A controlled randomized clinical trial to assess postoperative analgesia after thiopental–isoflurane anaesthesia or total intravenous anaesthesia with alfaxalone in dogs

Alfaxalone, a synthetic neuroactive steroid, has been attributed with properties including sedation, anaesthesia and analgesia. The clinical relevance of any analgesic properties of alfaxalone has not been demonstrated. This study was a prospective, blinded, randomized, negative control clinical trial in 65 healthy dogs presented for ovariohysterectomy. Anaesthesia was induced and maintained, for Group 1 (TIVA) dogs (n = 30) with intravenous alfaxalone alone and for Group 2 dogs (n = 35) with thiopental followed by isoflurane in 100% oxygen inhalation. After ovariohysterectomy, quantitative measures of pain or nociception were recorded at 15 min intervals for 4 hr using three independent scoring systems, a composite measure pain scale (CMPS), von Frey threshold testing and measures of fentanyl rescue analgesia. The mean CMPS scores of Group 2 (THIO/ISO) dogs remained higher than Group 1 (TIVA) dogs from 15 to 135 min post‐surgery but this difference was not statistically significant. There were no significant differences between groups in the proportions of dogs requiring rescue fentanyl analgesia, the total fentanyl dose used or the time to first fentanyl dose. The Von Frey threshold testing was found to be unsuitable for measurement of pain in this experimental model. When administered as total intravenous anaesthesia, alfaxalone did not provide analgesia in the postoperative period.     

Serum biochemical indicators of hepatobiliary function in dogs following prolonged anaesthesia with sevoflurane or isoflurane

Objective To investigate the changes in serum enzymes considered as biochemical indicators of hepatobiliary function in dogs following 5 hours of anaesthesia with isoflurane (ISO) or sevoflurane (SEVO). Study design Experimental randomized crossover study, with intervals of at least 15 days between successive treatments. Animals Eight healthy adult mongrel dogs, four male, four female, weight 13.6–21.6 kg. Methods Treatments consisted of anaesthesia with ISO or SEVO at 1 or 1.5 minimum alveolar concentration (MAC) delivered in oxygen. MAC was taken as 1.39% for ISO and 2.36% for SEVO. Anaesthesia was induced by mask then, after endotracheal intubation, maintained according to the treatment protocol using a small animal circle system. Cardiopulmonary monitoring was carried out. Venous blood samples, obtained by needle puncture, were taken at 24 hours and 2, 7 and 14 days post anaesthesia. Serum concentrations of total protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, (LDH), alkaline phosphatase (ALP), gamma‐glutamyltransferese and total bilirubin were measured. Changes with time and with treatment were compared by Friedman analysis, Wilcoxon Signed test and Kruskal‐Wallis test as relevant. p‐ value < 0.05 was considered significant. Results Compared to base‐line values, at 24 hours post‐anaesthesia there were significant increases in AST, ALT, ALP and LDH following one or more of the treatments, but by 2 days residual changes were not significant. At 24 hours, AST for treatment 1.5 MAC ISO was higher than 1 MAC ISO (p < 0.002), and LDH higher for 1.5 MAC SEVO than 1 MAC SEVO. Conclusion and clinical relevance Both ISO and SEVO, at concentrations used for clinical anaesthesia, produce transient moderate effects on some hepatobiliary enzyme concentrations in dogs.     

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.     

Effect of hypothermia on recovery from general anaesthesia in the dog

OBJECTIVE: To discern the effects of anaesthesia protocols and decreasing core body temperature on time to recovery from general anaesthesia. MATERIALS AND METHODS: Healthy adult dogs undergoing desexing surgery were enrolled. More excitable dogs were premedicated with intramuscular acepromazine and morphine; calmer dogs were not premedicated. Anaesthesia was induced using halothane, isoflurane or sevoflurane delivered by mask, or by intravenous propofol, and maintained in standard fashion using one of the three inhalant agents. Thermostat controlled heat mats were used during surgical preparation and surgery. Oesophageal temperature was recorded throughout surgery. The time from cessation of anaesthetic administration until the dog successfully raised itself to sternal recumbency was considered the time of recovery. RESULTS: Sixty-nine dogs completed the study, 42 males anaesthetised for 60.4 +/- 20.5 min, and 27 females anaesthetised for 85.4 +/- 33.2 min. Oesophageal temperature at the end of surgery was 36.8 +/- 0.80 degrees C. Oesophageal temperature had a significant effect on recovery time, with lower temperatures contributing to slower recoveries. Premedication significantly lengthened recovery times. The choice of induction or maintenance anaesthetic agent had no effect on recovery time. DISCUSSION: Hypothermia is a common complication of general anaesthesia and surgery. Amongst other deleterious effects, it is associated with slower recovery from anaesthesia, likely due to a number of different mechanisms.     

