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      The efficacy and safety of epidural dexmedetomidine and clonidine with bupivacaine in patients undergoing lower limb orthopedic surgeries

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          Abstract

          Background and Aims:

          Alpha (α-2) adrenergic agonists have both analgesic and sedative properties when used as an adjuvant in regional anesthesia. A prospective randomized double-blind study was carried out to evaluate the efficacy of epidural route and to compare the efficacy and clinical profile of dexmedetomidine and clonidine as an adjuvant to bupivacaine with special emphasis on their quality of analgesia, sedation and the ability to provide the smooth intra-operative and postoperative course.

          Material and Methods:

          The study was conducted in prospective, randomized and double-blind manner. It included 60 American Society of Anesthesiologists Class I and II patients undergoing lower limb surgery under epidural anesthesia. Patients were randomly divided into Group A receiving 0.5% isobaric bupivacaine 15 ml with dexmedetomidine 1 μg/kg and Group B receiving 0.5% isobaric bupivacaine 15 ml with clonidine 2 μg/kg epidurally. Onset and duration of sensory and motor blocks, duration of analgesia, sedation, and adverse effects were assessed.

          Results:

          Demographic data, surgical characteristics cardio-respiratory parameters, side-effect profile were comparable and statistically not significant in both the groups. However, sedation scores with dexmedetomidine were better than clonidine and turned out to be statistically significant. The onset times for sensory and motor blocks were significantly shorter in Group A as compared to Group B. The duration of analgesia and motor block was significantly longer in A Group as compared to Group B.

          Conclusion:

          Dexmedetomidine is a superior neuraxial adjuvant to bupivacaine when compared to clonidine for early onset of analgesia, superior intra-operative analgesia, stable cardio-respiratory parameters, prolonged postoperative analgesia and providing patient comfort.

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          Most cited references36

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          The effects of increasing plasma concentrations of dexmedetomidine in humans.

          This study determined the responses to increasing plasma concentrations of dexmedetomidine in humans. Ten healthy men (20-27 yr) provided informed consent and were monitored (underwent electrocardiography, measured arterial, central venous [CVP] and pulmonary artery [PAP] pressures, cardiac output, oxygen saturation, end-tidal carbon dioxide [ETCO2], respiration, blood gas, and catecholamines). Hemodynamic measurements, blood sampling, and psychometric, cold pressor, and baroreflex tests were performed at rest and during sequential 40-min intravenous target infusions of dexmedetomidine (0.5, 0.8, 1.2, 2.0, 3.2, 5.0, and 8.0 ng/ml; baroreflex testing only at 0.5 and 0.8 ng/ml). The initial dose of dexmedetomidine decreased catecholamines 45-76% and eliminated the norepinephrine increase that was seen during the cold pressor test. Catecholamine suppression persisted in subsequent infusions. The first two doses of dexmedetomidine increased sedation 38 and 65%, and lowered mean arterial pressure by 13%, but did not change central venous pressure or pulmonary artery pressure. Subsequent higher doses increased sedation, all pressures, and calculated vascular resistance, and resulted in significant decreases in heart rate, cardiac output, and stroke volume. Recall and recognition decreased at a dose of more than 0.7 ng/ml. The pain rating and mean arterial pressure increase to cold pressor test progressively diminished as the dexmedetomidine dose increased. The baroreflex heart rate slowing as a result of phenylephrine challenge was potentiated at both doses of dexmedetomidine. Respiratory variables were minimally changed during infusions, whereas acid-base was unchanged. Increasing concentrations of dexmedetomidine in humans resulted in progressive increases in sedation and analgesia, decreases in heart rate, cardiac output, and memory. A biphasic (low, then high) dose-response relation for mean arterial pressure, pulmonary arterial pressure, and vascular resistances, and an attenuation of the cold pressor response also were observed.
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            Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions.

