Reversal of xylazine-induced sedation in dairy calves with atipamezole: A field trial

Dairy calves immobilized with xylazine (XYL) were given atipamezole-HCl (ATI) at different XYL:ATI dose ratios (w/w) for reversal and the antagonistic effect of xylazine was evaluated. Control animals received saline for comparison. Intramuscular administration of xylazine (0.139–0.357 mg/kg) induced sedation with complete immobilization in all animals (n=195) and there were no spontaneous recoveries before injection of atipamezole or saline. Atipamezole was given 10–81 min and saline 25 min after xylazine administration. Intramuscular administration of atipamezole at XYL:ATI dose ratios of 5:2 (n=11), 10:3 (n=21), 4:1 (n=21) and 5:1 (n=25) effectively antagonized the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 6.09 (3.12), 5.15 (2.87), 6.35 (2.54) and 7.86 (3.11) min, respectively. The mean time to standing for control animals (n=11) was 94.1 (3.0) min. Intravenous administration of atipamezole at XYL:ATI dose ratios of 10:3 (n=7), 4:1 (n=33), 5:1 (n=16), 8:1 (n=27) and 10:1 (n=9) rapidly reversed the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 0.98 (0.22), 1.32 (0.48), 1.09 (0.34), 1.39 (0.52) and 1.60 (0.69) min, respectively. The mean time to standing for control animals (n=14) was 88.1 (13.1) min.Animals given high doses of atipamezole (dose ratio groups 5:2 intramuscularly, 10:3 intravenously and 4:1 intravenously) showed signs of excitement while in animals given low doses of atipamezole (dose ratio groups 5:1 intramuscularly and 10:1 intravenously) resedation and relapse into recumbency occurred. Medium doses of atipamezole (dose ratio groups 10:3 intramuscularly, 4:1 intramuscularly, 5:1 intravenously and 8:1 intravenously) did not cause any undesirable side-effects or resedation, and can be recommended for reversal of xylazine-induced sedation in dairy calvesAbbreviations ATI atipamezole-HCl - BW body weight - IM intramuscular - IV intravenous - SD standard deviation - XYL xylazine     

Xylazine-induced sedation in axis deer (Axis axis) and its reversal by atipamezole

Eight free-ranging axis deer (Axis axis) were captured in drive nets and injected with xylazine (3.4±0.1 mg/kg; mean ±SEM) intramuscularly using a hand-held syringe. Xylazine induced complete immobilization and sedation in three animals, heavy sedation in three, and moderate sedation in two. The mean induction time was 10.4±1.0 min. The mean rectal temperature, heart and respiratory rates of immobilized animals were 39.2±0.4°C, 75.5±6.5 beats/min and 62.1±4.2 breaths/min, respectively.All the animals were given atipamezole intravenously for reversal. The mean time from injection of xylazine to administration of atipamezole was 37.8±4.6 min. A dose ratio (w/w) for xylazine:atipamezole-HCl of 10:1 was used. The mean time from injection of atipamezole to mobility was 2.41±0.58 min.Atipamezole given intravenously effectively antagonized xylazine-induced sedation in axis deer. Only one animal showed signs of overalertness after reversal and no cases of resedation were observed.Abbreviations i.m. intramuscular(ly) - i.v. intravenous(ly) - SEM standard error of the mean     

Comparison of intranasal and intramuscular ketamine‐midazolam combination in cats

ObjectiveThe aim of the present study was to compare intranasal (INS) and intramuscular (IM) routes of administration of a ketamine-midazolam combination in cats.Study designRandomized block design.AnimalsTwelve healthy mixed breed cats (six males and six females).MethodsThe drug combination was ketamine (14 mg kg⁻¹) and midazolam (0.5 mg kg⁻¹). In the IM group, drugs were injected into quadratus femoris muscle; in the INS. group, the combination dropped equally into the two nostrils. Pulse and respiratory rates, peripheral haemoglobin oxygen saturation (SpO₂) and rectal temperature were monitored before and at intervals after drug administration. Time to onset and duration of sedation and, during recovery to head up, sternal recumbency and recovery were recorded.ResultsThere were no significant differences between the groups in any time measured except for recovery to sternal recumbency, where time was lower in the INS than in the IM (p = 0.034). Respiratory rate was greater in the INS than in the IM group (p = 0.029), but there was no difference between groups in other physiological parameters. In both groups SpO₂ was low before and fell further during sedation.ConclusionsThe results substantiated that INS ketamine-midazolam can produce effective sedation in cats.Clinical relevanceIntranasal (INS) administration of ketamine-midazolam is atraumatic, and its use may avoid the pain of injection of ketamine combinations when this drug is used to induce sedation in cats.     