Dexmedetomidine constant rate infusion for 24 hours during and after propofol or isoflurane anaesthesia in dogs

OBJECTIVE: To evaluate cardiovascular and respiratory effects and pharmacokinetics of a 24-hour intravenous constant rate infusion (CRI) of dexmedetomidine (DMED) during and after propofol (PRO) or isoflurane (ISO) anaesthesia in dogs. STUDY DESIGN: Prospective, randomized, cross-over study. ANIMALS: Ten healthy adult Beagles. METHODS: Instrumented dogs received a DMED-loading bolus (25 microg m(-2)) at time 0 followed by a 24-hour CRI (25 microg m(-2) hour(-1)), with PRO or ISO induction/maintenance of anaesthesia during the first 2 hours (PRO and ISO treatment groups, respectively). Cardiovascular, respiratory, blood gas, airway gas, serum chemistry variables and DMED plasma concentration data were collected at -15, 5, 15, 30, 45, 60, 90 and 120 minutes. A number of cardiorespiratory and tissue oxygenation variables were calculated from the above data. After the 2-hours of anaesthesia, heart and respiratory rates and electrocardiograms were recorded and DMED plasma concentrations were determined for up to 26 hours. RESULTS: Vasopressor effects and the decrease in heart rate (HR) and cardiac index induced by DMED were greater for PRO than ISO, but were within clinically acceptable ranges. Adequate oxygenation was maintained above the critical O(2) delivery level. The overall incidence of unfavourable arrhythmias was low and tended to vary inversely with HR. Mean DMED plasma concentration ranged from 0.23 to 0.47 ng mL(-1) for both groups during the 24-hour CRI with a mean elimination half-life of approximately 0.46 hour. CONCLUSION AND/CLINICAL RELEVANCE: DMED CRI resulted in typical alpha(2)-agonist induced haemodynamic changes with minimal respiratory effects, and appeared to be an efficacious adjunct during and after PRO or ISO anaesthesia in healthy dogs.     

The risk of passive regurgitation during general anaesthesia in a population of referred dogs in the UK

Objective To evaluate the risk of passive regurgitation during anaesthesia, and to identify major factors associated with this in dogs attending the Queen Mother Hospital for Animals (QMHA), the Royal Veterinary College. Study design A case‐control study nested within the cohort of dogs undergoing anaesthesia with inhalation agents. Animal population All dogs undergoing general anaesthesia at the referral hospital between October 2006 and September 2008 (4271 cases). Methods All dogs anaesthetized at the QMHA during the study period were included. Regurgitating cases were defined as dogs for which reflux material was observed at the external nares or in the mouth, either during anaesthesia or before return to normal consciousness immediately after general anaesthesia. The risk of regurgitation was estimated and risk factors for regurgitation were evaluated with multivariable logistic regression (p < 0.05). Results The overall risk of regurgitation was 0.96% (41 cases out of 4271 anaesthetics, 95% confidence interval [95% CI] 0.67–1.25%). Exclusion of animals where pre‐existing disease was considered a contributing factor to regurgitation (n = 14) resulted in a risk of passive regurgitation of 0.63% (27 cases of 4257 anaesthetics, 95% CI 0.40–0.87%). In the multivariable logistic regression model, procedure and patient weight were significantly associated with regurgitation. Dogs undergoing orthopaedic surgery were 26.7 times more likely to regurgitate compared to dogs undergoing only diagnostic procedures. Dogs weighing more than 40 kg were approximately five times more likely to regurgitate than those weighing <20 kg. Conclusions and clinical relevance This study highlights the rare but important occurrence of perioperative regurgitation and identifies that dogs undergoing orthopaedic procedures, and those weighing more than 40 kg, are particularly at risk. Further work is required to evaluate the reasons for these observations.     

A comparison of the duration and quality of recovery from isoflurane, sevoflurane and desflurane anaesthesia in dogs undergoing magnetic resonance imaging

