The minimum infusion rate of alfaxalone during its co-administration with lidocaine at three different doses by constant rate infusion in goats

Objective

To determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement in response to standardized stimulation while co-administered with lidocaine at three different doses by constant infusion rate infusion (CRI) in goats.

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.     

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.     

Effects of a constant rate infusion of magnesium sulphate in healthy dogs anaesthetized with isoflurane and undergoing ovariohysterectomy

ObjectiveTo determine the effects of intravenous (IV) magnesium sulphate (MgSO₄) as a bolus followed by a constant rate infusion (CRI) on anaesthetic requirements, neuroendocrine stress response to surgery, haemostasis and postoperative analgesia in healthy dogs undergoing ovariohysterectomy.Study designBlinded randomized clinical trial.AnimalsSixteen female dogs.MethodsAfter intramuscular premedication with acepromazine (0.05 mg kg^?1) and morphine (0.3 mg kg^?1), anaesthesia was induced with diazepam (0.2 mg kg^?1) and propofol (2 mg kg^?1) intravenously and maintained with isoflurane in oxygen in all dogs. Dogs were randomly assigned to two groups, M and C. Group M received MgSO₄ (50 mg kg^?1 over 15 minutes, followed by a 15 mg kg^?1 hour^?1 CRI). Group C received an equivalent bolus and CRI of lactated Ringer's solution. In addition, all dogs received lactated Ringer's solution (10 mL kg^?1 over 15 minutes followed by 10 mL kg^?1 hour^?1). End-tidal isoflurane and carbon dioxide tensions, cardio-respiratory variables, arterial blood gases, electrolytes, ACTH and cortisol concentrations were measured at different time points. Thromboelastography (TEG) was performed pre- and post-anaesthesia. Postoperative pain was evaluated using the short form of the Glasgow Composite Pain Scale. Data were analysed with repeated measures anova and Mann–Whitney U tests (p< 0.05).ResultsNo statistically significant differences between groups were found in any of the measured variables. However, the alpha angle and maximal amplitude recorded by TEG in group M were significantly increased post-anaesthesia, but remained within the reference interval. One dog in Group M and two in Group C received rescue analgesia during recovery.Conclusions and clinical relevanceAs used in this study, MgSO₄ failed to decrease isoflurane requirements, postoperative pain and stress hormone concentrations; however, it did not produce any cardio-respiratory or major haemostatic side effects. Administration of intravenous MgSO₄ together with an opioid during ovariohysterectomy in dogs does not seem to provide any clinical advantage.     

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.     

Effects of constant rate infusion of lidocaine and ketamine, with or without morphine, on isoflurane MAC in horses

REASONS FOR PERFORMING STUDY: Lidocaine and ketamine are administered to horses as a constant rate infusion (CRI) during inhalation anaesthesia to reduce anaesthetic requirements. Morphine decreases the minimum alveolar concentration (MAC) in some domestic animals; when administered as a CRI in horses, morphine does not promote haemodynamic and ventilatory changes and exerts a positive effect on recovery. Isoflurane-sparing effect of lidocaine, ketamine and morphine coadministration has been evaluated in small animals but not in horses. OBJECTIVES: To determine the reduction in isoflurane MAC produced by a CRI of lidocaine and ketamine, with or without morphine. HYPOTHESIS: Addition of morphine to a lidocaine-ketamine infusion reduces isoflurane requirement and morphine does not impair the anaesthetic recovery of horses. METHODS: Six healthy adult horses were anaesthetised 3 times with xylazine (1.1 mg/kg bwt i.v.), ketamine (3 mg/kg bwt i.v.) and isoflurane and received a CRI of lidocaine-ketamine (LK), morphine-lidocaine-ketamine (MLK) or saline (CTL). The loading doses of morphine and lidocaine were 0.15 mg/kg bwt i.v and 2 mg/kg bwt i.v. followed by a CRI at 0.1 mg/kg bwt/h and 3 mg/kg bwt/h, respectively. Ketamine was given as a CRI at 3 mg/kg bwt/h. Changes in MAC characterised the anaesthetic-sparing effect of the drug infusions under study and quality of recovery was assessed using a scoring system. Results: Mean isoflurane MAC (mean ± s.d.) in the CTL, LK and MLK groups was 1.25 ± 0.14%, 0.64 ± 0.20% and 0.59 ± 0.14%, respectively, with MAC reduction in the LK and MLK groups being 49 and 53% (P<0.001), respectively. No significant differences were observed between groups in recovery from anaesthesia. Conclusions and clinical relevance: Administration of lidocaine and ketamine via CRI decreases isoflurane requirements. Coadministration of morphine does not provide further reduction in anaesthetic requirements and does not impair recovery.     

