Pharmacokinetic profile and physiological effects of oral and compounded intravenous gabapentin in goats.

OBJECTIVE: To determine the pharmacokinetics and physiological effects following oral and intravenous (IV) administration of gabapentin in goats. STUDY DESIGN: Prospective, crossover study with a 3 week washout period between treatments. ANIMALS: A total of eight healthy, client-owned, female goats. METHODS: Gabapentin (10 mg kg-1) was administered to goats either orally or IV. Gabapentin concentrations were measured in serum samples collected 0-96 hours post-administration using liquid chromatography-quadrupole time-of-flight mass spectrometry. Heart rate, respiratory rate, blood pressure and temperature were recorded before and throughout the study. Correlations of the mean serum concentrations of gabapentin to those of each physiological parameter were determined using the Pearson method. RESULTS: The mean and standard deviation of oral bioavailability for gabapentin was 60.9 ± 11.2%. Maximum serum concentration of gabapentin was lower following oral (1.19 ± 0.29 µg mL-1) than after IV administration (59.76 ± 14.38 µg mL-1, p < 0.0001). Half-lives were longer following PO (8.18 ± 0.57 hours) than after IV administration (1.79 ± 0.06 hours, p < 0.0001). Time to maximum concentration was 6.86 ± 2.27 hours following oral administration. Heart rate was inversely correlated with serum gabapentin concentrations. Slight ataxia was observed in three animals, and one became recumbent following IV gabapentin. CONCLUSIONS AND CLINICAL RELEVANCE: Gabapentin is well-absorbed following oral administration to goats but yielded significantly lower serum concentrations than the IV route. The longer half-life of gabapentin following oral than after IV administration may result from prolonged absorption throughout the caprine gastrointestinal tract. IV gabapentin may cause slight ataxia in some goats.

Veterinary students' attitudes toward anesthesiology as a specialty.

OBJECTIVE: To identify the perceptions of veterinary students interested in specialization regarding veterinary anesthesiology. STUDY DESIGN: Cross-sectional, multi-institutional, voluntary, anonymous, nonrandomized survey. POPULATION: Veterinary students (303 of 557 total respondents) from 10 veterinary schools. METHODS: Quantitative data were obtained via 5-point Likert scale questions about anesthesia-related topics. Open-ended questions were used to obtain qualitative data. A multivariate logistic regression model assessed the likelihood of choosing a career as an anesthesiologist. Spearman's rank correlation coefficient was used to assess the relationship between 'anesthesia is interesting' and other variables. RESULTS: Of the respondents, 14 (6%) indicated veterinary anesthesia as their chosen specialty. There was a significant positive relationship between 'anesthesia is interesting' and the following variables: age, enjoyment in anesthesia class, belief in the importance of anesthesia for their career, belief in the importance of analgesia for their career, belief that anesthesia and analgesia have a large impact on patient care, interest in pharmacology, interest in physiology, interest in learning technical skills, belief that anesthesiologists are respected by their colleagues and belief that anesthesiologists are an important part of the health care team. More weeks on the anesthesia clinical rotation was positively and significantly associated with increased rotation enjoyment. Enjoyment in the anesthesia class [p = 0.001, Exp(ß) = 2.1, 95% confidence interval (CI): 1.3-3.4] and belief that anesthesia is interesting [p = 0.013, Exp(ß) = 2.6, 95% CI: 1.2-5.4] were predictors that respondents would be more likely to consider a career as a veterinary anesthesiologist. CONCLUSIONS: Those veterinary students with an interest in pharmacology and who enjoyed their anesthesia course were more likely to consider a career as a veterinary anesthesiologist. If students indicated no interest in specializing in veterinary anesthesia, they appreciated the value the specialty brings to animal care and believed that veterinary anesthesiologists are respected by their peers.

Flumazenil Treatment for Diazepam-Associated Neurological Signs in a Cat With a Portosystemic Shunt.

