Comparison of intranasal and intramuscular ketamine‐midazolam combination in cats

ObjectiveThe aim of the present study was to compare intranasal (INS) and intramuscular (IM) routes of administration of a ketamine-midazolam combination in cats.Study designRandomized block design.AnimalsTwelve healthy mixed breed cats (six males and six females).MethodsThe drug combination was ketamine (14 mg kg⁻¹) and midazolam (0.5 mg kg⁻¹). In the IM group, drugs were injected into quadratus femoris muscle; in the INS. group, the combination dropped equally into the two nostrils. Pulse and respiratory rates, peripheral haemoglobin oxygen saturation (SpO₂) and rectal temperature were monitored before and at intervals after drug administration. Time to onset and duration of sedation and, during recovery to head up, sternal recumbency and recovery were recorded.ResultsThere were no significant differences between the groups in any time measured except for recovery to sternal recumbency, where time was lower in the INS than in the IM (p = 0.034). Respiratory rate was greater in the INS than in the IM group (p = 0.029), but there was no difference between groups in other physiological parameters. In both groups SpO₂ was low before and fell further during sedation.ConclusionsThe results substantiated that INS ketamine-midazolam can produce effective sedation in cats.Clinical relevanceIntranasal (INS) administration of ketamine-midazolam is atraumatic, and its use may avoid the pain of injection of ketamine combinations when this drug is used to induce sedation in cats.     

Pharmacokinetics of intravenous ketorolac in cats undergoing gonadectomy

AIM: To determine the pharmacokinetics of ketorolac tromethamine (0.5?mg/kg) when administered I/V to cats undergoing gonadectomy.

METHODS: Ketorolac was administered to nine female and three male shorthair domestic cats as an I/V bolus of 0.5?mg/kg after intubation, and 20 minutes prior to ovariectomy or orchiectomy. Intra-operative cardiorespiratory variables were monitored and blood samples were collected over 24 hours. Concentrations of ketorolac in serum were determined by high-performance liquid chromatography to establish pharmacokinetic parameters.

RESULTS: During surgery, mean end tidal isoflurane concentration was 1.63 (SD 0.24)% and normocapnia and spontaneous ventilation were maintained in all animals. The kinetics of ketorolac was described by a two-compartment model. The distribution and elimination half-lives were 0.09 (SD 0.06) and 4.14 (SD 1.18) hours, respectively. The body clearance was 56.8 (SD 33.1) mL/h/kg. The volume of distribution at steady-state and the mean residence time were 323.9 (SD 115.7) mL/kg and 6.47 (SD 2.86) hours, respectively.

CONCLUSION AND CLINICAL RELEVANCE: On the basis of the results, concentrations of ketorolac in serum in cats were above the human effective concentrations for 5–6 hours postoperatively. However, other studies including a control group are advocated to further investigate the ketorolac kinetics and the analgesic efficacy in this species.     

The effects of diazepam or midazolam on the dose of propofol required to induce anaesthesia in cats

ObjectivesAssess effects of benzodiazepine administration on the propofol dose required to induce anaesthesia in healthy cats, investigate differences between midazolam and diazepam, and determine an optimal benzodiazepine dose for co-induction.Study designProspective, randomised, blinded, placebo-controlled clinical trial.AnimalsNinety client-owned cats (ASA I and II) with a median (interquartile range) body mass of 4.0 (3.4–4.9) kg.MethodsAll cats received 0.01 mg kg⁻¹ acepromazine and 0.2 mg kg⁻¹ methadone intravenously (IV). Fifteen minutes later, sedation was scored on a scale of 1–5, with 5 indicating greatest sedation. Propofol, 2 mg kg⁻¹, administered IV, was followed by either midazolam or diazepam at 0.2, 0.3, 0.4 or 0.5 mg kg⁻¹ or saline 0.1 mL kg⁻¹. Further propofol was administered until endotracheal intubation was possible. Patient signalment, sedation score, propofol dosage and adverse reactions were recorded.ResultsMidazolam and diazepam (all doses) significantly reduced the propofol dose required compared with saline (p < 0.001). There was no difference between midazolam and diazepam in propofol dose reduction (p = 0.488). All individual doses of midazolam reduced propofol requirement compared with saline (0.2 mg kg⁻¹, p = 0.028; 0.3 mg kg⁻¹, p = 0.006; 0.4 mg kg⁻¹, p < 0.001; 0.5 mg kg⁻¹, p = 0.009). Diazepam 0.2 mg kg⁻¹ did not reduce the propofol dose compared with saline (p = 0.087), but the remaining doses did (0.3 mg kg⁻¹, p = 0.001; 0.4 mg kg⁻¹, p = 0.032; 0.5 mg kg⁻¹, p = 0.041). Cats with sedation scores of 3 required less propofol than cats with scores of 2 (p = 0.008). There was no difference between groups in adverse events.Conclusions and clinical relevanceMidazolam (0.2–0.5 mg kg⁻¹) and diazepam (0.3–0.5 mg kg⁻¹) administered IV after 2 mg kg⁻¹ propofol significantly reduced the propofol dose required for tracheal intubation.     

Pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol following a single induction dose administered intravenously in cats

ObjectiveTo compare the pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol administered intravenously (IV) as a single induction dose in cats.Study designProspective experimental study.AnimalsSix healthy adult cats, three female intact, three male castrated, weighing 4.8 ± 1.8 kg.MethodsCats received 8 mg kg⁻¹ IV of propofol (P) or propofol with 2% benzyl alcohol (P28) using a randomized crossover design. Venous blood samples were collected at predetermined time points to 24 hours after drug administration to determine drug plasma concentrations. Physiologic and behavioral variables were also recorded. Propofol and benzyl alcohol concentrations were determined using high pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were described using a 2-compartment model. Pharmacokinetic and pharmacodynamic parameters were analyzed using repeated measures anova (p < 0.05).ResultsPlasma concentrations of benzyl alcohol were below the lower limits of quantification (LLOQ) at all time points for two of the six cats (33%), and by 30 minutes for the remaining four cats. Propofol pharmacokinetics, with or without 2% benzyl alcohol, were characterized by rapid distribution, a long elimination phase, and a large volume of distribution. No differences were noted between treatments with the exception of clearance from the second compartment (CLD2), which was 23.6 and 38.8 mL kg⁻¹ minute⁻¹ in the P and P28 treatments, respectively. Physiologic and behavioral variables were not different between treatments with the exception of heart rate at 4 hours post administration.Conclusions and clinical relevanceThe addition of 2% benzyl alcohol as a preservative minimally altered the pharmacokinetics and pharmacodynamics of propofol 1% emulsion when administered as a single IV bolus in this group of cats. These data support the cautious use of propofol with 2% benzyl alcohol for induction of anesthesia in healthy cats.     

Determination of the sevoflurane sparing effect of methadone in cats

ObjectiveTo determine the magnitude and duration of sevoflurane minimum alveolar concentration (MAC) reduction following a single intravenous (IV) dose of methadone in cats.Study designProspective experimental study.AnimalsEight (four females and four males) healthy mixed-breed adult (1–2 years) cats weighing 5.82 ± 0.42 kg.MethodsAnesthesia was induced and maintained with sevoflurane. Intravenous catheters facilitated administration of methadone and lactated Ringer’s solution. After baseline MAC determination in triplicate using a tail clamp technique, 0.3 mg kg^?1 of methadone was administered IV. End-tidal sevoflurane concentration (e′SEVO) was reduced and MAC was redetermined. In an effort to determine the duration of MAC reduction, measurements were repeated in a stepwise manner until MAC values returned to baseline. After the last stimulation, the e′SEVO was increased to 1.2 individual MAC for 15 minutes, then sevoflurane was discontinued and cats were allowed to recover from anesthesia.ResultsBaseline sevoflurane MAC was 3.18 ± 0.06%. When compared with baseline the sevoflurane MAC after methadone administration was significantly reduced by 25, 15 and 7% at 26, 76 and 122 minutes, respectively. The final MAC value (3.09 ± 0.07%) determined 156 minutes after methadone administration was not significantly different from baseline.Conclusions and clinical relevanceIntravenous methadone (0.3 mg kg^?1) significantly decreased MAC of sevoflurane in cats but the effect was short-lived.     

