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.     

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.     

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

ObjectiveTo compare the clinical usefulness of constant rate infusion (CRI) protocols of romifidine with or without butorphanol for sedation of horses.Study designProspective ‘blinded’ controlled trial using block randomization.AnimalsForty healthy Freiberger stallions.MethodsThe horses received either intravenous (IV) romifidine (loading dose: 80 μg kg^?1; infusion: 30 μg kg^?1 hour^?1) (treatment R, n = 20) or romifidine combined with butorphanol (romifidine loading: 80 μg kg^?1; infusion: 29 μg kg^?1 hour^?1, and butorphanol loading: 18 μg kg^?1; infusion: 25 μg kg^?1 hour^?1) (treatment RB, n = 20). Twenty-one horses underwent dentistry and ophthalmic procedures, while 19 horses underwent only ophthalmologic procedure and buccal examination. During the procedure, physiologic parameters and occurrence of head/muzzle shaking or twitching and forward movement were recorded. Whenever sedation was insufficient, additional romifidine (20 μg kg^?1) was administered IV. Recovery time was evaluated by assessing head height above ground. At the end of the procedure, overall quality of sedation for the procedure was scored by the dentist and anaesthetist using a visual analogue scale. Statistical analyses used two-way anova or linear mixed models as relevant.ResultsSedation quality scores as assessed by the anaesthetist were R: median 7.55, range: 4.9–9.0 cm, RB: 8.8, 4.7–10.0 cm, and by the dentist R: 6.6, 3.0–8.2 cm, RB: 7.9, 6.6–8.8 cm. Horses receiving RB showed clinically more effective sedation as demonstrated by fewer poor scores and a tendency to reduced additional drug requirements. More horses showed forward movement and head shaking in treatment RB than treatment R. Three horses (two RB, one R) had symptoms of colic following sedation.Conclusions and clinical relevanceThe described protocols provide effective sedation under clinical conditions but for dentistry procedures, the addition of butorphanol is advantageous.     

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

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

A clinical study on the effect in horses during medetomidine-isoflurane anaesthesia, of butorphanol constant rate infusion on isoflurane requirements, on cardiopulmonary function and on recovery characteristics

ObjectiveTo test if the addition of butorphanol by constant rate infusion (CRI) to medetomidine–isoflurane anaesthesia reduced isoflurane requirements, and influenced cardiopulmonary function and/or recovery characteristics.Study designProspective blinded randomised clinical trial.Animals61 horses undergoing elective surgery.MethodsHorses were sedated with intravenous (IV) medetomidine (7 μg kg^?1); anaesthesia was induced with IV ketamine (2.2 mg kg^?1) and diazepam (0.02 mg kg^?1) and maintained with isoflurane and a CRI of medetomidine (3.5 μg kg^?1 hour^?1). Group MB (n = 31) received butorphanol CRI (25 μg kg^?1 IV bolus then 25 μg kg^?1 hour^?1); Group M (n = 30) an equal volume of saline. Artificial ventilation maintained end-tidal CO₂ in the normal range. Horses received lactated Ringer’s solution 5 mL kg^?1 hour^?1, dobutamine <1.25 μg kg^?1 minute^?1 and colloids if required. Inspired and exhaled gases, heart rate and mean arterial blood pressure (MAP) were monitored continuously; pH and arterial blood gases were measured every 30 minutes. Recovery was timed and scored. Data were analyzed using two way repeated measures anova, independent t-tests or Mann–Whitney Rank Sum test (p < 0.05).ResultsThere was no difference between groups with respect to anaesthesia duration, end-tidal isoflurane (MB: mean 1.06 ± SD 0.11, M: 1.05 ± 0.1%), MAP (MB: 88 ± 9, M: 87 ± 7 mmHg), heart rate (MB: 33 ± 6, M: 35 ± 8 beats minute^?1), pH, PaO₂ (MB: 19.2 ± 6.6, M: 18.2 ± 6.6 kPa) or PaCO_2. Recovery times and quality did not differ between groups, but the time to extubation was significantly longer in group MB (26.9 ± 10.9 minutes) than in group M (20.4 ± 9.4 minutes).Conclusion and clinical relevanceButorphanol CRI at the dose used does not decrease isoflurane requirements in horses anaesthetised with medetomidine–isoflurane and has no influence on cardiopulmonary function or recovery.     

Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine

ObjectiveTo evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine.Study designProspective, randomized, blinded clinical trial.AnimalsForty horses undergoing elective surgery.MethodsAfter sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg^?1 initially, then 2 mg kg^?1 hour^?1) and ketamine (2 mg kg^?1 hour^?1), both CRIs reducing to 1.5 mg kg^?1 hour^?1 after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 μg kg^?1 hour^?1, reducing after 50 minutes to 2.75 μg kg^?1 hour^?1, and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE′ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 μg kg^?1) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05.ResultsFE′ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE′ISO in MILK was 0.65 (0.4–1.0) %, and in ILK was 1 (0.62–1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups.Conclusion and clinical relevanceA CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.     

Evaluation of the perioperative stress response from dexmedetomidine infusion alone,with butorphanol bolus or remifentanil infusion compared with ketamine and morphine infusions in isoflurane-anesthetized horses

ObjectiveTo evaluate perioperative stress-related hormones in isoflurane-anesthetized horses administered infusions of dexmedetomidine alone or with butorphanol or remifentanil, compared with ketamine–morphine.Study designRandomized, prospective, nonblinded clinical study.AnimalsA total of 51 horses undergoing elective surgical procedures.MethodsHorses were premedicated with xylazine, anesthesia induced with ketamine–diazepam and maintained with isoflurane and one of four intravenous infusions. Partial intravenous anesthesia (PIVA) was achieved with dexmedetomidine (1.0 μg kg^–1 hour^–1; group D; 12 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and butorphanol bolus (0.05 mg kg^–1; group DB; 13 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and remifentanil (3.0 μg kg^–1 hour^–1; group DR; 13 horses); or ketamine (0.6 mg kg^–1 hour^–1) and morphine (0.15 mg kg^–1, 0.1 mg kg^–1 hour^–1; group KM; 13 horses). Infusions were started postinduction; butorphanol bolus was administered 10 minutes before starting surgery. Blood was collected before drugs were administered (baseline), 10 minutes after ketamine–diazepam, every 30 minutes during surgery and 1 hour after standing. Mean arterial pressure (MAP), pulse rate, end-tidal isoflurane concentration, cortisol, nonesterified fatty acids (NEFA), glucose and insulin concentrations were compared using linear mixed models. Significance was assumed when p < 0.05.ResultsWithin D, cortisol was lower at 120–180 minutes from starting surgery compared with baseline. Cortisol was higher in KM than in D at 60 minutes from starting surgery. Within all groups, glucose was higher postinduction (except DR) and 60 minutes from starting surgery, and insulin was lower during anesthesia and higher after standing compared with baseline. After standing, NEFA were higher in KM than in DB. In KM, MAP increased at 40–60 minutes from starting surgery compared with 30 minutes postinduction.Conclusions and clinical relevanceDexmedetomidine suppressed cortisol release more than dexmedetomidine–opioid and ketamine–morphine infusions. Ketamine–morphine PIVA might increase catecholamine activity.     

Evaluation of cardiorespiratory and biochemical effects of ketamine‐propofol and guaifenesin‐ketamine‐xylazine anesthesia in donkeys (Equus asinus)

