Dexmedetomidine Constant Rate Infusion Research Articles

Dexmedetomidine preconditioning reduces ischaemia-reperfusion injury in equine model of large colon volvulus.

Large colon volvulus is a cause of colic in horses with high morbidity and mortality when not promptly treated. More treatment options are needed to improve the outcome of these cases by protecting against the damage caused by ischaemia and reperfusion injury. To determine the effect of preconditioning with dexmedetomidine prior to induction of ischaemia-reperfusion (IR) injury in a large colon volvulus model in the horse. Randomised blinded in vivo experiments. Horses received either a dexmedetomidine (DEX) or saline (CON) constant rate infusion (CRI) immediately following induction of anaesthesia. Venous, arterial, and transmural occlusion of a section of the large colon was performed for 3 h, after which the ligatures and clamps were removed to allow for reperfusion for 3 h. Biopsies of the large colon were taken at baseline, 1 and 3 h of ischaemia, and at 1 and 3 h of reperfusion. The severity of crypt epithelial loss (DEX = 2.1 [0.8-2.8], CON = 3.1 [2.5-4], p = 0.03) and mucosal haemorrhage was decreased (DEX = 2.1 [1.3-3], CON = 3.5 [2.5-4], p = 0.03) in group DEX compared to group CON when graded on a scale of 0-4. Crypt length remained longer (DEX = 369.5 ± 91.7 μm, CON = 238.5 ± 72.6 μm, p = 0.02) and interstitium to crypt (I:C) ratio remained lower (DEX = 1.4 (1-1.7), CON = 2.6 [1.8-5.9], p = 0.03) in group DEX compared to group CON during reperfusion. Clinical applicability of pharmacologic preconditioning is limited. Preconditioning with a dexmedetomidine CRI prior to IR injury demonstrated a protective effect histologically on the large colon in the horse. Further investigation into postconditioning with dexmedetomidine is warranted as a possible intervention in colic cases suspected of being large colon volvulus.

Nicardipine constant rate infusion alleviates the cardiovascular effects of dexmedetomidine infusions without affecting the minimal alveolar concentration in sevoflurane-anesthetized dogs

Two randomized crossover trials evaluated the effects of nicardipine constant rate infusion (CRI) on 1) the anesthetic potency of sevoflurane and 2) the ability to attenuate dexmedetomidine-induced cardiovascular depression in anesthetized dogs. First, six healthy Beagle dogs weighing 11.7 ± 0.9 kg were allocated to one of three treatments that administered a CRI of carrier (saline) or dexmedetomidine 0.5 or 3.0 μg/kg/h following a loading dose. The minimum alveolar concentration (MAC) of sevoflurane was determined utilizing electric stimuli before and after the loading dose of nicardipine (20 μg/kg intravenously for 10 min), followed by CRI at 40 μg/kg/h with 60 min of equilibration. Subsequently, cardiovascular and blood gas variables were evaluated in another trial under sevoflurane anesthesia at the individual 1.5 MAC. After baseline measurements, the dogs were assigned to two treatments (dexmedetomidine CRI at 0.5 or 3.0 μg/kg/h following a loading dose) with sevoflurane doses adjusted to 1.5 times of MAC equivalent, and the measurements were repeated every 15 min for 120 min. After 60 min, nicardipine CRI at 40 μg/kg/h with a loading dose was added to the dexmedetomidine CRI. Dexmedetomidine infusions significantly decreased the sevoflurane MAC but nicardipine did not significantly alter the MAC either with or without dexmedetomidine CRI in dogs. Dexmedetomidine dose-dependently decreased the cardiac index and increased the systemic vascular resistance index; these effects were fully counteracted by concomitant nicardipine CRI. Nicardipine CRI can be useful for controlling the cardiovascular depression elicited by dexmedetomidine in anesthetized dogs without affecting the anesthetic potency of sevoflurane.

Dexmedetomidine Sedation in Dogs: Impact on Electroencephalography, Behavior, Analgesia, and Antagonism with Atipamezole.