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.     

Total intravenous anaesthesia by boluses or by continuous rate infusion of propofol in mute swans (Cygnus olor)

ObjectiveTo investigate intravenous (IV) propofol given by intermittent boluses or by continuous rate infusion (CRI) for anaesthesia in swans.Study designProspective randomized clinical study.AnimalsTwenty mute swans (Cygnus olor) (eight immature and 12 adults) of unknown sex undergoing painless diagnostic or therapeutic procedures.MethodsInduction of anaesthesia was with 8 mg kg^?1 propofol IV. To maintain anaesthesia, ten birds (group BOLI) received propofol as boluses, whilst 10 (group CRI) received propofol as a CRI. Some physiological parameters were measured. Anaesthetic duration was 35 minutes. Groups were compared using Mann–Whitney U-test. Results are median (range).ResultsAnaesthetic induction was smooth and tracheal intubation was achieved easily in all birds. Bolus dose in group BOLI was 2.9 (1.3–4.3) mg kg^?1; interval between and number of boluses required were 4 (1–8) minutes and 6 (4–11) boluses respectively. Total dose of propofol was 19 (12.3–37.1) mg kg^?1. Awakening between boluses was very abrupt. In group CRI, propofol infusion rate was 0.85 (0.8–0.9) mg kg^?1 minute^?1, and anaesthesia was stable. Body temperature, heart and respiratory rates, oxygen saturation (by pulse oximeter) and reflexes did not differ between groups. Oxygen saturations (from pulse oximeter readings) were low in some birds. Following anaesthesia, all birds recovered within 40 minutes. In 55 % of all, transient signs of central nervous system excitement occurred during recovery.Conclusions and clinical relevance8 mg kg^?1 propofol appears an adequate induction dose for mute swans. For maintenance, a CRI of 0.85 mg kg^?1 minute^?1 produced stable anaesthesia suitable for painless clinical procedures. In contrast bolus administration, was unsatisfactory as birds awoke very suddenly, and the short intervals between bolus requirements hampered clinical procedures. Administration of additional oxygen throughout anaesthesia might reduce the incidence of low arterial haemoglobin saturation.     

Effect of alfaxalone infusion on the electroencephalogram of dogs anaesthetized with halothane

ObjectiveTo describe the effects of alfaxalone on the canine electroencephalogram (EEG).Study designExperimental study.AnimalsEight healthy adult Huntaway dogs.MethodsAnaesthesia was induced with propofol and maintained with halothane (0.85-0.95 end-tidal volume %) in oxygen. Animals were ventilated to maintain stable end-tidal CO₂ and halothane concentrations. Following a 30 minute stabilisation period, alfaxalone (0.5 mg kg^?1) was infused intravenously over a 5 minute period. The electroencephalogram was recorded from the beginning of the stabilisation period until 60 minutes following the start of alfaxalone treatment. Data were subjected to fast Fourier transformation, and median frequency, 95% spectral edge frequency and total EEG power were calculated. Two-factorial repeated measures anova (time and EEG channels were factors) was used for statistical analysis (p<0.05).ResultsA shift in the dominant frequency band from beta to delta after alfaxalone treatment and occasional burst suppression were observed. Median frequency decreased significantly below baseline (9.2 ± 1.4 Hz) (mean ± SD) during alfaxalone infusion. The lowest value (4.8 ± 1.2 Hz) was recorded 5 minutes after the start of infusion. Spectral edge frequency also decreased below baseline (26.2 ± 1.5 Hz) and the lowest value (22.6 ± 1.5 Hz) also was detected at 5 minutes after the start of infusion. Total EEG power did not change significantly. In some frequencies EEG power increased soon after the start of alfaxalone infusion, then decreased below baseline later (biphasic pattern).Conclusions and clinical relevanceAlfaxalone induced biphasic changes on EEG and decreased F₅₀ and F₉₅ in halothane anaesthetized dogs.     

