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.     

The isoflurane sparing effect of a medetomidine constant rate infusion in horses

This clinical study analysed the anaesthetic sparing effect of a medetomidine constant rate infusion (CRI) during isoflurane anaesthesia in horses. Forty healthy horses undergoing different types of orthopaedic and soft tissue surgeries were studied in a randomized trial. Orthopaedic surgeries were primarily arthroscopies and splint bone extractions. Soft tissue surgeries were principally castrations with one ovariectomy. All horses received 0.03 mg kg^?1 acepromazine IM 1 hour prior to sedation. Group A (11 orthopaedic and nine soft tissue surgeries), was sedated with 1.1 mg kg^?1 xylazine IV, group B (13 orthopaedic and seven soft tissue surgeries) with 7 µg kg^?1 medetomidine IV. Anaesthesia was induced in both groups with 2.2 mg kg^?1 ketamine and diazepam 0.02 mg kg^?1 IV. Maintenance of anaesthesia was with isoflurane (ISO) in 100% oxygen, depth of anaesthesia was always adjusted by the first author. Group B received an additional CRI of 3.5 µg kg^?1 hour^?1 medetomidine. Respiratory rate (RR), heart rate (HR), mean arterial blood pressure (MAP), Fe ′ISO and Fe ′CO₂ were monitored with a methane insensitive monitor (Cardiocap 5, Ohmeda, Anandic, Diessenhofen) and noted every 5 minutes. Arterial blood was withdrawn for gas analysis (PaO₂, PaCO₂) 5 minutes after the induction of anaesthesia and every 30 minutes thereafter. Dobutamine (DOB) was given as a CRI to maintain mean arterial blood pressure above 70 mm Hg. Data were averaged over time (sum of measurements/number of measurements) and tested for differences between groups by unpaired t‐tests. There were no significant differences between the groups in terms of body mass (group A, 508 ± 73.7 kg; group B, 529.25 ± 78.4 kg) or duration of anaesthesia (group A, 125.5 ± 36 minutes; group B, 121.5 ± 48.4 minutes). The mean Fe ′ISO required to maintain a surgical plane of anaesthesia was significantly higher in group A (1.33 ± 0.13%) than in group B (1.07 ± 0.19%; p = 2.78 × 10^?5). Heart rate was different between the two groups (group A, 42.2 ± 8.3; group B, 32.6 ± 3.5; p = 8.8 × 10^?5). Dobutamine requirements were higher in group A (group A, 0.72 ± 0.24 μg kg^?1 minute^?1; group B, 0.53 ± 0.23 μg kg^?1 minute^?1; p = 0.023). Respiratory rate, Fe ′CO₂, PaO₂, PaCO₂ were not different between the groups. Adjustment of anaesthetic depth subjectively was easier with the medetomidine infusion and isoflurane (group B) than with isoflurane as a sole agent (group A). In group A 12 horses and in group B five horses showed purposeful movements on 27 (A) and 12 (B) occasions. They were given thiopental (group A, 0.0114 mg kg^?1 minute^?1; group B, 0.0023 mg kg^?1 minute^?1). In group A, a further 17 horses were given ketamine to deepen anaesthesia (52 occasions, 0.00426 mg kg^?1 minute^?1) whereas in group B only nine horses needed ketamine (34 occasions, 0.00179 mg kg^?1 minute^?1). An infusion of 3.5 µg kg^?1 MED during ISO anaesthesia resulted in a significantly reduced ISO requirement.     

