Sedative Effects Of Dexmedetomidine Research Articles

Regulation of I1-imidazoline receptors on the sedation effect of dexmedetomidine in mice.

Dexmedetomidine has been used as a sedative drug in the clinic for a long time. Many studies demonstrated that the sedative mechanism of dexmedetomidine might be related to the activation of α2-adrenoceptor (α2AR). In addition, it was reported that dexmedetomidine had some affinity for the I1-imidazoline receptor (I1R); however, the role of I1R in dexmedetomidine-induced sedative effects and its possible mechanism are poorly studied. In the present study, we found that agmatine, an I1R agonist, was able to enhance the sedative effect of dexmedetomidine in mice. Efaroxan, an α2AR and I1R antagonist, could prevent and rescue the sedative action of dexmedetomidine in mice, and its preventive effect was better than atipamezole, the specific α2AR antagonist. Knockout of imidazoline receptor antisera-selected (IRAS), the functional I1R candidate protein, suppressed the dexmedetomidine-induced sedation. Moreover, IRAS knockout led to the inhibition of agmatine and efaroxan in regulating dexmedetomidine-induced sedative effects in mice, but not of atipamezole. We then used CHO cell lines that stably expressed α2AR and IRAS to investigate the possible molecular mechanism of IRAS in regulating the dexmedetomidine-induced sedative effect. The results showed that IRAS expression significantly up-regulated dexmedetomidine-induced ERK phosphorylation, which was enhanced by agmatine and inhibited by efaroxan at low concentrations. Therefore, by taking advantage of pharmacological and genetic approaches, our finding revealed the evidence that IRAS plays an important role in the sedative effects of dexmedetomidine, and the ERK signal pathway may be involved in the mechanism of IRAS in regulating dexmedetomidine-induced sedation. This study may offer valuable insights for the advancement of novel anesthetic adjuvants.

The Effect of Dexmedetomidine Sedation on Lower Gastrointestinal Motility in Children—Is It Suitable for Anorectal Manometry?

Anorectal manometry is one of the most frequently performed gastrointestinal motility studies in children. It is an important study in diagnosing Hirschsprung disease (HD). These procedures can be uncomfortable, painful and emotionally distressing. Nitrous oxide or midazolam are the only pharmacologic options available, as clinical experience suggests that they do not alter manometry readings. Our study was designed to determine whether Dexmedetomidine (DEX) could provide adequate sedation without disrupting anal and rectal pressure. The effect of DEX on anorectal function has never been studied in children. This prospective study recorded anorectal manometry (ARM) measurements prior to the administration of DEX and then repeated the measurements at 1 and 5 min after DEX. The main ARM measurements included resting intra-anal sphincter pressure (IASP) and the presence and characteristics of the recto-anal inhibitory reflex (RAIR). DEX was administered as a bolus followed by a continuous infusion. Twenty patients were included (60% female; mean age 10.8 ± 4.6 years). The RAIR became absent in 2/16 (12.5%) patients after DEX administration. DEX may alter physiologic ARM and IASP recordings necessary to diagnose gastrointestinal medical conditions.

Alpha2 Adrenergic Modulation of Spike-Wave Epilepsy: Experimental Study of Pro-Epileptic and Sedative Effects of Dexmedetomidine.

In the present report, we evaluated adrenergic mechanisms of generalized spike-wave epileptic discharges (SWDs), which are the encephalographic hallmarks of idiopathic generalized epilepsies. SWDs link to a hyper-synchronization in the thalamocortical neuronal activity. We unclosed some alpha2-adrenergic mechanisms of sedation and provocation of SWDs in rats with spontaneous spike-wave epilepsy (WAG/Rij and Wistar) and in control non-epileptic rats (NEW) of both sexes. Dexmedetomidine (Dex) was a highly selective alpha-2 agonist (0.003-0.049 mg/kg, i.p.). Injections of Dex did not elicit de novo SWDs in non-epileptic rats. Dex can be used to disclose the latent form of spike-wave epilepsy. Subjects with long-lasting SWDs at baseline were at high risk of absence status after activation of alpha2- adrenergic receptors. We create the concept of alpha1- and alpha2-ARs regulation of SWDs via modulation of thalamocortical network activity. Dex induced the specific abnormal state favorable for SWDs-"alpha2 wakefulness". Dex is regularly used in clinical practice. EEG examination in patients using low doses of Dex might help to diagnose the latent forms of absence epilepsy (or pathology of cortico-thalamo-cortical circuitry).

