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.     

Sedative and analgesic effects of romifidine in camels (Camelus dromedarius)

ObjectiveTo evaluate the clinical effectiveness and the sedative and analgesic effects of intravenous (IV) romifidine in camels.Study designRandomized prospective study.AnimalsEighteen healthy adult Dromedary camels.MethodsRomifidine was administered IV to camels (n = 6) at three different doses (40, 80 or 120 μg kg^?1). Time of onset, degree and duration of sedation and analgesia were recorded immediately after drug administration. Heart rate, respiratory rate, ruminal contractions, muscle relaxation, response to auditory and tactile stimulation, distance between ears, distance from lower lip to the ground, and degree of ataxia were also recorded pre-administration and at 5, 15, 30, 45, 60, 90, 120 and 180 minutes post-administration. Plasma glucose, blood urea nitrogen and creatinine were measured.ResultsRomifidine produced dose dependent sedation and analgesia. Significant decreases in heart rate (p < 0.001), ruminal contractions (p < 0.05), distance from lower lip to the ground (p < 0.001), response to auditory and tactile stimuli (p < 0.01), and significant increases in the degree of ataxia (p < 0.01), distance between the ear tips (p < 0.001) and blood glucose (p < 0.01) concentration were recorded after administration of romifidine until recovery. However, no significant changes in rectal temperature and respiratory rate were recorded.Conclusions and clinical relevanceIntravenous administration of romifidine at three different doses appeared to be an effective sedative and analgesic agent for camels. Bradycardia, ruminal atony, and hyperglycemia were the most important adverse effects after IV administration of romifidine. The IV administration of romifidine at a dose rate of 120 μg kg^?1 caused profound sedation and analgesia. Romifidine could be used for chemical restraint for a variety of diagnostic and minor surgical procedures in camels.     

Sedative effects of three doses of romifidine in comparison with medetomidine in cats

ObjectiveTo compare the sedative effects of three doses of romifidine with one dose of medetomidine.Study designProspective blinded experimental cross-over.AnimalsFive adult Domestic Short Hair cats.MethodsCats were administered romifidine at 80, 120 and 160 μg kg^?1 or medetomidine at 20 μg kg^?1 (M20) intramuscularly (IM). Sedative effects were assessed for 3 hours by summing the scores given to posture, auditory response, resistance to positioning, muscular relaxation, and response to noxious stimuli, giving a total sedation score (TS). The area under the curve (AUC) of TS ≥7 (the score considered as clinically useful sedation) was calculated. Times to stages of sedation were determined. Some physiological parameters were measured. Data to compare treatments were analysed by anova or Kruskal–Wallis test as relevant.ResultsAll treatments gave a TS considered clinically useful. There were no significant differences between treatments for times to onset of sedation, maximum TS reached, or AUC. Differences between romifidine treatments for other sedation parameters were not significant but the time to maximum TS and to recovery was shortest in M20. Heart rate (HR) fell significantly with all treatments and, although with M20 it recovered at 65 minutes, it remained significantly depressed for 3 hours after all romifidine treatments. Most cats vomited, and/or hypersalivated after all treatments.ConclusionsDoses of 80, 120 and 160 μg kg^?1 romifidine IM produce sedation in cats which is similar to that following medetomidine 20 μg kg^?1. Recovery from sedation and of physiological parameters was quickest after M20.Clinical relevanceDoses of romifidine considerably lower than those investigated by previous authors give a clinically useful level of sedation, and their use might result in less side effects and a quicker recovery.     

