Minimum end‐tidal sevoflurane concentration necessary to prevent movement during a constant rate infusion of morphine,or morphine plus dexmedetomidine in ponies

ObjectiveTo compare the effects of a constant rate infusion (CRI) of dexmedetomidine and morphine to those of morphine alone on the minimum end-tidal sevoflurane concentration necessary to prevent movement (MAC_NM) in ponies.Study designProspective, randomized, crossover, ‘blinded’, experimental study.AnimalsFive healthy adult gelding ponies were anaesthetized twice with a 3-week washout period.MethodsAfter induction of anaesthesia with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (Fe‘SEVO 2.5%) in 55% oxygen. Monitoring included pulse oximetry, electrocardiography and measurement of anaesthetic gases, arterial blood pressure and body temperature. The ponies were mechanically ventilated and randomly allocated to receive IV treatment M [morphine 0.15 mg kg^?1 (T10-T15) followed by a CRI (0.1 mg kg^?1 hour^?1)] or treatment DM [dexmedetomidine 3.5 μg kg^?1 plus morphine 0.15 mg kg^?1 (T10-T15) followed by a CRI of dexmedetomidine 1.75 μg kg^?1 hour^?1 and morphine 0.1 mg kg^?1 hour^?1]. At T60, a stepwise MAC_NM determination was initiated using constant current electrical stimuli at the skin of the lateral pastern region. Triplicate MAC_NM estimations were obtained and then averaged in each pony. Wilcoxon signed-rank test was used to detect differences in MAC between treatments (a = 0.05).ResultsSevoflurane-morphine MAC_NM values (median (range) and mean ± SD) were 2.56 (2.01–4.07) and 2.79 ± 0.73%. The addition of a continuous infusion of dexmedetomidine significantly reduced sevoflurane MAC_NM values to 0.89 (0.62–1.05) and 0.89 ± 0.22% (mean MAC_NM reduction 67 ± 11%).Conclusion and clinical relevanceCo-administration of dexmedetomidine and morphine CRIs significantly reduced the MAC_NM of sevoflurane compared with a CRI of morphine alone at the reported doses.     

Effects of continuous intravenous infusion of morphine and morphine‐tramadol on the minimum alveolar concentration of sevoflurane and electroencephalographic entropy indices in dogs

ObjectiveTo compare the effects of continuous rate infusions (CRIs) of intravenous (IV) morphine and morphine-tramadol on the minimum alveolar concentration (MAC) of sevoflurane, and on electroencephalographic entropy indices in dogs.DesignProspective study.AnimalsEight young, healthy German shepherds, weighing 26.3 ± 3.1 kg (mean ± SD).MethodsAnaesthesia was induced and maintained with sevoflurane. A standard tail-clamp technique was used for MAC determination. Within one anaesthetic period, MAC was first determined during sevoflurane anaesthesia alone (MAC_B); then during morphine infusion (MAC_M), (loading dose 0.5 mg kg⁻¹IM; CRI, 0.2 mg kg⁻¹hour⁻¹⁾ then finally during morphine-tramadol infusion (tramadol loading dose 1.5 mg kg⁻¹IV; CRI, 2.6 mg kg⁻¹ hour⁻¹) (MAC_MT). At each change, periods of 45 minutes were allowed for equilibration. Stated entropy (SE), response entropy (RE), and RE-SE differences were measured five minutes prior to and during tail clamping.ResultsThe MAC_B was 2.1 ± 0.3vol%. The morphine and morphine-tramadol infusions reduced MAC to 1.6 ± 0.3vol% and 1.3 ± 0.3vol%, respectively. MAC was decreased below baseline more during morphine-tramadol than during morphine alone (39 ± 9% versus 25 ± 6%, respectively; p = 0.003). All SE and RE and most RE-SE differences were increased significantly (p < 0.05) over pre-stimulation in all groups when the dogs responded purposefully to noxious stimulation. When no response to noxious stimulation occurred, the entropy indices did not change.Conclusion and clinical relevanceIn dogs, combined morphine-tramadol CRI decreased sevoflurane MAC more than morphine CRI alone. Entropy indices changed during nociceptive responses in anaesthetized animals, suggesting that entropy measurements may be useful in determining anaesthetic depth in dogs.     

