Dexmedetomidine Sedation in Dogs: Impact on Electroencephalography, Behavior, Analgesia, and Antagonism with Atipamezole.

This study aimed to assess the impact of dexmedetomidine constant rate infusion (CRI) on key parameters in dogs. Six dogs received a 60 µg/kg/h dexmedetomidine infusion over 10 min, followed by three 15 min decremental CRIs (3, 2, and 1 µg/kg/h). A subsequent reversal phase employed 600 µg/kg/h atipamezole over 5 min. Continuous electroencephalogram (EEG) assessment, and cardiorespiratory and analgesia monitoring (every 3 min) were conducted, including analgesia evaluation through responses to electric stimulation. Dexmedetomidine induced profound sedation, evidenced by lateral recumbency and immobility. Patient State Index (PSI) decreased from awake (90.4 ± 4.3) to Phase 1 (50.9 ± 30.7), maintaining sedation (29.0 ± 18.1 to 33.1 ± 19.1 in Phases 2-4). Bradycardia (37.8 ± 3.5 bpm, lowest at Phase 3) and hypertension (133.7 ± 17.0 mmHg, highest at Phase 1) were observed, with minimal analgesia. Atipamezole promptly reversed sedation, restoring cognitive function (tail wagging behavior), and normalizing cardiovascular parameters. During atipamezole CRI, the EEG exhibited a transition from delta waves to alpha and low beta waves. This transition was observed alongside gradual increases in PSI and electromyographic activities. Additionally, spindle activities disappeared during this process. This study's results suggest potential clinical utility for EEG-guided dexmedetomidine sedation with reversal using atipamezole, warranting further investigation.

Ketamine-Propofol Coadministration for Induction and Infusion Maintenance in Anesthetized Dogs: Effects on Electroencephalography and Antinociception.

The effects of concurrent ketamine and propofol (ketofol) constant rate infusion (CRI) were examined in six dogs. The K:P ratio was 1:2, with an initial CRI of 0.25/0.5 mg/kg/min over ten minutes, followed by a 0.5 mg/kg ketamine bolus for induction. During induction, a comprehensive EEG frequency spectrum from delta to gamma was observed, accompanied by subanesthetic-dose ketofol-induced behavioral excitation, including nystagmus, tongue flicking, salivation and active muscle activity. The dogs were maintained on three 15 min decremental doses of ketofol CRI (0.8/1.6, 0.4/0.8 and 0.2/0.4 mg/kg/min). This phase featured a significant decrease in the Patient State Index, electromyographic activity and a shift to low beta waves (SEF95: 13-18 Hz). Additionally, profound antinociception to electric stimulation and a stable heart rate and blood pressure (MBP 81.5-110 mmHg) were observed, as well as a merging of ketamine and propofol EEG characteristics during maintenance. In the recovery phase, a return to beta and gamma EEG patterns and excitement behavior occurred, accompanied by a significant reduction in antinociception, highlighting features of low doses of ketofol. This study reveals biphasic EEG dynamic changes, associated behaviors and robust antinociception and cardiovascular function, suggesting the utility of ketofol as a total intravenous anesthetic combination in dogs.

Electroencephalographic and Cardiovascular Changes Associated with Propofol Constant Rate of Infusion Anesthesia in Young Healthy Dogs.

This study aimed to evaluate electroencephalography (EEG) and cardiovascular changes associated with propofol constant rate of infusion (CRI) anesthesia in dogs. Six dogs were each given propofol CRI to induce different anesthetic phases including induction (1 mg/kg/min for 10 min), and decremental maintenance doses of 2.4 mg per kg per min, 1.6 mg per kg per min, and 0.8 mg per kg per minute over 45 min. Processed EEG indices including patient state index (PSI), (burst) suppression ratio (SR), and spectral edge frequency (95%) were obtained continuously until the dogs recovered to sternal recumbency. The dogs were intubated and ventilated. Cardiovascular and EEG index values were compared between anesthetic phases. The PSI, SR, mean arterial blood pressure, and subjective anesthetic depth scores were highly correlated throughout anesthetic depth changes. The PSI decreased from 85.0 ± 17.3 at awake to 66.0 ± 29.0 at induction, and then sharply reduced to 19.7 ± 23.6 during maintenance and returned to 61.5 ± 19.2 at extubation. The SR increased from 15.4 ± 30.9% at induction to 70.9 ± 39.8% during maintenance and decreased to 3.4 ± 8.9% at extubation. We concluded that EEG indices can be used to aid in tracking ongoing brain state changes during propofol anesthesia in dogs.

Perioperative Brain Function Monitoring with Electroencephalography in Horses Anesthetized with Multimodal Balanced Anesthetic Protocol Subjected to Surgeries.

