RESEARCH PAPER: Romifidine as a constant rate infusion in isoflurane anaesthetized horses: a clinical study

Objective To evaluate the effects of a constant rate infusion (CRI) of romifidine on the requirement of isoflurane, cardiovascular performance and recovery in anaesthetized horses undergoing arthroscopic surgery. Study design Randomized blinded prospective clinical trial. Animals Thirty horses scheduled for routine arthroscopy. Methods After premedication (acepromazine 0.02 mg kg^?1, romifidine 80 μg kg^?1, methadone 0.1 mg kg^?1) and induction (midazolam 0.06 mg kg^?1 ketamine 2.2 mg kg^?1), anaesthesia was maintained with isoflurane in oxygen. Horses were assigned randomly to receive a CRI of saline (group S) or 40 μg kg^?1 hour^?1 romifidine (group R). The influences of time and treatment on anaesthetic and cardiovascular parameters were evaluated using an analysis of variance. Body weight (t‐test), duration of anaesthesia (t‐test) and recovery score (Wilcoxon Rank Sum Test) were compared between groups. Significance was set at p < 0.05. Results All but one horse were positioned in the dorsal recumbent position and ventilated from the start of anaesthesia. End tidal isoflurane concentrations were similar in both groups at similar time points and over the whole anaesthetic period. Cardiac output was significantly lower in horses of the R group, but there were no significant differences between groups in cardiac index, body weight or age. All other cardiovascular parameters were similar in both groups. Quality of recovery did not differ significantly between groups, but more horses in group R stood without ataxia at the first attempt. One horse from group S had a problematic recovery. Conclusions and clinical relevance No inhalation anaesthetic sparing effect or side effects were observed by using a 40 μg kg^?1 hour^?1 romifidine CRI in isoflurane anaesthetized horses under clinical conditions. Cardiovascular performance remained acceptable. Further studies are needed to identify the effective dose of romifidine that will induce an inhalation anaesthetic sparing effect in anaesthetized horses.     

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

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

Anaesthetic and cardiorespiratory effects of a constant-rate infusion of alfaxalone in desflurane-anaesthetised sheep

A prospective, randomised, blinded controlled study was performed to determine the anaesthetic and cardiorespiratory effects of a constant-rate infusion (CRI) of alfaxalone in 12?sheep anaesthetised with desflurane, and undergoing experimental orthopaedic surgery. Sheep were sedated with dexmedetomidine (4 μg/kg, intravenously) and butorphanol (0.3 mg/kg, intravenously). Anaesthesia was induced with alfaxalone (1 mg/kg/minute to effect, intravenously) and maintained with desflurane in oxygen and?alfaxalone 0.07 mg/kg/minute or saline for 150 minutes (range 150-166 minutes). The anaesthetic induction dose of alfaxalone, the desflurane expiratory fraction required for anaesthetic maintenance, cardiorespiratory measurements and blood-gases were recorded at predetermined intervals. Quality of sedation, anaesthetic induction and recovery were assessed. The alfaxalone induction dose was 1.7 mg/kg (1.2 to 2.6 mg/kg). The desflurane expiratory fraction was lower (22 per cent) in sheep receiving alfaxalone CRI (P?=?0). Also, heart rate (P?=?0), cardiac index (P?=?0.002), stroke index (P?=?0) and contractility (P?=?0) were higher, and systemic vascular resistance (P?=?0.002) was lower. Although respiratory rate tended to be higher with alfaxalone, there was no difference in PCO(2) between the groups. Recovery times were significantly longer in sheep given alfaxalone (25.4 v 9.5 minutes) but recovery quality was similar. Alfaxalone reduced requirements of desflurane and maintained similar cardiorespiratory function, but recovery time was more prolonged.     