Pharmacokinetics of midazolam and its major metabolite 1‐hydroxymidazolam in the ball python (Python regius) after intracardiac and intramuscular administrations

Midazolam is a benzodiazepine with sedative, muscle relaxant, anxiolytic, and anticonvulsant effects. Twelve ball pythons (Python regius) were used in a parallel study evaluating the pharmacokinetics of 1 mg/kg midazolam following a single intracardiac (IC) or intramuscular (IM) administration. Blood was collected from a central venous catheter placed 7 days prior, or by cardiocentesis, at 15 time points starting just prior to and up to 72 hr after drug administration. Plasma concentrations of midazolam and 1‐hydroxymidazolam were determined by the use of high‐performance liquid chromatography tandem‐mass spectrometry and pharmacokinetic parameters were estimated using noncompartmental analysis. The mean ± SD terminal half‐lives of IC and IM midazolam were 12.04 ± 3.25 hr and 16.54 ± 7.10 hr, respectively. The area under the concentration‐time curve extrapolated to infinity, clearance, and apparent volume of distribution in steady‐state of IC midazolam were 19,112.3 ± 3,095.9 ng*hr/ml, 0.053 ± 0.008 L hr^?1 kg^?1, and 0.865 ± 0.289 L/kg, respectively. The bioavailability of IM midazolam was estimated at 89%. Maximum plasma concentrations following an IM administration were reached 2.33 ± 0.98 hr and 24.00 ± 14.12 hr postinjection for midazolam and 1‐hydroxymidazolam, respectively, and 22.33 ± 20.26 hr postinjection for 1‐hydroxymidazolam following IC administration.     

Sedative, analgesic and cardiorespiratory effects of romifidine in cats

OBJECTIVE: To evaluate the sedative, analgesic, and cardiorespiratory effects of intramascular (IM) romifidine in cats. STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: Ten healthy adult cats. METHODS: Romifidine (100, 200, and 400 microg kg(-1)) or xylazine (1 mg kg(-1)) was given IM in a cross-over study design. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), hemoglobin saturation, oscillometric arterial pressure, and scores for sedation, muscle relaxation, position, auditory response, and analgesia were determined before and after drug administration. Time to recumbency, duration of recumbency, and time to recover from sedation were determined. Subjective evaluation and cardiorespiratory variables were recorded before and at regular intervals for 60 minutes after drug administration. RESULTS: Bradycardia developed in all cats that were given romifidine or xylazine. No other significant differences in physiologic parameters were observed from baseline values or between treatments. Increasing the dose of romifidine did not result in increased sedation or muscle relaxation. Cats given xylazine showed higher sedation and muscle relaxation scores over time. Analgesia scores were significantly higher after administration of romifidine (400 microg kg(-1)) and xylazine (1 mg kg(-1)) than after romifidine at 100 or 200 microg kg(-1). Duration of lateral recumbency was not significantly different between treatments; however, cats took longer to recover after administration of 400 micro g kg(-1) romifidine. CONCLUSIONS AND CLINICAL RELEVANCE: Bradycardia is the most important adverse effect after IM administration of romifidine at doses ranging from 100 to 400 microg kg(-1) or 1 mg kg(-1) of xylazine in cats. The sedative effects of romifidine at 200 microg kg(-1) are comparable to those of 1 mg kg(-1) of xylazine, although muscle relaxation and analgesia were significantly less with romifidine than with xylazine.     

Cardiopulmonary and anesthetic effects of the combination of butorphanol,midazolam and alfaxalone in Beagle dogs

ObjectiveTo evaluate the physiological variables, arterial blood gas values, induction of anesthesia quality, and recovery quality using the combination of butorphanol, midazolam and alfaxalone in dogs.AnimalsTen healthy adult Beagle dogs weighing 8.3 ± 3.1 kg.MethodsRectal temperature (T), pulse rate (PR), respiratory rate (f_R), mean arterial pressure (MAP), and arterial blood gases were measured and recorded prior to intravenous (IV) administration of butorphanol, prior to administration of both midazolam and alfaxalone IV 10 minutes later, then every 5 minutes for 20 minutes. M-mode echocardiographic left ventricular (LV) indices were measured before and 5 minutes after administration of alfaxalone. Qualitative scores for induction of anesthesia and recovery were allocated, duration of anesthesia and recovery were calculated, and adverse events were recorded.ResultsScores for induction and recovery quality were excellent. No significant adverse events were observed. Mean ± SD time from induction to extubation and to standing (full recovery) was 29 ± 6 and 36 ± 8 minutes, respectively. There were statistically significant changes in PR, f_R and MAP after drug administration. Transient hypercarbia developed after alfaxalone injection. The echocardiographic LV indices were reduced after alfaxalone injection, although those changes were not statistically significant.Conclusions and clinical relevanceThe combination of butorphanol, midazolam and alfaxalone provided excellent quality of induction of anesthesia and exerted minimal cardiopulmonary effects in healthy dogs.     

