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

ObjectiveTo elaborate constant rate infusion (CRI) protocols for xylazine (X) and xylazine/butorphanol (XB) which will result in constant sedation and steady xylazine plasma concentrations.Study designBlinded randomized experimental study.AnimalsTen adult research horses.MethodsPart I: After normal height of head above ground (HHAG = 100%) was determined, a loading dose of xylazine (1 mg kg^?1) with butorphanol (XB: 18 μg kg^?1) or saline (X: equal volume) was given slowly intravenously (IV). Immediately afterwards, a CRI of butorphanol (XB: 25 μg kg^?1 hour^?1) or saline (X) was administered for 2 hours. The HHAG was used as a marker of depth of sedation. Sedation was maintained for 2 hours by additional boluses of xylazine (0.3 mg kg^?1) whenever HHAG >50%. The dose of xylazine (mg kg^?1 hour^?1) required to maintain sedation was calculated for both groups. Part II: After the initial loading dose, the calculated xylazine infusion rates were administered in parallel to butorphanol (XB) or saline (X) and sedation evaluated. Xylazine plasma concentrations were measured by HPLC-MS-MS at time points 0, 5, 30, 45, 60, 90, and 120 minutes. Data were analyzed using paired t-test, Wilcoxon signed rank test and a 2-way anova for repeated measures (p < 0.05).ResultsThere was no significant difference in xylazine requirements (X: 0.69, XB: 0.65 mg kg^?1 hour^?1) between groups. With treatment X, a CRI leading to prolonged sedation was developed. With XB, five horses (part I: two, part II: three) fell down and during part II four horses appeared insufficiently sedated. Xylazine plasma concentrations were constant after 45 minutes in both groups.ConclusionXylazine bolus, followed by CRI, provided constant sedation. Additional butorphanol was ineffective in reducing xylazine requirements and increased ataxia and apparent early recovery from sedation in unstimulated horses.Clinical relevanceData were obtained on unstimulated healthy horses and extrapolation to clinical conditions requires caution.     

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

ObjectiveTo compare the clinical usefulness of constant rate infusion (CRI) protocols of romifidine with or without butorphanol for sedation of horses.Study designProspective ‘blinded’ controlled trial using block randomization.AnimalsForty healthy Freiberger stallions.MethodsThe 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.ResultsSedation 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 relevanceThe described protocols provide effective sedation under clinical conditions but for dentistry procedures, the addition of butorphanol is advantageous.     

The effects of a loading dose followed by constant rate infusion of xylazine compared with romifidine on sedation,ataxia and response to stimuli in horses

ObjectiveTo compare xylazine and romifidine constant rate infusion (CRI) protocols regarding degree of sedation, and effects on postural instability (PI), ataxia during motion (A) and reaction to different stimuli.Study designBlinded randomized experimental cross-over study.AnimalsTen adult horses.MethodsDegree of sedation was assessed by head height above ground (HHAG). Effects on PI, A and reaction to visual, tactile and acoustic stimulation were assessed by numerical rating scale (NRS) and by visual analogue scale (VAS). After baseline measurements, horses were sedated by intravenous loading doses of xylazine (1 mg kg^?1) or romifidine (80 μg kg^?1) administered over 3 minutes, immediately followed by a CRI of xylazine (0.69 mg kg^?1 hour^?1) or romifidine (30 μg kg^?1 hour^?1) which was administered for 120 minutes. Degree of sedation, PI, A and reaction to the different stimuli were measured at different time points before, during and for one hour after discontinuing drug administration. Data were analysed using two-way repeated measures anova, a Generalized Linear Model and a Wilcoxon Signed Rank Test (p < 0.05).ResultsSignificant changes over time were seen for all variables. With xylazine HHAG was significantly lower 10 minutes after the loading dose, and higher at 150 and 180 minutes (i.e. after CRI cessation) compared to romifidine. Reaction to acoustic stimulation was significantly more pronounced with xylazine. Reaction to visual stimulation was greater with xylazine at 145 and 175 minutes. PI was consistently but not significantly greater with xylazine during the first 30 minutes. Reaction to touch and A did not differ between treatments. Compared to romifidine, horses were more responsive to metallic noise with xylazine.ConclusionsTime to maximal sedation and to recovery were longer with romifidine than with xylazine.Clinical relevanceWith romifidine sufficient time should be allowed for complete sedation before manipulation.     

