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.     

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.     

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.     

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.     

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 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.     

Effects of constant rate infusions of dexmedetomidine,remifentanil and their combination on minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs.Study designRandomized crossover experimental study.AnimalsA total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg.MethodsAnesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg^–1 hour^–1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 μg kg^–1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 μg kg^–1 hour^–1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 μg kg^–1 minute^–1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED₅₀) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 μg kg^–1 hour^–1, obtained using log-linear regression analysis.ResultsThe sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED₅₀ values were lower when combined with dexmedetomidine than those obtained during saline–remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 μg kg^–1 hour^–1.Conclusions and clinical relevanceCombined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.     

A clinical study on the effect in horses during medetomidine-isoflurane anaesthesia, of butorphanol constant rate infusion on isoflurane requirements, on cardiopulmonary function and on recovery characteristics

ObjectiveTo test if the addition of butorphanol by constant rate infusion (CRI) to medetomidine–isoflurane anaesthesia reduced isoflurane requirements, and influenced cardiopulmonary function and/or recovery characteristics.Study designProspective blinded randomised clinical trial.Animals61 horses undergoing elective surgery.MethodsHorses were sedated with intravenous (IV) medetomidine (7 μg kg^?1); anaesthesia was induced with IV ketamine (2.2 mg kg^?1) and diazepam (0.02 mg kg^?1) and maintained with isoflurane and a CRI of medetomidine (3.5 μg kg^?1 hour^?1). Group MB (n = 31) received butorphanol CRI (25 μg kg^?1 IV bolus then 25 μg kg^?1 hour^?1); Group M (n = 30) an equal volume of saline. Artificial ventilation maintained end-tidal CO₂ in the normal range. Horses received lactated Ringer’s solution 5 mL kg^?1 hour^?1, dobutamine <1.25 μg kg^?1 minute^?1 and colloids if required. Inspired and exhaled gases, heart rate and mean arterial blood pressure (MAP) were monitored continuously; pH and arterial blood gases were measured every 30 minutes. Recovery was timed and scored. Data were analyzed using two way repeated measures anova, independent t-tests or Mann–Whitney Rank Sum test (p < 0.05).ResultsThere was no difference between groups with respect to anaesthesia duration, end-tidal isoflurane (MB: mean 1.06 ± SD 0.11, M: 1.05 ± 0.1%), MAP (MB: 88 ± 9, M: 87 ± 7 mmHg), heart rate (MB: 33 ± 6, M: 35 ± 8 beats minute^?1), pH, PaO₂ (MB: 19.2 ± 6.6, M: 18.2 ± 6.6 kPa) or PaCO_2. Recovery times and quality did not differ between groups, but the time to extubation was significantly longer in group MB (26.9 ± 10.9 minutes) than in group M (20.4 ± 9.4 minutes).Conclusion and clinical relevanceButorphanol CRI at the dose used does not decrease isoflurane requirements in horses anaesthetised with medetomidine–isoflurane and has no influence on cardiopulmonary function or recovery.     

The effect of buprenorphine on isoflurane minimum alveolar concentration in dogs

ObjectiveTo determine the effect of intravenous (IV) buprenorphine on the isoflurane (ISO) minimum alveolar concentration (ISOMAC) in dogs.Study designRandomized, crossover, design.AnimalsSix healthy, adult (2–3 years old), intact dogs (two males and four females) weighing 7.4–11.0 kg.MethodsEach dog was studied on three occasions, 1 week apart, and baseline ISOMAC (MAC_B) was determined on each occasion. ISOMAC was defined as the mean of the end-tidal ISO concentrations that prevented and allowed purposeful movement in response to a noxious stimulus. After MAC_B determination, dogs were randomly given buprenorphine (BUP) at either 0.01, 0.05 or 0.1 mg kg^?1 IV, and ISOMAC was determined at two time periods after BUP administration. The first post-treatment determination (MAC_T1) was initiated 45 minutes after BUP administration and the second determination (MAC_T2) was initiated 4 hours after BUP administration. MAC values were determined in duplicate and the mean values were used for statistical analysis.ResultsIsoflurane minimum alveolar concentration was decreased at 141 minutes (the time of MAC_T1 determination) by 25%, 35%, and 27% after administration of BUP at 0.01, 0.05, and 0.1 mg kg^?1, respectively (p ≤ 0.05). The MAC reductions were not statistically different among doses. The reductions in ISOMAC at 342 minutes (the time of MAC_T2 determination) ranged from 13 to 16%, and were not statistically different among doses.Conclusions and clinical significanceBuprenorphine at 0.01, 0.05, and 0.1 mg kg^?1 significantly decreased ISOMAC in dogs at 141 minutes but not at 342 minutes. When using BUP for MAC reduction re-dosing may be required for procedures of long duration, and there may be no advantage to using the 0.1 mg kg^?1 dose.     

