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.

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.     

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.     

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.     

Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise

Reason for performing study: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objectives: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatographymass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Results: Median back‐extrapolated time zero plasma concentration was significantly lower and median plasma half‐life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Conclusions and potential relevance: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.     

A comparison of recovery times and characteristics with sevoflurane and isoflurane anaesthesia in horses undergoing magnetic resonance imaging

Objective To compare recovery times and quality following maintenance of anaesthesia with sevoflurane or isoflurane after a standard intravenous induction technique in horses undergoing magnetic resonance imaging (MRI). Study design Prospective, randomised, blinded clinical study. Animals One hundred ASA I/II horses undergoing MRI. Materials and methods Pre‐anaesthetic medication with intravenous acepromazine and romifidine was followed by induction of anaesthesia with diazepam and ketamine. The animals were randomised into two groups to receive either sevoflurane or isoflurane in oxygen. Horses were subjectively scored (0–5) for temperament before sedation, for quality of sedation, induction and maintenance and anaesthetic depth on entering the recovery area. Recoveries were videotaped and scored by an observer, unaware of the treatment, using two scoring systems. Times to the first movement, head lift, sternal recumbency and standing were recorded along with the number of attempts to achieve sternal and standing positions. Variables were compared using a Student t‐test or Mann–Whitney U‐test (p < 0.05), while the correlation between subjective recovery score and other relevant variables was tested calculating the Spearman Rank correlation coefficient and linear regression modelling performed when significant. Results Seventy‐seven horses entered the final analysis, 38 received isoflurane and 39 sevoflurane. Body mass, age and duration of anaesthesia were similar for both groups. There were no differences in recovery times, scoring or number of attempts to achieve sternal recumbency and standing between groups. Weak, but significant, correlations were found between the subjective recovery score for the pooled data from both groups and both temperament and time in sternal recumbency. Conclusions No differences in recovery times or quality were detected following isoflurane or sevoflurane anaesthesia after intravenous induction. Clinical relevance Sevoflurane affords no obvious advantage in recovery over isoflurane following a standard intravenous induction technique in horses not undergoing surgery.     

Pharmacokinetics of detomidine and its metabolites following intravenous and intramuscular administration in horses

Reasons for performing study: Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. Objectives: To describe the pharmacokinetics of detomidine and its metabolites, 3‐hydroxy‐detomidine (OH‐detomidine) and detomidine 3‐carboxylic acid (COOH‐detomidine), after i.v. and i.m. administration of a single dose to horses. Methods: Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 μg/kg bwt and 4 a single dose i.m. 30 üg/kg bwt. In Phase 2, treatments were reversed. Plasma detomidine, OH‐detomidine and COOH‐detomidine were measured at predetermined time points using liquid chromatography‐mass spectrometry. Results: Following i.v. administration, detomidine was distributed rapidly and eliminated with a half‐life (t_1/2(el)) of approximately 30 min. Following i.m. administration, detomidine was distributed and eliminated with t_1/2(el) of approximately one hour. Following, i.v. administration, detomidine clearance had a mean, median and range of 12.41, 11.66 and 10.10–18.37 ml/min/kg bwt, respectively. Detomidine had a volume of distribution with the mean, median and range for i.v. administration of 470, 478 and 215–687 ml/kg bwt, respectively. OH‐detomidine was detected sooner than COOH‐detomidine; however, COOH‐detomidine had a much greater area under the curve. Conclusions and potential relevance: These pharmacokinetic parameters provide information necessary for determination of peak plasma concentrations and clearance of detomidine in mature horses. The results suggest that, when a longer duration of plasma concentration is warranted, the i.m. route should be considered.     

