Correlation between clinical signs of depth of anaesthesia and cerebral state index responses in dogs with different target-controlled infusions of propofol

ObjectiveTo evaluate if the cerebral state index (CSI), measured by a Cerebral State Monitor (CSM), can predict depth of anaesthesia as assessed clinically or by estimated propofol plasma concentrations.Study designProspective clinical study.AnimalsFourteen mixed breed dogs, weighing 24.5 ± 4.7 kg, scheduled to undergo neutering procedures.MethodsDogs were premedicated with 0.05 mg kg^?1 acepromazine intramuscularly. The CSM and cardiovascular monitoring equipment were attached. Anaesthesia was induced with propofol using a target controlled infusion (TCI) to varying plasma propofol targets (PropCp). Following endotracheal intubation the dogs were ventilated with oxygen. Anaesthetic maintenance was with propofol by TCI. A PropCp of 3 μg dL^?1 was set initially, then PropCps were increased in 1 μg dL^?1 steps to 7, 9 and then 11 μg dL^?1. Each PropCp was held constant for a 5 minute period, at the end of which depth of anaesthesia was classified using a previously evaluated scale of ‘planes’ based on palpebral and corneal reflexes and eye position. Cerebral state index (CSI), burst suppression (BSR) and electromyogram were measured at these time points. The prediction probability (PK) of these variables, or of the PropCp in predicting depth of anaesthesia was calculated.ResultsThe PKs for predicting anaesthetic planes were 0.74, 0.91, 0.76 and 0.78 for CSI, BSR, EMG and PropCp, respectively. The PKs for PropCp to predict CSI, BSR and EMG were 0.65, 0.71 and 0.65 respectively.Conclusion and clinical relevance The Cerebral State Monitor was able to detect very deep planes of anaesthesia when BSR occurs, but was not able to distinguish between the intermediate anaesthetic planes likely to be used in clinical anaesthesia.     

Brain monitoring in dogs using the cerebral state index during the induction of anaesthesia via target-controlled infusion of propofol

The aim of this study was to evaluate the correlation between the cerebral state index (CSI) and the estimated propofol plasma concentrations in dogs during induction of anaesthesia. Fifteen healthy dogs undergoing scheduled routine surgical procedures were enrolled in this study. Target controlled infusion (TCI) software, based on the pharmacokinetic model for propofol, was used to control the syringe pump and to estimate plasma propofol concentrations (PropCp) and the CSI values every five-seconds. Three electrodes placed in the centre of the forehead, on the left side of the forehead and on the left mastoid were used to collect the electroencephalographic (EEG) signal converted by the cerebral state monitor into the CSI. The cerebral electrical changes induced by increasing propofol concentrations appear to be detected by CSI monitoring in dogs. The negative correlation between CSI and PropCp demonstrates that the CSI could be used to assess electrical brain activity in dogs during the induction of anaesthesia with propofol.     

Biochemical and haematological changes following prolonged halothane anaesthesia in horses

Six healthy horses were anaesthetised with halothane (1·2 times the horse minimal alveolar concentration) in oxygen for more than 12 hours. Serum bilirubin, aspartate aminotransferase, alkaline phosphatase and L-iditol dehydrogenase values were significantly (P<0·05) increased for up to nine days after anaesthesia. These changes suggest au anaesthesia related liver dysfunction. Creatine kinase increased to an average of more than 1400 iu litre⁻¹ 24 hours after anaesthesia and this change is indicative of muscle cell disruption. Renal-associated biochemical results, (that is serum creatinine and inorganic phosphate concentrations) were significantly increased transiently and are indicative of reduced renal function during and immediately after anaesthesia. Plasma concentrations of eicosanoids (6-keto-PGF_1a, PGF_2a, pge and thromboxane) following anaesthesia were not different from preanaesthetic values. The magnitude of liver and muscle cell related increases in serum enzyme activities resulting from prolonged halothane anaesthesia was in excess of that previously reported for anaesthesia of shorter duration.     

