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.     

Postoperative respiratory effects of intravenous fentanyl compared to intravenous methadone in dogs following spinal surgery

Objective

To evaluate the 24-hour postoperative respiratory effects of either intravenous fentanyl administered as a constant rate infusion or boluses of methadone, in dogs following spinal surgery, assessed by serial arterial blood gas analyses.

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).

The effect of inhalant anesthetic and body temperature on peri-anesthetic serum concentrations of transdermally administered fentanyl in dogs

Objectives To determine whether moderate hypothermia during anesthesia significantly affects the serum concentration of transdermally delivered fentanyl and whether halothane or isoflurane affect these concentrations. Study Design Randomized cross‐over experimental trial. Animals Six mature, healthy Beagles (three males, three females) weighing 10.6 ± 0.43 kg. Methods A 50‐µg hour^?1 fentanyl patch was applied 36 hours prior to anesthesia. Anesthesia was induced at time 0 (t = 0). Each dog received four treatments: isoflurane + normothermia (ISO‐NORM), isoflurane + hypothermia (ISO‐HYPO), halothane + normothermia (HAL‐NORM), and halothane + hypothermia (HAL‐HYPO). Dogs were intubated and maintained at 1.5 times MAC. Animals in the hypothermia treatments were cooled to 35 °C during anesthesia. Serum fentanyl analysis was performed at ?36, ?24, ?12, 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 18, and 26 hours. Direct arterial blood pressures and arterial blood gases were monitored. Results The mean body temperatures (±SEM) during the anesthetic period for the four treatments were: ISO‐NORM = 37.7 ± 0.07 °C, ISO‐HYPO = 35.8 ± 0.1 °C, HAL‐NORM = 37.7 ± 0.06 °C, and HAL‐HYPO = 35.8 ± 0.13 °C. The mean (±SEM) serum fentanyl concentrations (SFC) for both hypothermia treatments were significantly lower than baseline concentrations at t = 1 hour and persisted for the duration of anesthesia for the ISO‐HYPO treatment but only from t = 1 to 2 hours for the HAL‐HYPO treatment. Serum fentanyl concentrations returned to baseline within one hour of the end of anesthesia, regardless of body temperature. There were no significant differences between treatments for systolic or diastolic blood pressure but mean blood pressures were higher during normothermia versus hypothermia during the last hour of anesthesia. Conclusions and clinical relevance Hypothermia during inhalation anesthesia produced a significant reduction in SFC using transdermal administration and was more protracted with isoflurane than halothane anesthesia. While significant reductions in SFC occurred, the SFC were still within the range believed to confer analgesia.     

Hemodynamic effects of incremental doses of acepromazine in isoflurane-anesthetized dogs

ObjectiveTo evaluate the effects of incremental doses of acepromazine on hemodynamics in isoflurane-anesthetized dogs.Study designProspective, experimental study.AnimalsHealthy, adult, mixed-breed dogs (two male and four female) weighing 16.8 ± 5.1 kg (mean ± standard deviation).MethodsDogs were anesthetized with propofol (7 mg kg^–1) intravenously (IV) and isoflurane. Thermodilution and arterial catheters were placed for hemodynamic monitoring and arterial blood sampling for blood gas analysis. Baseline measurements were performed with stable expired concentration of isoflurane (Fe′Iso) at 1.8%. Each dog was then administered four incremental acepromazine injections (10, 15, 25 and 50 μg kg^–1) IV, and measurements were repeated 20 minutes after each acepromazine injection with Fe′Iso decreased to 1.2%. The four acepromazine injections resulted in cumulative doses of 10, 25, 50 and 100 μg kg^–1 (time points ACP₁₀, ACP₂₅, ACP₅₀ and ACP₁₀₀, respectively).ResultsCompared with baseline, cardiac index (CI) increased significantly by 34%, whereas systemic vascular resistance index (SVRI) decreased by 25% at ACP₅₀ and ACP₁₀₀. Arterial oxygen content (CaO₂) was significantly lower than baseline after all acepromazine injections (maximum decreases of 11%) and was lower at ACP₅₀ and ACP₁₀₀ than at ACP₁₀. No significant change was found in heart rate, stroke index, oxygen delivery index and systolic, mean and diastolic blood pressures. Hypotension (mean arterial pressure < 60 mmHg) was observed in one dog at baseline, ACP₁₀, ACP₂₅ and ACP₁₀₀, and in two dogs at ACP₅₀.Conclusions and clinical relevanceCompared with isoflurane alone, anesthesia with acepromazine–isoflurane resulted in increased CI and decreased SVRI and CaO₂ values. These effects were dose-related, being more pronounced at ACP₅₀ and ACP₁₀₀. Under the conditions of this study, acepromazine administration did not change blood pressure.     

