Influence of general anaesthesia on the intravenous acetaminophen pharmacokinetics in Beagle dogs

ObjectiveTo determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs.Study designProspective, crossover, randomized experimental study.AnimalsA group of nine healthy Beagle dogs.MethodsAcetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg^–1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 μg kg^–1) intramuscularly, anaesthesia was induced with propofol (2–3 mg kg^–1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe′Iso 1.3–1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05).ResultsA two-compartmental model best described time–concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94–3.65) and 1.72 (0.89–2.60) L kg^–1, clearance values 1.52 (0.71–2.30) and 1.60 (0.91–1.78) L kg^–1 hour^–1 or terminal elimination half-life values 2.45 (1.45–8.71) and 3.57 (1.96–6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded.Conclusions and clinical relevanceIV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts.     

Context-sensitive half-time of fentanyl in dogs

Context-sensitive half-times (CSHTs) of fentanyl in dogs were determined using pharmacokinetic models reported by Murphy et al. and Sano et al., and compared with a human model. The CSHT was defined as the time required for a 50% decrease in drug concentration in the central compartment after the termination of infusion. Although CSHTs increased gradually as the infusion time increased, the CSHTs in dogs were shorter than those in humans. The CSHTs at steady-state were 31.3 and 69.2 min in dogs, and 306.5 min in humans. The CSHTs of fentanyl in dogs are apparently shorter than those in humans; therefore, a continuous infusion of fentanyl may be a rational regimen in dogs, even if duration of infusion is extended.     

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.     

Evaluation of the nociception–antinociception balance using the Parasympathetic Tone Activity index in dogs anaesthetized for castration

ObjectiveTo evaluate the performance of the Parasympathetic Tone Activity (PTA) index in assessing the nociception–antinociception balance in anaesthetized dogs undergoing castration.Study designProspective clinical study.AnimalsA group of 22 healthy client-owned dogs.MethodsThe dogs underwent general anaesthesia, with continuous monitoring of mean and instantaneous PTA (PTAm, PTAi), mean arterial pressure and heart rate. The values of these variables were divided according to the occurrence or absence of a haemodynamic reaction (HDR) at different time points: during surgical preparation, cutaneous incision, testicles extraction, cutaneous suture, after fentanyl administration, and after dexmedetomidine administration during recovery. Data were collected initially and 1, 3 and 5 minutes after each time point. The performance of the dynamic variation of the PTA (ΔPTA) to predict HDR or its resolution within 3 or 5 minutes was assessed using receiver operating characteristic (ROC) curves analysis. A p value < 0.05 was considered significant.ResultsDuring HDR, a decrease in PTAi (–34% and –31%) and PTAm (–26% and –30%) occurred at 3 (p = 0.005; p = 0.004) and 5 minutes (p = 0.001), respectively. After fentanyl administration, a decrease in haemodynamic variables occurred with a 45% increase in PTAi (p = 0.004). The ROC curve analysis of pooled data of the ΔPTAi for the prediction of HDR within 3 minutes indicated an area under the curve (AUC) of 0.70 (p = 0.0016) (threshold value: –16%). After fentanyl administration, the ROC curve analysis of ΔPTAi for the prediction of resolution of HDR within 3 minutes indicated an AUC of 0.69 (threshold value: +12%).Conclusions and clinical relevanceThe PTAi appears to be an interesting tool to assess the nociception–antinociception balance. However, further studies with a variety of clinical scenarios and anaesthesia protocols are required to conclude on its performance.     

Population pharmacokinetics of transdermal fentanyl solution following a single dose administered prior to soft tissue and orthopedic surgery in dogs

A novel, long-acting transdermal fentanyl solution (TFS) that delivers sustained plasma fentanyl concentrations following a single application for the control of postoperative pain has recently been approved for use in dogs. The pharmacokinetics (PKs) of this formulation have been evaluated in healthy laboratory dogs, but they have not been reported in a clinical population of dogs for which it is indicated. Plasma fentanyl concentrations were determined from 215 dogs following a single, small-volume (～50 μL/kg) dose of TFS administered 2-4 h prior to orthopedic or soft tissue surgery. A population PK model was fit, and a 1-compartment open PK model with first-order absorption and an absorption lag-time best described the data. No tested clinical covariates had a significant effect on the PKs. The final model adequately described the population PKs and gave results consistent with laboratory PK studies in healthy dogs. The PKs were primarily characterized by a rapid initial increase in plasma fentanyl concentrations and a long terminal half-life of 74.0 (95% C.I. [54.7-113]) h governed by flip-flop kinetics for the typical subject. The plasma fentanyl concentrations were sustained over days in the range considered to be analgesic for postoperative pain in dogs.     

