A comparison of cardiopulmonary effects and anaesthetic requirements of two dexmedetomidine continuous rate infusions in alfaxalone-anaesthetized Greyhounds

Objective

To determine the effects of two dexmedetomidine continuous rate infusions on the minimum infusion rate of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent haemodynamic and recovery effects in Greyhounds undergoing laparoscopic ovariohysterectomy.

Postinduction apnoea in dogs premedicated with acepromazine or dexmedetomidine and anaesthetized with alfaxalone or propofol

Objective

To compare incidence and duration of postinduction apnoea in dogs after premedication with methadone and acepromazine (MA) or methadone and dexmedetomidine (MD) followed by induction with propofol (P) or alfaxalone (A).

Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs

ObjectiveTo determine the cardiorespiratory and anesthetic effects of 2, 6, and 20 mg kg⁻¹ IV alfaxalone in hydroxypropyl beta cyclodextrin (Alfaxan) in dogs.Study designBlinded four-way crossover randomized by dose.AnimalsEight healthy adult purpose-bred mixed breed dogs (four male, four female) weighing between 12 and 28 kg.MethodsFour (0, 2, 6, 20 mg kg⁻¹) IV treatments of alfaxalone were administered to each dog with a 3-hour washout period between doses. Measurements of heart rate, aortic systolic, mean, and diastolic blood pressures, pulmonary arterial and right atrial mean pressures, cardiac output, respiratory rate, tidal and minute volumes, and arterial blood pH, blood gases (PaO₂, PaCO₂) were performed prior to and at predetermined intervals after drug administration. Systemic vascular resistance and rate pressure product were calculated. The quality of induction, maintenance, and recovery from anesthesia were categorically scored as was the response to noxious stimulation.ResultsThe administration of alfaxalone resulted in dose-dependent changes in cardiovascular and respiratory parameters. Decreases in arterial blood pressure and increases in heart rate occurred at higher doses with most variables returning to baseline in 15–30 minutes. Respiratory rate, minute volume, and PaO₂ decreased and apnea was the most common side effect. The duration of anesthesia increased with dose, and induction, maintenance, and recovery were judged to be good to excellent with all doses studied.Conclusions and clinical relevanceAlfaxalone produced good to excellent short-term anesthesia in unpremedicated dogs. Cardiorespiratory effects were minimal at lower doses. Anesthesia was judged to be good to excellent and associated with unresponsiveness to noxious stimulation for the majority of anesthesia. Hypoventilation and apnea were the most prominent and dose-dependent effects.     

Sparing effect of tramadol,lidocaine, dexmedetomidine and their combination on the minimum alveolar concentration of sevoflurane in dogs

BackgroundProblems associated with using inhalational anaesthesia are numerous in veterinary anaesthesia practice. Decreasing the amount of used inhalational anaesthetic agents and minimising of cardiorespiratory disorders are the standard goals of anaesthetists.ObjectiveThis experimental study was carried out to investigate the sparing effect of intravenous tramadol, lidocaine, dexmedetomidine and their combinations on the minimum alveolar concentration (MAC) of sevoflurane in healthy Beagle dogs.MethodsThis study was conducted on six beagle dogs. Sevoflurane MAC was determined by the tail clamp method on five separate occasions. The dogs received no treatment (control; CONT), tramadol (TRM: 1.5 mg kg^-1 intravenously followed by 1.3 mg kg^-1 h^-1), lidocaine (LID: 2 mg kg^-1 intravenously followed by 3 mg kg^-1 h^-1), dexmedetomidine (DEX: 2 μg kg^-1 intravenously followed by 2 μg kg^-1 h^-1), and their combination (COMB), respectively. Cardiorespiratory variables were recorded every five minutes and immediately before the application of a noxious stimulus.ResultsThe COMB treatment had the greatest sevoflurane MAC-sparing effect (67.4 ± 13.9%) compared with the other treatments (5.1 ± 25.3, 12.7 ± 14.3, and 40.3 ± 15.1% for TRM, LID, and DEX treatment, respectively). The cardiopulmonary variables remained within the clinically acceptable range following COMB treatment, although the mean arterial pressure was higher and accompanied by bradycardia.ConclusionsTramadol-lidocaine-dexmedetomidine co-infusion produced a remarkable sevoflurane MAC-sparing effect in clinically healthy beagle dogs and could result in the alleviation of cardiorespiratory depression caused by sevoflurane. Cardiorespiratory variables should be monitored carefully to avoid undesirable side effects induced by dexmedetomidine.     