A 7-month-old female spayed domestic short hair cat was presented for evaluation of inadequate clinical response to medical management for hepatic encephalopathy (HE). An abdominal computed tomography (CT) was to be performed but the cat developed 2 grand mal seizures shortly after presentation. Minimal handling and no drugs had been administered before the seizures. A single dose of diazepam (0.3 mg/kg, IV) was administered after each seizure. Another seizure occurred 24 hours after hospitalization and diazepam (0.5 mg/kg, IV) was once again administered. Seizures ceased but neurological signs worsened and included head pressing, loss of menace response, and a stuporous mentation. Due to unresponsiveness to treatment that included administration of intravenous fluids, levetiracetam, ampicillin/sulbactam, and retention enemas (water with lactulose), a dose of flumazenil (0.01 mg/kg) was administered IV and resulted in immediate but transient improvement of clinical signs. The stuporous state returned after 60 min post-treatment and an additional dose of IV flumazenil (0.01 mg/kg) was administered with the same outcome. Based on this positive clinical response, IV infusion of flumazenil was initiated at 0.01 mg/kg/h following a loading dose of 0.005 mg/kg. Due to minimal improvement in neurological signs, flumazenil IV infusion was increased gradually until reaching the effective dose of 0.1 mg/kg/h. Flumazenil IV infusion was continued for 24 hours with improvements in neurological signs, which did not return upon gradual decrease of the flumazenil dose. This is the first report describing the use of a flumazenil IV infusion to improve neurological signs in a cat with a PSS and HE treated with diazepam.

Gabapentin, melatonin, and acepromazine combination prior to hospital visits decreased stress scores in aggressive and anxious dogs in a prospective clinical trial.

OBJECTIVE: To evaluate sedative and behavioral effects of a client-administered preappointment protocol with PO gabapentin and melatonin and oral-transmucosal acepromazine (GMA protocol). ANIMALS: 45 client-owned dogs between 1 and 12 years old that underwent standardize examinations between February and August 2021. METHODS: In this clinical trial, dogs with a history of anxiety, fearfulness, and/or aggression during hospital visits were assessed and videotaped before (baseline) and after administration of the GMA protocol. For the second visit, owners administered PO gabapentin (20 to 25 mg/kg) in the evening prior to the next visit and PO gabapentin (20 to 25 mg/kg), PO melatonin (3 to 5 mg/dog), and oral-transmucosal acepromazine (0.05 mg/kg) 90 to 120 minutes prior to the second appointment. Examinations were performed, and behavioral stress and sedation levels were evaluated with semiquantitative rating scales. Randomized videos were analyzed, and a paired t test was used to compare stress and sedation scores between baseline and GMA. A Pearson correlation coefficient was used to evaluate the effect of age on the scores. RESULTS: Stress scores were significantly lower after the GMA protocol, and sedation scores were significantly higher when compared to baseline (21.84 vs 27.11 and 1.39 vs 0.68, respectively). A significant correlation between increasing age and lower stress scores post-GMA and higher sedation scores post-GMA were observed. CLINICAL RELEVANCE: Preappointment administration of the GMA protocol reduced signs of stress, fear, and fear-based aggression during hospital visits and provided sedation in this dog population. This protocol could represent an adjunct tool for veterinarians to improve quality of care and reduce animal-related injury.

Anesthetic Considerations in Dogs and Cats with Diabetes Mellitus.

Understanding the effects of diabetes and hyperglycemia on hydration, acid-base status, and immune function is paramount to safely anesthetizing diabetic cats and dogs. Preoperative stabilization of glucose concentrations, hydration, and electrolyte imbalances is key to minimizing morbidity and mortality. Blood glucose monitoring perioperatively will help guide insulin and dextrose administration. Specific anesthetic considerations, and peri-anesthetic management of animals with diabetes mellitus, including anesthetic drugs and recommended insulin protocols are discussed.

Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial.