The incidence of spontaneous movements (myoclonus) in dogs undergoing total intravenous anaesthesia with propofol

ObjectiveTo evaluate the incidence of myoclonus (involuntary movements during anaesthesia, unrelated to inadequate hypnosis or analgesia, and of sufficient severity to require treatment) in dogs anaesthetized with a TIVA of propofol with or without the use of fentanyl.Study designRetrospective clinical study.AnimalsDogs, undergoing general anaesthesia for clinical procedures between January 2012 and January 2013 and subject to TIVA with propofol.MethodsA retrospective analysis reviewed the medical and anaesthetic records. Animals with existing or potential neurological or neuromuscular pathology in the anamnesis or upon clinical examination and cases with incomplete clinical records were excluded. Myoclonus was considered as involuntary muscle contractions which did not cease following a bolus administration of propofol or fentanyl and, due to their intensity and duration, made continuation of the procedure impracticable without other drug administration. Tremors, paddling or muscle spasms, explicable as insufficient hypnosis or analgesia, and transient excitatory phenomena only present during the awakening phase, were not considered as myoclonus.ResultsOut of a total of 492 dogs undergoing anaesthesia, six mixed breed dogs (1.2%), one male and five females, American Society of Anaesthesiologists (ASA) physical status I, median (range) weight 20.5 (7–37) kg and age 1.5 (1–5) years had myoclonus according to the aforementioned definition. In all subjects, myoclonus appeared within 20 minutes after induction of anaesthesia, and mainly involved the limb muscles. All subjects appeared to be in an adequate plane of anaesthesia before and during myoclonus.Conclusions and clinical relevanceThis study shows that 1.2% of dogs, undergoing TIVA with propofol with or without fentanyl administration, developed myoclonus, which required to be, and were treated successfully pharmacologically. The cause of this phenomenon is yet to be determined.     

Propofol and fentanyl infusions in dogs of various breeds undergoing surgery

ObjectiveTo report the cardiovascular variables, anaesthetic effects and recovery quality of an anaesthesia technique using variable rate infusion propofol combined with constant rate infusion fentanyl in dogs undergoing elective surgery.Study designProspective clinical trial.AnimalsA total of 27 dogs, aged 2.7 ± 2.65 years and weighing 24 ± 11 kg.MethodsFollowing intramuscular acepromazine (0.03 or 0.05 mg kg^?1) and subcutaneous carprofen (4 mg kg^?1) pre-medication, anaesthesia was induced with propofol (4.0 ± 0.5 mg kg^?1) intravenously (IV). All dogs were ventilated with 100% oxygen to maintain normocapnia. Propofol was infused at 0.4 mg kg^?1 minute^?1 for 20 minutes and then at 0.3 mg kg^?1minute^?1. If mean arterial blood pressure (MAP) decreased below 70 mmHg, propofol infusion was reduced by 0.1 mg kg^?1 minute^?1. Five minutes after induction of anaesthesia, fentanyl was administered (2 μg kg^?1) IV followed by the infusion at 0.5 μg kg^?1 minute^?1 and atropine (40 μg kg^?1) IV. Heart rate, MAP, respiratory rate, tidal volume, end-tidal carbon dioxide, presence of reflexes, movements and recovery times and quality were recorded.ResultsMean anaesthetic duration was 131 ± 38.5 minutes. Mean heart rate peaked 10 minutes after atropine injection and gradually declined, reaching pre-anaesthetic values at 55 minutes. MAP easily was maintained above 70 mmHg. Mean times to return of spontaneous ventilation, extubation, head lift and sternal recumbency were 21 ± 10.1, 33 ± 14.6, 43 ± 19.7 and 65 ± 23.4 minutes, respectively. Recovery was smooth and quiet. The time to sternal recumbency was significantly correlated with the duration of anaesthesia and total dose of propofol; time to extubation was correlated to total dose of propofol.Conclusion and clinical relevancePropofol and fentanyl infusions provided stable cardiovascular function and satisfactory conditions for surgery. Some modifications of infusion rates are required to improve the long-recovery times.     

