N).Conclusion and clinical relevanceLow dose rate ketamine infusions minimally affect thermal and mechanical antinociception in cats. Further studies with different nociceptive testing methods are necessary to assess whether ketamine could be a useful analgesic in cats.  相似文献   

3.
ObjectiveTo investigate the impact of intramuscular (IM) co-administration of the peripheral α2-adrenoceptor agonist vatinoxan (MK-467) with medetomidine and butorphanol prior to intravenous (IV) ketamine on the cardiopulmonary and anaesthetic effects in dogs, followed by atipamezole reversal.Study designRandomized, masked crossover study.AnimalsA total of eight purpose-bred Beagle dogs aged 3 years.MethodsEach dog was instrumented and administered two treatments 2 weeks apart: medetomidine (20 μg kg–1) and butorphanol (100 μg kg–1) premedication with vatinoxan (500 μg kg–1; treatment MVB) or without vatinoxan (treatment MB) IM 20 minutes before IV ketamine (4 mg kg–1). Atipamezole (100 μg kg–1) was administered IM 60 minutes after ketamine. Heart rate (HR), mean arterial (MAP) and central venous (CVP) pressures and cardiac output (CO) were measured; cardiac (CI) and systemic vascular resistance (SVRI) indices were calculated before and 10 minutes after MVB or MB, and 10, 25, 40, 55, 70 and 100 minutes after ketamine. Data were analysed with repeated measures analysis of covariance models. A p-value <0.05 was considered statistically significant. Sedation, induction, intubation and recovery scores were assessed.ResultsAt most time points, HR and CI were significantly higher, and SVRI and CVP significantly lower with MVB than with MB. With both treatments, SVRI and MAP decreased after ketamine, whereas HR and CI increased. MAP was significantly lower with MVB than with MB; mild hypotension (57–59 mmHg) was recorded in two dogs with MVB prior to atipamezole administration. Sedation, induction, intubation and recovery scores were not different between treatments, but intolerance to the endotracheal tube was observed earlier with MVB.Conclusions and clinical relevanceHaemodynamic performance was improved by vatinoxan co-administration with medetomidine–butorphanol, before and after ketamine administration. However, vatinoxan was associated with mild hypotension after ketamine with the dose used in this study. Vatinoxan shortened the duration of anaesthesia.  相似文献   

4.
ObjectiveTo evaluate the effects of intravenous lidocaine (L) and ketamine (K) alone and their combination (LK) on the minimum alveolar concentration (MAC) of sevoflurane (SEVO) in dogs.Study designProspective randomized, Latin-square experimental study.AnimalsSix, healthy, adult Beagles, 2 males, 4 females, weighing 7.8 – 12.8 kg.MethodsAnesthesia was induced with SEVO in oxygen delivered by face mask. The tracheas were intubated and the lungs ventilated to maintain normocapnia. Baseline minimum alveolar concentration of SEVO (MACB) was determined in duplicate for each dog using an electrical stimulus and then the treatment was initiated. Each dog received each of the following treatments, intravenously as a loading dose (LD) followed by a constant rate infusion (CRI): lidocaine (LD 2 mg kg−1, CRI 50 μg kg−1minute−1), lidocaine (LD 2 mg kg−1, CRI 100 μgkg−1 minute−1), lidocaine (LD 2 mg kg−1, CRI 200 μg kg−1 minute−1), ketamine (LD 3 mg kg−1, CRI 50 μg kg−1 minute−1), ketamine (LD 3 mgkg−1, CRI 100 μg kg−1 minute−1), or lidocaine (LD 2 mg kg−1, CRI 100 μg kg−1 minute−1) + ketamine (LD 3 mg kg−1, CRI 100 μg kg−1 minute−1) in combination. Post-treatment MAC (MACT) determination started 30 minutes after initiation of treatment.ResultsLeast squares mean ± SEM MACB of all groups was 1.9 ± 0.2%. Lidocaine infusions of 50, 100, and 200 μg kg−1 minute−1 significantly reduced MACB by 22.6%, 29.0%, and 39.6%, respectively. Ketamine infusions of 50 and 100 μg kg−1 minute−1 significantly reduced MACB by 40.0% and 44.7%, respectively. The combination of K and L significantly reduced MACB by 62.8%.Conclusions and clinical relevanceLidocaine and K, alone and in combination, decrease SEVO MAC in dogs. Their use, at the doses studied, provides a clinically important reduction in the concentration of SEVO during anesthesia in dogs.  相似文献   