Comparative study between atropine and hyoscine-N-butylbromide for reversal of detomidine induced bradycardia in horses

Reasons for performing study: Bradycardia may be implicated as a cause of cardiovascular instability during anaesthesia. Hypothesis: Hyoscine would induce positive chronotropism of shorter duration than atropine, without adversely impairing intestinal motility in detomidine sedated horses. Methods: Ten minutes after detomidine (0.02 mg/kg bwt, i.v.), physiological saline (control), atropine (0.02 mg/kg bwt) or hyoscine (0.2 mg/kg bwt) were randomly administered i.v. to 6 horses, allowing one week intervals between treatments. Investigators blinded to the treatments monitored cardiopulmonary data and intestinal auscultation for 90 min and 24 h after detomidine, respectively. Gastrointestinal transit was assessed for 96 h via chromium detection in dry faeces. Results: Detomidine significantly decreased heart rate (HR) and cardiac index (CI) from baseline for 30 and 60 min, respectively (control). Mean ± s.d. HR increased significantly 5 min after atropine (79 ± 5 beats/min) and hyoscine (75 ± 8 beats/min). After this time, HR was significantly higher after atropine in comparison to other treatments, while hyoscine resulted in intermediate values (lower than atropine but higher than controls). Hyoscine and atropine resulted in significantly higher CI than controls for 5 and 20 min, respectively; but this effect coincided with significant hypertension (mean arterial pressures >180 mmHg). Auscultation scores decreased from baseline in all treatments. Time to return to auscultation scores ≥12 (medians) did not differ between hyoscine (4 h) and controls (4 h) but atropine resulted in significantly longer time (10 h). Atropine induced colic in one horse. Gastrointestinal transit times did not differ between treatments. Conclusion: Hyoscine is a shorter acting positive chronotropic agent than atropine, but does not potentiate the impairment in intestinal motility induced by detomidine. Because of severe hypertension, routine use of anticholinergics combined with detomidine is not recommended. Potencial relevance: Hyoscine may represent an alternative to atropine for treating bradycardia.     

Effects of hypercapnic hyperpnea on recovery from isoflurane or sevoflurane anesthesia in horses

Objective To test the hypothesis that hypercapnic hyperpnea produced using endotracheal insufflation with 5–10% CO₂ in oxygen could be used to shorten anesthetic recovery time in horses, and that recovery from sevoflurane would be faster than from isoflurane. Study design Randomized crossover study design. Animals Eight healthy adult horses. Methods After 2 hours’ administration of constant 1.2 times MAC isoflurane or sevoflurane, horses were disconnected from the anesthetic circuit and administered 0, 5, or 10% CO₂ in balance O₂ via endotracheal tube insufflation. End‐tidal gas samples were collected to measure anesthetic washout kinetics, and arterial and venous blood samples were collected to measure respiratory gas partial pressures. Horses recovered in padded stalls without assistance, and each recovery was videotaped and evaluated by reviewers who were blinded to the anesthetic agent and insufflation treatment used. Results Compared to isoflurane, sevoflurane caused greater hypoventilation and was associated with longer times until standing recovery. CO₂ insufflation significantly decreased anesthetic recovery time compared to insufflation with O₂ alone without significantly increasing PaCO₂. Pharmacokinetic parameters during recovery from isoflurane with CO₂ insufflation were statistically indistinguishable from sevoflurane recovery without CO₂. Neither anesthetic agent nor insufflation treatment affected recovery quality from anesthesia. Conclusions and clinical relevance Hypercapnic hyperpnea decreases time to standing without influencing anesthetic recovery quality. Although the lower blood gas solubility of sevoflurane should favor a shorter recovery time compared to isoflurane, this advantage is negated by the greater respiratory depression from sevoflurane in horses.     

Serum concentrations and effects of detomidine delivered orally to horses in three different mediums

Objective To compare the effect of orally delivered detomidine on head posture when administered alone or in combination with two different food items, and to determine the serum concentrations of detomidine after oral delivery. Study Design Prospective randomized experimental study. Animals Fifteen adult grade mares weighing 328–537 kg. Methods The horses were randomly assigned to one of the three treatment groups (five horses each). The groups were given detomidine (0.06 mg kg^?1): alone; mixed with 3 mL of an apple sauce and gum mixture; or mixed with 3 mL molasses. Head droop, measured before treatment and at 15, 30, 45, 60, 75, 90, and 105 minutes after treatment, was used to evaluate sedation. Yohimbine (0.1 mg kg^?1 IV) was administered after the 90‐minute evaluation. Blood samples were collected from the detomidine‐alone group before treatment and at 15, 30, 45, 60, 75, and 90 minutes after treatment. Sera were analyzed for detomidine equivalent concentrations by an ELISA. Head droop percentages were compared using a repeated measures analysis of variance. Results Significant mean head droop developed in each treatment group by 30 minutes and persisted until reversal with yohimbine. After yohimbine administration, head positions returned to 87–91% of pre‐treatment levels. There were no significant differences among the oral treatment groups at any time. Mean serum detomidine equivalents increased slowly until 45‐minute post‐administration, but never exceeded 30 ng mL^?1. Conclusions Orally administered detomidine results in measurable serum drug concentrations using any of the delivery mediums investigated, and can be expected to produce profound head droop in horses approximately 45 minutes after administration.     

