Assessment of the effect of gabapentin on blood pressure in cats with and without chronic kidney disease.

OBJECTIVES: The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD). METHODS: A randomized, blinded, placebo-controlled crossover study was performed. A total of 29 cats were included: 13 cats with stable CKD (IRIS stage 2-4) and 16 apparently healthy cats (serum creatinine <1.6 mg/dl and urine specific gravity >1.035). The cats were evaluated twice, approximately 1 week apart, and BP (Doppler sphygmomanometry) was obtained 3 h after cats received either a single dose of gabapentin 10mg/kg PO or placebo. For each cat, BP readings were obtained at each visit using the same Doppler and sphygmomanometer unit, and the same cat holder and Doppler operator, in the same location. RESULTS: After administration of a single dose of gabapentin (10 mg/kg PO), BP was significantly lower (median 122 mmHg, range 82-170) than after administration of the placebo (median 150 mmHg, range 102-191; P = 0.001). In the CKD subgroup, BP was significantly lower after administration of gabapentin (median 129 mmHg, range 96-170) than after administration of the placebo (median 155 mmHg, range 102-191; P = 0.008). In the healthy cat subgroup, BP was significantly lower after administration of gabapentin (median 121 mmHg, range 82-139) than after administration of the placebo (median 137 mmHg, range 102-177; P = 0.002). The median change in BP was -12 mmHg (range -95 to 10) for healthy cats and -12 mmHg (range -43 to 21) for cats with CKD (no significant difference between subgroups). CONCLUSIONS AND RELEVANCE: Gabapentin may decrease arterial BP in cats with and without CKD and these findings should be taken into account when gabapentin is administered to patients in which measurement of BP is needed.

Vincristine-induced adverse events related to body weight in dogs treated for lymphoma.

BACKGROUND: Traditional dosing of chemotherapy drugs based on body surface area may overdose small dogs, leading to an increased frequency of adverse events (AEs). HYPOTHESIS/OBJECTIVES: Evaluate the frequency of hematologic and gastrointestinal AEs in dogs with newly diagnosed lymphoma treated with vincristine weighing ≤15 kg in comparison to dogs weighing >15 kg. We hypothesized that dogs weighing ≤15 kg would experience a higher frequency of AEs. ANIMALS: One hundred and thirty-eight dogs with newly diagnosed lymphoma were treated with vincristine. METHODS: A multicenter retrospective study reviewing hematologic data and medical record information. Complete blood counts were performed no more than 24 hours before vincristine administration and then between 4 and 8 days post-administration. Data were evaluated using logistic regression or ordinal logistic regression. RESULTS: Thirty-eight dogs weighing ≤15 kg and 100 dogs weighing >15 kg were included. The median vincristine dose for both groups was 0.6 mg/m2. Seventeen (12.3%) instances of neutropenia occurred with no significant difference in overall frequency or grade between groups. Thirty initially asymptomatic substage A dogs (29.4%) experienced gastrointestinal AEs. Because of the widespread use of gastrointestinal supportive care medications, statistical comparison between groups could not be performed. Seven instances of hospitalization occurred (5.0%) and the risk of hospitalization did not differ significantly between groups (P = .37). CONCLUSIONS AND CLINICAL IMPORTANCE: Vincristine dosed at ≤0.6 mg/m2 does not increase the risk of hematologic AEs in dogs weighing ≤15 kg.

