John A. E. Hubbell

Evaluation of the analgesic properties of acepromazine maleate, oxymorphone, medetomidine and a combination of acepromazine-oxymorphone.

OBJECTIVE To determine the presence and duration of analgesia after oxymorphone, acepromazine maleate, acepromazine-oxymorphone combination and medetomidine administration in dogs. STUDY DESIGN Blinded, controlled study. ANIMALS Six adult beagle dogs. METHODS Each dog participated in five trials receiving acepromazine maleate (0.2 mg kg-1 IM), oxymorphone (0.2 mg kg-1 IM), acepromazine-oxymorphone drug combination (0.2 mg kg-1 each IM), medetomidine (20 μg kg-1 IM) and sterile saline (control). Two specially designed instruments were used for analgesia determination: a heat device (HD) utilized a linear ramped intensity incandescent bulb and a pressure device (PD) consisted of a pneumatic cylinder that protruded a 2.5-cm bolt. The minimum pressure and heat necessary to produce an avoidance response were determined. Analgesia testing was performed prior to and at 30-minute intervals for six hours after drug administration. RESULTS Oxymorphone, acepromazine-oxymorphone and medetomidine significantly elevated both pressure and heat response thresholds compared to controls and acepromazine. Both medetomidine and acepromazine-oxymorphone provided a significantly longer duration of analgesia than oxymorphone. No adverse effects were observed at any of the thermal or pressure application sites. CONCLUSIONS Oxymorphone, medetomidine and acepromazine-oxymorphone produced significant analgesia with medetomidine and acepromazine-oxymorphone providing the longest duration of analgesia.

The use of sedatives, analgesic and anaesthetic drugs in the horse: an electronic survey of members of the American Association of Equine Practitioners (AAEP).

REASONS FOR PERFORMING STUDY To determine the sedative, analgesic and anaesthetic drugs and techniques that are used by equine veterinarians. HYPOTHESIS OR OBJECTIVES: To provide equine veterinarians with information concerning veterinary use of anaesthetic techniques, a reflection of the collective experiences of the profession. METHODS A survey was conducted of those members of the American Association of Equine Practitioners (AAEP) with an electronic mail address on file with the organisation using proprietary, web-based software. The survey was comprised of 30 questions divided into 8 sections: nonsteroidal anti-inflammatory drugs; local anaesthesia; alternative techniques; standing chemical restraint; epidural anaesthesia; short-term anaesthesia; long-term anaesthesia; and a place for the respondent to make comments. RESULTS The response rate was 13.8% (952/6911) AAEP member veterinarians primarily use phenylbutazone and flunixin as anti-inflammatory drugs, and lidocaine and mepivacaine for local anaesthesia. Combinations of drugs are preferred for standing chemical restraint. While many veterinarians frequently utilise short-term anaesthesia, longer anaesthesia is less frequently performed. CONCLUSIONS Most AAEP member veterinarians use sedatives in combination to provide standing chemical restraint. Extra-label use of drugs is a core component of current equine sedation and anaesthetic practice. POTENTIAL RELEVANCE Equine veterinarians can compare their choices of anaesthetic drugs with others practising equine medicine and surgery and may be stimulated to investigate alternative methods of providing comfort to horses.

Effect of intravenous lidocaine administration on laminar inflammation in the black walnut extract model of laminitis

REASONS FOR PERFORMING STUDY Laminitis is a serious complication of horses suffering from sepsis/endotoxaemia-related events. Laminitis in horses and organ injury in human sepsis are both reported to involve inflammatory injury to the laminae/organs including early activation of endothelium and leucocytes leading to emigration of neutrophils into the tissue interstitium. In the black walnut extract (BWE) model, systemic inflammatory events coincide with marked increase in laminar mRNA concentrations of inflammatory genes including proinflammatory cytokines (i.e. IL-1beta, IL-6), COX-2, chemokines (i.e. IL-8) and endothelial adhesion molecules (i.e. ICAM-1 and E-selectin). In models of human sepsis, i.v. lidocaine has been reported to decrease leucocyte and endothelial activation, and the expression of proinflammatory cytokines and chemokines. OBJECTIVES To evaluate the effect of i.v. lidocaine therapy on the inflammatory processes documented to occur in the BWE model of laminitis. METHODS Twelve horses were administered BWE and treated immediately with either lidocaine (1.3 mg/kg bwt bolus, followed by 0.05 mg/kg bwt/min CRI, n=6) or saline (n=6) for 10 h. At 10 h post BWE administration, laminar samples were obtained under general anaesthesia for assessment of proinflammatory gene expression (using RT-qPCR) and leucocyte emigration (via CD13 immunohistochemistry). At 0, 3 and 10 h post BWE administration, skin samples were obtained for assessment of leucocyte emigration (via calprotectin immunohistochemistry). RESULTS No significant differences between groups were noted for inflammatory gene mRNA concentrations (IL-1beta, IL-6, IL-8, COX-2) or for number of leucocytes present within the laminar interstitium or skin dermis. Increased (P<0.05) laminar E-selectin mRNA concentrations were present in the LD group (vs. SAL group). CONCLUSIONS Continuous administration of i.v. lidocaine does not inhibit inflammatory events in either the laminae or skin in the horse administered black walnut extract. POTENTIAL RELEVANCE This work questions the use of continuous i.v. administration of lidocaine as an effective anti-inflammatory therapy for systemic inflammation.