Effects of methadone on the minimum alveolar concentration of isoflurane in dogs

ObjectiveTo investigate the effects of methadone on the minimum alveolar concentration of isoflurane (ISO_MAC) in dogs.Study designProspective, randomized cross-over experimental study.AnimalsSix adult mongrel dogs, four males and two females, weighing 22.8 ± 6.6 kg.MethodsAnimals were anesthetized with isoflurane and mechanically ventilated on three separate days, at least 1 week apart. Core temperature was maintained between 37.5 and 38.5 °C during ISO_MAC determinations. On each study day, ISO_MAC was determined using electrical stimulation of the antebrachium (50 V, 50 Hz, 10 mseconds) at 2.5 and 5 hours after intravenous injection of physiological saline (control) or one of two doses of methadone (0.5 or 1.0 mg kg^?1).ResultsMean (±SD) ISO_MAC in the control treatment was 1.19 ± 0.15% and 1.18 ± 0.15% at 2.5 and 5 hours, respectively. The 1.0 mg kg^?1 dose of methadone reduced ISO_MAC by 48% (2.5 hours) and by 30% (5 hours), whereas the 0.5 mg kg^?1 dose caused smaller reductions in ISO_MAC (35% and 15% reductions at 2.5 and 5 hours, respectively). Both doses of methadone decreased heart rate (HR), but the 1.0 mg kg^?1 dose was associated with greater negative chronotropic actions (HR 37% lower than control) and mild metabolic acidosis at 2.5 hours. Mean arterial pressure increased in the MET1.0 treatment (13% higher than control) at 2.5 hours.Conclusions and clinical relevanceMethadone reduces ISO_MAC in a dose-related fashion and this effect is lessened over time. Although the isoflurane sparing effect of the 0.5 mg kg^?1 dose of methadone was smaller in comparison to the 1.0 mg kg^?1 dose, the lower dose is recommended for clinical use because it results in less evidence of cardiovascular impairment.     

Effects of tramadol on the minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effect of tramadol on sevoflurane minimum alveolar concentration (MAC_SEVO) in dogs. It was hypothesized that tramadol would dose-dependently decrease MAC_SEVO.Study designRandomized crossover experimental study.AnimalsSix healthy, adult female mixed-breed dogs (24.2 ± 2.6 kg).MethodsEach dog was studied on two occasions with a 7-day washout period. Anesthesia was induced using sevoflurane delivered via a mask. Baseline MAC (MAC_B) was determined starting 45 minutes after tracheal intubation. A noxious stimulus (50 V, 50 Hz, 10 ms) was applied subcutaneously over the mid-humeral area. If purposeful movement occurred, the end-tidal sevoflurane was increased by 0.1%; otherwise, it was decreased by 0.1%, and the stimulus was re-applied after a 20-minute equilibration. After MAC_B determination, dogs randomly received a tramadol loading dose of either 1.5 mg kg^?1 followed by a continuous rate infusion (CRI) of 1.3 mg kg^?1 hour^?1 (T1) or 3 mg kg^?1 followed by a 2.6 mg kg^?1 hour^?1 CRI (T2). Post-treatment MAC determination (MAC_T) began 45 minutes after starting the CRI. Data were analyzed using a mixed model anova to determine the effect of treatment on percentage change in baseline MAC_SEVO (p < 0.05).ResultsThe MAC_B values were 1.80 ± 0.3 and 1.75 ± 0.2 for T1 and T2, respectively, and did not differ significantly. MAC_T decreased by 26 ± 8% for T1 and 36 ± 12% for T2. However, there was no statistically significant difference in the decrease between the two treatments.Conclusion and clinical relevanceTramadol significantly reduced MAC_SEVO but this was not dose dependent at the doses studied.     

The effect of midazolam on the end-tidal concentration of isoflurane necessary to prevent movement in dogs