This study aimed to investigate the use of electroencephalography (EEG) for detecting brain activity changes perioperatively in anesthetized horses subjected to surgery. Twelve adult horses undergoing various surgeries were evaluated after premedication with xylazine and butorphanol, induction with ketamine, midazolam, and guaifenesin, and maintenance with isoflurane. The frontal EEG electrodes were placed after the horse was intubated and mechanically ventilated. The EEG data were collected continuously from Stage (S)1-transition from induction to isoflurane maintenance, S2-during surgery, S3-early recovery before xylazine sedation (0.2 mg kg IV), and S4-recovery after xylazine sedation. The Patient State Index (PSI), (Burst) Suppression Ratio (SR), and 95% Spectral Edge Frequency (SEF95) were compared across the stages. The PSI was lowest in S2 (20.8 ± 2.6) and increased to 30.0 ± 27.7 (p = 0.005) in S3. The SR increased from S1 (5.5 ± 10.7%) to S3 (32.7 ± 33.8%, p = 0.0001). The spectral power analysis showed that S3 had a significantly higher content of delta wave activity (0.1-4 Hz) in the EEG and lower relative power in the 3 Hz to 15 Hz range when compared to S1 and S2. A similar result was observed in S4, but the lower power was in a narrower range, from 3 Hz to 7 Hz, which indicate profound central nervous system depression potentiated by xylazine, despite the cessation of isoflurane anesthesia. We concluded that the use of EEG provides clinically relevant information about perioperative brain state changes of the isoflurane-anesthetized horse.

A preliminary study comparing the sedative, cardiorespiratory, and histaminic-releasing effects of intramuscular and intravenous administration of pethidine (meperidine) with midazolam in healthy cats.

Pethidine is a synthetic opioid that is widely used in cats. However, the sedative, cardiorespiratory, and histaminic effects following administration of pethidine with midazolam in cats remain unclear. The objectives of this study were to evaluate and compare changes before and after intravenous (IV) and intramuscular (IM) administration of pethidine with midazolam in healthy cats. In this prospective randomized blind study, 12 cats were assigned equally to either the IV or IM treatment group. The IV group received pethidine 3 mg/kg and midazolam 0.1 mg/kg. The IM group received pethidine 6 mg/kg and midazolam 0.2 mg/kg. The sedative effects, heart rate, respiratory rate, non-invasive arterial blood pressures, and behavioral signs were recorded before and at 2, 5, 15, 30, 45, and 60 min after the injection. Blood samples were taken for an ELISA histamine assay at baseline and at 5 and 15 min after treatment. Cats that received IV treatment were rapidly induced a moderate degree of sedation but those received IM treatment were only mildly sedated. There was no significant difference in the cardiorespiratory values within and between the treatments over time. Plasma histamine concentrations increased by 3 and 5 times at 5 and 15 min after IV treatment, respectively, compared to baseline values. IM injections induced minimal changes in the plasma histamine concentration. In summary, intravenous pethidine with midazolam induced potentially superior sedative effects without serious side effects in clinically healthy cats. However, further studies with larger sample sizes are required to validate this finding.

Evidence of acrolein in synovial fluid of dogs with osteoarthritis as a potential inflammatory biomarker.

BACKGROUND: Acrolein is a known pro-inflammatory toxic aldehyde, propagating cellular damage and tissue inflammation in humans and animal models of various diseases. Osteoarthritis (OA) has a significant inflammatory component; however, presence of acrolein in synovial fluid of joints with OA has not been previously reported. The first aim of this study was to evaluate evidence of acrolein in the synovial fluid of dogs with OA as well as in Control joints. The second aim was to determine if evidence of acrolein can be detected in synovial fluid samples that have been in a frozen state for long periods of time. METHODS: In this pilot clinical study, synovial fluid samples were prospectively collected (i.e., New samples) from a single joint of both clinically healthy (New Control, n = 5) and dogs with OA (New OA, n = 16) and frozen until the time of analysis. Additionally, frozen synovial fluid samples from a biobank (i.e., Old samples) were used to evaluate ability to detect evidence of acrolein in long-term stored samples (median of 4.89 years) in Old Control (n = 5) and Old OA (n = 5) samples. Measurements of acrolein in all synovial fluid samples was based on detection of its major protein adduct, N ε - (3-formyl-3, 4-dehydropiperidino)lysine (FDP-lysine), using the western blot method. Synovial fluid matrix metalloproteinase 2 (MMP2) was measured in all samples using the western blot method as a positive control of OA inflammation. RESULTS: Acrolein-lysine adduct was detected in both Control (n = 10) and OA (n = 21) groups in both Old and New samples. Acrolein-lysine adduct and MMP2 were detectable at a lower level in the Old compared to New synovial fluid samples; however, the differences were not statistically significant (p > 0.1). The measured MMP2 levels were significantly higher in the OA compared to Control group samples (p = 0.033), but not for acrolein-lysine adduct (p = 0.30). CONCLUSIONS: This study confirmed evidence of acrolein in canine synovial fluid of both OA and Control groups. Freezing of synovial fluid for up to 5 years does not appear to significantly affect the ability to detect acrolein-lysine adduct and MMP2 in these samples.

Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol, tiletamine-zolazepam-xylazine-butorphanol, and ketamine-detomidine-butorphanol in pigs.

OBJECTIVE: To evaluate and compare the anesthetic, analgesic, and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol (TZDB), tiletamine-zolazepam-xylazine-butorphanol (TZXB), and ketamine-detomidine-butorphanol (KDB) in pigs and to assess anesthetic recovery duration and quality following administration of tolazoline as a reversal agent. ANIMALS: 11 healthy 2.5-month-old castrated male Landrace mixed-breed pigs. PROCEDURES: In a randomized, blinded crossover study design, pigs received the following anesthetic combinations, IM: TZDB (tiletamine-zolazepam [3 mg/kg {1.36 mg/lb}], detomidine [0.18 mg/kg {0.08 mg/lb}], and butorphanol [0.12 mg/kg {0.05 mg/lb}]); TZXB (tiletamine-zolazepam [4 mg/kg {1.8 mg/lb}], xylazine [4 mg/kg], and butorphanol [0.2 mg/kg {0.09 mg/lb}]); and KDB (ketamine [8 mg/kg {3.63 mg/lb}], detomidine [0.18 mg/kg], and butorphanol [0.3 mg/kg {0.14 mg/lb}]). A 7-day washout period was provided between treatments. At 45 minutes of anesthesia, pigs received tolazoline (2 mg/kg [0.9 mg/lb], IM; n = 6) treatment or control (5) treatment with saline (0.9% NaCl) solution. RESULTS: All anesthetic combinations induced anesthesia. Endotracheal intubation was completed within 5 minutes after anesthetic administration in all pigs, except in 2 pigs following administration of KDB. Durations (mean ± SD) of endotracheal intubation and lateral recumbency in pigs that did not receive tolazoline were 55.3 ± 4.8 minutes, 83.8 ± 15.8 minutes, and 28.2 ± 4.5 minutes and 112.4 ± 18.7 minutes, 117.2 ± 16.7 minutes, and 79.7 ± 6.0 minutes, respectively, for the TZDB, TZXB, and KDB anesthetic treatments. Tolazoline significantly shortened the duration of anesthetic recovery for all anesthetic treatments without affecting the recovery quality. CONCLUSIONS AND CLINICAL RELEVANCE: All 3 anesthetic combinations were suitable for providing anesthesia in pigs. Tolazoline administration shortened the duration of anesthetic recovery without affecting the quality of recovery.

Evaluation of Endotracheal Tube Cuff Pressure and the Use of Three Cuff Inflation Syringe Devices in Dogs.

Over-inflation of an endotracheal tube (ETT) cuff may lead to tracheal mucosal irritation, tracheal wall ischemia or necrosis, whereas under-inflation increases the risk of pulmonary aspiration as well as leaking anesthetic gas and polluting the environment. The objectives of this two-phase study were to (1) identify the incidence of improper ETT cuff inflation (both over- and under-inflation) using the minimum occlusive volume (MOV) technique coupled with a regular injectable syringe in the anesthetized dogs, and (2) evaluate the performance of two commercially available inflation syringe devices (Tru-Cuff and AG Cuffill®) with the regular injectable syringe in inflating the ETT cuff to a recommended safe cuff pressure range (20-30 cmH2O). Dogs undergoing general anesthesia at Purdue Veterinary Medicine Teaching Hospital were included. The ETT cuff pressure was assessed with an aneroid manometer after the syringe inflation. The results of the first objective showed that a total of 80 dogs enrolled and that 50 of these 80 dogs required ETT cuff inflation. Among the 50 dogs, only 14% had proper ETT cuff inflation; 76% of the ETT cuffs were over-inflated and 10% were under-inflated. Ninety dogs were enrolled for the second objective study and they were randomly and equally assigned to the three syringe device treatment groups. The results showed that 80% of the ETT cuffs were over-inflated in the regular injectable syringe treatment group, whereas only 6.7% and 3.3% ETT cuffs were over-inflated in the Tru-Cuff and AG Cuffill® syringe treatment groups, respectively. The AG Cuffill® syringe treatment group had a significantly (p < 0.05) higher percentage of properly inflated ETT cuffs (86.7%) compared to the other two groups (regular injectable syringe [3.3%]; Tru-Cuff syringe [50%]. We concluded that there was a high incidence of improper ETT cuff inflation when using MOV technique coupled with a regular injectable syringe. The use of an AG Cuffill® syringe significantly reduced improper ETT cuff inflation.