Comparison between continuous rate infusion and target-controlled infusion of propofol in dogs: a randomized clinical trial

ObjectiveTo compare a propofol continuous rate infusion (CRI) with a target-controlled infusion (TCI) in dogs.Study designRandomized prospective double-blinded clinical study.AnimalsA total of 38 healthy client-owned dogs.MethodsDogs premedicated intramuscularly with acepromazine (0.03 mg kg^–1) and an opioid (pethidine 3 mg kg^–1, morphine 0.2 mg kg^–1 or methadone 0.2 mg kg^–1) were allocated to P-CRI group (propofol 4 mg kg^–1 intravenously followed by CRI at 0.2 mg kg^–1 minute^–1), or P-TCI group [propofol predicted plasma concentration (Cp) of 3.5 μg mL^–1 for induction and maintenance of anaesthesia via TCI]. Plane of anaesthesia, heart rate, respiratory rate, invasive blood pressure, oxygen haemoglobin saturation, end-tidal carbon dioxide and body temperature were monitored by an anaesthetist blinded to the group. Numerical data were analysed by unpaired t test or Mann–Whitney U test, one-way analysis of variance and Dunnett’s post hoc test. Categorical data were analysed with Fisher’s exact test. Significance was set for p < 0.005.ResultsOverall, propofol induced a significant incidence of relative hypotension (mean arterial pressure 20% below baseline, 45%), apnoea (71%) and haemoglobin desaturation (65%) at induction of anaesthesia, with a higher incidence of hypotension and apnoea in the P-CRI than P-TCI group (68% versus 21%, p = 0.008; 84% versus 58%, p = 0.0151, respectively). Propofol Cp was significantly higher at intubation in the P-CRI than P-TCI group (4.83 versus 3.5 μg mL^–1, p < 0.0001), but decreased during infusion, while Cp remained steady in the P-TCI group. Total propofol administered was similar between groups.Conclusions and clinical relevanceBoth techniques provided a smooth induction of anaesthesia but caused a high incidence of side effects. Titration of anaesthesia with TCI caused fewer fluctuations in Cp and lower risk of hypotension compared with CRI.     

Efficacy and side effects of intraoperative analgesia with intrathecal bupivacaine and levobupivacaine: a retrospective study in 82 dogs

ObjectiveTo evaluate spinal (intrathecal) anaesthesia (SA) in addition to general anaesthesia in dogs, and report the incidence of side effects and cardiovascular response (CR) to surgery.Study designRetrospective clinical study.AnimalsOne hundred and fifteen dogs undergoing general anaesthesia for surgery caudal to the diaphragm between 2005 and 2008.MethodsRecords of anaesthetized dogs that had received SA with bupivacaine or levobupivacaine 0.5%, together with morphine or fentanyl were reviewed. Success rate of SA, complication rate and incidence of CR were recorded and examined in relation to the dose of local anaesthetic administered and the type of surgery. Univariate and Cusum analysis were performed to identify independent predictors of response to surgical stimulation and characterize the learning curve for the technique, respectively.ResultsEighty-two dogs received successful SA. The Cusum plot suggested that a failure rate of 10% is achieved when the procedure is performed more than 66 times. Median local anaesthetic dose related to weight was 0.40 mg kg^?1 (0.3–0.5), and to spinal cord length 0.1 mg cm^?1 (0.07–0.12). Morphine was added to the local anaesthetic in 56 and fentanyl in 22 dogs. CR post-stimulus occurred in 29 cases: 11 of 22 ovariohysterectomies, 14 of 33 hindlimb-surgeries, 2 of 10 caudal-abdominal-surgeries and 2 of 17 Caesarean sections. Anaesthetic dose related to weight was not a predictor of CR. Bradycardia occurred in seven, hypotension in 24, urinary retention in four and hypersalivation in 6 of 82 dogs.ConclusionsSA was practicable to apply, but in this study did not totally block CR, Side effects were minimal, with an incidence similar to that in humans.Clinical relevanceSA can be used in clinical cases with few side effects although monitoring of and ensuing treatment of hypotension is required. Comparative prospective studies are required to establish efficacy and a reliable dose.     

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.     