This study aimed to assess the impact of dexmedetomidine constant rate infusion (CRI) on key parameters in dogs. Six dogs received a 60 µg/kg/h dexmedetomidine infusion over 10 min, followed by three 15 min decremental CRIs (3, 2, and 1 µg/kg/h). A subsequent reversal phase employed 600 µg/kg/h atipamezole over 5 min. Continuous electroencephalogram (EEG) assessment, and cardiorespiratory and analgesia monitoring (every 3 min) were conducted, including analgesia evaluation through responses to electric stimulation. Dexmedetomidine induced profound sedation, evidenced by lateral recumbency and immobility. Patient State Index (PSI) decreased from awake (90.4 ± 4.3) to Phase 1 (50.9 ± 30.7), maintaining sedation (29.0 ± 18.1 to 33.1 ± 19.1 in Phases 2-4). Bradycardia (37.8 ± 3.5 bpm, lowest at Phase 3) and hypertension (133.7 ± 17.0 mmHg, highest at Phase 1) were observed, with minimal analgesia. Atipamezole promptly reversed sedation, restoring cognitive function (tail wagging behavior), and normalizing cardiovascular parameters. During atipamezole CRI, the EEG exhibited a transition from delta waves to alpha and low beta waves. This transition was observed alongside gradual increases in PSI and electromyographic activities. Additionally, spindle activities disappeared during this process. This study's results suggest potential clinical utility for EEG-guided dexmedetomidine sedation with reversal using atipamezole, warranting further investigation.

Comparison of cardiorespiratory effects and perioperative analgesia efficacy of dexmedetomidine or fentanyl continuous infusion during ovariohysterectomy in propofol-anesthetized dogs

The present study aimed to compare the cardiorespiratory, perioperative analgesic and blood gas analysis of the constant rate infusion of dexmedetomidine or fentanyl in 16 female dogs undergoing to elective ovariohysterectomy. The dogs were premedicated with morphine (0.5 mg/kg) and dexmedetomidine (5 µg/kg) or acepromazine (0.05 mg/kg), both intramuscularly (IM), in GDEX or GFEN, respectively. After anesthesia induction with propofol intravenously (IV), animals of GFEN received bolus of fentanyl (2.5 µg/kg) IV followed by continuous rate infusion (CRI) (10 µg/kg/h) and the GDEX received bolus of saline solution 0.9% (corresponding volume of fentanyl) followed by CRI of dexmedetomidine (1 µg/kg/h) and anesthesia was maintained with propofol (0.22 mg/kg/min). In the end of surgery all animals were evaluated using the Glasgow composite measure pain scale (GCPS) and a visual analogue scale (VAS). Data was compared with a statistical p value > 0,05. The mean heart rate was statistically lower in GDEX when compared to GFEN (p = 0.0498): 54.25 ± 3.919 and 88.38 ± 8.766 beats per minute, respectively. Opposed, the average mean blood pressure was statistically higher in GDEX when compared to GFEN (p = 0.0021): 99.38 ± 8.551 and 80.75 ± 11.12 mmHg, respectively. The GDEX and GFEN, in the firsts 4 and 2 postoperative hours, respectively, presented values significantly higher than baseline in the GCPS, occurring analgesic rescues for both groups. It is concluded that both drugs in the proposed rates were safe and efficient for nociceptive control during intraoperative, however, failed to promote efficient postoperative analgesia.

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

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

Intraoperative effect of low doses of ketamine or dexmedetomidine continuous rate infusions in healthy dogs receiving propofol total intravenous anaesthesia and epidural anaesthesia: A prospective, randomised clinical study