Comparison of the brainstem auditory evoked responses during sevoflurane or alfaxalone anaesthesia in adult cats

Objective

To compare the effects of general anaesthesia using sevoflurane or alfaxalone on the brainstem auditory evoked response (BAER) test in adult healthy cats.

Intravenous sufentanil‐midazolam versus sevoflurane anaesthesia in medetomidine pre‐medicated Himalayan rabbits undergoing ovariohysterectomy

ObjectiveTo compare physiological effects of sufentanil-midazolam with sevoflurane for surgical anaesthesia in medetomidine premedicated rabbits.Study designProspective, randomized controlled experimental study.AnimalsEighteen female Himalayan rabbits, weight 2.1 ± 0.1 kg.MethodsPremedication with 0.1 mg kg⁻¹ medetomidine and 5 mg kg⁻¹ carprofen subcutaneously, was followed by intravenous anaesthetic induction with sufentanil (2.3 μg mL⁻¹) and midazolam (0.45 mg mL⁻¹). After endotracheal intubation, anaesthesia was maintained with sufentanil-midazolam (n = 9) or sevoflurane (n = 9). Ovariohysterectomy was performed. Intermittent positive pressure ventilation was performed as required. Physiological variables were studied perioperatively. Group means of physiologic data were generated for different anaesthetic periods. Data were compared for changes from sedation, and between groups by anova. Post-operatively, 0.05 mg kg⁻¹ buprenorphine was administered once and 5 mg kg⁻¹ carprofen once daily for 2–3 days. Rabbits were examined and weighed daily until one week after surgery.ResultsSmooth induction of anaesthesia was achieved within 5 minutes. Sufentanil and midazolam doses were 0.5 μg kg⁻¹ and 0.1 mg kg⁻¹, during induction and 3.9 μg kg⁻¹ hour⁻¹ and 0.8 mg kg⁻¹ hour⁻¹ during surgery, respectively. End-tidal sevoflurane concentration was 2.1% during surgery. Assisted ventilation was required in nine rabbits receiving sufentanil-midazolam and four receiving sevoflurane. There were no differences between groups in physiologic data other than arterial carbon dioxide. In rabbits receiving sevoflurane, mean arterial pressure decreased pre-surgical intervention, heart rate increased 25% during and after surgery and body weight decreased 4% post-operatively. Post-operative problems sometimes resulted from catheterization of the ear artery.ConclusionSevoflurane and sufentanil-midazolam provided surgical anaesthesia of similar quality. Arterial blood pressure was sustained during sufentanil-midazolam anaesthesia and rabbits receiving sevoflurane lost body weight following ovariohysterectomy. Mechanical ventilation was required with both anaesthetic regimens.Clinical relevanceAnaesthesia with sufentanil-midazolam in medetomidine premedicated healthy rabbits is useful in the clinical and the research setting, as an alternative to sevoflurane.     

Evaluation of tumescent local anesthesia in cats undergoing unilateral mastectomy

