Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain.

Enzymatic digestion of the extracellular matrix with chondroitinase-ABC reinstates juvenile-like plasticity in the adult cortex as it also disassembles the perineuronal nets (PNNs). The disadvantage of the enzyme is that it must be applied intracerebrally and it degrades the ECM for several weeks. Here, we provide two minimally invasive and transient protocols for microglia-enabled PNN disassembly in mouse cortex: repeated treatment with ketamine-xylazine-acepromazine (KXA) anesthesia and 60-Hz light entrainment. We also discuss how to analyze PNNs within microglial endosomes-lysosomes. For complete details on the use and execution of this protocol, please refer to Venturino et al. (2021).

Intraocular pressure and pupil diameter in healthy cats anesthetized with isoflurane and pre-medicated with isolated acepromazine or in combination with tramadol / [Pressão intraocular e diâmetro pupilar em gatos saudáveis anestesiados com isoflurano e pré-medicados com acepromazina isolada ou em combinação com tramadol]

The objective of this study was to determine changes on intraocular pressure (IOP) and pupil diameter (PD) in healthy cats anesthetized with isoflurane, and premedicated with acepromazine alone or in combination with tramadol. Thirty cats were allocated in two groups (n=15/each) and were treated with acepromazine (AG) or acepromazine/tramadol (ATG). PD and IOP were assessed before and following 30 (PM1), and 40 minutes (PM2) of treatments. Anesthesia was induced with propofol, and IOP and DP were recorded (A10) at 10 minute intervals until the end of anesthesia (A40). IOP decreased in AG and ATG, when comparing baseline with PM1. IOP decreased only in AG, in comparisons between baseline and PM2. During anesthesia, IOP did not change within and between groups. Comparisons between baseline with those recorded at PM1 and 2 showed that PD increased in the ATG. During anesthesia, PD decreased significantly in AG and ATG. Both protocols maintained the IOP within the reference range to perform corneal or intraocular surgery in healthy cats but did not sustain pre-anesthetic pupil dilation observed in ATG.(AU)

O objetivo do presente artigo é determinar possíveis alterações na pressão intraocular (PIO) e no diâmetro pupilar (DP) em gatos saudáveis anestesiados com isoflurano e pré-medicados com acepromazina isolada ou em combinação com acepromazina/tramadol. Trinta gatos saudáveis foram distribuídos aleatoriamente em dois grupos (n=15/cada) e tratados com acepromazina (GA) ou acepromazina/tramadol (GAT). DP e PIO foram avaliadas antes (basal) e após 30 (PM1) e 40 minutos (PM2) dos tratamentos. A anestesia foi induzida com propofol, e a PIO e o DP foram registrados (A10) a cada 10 minutos até o final da anestesia com isoflurano (A40). Ao se compararem os valores obtidos no basal com PM1, a PIO diminuiu em GA e GAT; com PM2, a PIO reduziu apenas no GA. Durante a anestesia, a PIO não diferiu dentro e entre os grupos. Comparações entre os valores basais e os registrados em PM1 e em PM2 mostraram que a DP aumentou significativamente no GAT. Durante a anestesia, o DP diminuiu significativamente em GA e GAT. Ambos os protocolos mantêm a PIO dentro dos valores de referência para realizar cirurgias corneanas ou intraoculares em gatos saudáveis, mas não sustentam a dilatação pupilar pré-anestésica observada em GAT.(AU)

Hemodynamic, respiratory and sedative effects of progressively increasing doses of acepromazine in conscious dogs.