Pharmacokinetics of fentanyl after single intravenous injection and constant rate infusion in dogs

OBJECTIVE: To determine the plasma concentration and define the pharmacokinetic characteristics of fentanyl (10 microg kg(-1)) administered as a single intravenous (IV) injection followed by: (a) no further drug; or (b) a constant rate infusion (CRI) of fentanyl 10 microg kg(-1) hour(-1) lasting 1, 3 or 4 hours in dogs. Animals Fourteen healthy adult beagles (seven males and seven females). EXPERIMENTAL DESIGN: Randomized cross-over design. MATERIALS AND METHODS: Dogs were randomly assigned to four treatment groups. Drugs were administered to each dog in a randomized cross-over design with at least a 14-day washout interval between experiments. All dogs received an IV loading dose of fentanyl (10 microg kg(-1)). One group received no further fentanyl. In others, the loading dose was followed by a CRI of fentanyl (10 microg kg(-1) hour(-1)) for 1, 3 or 4 hours. Blood samples were collected and plasma fentanyl concentrations determined using high-performance liquid chromatography-mass spectrometry. Plasma pharmacokinetic estimates were obtained by plotting plasma concentrations versus time data and by fitting the change in concentration to a pharmacokinetic model, using a purpose-built program written by the Graduate School of Pharmaceutical Sciences (Kyoto University) in Visual Basic (VBA) on Excel (Microsoft Corporation). RESULTS: Plasma fentanyl concentration decreased rapidly after single IV injection: the plasma concentration-time curve best fitted a two-compartment model. Pharmacokinetic variables for IV injection were characterized by a short distribution half-time (t1/2alpha was 4.5 minutes), a relatively long elimination half time (t1/2beta was 45.7 minutes), a large volume of distribution (approximately 5 L kg(-1)) and high total body clearance (77.9 mL minute(-1) kg(-1)). Stable plasma fentanyl levels were obtained in all CRI groups although pharmacokinetic variables were influenced by the duration of administration. CONCLUSIONS AND CLINICAL RELEVANCE: While this study clarified the pharmacokinetic features of rapid IV fentanyl injection and CRI in dogs, the plasma concentration achieving analgesia was not and so further research is needed. Further studies on the effects of other sedatives and/or anaesthetics on fentanyl's disposition are also required as the drug is commonly used with other agents.     

Subarachnoid pressures and cardiorespiratory parameters during cisternal myelography in isoflurane anaesthetized dogs

ObjectiveTo measure subarachnoid pressures, systemic circulatory and respiratory effects, and to calculate cerebral perfusion pressure during cisternal myelography.Study designProspective clinical study.AnimalsForty‐three client owned dogs with clinical signs of spinal disease, weighing 6–56 kg.MethodsDogs were premedicated with butorphanol and diazepam intravenously (IV) and anaesthesia was induced with propofol and maintained with isoflurane vaporized in oxygen. Ventilation was spontaneous. Heart and respiratory rates, invasive mean arterial blood pressure (MAP), end tidal carbon dioxide and isoflurane concentration were measured continuously. Initial subarachnoid pressure (SaP₀) was measured in the cisterna magna with a needle pressure gauge. Iohexol 0.3 mL kg^?1 was injected at a rate of 4.1 mL minute^?1 into the cerebellomedullary cistern. The SaP was recorded during and at 120 seconds after contrast administration. The maximum SaP (SaP_max) and minimum calculated cerebral perfusion pressure (CPP_min) were recorded for each case.ResultsPrior to contrast injection, mean ± SD, MAP was 73 ± 20 mmHg and SaP₀ was 10 ± 3 mmHg. The cerebral perfusion pressure (CPP) was 64 ± 20 mmHg. The contrast injection increased the SaP₀ to 73 ± 33 mmHg (SaP_max). After injection, MAP increased to 97 ± 25 mmHg and the CPP decreased to 14 ± 34 mmHg. A negative correlation was found between the lowest CPP and body weight (ρ = ?0.77, p < 0.0001). Nine dogs had bradycardia, apnoea and hypertension, 21 dogs had at least one of these signs. The number of clinical signs showed significant correlation with body weight (ρ = ?0.68, p < 0.0001), SaP_max (ρ = ?0.66, p < 0.0001) and CPP_min (ρ = ?0.73, p < 0.0001).Conclusions and clinical relevanceCerebral perfusion can severely decrease during cisternal myelography using the standard dose of iohexol. Bradycardia, apnoea and systemic hypertension were associated with decreased CPP.     