Effects of ketamine or midazolam continuous rate infusions on alfaxalone total intravenous anaesthesia requirements and recovery quality in healthy dogs: a randomized clinical trial

ObjectiveTo determine the alfaxalone dose reduction during total intravenous anaesthesia (TIVA) when combined with ketamine or midazolam constant rate infusions and to assess recovery quality in healthy dogs.Study designProspective, blinded clinical study.AnimalsA group of 33 healthy, client-owned dogs subjected to dental procedures.MethodsAfter premedication with intramuscular acepromazine 0.05 mg kg^-1 and methadone 0.3 mg kg^-1, anaesthetic induction started with intravenous alfaxalone 0.5 mg kg^-1 followed by either lactated Ringer’s solution (0.04 mL kg^-1, group A), ketamine (2 mg kg^-1, group AK) or midazolam (0.2 mg kg^-1, group AM) and completed with alfaxalone until endotracheal intubation was achieved. Anaesthesia was maintained with alfaxalone (6 mg kg^-1 hour^-1), adjusted (±20%) every 5 minutes to maintain a suitable level of anaesthesia. Ketamine (0.6 mg kg^-1 hour^-1) or midazolam (0.4 mg kg^-1 hour^-1) were employed for anaesthetic maintenance in groups AK and AM, respectively. Physiological variables were monitored during anaesthesia. Times from alfaxalone discontinuation to extubation, sternal recumbency and standing position were calculated. Recovery quality and incidence of adverse events were recorded. Groups were compared using parametric analysis of variance and nonparametric (Kruskal-Wallis, Chi-square, Fisher’s exact) tests as appropriate, p < 0.05.ResultsMidazolam significantly reduced alfaxalone induction and maintenance doses (46%; p = 0.034 and 32%, p = 0.012, respectively), whereas ketamine only reduced the alfaxalone induction dose (30%; p = 0.010). Recovery quality was unacceptable in nine dogs in group A, three dogs in group AK and three dogs in group AM.Conclusions and clinical relevanceMidazolam, but not ketamine, reduced the alfaxalone infusion rate, and both co-adjuvant drugs reduced the alfaxalone induction dose. Alfaxalone TIVA allowed anaesthetic maintenance for dental procedures in dogs, but the quality of anaesthetic recovery remained unacceptable irrespective of its combination with ketamine or midazolam.     

Effect of alfaxalone infusion on the electroencephalogram of dogs anaesthetized with halothane

ObjectiveTo describe the effects of alfaxalone on the canine electroencephalogram (EEG).Study designExperimental study.AnimalsEight healthy adult Huntaway dogs.MethodsAnaesthesia was induced with propofol and maintained with halothane (0.85-0.95 end-tidal volume %) in oxygen. Animals were ventilated to maintain stable end-tidal CO₂ and halothane concentrations. Following a 30 minute stabilisation period, alfaxalone (0.5 mg kg^?1) was infused intravenously over a 5 minute period. The electroencephalogram was recorded from the beginning of the stabilisation period until 60 minutes following the start of alfaxalone treatment. Data were subjected to fast Fourier transformation, and median frequency, 95% spectral edge frequency and total EEG power were calculated. Two-factorial repeated measures anova (time and EEG channels were factors) was used for statistical analysis (p<0.05).ResultsA shift in the dominant frequency band from beta to delta after alfaxalone treatment and occasional burst suppression were observed. Median frequency decreased significantly below baseline (9.2 ± 1.4 Hz) (mean ± SD) during alfaxalone infusion. The lowest value (4.8 ± 1.2 Hz) was recorded 5 minutes after the start of infusion. Spectral edge frequency also decreased below baseline (26.2 ± 1.5 Hz) and the lowest value (22.6 ± 1.5 Hz) also was detected at 5 minutes after the start of infusion. Total EEG power did not change significantly. In some frequencies EEG power increased soon after the start of alfaxalone infusion, then decreased below baseline later (biphasic pattern).Conclusions and clinical relevanceAlfaxalone induced biphasic changes on EEG and decreased F₅₀ and F₉₅ in halothane anaesthetized dogs.     

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.     

Effect of propofol on oxidative stress status in erythrocytes from dogs under general anaesthesia

Background

Alterations of the normal redox balance might be attributed to increase of plasma free-radical concentration and a disruption of the antioxidant defense system. One of the adverse effects of general anaesthetics is the exogen sources of reactive oxygen radicals that are responsible for several diseases. The purposes of the current study were to evaluate the effect of propofol on oxidative stress and to compare the differences between propofol induction only and induction plus continuous infusion on antioxidant status in dogs.

Findings

Beagle dogs were evaluated in the present study. The dogs were assigned randomly to receive three treatments in a crossover model. The three treatments were: group 1 (n = 9), 2% isoflurane; group 2 (n = 9), anaesthesia induced with an intravenous (IV) bolus dose of 6 mg/kg propofol and maintained with 1.5–2% isoflurane; group 3 (n = 9), total IV anaesthesia (induction with 6 mg/kg propofol, infusion with 0.6 mg/kg/min propofol). The results of this study show that dogs exposed to isoflurane had decreased antioxidant enzymes activities, whereas dogs injected with propofol had increased antioxidant enzymes activities.

