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.

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.

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.

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.

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.

Analgesic effect of bupivacaine eluting porcine small intestinal submucosa (SIS) in ferrets undergoing acute abdominal hernia defect surgery.

BACKGROUND: Porcine small intestinal submucosa (SIS) is used as a biological implant for abdominal wall hernia repair to facilitate wound healing and augment local tissue strength. This prospective, randomized, blinded study evaluated local pain control provided by bupivacaine adsorbed to SIS for repair of acutely created abdominal wall full thickness muscle/fascial defects in ferrets. MATERIALS AND METHODS: Eighteen healthy ferrets were randomly and equally assigned to three groups: (1) SIS with bupivacaine subjected to surgery, (2) SIS with no bupivacaine subjected to surgery, and (3) anesthesia only control group. Ferrets in groups 1 and 2 were anesthetized with butorphanol and sevoflurane for the surgery. Control ferrets were anesthetized in the same fashion for the same duration without surgery. Behavior and pain were evaluated in all ferrets by behavioral observation, algometer, and palpometer measurements, and heart and respiratory rates each obtained before surgery and at various intervals for 96 h after surgery. When pain reached a predetermined threshold, buprenorphine was used as a rescue analgesic. The serum and combined tissue concentrations of bupivacaine were analyzed. RESULTS: Overall, the palpometer testing was better tolerated in the bupivacaine treated SIS group than by the untreated SIS group (P = 0.04). There was an observed physiologically significant difference in algometer and other palpometer readings as well as heart and respiratory rates. All ferrets in the untreated SIS group were rescued while 33% of the SIS-bupivacaine groups were rescued (P < 0.01). Peak serum concentrations of bupivacaine were in the range of 0.7 µg/mL with tissue level below detection levels and no clinical signs of toxicity were observed. CONCLUSIONS: Bupivacaine adsorbed to SIS provided some degree of pain relief over 2-4 days with no clinical adverse effects observed in the ferrets.

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.

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.

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.

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 carprofen and morphine on the minimum alveolar concentration of isoflurane in dogs.

The minimum alveolar concentration (MAC) of isoflurane in dogs was determined following carprofen (2.2 mg/kg per os) alone, morphine (1 mg/kg intravenously) alone, carprofen and morphine, and no drug control in eight healthy adult dogs. Isoflurane MAC following administration of morphine alone (0.81%+/-0.18%) or carprofen and morphine (0.68%+/-0.31%) was significantly less than the control MAC (1.24%+/-0.15%). Isoflurane MAC after carprofen alone (1.13%+/-0.13%) was not significantly different from the control value. Results indicated that administration of morphine alone or in combination with carprofen significantly reduced the MAC of isoflurane in dogs. The isoflurane MAC reduction was additive between the effects of carprofen and morphine.

Effect of orally administered tramadol alone or with an intravenously administered opioid on minimum alveolar concentration of sevoflurane in cats.

OBJECTIVE-To compare the effect of oral administration of tramadol alone and with IV administration of butorphanol or hydromorphone on the minimum alveolar concentration (MAC) of sevoflurane in cats. DESIGN-Crossover study. ANIMALS-8 Healthy 3-year-old cats. PROCEDURES-Cats were anesthetized with sevoflurane in 100% oxygen. A standard tail clamp method was used to determine the MAC of sevoflurane following administration of tramadol (8.6 to 11.6 mg/kg [3.6 to 5.3 mg/lb], PO, 5 minutes before induction of anesthesia), butorphanol (0.4 mg/kg [0.18 mg/lb], IV, 30 minutes after induction), hydromorphone (0.1 mg/kg [0.04 mg/lb], IV, 30 minutes after induction), saline (0.9% NaCl) solution (0.05 mL/kg [0.023 mL/lb], IV, 30 minutes after induction), or tramadol with butorphanol or with hydromorphone (same doses and routes of administration). Naloxone (0.02 mg/kg [0.009 mg/lb], IV) was used to reverse the effects of treatments, and MACs were redetermined. RESULTS-Mean +/- SEM MACs for sevoflurane after administration of tramadol (1.48 +/- 0.20%), butorphanol (1.20 +/- 0.16%), hydromorphone (1.76 +/- 0.15%), tramadol and butorphanol (1.48 +/- 0.20%), and tramadol and hydromorphone (1.85 +/- 0.20%) were significantly less than those after administration of saline solution (2.45 +/- 0.22%). Naloxone reversed the reductions in MACs. CONCLUSIONS AND CLINICAL RELEVANCE-Administration of tramadol, butorphanol, or hydromorphone reduced the MAC of sevoflurane in cats, compared with that in cats treated with saline solution. The reductions detected were likely mediated by effects of the drugs on opioid receptors. An additional reduction in MAC was not detected when tramadol was administered with butorphanol or hydromorphone.

A comparison of two combinations of xylazine-ketamine administered intramuscularly to alpacas and of reversal with tolazoline.