Effects of transdermal fentanyl solution application and subsequent naloxone hydrochloride administration on minimum alveolar concentration of isoflurane in dogs.

OBJECTIVE To assess the isoflurane-sparing effect of a transdermal formulation of fentanyl solution (TFS) and subsequent naloxone administration in dogs. DESIGN Experiment. ANIMALS 6 healthy mixed-breed dogs. PROCEDURES Minimum alveolar concentration (MAC) of isoflurane was determined in each dog with a tail clamp method (baseline). Two weeks later, dogs were treated with TFS (2.7 mg/kg [1.23 mg/lb]), and the MAC of isoflurane was determined 4 and 24 hours later. After the 4-hour MAC assessment, saline (0.9% NaCl) solution was immediately administered IV and MAC was reassessed. After the 24-hour MAC assessment, naloxone hydrochloride (0.02 mg/kg [0.01 mg/lb], IV) was immediately administered and MAC was reassessed. Heart rate, respiratory rate, arterial blood pressure, end-tidal partial pressure of CO2, and oxygen saturation as measured by pulse oximetry were recorded for each MAC assessment. RESULTS Mean ± SD MAC of isoflurane at 4 and 24 hours after TFS application was 45.4 ± 4.0% and 45.5 ± 4.5% lower than at baseline, respectively. Following naloxone administration, only a minimal reduction in MAC was identified (mean percentage decrease from baseline of 13.1 ± 2.2%, compared with 43.8 ± 5.6% for saline solution). Mean heart rate was significantly higher after naloxone administration (113.2 ± 22.2 beats/min) than after saline solution administration (76.7 ± 20.0 beats/min). No significant differences in other variables were identified among treatments. CONCLUSIONS AND CLINICAL RELEVANCE The isoflurane-sparing effects of TFS in healthy dogs were consistent and sustained between 4 and 24 hours after application, and these effects should be taken into consideration when anesthetizing or reanesthetizing TFS-treated dogs.

Evaluation of 25% Poloxamer As a Slow Release Carrier for Morphine in a Rat Model.

The objectives of this study were to evaluate poloxamer as a slow release carrier for morphine (M) and potential tissue irritation after subcutaneous poloxamer-morphine (PM) injection in a rat model. Based on the result of a previous in vitro work, 25% poloxamer, with and without morphine, and saline were administered in 14 rats' flanks. Blood for morphine concentrations was automatically sampled at multiple preprogrammed time points using the Culex™ unit for 48 h. Skin tissues from the injection sites were harvested and evaluated for histopathological changes. Following M or PM administration, it was determined that the half-life (t1/2) was significantly longer in the PM (5.5 ± 7.2 h) than M (0.7 ± 0.8 h) indicated a slow dissolution of poloxamer with morphine. The tmax was within 15 min and Cmax was approximately three times higher with M than with PM, reaching 716.8 (±153.7 ng/ml) of plasma morphine concentrations. There was no significant difference in total area under the curve and clearance of M versus PM. Histology inflammatory scores were similar between M, PM, and poloxamer but were significantly higher than saline control. We concluded that 25% poloxamer was capable of increasing the t1/2 of morphine, without a significant tissue irritation.

Hemodynamic influence of acepromazine or dexmedetomidine premedication in isoflurane-anesthetized dogs.

OBJECTIVE: To investigate hemodynamic effects of acepromazine and dexmedetomidine premedication in dogs undergoing general anesthesia induced with propofol and maintained with isoflurane in oxygen and assess the influence of these drugs on oxygen-carrying capacity and PCV. DESIGN: Prospective, randomized crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs received acepromazine (0.05 mg/kg [0.023 mg/lb]) or dexmedetomidine (15.0 µg/kg [6.82 µg/lb]) IM. Fifteen minutes later, anesthesia was induced with propofol and maintained at end-tidal isoflurane concentration of 1.28% (1 minimum alveolar concentration) for 30 minutes. Hemodynamic variables were recorded at predetermined times. The experiment was repeated 48 hours later with the alternate premedication. Results were analyzed by repeated-measures ANOVA with a mixed-models procedure. RESULTS: Bradycardia, hypertension, and significant cardiac output (CO) reduction developed after dexmedetomidine premedication but improved during isoflurane anesthesia. Hypotension developed after acepromazine administration and persisted throughout the isoflurane maintenance period, but CO was maintained throughout the anesthetic period when dogs received this treatment. Oxygen delivery and consumption were not different between treatments at most time points, whereas arterial oxygen content was lower with acepromazine premedication owing to lower PCV during isoflurane anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Acepromazine exacerbated hypotension, but CO did not change in dogs anesthetized with propofol and isoflurane. Dexmedetomidine reduced CO but prevented propofol-isoflurane-induced hypotension. In general, oxygen-carrying capacity and PCV were higher in dexmedetomidine-treated than in acepromazine-treated dogs anesthetized with propofol and isoflurane.