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.     

Effect of epidural and intravenous use of the neurokinin-1 (NK-1) receptor antagonist maropitant on the sevoflurane minimum alveolar concentration (MAC) in dogs

ObjectiveTo determine the effect of maropitant, an NK-1 receptor antagonist on the minimum alveolar concentration (MAC) of sevoflurane after intravenous and epidural administration to dogs.Study designProspective experimental study.AnimalsSeven, adult, spayed-female dogs (24.8 ± 1.9 kg).MethodsEach dog was anesthetized twice with sevoflurane in oxygen, with at least 10 days separating the anesthetic events. The minimum alveolar concentration (MAC) of sevoflurane was determined using the tail-clamp technique. During the first anesthetic event, the MAC of sevoflurane was determined initially and again after intravenous administration of maropitant (5 mg kg^?1) and an infusion (150 μg kg^?1 hour^?1). During the second anesthetic event, an epidural catheter was advanced to the 4th lumbar vertebra and MAC was determined after administration of saline and maropitant (1 mg kg^?1) epidurally. All MAC determinations were done in duplicate. The MAC values were adjusted to sea level and compared using student's t-test.ResultsThe baseline MAC for sevoflurane was 2.08 ± 0.25%. Intravenous maropitant decreased (p < 0.05) MAC by 16% (1.74 ± 0.17%). In contrast, epidural administration of either saline or maropitant did not change (p > 0.05) the MAC (2.17 ± 0.34% and 1.92 ± 0.12%, respectively).Conclusion and clinical relevanceMaropitant decreased the MAC of sevoflurane when administered intravenously to dogs but not after epidural administration.     

Effects of two continuous infusion doses of lidocaine on isoflurane minimum anesthetic concentration in chickens

ObjectiveTo assess the effect of two intravenous (IV) doses of lidocaine on the minimum anesthetic concentration (MAC) of isoflurane in chickens.Study designBlinded, prospective, randomized, experimental crossover study.AnimalsA total of six adult female chickens weighing 1.90 ± 0.15 kg.MethodsChickens were anesthetized with isoflurane and mechanically ventilated. Isoflurane MAC values were determined (T0) in duplicate using an electrical noxious stimulus and the bracketing method. After MAC determination, a low dose (LD; 3 mg kg^–1 followed by 3 mg kg^–1 hour^–1) or high dose (HD; 6 mg kg^?1 followed by 6 mg kg^?1 hour^–1) of lidocaine was administered IV. MAC determination was repeated at 1.5 (T1.5) and 3 (T3) hours of lidocaine administration and blood was collected for analysis of plasma lidocaine and monoethylglycinexylidide (MEGX) concentrations. Pulse rate, peripheral hemoglobin oxygen saturation, noninvasive systolic arterial pressure and cloacal temperature were recorded at T0, T1.5 and T3. Treatments were separated by 1 week. Data were analyzed using mixed-effects model for repeated measures.ResultsMAC of isoflurane (mean ± standard deviation) at T0 was 1.47 ± 0.18%. MAC at T1.5 and T3 was 1.32 ± 0.27% and 1.26 ± 0.09% (treatment LD); and 1.28 ± 0.06% and 1.30 ± 0.06% (treatment HD). There were no significant differences between treatments or times. Maximum plasma lidocaine concentrations at T3 were 496 ± 98 and 1200 ± 286 ng mL^–1 for treatments LD and HD, respectively, and were not significantly different from T1.5. With treatment HD, plasma concentration of MEGX was significantly higher at T3 than at T1.5. Physiological variables were not significantly different among times with either treatment.Conclusions and clinical relevanceAdministration of lidocaine did not significantly change isoflurane MAC in chickens. Within treatments, plasma lidocaine concentrations were not significantly different at 1.5 and 3 hours.     

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.     