Effect of detomidine or romifidine constant rate infusion on plasma lactate concentration and inhalant requirements during isoflurane anaesthesia in horses

Objective

Influence of detomidine or romifidine constant rate infusion (CRI) on plasma lactate concentration and isoflurane requirements in horses undergoing elective surgery.

Evaluation of the sedative,analgesic, clinicophysiological and haematological effects of intravenous detomidine,detomidine‐butorphanol,romifidine and romifidine‐butorphanol in standing donkeys

The aim of this investigation was to determine and evaluate the sedative, analgesic, clinicophysiological and haematological effects of intravenous (i.v.) injection of detomidine, detomidine‐butorphanol, romifidine and romifidine‐butorphanol. Six standing donkeys were used. Each donkey received 4 i.v. treatments and the order of treatment was randomised with a one‐week interval between each treatment. We found that i.v. injection of a combination of detomidine‐butorphanol or romifidine‐butorphanol produced potent neuroleptanalgesic effects thus providing better, safe and effective sedation with complete analgesia in standing donkeys compared with injection of detomidine or romifidine alone. The changes and reduction in pulse rate were within acceptable limits. The changes in clinicophysiological, haematological and biochemical values were mild and transient in these clinically healthy donkeys.     

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.     

Behavioural and cardiovascular effects of medetomidine constant rate infusion compared with detomidine for standing sedation in horses

ObjectiveTo compare the efficacy of a medetomidine constant rate infusion (CRI) with a detomidine CRI for standing sedation in horses undergoing high dose rate brachytherapy.Study designRandomized, controlled, crossover, blinded clinical trial.AnimalsA total of 50 horses with owner consent, excluding stallions.MethodsEach horse was sedated with intravenous acepromazine (0.02 mg kg^–1), followed by an α₂-adrenoceptor agonist 30 minutes later and then by butorphanol (0.1 mg kg^–1) 5 minutes later. A CRI of the same α₂-adrenoceptor agonist was started 10 minutes after butorphanol administration and maintained for the treatment duration. Treatments were given 1 week apart. Each horse was sedated with detomidine (bolus dose, 10 μg kg^–1; CRI, 6 μg kg^–1 hour^–1) or medetomidine (bolus dose, 5 μg kg^–1; CRI, 3.5 μg kg^–1 hour^–1). If sedation was inadequate, a quarter of the initial bolus of the α₂-adrenoceptor agonist was administered. Heart rate (HR) was measured via electrocardiography, and sedation and behaviour evaluated using a previously published scale. Between treatments, behaviour scores were compared using a Wilcoxon signed-rank test, frequencies of arrhythmias with chi-square tests, and HR with two-tailed paired t tests. A p value <0.05 indicated statistical significance.ResultsTotal treatment time for medetomidine was longer than that for detomidine (p = 0.04), and ear movements during medetomidine sedation were more numerous than those during detomidine sedation (p = 0.03), suggesting there may be a subtle difference in the depth of sedation. No significant differences in HR were found between treatments (p ≥ 0.09). Several horses had arrhythmias, with no difference in their frequency between the two infusions.Conclusions and clinical relevanceMedetomidine at this dose rate may produce less sedation than detomidine. Further studies are required to evaluate any clinical advantages to either drug, or whether a different CRI may be more appropriate.     