The present study aimed to determine the effect of either ketamine or dexmedetomidine constant rate infusion (CRI) on intraoperative propofol anaesthetic requirements during total intravenous anaesthesia (TIVA) in healthy dogs undergoing hindlimbs orthopaedic procedures receiving epidural anaesthesia. In this randomised, blinded clinical study, thirty-nine healthy client-owned dogs were premedicated intramuscularly (dexmedetomidine 4 μg/kg and methadone 0.3 mg/kg). General anaesthesia was induced to effect with propofol administered as intravenous bolus, and maintained with propofol TIVA (18 mg/kg/h), adjusted to meet the suitable clinical anaesthetic depth (indicatively±20%) based on clinical judgement. Lumbosacral epidural anaesthesia was performed using bupivacaine (1 mg/kg) and morphine preservative free (0.1 mg/kg). Dogs randomly received either saline (SP; loading dose 1 mL/kg, CRI 1 mL/kg/h), or ketamine (KP; loading dose 1.5 mg/kg, CRI 1.5 mg/kg/h), or dexmedetomidine (DP; loading dose 1 μg/kg/, CRI 1 μg/kg/h). Physiological variables were recorded intraoperatively at 5-min intervals using standard-of-care monitoring. Recovery quality and duration were recorded. Treatment groups were compared with parametric and non-parametric tests as appropriate, p < 0.05.Propofol rates and recovery scores were similar between groups. Overall mean and diastolic blood pressures were higher in group DP compared to group KP (12–14 mmHg, p = 0.016 and p = 0.015, respectively). More dogs required mechanical ventilation in group KP (12 dogs) than in either group SP or DP (7 dogs per group, p = 0.037).Ketamine or dexmedetomidine CRIs, at the studied rates, did not reduce propofol TIVA requirements in dogs undergoing orthopaedic surgery with epidural anaesthesia.

Cardiopulmonary function and intestinal blood flow in anaesthetised, experimentally endotoxaemic horses given a constant rate infusion of dexmedetomidine.

Endotoxaemia causes untoward inflammatory-mediated effects that might be attenuated by dexmedetomidine. To evaluate the effects of a dexmedetomidine intravenous (IV) infusion on systemic and intestinal haemodynamics and arterial blood gas values in sevoflurane-anaesthetised horses administered Escherichia coli O55:B5 lipopolysaccharides (LPS). Randomised controlled in vivo experiment. A total of 13 horses weighing 456±86kg (mean±standard deviation) and aged 13.9±9.0years donated for euthanasia underwent ventral midline celiotomy using sevoflurane anaesthesia. Baseline physiological variables were recorded after a 90-minute equilibration period. All horses were given 0.1mcg/kgbwt LPS IV. Horses were randomly assigned to no further treatment (group LPS; seven horses) or IV administration of dexmedetomidine (loading dose 1.75mcg/kgbwt followed by 1.75mcg/kgbwt/h; group LPS-Dex; six horses) with concurrent target sevoflurane dose reduction of 50%. Cardiac index (CI; thermodilution), intestinal blood flow, arterial blood parameters and plasma dexmedetomidine concentration measurements were recorded every 30minutes until euthanasia at 390minutes. Data were compared between and within groups to baseline using a mixed model analysis (significance P<.05). In LPS-Dex horses, intestinal blood flow and CI were transiently decreased after the dexmedetomidine loading dose, but no significant differences were found compared with baseline during the infusion. Sevoflurane dose was reliably reduced by approximately 40%. Significant differences were identified in creatinine (115 umol/L LPS-Dex; 195umol/L LPS), bicarbonate (29.7mmol/L LPS-Dex; 23mmol/L LPS) and base excess (2.0mmol/L LPS-Dex; -5.3mmol/L LPS). Dexmedetomidine plasma concentrations were highest after the loading dose and stable during infusion dosing. Experimental conditions are not reflective of clinical colic management. A dexmedetomidine infusion with sevoflurane dose reduction attenuated some deleterious changes in anaesthetised horses administered LPS without sustained negative cardiovascular effects and may be beneficial during colic surgery.

The effect of a dexmedetomidine constant rate infusion on cardiopulmonary function and colonic blood flow in anesthetized, experimentally endotoxemic horses

Introduction: Dexmedetomidine has shown anti-inflammatory properties in models of endotoxic shock and was evaluated here in equine endotoxemia.

