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.     

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.     

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.     

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.     

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.     

Microcirculation assessment of dexmedetomidine constant rate infusion during anesthesia of dogs with sepsis from pyometra: a randomized clinical study

ObjectiveTo compare dexmedetomidine and fentanyl constant rate infusions in anesthetic protocols for septic dogs with pyometra, using microcirculatory, hemodynamic and metabolic variables.Study designRandomized clinical study.AnimalsA total of 33 dogs with pyometra with two or more systemic inflammatory response syndrome variables undergoing ovariohysterectomy.MethodsDogs were randomized into two groups: group DG, dexmedetomidine (3 μg kg^–1 hour^–1; 17 dogs) and group FG, fentanyl (5 μg kg^–1 hour^–1; 16 dogs) infused during isoflurane anesthesia and mechanical ventilation. Microcirculation flow index (MFI), total vessel density and De Backer score were assessed using orthogonal polarization spectral imaging at the sublingual site. Heart rate, invasive blood pressure, temperature, arterial blood gas analysis and lactate concentration were obtained at various time points. Variables were recorded at baseline (BL), immediately before (T0), 30 (T30) and 60 (T60) minutes after infusion, and 60 minutes after surgery. Data were analyzed using the Shapiro-Wilk test. To compare variables between groups, the unpaired Student t test was used. Comparison between evaluation time points was performed with two-way anova for repeated measures. Where statistical significance was detected, the Bonferroni post hoc test was used.ResultsMFI was significantly higher in group FG at T30. Mean arterial pressure at T30 was higher in group DG (89 ± 15 mmHg) than in group FG (72 ± 13 mmHg). Lactate concentrations were not significantly different between groups at each time point. Both groups had similar clinical outcomes (mortality, extubation time and occurrence of hypotension and bradyarrhythmias).Conclusions and clinical relevanceDexmedetomidine (3 μg kg^–1 hour^–1) without a loading dose can be included in the maintenance of anesthesia in dogs with pyometra and sepsis without compromising microcirculation and hemodynamic values when compared with fentanyl (5 μg kg^–1 hour^–1).     

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.     

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.     

Development of a xylazine constant rate infusion with or without butorphanol for standing sedation of horses

ObjectiveTo elaborate constant rate infusion (CRI) protocols for xylazine (X) and xylazine/butorphanol (XB) which will result in constant sedation and steady xylazine plasma concentrations.Study designBlinded randomized experimental study.AnimalsTen adult research horses.MethodsPart I: After normal height of head above ground (HHAG = 100%) was determined, a loading dose of xylazine (1 mg kg^?1) with butorphanol (XB: 18 μg kg^?1) or saline (X: equal volume) was given slowly intravenously (IV). Immediately afterwards, a CRI of butorphanol (XB: 25 μg kg^?1 hour^?1) or saline (X) was administered for 2 hours. The HHAG was used as a marker of depth of sedation. Sedation was maintained for 2 hours by additional boluses of xylazine (0.3 mg kg^?1) whenever HHAG >50%. The dose of xylazine (mg kg^?1 hour^?1) required to maintain sedation was calculated for both groups. Part II: After the initial loading dose, the calculated xylazine infusion rates were administered in parallel to butorphanol (XB) or saline (X) and sedation evaluated. Xylazine plasma concentrations were measured by HPLC-MS-MS at time points 0, 5, 30, 45, 60, 90, and 120 minutes. Data were analyzed using paired t-test, Wilcoxon signed rank test and a 2-way anova for repeated measures (p < 0.05).ResultsThere was no significant difference in xylazine requirements (X: 0.69, XB: 0.65 mg kg^?1 hour^?1) between groups. With treatment X, a CRI leading to prolonged sedation was developed. With XB, five horses (part I: two, part II: three) fell down and during part II four horses appeared insufficiently sedated. Xylazine plasma concentrations were constant after 45 minutes in both groups.ConclusionXylazine bolus, followed by CRI, provided constant sedation. Additional butorphanol was ineffective in reducing xylazine requirements and increased ataxia and apparent early recovery from sedation in unstimulated horses.Clinical relevanceData were obtained on unstimulated healthy horses and extrapolation to clinical conditions requires caution.     

