Parasympathetic influence on the arrhythmogenicity of graded dobutamine infusions in halothane-anesthetized horses.

We investigated the influence of parasympathetic tone on the arrhythmogenicity of graded dobutamine infusions in horses anesthetized under clinical conditions. Six horses were used in 9 trials. Two consecutive series of graded dobutamine infusions were given IV; each continuous graded dobutamine infusion was administered for 20 minutes. The dobutamine infusion dosage (5, 10, 15, and 20 micrograms/kg of body weight/min) was increased at 5-minute intervals. Isovolumetric saline solution vehicle (v) or atropine (A; 0.04 mg/kg) was administered IV, or bilateral vagotomy (VG) was performed as a treatment before the second series of dobutamine infusions. Treatment was not administered prior to the first dobutamine infusion. Significant interaction between treatment and dosage of dobutamine infusion existed for differences from baseline for mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, heart rate, and cardiac index at dosages of 5 and 10 micrograms of dobutamine/kg/min, given IV and for heart rate at dosage of 15 micrograms of dobutamine/kg/min, given IV. Results for group-V horses were different from those for group-A and group-VG horses, but were not different between group-A and group-VG horses in all aforementioned cases, except for heart rate and cardiac index at dosage of 5 micrograms of dobutamine/kg/min, given IV. Normal sinus rhythm, second-degree atrioventricular block, and bradyarrhythmias predominated during low dobutamine infusion rates during the first infusion series (nontreated horses) and in group-V horses during the second infusion series. Only tachyarrhythmias were observed during the second infusion series in the horses of the A and VG groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alteration in the arrhythmogenic dose of epinephrine (ADE) following xylazine administration to halothane-anesthetized dogs

The arrhythmogenic dose of epinephrine (ADE) was determined in six dogs during halothane (1.35%) anesthesia before and after xylazine administration (1.1 mg/kg, i.v. bolus; 1.1 mg/kg/hr, i.v. infusion). The arrhythmogenic dose was determined by constant infusion of freshly mixed epinephrine (100 microgram/ml). The ADE was defined as the total dose of epinephrine which produced four or more intermittent or continuous premature ventricular contractions within a 15-sec period. Total dose was calculated as a function of infusion rate and time to arrhythmia. Following xylazine administration, ADE significantly decreased from 6.28 +/- 0.522 to 4.17 +/- 0.679 micrograms/kg. At the end of i.v. xylazine bolus administration, heart rate significantly decreased (115 +/- 4 to 99 +/- 4.9 b.p.m.), and mean arterial pressure significantly increased (83 +/- 4.0 to 122 +/- 3.4 mm Hg). Heart rate measured immediately prior to epinephrine-induced arrhythmia formation was significantly increased following xylazine administration (177 +/- 8 vs 78 +/- 3 b.p.m.). Mean arterial blood pressure was unchanged. Apparently, xylazine, a mixed alpha agonist, potentiated halothane-induced myocardial sensitization to ventricular arrhythmogenesis and was associated with a significant increase in heart rate, but not blood pressure, during subsequent epinephrine infusions.     

Effects of acetylpromazine or morphine on urine production in halothane-anesthetized dogs.

OBJECTIVE: To assess the influence of preanesthetic administration of acetylpromazine or morphine and fluids on urine production, arginine vasopressin (AVP; previously known as antidiuretic hormone) concentrations, mean arterial blood pressure (MAP), plasma osmolality (Osm), PCV, and concentration of total solids (TS) during anesthesia and surgery in dogs. ANIMALS: 19 adult dogs. PROCEDURE: Concentration of AVP, indirect MAP, Osm, PCV, and concentration of TS were measured at 5 time points (before administration of acetylpromazine or morphine, after administration of those drugs, after induction of anesthesia, 1 hour after the start of surgery, and 2 hours after the start of surgery). Urine output and end-tidal halothane concentrations were measured 1 and 2 hours after the start of surgery. All dogs were administered lactated Ringer's solution (20 ml/kg of body weight/h, i.v.) during surgery. RESULTS: Compared with values for acetylpromazine, preoperative administration of morphine resulted in significantly lower urine output during the surgical period. Groups did not differ significantly for AVP concentration, Osm, MAP, and end-tidal halothane concentration; however, PCV and concentration of TS decreased over time in both groups and were lower in dogs given acetylpromazine. CONCLUSIONS AND CLINICAL RELEVANCE: Preanesthetic administration of morphine resulted in significantly lower urine output, compared with values after administration of acetylpromazine, which cannot be explained by differences in AVP concentration or MAP When urine output is used as a guide for determining rate for i.v. administration of fluids in the perioperative period, the type of preanesthetic agent used must be considered.     