Pharmacokinetics and pharmacodynamics of intramuscular dexmedetomidine in dogs.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of dexmedetomidine after IM administration in dogs. ANIMALS: 6 healthy adult purpose-bred dogs (3 males, 3 females) with a mean ± SD body weight of 25.2 ± 1.8 kg. PROCEDURES: Each dog received 10 µg/kg dexmedetomidine, IM. Heart rate and respiratory rate were counted via cardiac auscultation and visual assessment of chest excursions. Sedation was assessed utilizing 2 sedation scoring systems. Plasma concentrations were determined using ultra performance liquid chromatography-mass spectrometry. Plasma concentrations versus time data after IM dexmedetomidine were analyzed using noncompartmental analysis for extravascular administration. RESULTS: Over the first 2 hours following IM injection of dexmedetomidine, plasma concentrations fluctuated in each dog. The geometric mean (range) maximum plasma concentration was 109.2 (22.4 to 211.5) ng/mL occurring at 20.5 (5 to 75) minutes, and the mean half-life was 25.5 (11.5 to 41.5) minutes. Heart rate was significantly lower than baseline from 30 minutes to 2 hours postdexmedetomidine administration, and respiratory rate was significantly lower than baseline from 45 minutes to 1.75 hours. Dogs were significantly more sedated from 30 minutes to 1.5 hours postdexmedetomidine administration. Median time to onset of sedation was 7.5 minutes (range, 2 to 10 minutes), and median time to peak sedation was 30 minutes (range, 15 to 60 minutes). CLINICAL RELEVANCE: Variations in plasma concentrations occurred in all dogs for the 2 hours postinjection of dexmedetomidine at 10 µg/kg, IM. This was likely due to alterations in absorption due to dexmedetomidine-induced local vasoconstriction. Despite variable plasma concentrations, all dogs were sedated following IM dexmedetomidine administration.

Risk of anesthesia-related complications in draft horses: a retrospective, single-center analysis.

OBJECTIVE: To report anesthetic-related complications and determine risks associated with anesthesia in draft horses. STUDY DESIGN: Retrospective study. ANIMALS: A total of 401 anesthetic records for draft horse breeds that underwent general anesthesia from January 2010 through December 2020 were reviewed; horses euthanized during general anesthesia were excluded. METHODS: Demographics, perioperative drugs used, procedure type and duration, time to extubation, number of attempts to stand, use of sling in recovery and perioperative morbidity and mortality were investigated. Morbidity and mortality statistical evaluation included univariable logistic regression analysis and ordinal regression analysis. RESULTS: American Society of Anesthesiologists (ASA) status I-II, ASA III-V and total mortality rate for all cases was 0.69% (2/288), 6.19% (7/113) and 2.24% (9/401), respectively, with Belgian horses being overrepresented (6/9). Cardiac arrest occurred in six out of nine horses that died without euthanasia, and five out of six of these horses underwent colic surgery. Factors associated with increased mortality risk included ASA status of III-V, increased body weight, emergency status and horses presenting for colic. Hypotension, hypercarbia and hypoxemia occurred in 56% (224/401), 46% (186/401) and 14% (58/401) of horses, respectively. During recovery from anesthesia, lighter horses and horses undergoing shorter anesthetic procedures were more likely to be successful on the first or second attempt to stand and were less likely to require a sling in recovery. CONCLUSIONS AND CLINICAL RELEVANCE: Draft horses undergoing general anesthesia had a higher mortality rate than previously reported for all types and breeds of horses.

Medication safety education: more than just a human concern?

The medication misuse epidemic continues to be a major concern for both human and veterinary health-care providers. Medication misuse of veterinary prescribed drugs is contributing to the public health crisis. Education of students regarding appropriate prescribing, communication with clients about medication storage, recognition of signs of vet shopping and animal abuse, and appropriate pain management strategies are essential steps for ensuring our students are prepared for the world that awaits them outside the halls of academic veterinary medicine. This is the moment where veterinarians can make a difference in the lives of patients, students, and the public health.

Utility of cardiac MRI to diagnose myocardial ischemia and fibrosis in dogs with cardiomegaly secondary to myxomatous mitral valve disease.

OBJECTIVE: To assess whether cardiac MRI or various biomarkers can be used to detect myocardial ischemia and fibrosis in dogs with cardiomegaly secondary to myxomatous mitral valve disease (MMVD). ANIMALS: 6 dogs with cardiomegaly secondary to naturally occurring stage B2 MMVD being treated only with pimobendan with or without enalapril and 6 control dogs with no cardiac disease. All dogs were ≥ 5 years old with no systemic illness. PROCEDURES: Serum cardiac troponin I and concentrations were measured, and dogs were anesthetized for cardiac MRI with ECG-triggered acquisition of native T1- and T2-weighted images. Gadolinium contrast was administered to evaluate myocardial perfusion and late gadolinium enhancement (LGE). Mean T1 and T2 values and regions of LGE were measured with dedicated software. Extracellular volume (ECV) was estimated on the basis of Hct and T1 values of myocardium and surrounding blood. Subjective analysis for myocardial perfusion deficits was performed. RESULTS: Dogs with MMVD had significantly (P = .013) higher cardiac troponin I concentrations than control dogs, but galectin-3 concentrations did not differ (P = .08) between groups. Myocardial fibrosis was detected in 4 dogs with MMVD and 3 control dogs; no dogs had obvious myocardial perfusion deficits. Native T1 and T2 values, postcontrast T1 values, and ECV values were not significantly different between groups (all P > .3). CLINICAL RELEVANCE: Results suggest that some dogs with cardiomegaly secondary to MMVD may not have clinically relevant myocardial fibrosis.

