Evaluation of combinations of nalbuphine with acepromazine or detomidine for sedation in ponies

The effect of combinations of nalbuphine (0.3 mg/kg) with either detomidine (10 μg/kg) or acepromazine (50 μg/kg) was investigated in ponies. Nalbuphine enhanced the degree of sedation produced by both sedatives; sedation with detomidine and nalbuphine was profound. Cardiovascular and respiratory effects were mild and could usually be attributed to the effect of the sedative itself. Side effects were minimal and gave no cause for concern. It was concluded that nalbuphine, in combination with acepromazine or detomidine, is a safe and effective sedative for use in ponies.     

Stress responses during total intravenous anaesthesia in ponies with detomidine - guaiphenesin - ketamine

Six ponies were anaesthetised for two hours with intermittent injections of a combination of guaiphenesin (72 mg/kg/hr), ketamine (1.4 mg/kg/hr) and detomidine (0.015 mg/kg/hr) after premedication with detomidine 0.01 mg/kg and induction of anaesthesia with guaiphenesin 50 mg/kg and ketamine 2 mg/kg. Induction of anaesthesia was smooth, the ponies were easily intubated and after intubation breathed 100% oxygen spontaneously. During anaesthesia mean pulse rate ranged between 31–44 beats per minute and mean respiratory rate between 12–23 breaths per minute. Mean arterial blood pressure remained between 110–130 mm Hg, mean arterial carbon dioxide tension between 6.1–6.9 kPa and pH between 737–7.42. Arterial oxygen tension was over 23 kPa throughout anaesthesia. Plasma glucose increased to more than 25 mmol per litre during anaesthesia; there was no change in lactate or ACTH concentration and plasma cortisol concentration decreased. Recovery was rapid and smooth. A guaiphenesin, ketamine and detomidine combination appeared to offer potential as a total intravenous technique for maintenance of anaesthesia in horses.     

Simultaneous infusions of propofol and ketamine in ponies premedicated with detomidine: a pharmacokinetic study

The pharmacokinetics of propofol and ketamine administered together by infusion were investigated in four ponies. Blood propofol and plasma ketamine and norketamine concentrations were measured by high performance liquid chromatography. After premedication with detomidine (20 μg kg⁻¹) anaesthesia was induced with ketamine (2·2 mg kg ⁻¹ intravenously). The trachea was intubated and the ponies were allowed to breathe 100 per cent oxygen. A bolus dose of propofol (0·5 mg kg⁻¹) was then administered intravenously and propofol and ketamine were infused for 60 and 45 minutes, respectively. The average mean infusion rate of propofol was 0·136 mg kg⁻¹ min⁻¹, and the ketamine infusion rate was maintained at 50 μg kg⁻¹ min⁻¹. The mean (SD) elimination half-lives of propofol and ketamine were 69·0 (8·0) and 89·8 (26·7) minutes, the mean volumes of distribution at steady state were 0·894 (0·161) litre kg⁻¹ and 1·432 (0·324) litre kg⁻¹ the mean body clearances were 33·1 (4·5) and 23·9 (3·8) ml kg⁻¹ min⁻¹ and the mean residence times for the infusion were 87·1 (4·1) and 110·7 (8·2) minutes, respectively. Norketamine, the main metabolite of ketamine, was detected throughout the sampling period. The mean residence time for norketamine was 144 (16) minutes. All the ponies recovered quickly from the anaesthesia; the mean times to sternal recumbency and standing were 11·1 (5·3) and 30·0 (20·8) minutes, respectively, from the end of the infusion.     