A clinical trial of propofol infusion anaesthesia in dogs

Studies were carried out on 40 dogs premedicated with acepromazine (0·05 mg. kg^-1) and atropine (0·02 mg. kg^-1) to determine the minimum infusion rate of propofol needed to maintain anaesthesia and to compare the quality of the anaesthesia with that produced by halothane/nitrous oxide/oxygen. In 30 dogs anaesthesia was induced with propofol and maintained with a continuous infusion and in the other ten dogs anaesthesia was induced with thiopentone and maintained with the inhalation agents. An infusion rate of 0·4 mg. kg^-1 min^-1 of propofol produced surgical anaesthesia in dogs breathing oxygen or oxygen-enriched air. Cardiovascular and respiratory effects were similar to those in dogs anaesthetized with halothane/nitrous oxide and with both anaesthetic regimens myocardial oxygen consumption appeared to increase with increasing duration of anaesthesia. A possible familial susceptibility resulting in a more prolonged recovery was revealed and propofol infusion was associated with a 16 per cent incidence of vomiting in the recovery period. It was concluded that in canine anaesthesia the continuous infusion of propofol to maintain anaesthesia in healthy dogs was safe but less satisfactory than the use of halothane/nitrous oxide.     

Rumen degradation characteristics of sweet potato foliage and performance by local and crossbred calves fed milk and foliage from three cultivars

The study investigated rumen dry matter (DM) degradability characteristics in a completely randomized design and the effects of milk, sweet potato foliage (SPF) from three cultivars (A = TIS-87/0087; B = TIS-8164; C = TIS-2532.OP.1.13), dried brewers' grains (DBG) and cottonseed meal (CSM) as supplements to Panicum maximum (Panicum) for pre-weaned calves in randomized complete block designs. Diet 1 = milk + SPF-A foliage + Panicum, Diet 2 = milk + SPF-B foliage + Panicum, Diet 3 = milk + SPF-C foliage + Panicum, and Diet 4 = milk + DBG & CSM + Panicum (as control). Dry matter (130 ± 0.4 to 864 ± 3.9 g kg^− 1), ash (54 ± 4.2 to 173 ± 2.8 g kg^− 1 DM), OM (827 ± 4.2 to 946 ± 5.7 g kg^− 1 DM), N (7.4 ± 0.6 to 38.6 ± 1.4 g kg^− 1 DM), and NDF (439 ± 1.4 to 774 ± 8.5 g kg^− 1 DM) contents were highly significant (P < 0.01). In Trial I, 16 pre-weaned calves were used over 70 d with milk intake (34.8 ± 4.4 ml kg W^− 0.75 d^− 1), Panicum DMI (22.3 ± 2.77 g kg W^− 0.75 d^− 1), total DMI (35.7 ± 2.83 g kg W^− 0.75 d^− 1), and LWG (198 ± 44.6 g d^− 1) not significantly different (P > 0.05). Supplement DMI varied (P < 0.05) from 11.6 g kg W^− 0.75 d^− 1 in Diet 3 to 16.6 g kg W^− 0.75 d^− 1 in Diet 4. In Trial II, 16 pre-weaned local and crossbred calves were involved over 77 d with initial age of calves, Panicum intake, metabolic DMI, and LWG similar (P > 0.05) among crosses. Birthweight varied (P < 0.05) from 17.3 kg for N'Dama × Jersey crosses to 21.2 kg for White Fulani × Brown Swiss crosses. Supplement and total DMI ranged (P < 0.05) from 172 to 483 g d^− 1 for N'Dama × Jersey crosses to 233 and 674 g d^− 1 for non-inseminate or purebred calves, respectively. The LWG in the White Fulani × Brown Swiss and the N'Dama × Jersey calves were respectively 30% and 24% better, though not significantly, than purebred calves. In Trial III, rumen DM degradability characteristics of feeds in three N'Dama steers showed no significant differences (P > 0.05) in slowly degradable fraction (b) and rate of degradation of b (c). Soluble fraction (a), 48-h degradation, potential degradability (PD) and effective degradability (ED) varied significantly (P < 0.05) and were lowest in Panicum, but similar for foliage among the three sweet potato cultivars. Panicum fodder showed improvements in degradation characteristics with supplementation.     

Comparison of propofol with ketofol,a propofol‐ketamine admixture,for induction of anaesthesia in healthy dogs