Evaluation of the clinical efficacy and safety of dexmedetomidine or medetomidine in cats and their reversal with atipamezole

OBJECTIVE: To evaluate and compare the clinical effects of dexmedetomidine (DEX) and medetomidine (MED) in cats, and their reversal with atipamezole (ATI). Study design Prospective blinded randomized multi-centre clinical trial. Animals One hundred and twenty client-owned cats. METHODS: Cats were randomly allocated to receive a single intramuscular (IM) injection of either DEX (0.04 mg kg(-1), n = 62) or MED (0.08 mg kg(-1), n = 58) for minor procedures requiring sedation and analgesia. Afterwards, ATI (0.2 mg kg(-1)) was administered IM to half the cats, randomly assigned. Prior to, during and after the procedure the sedative, analgesic and cardiorespiratory effects and body temperature were assessed. RESULTS: Dexmedetomidine and MED produced clinically and statistically comparable effects. The intended procedure(s) could be performed in over 90% of cats. Sedation and analgesia were apparent within 5 minutes, peak effects were observed at approximately 30 minutes and spontaneous recovery occurred by 180 minutes of injection. Heart and respiratory rate and body temperature decreased significantly over time and had not returned to baseline values 180 minutes after administration. ATI administration completely reversed the sedative and analgesic effects, returned the heart rate to normal and prevented any further reductions in respiratory rate and body temperature in both DEX- and MED-treated cats. The reporting of adverse events was low and the most commonly observed event was vomiting (7%). No serious adverse events or concerns regarding safety were reported. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine (0.04 mg kg(-1)) produced comparable sedative and analgesic effects to MED (0.08 mg kg(-1)) in cats. DEX produced adequate sedation and analgesia for radiography, grooming, dental care and lancing of abscesses. ATI fully reversed the clinical effects of DEX.     

Comparison of sedation and mechanical antinociception induced by intravenous administration of acepromazine and four dose rates of dexmedetomidine in donkeys

Objective

To assess and compare the sedative and antinociceptive effects of four dosages of dexmedetomidine in donkeys.

Comparison of the sedative effects of intranasal or intramuscular dexmedetomidine at low doses in healthy dogs: a randomized clinical trial

ObjectiveTo compare the sedative effects of dexmedetomidine administered either intranasally or intramuscularly to healthy dogs.Study designProspective, randomized, blinded, clinical trial.AnimalsA group of 16 client-owned healthy dogs.MethodsDogs were randomly allocated to one of two groups that were administered dexmedetomidine 5 μg kg^–1 via either the intranasal route (IN_Dex), through a mucosal atomization device in one nostril, or the intramuscular route (IM_Dex), into the epaxial muscles. Ease of intranasal administration, sedation score, onset of sedation, cardiopulmonary variables, mechanical nociceptive thresholds (MNTs) and response to venous catheterization were recorded at 0 (baseline), 5, 10, 15, 20, 25, 30, 35, 40 and 45 minutes, following drug administration. Data were compared with the one-way anova, Mann-Whitney U test, and chi-square test, where appropriate.ResultsGroups were not different for age, sex, weight, body condition score or temperament. Sedation scores, MNTs and response to intravenous catheter placement were not different when dexmedetomidine was administered by either route (p = 0.691; p = 0.630 and p = 0.435, respectively). Onset of sedation was not different between groups IN_Dex and IM_Dex reaching a score of 4.2 ± 0.9 and 5.5 ± 1.2 at 9 ± 5 and 8 ± 4 minutes, respectively (p = 0.467). The highest sedation score was achieved at 30 and 35 minutes and sedation scores were 9.7 ± 2.0 and 9.5 ± 2.3 in groups IN_Dex and IM_Dex, respectively (p = 0.799). Respiratory rate was higher in group IN_Dex (p = 0.014), while there were no differences between routes in heart rate (p = 0.275), systolic (p = 0.957), diastolic (p = 0.837) or mean arterial pressure (p = 0.921).Conclusions and clinical relevanceIntranasal administration of dexmedetomidine at 5 μg kg^–1 provides effective sedation in healthy dogs.     