The effects of propofol, isoflurane and sevoflurane on vecuronium infusion rates for surgical muscle relaxation in dogs

OBJECTIVE: To compare the constant rate infusion (CRI) of vecuronium required to maintain a level of neuromuscular blockade adequate for major surgeries, e.g. thoracotomy or laparotomy, in dogs anaesthetized with a CRI of fentanyl and either propofol, isoflurane or sevoflurane. STUDY DESIGN: Prospective, randomized, cross-over study. ANIMALS: Thirteen male beagles (age, 9-22 months; body mass 6.3-11.3 kg). MATERIALS AND METHODS: Dogs were anaesthetized with propofol (24 mg kg(-1) hour(-1) IV CRI; group P), isoflurane (1.3% end-tidal concentration; group I) or sevoflurane (2.3% end-tidal concentration; group S) with fentanyl (5 microg kg(-1) hour(-1) IV, CRI). Sixty to seventy minutes after induction of anaesthesia, vecuronium was administered at a rate of 0.4, 0.3 and 0.2 mg kg(-1) hour(-1) in groups P, I and S respectively. To determine the degree of neuromuscular block, a peripheral nerve was stimulated electrically using the train-of-four (TO4) stimulus pattern. Evoked muscle contractions were evaluated using a neuromuscular monitoring device. Once the TO4 ratio reached 0, the continuous infusion rate was decreased and adjusted to maintain a TO4 count of 1. Continuous infusion was continued for 2 hours. The infusion rate of vecuronium was recorded 20, 40, 60, 80, 100 and 120 minutes after the start of infusion. RESULTS: The mean continuous infusion rates of vecuronium during stable infusion were 0.22 +/- 0.04 (mean +/- SD), 0.10 +/- 0.02 and 0.09 +/- 0.02 mg kg(-1) hour(-1) in groups P, I and S respectively. There were statistically significant differences between the rates in groups P and I and between the rates in groups P and S. Conclusions and clinical relevance In healthy dogs, the recommended maintenance infusion rate of vecuronium is 0.2 mg kg(-1) hour(-1) under CRI propofol-fentanyl anaesthesia and 0.1 mg kg(-1) hour(-1) during CRI fentanyl-isoflurane or sevoflurane anaesthesia.     

Cardiopulmonary effects of combined xylazine-guaiphenesin-ketamine infusion and extradural (inter-coccygeal lidocaine) anaesthesia in calves

