Dobutamine use in horses during romifidine and isoflurane anaesthesia.

This retrospective study aimed to assess the incidence of hypotension and the subsequent administration of dobutamine in horses anesthetized with isoflurane and romifidine during elective surgery. Time from induction of anaesthesia to administration of dobutamine was registered, as well as the time and dose needed to restore mean arterial pressure (MAP) ≥ 70 mmHg. Additionally, the influence of patient and anaesthesia related parameters on the need for dobutamine supplementation was evaluated. In total, 118 horses were included in this retrospective study. Dobutamine was administered to effect when MAP<70 mmHg. Data registered: patient weight, acepromazine premedication, body position, administration of intraoperative ketamine bolus, locoregional anaesthesia, mechanical ventilation, duration of anaesthesia, dose and duration of dobutamine administration, heart rate, MAP before dobutamine administration, MAP and time required to increase MAP≥70 mmHg. Dobutamine infusion was needed in 54.2% of the horses 30 ± 17 min after isoflurane-romifidine anaesthesia started. Dobutamine 0.55 ± 0.18 µg kg-1 min-1 achieved a MAP≥70 mmHg in 12 ± 8 min. Duration of dobutamine infusion was 56 ± 37 min. An univariable logistic regression showed a significant association between dobutamine and acepromazine administration (p = 0.01; OR = 3.43), anaesthesia time (p = 0.02; OR = 2.41) and dorsal recumbency (p < 0.001; OR = 8.40). In a multivariable logistic regression, only dorsal recumbency significantly increased the need for dobutamine supplementation (p < 0.001; OR = 7.70). There was no significant association between patient weight (p = 0.11; OR = 1), locoregional anaesthesia (p = 0.07; OR = 0.47), administration of a ketamine bolus (p = 0.95; OR = 0.98) or volume controlled ventilation (p = 0.94; OR = 1.04) and dobutamine administration. Low doses of dobutamine were suitable to restore MAP above 70 mmHg within a limited time period. Only dorsal recumbency increased the need of dobutamine administration.

Tramadol Administered Intravenously Either as a Bolus or a Slow Injection in Pain Management of Romifidine-Sedated Calves Undergoing Umbilical Hernia Repair.

Umbilical hernias in calves occur with relative frequency. Most abdominal surgeries can be performed in cattle using standing sedation and local blocks. Romifidine is widely used in calves, alone or in combination with opioids. Tramadol administered as an intravenous slow injection provided better analgesia than an IV bolus in cows. The aim of the present study was to compare the response to surgical stimulus, and sedative effects of tramadol administered intravenously either as a bolus or a slow injection in romifidinesedated calves. Twenty Frisian calves undergoing umbilical hernia repair received romifidine (0.08 mg/kg IM; time 0) followed by tramadol (1 mg/kg IV) 5 min later either as a bolus (n = 10, B group) or a slow injection over 10 min (n = 10, SI group). Surgical area was infiltrated with lidocaine (4 mg/kg). Heart rate (HR), respiratory rate (RR), systolic, dyastolic and mean arterial pressure (SAP, DAP, MAP), sedation scores and response to surgical stimulus were recorded for up to 55 min. After the calves recovered a standing position, postoperative pain scores were assessed for up to 50 min. Sedation scores were significantly higher in the SI group than in the B group at 55 min (p < 0.05). HR, RR, SAP and response to surgical stimulus were significantly higher in the B group than in the SI group (p < 0.05). No significant differences were recorded in postoperative pain scores between groups (p > 0.05). Romifidine IM followed by intravenous tramadol, as a bolus or slow injection and local infiltration with lidocaine provided adequate sedation and analgesia in calves undergoing umbilical hernia repair.

Comparative evaluation of sedative and anti-nociceptive effects of epidural romifidine, romifidine-lidocaine, and lidocaine in donkeys (Equus asinus).