5.
ObjectiveTo determine the effect of intravenous ketamine on the minimum alveolar concentration of sevoflurane needed to block autonomic response (MACBAR) to a noxious stimulus in dogs.Study designRandomized, crossover, prospective design.AnimalsEight, healthy, adult male, mixed-breed dogs, weighing 11.2–16.1 kg.MethodsDogs were anesthetized with sevoflurane on two occasions, 1 week apart, and baseline MACBAR (B-MACBAR) was determined on each occasion. MACBAR was defined as the mean of the end-tidal sevoflurane concentrations that prevented and allowed an increase (≥15%) in heart rate or invasive mean arterial pressure in response to a noxious electrical stimulus (50 V, 50 Hz, 10 ms). Dogs then randomly received either a low-dose (LDS) or high-dose series (HDS) of ketamine, and treatment MACBAR (T-MACBAR) was determined. The LDS had an initial loading dose (LD) of 0.5 mg kg?1 and constant rate infusion (CRI) at 6.25 μg kg?1 minute?1, followed, after T-MACBAR determination, by a second LD (1 mg kg?1) and CRI (12.5 μg kg?1 minute?1). The HDS had an initial LD (2 mg kg?1) and CRI (25 μg kg?1 minute?1) followed by a second LD (3 mg kg?1) and CRI (50 μg kg?1 minute?1). Data were analyzed with a mixed-model anova and are presented as LSM ± SEM.ResultsThe B-MACBAR was not significantly different between treatments. Ketamine at 12.5, 25, and 50 μg kg?1 minute?1 decreased sevoflurane MACBAR, and the maximal decrease (22%) occurred at 12.5 μg kg?1 minute?1. The percentage change in MACBAR was not correlated with either the log plasma ketamine or norketamine concentration.Conclusions and clinical relevanceKetamine at clinically relevant doses of 12.5, 25, and 50 μg kg?1 minute?1 decreased sevoflurane MACBAR, although the reduction was neither dose-dependent nor linear.  相似文献   

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7.
ObjectiveTo determine if buprenorphine plus dexmedetomidine administered via the oral transmucosal route produces sufficient sedation in cats so that students can insert intravenous catheters.Study DesignProspective, randomized, blinded, clinical trial.AnimalsEighty‐seven shelter‐owned female cats aged 4–48 months, weighing 1.1–4.9 kg.MethodsCats were randomly allocated to two treatment groups based on route of drug administration: oral transmucosal (OTM), or intramuscular (IM). Buprenorphine (20 μg kg?1) plus dexmedetomidine (20 μg kg?1) were administered as pre‐medicants via one of these two routes. Prior to and 20 minutes after drug administration, heart and respiratory rates, systolic arterial pressure, and posture were measured and recorded. Twenty minutes after drug administration the same variables plus each cat’s response to clipper sound, clipping, and restraint were recorded; higher scores indicated more sedation.ResultsThere were no significant differences between the two groups prior to pre‐medication. Within each treatment group heart rate was significantly lower 20 minutes after treatment, but it did not differ significantly between the two groups. Twenty minutes after treatment, respiratory rate was significantly less in the OTM group, but did not differ significantly between the two groups. Systolic arterial pressure did not differ within or between the two groups at either time. Scores for posture increased significantly within both groups, and cats in the IM group had higher scores after treatment. Twenty minutes after treatment, cats in the IM group had higher scores for clipping and restraint than OTM cats. Ketamine (IM) was necessary to facilitate catheterization in 25% and 16% of cats in the OTM and IM groups, respectively, but this was not significantly different.Conclusions and clinical relevanceAdministration of dexmedetomidine plus buprenorphine by the OTM route is easy to perform, but produces less sedation than the IM route for IV catheterization in cats.  相似文献   