Effects of isoflurane, remifentanil and dexmedetomidine on selected EEG parameters derived from a Narcotrend Monitor before and after nociceptive stimulation at different MAC multiples in cats

BackgroundThe aim of this prospective and complete cross-over study was to evaluate the effects of isoflurane, remifentanil and dexmedetomidine on EEG parameters derived from the Narcotrend® Monitor before and after nociceptive stimulation at different isoflurane MAC (minimal alveolar concentration) multiples. Seven adult European Domestic Short Hair cats were used. Each cat went through 3 experimental treatments. Group I received isoflurane, group IR received isoflurane and a constant rate infusion (CRI) of remifentanil (18 μg/kg/h IV), and group ID received isoflurane and a CRI of dexmedetomidine (3 μg/kg/h IV). The isoflurane MAC in each group was determined via supramaximal electrical stimulation. The EEG parameters were derived by a Narcotrend Monitor at specific time points before and after nociceptive stimulation at 0.75, 1.0 and 1.5 MAC.The depth of anaesthesia was also assessed by a clinical score.ResultsThe mean MAC sparing effects in group IR and group ID were 9.8 and 55.2%, respectively. The best correlation of EEG and MAC multiples was found for the Narcotrend Index (NI) in group I (r = − 0.67). The NI was also able to differentiate between 0.75 MAC and 1.5 MAC in group IR. Spectral edge frequency had a lower correlation with MAC multiples in group I (r = − 0.62) but was able to differentiate between 0.75 MAC and 1.5 MAC in groups I and IR, and between 1.0 MAC and 1.5 MAC in group IR. Narcotrend Index, SEF 95 and MF increased significantly after nociceptive stimulation at 1.0 MAC in group I, and SEF 95 increased significantly at 0.75 MAC in group ID. The clinical score correlated closer than any of the EEG parameters with MAC in all groups, with highest correlation values in group I (r = − 0.89). Noxious stimulation led to a significant increase of the clinical score at 0.75 MAC and 1.0 MAC in group I.ConclusionsThe EEG parameters derived from the Narcotrend Monitor show correlation to isoflurane MAC multiples in cats, but the anaesthetic protocol and especially the addition of dexmedetomidine have great influence on the reliability. The Narcotrend Monitor can be used as an additional tool to assess anesthetic depth in cats.

Evaluation of the effectiveness of preoperative administration of maropitant citrate and metoclopramide hydrochloride in preventing postoperative clinical gastroesophageal reflux in dogs.

To investigate the prophylactic effectiveness of preoperative administration of maropitant citrate and metoclopramide hydrochloride in preventing postoperative clinical gastroesophageal reflux (GER) in dogs and to identify risk factors for clinical postoperative GER in dogs. 93 client-owned dogs undergoing surgery at the Washington State University Veterinary Teaching Hospital between March 2016 and February 2017. Dogs were randomly assigned to either the intervention group (preoperatively received maropitant and metoclopramide) or the control group (did not preoperatively receive maropitant and metoclopramide). After surgery, all dogs were recovered and monitored, and occurrences of GER were noted. The prophylactic effectiveness of maropitant and metoclopramide was evaluated, and univariate and multivariate logistic regression analyses were performed to identify variables associated with postoperative clinical GER in dogs. No meaningful difference in the incidence of clinical GER during the postoperative period was detected between the control and intervention groups. Results indicated that variables associated with significantly increased odds of postoperative clinical GER included the male sex (OR, 9.2; 95% confidence interval [CI], 1.26 to 195.0), an overweight BCS (OR, 12.3; 95% CI, 2.1 to 135.1), gastrointestinal surgery (OR, 30.5; 95% CI, 3.0 to 786.9), and requirement for a dexmedetomidine constant rate infusion after surgery (OR, 9.6; 95% CI, 1.3 to 212.5). Findings indicated that incidence of clinical GER during the postoperative period was not lower for dogs that received preoperative prophylactic administration of metoclopramide and maropitant, compared with incidence dogs that did not receive the prophylactic treatment. Further research is required into alternative measures to prevent postoperative clinical GER in dogs.