Chronotropic effect of propofol or alfaxalone following fentanyl administration in healthy dogs

ObjectiveTo compare the effect of alfaxalone and propofol on heart rate (HR) and blood pressure (BP) after fentanyl administration in healthy dogs.Study designProspective, randomised clinical study.AnimalsFifty healthy client owned dogs (ASA I/II) requiring general anaesthesia for elective magnetic resonance imaging for neurological conditions.MethodsAll dogs received fentanyl 7 μg kg⁻¹ IV and were allocated randomly to receive either alfaxalone (n = 25) or propofol (n = 25) to effect until endotracheal (ET) intubation was possible. Heart rate and oscillometric BP were measured before fentanyl (baseline), after fentanyl (Time F) and after ET intubation (Time GA). Post-induction apnoea were recorded. Data were analysed using Fisher’s exact test, Mann Whitney U test and one-way anova for repeated measures as appropriate; p value <0.05 was considered significant.ResultsDogs receiving propofol showed a greater decrease in HR (-14 beat minute⁻¹, range -47 to 10) compared to alfaxalone (1 beat minute⁻¹, range -33 to 26) (p = 0.0116). Blood pressure decreased over the three time periods with no difference between groups. Incidence of post-induction apnoea was not different between groups.ConclusionFollowing fentanyl administration, anaesthetic induction with propofol resulted in a greater negative chronotropic effect while alfaxalone preserved or increased HR.Clinical relevanceFollowing fentanyl administration, HR decreases more frequently when propofol rather than alfaxalone is used as induction agent. However, given the high individual variability and the small change in predicted HR (-7.7 beats per minute after propofol), the clinical impact arising from choosing propofol or alfaxalone is likely to be small in healthy animals. Further studies in dogs with myocardial disease and altered haemodynamics are warranted.     

Hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats

ObjectiveTo characterize the hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats.Study designProspective experimental study.AnimalsSix healthy adult female cats weighing 4.6 ± 0.8 kg.MethodsDexmedetomidine was administered intravenously using target-controlled infusions to maintain nine plasma concentrations between 0 and 20 ng mL^?1 in isoflurane-anesthetized cats. The isoflurane concentration was adjusted for each dexmedetomidine concentration to maintain the equivalent of 1.25 times the minimum alveolar concentration, based on a previous study. Heart rate, systemic and pulmonary arterial pressures, central venous pressure, pulmonary artery occlusion pressure, body temperature, and cardiac output were measured at each target plasma dexmedetomidine concentration. Additional variables were calculated. Arterial and mixed-venous blood samples were collected for blood gas, pH, and (on arterial blood only) electrolyte, glucose and lactate analysis. Plasma dexmedetomidine concentration was determined for each target. Pharmacodynamic models were fitted to the data.ResultsHeart rate, arterial pH, arterial bicarbonate concentration, mixed-venous PO₂, mixed-venous pH, mixed-venous hemoglobin oxygen saturation, cardiac index, stroke index, and venous admixture decreased following dexmedetomidine administration. Arterial blood pressure, central venous pressure, pulmonary arterial pressure, pulmonary arterial occlusion pressure, packed cell volume, PaO₂, PaCO₂, arterial hemoglobin concentration, mixed-venous PCO₂, mixed-venous hemoglobin concentration, ionized calcium concentration, glucose concentration, rate-pressure product, systemic and pulmonary vascular resistance indices, left ventricular stroke work index, arterial oxygen concentration, and oxygen extraction increased following dexmedetomidine administration. Most variables changed in a dexmedetomidine concentration-dependent manner.Conclusion and clinical relevanceThe use of dexmedetomidine as an anesthetic adjunct is expected to produce greater negative hemodynamic effects than a higher, equipotent concentration of isoflurane alone.     