Effect of fentanyl target-controlled infusions on isoflurane minimum anaesthetic concentration and cardiovascular function in red-tailed hawks (Buteo jamaicensis)

ObjectiveTo determine the impact of three different target plasma concentrations of fentanyl on the minimum anaesthetic concentration (MAC) for isoflurane in the red-tailed hawk and the effects on the haemodynamic profile.Study designExperimental study.Animal populationSix healthy adult red-tailed hawks (Buteo jamaicensis) of unknown sex with body weights (mean ± SD) of 1.21 ± 0.15 kg.MethodsThis study was undertaken in two phases. In the first phase anaesthesia was induced with isoflurane in oxygen via facemask and maintained with isoflurane delivered in oxygen via a Bain circuit. Following instrumentation baseline determination of the MAC for isoflurane was made for each animal using the bracketing method and a supramaximal electrical stimulus. End-tidal isoflurane concentration (E′Iso) was then set at 0.75 × MAC and after an appropriate equilibration period a bolus of fentanyl (20 μg kg^?1) was administered intravenously (IV) in order to determine the pharmacokinetics of fentanyl in the isoflurane-anaesthetized red-tailed hawk. During the second phase anaesthesia was induced in a similar manner and E′Iso was set at 0.75 × MAC for each individual. Fentanyl was infused IV to achieve target plasma concentrations between 8 and 32 ng mL^?1. At each fentanyl plasma concentration, the MAC for isoflurane and cardiovascular variables were determined. Data were analyzed by use of repeated-measures anova.ResultsMean ± SD fentanyl plasma concentrations and isoflurane MACs were 0 ± 0, 8.51 ± 4, 14.85 ± 4.82 and 29.25 ± 11.52 ng mL^?1, and 2.05 ± 0.45%, 1.42 ± 0.53%, 1.14 ± 0.31% and 0.93 ± 0.32% for the target concentrations of 0, 8, 16 and 32 ng mL^?1, respectively. At these concentrations fentanyl significantly (p = 0.0016) decreased isoflurane MAC by 31%, 44% and 55%, respectively. Dose had no significant effect on heart rate, systolic, diastolic or mean arterial blood pressure.Conclusions and clinical relevanceFentanyl produced a dose-related decrease of isoflurane MAC with minimal effects on measured cardiovascular parameters in red-tailed hawks.     

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. 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 regimes myocardial oxygen consumption appeared to increase with increasing duration of anaesthesia. Propofol infusion was associated with a 16 per cent incidence of vomiting in the recovery period. Maintenance of anaesthesia in healthy dogs by the continuous infusion of propofol appeared to be safe but less satisfactory than the use of halothane/nitrous oxide.     

Effect of fentanyl,with or without treatment of bradycardia,on the minimum alveolar concentration of isoflurane and cardiovascular function in dogs

ObjectiveTo determine the effect of fentanyl on the minimum alveolar concentration of isoflurane (MAC_ISO) and cardiovascular variables in dogs, and how the treatment of bradycardia affects them.Study designProspective, randomized crossover-controlled trial.AnimalsA total of six male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation) and aged 13 months.MethodsTo each dog, two treatments were assigned on different days: fentanyl (FENTA) or fentanyl plus glycopyrrolate (FENTA_glyco) to maintain heart rate (HR) between 100 and 132 beats minute^?1. Determinations of MAC_ISO were performed with 10 plasma fentanyl target concentrations ([Fenta]_Target (0, 0.16, 0.32, 0.64, 1.25, 2.5, 5.0, 10.0, 20.0 and 40.0 ng mL^?1) for FENTA and 5 [Fenta]_Target (0, 1.25, 2.5, 5.0, 10.0 ng mL^?1)) for FENTA_glyco. During each MAC_ISO determination, cardiovascular variables [mean arterial pressure (MAP), HR and cardiac index (CI)] were measured, and systemic vascular resistance index (SVRI) calculated. Pharmacodynamic models were used to describe the plasma fentanyl concentration [Fenta]–response relationship for the effect on MAC_ISO and cardiovascular variables. A mixed-model analysis of variance followed by Dunnett’s or Tukey’s test, and the Bonferroni adjustment were used for comparisons within and between each treatment, respectively. Significance was set as p < 0.05.ResultsFentanyl decreased MAC_ISO by a maximum of 84%. The [Fenta] producing 50% decrease in MAC, HR and CI were 2.64, 3.65 and 4.30 ng mL^?1 (typical values of population model), respectively. The prevention of fentanyl-mediated bradycardia caused no significant effect on MAC_ISO, but increased HR, MAP and CI, and decreased SVRI when compared with isoflurane alone.Conclusions and clinical relevanceFentanyl caused a plasma concentration-dependent decrease in MAC_ISO, HR and CI and an increase in SVRI. Cardiovascular improvements associated with fentanyl in isoflurane-anesthetized dogs only occurred when the fentanyl-mediated bradycardia was prevented.     