Experimental study on the effects of isoflurane with and without remifentanil or dexmedetomidine on heart rate variability before and after nociceptive stimulation at different MAC multiples in cats

BackgroundHeart rate variability (HRV) provides information about autonomic nervous system (ANS) activity and is therefore a possible tool with which to assess anaesthetic depth. The aim of the present study was to evaluate the effects of isoflurane, remifentanil and dexmedetomidine on HRV before and after nociceptive stimulation at different anaesthetic depths.Seven healthy domestic short-hair cats were used, and each cat was anaesthetized three times – group I with isoflurane alone, group IR with isoflurane and a constant rate infusion (CRI) of remifentanil (18 μg/kg/h), and group ID with isoflurane and a CRI of dexmedetomidine (3 μg/kg/h). Minimum alveolar concentration (MAC) values were determined via electrical supramaximal nociceptive stimulation for each treatment group. Nociceptive stimulation was repeated at 3 different MAC multiples (0.75, 1.0 and 1.5 MAC), and electrocardiographic recordings were performed for 3 min before and after stimulation. Only the 1 min epochs were used for further statistical analysis. Electrocardiographic data were exported for offline HRV analysis.ResultsThe mean isoflurane MAC ± standard deviation (SD) was 1.83 ± 0.22 vol% in group I, 1.65 ± 0.13 vol% in group IR and 0.82 ± 0.20 vol% in group ID. Nociception was indicated by several HRV parameters, however, with high variability between treatments. The best correlation with MAC was found for the SD of heart rate (STD HR) in group I (rs = − 0.76, p = 0.0001, r2 = 0.46). STD HR was also able to distinguish 0.75 MAC from 1.5 MAC and 1.0 MAC from 1.5 MAC in group I, as well as 0.75 MAC from 1.5 MAC in group ID.ConclusionsThe choice of anaesthetic protocol influences the HRV parameters in cats. Frequency domain parameters respond to nociception at lower MAC levels. The STD HR has the potential to provide additional information for the assessment of anaesthetic depth in isoflurane-anaesthetized cats. The utility of HRV analysis for the assessment of anaesthetic depth in cats is still questionable.

Dexmedetomidine low dose followed by constant rate infusion and antagonism by atipamezole in isoflurane-anesthetized cats: an echocardiographic study

ObjectiveTo investigate the effects of a low dose of dexmedetomidine (DEX) followed by constant rate infusion (CRI) and reversal with atipamezole on systolic and diastolic functions in isoflurane-anesthetized healthy cats. Study designProspective cohort study. AnimalsA group of 11 client-owned adult cats. MethodsBaseline transthoracic echocardiography (TTE) was performed, followed by intramuscular (IM) administration of DEX (5 μg kg−1). After 10 minutes, sedation was scored, adverse effects were recorded and another TTE performed. Approximately 40 minutes after DEX administration, anesthesia was induced by isoflurane mask and maintained with 1.2% end-tidal isoflurane and DEX CRI (1 μg kg−1 hour−1) for 80 minutes. Physiological variables were recorded every 10 minutes, and TTE was repeated 10, 30 and 60 minutes after the start of anesthesia. CRI was stopped, atipamezole (30 μg kg−1) was administered IM and a final TTE was performed after 10 minutes. Repeated measures over time were submitted to one-way analysis of variance or Kruskal–Wallis test according to data distribution; significance was assumed at p < 0.05. ResultsAfter DEX premedication, mild sedation and a slight but significant increase in systolic arterial pressure occurred, and vomiting was a common adverse effect. The cardiac output (CO) and heart rate decreased during anesthesia, with no changes after administration of atipamezole. Trivial valvular insufficiencies were commonly seen after DEX premedication and during CRI. Myocardial radial and longitudinal systolic functions were not affected by sedation or by anesthesia. The late phase of diastole on both right and left ventricles was affected by isoflurane–DEX CRI. Global left ventricular myocardial performance was not impaired. Conclusionsand clinical relevance Decreased CO and late diastolic impairment were observed in healthy cats administered a low dose of DEX for premedication followed by anesthesia with isoflurane and DEX CRI.