Analgesic effect of intra-articularly administered morphine, dexmedetomidine, or a morphine-dexmedetomidine combination immediately following stifle joint surgery in dogs.

OBJECTIVE: To compare the analgesic effects of intra-articularly administered saline (0.9% NaCl) solution, morphine, dexmedetomidine, and a morphine-dexmedetomidine combination in dogs undergoing stifle joint surgery for cranial cruciate ligament rupture. DESIGN: Randomized, controlled, clinical trial. ANIMALS: 44 dogs with cranial cruciate ligament rupture that underwent tibial tuberosity advancement (TTA) or tibial plateau leveling osteotomy (TPLO). PROCEDURES: Dogs received intra-articular injections of saline solution (0.2 mL/kg [0.09 mL/lb]), morphine (0.1 mg/kg [0.045 mg/lb]), dexmedetomidine (2.5 µg/kg [1.14 µg/lb]), or a combination of morphine (0.1 mg/kg) and dexmedetomidine (2.5 µg/kg). Intra-articular injections of the stifle joint were performed after completion of the corrective osteotomy procedure, just prior to skin closure. Signs of pain were assessed every 2 hours thereafter on the basis of mean behavioral and objective pain scores. Dogs with pain scores exceeding predetermined thresholds were given hydromorphone (0.05 mg/kg [0.023 mg/lb], SC) as rescue analgesia. RESULTS: Time to rescue analgesia did not significantly differ between dogs that underwent TTA versus TPLO. No significant difference in time to rescue analgesia was found among dogs receiving intra-articular injections of dexmedetomidine (median, 6 hours; range, 2 to 10 hours), morphine (median, 7 hours; range, 4 to 10 hours), or saline solution (median, 5 hours; range, 4 to 10 hours). However, time to rescue analgesia for dogs receiving intra-articular injection of the morphine-dexmedetomidine combination (median, 10 hours; range, 6 to 14 hours) was significantly longer than the time to rescue analgesia for other treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Intra-articular administration of the morphine-dexmedetomidine combination provided longer-lasting postoperative analgesia, compared with either morphine or dexmedetomidine alone, in dogs undergoing TTA or TPLO.

Influence of ketamine on the cardiopulmonary effects of intramuscular administration of dexmedetomidine-buprenorphine with subsequent reversal with atipamezole in dogs.

OBJECTIVE: To compare the cardiorespiratory effects of IM administration of dexmedetomidine-buprenorphine (DB) and dexmedetomidine-buprenorphine-ketamine (DBK) in dogs with subsequent reversal with atipamezole. DESIGN: Prospective, randomized crossover study. ANIMALS: 5 healthy dogs. PROCEDURES: Dogs were instrumented for cardiac output (CO) measurement and received DB (15 µg of dexmedetomidine/kg [6.8 µg/lb] and 40 µg of buprenorphine/kg [18.2 µg/lb]) or DBK (DB plus 3 mg of ketamine/kg [1.36 mg/lb]) in randomized order while breathing room air. Atipamezole (150 µg/kg [68.2 µg/lb], IM) was administered 1 hour later. Hemodynamic data were collected in the conscious dogs and then at 5, 10, 15, 20, 30, 45, and 60 minutes after drug administration. Lactate concentration was measured in mixed venous blood samples. Oxygen delivery (Do(2)) and oxygen consumption ([Formula: see text]o(2)) were calculated. RESULTS: Heart rate (HR), CO, and Do(2) decreased after DB and DBK administration. The [Formula: see text]o(2) did not change in the DB group but decreased in the DBK group. The HR was higher in the DBK group than in the DB group throughout the study, but the CO, Do(2), and [Formula: see text]o(2) values were similar for the 2 groups. Blood lactate concentrations remained low (< 1 mmol/L) throughout the study. Arterial hypoxemia and hypercapnea occurred in both groups. Mean arterial blood pressure and pulmonary artery wedge pressure were markedly increased in both groups, but to a greater extent in the DBK group. After atipamezole administration, HR, CO, and Do(2) returned to the baseline values. CONCLUSIONS AND CLINICAL RELEVANCE: Adding ketamine to the DB combination allowed dogs to maintain a higher HR and delayed the onset of sinus arrhythmias but failed to provide a significantly higher CO because of a reduction in stroke volume.

