Effects of dexmedetomidine alone or in combination with opioids on intraocular pressure in healthy Beagle dogs

ObjectiveTo evaluate the effects of dexmedetomidine alone or in combination with different opioids on intraocular pressure (IOP) in dogs.Study designExperimental, prospective, crossover, randomized, blinded study.AnimalsA total of six Beagle dogs (two males and four females) aged 2 years and weighing 15.9 ± 2.9 kg (mean ± standard deviation).MethodsDogs were distributed randomly into seven treatments (n = 6 per treatment) and were administered dexmedetomidine alone (10 μg kg^–1; Dex) or in combination with butorphanol (0.15 mg kg^–1; DexBut), meperidine (5 mg kg^–1; DexMep), methadone (0.5 mg kg^–1; DexMet), morphine (0.5 mg kg^–1; DexMor), nalbuphine (0.5 mg kg^–1; DexNal) or tramadol (5 mg kg^–1; DexTra). All drugs were administered intramuscularly. IOP was measured before drug injection (time 0, baseline) and every 15 minutes thereafter for 120 minutes (T15–T120).ResultsThere were significant reductions in IOP compared with baseline in treatments Dex and DexMep at times T30–T120, and in treatment DexMet at T15–T90. IOP decreased compared with baseline in treatments DexBut, DexNal and DexTra at all evaluation times. No changes in IOP were seen in treatment DexMor. The mean IOP values in treatment DexMet at T105–T120 were higher than those for other treatments.Conclusions and clinical relevanceDexmedetomidine alone or in combination with butorphanol, meperidine, methadone, nalbuphine or tramadol resulted in decreased IOP for 120 minutes in dogs. The magnitude of the reduction was small and lacked clinical significance.     

Sedative, cardiovascular, haematologic and biochemical effects of four different drug combinations administered intramuscularly in cats

ObjectiveTo compare effects of four drug combinations on sedation, echocardiographic, haematologic and biochemical variables and recovery in cats.Study designExperimental randomized ‘blinded’ cross-over study.AnimalsSix healthy cats.Materials and MethodsTreatments were administered intramuscularly: midazolam 0.4 mg kg^?1 and butorphanol 0.4 mg kg^?1 (MB); midazolam 0.4 mg kg^?1, butorphanol 0.4 mg kg^?1 and ketamine 3 mg kg^?1 (MBK); midazolam 0.4 mg kg^?1, butorphanol 0.4 mg kg^?1 and dexmedetomidine 5 μg kg^?1 (MBD); ketamine 3 mg kg^?1 and dexmedetomidine 5 μg kg^?1(KD). Sedation was evaluated at time-points over 10 minutes post injection. Echocardiography, systolic arterial blood pressure (SAP) measurement and blood sampling were performed at baseline and from 10 minutes after treatment. Quality of recovery was scored. Data were analysed by anova for repeated measures. p < 0.05 was considered significant.ResultsThe lowest sedation score was obtained by MB, (median 10.5 [7; 20]), highest by KD (36.5 [32; 38]). Quality of recovery was best with KD (0.5 [0; 2]), and worst with MB (7.5 [4; 11]). Relative to baseline measurements, treatments decreased SAP by 17%, 25%, 13%, 5% in MB, MBK, MBD and KD, respectively. Heart rate decreased (p < 0.05) after MBD (44%) and KD (34%). All treatments decreased stroke volume by 24%, 21%, 24%, 36%, and cardiac output by 23%, 34%, 54%, 53% in MB, MBK, MBD and KD, respectively. Packed cell volume was decreased (p < 0.05) by 20%, 31%, 29% in MBK, MBD and KD, respectively. Plasma glucose was increased after MBD (31%) and KD (52%) and lactate concentration was decreased (p < 0.05) after MBK (58%), MBD (72%) and KD (65%).Conclusions and clinical relevanceThe MB combination did not produce sedation in healthy cats. Treatment MBK led to acceptable sedation and minimal cardiovascular changes. Both treatments with dexmedetomidine produced excellent sedation and recovery but induced more cardiovascular depression and haematologic changes.     