The isoflurane-sparing and clinical effects of a constant rate infusion of remifentanil in dogs

OBJECTIVE: To evaluate the isoflurane-sparing and clinical effects of two constant rate infusions of remifentanil in healthy dogs undergoing orthopaedic surgery. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Forty-one American Society of Anesthesiologists I-II client-owned dogs (age, 7 months-9 years; body mass 11-59 kg). METHODS: Dogs were randomly assigned to one of three groups and received either: intramuscular (IM) meperidine 2 mg kg(-1) every 2 hours throughout surgery (control group (C); n = 13); remifentanil infused intravenously (IV) at 0.1 microg kg(-1) minute(-1) (low remifentanil group (L); n = 14) or remifentanil infused at 0.25 microg kg(-1) minute(-1) IV (high remifentanil group (H); n = 14). Anaesthesia was induced with thiopental administered to effect and maintained using isoflurane in 100% oxygen. During controlled ventilation when the end-tidal CO(2) was maintained between 4.65 and 5.98 kPa [35-45 mmHg], the end-tidal isoflurane concentration (e'iso%), mean arterial blood pressure (MAP) and heart rate (HR) were measured every 5 minutes. Bradycardia (HR < 40 minute(-1) lasting >5 minutes) was corrected with 0.01 mg kg(-1) IV glycopyrrolate. Data were analysed using the Kruskal-Wallis test with a post-hoc Mann-Whitney U-test and Bonferroni correction. Statistical significance was accepted at < or = 0.05. Data are expressed as mean +/- standard deviation. RESULTS: The e'iso% was reduced in a dose-dependent manner by remifentanil. In C, e'iso% was 1.28 +/-0.13 and was significantly different from L (0.78 +/- 0.17, p < 0.001) and H (0.65 +/- 0.16, p < 0.001). HR was significantly different between groups (p < 0.001). There were no significant differences in MAP between groups. Glycopyrrolate was required in two, three and six dogs in the C, L and H groups respectively. CONCLUSIONS: Remifentanil infusion reduced the isoflurane concentration required for surgical anaesthesia during orthopaedic surgery. CLINICAL RELEVANCE: Remifentanil infusions may be a useful additive to isoflurane anaesthesia in healthy dogs.     

A comparison of cardiorespiratory variables during isoflurane-fentanyl and propofol-fentanyl anaesthesia for surgery in injured cats