Lack of arrhythmogenicity of aminophylline in dogs

This study was designed to determine if doses of aminophylline up to 10 mg/kg given i.v. would produce ventricular arrhythmias in seven healthy dogs anaesthetized with fentanyl-dropelidol-pentobarbital. Arrhythmias were sought by inspection of ECGs before and after attempts at provoking them with 5 pg/ kg boluses of epinephrine given i.v., or by programmed electrical stimulation. After cumulative doses of 10 nig aminophylline/kg body weight, producing an estimated plasma concentration of greater than 30 pginil, no ventricular ectopia other than escape depolarizations were observed. We were unable t o document
an arrhythmogenic effect of aminophylline when given rapidly by the i.v. route. I t is possible that the anaesthetic regimen reduced the arrhythmogenic property of aminophylline, or that arrhythmias might be produced in either obese or ill dogs; but it is unlikely that chronic administration of aminophylline would be more arrhythmogenic.     

Cardiovascular effects of butorphanol in halothane-anesthetized dogs

Cardiovascular effects of butorphanol (0.2 mg/kg of body weight, IV) and responses associated with subsequent administration of naloxone (0.04 mg/kg, IV) were studied in halothane (1.2% end-tidal concentration)-anesthetized dogs. Transient, but statistically significant (P less than 0.05), decreases in heart rate, mean and diastolic arterial blood pressures, and rate-pressure product were observed after butorphanol administration. Cardiac index, stroke volume, and systemic vascular resistance did not change significantly. Except for the decrease in heart rate, changes in the values of the cardiovascular variables measured after butorphanol administration did not appear to be clinically relevant. Sixty minutes after butorphanol administration, naloxone was given. Statistically significant (P less than 0.05) increases in heart rate, arterial blood pressures, cardiac index, and rate-pressure product, along with dysrhythmias were observed. Stroke volume and systemic vascular resistance remained unchanged after administration of naloxone. Naloxone administration was associated with changes indicative of increased myocardial oxygen consumption.     

Effect of xylazine on the arrhythmogenic dose of epinephrine in thiamylal/halothane-anesthetized horses.

The effect of xylazine on the arrhythmogenic dose of epinephrine (ADE) was studied in 9 horses. Anesthesia was induced by administration of guaifenesin (50 mg/kg of body weight, IV) followed by thiamylal (4 to 6 mg/kg, IV) and was maintained at 1 minimal alveolar concentration (MAC) of halothane (0.89%). Base apex ECG and facial artery pressure were recorded. Epinephrine was infused in a sequence of arithmetically spaced increasing rates (initial rate 0.25 micrograms/kg/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate to the nearest 0.25 micrograms/kg/min at which at least 4 premature ventricular depolarizations occurred in a 15-second period. Xylazine (1.1 mg/kg, IV) was administered after the control ADE was determined. Xylazine did not significantly alter the ADE (control, 1.12 +/- 0.38 micrograms/kg/min; xylazine, 1.21 +/- 0.46 micrograms/kg/min). Blood pressure increased transiently for 8 minutes after xylazine administration. Baseline systolic and diastolic arterial pressures and heart rate were not significantly different from control baseline pressures and heart rate 15 minutes after xylazine administration. Blood pressure and heart rate increased significantly during control and xylazine ADE determinations. Significant differences in pH, PaO2, PaCO2, or base excess were not observed between baseline and ADE in the control or xylazine groups. One horse developed atrial fibrillation, and 2 horses developed ventricular fibrillation during ADE determinations.     