The effect of midazolam on the end-tidal concentration of isoflurane necessary to prevent movement in dogs

ObjectiveTo determine the possible additive effect of midazolam, a GABA_A agonist, on the end-tidal concentration of isoflurane that prevents movement (MAC_NM) in response to noxious stimulation.Study designRandomized cross-over experimental study.AnimalsSix healthy, adult intact male, mixed-breed dogs.MethodsAfter baseline isoflurane MAC_NM (MAC_NM-B) determination, midazolam was administered as a low (LDS), medium (MDS) or high (HDS) dose series of midazolam. Each series consisted of two dose levels, low and high. The LDS was a loading dose (Ld) of 0.2 mg kg^?1 and constant rate infusion (CRI) (2.5 μg kg^?1 minute^?1) (LDL), followed by an Ld (0.4 mg kg^?1) and CRI (5 μg kg^?1 minute^?1) (LDH). The MDS was an Ld (0.8 mg kg^?1) and CRI (10 μg kg^?1 minute^?1) (MDL) followed by an Ld (1.6 mg kg^?1) and CRI (20 μg kg^?1 minute^?1) (MDH). The HDS was an Ld (3.2 mg kg^?1) and CRI (40 μg kg^?1 minute^?1) (HDL) followed by an Ld (6.4 mg kg^?1) and CRI (80 μg kg^?1 minute^?1) (HDH). MAC_NM was re-determined after each dose in each series (MAC_NM-T).ResultsThe median MAC_NM-B was 1.42. MAC_NM-B did not differ among groups (p >0.05). Percentage reduction in MAC_NM was significantly less in the LDS (11 ± 5%) compared with MDS (30 ± 5%) and HDS (32 ± 5%). There was a weak correlation between the plasma midazolam concentration and percentage MAC_NM reduction (r = 0.36).Conclusion and clinical relevanceMidazolam doses in the range of 10–80 μg kg^?1 minute^?1 significantly reduced the isoflurane MAC_NM. However, doses greater than 10 μg kg^?1 minute^?1 did not further decrease MAC_NM indicating a ceiling effect.     

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.     

Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy

ObjectiveTo determine the induction doses, then minimum infusion rates of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent, cardiopulmonary effects, recovery characteristics and alfaxalone plasma concentrations in cats undergoing ovariohysterectomy after premedication with butorphanol-acepromazine or butorphanol-medetomidine.Study designProspective randomized blinded clinical study.AnimalsTwenty-eight healthy cats.MethodsCats undergoing ovariohysterectomy were assigned into two groups: together with butorphanol [0.2 mg kg^?1 intramuscularly (IM)], group AA (n = 14) received acepromazine (0.1 mg kg^?1 IM) and group MA (n = 14) medetomidine (20 μg kg^?1 IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg^?1 intravenously (IV) every 20 seconds], initially maintained with 8 mg kg^?1 hour^?1 alfaxalone IV and infusion adjusted (±0.5 mg kg^?1 hour^?1) every five minutes according to alterations in heart rate (HR), respiratory rate (f_R), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg^?1) or if f_R >40 breaths minute^?1 (0.25 mg kg^?1). Venous blood samples were obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg^?1 IV) was administered postoperatively. Data were analysed using linear mixed models, Chi-squared, Fishers exact and t-tests.ResultsAlfaxalone anaesthesia induction dose (mean ± SD), was lower in group MA (1.87 ± 0.5; group AA: 2.57 ± 0.41 mg kg^?1). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62 ± 1.37, group MA: 10.76 ± 0.96 mg kg^?1 hour^?1) did not differ significantly between groups. Plasma concentrations ranged between 0.69 and 10.76 μg mL^?1. In group MA, f_R, end-tidal carbon dioxide, temperature and DBP were significantly higher and HR lower.Conclusion and clinical relevanceAlfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedications, the authors recommend initial alfaxalone TIVA rates of 10 mg kg^?1 hour^?1.     

Cardiovascular,respiratory, electrolyte and acid–base balance during continuous dexmedetomidine infusion in anesthetized dogs

ObjectiveTo evaluate the cardiovascular, respiratory, electrolyte and acid–base effects of a continuous infusion of dexmedetomidine during propofol–isoflurane anesthesia following premedication with dexmedetomidine.Study designProspective experimental study.AnimalsFive adult male Walker Hound dogs 1–2 years of age averaging 25.4 ± 3.6 kg.MethodsDogs were sedated with dexmedetomidine 10 μg kg^?1 IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg^?1) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg^?1 IV was administered over 5 minutes followed by an infusion of 0.5 μg kg^?1 hour^?1. Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid–base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD.ResultsNo statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute^?1, 78 ± 18 beats minute^?1 and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute^?1, 78 ± 14 beats minute^?1 and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO₂, PaCO₂, pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion.Conclusions and clinical relevanceDexmedetomidine infusion using a loading dose of 0.5 μg kg^?1 IV followed by a constant rate infusion of 0.5 μg kg^?1 hour^?1 does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg^?1, in propofol–isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2 minutes before onset of infusion showed typical significant effects on cardiovascular parameters.     