ObjectivesTo evaluate the cardiorespiratory and biochemical effects of ketamine-propofol (KP) or guaifenesin-ketamine-xylazine (GKX) anesthesia in donkeys.Study designProspective crossover trial.AnimalsEight healthy, standard donkeys, aged 10 ± 5 years and weighing 153 ± 23 kg.MethodsDonkeys were premedicated with 1.0 mg kg^?1 of xylazine (IV) in both treatments. Eight donkeys were administered ketamine (1.5 mg kg^?1) and propofol (0.5 mg kg^?1) for induction, and anesthesia was maintained by constant rate infusion (CRI) of ketamine (0.05 mg kg^?1 minute^?1) and propofol (0.15 mg kg^?1 minute^?1) in the KP treatment. After 10 days, diazepam (0.05 mg kg^?1) and ketamine (2.2 mg kg^?1) were administered for induction, and anesthesia was maintained by a CRI (2.0 mL kg^?1 hour^?1) of ketamine (2.0 mg mL^?1), xylazine (0.5 mg mL^?1) and guaifenesin (50 mg mL^?1) solution. Quality of anesthesia was assessed along with cardiorespiratory and biochemical measurements.ResultsAnesthetic induction took longer in GKX than in KP. The induction was considered good in 7/8 with KP and in 6/8 in GKX. Anesthetic recovery was classified as good in 7/8 animals in both treatments. Xylazine administration decreased heart rate (HR) in both treatments, but in KP the HR increased and was higher than GKX throughout the anesthetic period. Respiratory rate was higher in GKX than in KP. PaO₂ decreased significantly in both groups during the anesthetic period. Glucose concentrations [GLU] increased and rectal temperature and PCV decreased in both treatments. Arterial lactate [LAC] increased at recovery compared with all time points in KP. [GLU] and calcium were higher in GKX than in KP at recovery.Conclusion and clinical relevanceThese protocols induced significant hypoxemia but no other cardiorespiratory or metabolic changes. These protocols could be used to maintain anesthesia in donkeys, however, they were not tested in animals undergoing surgery.     

Plasma histamine concentrations in horses administered sodium penicillin,guaifenesin–xylazine–ketamine and isoflurane with morphine or butorphanol

ObjectiveVarious drugs administered to horses undergoing surgical procedures can release histamine. Histamine concentrations were evaluated in horses prepared for surgery and administered butorphanol or morphine intraoperative infusions.Study designProspective studies with one randomized.AnimalsA total of 44 client-owned horses.MethodsIn one study, anesthesia was induced with xylazine followed by ketamine–diazepam. Anesthesia was maintained with guaifenesin–xylazine–ketamine (GXK) during surgical preparation. For surgery, isoflurane was administered with intravenous (IV) morphine (group M: 0.15 mg kg^–1 and 0.1 mg kg^–1 hour^–1; 15 horses) or butorphanol (group B: 0.05 mg kg^–1 and 0.01 mg kg^–1 hour^–1; 15 horses). Histamine and morphine concentrations were measured using enzyme-linked immunoassay before opioid injection (time 0), and after 1, 2, 5, 30, 60 and 90 minutes. In a subsequent study, plasma histamine concentrations were measured in 14 horses before drug administration (baseline), 15 minutes after IV sodium penicillin and 15 minutes after starting GXK IV infusion. Statistical comparison was performed using anova for repeated measures. Pearson correlation compared morphine and histamine concentrations. Data are presented as mean ± standard deviation. Significance was assumed when p ≤ 0.05.ResultsWith histamine, differences occurred between baseline (3.2 ± 2.4 ng mL^–1) and GXK (5.2 ± 7.1 ng mL^–1) and between baseline and time 0 in group B (11.9 ± 13.4 ng mL^–1) and group M (11.1 ± 12.4 ng mL^–1). No differences occurred between baseline and after penicillin or between groups M and B. Morphine concentrations were higher at 1 minute following injection (8.1 ± 5.1 ng mL^–1) than at 30 minutes (4.9 ± 3.1 ng mL^–1) and 60 minutes (4.0 ± 2.5 ng mL^–1). Histamine correlated with morphine at 2, 30 and 60 minutes.Conclusions and clinical relevanceGXK increased histamine concentration, but concentrations were similar with morphine and butorphanol.     

Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses

ObjectiveTo evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses.Study designProspective, blinded, randomized cross-over study.AnimalsTen healthy adult horses weighing 527–645 kg and aged 11–21 years old.MethodsElectrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg^?1, romifidine 0.08 mg kg^?1, or xylazine, 1 mg kg^?1, was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation.ResultsThe administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively.Conclusions and clinical relevanceDetomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.     