Influence of nifedipine on xylazine-induced acute pressor response in halothane-anesthetized dogs

Effects and interaction of nifedipine (Ca channel blocker) and xylazine (mixed alpha agonist) during halothane anesthesia were examined in 6 dogs. After achievement of steady-state halothane (1.35%) anesthesia, blood pressure (BP) and heart rate (HR) were recorded in these dogs during 3-minute saline or nifedipine (20 micrograms/kg) infusion periods. Seven minutes after the end of saline or nifedipine infusion, xylazine (1.1 mg/kg of body weight) was infused over a 2-minute period. After saline pretreatment, xylazine administration increased diastolic BP (33.67 +/- 3.91 mm of Hg) and decreased HR. Nifedipine infusion induced a transient reduction in BP, accompanied by a more persistent increase in HR. Compared with saline pretreatment, nifedipine pretreatment significantly decreased the acute increase in diastolic BP (33.67 +/- 3.91 vs 14.00 +/- 2.94 mm of Hg) which occurred during xylazine injection. After saline and nifedipine infusions, xylazine administration decreased HR 30 +/- 15.02 and 36.5 +/- 10.36 beats/min, respectively. A pronounced sinus arrhythmia and/or 2nd-degree atrioventricular block developed in all dogs during xylazine injection after saline infusion. Arrhythmias were not observed in the dogs after nifedipine infusion. Nifedipine's Ca blocking action depressed xylazine-induced acute vasoconstriction and concomitant increase in diastolic BP. Because alpha 2-, but not alpha 1-adrenoceptor-mediated vasoconstriction is Ca-dependent, these results indicate that a portion of the acute pressor response induced by IV xylazine in halothane-anesthetized dogs may be alpha 2-mediated. Seemingly, nifedipine-induced hypotension and damping of xylazine-induced increases in BP attenuated xylazine's actions on cardiac rate and rhythm.     

Hemodynamic effects of high-frequency oscillatory ventilation in halothane-anesthetized dogs

Hemodynamic effects of spontaneous ventilation, intermittent positive-pressure ventilation (IPPV), and high-frequency oscillatory ventilation (HFOV) were compared in 6 dogs during halothane anesthesia. Anesthesia was induced with IV thiamylal Na and was maintained with halothane (end-tidal concentration, 1.09%). During placement of catheters, dogs breathed spontaneously through a conventional semiclosed anesthesia circuit. Data were collected, and dogs were mechanically ventilated, using IPPV or HFOV in random order. Ventilation was adjusted to maintain PaCO2 between 38 and 43 mm of Hg during IPPV and HFOV. Cardiac index, aortic blood pressure, and maximum rate of increase of left ventricular pressure were significantly (P less than 0.05) less during HFOV than during spontaneous ventilation, whereas right atrial and pulmonary artery pressure were significantly greater during HFOV than during spontaneous ventilation. During IPPV, only the maximum rate of increase of left ventricular pressure was significantly less than that during spontaneous ventilation.     

The effects of atropine and methotrimeprazine on the epinephrine-induced arrhythmias in halothane-anesthetized dogs.

The effects of atropine and methotrimeprazine on epinephrine-induced ventricular arrhythmias were evaluated in halothane-anesthetized dogs. Ten mixed-breed dogs were assigned to 3 treatments (saline, atropine, and methotrimeprazine) in a randomized complete block design. Anesthesia was induced and maintained with halothane (1.5 minimum alveolar concentration) in oxygen. Controlled ventilation was used throughout to maintain eucapnia. Saline, atropine (0.05 mg/kg, i.v.) or methotrimeprazine (0.5 mg/kg, i.v.) were administered and, 5 minutes later the arrhythmogenic dose of epinephrine (ADE) was measured by i.v. infusion of progressively increasing infusion rates of epinephrine, until the ventricular arrhythmia criterion was met (at least 4 ectopic ventricular contractions (EVCs) during a 15-second period). Data were analyzed using a student's t-test for ADE values and multivariate profile analysis for heart rate (HR), arterial blood pressure (ABP), and rate pressure product (RPP). The ADE increased in atropine- and methotrimeprazine-treated groups, whereas 1 and 4 animals from these groups did not develop any ventricular arrhythmia, respectively. Epinephrine induced multiform premature ventricular contractions (PVCs) in the atropine group, whereas ventricular escape beats were observed in the control and methotrimeprazine groups. Heart rate and RPP decreased, and ABP increased at the time of ADE observation in the control group. Epinephrine infusion in the atropine group caused marked increases in HR, ABP, and RPP, which were associated with pulsus alternans in 2 animals. It was concluded that 1) the presence of cholinergic blockade influences the type of ventricular arrhythmia induced by epinephrine; 2) increased ADE values recorded following atropine administration must be cautiously interpreted, since in this situation the PVCs were associated with signs of increased myocardial work and ventricular failure; and 3) the use of a broader arrhythmia criterion (EVCs instead of PVCs) may not allow a direct comparison between ADE values, since it includes ventricular arrhythmias mediated by different mechanisms.     

Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs

Opioids used in the pre‐operative period may frequently induce vomiting. Acepromazine is commonly combined with opioids as a pre‐anesthetic drug, and has antiemetic properties. The purpose of this study was to evaluate the antiemetic properties of acepromazine in dogs receiving opioids as a pre‐anesthetic. One hundred and sixteen dogs (ASA I or II), 58 males and 58 females; purebreds and mixed breeds; 3 months?13.4 years of age; weighing 1.8–57.7 kg admitted for elective surgical procedures, were randomly assigned to one of the three groups. All groups received acepromazine (0.05 mg kg^?1 IM). Group I (n = 40) received acepromazine 15 minutes prior to opioid administration. Group II (n = 38) received acepromazine in combination with the opioid. Group III (n = 38) received acepromazine 15 minutes after opioid administration. One of the three different opioids was administered IM to each dog: morphine at 0.5 mg kg^?1, hydromorphone at 0.1 mg kg^?1, or oxymorphone at 0.075 mg kg^?1. Statistical analysis included a χ²‐test for the incidence of vomiting and a Kruskal–Wallis nonparametric test for the sedation comparison between groups. The dogs receiving acepromazine before the opioid (Group I) had significantly lower incidence of vomiting (18%) than those in Groups II (45%) and III (55%). The degree of sedation assessed 15 minutes after administration of the last drug (s) in each group was significantly lower in the dogs receiving the combination of acepromazine and opioid (Group II) than in those receiving opioid as the first drug (Group III). Time to vomiting was less than 8 minutes in all groups. In conclusion, acepromazine administered 15 minutes before opioid reduces the incidence of vomiting induced by opioids.     

Effects of intramuscular sedative and opioid combinations on tear production in dogs

The effect of commonly used sedation protocols on tear production rate was evaluated in dogs. Schirmer I tear tests were examined before and after intramuscular injection of acepromazine and oxymorphone (ACE + OXY; n  = 7), diazepam and butorphanol (DIA + BUT; n  = 8), and xylazine and butorphanol (XYL + BUT; n  = 8). Two Schirmer I tear tests were also performed 15–25 min apart in dogs which received no sedative drugs (control; n  = 4). Tear production rate decreased to 15 ± 2, 17 ± 1, and 6 ± 1 mm min⁻¹, respectively, while control animals averaged 21 ± 2 mm min⁻¹ at the same time point. Because XYL + BUT profoundly decreased tear production rate, we evaluated the two drugs separately. While BUT mildly decreased tear production when given alone to dogs (18 ± 1 mm min⁻¹; n  = 5), xylazine had no effect on tear production. Thus it appears that the two agents act synergistically to decrease tear production rate in dogs. Moreover, sterile ocular lubricant or tear replacement should be used during XYL + BUT sedation.     

Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs

Objective To evaluate the anti‐emetic properties of acepromazine in dogs receiving opioids as pre‐anesthetic medication. Study design Randomized prospective clinical study. Animals One hundred and sixteen dogs (ASA I or II), admitted for elective surgical procedures. The dogs were a mixed population of males and females, purebreds and mixed breeds, 0.25–13.4 years of age, weighing 1.8–57.7 kg. Methods A prospective clinical trial in which the dogs were randomly assigned to one of three groups. All groups received acepromazine (0.05 mg kg^?1 intramuscularly (IM)). Group I received acepromazine 15 minutes prior to opioid administration. Group II received acepromazine in combination with the opioid. Group III received acepromazine 15 minutes after opioid administration. One of three different opioids was administered IM to each dog: morphine sulfate at 0.5 mg kg^?1; hydromorphone hydrochloride at 0.1 mg kg^?1; or oxymorphone hydrochloride at 0.075 mg kg^?1. Results Dogs receiving acepromazine before the opioid (group I) had a significantly lower incidence of vomiting (18%) than dogs in groups II (45%) and III (55%). The degree of sedation was significantly lower in the dogs receiving the combination of acepromazine and the opioid (group II) than in dogs receiving the opioid as the first drug (group III). Conclusions and clinical relevance Acepromazine administered 15 minutes before the opioid lowers the incidence of vomiting induced by opioids.     