ObjectiveTo determine the possible additive effect of midazolam, a GABA_A agonist, on the end-tidal concentration of isoflurane that prevents movement (MAC_NM) in response to noxious stimulation.Study designRandomized cross-over experimental study.AnimalsSix healthy, adult intact male, mixed-breed dogs.MethodsAfter baseline isoflurane MAC_NM (MAC_NM-B) determination, midazolam was administered as a low (LDS), medium (MDS) or high (HDS) dose series of midazolam. Each series consisted of two dose levels, low and high. The LDS was a loading dose (Ld) of 0.2 mg kg^?1 and constant rate infusion (CRI) (2.5 μg kg^?1 minute^?1) (LDL), followed by an Ld (0.4 mg kg^?1) and CRI (5 μg kg^?1 minute^?1) (LDH). The MDS was an Ld (0.8 mg kg^?1) and CRI (10 μg kg^?1 minute^?1) (MDL) followed by an Ld (1.6 mg kg^?1) and CRI (20 μg kg^?1 minute^?1) (MDH). The HDS was an Ld (3.2 mg kg^?1) and CRI (40 μg kg^?1 minute^?1) (HDL) followed by an Ld (6.4 mg kg^?1) and CRI (80 μg kg^?1 minute^?1) (HDH). MAC_NM was re-determined after each dose in each series (MAC_NM-T).ResultsThe median MAC_NM-B was 1.42. MAC_NM-B did not differ among groups (p >0.05). Percentage reduction in MAC_NM was significantly less in the LDS (11 ± 5%) compared with MDS (30 ± 5%) and HDS (32 ± 5%). There was a weak correlation between the plasma midazolam concentration and percentage MAC_NM reduction (r = 0.36).Conclusion and clinical relevanceMidazolam doses in the range of 10–80 μg kg^?1 minute^?1 significantly reduced the isoflurane MAC_NM. However, doses greater than 10 μg kg^?1 minute^?1 did not further decrease MAC_NM indicating a ceiling effect.     

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.     

Effects of intravenous lidocaine, ketamine, and the combination on the minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effects of intravenous lidocaine (L) and ketamine (K) alone and their combination (LK) on the minimum alveolar concentration (MAC) of sevoflurane (SEVO) in dogs.Study designProspective randomized, Latin-square experimental study.AnimalsSix, healthy, adult Beagles, 2 males, 4 females, weighing 7.8 – 12.8 kg.MethodsAnesthesia was induced with SEVO in oxygen delivered by face mask. The tracheas were intubated and the lungs ventilated to maintain normocapnia. Baseline minimum alveolar concentration of SEVO (MAC_B) was determined in duplicate for each dog using an electrical stimulus and then the treatment was initiated. Each dog received each of the following treatments, intravenously as a loading dose (LD) followed by a constant rate infusion (CRI): lidocaine (LD 2 mg kg⁻¹, CRI 50 μg kg⁻¹minute⁻¹), lidocaine (LD 2 mg kg⁻¹, CRI 100 μgkg⁻¹ minute⁻¹), lidocaine (LD 2 mg kg⁻¹, CRI 200 μg kg⁻¹ minute⁻¹), ketamine (LD 3 mg kg⁻¹, CRI 50 μg kg⁻¹ minute⁻¹), ketamine (LD 3 mgkg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹), or lidocaine (LD 2 mg kg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹) + ketamine (LD 3 mg kg⁻¹, CRI 100 μg kg⁻¹ minute⁻¹) in combination. Post-treatment MAC (MAC_T) determination started 30 minutes after initiation of treatment.ResultsLeast squares mean ± SEM MAC_B of all groups was 1.9 ± 0.2%. Lidocaine infusions of 50, 100, and 200 μg kg⁻¹ minute⁻¹ significantly reduced MAC_B by 22.6%, 29.0%, and 39.6%, respectively. Ketamine infusions of 50 and 100 μg kg⁻¹ minute⁻¹ significantly reduced MAC_B by 40.0% and 44.7%, respectively. The combination of K and L significantly reduced MAC_B by 62.8%.Conclusions and clinical relevanceLidocaine and K, alone and in combination, decrease SEVO MAC in dogs. Their use, at the doses studied, provides a clinically important reduction in the concentration of SEVO during anesthesia in dogs.     

The effect of fentanyl on the end‐tidal sevoflurane concentration needed to prevent motor movement in dogs