Effects of constant rate infusions of dexmedetomidine,remifentanil and their combination on minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs.Study designRandomized crossover experimental study.AnimalsA total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg.MethodsAnesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg^–1 hour^–1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 μg kg^–1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 μg kg^–1 hour^–1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 μg kg^–1 minute^–1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED₅₀) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 μg kg^–1 hour^–1, obtained using log-linear regression analysis.ResultsThe sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED₅₀ values were lower when combined with dexmedetomidine than those obtained during saline–remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 μg kg^–1 hour^–1.Conclusions and clinical relevanceCombined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.     

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.     

Effects of dexmedetomidine alone or in combination with opioids on intraocular pressure in healthy Beagle dogs

ObjectiveTo evaluate the effects of dexmedetomidine alone or in combination with different opioids on intraocular pressure (IOP) in dogs.Study designExperimental, prospective, crossover, randomized, blinded study.AnimalsA total of six Beagle dogs (two males and four females) aged 2 years and weighing 15.9 ± 2.9 kg (mean ± standard deviation).MethodsDogs were distributed randomly into seven treatments (n = 6 per treatment) and were administered dexmedetomidine alone (10 μg kg^–1; Dex) or in combination with butorphanol (0.15 mg kg^–1; DexBut), meperidine (5 mg kg^–1; DexMep), methadone (0.5 mg kg^–1; DexMet), morphine (0.5 mg kg^–1; DexMor), nalbuphine (0.5 mg kg^–1; DexNal) or tramadol (5 mg kg^–1; DexTra). All drugs were administered intramuscularly. IOP was measured before drug injection (time 0, baseline) and every 15 minutes thereafter for 120 minutes (T15–T120).ResultsThere were significant reductions in IOP compared with baseline in treatments Dex and DexMep at times T30–T120, and in treatment DexMet at T15–T90. IOP decreased compared with baseline in treatments DexBut, DexNal and DexTra at all evaluation times. No changes in IOP were seen in treatment DexMor. The mean IOP values in treatment DexMet at T105–T120 were higher than those for other treatments.Conclusions and clinical relevanceDexmedetomidine alone or in combination with butorphanol, meperidine, methadone, nalbuphine or tramadol resulted in decreased IOP for 120 minutes in dogs. The magnitude of the reduction was small and lacked clinical significance.     

Inhibition and facilitation of nociceptively evoked muscular activity by fentanyl or dexmedetomidine in isoflurane-anaesthetized pigs

ObjectiveTo investigate motor and cardiovascular responses to dexmedetomidine or fentanyl in isoflurane-anaesthetized pigs.Study designExperimental, balanced, block randomized, two-group design.AnimalsA group of 16 crossbred pigs, 55 ± 8 days (mean ± standard deviation) old.MethodsDeltoid electromyography (EMG) was recorded during isoflurane anaesthesia. Electrical stimulation using 5, 10, 20 and 40 mA of the distal right thoracic limb elicited a nociceptive withdrawal reflex (NWR), quantified by the area under the curve (AUC) for the simulation intensity versus EMG amplitude response curve. Latency to movement evoked by clamping a claw for maximum 60 seconds was noted. Arterial blood pressure and pulse rate were recorded. Data were sampled at baseline and during dexmedetomidine 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 μg kg^–1 hour^–1 or fentanyl 5, 10, 20, 40, 80 and 160 μg kg^–1 hour^–1 infusions. The influence of infusion rate on NWR AUC and spontaneous EMG was analysed using a mixed model, with p < 5%.ResultsNWR AUC increased at fentanyl 5 μg kg^–1 hour^–1 but decreased at fentanyl 40, 80 and 160 μg kg^–1 hour^–1 and dexmedetomidine 4.0 and 8.0 μg kg^–1 hour^–1. All pigs at fentanyl 80 μg kg^–1 hour^–1, and three pigs at dexmedetomidine 8.0 μg kg^–1 hour^–1 had mechanical latencies greater than 60 seconds. Spontaneous EMG activity increased accompanied by visually evident ‘shivering’ at fentanyl 5, 10 and 20 μg kg^–1 hour^–1 but decreased at dexmedetomidine 2, 4 and 8 μg kg^–1 hour^–1. Clinically relevant effects of increasing infusion rates on blood pressure or pulse rate were not observed.Conclusion and clinical relevanceIf anaesthetic plane or antinociception is evaluated in pigs, response to claw clamping and NWR will not necessarily give uniform results when comparing drugs. If only one method is used, results should be interpreted cautiously.     