OBJECTIVE: To evaluate the effects of alfaxalone administered IM with or without buprenorphine or hydromorphone in healthy rabbits (Oryctolagus cuniculus). ANIMALS: 24 male rabbits undergoing elective orchiectomy between August 21, 2021, and November 6, 2021. PROCEDURES: In this controlled clinical trial, rabbits were randomly assigned to receive alfaxalone (4 mg/kg, IM) alone (group A; n = 8) or with buprenorphine (0.03 mg/kg, IM; group BA; 8) or hydromorphone (0.1 mg/kg, IM; group HA; 8). Vital signs and sedation scores were recorded immediately prior to (T0) and 10 minutes after (T1) treatment. Ease of IV catheter placement and pain scores were also evaluated. All rabbits received ketamine (2.5 mg/kg, IV), midazolam (0.13 mg/kg, IV), and meloxicam (0.5 mg/kg, SC) before orchiectomy but after IM treatments. Results were compared across groups with ANOVA or Fisher exact tests and across time with paired t tests. RESULTS: Sedation score, median time to recumbency, and ease of catheter placement did not differ among groups. Supraglottic airway device placement was possible for 1 rabbit in group A, 1 in group BA, and 2 in group HA. Mean respiratory rate at T1 versus T0 was significantly decreased for groups BA (63.8 vs 128.6 breaths/min) and HA (66.7 vs 123.2 breaths/min). Mean postoperative pain scores were significantly lower for rabbits in group HA (0.58), compared with those in groups A (2.25) and BA (2.06). CLINICAL RELEVANCE: All 3 treatments provided reliable sedation; however, alfaxalone (4 mg/kg, IM) combined with hydromorphone (0.1 mg/kg, IM) may be a better choice for painful procedures.

Effect of inhaled albuterol on whole blood potassium concentrations in dogs.

BACKGROUND: Albuterol by inhalation (IH) is a common treatment for hyperkalemia in humans but its effect on blood potassium concentrations in dogs is unknown. OBJECTIVE: Determine whether albuterol (IH) decreases blood potassium concentrations in healthy normokalemic dogs and if effects are dose-dependent. ANIMALS: Ten healthy dogs. METHODS: Prospective, crossover experimental study. Albuterol sulfate was administered at a low-dose (90 µg) in phase I and, 7 days later, high-dose (450 µg) in phase II. Blood potassium and glucose concentrations (measured via blood gas analyzer) and heart rates were obtained at baseline and then 3, 5, 10, 15, 30, 60, 90, 120, 180, and 360 minutes after inhaler actuation. RESULTS: Blood potassium concentrations decreased rapidly after albuterol delivery with a significant reduction compared to baseline within 30 minutes in both phases (P = .05). The potassium nadir concentration of phase I occurred at 60 minutes (mean, SD; 4.07 mmol/L, 0.4) and was significantly decreased from baseline, (4.30 mmol/L, 0.3; t(9) = 2.40, P = .04). The potassium nadir concentration of phase II occurred at 30 minutes (mean, SD; 3.96 mmol/L, 0.39) and was also significantly decreased from baseline, (4.33 mmol/L, 0.4; t(9) = 2.22, P = .05). The potassium nadir concentration decreased by 0.1 mmol/L for each 10 µg/kg increase in dose of albuterol (P = .01). Five dogs had ≥1 hyperglycemic measurement (ie, >112 mg/dL). No median heart rate was tachycardic nor was any mean blood glucose concentration hyperglycemic at any time point. CONCLUSION AND CLINICAL IMPORTANCE: Albuterol IH decreases blood potassium concentrations in a dose-dependent manner without clinically meaningful alterations to heart rate or blood glucose concentrations in healthy dogs. The mean decrease in potassium concentration at the high-dose of albuterol was modest (0.38 mmol/L).

Randomized, blinded, controlled clinical trial to assess gastroesophageal reflux and regurgitation in dogs undergoing general anesthesia after hydromorphone premedication with or without acepromazine or dexmedetomidine.