The impact of MK‐467 on plasma drug concentrations,sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal

The effect of MK‐467, a peripheral α₂‐adrenoceptor antagonist, on plasma drug concentrations, sedation and cardiopulmonary changes induced by intramuscular (IM) medetomidine was investigated in eight sheep. Additionally, the interactions with atipamezole (ATI) used for reversal were also evaluated. Each animal was treated four times in a randomized prospective crossover design with 2‐week washout periods. Medetomidine (MED) 30 μg/kg alone or combined in the same syringe with MK‐467 300 μg/kg (MMK) was injected intramuscular, followed by ATI 150 μg/kg (MED + ATI and MMK + ATI) or saline intramuscular 30 min later. Plasma was analysed for drug concentrations, and sedation was subjectively assessed with a visual analogue scale. Systemic haemodynamics and blood gases were measured before treatments and at intervals thereafter. With MK‐467, medetomidine plasma concentrations were threefold higher prior to ATI, which was associated with more profound sedation and shorter onset. No significant differences were observed in early cardiopulmonary changes between treatments. Atipamezole reversed the medetomidine‐related cardiopulmonary changes after both treatments. Sedation scores decreased more rapidly when MK‐467 was included. In this study, MK‐467 appeared to have a pronounced effect on the plasma concentration and central effects of medetomidine, with minor cardiopulmonary improvement.     

Effects of subcutaneous alfaxalone alone and in combination with dexmedetomidine and buprenorphine in guinea pigs (Cavia porcellus)

Objective

To characterize alfaxalone administered subcutaneously (SC) in guinea pigs, both alone and in combination with dexmedetomidine and buprenorphine.

Comparison of intraocular pressure and pupil diameter after sedation with either acepromazine or dexmedetomidine in healthy dogs

Objective

To compare intraocular pressure (IOP) and pupillary diameter (PD) following intravenous (IV) administration of dexmedetomidine and acepromazine in dogs.

Effects of intramuscular alfaxalone alone or in combination with diazepam in swine

ObjectiveTo describe the use of intramuscular (IM) premedication with alfaxalone alone or in combination with diazepam in pigs.Study designRandomised‐controlled trial.AnimalsTwelve healthy 2 month‐old Landrace x Large White pigs weighing 21.3 ± 2.4 kg.MethodsAnimals were distributed randomly into two groups: group A (n = 6) 5 mg kg^?1 of IM alfaxalone; and group AD (n = 6) 5 mg kg^?1 of IM alfaxalone + 0.5 mg kg^?1 of IM diazepam mixed in the same syringe. The total volume of injectate was standardized at 14 mL by dilution in 0.9% sodium chloride. Pain on injection, the degree of sedation and the quality of and time to induction of recumbency were evaluated. Once pigs were recumbent, reflexes were evaluated. Pulse and respiratory rates and arterial oxygen saturation were recorded at 5 and 10 minutes after drug administration. Pigs were then moved to another room for subsequent anaesthesia.ResultsTwo animals of group A and one of group AD showed slight pain on drug injection. Time to lateral recumbency (in seconds) was shorter in group AD (mean 203 ± SD 45 range 140–260) than group A (302 ± 75, range 220–420; p < 0.05). In group AD sedation was deeper, and on recumbency there was better muscle relaxation. When moved for anaesthesia, two pigs in Group A showed slight resistance but did not vocalize. There were no differences in physiologic measurements between groups, although in both groups, respiratory rate was significantly lower at ten compared with five minutes post drug injection. There was no apneoa.Conclusions and clinical relevanceIM administration of alfaxalone combined with diazepam resulted in a rapid onset of recumbency and deep sedation, with minimal side effects. The combination might be useful for premedication, but volume of injectate will limit its use to small pigs.     

Sedative effects of two doses of alfaxalone in combination with methadone and a low dose of dexmedetomidine in healthy Beagles