Correction: Comparison of desflurane and propofol at equipotent doses in combination with constant rate infusion of dexmedetomidine on global and peripheral perfusion and oxygenation in horses

Correction: Comparison of desflurane and propofol at equipotent doses in combination with constant rate infusion of dexmedetomidine on global and peripheral perfusion and oxygenation in horses

The clinical effects of a low dose dexmedetomidine constant rate infusion in isoflurane anesthetized cats

The aim of this study was to evaluate the effects of a low dose dexmedetomidine constant rate infusion (CRI) on cardiopulmonary function, inhalant anesthetic concentration and recovery in isoflurane anesthetized cats. In a prospective, randomized, blinded, controlled design, 12 cats undergoing anesthesia for ovariohysterectomy were administered hydromorphone (0.1mg/kg) intramuscularly, propofol (4.3–7.8mg/kg) intravenously and maintained with isoflurane. During isoflurane anesthesia, the cats were administered either a dexmedetomidine loading dose (0.5μg/kg) followed by a dexmedetomidine CRI (0.5μg/kg/h) (group LDD), or a saline loading dose followed by a saline CRI (group SAL). Heart rate (HR), respiratory rate, blood pressure, temperature, oxygen saturation (SpO2), end tidal carbon dioxide concentration (ETCO2), end tidal isoflurane concentration (ETISO) and anesthetic depth were recorded at nine time points (T0–T8). Overall effects (T1–8) and individual time point results were compared between groups. There were no significant differences in baseline variables (T0), age, weight, propofol dose, anesthesia and surgery time, time to extubation or recovery score between groups. Among the physiological variables measured, significant differences were observed in respiratory rate, ETCO2, and mean and diastolic blood pressure, between groups at individual time points. Systolic blood pressure, HR, SpO2, ETISO and temperature were not significantly different between groups at individual time points. Overall, ETCO2 and ETISO were significantly lower and respiratory rate was significantly higher for LDD compared to SAL. At the doses administered, a CRI of dexmedetomidine reduced isoflurane requirements in anesthetized cats undergoing ovariohysterectomy. The utility of a low dose dexmedetomidine CRI in the perioperative setting requires further investigation, since intraoperative cardiopulmonary values during dexmedetomidine infusion were not different from those receiving saline.

The cardiovascular status of isoflurane-anaesthetized horses with and without dexmedetomidine constant rate infusion evaluated at equivalent depths of anaesthesia

ObjectiveTo compare cardiac index and oxygen extraction at equivalent depths of anaesthesia between isoflurane-anaesthetized horses and horses anesthetized with isoflurane and dexmedetomidine CRI. Study designSequential, blinded, randomized, balanced, crossover study. AnimalsEight horses weighing a mean ± standard deviation of 478 ± 58 kg. MethodsHorses were premedicated with 0.03 mg kg−1 acepromazine intramuscularly (IM) and 8 μg kg−1 dexmedetomidine intravenously (IV). Anaesthesia was induced with 2.5 mg kg−1 ketamine and 0.1 mg kg−1 midazolam IV and maintained with isoflurane in oxygen and air. Horses were mechanically ventilated. Fractional concentration of end-tidal isoflurane (Fe’Iso) was stabilized at 1.7% with a CRI of 0.9% NaCl (IsoNaCl), or at 1.1% with 1.75 μg kg−1 hour−1 dexmedetomidine (IsoDex). Mean arterial blood pressure was maintained above 60 mmHg by dobutamine infusion. Following nociceptive electrical stimulation, Fe’Iso was stabilized at a 0.1% lower concentration and nociceptive stimulation was repeated. This procedure was continued until the horse moved. Fe’Iso values prior to the concentration at which movement occurred were considered to indicate equivalent depths of anaesthesia between treatments. Cardiac index and oxygen extraction were compared at equivalent depths of anaesthesia using a paired Student’s t-test. ResultsCardiac index differed between IsoNaCl at 61 ± 12 mL kg−1 minute−1 and IsoDex at 48 ± 10 mL kg−1 minute−1 (p = 0.047). In addition, oxygen extraction differed between IsoNaCl at 3.4 ± 0.8 mL kg−1 minute−1 and IsoDex at 4.5 ± 0.5 mL kg−1 minute−1 (p = 0.0042). Two horses receiving IsoNaCl were administered dobutamine at equivalent depths of anaesthesia (7.0 and 28.8 μg kg−1 hour−1, respectively). Conclusions and clinical relevanceCardiovascular function in horses receiving isoflurane and 1.75 μg kg−1 minute−1 dexmedetomidine is more compromised than in horses receiving a higher concentration of isoflurane and 0.9% NaCl CRI.

