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.     

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.     

Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine

ObjectiveTo evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine.Study designProspective, randomized, blinded clinical trial.AnimalsForty horses undergoing elective surgery.MethodsAfter sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg^?1 initially, then 2 mg kg^?1 hour^?1) and ketamine (2 mg kg^?1 hour^?1), both CRIs reducing to 1.5 mg kg^?1 hour^?1 after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 μg kg^?1 hour^?1, reducing after 50 minutes to 2.75 μg kg^?1 hour^?1, and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE′ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 μg kg^?1) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05.ResultsFE′ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE′ISO in MILK was 0.65 (0.4–1.0) %, and in ILK was 1 (0.62–1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups.Conclusion and clinical relevanceA CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.     

Determination of acute tolerance and hyperalgesia to remifentanil constant rate infusion in dogs undergoing sevoflurane anaesthesia

ObjectiveTo determine if acute opioid tolerance (AOT) or opioid-induced hyperalgesia (OIH) could develop and limit the remifentanil-induced reduction in the sevoflurane minimum alveolar concentration (MAC). The response to mechanical nociceptive threshold (MNT) was evaluated and related to OIH.Study designA crossover, randomized, experimental animal study.AnimalsA total of nine Beagle dogs.MethodsThe dogs were anaesthetized with sevoflurane in 50% oxygen. Baseline sevoflurane MAC was measured (MACb1). Remifentanil (0.3 μg kg^–1 minute^–1) or 0.9% saline constant rate infusion (CRI) was administered intravenously (IV). Sevoflurane MAC was determined 20 minutes after CRI was initiated (MACpostdrug1), 30 minutes after MACpostdrug1 determination (MACpostdrug2) and after 1 week (MACb2). The MNT was determined at baseline (before anaesthesia), 3 and 7 days after anaesthesia. An increase of MACpostdrug2 ≥0.25% compared to MACpostdrug1 was considered evidence of AOT. A decrease in MNT at 3 and 7 days or an increase in MACb2 or both with respect to MACb1 were considered evidence of OIH.ResultsRemifentanil CRI reduced sevoflurane MACpostdrug1 by 43.7% with respect to MACb1. MACpostdrug2 was no different from MACpostdrug1 with the saline (p = 0.62) or remifentanil (p = 0.78) treatments. No significant differences were observed in the saline (p = 0.99) or remifentanil (p = 0.99) treatments between MACb1 and MACb2, or for MNT values between baseline, 3 and 7 days.Conclusion and clinical relevanceIn dogs, under the study conditions, remifentanil efficacy in reducing sevoflurane MAC did not diminish in the short term, suggesting remifentanil did not induce AOT. Hyperalgesia was not detected 3 or 7 days after the administration of remifentanil. Contrary to data from humans and rodents, development of AOT or OIH in dogs is not supported by the findings of this study.     

The hemodynamic effects of medetomidine continuous rate infusions in the dog

ObjectiveTo characterize the hemodynamic effects of continuous rate infusions (CRI) of medetomidine administered at doses ranging from 0 to 3 μg kg^?1 hour^?1.Study designProspective, blinded, randomized experimental trial.AnimalsSix adult purpose-bred mongrel dogs.MethodsAnesthesia was induced with sevoflurane for placement of arterial and venous catheters. Dogs recovered from anesthesia after which baseline hemodynamic measurements were obtained via lithium dilution cardiac output (CO) determination, with subsequent measurements via pulse power analysis to provide continuous CO determinations. Medetomidine, 1, 2, or 3 μg kg^?1 hour^?1 or a volume equivalent placebo, was administered via CRI for 60 minutes. Systolic, mean, and diastolic arterial pressure, heart rate (HR), CO and stroke volume were measured and stroke index (SI), cardiac index (CI), total peripheral resistance (TPR), and total peripheral resistance index (TPRI) were calculated at 3, 7, 10, 20, 30, 45, 60, 90, and 120 minutes from the start of the infusion.ResultsIncrease in dose decreased SI by 25%, 19%, and 30%, HR by 33%, 57%, and 60%, CI by 50%, 65%, 70% and increased TPRI by 109%, 235%, and 222% from baseline to the 60-minute measurement for the 1, 2, and 3 μg kg^?1 hour^?1 doses, respectively. HR, TPRI, and CI all showed significant differences over the duration of the study from the placebo treatment.ConclusionsMedetomidine CRI produces clinically relevant changes in CO, TPR, and HR. The demonstrated decrease in CO is largely because of bradycardia and the degree of cardiovascular depression appears to be dose-dependent. These findings are consistent with previously described hemodynamic changes with single bolus administration of medetomidine.Clinical relevanceLow-dose medetomidine CRIs produce clinically relevant hemodynamic depression at doses as low as 1 μg kg^?1 hour^?1 and should be used cautiously 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.     