Background: Local and regional anesthetic procedures are valuable tools in veterinary practice. Caudal epidural administration of local anesthetic agents is widely reported for surgical interventions of the tail, anus, rectum, vulva, vagina, urethra, and bladder in the standing horse. Epidural analgesia is also obtained using various drugs such as alpha-2 adrenoceptor agonists, dissociative anesthetics, and opioids. The present study evaluates the anti-nociceptive and sedative effects of epidural administration of romifidine, a romifidine-lidocaine combination, and lidocaine alone in donkeys. Materials and methods: In a randomized prospective study, twenty-four healthy adult donkeys were assigned to four groups (three experimental and one control; n = 6) received either 50 µg/kg of romifidine, 0.30 mg/kg of lidocaine, combined romifidine (50 µg/kg) and lidocaine (0.30 mg/kg) diluted in 0.9% sterile normal saline solution to a total injection volume of 12 ml, or an equivalent volume of sterile saline epidurally. After epidural injection of each treatment, the onset, degree, and duration of sedation and anatomical extension of anti-nociception were documented. Observations began immediately (time 0) pre-administration and at 5, 15, 30, 45, 60, and 30-min intervals subsequently until 210 min after drug injection. Time to onset of perineal analgesia was documented every minute after the epidural injection by evaluating the animal's response to pinpricks. Results: Only romifidine and romifidine-lidocaine induced mild to moderate sedation. Romifidine, romifidine-lidocaine, and lidocaine induced complete bilateral caudal epidural analgesia with loss of sensation in the perineum, tail, inguinal region, caudal aspect of the upper hind limb, chest areas, and extended distally to the dorsal metatarsal area. Sedation lasted longer (p < 0.05) with romifidine (160 ± 15.4 min) than with romifidine-lidocaine (141.6 ± 13.2 min). Longer-lasting analgesia (p < 0.05) was obtained with romifidine (158.3 ± 9.8 min) and romifidine-lidocaine (165 ± 9.4 min) than with lidocaine (75.8 ± 8 min). Conclusions: Epidural administration of a single dose of romifidine or a combination of romifidine-lidocaine produced mild to moderate sedation and complete anti-nociception in the perineal and inguinal regions of donkeys. The clinical usefulness of epidural romifidine or romifidine-lidocaine combinations to perform obstetric procedures in donkeys needs to be assessed.

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

OBJECTIVE: To evaluate the effects of detomidine or romifidine on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing isoflurane anaesthesia. STUDY DESIGN: Prospective, randomized, blinded, clinical study. ANIMALS: A total of 63 healthy horses undergoing elective surgery during general anaesthesia. METHODS: Horses 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). RESULTS: No 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 RELEVANCE: Detomidine 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.

Comparative Study of the Sedative and Anti-nociceptive Effects of Sacrococcygeal Epidural Administration of Romifidine, Lidocaine, and Romifidine/Lidocaine in the Dromedary Camel.

In a randomized prospective study, comparative sedative and anti-nociceptive effects of epidural administration of romifidine (RO), lidocaine (LD), and a combination of romifidine-lidocaine (ROLD) in camel were evaluated. Eighteen healthy adult dromedary camels were assigned randomly to three treatment groups (n = 6), each receiving 50 µg/kg of RO, 0.30 mg/kg of LD, or a combination of both RO and LD. All treatments were expanded in 0.9% sterile normal saline solution to a final dose volume of 20 ml and administered directly into the sacrococcygeal space. After epidural injection of each treatment, the onset time, duration, anatomical extension of anti-nociception, and sedation were documented. Anti-nociception was tested at different areas using a pinprick test and artery forceps pinching at the perineum and inguinal area. RO and ROLD treatments resulted in mild to severe sedation and complete bilateral analgesia with loss of sensation in the tail, perineum, scrotum in males, vulva in females, the caudal aspect skin of the upper hind limb, and inguinal region (udder in females and the prepuce in males). The anatomic extent of anti-nociception reached the chest cranially and the footpad distally. Camels who received LD showed the shortest duration (P < 0.001) to the onset of perineal anti-nociception (3.67 ± 0.33 min) followed by those who received RO LD (4.00 ± 0.37 min) and RO (6.67 ± 0.33 min), respectively. RO and ROLD resulted in significantly (P < 0.001) longer periods of analgesia (158.33 ± 4.01 min and 165 ± 3.87 min, respectively) than LD (75.83 ± 3.27). An epidural RO and ROLD would appear to produce a very effective and acceptable anti-nociceptive effect in the perineal and inguinal regions of camels.

Methadone or Butorphanol as Pre-Anaesthetic Agents Combined with Romifidine in Horses Undergoing Elective Surgery: Qualitative Assessment of Sedation and Induction.