A comprehensive overview of clinical research on dexmedetomidine in the past 2decades: A bibliometric analysis.

Introduction: Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist with sedative, analgesic, anxiolytic, and opioid-sparing properties. A large number of dexmedetomidine-related publications have sprung out in the last 2decades. However, no bibliometric analysis for clinical research on dexmedetomidine has been published to analyze hot spots, trends, and frontiers in this field. Methods: The clinical articles and reviews related to dexmedetomidine, published from 2002 to 2021 in the Web of Science Core Collection, were retrieved on 19 May 2022, using relevant search terms. VOSviewer and CiteSpace were used to conduct this bibliometric study. Results: The results showed that a total of 2,299 publications were retrieved from 656 academic journals with 48,549 co-cited references by 2,335 institutions from 65 countries/regions. The United States had the most publications among all the countries (n = 870, 37.8%) and the Harvard University contributed the most among all institutions (n = 57, 2.48%). The most productive academic journal on dexmedetomidine was Pediatric Anesthesia and the first co-cited journal was Anesthesiology. Mika Scheinin is the most productive author and Pratik P Pandharipande is the most co-cited author. Co-cited reference analysis and keyword analysis illustrated hot spots in the dexmedetomidine field including pharmacokinetics and pharmacodynamics, intensive care unit sedation and outcome, pain management and nerve block, and premedication and use in children. The effect of dexmedetomidine sedation on the outcomes of critically ill patients, the analgesic effect of dexmedetomidine, and its organ protective property are the frontiers in future research. Conclusion: This bibliometric analysis provided us with concise information about the development trend and provided an important reference for researchers to guide future research.

Minimizing Motion Artifacts in Intravital Microscopy Using the Sedative Effect of Dexmedetomidine.

Among intravital imaging instruments, the intravital two-photon fluorescence excitation microscope has the advantage of enabling real-time 3D fluorescence imaging deep into cells and tissues, with reduced photobleaching and photodamage compared with conventional intravital confocal microscopes. However, excessive motion of organs due to involuntary movement such as breathing may result in out-of-focus images and severe fluorescence intensity fluctuations, which hinder meaningful imaging and analysis. The clinically approved alpha-2 adrenergic receptor agonist dexmedetomidine was administered to mice during two-photon fluorescence intravital imaging to alleviate this problem. As dexmedetomidine blocks the release of the neurotransmitter norepinephrine, pain is suppressed, blood pressure is reduced, and a sedation effect is observed. By tracking the quality of focus and stability of detected fluorescence in two-photon fluorescence images of fluorescein isothiocyanate-sensitized liver vasculature in vivo, we demonstrated that intravascular dexmedetomidine can reduce fluorescence fluctuations caused by respiration on a timescale of minutes in mice, improving image quality and resolution. The results indicate that short-term dexmedetomidine treatment is suitable for reducing involuntary motion in preclinical intravital imaging studies. This method may be applicable to other animal models.

Analgesic and Sedative Effects of Different Doses of Dexmedetomidine Combined with Butorphanol in Continuous Analgesia after a Cesarean Section