OBJECTIVE: To compare haemodynamic and respiratory variables during isoflurane-fentanyl (IF) and propofol-fentanyl (PF) anaesthesia for surgery in injured cats. STUDY DESIGN: Prospective, randomized, controlled clinical study. ANIMALS: Thirty-three client-owned injured cats undergoing orthopaedic surgery. MATERIALS AND METHODS: Pre-anaesthetic medication was intravenous midazolam 1 mg kg(-1), butorphanol 0.4 mg kg(-1) and ketamine 2 mg kg(-1). Anaesthesia was induced with propofol (P) and maintained with either: (a) a continuous rate infusion (CRI) of fentanyl (F) 0.02 mg kg(-1) hour(-1) and isoflurane (initial end-tidal concentration of 1%), (b) a fentanyl CRI (dose as before) and sevoflurane (initial end-tidal concentration of 2%) or (c) a CRI of propofol (12 mg kg(-1) hour(-1)). All three techniques were given to effect until surgical anaesthesia was achieved. Heart rate and rhythm (ECG), mean arterial blood pressure, respiratory rate, tidal volume and end-tidal CO(2) concentration were recorded. Venous blood gas analysis was performed before and after sedation, and at the end of anaesthesia. Blood chemistry and blood cell counts were assessed before, at the end of, and 24 hours after anaesthesia. The variables recorded from cats anaesthetized with IF and PF were compared. RESULTS: Mean end-expiratory isoflurane concentration was 1.19 +/- 0.19%. The propofol infusion rate was 11.4 +/- 0.8 mg kg(-1) hour(-1). No significant differences between the two groups in heart rate were identified; no cardiac dysrhythmias were recorded. Mean arterial blood pressure was significantly lower in IF cats during skin incision (p = 0.01), during surgery without intense surgical stimulation (p < 0.01) and during surgery with intense surgical stimulation (p = 0.01). Nine of 11 cats in the IF group were markedly hypotensive (34-49 mmHg) while seven of 11 cats in group PF were mildly hypotensive (49-59 mmHg). One of 11 cats in group IF and nine of 11 cats in group PF required intermittent positive pressure ventilation (IPPV) to maintain end-tidal CO(2) levels below 6.66 kPa (50 mmHg). CONCLUSION AND CLINICAL RELEVANCE: Despite the necessity to ventilate the lungs of cats in the PF group, arterial blood pressure was better maintained. Propofol-fentanyl anaesthesia is better for surgery in injured cats providing the means to impose IPPV are available.     

Effects of morphine and fentanyl constant rate infusion on urine output in healthy and traumatized dogs

ObjectiveTo determine whether healthy and traumatized dogs receiving a constant rate infusion (CRI) of either morphine or fentanyl have decreased urine production.Study designProspective randomized controlled study.Animal populationEighteen privately owned previously healthy dogs that had undergone trauma were included. Twenty-three privately owned healthy dogs were used as the controls.MethodsTraumatized dogs were randomized into one of two groups. Group Tmorphine received a CRI of morphine (0.12 mg kg⁻¹ hour⁻¹) and group Tfentanyl received a CRI of fentanyl (3 μg kg⁻¹ hour⁻¹) both administered in lactated Ringer’s solution (LRS) at a rate of 60 mL kg⁻¹ day⁻¹. Control healthy dogs were randomized into one of three groups. The LRS control group (CLRS) (n = 8) received LRS at a rate of 60 mL kg⁻¹ day⁻¹. Group Cmorphine (n = 8) and group Cfentanyl (n = 7) received the same infusions as Tmorphine and Tfentanyl, respectively. Collected data were identical for all groups and consisted of measuring total fluid administered, urine output, and urine specific gravity (USG) for a 24-hour period. An analysis of variance (anova) was used for statistical analysis and a p < 0.05 was considered statistically significant.ResultsUrine output was significantly decreased (p < 0.05) in all groups compared with the LRS control group. The end mean USG was significantly lower (p = 0.003) in the LRS control group compared with all other groups.ConclusionsThere was a decrease in urine output with a CRI of morphine or fentanyl in both healthy and traumatized dogs.Clinical relevanceDecreased urine output caused by an opioid effect might lead to improper assessments of renal function and urine production.     

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

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

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.     

Influence of a constant rate infusion of dexmedetomidine on cardiopulmonary function and recovery quality in isoflurane anaesthetized horses