OBJECTIVE: To investigate whether premedication with hydromorphone alone or combined with acepromazine or dexmedetomidine affects the incidence of gastroesophageal reflux (GER) and regurgitation in dogs undergoing general anesthesia for elective orthopedic surgery. ANIMALS: 39 healthy client-owned dogs undergoing general anesthesia for elective orthopedic surgery between November 2016 and November 2018. PROCEDURES: For this prospective, randomized, controlled, blinded clinical trial, dogs were randomly assigned to be premedicated with hydromorphone (0.1 mg/kg, IM) alone (group H [control group]) or with either acepromazine (0.05 mg/kg, IM; group AH) or dexmedetomidine (6 µg/kg, IM; group DH) before undergoing general anesthesia induced with propofol and maintained with isoflurane. A pH sensor-tipped probe was used to identify episodes of GER (esophageal pH < 4 or > 7.5 for ≥ 30 seconds). Results for GER, regurgitation, vomiting, propofol dose, and durations of food withholding and anesthesia were compiled and compared across groups. RESULTS: There were 13 dogs in each group, and no meaningful differences were detected in age, body weight, sex, breed, or durations of anesthesia or food withholding across groups. Overall, 16 of the 39 (41%) dogs developed GER: 9 in group H, 6 in group AH, and 1 in group DH. The incidence of GER was significantly lower for group DH versus group H. Six of the 39 (15%) dogs regurgitated: 4 in group H and 2 in group AH. CONCLUSIONS AND CLINICAL RELEVANCE: The combined use of dexmedetomidine and hydromorphone as premedication may be a better choice to reduce GER in healthy dogs undergoing orthopedic surgery than would the use of hydromorphone with or without acepromazine. Additional research is warranted.

Postoperative regurgitation and respiratory complications in brachycephalic dogs undergoing airway surgery before and after implementation of a standardized perianesthetic protocol.

OBJECTIVE: To determine whether implementation of a standardized perianesthetic protocol was associated with reduced incidence of postoperative regurgitation, pneumonia, and respiratory distress in brachycephalic dogs undergoing general anesthesia for airway surgery. ANIMALS: 84 client-owned dogs. PROCEDURES: A perianesthetic protocol that included preoperative administration of metoclopramide and famotidine, restrictive use of opioids, and recovery of patients in the intensive care unit was fully implemented for brachycephalic dogs in July 2014. Medical records of brachycephalic dogs (specifically Boston Terriers, French Bulldogs, English Bulldogs, and Pugs) undergoing anesthesia for airway surgery before (group A) and after (group B) protocol implementation were reviewed. Patient characteristics, administration of medications described in the protocol, surgical procedures performed, anesthesia duration, recovery location, and postoperative development of regurgitation, pneumonia, and respiratory distress were recorded. Data were compared between groups. RESULTS: The proportion of dogs with postoperative regurgitation in group B (4/44 [9%]) was significantly lower than that in group A (14/40 [35%]). No intergroup differences in patient characteristics (including history of regurgitation), procedures performed, or anesthesia duration were found. Rates of development of postoperative pneumonia and respiratory distress did not differ between groups. A history of regurgitation was associated with development of postoperative regurgitation. CONCLUSIONS AND CLINICAL RELEVANCE: Implementation of the described protocol was associated with decreased incidence of postoperative regurgitation in brachycephalic dogs undergoing anesthesia. Prospective studies are warranted to elucidate specific causes of this finding.

IL-33 signaling is essential to attenuate viral-induced encephalitis development by downregulating iNOS expression in the central nervous system.