Effect of dexmedetomidine constant rate infusion on the bispectral index during alfaxalone anaesthesia in dogs

ObjectiveTo assess the effect of two rates of infusion of dexmedetomidine on the bispectral index (BIS) in dogs anaesthetized with alfaxalone constant rate infusion (CRI). Study designProspective, randomized, ‘blinded’ experimental study. AnimalsSix healthy Beagles (three females and three males). MethodsDogs received as premedication saline (group D0), 1 μg kg−1 (group D1) or 2 μg kg−1 (group D2) dexmedetomidine, intravenously (IV). Anaesthesia was induced with alfaxalone (6 mg kg−1 to effect IV) and maintained with alfaxalone at 0.07 mg kg−1 minute−1 and a CRI of saline (D0) or dexmedetomidine 0.5 μg kg−1 hour−1 (D1) or 1 μg kg−1 hour−1 (D2) for 90 minutes. BIS, electromyography (EMG), signal quality index (SQI) and suppression ratio (SR) were measured at 10 minute intervals and the median values were calculated. Nociceptive stimuli were applied every 30 minutes and BIS and cardiorespiratory values were compared before and after stimuli. Cardiorespiratory parameters were recorded throughout the study. ResultsBIS and EMG values differed significantly among groups, being lower in D2 (71 ± 8) than in D0 (85 ± 10) and D1 (84 ± 9). SQI was always over 90% and SR was zero throughout all the treatments. There were no significant differences between pre- and post-stimulus values of BIS, EMG and SQI for any treatment, although in D0 and D1, heart rate, respiratory rate and arterial pressures increased significantly after the nociceptive stimulus. Conclusions and clinical relevanceAdministration of dexmedetomidine (2 μg kg−1 + CRI 1 μg kg−1 hour−1) decreases the BIS values and avoids the autonomic responses of a nociceptive stimulus during alfaxalone anaesthesia at 0.07 mg kg−1 minute−1 in dogs. However, further studies are needed to verify whether this combination produces an adequate degree of hypnosis under surgical situations.

Effects of a dexmedetomidine constant rate infusion and atropine on changes in global perfusion variables induced by hemorrhage followed by volume replacement in isoflurane-anesthetized dogs.

To evaluate the effects of a dexmedetomidine constant rate infusion (CRI) and atropine on changes in global perfusion variables induced by hemorrhage and volume replacement (VR) in isoflurane-anesthetized dogs. 8 adult dogs. Each dog was anesthetized twice, with a 2-week interval between anesthetic sessions. Anesthesia was maintained with 1.3 times the minimum alveolar concentration of isoflurane with and without dexmedetomidine (1.6 μg/kg, IV bolus, followed by 2 μg/kg/h, CRI). Dogs were mechanically ventilated and received an atracurium neuromuscular blockade during both sessions. During anesthesia with isoflurane and dexmedetomidine, atropine was administered 30 minutes before baseline measurements were obtained. After baseline data were recorded, 30% of the total blood volume was progressively withdrawn and VR was achieved with an equal proportion of autologous blood. Following hemorrhage, cardiac index, oxygen delivery index, and mixed-venous oxygen saturation were significantly decreased and the oxygen extraction ratio was significantly increased from baseline. The anaerobic threshold was not achieved during either anesthetic session. When dogs were anesthetized with isoflurane and dexmedetomidine, they had a significantly lower heart rate, cardiac index, and mixed-venous oxygen saturation during VR than they did when anesthetized with isoflurane alone. Plasma lactate concentration, mixed venous-to-arterial carbon dioxide difference, base excess, and anion gap were unaltered by hemorrhage and VR and did not differ between anesthetic sessions. Results indicated that the use of a dexmedetomidine CRI combined with atropine in isoflurane-anesthetized dogs that underwent volume-controlled hemorrhage followed by VR did not compromise global perfusion sufficiently to result in anaerobic metabolism.