ObjectiveThe objectives of this study were to determine the effects of fentanyl on the end-tidal concentration of sevoflurane needed to prevent motor movement (MAC_NM) in response to noxious stimulation, and to evaluate if acute tolerance develops.Study designRandomized cross-over experimental study.AnimalsSix healthy, adult (2–3 years old), intact male, mixed-breed dogs weighing 16.2 ± 1.1 kg.MethodsSix dogs were randomly assigned to receive one of three separate treatments over a 3 week period. After baseline sevoflurane MAC_NM (MAC_NM-B) determination, fentanyl treatments (T) were administered as a loading dose (Ld) and constant rate infusion (CRI) as follows: T1-Ld of 7.5 μg kg^?1 and CRI at 3 μg kg^?1 hour^?1; T2-Ld of 15 μg kg^?1 and CRI at 6.0 μg kg ^?1 hour^?1; T3-Ld of 30 μg kg^?1 and CRI at 12 μg kg^?1 hour^?1. The MAC_NM was defined as the minimum end-tidal sevoflurane concentration preventing motor movement. The first post-treatment MAC_NM (MAC_NM-I) determination was initiated 90 minutes after the start of the CRI, and a second MAC_NM (MAC_NM-II) determination was initiated 3 hours after MAC_NM-I was established.ResultsThe overall least square mean MAC_NM-B for all groups was 2.66%. All treatments decreased (p < 0.05) MAC_NM, and the decrease from baseline was 22%, 35% and 41% for T1, T2 and T3, respectively. Percentage change in T1 differed (p < 0.05) from T2 and T3; however, T2 did not differ from T3. MAC_NM-I was not significantly different from MAC_NM-II within treatments.Conclusions and clinical relevanceFentanyl doses in the range of 3–12 μg kg^?1 hour^?1 significantly decreased the sevoflurane MAC_NM. Clinically significant tolerance to fentanyl did not occur under the study conditions.     

Effect of intravenous butorphanol infusion on the minimum alveolar concentration of isoflurane in cats

ObjectiveTo determine the effect of butorphanol, administered by intravenous (IV) infusion, on the minimum alveolar concentration of isoflurane (MAC_ISO) in cats and to examine the dosage dependence of this effect.Study designRandomized, placebo-controlled, crossover experimental study.AnimalsA group of six healthy adult male neutered cats.MethodsCats were anesthetized with isoflurane in oxygen. A venous catheter was placed for fluid and drug administration, and an arterial catheter was placed for measurement of arterial pressure and blood sampling. Four treatments were administered at random with at least 2 week interval between treatments: saline (control), butorphanol low dosage (treatment LD; 0.25 mg kg^–1 IV bolus followed by 85 μg kg^–1 minute^–1 for 20 minutes, then 43 μg kg^–1 minute^–1 for 40 minutes, then 19 μg kg^–1 minute^–1), medium dosage (treatment MD, double the dosages in LD) and high dosage (treatment HD, quadruple the dosages in LD). MAC_ISO was determined in duplicate using the bracketing technique and tail clamping. Pulse rate, arterial pressure, hemoglobin oxygen saturation, end-tidal partial pressure of carbon dioxide and arterial blood gas and pH were measured.ResultsButorphanol reduced MAC_ISO in a dosage-dependent manner, by 23 ± 8%, 37 ± 12% and 68 ± 10% (mean ± standard deviation) in treatments LD, MD and HD, respectively. The main cardiopulmonary effect observed was a decrease in pulse rate, significant in treatment HD compared with control.Conclusions and clinical relevanceButorphanol caused a dosage-dependent MAC_ISO reduction in cats. IV infusion of butorphanol may be of interest for partial IV anesthesia in cats.     

Pharmacokinetics of morphine in combination with dexmedetomidine and maropitant following intramuscular injection in dogs anaesthetized with halothane

The purpose of this study was to evaluate the pharmacokinetics of morphine in combination with dexmedetomidine and maropitant injected intramuscularly in dogs under general anaesthesia. Eight healthy dogs weighing 25.76 ± 3.16 kg and 3.87 ± 1.64 years of age were used in a crossover study. Dogs were randomly allocated to four groups: (1) morphine 0.6 mg/kg; (2) morphine 0.3 mg/kg + dexmedetomidine 5 μg/kg; (3) morphine 0.3 mg/kg + maropitant 1 mg/kg; (4) morphine 0.2 mg/kg + dexmedetomidine 3 μg/kg + maropitant 0.7 mg/kg. Blood samples were collected before, 15 and 30 min, and 1, 2, 3 4, 6 and 8 hr after injection of the test drugs. Plasma concentration of the drugs was determined by liquid chromatography-mass spectrometry. The elimination half-life (T_1/2) of morphine was higher and the clearance rate (CL) was lower when combined with dexmedetomidine (T_1/2 = 77.72 ± 20.27 min, CL = 119.41 ± 23.34 ml kg⁻¹ min⁻¹) compared to maropitant (T_1/2 = 52.73 min ± 13.823 ml kg⁻¹ min⁻¹, CL = 178.57 ± 70.55) or morphine alone at higher doses (T_1/2 = 50.53 ± 12.55 min, CL = 187.24 ± 34.45 ml kg⁻¹ min⁻¹). Combining morphine with dexmedetomidine may increase the dosing interval of morphine and may have a clinical advantage.     