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

Exogenously administered vasopressors (sympathomimetics) were evaluated in halothane-anesthetized dogs to determine the effects of these drugs on cardiovascular function before and after hemorrhage. Six dogs were anesthetized with thiamylal sodium (20 mg/kg of body weight) and halothane (1.25 minimal alveolar concentration) in 100% oxygen. After instrumentation, cardiac output, systemic arterial blood pressure (SAP), heart rate (HR), left ventricular pressure, pulmonary arterial pressure, and an index of cardiac contractility (dP/dT) were measured. Stroke volume, cardiac index (CI), stroke index (SI), rate-pressure product, and systemic vascular resistance (SVR) were calculated. Epinephrine (0.1, 0.3, and 0.5 micrograms/kg/min [low, medium, and high doses, respectively]) and dobutamine (1, 5, and 10 micrograms/kg/min [low, medium, and high doses, respectively]) were infused. Methoxamine was given in a bolus of 0.22 mg/kg, IV. All measurements were taken at 2.5 minutes after infusion, and were repeated after removal of 40% of the estimated blood volume. Dobutamine administered at the low dose before hemorrhage increased SAP and dP/dT. At the high and medium dose, dobutamine significantly increased CI, dP/dT, and SAP, with no significant change in HR or SVR. The medium dose of epinephrine was the most effective dose of epinephrine at increasing key variables (CI, SI, dP/dT). The response of CI and SI to this dose was not significantly different from the changes seen with high-dose administration of dobutamine. The dP/dT was significantly lower with epinephrine than with dobutamine, and SVR and HR were unchanged with epinephrine, except at the low dose, which decreased SVR.     

Blood pressure response to phenylephrine infusion in halothane-anesthetized dogs given acetylpromazine maleate

To quantitate acetylpromazine-induced alpha-adrenergic receptor blockade, phenylephrine was infused into dogs. The amount of phenylephrine necessary to increase the mean arterial blood pressure (MAP) 50% above base line, with or without the prior administration of acetylpromazine, served to quantify the degree of acetylpromazine-induced alpha-adrenergic receptor blockade. Seven dogs were anesthetized with thiopental, maintained on halothane in oxygen, and mechanically ventilated. All infusions were made through a catheter in the cephalic vein. Continuous recordings were made of MAP and a lead II ECG. After induction of anesthesia, instrumentation, and stabilization of heart rate, MAP, and ventilation, 6 group I dogs were infused with phenylephrine until a 50% increase in MAP was recorded (phenylephrine control). On subsequent research days, each dog was anesthetized, instrumented as described, and given (IV) 1 of 3 dosages of acetylpromazine in the following order--0.05, 0.125, and 0.25 mg/kg. The dose of phenylephrine necessary to increase MAP 50% in the presence of acetylpromazine was recorded. Five group II dogs were studied as in group I, but each dog was given (IM) atropine (0.04 mg/kg) before anesthetization. Two dosages of acetylpromazine were studied in the following order--0.05 and 0.25 mg/kg. Group I dogs, when compared with their phenylephrine controls, were given significantly more phenylephrine to raise MAP 50% at each dose of acetylpromazine studied. The same trend was observed in group II dogs, but at smaller doses of phenylephrine, probably as a result of the positive chronotropic effect of atropine on the heart.     

Pharmacogenetics of opioid analgesics in dogs

Genetic variation causes interindividual variability in drug absorption, distribution, metabolism and excretion. These pharmacokinetic processes will influence the observed efficacy and toxicity of a drug. Polymorphisms in the genes encoding the metabolizing enzymes, transport proteins and receptors have been linked to the inconsistency in responses to opioid treatment in humans and laboratory animals. Pharmacogenetics is relatively less developed field in veterinary medicine compared to significant advances in knowledge on genetic basis of variation in drug responses and clinical applications in human medicine. This review discusses the opioid drug metabolism and possible genetic polymorphism of metabolizing enzymes in dogs. Polymorphism of genes encoding opioid drug transporter proteins and its effect on opioid response and opioid receptor gene variants are also discussed. Due to the scarcity of studies reported on opioid pharmacogenetics in dogs, relevant studies in humans and rodents have also been discussed to indicate current trends and potential targets for research in dogs.     