Minimum end‐tidal sevoflurane concentration necessary to prevent movement during a constant rate infusion of morphine,or morphine plus dexmedetomidine in ponies

ObjectiveTo compare the effects of a constant rate infusion (CRI) of dexmedetomidine and morphine to those of morphine alone on the minimum end-tidal sevoflurane concentration necessary to prevent movement (MAC_NM) in ponies.Study designProspective, randomized, crossover, ‘blinded’, experimental study.AnimalsFive healthy adult gelding ponies were anaesthetized twice with a 3-week washout period.MethodsAfter induction of anaesthesia with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (Fe‘SEVO 2.5%) in 55% oxygen. Monitoring included pulse oximetry, electrocardiography and measurement of anaesthetic gases, arterial blood pressure and body temperature. The ponies were mechanically ventilated and randomly allocated to receive IV treatment M [morphine 0.15 mg kg^?1 (T10-T15) followed by a CRI (0.1 mg kg^?1 hour^?1)] or treatment DM [dexmedetomidine 3.5 μg kg^?1 plus morphine 0.15 mg kg^?1 (T10-T15) followed by a CRI of dexmedetomidine 1.75 μg kg^?1 hour^?1 and morphine 0.1 mg kg^?1 hour^?1]. At T60, a stepwise MAC_NM determination was initiated using constant current electrical stimuli at the skin of the lateral pastern region. Triplicate MAC_NM estimations were obtained and then averaged in each pony. Wilcoxon signed-rank test was used to detect differences in MAC between treatments (a = 0.05).ResultsSevoflurane-morphine MAC_NM values (median (range) and mean ± SD) were 2.56 (2.01–4.07) and 2.79 ± 0.73%. The addition of a continuous infusion of dexmedetomidine significantly reduced sevoflurane MAC_NM values to 0.89 (0.62–1.05) and 0.89 ± 0.22% (mean MAC_NM reduction 67 ± 11%).Conclusion and clinical relevanceCo-administration of dexmedetomidine and morphine CRIs significantly reduced the MAC_NM of sevoflurane compared with a CRI of morphine alone at the reported doses.     

Comparison of analgesia provided by lidocaine, lidocaine-morphine or lidocaine-tramadol delivered epidurally in dogs following orchiectomy

ObjectiveTo evaluate and compare the postoperative analgesia provided by epidural lidocaine, lidocaine/morphine or lidocaine/tramadol in dogs following elective orchiectomy.Study designProspective experimental trial.AnimalsThirty-six mongrel dogs aged 2-8 years old, weighing 6.6-22 kg.MethodsThe dogs received 6.0 mg kg^?1 of lidocaine combined with 1.0 mg kg^?1 of tramadol, 0.1 mg kg^?1 of morphine or 0.01 mL kg^?1 of 0.9% NaCl epidurally. Analgesia was assessed at 4, 8, 12, 18 and 24 hours (T4, T8, T12 and T24) after the offset of lidocaine using a scale composed of physiologic and behavioral parameters. Rescue analgesia with morphine (0.2 mg kg^?1, IM) was performed if the evaluation score exceeded 10 during the postoperative period. The scores over time were analyzed using the Friedman’s two-way analysis of variance and the comparison between groups was made by the Kruskal-Wallis test with statistical significances accepted if p = 0.05.ResultsThere were no differences in the pain scores between the morphine and tramadol groups over time and no rescue analgesia was administered. In the NaCl group, rescue analgesia was needed at T4, T8 and T12. Within this group, the final evaluation times (T18 and T24) had lower pain scores than at T4, T8 and T12.Conclusions and clinical relevanceEpidural lidocaine/tramadol provided an analgesic effect comparable to that of epidural lidocaine/morphine during the first 12 hours after surgical castration without substantial side effects, suggesting that tramadol may be an effective postoperative analgesic in dogs submitted to this surgical procedure.     

