Development of a romifidine constant rate infusion with or without butorphanol for standing sedation of horses

ObjectiveTo determine constant rate infusion (CRI) protocols for romifidine (R) and romifidine combined with butorphanol (RB) resulting in constant sedation and romifidine plasma concentrations.Study designBlinded randomized crossover study.AnimalsTen adult research horses.MethodsPart I: After determining normal height of head above ground (HHAG = 100%), loading doses of romifidine (80 μg kg^?1) with butorphanol (RB: 18 μg kg^?1) or saline (R) were given intravenously (IV). Immediately afterwards, a butorphanol (RB: 25 μg kg^?1 hour^?1) or saline (R) CRI was administered for 2 hours. The HHAG was used as marker of sedation depth. Sedation was maintained for 2 hours by additional romifidine (20 μg kg^?1) whenever HHAG > 50%. The dose rate of romifidine (μg kg^?1 hour^?1) required to maintain sedation was calculated for both treatments. Part II: After loading doses, the romifidine CRIs derived from part I were administered in parallel to butorphanol (RB) or saline (R). Sedation and ataxia were evaluated periodically. Romifidine plasma concentrations were measured by HPLC-MS-MS at 0, 5, 10, 15, 30, 45, 60, 90, 105, and 120 minutes. Data were analyzed using paired t-test, Fisher's exact test, Wilcoxon signed rank test, and two-way anova for repeated measures (p < 0.05).ResultsThere was no significant difference in romifidine requirements (R: 30; RB: 29 μg kg^?1 hour^?1). CRI protocols leading to constant sedation were developed. Time to first additional romifidine bolus was significantly longer in RB (mean ± SD, R: 38.5 ± 13.6; RB: 50.5 ± 11.7 minutes). Constant plasma concentrations of romifidine were achieved during the second hour of CRI. Ataxia was greater when butorphanol was added.ConclusionRomifidine bolus, followed by CRI, provided constant sedation assessed by HHAG. Butorphanol was ineffective in reducing romifidine requirements in unstimulated horses, but prolonged the sedation caused by the initial romifidine bolus.Clinical relevanceBoth protocols need to be tested under clinical conditions.     

Influence of a constant rate infusion of dexmedetomidine on cardiopulmonary function and recovery quality in isoflurane anaesthetized horses

ObjectiveTo investigate the influence of a dexmedetomidine constant rate infusion (CRI) in horses anaesthetized with isoflurane.Study designProspective, randomized, blinded, clinical study.AnimalsForty adult healthy horses (weight mean 491 ± SD 102 kg) undergoing elective surgery.MethodsAfter sedation [dexmedetomidine, 3.5 μg kg^?1 intravenously (IV)] and induction IV (midazolam 0.06 mg kg^?1, ketamine 2.2 mg kg^?1), anaesthesia was maintained with isoflurane in oxygen/air (FiO₂ 55–60%). Horses were ventilated and dobutamine was administered when hypoventilation [arterial partial pressure of CO₂ > 8.00 kPa (60 mmHg)] and hypotension [arterial pressure 70 mmHg] occurred respectively. During anaesthesia, horses were randomly allocated to receive a CRI of dexmedetomidine (1.75 μg kg^?1 hour^?1) (D) or saline (S). Monitoring included end-tidal isoflurane concentration, cardiopulmonary parameters, and need for dobutamine and additional ketamine. All horses received 0.875 μg kg^?1 dexmedetomidine IV for the recovery period. Age and weight of the horses, duration of anaesthesia, additional ketamine and dobutamine, cardiopulmonary data (anova), recovery scores (Wilcoxon Rank Sum Test), duration of recovery (t-test) and attempts to stand (Mann–Whitney test) were compared between groups. Significance was set at p < 0.05.ResultsHeart rate and arterial partial pressure of oxygen were significantly lower in group D compared to group S. An interaction between treatment and time was present for cardiac index, oxygen delivery index and systemic vascular resistance. End-tidal isoflurane concentration and heart rate significantly increased over time. Packed cell volume, systolic, diastolic and mean arterial pressure, arterial oxygen content, stroke volume index and systemic vascular resistance significantly decreased over time. Recovery scores were significantly better in group D, with fewer attempts to stand and significantly longer times to sternal position and first attempt to stand.Conclusions and clinical relevance A dexmedetomidine CRI produced limited cardiopulmonary effects, but significantly improved recovery quality.     