Serum concentrations of gabapentin in cats with chronic kidney disease.

OBJECTIVES: The purpose of this study was to assess serum concentrations of gabapentin in cats with chronic kidney disease (CKD) vs clinically healthy cats. METHODS: Five healthy cats were enrolled in a pharmacokinetic study. A single 20 mg/kg dose of gabapentin was administered orally and blood was obtained at 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24 and 36 h via a jugular catheter. Serum gabapentin concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Non-compartmental pharmacokinetic analysis was performed. The same five healthy cats plus 25 cats with stable International Renal Interest Society stage 2 (n = 14) and 3 (n = 11) CKD were enrolled in a limited sampling study. Cats in both groups received a single 10 mg/kg dose of gabapentin, and serum gabapentin concentrations and compliance scores were obtained 3 and 8 h post-administration. RESULTS: Cats with CKD had significantly higher dose-normalized serum gabapentin concentrations than normal cats at 3 h (P = 0.0012 CKD vs normal 10 mg/kg; P = 0.008 CKD vs normal 20 mg/kg) and 8 h (P <0.0001 CKD vs normal 10 mg/kg; P <0.0001 CKD vs normal 20 mg/kg). Both 3 and 8 h dose-normalized serum gabapentin concentrations were significantly correlated with serum creatinine (3 h: P = 0.03, r = 0.39; 8 h: P = 0.001, r = 0.57) and symmetric dimethylarginine (3 h: P = 0.03, r = 0.41; 8 h: P = 0.007, r = 0.48). There was a significant correlation between 3 h serum gabapentin concentrations and compliance scores (P = 0.0002, r = 0.68). CONCLUSIONS AND RELEVANCE: Cats with CKD that received 10 mg/kg of gabapentin had significantly higher dose-normalized serum concentrations than normal cats that received 20 mg/kg, supporting the need to dose-reduce in this patient population.

Evaluation of perfusion index as a noninvasive tool to determine epidural anesthesia effectiveness in dogs.

OBJECTIVE: To evaluate perfusion index (PI) as a noninvasive tool to determine effectiveness and onset of epidural anesthesia in dogs. STUDY DESIGN: Prospective clinical trial. ANIMALS: A total of 21 adult dogs, aged 6.5 ± 3 years and weighing 34.9 ± 6.4 kg, undergoing a tibial plateau leveling osteotomy. METHODS: Dogs were premedicated intramuscularly with acepromazine (0.03 mg kg-1) and hydromorphone (0.1 mg kg-1) and anesthetized with intravenous propofol (to effect) and isoflurane in oxygen. A surface transflectance probe was secured to the tail base to monitor PI and a dorsal pedal artery catheter was placed for invasive blood pressure monitoring. A lumbosacral epidural was performed with the dog in sternal recumbency. Dogs were randomly assigned for inclusion of epidural morphine (0.1 mg kg-1) or morphine (0.1 mg kg-1) and lidocaine (4 mg kg-1). PI was recorded following instrumentation of each dog just prior to the epidural (baseline), at 10 minute intervals for 30 minutes, before and after the surgical skin incision and before and after completion of the osteotomy. Physiological variables and end-tidal isoflurane were recorded at the same time points. RESULTS: There was no significant difference in PI between the groups at any time point. There was a significant change in end-tidal isoflurane before and after the skin incision in the epidural morphine and epidural morphine-lidocaine groups (p = 0.04, p = 0.05, respectively) and before and after the osteotomy in each group for heart rate (p = 0.001, p = 0.04), diastolic (p = 0.01, p = 0.01) and mean arterial blood pressure (p = 0.03, p = 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: PI did not provide an objective means for determining the onset or effectiveness of epidural anesthesia in anesthetized dogs and alternate methods of noninvasive assessment should be investigated.