RESEARCH PAPER: Romifidine as a constant rate infusion in isoflurane anaesthetized horses: a clinical study

Objective To evaluate the effects of a constant rate infusion (CRI) of romifidine on the requirement of isoflurane, cardiovascular performance and recovery in anaesthetized horses undergoing arthroscopic surgery. Study design Randomized blinded prospective clinical trial. Animals Thirty horses scheduled for routine arthroscopy. Methods After premedication (acepromazine 0.02 mg kg^?1, romifidine 80 μg kg^?1, methadone 0.1 mg kg^?1) and induction (midazolam 0.06 mg kg^?1 ketamine 2.2 mg kg^?1), anaesthesia was maintained with isoflurane in oxygen. Horses were assigned randomly to receive a CRI of saline (group S) or 40 μg kg^?1 hour^?1 romifidine (group R). The influences of time and treatment on anaesthetic and cardiovascular parameters were evaluated using an analysis of variance. Body weight (t‐test), duration of anaesthesia (t‐test) and recovery score (Wilcoxon Rank Sum Test) were compared between groups. Significance was set at p < 0.05. Results All but one horse were positioned in the dorsal recumbent position and ventilated from the start of anaesthesia. End tidal isoflurane concentrations were similar in both groups at similar time points and over the whole anaesthetic period. Cardiac output was significantly lower in horses of the R group, but there were no significant differences between groups in cardiac index, body weight or age. All other cardiovascular parameters were similar in both groups. Quality of recovery did not differ significantly between groups, but more horses in group R stood without ataxia at the first attempt. One horse from group S had a problematic recovery. Conclusions and clinical relevance No inhalation anaesthetic sparing effect or side effects were observed by using a 40 μg kg^?1 hour^?1 romifidine CRI in isoflurane anaesthetized horses under clinical conditions. Cardiovascular performance remained acceptable. Further studies are needed to identify the effective dose of romifidine that will induce an inhalation anaesthetic sparing effect in anaesthetized horses.     

Comparison of morphine and butorphanol as pre-anaesthetic agents in combination with romifidine for field castration in ponies

OBJECTIVE: The aim of this study was to compare two different alpha2 agonist-opioid combinations in ponies undergoing field castration. STUDY DESIGN: Prospective double-blind randomized clinical trial. ANIMAL POPULATION: Fifty-four ponies undergoing field castration. MATERIALS AND METHODS: The ponies were randomly allocated to receive one of three different pre-anaesthetic medications [intravenous (IV) romifidine 100 microg kg(-1) and butorphanol 50 micro kg(-1); romifidine 100 microg kg(-1) and morphine 0.1 mg kg(-1) IV, or romifidine 100 microg kg(-1) and saline IV] before induction of anaesthesia with ketamine 2.2 mg kg(-1) IV. Further doses of romifidine (25 microg kg(-1)) and ketamine (0.5 mg kg(-1)) were given when required to maintain anaesthesia. Quality of sedation, induction of anaesthesia, maintenance of anaesthesia, recovery, and surgical condition were assessed using a visual analogue scale scoring system and compared. The effects of the different drug combinations on heart and respiratory rate were evaluated and the recovery time was recorded. RESULTS: Anaesthesia was considered adequate for surgery in all ponies. No anaesthetic complications were observed. Quality of sedation was significantly better in the butorphanol group compared with the control group (p = 0.0428). Overall quality of anaesthesia was better in the butorphanol group compared with morphine (p = 0.0157) and control (p < 0.05) groups. Quality of induction of anaesthesia and recovery were not significantly different between groups, nor were the surgical conditions, recovery time and the number of repeated anaesthetic doses required during the procedure. Muscle twitches were observed in both the control and morphine groups. Maintenance of anaesthesia was judged to be smoother in the butorphanol group compared with the morphine and control groups (p = 0.006). Heart rate decreased significantly (p < 0.01) in all groups after administration of sedatives but did not differ significantly between groups at any time point. CONCLUSION: The combination of butorphanol and romifidine was found to provide better sedation compared with the other drug combinations. CLINICAL RELEVANCE: The combination of butorphanol and romifidine provided better sedation, but morphine was found to be a suitable alternative to butorphanol. Use of morphine and butorphanol in combination with alpha2 agonists should be further investigated to assess their analgesic effects.     