Conclusions

The results of this study showed that an infusion dose of propofol has antioxidant effects in dogs. These effects may be beneficial to patients in whom free radicals play a role in oxidative stress, such as those with ischemia. Further studies are needed to evaluate whether these antioxidant effects of the anaesthetic are of clinical value.     

Sedative and physiologic effects of low-dose intramuscular alfaxalone in dogs

Objective

To describe the sedative and physiologic effects of two doses of alfaxalone administered intramuscularly in dogs.

Neurophysiological assessment of the sedative and analgesic effects of a constant rate infusion of dexmedetomidine in the dog

The sedative and analgesic effects of continuous rate infusion (CRI) of dexmedetomidine (DEX) were investigated in Beagle dogs (n = 8) using auditory and somatosensory evoked potentials (AEPs and SEPs) recorded before, during and after a CRI of saline or DEX (1.0, 3.0, 5.0 μg/kg bolus, followed by 1.0, 3.0, 5.0 μg/kg/h CRI, respectively).The results showed a significant reduction in AEP at doses of 1.0 μg/kg/h and above and a significant reduction of the SEP at doses of 3.0 and 5.0 μg/kg/h. Neither the AEP nor the SEP was further reduced at 5.0 μg/kg/h when compared to 3.0 μg/kg/h, although a slower return towards baseline values was observed at 5.0 μg/kg/h. The mean plasma levels (±SEM) of DEX during infusion were 0.533 ± 0.053 ng/mL for the 1.0 μg/kg/h dose, 1.869 ± 0.063 ng/mL for the 3.0 μg/kg/h dose and 4.017 ± 0.385 for the 5.0 μg/kg/dose. It was concluded that in adult dogs, a CRI of DEX had a sedative and analgesic effect that could be described quantitatively using neurophysiological parameters. Sedation was achieved at lower plasma levels than required for analgesia, and DEX had a longer (but not larger) effect with infusion rates above 3.0 μg/kg/h.     

Clinical evaluation of Alfaxan-CD® as an intravenous anaesthetic in young cats

Objective   To describe and evaluate the use of Alfaxan-CD ® as an intravenous anaesthetic in young cats.
Design   Thirty-five Domestic Short-hair cats aged from 3 to 12 months were admitted into the University Veterinary Teaching Hospital-Sydney for elective surgery. Anaesthesia was induced with Alfaxan-CD® and maintained with isoflurane: 22 cats received no premedication and 13 cats received acepromazine (0.03 mg/kg) and butorphanol (0.3 mg/kg) subcutaneously 30 min prior to induction.
Qualitative and quantitative data for induction and recovery were recorded. Physiological parameters were recorded at 0, 2 and 5 min post induction, and every 5 min thereafter until the end of the procedure.
Results   Intravenous injection of Alfaxan-CD® resulted in rapid induction of anaesthesia with a mean time to intubation of 122 s. The mean dose of Alfaxan-CD® used was 4.2 mg/kg in unpremedicated cats and 2.7 mg/kg in premedicated cats. All cats maintained a heart rate above 95 beats/min. No cat developed hypoxaemia. Hypercapnoea was detected in 4 cats and hypotension was observed in 18 cats. Time to extubation ranged from 1 to 9 min. The mean time to sternal recumbency for premedicated cats was 11 min; 77% of premedicated cats and 23% of unpremedicated cats had a recovery score of 1 or 2.
Conclusion   Alfaxan-CD® is an effective anaesthetic agent in young healthy cats, providing a smooth induction and rapid recovery. Cats that were premedicated with acepromazine and butorphanol prior to induction with Alfaxan-CD® had better recovery scores than those that were not premedicated.     

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.     

Sedative effects of two doses of alfaxalone in combination with methadone and a low dose of dexmedetomidine in healthy Beagles

ObjectiveTo evaluate the sedative effects of two doses of alfaxalone when added to a combination of dexmedetomidine and methadone injected intramuscularly (IM) in healthy Beagles.Study designRandomized, blinded, crossover, experimental study.AnimalsA group of six adult Beagles.MethodsDogs were sedated on three different occasions with IM dexmedetomidine (3 μg kg^–1) and methadone (0.3 mg kg^–1) combined with two doses of alfaxalone (0.5 and 1 mg kg^–1; A0.5 and A1, respectively) or saline (A0). Quality of sedation, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35 and 45 minutes. Pulse and respiratory rates, oxygen saturation of haemoglobin (SpO₂) and noninvasive blood pressure (NIBP) were recorded every 5 minutes. Onset of sedation and duration of recumbency, response to venous catheterization and recovery quality were assessed. Physiological variables (analysis of variance) were analysed between treatments and within treatments compared with baseline (Student t test). Nonparametric data were analysed using Friedman and Cochran’s Q tests. Significance was p < 0.05.ResultsSedation scores were significantly higher when alfaxalone was co-administered (area under the curve; p = 0.024, A0.5; p = 0.019, A1), with no differences between doses. Onset of sedation was similar, but duration of recumbency was longer in A0.5 than in A0 [median (minimum–maximum), 43 (35–54) versus 30 (20–47) minutes, p = 0.018], but not in A1. Response to venous catheterization and tail clamping, and quality of recovery (acceptable) presented no differences between treatments. A decrease in all physiological variables (compared with baseline) was observed, except for NIBP, with no differences between treatments. All dogs required oxygen supplementation due to reduced SpO₂.Conclusions and clinical relevanceAdding alfaxalone to methadone and dexmedetomidine enhanced sedation and duration of recumbency. Although cardiopulmonary depression was limited, oxygen supplementation is advisable.     