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.     

Minimum infusion rate and hemodynamic effects of propofol, propofol-lidocaine and propofol-lidocaine-ketamine in dogs

ObjectiveTo evaluate the effects of a constant rate infusion (CRI) of lidocaine alone or in combination with ketamine on the minimum infusion rate (MIR) of propofol in dogs and to compare the hemodynamic effects produced by propofol, propofol-lidocaine or propofol-lidocaine-ketamine anesthesia.Study designProspective, randomized cross-over experimental design.AnimalsFourteen adult mixed-breed dogs weighing 15.8 ± 3.5 kg.MethodsEight dogs were anesthetized on different occasions to determine the MIR of propofol alone and propofol in combination with lidocaine (loading dose [LD] 1.5 mg kg^?1, CRI 0.25 mg kg^?1 minute^?1) or lidocaine (LD 1.5 mg kg^?1, CRI 0.25 mg kg^?1 minute^?1) and ketamine (LD 1 mg kg^?1, CRI 0.1 mg kg^?1 minute^?1). In six other dogs, the hemodynamic effects and bispectral index (BIS) were investigated. Each animal received each treatment (propofol, propofol-lidocaine or propofol-lidocaine-ketamine) on the basis of the MIR of propofol determined in the first set of experiments.ResultsMean ± SD MIR of propofol was 0.51 ± 0.08 mg kg^?1 minute^?1. Lidocaine-ketamine significantly decreased the MIR of propofol to 0.31 ± 0.07 mg kg^?1 minute^?1 (37 ± 18% reduction), although lidocaine alone did not (0.42 ± 0.08 mg kg^?1 minute^?1, 18 ± 7% reduction). Hemodynamic effects were similar in all treatments. Compared with the conscious state, in all treatments, heart rate, cardiac index, mean arterial blood pressure, stroke index and oxygen delivery index decreased significantly, whereas systemic vascular resistance index increased. Stroke index was lower in dogs treated with propofol-lidocaine-ketamine at 30 minutes compared with propofol alone. The BIS was lower during anesthesia with propofol-lidocaine-ketamine compared to propofol alone.Conclusions and clinical relevanceLidocaine-ketamine, but not lidocaine alone, reduced the MIR of propofol in dogs. Neither lidocaine nor lidocaine in combination with ketamine attenuated cardiovascular depression produced by a continuous rate infusion of propofol.     

Effect of maropitant,a neurokinin‐1 receptor antagonist,on the minimum alveolar concentration of sevoflurane during stimulation of the ovarian ligament in cats

ObjectiveDetermine if maropitant decreases the minimum alveolar concentration (MAC) of sevoflurane during stimulation of the ovarian ligament in cats.Study designProspective study.AnimalsFifteen, female cats weighing 2.5 ± 0.6kg (mean ± SD).MethodsAnesthesia was induced and maintained with sevoflurane. The right ovary was accessed via laparoscopy. A suture around the ovary and ovarian ligament was exteriorized through the abdominal wall for stimulation. A stimulus–response curve was created to identify the optimal force for MAC comparisons. In 10 cats, MAC was determined with only sevoflurane (baseline) then after 1 and 5 mg kg^?1 intravenous maropitant administration. The stimulation tension force used was 4.9 N. Repeated measures anova was used to compare the groups. MAC was defined as the average of the cross‐over concentrations and reported MAC is adjusted to sea‐level and depicted as mean ± SD.ResultsThe stimulus‐response curve was hyperbolic and plateaued at 4.3 ± 3 N. The optimal tension force chosen to compare MAC was 4.9 N. The baseline sevoflurane MAC was 2.96 ± 0.3%. Maropitant, 1 mg kg^?1, decreased the MAC to 2.51 ± 0.3% (15%, p < 0.01). The higher maropitant dose of 5 mg kg^?1 did not change MAC further when compared to the low dose (2.46 ± 0.4%, p = 0.33).Conclusion and clinical relevanceThe ovarian ligament stimulation model is suitable to determine MAC during visceral stimulation in cats. Maropitant decreased the anesthetic requirements during visceral ovarian and ovarian ligament stimulation in cats. Maropitant (1 mg kg^?1) decreases MAC by 15%; a higher dose had no additional effect.     