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.     

Evaluation of the isoflurane-sparing effects of lidocaine infusion during umbilical surgery in calves

ObjectiveTo evaluate the isoflurane-sparing effects of lidocaine administered by constant rate infusion (CRI) during umbilical surgery in calves.Study designRandomized ‘blinded’ prospective clinical study.AnimalsThirty calves (mean 4.7 ± SD 2.5 weeks old) undergoing umbilical surgery.MethodsAfter premedication with xylazine (0.1 mg kg^?1, IM), anaesthesia was induced with ketamine (4 mg kg^?1, IV) and maintained with isoflurane in O₂ administered through a circle breathing system. The calves were assigned randomly to receive a bolus of 2 mg kg^?1 lidocaine IV after induction of anaesthesia, followed by CRI of 50 μg kg^?1 minute^?1 (group L, n = 15) or a bolus and CRI of 0.9% sodium chloride (NaCl, group S, n = 15). End-tidal isoflurane was adjusted to achieve adequate depth of anaesthesia. Heart rate, direct arterial blood pressure and body temperature were measured intraoperatively. Groups were compared by t- tests, anova or Mann–Whitney rank sum test as appropriate.ResultsThe end-tidal concentration of isoflurane (median, IQR) was significantly lower in group L [1.0% (0.94–1.1)] compared to group S [1.2% (1.1–1.5)], indicating a 16.7% reduction in anaesthetic requirement during lidocaine CRI. Cardiopulmonary parameters and recovery times did not differ significantly between groups.Conclusion and clinical relevanceLidocaine CRI may be used as a supplement to inhalation anaesthesia during umbilical surgery in calves in countries where such a protocol would be within the legal requirements for veterinary use in food animals. This study did not show any measurable benefit to the calves other than a reduction in isoflurane requirement.     

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.     

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 intravenous lidocaine, ketamine, and the combination on the minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effects of intravenous lidocaine (L) and ketamine (K) alone and their combination (LK) on the minimum alveolar concentration (MAC) of sevoflurane (SEVO) in dogs.Study designProspective randomized, Latin-square experimental study.AnimalsSix, healthy, adult Beagles, 2 males, 4 females, weighing 7.8 – 12.8 kg.MethodsAnesthesia was induced with SEVO in oxygen delivered by face mask. The tracheas were intubated and the lungs ventilated to maintain normocapnia. Baseline minimum alveolar concentration of SEVO (MAC_B) was determined in duplicate for each dog using an electrical stimulus and then the treatment was initiated. Each dog received each of the following treatments, intravenously as a loading dose (LD) followed by a constant rate infusion (CRI): lidocaine (LD 2 mg kg⁻¹, CRI 50 μg kg⁻¹minute⁻¹), lidocaine (LD 2 mg kg⁻¹, CRI 100 μgkg⁻¹ minute⁻¹), lidocaine (LD 2 mg kg⁻¹, CRI 200 μg kg⁻¹ minute⁻¹), ketamine (LD 3 mg kg⁻¹, CRI 50 μg kg⁻¹ minute⁻¹), ketamine (LD 3 mgkg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹), or lidocaine (LD 2 mg kg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹) + ketamine (LD 3 mg kg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹) in combination. Post-treatment MAC (MAC_T) determination started 30 minutes after initiation of treatment.ResultsLeast squares mean ± SEM MAC_B of all groups was 1.9 ± 0.2%. Lidocaine infusions of 50, 100, and 200 μg kg⁻¹ minute⁻¹ significantly reduced MAC_B by 22.6%, 29.0%, and 39.6%, respectively. Ketamine infusions of 50 and 100 μg kg⁻¹ minute⁻¹ significantly reduced MAC_B by 40.0% and 44.7%, respectively. The combination of K and L significantly reduced MAC_B by 62.8%.Conclusions and clinical relevanceLidocaine and K, alone and in combination, decrease SEVO MAC in dogs. Their use, at the doses studied, provides a clinically important reduction in the concentration of SEVO during anesthesia in dogs.     