An investigation into the detection of the pulse in conscious and anaesthetized dogs

ObjectivesTo record the success rate of veterinary professionals and students at identifying the pulse in conscious and anaesthetized dogs. To explore the influence of clinical experience, pulse location, anaesthesia and likely confounding variables on the success of pulse palpation.Study designProspective, observational, randomized study.AnimalsA total of 54 client-owned dogs scheduled for general anaesthesia.MethodsFor each dog, three participants (senior anaesthetist, anaesthesia resident/nurse, veterinary student/animal care assistant) attempted pulse palpation at three locations (femoral, radial and dorsal pedal pulse) in conscious and anaesthetized dogs. The time to pulse palpation was measured with a stopwatch for each attempt and data were modelled using a multivariate Cox regression survival analysis (significance p < 0.05).ResultsThe overall success rate of pulse palpation was 77%, with a median time of 10.91 seconds (interquartile range 9.09 seconds). Success rate was lower in conscious dogs (67%) than in anaesthetized dogs (87%). There was a 77% lower likelihood of success at the radial than at the femoral pulse [hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.38–0.69, p < 0.001]. Veterinary students/animal care assistants had a 71% lower likelihood of success than senior anaesthetists (HR 0.29, 95% CI 0.22–0.39, p < 0.001). Age, weight and American Society of Anesthesiologists physical status had no significant influence. Premedication/anaesthetic drugs, heart rate or mean arterial pressure had no significant influence on the time to pulse palpation in anaesthetized dogs. The median time to palpation was less than 10 seconds for all experience groups at the femoral location.ConclusionsPalpation of the femoral location had the greatest likelihood of success with the least amount of time. Monitoring the femoral pulse during induction of anaesthesia is suggested as a method for confirming spontaneous circulation. Pulse palpation improves with clinical experience.     

Influence of fentanyl on intra-abdominal pressure during laparoscopy in dogs

ObjectiveTo evaluate the influence of fentanyl on intra-abdominal pressures in spontaneously breathing dogs during capnoperitoneum.Study designProspective clinical study.AnimalsEleven healthy client-owned and five healthy experimental dogs undergoing laparoscopy.MethodsDogs were premedicated with acepromazine (0.03 mg kg^?1 IV) and carprofen (4 mg kg^?1 IV). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen. The abdomen was insufflated with CO₂ (11–16 cm H₂O). Intra-abdominal pressures were measured with a transducer. Respiratory variables were measured with a spirometry sensor and side-stream capnography. Following preparation, fentanyl (1 μg kg^?1) was injected over 30 seconds IV. Data were recorded 5 minutes before, during and 5 minutes after treatment. The following time points were selected for statistical analysis (anova, p < 0.05): ?160, ?140, ?120, ?100, ?80, ?60, ?40, ?20, 0, 30, 50, 70, 90, 110, 130 and 150 seconds after the start of fentanyl injection.ResultsIntra-abdominal pressure increased during inspiration in 15 dogs but decreased in one dog. Fentanyl treatment did not alter these patterns. Peak inspiratory and end-expiratory intra-abdominal pressures continuously decreased over time during the whole experiment and fentanyl exaggerated the decrease in inspiratory pressures but did not affect the rate of decrease in expiratory pressures. Differences between intra-abdominal pressures were stable before, but decreased after fentanyl administration from 4.1 ± 1.4 to 3.3 ± 1.2 cm H₂O (at 0 and 150 seconds time points). End-tidal CO₂ partial pressures increased from 6.0 ± 0.8 to 6.6 ± 0.9 kPa, respiratory rate decreased from 10.8 ± 2.6 to 7.8 ± 2.2 breaths per minute and tidal volume decreased from 13.7 ± 4.4 to 12.4 ± 2.9 mL kg^?1 after fentanyl but these variables did not change before fentanyl treatment. Airway pressures did not change.Conclusions and clinical relevanceFentanyl did not increase intra-abdominal pressures in dogs.     

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.     

Fentanyl‐induced asystole in two dogs

Fentanyl is used in small animals for perioperative analgesia during anaesthesia. Severe bradycardia and asystole were observed on bolus administration of a 3 µg/kg loading dose of fentanyl in two dogs under isoflurane anaesthesia. Premedication with 10 µg/kg glycopyrrolate did not prevent asystole in the first case; and although bradycardia was treated with 5 µg/kg glycopyrrolate administered intravenously in the second case, the heart rate continuously decreased and asystole subsequently developed. Asystole in both cases was quickly corrected by intravenous administration of 0 · 04 mg/kg atropine and closed chest compressions. This case report describes asystole induced by fentanyl administration in isoflurane anaesthetised dogs. Atropine was more effective than glycopyrrolate in the treatment of fentanyl‐induced asystole.     