While butorphanol is the most commonly used opioid in horses, methadone is not licensed in most countries. Our aim was to compare the effects of both drugs, combined with romifidine, regarding the quality of sedation and induction in horses undergoing elective surgery. Results indicate the suitability of both methadone and butorphanol in this patient population. Animals were scored 10 min after intravenous injection of sedatives. Despite lower overall sedation (OS) score in horses receiving methadone (p = 0.002), the quality and time of induction and intubation remained unchanged. None of the horses had the lowest OS score (no sedation), nor the highest score for ataxia (horse falling). Methadone induced a tendency for minor noise reaction yet minor head lowering scores, the latter being probably the most influencing parameter when scoring OS. Measured physiological parameters decreased in both groups, with greater bradycardia recorded after methadone (p = 0.017), including a higher incidence of atrioventricular blocks that resolved during general anaesthesia. The quality of induction was good-excellent in most of the animals. While comparisons between the degree of antinociception were beyond the scope of this study, analgesic potency might influence the choice when considering opioids as pre-anaesthetic drugs in combination with romifidine before surgery in equines.

Recovery Quality After Romifidine Versus Detomidine Infusion During Isoflurane Anesthesia in Horses.

To examine the influence of detomidine or romifidine on recovery quality from isoflurane anesthesia, 78 anesthetic records were reviewed, from horses that had received romifidine (group R) during premedication [80-120 µg kg-1 IV], anesthetic maintenance (40 µg kg-1 hour-1 IV), and recovery (20 µg kg-1 IV) or detomidine (group D), at doses of 10-20 µg kg-1 IV, 5 µg kg-1 hour-1 IV, and 2.5 µg kg-1 IV, respectively. Duration of the different recovery phases, the number of attempts to sternal and standing, scores for transition to standing (TrSta), balance and coordination once standing (BC), and final recovery score (FS) were compared between groups using a Mann-Whitney U-test, independent t-test, or chi-squared test, as appropriate (alpha 0.05). Parametric data are represented as the mean ± standard deviation, and nonparametric data as the median (interquartile range). Compared with group D (25 horses), horses in group R (53 horses) needed significantly fewer attempts to achieve sternal recumbency [R 1 (1-1) vs. D 1 (1-2)], remained significantly longer in sternal recumbency [R 10 (3-14,5) vs. D 5 (1-9,5) minutes], needed significantly less attempts to stand [R 1 (1-1) vs. D 2 (1-4)], and a significantly shorter time to stand after making their first attempt [R 0 (0-0) vs. D 3 (0-6) minutes], with significantly better scores for TrSta, BC, and FS in group R. The results suggest that, at the doses used, romifidine provides a better recovery quality.

Recovery quality following a single post-anaesthetic dose of dexmedetomidine or romifidine in sevoflurane anaesthetised horses.

BACKGROUND: Post-anaesthetic sedation is administered to horses to improve recovery quality from inhalant anaesthesia and reduce the risk of catastrophic injury. A single dose of dexmedetomidine for this purpose has not been evaluated clinically. OBJECTIVES: To determine whether dexmedetomidine improves recovery quality from sevoflurane anaesthesia compared to a previously studied dose of romifidine. STUDY DESIGN: Prospective, randomised, masked clinical trial. METHODS: Ninety-nine, adult, client-owned horses anaesthetised for elective procedures completed the trial. Anaesthetic protocol was standardised. Horses were randomly assigned to receive either dexmedetomidine 1 mcg/kg bwt (D) or romifidine 20 mcg/kg bwt (R) intravenously at their first spontaneous breath in recovery. Recoveries were reviewed and independently assigned subjective visual analogue scale (VAS) scores (0-100 mm, worst to best) for overall quality and standing ataxia scores (1-4, none to severe) by two anaesthesiologists blinded to treatment group. Objective anaesthesia and recovery data were also recorded. Comparisons were made using the Chi-square, Wilcoxon rank sum, linear models or Welch-Satterthwaite two-sample t-test (P ≤ .05). Predictors of VAS score were analysed independent of treatment group. RESULTS: There were no significant differences between groups except end-tidal sevoflurane (FE´Sevo) concentration and post-induction extra ketamine dosing. Including FE´Sevo and additional ketamine in the analysis as covariates, VAS scores and time to standing were not significantly different between groups. Increased age, not receiving a nerve block, increased duration of hypotension, and having a nervous temperament were significant predictors of VAS score. MAIN LIMITATIONS: No universal recovery scale exists for inter-study comparisons. CONCLUSIONS: After sevoflurane anaesthesia, sedation with dexmedetomidine or romifidine provides clinically similar recovery time and quality.