Comparison of the effects of propofol or alfaxalone for anaesthesia induction and maintenance on respiration in cats

ObjectiveTo compare the effects of propofol and alfaxalone on respiration in cats.Study designRandomized, ‘blinded’, prospective clinical trial.AnimalsTwenty cats undergoing ovariohysterectomy.MethodsAfter premedication with medetomidine 0.01 mg kg⁻¹ intramuscularly and meloxicam 0.3 mg kg⁻¹ subcutaneously, the cats were assigned randomly into two groups: group A (n = 10) were administered alfaxalone 5 mg kg⁻¹ minute⁻¹ followed by 10 mg kg⁻¹ hour⁻¹ intravenously (IV) and group P (n = 10) were administered propofol 6 mg kg⁻¹ minute⁻¹ followed by 12 mg kg⁻¹hour⁻¹ IV for induction and maintenance of anaesthesia, respectively. After endotracheal intubation, the tube was connected to a non-rebreathing system delivering 100% oxygen. The anaesthetic maintenance drug rate was adjusted (± 0.5 mg kg⁻¹ hour⁻¹) every 5 minutes according to a scoring sheet based on physiologic variables and clinical signs. If apnoea > 30 seconds, end-tidal carbon dioxide (Pe′CO₂) > 7.3 kPa (55 mmHg) or arterial haemoglobin oxygen saturation (SpO₂) < 90% occurred, manual ventilation was provided. Methadone was administered postoperatively. Data were analyzed using independent-samples t-tests, Fisher's exact test, linear mixed-effects models and binomial test.ResultsManual ventilation was required in two and eight of the cats in group A and P, respectively (p = 0.02). Two cats in both groups showed apnoea. Pe′CO₂ > 7.3 kPa was recorded in zero versus four and SpO₂ < 90% in zero versus six cats in groups A and P respectively. Induction and maintenance dose rates (mean ± SD) were 11.6 ± 0.3 mg kg⁻¹ and 10.7 ± 0.8 mg kg⁻¹ hour⁻¹ for alfaxalone and 11.7 ± 2.7 mg kg⁻¹ and 12.4 ± 0.5 mg kg⁻¹ hour⁻¹ for propofol.Conclusion and clinical relevanceAlfaxalone had less adverse influence on respiration than propofol in cats premedicated with medetomidine. Alfaxalone might be better than propofol for induction and maintenance of anaesthesia when artificial ventilation cannot be provided.     

Cardiopulmonary and isoflurane‐sparing effects of epidural or intravenous infusion of dexmedetomidine in cats undergoing surgery with epidural lidocaine