Effects of a four-week group class created for dogs at least eight years of age on the development and progression of signs of cognitive dysfunction syndrome.

OBJECTIVE: To assess the effects of a 4-week group class specifically created for dogs ≥ 8 years old (senior dogs) on the development and progression of signs consistent with cognitive dysfunction syndrome (CDS). ANIMALS: 86 dogs with or without signs of CDS at the time of study enrollment. PROCEDURES: Dog owners completed a proprietary CDS survey at baseline and then 3, 6, and 12 months after completion of the baseline survey. Twenty owners with their dogs attended 4 weekly 50-minute classes that were specifically developed for senior dogs, addressed common behavior problems for these dogs, and included training and enrichment activities. Survey results were compared between class and nonclass groups and within groups at 3, 6, and 12 months. RESULTS: The association between age and CDS score was significant, such that older dogs had signs consistent with a higher degree of impairment. Cognitive dysfunction syndrome scores for dogs that attended the class did not significantly differ at 12 months, compared with scores at 3 months, whereas the CDS scores for dogs that did not attend the class were significantly increased at 12 months, compared with scores at 3 months. CONCLUSIONS AND CLINICAL RELEVANCE: Signs of CDS developed or worsened as dogs aged. Participation in the senior dog class mitigated the progression of signs of CDS and may improve a senior dog's quality of life.

Evaluation of intramuscular anesthetic protocols in healthy domestic horses.

OBJECTIVE: To assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses. STUDY DESIGN: Randomized, blinded, three-way crossover prospective design. ANIMALS: A total of eight healthy adult horses weighing 470-575 kg. METHODS: Horses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine-zolazepam (1.2 mg kg-1), ketamine (1 mg kg-1) and detomidine (0.04 mg kg-1) (treatment TKD); ketamine (3 mg kg-1) and detomidine (0.04 mg kg-1) (treatment KD); and tiletamine-zolazepam (2.4 mg kg-1) and detomidine (0.04 mg kg-1) (treatment TD). Parametric data were analyzed using mixed model linear regression. Nonparametric data were compared using Skillings-Mack test. A p value <0.05 was considered statistically significant. RESULTS: All horses in treatment TD became recumbent. In treatments KD and TKD, one horse remained standing. PaO2 15 minutes after recumbency was significantly lower in treatments TD (p < 0.0005) and TKD (p = 0.001) than in treatment KD. Times to first movement (25 ± 15 minutes) and sternal recumbency (55 ± 11 minutes) in treatment KD were faster than in treatments TD (57 ± 17 and 76 ± 19 minutes; p < 0.0005, p = 0.001) and TKD (45 ± 18 and 73 ± 31 minutes; p = 0.005, p = 0.021). There were no differences in induction quality, muscle relaxation score, number of attempts to stand or recovery quality. CONCLUSIONS AND CLINICAL RELEVANCE: In domestic horses, IM injections of tiletamine-zolazepam-detomidine resulted in more reliable recumbency with a longer duration when compared with ketamine-detomidine and tiletamine-zolazepam-ketamine-detomidine. Recoveries were comparable among protocols.

Effects of perioperative saphenous and sciatic nerve blocks, lumbosacral epidural or morphine-lidocaine-ketamine infusion on postoperative pain and sedation in dogs undergoing tibial plateau leveling osteotomy.

OBJECTIVE: To compare the quality of postoperative analgesia and sedation after preoperative saphenous and sciatic nerve blockade, preoperative lumbosacral epidural injection and perioperative intravenous (IV) morphine, lidocaine and ketamine infusions in dogs undergoing stifle arthroscopy and tibial plateau leveling osteotomy (TPLO) under general anesthesia. STUDY DESIGN: Prospective, blinded, randomized, clinical comparison study. ANIMALS: A total of 45 dogs weighing 33.9 (15.9-56.7) kg and aged 5.2 (1.0-12.0) years, mean (range), undergoing elective unilateral TPLO for spontaneous cranial cruciate ligament rupture. METHODS: Client-owned dogs were enrolled. Dogs were randomly assigned to one of three groups: group MLK, perioperative IV morphine, lidocaine and ketamine infusion; group EPID, lumbosacral epidural with ropivacaine and morphine; or group SSNB, saphenous and sciatic nerve blockade with ropivacaine. Routine stifle arthroscopy followed by TPLO surgery was performed. Sedation and pain scores were assessed at 0, 2, 4, 8 and 24 hours following extubation. Rescue analgesia was administered as prescribed by Glasgow composite pain score-short form score >5. RESULTS: Sedation scores for MLK were higher than EPID and SSNB. Pain scores for SSNB were lower than those for EPID and MLK. No significant differences were found in anesthesia duration or surgery duration among groups. No dogs required rescue analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Although analgesia was adequate in all groups, the best combination of analgesia without increased sedation was recorded for SSNB.