Influence of a constant rate infusion of dexmedetomidine on cardiopulmonary function and recovery quality in isoflurane anaesthetized horses

ObjectiveTo investigate the influence of a dexmedetomidine constant rate infusion (CRI) in horses anaesthetized with isoflurane.Study designProspective, randomized, blinded, clinical study.AnimalsForty adult healthy horses (weight mean 491 ± SD 102 kg) undergoing elective surgery.MethodsAfter sedation [dexmedetomidine, 3.5 μg kg^?1 intravenously (IV)] and induction IV (midazolam 0.06 mg kg^?1, ketamine 2.2 mg kg^?1), anaesthesia was maintained with isoflurane in oxygen/air (FiO₂ 55–60%). Horses were ventilated and dobutamine was administered when hypoventilation [arterial partial pressure of CO₂ > 8.00 kPa (60 mmHg)] and hypotension [arterial pressure 70 mmHg] occurred respectively. During anaesthesia, horses were randomly allocated to receive a CRI of dexmedetomidine (1.75 μg kg^?1 hour^?1) (D) or saline (S). Monitoring included end-tidal isoflurane concentration, cardiopulmonary parameters, and need for dobutamine and additional ketamine. All horses received 0.875 μg kg^?1 dexmedetomidine IV for the recovery period. Age and weight of the horses, duration of anaesthesia, additional ketamine and dobutamine, cardiopulmonary data (anova), recovery scores (Wilcoxon Rank Sum Test), duration of recovery (t-test) and attempts to stand (Mann–Whitney test) were compared between groups. Significance was set at p < 0.05.ResultsHeart rate and arterial partial pressure of oxygen were significantly lower in group D compared to group S. An interaction between treatment and time was present for cardiac index, oxygen delivery index and systemic vascular resistance. End-tidal isoflurane concentration and heart rate significantly increased over time. Packed cell volume, systolic, diastolic and mean arterial pressure, arterial oxygen content, stroke volume index and systemic vascular resistance significantly decreased over time. Recovery scores were significantly better in group D, with fewer attempts to stand and significantly longer times to sternal position and first attempt to stand.Conclusions and clinical relevance A dexmedetomidine CRI produced limited cardiopulmonary effects, but significantly improved recovery quality.     

A comparative study of xylazine-induced mechanical hypoalgesia in donkeys and horses

ObjectiveTo compare the effects of xylazine on mechanical nociceptive thresholds in donkeys and horses.Study designRandomized, controlled, crossover, Latin-square, operator-blinded design.AnimalsSix 3.1 ± 0.89 year old standard donkeys weighing 145.0 ± 30.5 kg and six 9.6 ± 4.4 year old Thoroughbred horses weighing 456.0 ± 69.0 kg.MethodsEach animal received one of four doses of xylazine (0.5, 0.7, 0.9, and 1.1 mg kg^?1), or acepromazine (0.05 mg kg^?1) or saline solution (0.9%) intravenously and mechanical nociceptive thresholds were assessed over 90 minutes. The areas under the threshold change versus time curve values for 60 minutes (AUC_0-60) post-drug administration were used to compare the effect of treatment. A 1-week interval was allowed between successive trials on each animal.ResultsAll doses of xylazine, but not acepromazine or saline, increased mechanical thresholds for up to 60 minutes. Xylazine-induced hypoalgesia was dose-dependent and corresponding AUC_0-60 values for each treatment were not significantly different between donkeys and horses (p≥ 0.0697).ConclusionThe hypoalgesic effects of xylazine at four different doses were not different between donkeys and horses.Clinical relevanceXylazine induced a similar degree of mechanical hypoalgesia in donkeys and horses suggesting that similar doses are needed for both species with regard to analgesia.     