Evaluation of the perioperative stress response from dexmedetomidine infusion alone,with butorphanol bolus or remifentanil infusion compared with ketamine and morphine infusions in isoflurane-anesthetized horses

ObjectiveTo evaluate perioperative stress-related hormones in isoflurane-anesthetized horses administered infusions of dexmedetomidine alone or with butorphanol or remifentanil, compared with ketamine–morphine.Study designRandomized, prospective, nonblinded clinical study.AnimalsA total of 51 horses undergoing elective surgical procedures.MethodsHorses were premedicated with xylazine, anesthesia induced with ketamine–diazepam and maintained with isoflurane and one of four intravenous infusions. Partial intravenous anesthesia (PIVA) was achieved with dexmedetomidine (1.0 μg kg^–1 hour^–1; group D; 12 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and butorphanol bolus (0.05 mg kg^–1; group DB; 13 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and remifentanil (3.0 μg kg^–1 hour^–1; group DR; 13 horses); or ketamine (0.6 mg kg^–1 hour^–1) and morphine (0.15 mg kg^–1, 0.1 mg kg^–1 hour^–1; group KM; 13 horses). Infusions were started postinduction; butorphanol bolus was administered 10 minutes before starting surgery. Blood was collected before drugs were administered (baseline), 10 minutes after ketamine–diazepam, every 30 minutes during surgery and 1 hour after standing. Mean arterial pressure (MAP), pulse rate, end-tidal isoflurane concentration, cortisol, nonesterified fatty acids (NEFA), glucose and insulin concentrations were compared using linear mixed models. Significance was assumed when p < 0.05.ResultsWithin D, cortisol was lower at 120–180 minutes from starting surgery compared with baseline. Cortisol was higher in KM than in D at 60 minutes from starting surgery. Within all groups, glucose was higher postinduction (except DR) and 60 minutes from starting surgery, and insulin was lower during anesthesia and higher after standing compared with baseline. After standing, NEFA were higher in KM than in DB. In KM, MAP increased at 40–60 minutes from starting surgery compared with 30 minutes postinduction.Conclusions and clinical relevanceDexmedetomidine suppressed cortisol release more than dexmedetomidine–opioid and ketamine–morphine infusions. Ketamine–morphine PIVA might increase catecholamine activity.     

Postoperative analgesic effects of either a constant rate infusion of fentanyl,lidocaine, ketamine,dexmedetomidine, or the combination lidocaine‐ketamine‐dexmedetomidine after ovariohysterectomy in dogs

ObjectiveTo evaluate the postoperative analgesic effects of a constant rate infusion (CRI) of either fentanyl (FENT), lidocaine (LIDO), ketamine (KET), dexmedetomidine (DEX), or the combination lidocaine-ketamine-dexmedetomidine (LKD) in dogs.Study designRandomized, prospective, blinded, clinical study.AnimalsFifty-four dogs.MethodsAnesthesia was induced with propofol and maintained with isoflurane. Treatments were intravenous (IV) administration of a bolus at start of anesthesia, followed by an IV CRI until the end of anesthesia, then a CRI at a decreased dose for a further 4 hours: CONTROL/BUT (butorphanol 0.4 mg kg⁻¹, infusion rate of saline 0.9% 2 mLkg⁻¹ hour⁻¹); FENT (5 μg kg⁻¹, 10 μg kg⁻¹hour⁻¹, then 2.5 μg kg⁻¹ hour⁻¹); KET (1 mgkg⁻¹, 40 μg kg⁻¹ minute⁻¹, then 10 μg kg⁻¹minute⁻¹); LIDO (2 mg kg⁻¹, 100 μg kg⁻¹ minute⁻¹, then 25 μg kg⁻¹ minute⁻¹); DEX (1 μgkg⁻¹, 3 μg kg⁻¹ hour⁻¹, then 1 μg kg⁻¹ hour⁻¹); or a combination of LKD at the aforementioned doses. Postoperative analgesia was evaluated using the Glasgow composite pain scale, University of Melbourne pain scale, and numerical rating scale. Rescue analgesia was morphine and carprofen. Data were analyzed using Friedman or Kruskal–Wallis test with appropriate post-hoc testing (p < 0.05).ResultsAnimals requiring rescue analgesia included CONTROL/BUT (n = 8), KET (n = 3), DEX (n = 2), and LIDO (n = 2); significantly higher in CONTROL/BUT than other groups. No dogs in LKD and FENT groups received rescue analgesia. CONTROL/BUT pain scores were significantly higher at 1 hour than FENT, DEX and LKD, but not than KET or LIDO. Fentanyl and LKD sedation scores were higher than CONTROL/BUT at 1 hour.Conclusions and clinical relevanceLKD and FENT resulted in adequate postoperative analgesia. LIDO, CONTROL/BUT, KET and DEX may not be effective for treatment of postoperative pain in dogs undergoing ovariohysterectomy.     