Effect of intravenous administration of lactated Ringer's solution or hetastarch for the treatment of isoflurane-induced hypotension in dogs

OBJECTIVE To determine the effect of IV administration of crystalloid (lactated Ringers solution [LRS]) or colloid (hetastarch) fluid on isoflurane-induced hypotension in dogs. ANIMALS 6 healthy Beagles. PROCEDURES On 3 occasions, each dog was anesthetized with propofol and isoflurane and instrumented with a thermodilution catheter (pulmonary artery). Following baseline assessments of hemodynamic variables, end-tidal isoflurane concentration was increased to achieve systolic arterial blood pressure (SABP) of 80 mm Hg. At that time (0 minutes), 1 of 3 IV treatments (no fluid, LRS [80 mL/kg/h], or hetastarch [80 mL/kg/h]) was initiated. Fluid administration continued until SABP was within 10% of baseline or to a maximum volume of 80 mL/kg (LRS) or 40 mL/kg (hetastarch). Hemodynamic variables were measured at intervals (0 through 120 minutes and additionally at 150 and 180 minutes in LRS- or hetastarch-treated dogs). Several clinicopathologic variables including total protein concentration, PCV, colloid osmotic pressure, and viscosity of blood were assessed at baseline and intervals thereafter (0 through 120 minutes). RESULTS Administration of 80 mL of LRS/kg did not increase SABP in any dog, whereas administration of <or= 40 mL of hetastarch/kg increased SABP in 4 of 6 dogs. Fluid administration increased cardiac index and decreased systemic vascular resistance. Compared with hetastarch treatment, administration of LRS decreased blood viscosity. Treatment with LRS decreased PCV and total protein concentration, whereas treatment with hetastarch increased colloid osmotic pressure. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that IV administration of hetastarch rather than LRS is recommended for the treatment of isoflurane-induced hypotension in dogs.

Effect of 50% and maximal inspired oxygen concentrations on respiratory variables in isoflurane-anesthetized horses

BackgroundThe purpose of this study was to compare the effects of 0.5 fraction of inspired oxygen (FiO2) and >0.95 FiO2 on pulmonary gas exchange, shunt fraction and oxygen delivery (DO2) in dorsally recumbent horses during inhalant anesthesia. The use of 0.5 FiO2 has the potential to reduce absorption atelectasis (compared to maximal FiO2) and augment alveolar oxygen (O2) tensions (compared to ambient air) thereby improving gas exchange and DO2. Our hypothesis was that 0.5 FiO2 would reduce ventilation-perfusion mismatching and increase the fraction of pulmonary blood flow that is oxygenated, thus improving arterial oxygen content and DO2.ResultsArterial partial pressures of O2 were significantly higher than preanesthetic levels at all times during anesthesia in the >0.95 FiO2 group. Arterial partial pressures of O2 did not change from preanesthetic levels in the 0.5 FiO2 group but were significantly lower than in the >0.95 FiO2 group from 15 to 90 min of anesthesia. Alveolar to arterial O2 tension difference was increased significantly in both groups during anesthesia compared to preanesthetic values. The alveolar to arterial O2 tension difference was significantly higher at all times in the >0.95 FiO2 group compared to the 0.5 FiO2 group. Oxygen delivery did not change from preanesthetic values in either group during anesthesia but was significantly lower than preanesthetic values 10 min after anesthesia in the 0.5 FiO2 group. Shunt fraction increased in both groups during anesthesia attaining statistical significance at varying times. Shunt fraction was significantly increased in both groups 10 min after anesthesia but was not different between groups. Alveolar dead space ventilation increased after 3 hr of anesthesia in both groups.ConclusionsReducing FiO2 did not change alveolar dead space ventilation or shunt fraction in dorsally recumbent, mechanically ventilated horses during 3 hr of isoflurane anesthesia. Reducing FiO2 in dorsally recumbent isoflurane anesthetized horses does not improve oxygenation or oxygen delivery.

Antagonism of detomidine sedation in the horse using intravenous tolazoline or atipamezole.