Effects of different doses of dexmedetomidine on anaesthetic induction with alfaxalone – a clinical trial

ObjectiveTo document the effects of two doses of dexmedetomidine on the induction characteristics and dose requirements of alfaxalone.Study designRandomized controlled clinical trial.AnimalsSixty one client owned dogs, status ASA I-II.MethodsDogs were allocated randomly into three groups, receiving as pre-anaesthetic medication, no dexmedetomidine (D₀), 1 μg kg^?1 dexmedetomidine (D₁) intramuscularly (IM) or 3 μg kg^?1 dexmedetomidine IM (D₃). All dogs also received 0.2 mg kg^?1 methadone IM. Level of sedation was assessed prior to induction of anaesthesia. Induction of general anaesthesia was performed with alfaxalone administered intravenously to effect at a rate of 1 mg kg^?1 minute^?1; the required dose to achieve tracheal intubation was recorded. Anaesthesia was maintained with isoflurane in oxygen. Cardiopulmonary parameters were recorded throughout the anaesthetic period. Quality of intubation, induction and recovery of anaesthesia were recorded. Quantitative data were compared with one-way anova or Kruskal-Wallis test. Repeated measures were log-transformed and analysed with repeated measures anova (p < 0.05).ResultsTreatment groups were similar for categorical data, with exception of sedation level (p < 0.001). The doses (mean ± SD) of alfaxalone required for intubation were D₀ 1.68 ± 0.24, D₁ 1.60 ± 0.36 and D₃ 1.41 ± 0.43, the difference between D₀ and D₃ being statistically significant (p = 0.036). Heart and respiratory rates during the anaesthetic period were significantly different over time and between groups (p < 0.001); systolic arterial blood pressure was significantly different over time (p < 0.001) but not between groups (p = 0.833). Induction quality and recovery scores were similar between groups (p = 1.000 and p = 0.414, respectively).Conclusions and clinical relevanceThe administration of alfaxalone resulted in a good quality anaesthetic induction which was not affected by the dose of dexmedetomidine. Dexmedetomidine at 3 μg kg^?1 IM combined with methadone provides good sedation and enables a reduction of alfaxalone requirements.     

Glomerular filtration rate after tramadol, parecoxib and pindolol following anaesthesia and analgesia in comparison with morphine in dogs

ObjectiveTo compare the effects of morphine, parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol on nociceptive thresholds in awake animals and their effect on glomerular filtration rate (GFR) in dogs subjected to 30 minutes of anesthesia.AnimalsEight adult mixed breed experimental dogs.Study designRandomized, controlled trial.MethodsDogs received 0.05 mg kg^?1 acepromazine subcutaneously (SC) as anaesthetic pre-medication. Thirty to sixty minutes later, they received either tramadol 3 mg kg^?1 intravenously, (IV), parecoxib (1 mg kg^?1 IV), a combination of tramadol 3 mg kg^?1 (IV), parecoxib 1 mg kg^?1 (IV) and pindolol 5 μg kg^?1 (SC), morphine (0.1 mg kg^?1 (IV) or 0.9% saline (2 mL). Anaesthesia was then induced with IV propofol to effect (2.9 ± 0.8 mg kg^?1) and maintained with halothane in oxygen for 30 minutes. Systolic arterial blood pressure was maintained above 90 mmHg with IV fluids and by adjusting the inspired halothane concentration. Post-treatment nociceptive thresholds to mechanical stimuli, expressed as percent of pre-treatment values, were compared between the treatments to assess the analgesic efficacy of the drugs. Plasma iohexol clearance (ICL), a measure of GFR, was estimated both before and 24 hours after induction of anaesthesia to study the drugs’ effects on renal perfusion. Nociceptive threshold and GFR data were compared using mixed model analysis in sas^®9.1.ResultsBoth tramadol and parecoxib produced similar analgesia, which was less than that of morphine. Their combination with pindolol produced analgesia comparable with morphine. None of the test drugs, either alone or in combination, reduced GFR.ConclusionTramadol and parecoxib (either alone or in combination) can increase nociceptive thresholds in awake dogs and have minimal effects on renal perfusion in normotensive dogs subjected to anaesthesia.     