8.
ObjectiveTo evaluate the cardiorespiratory effects and plasma concentrations of medetomidine-midazolam-ketamine (MMK) combinations administered by intramuscular (IM) or subcutaneous (SC) injection in sable ferrets (Mustela putorius furo).Study designProspective randomized experimental study.AnimalsEighteen adult ferrets: weight median 1.19 (range 0.81–1.60) kg.MethodsAnimals were allocated to one of three groups: group IM07 received 20 μg kg?1 medetomidine, 0.5 mg kg?1 midazolam and 7 mg kg?1 ketamine IM; group IM10 20 μg kg?1 medetomidine, 0.5 mg kg?1 midazolam and 10 mg kg?1 ketamine IM; and group SC10 20 μg kg?1 medetomidine, 0.5 mg kg?1 midazolam and 10 mg kg?1 ketamine SC. Following instrumentation, cardiorespiratory parameters and plasma drug concentrations were measured every 5 minutes (T5–T30) for 30 minutes Ferrets were then euthanased. Data were analysed using anova for repeated measures. p < 0.05 was considered significant.ResultsResults are mean ± SD. Induction of anaesthesia (minutes) in IM07 and IM10 [2 (1)] was significantly faster than in SC10 [5 (2)]. All groups demonstrated the following: results given as groups IM07, IM10 and SC10 respectively. Mean arterial blood pressures (mmHg) were initially high [186 (13); 174 (33) and 174 (9) at T5] but decreased steadily. Pulse rates were initially 202 (20), 213 (17) and 207 (33) beats minute?1, decreasing with time. PaO2 (mmHg) was low [54.0 (8), 47.7 (10) and 38.5 (1)] at T5, although in groups IM07 and IM10 it increased over time. Plasma concentrations of all drugs were highest at T5 (36, 794 and 8264 nmol L?1 for medetomidine, midazolam and ketamine, respectively) and decreased thereafter: for both midazolam and ketamine, concentrations in IM07 and IM10 were higher than SC10.Conclusions and clinical relevanceMMK combinations containing either 7 or 10 mg kg?1 ketamine and given IM are suitable combinations for anaesthetising ferrets, although the observed degree of hypoxaemia indicates that oxygen administration is vital.  相似文献   

9.
ObjectiveTo evaluate the clinical and physiological effects of epidural injection of ketamine in camels.Study designRandomized prospective study.AnimalsTen healthy immature male dromedary camels.MethodsKetamine was administered epidurally at doses of 1 and 2 mg kg?1 (five animals in each treatment). The drug was injected into the first intercoccygeal epidural space. Anti-nociception, sedation, ataxia, and effect on cardiopulmonary, rectal temperature and some selected haematological parameters were recorded at different intervals before (baseline) and after the drug administration. Data were analyzed by anova or U Mann–Whitney tests, as relevant and significance was taken as p < 0.05.ResultsEpidural ketamine at the 2 mg kg?1 dose produced complete anti-nociception in the tail, anus and perineum, whilst the 1 mg kg?1 dose produced complete anti-nociception only in the tail. Epidural ketamine resulted in mild to moderate sedation at the 1 mg kg?1 dose and deep sedation at the 2 mg kg?1 dose. Ataxia was observed in all test subjects and was severe, resulting in recumbency, in the 2 mg kg?1 group. Respiratory rate and rectal temperature did not change significantly after injection of either treatment. Following epidural injection of 2 mg kg?1 of ketamine, heart rate increased significantly from the pre-injection baseline of 55 ± 2 to 76 ± 4 (mean ± SD) beats minute?1, but after the lower dose changes were not significant. The only significant changes in measured haematologic parameters were decreases in total erythrocyte count at 45 minutes and total leukocyte count from 45–75 minutes, in the 2 mg kg?1 group.ConclusionEpidural ketamine injection was associated with caudal anti-nociception, sedation and ataxia in the dromedary camels; the intensity and duration of which was dose dependant.Clinical relevanceNeither of the doses of epidural ketamine injection in our study was applicable for standing surgical procedures in dromedary camels.  相似文献   