Combined effects of dexmedetomidine and vatinoxan infusions on minimum alveolar concentration and cardiopulmonary function in sevoflurane-anesthetized dogs

ObjectiveTo evaluate the effects of combined infusions of vatinoxan and dexmedetomidine on inhalant anesthetic requirement and cardiopulmonary function in dogs.Study designProspective experimental study.MethodsA total of six Beagle dogs were anesthetized to determine sevoflurane minimum alveolar concentration (MAC) prior to and after an intravenous (IV) dose (loading, then continuous infusion) of dexmedetomidine (4.5 μg kg^–1 hour^–1) and after two IV doses of vatinoxan in sequence (90 and 180 μg kg^–1 hour^–1). Blood was collected for plasma dexmedetomidine and vatinoxan concentrations. During a separate anesthesia, cardiac output (CO) was measured under equivalent MAC conditions of sevoflurane and dexmedetomidine, and then with each added dose of vatinoxan. For each treatment, cardiovascular variables were measured with spontaneous and controlled ventilation. Repeated measures analyses were performed for each response variable; for all analyses, p < 0.05 was considered significant.ResultsDexmedetomidine reduced sevoflurane MAC by 67% (0.64 ± 0.1%), mean ± standard deviation in dogs. The addition of vatinoxan attenuated this to 57% (0.81 ± 0.1%) and 43% (1.1 ± 0.1%) with low and high doses, respectively, and caused a reduction in plasma dexmedetomidine concentrations. Heart rate and CO decreased while systemic vascular resistance increased with dexmedetomidine regardless of ventilation mode. The co-administration of vatinoxan dose-dependently modified these effects such that cardiovascular variables approached baseline.Conclusions and clinical relevanceIV infusions of 90 and 180 μg kg^–1 hour^–1 of vatinoxan combined with 4.5 μg kg^–1 hour^–1 dexmedetomidine provide a meaningful reduction in sevoflurane requirement in dogs. Although sevoflurane MAC-sparing properties of dexmedetomidine in dogs are attenuated by vatinoxan, the cardiovascular function is improved. Doses of vatinoxan >180 μg kg^–1 hour^–1 might improve cardiovascular function further in combination with this dose of dexmedetomidine, but beneficial effects on anesthesia plane and recovery quality may be lost.     

The Komesaroff anaesthetic machine for delivering sevoflurane to dogs

Objective To quantify the vapour output of the Komesaroff machine when using sevoflurane and to determine its performance for inducing and maintaining sevoflurane anaesthesia in dogs. Study design Prospective experimental study. Animals Six clinically normal beagles, aged 3–6 years and weighing 20 ± 1.65 kg (mean ± SEM). Methods The first study was performed using five Komesaroff vaporizers to measure the sevoflurane concentration delivered at each tap setting (I to IV) at 5, 10, 15, 20, 25, 30 and 35 minutes. For this study a ventilator was connected to the Komesaroff machine and set to deliver a tidal volume of 250 mL at 10 cycles minute^?1; oxygen flow was 100 mL minute^?1. A three‐litre reservoir bag was attached to the Y‐piece connector to act as a lung model. In the second study anaesthesia was induced in dogs with sevoflurane delivered by face‐mask mask and carried in 2 L minute^?1 100% oxygen and with the vaporizer set at the fully open position. The quality and speed of induction were recorded. After orotracheal intubation, anaesthesia was maintained for 60 minutes with sevoflurane using an oxygen flow of 100 mL minute^?1. The dogs were allowed to breathe spontaneously. The respiratory rate (RR), heart rate (HR), oesophageal temperature, systolic (SAP) mean (MAP) and diastolic (DAP) arterial pressure, end‐tidal CO₂ concentration (Fe ′_CO2) end‐tidal (Fe ′_SEVO) and peak‐inspired (Fi _SEVO) percentages of sevoflurane, and vaporizer tap setting were recorded every 5 minutes during anaesthesia. Results The delivery of sevoflurane was constant for each vaporizer setting. The mean output of sevoflurane was 0.44 ± 0.01% for setting I, 2.59 ± 0.18% for setting II, 3.28 ± 0.22% for setting III and 3.1 ± 0.5% for setting IV. In the second study, the mean induction time was 7.72 ± 0.60 minutes and the quality of the induction was good in all dogs. The mean vaporizer tap setting for the maintenance of anaesthesia was 3.48 ± 0.12 and the mean values for Fe ′_SEVO and Fi _SEVO were 2.42 ± 0.04% and 2.87 ± 0.06%, respectively. The pedal withdrawal reflex persisted throughout anaesthesia. Conclusions It proved impossible to produce surgical anaesthesia with sevoflurane delivered by the Komesaroff machine despite the highest possible sevoflurane concentration being delivered. Clinical relevance Sevoflurane delivered from the Komesaroff machine cannot be relied upon to maintain surgical anaesthesia in spontaneously breathing dogs.     

Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy

ObjectiveTo determine the induction doses, then minimum infusion rates of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent, cardiopulmonary effects, recovery characteristics and alfaxalone plasma concentrations in cats undergoing ovariohysterectomy after premedication with butorphanol-acepromazine or butorphanol-medetomidine.Study designProspective randomized blinded clinical study.AnimalsTwenty-eight healthy cats.MethodsCats undergoing ovariohysterectomy were assigned into two groups: together with butorphanol [0.2 mg kg^?1 intramuscularly (IM)], group AA (n = 14) received acepromazine (0.1 mg kg^?1 IM) and group MA (n = 14) medetomidine (20 μg kg^?1 IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg^?1 intravenously (IV) every 20 seconds], initially maintained with 8 mg kg^?1 hour^?1 alfaxalone IV and infusion adjusted (±0.5 mg kg^?1 hour^?1) every five minutes according to alterations in heart rate (HR), respiratory rate (f_R), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg^?1) or if f_R >40 breaths minute^?1 (0.25 mg kg^?1). Venous blood samples were obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg^?1 IV) was administered postoperatively. Data were analysed using linear mixed models, Chi-squared, Fishers exact and t-tests.ResultsAlfaxalone anaesthesia induction dose (mean ± SD), was lower in group MA (1.87 ± 0.5; group AA: 2.57 ± 0.41 mg kg^?1). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62 ± 1.37, group MA: 10.76 ± 0.96 mg kg^?1 hour^?1) did not differ significantly between groups. Plasma concentrations ranged between 0.69 and 10.76 μg mL^?1. In group MA, f_R, end-tidal carbon dioxide, temperature and DBP were significantly higher and HR lower.Conclusion and clinical relevanceAlfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedications, the authors recommend initial alfaxalone TIVA rates of 10 mg kg^?1 hour^?1.     

Comparison of postoperative effects between lidocaine infusion,meloxicam, and their combination in dogs undergoing ovariohysterectomy

ObjectiveTo compare the postoperative analgesic effects of intravenous (IV) lidocaine, meloxicam, and their combination in dogs undergoing ovariohysterectomy.Study designProspective, randomized, double‐blind, controlled clinical trial.AnimalsTwenty‐seven dogs aged (mean ± SD) 16.1 ± 7.5 months and weighing 22.4 ± 17.9 kg scheduled for ovariohysterectomy.MethodsAnaesthesia was induced with propofol and maintained with isoflurane. Dogs (n = 9 in each group) were allocated to receive just prior to and during surgery one of the following regimens: M group, 0.2 mg kg^?1 IV meloxicam then a continuous rate infusion (CRI) of lactated Ringer's at 10 mL kg^?1 hour^?1; L group, a bolus of lidocaine (1 mg kg^?1 IV) then a CRI of lidocaine at 0.025 mg kg^?1 minute^?1; and M + L group, both the above meloxicam and lidocaine treatments. Pain and sedation were scored, and venous samples taken for serum cortisol and glucose measurement before and at intervals for 12 hours after anaesthesia. Pain scores were assessed using a multi‐parameter subjective scoring scale (cumulative scale 0–21) by three observers. The protocol stated that dogs with a total score exceeding 9 or a sub‐score above 3 in any one category would receive rescue analgesia. Sedation was scored on a scale of 0–4.ResultsThere were no significant differences in subjective pain scores, serum cortisol, and glucose concentrations between the three groups. The highest pain score at any time was 5, and no dog required rescue analgesia. None of the three regimens caused any observable side effects during or after anaesthesia. At 1 and 2 hours after extubation dogs in group L were significantly more sedated than in the other two groups.Conclusions and Clinical relevanceThis study suggests that, with the scoring system used, IV lidocaine and meloxicam provide similar and adequate post‐operative analgesia in healthy dogs undergoing ovariohysterectomy.