Effect of constant rate infusion of detomidine with and without vatinoxan on blood glucose and insulin concentrations in horses.

OBJECTIVE: To assess the effects of an α2-adrenoceptor agonist (detomidine) constant rate infusion (CRI) with and without an α2-adrenoceptor antagonist (vatinoxan) CRI on blood insulin and glucose concentrations, heart rate, intestinal borborygmi, and sedation during and after infusion in horses. STUDY DESIGN: Randomized, blinded, crossover, experimental study. ANIMALS: A total of nine healthy, adult Finnhorse mares. METHODS: Horses were treated with an intravenous (IV) detomidine loading dose (0.01 mg kg-1), followed by CRI (0.015 mg kg-1 hour-1), and the same doses of detomidine combined with an IV vatinoxan loading dose (0.15 mg kg-1), followed by CRI (detomidine and vatinoxan; 0.05 mg kg-1 hour-1) with an 18 day washout period. Infusion time was 60 minutes and horses were monitored for 240 minutes after the infusion. Heart rate, borborygmi score and sedation were assessed, and blood glucose, insulin and triglyceride concentrations were measured. Data were analyzed using repeated measures ancova and Wilcoxon signed-rank tests. Values of p < 0.05 were considered statistically significant. RESULTS: Insulin concentration decreased during (median nadir 1.7, range 0.0-2.9 µIU mL-1 at 60 minutes, p < 0.0001) and increased after detomidine CRI (median 36.6, range 11.7-78.4 µIU mL-1 at 180 minutes, p = 0.0001) significantly compared with detomidine and vatinoxan CRI. A significant elevation of blood glucose (peak 11.5 ± 1.6 mmol L-1 at 60 minutes, p < 0.0001) was detected during detomidine CRI. Vatinoxan alleviated the insulin changes and abolished the significant increase in blood glucose. Vatinoxan alleviated the decrease in heart rate (p = 0.0001) during detomidine infusion. No significant differences were detected in sedation scores between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Vatinoxan attenuated the negative adverse effects of detomidine CRI and thus is potentially beneficial when used in combination with an α2-adrenoceptor agonist CRI in horses.

Pharmacokinetics of dexmedetomidine in anaesthetized horses following repeated subcutaneous administration and intravenous constant rate infusion.

BACKGROUND: The inclusion of dexmedetomidine (DEX) within a balanced general anaesthesia protocol is effective in improving the clinical outcome and recovery quality of anaesthesia in horses. This study aimed to determine the pharmacokinetic profile of DEX following repeated subcutaneous (SC) administration at 2 µg/kg every 60 min till the end of the procedure in comparison to intravenous constant rate infusion (CRI) at 1 µg/kg/h in anaesthetized horses undergoing diagnostic procedures up to the end of the diagnostic procedure. RESULTS: In the CRI and SC groups DEX maximum concentrations (Cmax) were 0.83 ± 0.27 ng/mL and 1.14 ± 0.71 ng/mL, respectively, reached at a time (Tmax) of 57.0 ± 13.4 min and 105.5 ± 29.9 min. Mean residence time to the last measurable concentration (MRTlast) was 11.7 ± 6.2 and 55.8 ± 19.7 min for the CRI group and SC groups, respectively. The apparent elimination half-life was 18.0 ± 10.0 min in the CRI group and 94.8 ± 69.8 min for the SC group, whereas the area under the curve (AUC0-last) resulted 67.7 ± 29.3 and 83.2 ± 60.5 min*ng/mL for CRI and SC group, respectively. Clearance was 16.26 ± 8.07 mL/min/kg for the CRI group. No signs of adverse effects were recorded in both groups. CONCLUSIONS: The pharmacokinetic profile of DEX following repeated SC administration in anaesthetized horses was comparable to intravenous CRI administration during the intranaesthetic period and beneficial during the recovery phase from general anaesthesia. The SC route could be considered as an alternative to CRI for improving the recovery quality of equine patients undergoing general anaesthesia.

Plasma concentration, cardiorespiratory and analgesic effects of ketamine-fentanyl infusion in dogs submitted to mastectomy.