10.
Objective To determine if a combination of detomidine and ketamine can be used for effective chemical immobilization of chimpanzees. Study design Observational study. Animals Twenty‐one adult captive chimpanzees (12 males, nine females), age 8–46 years, weighing 40.4–68.4 kg. Methods The chimpanzees were immobilized with intramuscular (IM) detomidine and ketamine by a darting system. Based on estimated weights, doses administered were 50 μg kg?1 detomidine and 4 mg kg?1 ketamine in groups 1 and 2, and 60 μg kg?1 and 5 mg kg?1 respectively in group 3. Eight minutes in group 1 and 15 minutes in groups 2 and 3 were allowed from the time of apparent immobilization before removing the animals from their enclosures. Body temperature, arterial haemoglobin saturation and pulse rate were measured. The time from injection to induction (recumbency and absence of voluntary movement), total anaesthetic and recovery times (with or without atipamezole) were recorded. Results Immobilization occurred within 5 minutes after darting in most animals. Early handling of the chimpanzees often resulted in arousal and required further doses of ketamine IM. Most animals were hypoxaemic and hypothermic. Occasionally, bradycardia was observed. Atipamezole resulted in an acceptable quality of recovery 10 minutes after IM injection. The duration of immobilization varied widely when no antagonist was administered. Conclusions and clinical relevance The combination detomidine (60 μg kg?1) and ketamine (5–6 mg kg?1) can be used for the immobilization of chimpanzees for non‐ to minimally invasive procedures. A period of 15 minutes should be allowed before handling to avoid unwanted arousal. Oxygen administration is recommended to reduce hypoxaemia. Administration of atipamezole is justified to hasten recovery.  相似文献   

11.
ObjectiveTo investigate MK-467 as part of premedication in horses anaesthetized with isoflurane.Study designExperimental, crossover study with a 14 day wash-out period.AnimalsSeven healthy horses.MethodsThe horses received either detomidine (20 μg kg−1 IV) and butorphanol (20 μg kg−1 IV) alone (DET) or with MK-467 (200 μg kg−1 IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg−1) and midazolam (0.06 mg kg−1) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO2) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (PaO2/FiO2) and tissue oxygen delivery (DO2) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05.ResultsThe induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and PaO2/FiO2 (40 minutes after induction), DO2 and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller.Conclusions and clinical relevanceMK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP.  相似文献   

12.
ObjectiveTo evaluate the cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs.Study designExperimental, blinded, randomized, crossover study.AnimalsSix mixed breed dogs (two males and four females) weighing 10 ± 4 kg.MethodsThe animals were randomly divided into four treatments: D (10 μg kg?1 of dexmedetomidine), DM (dexmedetomidine 10 μg kg?1 and methadone 0.5 mg kg?1); DMO (dexmedetomidine 10 μg kg?1 and morphine 0.5 mg kg?1), and DT (dexmedetomidine 10 μg kg?1 and tramadol 2 mg kg?1). The combinations were administered intramuscularly in all treatments. The variables evaluated were heart rate (HR), respiratory rate (fR), rectal temperature (RT), systolic arterial pressure (SAP), sedation scale and pedal withdrawal reflex. These variables were measured at T0 (immediately before the administration of the protocol) and every 15 minutes thereafter until T105.ResultsA decrease in HR and fR occurred in all the treatments compared with T0, but no significant difference was observed between the treatments. The RT decreased from T45 onward in all the treatments. The SAP did not show a difference between the treatments, but in the DT treatment, the SAP was lower at T30 and T45 compared with T0. The D treatment had lower scores of sedation at T15 to T75 compared with the other treatments, and the DMO and DM treatments showed higher scores at T60 and T75 compared with DT.Conclusions and clinical relevanceThe treatments with morphine and methadone added to the dexmedetomidine showed higher sedation scores than the control treatment and the treatment with tramadol added to the dexmedetomidine showed no relevant differences in any of the variables evaluated in the study.  相似文献   