Pharmacokinetic-pharmacodynamic modelling of the antinociceptive effect of a romifidine infusion in standing horses.

OBJECTIVE: To evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration. STUDY DESIGN: Prospective, experimental, nonrandomized trial. ANIMALS: A total of 10 healthy adult warmblood horses. METHODS: Romifidine (loading dose: 0.08 mg kg-1, infusion: 0.03 mg kg-1 hour-1) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The nociceptive withdrawal reflex was elicited by electrical stimulation at the thoracic limb using a dedicated threshold tracking algorithm and recorded by electromyography at the deltoid muscle. A pharmacokinetic-pharmacodynamic model was established and correlation between romifidine plasma concentration and main output variables tested. RESULTS: A two compartmental model best described the romifidine pharmacokinetic profile. The nociceptive thresholds increased compared with baseline in all horses from 10 to 146 minutes after romifidine administration (p < 0.001). Peak effect reached 5.7 ± 2.3 times the baseline threshold (mean ± standard deviation). The effect/concentration relationship followed a counter-clockwise hysteresis loop. The mean plasma concentration was weakly correlated to nociceptive thresholds (p < 0.0071, r = 0.392). The sedative effects were significant until 160 minutes but variable, not correlated to plasma concentration (p = 0.067), and weakly correlated to nociceptive thresholds (p < 0.0001, r = 0.33). CONCLUSIONS AND CLINICAL RELEVANCE: Romifidine elicited a marked antinociceptive effect. Romifidine-induced antinociception appeared with a delayed onset and lasted longer than sedation after discontinuing its administration.

Dose-dependent effect of romifidine on intraocular pressure in clinically healthy buffalo (Bubalus bubalis).

In the present study, changes in intraocular pressure (IOP) associated with romifidine sedation in buffalo were evaluated. Eighteen healthy adult, non-pregnant, buffalo without ocular abnormalities were used in a prospective randomized trial. Buffalo were allocated into three groups (six each). Buffalo in the treated groups received an intramuscular injection (IM) of romifidine at 40 or 50 µg/kg. The control group was administrated an equivalent volume of sterile saline (0.9% NaCl; 0.4 ml/100 kg). Baseline IOP (T0) values were obtained using applanation tonometry. Immediately afterwards, romifidine was administered and IOP values of both eyes were measured at 5, 15, 30, 45, 60, 90, 120, and 180 min post-administration. The pre-administration values (T0) of IOP for both the left and right eyes ranged from 30-36 (mean, 33 ± 1.5) mmHg and 30-35 (mean, 33.7 ± 1.4), respectively. IOP values decreased significantly after administration of both doses of romifidine compared with the placebo (P < 0.01). Compared with the control, the IOP decreased significantly in animals treated with both doses from 5-90 min post-administration in both eyes (P < 0.05). In the right eye, the lowest IOP value in the romifidine treated groups was observed at T30 (21.6 ± 1.0 and 23.3 ± 1.4 mmHg), respectively. In the left eye, the lowest IOP was observed at T60 (22.5 ± 3.0 and 23.3 ± 2.8 mmHg), respectively. In conclusion, romifidine could be recommended as an alternative analgesic in buffalo, especially for ocular affections associated with increased IOP. A dose of 40 µg/kg could be used at a low cost.

[Evaluation of a field-suitable injection anesthesia protocol for the castration of 8 to 14 days old piglets]. / Ermittlung eines feldtauglichen Injektionsanästhesieprotokolls zur Kastration von 8 bis 14-tägigen Ferkeln.

