Pharmacokinetics of dexmedetomidine in anaesthetized horses following repeated subcutaneous administration and intravenous constant rate infusion.

BACKGROUND: The inclusion of dexmedetomidine (DEX) within a balanced general anaesthesia protocol is effective in improving the clinical outcome and recovery quality of anaesthesia in horses. This study aimed to determine the pharmacokinetic profile of DEX following repeated subcutaneous (SC) administration at 2 µg/kg every 60 min till the end of the procedure in comparison to intravenous constant rate infusion (CRI) at 1 µg/kg/h in anaesthetized horses undergoing diagnostic procedures up to the end of the diagnostic procedure. RESULTS: In the CRI and SC groups DEX maximum concentrations (Cmax) were 0.83 ± 0.27 ng/mL and 1.14 ± 0.71 ng/mL, respectively, reached at a time (Tmax) of 57.0 ± 13.4 min and 105.5 ± 29.9 min. Mean residence time to the last measurable concentration (MRTlast) was 11.7 ± 6.2 and 55.8 ± 19.7 min for the CRI group and SC groups, respectively. The apparent elimination half-life was 18.0 ± 10.0 min in the CRI group and 94.8 ± 69.8 min for the SC group, whereas the area under the curve (AUC0-last) resulted 67.7 ± 29.3 and 83.2 ± 60.5 min*ng/mL for CRI and SC group, respectively. Clearance was 16.26 ± 8.07 mL/min/kg for the CRI group. No signs of adverse effects were recorded in both groups. CONCLUSIONS: The pharmacokinetic profile of DEX following repeated SC administration in anaesthetized horses was comparable to intravenous CRI administration during the intranaesthetic period and beneficial during the recovery phase from general anaesthesia. The SC route could be considered as an alternative to CRI for improving the recovery quality of equine patients undergoing general anaesthesia.

Comparison of intraperitoneal and incisional lidocaine or ropivacaine irrigation for postoperative analgesia in dogs undergoing major abdominal surgeries.

This study compared the postoperative analgesic efficacy of intraperitoneal and incisional lidocaine versus ropivacaine in dogs undergoing major abdominal surgeries. Dogs randomly received intraperitoneal lidocaine irrigation (4 mg kg-1, diluted to 5 ml kg-1, L group), ropivacaine (4 mg kg-1, diluted to 5 ml kg-1, R group) or 0.9% saline (5 ml kg-1, C group). Prior to skin closure, dogs received incisional lidocaine 2 mg kg-1 (group L), incisional ropivacaine 2 mg kg-1 (group R) or incisional saline 0.2 ml kg-1 (group C). Pain was assessed at different time points up to 24 hours after extubation, using the Short Form-Glasgow Composite Measure Pain Scale and VAS Scale. In group C, postoperative pain scores were significantly higher than in groups L and R from T0.5 to T6 (p < 0.05). In R group, postoperative pain scores were significantly lower than in groups L and C from T12 to T24 (p < 0.05). Rescue analgesia was administered to 5/11 dogs in L group, 1/10 dogs in R group and 8/10 dogs in C group. Groups L and R experienced a significantly lower postoperative pain during the first 6 hours after extubation, compared with group C. Ropivacaine provided lower postoperative pain scores than lidocaine and saline up to 24 hours after extubation. According to the obtained results, ropivacaine seemed to provide better and longer lasting postoperative analgesia compared with lidocaine. Therefore, intraperitoneal and incisional administration of ropivacaine in dogs undergoing major abdominal surgeries is recommended.

Comparison of two multimodal intramuscular anaesthetic protocols in uncooperative feline patients: effects on sedation and echocardiographic measurements.

OBJECTIVES: The aims of this study were to compare the sedative effect, feasibility of venous angiocatheter placement and influence on heart rate (HR), systemic blood pressure (SBP) and echocardiographic variables of two multimodal anaesthetic protocols in uncooperative cats; and to compare their influence on HR, SBP and echocardiographic variables 20 mins after sedation and after elective ovariectomy. METHODS: Eighteen stray female cats randomly received intramuscular (IM) ketamine (2 mg/kg) and methadone (0.3 mg/kg) plus dexmedetomidine (7 µg/kg; group D, n = 9) or alfaxalone (2 mg/kg; group A, n = 9). A sedation score (0-15 [from none to good sedation]) was assigned at 5 mins, 10 mins, 15 mins and 20 mins after IM injection. Venous angiocatheter placement and echocardiographic examination feasibility scores (both from 0 to 3 [from very difficult to very easy]) were recorded at 20 mins. Echocardiography, HR and blood pressure measurements (Doppler and oscillometric methods) were performed at 20 mins and at the end of surgery. RESULTS: Sedation and angiocatheter feasibility scores did not differ significantly between groups (P >0.05); the feasibility score of echocardiographic examination was higher in cats in group D (P = 0.01). HR was higher in group A at 20 mins and after surgery (P <0.05). The systolic arterial pressure obtained with the Doppler method was statistically significantly higher in cats in group D than in group A at 20 mins (P = 0.01), while postoperatively there were no differences between groups. Cats in group D showed significantly higher atrial diameters (P <0.05) and slower atrial flows (P = 0.04) compared with group A; ventricular thickness and atrial function did not differ between groups (P >0.05). Most echocardiographic variables were not different at 20 mins vs postoperatively. CONCLUSIONS AND RELEVANCE: Both protocols allowed for effective sedation; however, cats in group D presented alterations in some echocardiographic measurements; the use of alfaxalone, combined with ketamine and methadone, is recommended to obtain a reliable echocardiographic evaluation in uncooperative cats.