Behavioral and Cardiopulmonary Effects of a Constant Rate Infusion of Remifentanil–Xylazine for Sedation in Horses

Xylazine and remifentanil in constant rate infusion (CRI) could be used for sedation in horses without adverse effects. The objective was to evaluate behavioral and cardiopulmonary effects of an intravenous (IV) infusion of xylazine and remifentanil for sedation in horses. Xylazine (0.8 mg/kg IV) followed after 3 minutes by a CRI of xylazine and remifentanil (0.65 mg/kg/h and 6 μg/kg/h, respectively) was administered in 10 healthy horses for 60 minutes. Sedation, ataxia, and cardiopulmonary, hematological, and blood gases variables were evaluated. Heart rate decreased significantly during the first 25 minutes after CRI of xylazine and remifentanil, whereas the respiratory rate showed a significant decrease at 20 minutes and remained significantly low until the endpoint. There were no statistically significant fluctuations in blood arterial pressure, blood pH, partial pressure of arterial carbon dioxide, lactate, creatinine, calcium, chlorine, and sodium, compared with baseline values. Blood partial pressure of arterial oxygen and bicarbonate values were significantly higher compared with baseline values, whereas potassium decreased. Sedation and ataxia developed immediately after the administration of xylazine in all horses. All horses recovered successfully within 10 minutes after interruption of the CRI of xylazine and remifentanil, with no ataxia. No adverse effects were observed. The use of a combination of xylazine and remifentanil as sedation protocol has no adverse effects at the described dosage.     

Cardiopulmonary effects of an infusion of remifentanil or morphine in horses anesthetized with isoflurane and dexmedetomidine

ObjectiveTo examine the cardiopulmonary effects of infusions of remifentanil or morphine, and their influence on recovery of horses anesthetized with isoflurane and dexmedetomidine.Study designRandomized crossover study with 7-day rest periods.AnimalsSix adult horses (507 ± 61 kg).MethodsAfter the horses were sedated with xylazine, anaesthesia was induced with ketamine and diazepam, and maintained with isoflurane. After approximately 60 minutes, a dexmedetomidine infusion was started (0.25 μg kg^?1 then 1.0 μg^?1 kg^?1 hour^?1) in combination with either saline (group S), morphine (0.15 mg kg^?1 then 0.1 mg kg^?1 hour^?1; group M), or remifentanil (6.0 μg kg^?1 hour^?1; group R) for 60 minutes. Mean arterial pressure, heart rate, end-tidal carbon dioxide tension, and end-tidal isoflurane concentration were recorded every 5 minutes. Core body temperature, cardiac output, right ventricular and arterial blood-gas values were measured every 15 minutes. Cardiac index, systemic vascular resistance (SVR), intrapulmonary shunt fraction, alveolar dead space, oxygen delivery and extraction ratio were calculated. Recoveries were videotaped and scored by two observers blinded to the treatment. Data were analyzed using repeated measures anova followed by Dunnett’s or Bonferroni’s significant difference test. Recovery scores were analyzed using a Kruskal–Wallis test.ResultsNo significant differences were found among groups. Compared to baseline, heart rate decreased and SVR increased significantly in all groups, and cardiac index significantly decreased in groups S and M. Hemoglobin concentration, oxygen content and oxygen delivery significantly decreased in all groups. The oxygen extraction ratio significantly increased in groups M and R. Lactate concentration significantly increased in group S. Recovery scores were similar among groups.Conclusions and clinical relevanceDexmedetomidine alone or in combination with remifentanil or morphine infusions was infused for 60 minutes without adverse effects in the 6 healthy isoflurane-anesthetized horses in this study.     

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

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

Postoperative analgesic effects of either a constant rate infusion of fentanyl,lidocaine, ketamine,dexmedetomidine, or the combination lidocaine‐ketamine‐dexmedetomidine after ovariohysterectomy in dogs