Effect of intravenous lidocaine and ketamine on isoflurane minimum alveolar concentration in goats

This study evaluated the effects of IV lidocaine (L) and ketamine (K), alone and in combination (LK), on the isoflurane MAC (ISO_MAC) in goats. It was hypothesized that L and K would reduce ISO_MAC and that the effect of LK would be additive. Eight adult goats (24–51 kg) were used in the study. Each goat was studied on four occasions, at weekly intervals, using a randomized crossover design. Anesthesia was induced with isoflurane (ISO) in O₂ and goats were intubated and ventilated to normocapnia. End‐tidal ISO (ET_ISO) and CO₂ were monitored with a calibrated infrared analyzer. Body temperature was maintained in the normal range using a heating pad. Approximately 45 minutes after intubation, and with the ET_ISO having been held constant for at least 20 minutes, determination of the baseline MAC (MAC_B) was initiated. A noxious stimulus, which consisted of clamping a claw between the jaws of a 10‐inch Vulsellum forceps, was administered for 60 seconds or until purposeful movement occurred. If purposeful movement occurred, the ET_ISO was increased by 0.1 vols% otherwise it was decreased by 0.1 vols% and the stimulus was reapplied following a 20 minute equilibration period. Following MAC_B determination treatments were administered as a loading dose (Ld) in 10 mL 0.9% NaCl over 3 minutes followed by a constant rate infusion to a final volume of 60 mL hour^–1 in 0.9% NaCl, as follows: L (Ld 2.5 mg kg^–1 + 100 μg kg^–1 minutes^–1); K (Ld 1.5 mg kg^–1 + 50 μg kg^–1minutes); LK or 0.9% NaCl. Post‐treatment MAC (MAC_T) determination began 45 minutes after the start of the loading dose. MAC_B and MAC_T were determined in triplicate and the mean value was used for data analysis. Difference in percent change in MAC was tested using a mixed‐model anova . Means separation among levels of treatment was tested using the Tukey‐Kramer method. The mean MAC_B for all treatments was 1.13 ± 0.03 vols%. L, K and LK reduced (p < 0.05) MAC_B by 19%, 49% and 69%, respectively. No change (p > 0.05) occurred with saline. It was concluded that L and K caused clinically significant decreases in ISO_MAC; however, the percent MAC reduction with L was less than expected given the MAC reduction reported with L for other species. The combination (LK) caused a profound decrease in ISO_MAC and this effect was additive.     

The effect of ketamine on the MACBAR of sevoflurane in dogs

ObjectiveTo determine the effect of intravenous ketamine on the minimum alveolar concentration of sevoflurane needed to block autonomic response (MAC_BAR) to a noxious stimulus in dogs.Study designRandomized, crossover, prospective design.AnimalsEight, healthy, adult male, mixed-breed dogs, weighing 11.2–16.1 kg.MethodsDogs were anesthetized with sevoflurane on two occasions, 1 week apart, and baseline MAC_BAR (B-MAC_BAR) was determined on each occasion. MAC_BAR was defined as the mean of the end-tidal sevoflurane concentrations that prevented and allowed an increase (≥15%) in heart rate or invasive mean arterial pressure in response to a noxious electrical stimulus (50 V, 50 Hz, 10 ms). Dogs then randomly received either a low-dose (LDS) or high-dose series (HDS) of ketamine, and treatment MAC_BAR (T-MAC_BAR) was determined. The LDS had an initial loading dose (LD) of 0.5 mg kg^?1 and constant rate infusion (CRI) at 6.25 μg kg^?1 minute^?1, followed, after T-MAC_BAR determination, by a second LD (1 mg kg^?1) and CRI (12.5 μg kg^?1 minute^?1). The HDS had an initial LD (2 mg kg^?1) and CRI (25 μg kg^?1 minute^?1) followed by a second LD (3 mg kg^?1) and CRI (50 μg kg^?1 minute^?1). Data were analyzed with a mixed-model anova and are presented as LSM ± SEM.ResultsThe B-MAC_BAR was not significantly different between treatments. Ketamine at 12.5, 25, and 50 μg kg^?1 minute^?1 decreased sevoflurane MAC_BAR, and the maximal decrease (22%) occurred at 12.5 μg kg^?1 minute^?1. The percentage change in MAC_BAR was not correlated with either the log plasma ketamine or norketamine concentration.Conclusions and clinical relevanceKetamine at clinically relevant doses of 12.5, 25, and 50 μg kg^?1 minute^?1 decreased sevoflurane MAC_BAR, although the reduction was neither dose-dependent nor linear.     