BACKGROUND: The analgesic and cardiorespiratory effects of ketamine, fentanyl, or ketamine-fentanyl constant rate infusion (CRI) in dogs undergoing mastectomy were evaluated. Seventeen female dogs received CRI of ketamine (GK [n = 6]: bolus 0.5 mg/kg; CRI 20 µg/kg/min in intra- and postoperative periods], fentanyl (GF [n = 5]: bolus 20 µg/kg; intraoperative CRI 5 20 µg/kg/hour and postoperative CRI 2 20 µg/kg/hour), or combination of ketamine-fentanyl (GKF [n = 6]: aforementioned doses) for 8 h. Cardiorespiratory, blood gas analyses, plasma drug concentrations, sedation score (SS), Pain Scores were evaluated. RESULTS: The heart rate decreased in the GF and GKF (p < 0.04); the mean arterial pressure was lower in the GKF than in the GK at 35 min (p < 0.001). Maximum plasma concentrations were observed 5 min after bolus in the GK (2847.06 ± 2903.03 ng/mL) and GKF (2811.20 ± 1931.76 ng/mL). Plasma concentration in intraoperative period of ketamine was of > 100 ng/mL in 5/5 and 2/5 animals in the GKF and GK, respectively; and > 1.1 ng/mL of fentanyl in 4/5 and 3/5 in GKF and GF, respectively. CONCLUSION: Ketamine with/without fentanyl provided analgesia without significant cardiorespiratory and guaranteed the minimal plasma levels with analgesic potential during the 8 h.

Use of dexmedetomidine repeated subcutaneous administration for balanced anaesthesia in horses.

BACKGROUND: A balanced anaesthetic protocol is a common concept in modern veterinary anaesthesia and aims to maintain good intraoperative cardiopulmonary function. In horses, alpha-2-agonists produce sedation and analgesia and have been shown to reduce inhalational anaesthetic requirements when administered intravenously. Furthermore, these drugs can improve recovery quality. Preliminary investigations of subcutaneous dexmedetomidine administration in humans demonstrated a reduced haemodynamic impact if compared with the intravenous route suggesting that dexmedetomidine is adequately absorbed with both administration routes. The aim of the study was to compare two different dexmedetomidine (DEX) administration routes: intravenous constant rate infusion (CRI) versus repeated subcutaneous (SC) injections on cardiopulmonary function and recovery in anaesthetized horses. RESULTS: No significant differences between groups in heart rate and systolic arterial pressure were detected. A significantly higher mean and diastolic arterial pressure were detected in the SC group at T25 (p = 0.04; p = 0.02), T75 (p = 0.02; p = 0.009), and T85 (p = 0.001; p = 0.005). In SC group there was a significantly lower dobutamine infusion rate (p = 0.03) and a significantly higher urinary output (p = 0.02). Moreover, recovery quality was higher (p = 0.01). CONCLUSIONS: Cardiopulmonary effects in both groups were comparable and within clinical ranges with less dobutamine requirement in the subcutaneous group. Recovery was of better quality with fewer attempts in horses receiving subcutaneous dexmedetomidine. The present study suggests that intravenous constant rate infusion and subcutaneous repeated administration of dexmedetomidine at indicated dosage can be useful in balanced anaesthesia without any systemic or local adverse effects; moreover, in healthy horses undergoing general anaesthesia, repeated subcutaneous dexmedetomidine administration may be a suitable alternative if constant rate infusion is not feasible.

Opioid-sparing effect of a medetomidine constant rate infusion during thoraco-lumbar hemilaminectomy in dogs administered a ketamine infusion.

OBJECTIVE: To evaluate the perioperative opioid-sparing effect of a medetomidine (MED) infusion compared to a saline (SAL) infusion in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery. STUDY DESIGN: Randomized, partially blinded, clinical study. ANIMALS: A total of 44 client-owned adult dogs. METHODS: All dogs were administered a 1 µg kg-1 MED loading dose, followed by a 1.7 µg kg-1 hour-1 constant rate infusion (CRI) intravenously or equivalent volumes of SAL. Infusions were started 10-15 minutes before surgical incision and continued throughout the surgical procedure. All dogs were administered a standardized anaesthetic and analgesic protocol (including a ketamine CRI). Multiparametric monitoring, including invasive arterial blood pressure, was performed. A trained investigator, unaware of the treatment, performed pain scores for 4 hours postoperatively. Rescue analgesia consisted of fentanyl administered intraoperatively and methadone postoperatively. Data were tested for normality and analysed with Fisher's exact test, Mann-Whitney U-test, analysis of variance and Kaplan-Meier survival analysis. Data are shown as median (interquartile range) and p-value was set at < 0.05. RESULTS: The total dose of fentanyl was significantly lower with MED 0 (0-0.8) µg kg-1 hour-1 compared to SAL 3 (1.8-5.3) µg kg-1 hour-1 (p = 0.004). In the MED group, one dog compared to 12 dogs in the SAL group required a fentanyl CRI (p = 0.001). There were no statistically significant differences between groups regarding the total dose of methadone administered. CONCLUSIONS AND CLINICAL RELEVANCE: The addition of a low-dose medetomidine CRI to the anaesthetic protocol decreased the need for a fentanyl CRI in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery during administration of a ketamine CRI.