Opioid-sparing effect of a medetomidine constant rate infusion during thoraco-lumbar hemilaminectomy in dogs administered a ketamine infusion

ObjectiveTo evaluate the perioperative opioid-sparing effect of a medetomidine (MED) infusion compared to a saline (SAL) infusion in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery.Study designRandomized, partially blinded, clinical study.AnimalsA total of 44 client-owned adult dogs.MethodsAll dogs were administered a 1 μg kg^–1 MED loading dose, followed by a 1.7 μg kg^–1 hour^–1 constant rate infusion (CRI) intravenously or equivalent volumes of SAL. Infusions were started 10–15 minutes before surgical incision and continued throughout the surgical procedure. All dogs were administered a standardized anaesthetic and analgesic protocol (including a ketamine CRI). Multiparametric monitoring, including invasive arterial blood pressure, was performed. A trained investigator, unaware of the treatment, performed pain scores for 4 hours postoperatively. Rescue analgesia consisted of fentanyl administered intraoperatively and methadone postoperatively. Data were tested for normality and analysed with Fisher’s exact test, Mann–Whitney U-test, analysis of variance and Kaplan–Meier survival analysis. Data are shown as median (interquartile range) and p-value was set at < 0.05.ResultsThe total dose of fentanyl was significantly lower with MED 0 (0–0.8) μg kg^–1 hour^–1 compared to SAL 3 (1.8–5.3) μg kg^–1 hour^–1 (p = 0.004). In the MED group, one dog compared to 12 dogs in the SAL group required a fentanyl CRI (p = 0.001). There were no statistically significant differences between groups regarding the total dose of methadone administered.Conclusions and clinical relevanceThe addition of a low-dose medetomidine CRI to the anaesthetic protocol decreased the need for a fentanyl CRI in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery during administration of a ketamine CRI.     

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.     

Inhibition and facilitation of nociceptively evoked muscular activity by fentanyl or dexmedetomidine in isoflurane-anaesthetized pigs

ObjectiveTo investigate motor and cardiovascular responses to dexmedetomidine or fentanyl in isoflurane-anaesthetized pigs.Study designExperimental, balanced, block randomized, two-group design.AnimalsA group of 16 crossbred pigs, 55 ± 8 days (mean ± standard deviation) old.MethodsDeltoid electromyography (EMG) was recorded during isoflurane anaesthesia. Electrical stimulation using 5, 10, 20 and 40 mA of the distal right thoracic limb elicited a nociceptive withdrawal reflex (NWR), quantified by the area under the curve (AUC) for the simulation intensity versus EMG amplitude response curve. Latency to movement evoked by clamping a claw for maximum 60 seconds was noted. Arterial blood pressure and pulse rate were recorded. Data were sampled at baseline and during dexmedetomidine 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 μg kg^–1 hour^–1 or fentanyl 5, 10, 20, 40, 80 and 160 μg kg^–1 hour^–1 infusions. The influence of infusion rate on NWR AUC and spontaneous EMG was analysed using a mixed model, with p < 5%.ResultsNWR AUC increased at fentanyl 5 μg kg^–1 hour^–1 but decreased at fentanyl 40, 80 and 160 μg kg^–1 hour^–1 and dexmedetomidine 4.0 and 8.0 μg kg^–1 hour^–1. All pigs at fentanyl 80 μg kg^–1 hour^–1, and three pigs at dexmedetomidine 8.0 μg kg^–1 hour^–1 had mechanical latencies greater than 60 seconds. Spontaneous EMG activity increased accompanied by visually evident ‘shivering’ at fentanyl 5, 10 and 20 μg kg^–1 hour^–1 but decreased at dexmedetomidine 2, 4 and 8 μg kg^–1 hour^–1. Clinically relevant effects of increasing infusion rates on blood pressure or pulse rate were not observed.Conclusion and clinical relevanceIf anaesthetic plane or antinociception is evaluated in pigs, response to claw clamping and NWR will not necessarily give uniform results when comparing drugs. If only one method is used, results should be interpreted cautiously.     