Short-term efficacy of epidural pain management in dogs undergoing cystoscopy.

BACKGROUND: The effects of epidural anesthesia in dogs undergoing cystoscopy are unknown. OBJECTIVE: To investigate the effect of epidural analgesia on postcystoscopy pain in dogs. ANIMALS: Twenty-six dogs undergoing routine cystoscopy for lower urinary tract disease. METHODS: Prospective, randomized, blinded observational study. Dogs were assigned either to a treatment group that received epidural anesthesia (preservative free morphine sulfate, 0.09 mg/kg; 1% ropivacaine, 0.2 mg/kg; total volume delivered, 1 mL/4.5 kg of body weight to a maximum of 10 mL; n = 9) or to a nonepidural control group (n = 13). Vital signs were monitored for 24 hours, and sedation and pain scores, behavioral assessments, and presence or absence of complications was evaluated for 5 days postprocedure. RESULTS: All dogs tolerated the epidural without complications. Four dogs were removed from the study because of status unblinding, lack of patient cooperation, or incomplete follow-up. No significant differences were noted in postprocedural pain scores in dogs that received epidural analgesia. Significant differences in postprocedural pain scores were noted in the nonepidural control group. No significant differences were noted in vital signs, behavioral assessments, or the proportion of dogs with a 50% increase in pain scores between the epidural and nonepidural groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Epidural anesthesia was well-tolerated. Dogs not receiving the epidural had poor postprocedural pain control. A consistent benefit for the epidural vs nonepidural group could not be identified. Additional studies are required to better assess the impact and efficacy of epidural anesthesia for cystoscopic procedures.

Anesthetic risk during subsequent anesthetic events in brachycephalic dogs that have undergone corrective airway surgery: 45 cases (2007-2019).

OBJECTIVE: To determine whether previous corrective upper airway surgery in brachycephalic dogs would decrease perianesthetic complications in subsequent anesthetic events. ANIMALS: 45 client-owned dogs. PROCEDURES: Brachycephalic dogs undergoing any combination of staphylectomy, nasal alaplasty, or laryngeal sacculectomy that were anesthetized at a later date for additional surgical procedures or imaging from August 2, 2007, to February 8, 2019, had their medical records reviewed during both anesthetic events for signalment, American Society of Anesthesiologists status, perianesthetic drug administration, anesthetic duration, presence and total time of positive-pressure ventilation, procedure invasiveness, and perianesthetic complications such as bradycardia, hypothermia, hypotension, cardiac arrhythmias, hypertension, vomiting or regurgitation, dysphoria, respiratory distress, hypoxemia, reintubation, and prolonged periods of recovery. RESULTS: The odds of having complications during the postanesthetic period following subsequent anesthetic events were decreased by 79% in dogs having previous surgical intervention to correct clinical signs of brachycephalic airway syndrome. Intra-anesthetic bradycardia increased the odds of developing a postanesthetic complication by 4.56 times. Every 15-minute increase in anesthetic duration increased the odds of having a postanesthetic complication by 12% and having an intra-anesthetic complication by 11%. CONCLUSIONS AND CLINICAL RELEVANCE: Previous corrective upper airway surgery decreased odds of postanesthetic complications in brachycephalic dogs that underwent subsequent anesthetic events. Findings in this study indicated that corrective upper airway surgery for brachycephalic dogs may reduce postanesthetic complications following subsequent anesthetic events, which may reduce perianesthetic morbidity in patients undergoing multiple surgical or diagnostic imaging procedures.