ObjectiveTo compare the cardiorespiratory, anesthetic-sparing effects and quality of anesthetic recovery after epidural and constant rate intravenous (IV) infusion of dexmedetomidine (DEX) in cats given a low dose of epidural lidocaine under propofol-isoflurane anesthesia and submitted to elective ovariohysterectomy.Study designRandomized, blinded clinical trial.AnimalsTwenty-one adult female cats (mean body weight: 3.1 ± 0.4 kg).MethodsCats received DEX (4 μg kg^?1, IM). Fifteen minutes later, anesthesia was induced with propofol and maintained with isoflurane. Cats were divided into three groups. In GI cats received epidural lidocaine (1 mg kg^?1, n = 7), in GII cats were given epidural lidocaine (1 mg kg^?1) + DEX (4 μg kg^?1, n = 7), and in GIII cats were given epidural lidocaine (1 mg kg^?1) + IV constant rate infusion (CRI) of DEX (0.25 μg kg^?1 minute^?1, n = 7). Variables evaluated included heart rate (HR), respiratory rate (f_R), systemic arterial pressures, rectal temperature (RT), end-tidal CO₂, end-tidal isoflurane concentration (e′ISO), arterial blood gases, and muscle tone. Anesthetic recovery was compared among groups by evaluation of times to recovery, HR, f_R, RT, and degree of analgesia. A paired t-test was used to evaluate pre-medication variables and blood gases within groups. anova was used to compare parametric data, whereas Friedman test was used to compare muscle relaxation.ResultsEpidural and CRI of DEX reduced HR during anesthesia maintenance. Mean ± SD e′ISO ranged from 0.86 ± 0.28% to 1.91 ± 0.63% in GI, from 0.70 ± 0.12% to 0.97 ± 0.20% in GII, and from 0.69 ± 0.12% to 1.17 ± 0.25% in GIII. Cats in GII and GIII had longer recovery periods than in GI.Conclusions and clinical relevanceEpidural and CRI of DEX significantly decreased isoflurane consumption and resulted in recovery of better quality and longer duration, despite bradycardia, without changes in systemic blood pressure.     

Anaesthesia with medetomidine,midazolam and ketamine in six gorillas after premedication with oral zuclopenthixol dihydrochloride

ObjectiveTo evaluate the effects of medetomidine, midazolam and ketamine (MMK) in captive gorillas after premedication with oral zuclopenthixol.Study designCase series.AnimalsSix gorillas, two males and four females, aged 9–52 years and weighing 63–155 kg.MethodsThe gorillas were given zuclopenthixol dihydrochloride 0.2 ± 0.05 mg kg^?1 per os twice daily for 3 days for premedication. On the day of anaesthesia the dose of zuclopenthixol was increased to 0.27 mg kg^?1 and given once early in the morning. Anaesthesia was induced with medetomidine 0.04 ± 0.004 mg kg^?1, midazolam 0.048 ± 0.003 mg kg^?1 and ketamine 4.9 ± 0.4 mg kg^?1 intramuscularly (IM). Upon recumbency, the trachea was intubated and anaesthesia was maintained on 1–2% isoflurane in oxygen. Physiological parameters were monitored every 10 minutes and arterial blood gas analysis was performed once 30–50 minutes after initial darting. At the end of the procedure, 42–115 minutes after initial darting, immobilisation was antagonized with atipamezole 0.21 ± 0.03 mg kg^?1 and sarmazenil 5 ± 0.4 μg kg^?1 IM.ResultsRecumbency was reached within 10 minutes in five out of six animals. One animal required two additional darts before intubation was feasible. Heart rate ranged from 60 to 85 beats minute^?1, respiratory rate from 17 to 46 breaths minute^?1 and temperature from 36.9 to 38.3 °C. No spontaneous recoveries were observed and anaesthetic level was stable. Blood gas analyses revealed mild respiratory acidosis, and mean PaO₂ was 24.87 ± 17.16 kPa (187 ± 129 mmHg) with all values being above 13.4 kPa (101 mmHg). Recovery was smooth and gorillas were sitting within 25 minutes.Conclusion and clinical relevanceThe drug combination proved to be effective in anaesthetizing captive gorillas of various ages and both sexes, with minimal cardio-respiratory changes.     