ObjectiveThe present study is designed to study the analgesic and sedative effect of different doses of dexmedetomidine combined with butorphanol in continuous analgesia after a cesarean section.MethodsA total of 60 puerperae undergoing a cesarean section recruited from a single center were divided into three groups according to the postoperative continuous analgesia protocol: control group (100 mL of normal saline containing 10 µg/kg fentanyl and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h), DB1 group (100 mL of normal saline containing 1.0 µg/kg dexmedetomidine, 4 mg of butorphanol, 10 µg/kg fentanyl, and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h), and DB2 group (100 mL normal saline containing 2.0 µg/kg dexmedetomidine, 4 mg of butorphanol, 10 µg/kg fentanyl, and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h). We compared the blood pressure, heart rate, oxygen saturation, VAS score, Ramsay score, and adverse reactions of puerperae among the three groups after surgery.ResultsThe baseline data all have no significant difference in the three groups (p > 0.05). Compared with those in the control group, the systolic blood pressure, diastolic blood pressure, heart rate, and VAS score of the puerperae in the DB1 group and DB2 group were significantly decreased at 6, 24, and 48 h (P < 0.05), while the Ramsay scores of the puerperae in DB1 group and DB2 group were significantly increased at 6, 24, and 48 h (p < 0.05). At the same time, the systolic blood pressure, diastolic blood pressure, heart rate, and VAS score of the puerperae in the DB2 group were significantly lower than those in the DB1 group (P < 0.05), while the Ramsay scores of the puerperae in DB2 group were significantly higher than those in the DB1 group (P < 0.05). Also, there is no significant difference in oxygen saturation and adverse reactions of puerperae among the three groups after surgery (p > 0.05).ConclusionDexmedetomidine combined with butorphanol can improve the analgesic and sedative effects in continuous analgesia after a cesarean section, and the analgesic and sedative effects of dexmedetomidine in the high-dose group are better than those in the low-dose group.

Comparative Study of Hemodynamic Infusion of Dexmedetomidine With Alternative Sufentanil-Midazolam Injection for Sedation of Patients Undergoing Cataract Surgery

In order to induce sedation during cataract surgery, various medications with different side effects are used in separation or in combination. Dexmedetomidine has no effect on the respiratory system, but being dependent on dosage, it may cause cardiovascular disorders. The present study aims to compare the hemodynamic and sedative effects of dexmedetomidine and the combination of sufentanil-midazolam on patients undergoing cataract surgery. In a randomized clinical trial study, 60 patients were randomly divided into two dexmedetomidine and sufentanil-midazolam groups. In sufentanil-midazolam group, dexmedetomidine (DEX infusion at 0.5 μg/ kg for 10 minutes, then adjusted to 0.2 µg/kg/h) was prescribed. In the sufentanil-midazolam group, sufentanil (0.1 μg/kg for 5 minutes) and midazolam (0.2 µg/kg) were injected five minutes before the operation. Hemodynamic variables (Systolic blood pressure, diastolic blood pressure, heart rate), complications (nausea, vomiting, hypoxia), sedation level, and pain intensity were recorded (at the beginning of the study, 5, 10 minutes after anesthesia, at the start of surgery, 5, 10, 15 minutes after the surgery) as well as patient’s satisfaction, surgeon's satisfaction, and complications. Results suggest that apart from gender, other primary characteristics of patients, including age, history of blood pressure, diabetes history, ASA score, mean of systolic, diastolic blood pressure, heart rate, and SPO2 levels, were similar in both groups (P&gt;0.05). Systolic blood pressure patients receiving dexmedetomidine declined significantly more than that of patients receiving sufentanil-midazolam (P&gt;0.5). Diastolic blood pressure suddenly fell 5 minutes after the infusion of sufentanil-midazolam (P&gt;0.05), but then a relative increase and finally a relative decrease occurred, while diastolic blood pressure in patients receiving dexmedetomidine decreased steadily. The mean heart rate in patients receiving dexmedetomidine and sufentanil-midazolam declined gently (P&gt;0.05). SPO2 was reduced significantly in the sufentanil-midazolam group (P&lt;0.05). Drugs used in both groups reduced pain intensity equally (P&gt;0.05). From the beginning of the study, dexmedetomidine produced a relatively stable sedation level (score 2) based on Ramsay's criteria, while the combination of sufentanil-midazolam-medications causes deeper sedation (score 3) in patients (P&lt;0.05). Despite this fact, 23.33% of the patient receiving sufentanil-midazolam could have movements during the surgery, which was 6.66% higher in patients receiving dexmedetomidine (P=0.071). The satisfaction of patients receiving dexmedetomidine was significantly higher (P=0.044), while the surgeon's satisfaction was almost identical in both anesthesia procedures (P=0.94). In the end, the results of the present study showed that although dexmedetomidine is associated with few respiratory problems and higher satisfaction of patients, it decreases blood pressure and heart rate progressively. However, it seems that this medicine is more effective than a combination of midazolam-sufentanil because of more patient satisfaction, lack of hypoxia, fewer complications, and more suitable immobility.

