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.     

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.     

Sedative and analgesic effects of buprenorphine,combined with either acepromazine or dexmedetomidine,for premedication prior to elective surgery in cats and dogs

ObjectiveTo evaluate the sedative and analgesic effects of intramuscular buprenorphine with either dexmedetomidine or acepromazine, administered as premedication to cats and dogs undergoing elective surgery.Study designProspective, randomized, blinded clinical study.AnimalsForty dogs and 48 cats.MethodsAnimals were assigned to one of four groups, according to anaesthetic premedication and induction agent: buprenorphine 20 μg kg^?1 with either dexmedetomidine (dex) 250 μg m^?2 or acepromazine (acp) 0.03 mg kg^?1, followed by alfaxalone (ALF) or propofol (PRO). Meloxicam was administered preoperatively to all animals and anaesthesia was always maintained using isoflurane. Physiological measures and assessments of pain, sedation and mechanical nociceptive threshold (MNT) were made before and after premedication, intraoperatively, and for up to 24 hours after premedication. Data were analyzed with one-way, two-way and mixed between-within subjects anova, Kruskall–Wallis analyses and Chi squared tests. Results were deemed significant if p ≤ 0.05, except where multiple comparisons were performed (p ≤ 0.005).ResultsCats premedicated with dex were more sedated than cats premedicated with acp (p < 0.001) and ALF doses were lower in dex cats (1.2 ± 1.0 mg kg^?1) than acp cats (2.5 ± 1.9 mg kg^?1) (p = 0.041). There were no differences in sedation in dogs however PRO doses were lower in dex dogs (1.5 ± 0.8 mg kg^?1) compared to acp dogs (3.3 ± 1.1 mg kg^?1) (p < 0.001). There were no differences between groups with respect to pain scores or MNT for cats or dogs.ConclusionChoice of dex or acp, when given with buprenorphine, caused minor, clinically detectable, differences in various characteristics of anaesthesia, but not in the level of analgesia.Clinical relevanceA combination of buprenorphine with either acp or dex, followed by either PRO or ALF, and then isoflurane, accompanied by an NSAID, was suitable for anaesthesia in dogs and cats undergoing elective surgery. Choice of sedative agent may influence dose of anaesthetic induction agent.     

Evaluation of urine specific gravity as a predictor of hypotension during anaesthesia in healthy dogs premedicated with dexmedetomidine

ObjectiveTo investigate the relationship between urine specific gravity (USG) and the risk of arterial hypotension during general anaesthesia (GA) in healthy dogs premedicated with dexmedetomidine and methadone.Study designProspective clinical cohort study.AnimalsA total of 75 healthy client-owned dogs undergoing GA for elective tibial plateau levelling osteotomy.MethodsAfter placing an intravenous catheter, dogs were premedicated with dexmedetomidine (5 μg kg^–1) and methadone (0.3 mg kg^–1) intravenously. After induction of GA with alfaxalone to effect, the bladder was expressed and USG measured. An arterial catheter was placed, and residual blood was used to measure packed cell volume (PCV) and total protein (TP). GA was maintained with isoflurane vaporised in oxygen and a femoral and sciatic nerve block were performed. Arterial blood pressure < 60 mmHg was defined as hypotension and recorded by the anaesthetist. Treatment for hypotension was performed in a stepwise manner following a flow chart. Frequency of hypotension, treatment and response to treatment were recorded. Logistic regression modelling was used to assess the association between USG, TP and PCV and incidence of perioperative hypotension; p < 0.05.ResultsData from 14 dogs were excluded. Of the 61 dogs, 16 (26%) were hypotensive during GA, 15 dogs needed treatment of which 12 were responsive to a decrease in inhalant vaporiser setting. The logistic regression model was not statistically significant (p = 0.8). There was no significant association between USG (p = 0.6), TP (p = 0.4), PCV (p = 0.8) and arterial hypotension during GA.Conclusions and clinical relevanceIn healthy dogs premedicated with dexmedetomidine and methadone and maintained under GA with isoflurane and a femoral and sciatic nerve block, there was no relationship between the specific gravity of urine collected after premedication and intraoperative arterial hypotension.     

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.     