Combined effects of dexmedetomidine and vatinoxan infusions on minimum alveolar concentration and cardiopulmonary function in sevoflurane-anesthetized dogs

ObjectiveTo evaluate the effects of combined infusions of vatinoxan and dexmedetomidine on inhalant anesthetic requirement and cardiopulmonary function in dogs.Study designProspective experimental study.MethodsA total of six Beagle dogs were anesthetized to determine sevoflurane minimum alveolar concentration (MAC) prior to and after an intravenous (IV) dose (loading, then continuous infusion) of dexmedetomidine (4.5 μg kg^–1 hour^–1) and after two IV doses of vatinoxan in sequence (90 and 180 μg kg^–1 hour^–1). Blood was collected for plasma dexmedetomidine and vatinoxan concentrations. During a separate anesthesia, cardiac output (CO) was measured under equivalent MAC conditions of sevoflurane and dexmedetomidine, and then with each added dose of vatinoxan. For each treatment, cardiovascular variables were measured with spontaneous and controlled ventilation. Repeated measures analyses were performed for each response variable; for all analyses, p < 0.05 was considered significant.ResultsDexmedetomidine reduced sevoflurane MAC by 67% (0.64 ± 0.1%), mean ± standard deviation in dogs. The addition of vatinoxan attenuated this to 57% (0.81 ± 0.1%) and 43% (1.1 ± 0.1%) with low and high doses, respectively, and caused a reduction in plasma dexmedetomidine concentrations. Heart rate and CO decreased while systemic vascular resistance increased with dexmedetomidine regardless of ventilation mode. The co-administration of vatinoxan dose-dependently modified these effects such that cardiovascular variables approached baseline.Conclusions and clinical relevanceIV infusions of 90 and 180 μg kg^–1 hour^–1 of vatinoxan combined with 4.5 μg kg^–1 hour^–1 dexmedetomidine provide a meaningful reduction in sevoflurane requirement in dogs. Although sevoflurane MAC-sparing properties of dexmedetomidine in dogs are attenuated by vatinoxan, the cardiovascular function is improved. Doses of vatinoxan >180 μg kg^–1 hour^–1 might improve cardiovascular function further in combination with this dose of dexmedetomidine, but beneficial effects on anesthesia plane and recovery quality may be lost.     

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.     

Opioid-sparing effect of a medetomidine constant rate infusion during thoraco-lumbar hemilaminectomy in dogs administered a ketamine infusion

