Cardiovascular Effects Of Dexmedetomidine Research Articles

Sedative and cardiorespiratory effects of dexmedetomidine alone or combined with acepromazine in healthy cats

The purpose of this study was to assess sedation, emesis and cardiovascular effects of dexmedetomidine alone or combined with acepromazine in healthy cats. Fourteen male cats aged 0.9 ± 0.5 years and weighing 3.7 ± 0.7 kg were randomly assigned to one of two experimental groups: GD, dexmedetomidine 5 µg/kg; and GDA, dexmedetomidine 5 µg/kg with acepromazine 0.03 mg/kg, all intramuscularly. Measurements were recorded at baseline, at 20 minutes and then at 10–minute intervals following sedation and included heart rate (HR), respiratory rate (FR), systolic arterial pressure (SAP), rectal temperature (RT), number of episodes of emesis and sedation score (0–4). Data were compared using ANOVA for repeated measures followed by Šídák and Dunnet test. Sedation scores were compared between groups at T20 using Mann-Whitney test. Significance was considered when P <0.05. At T20, HR was significantly lower in GDA (99 ± 14 beats/min) compared with GD (133 ± 19 beats/min) and SAP was significantly lower in both groups compared with baseline (126 ± 14 vs. 148 ± 26 and 111 ± 13 vs. 144 ± 17 mmHg in GD and GDA, respectively). Duration of sedation was similar between groups, although sedation scores differed significantly at T20, with 1 (0–4) in GD and 4 (4–4) in GDA. More episodes of emesis were recorded in GD compared with GDA. The combination of dexmedetomidine and acepromazine produced more profound sedation with faster onset and lower incidence of emesis compared with dexmedetomidine alone in healthy cats.

A Comparative Study Evaluating the Efficacy of Lignocaine and Dexmedetomidine with Lignocaine and Adrenaline in Third Molar Surgery.

The aim of this study was to compare the anesthetic efficacy, duration of action, pain, and cardiovascular effects of dexmedetomidine when added to 2% lignocaine hydrochloride in bilateral symmetrical impacted third molars. This study comprised of 40 healthy patients who required extraction of identical bilateral impacted lower third molars. The left side of the patients was designated as test side where patients received local anesthesia with lignocaine plus dexmedetomidine (2% lignocaine + dexmedetomidine 1μ/ml), and the right side of the patients was designated as control side where patients received local anesthesia with lignocaine plus adrenaline (2% lignocaine in 1:80,000 adrenaline). Both surgical interventions were performed at two different appointments with a minimum time interval of 2weeks. The time to onset and duration of action were noted as primary outcome variables, while the secondary outcome variables included pain and hemodynamic changes associated with dexmedetomidine if any. Onset of action of the local anesthesia was found to be faster in addition to having a relatively longer duration of action when the newer drug dexmedetomidine was added to lignocaine when compared with the conventional combination of lignocaine and adrenaline (P < 0.05). There were no significant changes in the systolic blood pressure, diastolic blood pressure, and heart rate from the baseline following the injection of dexmedetomidine. The study demonstrated that the combination of dexmedetomidine with lignocaine enhances the local anesthetic potency of lignocaine without significant systemic effects when locally injected into oral mucosa.

Pharmacokinetics of dexmedetomidine during administration of vatinoxan in male neutered cats anesthetized with isoflurane

Dexmedetomidine is an alpha-2 adrenoceptor agonist, and vatinoxan is an alpha-2 antagonist believed to poorly cross the blood-brain barrier in cats. Dexmedetomidine-vatinoxan combinations are of interest in anesthetized cats because the anesthetic sparing effect of dexmedetomidine may be preserved while vatinoxan attenuates the adverse cardiovascular effects of dexmedetomidine. The aim of this study was to characterize the pharmacokinetics of dexmedetomidine in cats during administration of isoflurane and vatinoxan. Six healthy adult male castrated cats were anesthetized with isoflurane in oxygen. Vatinoxan was administered using a target-controlled infusion system intended to maintain a plasma concentration of 4 µg/ml. Dexmedetomidine, 35 µg/kg was administered intravenously over 5 min. Plasma dexmedetomidine and vatinoxan concentrations were measured at selected time points ranging from prior to 8 hr after dexmedetomidine administration using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed-effect modeling. A three-compartment model best fitted the data. Typical value (% interindividual variability) for the three-compartment volumes (ml/kg), the metabolic clearance and the two intercompartment distribution clearances (ml min-1 kg-1 ) were 168 (259), 318 (35), 1,425 (18), 12.4 (31), 39.1 (18), and 29.6 (17), respectively. Mean ± standard deviation plasma vatinoxan concentration was 2.6 ± 0.6 µg/ml.