Effects of different doses of L-659'066 on the bispectral index and clinical sedation in dogs treated with dexmedetomidine

ObjectiveTo evaluate the effects of three doses of L-659’066 (MK-467) on the bispectral index (BIS) and clinical sedation in dexmedetomidine-sedated Beagles.Study designRandomized, experimental cross over study.AnimalsEight purpose-bred healthy laboratory Beagles.MethodsDexmedetomidine (10 μg kg^?1 IV [DEX]) was administered alone or in combination with three doses of L-659’066 (250 μg kg^?1 [DL250]; 500 μg kg^?1 [DL500] and 750 μg kg^?1 [DL750] IV) in the same syringe in a randomized crossover manner. The bispectral index (BIS), electromyography (EMG) and sedation score were recorded at baseline and 5, 10, 20, 30, 45 and 60 minutes after treatment.ResultsWhen compared to DEX, BIS and EMG were significantly higher and the sedation score significantly lower with DL500 and DL750. With DEX, BIS was significantly decreased at times 20, 30 and 60 minutes whereas the sedation scores were significantly increased at all time points after drug administration in all groups. Bioequivalence for clinical sedation was detected between DEX and all doses of L-659’066, reaching European Medicines Agency (EMA) standards.Conclusions and clinical relevanceAlthough L-659’066 interfered with dexmedetomidine induced sedation, the degree of the reduction was not clinically relevant. Despite performing better when dexmedetomidine was used alone, BIS did not reflect the clinical sedative status when the antagonist was added.     

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.     

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.     

Cardiovascular responses to transvenous electrical cardioversion of atrial fibrillation in anaesthetized horses

ObjectiveTo examine the influence of direct current shock application in anaesthetized horses with atrial fibrillation (AF) and to study the effects of cardioversion to sinus rhythm (SR).Study designProspective clinical study.AnimalsEight horses successfully treated for AF (transvenous electrical cardioversion after amiodarone pre-treatment).MethodsCardioversion catheters and a pacing catheter were placed under sedation [detomidine 10 μg kg^?1 intravenously (IV)]. After additional sedation (5–10 μg kg^?1 detomidine, 0.1 mg kg^?1 methadone IV), anaesthesia was induced with ketamine, 2.2 mg kg^?1 and midazolam, 0.06 mg kg^?1 (IV) in a sling and maintained with isoflurane in oxygen. Flunixin meglumine, 1.1 mg kg^?1, was administered IV. Shocks were delivered as biphasic truncated exponential waves, synchronized with the R-wave of the electrocardiogram. Monitoring included pulse oximetry, electrocardiography, capnography, inhalational anaesthetic agent concentration, arterial blood pressure, LiDCO and PulseCO cardiac index (CI) and arterial blood gases. Values before and after the first unsuccessful shock and before and after cardioversion to SR were compared.ResultsValues before the first shock were comparable to reported values in healthy, isoflurane anaesthetized horses. Reliable CI measurements could not be obtained using the PulseCO technique. Intermittent positive pressure ventilation was required in most horses (bradypnea and/or PaCO₂ >8 kPa, 60 mmHg), while dobutamine was administered in two horses (0.3–0.5 μg kg^?1 minute^?1). After the 1st unsuccessful shock application, systolic arterial pressure (SAP) was decreased (p = 0.025), other recorded values were not influenced (CI measurements not available for this analysis). SR was associated with increases in CI (p = 0.039) and stroke index (p = 0.002) and a decrease in SAP (p = 0.030).Conclusions and clinical relevanceDespite the presence of AF, cardiovascular function was well maintained during anaesthesia and was not affected by shock application. Cardiac index and stroke index increased and SAP decreased after cardioversion.     