INTRODUCTION: The aim of this study was to find an intramuscularly (IM) injectable anaesthetic combination for 8 to 14-days old piglets, that guarantees a calm induction and sufficient quality of anaesthesia without excitations with a maximum of two hours long lasting recovery. In preliminary dose finding trials, different combinations of -ketamine, azaperone and romifidine were compared. A constant dose of 0.2 mg/kg of butorphanol was added to each combination and all piglets received 0.4 mg/kg meloxicam. Subsequently a dosage algorithm for the main trial was developed. In case of insufficient analgesia, lidocaine 2% (0.25 ml) was injected intratesticular. If two piglets showed an insufficient anaesthetic induction phase, depth of anaesthesia or recovery, the next dosage in the algorithm was tried. With the combination of 3 mg/kg azaperone, 0.2 mg/kg romifidine, 15 mg/kg ketamine and 0.2 mg/kg butorphanol the requirement of a smooth anaesthesia induction, sufficient anaesthesia and a recovery without excitation was fulfilled but the recovery lasted more than 120 minutes.

INTRODUCTION: Le but de la présente étude était de mettre au point une combinaison d'anesthésiques injectables par voie intra-musculaire pour les porcelets âgés de 8 à 14 jours qui garantisse une induction calme, une qualité d'anesthésie suffisante (sans mouvement de défense durant l'intervention) et une phase de réveil dépourvue d'excitation et ne durant pas plus de deux heures. Dans le cadre d'un essai préliminaire, on a comparé, afin de définir les doses respectives, des combinaisons de kétamine, d'azapérone et de romifidine. Les résultats ont servi de base pour l'algorithme de dosage de l'essai principal. Les dosages testés étaient les suivants : 1, 2 ou 3 mg/kg d'azapérone, 10 ou 15 mg/kg de kétamine et 0.15 ou 0.2 mg/kg de romifidine. En outre, tous les animaux recevaient du méloxicam (0.4 mg/kg) et du butorphanol (0.2 mg/kg) IM. En cas d'analgésie insuffisante, de la lidocaïne 2% (0.25 ml) était appliquée en intra-testiculaire. Si deux porcelets montraient une phase d'induction, de castration ou de réveil insuffisante, on passait au dosage suivant. Avec la combinaison de 3 mg/kg d'azapérone, 0.2 mg/kg de romifidine, 15 mg/kg de kétamine et de 0.2 mg/kg de butorphanol, les exigences d'une induction calme, d'une qualité d'anesthésie suffisante et d'un réveil dépourvu d'excitation étaient remplies. Toutefois les porcelets dormaient plus de 120 minutes.

Changes in energy metabolism, and levels of stress-related hormones and electrolytes in horses after intravenous administration of romifidine and the peripheral α-2 adrenoceptor antagonist vatinoxan.

BACKGROUND: Romifidine, an α-2 adrenoceptor agonist, is a widely-used sedative in equine medicine. Besides the desired sedative and analgesic actions, α-2 adrenoceptor agonists have side effects like alterations of plasma concentrations of glucose and certain stress-related hormones and metabolites in various species. Vatinoxan (previously known as MK-467), in turn, is an antagonist of α-2 adrenoceptors. Because vatinoxan does not cross the blood brain barrier in significant amounts, it has only minor effect on sedation induced by α-2 adrenoceptor agonists. Previously, vatinoxan is shown to prevent the hyperglycaemia, increase of plasma lactate concentration and the decrease of insulin and non-esterified free fatty acids (FFAs) caused by α-2 adrenoceptor agonists in different species. The aim of our study was to investigate the effects of intravenous romifidine and vatinoxan, alone and combined, on plasma concentrations of glucose and some stress-related hormones and metabolites in horses. RESULTS: Plasma glucose concentration differed between all intravenous treatments: romifidine (80 µg/kg; ROM), vatinoxan (200 µg/kg; V) and the combination of these (ROM + V). Glucose concentration was the highest after ROM and the lowest after V. Serum FFA concentration was higher after V than after ROM or ROM + V. The baseline serum concentration of insulin varied widely between the individual horses. No differences were detected in serum insulin, cortisol or plasma adrenocorticotropic hormone (ACTH) concentrations between the treatments. Plasma lactate, serum triglyceride or blood sodium and chloride concentrations did not differ from baseline or between the treatments. Compared with baseline, plasma glucose concentration increased after ROM and ROM + V, serum cortisol, FFA and base excess increased after all treatments and plasma ACTH concentration increased after V. Serum insulin concentration decreased after V and blood potassium decreased after all treatments. CONCLUSIONS: Romifidine induced hyperglycaemia, which vatinoxan partially prevented despite of the variations in baseline levels of serum insulin. The effects of romifidine and vatinoxan on the insulin concentration in horses need further investigation.