OBJECTIVE: To evaluate the anesthetic and cardiorespiratory effects of two doses of intramuscular (IM) xylazine/ketamine in alpacas, and to determine if tolazoline would reduce the anesthetic recovery time. STUDY DESIGN: Prospective randomized crossover study. ANIMALS: Six castrated male alpacas. METHODS: Each alpaca received a low dose (LD) (0.8 mg kg(-1) xylazine and 8 mg kg(-1) ketamine IM) and high dose (HD) (1.2 mg kg(-1) xylazine and 12 mg kg(-1) ketamine IM) with a minimum of one week between trials. Time to sedation, duration of lateral recumbency and analgesia, pulse rate, respiratory rate, hemoglobin oxygen saturation, arterial blood pressure, blood-gases, and the electrocardiogram were monitored and recorded during anesthesia. With each treatment three alpacas were randomly selected to receive tolazoline (2 mg kg(-1) IM) after 30 minutes of lateral recumbency. RESULTS: Onset of sedation, lateral recumbency and analgesia was rapid with both treatments. The HD was able to provide > or =30 minutes of anesthesia in five of six alpacas. The LD provided > or =30 minutes of anesthesia in three of six alpacas. Respiratory depression and hypoxemia occurred with the HD treatment during the first 10 minutes of lateral recumbency: two animals were severely hypoxemic and received nasal oxygen for 5 minutes. Heart rate decreased, but there were no significant changes in arterial blood pressure. Tolazoline significantly shortened the duration of recumbency with the HD. CONCLUSIONS: The HD provided more consistent clinical effects in alpacas than the LD. Intramuscular tolazoline shortened the duration of lateral recumbency in alpacas anesthetized with the HD combination. CLINICAL RELEVANCE: Both doses of the combination were effective in providing restraint in alpacas and the duration of restraint was dose dependent. Supplemental oxygen should be available if using the HD and IM administration of tolazoline will shorten the recovery time.

Evaluation of two methods of endotracheal tube selection in dogs.

This study evaluated two methods of endotracheal tube selection using 28 fresh canine carcasses of various ages, weights, and genders. The two selection methods were 1) nasal septal width pairing with outer diameter of an endotracheal tube, and 2) digital palpation of the tracheal outer diameter to determine the endotracheal tube size. All dogs were dolichocephalic breeds. Results of this study showed that the canine nasal septal width method of endotracheal tube selection was correlated with the size of the tracheal internal (r=0.72) and outer (r=0.73) diameters. However, evidence shows that the digital palpation method is slightly more effective than the nasal width method in selecting the best-fitting endotracheal tube. The percentage of the best-fit tube selection for the nasal septal width method was 21%, while the digital palpation method was 46%. With these two methods, selecting an endotracheal tube that is too small is possible, especially when the tube internal diameter is > or =7 mm.

Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.

Pharmacokinetic analysis of buprenorphine administered to six healthy dogs via the oral transmucosal (OTM) route at doses of 20 and 120 microg/kg was conducted using liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS). Bioavailability was 38% plus or minus 12% for the 20 microg/kg dose and 47%+/-16% for the 120 microg/kg dose. Maximum plasma concentrations were similar for buprenorphine doses of 20 microg/kg IV and 120 microg/kg OTM. Sedation and salivation were common side effects, but no bradycardia, apnea, or cardiorespiratory depressive effects were seen. When the two OTM dosing rates were normalized to dose, LC-ESI-MS/MS analysis of buprenorphine and its metabolites detected no significant difference (P>.05), indicating dose proportionality. The results of this study suggest that OTM buprenorphine may be an alternative for pain management in dogs.

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.

Oxygenation in medetomidine-sedated dogs with and without 100% oxygen insufflation.

Oxygenation status was evaluated in medetomidine-sedated dogs breathing room air (M) or 100 percent oxygen (MO2). Medetomidine (40 microg/kg IV) administration resulted in peripheral vasoconstriction and decreased venous saturation as measured by an increased oxygen extraction ratio in peripheral tissues. Providing 100 percent oxygen insufflation via face mask reduced desaturation by increasing oxygen content but did not prevent vasoconstriction or reduce the oxygen extraction ratio in peripheral tissues. Atipamezole (200 microg/kg IV) reversed medetomidine-induced vasoconstriction and increased oxygen supply to tissues as indicated by a lower tissue oxygen extraction ratio. The authors conclude that 100 percent oxygen insufflation via face mask during medetomidine sedation (40 micrograms/kg [corrected] IV) benefits tissue oxygenation in healthy dogs.

A comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-butorphanol and tiletamine-zolazepam-butorphanol- medetomidine in cats.

Using a randomized crossover design, this study compared the anesthetic and cardiorespiratory effects of three intramuscular anesthetic combinations in seven 2-year-old cats: tiletamine-zolazepam (8 mg/kg) and butorphanol (0.2 mg/kg) (TT); tiletamine-zolazepam (3 mg/kg), butorphanol (0.15 mg/kg), and medetomidine (15 microg/kg) (TTD); or the TTD protocol plus atipamezole (75 microg/kg IM) given 20 minutes later to reverse medetomidine. Analgesia was assessed using algometry and needle pricking. All three combinations effectively induced anesthesia suitable for orotracheal intubation within 5 minutes after injection. Hemoglobin oxygen saturation was lower than 90% at least once in all three groups between 5 and 15 minutes after drug administration. Blood pressure and heart and respiratory rates were within normal ranges. Both TT and TTD appeared to be effective injectable anesthetic combinations. TTD provided significantly better analgesia with a longer duration than did TT. Atipamezole administration shortened the duration of analgesia and decreased blood pressure but did not shorten total recovery time.