OBJECTIVE: To evaluate the effects of progressively increasing doses of acepromazine on cardiopulmonary variables and sedation in conscious dogs. STUDY DESIGN: Prospective, experimental study. ANIMALS: A group of six healthy, adult, mixed-breed dogs weighing 16.5 ± 5.0 kg (mean ± standard deviation). METHODS: Dogs were instrumented with thermodilution and arterial catheters for evaluation of hemodynamics and arterial blood gases. On a single occasion, acepromazine was administered intravenously to each dog at 10, 15, 25 and 50 µg kg-1 at 20 minute intervals, resulting in cumulative acepromazine doses of 10 µg kg-1 (ACP10), 25 µg kg-1 (ACP25), 50 µg kg-1 (ACP50) and 100 µg kg-1 (ACP100). Hemodynamic data and sedation scores were recorded before (baseline) and 20 minutes after each acepromazine dose. RESULTS: Compared with baseline, all acepromazine doses significantly decreased stroke index (SI), mean arterial pressure (MAP) and arterial oxygen content (CaO2) with maximum decreases of 16%, 17% and 21%, respectively. Cardiac index (CI) decreased by up to 19% but not significantly. Decreases of 26-38% were recorded for oxygen delivery index (DO2I), with significant differences for ACP50 and ACP100. Systemic vascular resistance index (SVRI) and heart rate did not change significantly. No significant difference was found among acepromazine doses for hemodynamic data. After ACP10, mild sedation was observed in five/six dogs and moderate sedation in one/six dogs, whereas after ACP25, ACP50 and ACP100, moderate sedation was observed in five/six or six/six dogs. CONCLUSIONS AND CLINICAL RELEVANCE: In conscious dogs, acepromazine decreased MAP, SI, CaO2 and DO2I, but no significant dose effect was detected. SVRI was not significantly changed, suggesting that the reduction in MAP resulted from decreased CI. The ACP25, ACP50 and ACP100 doses resulted in moderate sedation in most dogs; ACP10 resulted in only mild sedation.

Acepromazine and Chlorpromazine as Pharmaceutical-grade Alternatives to Chlorprothixene for Pupillary Light Reflex Imaging in Mice.

Studies of visual responses in isoflurane-anesthetized mice often use the sedative chlorprothixene to decrease the amount of isoflurane used because excessive isoflurane could adversely affect light-evoked responses. However, data are not available to justify the use of this nonpharmaceutical-grade chemical. The current study tested whether pharmaceutical-grade sedatives would be appropriate alternatives for imaging pupillary light reflexes. Male 15-wk-old mice were injected intraperitoneally with 1 mg/kg chlorprothixene, 5 mg/kg acepromazine, 10 mg/kg chlorpromazine, or saline. After anesthetic induction, anesthesia maintenance used 0.5% and 1% isoflurane for sedative- and saline-injected mice, respectively. A photostimulus (16.0 log photons cm-2 s-1; 470 nm) was presented to the right eye for 20 min, during which the left eye was imaged for consensual pupillary constriction and involuntary pupil drift. Time to immobilization, loss of righting reflex, physiologic parameters, gain of righting reflex, and degree of recovery were assessed also. The sedative groups were statistically indistinguishable for all measures. By contrast, pupillary drift occurred far more often in saline-treated mice than in the sedative groups. Furthermore, saline-treated mice took longer to reach maximal pupil constriction than all sedative groups and had lower heart rates compared with chlorpromazine- and chlorprothixene-sedated mice. Full recovery (as defined by purposeful movement, response to tactile stimuli, and full alertness) was not regularly achieved in any sedative group. In conclusion, at the doses tested, acepromazine and chlorpromazine are suitable pharmaceutical-grade alternatives to chlorprothixene for pupil imaging and conceivably other in vivo photoresponse measurements; however, given the lack of full recovery, lower dosages should be investigated further for use in survival procedures.

Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization.

In this study, the effect of four anaesthetic protocols that included the combination of xylazine (X) and ketamine (K) with acepromazine (A) and opioids (methadone (Me), morphine (Mo) or tramadol (T)) was evaluated in laboratory rats of both sexes. Ultrasonic vocalization (USV) was used as an indicator of pain during the recovery period. The objective was to evaluate the physiological parameters and the analgesic effect of each protocol to determine which protocol was the safest and fulfil the requirements of a balanced anaesthesia. The better protocols were the XKA protocol for both sexes and the XKMe protocol for females because the combinations achieve surgical plane of anaesthesia in rats. However, pain assessment during the formalin test revealed that rats anaesthetized with XKA produced more numbers of USV, suggesting that it is not a good protocol for the control of immediate postoperative pain. All protocols produced depression in body temperature and respiratory and heart rates, and had important effects, such as micturition and maintenance of open eyes. Only rats anaesthetized with XKA protocol did not present piloerection. These results demonstrated that good monitoring and care during anaesthesia must be included to prevent complications that compromise the life of the animal and to ensure a good recovery. The inclusion of analgesia in anaesthesia protocols must be used routinely, ensuring minimal presence of pain and thus more reliable results in the experimental procedures.

Sedative and cardiorespiratory effects of intramuscular administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs.