Pharmacokinetics and pharmacodynamics of intravenous medetomidine in the horse

ObjectiveTo describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse.Study designProspective experimental trial.AnimalsEight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg.MethodsMedetomidine (10 μg kg^?1) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis.ResultsPharmacokinetic analysis estimated that medetomidine peaked (8.86 ± 3.87 ng mL^?1) at 6.4 ± 2.7 minutes following administration and was last detected at 165 ± 77 minutes post administration. Medetomidine had a clearance of 39.6 ± 14.6 mL kg^?1 minute^?1 and a volume of distribution of 1854 ± 565 mL kg^?1. The elimination half-life was 29.1 ± 12.5 minutes. Glucose concentration reached a maximum of 176 ± 46 mg dL^?1 approximately 1 hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107 ± 12 to 20 ± 10 cm within 10 minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45 minutes and horses were less responsive to sound.Conclusion and clinical relevance Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration.     

Pharmacokinetics and selected pharmacodynamics of romifidine following low‐dose intravenous administration in combination with exercise to quarter horses

Romifidine is an alpha‐2 adrenergic agonist used for sedation and analgesia in horses. As it is a prohibited substance, its purported use at low doses in performance horses necessitates further study. The primary goal of the study reported here was to describe the serum concentrations and pharmacokinetics of romifidine following low‐dose administration immediately prior to exercise, utilizing a highly sensitive liquid chromatography–tandem mass spectrometry assay that is currently employed in many drug testing laboratories. An additional objective was to describe changes in heart rate and rhythm following intravenous administration of romifidine followed by exercise. Eight adult Quarter Horses received a single intravenous dose of 5 mg (0.01 mg/kg) romifidine followed by 1 h of exercise. Blood samples were collected and drug concentrations measured at time 0 and at various times up to 72 h. Mean ± SD systemic clearance, steady‐state volume of distribution and terminal elimination half‐life were 34.1 ± 6.06 mL/min/kg and 4.89 ± 1.31 L/kg and 3.09 ± 1.18 h, respectively. Romifidine serum concentrations fell below the LOQ (0.01 ng/mL) and the LOD (0.005 ng/mL) by 24 h postadministration. Heart rate and rhythm appeared unaffected when a low dose of romifidine was administered immediately prior to exercise.     

Sedative, analgesic and cardiorespiratory effects of romifidine in cats

OBJECTIVE: To evaluate the sedative, analgesic, and cardiorespiratory effects of intramascular (IM) romifidine in cats. STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: Ten healthy adult cats. METHODS: Romifidine (100, 200, and 400 microg kg(-1)) or xylazine (1 mg kg(-1)) was given IM in a cross-over study design. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), hemoglobin saturation, oscillometric arterial pressure, and scores for sedation, muscle relaxation, position, auditory response, and analgesia were determined before and after drug administration. Time to recumbency, duration of recumbency, and time to recover from sedation were determined. Subjective evaluation and cardiorespiratory variables were recorded before and at regular intervals for 60 minutes after drug administration. RESULTS: Bradycardia developed in all cats that were given romifidine or xylazine. No other significant differences in physiologic parameters were observed from baseline values or between treatments. Increasing the dose of romifidine did not result in increased sedation or muscle relaxation. Cats given xylazine showed higher sedation and muscle relaxation scores over time. Analgesia scores were significantly higher after administration of romifidine (400 microg kg(-1)) and xylazine (1 mg kg(-1)) than after romifidine at 100 or 200 microg kg(-1). Duration of lateral recumbency was not significantly different between treatments; however, cats took longer to recover after administration of 400 micro g kg(-1) romifidine. CONCLUSIONS AND CLINICAL RELEVANCE: Bradycardia is the most important adverse effect after IM administration of romifidine at doses ranging from 100 to 400 microg kg(-1) or 1 mg kg(-1) of xylazine in cats. The sedative effects of romifidine at 200 microg kg(-1) are comparable to those of 1 mg kg(-1) of xylazine, although muscle relaxation and analgesia were significantly less with romifidine than with xylazine.     