BACKGROUND: Viral encephalitis is a common cause of lethal infections in humans, and several different viruses are documented to be responsible. Rocio virus is a flavivirus that causes a severe lethal encephalitis syndrome in humans and also mice, providing an interesting model to study the CNS compartmentalized immune response. Interleukin 33 (IL-33), a member of the IL-1 family, is an immunomodulatory cytokine that is highly expressed in the CNS. However, the role of IL-33 on viral encephalitis remains unclear. Therefore, we aimed to explore how the IL-33/ST2 axis regulates the local immune response during Rocio virus infection. METHODS: Wild-type (WT), ST2 (ST2(-/-)), and nitric oxide synthase-deficient mice (iNOS(-/-)) and Stat6 (Stat6(-/-))-deficient mice were infected with different concentrations of the Rocio virus by intraperitoneal route, the cytokine mRNA level in CNS was analyzed by qPCR, and cellular immunophenotyping was performed on infected mice by the flow cytometry of isolated CNS mononuclear cells. RESULTS: We have shown that the mRNA expression of IL-33 and ST2 receptors is increased in the CNS of Rocio virus-infected WT mice and that ST2(-/-) mice showed increased susceptibility to infection. ST2 deficiency was correlated with increased tissue pathology, cellular infiltration, and tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) mRNA levels and higher viral load in the CNS, compared with wild-type mice. The increased Th1 cytokine levels released in the CNS acted on infiltrating macrophages, as evidenced by flow cytometry characterization of cellular infiltrates, inducing the expression of iNOS, contributing to brain injury. Moreover, iNOS(-/-) mice were more resistant to Rocio virus encephalitis, presenting a lower clinical score and reduced mortality rate, despite the increased tissue pathology. CONCLUSIONS: We provide evidences of a specific role for IL-33 receptor signaling in nitric oxide induction through local IFN-γ modulation, suggesting that nitric oxide overproduction might have an important role in the progression of experimental viral encephalitis.

Doppler blood pressure measurement in pigs during anaesthesia.

To determine the accuracy of Doppler blood pressure measurement in anaesthetised pigs eight large white pigs (Sus scrofa) were anaesthetised with zolazepam and tiletamine as Zoletil 100 (4 mg/kg) and xylazine (2 mg/kg) by intramuscular injection followed by isoflurane in 100% oxygen. Blood pressure measurements were recorded using a Doppler probe on the radial artery and a catheter in the femoral artery connected to a transducer. The sample mean of the Doppler measurements were compared with the sample mean of the invasive systolic arterial blood pressure while accounting for the heart rate, end-tidal CO2 and temperature. The predicted error of the Doppler was greatest when pigs were hypotensive and normothermic: 11 mmHg (CI: 6-15). Doppler measurements should be interpreted with caution in anaesthetised pigs that are hypotensive and normothermic.

Multiple potassium channels mediate nitric oxide-induced inhibition of rat vascular smooth muscle cell proliferation.

Several nitric oxide (NO) effects in the cardiovascular system are mediated by soluble guanylate cyclase (sGC) activation but potassium channels (KC) are also emerging as important effectors of NO actions. We investigated the relationship among vascular smooth muscle cell proliferation, NO, cyclic GMP, and KC using the A7r5 smooth muscle cell line derived from rat aorta. NO donors (two nitrosothiols, S-nitroso-acetyl-d,l-penicillamine, SNAP, and S-nitroso-glutathione, GSNO, and an organic nitrate, glyceryl trinitrate, GTN; 1-1000 microM) dose-dependently inhibited cell proliferation. ODQ (a selective inhibitor of sGC; 0.1 and 1 microM) and KT5823 (a selective inhibitor of cGMP-dependent protein kinase, 1 microM) prevented NO effects, confirming that sGC is a key target. In this report, we show that tetraethylammonium (TEA, a non-selective blocker of KC, 300 microM), and 4-aminopyridine (a selective blocker of voltage-dependent KC, 100 microM) prevented SNAP inhibitory effects on cell proliferation, whereas glibenclamide (a selective blocker of ATP-dependent KC, 1 microM) was ineffective. Iberiotoxin (a selective blocker of high conductance calcium-activated KC, 100 nM), as well charybdotoxin (a blocker of high and intermediate conductance calcium-activated KC, 100 nM) and apamine (a selective blocker of small conductance calcium-activated KC, 100 nM), blocked the antiproliferative effect induced by SNAP. NS1619 (an opener of high conductance calcium-activated KC, 1-100 microM), inhibited cell proliferation. In addition, sub-effective concentrations of ODQ (100 nM) and TEA (10 microM) synergized in blocking SNAP antiproliferative effects. Thus, voltage-dependent and calcium-activated but not ATP-dependent KC appear to have a prominent role, besides sGC activation, in NO-induced inhibition of vascular smooth muscle cell proliferation.