OBJECTIVE: To evaluate the sedative and cardiorespiratory effects of IM administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs. ANIMALS: 6 young healthy mixed-breed hounds. PROCEDURES: Dogs received each of 3 treatments (alfaxalone [2 mg/kg] and butorphanol [0.4 mg/kg] combined with acepromazine [0.02 mg/kg; AB-ace], midazolam [0.2 mg/kg; AB-mid], or dexmedetomidine [0.005 mg/kg; AB-dex], IM) in a blinded, randomized crossover-design study with a 1-week washout period between treatments. Sedation scores and cardiorespiratory variables were recorded at predetermined time points. Data were analyzed by use of mixed-model ANOVA and linear generalized estimating equations with post hoc adjustments. RESULTS: All treatments resulted in moderate to deep sedation (median score, ≥ 15/21) ≤ 5 minutes after injection. Sedation scores did not differ among treatments until the 40-minute time point, when the score was higher for AB-dex than for other treatments. Administration of AB-dex resulted in median scores reflecting deep sedation until 130 minutes, versus 80 and 60 minutes for AB-ace and AB-mid, respectively, after injection. Heart rate, cardiac output, and oxygen delivery decreased significantly after AB-dex, but not AB-ace or AB-mid administration. Respiratory variables remained within clinically acceptable ranges after all treatments. Undesirable recovery characteristics were observed in 4 dogs after AB-mid treatment. Four dogs required atipamezole administration 180 minutes after AB-dex injection. CONCLUSIONS AND CLINICAL RELEVANCE: All protocols produced reliable sedation. The results indicated that in young, healthy dogs, AB-mid may produce undesirable recovery characteristics; AB-dex treatment caused cardiovascular depression and should be used with caution.

A comparative study of the cardiopulmonary and sedative effects of a single intramuscular dose of ketamine anesthetic combinations in rabbits.

The aim of this prospective, randomized, blinded crossover study was compare the cardiopulmonary and sedative effects of ketamine in combination with acepromazine, diazepam, dexmedetomidine, midazolam or xylazine, injected intramuscularly in rabbits, using eight one-year-old male New Zealand rabbits (4.1 ± 0.40 kg). All treatments included ketamine (K; 30 mg/kg) in combination with one of the following: acepromazine 0.5 mg/kg (treatment KA); diazepam 1 mg/kg (KD); dexmedetomidine 0.025 mg/kg (KDex); midazolam 1 mg/kg (KM); or xylazine 3 mg/kg (KX) mixed in the same syringe and injected intramuscularly. Cardiopulmonary variables, blood gases and sedative scores were measured before injection (T0 or baseline) and every 10 min thereafter, over a 60-min period. There were reductions in heart rate, compared with the baseline, at all evaluation times in treatment KX. Treatments KDex, KM and KX presented reductions in respiratory rate at all evaluation times, in comparison with the baseline. There were reductions in mean arterial pressure in KA and KX at times T10-T60 and in PaO2 in KDex, KM and KX at T10-T50. The sedation scores were similar in KA, KDex, KM and KX at T10-T20. Ketamine in combination with acepromazine, dexmedetomidine, midazolam or xylazine promoted similar sedative effects for twenty minutes, but the α2-agonists can promote hypoxemia.

[Perioperative hypothermia in dogs receiving combined administration of acepromazin and metamizol]. / Untersuchung der perioperativen Hypothermie bei kombinierter Gabe von Acepromazin und Metamizol beim Hund.

OBJECTIVE: Evaluation the development of perioperative body temperature while administrating a combination of acepromazine and metamizol (AM) versus anesthesia with acepromazine (A) alone. MATERIAL AND METHODS: In this prospective, quasi-randomized controlled study 20 dogs undergoing standardized tibial plateau leveling osteotomy were alternatingly assigned to group A or group AM (n = 10 each). The patients' body temperature values were recorded from the time of premedication up to its post-surgical return to reference values. RESULTS: Body temperature decreases during anesthesia in both groups were comparable (p = 0.12). Postoperatively on the other hand, temperature development differed significantly between the two groups (p = 0.0455). In 6 dogs of the group AM, body temperature continued to decrease following extubation prior to returning to normothermic values. CONCLUSION: Intraoperatively, all patients developed hypothermia, regardless of the investigated anesthetic medication administered. Postoperatively, patients not receiving metamizol reached normothermia more rapidly.

Effects of 3 morphine doses, in combination with acepromazine, on sedation and some physiological parameters in dogs.

