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 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.     

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.     

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.     

Comparison of analgesic efficacy of epidural methadone or ropivacaine/methadone with or without pre‐operative oral tepoxalin in dogs undergoing tuberositas tibiae advancement surgery

ObjectiveTo investigate the clinical efficacy of four analgesia protocols in dogs undergoing tibial tuberosity advancement (TTA).Study designProspective, randomized, blinded study.AnimalsThirty-two client owned dogs undergoing TTA-surgery.MethodsDogs (n= 8 per treatment) received an oral placebo (PM and PRM) or tepoxalin (10 mg kg^?1) tablet (TM and TRM) once daily for 1 week before surgery. Epidural methadone (0.1 mg kg^?1) (PM and TM) or the epidural combination methadone (0.1 mg kg^?1)/ropivacaine 0.75% (1.65 mg kg^?1) (PRM and TRM) was administered after induction of anaesthesia. Intra-operative fentanyl requirements (2 μg kg^?1 IV) and end-tidal isoflurane concentration after 60 minutes of anaesthesia (Fe′ISO₆₀) were recorded. Post-operative analgesia was evaluated hourly from 1 to 8 and at 20 hours post-extubation with a visual analogue scale (VAS) and the University of Melbourne Pain Scale (UMPS). If VAS > 50 and/or UMPS > 10, rescue methadone (0.1 mg kg^?1) was administered IV. Analgesic duration (time from epidural until post-operative rescue analgesia) and time to standing were recorded. Normally distributed variables were analysed with an F-test (α = 0.05) or t-test for pairwise inter-treatment comparisons (Bonferonni adjusted α = 0.0083). Non-normally distributed data were analysed with the Kruskall–Wallis test (α = 0.05 or Bonferonni adjusted α = 0.005 for inter-treatment comparison of post-operative pain scores).ResultsMore intra-operative analgesia interventions were required in PM [2 (0–11)] [median (range)] and TM [2 (1–2)] compared to PRM (0) and TRM (0). Fe′ISO₆₀ was significantly lower in (PRM + TRM) compared to (PM + TM). Analgesic duration was shorter in PM (459 ± 276 minutes) (mean ± SD) and TM (318 ± 152 minutes) compared to TRM (853 ± 288 minutes), but not to PRM (554 ± 234 minutes). Times to standing were longer in the ropivacaine treatments compared to TM.Conclusions and clinical relevanceInclusion of epidural ropivacaine resulted in reduction of Fe′ISO₆₀, avoidance of intra-operative fentanyl administration, a longer duration of post-operative analgesia (in TRM) and a delay in time to standing compared to TM.     

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.     

Isoflurane minimum alveolar concentration sparing effects of fentanyl in the dog

Objective

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

Reduction of isoflurane MAC by fentanyl or remifentanil in rats

Objective The main objective of the study was to determine the effects of three different infusion rates of fentanyl and remifentanil on the minimum alveolar concentration (MAC) of isoflurane in the rat. A secondary objective was to assess the cardiovascular and respiratory effects of the two opioid drugs. Animal population Thirty‐seven male Wistar rats were randomly allocated to one of six treatment groups. Material and methods For all treatment groups anaesthesia was induced with 5% isoflurane in oxygen using an induction chamber. A 14‐gauge catheter was used for endotracheal intubation, and anaesthesia was maintained with isoflurane delivered in oxygen via a T‐piece breathing system. A baseline determination of the minimum alveolar concentration of isoflurane (MAC_ISO) was made for each animal. Fentanyl (15, 30, 60 µg kg^?1 hour^?1) or remifentanil (60, 120, 240 µg kg^?1 hour^?1) were infused intravenously into a previously cannulated tail vein. Thirty minutes after the infusion started, a second MAC_ISO (MAC_ISO+drug) was determined. The carotid artery was cannulated to monitor the arterial pressure and to take samples for arterial gas measurements. Cardiovascular (heart rate and arterial pressure) and respiratory (respiratory rate and presence/absence of apnoea) effects after opioid infusion were also recorded. Results Fentanyl (15, 30, 60 µg kg^?1 hour^?1) and remifentanil (60, 120, 240 µg kg^?1 hour^?1) similarly reduced isoflurane MAC in a dose‐dependent fashion: by 10% at lower doses, 25% at medium doses and by 60% at higher doses of both the drugs. Both opioids reduced the respiratory rate in a similar way for all doses tested. No episodes of apnoea were recorded in the remifentanil groups, while administration of fentanyl resulted in apnoea in three animals (one at each dose level). The effects on the cardiovascular system were similar with both drugs. Conclusions We conclude that the intraoperative use of remifentanil in the rat reduces the MAC of isoflurane, and that this anaesthetic sparing effect is dose‐dependent and similar to that produced by fentanyl at the doses tested. Clinical relevance The use of remifentanil during inhalant anaesthesia in the rat can be considered an intravenous alternative to fentanyl, providing similar reduction in isoflurane requirements. Due to its rapid offset, it is recommended that alternative pain relief be instituted before it is discontinued.     