ObjectiveTo evaluate the analgesic efficacy and safety of tumescent local anesthesia (TLA) in cats undergoing unilateral mastectomy.Study designProspective clinical trial.AnimalsA total of 12 ovariohysterectomized female cats.MethodsAll animals were premedicated with pethidine (4 mg kg^–1) intramuscularly (IM), followed by induction of anesthesia with propofol (5 mg kg^–1) intravenously and maintenance with isoflurane in oxygen. A refrigerated TLA solution (15 mL kg^–1, 8 °C) was injected using a Klein cannula. The solution was composed of 0.5 mL of epinephrine (1 mg mL^–1) and 40 mL of 2% lidocaine added to 210 mL lactated Ringer’s solution (final lidocaine concentration 0.32%). Heart and respiratory rates, systolic arterial blood pressure, temperature and oxygen saturation were measured during anesthesia. Blood samples were collected from the jugular vein for measurement of plasma lidocaine concentration using high performance liquid chromatography. Postoperative pain scores were evaluated hourly for 6 hours. Analgesic rescue was performed with tramadol (2 mg kg^–1) IM and meloxicam (0.15 mg kg^–1) subcutaneously.ResultsPlasma lidocaine concentration peaked at 90 minutes after injection of TLA, but no concentration considered toxic for the species was measured. The median postoperative analgesia time was 6 hours after injection of TLA.ConclusionsThis study found that TLA prevented sympathetic response to noxious stimuli during anesthesia and provided satisfactory postoperative analgesia in cats submitted to total unilateral mastectomy, with no apparent signs of toxicity.Clinical relevanceTLA can prevent sympathetic stimulation resulting from noxious stimuli during anesthesia, promoting good intraoperative conditions, proving to be a viable addition to analgesia in cats submitted to a total unilateral mastectomy.     

Pharmacokinetics of vatinoxan in male neutered cats anesthetized with isoflurane

ObjectiveTo characterize the pharmacokinetics of vatinoxan in isoflurane-anesthetized cats.Study designProspective experimental study.AnimalsA group of six adult healthy male neutered cats.MethodsCats were anesthetized using isoflurane in oxygen. Venous catheters were placed to administer the drug and sample blood. Vatinoxan, 1 mg kg^–1, was administered intravenously over 5 minutes. Blood was sampled before and at various times during and up to 8 hours after vatinoxan administration. Plasma vatinoxan concentration was measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time–concentration data using population methods and nonlinear mixed effect modeling.ResultsA three-compartment model best fitted the data. Typical value (% interindividual variability) for the three volumes (mL kg^–1), the metabolic clearance and two distribution clearances (mL minute^–1 kg^–1) were 34 (55), 151 (35), 306 (18), 2.3 (34), 42.6 (25) and 5.6 (0), respectively. Hypotension increased the second distribution clearance to 10.6.Conclusion and clinical relevanceThe pharmacokinetics of vatinoxan in anesthetized cats were characterized by a small volume of distribution and a low clearance. An intravenous bolus of 100 μg kg^–1 of vatinoxan followed by constant rate infusions of 55 μg kg^–1 minute^–1 for 20 minutes, then 22 μg kg^–1 minute^–1 for 60 minutes and finally 10 μg kg^–1 minute^–1 for the remainder of the infusion time is expected to maintain the plasma concentration within 90%–110% of the plasma vatinoxan concentration previously shown to attenuate the cardiovascular effects of dexmedetomidine (25 μg kg^–1) in conscious cats.     

Evaluation of alfaxalone and midazolam with or without flumazenil reversal in Egyptian fruit bats (Rousettus aegyptiacus)

ObjectivesTo evaluate alfaxalone–midazolam anesthesia in Egyptian fruit bats (Rousettus aegyptiacus) and the effect of flumazenil administration on recovery time and quality.Study designRandomized, blinded, crossover and controlled, experimental trial.AnimalsA total of 10 male Egyptian fruit bats.MethodsBats were anesthetized with alfaxalone (15 mg kg^?1) and midazolam (2 mg kg^?1) administered subcutaneously. During anesthesia, vital signs, muscle tone and reflexes were monitored every 10 minutes. Flumazenil (0.3 mg kg^?1) or saline at an equal volume was administered subcutaneously 60 minutes after anesthetic administration. Time to induction, time to first movement and recovery time (flying) were measured. Quality of induction, anesthesia and recovery were assessed on a 1–3 scale (1, poor; 2, good; 3, excellent).ResultsTime to induction was 4.2 ± 1.9 minutes (mean ± standard deviation), with median quality score of 2 (range, 1–3). Anesthesia quality score was 3 (1–3). During anesthesia, heart rate and respiratory frequency decreased significantly and penis relaxation, indicating muscle tone, increased significantly. Administration of flumazenil significantly reduced mean recovery time compared with saline (10 ± 5 versus 45 ± 17 minutes, respectively), and significantly improved the quality of recovery [2.5 (2–3) versus 1 (1–2), respectively].Conclusions and clinical relevanceAlfaxalone–midazolam anesthesia resulted in good induction, muscle relaxation and sufficient anesthesia to perform routine diagnostic and therapeutic procedures for approximately 40 minutes. Reversal of midazolam with flumazenil is recommended, resulting in quicker and better recovery.     