Clinical applicability of detomidine and methadone constant rate infusions for surgery in standing horses.

OBJECTIVE: To determine the required rate of a detomidine infusion (loading dose 5 µg kg-1; initial rate 12.5 µg kg-1 hour-1) added to a constant infusion of methadone (0.2 mg kg-1; 0.05 mg kg-1 hour-1) for sedation in standing horses and ponies undergoing elective surgeries with appropriate local anaesthetic techniques. STUDY DESIGN: Prospective, clinical study. ANIMALS: Adult, healthy, client-owned, non-food-producing horses or ponies sedated for elective standing surgeries longer than 45 minutes. METHODS: At baseline (in the stables before administration of sedative agents), at 10 minutes after sedation and every 5 minutes thereafter, ataxia, sedation and surgical condition were evaluated; each scored 0-3. These scores were used to adjust the detomidine administration rate using the Ghent Sedation Algorithm. A 10 cm visual analogue scale (VAS) was used by the main surgeon at the end of the procedure to evaluate the surgical conditions. Heart rate, systolic arterial pressure and respiratory frequency were also recorded at each time point. For statistical analysis, anova for normal, Kruskal-Wallis H-test for non-normal variables, and Mann-Whitney U test for VAS were used. RESULTS: From the 42 horses/ponies included in this study, 28 underwent dental procedures and 14 other types of procedures. Overall, dental procedures required higher mean detomidine rates compared with other types of surgeries (16.9 ± 4.5 versus 9.0 ± 1.9 µg kg-1 hour-1) (p < 0.001). Dental procedures were assigned similar VAS scores, median (range), of 7.8 (5.8-10) with other procedures, 8.7 (2.8-10). Cardiovascular changes were not clinically significant. No signs or behavioural changes of abdominal pain were observed postoperatively. CONCLUSIONS AND CLINICAL RELEVANCE: Satisfactory surgical conditions were achieved using a combination of detomidine and methadone infusions with locoregional anaesthesia, with no adverse effects. Dental procedures required higher detomidine dose rates compared with other surgeries.

COMPARISON OF ISOFLURANE GAS VERSUS A GUAIFENESIN, KETAMINE, AND MEDETOMIDINE CONSTANT-RATE INFUSION FOR MAINTENANCE ANESTHESIA IN AMERICAN BLACK BEARS (URSUS AMERICANUS).

Published anesthetic protocols for captive and free-ranging bears are limited to injectable inductions with maintenance via inhalants or additional injectable boluses. Though common in other species, intravenous (IV) continuous-rate infusions (CRI) using guaifenesin combinations have not been evaluated in ursids. This study evaluated the use of a CRI compared to an inhalant for maintenance anesthesia. Seven healthy American black bears (Ursus americanus) were anesthetized in a crossover design with two different anesthetic maintenance protocols. Bears were immobilized with ketamine (2.02 ± 0.14 mg/kg) and medetomidine (0.04 ± 0.003 mg/kg) for both protocols. The anesthetic maintenance control protocol consisted of isoflurane gas (ISO) started at 2% delivered by endotracheal tube; the experimental protocol consisted of guaifenesin, medetomidine, ketamine (GMK) IV CRI started at 50 mg/kg/hr guaifenesin, 0.01 mg/kg/hr medetomidine, and 1 mg/kg/hr ketamine. Induction and recovery parameters including time to first effect, recumbency, and hands on; duration of maintenance protocol; and time from reversals administered to head up, standing on all four feet, no ataxia, and to fully recovered were recorded and compared between protocols. Heart rate, respiratory rate, rectal temperature, blood pressure, end tidal carbon dioxide, and hemoglobin oxygen saturation were recorded at 5-min intervals and compared between protocols. Venous blood gases were obtained at the start, middle, and end of the maintenance anesthesia and compared between protocols. All bears exhibited hypertension with mild respiratory acidosis throughout procedures. Measured physiologic parameters did not differ significantly between the isoflurane and the GMK CRI maintenance protocols, with the exception of higher endpoint (ISO) pCO2 measurements. No adverse events were recorded with either protocol, and adequate depth of anesthesia was maintained with both protocols. GMK CRI provides a safe, effective, and more portable alternative to inhalant anesthetics for maintenance anesthesia in bears in captivity or in the field.

Comparison of two intravenous anesthetic infusion regimens for alfaxalone in cats.