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.     

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.     

The effect of remifentanil infusion on sevoflurane minimum alveolar concentration–no movement (MACNM) and bispectral index in dogs

ObjectiveTo determine the effect of remifentanil infusion on the minimum alveolar concentration of sevoflurane preventing movement (SEVOMAC_NM) and bispectral index (BIS) in dogs.Study designProspective, unmasked study.AnimalsA total of 10 adult Beagle dogs weighing 9.0 ± 1.1 kg.MethodsDogs were anesthetized with sevoflurane and baseline SEVOMAC_NM was determined. Remifentanil was infused at 5, 10 and 20 μg kg^–1 hour^–1, in sequence, with 20 minutes washout between infusions. Variables monitored throughout anesthesia included heart rate (HR), oscillometric blood pressure, end-tidal partial pressure of carbon dioxide, end-tidal sevoflurane concentration (Fe′Sevo) and BIS. SEVOMAC_NM after remifentanil infusion (SEVOMAC_NM-REMI) determination started 20 minutes after the start of each infusion. Venous blood samples were collected for plasma remifentanil concentration determination at baseline, SEVOMAC_NM-REMI determination time points, and 20 minutes after each infusion was stopped. A mixed model analysis was used to determine the effect of remifentanil infusion on response variables. The relationships between BIS and Fe′Sevo, plasma remifentanil concentrations and the percentage decrease in baseline SEVOMAC_NM were evaluated (p < 0.05).ResultsThe overall SEVOMAC_NM at baseline was 2.47 ± 0.11%. Addition of remifentanil at all infusion rates significantly decreased SEVOMAC_NM, but the medium and high doses resulted in significantly greater decreases in SEVOMAC_NM than the lower dose. There was no difference in SEVOMAC_NM percentage change between infusions 10 and 20 μg kg^–1 hour^–1. Plasma remifentanil concentrations were significantly different in all infusion rates. Baseline BIS value was 70 ± 1 and was lower than the BIS values recorded during all remifentanil infusions. BIS values were not significantly different among infusion rates. HR was lower and mean arterial pressure was higher during remifentanil infusions than at baseline.Conclusions and clinical relevanceAll remifentanil infusions decreased SEVOMAC_NM in dogs. Remifentanil infusion at any rate studied did not reduce BIS values.     

Anesthetic management of an off-pump open-heart surgery in a dog

ObservationsA 9 year-old, 40 kg, female spayed Bouvier des Flandres was anesthetized for surgical removal of an intra-cardiac mass. Pre-anesthetic work-up included thoracic radiographs, which revealed moderate pleural effusion, and cardiac ultrasound, which identified a mass attached to the wall of the right ventricular outflow tract (RVOT). The mass caused dynamic obstruction of the RVOT during systole. The dog was pre-medicated with intravenous (IV) hydromorphone (0.05 mg kg^?1). Following pre-oxygenation, anesthesia was induced with ketamine (3.75 mg kg^?1, IV) and diazepam (0.18 mg kg^?1, IV). Anesthesia was maintained with isoflurane in oxygen, an intravenous constant rate infusion (CRI) of fentanyl (10–30 μg kg^?1 hour^?1) and a CRI of lidocaine (50–200 μg kg^?1 minute^?1). A right lateral thoracotomy was performed. The heart was stopped transiently with a cold cardioplegic solution for 7.83 minutes to allow the removal of the mass through an open-heart procedure. No cardiopulmonary bypass was used. The heart was successfully restarted after cardiopulmonary resuscitation with internal cardiac massage and internal defibrillation. The dog recovered uneventfully from anesthesia without any apparent neurological sequelae. Post-operative analgesia consisted of intercostal nerve blocks with bupivacaine, CRIs of fentanyl (2–5 μg kg^?1 hour^?1) and lidocaine (40 μg kg^?1 minute^?1) and with oral meloxicam (0.1 mg kg^?1). Five days following surgery, the dog was discharged from the hospital. Histopathology and immunohistochemistry of the mass identified an ectopic thyroid carcinoma.ConclusionsThis case showed the feasibility of whole body hypothermia and using a cold cardioplegic solution to induce cardiac arrest for a short open-heart procedure.     