REASONS FOR PERFORMING STUDY The ability to shorten the duration of sedation would potentially improve safety and utility of detomidine. OBJECTIVES To determine the effects of tolazoline and atipamezole after detomidine sedation. HYPOTHESIS Administration of tolazoline or atipamezole would not affect detomidine sedation. METHODS In a randomised, placebo-controlled, double-blind, descriptive study, detomidine (0.02 mg/kg bwt i.v.) was administered to 6 mature horses on 4 separate occasions. Twenty-five mins later, each horse received one of 4 treatments: Group 1 saline (0.9% i.v.) as a placebo control; Group 2 atipamezole (0.05 mg/kg bwt i.v.); Group 3 atipamezole (0.1 mg/kg bwt i.v.); and Group 4 tolazoline (4.0 mg/kg bwt i.v.). Sedation, muscle relaxation and ataxia were scored by 3 independent observers at 9 time points. Horses were led through an obstacle course at 7 time points. Course completion time was recorded and the ability of the horse to traverse the course was scored by 3 independent observers. Horses were videotaped before, during and after each trip through the obstacle course. RESULTS Atipamezole and tolazoline administration incompletely antagonised the effects of detomidine, but the time course to recovery was shortened. CONCLUSIONS AND POTENTIAL RELEVANCE Single bolus administration of atipamezole or tolazoline produced partial reversal of detomidine sedation and may be useful for minimising detomidine sedation.

Pharmacokinetics of midazolam after intravenous administration to horses

REASONS FOR PERFORMING THE STUDY Midazolam is used to control seizures in horses and to enhance muscle relaxation, but its pharmacokinetics are unknown. OBJECTIVE To determine the pharmacokinetics and sedative effects of midazolam in horses. STUDY DESIGN Blinded, randomised, crossover design. METHODS Midazolam was administered i.v. at either 0.05 or 0.1 mg/kg bwt to 6 horses on 2 occasions at least 7 days apart using a crossover design. Blood samples were collected before and at predetermined times through 24 h after administration. Serum midazolam concentrations were determined by a liquid chromatography tandem-mass spectrometry method. Heart and respiratory rates and indices of sedation, ataxia, and sensitivity to stimuli were recorded before and at predetermined times after midazolam administration. RESULTS Pharmacokinetic analysis was performed on samples from 5 horses in each group. Median total clearance was 10.6 ml/min/kg (range 6.1-15.2 ml/min/kg) and 10.4 ml/min/kg (range 8.4-17.6 ml/min/kg), and median volume of distribution at steady state was 2094 ml/kg (range 2076-2413 ml/kg) and 2822 ml/kg (range 2270-7064 ml/kg) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Median distribution half-life was 24 min (range 6-42 min) and 39 min (range 33.6-72 min) and median terminal half-life was 216 min (range 120-248 min) and 408 min (range 192-924 min) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Cardiorespiratory parameters and sedation scores did not change. Midazolam caused agitation, postural sway, weakness, and one horse became recumbent after the 0.1 mg/kg bwt dose. CONCLUSIONS Midazolam produces ataxia and postural sway of short duration after i.v. administration to horses. Sedation was not evident after midazolam administration. Drug redistribution is likely the primary mechanism for the termination of effect. POTENTIAL RELEVANCE Midazolam produces muscle relaxation but not sedation in adult horses.

Effect of dexmedetomidine, morphine-lidocaine-ketamine, and dexmedetomidine-morphine-lidocaine-ketamine constant rate infusions on the minimum alveolar concentration of isoflurane and bispectral index in dogs

OBJECTIVE To determine the effect of dexmedetomidine, morphine-lidocaine-ketamine (MLK), and dexmedetomidine-morphine-lidocaine-ketamine (DMLK) constant rate infusions on the minimum alveolar concentration (MAC) of isoflurane and bispectral index (BIS) in dogs. ANIMALS 6 healthy adult dogs. PROCEDURES Each dog was anesthetized 4 times with a 7-day washout period between anesthetic episodes. During the first anesthetic episode, the MAC of isoflurane (baseline) was established. During the 3 subsequent anesthetic episodes, the MAC of isoflurane was determined following constant rate infusion of dexmedetomidine (0.5 μg/kg/h), MLK (morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine, 0.6 mg/kg/h), or DMLK (dexmedetomidine, 0.5 μg/kg/h; morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine 0.6 mg/kg/h). Among treatments, MAC of isoflurane was compared by means of a Friedman test with Conover posttest comparisons, and heart rate, direct arterial pressures, cardiac output, body temperature, inspired and expired gas concentrations, arterial blood gas values, and BIS were compared with repeated-measures ANOVA and a Dunn test for multiple comparisons. RESULTS Infusion of dexmedetomidine, MLK, and DMLK decreased the MAC of isoflurane from baseline by 30%, 55%, and 90%, respectively. Mean heart rates during dexmedetomidine and DMLK treatments was lower than that during MLK treatment. Compared with baseline values, mean heart rate decreased for all treatments, arterial pressure increased for the DMLK treatment, cardiac output decreased for the dexmedetomidine treatment, and BIS increased for the MLK and DMLK treatments. Time to extubation and sternal recumbency did not differ among treatments. CONCLUSIONS AND CLINICAL RELEVANCE Infusion of dexmedetomidine, MLK, or DMLK reduced the MAC of isoflurane in dogs.