Effect of different inspired fractions of oxygen on F-shunt and arterial partial pressure of oxygen in isoflurane-anaesthetized and mechanically ventilated Shetland ponies

ObjectiveTo determine the effect of fraction of inspired oxygen (FiO₂) on intrapulmonary shunt fraction as measured by F-shunt in ponies during isoflurane anaesthesia.Study designProspective, randomized clinical study.AnimalsA group of 23 adult Shetland ponies undergoing a total of 32 anaesthetic procedures.MethodsPonies were premedicated intravenously (IV) with detomidine (0.01 mg kg^–1) and either morphine (0.1 mg kg^–1) or butorphanol (0.02 mg kg^–1). Anaesthesia was induced with ketamine (2.2 mg kg^–1) and midazolam (0.07 mg kg^–1) administered IV. Ponies were randomly allocated to maintenance of anaesthesia with isoflurane in oxygen (group TH; FiO₂ = 0.95) or a mixture of oxygen and medical air (group TL; FiO₂ = 0.65); all ponies were given a constant rate of infusion of detomidine. Animals were mechanically ventilated to maintain PaCO₂ between 40 and 50 mmHg. Arterial blood gas analysis was performed every 30 minutes. The F-shunt equation was calculated for each time point T0, T30, T60 and T90. Data were analysed using linear mixed model analysis and presented as mean ± standard deviation (p < 0.05).ResultsPaO₂ was greater in group TH than in group TL (TH: 406 ± 90, 438 ± 83, 441 ± 69 and 464 ± 53 mmHg versus TL: 202 ± 90, 186 ± 84, 172 ± 85 and 191 ± 98 mmHg at T0, T30, T60 and T90, respectively; p < 0.0001). In TH, F-shunt was < TL. Significant differences were found at T60 (TH: 13.2% ± 4.3 versus TL: 19.4% ± 8.3; p = 0.016) and T90 (TH: 11.7% ± 3.5 versus TL: 18.6% ± 9.5; p = 0.036).Conclusions and clinical relevanceOur findings do not support a beneficial effect of using a reduced FiO₂ to improve oxygenation in anaesthetized and mechanically ventilated Shetland ponies.     

Determination of the minimum alveolar concentration (MAC) and cardiopulmonary effects of sevoflurane in sheep

Objective

To determine sevoflurane’s minimum alveolar concentration (MAC_SEVO) and its cardiopulmonary effects in sheep.

Pharmacokinetics of intra‐articular morphine in horses with lipopolysaccharide‐induced synovitis

ObjectiveTo describe the pharmacokinetics of intra-articularly (IA) administered morphine.Study designExperimental randomized, cross-over study.AnimalsEight adult healthy mixed breed horses aged 6.5 ± 2.3 (mean ± SD) years and weighing 535 ± 86 kg.MethodsUnilateral radiocarpal synovitis was induced by IA injection of 3 μg lipopolysaccharide (LPS) on two occasions (right and left radiocarpal joint, respectively) separated by a 3-week wash-out period. Treatments were administered 4 hours post-LPS-injection: Treatment IA; preservative free morphine IA (0.05 mg kg^?1) plus saline intravenous (IV) and treatment IV; saline IA plus preservative free morphine IV (0.05 mg kg^?1). Concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide (M6G) were determined repeatedly in serum and synovial fluid (SF) by high-performance liquid chromatography mass spectrometry, at 2 and 4 hours and then at 4 hours intervals until 28 hours post-treatment.ResultsInjection of LPS elicited a marked and comparable synovitis in all LPS-injected radiocarpal joints. IA administered morphine was detectable in SF of all eight joints 24 hours post-treatment and in 6/8 joints 28 hours post-treatment. The terminal half-life of morphine in SF was estimated to be 2.6 hours. IA administration of morphine resulted in mean serum concentrations of morphine below 5 ng mL^?1 from 2 to 28 hours after treatment.Conclusions and clinical relevanceIntra-articularly administered morphine remained within the joint for at least 24 hours. At the same time only very low serum concentrations of morphine and M6G were detected. The present results suggest that IA morphine at 0.05 mg kg^?1 may be used for IA analgesia lasting at least 24 hours and give strong support to the theory that previously observed analgesic and anti-inflammatory effects of IA morphine in horses are most likely to be mediated peripherally.     