ObjectiveTo evaluate the perioperative opioid-sparing effect of a medetomidine (MED) infusion compared to a saline (SAL) infusion in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery.Study designRandomized, partially blinded, clinical study.AnimalsA total of 44 client-owned adult dogs.MethodsAll dogs were administered a 1 μg kg^–1 MED loading dose, followed by a 1.7 μg kg^–1 hour^–1 constant rate infusion (CRI) intravenously or equivalent volumes of SAL. Infusions were started 10–15 minutes before surgical incision and continued throughout the surgical procedure. All dogs were administered a standardized anaesthetic and analgesic protocol (including a ketamine CRI). Multiparametric monitoring, including invasive arterial blood pressure, was performed. A trained investigator, unaware of the treatment, performed pain scores for 4 hours postoperatively. Rescue analgesia consisted of fentanyl administered intraoperatively and methadone postoperatively. Data were tested for normality and analysed with Fisher’s exact test, Mann–Whitney U-test, analysis of variance and Kaplan–Meier survival analysis. Data are shown as median (interquartile range) and p-value was set at < 0.05.ResultsThe total dose of fentanyl was significantly lower with MED 0 (0–0.8) μg kg^–1 hour^–1 compared to SAL 3 (1.8–5.3) μg kg^–1 hour^–1 (p = 0.004). In the MED group, one dog compared to 12 dogs in the SAL group required a fentanyl CRI (p = 0.001). There were no statistically significant differences between groups regarding the total dose of methadone administered.Conclusions and clinical relevanceThe addition of a low-dose medetomidine CRI to the anaesthetic protocol decreased the need for a fentanyl CRI in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery during administration of a ketamine CRI.     

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.     

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

ObjectiveTo evaluate the effects of detomidine or romifidine on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing isoflurane anaesthesia.Study designProspective, randomized, blinded, clinical study.AnimalsA total of 63 healthy horses undergoing elective surgery during general anaesthesia.MethodsHorses were randomly allocated to three groups of 21 animals each. In group R, horses were given romifidine intravenously (IV) for premedication (80 μg kg^–1), maintenance (40 μg kg^–1 hour^–1) and before recovery (20 μg kg^–1). In group D2.5, horses were given detomidine IV for premedication (15 μg kg^–1), maintenance (5 μg kg^–1 hour^–1) and before recovery (2.5 μg kg^–1). In group D5, horses were given the same doses of detomidine IV for premedication and maintenance but 5 μg kg^–1 prior to recovery. Premedication was combined with morphine IV (0.1 mg kg^–1) in all groups. Cardiovascular and blood gas variables, expired fraction of isoflurane (Fe′Iso), dobutamine or ketamine requirements, recovery times, recovery events scores (from sternal to standing position) and visual analogue scale (VAS) were compared between groups using either anova followed by Tukey, Kruskal-Wallis followed by Bonferroni or chi-square tests, as appropriate (p < 0.05).ResultsNo significant differences were observed between groups for Fe′Iso, dobutamine or ketamine requirements and recovery times. Cardiovascular and blood gas measurements remained within physiological ranges for all groups. Group D5 horses had significantly worse scores for balance and coordination (p = 0.002), overall impression (p = 0.021) and final score (p = 0.008) than group R horses and significantly worse mean scores for VAS than the other groups (p = 0.002).Conclusions and clinical relevanceDetomidine or romifidine constant rate infusion provided similar conditions for maintenance of anaesthesia. Higher doses of detomidine at the end of anaesthesia might decrease the recovery quality.     

Effects of fentanyl–lidocaine–ketamine versus sufentanil–lidocaine–ketamine on the isoflurane requirements in dogs undergoing total ear canal ablation and lateral bulla osteotomy