The echocardiographic effects of romifidine in dogs with and without prior or concurrent administration of glycopyrrolate

Objective To determine the cardiopulmonary response to romifidine (RO) in the dog with or without prior or concurrent administration of glycopyrrolate. Study Design Randomized, cross‐over experimental study. Animals Six (three male, three female) cross‐bred dogs weighing 23 ± 2.4 kg. Methods Two‐dimensional guided M‐mode echocardiography was performed in conscious dogs simultaneously with measurement of systolic arterial blood pressure (SBP) and heart rate (HR). Dimensions of the left ventricle (LVID), interventricular septum (IVS), and left ventricular free wall (LVFW) were obtained in systole (S) and diastole (D). Amplitude of motion (Amp) of the IVS and LVFW were also measured. From these, measures of wall stress (WS) and fractional shortening (FS) of the left ventricle were derived. Baseline echocardiographic measurements were recorded, following which one of the five treatments was administered. Glycopyrrolate (G) 0.01 mg kg^?1, or saline (S) 0.5 mL, was administered IM as pre‐medication (Gp or Sp), or G was administered concurrently (Gc) with romifidine (RO). Treatments were: T₁, Sp + RO (40 μg kg^?1); T₂, Gp + RO (40 μg kg^?1); T₃, Sp + RO (120 μg kg^?1); T₄, Gp + RO (120 μg kg^?1); and T₅, Sp + Gc +RO (120 μg kg^?1). Romifidine or RO + Gc was administered SC 20 minutes after pre‐medication (time 0), and further measurements were taken 10, 20, 30, 60, and 90 minutes after RO. Results Echocardiographic indices of cardiac systolic function (LVID‐S, FS, Amp‐LVFW) and HR were decreased in RO‐sedated dogs (p < 0.0001) . The magnitude of change in cardiac indices was least with low‐dose RO. At most sampling times, high‐dose RO produced significantly more alteration in cardiac indices. Systolic blood pressure increased in all treatment groups, with the greatest increases in those groups receiving G. Glycopyrrolate significantly increased HR; however, cardiac indices were further reduced. Wall stress significantly increased, with a more dramatic increase in groups receiving G. Conclusions Indices of LV systolic function were reduced in RO‐sedated dogs in a dose‐related manner. Glycopyrrolate further reduced these indices and dramatically increased measurements of wall stress in dogs sedated with RO. Clinical relevance Use of low‐dose RO minimizes cardiac dysfunction; however, it should still be used cautiously in dogs with cardiomyopathy or heart failure. The routine use of G is not recommended to alleviate the bradycardia associated with RO in conscious dogs.     

Pharmacokinetics of topically applied ciprofloxacin in equine tears

OBJECTIVE: To evaluate the pharmacokinetics of topically applied ciprofloxacin 0.3% ophthalmic solution in tears of healthy horses. ANIMAL STUDIED: Twenty healthy, adult, mixed-breed horses. PROCEDURES: Twenty study horses were confirmed free of ophthalmic disease by complete ophthalmic examination. Seventy microliters of 0.3% ciprofloxacin (Ciloxan) was placed in the ventral cul-de-sac of each eye using a microliter syringe and 19-g cannula. Population kinetics were carried out by sampling the tear film from the lower cul-de-sac of each eye with tear test strips at 5, 10, 15 and 30 min and 1, 2, 4 and 6 h post administration for a total of five samples at each time-point. Sample collection time was 15 s. Concentrations of ciprofloxacin were determined using high performance liquid chromatography. RESULTS: Mean (+/-SD) of the Schirmer tear test results from all eyes was 23.4 +/- 4.8 mm wetting in 1 min. Mean concentration of ciprofloxacin in the tears at 5 min post administration was 498.4 +/- 266.8 microg/g. Mean concentration rapidly declined and began to plateau at 30 min. The mean tear concentrations of ciprofloxacin at 30 min and at 1, 2, 4 and 6 h were 66.6 +/- 56.0, 60.25 +/- 55.7, 42.25 +/- 30.9, 36.25 +/- 32.0, and 45.5 +/- 46.5 microg/g, respectively. CONCLUSIONS: The pharmacokinetics of ciprofloxacin in normal horses are similar to those in rabbits and humans. Topical application of ciprofloxacin resulted in a mean tear concentration of ciprofloxacin that remained above the MIC(90) levels for most pathogenic bacteria for 6 h post administration.     