Comparison of invasive and oscillometric blood pressure measurement techniques in anesthetized sheep, goats, and cattle

OBJECTIVE To determine the level of agreement between an oscillometric (O-NIBP) and an invasive method (IBP) of monitoring arterial blood pressure (ABP) in anesthetized sheep, goats, and cattle. STUDY DESIGN Prospective clinical study. ANIMALS Twenty sheep and goats, 20 cattle weighing < 150 kg body weight, and 20 cattle weighing 150 kg body weight. METHODS Animals were anesthetized and systolic ABP (SABP), mean ABP (MABP), and diastolic ABP (DABP) were measured using IBP and O-NIBP. Differences between IBP and O-NIBP, and 95% limits of agreement (LOA) between SABP, MABP, and DABP values were assessed by the Bland-Altman method. RESULTS Mean difference ± standard deviation (range) between SABP, DABP, and MABP measurements in sheep and goats was 0 ± 16 (-57 to 38) mmHg, 13 ± 16 (-37 to 70) mmHg, and 8 ± 13 (-34 to 54) mmHg, respectively. Mean difference between SABP, DABP, and MABP measurements in small cattle was 0 ± 19 (-37 to 37) mmHg, 6 ± 18 (-77 to 48) mmHg, and 4 ± 16 (-73 to 48) mmHg, respectively. Mean difference between SABP, DABP, and MABP measurements in large cattle was -18 ± 32 (-107 to 71) mmHg, 7 ± 29 (-112 to 63) mmHg, and -5 ± 28 (-110 to 60) mmHg, respectively. The 95% LOAs for SABP, DABP, and MABP were -31 to +31, -19 to +44, and -19 to +34 mmHg, respectively in sheep and goats; were -37 to +37, -19 to +44, and -19 to +34 mmHg, respectively in small cattle; and were -81 to +45, -50 to +63, and -59 to +50 mmHg, respectively in large cattle. CONCLUSIONS Agreement was poor between O-NIBP and IBP monitoring techniques. CLINICAL RELEVANCE Arterial BP should be monitored in anesthetized sheep, goats, and cattle using IBP.

Evaluation of a midazolam-ketamine-xylazine infusion for total intravenous anesthesia in horses.

OBJECTIVE To evaluate the use of midazolam, ketamine, and xylazine for total IV anesthesia (TIVA) in horses. ANIMALS 6 healthy Thoroughbred mares. PROCEDURES Horses were sedated with xylazine (1.0 mg/kg, IV). Anesthesia was induced with midazolam (0.1 mg/kg, IV) followed by ketamine (2.2 mg/kg, IV) and was maintained with an IV infusion of midazolam (0.002 mg/kg/min), ketamine (0.03 mg/kg/min), and xylazine (0.016 mg/kg/min). Horses underwent surgical manipulation and injection of the palmar digital nerves; duration of the infusion was 60 minutes. Additional ketamine (0.2 to 0.4 mg/kg, IV) was administered if a horse moved its head or limbs during procedures. Cardiopulmonary and arterial blood variables were measured prior to anesthesia; at 10, 20, 30, 45, and 60 minutes during infusion; and 10 minutes after horses stood during recovery. Recovery quality was assessed by use of a numeric (1 to 10) scale with 1 as an optimal score. RESULTS Anesthesia was produced for 70 minutes after induction; supplemental ketamine administration was required in 4 horses. Heart rate, respiratory rate, arterial blood pressures, and cardiac output remained similar to preanesthetic values throughout TIVA. Arterial partial pressure of oxygen and oxygen saturation of arterial hemoglobin were significantly decreased from preanesthetic values throughout anesthesia; oxygen delivery was significantly decreased at 10- to 30-minute time points. Each horse stood on its first attempt, and median recovery score was 2. CONCLUSIONS AND CLINICAL RELEVANCE Midazolam, ketamine, and xylazine in combination produced TIVA in horses. Further studies to investigate various dosages for midazolam and ketamine or the substitution of other α(2)-adrenoceptor for xylazine are warranted.