Cardiopulmonary effects of romifidine and detomidine used as premedicants for ketamine/halothane anaesthesia in ponies

The cardiopulmonary effects of romifidine at 80 microg/kg (R80) or 120 pg/kg (R120), and detomidine at 20 pg/kg (D20) when used as premedicants for ketamine/halothane anaesthesia were investigated in six ponies. Using a blinded crossover design, acepromazine (0-04 mg/kg) was administered followed by the alpha-2 agonist. Anaesthesia was induced with ketamine at 2.2 mg/kg and maintained with halothane (expired concentration 1.0 per cent) in oxygen for three hours. During anaesthesia, arterial blood pressure, cardiac index, PaO2 and PmvO2 decreased, and systemic vascular resistance and PaCO2 increased. The cardiac indices for R80, R120 and D20 were, respectively, 39, 39 and 32 ml/kg/minute at 30 minutes and 29, 29 and 26 ml/kg/minute at 180 minutes. The alpha-2 agonists had similar cardiovascular effects, but PaO2 was significantly lower with R120. The quality of anaesthesia was similar in all three groups.     

Antagonism of pancuronium neuromuscular blockade in halothane-anesthetized ponies using neostigmine and edrophonium

Efficacy of neostigmine (0.04 mg/kg of body weight) and edrophonium (1 mg/kg), as antagonists for pancuronium neuromuscular blockade in halothane-anesthetized ponies, was evaluated. Neostigmine and edrophonium were satisfactory antagonists, with edrophonium having a significantly (P less than 0.01) more rapid onset of action than did neostigmine. Muscarinic activity of neostigmine and edrophonium was also evaluated. Neither antagonist was administered with atropine. Gastrointestinal effects, increased salivation, and increased airway secretions were minimal with edrophonium, but were marked after neostigmine. Blood pressure increased within 1 to 2 minutes of antagonist administration. Heart rate decreased after edrophonium injection, but this occurred after blood pressure increase. Heart rate increased or did not change after neostigmine administration.     

Ketamine, Telazol, xylazine and detomidine. A comparative anesthetic drug combinations study in ponies.

This study was designed to assess the effects of 5 anesthetic drug combinations in ponies: (1) ketamine 2.75 mg/kg, xylazine 1.0 mg/kg (KX), (2) Telazol 1.65 mg/kg, xylazine 1.0 mg/kg (TX), (3) Telazol 2 mg/kg, detomidine 20 micrograms/kg (TD-20), (4) Telazol 2 mg/kg, detomidine 40 micrograms/kg (TD-40), (5) Telazol 3 mg/kg, detomidine 60 micrograms/kg (TD-60). All drugs were given iv with xylazine or detomidine preceding ketamine or Telazol by 5 min. Heart rate was decreased significantly from 5 min to arousal after TD-20 but only at 60 and 90 min after TD-40 and TD-60 respectively. Respiratory rate was decreased significantly for all ponies. Induction time did not differ between treatments. Duration of analgesia was 10 min for KX, 22.2 min for TX, 27.5 min for TD-20, 32.5 min for TD-40, and 70 min for TD-60. Arousal time was significantly longer with detomidine and Telazol. Smoothness of recovery was judged best in ponies receiving KX and TD-40. All ponies stood unassisted 30 min after signs of arousal.     

Antagonism of ketamine-xylazine anesthesia in rats by administration of yohimbine, tolazoline, or 4-aminopyridine

Antagonism of ketamine-xylazine (85 mg of ketamine/kg of body weight and 15 mg of xylazine/kg, IM) anesthesia in rats by yohimbine (YOH; 1, 5, 10, and 20 mg/kg, IP), tolazoline (TOL; 10, 20, or 50 mg/kg, IP), 4-aminopyridine (4-AP; 1 or 5 mg/kg, IP), or a combination of yohimbine and 4-aminopyridine (YOH:4-AP, 1 mg/kg:1 mg/kg or 5 mg/kg:1 mg/kg, IP) was studied. All dosages of YOH, TOL, 4-AP, and YOH:4-AP reduced the time to appearance of corneal and pedal reflexes. Only TOL was effective in reducing time to appearance of the crawl reflex and recovery time. Yohimbine, 4-AP, YOH:4-AP, and TOL were effective in reversing respiratory depression caused by ketamine-xylazine anesthesia, but anesthetic-induced hypothermia was not antagonized. When given to non-anesthetized rats, the antagonists had little influence on respiratory rate, but all antagonists caused significant (P less than 0.05) reduction in core body temperature for at least 90 minutes. When YOH was used as an anesthetic antagonist at dosage of 20 mg/kg, 20% mortality was observed and was attributable to acute respiratory arrest. The use of 4-AP and YOH:4-AP at the dosages studied induced moderate to severe muscular tremors. In conclusion, TOL at dosage of 20 mg/kg given IP, appears to be an appropriate antagonist for ketamine-xylazine anesthesia in rats.     