OBJECTIVE: To compare the performance of an alfaxalone constant rate intravenous (IV) infusion versus a 3-step IV infusion, both following a loading dose, for the maintenance of a target plasma alfaxalone concentration of 7.6 mg L-1 (effective plasma alfaxalone concentration for immobility in 99% of the population) in cats. STUDY DESIGN: Prospective randomized crossover study. ANIMALS: A group of six healthy, adult male neutered cats. METHODS: Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for drug administration. An IV bolus of alfaxalone (2 mg kg-1) was administered, followed by either 0.2 mg kg-1 minute-1 for 240 minutes (single infusion; SI) or 0.4 mg kg-1 minute-1 for 10 minutes, then 0.3 mg kg-1 minute-1 for 30 minutes, and then 0.2 mg kg-1 minute-1 for 200 minutes (3-step infusion; 3-step). Plasma alfaxalone concentration was measured at six time points during the infusions. Measures of performance were calculated for each infusion regimen and compared using the paired Wilcoxon signed-rank test. RESULTS: Median (range) absolute performance error, divergence, median prediction error and wobble were 15 (8-19)%, -8 (-12 to -6)% hour-1, -12 (-19 to -7)% and 10 (8-19)%, respectively, in the SI treatment, and 6 (2-16)%, 0 (-13 to 2)% hour-1, 1 (-16 to 4)% and 4 (3-6)% respectively, in the 3-step treatment and were significantly smaller in the 3-step treatment than in the SI treatment. CONCLUSION AND CLINICAL RELEVANCE: After IV administration of a bolus dose, a 3-step infusion regimen can better maintain stable plasma alfaxalone concentrations close to the target concentration than a single constant rate infusion.

Comparison of fentanyl and hydromorphone constant rate infusions for pain management in dogs in an intensive care unit.

OBJECTIVE: To compare the efficacy and quality of analgesia provided by constant rate infusions (CRIs) of hydromorphone and fentanyl in dogs in the intensive care unit (ICU). STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A total of 29 client-owned dogs. METHODS: Dogs prescribed a µ-opioid agonist infusion for postsurgical or medical pain were randomized to be administered either hydromorphone (0.025 or 0.05 mg kg-1 bolus, followed by a 0.03 mg kg-1 hour-1 infusion) or fentanyl (2.5 or 5 µg kg-1 bolus, followed by a 3 µg kg-1 hour-1 infusion). The technical staff and clinicians were blinded as to which drug was administered. Pain scores, using the Colorado State University Canine Acute Pain Scale, sedation scores and nausea scores were assigned at regular intervals and compared between groups. Dose escalation and de-escalation of the study drug were performed according to set protocols. Adverse clinical signs and all other medications administered were recorded and compared between groups. The study drug was discontinued if the animal remained painful despite dose escalations, or if adverse effects were noted. RESULTS: The pain scores were of low magnitude and were not significantly different between groups. The use of concurrent analgesia, sedation/anxiolytic medications and antacid/antiemetic medications was not different between groups. Sedation and nausea scores were not statistically different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Hydromorphone and fentanyl CRIs appear to be equally effective for adequate pain relief in dogs, with no significant differences in adverse effects. Therefore, either drug may be chosen for control of postsurgical or medical pain in an ICU setting.

Effects of two fentanyl constant rate infusions on thermal thresholds and plasma fentanyl concentrations in awake cats.

OBJECTIVE: To determine the pharmacokinetics and effects on thermal thresholds (TT) of two fentanyl constant rate infusions in awake cats. STUDY DESIGN: A blinded, randomized crossover study. ANIMALS: A group of six healthy female cats, aged 3 ± 1 years, weighing 4.1 ± 0.7 kg. METHODS: Skin temperature (TSKIN) and TT were evaluated using a wireless TT device. TSKIN, TT, sedation score (SS) and blood samples were collected before an intravenous loading dose (LD; over 5 seconds) and at specific time points during (360 minutes) and after infusion. Each cat was administered two treatments: fentanyl (LD 3 µg kg-1, infusion 3 µg kg-1 hour-1; treatment F3) or fentanyl (LD 5 µg kg-1, infusion 5 µg kg-1 hour-1; treatment F5). SS between treatments was analyzed using a Kruskal-Wallis test. Statistical analysis of TT and TSKIN was performed using analysis of variance with appropriate post hoc test (p < 0.05). RESULTS: TSKIN did not vary over time for each treatment. SS did not differ between treatments. TTs were significantly higher than baseline at 15 minutes after LD for F3 and F5. TT was significantly increased at 30, 90, 120, 180 and 300 minutes in treatment F5 but not in F3. Plasma fentanyl concentrations decreased rapidly in both treatments over the first 30 minutes after infusion. The terminal half-life was 3.31 (2.93-4.41) hours for F3 and 3.67 (3.39-4.32) hours for F5 (median, range). Systemic clearance for treatments F3 and F5 was 1.95 (1.46-2.44) and 2.25 (1.98-2.47) L hour-1 kg-1 (median, range), respectively. Plasma concentrations <1.84 ng mL-1 were not associated with a significant increase in TT. CONCLUSIONS: and clinical relevance A fentanyl infusion rate of 5 µg kg-1 hour-1 increased TT during the infusion period. Effects on TT were lost rapidly with cessation of the infusion.