ObjectiveTo compare the isoflurane-sparing effects of sufentanil–lidocaine–ketamine (SLK) and fentanyl–lidocaine–ketamine (FLK) infusions in dogs undergoing total ear canal ablation and lateral bulla osteotomy (TECA–LBO).Study designRandomized blinded clinical study.AnimalsA group of 20 client-owned dogs undergoing TECA–LBO.MethodsIntravenous (IV) administration of lidocaine (3 mg kg^–1) and ketamine (0.6 mg kg^–1) with fentanyl (5.4 μg kg^–1; n = 10; FLK group) or sufentanil (0.72 μg kg^–1; n = 10; SLK group) was immediately followed by the corresponding constant rate infusion (CRI) (lidocaine 3 mg kg^–1 hour^–1; ketamine 0.6 mg kg^–1 hour^–1; either fentanyl 5.4 μg kg^–1 hour^–1 or sufentanil 0.72 μg kg^–1 hour^–1). Anaesthesia was induced with propofol 3–5 mg kg^–1 IV and was maintained with isoflurane. End-tidal isoflurane concentration (Fe′Iso) was decreased in 0.2% steps every 15 minutes until spontaneous movements were observed (treated with propofol 1 mg kg^–1 IV) or an increase of > 30% in heart rate or mean arterial pressure from baseline occurred (treated with rescue fentanyl or sufentanil). Quality of recovery and pain were assessed at extubation using the short-form Glasgow Composite Pain Scale (SF-GCPS), Colorado State University Canine Acute Pain scale (CSU-CAP), and visual analogue scale (VAS). Data were analysed with analysis of variance, t tests, Fisher test and Spearman coefficient (p < 0.05).ResultsFe′Iso decreased significantly in SLK group (45%; p = 0.0006) but not in FLK (15%; p = 0.1135) (p = 0.0136). SLK group had lower scores for recovery quality (p = 0.0204), SF-GCPS (p = 0.0071) and CSU-CAP (p = 0.0273) than FLK at extubation. Intraoperative rescue analgesia and VAS were not significantly different between groups.Conclusions and clinical relevanceCompared with FLK infusion, CRI of SLK at these doses decreased isoflurane requirements, decreased pain scores and improved recovery quality at extubation in dogs undergoing TECA–LBO.     

Total intravenous anesthesia with ketamine–medetomidine–propofol in horses

Propofol is a potentially useful intravenous anesthetic agent for total intravenous anesthesia (TIVA) in horses. The purpose of this study was to compare the anesthetic and cardiorespiratory effects of TIVA following the administration of propofol alone(P–TIVA) and ketamine–medetomidine–propofol (KM–P–TIVA) in adult horses. The carotid artery was translocated to a subcutaneous position during TIVA with P–TIVA (n = 6) or KM–P–TIVA (n = 6). All horses were premedicated with medetomidine [0.005 mg kg^–1, intravenously (IV)]. Anesthesia was induced with midazolam (0.04 mg kg^–1 IV) and ketamine (2.5 mg kg IV). All horses were orotracheally intubated and breathed 100% oxygen. The KM drug combination (ketamine 40 mg mL^–1 and medetomidine 0.05 mg mL^–1) was infused at a rate of 0.025 mL kg^–1 hour^–1. Subsequently, a loading dose of propofol (0.5 mg kg^–1, bolus IV) was administered to all horses; surgical anesthesia (determined by horse response to incision and surgical manipulation, positive response being purposeful or spontaneous movement of limbs or head) was maintained by varying the propofol infusion rate as needed. Arterial blood pressure and HR were also monitored. Both methods of producing TIVA provided excellent general anesthesia for the surgical procedure. Anesthesia time was 115 ± 17 (mean ± SD) and 112 ± 11 minutes in horses anesthetized with KM–P–TIVA and P–TIVA, respectively. The infusion rate of propofol required to maintain surgical anesthesia with KM–P–TIVA was significantly less than for P–TIVA (mean infusion rate of propofol during anesthesia; KM–P–TIVA 0.15 0.02 P–TIVA 0.23 ± 0.03 mg kg^–1 minute^–1, p = 0.004). Apnea occurred in all horses lasting 1–2 minutes and intermittent positive pressure ventilation was started. Cardiovascular function was maintained during both methods of producing TIVA. There were no differences in the time to standing after the cessation of anesthesia (KM–P–TIVA 62 ± 10 minutes versus P–TIVA 87 ± 36 minutes, p = 0.150). The quality of recovery was good in KM–P–TIVA and satisfactory in P–TIVA. KM–P–TIVA and P–TIVA produced clinically useful general anesthesia with minimum cardiovascular depression. Positive pressure ventilation was required to treat respiratory depression. Respiratory depression and apnea must be considered prior to the use of propofol in the horse.