Alexander Valverde

Objective: To characterize the cardiovascular effects of 3 increasing doses of glycopyrrolate in healthy rabbits anesthetized with isoflurane. Methods: 9 healthy 1-year-old female New Zealand white rabbits were anesthetized with isoflurane and received increasing doses of glycopyrrolate at low dose (LD; 0.025 mg/kg), medium dose (MD; 0.05 mg/kg), and high dose (HD; 0.1 mg/kg) IV. Heart rate was recorded at baseline and 3, 5, 10, 20, and 30 minutes after administration of each dose. An arterial blood sample was collected to measure plasma glycopyrrolate concentrations at baseline and 3 and 30 minutes after administration of each dose. Analysis of plasma glycopyrrolate concentrations was performed using LC-MS-MS. Results: The HD led to a significantly higher heart rate δ value than LD and MD only at 3 minutes (all P < .003). The HD caused significantly higher systolic arterial pressure and mean arterial pressure δ values at 3, 5, 20, and 30 minutes ( P < .05) and diastolic arterial pressure at 3, 20, and 30 minutes ( P < .05) than LD. The MD caused a significantly higher diastolic arterial pressure δ value at 20 and 30 minutes ( P < .05) and mean arterial pressure at 5, 20, and 30 minutes ( P < .05) than LD. The mean plasma concentration that elicited a significant increase in heart rate was 62 ± 16.11 ng/mL. Conclusions: A brief increase (< 5 minutes) in HR in nonbradycardic rabbits was observed with 0.1 mg/kg of glycopyrrolate during isoflurane anesthesia. Clinical Relevance: Even at HDs, clinical effects of glycopyrrolate in rabbits appear very short lived.

Glycopyrrolate is an alternative to atropine to treat bradyarrhythmias in anesthetized rabbits; however, there are no pharmacokinetic studies in the literature. Six female New Zealand White rabbits received glycopyrrolate 0.05 mg/kg intravenously (IV) in the cephalic vein or intramuscularly (IM) in a complete crossover design. Blood was collected via jugular catheter to determine glycopyrrolate concentrations at baseline, 3, 5, 10, 20, 30, 45, 60 min and 2, 4, 6, 8, 12 and 24 h post‐administration. Quantification of plasma glycopyrrolate was performed using liquid chromatography–tandem mass spectrometry. Non‐compartmental analysis showed fast clearance (104.03 ± 45.55 mL/kg/min), volume of distribution at steady state of 0.75 ± 0.54 L/kg and terminal half‐life of 2.49 ± 1.1 h after IV administration. Terminal half‐life was 3.34 ± 1.10 h, T _max was 0.07 ± 0.01 h, and C _max was 2.96 ± 2 ng/mL for the IM route. Absolute bioavailability for the IM route was 10.07% ± 3.39%, suggesting higher doses may be needed for this route of administration. This study reports the pharmacokinetic parameters of glycopyrrolate in rabbits after IV and IM administration and may help design future evidence‐based administration protocols in this species.

The objective of this prospective study was to investigate whether repeated consecutive general anesthesia in horses undergoing 2 different anesthetic protocols could lead to improved recovery scores. Six healthy female Standardbred horses (453 ± 57 kg; 6.5 ± 4.2 y old) underwent 4 anesthetic protocols over 12 to 13 wk. Procedures 1 and 4 were arthroscopic surgeries [induction: xylazine, diazepam, and ketamine; and maintenance: Fe′Isoflurane (1.1%), lidocaine (2 mg/kg body weight [BW], 50 to 100 μg/min per kg BW), dexmedetomidine (2.5 μg/h per kg BW)]. Procedures 2 and 3 were preparation for magnetic resonance imaging (MRI) [induction: xylazine, guaifenesin, and ketamine; and maintenance: Fe′Isoflurane (1.3%)], as well as mechanical ventilation during all events. For recovery, horses were placed in 2 different recovery stalls, one for procedures 1 and 4, and a different one for procedures 2 and 3, and received xylazine, 0.15 to 0.25 mg/kg BW, IV. Recovery was scored using a numerical score and descriptive scale. A 1-way analysis of variance (ANOVA) was used to compare recovery scores, cardiopulmonary variables, anesthetic times, and drug dosages between procedures (P < 0.05). Anesthetic protocols for procedures 3 (10.5 ± 2.5) and 4 (10.2 ± 3.1) had better (P = 0.0348) recovery numerical scores than those for procedure 2 (14.3 ± 1.9) and were similar to those for procedure 1 (11.5 ± 2.3), but overall descriptive scores were not significantly different (1 = 1.7 ± 0.5, 2 = 1.8 ± 0.4, 3 = 1.3 ± 0.5, 4 = 1.3 ± 0.5). Balance and coordination (P = 0.0172) and knuckling (P = 0.0193) were associated with worse recovery in procedure 2. Anesthesia time was longer (P < 0.0001) in procedures 2 (157 ± 11 min) and 3 (96 ± 5 min) than in procedures 1 (72 ± 9 min) and 4 (60 ± 5 min). In conclusion, the quality of recovery is influenced by anesthetic protocol and in this study, quality improved in procedures 3 and 4 compared to procedure 2.