This study evaluated the effects of 3 morphine doses combined with acepromazine, on sedation and physiological parameters in 5 clinically healthy dogs. Four treatments were administered intramuscularly in a randomized, blinded, crossover design: acepromazine, 0.05 mg/kg, alone (ACP) and acepromazine plus morphine at doses of 0.25, 0.5, and 1.0 mg/kg body weight (BW) (AM0.25, AM0.5, and AM1.0, respectively). Sedation scores and cardiorespiratory variables were evaluated for 120 min after drug administration. The sedation scores were significantly higher with the AM0.25 and AM1.0 treatments than with the ACP treatment. At 30 min the scores were 36% to 66% higher with AM1.0 than with AM0.25 and AM0.5, respectively, but these differences were not significant. The physiological variables remained acceptable for dogs. The results of this study do not support the use of AM0.5 over AM0.25 to improve sedation in dogs, but they do indicate that sedation may be greater with AM1.0 than with AM0.25 and AM0.5. Studies with a greater number of samples are warranted to confirm this statement.

Cette étude visait à évaluer les effets de trois doses de morphine combinées à de l'acépromazine, sur la sédation et des paramètres physiologiques chez cinq chiens cliniquement en santé. Quatre traitements furent administrés par voie intramusculaire dans un design croisé randomisé à l'aveugle : acépromazine, 0,05 mg/kg seule (ACP) et acépromazine plus morphine à des doses de 0,25, 0,5, et 1,0 mg/kg de poids corporel (AM0,25, AM0,5, et AM1,0, respectivement). Les pointages de sédation et des variables cardiorespiratoires furent évalués pour 120 min après l'administration des drogues. Les pointages de sédation étaient significativement plus élevés avec les traitements AM0,25 et AM1,0 qu'avec le traitement ACP. À 30 min, les pointages étaient 36 % et 66 % plus élevés avec AM1,0 qu'avec AM0,25 et AM0,5, respectivement, mais ces différences n'étaient pas significatives. Les variables physiologiques sont demeurées acceptables pour les chiens. Les résultats de cette étude ne militent pas en faveur de l'utilisation d'AM0,5 par rapport à AM0,25 pour améliorer la sédation chez les chiens, mais ils indiquent que la sédation peut être plus grande avec AM1,0 qu'avec AM0,25 et AM0,5. Des études avec un plus grand nombre d'échantillons sont requises pour confirmer cet énoncé.(Traduit par Docteur Serge Messier).

Investigation of associations between preoperative acepromazine or dexmedetomidine administration and development of arterial hypotension or bradycardia in dogs undergoing ovariohysterectomy.

OBJECTIVE To evaluate potential associations between preanesthetic administration of acepromazine or dexmedetomidine and development of arterial hypotension or bradycardia in isoflurane-anesthetized dogs undergoing ovariohysterectomy. ANIMALS 341 dogs. PROCEDURES Medical records were searched to identify dogs that underwent ovariohysterectomy between January 2009 and December 2010 and received hydromorphone with acepromazine or dexmedetomidine as preanesthetic agents. Demographic data, sedative and anesthetic drugs, duration of anesthesia, average vaporizer setting, positive pressure ventilation, occurrence of hypotension (mean arterial pressure < 60 mm Hg) or bradycardia (> 50% reduction in heart rate, compared with the preanesthetic value), time to first occurrence and duration of hypotension, and treatment with dopamine or anticholinergic agents were recorded. Data were compared between dogs that received acepromazine and dexmedetomidine. Logistic regression was used to investigate associations between the treatments of interest (and other putative risk factors) and development of hypotension or bradycardia. RESULTS For dogs that received acepromazine, the odds of developing hypotension were 2.61 times those for dogs that received dexmedetomidine. Hypotension occurred earlier and lasted longer in dogs that received acepromazine, and this group was treated with dopamine more frequently than the group that received dexmedetomidine. Lower body weight was associated with increased odds of hypotension. Odds of developing bradycardia were greater for dogs sedated with dexmedetomidine (vs acepromazine) and for dogs that underwent anesthetic induction with propofol or a ketamine-benzodiazepine combination (vs thiopental). CONCLUSIONS AND CLINICAL RELEVANCE Anesthetic complications differed between isoflurane-anesthetized dogs undergoing ovariohysterectomy after premedication with acepromazine or dexmedetomidine in this study; future prospective investigations are warranted to investigate these effects in other, less homogenous populations of dogs.

Effect of premedication on dose requirement, cardiovascular effects and recovery quality of alfaxalone total intravenous anaesthesia in dogs.