13.
ObjectiveTo evaluate a combination of acepromazine, dexmedetomidine and ketamine (ADK) on induction and recovery from anaesthesia, and on physiological parameters in hares undergoing non‐invasive procedures.Study designProspective clinical study.AnimalsSixteen European hares (Lepus europaeus), seven males and nine females, aged (mean ± SD) 3.25 ± 0.9 months and weight 2.1 ± 0.6 kg.MethodsAcepromazine 1% (A), dexmedetomidine 0.05% (D) and ketamine 5% (K) were mixed and given intramuscularly (IM) at 0.25 mL kg?1, representing 10 mg kg?1 K, 0.25 mg kg?1 A, 12.5 μg kg?1 D. If the righting reflex was present after four minutes, a second injection of 0.15 mL kg?1 (6 mg kg?1 K, 0.15 mg kg?1 A, 7.5 μg kg?1 D) was administered IM. Surgical anaesthesia was judged as present when righting, palpebral, ear‐pinch and pedal withdrawal reflexes were absent. Anaesthetized hares were tagged, and underwent blood sampling and ocular ultrasound examination. Physiological parameters were recorded every ten minutes, and were compared by Kruskal‐Wallis tests.ResultsA single dose induced loss of righting reflex in 11/16 (69%) hares within four minutes; the second dose was effective in the remaining hares. Ten minutes after the loss of the righting reflex, a surgical plane of anaesthesia was present in all hares. Sleep time to regaining righting reflex was 34 ± 11 (range 21–62) minutes and recovery was calm. Although there were some statistical differences over time, cardiovascular parameters remained within an acceptable range but there was respiratory depression and hares were hypoxemic.Conclusions and clinical relevanceThe ADK mixture produced a smooth and rapid induction of anaesthesia, a low incidence of untoward side effects and full recovery after four hours. Supplementary oxygen might be advisable if a deeper plane of anaesthesia was required. Chemical restraint was adequate to perform non‐invasive procedures.  相似文献   

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15.
ObjectiveTo study the anaesthetic and cardiorespiratory effects of intramuscular (IM) administration of different combinations of romifidine and ketamine in cats.Study designProspective, randomized, cross-over experiment.AnimalsSeven healthy adult cats weighing (mean ± SD) 3.4 ± 0.7 kg and aged 4.6 ± 3.2 years.MethodsAnimals received romifidine 100 μg kg?1 with ketamine 7.5 (R100/K7.5) and 10 mg kg?1 (R100/K10), romifidine 200 μg kg?1 with ketamine 5 (R200/K5), 7.5 (R200/K7.5) and 10 mg kg?1 (R200/K10) by IM injection. The time required to perform orotracheal intubation (IT) was measured and the ease of intubation assessed. The onset of anaesthesia (OA), duration of anaesthesia (DA) and anaesthesia recovery times (AR) were measured. Analgesia and muscle relaxation scores were recorded every 5 minutes for 60 minutes after OA. Heart rate, systolic arterial pressure, arterial haemoglobin saturation, respiratory rate, end-tidal carbon dioxide and oesophageal temperature were also measured.ResultsThe IT, OA and DA were not significantly different between the treatments. The analgesia and muscle relaxation scores were similar between all treatments at most time points. The cardiorespiratory variables were not significantly different between the treatments in most cases. The adverse effects were dose dependent and similar to those previously described for other combinations of α2-agonists and ketamine.Conclusions and clinical relevanceAnaesthesia produced by the studied combinations of romifidine and ketamine may only be reliable when conducting brief and noninvasive procedures in cats. The OA times were slower and the DA shorter than those reported for other alpha-2 agonists combined with ketamine. A dose-related increase in the intensity of the anaesthetic effects could not be demonstrated in this study.  相似文献   