Evaluation of anesthetic, analgesic, and cardiorespiratory effects in dogs after intramuscular administration of dexmedetomidine-butorphanol-tiletamine-zolazepam or dexmedetomidine-tramadol-ketamine drug combinations.

OBJECTIVE: To compare anesthetic, analgesic, and cardiorespiratory effects in dogs after IM administration of dexmedetomidine (7.5 µg/kg)-butorphanol (0.15 mg/kg)-tiletamine-zolazepam (3.0 mg/kg; DBTZ) or dexmedetomidine (15.0 µg/kg)-tramadol (3.0 mg/kg)-ketamine (3.0 mg/kg; DTrK) combinations. ANIMALS: 6 healthy adult mixed-breed dogs. PROCEDURES: Each dog received DBTZ and DTrK in a randomized, crossover-design study with a 5-day interval between treatments. Cardiorespiratory variables and duration and quality of sedation-anesthesia (assessed via auditory stimulation and sedation-anesthesia scoring) and analgesia (assessed via algometry and electrical nerve stimulation) were evaluated at predetermined intervals. RESULTS: DBTZ or DTrK induced general anesthesia sufficient for endotracheal intubation ≤ 7 minutes after injection. Anesthetic quality and time from drug administration to standing recovery (131.5 vs 109.5 minutes after injection of DBTZ and DTrK, respectively) were similar between treatments. Duration of analgesia was significantly longer with DBTZ treatment, compared with DTrK treatment. Analgesic effects were significantly greater with DBTZ treatment than with DTrK treatment at several time points. Transient hypertension (mean arterial blood pressure > 135 mm Hg), bradycardia (heart rate < 60 beats/min), and hypoxemia (oxygen saturation < 90% via pulse oximetry) were detected during both treatments. Tidal volume decreased significantly from baseline with both treatments and was significantly lower after DBTZ administration, compared with DTrK, at several time points. CONCLUSIONS AND CLINICAL RELEVANCE: DBTZ or DTrK rapidly induced short-term anesthesia and analgesia in healthy dogs. Further research is needed to assess efficacy of these drug combinations for surgical anesthesia. Supplemental 100% oxygen should be provided when DBTZ or DTrK are used.

Hemodynamic effects in dogs after intramuscular administration of a combination of dexmedetomidine-butorphanol-tiletamine-zolazepam or dexmedetomidine-butorphanol-ketamine.

OBJECTIVE: To evaluate hemodynamic effects in dogs after IM administration of dexmedetomidine (7.5 µg/kg, butorphanol (0.15 mg/kg), and tiletamine-zolazepam (3 mg/kg [DBTZ]) or dexmedetomidine (15 µg/kg), butorphanol (0.3 mg/kg), and ketamine (3 mg/kg [DBK]). ANIMALS: 5 healthy adult mixed-breed dogs. PROCEDURES: Each dog received DBTZ and DBK in a randomized crossover study with a 48-hour interval between treatments. Anesthesia was induced and maintained with sevoflurane in 100% oxygen while instrumentation with Swan-Ganz and arterial catheters was performed. Following instrumentation, hemodynamic measurements were recorded at 3.54% (1.5 times the minimum alveolar concentration) sevoflurane; then sevoflurane administration was discontinued, and dogs were allowed to recover. Six hours after cessation of sevoflurane administration, baseline hemodynamic measurements were recorded, each dog was given an IM injection of DBTZ or DBK, and hemodynamic measurements were obtained at predetermined intervals for 70 minutes. RESULTS: DBTZ and DBK induced hypoventilation (Paco2, approx 60 to 70 mm Hg), respiratory acidosis (pH, approx 7.2), hypertension (mean arterial blood pressure, approx 115 to 174 mm Hg), increases in systemic vascular resistance, and reflex bradycardia. Cardiac output, oxygen delivery, and oxygen consumption following DBTZ or DBK administration were similar to those following sevoflurane administration to achieve a surgical plane of anesthesia. Blood l-lactate concentrations remained within the reference range at all times for all protocols. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs, both DBTZ and DBK maintained oxygen delivery and oxygen consumption to tissues and blood lactate concentrations within the reference range. However, ventilation should be carefully monitored and assisted when necessary to prevent hypoventilation.