Evaluation of the perioperative stress response from dexmedetomidine infusion alone,with butorphanol bolus or remifentanil infusion compared with ketamine and morphine infusions in isoflurane-anesthetized horses

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.     

Evaluation of the isoflurane‐sparing effects of fentanyl,lidocaine, ketamine,dexmedetomidine, or the combination lidocaine‐ketamine‐dexmedetomidine during ovariohysterectomy in dogs

ObjectiveTo evaluate the isoflurane‐sparing effects of an intravenous (IV) constant rate infusion (CRI) of fentanyl, lidocaine, ketamine, dexmedetomidine, or lidocaine‐ketamine‐dexmedetomidine (LKD) in dogs undergoing ovariohysterectomy.Study designRandomized, prospective, blinded, clinical study.AnimalsFifty four dogs.MethodsAnesthesia was induced with propofol and maintained with isoflurane with one of the following IV treatments: butorphanol/saline (butorphanol 0.4 mg kg^?1, saline 0.9% CRI, CONTROL/BUT); fentanyl (5 μg kg^?1, 10 μg kg^?1 hour^?1, FENT); ketamine (1 mg kg^?1, 40 μg kg^?1 minute^?1, KET), lidocaine (2 mg kg^?1, 100 μg kg^?1 minute^?1, LIDO); dexmedetomidine (1 μg kg^?1, 3 μg kg^?1 hour^?1, DEX); or a LKD combination. Positive pressure ventilation maintained eucapnia. An anesthetist unaware of treatment and end‐tidal isoflurane concentration (Fe′Iso) adjusted vaporizer settings to maintain surgical anesthetic depth. Cardiopulmonary variables and Fe′Iso concentrations were monitored. Data were analyzed using anova (p < 0.05).ResultsAt most time points, heart rate (HR) was lower in FENT than in other groups, except for DEX and LKD. Mean arterial blood pressure (MAP) was lower in FENT and CONTROL/BUT than in DEX. Overall mean ± SD Fe′Iso and % reduced isoflurane requirements were 1.01 ± 0.31/41.6% (range, 0.75 ± 0.31/56.6% to 1.12 ± 0.80/35.3%, FENT), 1.37 ± 0.19/20.8% (1.23 ± 0.14/28.9% to 1.51 ± 0.22/12.7%, KET), 1.34 ± 0.19/22.5% (1.24 ± 0.19/28.3% to 1.44 ± 0.21/16.8%, LIDO), 1.30 ± 0.28/24.8% (1.16 ± 0.18/32.9% to 1.43 ± 0.32/17.3%, DEX), 0.95 ± 0.19/54.9% (0.7 ± 0.16/59.5% to 1.12 ± 0.16/35.3%, LKD) and 1.73 ± 0.18/0.0% (1.64 ± 0.21 to 1.82 ± 0.14, CONTROL/BUT) during surgery. FENT and LKD significantly reduced Fe′Iso.Conclusions and clinical relevanceAt the doses administered, FENT and LKD had greater isoflurane‐sparing effect than LIDO, KET or CONTROL/BUT, but not at all times. Low HR during FENT may limit improvement in MAP expected with reduced Fe′Iso.     