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.

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.

Anaesthetic and cardiorespiratory effects of romifidine/ketamine combinations in cats

ObjectiveTo study the anaesthetic and cardiorespiratory effects of intramuscular (IM) administration of different combinations of romifidine and ketamine in cats.Study designProspective, randomized, cross-over experiment.AnimalsSeven healthy adult cats weighing (mean ± SD) 3.4 ± 0.7 kg and aged 4.6 ± 3.2 years.MethodsAnimals received romifidine 100 μg kg^?1 with ketamine 7.5 (R100/K7.5) and 10 mg kg^?1 (R100/K10), romifidine 200 μg kg^?1 with ketamine 5 (R200/K5), 7.5 (R200/K7.5) and 10 mg kg^?1 (R200/K10) by IM injection. The time required to perform orotracheal intubation (IT) was measured and the ease of intubation assessed. The onset of anaesthesia (OA), duration of anaesthesia (DA) and anaesthesia recovery times (AR) were measured. Analgesia and muscle relaxation scores were recorded every 5 minutes for 60 minutes after OA. Heart rate, systolic arterial pressure, arterial haemoglobin saturation, respiratory rate, end-tidal carbon dioxide and oesophageal temperature were also measured.ResultsThe IT, OA and DA were not significantly different between the treatments. The analgesia and muscle relaxation scores were similar between all treatments at most time points. The cardiorespiratory variables were not significantly different between the treatments in most cases. The adverse effects were dose dependent and similar to those previously described for other combinations of α₂-agonists and ketamine.Conclusions and clinical relevanceAnaesthesia produced by the studied combinations of romifidine and ketamine may only be reliable when conducting brief and noninvasive procedures in cats. The OA times were slower and the DA shorter than those reported for other alpha-2 agonists combined with ketamine. A dose-related increase in the intensity of the anaesthetic effects could not be demonstrated in this study.     

Identification of equine herpesvirus 3 (equine coital exanthema virus), equine gammaherpesviruses 2 and 5, equine adenoviruses 1 and 2, equine arteritis virus and equine rhinitis A virus by polymerase chain reaction

OBJECTIVE: To develop rapid (< 8 hour) tests using polymerase chain reaction (PCR) for the diagnosis of equine herpesvirus 3 (EHV3; equine coital exanthema virus), equine gammaherpesviruses 2 (EHV2) and EHV5, equine adenovirus 1 (EAdV1), EAdV2, equine arteritis virus (EAV), equine rhinitis A virus (ERAV; formerly equine rhinovirus 1) DESIGN: Either single round or second round (seminested) PCRs were developed and validated. METHODS: Oligonucleotide primers were designed that were specific for each virus, PCR conditions were defined and the specificity and sensitivity of the assays were determined. The application of the tests was validated using a number of independent virus isolates for most of the viruses studied. The PCRs were applied directly to clinical samples where samples were available. RESULTS: We developed a single round PCR for the diagnosis of EHV3, a seminested PCR for EHV2 and single round PCRs for EHV5, EAdV1, EAdV2 and RT-PCRs for EAV and ERAV. The PCR primer sets for each virus were designed and shown to be highly specific (did not amplify any recognised non-target template) and sensitive (detection of minimal amounts of virus) and, where multiple virus isolates were available all isolates were detected. CONCLUSION: The development and validation of a comprehensive panel of PCR diagnostic tests, predominantly for viruses causing equine respiratory disease, that can be completed within 8 hours from receipt of clinical samples, provides a major advance in the rapid diagnosis or exclusion diagnosis of these endemic equine virus diseases in Australia.     