Pharmacokinetics of dexmedetomidine,MK-467 and their combination following intramuscular administration in male cats

Objective

To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats.

Chemical immobilization of Weddell seals (Leptonychotes weddellii) by ketamine/midazolam combination

ObjectiveTo provide reliable, effective immobilization for Weddell seals under extreme field conditions using an injectable ketamine/midazolam combination.Study designObservational study.AnimalsThirty adult Weddell seals (12 male, 18 female) in Erebus Bay, Antarctica, body mass (mean ± SD) 412 ± 47 kg, aged 9–27 years.MethodsSeals were immobilized with a target dose of 2 mg kg^?1 ketamine hydrochloride and 0.1 mg kg^?1 midazolam hydrochloride (IM), based on visually estimated body mass. When required, maintenance doses were administered at a target of 0.5 mg kg^?1 ketamine hydrochloride and 0.025 mg kg^?1 midazolam hydrochloride (IV).ResultsComplete immobilization was achieved in 33 of 40 injections (14 of which were repeat events on the same individual). Time to immobilization averaged 12 ± 4 minutes, with a duration of initial immobility of 38 ± 19 minutes. Total immobilization time varied by handling protocol, including condition assessment and muscle biopsy (Protocol 1, 60 ± 13 minutes), condition assessment and instrument attachment (Protocol 2, 154 ± 13 minutes), and condition assessment, muscle biopsy and instrument retrieval (Protocol 3, 48 ± 8 minutes). Overall, a total immobilization time of 114 ± 60 minutes was accomplished with 4 ± 4 maintenance doses, and an average recovery time of 36 ± 17 minutes. Most effects of the anesthetic combination were unrelated to mass, age, sex or total body fat. However, leaner seals had longer duration of initial immobility (% and kg total body fat) and recovery times (kg fat). Apnea events were uncommon and treated effectively with doxapram. No animals died.Conclusions and clinical relevanceReliable and effective field immobilization of Weddell seals was accomplished with a low dose of ketamine hydrochloride and midazolam hydrochloride, utilizing IM injection initially and IV maintenance methods.     

The bioequivalence of a single intravenous administration of the anesthetic alfaxalone in cyclodextrin versus alfaxalone in cyclodextrin plus preservatives in cats

To demonstrate the bioequivalence of alfaxalone in cyclodextrin (Reference Product) to a formulation of alfaxalone in cyclodextrin also containing the preservatives ethanol, chlorocresol, and benzethonium chloride (Test Product) when administered for the purpose of inducing anesthesia in the cat. Blinded, single‐dose, randomized, two‐period, two‐sequence, cross‐over bioequivalence study with a 7‐day washout period between treatments. Twenty‐four (12 neutered males and 12 intact females), healthy, adult cats weighing 4.1±0.9 kg. Cats were administered 5 mg/kg IV of alfaxalone in the Reference or Test Product using a randomized cross‐over design. One‐milliliter venous blood samples were collected at predetermined time points to 12 hr after drug administration to determine alfaxalone plasma concentration over time. Alfaxalone concentrations were determined by a validated analytical testing method using HPLC‐MS/MS. Plasma profiles of alfaxalone concentration against time were analyzed by noncompartmental analysis. The pivotal variables for bioequivalence were AUC_last and C_max. Equivalence was achieved if the 90% confidence interval for AUC_last and C_max fell into the asymmetric ±20% interval (0.80–1.25). Physiological variables, quality of anesthesia visual analog scale (VAS) scoring and anesthetic event times were recorded. ANOVA or ANCOVA (single time point), RMANOVA or RMANCOVA (multiple time point) was used for normally distributed data. GLIMMIX was used for nonnormally distributed data. VAS scores were analyzed as for blood bioequivalence data. Variables were evaluated for safety and assessed at alpha = 0.10. C_max and AUC_last for Reference and Test Products were statistically bioequivalent. No physiological variables except for a drug by time interaction for respiratory rate differed between treatment groups, and this difference was not clinically relevant. No anesthetic event times or VAS scores for quality of anesthesia were different between treatment groups. Neither formulation caused pain upon injection. The Reference and Test Products are pharmaceutically bioequivalent formulations when administered as a single intravenous administration for the purpose of induction of anesthesia in cats.     