Intranasal dexmedetomidine in healthy beagles: An echocardiographic and pharmacokinetic/pharmacodynamic study

The aim of this study was to compare the sedative and cardiovascular effects of dexmedetomidine (DEX) administrated via intranasal (IN) and intramuscular (IM) routes. This masked, randomised, crossover study used six male beagle dogs, receiving 0.02 mg/kg dexmedetomidine either IN (DEX-IN) or IM (DEX-IM), and an equal volume of saline by the alternative route. Dexmedetomidine plasma concentration was measured before (TB) and at time points (T) 2, 5, 10, 15, 30, 45, 60, 90 and 120 min after drug administration (T0). Physiological variables, sedation scores and sedation times were recorded until recovery. Echocardiography was performed at TB and between T20–T40. Repeated data over time were analysed using a Scheirer-Ray-Hare test. Other data were compared using a Wilcoxon or Student’s t test.Times from T0 to sternal position and from lateral to sternal position were longer for DEX-IN than DEX-IM (P = 0.018 and P = 0.009, respectively). Time from sternal to standing position was shorter for DEX-IN than DEX-IM (P = 0.03). Dexmedetomidine plasma concentrations were significantly lower for DEX-IN than DEX-IM from T10 to T120. Heart rate was significantly lower for DEX-IM than DEX-IN from T5 to T20. Echocardiography showed a decrease in systolic function and calculated cardiac output in DEX-IM as compared to baseline. The DEX concentration-sedation curve for DEX-IN as compared to DEX-IM was leftward shifted, whereas the IN and IM DEX concentration-variation-in-heart-rate curves overlapped. Although reaching lower plasma concentrations, IN dexmedetomidine produced similar sedation to IM dexmedetomidine without affecting cardiovascular function.

Relationship between genetic variation in the α2A-adrenergic receptor and the cardiovascular effects of dexmedetomidine in the Chinese Han population.

There are differences in individual cardiovascular responses to the administration of dexmedetomidine, a highly selective α2A-adrenergic receptor (ADRA2A) agonist. The aim of this study was to investigate ADRA2A gene polymorphisms in the Chinese Han population and their association with the cardiovascular response to intravenous dexmedetomidine infusion. Sixty elective surgery patients of Chinese Han nationality were administered 1 µg/kg dexmedetomidine intravenously over 10 min as a premedication. ADRA2A C-1291G and A1780G polymorphism status was determined in these patients, and their relationships to changes in blood pressure and heart rate after dexmedetomidine administration were analyzed. There were neither significant differences in systolic or diastolic blood pressure changes in individuals with different A1780G and C-1291G genotypes after dexmedetomidine administration, nor in heart rates among the different A1780G genotypes. However, there were significant differences in changes in heart rates in patients with different C-1291G genotypes. There were no significant differences in the sedative effects of dexmedetomidine among different A1780G and C-1291G genotypes. Logistic regression revealed that the C-1291G polymorphism was associated with differential decreases in heart rate after intravenous infusion of dexmedetomidine. These findings indicate that the ADRA2A C-1291G polymorphism can affect heart rate changes in patients after intravenous infusion of dexmedetomidine.

Mechanism-based population pharmacokinetic and pharmacodynamic modeling of intravenous and intranasal dexmedetomidine in healthy subjects.

Dexmedetomidine is an α2-adrenoceptor agonist used for perioperative and intensive care sedation. This study develops mechanism-based population pharmacokinetic-pharmacodynamic models for the cardiovascular and central nervous system (CNS) effects of intravenously (IV) and intranasally (IN) administered dexmedetomidine in healthy subjects. Single doses of 84 μg of dexmedetomidine were given once IV and once IN to six healthy men. Plasma dexmedetomidine concentrations were measured for 10 h along with plasma concentrations of norepinephrine (NE) and epinephrine (E). Blood pressure, heart rate, and CNS drug effects (three visual analog scales and bispectral index) were monitored to assess the pharmacological effects of dexmedetomidine. PK-PD modeling was performed for recently published data (Eur J Clin Pharmacol 67: 825, 2011). Pharmacokinetic profiles for both IV and IN doses of dexmedetomidine were well fitted using a two-compartment PK model. Intranasal bioavailability was 82%. Dexmedetomidine inhibited the release of NE and E to induce their decline in blood. This decrease in NE was captured with an indirect response model. The concentrations of the mediator NE served via a biophase/transduction step and nonlinear pharmacologic functions to produce reductions in blood pressure and heart rate, while a direct effect model was used for the CNS effects. The comprehensive panel of two biomarkers and seven response measures were well captured by the population PK/PD models. The subjects were more sensitive to the CNS (lower EC 50 values) than cardiovascular effects of dexmedetomidine.