Analgesic and cardiopulmonary effects of intrathecally administered romifidine or romifidine and ketamine in goats (Capra hircus)

The study was conducted to evaluate the effects of romifidine alone (50 microg/kg) and a combination of romifidine (50 microg/kg) and ketamine (2.5 mg/kg) after intrathecal administration in goats. Ten adult goats of either sex weighing between 15 and 20 kg were randomly placed in 2 groups (groups I and II). The agents were administered at the lumbosacral subarachnoid space. Clinico-physiological parameters such as analgesia, motor incoordination, sedation, salivation, heart rate, respiratory rate, arterial pressure, central venous pressure and rectal temperature were studied. Other haematobiochemical parameters monitored were packed cell volume, haemoglobin, plasma proteins, glucose, urea and creatinine. The onset of analgesia was faster in group II (35.5 +/- 6.25 s) compared to that of group I (5.2 +/- 0.54 min). Analgesia of the tail, perineum, hind limbs, flank and thorax was mild to moderate in group I, but complete analgesia of tail, perineum and hind limbs was recorded in group II. Motor incoordination was mild in group I and severe in group II. Significant reduction in heart rate (more pronounced in group I) and respiratory rate (more pronounced in group II), and a significant increase in central venous pressure were recorded in both groups. Mean arterial pressure was reduced in both groups, but more markedly in group I. Sedation, electrocardiogram, rectal temperature and haemato-biochemical parameters did not show significant differences between the 2 groups. The results of this study indicated a possible synergistic analgesic interaction between intrathecally administered romifidine and ketamine, without causing any marked systemic effects in goats.     

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.     

Comparison of morphine and carprofen administered alone or in combination for analgesia in dogs undergoing ovariohysterectomy

In this study the analgesic efficacy of the pure agonistic opioid morphine and the cyclo-oxygenase type-2-selective carprofen were compared since there is no previous specific comparative study for these two common analgesics. Forty-five bitches undergoing elective ovariohysterectomy were randomly assigned to one of three groups; receiving morphine 0.4 mg/kg bodyweight pre-operatively and 0.2 mg/kg every 4-6 hours thereafter (Morphine group), receiving a once-off carprofen 4 mg/kg injection (Carprofen group) or receiving both morphine and carprofen (MorphCarp group). The dogs were premedicated with acepromazine 0.01 mg/kg and induced with either thiopentone 5-10 mg/kg or propofol 4-6 mg/kg. General anaesthesia was maintained with halothane in oxygen. The degree of pain was assessed over a 24-hour period under blinded conditions using a pain scale modified from the University of Melbourne pain scale and the Glasgow composite pain tool. Physiological parameters such as respiratory rate, pulse rate and body temperature were also assessed over the same time period. There was no significant difference in pain-scores and thus analgesia offered by the three analgesia protocols at any assessment point across the three groups, but there were differences within groups across time points. Baseline total pain-scores were lower than scores at all post-operative points within all three groups. Both morphine and carprofen provided good analgesia without any obvious adverse effects. This study indicates that at the dosages indicated above, carprofen administered on its own produces analgesia equal to that produced by morphine and that the two drugs administered together do not produce better analgesia than either drug administered on its own.     

Preliminary investigation of concurrent administration of phenylbutazone and romifidine in healthy horses