Cardiovascular effects of desflurane following acute hemorrhage in dogs

Objective: To determine the cardiovascular effects of desflurane in dogs following acute hemorrhage. Design: Experimental study. Animals: Eight mix breed dogs. Interventions: Hemorrhage was induced by withdrawal of blood until mean arterial pressure (MAP) dropped to 60 mmHg in conscious dogs. Blood pressure was maintained at 60 mmHg for 1 hour by further removal or replacement of blood. Desflurane was delivered by facemask until endotracheal intubation could be performed and a desflurane expiratory end‐tidal concentration of 10.5 V% was maintained. Measurements and main results: Systolic, diastolic, and mean arterial blood pressure (SAP, DAP and MAP), central venous pressure (CVP), cardiac output (CO), stroke volume (SV), cardiac index (CI), systemic vascular resistance (SVR), heart rate (HR), respiratory rate (RR), partial pressure of carbon dioxide in arterial blood (PaCO₂), and arterial pH were recorded before and 60 minutes after hemorrhage, and 5, 15, 30, 45 and 60 minutes after intubation. Sixty minutes after hemorrhage, SAP, DAP, MAP, CVP, CO, CI, SV, PaCO₂, and arterial pH decreased, and HR and RR increased when compared with baselines values. Immediately after intubation, MAP and arterial pH decreased, and PaCO₂ increased. Fifteen minutes after intubation SAP, DAP, MAP, arterial pH, and SVR decreased. At 30 and 45 minutes, MAP and DAP remained decreased and PaCO₂ increased, compared with values measured after hemorrhage. Arterial pH increased after 30 minutes of desflurane administration compared with values measured 5 minutes after intubation. Conclusions: Desflurane induced significant changes in blood pressure and arterial pH when administered to dogs following acute hemorrhage.     

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.     

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.     

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.     

Cardiovascular and respiratory effects of ketamine infusions in isoflurane-anesthetized dogs before and during noxious stimulation

OBJECTIVE: To characterize the effects of ketamine administration on the cardiovascular and respiratory systems and on acid-base balance and to record adverse effects of ketamine in isoflurane-anesthetized dogs. ANIMALS: 6 healthy adult mongrel dogs. PROCEDURE: Dogs were anesthetized with isoflurane (1.25 times the individual minimum alveolar concentration) in oxygen, and ketamine was administered IV to target pseudo-steady-state plasma concentrations of 0, 0.5, 1, 2, 5, 8, and 11 microg/mL. Isoflurane concentration was reduced to an equipotent concentration. Cardiovascular, respiratory, and acid-base variables; body temperature; urine production; and adverse effects were recorded before and during noxious stimulation. Cardiac index, stroke index, rate-pressure product, systemic vascular resistance index, pulmonary vascular resistance index, left ventricular stroke work index, right ventricular stroke work index, arterial oxygen concentration, mixed-venous oxygen concentration, oxygen delivery, oxygen consumption, oxygen extraction ratio, alveolar-arterial oxygen partial pressure gradient, and venous admixture were calculated. Plasma ketamine and norketamine concentrations were measured. RESULTS: Overall, ketamine administration improved ventilation, oxygenation, hemodynamics, and oxygen delivery in isoflurane-anesthetized dogs in a dosedependent manner. With the addition of ketamine, core body temperature was maintained or increased and urine production was maintained at an acceptable amount. However, at the higher plasma ketamine concentrations, adverse effects such as spontaneous movement and profuse salivation were observed. Myoclonus and dysphoria were observed during recovery in most dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of ketamine appears to be a suitable technique for balanced anesthesia with isoflurane in dogs. Plasma ketamine concentrations between 2 to 3 microg/mL elicited the most benefits with minimal adverse effects.     