ObjectiveTo compare anaesthetic induction in healthy dogs using propofol or ketofol (a propofol-ketamine mixture).Study designProspective, randomized, controlled, ‘blinded’ study.AnimalsSeventy healthy dogs (33 males and 37 females), aged 6–157 months and weighing 4–48 kg.MethodsFollowing premedication, either propofol (10 mg mL^?1) or ketofol (9 mg propofol and 9 mg ketamine mL^?1) was titrated intravenously until laryngoscopy and tracheal intubation were possible. Pulse rate (PR), respiratory rate (f_R) and arterial blood pressure (ABP) were compared to post-premedication values and time to first breath (TTFB) recorded. Sedation quality, tracheal intubation and anaesthetic induction were scored by an observer who was unaware of treatment group. Mann–Whitney or t-tests were performed and significance set at p = 0.05.ResultsInduction mixture volume (mean ± SD) was lower for ketofol (0.2 ± 0.1 mL kg^?1) than propofol (0.4 ± 0.1 mL kg^?1) (p < 0.001). PR increased following ketofol (by 35 ± 20 beats minute^?1) but not consistently following propofol (4 ± 16 beats minute^?1) (p < 0.001). Ketofol administration was associated with a higher mean arterial blood pressure (MAP) (82 ± 10 mmHg) than propofol (77 ± 11) (p = 0.05). TTFB was similar, but ketofol use resulted in a greater decrease in f_R (median (range): ketofol -32 (-158 to 0) propofol -24 (-187 to 2) breaths minute^?1) (p < 0.001). Sedation was similar between groups. Tracheal intubation and induction qualities were better with ketofol than propofol (p = 0.04 and 0.02 respectively).Conclusion and clinical relevanceInduction of anaesthesia with ketofol resulted in higher PR and MAP than when propofol was used, but lower f_R. Quality of induction and tracheal intubation were consistently good with ketofol, but more variable when using propofol.     

Effects of intermittent suckling on the performance and digestive efficiency of Iberian piglets weaned at 35 days of age

During two consecutive replicates Iberian sows (n = 20) were subjected either to a conventional lactation (C) or intermittent suckling (IS). Piglets in the C treatment had free access to the dam. Piglets on IS treatment were separated from the sow during 6 h on days 29 and 30, 8 h on days 31 and 32, and 10 h on days 33 and 34. Litters on both treatments were weaned at 35 days of age and offered a starter diet until day 60 of age. The apparent digestibility (ApD) of nutrients and gross energy (GE) of the post-weaning diet was measured using Cr₂O₃ as external indigestible marker. Litters on IS tended to increase solid feed intake during the milk restriction (125 ± 12 vs. 70 ± 19 g piglet^− 1 day^− 1; P = 0.08). Feed intake was improved by IS during the second week post-weaning (676 ± 17 vs. 497 ± 12 g piglet^− 1 day^− 1, P < 0.01), but differences were totally offset after the 7th week of age. Differences in average growth rate of litters on C and IS treatments did not attain statistical significance during the period of restriction and in the first week post-weaning. Litters on IS showed increased growth rate during the second week post-weaning (422 ± 31 vs. 289 ± 33 g piglet^− 1 day^− 1; P = 0.01), but slower daily gains from the 3rd week post-weaning to 60 day of age than litters on C treatment (371 ± 14 vs. 432 ± 15 g piglet^− 1 day^− 1; P < 0.05). Nevertheless, neither at weaning nor at 60 days of age average body weight of piglets differed between treatments (7.71 ± 0.31 vs. 7.94 ± 0.30 kg for C and IS, at 35 days of age, 15.62 ± 0.65 vs. 16.20 ± 0.62 kg, at day 60). The apparent digestibility of nutrients of the starter diet offered after weaning remained unaffected by the treatment, except for a trend for higher ApD of GE for the piglets on IS treatment (P = 0.08). ApD for CP and GE was 78.1 ± 0.6 and 78.8 ± 0.3%, respectively. No significant differences in the proportions of total viscera and gastrointestinal tract to empty body weight (EBW) were observed between C and IS piglets at weaning and 60 d of age. In conclusion, the increase in feed intake observed prior and early after weaning as a consequence of intermittent suckling during the last week of 35 d lactation had no effect on nutrient digestibility measured at two weeks after weaning and failed on improving Iberian piglet performance.     

Pharmacokinetics of marbofloxacin after a single oral dose to loggerhead sea turtles (Caretta caretta)

The single-dose disposition kinetics of marbofloxacin (MBX) were determined in clinically healthy loggerhead sea turtles (n = 5) after oral (PO) administration of 2 mg kg⁻¹ bodyweight. Marbofloxacin plasma concentrations were determined by DAD–HPLC (LOD/LOQ 0.015/0.05 μg ml⁻¹). Data were subjected to non-compartmental analysis. Following PO administration, marbofloxacin achieved maximum plasma concentrations of 11.66 ± 2.53 mg L⁻¹ at 15.00 ± 3.00 h. The absence of general adverse reactions in the turtles of the study, and the favourable pharmacokinetic properties (long half-life and high maximum plasma concentration) of MBX administered PO at the single-dose of 2 mg kg⁻¹ suggest the possibility of its safe and effective clinical use in loggerhead sea turtles.     