Cardiovascular effects of doxacurium chloride in isoflurane-anaesthetised dogs

The cardiovascular effects of doxacurium were studied in 6 isoflurane-anaesthetised dogs. Each dog was anaesthetised twice, receiving doxacurium (0.008 mg/kg bwt) or placebo iv. Dogs were ventilated to normocapnia. Heart rate, cardiac index, systolic, diastolic, and mean arterial blood pressures, stroke volume, pulmonary vascular resistance, pulmonary artery wedge pressure, systemic vascular resistance, and pulmonary arterial pressure were determined. Neuromuscular blockade was assessed using the train-of-four technique. After recording baseline values, dogs randomly received either doxacurium or placebo iv, and data were recorded at 5, 10, 15, 30, 45, 60, 75, 90, 105 and 120 min. At 120 min, dogs treated with doxacurium received edrophonìum (0.5 mg/kg bwt iv) to antagonise neuromuscular blockade; dogs treated with placebos received saline iv. No statistically significant differences were detected after doxacurium compared to placebo. In both the doxacurium and placebo groups, significant increases in systolic arterial blood pressure, cardiac index, and stroke volume and a significant decrease in systemic vascular resistance occurred with time. Doxacurium depressed twitch tension 100% in all dogs (time to maximal twitch depression, 11 ± 7 min). First twitch tension was less than 10% of baseline values in all dogs at the time (120 min) of edrophonium administration. Additional edrophonium (1.0 ± 0.4 mg/kg iv) was required to obtain a fourth twitch to first twitch ratio of greater than 0.70. In conclusion, doxacurium is a long-acting neuromuscular blocking agent with no significant cardiovascular effects in isoflurane-anesthetised dogs. In dogs, doxacurium is indicated primarily for long surgical procedures requiring neuromuscular blockade and cardiovascular stability.     

Combined use of detomidine with opiates in the horse

The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Side effects seen were increased ataxia (greatest following methadone and butorphanol) and excitement (usually muzzle tremors and muscle twitching). Following pethidine, generalised excitement was sometimes seen. Marked cardiovascular changes occurred in the first few minutes after morphine or pethidine injection, but within 5 mins cardiovascular changes were minimal. Following morphine or pethidine there was a significant increase in arterial carbon dioxide tension. Fourteen clinical cases were successfully sedated using detomidine/butorphanol combinations.     

Reversal of profound rocuronium or vecuronium-induced neuromuscular block with sugammadex in isoflurane-anaesthetised dogs

This study evaluated the use of sugammadex for reversal of profound neuromuscular blockade induced with rocuronium or vecuronium in dogs. Anaesthesia was induced and maintained with isoflurane in oxygen in eight dogs on two occasions. Neuromuscular blockade was monitored using peroneal nerve stimulation and acceleromyography. Rocuronium 0.6 mg/kg or vecuronium 0.1mg/kg was administered intravenously (IV), followed 5 min later by sugammadex 8 mg/kg IV. Lag and onset time of rocuronium and vecuronium, lag time from sugammadex injection to recovery of first twitch response, recovery of T1/T0 to 25% and 75%, recovery index, and time to recovery of the train-of-four ratio (T4/T1) to 0.9 were recorded. Cardiovascular and respiratory parameters were also noted. Statistical analysis was performed using one-way ANOVA. Onset time for rocuronium (37 ± 18s; [mean ± SD]) was significantly shorter than for vecuronium (62 ± 15s) (P<0.04). No other significant differences were found between the two groups. After both rocuronium and vecuronium blockade, T4/T1 recovered to 0.9 in under 2 min after sugammadex (58.1 ± 67.8s and 98.1 ± 70.3s, respectively; P<0.32). Sugammadex can reverse profound neuromuscular blockade induced by vecuronium or rocuronium safely and rapidly in isoflurane-anaesthetised dogs.     