COMPARISON OF PROPOFOL CONSTANT RATE INFUSION AND ISOFLURANE FOR MAINTENANCE OF ANESTHESIA IN SPEKE'S GAZELLE, GAZELLA SPEKEI.

The aims of this study were to determine if a propofol constant rate infusion (CRI) in Speke's gazelle, Gazella spekei, would serve as an effective alternative maintenance anesthetic, result in shorter recovery times, and improve anesthetic recovery quality when compared with isoflurane. Eight adult gazelle were enrolled in this complete crossover study with a minimum 3-wk washout period. All gazelle were induced with 10 mg/kg intravenous propofol and maintained with either propofol CRI (0.4 mg/kg/min) or isoflurane (1-3%) for 45 min. Animals were monitored for anesthetic depth and physiologic variables including heart and respiratory rates, oxygen saturation, end-tidal carbon dioxide, indirect blood pressure, and temperature every 5 min. Blood gas samples were analyzed within the first 10 min following anesthetic induction and within the last 10 min of anesthesia. Recovery times were recorded. Recovery quality was classified by a residual ataxia grading scale. Seven gazelle completed the study by undergoing both anesthetic treatments; one female (12 yr old) developed complications 2 days after isoflurane anesthesia, consisting of seizures, azotemia, leukocytosis, hypocalcemia, and hypomagnesemia but was treated successfully. Propofol anesthesia resulted in lower respiratory rates compared with isoflurane and a decrease in respiratory rate over time. Propofol CRI maintained blood pressure values closer to physiologically normal ranges compared with isoflurane for 45 min of anesthesia. Recovery times were comparable between propofol and isoflurane treatments. While individuals receiving propofol had higher residual ataxia scores compared with individuals receiving isoflurane, differences were not clinically important. This study demonstrated that propofol CRI (0.4 mg/kg/min) is an effective maintenance anesthetic agent in healthy adult Speke's gazelle for noninvasive procedures with endotracheal intubation and intermittent positive pressure ventilation.

Simple equation for calculation of plasma clearance for evaluation of renal function without urine collection in rats.

To develop an equation for the evaluation of renal function in rats using three dilutions of plasma samples and to validate this method by comparison with a reference method. The investigation was conducted in Sprague-Dawley (SD) rats after delivery of three doses of iohexol, with blood samples collected before and after dosage using a quantitative blood collection method. Plasma iohexol concentrations were detected by high performance liquid chromatography (HPLC). The extraction recovery of iohexol from plasma was >97.30% and the calibration curve was linear (r2 = 0.9997) over iohexol concentrations ranging from 10 to 1000 µg/mL. The method had an RE of <9.310 and intra- and inter-day RSD of <5.137% and <3.693%, respectively. The plasma clearance values obtained from the equation correlated closely (r = 0.763) with those obtained using the reference method. The relatively correlation in the results obtained using the method under investigation and the reference method indicate that this new equation can be used for preliminary assessment of renal function in rats.

Intracranial pressure, its components and cerebrospinal fluid pressure-volume compensation.

Clinical measurement of intracranial pressure (ICP) is often performed to aid diagnosis of hydrocephalus. This review discusses analysis of ICP and its components' for the investigation of cerebrospinal fluid (CSF) dynamics. The role of pulse, slow and respiratory waveforms of ICP in diagnosis, prognostication and management of hydrocephalus is presented. Two methods related to ICP measurement are listed: an overnight monitoring of ICP and a constant-rate infusion study. Due to the dynamic nature of ICP, a 'snapshot' manometric measurement of ICP is of limited use as it might lead to unreliable results. Therefore, monitoring of ICP over longer time combined with analysis of its waveforms provides more detailed information on the state of pressure-volume compensation. The infusion study implements ICP signal processing and CSF circulation model analysis in order to assess the cerebrospinal dynamics variables, such as CSF outflow resistance, compliance of CSF space, pressure amplitude, reference pressure, and CSF formation. These parameters act as an aid tool in diagnosis and prognostication of hydrocephalus and can be helpful in the assessment of a shunt malfunction.

Comparison of anesthesia with a morphine-lidocaine-ketamine infusion or a morphine-lidocaine epidural on time to extubation in dogs.