OBJECTIVE: To investigate alfaxalone total intravenous anaesthesia (TIVA) following premedication with methadone combined with acepromazine (ACP) or dexmedetomidine in bitches undergoing ovariohysterectomy. STUDY DESIGN: Prospective, blinded, randomized, experimental study. ANIMALS: A group of 12 female Beagles. METHODS: Dogs were premedicated intravenously with methadone (0.2 mg kg-1) combined with ACP (20 µg kg-1, group AM) or dexmedetomidine (5 µg kg-1, group DM). Anaesthesia was induced with alfaxalone (2 mg kg-1). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg-1 minute-1 and adjusted every 5 minutes based on clinical assessment. Mechanical ventilation was initiated when necessary to maintain normocapnia. Anaesthetic monitoring included electrocardiogram, heart rate (HR), invasive diastolic (DAP), systolic (SAP) and mean arterial blood pressure, arterial haemoglobin oxygen saturation, respiratory variables and oesophageal temperature. Data were recorded every 5 minutes. A mixed model statistical approach was used to compare cardiovascular variables within and between groups (α = 0.05). A Wilcoxon rank-sum test was used to compare body temperature, VRI alfaxalone rate, administered rescue analgesia, sedation, induction, intubation, recovery scores and recovery times between treatments. RESULTS: Overall HR, SAP and DAP differed between groups (p = 0.001, 0.016, 0.019, respectively). The mean VRI dose rate of alfaxalone differed between groups DM [0.13 (0.11-0.14) mg kg-1 minute-1] and AM [0.18 (0.13-0.19) mg kg-1 minute-1; p = 0.030]. Rescue analgesia was administered more in group AM (p = 0.019). No significant difference in recovery times and scores was observed between protocols. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone TIVA following dexmedetomidine/methadone premedication produced a more stable plane of anaesthesia to perform ovariohysterectomy than ACP/methadone. A dose reduction of alfaxalone of 27.7% was obtained in group DM compared with group AM. Recovery quality and recovery times were comparable between both groups.

Effect of three doses of nalbuphine on reversal of sedation and cardiopulmonary effects of morphine-acepromazine in healthy dogs.

OBJECTIVE: To evaluate the efficacy of three doses of nalbuphine in reversing sedative and cardiopulmonary effects of morphine-acepromazine in dogs. STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: A group of eight healthy Beagle dogs, aged 5-6 years and weighing 12.5 ± 2.1 kg. METHODS: Dogs were administered morphine (0.5 mg kg-1) and acepromazine (0.05 mg kg-1) intravenously (IV). After 20 minutes, dogs were administered one of four treatments IV: saline (control); or nalbuphine (0.3 mg kg-1; treatment N0.3), (0.6 mg kg-1; treatment N0.6) or (1.0 mg kg-1; treatment N1.0), in random order separated by 1 week. Sedation was scored using a numeric descriptive scale (NDS) and simple numerical scale (SNS). Heart rate, systolic arterial pressure (SAP), respiratory rate (fR) and rectal temperature (RT) were recorded before (BL), 20 minutes after morphine-acepromazine (T0), then 10 (T10), 30, 60 and 90 minutes after saline or nalbuphine. Arterial blood gases were measured at BL, T0 and T10. Values were compared with BL, T0 and among treatments using anova (p < 0.05) and the Bonferroni correction (p < 0.008). RESULTS: NDS for N0.6 and SNS for N0.6 and N1.0 at T30, and both scores for all nalbuphine treatments at T60-T90 were lower compared with T0 (p < 0.05). Sedation scores were not different among nalbuphine treatments. SNS scores were lower than control at T10 for N0.3 and N0.6 (p < 0.05). SAP and fR were lower than BL for all treatments at some time points (p < 0.05). RT was higher than control at T60 in the nalbuphine treatments (p < 0.001). PaO2 was lower in N0.3 at T0 compared with BL (p = 0.036). CONCLUSIONS AND CLINICAL RELEVANCE: All nalbuphine doses decreased the degree of sedation, without differences among them. Administration of nalbuphine resulted in minimal changes in measured cardiopulmonary variables.

Effects of Intramuscular Alfaxalone/Acepromazine on Echocardiographic, Biochemical, and Blood Gas Measurements in Healthy Cats.