The effects of age, isoflurane and sevoflurane on atracurium in lambs

ObjectiveTo determine the effects of age, sevoflurane and isoflurane on atracurium-induced neuromuscular blockade in 3–16 week-old lambs.Study designProspective randomized experimental trial.AnimalsTwenty-six Scottish blackface ewe-lambs were anaesthetized for spinal surgery when either 3–6 (mean age 4.6 weeks; n = 18) or 12–16 weeks (mean age 13.7 weeks; n = 15) of age; seven animals were anaesthetized at both ages.MethodsAfter intramuscular injection of medetomidine (10 μg kg^?1) anaesthesia was induced in the younger lambs either with isoflurane or sevoflurane in oxygen delivered by mask, and in the older lambs with ketamine (4 mg kg^?1), and midazolam (0.2 mg kg^?1) administered intravenously (IV). In both groups anaesthesia was maintained with fixed end-tidal concentrations of either sevoflurane (2.8%) or isoflurane (1.8%) delivered in oxygen. Before surgery meloxicam (0.6 mg kg^?1), morphine (0.5 mg kg^?1) and ketamine (1 mg kg^?1 followed by 10 μg kg^?1 minute^?1) were administered IV. The lungs were ventilated mechanically to maintain normocapnia. Neuromuscular block was achieved with a loading dose (LD) of atracurium (0.5 mg kg^?1 IV). The peroneal nerve was stimulated (train-of-four every 12 seconds). Evoked responses in the digital extensor muscles were evaluated by palpation and observation. Maintenance doses (MD) of atracurium (0.17 mg kg^?1 IV) were administered when the first twitch (T1) returned. The onset and duration of LD action (T1 absent) and the duration of MD were recorded. Data were analysed using Student's t test, Mann–Whitney U test, repeated–measures anova, Wilcoxon's matched pairs test or Pearson correlation coefficient as relevant (p < 0.05).ResultsOnset of LD action developed significantly (p < 0.05) more rapidly in isoflurane compared with sevoflurane-anaesthetized lambs (55 ± 18 cf. 80 ± 37 seconds). Duration of action of LDs and MDs was longer (p < 0.05) in lambs aged 12–16 than 3–6 weeks (33 ± 5.4 cf. 25 ± 6.4 and 26 ± 4.2 cf. 18 ± 5.5 minutes) but were independent of the anaesthetic used.Conclusions and clinical relevanceThe effect of atracurium is age-dependent in lambs being prolonged in older animals. The onset of neuromuscular blockade is more rapid in isoflurane compared with sevoflurane-anaesthetized lambs.     

Anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in isoflurane‐anaesthetized sheep

ObjectiveTo determine the anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in sheep anaesthetized with isoflurane and undergoing orthopaedic surgery.Study designProspective, randomised, ‘blinded’ controlled study.AnimalsTwenty healthy sheep (weight mean 41.1 ± SD 4.5 kg).MethodsSheep were sedated with intravenous (IV) dexmedetomidine (4 μg kg⁻¹) and morphine (0.2 mg kg⁻¹). Anaesthesia was induced with propofol (1 mg kg⁻¹ minute⁻¹ to effect IV) and maintained with isoflurane in oxygen and a continuous rate infusion (CRI) of fentanyl 10 μg kg⁻¹ hour⁻¹ (group F) or saline (group P) for 100 minutes. The anaesthetic induction dose of propofol, isoflurane expiratory fraction (Fe’iso) required for maintenance and cardiorespiratory measurements were recorded and blood gases analyzed at predetermined intervals. The quality of recovery was assessed. Results were compared between groups using t-tests or Mann–Whitney as relevant.ResultsThe propofol induction dose was 4.7 ± 2.4 mg kg⁻¹. Fe’iso was significantly lower (by 22.6%) in group F sheep than group P (p = 0). Cardiac index (mean ± SD mL kg⁻¹ minute⁻¹) was significantly (p = 0.012) lower in group F (90 ± 15) than group P (102 ± 35). Other measured cardiorespiratory parameters did not differ statistically significantly between groups. Recovery times and recovery quality were statistically similar in both groups.Conclusions and clinical relevanceFentanyl reduced isoflurane requirements without clinically affecting the cardiorespiratory stability or post-operative recovery in anaesthetized sheep undergoing orthopaedic surgery.     