Dexmedetomidine: Applications for the Pediatric Patient With Congenital Heart Disease

This study aimed to provide a general description of the cardiovascular and hemodynamic effects of dexmedetomidine and an evidence-based review of the literature regarding its use in infants and children with congenital heart disease (CHD). A computerized bibliographic search of the literature on dexmedetomidine use in infants and children with CHD was performed. The cardiovascular effects of dexmedetomidine have been well studied in animal and adult human models. Adverse cardiovascular effects include occasional episodes of bradycardia, with rare reports of sinus pause or cardiac arrest. Both hypotension and hypertension also have been reported. The latter is related to peripheral α(2B) agonism leading to vasoconstriction. No adverse effects on the pulmonary vasculature have been noted even in patients with preexisting pulmonary hypertension. Although there are no direct effects on myocardial function, decreased cardiac output may result from changes in heart rate or increases in afterload. Although not currently Food and Drug Administration (FDA)-approved for the pediatric population, findings have shown dexmedetomidine to be effective in various clinical scenarios of patients with CHD including sedation during mechanical ventilation, prevention of procedure-related anxiety, prevention of emergence delirium and shivering after anesthesia, and treatment of withdrawal. Although dexmedetomidine may have limited utility for painful or invasive procedures, preliminary data suggest that the addition of ketamine to the regimen may offer benefits. When used during the perioperative period, additional benefits include blunting of the sympathetic stress response with a reduction of endogenous catecholamine release, a decrease in intraoperative anesthetic requirements, and a limitation of postoperative opioid requirements.

Evaluation of cardiorespiratory effects of combinations of dexmedetomidine and atropine in cats

The cardiovascular effects of dexmedetomidine alone or in combination with atropine were studied in six cats. Cats underwent four treatments in a randomized crossover design as follows: DEX15, saline+dexmedetomidine 15microg/kg; DEX30, saline+dexmedetomidine 30microg/kg; ADEX15, atropine+dexmedetomidine 15microg/kg; ADEX30, atropine+dexmedetomidine 30microg/kg. Pulse rate (PR) and systolic arterial pressure (SAP) decreased in DEX15 and DEX30. Premedication with atropine was effective in preventing bradycardia (PR<100 beats/min) and resulted in a biphasic effect in blood pressure. Hypertension was followed by a gradual decrease in SAP. Rate pressure product decreased in DEX15 and DEX30 whereas in ADEX15 and ADEX30 it remained within baseline values for at least 60min. Although premedication with atropine in cats sedated with dexmedetomidine prevents bradycardia, it induces hypertension and increases myocardial oxygen consumption. The magnitude of cardiovascular effects produced by dexmedetomidine in cats does not seem to be dose-related.

The cardiovascular effects of dexmedetomidine given by continuous infusion during isoflurane anesthesia in dogs

In a previous study we showed that the MAC of isoflurane was decreased by 18 ± 12% and 59 ± 7% by constant rate infusions of dexmedetomidine at 0.5 and 3 μg kg–1 hour–1. The purpose of this study was to document the cardiovascular changes associated with these infusions of dexmedetomidine at 1.3 MAC isoflurane/ dexmedetomidine. Dogs were anesthetized with isoflurane in oxygen given by mask. A cephalic venous catheter, a dorsal pedal arterial catheter and a balloon tipped, Swan–Ganz, pulmonary arterial catheter were placed percutaneously. After instrumentation the dogs were maintained at 1.3 MAC isoflurane for 60 minutes. At this time a set of measurements was made including, heart rate, respiratory rate, core body temperature, pulmonary and systemic arterial blood pressures (SAP, MAP, DAP, CVP, SPAP, MPAP, DPAP and PAOP), cardiac output and arterial and mixed venous blood samples were collected for the measurement of blood gases, pH, hemoglobin concentration, PCV and total protein. Calculated variables included base excess (BE), (HCO3−), cardiac index, systemic and pulmonary vascular resistance indices, oxygen delivery, oxygen consumption, oxygen utilization ratio and shunt fraction. After these measurements to dogs were randomly assigned to receive a loading dose of 0.5 or 3 μg kg–1 of dexmedetomidine given over 6 minutes followed by an infusion of 0.5 (LD) or 3 μg kg–1 hour–1 (HD), respectively. The concentration of isoflurane was reduced by the above percentages, respectively, to maintain 1.3 MAC. Full sets of measurements were repeated at 10, 30, 60, 90, 120, 150 and 180 minutes after the start of the loading dose. Measured and calculated variables were compared with baseline using an anovaand a post-hoc Tukey's test. Significance was set at p = 0.05 and results are given as mean ± SD. The initial concentration of isoflurane was 1.73 ± 0.02% and was reduced to 1.41 ± 0.02 and 0.72 ± 0.09% for the LD and HD, respectively. Heart rate decreased with both doses but no other parameter changed significantly with the LD. With the HD there were significant changes in SAP, MAP, DAP, CVP, MPAP, PAOP, CI, SVRI, PCV, DO2 and shunt fraction. The LD appeared to have minimal effect on the cardiopulmonary values measured, whereas the HD caused typical changes expected with an alpha-2 agonist.