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.     

Cardiovascular effects of epidural administration of methadone, ropivacaine 0.75% and their combination in isoflurane anaesthetized dogs

ObjectiveTo compare the cardiovascular effects of four epidural treatments in isoflurane anaesthetised dogs.Study designProspective, randomized. experimental study.AnimalsSix female, neutered Beagle dogs (13.3 ± 1.0 kg), aged 3.6 ± 0.1 years.MethodsAnaesthesia was induced with propofol (8.3 ± 1.1 mg kg^?1) and maintained with isoflurane in a mixture of oxygen and air [inspiratory fraction of oxygen (FiO₂) = 40%], using intermittent positive pressure ventilation. Using a cross-over model, NaCl 0.9% (P); methadone 1% 0.1 mg kg^?1 (M); ropivacaine 0.75% 1.65 mg kg^?1 (R) or methadone 1% 0.1 mg kg^?1 + ropivacaine 0.75% 1.65 mg kg^?1 (RM) in equal volumes (0.23 mL kg^?1) using NaCl 0.9%, was administered epidurally at the level of the lumbosacral space. Treatment P was administered to five dogs only. Cardiovascular and respiratory variables, blood gases, and oesophageal temperature were recorded at T-15 and for 60 minutes after epidural injection (T0).ResultsMean overall heart rate (HR in beats minute^?1) was significantly lower after treatment M (119 ± 16) (p = 0.0019), R (110 ± 18) (p < 0.0001) and RM (109 ± 13) (p < 0.0001), compared to treatment P (135 ± 21). Additionally, a significant difference in HR between treatments RM and M was found (p = 0.04). After both ropivacaine treatments, systemic arterial pressures (sAP) were significantly lower compared to other treatments. No significant overall differences between treatments were present for central venous pressure, cardiac output, stroke volume, systemic vascular resistance, oxygen delivery and arterial oxygen content (CaO₂). Heart rate and sAP significantly increased after treatment P and M compared to baseline (T-15). With all treatments significant reductions from baseline were observed in oesophageal temperature, packed cell volume and CaO₂. A transient unilateral Horner’s syndrome occurred in one dog after treatment R.Conclusions and clinical relevanceClinically important low sAPs were observed after the ropivacaine epidural treatments in isoflurane anaesthetised dogs. Systemic arterial pressures were clinically acceptable when using epidural methadone.     

Minimum anesthetic concentration of isoflurane and sparing effect of midazolam in Quaker parrots (Myiopsitta monachus)

ObjectiveTo determine the effects of midazolam on the minimum anesthetic concentration (MAC) reduction of end-tidal isoflurane concentration (Fe′Iso) measured using an electrical stimulus in Quaker parrots (Myiopsitta monachus).Study designRandomized crossover experimental study.AnimalsA group of six adult Quaker parrots, weighing 98–124 g.MethodsBirds were anesthetized with isoflurane in oxygen delivered by mask, then tracheally intubated and mechanically ventilated. Three treatments were applied with a 4 day interval between anesthetic events. Each anesthetized bird was administered midazolam (1 mg kg⁻¹; treatment MID1), midazolam (2 mg kg⁻¹; treatment MID2) or electrolyte solution (control) intramuscularly. The treatments were administered using a replicated Latin square design and the observers were blinded. Based on a pilot bird, the starting Fe′Iso was 1.8%. After equilibration for 10 minutes, a supramaximal stimulus was delivered using an electrical current (20 V and 50 Hz for 10 ms) and birds were observed for non-reflex movement. The Fe′Iso was titrated by 0.1% until a crossover event was observed. The MAC was estimated using logistic regression.ResultsThe MAC of isoflurane (MAC_ISO) was estimated at 2.52% [95% confidence interval (CI), 2.19–2.85] with a range of 1.85–2.65%. MAC_ISO in MID1 was 2.04% (95% CI, 1.71–2.37) and in MID2 was 1.81% (95% CI, 1.48–2.14); reductions in MAC_ISO from control of 19% (p = 0.001) and 28% (p < 0.001), respectively. Heart rate, temperature, sex and anesthetic time were not different among treatments.ConclusionsMidazolam (1–2 mg kg⁻¹) intramuscularly resulted in a significant isoflurane-sparing effect in response to a noxious stimulus in Quaker parrots without observable adverse effects.Clinical relevanceMidazolam can be used as part of a balanced anesthetic approach using isoflurane in Quaker parrots, and potentially in other psittacine species.     

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.     

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.     

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.     