丁氨丙磷在马体内的药代动力学研究

健康赛马6匹,随机分为2组,分别以5 mg/kg体重和2.5 mg/kg体重2个剂量静注复方丁氨丙磷注射液。用液相色谱-质谱法(LC-MS)测定血清中药物浓度,采用3p97药代动力学程序软件对所得药-时数据进行处理。结果表明,血清中丁氨丙磷的浓度下降很快,无论高剂量组还是低剂量组,24 h后血清中均无丁氨丙磷检出(检测限10 ng/mL)。高剂量和低剂量静注药-时数据均符合权重1/C2的二室模型。平均最高浓度分别为高剂量组87.81μg/mL和低剂量组10.22μg/mL,Tmax均为1 min。血药浓度-时间方程为高剂量:C=98.40e-0.31t 6.15e-0.0089t,低剂量:C=6.87e-0.048t 6.15e-0.0079t,高、低剂量组的消除相半衰期t1/2beta分别为77.78 min和87.37 min。药-时曲线下面积(AUC)高剂量组为1 005.55(μg/mL).min和低剂量组为565.16(μg/mL).min,说明该药在马体内的消除速度比较快。     

Problems associated with perioperative morphine in horses: a retrospective case analysis

Objective To identify the incidence of adverse effects caused by morphine 100–170 µg kg^?1 administration during surgery in horses. Design Retrospective case record analysis (1996–2000). Animals Eighty‐four healthy (ASA 1 or 2) horses, mean age 5.5 ± 3.1 (SD) years (2 months to 16 years), mean weight 524 ± 14 kg (100–950). Methods Physiological data and evidence of complications were collected from the anaesthetic records of all animals anaesthetized with romifidine, ketamine, diazepam and halothane and undergoing laryngeal surgery or orchiectomy at the Royal (Dick) School of Veterinary Studies. Cases were divided into those receiving (group M+; n = 18) and those not receiving morphine (M?; n = 29), and the data compared. Values for heart and respiratory rate and mean arterial pressure were compared at 15‐minute intervals between 30 and 120 minutes after induction using anova for repeated measures. The incidence of intraoperative problems was compared using Fisher's exact test. Recovery scores were compared using Student's unpaired t‐test. The records of a further 37 horses undergoing umbilical herniorrhaphy (n = 5), arthroscopy (n = 29) or tarsal arthrodesis (n = 3) were also studied but not analysed statistically due to disparate treatment distribution. Results There were no significant differences between the M+ and M? groups. The incidence of post‐operative complications such as box‐walking and colic were similar in each group. Conclusions Morphine doses of 100–170 µg kg^?1 do not increase the risk of problems when used to provide perioperative analgesia in horses anaesthetized with romifidine, ketamine, diazepam and halothane. Clinical relevance Morphine provides an acceptable and relatively inexpensive way to provide perioperative analgesia in horses.     

Empirical Percentile Growth Curves with Z-scores Considering Seasonal Compensatory Growths for Japanese Thoroughbred Horses

Percentile growth curves are often used as a clinical indicator to evaluate variations of children’s growth status. In this study, we propose empirical percentile growth curves using Z-scores adapted for Japanese Thoroughbred horses, with considerations of the seasonal compensatory growth that is a typical characteristic of seasonal breeding animals. We previously developed new growth curve equations for Japanese Thoroughbreds adjusting for compensatory growth. Individual horses and residual effects were included as random effects in the growth curve equation model and their variance components were estimated. Based on the Z-scores of the estimated variance components, empirical percentile growth curves were constructed. A total of 5,594 and 5,680 body weight and age measurements of male and female Thoroughbreds, respectively, and 3,770 withers height and age measurements were used in the analyses. The developed empirical percentile growth curves using Z-scores are computationally feasible and useful for monitoring individual growth parameters of body weight and withers height of young Thoroughbred horses, especially during compensatory growth periods.