            This research determined the safety and efficacy of two small-dose infusions of dexmedetomidine by evaluating sedation, analgesia, cognition, and cardiorespiratory function. Seven healthy young volunteers provided informed consent and participated on three occasions with random assignment to drug or placebo. Heart rate, blood pressure, respiratory rate, ETCO(2), O(2) saturation, and processed electroencephalogram (bispectral analysis) were monitored. Baseline hemodynamic measurements were acquired, and psychometric tests were performed (visual analog scale for sedation; observer's assessment of alertness/sedation scale; digit symbol substitution test; and memory). The pain from a 1-min cold pressor test was quantified with a visual analog scale. After a 10-min initial dose of saline or 6 microg. kg(-1). h(-1) dexmedetomidine, volunteers received 50-min IV infusions of saline, or 0.2 or 0.6 microg. kg(-1). h(-1) dexmedetomidine. Measurements were repeated at the end of infusion and during recovery. The two dexmedetomidine infusions resulted in similar and significant sedation (30%-60%), impairment of memory (approximately 50%), and psychomotor performance (28%-41%). Hemodynamics, oxygen saturation, ETCO(2), and respiratory rate were well preserved throughout the infusion and recovery periods. Pain to the cold pressor test was reduced by 30% during dexmedetomidine infusion. Small-dose dexmedetomidine provided sedation, analgesia, and memory and cognitive impairment. These properties might prove useful in a postoperative or intensive care unit setting. IMPLICATIPNS: The alpha(2) agonist, dexmedetomidine, has sedation and analgesic properties. This study quantified these effects, as well as cardiorespiratory, memory and psychomotor effects, in healthy volunteers. Dexmedetomidine infusions resulted in reversible sedation, mild analgesia, and memory impairment without cardiorespiratory compromise.
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              Dexmedetomidine: a novel sedative-analgesic agent.

              Since the first report of clonidine, an alpha2-adrenoceptor agonist, the indications for this class of drugs have continued to expand. In December 1999, dexmedetomidine was approved as the most recent agent in this group and was introduced into clinical practice as a short-term sedative (<24 hours). Alpha2-adrenoceptor agonists have several beneficial actions during the perioperative period. They decrease sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery; reduce anesthetic and opioid requirements; and cause sedation and analgesia. They allow psychomotoric function to be preserved while letting the patient rest comfortably. With this combination of effects, alpha2-adrenoceptor agonists may offer benefits in the prophylaxis and adjuvant treatment of perioperative myocardial ischemia. Furthermore, their role in pain management and regional anesthesia is expanding. Side effects consist of mild to moderate cardiovascular depression, with slight decreases in blood pressure and heart rate. The development of new, more selective alpha2-adrenoceptor agonists with improved side effect profiles may provide a new concept for the administration of perioperative anesthesia and analgesia. This review aims to give background information to improve understanding of the properties and applications of the novel alpha2-adrenoceptor agonist, dexmedetomidine.
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                Author and article information

                Journal
                J Anaesthesiol Clin Pharmacol
                J Anaesthesiol Clin Pharmacol
                JOACP
                Journal of Anaesthesiology, Clinical Pharmacology
                Medknow Publications & Media Pvt Ltd (India )
                0970-9185
                2231-2730
                Apr-Jun 2016
                : 32
                : 2
                : 203-209
                Affiliations
                [1]Department of Anaesthesiology, Karnataka Institute of Medical Sciences, Hubli, Karnataka, India
                Author notes
                Address for correspondence: Dr. Safiya I Shaikh, Department of Anaesthesiology, Karnataka Institute of Medical Sciences, Hubli - 580 022, Karnataka, India. E-mail: ssafiya11@ 123456yahoo.com
                Article
                JOACP-32-203
                10.4103/0970-9185.182104
                4874075
                27275050
                e21a1e8c-63c8-43fa-9307-245c00642b99
                Copyright: © 2016 Journal of Anaesthesiology Clinical Pharmacology

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                Categories
                Original Article

                Anesthesiology & Pain management
                alpha 2-adrenergic agonists,bupivacaine and sedation,clonidine,dexmedetomidine,epidural

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