Comparison of two injectable anaesthetic protocols in Egyptian fruit bats (Rousettus aegyptiacus) undergoing gonadectomy.

Egyptian fruit bats have gained increasing interest being a natural reservoir for emerging zoonotic viruses. Anaesthesia is often required to allow safe handling of bats. We aimed to compare the sedative and cardiopulmonary effects of two balanced anaesthetic protocols in bats undergoing gonadectomy. Group DK (n = 10) received intramuscular dexmedetomidine (40 µg/kg) and ketamine (7 mg/kg), whereas group DBM (n = 10) received intramuscular dexmedetomidine (40 µg/kg), butorphanol (0.3 mg/kg) and midazolam (0.3 mg/kg). Induction time and cardiopulmonary parameters were recorded. If anaesthetic plan was inadequate, isoflurane was titrated-to-effect. At the end of surgery venous blood gas analysis was performed and atipamezole or atipamezole-flumazenil was administered for timed and scored recovery. In DBM group heart rate and peripheral oxygen saturation were significantly higher (p = 0.001; p = 0.003 respectively), while respiratory rate was significantly lower (p = 0.001). All bats required isoflurane supplementation with no significant differences between groups. Induction and recovery times showed no significant differences. In group DK a better recovery was scored (p = 0.034). Sodium and chloride were significantly higher in DBM group (p = 0.001; p = 0.002 respectively). Both anaesthetic protocols were comparable and can be recommended for minor procedures in bats.

Use of dexmedetomidine repeated subcutaneous administration for balanced anaesthesia in horses.

BACKGROUND: A balanced anaesthetic protocol is a common concept in modern veterinary anaesthesia and aims to maintain good intraoperative cardiopulmonary function. In horses, alpha-2-agonists produce sedation and analgesia and have been shown to reduce inhalational anaesthetic requirements when administered intravenously. Furthermore, these drugs can improve recovery quality. Preliminary investigations of subcutaneous dexmedetomidine administration in humans demonstrated a reduced haemodynamic impact if compared with the intravenous route suggesting that dexmedetomidine is adequately absorbed with both administration routes. The aim of the study was to compare two different dexmedetomidine (DEX) administration routes: intravenous constant rate infusion (CRI) versus repeated subcutaneous (SC) injections on cardiopulmonary function and recovery in anaesthetized horses. RESULTS: No significant differences between groups in heart rate and systolic arterial pressure were detected. A significantly higher mean and diastolic arterial pressure were detected in the SC group at T25 (p = 0.04; p = 0.02), T75 (p = 0.02; p = 0.009), and T85 (p = 0.001; p = 0.005). In SC group there was a significantly lower dobutamine infusion rate (p = 0.03) and a significantly higher urinary output (p = 0.02). Moreover, recovery quality was higher (p = 0.01). CONCLUSIONS: Cardiopulmonary effects in both groups were comparable and within clinical ranges with less dobutamine requirement in the subcutaneous group. Recovery was of better quality with fewer attempts in horses receiving subcutaneous dexmedetomidine. The present study suggests that intravenous constant rate infusion and subcutaneous repeated administration of dexmedetomidine at indicated dosage can be useful in balanced anaesthesia without any systemic or local adverse effects; moreover, in healthy horses undergoing general anaesthesia, repeated subcutaneous dexmedetomidine administration may be a suitable alternative if constant rate infusion is not feasible.

Oral Transmucosal or Intramuscular Administration of Dexmedetomidine-Methadone Combination in Dogs: Sedative and Physiological Effects.

The aim of this study was to compare the sedative and physiological effects following either oral transmucosal (OTM) or intramuscular administration of dexmedetomidine-methadone combination in healthy dogs. Thirty dogs were randomly assigned to receive a dexmedetomidine-methadone combination either by the OTM (n = 15) or intramuscular (n = 15) route. Sedation was scored 10, 20, and 30 min after drugs administration. Heart rate (HR), non-invasive blood pressure (NIBP), respiratory rate (fR), and body rectal temperature were recorded before drugs administration and then every 10 min for 30 min. Propofol dose required for orotracheal intubation was recorded. Sedation scores increased over time within both groups with higher values in intramuscular group (p < 0.05). Within each group, HR decreased significantly compared with baseline (p < 0.001) and was significantly lower in intramuscular group compared with the OTM group (p < 0.001). In both groups, NIBP increased significantly compared with baseline (p < 0.05). In the intramuscular group, fR was lower compared with the OTM group at all the observational time points (p < 0.001). Propofol dose was lower in the intramuscular group (p < 0.05). Compared to intramuscular dexmedetomidine-methadone, OTM combination produced lower but effective sedation in healthy dogs.

Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis.

The aim of this study was to evaluate the efficacy of oral transmucosal (OTM) cannabidiol (CBD), in addition to a multimodal pharmacological treatment for chronic osteoarthritis-related pain in dogs. Twenty-one dogs were randomly divided into two groups: in group CBD (n = 9), OTM CBD (2 mg kg-1 every 12 h) was included in the therapeutic protocol (anti-inflammatory drug, gabapentin, amitriptyline), while in group C (n = 12), CBD was not administered. Dogs were evaluated by owners based on the Canine Brief Pain Inventory scoring system before treatment initiation (T0), and one (T1), two (T2), four (T3) and twelve (T4) weeks thereafter. Pain Severity Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0043) and T3 (p = 0.016). Pain Interference Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0007) and T4 (p = 0.004). Quality of Life Index was significantly higher in CBD group at T1 (p = 0.003). The addition of OTM CBD showed promising results. Further pharmacokinetics and long-term studies in larger populations are needed to encourage its inclusion into a multimodal pharmacological approach for canine osteoarthritis-related pain.