Effect of propofol on oxidative stress status in erythrocytes from dogs under general anaesthesia

Background

Alterations of the normal redox balance might be attributed to increase of plasma free-radical concentration and a disruption of the antioxidant defense system. One of the adverse effects of general anaesthetics is the exogen sources of reactive oxygen radicals that are responsible for several diseases. The purposes of the current study were to evaluate the effect of propofol on oxidative stress and to compare the differences between propofol induction only and induction plus continuous infusion on antioxidant status in dogs.

Findings

Beagle dogs were evaluated in the present study. The dogs were assigned randomly to receive three treatments in a crossover model. The three treatments were: group 1 (n = 9), 2% isoflurane; group 2 (n = 9), anaesthesia induced with an intravenous (IV) bolus dose of 6 mg/kg propofol and maintained with 1.5–2% isoflurane; group 3 (n = 9), total IV anaesthesia (induction with 6 mg/kg propofol, infusion with 0.6 mg/kg/min propofol). The results of this study show that dogs exposed to isoflurane had decreased antioxidant enzymes activities, whereas dogs injected with propofol had increased antioxidant enzymes activities.

Conclusions

The results of this study showed that an infusion dose of propofol has antioxidant effects in dogs. These effects may be beneficial to patients in whom free radicals play a role in oxidative stress, such as those with ischemia. Further studies are needed to evaluate whether these antioxidant effects of the anaesthetic are of clinical value.     

Blood lactate disappearance after maximal exercise in trained and detrained horses

The influence of training on blood lactate concentrations during treadmill exercise and a 40-minute inactive recovery period was examined in seven trained and seven detrained thorough-bred horses. Lactate concentrations were measured in venous blood collected at the end of each exercise state, and at intervals for 40 minutes afterwards. Measurements were made of maximum oxygen uptake (V̇O_2max, ml kg⁻¹ min⁻¹), VLA4 (velocity at which blood lactate concentration was 4 mmol litre⁻¹); LA8 (lactate concentration [mmol litre⁻¹] during exercise at 8 m sec⁻¹), peak lactate (highest lactate concentration after exercise), LA40 (lactate concentration 40 minutes after exercise), the time of peak lactate concentration (minutes after exercise) and the rate of disappearance of blood lactate (Rt_d). The trained horses had a significantly lower LA8 (2·1 ± 0·1 vs 6·5 ± 1 mmol litre⁻¹, P<0·01), higher VLA4 (9·8 ± 0·2 vs 5·8 ± 0·6 m sec⁻¹, P<0·01) and higher V̇0_2max (156·3 ± 3·8 vs 107·1 ± 3·9 ml kg⁻¹ min⁻¹, P<0·001). The value of Rt_d and the time of peak lactate concentration were not significantly different.     

The effect of preanaesthetic oral trazodone hydrochloride on the induction dose of propofol: a preliminary retrospective study

ObjectiveTo determine whether the administration of trazodone to dogs 2 hours prior to radiotherapy treatment reduced the dose of propofol required to induce anaesthesia.Study designRetrospective, crossover, case-matched study.AnimalsRecords of 30 client-owned dogs.MethodsAnaesthetic records from all dogs undergoing weekly radiotherapy treatment between January 2020 and December 2020 were retrospectively assessed. All dogs were premedicated with 10 μg kg^–1 alfentanil and 12 μg kg^–1 atropine intravenously (IV) and anaesthesia was induced with IV propofol. In part 1, the propofol induction dose was compared between anaesthetics when trazodone was administered prior to the anaesthetic (T) versus not (NT). For part 2, control dogs not administered trazodone during the treatment course were case-matched based on bodyweight and tumour location and type. The propofol induction dose was compared between the first (C1) and last (C2) anaesthetic to identify the effects of confounding factors. A Wilcoxon signed-rank test for repeated measurements was performed to identify any significant differences in the propofol induction dose between NT and T in the study dogs and between C1 and C2 in the control dogs.ResultsIn part 1, 15 study dogs that were administered trazodone prior to at least one anaesthetic were identified. A significant difference in propofol induction dose between groups NT and T was identified [3.3 (2.1–7.4) and 2.0 (1.5–5.0) mg kg^–1, respectively; p = 0.003]. In part 2, 15 dogs were case-matched to the study cohort. The dose of propofol administered did not differ between the first and last anaesthetic [2.5 (1.6–6.4) and 2.6 (1.9–8.9) mg kg^–1, respectively; p = 0.638].Conclusions and clinical relevancePreanaesthetic trazodone administration reduced the induction dose of propofol compared to when it was not administered to dogs following premedication with IV atropine and alfentanil.     