16.
ObjectiveTo assess the differences in the pharmacokinetic profiles of S-ketamine, R-ketamine and their metabolites, S-norketamine and R-norketamine, and to measure relevant physiologic variables after intravenous administration of racemic (RS) ketamine or S-ketamine alone in Beagle dogs sedated with medetomidine.Study designExperimental, blinded and randomized crossover study.AnimalsA total of six (three female and three male) adult Beagle dogs.MethodsMedetomidine (450 μg m–2) was administered intramuscularly, followed by either S-ketamine (2 mg kg–1) or RS-ketamine (4 mg kg–1) 20 minutes later, both administered intravenously. Blood samples were collected before medetomidine administration and at multiple time points 1–900 minutes following the ketamine administration. Plasma samples were analysed using liquid chromatography–tandem mass spectrometry. Heart rate, respiratory rate, noninvasive blood pressure, haemoglobin saturation with oxygen and body temperature were measured at baseline, before ketamine administration, and 1, 2, 5, 10, 15, 20 and 30 minutes after ketamine administration. All cardiovascular variables, blood glucose, haemoglobin and lactate concentrations were analysed using different linear mixed effects models; the significance was set at p < 0.05.ResultsS-ketamine showed a two-compartment kinetic profile; no statistically significant differences were observed between its concentrations or in the calculated pharmacokinetic parameters following S- or RS-ketamine. When the racemic mixture was administered, no differences were detected between R- and S-ketamine concentrations, but the area under the curve (AUC) for R-norketamine was significantly lower than that for S-norketamine. Clinically relevant physiologic variables did not show statistically significant differences following the administration of the racemic mixture or of S-ketamine alone.Conclusions and clinical relevanceThis study performed in dogs showed that RS-ketamine and S-ketamine combined with medetomidine showed enantioselective pharmacokinetics as S- and R-norketamine AUCs were different, but S-ketamine levels were identical.  相似文献   

17.
ObjectiveTo determine the dose of naltrexone necessary to fully antagonize a high dose of remifentanil in cats.Study designProspective experimental study.AnimalsSix healthy adult cats weighing 4.9 ± 0.7 kg.MethodsIn a first phase, remifentanil (200 μg kg?1 followed by 60 μg kg?1 minute?1) was administered intravenously to two cats, causing an increase in locomotor activity. Naltrexone (100 μg kg?1) was then administered intravenously every minute until the increase in locomotor activity had been reversed. In a second phase, six cats were used. Baseline thermal threshold was determined, naltrexone (600 μg kg?1) was administered intravenously and 30 minutes later thermal threshold determination repeated. Remifentanil (200 μg kg?1 followed by 60 μg kg?1 minute?1) was administered intravenously and thermal threshold determination repeated at 60, 120, 180, and/or 240 minutes after naltrexone administration. Thermal threshold determinations were started shortly after the start of the continuous rate infusion (CRI) of remifentanil and this CRI was discontinued immediately after thermal threshold determination. If an increase in thermal threshold was found, naltrexone administration was repeated at decreasing intervals in the next experiment (all cats were not used for all dosing intervals). Experiments were repeated until a naltrexone dosing interval was found that prevented increases in thermal threshold for 4 hours in all six cats.ResultsIn the first phase, both cats became severely dysphoric following remifentanil administration. A cumulative naltrexone dose of 300 μg kg?1 was necessary to restore normal behavior in both cats. In the second phase, hourly administration of naltrexone (600 μg kg?1) prevented increases in thermal threshold associated with hourly administration of remifentanil for 4 hours. Less frequent administration did not prevent increases in thermal threshold consistently.ConclusionsHourly administration of naltrexone (600 μg kg?1) antagonizes the behavioral and antinociceptive effects of a high dose of remifentanil in cats.Clinical relevanceNaltrexone may be useful for the treatment of opioid overdose in cats.  相似文献   