Platelet activation in ponies with airway inflammation

REASON FOR PERFORMING STUDY: Platelet activation occurs in human obstructive airway diseases and in laboratory animal models. However, there is limited evidence that platelets may be involved in equine recurrent airway obstruction (RAO) and other inflammatory diseases. This study investigated whether platelet activation also occurred in RAO. HYPOTHESIS: Platelet function is altered in ponies with active RAO. This alteration can be detected ex vivo by measuring platelet adhesion. METHODS: An in vitro platelet adhesion assay measuring acid phosphatase (AcP) activity colorimetrically was adapted for use with equine platelets and responses to selected agonists were established. Platelet adhesion and aggregation was evaluated in vitro on platelets isolated from 6 ponies with RAO before, during and after a 7 h natural antigen challenge. Three ponies with no history of airway disease were also studied. RESULTS: Adhesion of equine platelets to serum coated plastic was detected at concentrations of 10-100 radicaló 10(9)/l. Adhesion increased in response to stimulation with platelet activating factor and thrombin, but not equine interleukin 8. Prior to the antigen challenge, adhesion of nonstimulated platelets was low and increased significantly (P<0.05) 24 h after initiation of the challenge in RAOs, but not in the normal animals. No changes in platelet aggregation were noted in either group. CONCLUSIONS: The described assay offers an alternative method to evaluate platelet function in healthy and diseased horses and can detect changes not observed using a classic aggregation assay. Circulating platelets are activated 24 h after antigen challenge of ponies with RAO and may play a role in pulmonary inflammation and/or the pathophysiology of RAO. POTENTIAL RELEVANCE: Investigating platelet function in RAO and airway inflammation may reveal new aspects of the pathogenesis of inflammatory lung disease in the horse.     

Chronic oral therapy with enalapril in normal ponies

Enalapril is an angiotensin converting enzyme (ACE) inhibitor that is frequently used in human, feline and canine patients with cardiac disease. Its use has been associated with impotence in human patients. The purpose of this study was to evaluate if enalapril (0.5 mg/kg PO, q24h) is likely to alter behavior in stallions and to assess its effect on ACE activity at the standard dose used in dogs and cats. Twelve pony stallions were evaluated by physical examination and echocardiography followed by treatment with enalapril (n = 6) or placebo (n = 6) for 2 months. After one month, blood was drawn and stored to evaluate ACE activity in the 2 groups. At the end of the study, repeat physical examination and echocardiography were performed. Physical examination, echocardiographic indices, and reproductive performance were unchanged and there was no suppression of ACE activity. Results of this study suggest that enalapril (0.5 mg/kg PO, q24h) is either poorly absorbed in the horse or is inadequately converted to the active form of the drug, enalaprilat.     