ObjectiveTo investigate the influence of a dexmedetomidine constant rate infusion (CRI) in horses anaesthetized with isoflurane.Study designProspective, randomized, blinded, clinical study.AnimalsForty adult healthy horses (weight mean 491 ± SD 102 kg) undergoing elective surgery.MethodsAfter sedation [dexmedetomidine, 3.5 μg kg^?1 intravenously (IV)] and induction IV (midazolam 0.06 mg kg^?1, ketamine 2.2 mg kg^?1), anaesthesia was maintained with isoflurane in oxygen/air (FiO₂ 55–60%). Horses were ventilated and dobutamine was administered when hypoventilation [arterial partial pressure of CO₂ > 8.00 kPa (60 mmHg)] and hypotension [arterial pressure 70 mmHg] occurred respectively. During anaesthesia, horses were randomly allocated to receive a CRI of dexmedetomidine (1.75 μg kg^?1 hour^?1) (D) or saline (S). Monitoring included end-tidal isoflurane concentration, cardiopulmonary parameters, and need for dobutamine and additional ketamine. All horses received 0.875 μg kg^?1 dexmedetomidine IV for the recovery period. Age and weight of the horses, duration of anaesthesia, additional ketamine and dobutamine, cardiopulmonary data (anova), recovery scores (Wilcoxon Rank Sum Test), duration of recovery (t-test) and attempts to stand (Mann–Whitney test) were compared between groups. Significance was set at p < 0.05.ResultsHeart rate and arterial partial pressure of oxygen were significantly lower in group D compared to group S. An interaction between treatment and time was present for cardiac index, oxygen delivery index and systemic vascular resistance. End-tidal isoflurane concentration and heart rate significantly increased over time. Packed cell volume, systolic, diastolic and mean arterial pressure, arterial oxygen content, stroke volume index and systemic vascular resistance significantly decreased over time. Recovery scores were significantly better in group D, with fewer attempts to stand and significantly longer times to sternal position and first attempt to stand.Conclusions and clinical relevance A dexmedetomidine CRI produced limited cardiopulmonary effects, but significantly improved recovery quality.     

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

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

Anaesthetic Management of Baboons Undergoing Heterotopic Porcine Cardiac Xenotransplantation

A detailed anaesthetic technique for baboons (Papio anubis) undergoing heterotopic abdominal cardiac xenotransplantation is described. Twenty-two baboons served as transplant recipients. Donors were either crossbred farm pigs (Sus scrofa) (n = 4) or transgenic pigs (Sus scrofa) (n = 18) expressing human complement regulatory proteins on the endothelium. Intra-operative management was complicated by the physiological consequences of infrarenal, abdominal aortic cross-clamping, in addition to the immunological sequelae related to cross-species transplantation. In choosing anaesthetics for this procedure, we considered the need for maximal cardiac stability throughout a long surgical procedure that required abdominal aortic cross-clamping to facilitate the implantation of an oversized porcine cardiac graft. Baboons received a balanced anaesthetic consisting of inhaled isoflurane in oxygen, intravenous fentanyl and intravenous pancuronium. The pharmacological techniques employed were found to be safe and reliable and were well tolerated by our recipients without any significant side-effects.     

Evaluation of Masimo signal extraction technology pulse oximetry in anaesthetized pregnant sheep

ObjectiveEvaluation of the accuracy of Masimo signal extraction technology (SET) pulse oximetry in anaesthetized late gestational pregnant sheep.Study designProspective experimental study.AnimalsSeventeen pregnant Merino ewes.MethodsAnimals included in study were late gestation ewes undergoing general anaesthesia for Caesarean delivery or foetal surgery in a medical research laboratory. Masimo Radical-7 pulse oximetry (SpO₂) measurements were compared to co-oximetry (SaO₂) measurements from arterial blood gas analyses. The failure rate of the pulse oximeter was calculated. Accuracy was assessed by Bland &; Altman's (2007) limits of agreement method. The effect of mean arterial blood pressure (MAP), perfusion index (PI) and haemoglobin (Hb) concentration on accuracy were assessed by regression analysis.ResultsForty arterial blood samples paired with SpO₂ and blood pressure measurements were obtained. SpO₂ ranged from 42 to 99% and SaO₂ from 43.7 to 99.9%. MAP ranged from 24 to 82 mmHg, PI from 0.1 to 1.56 and Hb concentration from 71 to 114 g L^?1. Masimo pulse oximetry measurements tended to underestimate oxyhaemoglobin saturation compared to co-oximetry with a bias (mean difference) of ?2% and precision (standard deviation of the differences) of 6%. Accuracy appeared to decrease when SpO₂ was <75%, however numbers were too small for statistical comparisons. Hb concentration and PI had no significant effect on accuracy, whereas MAP was negatively correlated with SpO₂ bias.Conclusions and clinical relevanceMasimo SET pulse oximetry can provide reliable and continuous monitoring of arterial oxyhaemoglobin saturation in anaesthetized pregnant sheep during clinically relevant levels of cardiopulmonary dysfunction. Further work is needed to assess pulse oximeter function during extreme hypotension and hypoxaemia.     