Intramuscular alfaxalone and methadone with or without ketamine in healthy cats: effects on sedation and echocardiographic measurements

ObjectiveTo evaluate the effect of alfaxalone and methadone administered intramuscularly (IM), with or without ketamine, on sedation and echocardiographic measurements in healthy cats.Study designA randomized, blinded, clinical study.AnimalsA group of 24 client-owned cats.MethodsBaseline echocardiographic evaluation (bEchoCG) was performed. Cats were given IM alfaxalone (2 mg kg^–1) and methadone (0.3 mg kg^–1) with (AMK group) or without (AM group) ketamine (1 mg kg^–1). A sedation score (0–5, indicating none to good sedation) was assigned at 5 (T5), 10 (T10) and 15 (T15) minutes after IM injection. At T15, a second echocardiographic evaluation (sEchoCG) was performed. Data are shown as median (range). Significance was p < 0.05.ResultsFinally, 21 cats were included. Sedation score was significantly higher in the AMK (11 cats) than in the AM group (10 cats): 4 (1–5) versus 0.5 (0–4) at T5 (p = 0.003); 4 (1–5) versus 1.5 (0–5) at T10 (p = 0.043); and 4 (1–5) versus 2 (0–5) at T15 (p = 0.024). All echocardiographic measurements obtained were within reference ranges. Between the groups, aortic root area (p = 0.009) and end-diastolic aortic dimension (p = 0.011) were significantly higher in the AM group at bEchoCG and sEchoCG, respectively. Within each group, values at bEchoCG and sEchoCG showed no significant differences, except for pulmonary peak velocity (0.85 m second^–1; p = 0.028) in the AMK group and ejection time (154 m second; p = 0.03) in the AM group; both variables decreased after sedation.Conclusions and clinical relevanceIn this population of healthy cats, neither protocol produced clinically meaningful effects on the echocardiographic variables evaluated. Alfaxalone with methadone produced mild sedation, whereas the addition of 1 mg kg^–1 ketamine induced adequate sedation for diagnostic procedures.     

Sedative and analgesic effects of medetomidine in beagle dogs infected and uninfected with heartworm

The sedative and analgesic effects of medetomidine were evaluated in heartworm-infected (HW+) and uninfected (HW–) beagle dogs by intravenous (IV) and intramuscular (IM) administration of 30 µg/kg and 40 µg/kg doses, respectively. Posture, response to noise and the pedal reflex were monitored. A procedure for mock radiographic positioning was performed to evaluate its overall clinical use. Observation times were 0, 15, 30, 60, 90, 120 and 180 min. In addition, the times from injection until the dog could not stand on its feet (down time), from lateral to sternal recumbency (sternal recumbency time), and from sternal recumbency to rising again (rising time) were also noted.Medetomidine produced rapid sedation and analgesia by both routes. Down times for the IM and IV routes were similar, which verified the manufacturer's recommended doses. The HW+ dogs had shorter down times, probably owing to increased blood flow to the brain caused by adrenergic alpha-2 activity. Sternal recumbency and rising times did not differ between the groups, suggesting a similar metabolism. Sedation and analgesia were adequate for performing the procedure in all dogs. HW– dogs showed less resistance to handling during the procedure than HW+ dogs. Overall, medetomidine seems to be a suitable agent for short-term chemical restraint in dogs, even with subclinical heartworm infestation.     

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.

Clinical pharmacokinetics of a dexmedetomidine–methadone combination in dogs undergoing routine anaesthesia after buccal or intramuscular administration

This study aimed to define the pharmacokinetic profiles of dexmedetomidine and methadone administered simultaneously in dogs by either an oral transmucosal route or intramuscular route and to determine the bioavailability of the oral transmucosal administration relative to the intramuscular one of both drugs, so as the applicability of this administration route in dogs. Twelve client‐owned dogs, scheduled for diagnostic procedures, were treated with a combination of dexmedetomidine hydrochloride (10 μg/kg) and methadone hydrochloride (0.4 mg/kg) through an oral transmucosal route or intramuscularly. Oral transmucosal administration caused ptyalism in most subjects, and intramuscular administration caused transient peripheral vasoconstriction. The results showed reduced and delayed absorption of both dexmedetomidine and methadone when administered through an oral transmucosal route, with median (range) C_max values of 0.82 (0.42–1.49) ng/ml and 13.22 (2.80–52.30) ng/ml, respectively. The relative bioavailability was low: 16.34% (dexmedetomidine) and 15.5% (methadone). Intramuscular administration resulted in a more efficient absorption profile, with AUC and C_max values for both drugs approximately 10 times higher. Dexmedetomidine and methadone administered simultaneously by an oral transmucosal route using injectable formulations were not well absorbed through the oral mucosa. Nevertheless, additional studies on these drugs combination using alternative administration routes are recommended.     