OBJECTIVE: To evaluate and compare the time to extubation in two commonly used methods of analgesia in dogs undergoing elective pelvic limb orthopedic procedures. STUDY DESIGN: Prospective, randomized, double-blinded clinical study. ANIMALS: Twenty-five adult, client-owned, healthy dogs aged 4.4 ± 1.6 years and weighing 38.5 ±3.5 kg. METHODS: All dogs were premedicated with dexmedetomidine (5-10 µg kg(-1)) intramuscularly (IM) and anesthesia was induced with propofol (2-6 mg kg(-1)) intravenously (IV). Atipamazole (0.05-0.1 mg kg(-1)) was administered IM after instrumentation. Anesthesia was maintained with isoflurane in oxygen. Dogs were randomly assigned to one of two groups. In one group, morphine (0.1 mg kg(-1)) and lidocaine (2% lidocaine added to a total volume of 0.2 mL kg(-1)) were administered epidurally and a saline placebo constant rate infusion (CRI) was administered IV (group EPI). In the other group (group MLK), morphine (4 µg kg(-1) minute(-1)), lidocaine (50 µg kg(-1) minute(-1)) and ketamine (10 µg kg(-1) minute(-1)) were administered as an IV CRI and a saline placebo was administered by epidural injection. Temperature at the discontinuation of isoflurane, temperature at extubation, time to extubation, duration of inhalation anesthesia and duration of surgery were recorded. RESULTS: No significant differences between the groups were found in time to extubation, temperature at the end of surgery, temperature at extubation and total surgical time. Total anesthesia time was significantly longer in group EPI. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of MLK at the doses reported in this study did not prolong the time to extubation in comparison with a morphine-lidocaine epidural nerve block. The results indicate that concern over prolonging the time to extubation is not a reason to avoid the administration of MLK.

Postoperative analgesic effects of either a constant rate infusion of fentanyl, lidocaine, ketamine, dexmedetomidine, or the combination lidocaine-ketamine-dexmedetomidine after ovariohysterectomy in dogs.

OBJECTIVE: To evaluate the postoperative analgesic effects of a constant rate infusion (CRI) of either fentanyl (FENT), lidocaine (LIDO), ketamine (KET), dexmedetomidine (DEX), or the combination lidocaine-ketamine-dexmedetomidine (LKD) in dogs. STUDY DESIGN: Randomized, prospective, blinded, clinical study. ANIMALS: Fifty-four dogs. METHODS: Anesthesia was induced with propofol and maintained with isoflurane. Treatments were intravenous (IV) administration of a bolus at start of anesthesia, followed by an IV CRI until the end of anesthesia, then a CRI at a decreased dose for a further 4 hours: CONTROL/BUT (butorphanol 0.4 mg kg(-1), infusion rate of saline 0.9% 2 mLkg(-1) hour(-1)); FENT (5 µg kg(-1), 10 µg kg(-1) hour(-1), then 2.5 µg kg(-1) hour(-1)); KET (1 mgkg(-1) , 40 µg kg(-1) minute(-1), then 10 µg kg(-1) minute(-1) ; LIDO (2 mg kg(-1), 100 µg kg(-1) minute(-1), then 25 µg kg(-1) minute(-1)); DEX (1 µgkg(-1), 3 µg kg(-1) hour(-1), then 1 µg kg(-1) hour(-1)); or a combination of LKD at the aforementioned doses. Postoperative analgesia was evaluated using the Glasgow composite pain scale, University of Melbourne pain scale, and numerical rating scale. Rescue analgesia was morphine and carprofen. Data were analyzed using Friedman or Kruskal-Wallis test with appropriate post-hoc testing (p < 0.05). RESULTS: Animals requiring rescue analgesia included CONTROL/BUT (n = 8), KET (n = 3), DEX (n = 2), and LIDO (n = 2); significantly higher in CONTROL/BUT than other groups. No dogs in LKD and FENT groups received rescue analgesia. CONTROL/BUT pain scores were significantly higher at 1 hour than FENT, DEX and LKD, but not than KET or LIDO. Fentanyl and LKD sedation scores were higher than CONTROL/BUT at 1 hour. CONCLUSIONS AND CLINICAL RELEVANCE: LKD and FENT resulted in adequate postoperative analgesia. LIDO, CONTROL/BUT, KET and DEX may not be effective for treatment of postoperative pain in dogs undergoing ovariohysterectomy.

A comparison of cardiopulmonary function, recovery quality, and total dosages required for induction and total intravenous anesthesia with propofol versus a propofol-ketamine combination in healthy Beagle dogs.