Dose requirement and cardiopulmonary effects of diluted and undiluted propofol for induction of anaesthesia in dogs

ObjectiveTo compare the dose, cardiopulmonary effects and quality of anaesthetic induction in dogs using propofol (10 mg mL^–1) and diluted propofol (5 mg mL^–1).Study designRandomized, blinded, clinical study.AnimalsA total of 28 client-owned dogs (12 males/16 females).MethodsFollowing intramuscular acepromazine (0.02 mg kg^–1) and methadone (0.2 mg kg^–1), propofol (UP, 10 mg mL^–1) or diluted propofol (DP, 5 mg mL^–1) was administered intravenously (0.2 mL kg^–1 minute^–1) by an anaesthetist unaware of the allocated group to achieve tracheal intubation. Sedation, intubation and induction quality were scored from 0 to 3. Pre- and post-induction pulse rate (PR), respiratory rate (f_R) and systolic (SAP), mean (MAP) and diastolic (DAP) arterial blood pressure were compared. Time to first breath and induction dose were recorded. Data were analysed for normality and Mann–Whitney U or Student t tests were performed where appropriate. Significance was set at p < 0.05. Data are presented as mean ± standard deviation or median (range).ResultsThe propofol dose administered to achieve induction was lower in the DP group (2.62 ± 0.48 mg kg^–1) than in the UP group (3.48 ± 1.17 mg kg^–1) (p = 0.021). No difference was observed in pre- and post-induction PR, SAP, MAP, DAP and f_R between groups. The differences between post-induction and pre-induction values of these variables were also similar between groups. Time to first breath did not differ between groups. Sedation scores were similar between groups. Quality of tracheal intubation was marginally better with UP 0 (0–1) than with DP 1 (0–2) (p = 0.036), but overall quality of induction was similar between groups [UP 0 (0–1) and DP 0 (0–1), p = 0.549].Conclusion and clinical relevanceDiluting propofol reduced the dose to induce anaesthesia without significantly altering the cardiopulmonary variables.     

Effect of anaesthesia on cell-mediated immunity in dogs undergoing mastectomy for mammary cancer

ObjectiveTo investigate if anaesthesia for canine cancer mastectomy further influences host cell-mediated immunity (CMI) promoting cancer progression.Study designA randomized, controlled, blinded clinical study.AnimalsA total of 20 bitches with malignant mammary tumours of clinical stage II or III undergoing the same type of mastectomy (regional mastectomy).MethodsDogs were randomly allocated to one of two anaesthetic groups (10 per group). The anaesthetic protocol of group A used minimally immunosuppressive drugs (tramadol, robenacoxib, propofol), whereas that of group B (control) used more immunosuppressive drugs (morphine, fentanyl, thiopental, isoflurane). For each animal, measurements of white blood cells (WBCs), neutrophils and lymphocytes, and flow cytometric assessment of T cells (CD3⁺), helper T cells (CD4⁺), cytotoxic T cells (CD8⁺) and CD5^low+ T cells were performed prior to anaesthesia (day 0) and on days 3 and 10 postsurgery. Data were analysed using a General Linear Model for repeated measures and presented as mean ± standard deviation, p ≤ 0.05.ResultsIn all animals, on day 3, WBCs and neutrophils were significantly increased (p < 0.0005), while flow cytometry revealed significantly decreased relative percentages of T cells (CD3⁺) (p = 0.003) and their subpopulations CD4⁺ (p = 0.006), CD8⁺ (p = 0.029) and CD5^low+ (p = 0.031). Specifically, on day 3, the cytotoxic T cells (CD8⁺) were significantly decreased (p = 0.05) only in group B, whereas the CD4⁺ (p = 0.006) and CD5^low+ (p = 0.008) T cells in group A. The only significant difference between groups was found preoperatively in the CD4⁺/CD8⁺ ratio, which was higher in group A (p = 0.006).Conclusions and clinical relevanceIn dogs with mammary cancer undergoing regional mastectomy, a significant decrease in components of CMI was observed on day 3 postsurgery in both anaesthetic groups. Some indication, however, for better preserved cellular immunity by less immunosuppressive anaesthetic/analgesic drugs was detected, rendering their use advisable.     