Deep sedation in natural orifice transluminal endoscopic surgery (NOTES): a comparative study with dogs.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has been mostly performed with the animal under general and inhalational anesthesia (IA-NOTES). To date, NOTES using propofol sedation (PS-NOTES) has not been investigated. This study aimed to assess the feasibility and safety of PS-NOTES for transgastric oophorectomy with carbon dioxide insufflation and to compare its success rates with those of conventional IA-NOTES. METHODS: In this prospective randomized study, NOTES oophorectomy was performed for 19 female dogs randomized to two conditions: PS (study group) and IA (control group). Sedation success rates (ability to visualize and resect ovaries without converting to IA), operative success rates (ability to resect and retrieve both ovaries in full using only NOTES), and vital parameters including hemodynamic and respiratory changes were documented. RESULTS: In the PS-NOTES group (n = 9), the sedation success rate was 100 %. The operative success rate was 67 % (6 of 9 animals) compared with 80 % (8 of 10 animals) in the IA-NOTES group. No purposeful movement occurred during surgical manipulation and no respiratory or cardiovascular complications in occurred the PS group. Heart rate (HR) and end-tidal carbon dioxide (ETCO(2)) were significantly higher in the PS group than in the IA group. Blood pressure (BP) was significantly higher in the PS group only during the middle part of the procedure. Only mild respiratory depression was noted in the PS group, as indicated by elevated but acceptable ETCO(2). Elevations in BP and HR are thought to be related to elevated CO(2) but did not appear to have an adverse impact on the course of the procedure. Recovery was uneventful for all the animals. CONCLUSION: The use of PS-NOTES appears to be feasible, resulting in outcomes comparable with those for IA in dogs. Further studies are needed to determine the applicability of this concept in human NOTES.

Radiofrequency ablation for dysplasia in Barrett's esophagus restores ß-catenin activation within esophageal progenitor cells.

BACKGROUND AND AIMS: Endoscopic therapies for Barrett's esophagus (BE) associated dysplasia, particularly radiofrequency ablation (RFA), are popular alternatives to surgery. The effect of such therapies on dysplastic stem/progenitor cells (SPC) is unknown. Recent studies suggest that AKT phosphorylation of ß-Catenin occurs in SPCs and may be a marker of activated SPCs. We evaluate the effect of RFA in restoring AKT-mediated ß-Catenin signaling in regenerative epithelium. METHODS: Biopsies were taken from squamous, non-dysplastic BE, dysplastic BE and esophageal adenocarcinoma (EAC). Also, post-RFA, biopsies of endoscopically normal appearing neosquamous epithelium were taken at 3, 6, and 12 months after successful RFA. Immunohistochemistry and Western blot analysis was performed for Pß-Catenin(552) (Akt-mediated phosphorylation of ß-Catenin), Ki-67 and p53. RESULTS: There was no difference in Pß-Catenin552 in squamous, GERD, small bowel and non-dysplastic BE. There was a fivefold increase in Pß-Catenin(552) in dysplasia and EAC compared to non-dysplastic BE (P < 0.05). Also, there was a persistent threefold increase in Pß-Catenin(552) in neosquamous epithelium 3 months after RFA compared to native squamous epithelium (P < 0.05) that correlated with increased Ki-67. Six months after RFA, Pß-Catenin(552) and Ki-67 are similar to native squamous epithelium. CONCLUSIONS: Enhanced AKT-mediated ß-Catenin activation is seen in BE-associated carcinogenesis. Three months after RFA, squamous epithelial growth from SPC populations exhibited increased levels of Pß-Catenin(552). This epithelial response becomes quiescent at 6 months after RFA. These data suggest that elevated Pß-Catenin(552) after RFA denotes a repair response in the neosquamous epithelium 3 months post-RFA.

Evaluation of dexmedetomidine and ketamine in combination with various opioids as injectable anesthetic combinations for castration in cats.

OBJECTIVE: To compare the efficacy and cardiorespiratory effects of dexmedetomidine-ketamine in combination with butorphanol, hydromorphone, or buprenorphine with or without reversal by atipamezole in cats undergoing castration. DESIGN: Prospective, randomized, split-plot, blinded study. ANIMALS: 30 healthy male cats. PROCEDURES: Cats were assigned to receive dexmedetomidine (25 ?g/kg [11.4 ?g/lb]) and ketamine (3 mg/kg [1.4 mg/lb]) with butorphanol (0.2 mg/kg [0.09 mg/lb]; DKBut; n = 10), hydromorphone (0.05 mg/kg [0.023 mg/lb]; DKH; 10), or buprenorphine (30 ?g/kg [13.6 ?g/lb]; DKBup; 10). Drugs were administered as a single IM injection. Supplemental isoflurane was administered to cats if the level of anesthesia was inadequate for surgery. At the conclusion of surgery, half the cats (5 cats in each treatment group) received atipamezole (250 ?g/kg [113.6 ?g/lb], IM) and the remainder received saline (0.9% NaCl) solution IM. All cats received meloxicam (0.2 mg/kg, SC) immediately prior to the conclusion of surgery. RESULTS: All drug combinations induced lateral recumbency, and intubation was achievable in 13 of 30 (43%) cats at 10 minutes after injection. Supplemental isoflurane was needed for the surgery in 1 of 10 of the DKBut-, 2 of 10 of the DKH-, and 7 of 10 of the DKBup-treated cats. Cats that received atipamezole had a significantly shorter recovery time. CONCLUSIONS AND CLINICAL RELEVANCE: DKBut and DKH combinations were suitable injectable anesthetic protocols for castration in cats commencing at 10 minutes after injection, but cats receiving DKBup may require additional time or anesthetics for adequate anesthesia.