Effect of butorphanol, midazolam or ketamine on romifidine based sedation in horses during standing cheek tooth removal.

BACKGROUND: Standing surgery, especially dental procedures, are commonly performed in horses. This leads to an increasing demand for reliable sedation protocols. Therefore, it was the purpose of this study to investigate the influence of butorphanol, midazolam or ketamine on romifidine based sedation in horses during cheek tooth removal. METHODS: Forty horses presented for tooth extraction were divided in four groups using matched pair randomization. Group R was sedated with romifidine (bolus 0.03 mg/kg, followed by a constant rate infusion (CRI) 0.05 mg/kg/h) and group RB with romifidine (same dose) and butorphanol (0.02 mg/kg; CRI 0.04 mg/kg/h). Group RM received romifidine (same dose) and midazolam (0.02 mg/kg; CRI 0.06 mg/kg/h) whereas group RK was administered romifidine (same dose) and ketamine (0.5 mg/kg; CRI 1.2 mg/kg/h). If sedation was not adequate a top up bolus of romifidine (0.01 mg/kg) was administered. The quality of sedation and the conditions for tooth extraction, the level of ataxia, chewing, head and tongue movement were evaluated by using a scoring system. The investigator was blinded to the applied sedation protocol. Furthermore, serum cortisol concentrations before, during and after the procedure were analyzed to gain more information about the stress level of the horses. RESULTS: Horses in group RM showed significantly less chewing and tongue activity compared to horses sedated with romifidine alone or with butorphanol additionally, but also significantly higher levels of ataxia. The quality of sedation was significantly better if romifidine was administered in combination with ketamine compared to romifidine alone. Furthermore, horses of group RK needed less additional romifidine boli compared to all other groups. Blood cortisol concentrations during surgery in groups RB and RM remained unchanged. Horses of group R showed higher cortisol concentrations during sedation compared to horses of groups RB and RM. CONCLUSION: Romifidine alone at an initial bolus dose of 0.03 mg/kg followed by a constant rate infusion of 0.05 mg/kg/h was insufficient to obtain an adequate level of sedation and led to increased stress levels, whereas the addition of butorphanol inhibited the stress response. The combination of romifidine with either midazolam or ketamine improved sedation quality and surgical conditions.

Pharmacokinetic profile and partitioning in red blood cells of romifidine after single intravenous administration in the horse.

The aims of this study were to assess the plasma concentrations of romifidine in horses after intravenous injection, to evaluate the red blood cell (RBC) partitioning of the anaesthetic drug, and to improve knowledge regarding its sedative effect in horses describing the pharmacokinetic model. Eight adult Standardbred horses received a single bolus of romifidine at a dosage of 100 µg/kg. Blood samples (5 mL) were collected immediately before romifidine administration (t0), and at 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 min after injection. A sedation score was recorded at the same time. The romifidine concentrations in plasma and red blood cells were determined by high performance liquid chromatography (HPLC). The plasma and red blood cell concentrations were correlated with the sedation at each time point. Romifidine produced a satisfactory level of sedation in all animals. The sedation was detectable in all horses for up to 105 min. All the animals returned to normal without any behavioural changes at 180 min. The romifidine concentrations in the red blood cells were significantly higher (P < 0.01) at all time points than those in the plasma. The T1/2ß was 148.67 ± 61.59 min and body clearance was 22.55 ± 6.67 mL/kg per min. The results showed that after a single bolus administration of romifidine, a partitioning in the RBCs was detected.

Evaluation of different dose rate combinations of ketamine, romifidine and azaperone for castration of 3-4 and 5-6 weeks old piglets.

INTRODUCTION: In this study dose rate combinations of ketamine, azaperone and romifidine were tested in 3-4 (G3-4) and 5-6 weeks (G5-6) old piglets according to a dose rate decision tree (DRT) to provide calm anaesthesia induction, reaction-free anaesthesia for castration and smooth recovery within 2 hours. When a combination failed to meet those criteria in 2 piglets, the next dosage of the DRT was tested. In G3-4 four combinations were tested in 14 piglets with dose rates of 10-20 mg/kg ketamine, 3 mg/kg azaperone and 0.15-0.20 mg/kg romifidine IM. Induction was smooth in all piglets, but depth of anaesthesia or recovery (11 and 6 piglets) were insufficient. In G5-6 five combinations were tested in 37 piglets with dose rates of 10-20 mg/kg ketamine, 3-4 mg/kg azaperone and 0.15-0.20 mg/kg romifidine IM. Induction was smooth in all piglets but 2. Depth of anaesthesia or recovery (17 and 7 piglets, respectively) were insufficient. In the present study with 3-4 and 5-6 weeks old piglets, acceptable quality of anaesthesia could not be achieved despite using high drug dose rates.