Effects of medetomidine,l‐methadone,and their combination on arterial blood gases in dogs

ObjectiveTo investigate the influence of l–methadone on medetomidine–induced changes in arterial blood gases and clinical sedation in dogs.Study designProspective experimental cross–over study (Latin square design).AnimalsFive 1–year–old purpose bred laboratory beagle dogs of both sexes.MethodsEach dog was treated three times: medetomidine (20 μg kg^?1 IV), l–methadone (0.1 mg kg^?1 IV) and their combination. Arterial blood was collected for blood gas analysis. Heart and respiratory rates were recorded, and clinical sedation and reaction to a painful stimulus were scored before drug administration and at various time points for 30 minutes thereafter.ResultsArterial partial pressure of oxygen decreased slightly after medetomidine administration and further after medetomidine/l–methadone administration (range 55.2–86.7 mmHg, 7.4–11.6 kPa, at 5 minutes). A slight increase was detected in arterial partial pressure of carbon dioxide after administration of l–methadone and medetomidine/l–methadone (42.6 ± 2.9 and 44.7 ± 2.4 mmHg, 5.7 ± 0.4 and 6.0 ± 0.3 kPa, 30 minutes after drug administration, respectively). Arterial pH decreased slightly after administration of l–methadone and medetomidine/l–methadone. Heart and respiratory rates decreased after administration of medetomidine and medetomidine/l–methadone, and no differences were detected between the two treatments. Most dogs panted after administration of l–methadone and there was slight sedation. Medetomidine induced moderate or deep sedation, and all dogs were deeply sedated after administration of medetomidine/l–methadone. Reaction to a noxious stimulus was strong or moderate after administration of methadone, moderate or absent after administration of medetomidine, and absent after administration of medetomidine/l–methadone.Conclusions and clinical relevanceAt the doses used in this study, l–methadone potentiated the sedative and analgesic effects and the decrease in arterial oxygenation induced by medetomidine in dogs, which limits the clinical use of this combination.     

Sedative and physiologic effects of low-dose intramuscular alfaxalone in dogs

Objective

To describe the sedative and physiologic effects of two doses of alfaxalone administered intramuscularly in dogs.

Sedative, analgesic, and cardiovascular effects of levomedetomidine alone and in combination with dexmedetomidine in dogs

OBJECTIVE: To determine whether a high dose of levomedetomidine had any pharmacologic activity or would antagonize the sedative and analgesic effects of dexmedetomidine in dogs. ANIMALS: 6 healthy Beagles. PROCEDURE: Each dog received the following treatments on separate days: a low dose of levomedetomidine (10 microg/kg), IV, as a bolus, followed by continuous infusion at a dose of 25 microg/kg/h; a high dose of levomedetomidine (80 microg/kg), IV, as a bolus, followed by continuous infusion at a dose of 200 microg/kg/h; and a dose of isotonic saline (0.9% NaCl) solution, IV, as a bolus, followed by continuous infusion (control). For all 3 treatments, the infusion was continued for 120 minutes. After 60 minutes, a single dose of dexmedetomidine (10 microg/kg) was administered IV. Sedation and analgesia were scored subjectively, and heart rate, blood pressure, respiratory rate, arterial blood gas partial pressures, and rectal temperatures were monitored. RESULTS: Administration of levomedetomidine did not cause any behavioral changes. However, administration of the higher dose of levomedetomidine enhanced the bradycardia and reduced the sedative and analgesic effects associated with administration of dexmedetomidine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of dexmedetomidine alone may have some cardiovascular benefits over administration of medetomidine, which contains both dexmedetomidine and levomedetomidine. Further studies are needed to confirm the clinical importance of the effects of levomedetomidine in dogs.     