The effects of intramuscular injection of alfaxalone ([ALF] 5 mg/kg), acepromazine ([ACE] 0.05 mg/kg), and an ALF-ACE combination ([AA] 0.025 mg/kg ACE followed by 2.5 mg/kg ALF) on the sedation, echocardiographic, biochemical, and blood gas indexes and recovery were evaluated in seven cats. No sedation was obtained with ACE, and sedation scores were higher with ALF than with AA treatment. Compared with baseline, an increase in heart rate occurred after ACE, and all treatments caused a decrease in systemic arterial pressure. Decreased left ventricular internal dimension in diastole, end-diastolic volume of the left ventricle, stroke volume, and left atrial dimension were identified after AA. There were minimal changes in echocardiographic variables after ALF. Biochemical and blood gas analysis showed no significant changes after all treatments. Although the difference in quality of recovery between the AA and ALF treatment groups was insignificant, all cats treated with AA or ALF showed ataxia. The AA combination did not change the recovery score, and tremor and twitching were identified more frequently with AA than ALF. ALF had no significant effects on echocardiographic, biochemical, or blood gas variables. ALF could be considered a useful sedative option for diagnostic procedures and echocardiography in cats.

Haemodynamic changes during propofol induction in dogs: new findings and approach of monitoring.

BACKGROUND: Propofol is one of the most widely used injectable anaesthetic agents in veterinary practice. Cardiovascular effects related to propofol use in dogs remain less well defined. The main objective of this study was to evaluate the haemodynamic changes during induction of general anaesthesia with propofol in healthy dogs, by a beat-to-beat continuous monitoring. All dogs were premedicated with intramuscular acepromazine (0.015 mg/kg) and methadone (0.15 mg/kg). Transthoracic echocardiography was used to measure the velocity time integral (VTI) of the left ventricular outflow tract. A syringe driver, programmed to deliver propofol 5 mg/kg over 30 s followed by a continuous infusion of 25 mg/kg/h, was used to induce and maintain anaesthesia. From the initiation of propofol administration, heart rate (HR) and mean invasive arterial blood pressure (MAP) were recorded every 5 s for 300 s, while aortic blood flow was continuously recorded and stored for 300 S. maximum cardiovascular depression was defined the lowest MAP (MAP_Tpeak) recorded during the monitored interval. VTI and VTI*HR were calculated at 0, 30, 90, 120, 150 and 300 s post administration of propofol, and at MAP_Tpeak. Haemodynamic effects of propofol in relation to plasma and biophase concentrations were also evaluated by pharmacokinetics simulation. RESULTS: The median (range) HR was significantly higher (p = 0.006) at the moment of maximum hemodynamic depression (Tpeak) [105(70-148) bpm] compared with pre-induction values (T0) [65(50-120) bpm]. The median (range) MAP was significantly lower (p < 0.001) at Tpeak [61(51-69) mmHg] compared with T0 [88(72-97) mmHg]. The median (range) VTI and VTI*HR were similar at the two time points [11.9(8.1-17.3) vs 13,3(9,4-16,5) cm, and 1172(806-1554) vs 1002(630-1159) cm*bpm, respectively]. CONCLUSIONS: Induction of anaesthesia with propofol causes a drop of arterial pressure in healthy dogs, however cardiac output is well maintained by compensatory chronotropic response. The magnitude of MAP_Tpeak may be strictly related with propofol plasma concentration.

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. STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: A group of 16 healthy adult dogs aged (mean ± standard deviation) 4.9 ± 3.3 years and weighing 15.7 ± 9.6 kg, without pre-existing ophthalmic disease. METHODS: IV dexmedetomidine hydrochloride (0.002 mg kg-1; DEX) or acepromazine maleate (0.015 mg kg-1; ACE) was administered randomly to 16 dogs (eight per group). The IOP and PD, measured using applanation tonometry and Schirmer's strips mm scale, respectively, and the heart rate (HR), systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures and respiratory rate (fR) were recorded at baseline, at time of injection, and then 5, 10, 15, 20 and 25 minutes after injection. A single ophthalmologist, unaware of treatment, performed all measurements under consistent light conditions. Values were compared with baseline and among treatments using a multivariate mixed-effects model (p ≤ 0.05). RESULTS: The IOP was significantly lower in the DEX group compared with the ACE group at 10 (p < 0.01) and 15 minutes (p < 0.01) after drug injection. PD was significantly smaller compared to baseline for the entire duration of the study (p < 0.01) in both groups. Dogs in the DEX group had significant lower HR (p < 0.01) and fR (p < 0.01), higher SAP (p < 0.01) and DAP (p < 0.01) at all time points, and higher MAP (p < 0.01) during the first 15 minutes following drug injection in comparison with the ACE group. CONCLUSIONS AND CLINICAL RELEVANCE: Our results suggest that premedication with IV dexmedetomidine temporarily decreases IOP when compared with IV acepromazine. Both drugs cause miosis.