Sedative-hypnotic effects of midazolam in goats after intravenous and intramuscular administration

Objective To examine the effect of dose and route of administration on the sedative‐hypnotic effects of midazolam. Design Prospective randomized controlled study Animals Six indigenous, African bred goats. Methods Pilot studies indicated that the optimum dose of midazolam for producing sedation was 0.6 mg kg^?1 for intramuscular (IM) injection, while the optimum intravenous (IV) doses causing hypnosis without, and with loss of palpebral reflexes were 0.6 mg kg^?1 and 1.2 mg kg^?1, respectively. These doses and routes of administration were compared with a saline placebo in a randomized block design in the main experiment, and the sedative‐hypnotic effects evaluated according to pre‐determined scales. Results Intramuscular midazolam produced sedation with or without sternal recumbency in all animals with the peak effect occurring 20 minutes after administration. The scores for IM sedation with midazolam were significantly different (p < 0.05) from placebo. Intravenous midazolam at 0.6 mg kg^?1 resulted in hypnosis, and at 1.2 mg kg^?1 increased reflex suppression was observed. The maximum scores for hypnosis at both doses were obtained 5 minutes after IV injection. The mean (± SD) duration of lateral recumbency was 10.8 (± 3.8) minutes after IV midazolam (0.6 mg kg^?1) compared to 20 (± 5.2) minutes after midazolam at 1.2 mg kg^?1. Compared to baseline, the heart rate increased significantly (p < 0.05) after high dose IV midazolam. Conclusion Intramuscular midazolam (0.6 mg kg^?1) produced maximum sedation 20 minutes after injection. Intravenous injection produced maximum hypnosis within 5 minutes. Increasing the IV dose from 0.6 to 1.2 mg kg^?1 resulted in increased reflex suppression and duration of hypnosis. Clinical relevance For a profound effect with rapid onset midazolam should be given IV in doses between 0.6 and 1.2 mg kg^?1.     

Pharmacokinetics of cephalexin in cats after oral administration of the antibiotic in tablet and paste preparations

Objective To determine the bioequivalence of a paste formulation of cephalexin with that of the tablet form.
Design A two-way cross-over study.
Animals Ten adult cats of mixed breed.
Procedure The cats, randomly allocated to two groups, received either the paste preparation or the tablet orally at 12-hour intervals for 48 h before a 12-hour blood collection period. Two weeks later the treatments were reversed and the blood sampling repeated. The serum concentrations of the antibiotic were determined. The pharmacokinetic factors were analysed using a computer.
Results There were no significant differences between the peak concentration of cephalexin, or the other pharmacokinetic factors obtained from the tablet and paste formulations. The serum profiles of cephalexin following four 12-hourly doses of each formulation were similar with the peak serum values occurring at approximately 2 h after administration.
Conclusion The paste formulation and the tablet form are bioequivalent.     

Post‐anesthesia deafness in dogs and cats following dental and ear cleaning procedures

Objective The present study was performed to document hearing loss in dogs and cats following procedures performed under anesthesia. Most cases of reported hearing loss were subsequent to dental and ear cleaning procedures. Study design Prospective and retrospective case survey. Animals Subjects were dogs and cats with deafness, personally communicated to one author, cases discussed on a veterinary information web site, and cases communicated through a survey of general practice and dental specialist veterinarians. Methods Reported deafness cases were characterized by species (dog, cat), breed, gender, age, and dog breed size. Results Sixty‐two cases of hearing loss following anesthesia were reported between the years 2002 and 2009. Five additional cases were reported by survey respondents. Forty‐three cases occurred following dental procedures. Sixteen cases occurred following ear cleaning. No relationship was observed between deafness and dog or cat breed, gender, anesthetic drug used, or dog size. Geriatric animals appeared more susceptible to post‐anesthetic, post‐procedural hearing loss. Conclusions Deafness may occur in dogs and cats following anesthesia for dental and ear cleaning procedures, but the prevalence is low. The hearing loss appears to be permanent. Clinical relevance Deafness can be a consequence following anesthesia for dental or ear cleaning procedures. Older animals may have greater susceptibility.