ObjectiveTo characterize the cardiorespiratory and electrocardiographic effects of the combined administration of phenylbutazone and romifidine.Study designProspective four-period, four-treatment, blinded, randomized, crossover trial.AnimalsFive, healthy, mixed breed horses.MethodsPrior to treatment administration, a catheter was introduced into the intra-thoracic cranial vena cava via the jugular vein and a subcutaneously located carotid artery was catheterised. All treatments were administered intravenously (IV) and consisted of saline placebo (PLC), phenylbutazone (PBZ, 4.4 mg kg^?1) romifidine (ROM, 80 μg kg^?1) and a combination of phenylbutazone (4.4 mg kg^?1) and romifidine (80 μg kg^?1). There was at least a 1 week washout period between treatments. Heart rate (HR), respiratory rate (f_R), systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures and central venous pressure (CVP) were recorded for baseline (prior to drug administration) and at 5 minute intervals thereafter for 30 minutes. Electrocardiographic abnormalities were recorded. Data were analyzed by anova.ResultsFor the cardiovascular variables there were no statistically significant (p > 0.05) differences between horses treated with ROM and PBZ_ROM. Statistically significant (p < 0.05) differences only occurred between treatments with romifidine (ROM and PBZ_ROM) and without romifidine (PLC and PBZ). Within treatments, for ROM, changes over time were statistically significant (p < 0.05) for HR, SAP, DAP, MAP and CVP. For PBZ_ROM, changes over time were statistically significant (p < 0.05) for CVP. Sino-atrial and atrio-ventricular blocks occurred in horses treated with ROM and PBZ_ROM.Conclusions and clinical relevanceThe combined IV administration of phenylbutazone and romifidine had no statistically significant effect on cardiorespiratory variables. These limited data suggest no evidence why both agents should not be included in a preoperative medication protocol for healthy horses but do not exclude the possibility of interactions occurring in a larger population.     

Pharmacokinetics and adverse effects of butorphanol administered by single intravenous injection or continuous intravenous infusion in horses

OBJECTIVE: To determine an infusion rate of butorphanol tartrate in horses that would maintain therapeutic plasma drug concentrations while minimizing development of adverse behavioral and gastrointestinal tract effects. ANIMALS: 10 healthy adult horses. PROCEDURE: Plasma butorphanol concentrations were determined by use of high-performance liquid chromatography following administration of butorphanol by single IV injection (0.1 to 0.13 mg/kg of body weight) or continuous IV infusion (loading dose, 17.8 microg/kg; infusion dosage, 23.7 microg/kg/h for 24 hours). Pharmacokinetic variables were calculated, and changes in physical examination data, gastrointestinal tract transit time, and behavior were determined over time. RESULTS: A single IV injection of butorphanol was associated with adverse behavioral and gastrointestinal tract effects including ataxia, decreased borborygmi, and decreased defecation. Elimination half-life of butorphanol was brief (44.37 minutes). Adverse gastrointestinal tract effects were less apparent during continuous 24-hour infusion of butorphanol at a dosage that resulted in a mean plasma concentration of 29 ng/ml, compared with effects after a single IV injection. No adverse behavioral effects were observed during or after continuous infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IV infusion of butorphanol for 24 hours maintained plasma butorphanol concentrations within a range associated with analgesia. Adverse behavioral and gastrointestinal tract effects were minimized during infusion, compared with a single injection of butorphanol. Continuous infusion of butorphanol may be a useful treatment to induce analgesia in horses.     

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.     

Pharmacokinetics and pharmacodynamics of enrofloxacin and a low dose of amikacin administered via regional intravenous limb perfusion in standing horses

OBJECTIVE: To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses. ANIMALS: 14 adult horses. PROCEDURES: Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joint were collected prior to (time 0) and at intervals after tourniquet release for determination of drug concentrations. For pharmacokinetic-pharmacodynamic analyses, minimum inhibitory concentrations (MICs) of 16 microg/mL (amikacin) and 0.5 microg/mL (enrofloxacin) were applied. RESULTS: After RILP with enrofloxacin, 3 horses developed vasculitis. The highest synovial fluid concentrations of enrofloxacin and amikacin were detected at time 0; median values (range) were 13.22 microg/mL (0.254 to 167.9 microg/mL) and 26.2 microg/mL (5.78 to 50.0 microg/mL), respectively. Enrofloxacin concentrations exceeded MIC for approximately 24 hours in STIF and synovial fluid and for 36 hours in BMIF. After perfusion of amikacin, concentrations greater than the MIC were not detected in any samples. Effective therapeutic concentrations of enrofloxacin were attained in all samples. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with orthopedic infections, RILP of enrofloxacin (1.5 mg/kg) should be considered as a treatment option. However, care must be taken during administration. A dose of amikacin > 250 mg is recommended to attain effective tissue concentrations via RILP in standing horses.