Evaluation of dexmedetomidine and ketamine in combination with opioids as injectable anesthesia for castration in dogs.

OBJECTIVE: To compare efficacy and cardiorespiratory effects of dexmedetomidine and ketamine in combination with butorphanol, hydromorphone, or buprenorphine (with or without reversal by atipamezole) in dogs undergoing castration. DESIGN: Prospective, randomized, split-plot, blinded study. ANIMALS: 30 healthy client-owned sexually intact male dogs. PROCEDURES: Dogs (n = 10 dogs/group) were assigned to receive dexmedetomidine (15 µg/kg [6.82 µg/lb]) and ketamine (3 mg/kg [1.36 mg/lb]) with butorphanol (0.2 mg/kg [0.09 mg/lb]; DKBut), the same dosages of dexmedetomidine and ketamine with hydromorphone (0.05 mg/kg [0.023 mg/lb]; DKH), or the same dosages of dexmedetomidine and ketamine with buprenorphine (40 µg/kg [18.18 µg/lb]; DKBup). All drugs were administered as a single IM injection for induction and maintenance of anesthesia for castration. At conclusion of the surgery, 5 dogs in each treatment group received atipamezole (150 µg/kg [68.18 µg/lb], IM), and the remainder received saline (0.9% NaCl) solution IM. Cardiorespiratory variables and quality of anesthesia were assessed. Supplemental isoflurane was administered to the dogs when anesthesia was considered inadequate during surgery. RESULTS: All drug combinations rapidly induced anesthesia. Dogs were intubated within 10 minutes after injection. Supplemental isoflurane was needed during surgery in 1, 3, and 4 dogs in the DKBup, DKBut, and DKH groups, respectively. Dogs that received atipamezole had a significantly shorter recovery time. Some dogs in each group had bradycardia and hypoxemia with hypertension. CONCLUSIONS AND CLINICAL RELEVANCE: DKBup was the most suitable injectable anesthetic combination used. Recovery was shortened by IM administration of atipamezole. There were minimal adverse effects in all groups.

Efficacy of oral transmucosal and intravenous administration of buprenorphine before surgery for postoperative analgesia in dogs undergoing ovariohysterectomy.

OBJECTIVE: To compare the efficacy of preoperative administration of buprenorphine (via oral transmucosal [OTM] and IV routes) for postoperative analgesia in dogs undergoing ovariohysterectomy. DESIGN: Prospective, randomized, blinded study. ANIMALS: 18 dogs undergoing routine ovariohysterectomy. PROCEDURES: Dogs were allocated to 3 groups (6 dogs/group) and were assigned to receive buprenorphine (20 µg/kg [9.09 µg/lb], IV; a low dose [20 µg/kg] via OTM administration [LOTM]; or a high dose [120 µg/kg [54.54 µg/lb] via OTM administration [HOTM]) immediately before anesthetic induction with propofol and maintenance with isoflurane for ovariohysterectomy. Postoperative pain was assessed by use of a dynamic interactive pain scale. Dogs were provided rescue analgesia when postoperative pain exceeded a predetermined threshold. Blood samples were collected, and liquid chromatography-electrospray ionization-tandem mass spectrometry was used to determine plasma concentrations of buprenorphine and its metabolites. Data were analyzed with an ANOVA. RESULTS: Body weight, surgical duration, propofol dose, isoflurane concentration, and cardiorespiratory variables did not differ significantly among treatment groups. Number of dogs requiring rescue analgesia did not differ significantly for the HOTM (1/6), IV (3/6), and LOTM (5/6) treatments. Similarly, mean ± SEM duration of analgesia did not differ significantly for the HOTM (20.3 ± 3.7 hours), IV (16.0 ± 3.8 hours), and LOTM (7.3 ± 3.3 hours) treatments. Plasma buprenorphine concentration was ≤ 0.60 ng/mL in 7 of 9 dogs requiring rescue analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Buprenorphine (HOTM) given immediately before anesthetic induction can be an alternative for postoperative pain management in dogs undergoing ovariohysterectomy.