Metabolism,pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses

ObjectiveTo describe the pharmacokinetics and selected pharmacodynamic variables of codeine and its metabolites in Thoroughbred horses following a single oral administration.Study designProspective experimental study.AnimalsA total of 12 Thoroughbred horses, nine geldings and three mares, aged 4–8 years.MethodsHorses were administered codeine (0.6 mg kg^–1) orally and blood was collected before administration and at various times until 120 hours post administration. Plasma and urine samples were collected and analyzed for codeine and its metabolites by liquid chromatography–mass spectrometry, and plasma pharmacokinetics were determined. Heart rate and rhythm, step counts, packed cell volume and total plasma protein were measured before and 4 hours after administration.ResultsCodeine was rapidly converted to the metabolites norcodeine, codeine-6-glucuronide (C6G), morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Plasma codeine concentrations were best represented using a two-compartment model. The C_max, t_max and elimination t_½ were 270.7 ± 136.0 ng mL^–1, 0.438 ± 0.156 hours and 2.00 ± 0.534 hours, respectively. M3G was the main metabolite detected (C_max 492.7 ± 35.5 ng mL^–1), followed by C6G (C_max 96.1 ± 33.8 ng mL^–1) and M6G (C_max 22.3 ± 4.96 ng mL^–1). Morphine and norcodeine were the least abundant metabolites with C_max of 3.17 ± 0.95 and 1.42 ± 0.79 ng mL^–1, respectively. No significant adverse or excitatory effects were observed.Conclusions and clinical relevanceFollowing oral administration, codeine is rapidly metabolized to morphine, M3G, M6G, C6G and norcodeine in horses. Plasma concentrations of M6G, a presumed active metabolite of morphine, were comparable to concentrations reported previously following administration of an analgesic dose of morphine to horses. Codeine was well tolerated based on pharmacodynamic variables and behavioral observations.     

The effects of medetomidine on the action of vecuronium in dogs anaesthetized with halothane and nitrous oxide

ObjectiveTo quantify the effects of medetomidine on the onset and duration of vecuronium-induced neuromuscular blockade in dogs.Study designRandomized, prospective clinical study.AnimalsTwenty-four, healthy, client-owned dogs of different breeds, aged between 6 months and 10 years and weighing between 5.0 and 40.0 kg undergoing elective surgery.MethodsDogs were randomly allocated to two groups. Pre-anaesthetic medication in group M+ was intramuscular acepromazine (ACP) 25 μg kg⁻¹, morphine 0.5 mg kg⁻¹ and medetomidine 5 μg kg⁻¹. Group M− received ACP and morphine only, at the same dose rate. After induction with thiopental, anaesthesia was maintained with halothane in oxygen and nitrous oxide. End-tidal halothane concentration was maintained at 1.1%. Neuromuscular blockade was produced with intravenous vecuronium (50 μg kg⁻¹) and monitored using a train of four stimulus applied at the ulnar nerve. The times taken for loss and reappearance of the four evoked responses (twitches [T]) were recorded. Normal and nonparametric data were analysed with an independent t-test and Mann-Whitney's U-test, respectively.ResultsThe fourth twitch (T4) disappeared at similar times in each group: 107 ± 19; [72–132] (mean ± SD; [range]) seconds in M+ and 98 ± 17 [72–120] seconds in M− dogs. The first twitch (T1) was lost at 116 ± 15; [96–132] seconds in group M+ and 109 ± 19; [72–132] seconds in M−. The fourth twitch returned significantly earlier in M+ dogs: 20.8 ± 3.8 [14–28] minutes compared with 23.8 ± 2.7 [20–27] minutes (p = 0.032). The duration of drug effect (T4 absent) was significantly shorter (p = 0.027) in M+ (18.9 ± 3.7 minutes) compared with M− dogs (22.2 ± 2.9 minutes). The recovery rate (interval between reappearance of T1 and T4) was significantly more rapid (p = 0.0003) in medetomidine recipients (3.0 ± 1.2 versus 5.2 ± 1.3 minutes).Conclusion and clinical relevance Medetomidine 5 μg kg⁻¹ as pre-anaesthetic medication shortened the duration of effect of vecuronium in halothane-anaesthetized dogs and accelerated recovery, but did not affect the onset time. These changes are of limited clinical significance.     