Cardiovascular and renal effects of constant rate infusions of remifentanil, dexmedetomidine and their combination in dogs anesthetized with sevoflurane

We evaluated changes in cardiovascular and renal functions as well as arginine vasopressin (AVP) secretion, with remifentanil and dexmedetomidine administration alone or in combination in sevoflurane-anesthetized dogs. Six healthy adult Beagle dogs received one of the following four treatments in a randomized crossover study: saline (C), remifentanil alone at successively increasing doses (R; 0.15, 0.60, and 2.40 µg/kg/min), dexmedetomidine alone (D; 0.5 µg/kg intravenously for initial 10 min followed by a constant rate infusion at 0.5 µg/kg/hr), and a combination of remifentanil and dexmedetomidine at the above-mentioned doses (RD). Sevoflurane doses were adjusted to 1.5 times of minimum alveolar concentration (MAC) equivalent according to MAC-sparing effects with remifentanil and dexmedetomidine as previously reported. Cardiovascular measurements, renal function data, and plasma AVP concentrations were determined before and every 60 min until 180 min after drug administration as per each treatment. In the R, D and RD, heart rate significantly decreased and mean arterial pressure significantly increased from baseline or with C. Cardiac index significantly decreased and systemic vascular resistance index increased with D and RD. Oxygen extraction ratio, renal blood flow, and glomerular filtration rate were not affected. The plasma AVP concentrations significantly decreased in D and RD, but increased in R. Only in D, the natriuresis was elicited. The combination of remifentanil and dexmedetomidine in sevoflurane-anesthetized dogs was acceptable in terms of the hemodynamics, oxygenation, and renal function. Remifentanil may interfere with dexmedetomidine-induced diuresis and inhibition of AVP secretion.     

Effects of different doses of dexmedetomidine on anaesthetic induction with alfaxalone – a clinical trial

ObjectiveTo document the effects of two doses of dexmedetomidine on the induction characteristics and dose requirements of alfaxalone.Study designRandomized controlled clinical trial.AnimalsSixty one client owned dogs, status ASA I-II.MethodsDogs were allocated randomly into three groups, receiving as pre-anaesthetic medication, no dexmedetomidine (D₀), 1 μg kg^?1 dexmedetomidine (D₁) intramuscularly (IM) or 3 μg kg^?1 dexmedetomidine IM (D₃). All dogs also received 0.2 mg kg^?1 methadone IM. Level of sedation was assessed prior to induction of anaesthesia. Induction of general anaesthesia was performed with alfaxalone administered intravenously to effect at a rate of 1 mg kg^?1 minute^?1; the required dose to achieve tracheal intubation was recorded. Anaesthesia was maintained with isoflurane in oxygen. Cardiopulmonary parameters were recorded throughout the anaesthetic period. Quality of intubation, induction and recovery of anaesthesia were recorded. Quantitative data were compared with one-way anova or Kruskal-Wallis test. Repeated measures were log-transformed and analysed with repeated measures anova (p < 0.05).ResultsTreatment groups were similar for categorical data, with exception of sedation level (p < 0.001). The doses (mean ± SD) of alfaxalone required for intubation were D₀ 1.68 ± 0.24, D₁ 1.60 ± 0.36 and D₃ 1.41 ± 0.43, the difference between D₀ and D₃ being statistically significant (p = 0.036). Heart and respiratory rates during the anaesthetic period were significantly different over time and between groups (p < 0.001); systolic arterial blood pressure was significantly different over time (p < 0.001) but not between groups (p = 0.833). Induction quality and recovery scores were similar between groups (p = 1.000 and p = 0.414, respectively).Conclusions and clinical relevanceThe administration of alfaxalone resulted in a good quality anaesthetic induction which was not affected by the dose of dexmedetomidine. Dexmedetomidine at 3 μg kg^?1 IM combined with methadone provides good sedation and enables a reduction of alfaxalone requirements.     

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.