Evaluation of the isoflurane‐sparing effects of fentanyl,lidocaine, ketamine,dexmedetomidine, or the combination lidocaine‐ketamine‐dexmedetomidine during ovariohysterectomy in dogs

ObjectiveTo evaluate the isoflurane‐sparing effects of an intravenous (IV) constant rate infusion (CRI) of fentanyl, lidocaine, ketamine, dexmedetomidine, or lidocaine‐ketamine‐dexmedetomidine (LKD) in dogs undergoing ovariohysterectomy.Study designRandomized, prospective, blinded, clinical study.AnimalsFifty four dogs.MethodsAnesthesia was induced with propofol and maintained with isoflurane with one of the following IV treatments: butorphanol/saline (butorphanol 0.4 mg kg^?1, saline 0.9% CRI, CONTROL/BUT); fentanyl (5 μg kg^?1, 10 μg kg^?1 hour^?1, FENT); ketamine (1 mg kg^?1, 40 μg kg^?1 minute^?1, KET), lidocaine (2 mg kg^?1, 100 μg kg^?1 minute^?1, LIDO); dexmedetomidine (1 μg kg^?1, 3 μg kg^?1 hour^?1, DEX); or a LKD combination. Positive pressure ventilation maintained eucapnia. An anesthetist unaware of treatment and end‐tidal isoflurane concentration (Fe′Iso) adjusted vaporizer settings to maintain surgical anesthetic depth. Cardiopulmonary variables and Fe′Iso concentrations were monitored. Data were analyzed using anova (p < 0.05).ResultsAt most time points, heart rate (HR) was lower in FENT than in other groups, except for DEX and LKD. Mean arterial blood pressure (MAP) was lower in FENT and CONTROL/BUT than in DEX. Overall mean ± SD Fe′Iso and % reduced isoflurane requirements were 1.01 ± 0.31/41.6% (range, 0.75 ± 0.31/56.6% to 1.12 ± 0.80/35.3%, FENT), 1.37 ± 0.19/20.8% (1.23 ± 0.14/28.9% to 1.51 ± 0.22/12.7%, KET), 1.34 ± 0.19/22.5% (1.24 ± 0.19/28.3% to 1.44 ± 0.21/16.8%, LIDO), 1.30 ± 0.28/24.8% (1.16 ± 0.18/32.9% to 1.43 ± 0.32/17.3%, DEX), 0.95 ± 0.19/54.9% (0.7 ± 0.16/59.5% to 1.12 ± 0.16/35.3%, LKD) and 1.73 ± 0.18/0.0% (1.64 ± 0.21 to 1.82 ± 0.14, CONTROL/BUT) during surgery. FENT and LKD significantly reduced Fe′Iso.Conclusions and clinical relevanceAt the doses administered, FENT and LKD had greater isoflurane‐sparing effect than LIDO, KET or CONTROL/BUT, but not at all times. Low HR during FENT may limit improvement in MAP expected with reduced Fe′Iso.     

Isoflurane minimum alveolar concentration sparing effects of fentanyl in the dog

Objective

To characterize the isoflurane-sparing effects of a high and a low dose of fentanyl in dogs, and its effects on mean arterial pressure (MAP) and heart rate (HR).