Cardiovascular effects of epidural administration of methadone, ropivacaine 0.75% and their combination in isoflurane anaesthetized dogs

ObjectiveTo compare the cardiovascular effects of four epidural treatments in isoflurane anaesthetised dogs.Study designProspective, randomized. experimental study.AnimalsSix female, neutered Beagle dogs (13.3 ± 1.0 kg), aged 3.6 ± 0.1 years.MethodsAnaesthesia was induced with propofol (8.3 ± 1.1 mg kg^?1) and maintained with isoflurane in a mixture of oxygen and air [inspiratory fraction of oxygen (FiO₂) = 40%], using intermittent positive pressure ventilation. Using a cross-over model, NaCl 0.9% (P); methadone 1% 0.1 mg kg^?1 (M); ropivacaine 0.75% 1.65 mg kg^?1 (R) or methadone 1% 0.1 mg kg^?1 + ropivacaine 0.75% 1.65 mg kg^?1 (RM) in equal volumes (0.23 mL kg^?1) using NaCl 0.9%, was administered epidurally at the level of the lumbosacral space. Treatment P was administered to five dogs only. Cardiovascular and respiratory variables, blood gases, and oesophageal temperature were recorded at T-15 and for 60 minutes after epidural injection (T0).ResultsMean overall heart rate (HR in beats minute^?1) was significantly lower after treatment M (119 ± 16) (p = 0.0019), R (110 ± 18) (p < 0.0001) and RM (109 ± 13) (p < 0.0001), compared to treatment P (135 ± 21). Additionally, a significant difference in HR between treatments RM and M was found (p = 0.04). After both ropivacaine treatments, systemic arterial pressures (sAP) were significantly lower compared to other treatments. No significant overall differences between treatments were present for central venous pressure, cardiac output, stroke volume, systemic vascular resistance, oxygen delivery and arterial oxygen content (CaO₂). Heart rate and sAP significantly increased after treatment P and M compared to baseline (T-15). With all treatments significant reductions from baseline were observed in oesophageal temperature, packed cell volume and CaO₂. A transient unilateral Horner’s syndrome occurred in one dog after treatment R.Conclusions and clinical relevanceClinically important low sAPs were observed after the ropivacaine epidural treatments in isoflurane anaesthetised dogs. Systemic arterial pressures were clinically acceptable when using epidural methadone.     

Cardiopulmonary effects of dexmedetomidine and ketamine infusions with either propofol infusion or isoflurane for anesthesia in horses

ObjectiveTo examine the cardiopulmonary effects of two anesthetic protocols for dorsally recumbent horses undergoing carpal arthroscopy.Study designProspective, randomized, crossover study.AnimalsSix horses weighing 488.3 ± 29.1 kg.MethodsHorses were sedated with intravenous (IV) xylazine and pulmonary artery balloon and right atrial catheters inserted. More xylazine was administered prior to anesthetic induction with ketamine and propofol IV. Anesthesia was maintained for 60 minutes (or until surgery was complete) using either propofol IV infusion or isoflurane to effect. All horses were administered dexmedetomidine and ketamine infusions IV, and IV butorphanol. The endotracheal tube was attached to a large animal circle system and the lungs were ventilated with oxygen to maintain end-tidal CO₂ 40 ± 5 mmHg. Measurements of cardiac output, heart rate, pulmonary arterial and right atrial pressures, and body temperature were made under xylazine sedation. These, arterial and venous blood gas analyses were repeated 10, 30 and 60 minutes after induction. Systemic arterial blood pressures, expired and inspired gas concentrations were measured at 10, 20, 30, 40, 50 and 60 minutes after induction. Horses were recovered from anesthesia with IV romifidine. Times to extubation, sternal recumbency and standing were recorded. Data were analyzed using one and two-way anovas for repeated measures and paired t-tests. Significance was taken at p=0.05.ResultsPulmonary arterial and right atrial pressures, and body temperature decreased from pre-induction values in both groups. PaO₂ and arterial pH were lower in propofol-anesthetized horses compared to isoflurane-anesthetized horses. The lowest PaO₂ values (70–80 mmHg) occurred 10 minutes after induction in two propofol-anesthetized horses. Cardiac output decreased in isoflurane-anesthetized horses 10 minutes after induction. End-tidal isoflurane concentration ranged 0.5%–1.3%.Conclusion and clinical relevanceBoth anesthetic protocols were suitable for arthroscopy. Administration of oxygen and ability to ventilate lungs is necessary for propofol-based anesthesia.