Propofol anaesthesia for surgery in late gestation pony mares

Objective To characterize propofol anaesthesia in pregnant ponies. Animals Fourteen pony mares, at 256 ± 49 days gestation, undergoing abdominal surgery to implant fetal and maternal vascular catheters. Materials and methods Pre‐anaesthetic medication with intravenous (IV) acepromazine (20 µg kg^?1), butorphanol (20 µg kg^?1) and detomidine (10 µg kg^?1) was given 30 minutes before induction of anaesthesia with detomidine (10 µg kg^?1) and ketamine (2 mg kg^?1) IV Maternal arterial blood pressure was recorded (facial artery) throughout anaesthesia. Arterial blood gas values and plasma concentrations of glucose, lactate, cortisol and propofol were measured at 20‐minute intervals. Anaesthesia was maintained with propofol infused initially at 200 µg kg^?1 minute^?1, and at 130–180 µg kg^?1 minute^?1 after 60 minutes, ventilation was controlled with oxygen and nitrous oxide to maintain PaCO₂ between 5.0 and 6.0 kPa (37.6 and 45.1 mm Hg) and PaO₂ between 13.3 and 20.0 kPa (100 and 150.4 mm Hg). During anaesthesia flunixin (1 mg kg^?1), procaine penicillin (6 IU) and butorphanol 80 µg kg^?1 were given. Lactated Ringer's solution was infused at 10 mL kg^?1 hour^?1. Simultaneous fetal and maternal blood samples were withdrawn at 85–95 minutes. Recovery from anaesthesia was assisted. Results Arterial blood gas values remained within intended limits. Plasma propofol levels stabilized after 20 minutes (range 3.5–9.1 µg kg^?1); disposition estimates were clearance 6.13 ± 1.51 L minute^?1 (mean ± SD) and volume of distribution 117.1 ± 38.9 L (mean ± SD). Plasma cortisol increased from 193 ± 43 nmol L^?1 before anaesthesia to 421 ± 96 nmol L^?1 60 minutes after anaesthesia. Surgical conditions were excellent. Fetal umbilical venous pH, PO₂ and PCO₂ were 7.35 ± 0.04, 6.5 ± 0.5 kPa (49 ± 4 mm Hg) and 6.9 ± 0.5 kPa (52 ± 4 mm Hg); fetal arterial pH, PO₂ and PCO₂ were 7.29 ± 0.06, 3.3 ± 0.8 kPa (25 ± 6 mm Hg) and 8.7 ± 0.9 kPa (65 ± 7 mm Hg), respectively. Recovery to standing occurred at 46 ± 17 minutes, and was generally smooth. Ponies regained normal behaviour patterns immediately. Conclusions and clinical relevance Propofol anaesthesia was smooth with satisfactory cardiovascular function in both mare and fetus; we believe this to be a suitable anaesthetic technique for pregnant ponies.     

Disposition and urinary excretion of phenylbutazone in normal and febrile greyhounds

Five days after the induction of acute systemic inflammation in greyhounds by intramuscular and subcutaneous injections of Freund's adjuvant, the hepatic concentrations of cytochromes P-450 and b₅, the activities of the hepatic microsomal enzymes aniline p-hydroxylase and aminopyrine n-demethylase and the disposition and urinary excretion of phenylbutazone were determined. The mean plasma concentrations of phenylbutazone after intravenous administration were described by the bi-exponential equations: Cp = 144·2e^−34·6t + 171·5e^−0·104t for five normal greyhounds and Cp = 113·6e^−16·13t + 163·1e^−0·108t for five febrile greyhounds. The elimination half-lives, total body clearances and apparent volumes of distribution were 6·7 hours, 18·4 ml kg⁻¹ hour⁻¹ and 0·18 litre kg⁻¹, for the normal greyhounds, and 6·4 hours, 19·5 ml kg⁻¹ hour⁻¹ and 0·18 litre kg⁻¹, for the febrile greyhounds. There were no significant differences between the pharmacokinetic parameters describing the distribution and elimination of phenylbutazone, or between the quantities of phenylbutazone, oxyphenbutazone and hydroxyphenylbutazone excreted in the urine. In the febrile greyhounds, there were significant decreases in the hepatic microsomal concentrations of cytochromes P-450 and b₅ and in the activities of aniline p-hydroxylase and aminopyrine n-demethylase.     