ObjectiveTo evaluate the sedative effects of two doses of alfaxalone when added to a combination of dexmedetomidine and methadone injected intramuscularly (IM) in healthy Beagles.Study designRandomized, blinded, crossover, experimental study.AnimalsA group of six adult Beagles.MethodsDogs were sedated on three different occasions with IM dexmedetomidine (3 μg kg^–1) and methadone (0.3 mg kg^–1) combined with two doses of alfaxalone (0.5 and 1 mg kg^–1; A0.5 and A1, respectively) or saline (A0). Quality of sedation, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35 and 45 minutes. Pulse and respiratory rates, oxygen saturation of haemoglobin (SpO₂) and noninvasive blood pressure (NIBP) were recorded every 5 minutes. Onset of sedation and duration of recumbency, response to venous catheterization and recovery quality were assessed. Physiological variables (analysis of variance) were analysed between treatments and within treatments compared with baseline (Student t test). Nonparametric data were analysed using Friedman and Cochran’s Q tests. Significance was p < 0.05.ResultsSedation scores were significantly higher when alfaxalone was co-administered (area under the curve; p = 0.024, A0.5; p = 0.019, A1), with no differences between doses. Onset of sedation was similar, but duration of recumbency was longer in A0.5 than in A0 [median (minimum–maximum), 43 (35–54) versus 30 (20–47) minutes, p = 0.018], but not in A1. Response to venous catheterization and tail clamping, and quality of recovery (acceptable) presented no differences between treatments. A decrease in all physiological variables (compared with baseline) was observed, except for NIBP, with no differences between treatments. All dogs required oxygen supplementation due to reduced SpO₂.Conclusions and clinical relevanceAdding alfaxalone to methadone and dexmedetomidine enhanced sedation and duration of recumbency. Although cardiopulmonary depression was limited, oxygen supplementation is advisable.     

Effects of methadone, alone or in combination with acepromazine or xylazine, on sedation and physiologic values in dogs

ObjectiveTo evaluate the effects of methadone, administered alone or in combination with acepromazine or xylazine, on sedation and on physiologic values in dogs.Study designRandomized cross-over design.AnimalsSix adult healthy mixed-breed dogs weighing 13.5 ± 4.9 kg.MethodsDogs were injected intramuscularly with physiologic saline (Control), or methadone (0.5mg kg⁻¹) or acepromazine (0.1 mg kg⁻¹) or xylazine (1.0 mg kg⁻¹), or acepromazine (0.05 mg kg⁻¹) plus methadone (0.5 mg kg⁻¹) or xylazine (0.5 mg kg⁻¹) plus methadone (0.5 mg kg⁻¹) in a randomized cross-over design, with at least 1-week intervals. Sedation, pulse rate, indirect systolic arterial pressure, respiratory rate (RR), body temperature and pedal withdrawal reflex were evaluated before and at 15-minute intervals for 90 minutes after treatment.ResultsSedation was greater in dogs receiving xylazine alone, xylazine plus methadone and acepromazine plus methadone. Peak sedative effect occurred within 30 minutes of treatment administration. Pulse rate was lower in dogs that received xylazine either alone or with methadone during most of the study. Systolic arterial pressure decreased only in dogs receiving acepromazine alone. When methadone was administered alone, RR was higher than in other treatments during most of the study and a high prevalence of panting was observed. In all treatments body temperature decreased, this effect being more pronounced in dogs receiving methadone alone or in combination with acepromazine. Pedal withdrawal reflex was absent in four dogs receiving methadone plus xylazine but not in any dog in the remaining treatments.Conclusions and clinical relevanceMethadone alone produces mild sedation and a high prevalence of panting. Greater sedation was achieved when methadone was used in combination with acepromazine or xylazine. The combination xylazine–methadone appears to result in better analgesia than xylazine administered alone. Both combinations of methadone/sedative were considered effective for premedication in dogs.     

Sedative and analgesic effects of two subanaesthetic doses of ketamine in combination with methadone and a low dose of dexmedetomidine in healthy dogs

ObjectiveTo evaluate the sedative, analgesic and recovery characteristics of two subanaesthetic ketamine doses in combination with dexmedetomidine and methadone for intramuscular sedation in healthy Beagles.Study designRandomized, blinded, crossover, experimental study.AnimalsSix healthy adult Beagles.MethodsDogs were randomly given three treatments: dexmedetomidine (3 μg kg^–1) and methadone (0.3 mg kg^–1) combined with ketamine at 1 and 2 mg kg^–1 (K1 and K2, respectively) or saline (K0), intramuscularly. Sedation score, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35, and 45 minutes posttreatment. Pulse rate (PR), respiratory rate, oxygen haemoglobin saturation and noninvasive blood pressure were also recorded at baseline and every 5 minutes until 45 minutes posttreatment. Onset and duration of recumbency, response to venous catheterization and recovery quality were also assessed. Sedation and physiological variables were compared between treatments and within treatments compared to baseline (analysis of variance). Nonparametric data were analysed with the Friedman and Cochran’s Q tests; p < 0.050.ResultsIncreased sedation was found at 15 (K0 and K1), 25 (all treatments) and 35 (K1) minutes compared with baseline. Sedation score, onset (3–12 minutes) and duration of recumbency (29–51 minutes) were similar between treatments. Recovery quality was considered acceptable in all cases. Response to tail clamping was inconsistent within treatments with no differences between them. None of the dogs responded to venous catheterization. There were no differences between treatments in physiological variables, except for PR which was higher in K2 than in K0. Oxygen supplementation was required in five and three dogs administered saline and ketamine, respectively.Conclusions and clinical relevanceThe addition of 1 or 2 mg kg^–1 of ketamine to methadone and dexmedetomidine combination did not enhance sedation or antinociception in healthy dogs. Recovery quality was unaffected.     