Comparison of intraperitoneal ropivacaine and ropivacaine–dexmedetomidine for postoperative analgesia in cats undergoing ovariohysterectomy

ObjectiveTo investigate the intraperitoneal (IP) administration of ropivacaine or ropivacaine–dexmedetomidine for postoperative analgesia in cats undergoing ovariohysterectomy.Study designProspective, randomized, blinded, positively controlled clinical study.AnimalsA total of 45 client-owned cats were enrolled.MethodsThe cats were administered intramuscular (IM) meperidine (6 mg kg⁻¹) and acepromazine (0.05 mg kg⁻¹). Anesthesia was induced with propofol and maintained with isoflurane. Meloxicam (0.2 mg kg⁻¹) was administered subcutaneously in all cats after intubation. After the abdominal incision, the cats were administered one of three treatments (15 cats in each treatment): IP instillation of 0.9% saline solution (group Control), 0.25% ropivacaine (1 mg kg⁻¹, group ROP) or ropivacaine and dexmedetomidine (4 μg kg⁻¹, group ROP–DEX). During anesthesia, heart rate (HR), electrocardiography, noninvasive systolic arterial pressure (SAP) and respiratory variables were monitored. Sedation and pain were assessed preoperatively and at various time points up to 24 hours after extubation using sedation scoring, an interactive visual analog scale, the UNESP-Botucatu multidimensional composite pain scale (MCPS) and mechanical nociceptive thresholds (MNT; von Frey anesthesiometer). Rescue analgesia (morphine, 0.1 mg kg⁻¹) IM was administered if the MCPS ≥6. Data were analyzed using the chi-square test, Tukey test, Kruskal–Wallis test and Friedman test (p < 0.05).ResultsHR was significantly lower in ROP–DEX compared with Control (p = 0.002). The pain scores, MNT, sedation scores and the postoperative rescue analgesia did not differ statistically among groups.Conclusions and clinical relevanceAs part of a multimodal pain therapy, IP ropivacaine–dexmedetomidine was associated with decreased HR intraoperatively; however, SAP remained within normal limits. Using the stated anesthetic protocol, neither IP ropivacaine nor ropivacaine–dexmedetomidine significantly improved analgesia compared with IP saline in cats undergoing ovariohysterectomy.     

Cardiovascular,respiratory, electrolyte and acid–base balance during continuous dexmedetomidine infusion in anesthetized dogs

ObjectiveTo evaluate the cardiovascular, respiratory, electrolyte and acid–base effects of a continuous infusion of dexmedetomidine during propofol–isoflurane anesthesia following premedication with dexmedetomidine.Study designProspective experimental study.AnimalsFive adult male Walker Hound dogs 1–2 years of age averaging 25.4 ± 3.6 kg.MethodsDogs were sedated with dexmedetomidine 10 μg kg^?1 IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg^?1) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg^?1 IV was administered over 5 minutes followed by an infusion of 0.5 μg kg^?1 hour^?1. Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid–base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD.ResultsNo statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute^?1, 78 ± 18 beats minute^?1 and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute^?1, 78 ± 14 beats minute^?1 and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO₂, PaCO₂, pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion.Conclusions and clinical relevanceDexmedetomidine infusion using a loading dose of 0.5 μg kg^?1 IV followed by a constant rate infusion of 0.5 μg kg^?1 hour^?1 does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg^?1, in propofol–isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2 minutes before onset of infusion showed typical significant effects on cardiovascular parameters.     

Cardiopulmonary effects of an infusion of remifentanil or morphine in horses anesthetized with isoflurane and dexmedetomidine