Pharmacokinetics and pharmacodynamics of intravenous romifidine and propranolol administered alone or in combination for equine sedation

Objective

Propranolol has been suggested for anxiolysis in horses, but its sedation efficacy and side effects, both when administered alone and in combination with α₂-adrenoceptor agonists, remain undetermined. This study aimed to document the pharmacokinetics and pharmacodynamics of propranolol, romifidine and their combination.

The effects of detomidine, romifidine or acepromazine on echocardiographic measurements and cardiac function in normal horses

OBJECTIVE: To evaluate by echo- and electrocardiography the cardiac effects of sedation with detomidine hydrochloride, romifidine hydrochloride or acepromazine maleate in horses. STUDY DESIGN: An experimental study using a cross-over design without randomization. ANIMALS: Eight clinically normal Standardbred trotters. MATERIALS AND METHODS: Echocardiographic examinations (two-dimensional, guided M-mode and colour Doppler) were recorded on five different days. Heart rate (HR) and standard limb lead electrocardiograms were also obtained. Subsequently, horses were sedated with detomidine (0.01 mg kg(-1)), romifidine (0.04 mg kg(-1)) or acepromazine (0.1 mg kg(-1)) administered intravenously and all examinations repeated. RESULTS: Heart rate before treatment with the three drugs did not differ significantly (p = 0.98). Both detomidine and romifidine induced a significant decrease (p < 0.001) in HR during the first 25 minutes after sedation; while acepromazine had a varying effect on HR. For detomidine, there was a significant increase in LVIDd (left ventricular internal diameter in diastole; p = 0.034) and LVIDs (left ventricular internal diameter in systole; p < 0.001). In addition, a significant decrease was found in IVSs (the interventricular septum in systole; p < 0.001), LVFWs (the left ventricular free wall in systole; p = 0.002) and FS% (fractional shortening; p < 0.001). The frequency of pulmonary regurgitation was increased significantly (p < 0.001). Romifidine induced a significant increase in LVIDs (p < 0.001) and a significant decrease in IVSs (p < 0.001) and FS% (p = 0.002). Acepromazine had no significant effect upon any of the measured values. CONCLUSIONS: and clinical relevance The results indicate that sedation of horses with detomidine and to a lesser extent romifidine at the doses given in this study has a significant effect on heart function, echocardiographic measurements of heart dimensions and the occurrence of valvular regurgitation. Although the clinical significance of these results may be minimal, the potential effects of sedative drugs should be taken into account when echocardiographic variables are interpreted in clinical cases.     

Effects of detomidine or romifidine during maintenance and recovery from isoflurane anaesthesia in horses

ObjectiveTo evaluate the effects of detomidine or romifidine on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing isoflurane anaesthesia.Study designProspective, randomized, blinded, clinical study.AnimalsA total of 63 healthy horses undergoing elective surgery during general anaesthesia.MethodsHorses were randomly allocated to three groups of 21 animals each. In group R, horses were given romifidine intravenously (IV) for premedication (80 μg kg^–1), maintenance (40 μg kg^–1 hour^–1) and before recovery (20 μg kg^–1). In group D2.5, horses were given detomidine IV for premedication (15 μg kg^–1), maintenance (5 μg kg^–1 hour^–1) and before recovery (2.5 μg kg^–1). In group D5, horses were given the same doses of detomidine IV for premedication and maintenance but 5 μg kg^–1 prior to recovery. Premedication was combined with morphine IV (0.1 mg kg^–1) in all groups. Cardiovascular and blood gas variables, expired fraction of isoflurane (Fe′Iso), dobutamine or ketamine requirements, recovery times, recovery events scores (from sternal to standing position) and visual analogue scale (VAS) were compared between groups using either anova followed by Tukey, Kruskal-Wallis followed by Bonferroni or chi-square tests, as appropriate (p < 0.05).ResultsNo significant differences were observed between groups for Fe′Iso, dobutamine or ketamine requirements and recovery times. Cardiovascular and blood gas measurements remained within physiological ranges for all groups. Group D5 horses had significantly worse scores for balance and coordination (p = 0.002), overall impression (p = 0.021) and final score (p = 0.008) than group R horses and significantly worse mean scores for VAS than the other groups (p = 0.002).Conclusions and clinical relevanceDetomidine or romifidine constant rate infusion provided similar conditions for maintenance of anaesthesia. Higher doses of detomidine at the end of anaesthesia might decrease the recovery quality.     