INTRODUCTION: Des combinaisons de doses de kétamine, azapérone et romifidine ont été testées sur la base d'un arbre de décision de dose afin de définir la dose qui assurait, chez des porcelets de 3-4 (G3-4) et de 5-6 (G5-6) semaines une induction tranquille, une anesthésie sans réaction lors de la castration et une phase de réveil calme, terminée en deux heures. Lorsqu'une combinaison de ces critères n'était pas obtenue chez 2 porcelets, on passait à la dose suivante proposée par l'arbre de décision. Dans le G3-4, 4 combinaisons avec des doses de 10-20 mg/kg de kétamine, 3 mg/kg d'azapérone et 0.15-0.20 mg/kg de romifidine IM ont été testées chez 14 porcelets. L'induction était calme chez tous les porcelets mais la profondeur de l'anesthésie ou la phase de réveil étaient insuffisantes chez 11 respectivement 6 porcelets. Dans le G5-6, 5 combinaisons avec des doses de 10-20 mg/kg de kétamine, 3-4 mg/kg d'azapérone et 0.15-0.20 mg/kg de romifidine IM ont été testées chez 37 porcelets. L'induction était calme à deux exceptions près mais la profondeur de l'anesthésie ou la phase de réveil étaient insuffisantes chez 17 respectivement 7 porcelets. Lors de la présente étude, il n'a pas été possible, malgré l'utilisation de doses élevées, d'obtenir chez des porcelets de 3-4 respectivement de 5-6 semaines une qualité d'anesthésie acceptable.

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. STUDY DESIGN: Prospective, randomised, blinded, clinical trial. ANIMALS: A total of 24 adult healthy horses. METHODS: All horses were administered intramuscular acepromazine (0.02 mg kg-1) and either intravenous detomidine (0.02 mg kg-1) (group D), romifidine (0.08 mg kg-1) (group R) or xylazine (1.0 mg kg-1) (group C) prior to anaesthesia. Group D was administered detomidine CRI (10 µg kg-1 hour-1) in lactated Ringer's solution (LRS), group R romifidine CRI (40 µg kg-1 hour-1) in LRS and group C an equivalent amount of LRS intraoperatively. Anaesthesia was induced with ketamine and diazepam and maintained with isoflurane in oxygen. Plasma lactate samples were taken prior to anaesthesia (baseline), intraoperatively (three samples at 30 minute intervals) and in recovery (at 10 minutes, once standing and 3 hours after end of anaesthesia). End-tidal isoflurane percentage (Fe'Iso) was analysed by allocating values into three periods: Prep (15 minutes after the start anaesthesia-start surgery); Surgery 1 (start surgery-30 minutes later); and Surgery 2 (end Surgery 1-end anaesthesia). A linear mixed model was used to analyse the data. A value of p<0.05 was considered significant. RESULTS: There was a difference in plasma lactate between 'baseline' and 'once standing' in all three groups (p<0.01); values did not differ significantly between groups. In groups D and R, Fe'Iso decreased significantly by 18% (to 1.03%) and by 15% (to 1.07%), respectively, during Surgery 2 compared with group C (1.26%); p<0.006, p<0.02, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Intraoperative detomidine or romifidine CRI in horses did not result in a clinically significant increase in plasma lactate compared with control group. Detomidine and romifidine infusions decreased isoflurane requirements during surgery.

Comparative antinociceptive and sedative effects of epidural romifidine and detomidine in buffalo (Bubalus bubalis).