Effects of vatinoxan in dogs premedicated with medetomidine and butorphanol followed by sevoflurane anaesthesia: a randomized clinical study

ObjectiveTo investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration.Study designA randomized, controlled, blinded, clinical trial.AnimalsA total of 28 client-owned dogs.MethodsDogs were premedicated with medetomidine (0.125 mg m^?2) and butorphanol (0.2 mg kg^?1) (group MB; n = 14), or medetomidine (0.25 mg m^?2), butorphanol (0.2 mg kg^?1) and vatinoxan (5 mg m^?2) (group MB-VATI; n = 14). Anaesthesia was induced 15 minutes later with propofol and maintained with sevoflurane in oxygen (targeting 1.3%). Before surgical incision, lidocaine (2 mg kg^?1) was injected intratesticularly. At the end of the procedure, meloxicam (0.2 mg kg^?1) was administered IV. The level of sedation, the qualities of induction, intubation and recovery, and Glasgow Composite Pain Scale short form (GCPS-SF) were assessed. Heart rate (HR), respiratory rate (f_R), mean arterial pressure (MAP), end-tidal concentration of sevoflurane (Fe′Sevo) and carbon dioxide (Pe′CO₂) were recorded. Blood samples were collected at 10 and 30 minutes after premedication for plasma medetomidine and butorphanol concentrations.ResultsAt the beginning of surgery, HR was 61 ± 16 and 93 ± 23 beats minute^?1 (p = 0.001), and MAP was 78 ± 7 and 56 ± 7 mmHg (p = 0.001) in MB and MB-VATI groups, respectively. No differences were detected in f_R, Pe′CO₂, Fe′Sevo, the level of sedation, the qualities of induction, intubation and recovery, or in GCPS-SF. Plasma medetomidine concentrations were higher in group MB-VATI than in MB at 10 minutes (p = 0.002) and 30 minutes (p = 0.0001). Plasma butorphanol concentrations were not different between groups.Conclusions and clinical relevanceIn group MB, HR was significantly lower than in group MB-VATI. Hypotension detected in group MB-VATI during sevoflurane anaesthesia was clinically the most significant difference between groups.     

The effect of ketamine on the MACBAR of sevoflurane in dogs

ObjectiveTo determine the effect of intravenous ketamine on the minimum alveolar concentration of sevoflurane needed to block autonomic response (MAC_BAR) to a noxious stimulus in dogs.Study designRandomized, crossover, prospective design.AnimalsEight, healthy, adult male, mixed-breed dogs, weighing 11.2–16.1 kg.MethodsDogs were anesthetized with sevoflurane on two occasions, 1 week apart, and baseline MAC_BAR (B-MAC_BAR) was determined on each occasion. MAC_BAR was defined as the mean of the end-tidal sevoflurane concentrations that prevented and allowed an increase (≥15%) in heart rate or invasive mean arterial pressure in response to a noxious electrical stimulus (50 V, 50 Hz, 10 ms). Dogs then randomly received either a low-dose (LDS) or high-dose series (HDS) of ketamine, and treatment MAC_BAR (T-MAC_BAR) was determined. The LDS had an initial loading dose (LD) of 0.5 mg kg^?1 and constant rate infusion (CRI) at 6.25 μg kg^?1 minute^?1, followed, after T-MAC_BAR determination, by a second LD (1 mg kg^?1) and CRI (12.5 μg kg^?1 minute^?1). The HDS had an initial LD (2 mg kg^?1) and CRI (25 μg kg^?1 minute^?1) followed by a second LD (3 mg kg^?1) and CRI (50 μg kg^?1 minute^?1). Data were analyzed with a mixed-model anova and are presented as LSM ± SEM.ResultsThe B-MAC_BAR was not significantly different between treatments. Ketamine at 12.5, 25, and 50 μg kg^?1 minute^?1 decreased sevoflurane MAC_BAR, and the maximal decrease (22%) occurred at 12.5 μg kg^?1 minute^?1. The percentage change in MAC_BAR was not correlated with either the log plasma ketamine or norketamine concentration.Conclusions and clinical relevanceKetamine at clinically relevant doses of 12.5, 25, and 50 μg kg^?1 minute^?1 decreased sevoflurane MAC_BAR, although the reduction was neither dose-dependent nor linear.     