Effect of MK‐467 on organ blood flow parameters detected by contrast‐enhanced ultrasound in dogs treated with dexmedetomidine

ObjectiveTo evaluate the dexmedetomidine‐induced reduction in organ blood flow with quantitative contrast‐enhanced ultrasound (CEUS) method and to observe the influence of MK‐467 on such reduction.Study designRandomized cross‐over study.AnimalsSix adult purpose‐bred laboratory beagle dogs (mean body weight 15.3 ± 1.9 kg).MethodsContrast‐enhanced ultrasound was performed on six conscious healthy laboratory beagles. The animals on separate occasions underwent three treatments: awake without any medication (CTRL), dexmedetomidine 10 μg kg^?1 (DEX) and DEX + MK‐467 500 μg kg^?1 (DMK) intravenously (IV). The kidney (10–15 minutes post‐treatment), spleen (25–30 minutes post‐treatment), small intestine (40–45 minutes post‐treatment) and liver (50–55 minutes post‐treatment) were examined with CEUS. A time curve was generated and the following perfusion parameters were analysed: arrival time (AT), time to peak from injection (TTPinj), peak intensity (PI) and wash‐in rate (Wi). In addition to CEUS, renal glomerular filtration rate was indirectly estimated by the rate of iohexol elimination.ResultsAT and TTPinj were significantly higher for DEX than for CTRL in all studied organs. The same parameters were significantly higher for DEX than for DMK in the kidney, spleen and small intestine. PI was significantly lower for DEX than for CTRL or DMK in the kidney. Wi was significantly lower for DEX than for CTRL or DMK in the kidney and significantly lower than for CTRL only in the small intestine. Plasma concentration of iohexol was significantly higher after DEX than CTRL administration.ConclusionsContrast‐enhanced ultrasound was effective in detecting DEX‐induced changes in blood flow. MK‐467 attenuated these changes.Clinical relevanceClinicians should consider the effects of the sedation protocol when performing CEUS. Addition of MK‐467 might beneficially impact the haemodynamic function of sedation with alpha‐2 adrenoceptor agonists.     

Anesthesia induced by administration of xylazine hydrochloride alone or in combination with ketamine hydrochloride and reversal by administration of yohimbine hydrochloride in captive Axis deer (Axis axis)

OBJECTIVE: To determine the anesthetic dose and cardiopulmonary effects of xylazine hydrochloride when used alone or in combination with ketamine hydrochloride and evaluate the efficacy of yohimbine hydrochloride to reverse anesthetic effects in captive Axis deer. ANIMALS: 35 adult (10 males and 25 females) Axis deer (Axis axis). PROCEDURES: All deer were anesthetized by IM administration of xylazine (3.5 mg/kg; experiment 1), a combination of ketamine and xylazine (1.25 and 1.5 mg/kg, respectively; experiment 2), or another combination of ketamine and xylazine (2.5 and 0.5 mg/kg, respectively; experiment 3). In addition, female deer were also anesthetized by IM administration of a third combination of ketamine and xylazine (1.5 and 1 mg/kg, respectively; experiment 4). Ten to 40 minutes after induction, anesthesia was reversed by IV administration of yohimbine (5, 8, or 10 mg). RESULTS: In male deer, experiment 3 yielded the most rapid induction of anesthesia. In females, experiment 4 yielded the best induction of anesthesia without adverse effects. All doses of yohimbine reversed anesthesia. Duration of anesthesia before administration of yohimbine had no effect on recovery time. CONCLUSIONS AND CLINICAL RELEVANCE: A combination of ketamine and xylazine can be used to induce anesthesia in Axis deer. Furthermore, anesthetic effects can be reversed by administration of yohimbine.