ObjectiveTo examine the cardiopulmonary effects of infusions of remifentanil or morphine, and their influence on recovery of horses anesthetized with isoflurane and dexmedetomidine.Study designRandomized crossover study with 7-day rest periods.AnimalsSix adult horses (507 ± 61 kg).MethodsAfter the horses were sedated with xylazine, anaesthesia was induced with ketamine and diazepam, and maintained with isoflurane. After approximately 60 minutes, a dexmedetomidine infusion was started (0.25 μg kg^?1 then 1.0 μg^?1 kg^?1 hour^?1) in combination with either saline (group S), morphine (0.15 mg kg^?1 then 0.1 mg kg^?1 hour^?1; group M), or remifentanil (6.0 μg kg^?1 hour^?1; group R) for 60 minutes. Mean arterial pressure, heart rate, end-tidal carbon dioxide tension, and end-tidal isoflurane concentration were recorded every 5 minutes. Core body temperature, cardiac output, right ventricular and arterial blood-gas values were measured every 15 minutes. Cardiac index, systemic vascular resistance (SVR), intrapulmonary shunt fraction, alveolar dead space, oxygen delivery and extraction ratio were calculated. Recoveries were videotaped and scored by two observers blinded to the treatment. Data were analyzed using repeated measures anova followed by Dunnett’s or Bonferroni’s significant difference test. Recovery scores were analyzed using a Kruskal–Wallis test.ResultsNo significant differences were found among groups. Compared to baseline, heart rate decreased and SVR increased significantly in all groups, and cardiac index significantly decreased in groups S and M. Hemoglobin concentration, oxygen content and oxygen delivery significantly decreased in all groups. The oxygen extraction ratio significantly increased in groups M and R. Lactate concentration significantly increased in group S. Recovery scores were similar among groups.Conclusions and clinical relevanceDexmedetomidine alone or in combination with remifentanil or morphine infusions was infused for 60 minutes without adverse effects in the 6 healthy isoflurane-anesthetized horses in this study.     

Two doses of dexmedetomidine in combination with buprenorphine for premedication in dogs; a comparison with acepromazine and buprenorphine

ObjectiveTo assess as premedicants, the sedative, cardiorespiratory and propofol-sparing effects in dogs of dexmedetomidine and buprenorphine compared to acepromazine and buprenorphine.Study designProspective, randomised, blinded clinical studyAnimalsSixty healthy dogs (ASA grades I/II). Mean (SD) body mass 28.0 ± 9.1 kg, and mean age 3.4 ± 2.3 years.MethodsDogs were allocated randomly to receive 15 μg kg^?1 buprenorphine combined with either 30 μg kg^?1 acepromazine (group 1), 62.5 μg m^?2 dexmedetomidine (group 2), or 125 μg m^?2 dexmedetomidine (group 3) intramuscularly. After 30 minutes, anaesthesia was induced using a propofol target controlled infusion. Heart rate, respiratory rate, and oscillometric arterial blood pressure were recorded prior to induction, at endotracheal intubation and at 3 and 5 minutes post-intubation. Induction quality and pre-induction sedation were scored on 4 point scales. Propofol target required for endotracheal intubation was recorded. Data were analysed using Chi-squared tests, Kruskal-Wallis, one way and general linear model anova (p < 0.05).ResultsAge was significantly lower in group 1 (1.0 (1.0–3.8) years) than group 2 (5.0 (2.0–7.0) years), (median, (IQR)). There were no significant differences in sedation or quality of induction between groups. After premedication, heart rate was significantly lower and arterial blood pressures higher in groups 2 and 3 than group 1, but there was no significant difference between groups 2 and 3. Propofol targets were significantly lower in group 3 (1.5 (1.0–2.5) μg mL^?1) than group 1 (2.5 (2.0–3.0) μg mL^?1); no significant differences existed between group 2 (2.0 (1.5–2.5) μg mL^?1) and the other groups (median, (interquartile range)).Conclusions and Clinical relevanceWhen administered with buprenorphine, at these doses, dexmedetomidine had no advantages in terms of sedation and induction quality over acepromazine. Both doses of dexmedetomidine produced characteristic cardiovascular and respiratory effects of a similar magnitude.     