In this study, comparative antinociceptive and sedative effects of epidural administration of romifidine and detomidine in buffalo were evaluated. Eighteen healthy adult buffalo, allocated randomly in three groups (two experimental and one control; n=6) received either 50 µg/kg of romifidine or detomidine diluted in sterile saline (0.9 per cent) to a final volume of 20 ml, or an equivalent volume of sterile saline epidurally. Antinociception, sedation and ataxia parameters were recorded immediately after drug administration. Epidural romifidine and detomidine produced mild to deep sedation and complete antinociception of the perineum, inguinal area and flank, and extended distally to the coronary band of the hindlimbs and cranially to the chest area. Times to onset of antinociception and sedation were significantly shorter with romifidine than with detomidine. The antinociceptive and sedative effects were significantly longer with romifidine than with detomidine. Romifidine or detomidine could be used to provide a reliable, long-lasting and cost-effective method for achieving epidural anaesthesia for standing surgical procedures in buffalo. Romifidine induces a longer antinociceptive effect and a more rapid onset than detomidine. Consequently, epidural romifidine may offer better therapeutic benefits in the management of acute postoperative pain.

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. STUDY DESIGN: Randomized, crossover study. ANIMALS: Six adult horses weighing 561 ± 48 kg. METHODS: Propranolol (1 mg kg-1; treatment P), romifidine (0.1 mg kg-1; treatment R) or their combination (treatment PR) were administered intravenously with a minimum of 1 week between treatments. Alertness, behavioral responsiveness (visual and tactile) and physiologic variables were measured before and up to 960 minutes after drug administration. Blood was collected for blood gas and acid-base analyses and measurement of plasma drug concentrations. Data were analyzed using repeated-measures analysis of variance or Friedman with Holm-Sidak and Wilcoxon rank-sum tests (p < 0.05). RESULTS: Systemic clearance significantly decreased and the area under the concentration-time curve significantly increased for both drugs in PR compared with P and R. Both PR and R decreased behavioral responsiveness and resulted in sedation for up to 240 and 480 minutes, respectively. Sedation was deeper in PR for the first 16 minutes. Heart rate significantly decreased in all treatments for at least 60 minutes, and PR significantly increased the incidence of severe bradycardia (<20 beats minute-1). CONCLUSIONS AND CLINICAL RELEVANCE: Although not associated with reduced behavioral responsiveness or sedation alone, propranolol augmented romifidine sedation, probably through alterations in romifidine pharmacokinetics, in horses administered PR. The occurrence of severe bradycardia warrants caution in the co-administration of these drugs at the doses studied.

Dose-dependent antinociceptive and sedative effects of epidural romifidine in cattle.

The objective of this study was to evaluate the antinociceptive and sedative effects of epidural administration of romifidine in dairy cattle. Twenty-four dairy cows, divided randomly into four groups (three experimental and one control; n=6) received one of three doses of romifidine (30, 40 or 50 µg/kg) diluted in sterile saline (0.9 per cent) to a final volume of 25 ml or an equivalent volume of sterile saline. Antinociception and its anatomical extent was assessed by applying a standard stimulus (needle pin pricks) in different areas and by applying an electrical stimulus to the flank. The antinociceptive effect of romifidine was produced not only in the tail, anus, perineum, vulva and inguinal area but extended up to the coronary band of the hindlimbs and chest areas. Epidural romifidine induced mild-to-moderate sedation at 30 and 40 µg/kg doses and deep sedation at the 50 µg/kg dose. The antinociceptive and sedative effect was dose-dependent in terms of intensity and duration. Thus, epidural administration of romifidine was effective in providing antinociception and sedation in cattle, and can be used in standing flank and udder surgery in cattle.

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

OBJECTIVE: To evaluate the anti-nociceptive and sedative effects of slow intravenous (IV) injection of tramadol, romifidine, or a combination of both drugs in ponies. STUDY DESIGN: Within-subject blinded. ANIMALS: Twenty ponies (seven male, 13 female, weighing mean ± SD 268.0 ± 128 kg). METHODS: On 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(-1) followed 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. RESULTS: When compared to baseline, heart (HR, beats minute(-1) ) and respiratory rates (fR , breaths minute(-1) ) increased with treatment T (highest mean ± SD, HR 43 ± 1; fR 33 ± 2) and decreased with R (lowest HR 29 ± 1 and fR 10 ± 4) and RT (lowest HR 32 ± 1 and fR 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. CONCLUSION: Tramadol 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 RELEVANCE: Slow controlled administration of tramadol should reduce the occurrence of adverse behavioural side effects.