Quantitative and qualitative comparison of three scoring systems for assessing recovery quality after general anaesthesia in horses

Objective To assess the reproducibility and repeatability of two commonly used recovery quality scoring systems and compare them with those of a novel system based on a greater number of objective criteria. Animals The video‐recorded recoveries of ten client‐owned horses selected from all recovery recordings taken between September 2005 and March 2006 at the Royal (Dick) School of Veterinary Studies. Materials and methods A digital versatile disc (DVD) was produced using edited video recordings of ten horses recovering from general anaesthesia. Twelve experienced equine anaesthetists (raters) studied the DVD on three occasions, and scored the recovery quality of each horse using one of three scoring systems (P, D or E) on each occasion. The process was repeated 6 months later (t = 6) to measure intra‐observer reliability (repeatability). At first use (t = 0) raters were asked to comment on the advantages and disadvantages of each system. Results Inter‐rater variability was limited for each system: at each observation period raters accounted for 0.3–4.4% variation. System P was insensitive to differences between recoveries. In system D, score variability increased as recovery quality deteriorated. Intra‐rater variability varied with system: using system P, raters provided consistent scores between the observation periods for some, but not all horses (‘horse’ and ‘rater’ accounted for 9.7% and 1.9% of variation respectively). Raters were less consistent between t = 0 and t = 6 using system D, but each horse was scored with similar consistency. System E produced little variation at the level of horse (1.0%) and rater (1.9%). Raters broadly agreed on the principle advantages and disadvantages of the three systems. Conclusions and clinical relevance The systems examined showed reliability and reproducibility but practicality and simplicity of use appeared to be inextricably linked with imprecision. Further work is required to produce a suitable recovery quality scoring system.     

Anti‐nociceptive and sedative effects of romifidine,tramadol and their combination administered intravenously slowly in ponies

ObjectiveTo evaluate the anti-nociceptive and sedative effects of slow intravenous (IV) injection of tramadol, romifidine, or a combination of both drugs in ponies.Study designWithin-subject blinded.AnimalsTwenty ponies (seven male, 13 female, weighing mean ± SD 268.0 ± 128 kg).MethodsOn separate occasions, each pony received one of the following three treatments IV; romifidine 50 μg kg⁻ (R) tramadol 3 mg kg⁻¹ given over 15 minutes (T) or tramadol 3 mg kg⁻¹followed by romifidine 50 μg kg⁻¹ (RT). Physiologic parameters and caecal borborygmi (CB) were measured and sedation and response to electrical stimulation of the coronary band assessed before and up to 120 minutes following drugs administration. Results were analyzed using the Friedman’s test and 2 way anova as relevant.ResultsWhen compared to baseline, heart (HR, beats minute⁻¹) and respiratory rates (f_R, breaths minute⁻¹) increased with treatment T (highest mean ± SD, HR 43 ± 1; f_R 33 ± 2) and decreased with R (lowest HR 29 ± 1 and f_R 10 ± 4) and RT (lowest HR 32 ± 1 and f_R 9 ± 3). There were no changes in other measured physiological variables. The height of head from the ground was lower following treatments R and TR than T. There was slight ataxia with all three treatments. No excitatory behavioural effects were observed. The response to electrical stimulation was reduced for a prolonged period relative to baseline following all three treatments, the effect being significantly greatest with treatment RT.ConclusionTramadol combined with romifidine at the stated doses proved an effective sedative and anti-nociceptive combination in ponies, with no unacceptable behavioural or physiologic side effects.Clinical relevanceSlow controlled administration of tramadol should reduce the occurrence of adverse behavioural side effects.