ObjectiveTo evaluate the postoperative analgesic effects of a constant rate infusion (CRI) of either fentanyl (FENT), lidocaine (LIDO), ketamine (KET), dexmedetomidine (DEX), or the combination lidocaine-ketamine-dexmedetomidine (LKD) in dogs.Study designRandomized, prospective, blinded, clinical study.AnimalsFifty-four dogs.MethodsAnesthesia was induced with propofol and maintained with isoflurane. Treatments were intravenous (IV) administration of a bolus at start of anesthesia, followed by an IV CRI until the end of anesthesia, then a CRI at a decreased dose for a further 4 hours: CONTROL/BUT (butorphanol 0.4 mg kg⁻¹, infusion rate of saline 0.9% 2 mLkg⁻¹ hour⁻¹); FENT (5 μg kg⁻¹, 10 μg kg⁻¹hour⁻¹, then 2.5 μg kg⁻¹ hour⁻¹); KET (1 mgkg⁻¹, 40 μg kg⁻¹ minute⁻¹, then 10 μg kg⁻¹minute⁻¹); LIDO (2 mg kg⁻¹, 100 μg kg⁻¹ minute⁻¹, then 25 μg kg⁻¹ minute⁻¹); DEX (1 μgkg⁻¹, 3 μg kg⁻¹ hour⁻¹, then 1 μg kg⁻¹ hour⁻¹); or a combination of LKD at the aforementioned doses. Postoperative analgesia was evaluated using the Glasgow composite pain scale, University of Melbourne pain scale, and numerical rating scale. Rescue analgesia was morphine and carprofen. Data were analyzed using Friedman or Kruskal–Wallis test with appropriate post-hoc testing (p < 0.05).ResultsAnimals requiring rescue analgesia included CONTROL/BUT (n = 8), KET (n = 3), DEX (n = 2), and LIDO (n = 2); significantly higher in CONTROL/BUT than other groups. No dogs in LKD and FENT groups received rescue analgesia. CONTROL/BUT pain scores were significantly higher at 1 hour than FENT, DEX and LKD, but not than KET or LIDO. Fentanyl and LKD sedation scores were higher than CONTROL/BUT at 1 hour.Conclusions and clinical relevanceLKD and FENT resulted in adequate postoperative analgesia. LIDO, CONTROL/BUT, KET and DEX may not be effective for treatment of postoperative pain in dogs undergoing ovariohysterectomy.     

Minimum end‐tidal sevoflurane concentration necessary to prevent movement during a constant rate infusion of morphine,or morphine plus dexmedetomidine in ponies

ObjectiveTo compare the effects of a constant rate infusion (CRI) of dexmedetomidine and morphine to those of morphine alone on the minimum end-tidal sevoflurane concentration necessary to prevent movement (MAC_NM) in ponies.Study designProspective, randomized, crossover, ‘blinded’, experimental study.AnimalsFive healthy adult gelding ponies were anaesthetized twice with a 3-week washout period.MethodsAfter induction of anaesthesia with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (Fe‘SEVO 2.5%) in 55% oxygen. Monitoring included pulse oximetry, electrocardiography and measurement of anaesthetic gases, arterial blood pressure and body temperature. The ponies were mechanically ventilated and randomly allocated to receive IV treatment M [morphine 0.15 mg kg^?1 (T10-T15) followed by a CRI (0.1 mg kg^?1 hour^?1)] or treatment DM [dexmedetomidine 3.5 μg kg^?1 plus morphine 0.15 mg kg^?1 (T10-T15) followed by a CRI of dexmedetomidine 1.75 μg kg^?1 hour^?1 and morphine 0.1 mg kg^?1 hour^?1]. At T60, a stepwise MAC_NM determination was initiated using constant current electrical stimuli at the skin of the lateral pastern region. Triplicate MAC_NM estimations were obtained and then averaged in each pony. Wilcoxon signed-rank test was used to detect differences in MAC between treatments (a = 0.05).ResultsSevoflurane-morphine MAC_NM values (median (range) and mean ± SD) were 2.56 (2.01–4.07) and 2.79 ± 0.73%. The addition of a continuous infusion of dexmedetomidine significantly reduced sevoflurane MAC_NM values to 0.89 (0.62–1.05) and 0.89 ± 0.22% (mean MAC_NM reduction 67 ± 11%).Conclusion and clinical relevanceCo-administration of dexmedetomidine and morphine CRIs significantly reduced the MAC_NM of sevoflurane compared with a CRI of morphine alone at the reported doses.     