Effect of dietary chloride content on the elimination of bromide by dogs

The effect of dietary chloride content (0·2, 0·4 and 1·3 per cent chloride on a dry matter basis) on the disposition of a single oral dose of bromide (14 mg kg⁻¹ was evaluated in normal beagles. Increasing the dietary chloride content from 0·2 to 1·3 per cent resulted in a significant decrease in the mean apparent elimination half-life from 69 ± 22 days to 24 ± 7 days. The mean area under the concentration curve ( ) for dogs fed 1·3 per cent chloride was significantly smaller than the for dogs fed 0·2 per cent chloride. Dietary chloride had no effect on the maximum serum concentrations (C_max) or on the time (T_max) to reach the maximum concentrations. The steady-state serum bromide concentrations predicted from the single dose data for daily doses of 14 mg kg⁻¹ of bromide were significantly lower in dogs fed 1·3 per cent chloride (310 ± 150 mg litre⁻¹) than in dogs fed 0·2 per cent chloride (1950 ± 1140 mg litre⁻¹). The predicted mean daily doses of bromide necessary to maintain serum levels within the therapeutic range for dogs fed 1·3 per cent chloride (43 ± 13 mg kg⁻¹) were almost twice as high as the dose estimated for dogs fed 0·4 per cent chloride (22 ± 3 mg kg⁻¹) and nearly three times as high as the dose estimated for dogs fed 0·2 per cent chloride (15 ± 4 mg kg^−l). These differences were statistically significant (P=0·002).     

Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration

The pharmacokinetics of orphenadrine (ORPH) following a single intravenous (i.v.) dose was investigated in six camels (Camelus dormedarius). Orphenadrine was extracted from the plasma using a simple sensitive liquid–liquid extraction method and determined by gas chromatography/mass spectrometry (GC/MS). Following i.v. administration plasma concentrations of ORPH decline bi-exponentially with distribution half-life (t_1/2α) of 0.50 ± 0.07 h, elimination half-life (t_1/2β) of 3.57 ± 0.55 h, area under the time concentration curve (AUC) of 1.03 ± 0.10 g/h l⁻¹. The volume of distribution at steady state (Vd_ss) 1.92 ± 0.22 l kg⁻¹, volume of the central compartment of the two compartment pharmacokinetic model (V_c) 0.87 ± 0.09 l kg⁻¹, and total body clearance (Cl_T) of 0.60 ± 0.09 l/h kg⁻¹. Three orphenadrine metabolites were identified in urine samples of camels. The first metabolite N-desmethyl-orphenadrine resulted from N-dealkylation of ORPH with molecular ion m/z 255. The second N,N-didesmethyl-orphenadrine, resulted from N-didesmethylation with molecular ion m/z 241. The third metabolite, hydroxyl-orphenadrine, resulted from the hydroxylation of ORPH with molecular ion m/z 285. ORPH and its metabolites in camel were extensively eliminated in conjugated form. ORPH remains detectable in camel urine for three days after i.v. administration of a single dose of 350 mg orphenadrine aspartate.     

Comparison of alfaxalone and propofol administered as total intravenous anaesthesia for ovariohysterectomy in dogs

ObjectiveTo compare the anaesthetic and cardiopulmonary effects of alfaxalone with propofol when used for total intravenous anaesthesia (TIVA) during ovariohysterectomy in dogs.Study designA prospective non-blinded randomized clinical study.AnimalsFourteen healthy female crossbred bitches, aged 0.5–5 years and weight 16–42 kg.MethodsDogs were premedicated with acepromazine 0.01 mg kg^?1 and morphine 0.4 mg kg^?1. Anaesthesia was induced and maintained with either propofol or alfaxalone to effect for tracheal intubation followed by an infusion of the same agent. Dogs breathed spontaneously via a ‘circle’ circuit, with oxygen supplementation. Cardiopulmonary parameters (respiratory and heart rates, end-tidal carbon dioxide, tidal volume, and invasive blood pressures) were measured continuously and recorded at intervals related to the surgical procedure. Arterial blood samples were analysed for blood gas values. Quality of induction and recovery, and recovery times were determined. Non-parametric data were tested for significant differences between groups using the Mann–Whitney U-test and repeatedly measured data (normally distributed) for significant differences between and within groups by anova.ResultsBoth propofol and alphaxalone injection and subsequent infusions resulted in smooth, rapid induction and satisfactory maintenance of anaesthesia. Doses for induction (mean ± SD) were 5.8 ± 0.30 and 1.9 ± 0.07 mg kg^?1 and for the CRIs, 0.37 ± 0.09 and 0.11 ± 0.01 mg kg^?1 per minute for propofol and alfaxalone respectively. Median (IQR) recovery times were to sternal 45 (33–69) and 60 (46–61) and to standing 74 (69–76) and 90 (85–107) for propofol and alphaxalone respectively. Recovery quality was good. Cardiopulmonary effects did not differ between groups. Hypoventilation occurred in both groups.Conclusions and clinical relevanceFollowing premedication with acepromazine and morphine, both propofol and alphaxalone produce good quality anaesthesia adequate for ovariohysterectomy. Hypoventilation occurs suggesting a need for ventilatory support during prolonged infusion periods with either anaesthetic agent.     