Effect of fentanyl on the induction dose and minimum infusion rate of propofol preventing movement in dogs

Objective

To determine the effect of fentanyl on the induction dose of propofol and minimum infusion rate required to prevent movement in response to noxious stimulation (MIR_NM) in dogs.

Effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone preventing movement in dogs

Objective

To determine the effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone required to prevent movement in response to a noxious stimulus (MIR_NM) in dogs.

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.     

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.     

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.     

Cardiovascular effects of vasopressors in isoflurane-anesthetized dogs before and after hemorrhage

Exogenously administered vasopressors (sympathomimetics) were evaluated in isoflurane-anesthetized dogs to determine the effects of these drugs on cardiovascular function before and after hemorrhage. Six dogs were anesthetized with thiamylal sodium (20 mg/kg of body weight) and isoflurane (1.25 minimal alveolar concentration) in 100% oxygen. After instrumentation, cardiac output, systemic arterial blood pressure, heart rate (HR), left ventricular pressure, pulmonary arterial pressure, and an index of cardiac contractility (dP/dT) were measured. Stroke volume, cardiac index (CI), stroke index (SI), rate-pressure product, and systemic vascular resistance (SVR) were calculated. Epinephrine (0.1, 0.3, and 0.5 micrograms/kg/min [low, medium, and high doses, respectively]) and dobutamine (1, 5, and 10 micrograms/kg/min [low, medium, and high doses, respectively]) were infused. Methoxamine was given in a bolus of 0.22 mg/kg, IV. All measurements were taken at 2.5 minutes after infusion, and were repeated after removal of 40% of the estimated blood volume. Before hemorrhage, administration of high doses of dobutamine and medium and high doses of epinephrine were equally effective at increasing CI and SI. The dP/dT was increased to the greatest degree by administration of high doses of dobutamine. Administration of the low dose of dobutamine increased dP/dT, whereas administration of the low dose of epinephrine increased CI, HR, and SI, and decreased SVR. The HR and SVR were not increased by administration of any dose of dobutamine or of the medium and high doses of epinephrine. However, methoxamine increased SVR and decreased HR. Methoxamine decreased CI, SI, and dP/dT, but increased systemic arterial pressure to the same degree as that attributed to administration of high doses of dobutamine and epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of increasing dosages of norepinephrine in healthy isoflurane-anesthetized New Zealand White rabbits

ObjectiveTo characterize the cardiovascular effects of increasing dosages of norepinephrine (NE) in healthy isoflurane-anesthetized rabbits.Study designProspective experimental study.AnimalsA total of nine female ovariohysterectomized New Zealand White rabbits weighing 3.4 ± 0.2 kg (mean ± standard deviation).MethodsRabbits were premedicated intramuscularly with buprenorphine (0.05 mg kg^–1) and midazolam (0.5 mg kg^–1). Anesthesia was induced with intravenous propofol and maintained with a 1.1 × minimum alveolar concentration of isoflurane for this species to induce hypotension. Rabbits were administered NE infusions at three doses: low, 0.1 μg kg^–1 minute^–1; medium, 0.5 μg kg^–1 minute^–1; and high doses, 1 μg kg^–1 minute^–1 for 10 minutes each in that order. Cardiovascular variables including heart rate (HR), cardiac output (CO) by lithium dilution technique and systolic (SAP), mean (MAP) and diastolic (DAP) invasive arterial blood pressures measured in the auricular artery were recorded at baseline, 10 minutes after the start of the infusion of each NE treatment and 10 minutes after NE was discontinued. A linear mixed model and a type III anova with Tukey’s post hoc comparison was performed (p < 0.05).ResultsSignificant increases in SAP (28% and 90%), MAP (27% and 90%) and DAP (33% and 97%) were measured with medium and high dose treatments, respectively (p < 0.001), with no changes in CO. HR decreased and stroke volume increased significantly with high dose treatment (by 17% and 15%, respectively; p < 0.05). No arrhythmias were noticed with NE treatments.Conclusions and clinical relevanceThe infusion of NE at 0.5–1.0 μg kg^–1 minute^–1 is a potentially effective treatment for hypotension in healthy isoflurane-anesthetized New Zealand White rabbits.