The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study

BackgroundThe genetic polymorphisms of the alpha-2A adrenergic receptor (ADRA2A), which plays a significant role in sedation, anxiety relief, and antinociception, particularly in dexmedetomidine, may differ in the degree of sedation. This study aimed to investigate the effect of the genetic polymorphisms of ADRA2A (rs11195418, rs1800544, rs2484516, rs1800545, rs553668, rs3750625) on the sedative effects of dexmedetomidine. MethodsA total of 131 patients aged 50 years or more from May 2018 to August 2019 were included in this study. The ADRA2A gene variants were evaluated using the TaqMan Assay. Dexmedetomidine diluted in normal saline to a concentration of 4μg.mL-1 was infused at a dose of 2μg.kg-1 to achieve procedural sedation (modified Ramsay sedation scale 4 [mRSS 4]). ResultsA total of 131 patients were evaluated. The genetic polymorphisms (rs11195418) of the ADRA2A receptor gene demonstrated no variation in our participants. The ADRA2A receptor gene polymorphisms (rs1800544, rs2484516, rs1800545, rs553668, and rs3750625) exhibited no differences in total dexmedetomidine doses (p>0.217), bispectral index at mRSS 4 (p>0.620), and time to obtain mRSS 4 (p>0.349). ConclusionThis study suggested that the genetic polymorphisms of ADRA2A did not affect the sedative efficacy of dexmedetomidine.

Dexmedetomidine in modern anesthesiology and intensive care

Background. Sedation is a controlled medical depression of consciousness with the preservation of protective reflexes, independent effective breathing and response to physical stimulation and verbal commands. Sedation is indicated for patients in the intensive care unit in presence of agitation, delirium, withdrawal syndrome of alcohol, drugs or other potent medications and the need to protect the brain (blunt traumatic brain injury, posthypoxic encephalopathy). In addition, at the request of the patient, sedation can be used during invasive diagnostic and treatment procedures.&#x0D; Objective. To describe the role of dexmedetomidine in modern anesthesiology and intensive care.&#x0D; Materials and methods. Analysis of literature data on this issue.&#x0D; Results and discussion. When performing sedation, one should balance between the excessive sedation and its absence. Excessive sedation is accompanied by the lack of contact with the patient, inability to assess the neurological status of the patient, and respiratory depression. If the patient is optimally sedated, he is calm and able to cooperate; he is also adapted to mechanical lung ventilation and other procedures. The target level of sedation according to the Richmond excitation-sedation scale is from 0 to -1. Drugs such as benzodiazepines (diazepam, midazolam, lorazepam), barbiturates (sodium thiopental), propofol, ketamine, inhaled anesthetics (sevoflurane, dexflurane), dexmedetomidine, opioids (morphine, fentanyl, remifentanyl) are used for sedation. Dexmedetomidine is a highly selective α2-adrenoagonist, so it has anxiolytic, sedative, antinociceptive, sympatholytic, and hypothermic actions. In addition, this drug reduces heart rate, suppresses tremor and increases diuresis. The sedative effect of dexmedetomidine is due to the inhibition of neuronal activity in the locus coeruleus of the brain stem. The condition caused by dexmedetomidine is similar to the natural sleep. The use of dexmedetomidine allows to achieve the target level of sedation in a higher percentage of cases than the use of other drugs (propofol, midazolam) (Jacub S.M. et al., 2012). Cooperative sedation is a sedation with the possibility of interaction of the patient with the medical staff. Compared to other drugs, dexmedetomidine increases the patient’s ability to wake up and quickly orient, after which the patient can quickly return to a state of sedation. One of the major complications of critically serious diseases and their treatment is the deterioration of cognitive abilities. Dexmedetomidine has been shown to improve the patient’s cognitive performance by 6.8 points on the John Hopkins scale. In contrast, propofol reduces cognitive function by an average of 12.4 points (Mirski M.A. et al., 2010). Dexmedetomidine has no respiratory depressant effect. Patients on mechanical ventilation do not require discontinuation of dexmedetomidine prior to extubation. Importantly, dexmedetomidine increases coronary blood flow, reduces the incidence of perioperative myocardial ischemia and the risk of perioperative cardiac death. Dexmedetomidine reduces the intensity of pain in the postoperative period and the need for opioids, the incidence of delirium, and the duration of mechanical ventilation. The financial and economic reasonability of dexmedetomidine use has been proved.&#x0D; Conclusions. 1. Sedation is indicated for patients in the intensive care unit in presence of agitation, delirium, withdrawal syndrome and the need to protect the brain, as well as during invasive diagnostic and treatment procedures. 2. The target level of sedation is from 0 to -1 on the Richmond excitation-sedation scale. 3. Dexmedetomidine is a highly selective α2-adrenoagonist, which has anxiolytic, sedative, antinociceptive, sympatholytic, and hypothermic action. 4. Dexmedetomidine increases coronary blood flow and reduces the incidence of perioperative myocardial ischemia, the risk of perioperative cardiac death, pain, delirium incidence and the duration of mechanical ventilation.