Effects of inhibition of nitric oxide synthase on systemic arterial pressure and renal vascular resistance in cats

These studies were undertaken to examine the systemic and renal effects of the pharmacological inhibition of endothelium-derived nitric oxide (EDNO) in cats. In six healthy cats, the intravenous infusion of nitro-L-arginine at a dose of 100 μg kg⁻¹ bodyweight min⁻¹ resulted in a marked increase (P<0·001) in mean arterial pressure from the control value of 116·7 ± 4·6 mmHg to 154·2 ± 6·8 mmHg and an increase (P<0·05) in renal vascular resistance from the control value of 3·69 ± 0·33 mmHg min ml⁻¹ to 6·83 ± 1·15 mmHg min ml⁻¹. The increase in renal vascular resistance was generalised, with comparable increments in preglomerular and postglomerular vascular resistance. Mean values for glomerular capillary pressure (61·1 ± 61·9 vs 1·9 ± 1·6 mmHg), calculated from the sum of arterial colloid osmotic pressure plus proximal tubule stop-flow pressure, did not change in response to the infusion of nitro-L-arginine. However, there was a marked reduction in renal blood flow (29·4 ± 3·1 to 16·9 ± 2·3 ml min⁻¹, P<0·01) and glomerular filtration rate (5·22 ± 0·57 to 3·52 ± 0·45 ml min⁻¹, P<0·01). These results provide evidence that EDNO plays an important role in the basal regulation of systemic arterial blood pressure and renal haemodynamics in cats.     

Fentanyl or midazolam for co-induction of anaesthesia with propofol in dogs

ObjectivePropofol may cause adverse effects (e.g. apnoea, hypotension) at induction of anaesthesia. Co-induction of anaesthesia may reduce propofol requirements. The effect of fentanyl or midazolam on propofol dose requirements and cardiorespiratory parameters was studied.Study designRandomized, controlled, blinded clinical study.AnimalsSixty-six client owned dogs (35 male, 31 female, ASA I-II, age 6–120 months, body mass 4.7–48.0 kg) were selected.MethodsPre-medication with acepromazine (0.025 mg kg⁻¹) and morphine (0.25 mg kg⁻¹) was administered by intramuscular injection. After 30 minutes group fentanyl-propofol (FP) received fentanyl (2 μg kg⁻¹), group midazolam-propofol (MP) midazolam (0.2 mg kg⁻¹) injected over 30 seconds via a cephalic catheter and in a third group, control-propofol (CP), the IV catheter was flushed with an equivalent volume of heparinized saline. Anaesthesia was induced 2 minutes later, with propofol (4 mg kg⁻¹minute⁻¹) administered to effect. After endotracheal intubation anaesthesia was maintained with a standardized anaesthetic protocol. Pulse rate, respiratory rate (RR) and mean arterial pressure (MAP) were recorded before the co-induction agent, before induction, and 0, 2 and 5 minutes after intubation. Apnoea ≥30 seconds was recorded and treated. Sedation after pre-medication, activity after the co-induction agent, quality of anaesthetic induction and endotracheal intubation were scored.ResultsPropofol dose requirement was significantly reduced in FP [2.90 mg kg⁻¹(0.57)] compared to CP [3.51 mg kg⁻¹ (0.74)] and MP [3.58 mg kg⁻¹(0.49)]. Mean pulse rate was higher in MP than in CP or FP (p = 0.003). No statistically significant difference was found between groups in mean RR, MAP or incidence of apnoea. Activity score was significantly higher (i.e. more excited) (p = 0.0001), and quality of induction score was significantly poorer (p = 0.0001) in MP compared to CP or FP. Intubation score was similar in all groups.Conclusions and clinical relevanceFentanyl decreased propofol requirement but did not significantly alter cardiovascular parameters. Midazolam did not reduce propofol requirements and caused excitement in some animals.