Twelve adult horses were randomly assigned to 2 groups in a prospective experimental trial. A pneumatic tourniquet (425 mmHg) was placed, under sedation, proximal to the carpus on one randomly chosen thoracic limb. A cephalic vein catheter was placed distal to the tourniquet to establish an intravenous regional limb perfusion technique (IVRLP) with morphine (0.1 mg/kg) diluted with saline 0.9% to 0.1 mL/kg, and the tourniquet left in place for 30 minutes. Horses were euthanized at 1 h (Group I) or 6 h (Group II) following the IVRLP and synovial fluid from the radiocarpal, intercarpal, metacarpophalangeal, distal interphalangeal, and digital flexor tendon sheath was obtained from the injected and contralateral (control) limb immediately after. Morphine concentrations were determined using liquid chromatography-mass spectrometry. An unpaired t-test was used to compare morphine concentrations from both groups (P, 0.05). Synovial morphine concentrations were detected in the injected limb in all horses in Group I, except in one horse in the radiocarpal joint, and detected in 5 of 6 horses in Group II. Mean synovial concentrations ranged between 301.8 +/- 192.3 and 608 +/- 446.6 ng/mL in Group I and between 27.0 +/- 17.7 and 136.8 +/- 103.6 ng/mL in Group II and were significantly higher in Group I between paired anatomical sites of both groups for the radiocarpal and distal interphalangeal joints, and the digital flexor tendon sheath. In conclusion, concentrations of morphine after IVRLP can be detected in synovial fluid distal to the tourniquet at 1 and 6 hours in horses.

The objective of this study was to compare the rostral spread of lumbosacral epidural volumes of a mixture of dye and contrast medium, calculated using body weight (BW) or vertebral column length (LE), in 22 dog cadavers. The dogs weighed 4.6 to 52.0 kg. Dogs were paired within a, 10% difference for BW and LE and with the same body condition score (BCS). Pairs of dogs were injected while in sternal recumbency through an epidural catheter with a volume mixture of iopamidol and dye, calculated based on BW: 0.2 mL/kg in one of the cadavers and based on LE: 0.05 mL/cm (, 50 cm), 0.07 mL/cm (50 to, 70 cm), 0.08 mL/cm (70 to, 80 cm), and 0.11 mL/cm ($ 80 cm) in the other cadaver. The extent of rostral spread was determined using computed tomography for iopamidol and anatomical dissection for dye. Comparisons for dye and iopamidol within each dog, and for BW and LE within matched pairs, were completed with mixed linear models (P, 0.05). The number of vertebrae reached by dye was greater than the number reached by iopamidol in both BW and LE, but the rostral spread was not significantly different between BW and LE for all pairs. In conclusion, dye tends to spread further than iopamidol and therefore, these two methods should not be considered interchangeable when used in research studies.

The first objective of this prospective, randomized, crossover experimental trial was to compare the rostral spread of lumbosacral epidural volume calculated by body weight (BW) or vertebral column length (LE) in 6 small, isoflurane- anesthetized female beagle dogs (BW: 7.5 to 10.2 kg; LE measured from the occipital crest to the sacrococcygeal space: 46 to 56 cm). The second objective was to assess the response to a noxious stimulus once the dogs recovered from anesthesia and to determine the effects of the injection on cardiopulmonary variables. While in sternal position, dogs were injected through an epidural catheter with a volume mixture of bupivacaine 0.25% and iopamidol 15% based on BW: 0.2 mL/kg or LE: 0.05 mL/cm (, 50 cm) or 0.07 mL/cm ( 50 to, 70 cm). Rostral spread was determined by counting the number of vertebrae reached by iopamidol using computed tomography. After anesthesia, cardiopulmonary variables, motor function, and responses to nociceptive stimuli were evaluated. Comparisons were completed with mixed linear models and 2-way analysis of variance (ANOVA) ( P, 0.05). The volume of injectate (3.29 6 0.74 versus 1.81 6 0.21 mL; mean 6 SD) and the number of vertebrae (22 6 2 versus 19 6 2 vertebrae) reached by iopamidol were significantly greater for LE than for BW. Response to nociception, time to return of pain sensation, motor function, and cardiopulmonary variables were similar between groups. In conclusion, dosing based on LE resulted in larger rostral spread than when based on BW in dogs of small size.

Trazodone and gabapentin are common oral sedatives in cats, used alone or combined, but no pharmacokinetic studies exist for trazodone in this species. The objective of this study was to determine the pharmacokinetics of oral trazodone (T) alone, or in combination with gabapentin (G) in healthy cats. Cats (n = 6) were randomly allocated to receive T (3 mg/kg) intravenously (IV), T (5 mg/kg) orally (PO), or T (5 mg/kg) and G (10 mg/kg) PO with a 1‐week washout period between treatments. Heart rate, respiratory rate, indirect blood pressure, and level of sedation were assessed, and venous blood samples were collected serially over 24 h. Analysis of plasma trazodone concentration was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Oral T administration resulted in a bioavailability of 54.9(7–96)%, and 17.2(11–25)% when administered with G. T_max 0.17 (0.17–0.5) and 0.17 (0.17–0.75) h; C_max 1.67 ± 0.91 and 1.22 ± 0.54 μg/mL, AUC 5.23 (2.0–18.76) and 2.37 (1.17–7.80) h*μg/mL; T_1/2 5.12 ± 2.56 and 4.71 ± 1.07 h; for T and TG, respectively. Sedation was significant when compared to baseline in all groups from 20 or 45 min to 8 h indicating some lag between peak plasma concentration and sedative effects. Physiological variables remained within normal limits. This study concludes that oral trazodone is rapidly absorbed in healthy cats. Addition of gabapentin did not result in more profound sedation, showing no clinical advantage of combining these drugs in this study population.