A comparison between methadone and buprenorphine for perioperative analgesia in dogs undergoing ovariohysterectomy.

OBJECTIVE: To investigate whether preoperative methadone provides superior perioperative analgesia compared to buprenorphine in dogs undergoing ovariohysterectomy. METHODS: Eighty female dogs were recruited to an assessor-blinded, randomised, clinical trial. Dogs received a premedication dose of 0·05 mg/kg acepromazine or 10 µg/kg medetomidine combined with either 0·3 mg/kg methadone or 20 µg/kg buprenorphine intramuscularly. Anaesthesia was induced with propofol and maintained with isoflurane. Pain was assessed using two scoring schemes (a dynamic interactive visual analogue scale and the short form of the Glasgow Composite Pain Scale) before premedication, 30 minutes later and every hour for 8 hours after premedication. If indicated, rescue analgesia was provided with methadone. Meloxicam was administered after the final assessment. The area under the curve for change in pain scores over time and the requirement for rescue analgesia were compared between groups. RESULTS: Groups premedicated with buprenorphine had significantly higher pain scores than those premedicated with methadone. There was no interaction between opioid and sedative for any outcome measure. Rescue analgesia was required by significantly more dogs premedicated with buprenorphine (45%) than that of methadone (20%). CLINICAL SIGNIFICANCE: At the doses investigated, methadone produced superior postoperative analgesia compared to buprenorphine in dogs undergoing ovariohysterectomy.

Sedative and cardiorespiratory effects of low doses of xylazine with and without acepromazine in Nordestino donkeys.

BACKGROUND: Information on appropriate protocols for sedation of Nordestino donkeys is scarce. OBJECTIVES: To evaluate the sedative and cardiorespiratory effects of low doses of intravenous (i.v.) xylazine with and without acepromazine in 'Nordestino' donkeys. STUDY DESIGN: Seven healthy female Nordestino donkeys (150 ± 18 kg) were included in this blinded, randomised, crossover experiment. METHODS: Four treatments were administered, consisting of two i.v. injections, at baseline (T0, 1st injection) and 15 min later (T15, 2nd injection). Treatments included acepromazine 0.05 mg/kg bwt + saline (AS), saline + xylazine 0.5 mg/kg bwt (SX0.5), acepromazine + xylazine 0.25 mg/kg bwt (AX0.25) or acepromazine + xylazine 0.5 mg/kg bwt (AX0.5). Sedative and cardiorespiratory parameters were evaluated before T0 and 15, 20, 30, 45, 60, 75 and 90 min after treatment. Degree [height of head above ground (HHAG)] and quality of sedation [ataxia, responses to stimuli and visual analogue scale (VAS) scoring] and respiratory rate were evaluated by the main investigator in situ, and heart rate was measured by an assistant investigator. Three experienced evaluators assessed vídeos for ataxia and responses to stimuli. Normal data were analysed by repeated measures ANOVA, and non-normal by Kruskal-Wallis (P<0.05). RESULTS: HHAG was lower than baseline for 15 min after xylazine administration in AX0.25 and for 30 min in SX0.5 and AX0.5 groups. All treatments with xylazine increased VAS and ataxia scores in situ for 15 min after xylazine administration, with no differences between groups. Ataxia scores in situ were higher in SX0.5 and AX0.5 groups than AS for 15 and 30 min after xylazine administration, respectively. MAIN LIMITATIONS: Absence of a negative control group (saline-saline). CONCLUSION: Acepromazine added to xylazine at 0.25 mg/kg bwt produced briefer and milder sedation than xylazine at 0.5 mg/kg bwt.

Pharmacokinetics, pharmacodynamics, and metabolism of acepromazine following intravenous, oral, and sublingual administration to exercised Thoroughbred horses.