18.
ObjectiveTo develop a safe and effective immobilization protocol in rhesus monkeys, which is not based on dissociative anaesthetic agent.Study designProspective, randomised, experimental trial.AnimalsTwenty rhesus monkeys, weighing 2.6–8.0 kg, 1–3 years of age, of both sexes.MethodsThe monkeys received 50 μg kg?1 medetomidine, 0.25 mg kg?1 midazolam and 5 μg kg?1 fentanyl with 150 IU hyaluronidase intramuscularly (IM). The animals were closely observed for behavioural changes and reaction to sound stimulus. Pulse rate and oxygen saturation of haemoglobin (SpO2) were monitored every 5 minutes, for 20 minutes. After this period, 250 μg kg?1 atipamezole or a placebo was administered IM and behavioural changes were closely observed.ResultsFull immobilization was observed after mean 269 ± SD 116 seconds. Ten minutes after injection mean arterial oxygen saturation of haemoglobin was 94 ± 4%, but did not fall significantly further. The median pulse rate was 116 beats minute?1 5 minutes after the administration of the drug. This level further decreased to a median level of 108 beats minute?1 20 minutes after the drug's administration. The median time to recover from immobilization was significantly shorter after atipamezole administration when compared to placebo (2.7 versus 55 minutes). All animals awoke smoothly and no side effects such as vomiting or agitation were observed.ConclusionsShort term and reversible pharmacological immobilization was achieved using combination of midazolam, medetomidine, and fentanyl.Clinical relevanceThe present study demonstrates that 20-minute pharmacological immobilization with a combination of midazolam, medetomidine, and fentanyl is feasible in rhesus monkeys with minimal effect on heart rate.  相似文献   

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20.
ObjectiveTo evaluate the perioperative opioid-sparing effect of a medetomidine (MED) infusion compared to a saline (SAL) infusion in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery.Study designRandomized, partially blinded, clinical study.AnimalsA total of 44 client-owned adult dogs.MethodsAll dogs were administered a 1 μg kg–1 MED loading dose, followed by a 1.7 μg kg–1 hour–1 constant rate infusion (CRI) intravenously or equivalent volumes of SAL. Infusions were started 10–15 minutes before surgical incision and continued throughout the surgical procedure. All dogs were administered a standardized anaesthetic and analgesic protocol (including a ketamine CRI). Multiparametric monitoring, including invasive arterial blood pressure, was performed. A trained investigator, unaware of the treatment, performed pain scores for 4 hours postoperatively. Rescue analgesia consisted of fentanyl administered intraoperatively and methadone postoperatively. Data were tested for normality and analysed with Fisher’s exact test, Mann–Whitney U-test, analysis of variance and Kaplan–Meier survival analysis. Data are shown as median (interquartile range) and p-value was set at < 0.05.ResultsThe total dose of fentanyl was significantly lower with MED 0 (0–0.8) μg kg–1 hour–1 compared to SAL 3 (1.8–5.3) μg kg–1 hour–1 (p = 0.004). In the MED group, one dog compared to 12 dogs in the SAL group required a fentanyl CRI (p = 0.001). There were no statistically significant differences between groups regarding the total dose of methadone administered.Conclusions and clinical relevanceThe addition of a low-dose medetomidine CRI to the anaesthetic protocol decreased the need for a fentanyl CRI in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery during administration of a ketamine CRI.  相似文献   

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