Effectiveness of tapentadol hydrochloride for treatment of orthopedic pain in dogs: A pilot study.

This pilot study evaluated the short-term analgesic effect of oral tapentadol hydrochloride (tapentadol) in dogs with unilateral hind limb lameness secondary to naturally occurring cranial cruciate ligament rupture. Baseline data including pharmacodynamic parameters, sedation scores, lameness scores, and objective gait analyses were collected. Tapentadol was administered orally (30 mg/kg body weight). Four hours following administration of tapentadol all data were collected again. Plasma concentrations of tapentadol 4 hours after administration were assessed using high performance liquid chromatography tandem mass spectrometry. No significant side effects were noted. All dogs had measurable plasma concentrations of tapentadol (mean concentration: 18.9 ng/mL). There were no significant differences in pharmacodynamic parameters or sedation over time. Subjective lameness scores were significantly lower than baseline at 4 hours post-drug administration. No significant improvement was seen in objective gait analysis. Further studies are needed to assess dosing regimens which may lead to effective treatment of acute pain and long-term use.

Efficacité de l'hydrochlorure de tapentadol pour le traitement de douleur orthopédique chez des chiens : une étude pilote. La présente étude pilote a évalué l'effet analgésique à court terme d'hydrochlorure de patentadol (tapentadol) chez des chiens avec une boiterie unilatérale d'un membre arrière secondaire à une rupture du ligament croisé antérieur se produisant naturellement. Les données de base obtenues incluaient des paramètres pharmacodynamiques, des pointages de sédation, des pointages de boiterie et des analyses objectives de la posture. Du tapentadol fut administré oralement (30 mg/kg de poids corporel). Quatre heures suivant l'administration de tapentadol toutes les données furent prises à nouveau. Les concentrations plasmatiques de tapentadol 4 heures après l'administration furent déterminées en utilisant la chromatographie à haute performance en phase liquide en tandem avec la spectrométrie de masse. Aucun effet secondaire significatif ne fut noté. Tous les chiens avaient des concentrations plasmatiques mesurables de tapentadol (concentration moyenne : 18,9 ng/mL). Il n'y avait pas de différence significative dans le temps pour les paramètres pharmacodynamiques ou la sédation. Les pointages subjectifs de boiterie 4 heures postadministration du médicament étaient significativement plus faibles que les valeurs de base. Aucune amélioration significative ne fut observée dans l'analyse objective de la posture. Des études supplémentaires sont requises pour évaluer les régimes de dosage qui pourraient mener à un traitement efficace de la douleur aiguë et de l'utilisation à long-terme.(Traduit par Dr Serge Messier).

Sedative and cardiorespiratory effects of intramuscular administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs.

OBJECTIVE: To evaluate the sedative and cardiorespiratory effects of IM administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs. ANIMALS: 6 young healthy mixed-breed hounds. PROCEDURES: Dogs received each of 3 treatments (alfaxalone [2 mg/kg] and butorphanol [0.4 mg/kg] combined with acepromazine [0.02 mg/kg; AB-ace], midazolam [0.2 mg/kg; AB-mid], or dexmedetomidine [0.005 mg/kg; AB-dex], IM) in a blinded, randomized crossover-design study with a 1-week washout period between treatments. Sedation scores and cardiorespiratory variables were recorded at predetermined time points. Data were analyzed by use of mixed-model ANOVA and linear generalized estimating equations with post hoc adjustments. RESULTS: All treatments resulted in moderate to deep sedation (median score, ≥ 15/21) ≤ 5 minutes after injection. Sedation scores did not differ among treatments until the 40-minute time point, when the score was higher for AB-dex than for other treatments. Administration of AB-dex resulted in median scores reflecting deep sedation until 130 minutes, versus 80 and 60 minutes for AB-ace and AB-mid, respectively, after injection. Heart rate, cardiac output, and oxygen delivery decreased significantly after AB-dex, but not AB-ace or AB-mid administration. Respiratory variables remained within clinically acceptable ranges after all treatments. Undesirable recovery characteristics were observed in 4 dogs after AB-mid treatment. Four dogs required atipamezole administration 180 minutes after AB-dex injection. CONCLUSIONS AND CLINICAL RELEVANCE: All protocols produced reliable sedation. The results indicated that in young, healthy dogs, AB-mid may produce undesirable recovery characteristics; AB-dex treatment caused cardiovascular depression and should be used with caution.