The pharmacokinetics of dexmedetomidine administered as a constant rate infusion in horses

Dexmedetomidine, the most selective α2-adrenoceptor agonist in clinical use, is increasingly being used in both conscious and anaesthetized horses; however, the pharmacokinetics and sedative effects of this drug administered alone as an infusion are not previously described in horses. Seven horses received an infusion of 8 μg dexmedetomidine/kg/h for 150 min, venous blood samples were collected, and dexmedetomidine concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analyzed using noncompartmental pharmacokinetic analysis. Sedation was scored as the distance from the lower lip of the horse to the ground measured in centimetre. The harmonic mean (SD) plasma elimination half-life (Lambda z half-life) for dexmedetomidine was 20.9 (5.1) min, clearance (Cl) was 0.3 (0.20) L/min/kg, and volume of distribution at steady-state (Vdss ) was 13.7 (7.9) L/kg. There was a considerable individual variation in the concentration of dexmedetomidine vs. time profile. The level of sedation covaried with the plasma concentration of dexmedetomidine. This implies that for clinical use of dexmedetomidine constant rate infusion in conscious horses, infusion rates can be easily adjusted to effect, and this is preferable to an infusion at a predetermined value.

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 (MACNM) 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 MACNM determination was initiated using constant current electrical stimuli at the skin of the lateral pastern region. Triplicate MACNM 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 MACNM 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 MACNM values to 0.89 (0.62–1.05) and 0.89 ± 0.22% (mean MACNM reduction 67 ± 11%). Conclusion and clinical relevanceCo-administration of dexmedetomidine and morphine CRIs significantly reduced the MACNM of sevoflurane compared with a CRI of morphine alone at the reported doses.

Effects of lidocaine, dexmedetomidine or their combination on the minimum alveolar concentration of sevoflurane in dogs.

ABSTRACTThe aim of this study was to determine the effects of lidocaine (LIDO) and dexmedetomidine (DEX) or their combination (LIDO–DEX), administered by constant-rate infusion (CRI), on the minimum alveolar concentration (MAC) of sevoflurane in dogs. Seven healthy mongrel dogs were used with a 2-week washout interval between treatments in this study. Anesthesia was induced with propofol and maintained with sevoflurane in oxygen, and MAC of sevoflurane was determined after 90 min equilibration period in the dogs (SEV-MACBASAL). Then, sevoflurane MAC was determined again in the dogs after 45 min equilibration period of one of the following treatments: an intravenous loading dose of lidocaine 2 mg/kg followed by 6 mg/kg/hr CRI (SEV-MACLIDO); an intravenous loading dose of dexmedetomidine 2 µg/kg followed by 2 µg/kg/hr CRI (SEV-MACDEX); or their combination (SEV-MACLIDO-DEX). These SEV-MACs were determined in duplicate. Data were analyzed using ANOVA and post hoc Tuckey test when appropriate. The SEV-MACBASAL was 1.82 ± 0.06%, SEV-MACLIDO was 1.38 ± 0.08%, SEV-MACDEX was 1.22 ± 0.10%, and SEV-MACLIDO-DEX was 0.78 ± 0.06%. The CRI administration of lidocaine, dexmedetomidine and their combination produced a significant reduction in the MAC of sevoflurane by 26.1 ± 9.0% (P<0.0001), 43.7 ± 11.8% (P<0.0002) and 54.4 ± 9.8% (P<0.0001), respectively. The MAC reduction was significantly greater after the CRI combination of lidocaine and dexmedetomidine when compared with lidocaine CRI (P<0.0001) or dexmedetomidine CRI treatments (P<0.025).