The effect of fentanyl on the end‐tidal sevoflurane concentration needed to prevent motor movement in dogs

ObjectiveThe objectives of this study were to determine the effects of fentanyl on the end-tidal concentration of sevoflurane needed to prevent motor movement (MAC_NM) in response to noxious stimulation, and to evaluate if acute tolerance develops.Study designRandomized cross-over experimental study.AnimalsSix healthy, adult (2–3 years old), intact male, mixed-breed dogs weighing 16.2 ± 1.1 kg.MethodsSix dogs were randomly assigned to receive one of three separate treatments over a 3 week period. After baseline sevoflurane MAC_NM (MAC_NM-B) determination, fentanyl treatments (T) were administered as a loading dose (Ld) and constant rate infusion (CRI) as follows: T1-Ld of 7.5 μg kg^?1 and CRI at 3 μg kg^?1 hour^?1; T2-Ld of 15 μg kg^?1 and CRI at 6.0 μg kg ^?1 hour^?1; T3-Ld of 30 μg kg^?1 and CRI at 12 μg kg^?1 hour^?1. The MAC_NM was defined as the minimum end-tidal sevoflurane concentration preventing motor movement. The first post-treatment MAC_NM (MAC_NM-I) determination was initiated 90 minutes after the start of the CRI, and a second MAC_NM (MAC_NM-II) determination was initiated 3 hours after MAC_NM-I was established.ResultsThe overall least square mean MAC_NM-B for all groups was 2.66%. All treatments decreased (p < 0.05) MAC_NM, and the decrease from baseline was 22%, 35% and 41% for T1, T2 and T3, respectively. Percentage change in T1 differed (p < 0.05) from T2 and T3; however, T2 did not differ from T3. MAC_NM-I was not significantly different from MAC_NM-II within treatments.Conclusions and clinical relevanceFentanyl doses in the range of 3–12 μg kg^?1 hour^?1 significantly decreased the sevoflurane MAC_NM. Clinically significant tolerance to fentanyl did not occur under the study conditions.     

Clinical evaluation of ketamine and lidocaine intravenous infusions to reduce isoflurane requirements in horses under general anaesthesia

ObjectiveTo compare isoflurane alone or in combination with systemic ketamine and lidocaine for general anaesthesia in horses.Study designProspective, randomized, blinded clinical trial.AnimalsForty horses (ASA I-III) undergoing elective surgery.MethodsHorses were assigned to receive isoflurane anaesthesia alone (ISO) or with ketamine and lidocaine (LKI). After receiving romifidine, diazepam, and ketamine, the isoflurane end-tidal concentration was set at 1.3% and subsequently adjusted by the anaesthetist (unaware of treatments) to maintain a light plane of surgical anaesthesia. Animals in the LKI group received lidocaine (1.5 mg kg⁻¹ over 10 minutes, followed by 40 μg kg⁻¹ minute⁻¹) and ketamine (60 μg kg⁻¹ minute⁻¹), both reduced to 65% of the initial dose after 50 minutes, and stopped 15 minutes before the end of anaesthesia. Standard clinical cardiovascular and respiratory parameters were monitored. Recovery quality was scored from one (very good) to five (very poor). Differences between ISO and LKI groups were analysed with a two-sample t-test for parametric data or a Fischer's exact test for proportions (p < 0.05 for significance). Results are mean ± SD.ResultsHeart rate was lower (p = 0.001) for LKI (29 ± 4) than for ISO (34 ± 6). End-tidal concentrations of isoflurane (ISO: 1.57% ± 0.22; LKI: 0.97% ± 0.33), the number of horses requiring thiopental (ISO: 10; LKI: 2) or dobutamine (ISO:8; LKI:3), and dobutamine infusion rates (ISO:0.26 ± 0.09; LKI:0.18 ± 0.06 μg kg⁻¹ minute⁻¹) were significantly lower in LKI compared to the ISO group (p < 0.001). No other significant differences were found, including recovery scores.Conclusions and clinical relevanceThese results support the use of lidocaine and ketamine to improve anaesthetic and cardiovascular stability during isoflurane anaesthesia lasting up to 2 hours in mechanically ventilated horses, with comparable quality of recovery.