Objective To investigate the cardiopulmonary effects of a xylazine–guaiphenesin–ketamine infusion combined with inter‐coccygeal extradural (lidocaine) anaesthesia in calves. Study design Prospective study. Animals Five Holstein Friesian calves (one steer, four heifers) aged 6 weeks weighing 65.2 ± 2.7 kg. Materials and methods Calves were anaesthetized with isoflurane in oxygen for instrumentation. At least 12 hours later, xylazine (0.2 mg kg^?1 IM) was given. After 15 minutes, an infusion of xylazine hydrochloride (0.1 mg mL^?1), guaiphenesin (50 mg mL^?1) and ketamine (1 mg mL^?1) (X–G–K) was infused at a rate of 1.1 mL kg^?1 hour^?1 IV. Oxygen (4 L minute^?1) was delivered by nasotracheal tube 30 minutes later. Inter‐coccygeal (Co₁–Co₂) extradural anaesthesia (lidocaine 2%, 0.18 mL kg^?1) was administered 30 minutes later. Cardiopulmonary variables were obtained in the unsedated standing calves 10 minutes after xylazine, 15 and 30 minutes after X–G–K without O₂, 15 and 30 minutes after X–G–K with O₂ and 5, 15, 30, 45 and 60 minutes after extradural anaesthesia. Data were analysed using a repeated measurement analysis of variance including an autoregressive covariance structure of order 1 (correlations at different time intervals). Results Xylazine caused significant (p < 0.05) decreases in heart rate (HR), cardiac output (Qt) and index (CI), stroke volume and stroke index, mean, systolic and diastolic arterial blood pressure (MAP, SAP, DAP), left (LVWSI) and right ventricular stroke work index (RVWSI), mean, systolic and diastolic pulmonary arterial pressure (MPAP, SPAP, DPAP), arterial pH, arterial oxygen tension (P_aO₂), arterial base excess, arterial HCO₃^? concentration, arterial saturation, packed cell volume, arterial and venous oxygen content (C_aO₂, C_vO₂), O₂ consumption and O₂ delivery (V?O₂, ?O₂). Increases in systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were observed. During X–G–K infusion without O₂, HR, Qt and CI increased gradually while SVR, PVR and MAP decreased. Left ventricular stroke work index and P_aO₂ remained constant, while O₂ supplementation improved P_aO₂. Coccygeal extradural anaesthesia had little effect on cardiopulmonary variables. Respiratory rate (f) and P_aCO₂ significantly increased over the experiment. Conclusions and clinical relevance Xylazine caused adverse cardiopulmonary effects in calves. Improvement occurred during xylazine–guiaphenesin–ketamine infusion. Cardiac index and arterial blood pressure remained below baseline values while sustained increases in respiration rate and P_aCO₂ were observed. Inter‐coccygeal extradural anaesthesia had only minor effects. Oxygen supplementation proved advantageous during guiaphenesin, ketamine and xylazine infusion in healthy calves in combination with coccygeal extradural anaesthesia induced persistent cardiopulmonary depression.     

Development and optimization of a fentanyl pharmacokinetic model for target-controlled infusion in anaesthetized dogs

ObjectiveTo investigate pharmacokinetics (PK) of fentanyl administered by target-controlled infusion (TCI), and to develop a PK model optimized by covariates for TCI in anaesthetized dogs.Study designProspective clinical study.AnimalsA group of 20 client-owned dogs with spinal pain undergoing anaesthesia for magnetic resonance imaging.MethodsFentanyl was administered as an infusion to 20 anaesthetized dogs using a TCI system incorporating a previously described fentanyl two-compartment PK. Arterial blood samples were collected at specific time points during the infusion and over 60 minutes post-infusion for measurement of fentanyl plasma concentrations. The predictive performance of the Sano PK model was assessed by comparing predicted and measured plasma concentrations. A population PK analysis was then performed using a nonlinear mixed-effect modelling approach, allowing inter- and intra-individual variability estimation. Finally, a quantitative stepwise evaluation of the influence of various covariates such as weight, body condition score, size, size-related age, sex and type of premedication on the PK model was considered.ResultsOverall predictive performance of the Sano PK set of variables was not clinically acceptable in anaesthetized dogs. Fentanyl PK was best described by a three-compartment model. Weight and sex were found to affect the volume of distribution of the central compartment. Addition of these two covariate/variable associations resulted in a reduction of the objective function value (OFV) from –340.18 to –448.34, and of the median population weighted residual and the median population absolute weighted residual from 16.1% and 38.6% to 3.9% and 20.3%, respectively. Fentanyl infusions at measured concentrations up to 5.4 ng mL^–1 in sevoflurane-anaesthetized dogs resulted in stable anaesthesia and smooth recoveries without complications.Conclusions and clinical relevanceA population three-compartment PK model for fentanyl TCI in anaesthetized dogs was developed. Weight and sex have been detected and incorporated as significant covariates.     

A comparison of cardiopulmonary effects and anaesthetic requirements of two dexmedetomidine continuous rate infusions in alfaxalone-anaesthetized Greyhounds

Objective

To determine the effects of two dexmedetomidine continuous rate infusions on the minimum infusion rate of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent haemodynamic and recovery effects in Greyhounds undergoing laparoscopic ovariohysterectomy.