Pharmacokinetics of ciprofloxacin in ponies

The pharmacokinetics of ciprofloxacin was investigated in healthy, mature ponies. Ciprofloxacin was administered intravenously to six ponies at a dose of 5 mg per kg body weight. Seven days later, ciprofloxacin was administered orally to each pony at the same dose. Intravenous ciprofloxacin concentration vs. time data best fit a two-compartment open model with first-order elimination from the central compartment. Mean plasma half-life, based on the terminal phase, was 15 7.8 9 min (harmonic mean). Total body clearance of ciprofloxacin was 18.12 ± 3.99 mL/min/kg. Volume of distribution at steady-state was 3.45 ± 0.72 L/kg. From the pharmacokinetic data and reported minimum inhibitory concentrations for equine gram-negative pathogens, the appropriate dosage of ciprofloxacin was determined to be 5.32 mg per kg body weight at 12 h intervals. Bioavailability of oral ciprofloxacin in ponies was 6.8 ± 5.33%. Owing to the poor bioavailability, a dosage regimen could not be proposed for oral ciprofloxacin administration in horses. Ciprofloxacin concentrations were determined in tissues and body fluids at 1, 2 and 4 h after intravenous administration. At all times, tissue concentrations exceeded plasma concentrations of ciprofloxacin. Highest concentrations were achieved in kidneys and urine. Potentially therapeutic concentrations were obtained in cerebrospinal and joint fluid, but low concentrations were achieved in aqueous humour.     

Cardiovascular effects of xylazine and detomidine in horses

The cardiovascular effects of xylazine and detomidine in horses were studied. Six horses were given each of the following 5 treatments, at 1-week intervals: xylazine, 1.1 mg/kg, IV; xylazine, 2.2 mg/kg, IM; detomidine, 0.01 mg/kg, IV; detomidine, 0.02 mg/kg, IV; and detomidine, 0.04 mg/kg, IM. All treatments resulted in significantly decreased heart rate, increased incidence of atrioventricular block, and decreased cardiac output and cardiac index; cardiac output and cardiac index were lowest following IV administration of 0.02 mg of detomidine/kg. Mean arterial pressure was significantly reduced for various periods with all treatments; however, IV administration of 0.02 mg of detomidine/kg caused hypertension initially. Systemic vascular resistance was increased by all treatments. Indices of ventricular contractility and relaxation, +dP/dt and -dP/dt, were significantly depressed by all treatments. Significant changes were not detected in stroke volume or ejection fraction. The PCV was significantly reduced by all treatments. Respiratory rate was significantly decreased with all treatments, but arterial carbon dioxide tension did not change. Arterial oxygen tension was significantly decreased briefly with the 3 IV treatments only.     

Electroretinogram responses of the normal thoroughbred horse sedated with detomidine hydrochloride

Purpose The main objective was to record electroretinogram (ERG) parameters of normal thoroughbred mares using the HMsERG, a mini-Ganzfeld electroretinographic unit, and a contact lens electrode. The second objective was to determine whether IV detomidine hydrochloride at 0.015?mg/kg is consistently an effective choice for sedation of horses undergoing this ERG protocol. Methods The study population consisted of 30 normal thoroughbred mares. ERG data were harvested using a protocol that included three different light intensities (10, 3000, and 10?000?mcd?s/m(2) ) and a 30-Hz flicker at 3000?mcd?s/m(2) . Results Mean, median, standard deviation, and estimated normal ranges using the 5-95% of the data for a- and b-wave implicit times (IT), amplitudes (AMP), and b/a ratios were reported. Scotopic results at low intensity (10?mcd?s/m(2) ) had estimated ranges for b-wave IT of 41.8-72.9?ms and AMP of 19.8-173.3?μV. Middle intensity (3000?mcd?s/m(2) ) a-wave IT was 13.2-14.7?ms with a-wave AMP of 68.4-144?μV; the b-wave IT was 28.7-41.5?ms with b-wave AMP of 105.7-271.5?μV; and the b/a ratio was 0.95-2.71. The high-intensity (10?000?mcd?s/m(2) ) average recordings showed an a-wave IT of 13-14.9?ms, a-wave AMP of 85.7-186.8?μV; b-wave IT of 26.6-45.4?ms, b-wave AMP of 104.7-250.6?μV; and a b/a wave ratio of 0.7-2.0. The 30-Hz cone flicker showed an IT of 22.8-28.9?ms and AMP of 44.1-117.1?μV. Conclusions Results of normal thoroughbred ERG responses are reported. The protocol proved to be simple and safe and provided consistent results.