Evaluation of perfusion index as a noninvasive tool to determine epidural anesthesia effectiveness in dogs

ObjectiveTo evaluate perfusion index (PI) as a noninvasive tool to determine effectiveness and onset of epidural anesthesia in dogs.Study designProspective clinical trial.AnimalsA total of 21 adult dogs, aged 6.5 ± 3 years and weighing 34.9 ± 6.4 kg, undergoing a tibial plateau leveling osteotomy.MethodsDogs were premedicated intramuscularly with acepromazine (0.03 mg kg^–1) and hydromorphone (0.1 mg kg^–1) and anesthetized with intravenous propofol (to effect) and isoflurane in oxygen. A surface transflectance probe was secured to the tail base to monitor PI and a dorsal pedal artery catheter was placed for invasive blood pressure monitoring. A lumbosacral epidural was performed with the dog in sternal recumbency. Dogs were randomly assigned for inclusion of epidural morphine (0.1 mg kg^–1) or morphine (0.1 mg kg^–1) and lidocaine (4 mg kg^–1). PI was recorded following instrumentation of each dog just prior to the epidural (baseline), at 10 minute intervals for 30 minutes, before and after the surgical skin incision and before and after completion of the osteotomy. Physiological variables and end-tidal isoflurane were recorded at the same time points.ResultsThere was no significant difference in PI between the groups at any time point. There was a significant change in end-tidal isoflurane before and after the skin incision in the epidural morphine and epidural morphine–lidocaine groups (p = 0.04, p = 0.05, respectively) and before and after the osteotomy in each group for heart rate (p = 0.001, p = 0.04), diastolic (p = 0.01, p = 0.01) and mean arterial blood pressure (p = 0.03, p = 0.05).Conclusions and clinical relevancePI did not provide an objective means for determining the onset or effectiveness of epidural anesthesia in anesthetized dogs and alternate methods of noninvasive assessment should be investigated.     

Cardiovascular function,pulmonary gas exchange and tissue oxygenation in isoflurane-anesthetized,mechanically ventilated Beagle dogs with four levels of positive end-expiratory pressure

ObjectivesTo compare pulmonary gas exchange, tissue oxygenation and cardiovascular effects of four levels of end-expiratory pressure: no positive end-expiratory pressure (ZEEP), positive end-expiratory pressure (PEEP) of maximal respiratory system compliance (PEEPmaxC_rs), PEEPmaxC_rs + 2 cmH₂O (PEEPmaxC_rs+2), PEEPmaxC_rs + 4 cmH₂O (PEEPmaxC_rs+4), in isoflurane-anesthetized dogs.Study designProspective randomized crossover study.AnimalsA total of seven healthy male Beagle dogs, aged 1 year and weighing 10.2 ± 0.7 kg (mean ± standard deviation).MethodsThe dogs were administered acepromazine and anesthesia was induced with propofol and maintained with isoflurane. Ventilation was controlled for 4 hours with ZEEP, PEEPmaxC_rs, PEEPmaxC_rs+2 or PEEPmaxC_rs+4. Cardiovascular, pulmonary gas exchange and tissue oxygenation data were evaluated at 5, 60, 120, 180 and 240 minutes of ventilation and compared using a mixed-model anova followed by Bonferroni test. p < 0.05 was considered significant.ResultsCardiac index (CI) and mean arterial pressure (MAP) were lower in all PEEP treatments at 5 minutes when compared with ZEEP. CI persisted lower throughout the 4 hours only in PEEPmaxC_rs+4 with the lowest CI at 5 minutes (2.15 ± 0.70 versus 3.45 ± 0.94 L minute^–1 m^–2). At 180 and 240 minutes, MAP was lower in PEEPmaxC_rs+4 than in PEEPmaxC_rs, with the lowest value at 180 minutes (58 ± 7 versus 67 ± 7 mmHg). Oxygen delivery index (DO₂I) was lower in PEEPmaxC_rs+4 than in ZEEP at 5, 60, 120 and 180 minutes. Venous admixture was not different among treatments.Conclusion and clinical relevanceThe use of PEEP caused a transient decrease in MAP and CI in lung-healthy dogs anesthetized with isoflurane, which improved after 60 minutes of ventilation in all levels of PEEP except PEEPmaxC_rs+4. A clinically significant improvement in arterial oxygenation and DO₂I was not observed with PEEPmaxC_rs and PEEPmaxC_rs+2 in comparison with ZEEP, whereas PEEPmaxC_rs+4 decreased DO₂I.