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.     

Microcirculation assessment of dexmedetomidine constant rate infusion during anesthesia of dogs with sepsis from pyometra: a randomized clinical study

ObjectiveTo compare dexmedetomidine and fentanyl constant rate infusions in anesthetic protocols for septic dogs with pyometra, using microcirculatory, hemodynamic and metabolic variables.Study designRandomized clinical study.AnimalsA total of 33 dogs with pyometra with two or more systemic inflammatory response syndrome variables undergoing ovariohysterectomy.MethodsDogs were randomized into two groups: group DG, dexmedetomidine (3 μg kg^–1 hour^–1; 17 dogs) and group FG, fentanyl (5 μg kg^–1 hour^–1; 16 dogs) infused during isoflurane anesthesia and mechanical ventilation. Microcirculation flow index (MFI), total vessel density and De Backer score were assessed using orthogonal polarization spectral imaging at the sublingual site. Heart rate, invasive blood pressure, temperature, arterial blood gas analysis and lactate concentration were obtained at various time points. Variables were recorded at baseline (BL), immediately before (T0), 30 (T30) and 60 (T60) minutes after infusion, and 60 minutes after surgery. Data were analyzed using the Shapiro-Wilk test. To compare variables between groups, the unpaired Student t test was used. Comparison between evaluation time points was performed with two-way anova for repeated measures. Where statistical significance was detected, the Bonferroni post hoc test was used.ResultsMFI was significantly higher in group FG at T30. Mean arterial pressure at T30 was higher in group DG (89 ± 15 mmHg) than in group FG (72 ± 13 mmHg). Lactate concentrations were not significantly different between groups at each time point. Both groups had similar clinical outcomes (mortality, extubation time and occurrence of hypotension and bradyarrhythmias).Conclusions and clinical relevanceDexmedetomidine (3 μg kg^–1 hour^–1) without a loading dose can be included in the maintenance of anesthesia in dogs with pyometra and sepsis without compromising microcirculation and hemodynamic values when compared with fentanyl (5 μg kg^–1 hour^–1).     

Development of a romifidine constant rate infusion with or without butorphanol for standing sedation of horses

ObjectiveTo determine constant rate infusion (CRI) protocols for romifidine (R) and romifidine combined with butorphanol (RB) resulting in constant sedation and romifidine plasma concentrations.Study designBlinded randomized crossover study.AnimalsTen adult research horses.MethodsPart I: After determining normal height of head above ground (HHAG = 100%), loading doses of romifidine (80 μg kg^?1) with butorphanol (RB: 18 μg kg^?1) or saline (R) were given intravenously (IV). Immediately afterwards, a butorphanol (RB: 25 μg kg^?1 hour^?1) or saline (R) CRI was administered for 2 hours. The HHAG was used as marker of sedation depth. Sedation was maintained for 2 hours by additional romifidine (20 μg kg^?1) whenever HHAG > 50%. The dose rate of romifidine (μg kg^?1 hour^?1) required to maintain sedation was calculated for both treatments. Part II: After loading doses, the romifidine CRIs derived from part I were administered in parallel to butorphanol (RB) or saline (R). Sedation and ataxia were evaluated periodically. Romifidine plasma concentrations were measured by HPLC-MS-MS at 0, 5, 10, 15, 30, 45, 60, 90, 105, and 120 minutes. Data were analyzed using paired t-test, Fisher's exact test, Wilcoxon signed rank test, and two-way anova for repeated measures (p < 0.05).ResultsThere was no significant difference in romifidine requirements (R: 30; RB: 29 μg kg^?1 hour^?1). CRI protocols leading to constant sedation were developed. Time to first additional romifidine bolus was significantly longer in RB (mean ± SD, R: 38.5 ± 13.6; RB: 50.5 ± 11.7 minutes). Constant plasma concentrations of romifidine were achieved during the second hour of CRI. Ataxia was greater when butorphanol was added.ConclusionRomifidine bolus, followed by CRI, provided constant sedation assessed by HHAG. Butorphanol was ineffective in reducing romifidine requirements in unstimulated horses, but prolonged the sedation caused by the initial romifidine bolus.Clinical relevanceBoth protocols need to be tested under clinical conditions.