Effect of oral administration of gabapentin on the minimum alveolar concentration of isoflurane in dogs.

OBJECTIVE: To determine the effect of oral administration of gabapentin (20 mg/kg) on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 healthy adult dogs (3 males and 3 females with a mean ± SD body weight of 24.8 ± 1.3 kg). PROCEDURES: Each dog was anesthetized twice. Dogs were initially assigned to 1 of 2 treatments (gabapentin [20 mg/kg, PO] followed 2 hours later by anesthesia maintained with isoflurane or anesthesia maintained with isoflurane alone). A minimum of 7 days later, dogs received the other treatment. The MAC of isoflurane was determined by use of an iterative bracketing technique with stimulating electrodes placed in the maxillary buccal mucosa. Hemodynamic variables and vital parameters were recorded at the lowest end-tidal isoflurane concentration at which dogs did not respond to the stimulus. Effect of treatment on outcome variables was analyzed by use of a paired t test. RESULTS: Mean ± SD MAC of isoflurane was significantly lower when dogs received gabapentin and isoflurane (0.71 ± 0.12%) than when dogs received isoflurane alone (0.91 ± 0.26%). Mean reduction in MAC of isoflurane was 20 ± 14%. Hemodynamic variables did not differ significantly between treatments. Mean time to extubation was significantly less when dogs received gabapentin and isoflurane (6 ± 4 minutes) than when dogs received isoflurane alone (23 ± 15 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of gabapentin 2 hours before anesthesia maintained with isoflurane had a MAC-sparing effect with no effect on hemodynamic variables or vital parameters of dogs.

Pharmacokinetics and pharmacodynamic effects of oral transmucosal and intravenous administration of dexmedetomidine in dogs.

OBJECTIVE: To determine pharmacokinetic and pharmacodynamic properties of the injectable formulation of dexmedetomidine administered via the oral transmucosal (OTM) route to healthy dogs. ANIMALS: 6 healthy dogs. PROCEDURES: Injectable dexmedetomidine was administered IV (5 µg/kg) or via the OTM route (20 µg/kg) in a blinded, single-observer, randomized crossover study. Dogs received dexmedetomidine and a sham treatment at each administration. Serial blood samples were collected from a catheter in a saphenous vein. Heart rate, respiratory rate, and subjective sedation score were assessed for 24 hours after administration. Plasma samples were analyzed for dexmedetomidine concentrations by use of ultraperformance liquid chromatography-tandem mass spectrometry. RESULTS: For the OTM route, the mean ± SD maximum plasma concentration was 3.8 ± 1.3 ng/mL, which was detected 73 ± 33 minutes after administration. The mean maximum concentration for the IV dose, when extrapolated to the time of administration, was 18.6 ± 3.3 ng/mL. The mean terminal-phase half-life was 152 ± 146 minutes and 36 ± 6 minutes for OTM and IV administration, respectively. After IV administration, total clearance was 8.0 ± 1.6 mL/min/kg and volume of distribution at steady state was 371 ± 72 mL/kg. Bioavailability for OTM administration of dexmedetomidine was 11.2 ± 4.5%. Peak sedation scores did not differ significantly between routes of administration. Decreases in heart rate, respiratory rate, and peak sedation score were evident sooner after IV administration. CONCLUSIONS AND CLINICAL RELEVANCE: OTM administration of the injectable formulation of dexmedetomidine resulted in a similar degree of sedation and prolonged duration of action, compared with results for IV administration, despite relatively low bioavailability.

Pharmacokinetics and pharmacodynamics of alfaxalone after a single intramuscular or intravascular injection in mallard ducks (Anas platyrhynchos).