Comparative study of dexmedetomidine versus midazolam in monitored anaesthesia care in tympanoplasty surgery

Background: Monitored anaesthesia care (MAC) has become increasingly used for middle ear surgeries. Midazolam is most commonly used for sedation in MAC; likewise, dexmedetomidine has gained popularity for intravenous sedation for the procedures to be done under MAC. The present study was undertaken to evaluate and compare the perioperativeeffects of inj. dexmedetomidine and midazolam with respect to sedation, analgesia and hemodynamic stability. Method: Study was approved by the Institutional Medical Ethics Committee and written informed consent was obtained from all patients participating in the study. Total 60 patients of ASA Grade I and II, aged 18 - 60 years, undergoing tympanoplasty surgery under local anaesthesia with 2% Lignocaine plus adrenaline 1:200000 and sedation with infusion of either dexmedetomidine or midazolam drug. Patients were divided in two groups of 30 patients in each group by chit block method. Group D received Dexmedetomidine 1 mcg/kg IV bolus over 10 min followed by continuous IV infusion at 0.5 mcg/kg/hr. Group M received midazolam 40 mcg/kg IV over 10 min followed by continuous IV infusion at 20 mcg/kg/hr. Results: Perioperatively, sedative effects of dexmedetomidine and midazolam were almost comparable, analgesic effects of dexmedetomidine was better than midazolam IV infusion. The significant reduction in haemodynamic variables was noted with dexmedetomidine (p=0.001) provided better hemodynamic stability than midazolam. Oxygen saturation and respiratory rate were maintained within normal limits in both the groups. 80% of surgeons in either group showed significant satisfaction but the difference was not statistically significant between two groups. Conclusion: Dexmedetomidine is a safe agent as sedative in patients undergoing tympanoplasty surgery under local anaesthesia with MAC.

Sedation of mechanically ventilated patients in intensive care units: Dexemedetomidine versus ketofol

Background Patients in the ICUs are usually provided with sedation and analgesia to avoid pain and anxiety, facilitate invasive maneuvers, decrease stress and oxygen utilization, and facilitate mechanical ventilation. The Association of Critical Care Medicine recommends the use of nonbenzodiazepine drugs such as propofol and dexmedetomidine in sedating the intensive care patients to improve outcomes. Usual sedation protocols should be changed by incorporating propofol, dexmedetomidine, or drug combinations to reach arousal targets and decreasing benzodiazepine use. Objectives The study was conducted to compare between the sedative effect of dexmedetomidine versus ketamine–propofol combination (ketofol) in ICU patients on mechanical ventilation. Patients and methods A total of 90 patients who needed sedation for postoperative mechanical ventilation and monitoring in ICUs were randomly allocated into two groups: ketofol group, where sedation of the patients was done with ketofol at a loading dose of 500 μg/kg of ketamine and propofol mixture 1 : 1 (ketamine 8 mg/ml and propofol 8 mg/ml), followed by continuous infusion at 8–10 μg/kg/min, and dexmedetomidine group, where patients were sedated with an initial bolus dose of dexmedetomidine of 2 µg/kg intravenous infused over 10 min followed by infusion rate of 0.3–0.5 µg/kg/h. Patients’ hemodynamics, Ramsay sedation scale, and total analgesic requirement were recorded. Results Mean blood pressure and heart rate were statistically significantly lower in dexmedetomidine group than in ketofol group. Ramsay sedation score was clinically efficient in both groups but statistically higher in dexmedetomidine group than ketofol group. Dexmedetomidine group showed faster recovery time and less analgesic requirement than ketofol group. Conclusion Dexmedetomidine is an effective sedative drug for ICU patients, with more hemodynamic stability, less analgesic requirement, and rapid recovery time than ketofol.