OBJECTIVE: To compare cardiopulmonary function, recovery quality, and total dosages required for induction and 60 minutes of total intravenous anesthesia (TIVA) with propofol (P) or a 1:1 mg mL(-1) combination of propofol and ketamine (KP). STUDY DESIGN: Randomized crossover study. ANIMALS: Ten female Beagles weighing 9.4 ± 1.8 kg. METHODS: Dogs were randomized for administration of P or KP in a 1:1 mg mL(-1) ratio for induction and maintenance of TIVA. Baseline temperature, pulse, respiratory rate (fR), noninvasive mean blood pressure (MAP), and hemoglobin oxygen saturation (SpO2) were recorded. Dogs were intubated and spontaneously breathed room air. Heart rate (HR), fR, MAP, SpO2, end tidal carbon dioxide tension (Pe'CO2), temperature, and salivation score were recorded every 5 minutes. Arterial blood gas analysis was performed at 10, 30, and 60 minutes, and after recovery. At 60 minutes the infusion was discontinued and total drug administered, time to extubation, and recovery score were recorded. The other treatment was performed 1 week later. RESULTS: KP required significantly less propofol for induction (4.0 ± 1.0 mg kg(-1) KP versus 5.3 ±1.1 mg kg(-1) P, p = 0.0285) and maintenance (0.3 ± 0.1 mg kg(-1) minute(-1) KP versus 0.6 ±0.1 mg kg(-1) minute(-1) P, p = 0.0018). Significantly higher HR occurred with KP. Both P and KP caused significantly lower MAP compared to baseline. MAP was significantly higher with KP at several time points. P had minimal effects on respiratory variables, while KP resulted in significant respiratory depression. There were no significant differences in salivation scores, time to extubation, or recovery scores. CONCLUSIONS AND CLINICAL RELEVANCE: Total intravenous anesthesia in healthy dogs with ketamine and propofol in a 1:1 mg mL(-1) combination resulted in significant propofol dose reduction, higher HR, improved MAP, no difference in recovery quality, but more significant respiratory depression compared to propofol alone.

Influence of ketamine or xylazine supplementation on isoflurane anaesthetized horses--a controlled clinical trial.

OBJECTIVES: To determine the influence of ketamine or xylazine constant rate infusions on isoflurane requirements, cardiovascular parameters and quality of anaesthesia in horses undergoing elective surgery. STUDY DESIGN: Prospective, matched paired clinical trial. ANIMALS: Fifty four adult Warmblood horses. METHODS: After premedication with acepromazine, xylazine and butorphanol, anaesthesia was induced with ketamine-midazolam and maintained with isoflurane alone (I), isoflurane with either 1 mg kg(-1)  hour(-1) ketamine (IK) or same dose of xylazine (IX). End tidal concentration of isoflurane (Fe'Iso) was adjusted by the same anaesthetist in all horses according to a scoring system. Dobutamine was infused to maintain mean arterial pressure (MAP) ≥70 mmHg. Arterial blood gases, heart rate (HR), respiratory rate, MAP and cardiac output (lithium dilution) were measured. Groups I and IK received xylazine before recovery. Recovery quality was scored. RESULTS: Mean ± SD averaged Fe'Iso (volume%) was significantly lower in IX (0.95 ± 0.07) and IK (0.97 ± 0.08) than in I (1.16 ± 0.13). In group IX, HR was significantly lower and averaged MAP (90 ± 13 mmHg) significantly higher than in groups I (71 ± 7 mmHg) and IK (76 ± 7 mm Hg). Differences in other cardiopulmonary variables did not reach statistical significance. All horses recovered well with best score in group IX. CONCLUSIONS: Both CRIs of xylazine and of ketamine resulted in pronounced reduction of isoflurane requirements and blood pressure support based on routinely monitored parameters. Cardiac output appeared well maintained in all three protocols, but lithium dilution induced errors mean the results are untrustworthy. The work requires repetition with another mode of measurement of cardiac output. CLINICAL RELEVANCE: All three protocols provided good clinical anaesthesia with clinically acceptable cardiovascular effects.

Stability of 1% voriconazole solution in a constant-rate infusion pump for topical ocular delivery to horses.

OBJECTIVE: To establish the effect of storage in a constant-rate infusion (CRI) pump on the sterility and stability of voriconazole 1% solution. PROCEDURE: Nine vials of voriconazole (Vfend(®) I.V.) 1% solution were prepared. Approximately half of each solution was used to prime a commercially available CRI pump with attached subpalpebral lavage system (CRI/SPL unit) with the remaining solution stored in the commercial glass vial. Three CRI/SPL units and their three corresponding vials were stored at one of three temperatures: 23 °C, 33 °C, and 40 °C. The CRI pumps ran for 7 days, and the vials were stored for 30 days. Fungal and aerobic bacterial cultures were performed on the first and last day of the storage period for each vessel. Samples were obtained at regular intervals for determination of voriconazole concentration using high-performance liquid chromatography. RESULTS: No bacterial or fungal contamination was identified in any solution at any time point. All solutions stored in the commercial glass vial remained stable throughout the study period. Multiple CRI/SPL units became blocked with crystallized voriconazole. There was a significant increase in voriconazole concentration after passage through the CRI/SPL units. CONCLUSIONS: Voriconazole 1% solution is not compatible for use in a CRI/SPL unit at temperatures between 23 and 40 °C. Voriconazole 1% solution is stable in the commercial glass vial when stored at controlled temperatures as high as 40 °C for up to 30 days.