ObjectiveTo compare the recovery after anaesthesia with isoflurane, sevoflurane and desflurane in dogs undergoing magnetic resonance imaging (MRI) of the brain.Study designProspective, randomized clinical trial.AnimalsThirty‐eight dogs weighing 23.7 ± 12.6 kg.MethodsFollowing pre‐medication with meperidine, 3 mg kg^?1 administered intramuscularly, anaesthesia was induced intravenously with propofol (mean dose 4.26 ± 1.3 mg kg^?1), the trachea was intubated, and an inhalational anaesthetic agent was administered in oxygen. The dogs were randomly allocated to one of three groups: group I (n = 13) received isoflurane, group S (n = 12) received sevoflurane and group D (n = 13) received desflurane. Parameters recorded included cardiopulmonary data, body temperature, end‐tidal anaesthetic concentration, duration of anaesthesia, and recovery times and quality. Qualitative data were compared using chi‐squared and Fisher's exact tests and quantitative data with anova and Kruskal–Wallis test. Post‐hoc comparisons for quantitative data were undertaken with the Mann–Whitney U‐test.ResultsThe duration of anaesthesia [mean and standard deviation (SD)] in group I was: 105.3 (27.48) minutes, group S: 120.67 (19.4) minutes, and group D: 113.69 (26.68) minutes (p = 0.32). Times to extubation [group I: 8 minutes, (interquartile range 6–9.5), group S: 7 minutes (IQR 5–7), group D: 5 minutes (IQR 3.5–7), p = 0.017] and to sternal recumbency [group I: 11 minutes (IQR 9.5–13.5), group S: 9.5 minutes (IQR 7.25–11.75), group D: 7 minutes (range 3.5–11.5), p = 0.048] were significantly different, as were times to standing. One dog, following sevoflurane, had an unacceptable quality of recovery, but most other recoveries were calm, with no significant difference between groups.Conclusions and clinical relevanceAll three agents appeared suitable for use. Dogs’ tracheas were extubated and the dogs recovered to sternal recumbency most rapidly after desflurane. This may be advantageous for animals with some neurological diseases and for day case procedures.     

Recovery from neuromuscular block in dogs: restoration of spontaneous ventilation does not exclude residual blockade

ObjectiveTo evaluate if return of spontaneous ventilation to pre-relaxation values indicates complete recovery from neuromuscular blockade.Study designProspective, with each individual acting as its own control.AnimalsTen healthy adult female Beagle dogs weighing 6.2–9.4 kg.MethodsDogs were anesthetized with propofol, dexemedetomidine and isoflurane. Spontaneous ventilation was assessed by measuring end-tidal CO₂, expired tidal volume, peak inspiratory flow, respiratory rate and minute ventilation. Vecuronium 25 μg kg^?1 IV was administered and neuromuscular block was evaluated by measuring the train-of-four (TOF) ratio with acceleromyography in the hind limb. During spontaneous recovery from neuromuscular block, the TOF ratio when each ventilatory variable returned to baseline was recorded.ResultsThis dose of vecuronium produced moderate neuromuscular block in all dogs, with TOF ratio values of 0–18% at maximal block. Expired tidal volume, peak inspiratory flow and minute ventilation returned to pre-relaxation values when the median TOF ratio was ≤ 20%. The median TOF ratio was 42% when the end-tidal CO₂ returned to pre-relaxation values.Conclusions and clinical relevanceSignificant residual neuromuscular block could be measured at the hind limb with acceleromyography when ventilation had spontaneously returned to pre-vecuronium values. Monitoring spontaneous ventilation, including end-tidal CO₂, expired tidal volume, peak inspiratory flow or minute ventilation cannot be used as a surrogate for objective neuromuscular monitoring, and this practice may increase the risk of postoperative residual paralysis.     

Diabetes mellitus does not affect the neuromuscular blocking action of atracurium in dogs

Objective

To compare the duration of action of atracurium in diabetic and nondiabetic dogs.

A comparison in dogs of medetomidine,with or without MK‐467, and the combination acepromazine‐butorphanol as premedication prior to anaesthesia induced by propofol and maintained with isoflurane

ObjectiveTo compare the haemodynamic effects of three premedicant regimens during propofol-induced isoflurane anaesthesia.Study designProspective, randomized cross-over study.AnimalsEight healthy purpose-bred beagles aged 4 years and weighing mean 13.6 ± SD 1.9 kg.MethodsThe dogs were instrumented whilst under isoflurane anaesthesia prior to each experiment, then allowed to recover for 60 minutes. Each dog was treated with three different premedications given intravenously (IV): medetomidine 10 μg kg^?1 (MED), medetomidine 10 μg kg^?1 with MK-467 250 μg kg^?1 (MMK), or acepromazine 0.01 mg kg^?1 with butorphanol 0.3 mg kg^?1 (AB). Anaesthesia was induced 20 minutes later with propofol and maintained with isoflurane in oxygen for 60 minutes. Heart rate (HR), cardiac output, arterial blood pressures (ABP), central venous pressure (CVP), respiratory rate, inspired oxygen fraction, rectal temperature (RT) and bispectral index (BIS) were measured and arterial and venous blood gases analyzed. Cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery index (DO₂I), systemic oxygen consumption index (VO₂I) and oxygen extraction (EO₂) were calculated. Times to extubation, righting, sternal recumbency and walking were recorded. The differences between treatment groups were evaluated with repeated measures analysis of covariance.ResultsHR, CI, DO₂I and BIS were significantly lower with MED than with MMK. ABP, CVP, SVRI, EO₂, RT and arterial lactate were significantly higher with MED than with MMK and AB. HR and ABP were significantly higher with MMK than with AB. However, CVP, CI, SVRI, DO₂I, VO₂I, EO₂, T, BIS and blood lactate did not differ significantly between MMK and AB. The times to extubation, righting, sternal recumbency and walking were significantly shorter with MMK than with MED and AB.Conclusions and clinical relevanceMK-467 attenuates certain cardiovascular effects of medetomidine in dogs anaesthetized with isoflurane. The cardiovascular effects of MMK are very similar to those of AB.     