Neuraxial morphine induced pruritus in two cats and treatment with sub anaesthetic doses of propofol

HistoryTwo cats were presented for orthopaedic surgery.Physical ExaminationWith the exception of the orthopaedic injuries found, clinical examination showed no abnormality.ManagementAs part of anaesthetic management, one cat received intrathecal morphine, the other epidural morphine. Following recovery, intense grooming was observed. After ensuring adequate analgesia this behaviour was interpreted as pruritus.In the first cat, pruritus was initially managed with medetomidine constant rate infusion (CRI) at 1 and 1.5 μg kg^?1 hour^?1. The lower dose produced sedation and no relief from pruritus, the higher dose ablated pruritus but induced sedation. Two propofol (lipid emulsion formulation) boli of 0.1 mg kg^?1 ablated pruritus without causing sedation. The second cat was successfully treated with four boli of 0.1 mg kg^?1 propofol over 20 minutes.Follow–upFollowing treatment with propofol, pruritus did not recur in either cat and both were discharged from the hospital.ConclusionsThis is the first clinical report of morphine–induced pruritus in cats and management with low–dose propofol. These cases suggest an antipruritic mechanism for lipid–formulation propofol.     

Evaluation of the isoflurane‐sparing effects of fentanyl,lidocaine, ketamine,dexmedetomidine, or the combination lidocaine‐ketamine‐dexmedetomidine during ovariohysterectomy in dogs

ObjectiveTo evaluate the isoflurane‐sparing effects of an intravenous (IV) constant rate infusion (CRI) of fentanyl, lidocaine, ketamine, dexmedetomidine, or lidocaine‐ketamine‐dexmedetomidine (LKD) in dogs undergoing ovariohysterectomy.Study designRandomized, prospective, blinded, clinical study.AnimalsFifty four dogs.MethodsAnesthesia was induced with propofol and maintained with isoflurane with one of the following IV treatments: butorphanol/saline (butorphanol 0.4 mg kg^?1, saline 0.9% CRI, CONTROL/BUT); fentanyl (5 μg kg^?1, 10 μg kg^?1 hour^?1, FENT); ketamine (1 mg kg^?1, 40 μg kg^?1 minute^?1, KET), lidocaine (2 mg kg^?1, 100 μg kg^?1 minute^?1, LIDO); dexmedetomidine (1 μg kg^?1, 3 μg kg^?1 hour^?1, DEX); or a LKD combination. Positive pressure ventilation maintained eucapnia. An anesthetist unaware of treatment and end‐tidal isoflurane concentration (Fe′Iso) adjusted vaporizer settings to maintain surgical anesthetic depth. Cardiopulmonary variables and Fe′Iso concentrations were monitored. Data were analyzed using anova (p < 0.05).ResultsAt most time points, heart rate (HR) was lower in FENT than in other groups, except for DEX and LKD. Mean arterial blood pressure (MAP) was lower in FENT and CONTROL/BUT than in DEX. Overall mean ± SD Fe′Iso and % reduced isoflurane requirements were 1.01 ± 0.31/41.6% (range, 0.75 ± 0.31/56.6% to 1.12 ± 0.80/35.3%, FENT), 1.37 ± 0.19/20.8% (1.23 ± 0.14/28.9% to 1.51 ± 0.22/12.7%, KET), 1.34 ± 0.19/22.5% (1.24 ± 0.19/28.3% to 1.44 ± 0.21/16.8%, LIDO), 1.30 ± 0.28/24.8% (1.16 ± 0.18/32.9% to 1.43 ± 0.32/17.3%, DEX), 0.95 ± 0.19/54.9% (0.7 ± 0.16/59.5% to 1.12 ± 0.16/35.3%, LKD) and 1.73 ± 0.18/0.0% (1.64 ± 0.21 to 1.82 ± 0.14, CONTROL/BUT) during surgery. FENT and LKD significantly reduced Fe′Iso.Conclusions and clinical relevanceAt the doses administered, FENT and LKD had greater isoflurane‐sparing effect than LIDO, KET or CONTROL/BUT, but not at all times. Low HR during FENT may limit improvement in MAP expected with reduced Fe′Iso.