Evaluation of a romifidine constant rate infusion protocol with or without butorphanol for dentistry and ophthalmologic procedures in standing horses.

OBJECTIVE: To compare the clinical usefulness of constant rate infusion (CRI) protocols of romifidine with or without butorphanol for sedation of horses. STUDY DESIGN: Prospective 'blinded' controlled trial using block randomization. ANIMALS: Forty healthy Freiberger stallions. METHODS: The horses received either intravenous (IV) romifidine (loading dose: 80 µg kg(-1) ; infusion: 30 µg kg(-1)  hour(-1) ) (treatment R, n = 20) or romifidine combined with butorphanol (romifidine loading: 80 µg kg(-1) ; infusion: 29 µg kg(-1)  hour(-1) , and butorphanol loading: 18 µg kg(-1) ; infusion: 25 µg kg(-1)  hour(-1) ) (treatment RB, n = 20). Twenty-one horses underwent dentistry and ophthalmic procedures, while 19 horses underwent only ophthalmologic procedure and buccal examination. During the procedure, physiologic parameters and occurrence of head/muzzle shaking or twitching and forward movement were recorded. Whenever sedation was insufficient, additional romifidine (20 µg kg(-1) ) was administered IV. Recovery time was evaluated by assessing head height above ground. At the end of the procedure, overall quality of sedation for the procedure was scored by the dentist and anaesthetist using a visual analogue scale. Statistical analyses used two-way anova or linear mixed models as relevant. RESULTS: Sedation quality scores as assessed by the anaesthetist were R: median 7.55, range: 4.9-9.0 cm, RB: 8.8, 4.7-10.0 cm, and by the dentist R: 6.6, 3.0-8.2 cm, RB: 7.9, 6.6-8.8 cm. Horses receiving RB showed clinically more effective sedation as demonstrated by fewer poor scores and a tendency to reduced additional drug requirements. More horses showed forward movement and head shaking in treatment RB than treatment R. Three horses (two RB, one R) had symptoms of colic following sedation. CONCLUSIONS AND CLINICAL RELEVANCE: The described protocols provide effective sedation under clinical conditions but for dentistry procedures, the addition of butorphanol is advantageous.

Minimum end-tidal sevoflurane concentration necessary to prevent movement during a constant rate infusion of morphine, or morphine plus dexmedetomidine in ponies.

OBJECTIVE: To compare the effects of a constant rate infusion (CRI) of dexmedetomidine and morphine to those of morphine alone on the minimum end-tidal sevoflurane concentration necessary to prevent movement (MACNM ) in ponies. STUDY DESIGN: Prospective, randomized, crossover, 'blinded', experimental study. ANIMALS: Five healthy adult gelding ponies were anaesthetized twice with a 3-week washout period. METHODS: After induction of anaesthesia with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (Fe'SEVO 2.5%) in 55% oxygen. Monitoring included pulse oximetry, electrocardiography and measurement of anaesthetic gases, arterial blood pressure and body temperature. The ponies were mechanically ventilated and randomly allocated to receive IV treatment M [morphine 0.15 mg kg⁻¹ (T10-T15) followed by a CRI (0.1 mg kg⁻¹ hour⁻¹)] or treatment DM [dexmedetomidine 3.5 µg kg⁻¹ plus morphine 0.15 mg kg⁻¹ (T10-T15) followed by a CRI of dexmedetomidine 1.75 µg kg⁻¹ hour⁻¹ and morphine 0.1 mg kg⁻¹ hour⁻¹]. At T60, a stepwise MACNM determination was initiated using constant current electrical stimuli at the skin of the lateral pastern region. Triplicate MACNM estimations were obtained and then averaged in each pony. Wilcoxon signed-rank test was used to detect differences in MAC between treatments (α = 0.05). RESULTS: Sevoflurane-morphine MACNM values (median (range) and mean ± SD) were 2.56 (2.01-4.07) and 2.79 ± 0.73%. The addition of a continuous infusion of dexmedetomidine significantly reduced sevoflurane MACNM values to 0.89 (0.62-1.05) and 0.89 ± 0.22% (mean MACNM reduction 67 ± 11%). CONCLUSION AND CLINICAL RELEVANCE: Co-administration of dexmedetomidine and morphine CRIs significantly reduced the MACNM of sevoflurane compared with a CRI of morphine alone at the reported doses.