Cardiovascular effects of epidurally administered oxymorphone and an oxymorphone-bupivacaine combination in halothane-anesthetized dogs

OBJECTIVE: To evaluate cardiovascular effects of epidurally administered oxymorphone (OXY) and an OXY-bupivacaine combination (O/B) in halothane-anesthetized dogs. ANIMALS: 6 dogs. PROCEDURE: In a randomized crossover design study, dogs were anesthetized with halothane and given OXY, O/B, and saline solution (SAL). Eucapnia and end-tidal halothane concentration of 1.2% were established. Heart rate (HR), systemic and pulmonary arterial pressures, central venous pressure (CVP), and cardiac output were measured at baseline and 5, 15, 30, 45, 60, and 75 minutes after treatment. At 90 minutes, glycopyrrolate was administered IV, and measurements were repeated at 95 minutes. Cardiac index (CI), stroke volume, stroke index, systemic vascular resistance (SVR), and left ventricular work were calculated. End-tidal halothane concentration was decreased to 0.8% from 17 to 45 minutes and to 0.5% from 47 to 95 minutes for OXY and O/B, whereas for SAL, it was maintained at 1.5 and 1.2%, respectively. Samples were obtained at 0, 2, 5, 15, 30, 45, 60, and 95 minutes for measurement of serum opiate concentration and comparison with values after IM administration of OXY. RESULTS: HR decreased, but CVP and SVR increased in response to OXY and O/B. These changes were reversed after IV administration of glycopyrrolate, resulting in significant increase in CI, compared with that in response to SAL. Serum opiate concentration increased markedly and peaked within 15 minutes after OXY and O/B administration but did not differ from values after IM administration. CONCLUSIONS: Epidural administration of OXY results in rapid systemic uptake and decreased HR. Glycopyrrolate administration improves HR, resulting in improved CI at equipotent halothane concentrations.     

Effects of atracurium administered by continuous intravenous infusion in halothane-anesthetized horses

Atracurium (0.4 mg/ml in isotonic NaCl solution) was administered by IV infusion to 7 healthy adult horses for 2 hours. Over the 2-hour period, a 95 to 99% reduction of train-of-four hoof-twitch response was maintained by 0.17 +/- 0.01 mg of atracurium/kg of body weight/h, for a total of 161 +/- 6 mg of atracurium (mean +/- SEM) for horses 1 to 4, 6, and 7. Horse 5, a mare in estrus, required 0.49 mg of atracurium/kg/h to maintain comparable relaxation. Hoof-twitch recovery time from 10 to 75% of baseline strength was 19.8 +/- 2.5 minutes for all horses. The 10 to 75% recovery time for horse 5 was 18 minutes. Recovery time from discontinuation of halothane until standing was 86 +/- 14 minutes (range, 55 to 165 minutes). Horse 5 had a 165-minute recovery. Regarding recovery from anesthesia, 3 recoveries were rated as excellent, 1 recovery good, and 2 recoveries as fair. Horse 5 laid quietly until she stood with 1 strong, smooth effort.     

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.     

Effects of spontaneous, assisted, and controlled ventilatory modes in halothane-anesthetized geldings

Cardiopulmonary effects of spontaneous, assisted, and controlled ventilatory modes were determined with 6 young, healthy geldings anesthetized with halothane at a constant dose (1.3 minimum alveolar concentration). All horses were in lateral recumbency, and all modes of ventilation were studied at least once during each anesthetic exposure. Cardiac output did not differ between spontaneous and assisted ventilation modes, but both modes were associated with significantly (P less than 0.05) higher cardiac output than that with controlled ventilation. The PaCO2 differed significantly (P less than 0.01) between all modes of ventilation. Although controlled ventilation maintained a normal PaCO2, assisted ventilation reduced PaCO2 as compared with spontaneous ventilation with less cardiovascular depression than that with controlled ventilation. Mixed venous O2 tensions were higher with spontaneous and assisted ventilation modes than with controlled ventilation. Except for shorter inspiratory time and smaller inspiratory/expiratory ratio associated with spontaneous ventilation, there were no ventilatory mode-related effects on ventilatory variables.