Acepromazine is a tranquilizer used commonly in equine medicine. This study describes serum and urine concentrations and the pharmacokinetics and pharmacodynamics of acepromazine following intravenous, oral, and sublingual (SL) administration. Fifteen exercised adult Thoroughbred horses received a single intravenous, oral, and SL dose of 0.09 mg/kg of acepromazine. Blood and urine samples were collected at time 0 and at various times for up to 72 hr and analyzed for acepromazine and its two major metabolites (2-(1-hydroxyethyl) promazine and 2-(1-hydroxyethyl) promazine sulfoxide) using liquid chromatography-tandem mass spectrometry. Acepromazine was also incubated in vitro with whole equine blood and serum concentrations of the parent drug and metabolites determined. Acepromazine was quantitated for 24 hr following intravenous administration and 72 hr following oral and SL administration. Results of in vitro incubations with whole blood suggest additional metabolism by RBCs. The mean ± SEM elimination half-life was 5.16 ± 0.450, 8.58 ± 2.23, and 6.70 ± 2.62 hr following intravenous, oral, and SL administration, respectively. No adverse effects were noted and horses appeared sedate as noted by a decrease in chin-to-ground distance within 5 (i.v.) or 15 (p.o. and SL) minutes postadministration. The duration of sedation lasted 2 hr. Changes in heart rate were minimal.

Comparison of the effects of alfaxalone and propofol with acepromazine, butorphanol and/or doxapram on laryngeal motion and quality of examination in dogs.

OBJECTIVE: To compare the effects of alfaxalone and propofol, with and without acepromazine and butorphanol followed by doxapram, on laryngeal motion and quality of laryngeal examination in dogs. STUDY DESIGN: Randomized, crossover, blinded study. ANIMALS: Ten female Beagle dogs, aged 11-13 months and weighing 7.2-8.6 kg. METHODS: The dogs were administered four intravenous (IV) treatments: alfaxalone (ALF), alfaxalone+acepromazine and butorphanol (ALF-AB), propofol (PRO) and propofol+AB (PRO-AB). AB doses were standardized. Dogs were anesthetized 5 minutes later by administration of alfaxalone or propofol IV to effect. Arytenoid motion during maximal inspiration and expiration was captured on video before and after IV doxapram (0.25 mg kg-1). The change in rima glottidis surface area (RGSA) was calculated to measure arytenoid motion. An investigator blinded to the treatment scored laryngeal examination quality. RESULTS: A 20% increase in RGSA was the minimal arytenoid motion that was detectable. RGSA was significantly less in ALF before doxapram compared with all other treatments. A <20% increase in RGSA was measured in eight of 10 dogs in PRO and in all dogs in ALF before doxapram. After doxapram, RGSA was significantly increased for PRO and ALF; however, 20% of dogs in PRO and 50% of dogs in ALF still had <20% increase in RGSA. A <20% increase in RGSA was measured in five of 10 dogs in PRO-AB and ALF-AB before doxapram. All dogs in PRO-AB and ALF-AB with <20% increase in RGSA before doxapram had ≥20% increase in RGSA after doxapram. Examination quality was significantly better in PRO-AB and ALF-AB. CONCLUSIONS AND CLINICAL RELEVANCE: The use of acepromazine and butorphanol improved the quality of laryngeal examination. Any negative impact on arytenoid motion caused by these premedications was overcome with doxapram. Using either propofol or alfaxalone alone is not recommended for the evaluation of arytenoid motion.

Sedation of sheep following the administration of acepromazine with buprenorphine or morphine is similar.

The aim of this study was to compare sedation of sheep with acepromazine and buprenorphine or morphine. Twenty merino sheep received acepromazine (0.03mg/kg) with buprenorphine (0.02mg/kg, AB, n=10) or morphine (0.3mg/kg, AM, n=10) by intramuscular injection. Sedation was scored (SS) on a scale from 0 (no sedation) to 10 (heavy sedation). Response to restraint was scored (RS) on a scale from 0 (agitated) to 4 (relaxed). Three independent blinded observers and a single blinded observer determined the SS and RS, respectively. The SSs were summed (maximum 30). Data were compared using a t-test. Data is mean±SD (95% confidence interval). Each group comprised 2 wethers and 8 ewes. There was no difference between the AB and AM groups: weight 44±3.1kg and 44.7±3kg (p=0.58); SS 4.6±3.2 (2.4-6.9) and 6.6±3.5 (4.1-9.1) (p=0.21); and RS 1.6±1.3 (0.5-2.7) and 2±1.5 (0.7-3.3) (p=0.6). No adverse effects of the drugs were observed. Sedation with AB or AM at these doses is similar in sheep without observed adverse effects.