Intramuscular injection of alfaxalone in combination with butorphanol for sedation in cats

Objective

To assess quality of sedation following intramuscular (IM) injection of two doses of alfaxalone in combination with butorphanol in cats.

Comparison of intraoperative cardiorespiratory and behavioral responses to medetomidine combined with tramadol or butorphanol during standing laparoscopic ovariectomy in horses

The purpose of this study was to assess the cardiorespiratory and behavioral responses to the combination of medetomidine and tramadol (M-T) or butorphanol (M-B) in standing laparoscopic ovariectomy in horses. One ovary was removed under M-T and the contralateral ovary was removed under M-B with at least 4 weeks between operations at random. Horses were sedated using intravenous medetomidine (5 µg/kg) followed by tramadol (1 mg/kg) or butorphanol (10 µg/kg) after 5 min. Sedation was maintained through the repeated injection of medetomidine (1 µg/kg) and tramadol (0.4 mg/kg) or medetomidine (1 µg/kg) and butorphanol (4 µg/kg) every 15 min. Cardiorespiratory function and behavioral responses, including, sedation, ataxia, and analgesia, were assessed during the surgery. There were no significant differences in cardiorespiratory values and sedation and analgesia scores between M-T and M-B. Ataxia scores were significantly lower in M-T than in M-B. This result suggests that M-T could maintain smooth and stable standing surgery with minimal cardiorespiratory changes in horses.     

Antinociceptive effects of levomethadone in standing horses sedated with romifidine

ObjectiveTo evaluate the antinociceptive effect of a bolus of intravenous levomethadone administered to horses during romifidine constant rate infusion (CRI).Study designProspective, randomized, masked, crossover experimental study.AnimalsA group of eight adult Warmblood horses (seven geldings, one mare) aged 6.6 ± 4.4 years, weighing 548 ± 52 kg [mean ± standard deviation (SD)].MethodsLevomethadone 0.1 mg kg^–1 or an equivalent volume of saline (control) was administered intravenously to standing horses 60 minutes after starting a romifidine CRI. Blood samples to quantify romifidine and levomethadone plasma concentrations by capillary electrophoresis were collected up to 150 minutes after levomethadone administration. The nociceptive withdrawal reflex threshold (NWRT) was determined continuously using an automated threshold tracking device. Sedation and cardiopulmonary variables were assessed at regular intervals. A pharmacokinetic-pharmacodynamic (PK-PD) model was elaborated. Data are presented as mean ± SD or median (interquartile range, 25%–75%) where appropriate. Differences between groups were considered statistically significant for p < 0.05.ResultsHorses exhibited higher NWRTs after levomethadone administration than after saline (123 ± 9% versus 101 ± 9% relative to baseline, p < 0.05). The PK-PD model identified a contribution of levomethadone to the NWRT increase. Effect size was variable among individuals. No adverse reactions to levomethadone administration were observed. A slight effect of levomethadone on sedation scores was evident for the 60 minutes following its administration.Conclusions and Clinical RelevanceA single injection of levomethadone has the potential to increase the NWRT during romifidine CRI in horses and can be administered in combination with α₂-adrencoceptor agonists to enhance antinociception in horses. However, individual variation is marked.