Electrocardiographic evaluation of the degree of sedation and the isolated use of methadone in healthy dogs

ObjectiveThe present study aimed to investigate the influence of methadone on cardiorespiratory parameters, electrocardiogram and clinical sedation in dogs. Further possible side effects are reported.Study designProspective experimental cross-over study.DogsEight, 1–4-year-old, various breeds of dogs of both genders weighing 9–36 kg.MethodsEach dog was treated three times: methadone 0.3 mg kg^?1 (M0.3), 0.5 mg kg^?1 (M0.5) and 1.0 mg kg^?1 (M1.0) intramuscularly. Respiratory rate, heart rate and arterial blood pressure were recorded as well as electrocardiographic evaluation of lead II. Clinical sedation in each treatment received a score (0–3) after drug administration and at 30 minute intervals until scores and measurements returned to baseline values.ResultsA significant decrease in heart rate was seen with each dose of methadone and bradycardia (HR<60 bpm) was noted in a few dogs at each dose. A clinically significant arrhythmia occurred in one dog at 1 mg kg^?1 that required reversal with butorphanol. There was no significant difference in SAP, MAP and DAP between treatments. Some side effects such as salivation, defecation, vocalization and panting, after administration of methadone were observed. There were no differences in mean values of heart rate, P-wave and QRS complex duration and QT interval between treatments.Conclusion and clinical relevanceMethadone administration was associated with panting and a decrease in heart rate at all doses tested in this study. The cardiac rhythm should be monitored carefully in dogs when methadone is administered on its own, especially at higher doses.     

The cardiopulmonary effects of a peripheral alpha‐2‐adrenoceptor antagonist,MK‐467, in dogs sedated with a combination of medetomidine and butorphanol

ObjectiveTo compare the cardiopulmonary effects of intravenous (IV) and intramuscular (IM) medetomidine and butorphanol with or without MK-467.Study designProspective, randomized experimental cross-over.AnimalsEight purpose–bred beagles (two females, six males), 3–4 years old and weighing 14.5 ±1.6 kg (mean ± SD).MethodsAll dogs received four different treatments as follows: medetomidine 20 μg kg^?1 and butorphanol tartrate 0.1 mg kg^?1 IV and IM (MB), and MB combined with MK-467,500 μg kg^?1 (MBMK) IV and IM. Heart rate (HR), arterial blood pressures (SAP, MAP, DAP), central venous pressure (CVP), cardiac output, respiratory rate (f_R), rectal temperature (RT) were measured and arterial blood samples were obtained for gas analysis at baseline and at 3, 10, 20, 30, 45 and 60 minutes after drug administration. The cardiac index (CI), systemic vascular resistance index (SVRI) and oxygen delivery index (DO₂I) were calculated. After the follow-up period atipamezole 50 μg kg^?1 IM was given to reverse sedation.ResultsHR, CI and DO₂I were significantly higher with MBMK after both IV and IM administration. Similarly, SAP, MAP, DAP, CVP, SVRI and RT were significantly lower after MBMK than with MB. There were no differences in f_R between treatments, but arterial partial pressure of oxygen decreased transiently after all treatments. Recoveries were uneventful following atipamezole administration after all treatments.Conclusions and clinical relevanceMK-467 attenuated the cardiovascular effects of a medetomidine-butorphanol combination after IV and IM administration.     

Characterisation of tramadol,morphine and tapentadol in an acute pain model in Beagle dogs

ObjectiveTo evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive pain, the tail-flick model in dogs.Study designProspective part-randomized pre-clinical research trial.AnimalsFifteen male Beagle dogs (HsdCpb:DOBE), aged 12–15 months.MethodsOn different occasions separated by at least 1 week, dogs received intravenous (IV) administrations of tramadol (6.81, 10.0 mg kg^?1), tapentadol (2.15, 4.64, 6.81 mg kg^?1) or morphine (0.464, 0.681, 1.0 mg kg^?1) with subsequent measurement of tail withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1).ResultsTapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg^?1 and 0.71 mg kg^?1, respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociptive effect of tramadol in this experimental pain model in dogs.Conclusions and clinical relevanceDifferent breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting. This contrasts to many clinical situations described in the literature, where tramadol appears to provide useful analgesia in dogs for post-operative pain relief and in more chronically pain states.