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.     

Reduction of isoflurane MAC by fentanyl or remifentanil in rats

Objective The main objective of the study was to determine the effects of three different infusion rates of fentanyl and remifentanil on the minimum alveolar concentration (MAC) of isoflurane in the rat. A secondary objective was to assess the cardiovascular and respiratory effects of the two opioid drugs. Animal population Thirty‐seven male Wistar rats were randomly allocated to one of six treatment groups. Material and methods For all treatment groups anaesthesia was induced with 5% isoflurane in oxygen using an induction chamber. A 14‐gauge catheter was used for endotracheal intubation, and anaesthesia was maintained with isoflurane delivered in oxygen via a T‐piece breathing system. A baseline determination of the minimum alveolar concentration of isoflurane (MAC_ISO) was made for each animal. Fentanyl (15, 30, 60 µg kg^?1 hour^?1) or remifentanil (60, 120, 240 µg kg^?1 hour^?1) were infused intravenously into a previously cannulated tail vein. Thirty minutes after the infusion started, a second MAC_ISO (MAC_ISO+drug) was determined. The carotid artery was cannulated to monitor the arterial pressure and to take samples for arterial gas measurements. Cardiovascular (heart rate and arterial pressure) and respiratory (respiratory rate and presence/absence of apnoea) effects after opioid infusion were also recorded. Results Fentanyl (15, 30, 60 µg kg^?1 hour^?1) and remifentanil (60, 120, 240 µg kg^?1 hour^?1) similarly reduced isoflurane MAC in a dose‐dependent fashion: by 10% at lower doses, 25% at medium doses and by 60% at higher doses of both the drugs. Both opioids reduced the respiratory rate in a similar way for all doses tested. No episodes of apnoea were recorded in the remifentanil groups, while administration of fentanyl resulted in apnoea in three animals (one at each dose level). The effects on the cardiovascular system were similar with both drugs. Conclusions We conclude that the intraoperative use of remifentanil in the rat reduces the MAC of isoflurane, and that this anaesthetic sparing effect is dose‐dependent and similar to that produced by fentanyl at the doses tested. Clinical relevance The use of remifentanil during inhalant anaesthesia in the rat can be considered an intravenous alternative to fentanyl, providing similar reduction in isoflurane requirements. Due to its rapid offset, it is recommended that alternative pain relief be instituted before it is discontinued.     

Influence of a preload of hydroxyethylstarch 6% on the cardiovascular effects of epidural administration of ropivacaine 0.75% in anaesthetized dogs

ObjectiveTo evaluate the cardiovascular effects of a preload of hydroxyethylstarch 6% (HES), preceding an epidural administration of ropivacaine 0.75% in isoflurane anaesthetized dogs.AnimalsSix female, neutered Beagle dogs (mean 13.3 ± SD 1.0 kg; 3.6 ± 0.1 years).Study designRandomized experimental cross-over study (washout of 1 month).MethodsAnaesthesia was induced with propofol and maintained with isoflurane in oxygen/air. All dogs were anaesthetized twice to receive either treatment HESR (continuous rate infusion [CRI] of 7 mL kg^?1 HES started 30 minutes [T-30] prior to epidural administration of ropivacaine 0.75% 1.65 mg kg^?1 at T0) or treatment R (no HES preload and similar dose and timing of epidural ropivacaine administration). Baseline measurements were obtained at T-5. Heart rate (HR), mean (MAP), diastolic (DAP) and systolic (SAP) invasive arterial pressures, cardiac output (Lithium dilution and pulse contour analysis) and derived parameters were recorded every 5 minutes for 60 minutes. Statistical analysis was performed on five dogs, due to the death of one dog.ResultsClinically relevant decreases in MAP (<60 mmHg) were observed for 20 and 40 minutes following epidural administration in treatments HESR and R respectively. Significant decreases in MAP and DAP were present after treatment HESR for up to 20 minutes following epidural administration. No significant within-treatment and overall differences were observed for other cardiovascular parameters. A transient unilateral Horner's syndrome occurred in two dogs (one in each treatment). One dog died after severe hypotension, associated with epidural anaesthesia.Conclusions and clinical relevanceA CRI of 7 mL kg^?1 HES administered over 30 minutes before epidural treatment did not prevent hypotension induced by epidural ropivacaine 0.75%. Epidural administration of ropivacaine 0.75% in isoflurane anaesthetized dogs was associated with a high incidence of adverse effects in this study.