Clinical efficacy and cardiorespiratory effects of alfaxalone, or diazepam/fentanyl for induction of anaesthesia in dogs that are a poor anaesthetic risk

ObjectiveTo evaluate the clinical efficacy and cardiorespiratory effects of alfaxalone as an anaesthetic induction agent in dogs with moderate to severe systemic disease.Study designRandomized prospective clinical study.AnimalsForty dogs of physical status ASA III-V referred for various surgical procedures.MethodsDogs were pre-medicated with intramuscular methadone (0.2 mg kg^?1) and allocated randomly to one of two treatment groups for induction of anaesthesia: alfaxalone (ALF) 1–2 mg kg^?1 administered intravenously (IV) over 60 seconds or fentanyl 5 μg kg^?1 with diazepam 0.2 mg kg^?1± propofol 1–2 mg kg^?1 (FDP) IV to allow endotracheal intubation. Anaesthesia was maintained with isoflurane in oxygen and fentanyl infusion following both treatments. All dogs were mechanically ventilated to maintain normocapnia. Systolic blood pressure (SAP) was measured by Doppler ultrasound before and immediately after anaesthetic induction, but before isoflurane administration. Parameters recorded every 5 minutes throughout subsequent anaesthesia were heart and respiratory rates, end-tidal partial pressure of carbon dioxide and isoflurane, oxygen saturation of haemoglobin and invasive systolic, diastolic and mean arterial blood pressure. Quality of anaesthetic induction and recovery were recorded. Continuous variables were assessed for normality and analyzed with the Mann Whitney U test. Repeated measures were log transformed and analyzed with repeated measures anova (p < 0.05).ResultsTreatment groups were similar for continuous and categorical data. Anaesthetic induction quality was good following both treatments. Pre-induction and post-induction systolic blood pressure did not differ between treatments and there was no significant change after induction. The parameters measured throughout the subsequent anaesthetic procedures did not differ between treatments. Quality of recovery was very, quite or moderately smooth.Conclusions and clinical relevanceInduction of anaesthesia with alfaxalone resulted in similar cardiorespiratory effects when compared to the fentanyl-diazepam-propofol combination and is a clinically acceptable induction agent in sick dogs.     

A dose titration study into the effects of diazepam or midazolam on the propofol dose requirements for induction of general anaesthesia in client owned dogs,premedicated with methadone and acepromazine

ObjectiveTo assess the effect of a benzodiazepine co–induction on propofol dose requirement for induction of anaesthesia in healthy dogs, to describe any differences between midazolam and diazepam and to determine an optimal benzodiazepine dose for co–induction.Study designProspective, randomised, blinded placebo controlled clinical trial.AnimalsNinety client owned dogs (ASA I–III, median body mass 21.5kg (IQR 10–33)) presented for anaesthesia for a variety of procedures.MethodsDogs were randomised to receive saline 0.1 mL kg^?1, midazolam or diazepam at 0.2, 0.3, 0.4 or 0.5 mg kg^?1. All dogs received 0.01 mg kg^?1 acepromazine and 0.2 mg kg^?1 methadone intravenously (IV). Fifteen minutes later, sedation was assessed and scored prior to anaesthetic induction. Propofol, 1 mg kg^?1, was administered IV, followed by the treatment drug. Further propofol was administered until endotracheal intubation was possible. Recorded data included patient signalment, sedation score, propofol dosage and any adverse reactions.ResultsMidazolam (all groups combined) significantly reduced propofol dose requirement compared to saline (p < 0.001) and diazepam (p = 0.008). Midazolam (0.4 mg kg^?1) significantly reduced propofol dose requirement (p = 0.014) compared to saline, however other doses failed to reach statistical significance. Diazepam did not significantly reduce propofol dose requirement compared to saline (p = 0.089). Dogs weighing <5 kg, regardless of treatment group, required a greater propofol dose than those weighing 5–40 kg (p = 0.002) and those >40 kg (p = 0.008). Dogs which were profoundly sedated required less propofol than those which were mildly sedated (p < 0.001) and adequately sedated (p = 0.003).Conclusions and clinical relevanceMidazolam (0.4 mg kg^?1) given IV after 1 mg kg^?1 of propofol significantly reduced the further propofol dose required for intubation compared to saline. At the investigated doses, diazepam did not have significant propofol dose sparing effects.     

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.