Clinical pharmacology of methadone in dogs

ObjectiveTo investigate the pharmacokinetics and effects of methadone on behaviour and plasma concentrations of cortisol and vasopressin in healthy dogs.Study designRandomized, cross-over, experimental trial.AnimalsNine adult dogs (beagle and beagle cross breeds), four males and five females.MethodsMethadone hydrochloride, 0.4 mg kg^?1, was administered intravenously (IV) and subcutaneously (SC) with a crossover design. Drug and hormone analyses in plasma were performed using Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry and radioimmunoassay respectively. Behavioural data were collected using a standardized protocol.ResultsAfter IV administration, the plasma concentration of methadone at 10 minutes was 82.1 ± 9.2 ng mL^?1 (mean ± SD), the terminal half-life was 3.9 ± 1.0 hours, the volume of distribution 9.2 ± 3.3 L kg^?1 and plasma clearance 27.9 ± 7.6 mL minute^?1 kg^?1. After SC administration, time to maximal plasma concentration was 1.26 ± 1.04 hours and maximal plasma concentration of methadone was 23.9 ± 14.4 ng mL^?1, the terminal half-life was 10.7 ± 4.3 hours and bioavailability was 79 ± 22%. Concentrations of both cortisol and vasopressin were increased for an hour following IV methadone. The observed behavioural effects of methadone were decreased licking and swallowing and an increase in whining after SC administration. The latter finding is notable as it can be misinterpreted as pain when methadone is used as an analgesic.Conclusion and clinical relevanceWhen methadone was administered by the SC route, the half-life was longer, but the individual variation in plasma concentrations was greater compared with IV administration. Increased frequency of whining occurred after administration of methadone and may be a drug effect and not a sign of pain. Cortisol and vasopressin concentrations in plasma may not be suitable for evaluating analgesia after methadone treatment.     

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.     

Cardiovascular,respiratory, electrolyte and acid–base balance during continuous dexmedetomidine infusion in anesthetized dogs

ObjectiveTo evaluate the cardiovascular, respiratory, electrolyte and acid–base effects of a continuous infusion of dexmedetomidine during propofol–isoflurane anesthesia following premedication with dexmedetomidine.Study designProspective experimental study.AnimalsFive adult male Walker Hound dogs 1–2 years of age averaging 25.4 ± 3.6 kg.MethodsDogs were sedated with dexmedetomidine 10 μg kg^?1 IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg^?1) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg^?1 IV was administered over 5 minutes followed by an infusion of 0.5 μg kg^?1 hour^?1. Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid–base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD.ResultsNo statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute^?1, 78 ± 18 beats minute^?1 and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute^?1, 78 ± 14 beats minute^?1 and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO₂, PaCO₂, pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion.Conclusions and clinical relevanceDexmedetomidine infusion using a loading dose of 0.5 μg kg^?1 IV followed by a constant rate infusion of 0.5 μg kg^?1 hour^?1 does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg^?1, in propofol–isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2 minutes before onset of infusion showed typical significant effects on cardiovascular parameters.     

Evaluation of chemical restraint,isoflurane anesthesia and methadone or tramadol as preventive analgesia in spotted pacas (Cuniculus paca) subjected to laparoscopy

ObjectiveTo evaluate the efficacy and cardiopulmonary effects of ketamine–midazolam for chemical restraint, isoflurane anesthesia and tramadol or methadone as preventive analgesia in spotted pacas subjected to laparoscopy.Study designProspective placebo-controlled blinded trial.AnimalsA total of eight captive female Cuniculus paca weighing 9.3 ± 0.9 kg.MethodsAnimals were anesthetized on three occasions with 15 day intervals. Manually restrained animals were administered midazolam (0.5 mg kg^–1) and ketamine (25 mg kg^–1) intramuscularly. Anesthesia was induced and maintained with isoflurane 30 minutes later. Tramadol (5 mg kg^–1), methadone (0.5 mg kg^–1) or saline (0.05 mL kg^–1) were administered intramuscularly 15 minutes prior to laparoscopy. Heart rate (HR), respiratory rate, mean arterial pressure (MAP), peripheral oxygen saturation (SpO₂), end-tidal CO₂ partial pressure (Pe′CO₂), end-tidal concentration of isoflurane (Fe′Iso), pH, PaO₂, PaCO₂, bicarbonate (HCO₃^?), anion gap (AG) and base excess (BE) were monitored after chemical restraint, anesthesia induction and at different laparoscopy stages. Postoperative pain was assessed by visual analog scale (VAS) for 24 hours. Variables were compared using anova or Friedman test (p < 0.05).ResultsChemical restraint was effective in 92% of animals. Isoflurane anesthesia was effective; however, HR, MAP, pH and AG decreased, whereas Pe′CO₂, PaO₂, PaCO₂, HCO₃^? and BE increased. MAP was stable with tramadol and methadone treatments; HR, Fe′Iso and postoperative VAS decreased. VAS was lower for a longer time with methadone treatment; SpO₂ and AG decreased, whereas Pe′CO₂, PaCO₂ and HCO₃^? increased.Conclusions and clinical relevanceKetamine–midazolam provided satisfactory restraint. Isoflurane anesthesia for laparoscopy was effective but resulted in hypotension and respiratory acidosis. Tramadol and methadone reduced isoflurane requirements, provided postoperative analgesia and caused hypercapnia, with methadone causing severe respiratory depression. Thus, the anesthetic protocol is adequate for laparoscopy in Cuniculus paca; however, methadone should be avoided.