Pharmacokinetics and pharmacodynamics of alfaxalone was performed in mallard ducks (Anas platyrhynchos) after single bolus injections of 10 mg/kg administered intramuscularly (IM; n = 10) or intravenously (IV; n = 10), in a randomized cross-over design with a washout period between doses. Mean (±SD) Cmax following IM injection was 1.6 (±0.8) µg/ml with Tmax at 15.0 (±10.5) min. Area under the curve (AUC) was 84.66 and 104.58 min*mg/ml following IV and IM administration, respectively. Volume of distribution (VD ) after IV dose was 3.0 L/kg. The mean plasma clearance after 10 mg/kg IV was 139.5 (±67.9) ml min-1  kg-1 . Elimination half-lives (mean [±SD]) were 15.0 and 16.1 (±3.0) min following IV and IM administration, respectively. Mean bioavailability at 10 mg/kg IM was 108.6%. None of the ducks achieved a sufficient anesthetic depth for invasive procedures, such as surgery, to be performed. Heart and respiratory rates measured after administration remained stable, but many ducks were hyperexcitable during recovery. Based on sedation levels and duration, alfaxalone administered at dosages of 10 mg/kg IV or IM in mallard ducks does not induce clinically acceptable anesthesia.

Pharmacokinetics and pharmacodynamics of intranasal and intravenous naloxone hydrochloride administration in healthy dogs.

OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of naloxone hydrochloride in dogs following intranasal (IN) and IV administration. ANIMALS: 6 healthy adult mixed-breed dogs. PROCEDURES: In a blinded crossover design involving 2 experimental periods separated by a washout period (minimum of 7 days), dogs were randomly assigned to receive naloxone IN (4 mg via a commercially available fixed-dose naloxone atomizer; mean ± SD dose, 0.17 ± 0.02 mg/kg) or IV (0.04 mg/kg) in the first period and then the opposite treatment in the second period. Plasma naloxone concentrations, dog behavior, heart rate, and respiratory rate were evaluated for 24 hours/period. RESULTS: Naloxone administered IN was well absorbed after a short lag time (mean ± SD, 2.3 ± 1.4 minutes). Mean maximum plasma concentration following IN and IV administration was 9.3 ± 2.5 ng/mL and 18.8 ± 3.9 ng/mL, respectively. Mean time to maximum concentration following IN administration was 22.5 ± 8.2 minutes. Mean terminal half-life after IN and IV administration was 47.4 ± 6.7 minutes and 37.0 ± 6.7 minutes, respectively. Mean bioavailability of naloxone administered IN was 32 ± 13%. There were no notable changes in dog behavior, heart rate, or respiratory rate following naloxone administration by either route. CONCLUSIONS AND CLINICAL RELEVANCE: Use of a naloxone atomizer for IN naloxone administration in dogs may represent an effective alternative to IV administration in emergency situations involving opioid exposure. Future studies are needed to evaluate the efficacy of IN naloxone administration in dogs with opioid intoxication, including a determination of effective doses.

Effect of oral trazodone on the minimum alveolar concentration of isoflurane in dogs.

OBJECTIVE: To determine the effect of oral trazodone on the minimum alveolar concentration (MAC) of isoflurane in dogs. STUDY DESIGN: Prospective blinded, single-observer, randomized crossover experimental study. ANIMALS: Six adult (age 6.8 ± 1.6 months) healthy dogs (three males and three females), weighing 24.8 ± 3.4 kg (mean ± standard deviation). METHODS: Each dog was anesthetized twice with a minimum of 7 days between anesthetic episodes. Dogs were randomly assigned to be administered two treatments in a crossover design: premedication with trazodone (8 mg kg-1; TRAZ-ISO) orally 2 hours prior to an anesthetic episode or no (ISO). Dogs were anesthetized with intravenous propofol (6 mg kg-1) and isoflurane in >95% oxygen. Isoflurane MAC was determined using an iterative bracketing technique with electrodes placed in the buccal mucosa. Hemodynamic variables were compared at the lowest end-tidal isoflurane concentration at which each dog did not respond. A paired t test was used to assess the effect of treatment on outcome variables with significance set to a value of p < 0.05. RESULTS: The MAC concentration (mean ± standard deviation) in dogs administered TRAZ-ISO was 0.85 ± 0.17% compared with 1.02 ± 0.11% in those administered ISO (p = 0.01, 95% confidence interval -0.25 to -0.05), resulting in a mean MAC reduction of 17 ± 12%. There were no differences in hemodynamic variables between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Premedication of dogs with oral trazodone (8 mg kg-1) 2 hours prior to anesthetic induction has a significant isoflurane MAC sparing effect with no significant observed hemodynamic benefit.