A Population Pharmacokinetic Model of Intravenous Dexmedetomidine for Mechanically Ventilated Children after Neurosurgery.

Dexmedetomidine is a selective alpha-2 adrenergic agonist with concurrent sedative and analgesic effects, and it is being increasingly used in pediatric anesthesia and intensive care. This study aimed to investigate the pharmacokinetics of intravenous dexmedetomidine in mechanically ventilated children in the intensive care unit (ICU) after neurosurgery. Pediatric patients aged 2–12 years, who were mechanically ventilated in ICU after neurosurgery, were allocated into a low-dose (n = 15) or high-dose (n = 14) group. The low-dose group received dexmedetomidine at a loading dose of 0.25 µg/kg for 10 min, followed by a maintenance dose of 0.25 µg/kg/h for 50 min, whereas the high-dose group received dexmedetomidine at a loading dose of 0.5 µg/kg for 10 min, followed by a maintenance dose of 0.5 µg/kg/h for 50 min. Serial blood samples were collected for a pharmacokinetic analysis up to 480 min after the end of the infusion. The sedative effect of dexmedetomidine was assessed using the Bispectral Index and University of Michigan Sedation Scale. Adverse reactions, electrocardiography findings, and vital signs were monitored for a safety assessment. A population pharmacokinetic analysis was performed using non-linear mixed effects modeling. Dexmedetomidine induced a moderate-to-deep degree of sedation during infusion in both groups. The pharmacokinetics of dexmedetomidine were best described by a two-compartment disposition model with first-order elimination kinetics. The parameters were standardized for a body weight of 70 kg using an allometric power model. The population estimates (95% confidence interval) per 70 kg body weight were as follows: clearance of 81.0 (72.9–90.9) L/h, central volume of distribution of 64.2 (50.6–81.0) L, intercompartment clearance of 116.4 (90.6–156.0) L/h, and peripheral volume of distribution of 167 (132–217) L. No serious adverse reactions or hemodynamic changes requiring the discontinuation of dexmedetomidine were observed. Dexmedetomidine had increased clearance and volume of distribution in mechanically ventilated children in ICU after neurosurgery, thereby indicating the need to adjust the dosage to obtain a target plasma concentration.

COMPARATIVE STUDY OF INTRAVENOUS DEXMEDETOMIDINE AND MIDAZOLAM AS A PREOPERATIVE SEDATION UNDER SPINAL ANESTHESIA

INTRODUCTION: Preoperative anxiety is a frequent condition. Comfortable anesthesia induction and maintenance can be achieved by controlling anxiety. Various agents are used to relieve anxiety and provide sedation. We conducted this study to compare the sedative effects of dexmedetomidine versus midazolam for patients undergoing spinal anesthesia. AIMS AND OBJECTIVES : To compare the sedative effect of both drugs and observe intraoperative and postoperative comfort level, cardiovascular and respiratory changes and side effects of both drugs. MATERIALS AND METHODS: Sixty patients between 18-65 years of age requiring spinal anaesthesia for their procedures were selected randomly and division was done in 2 groups (Each group having 30 patients). Group D was given Inj. Dexmedetomidine at the dose of 1 mcg/kg within 10 mins in 100 ml NS and group M was given Inj Midazolam at the dose of 0.04 mg/kg in 100 ml NS within 10 mins. DISCUSSION: Anxiety is more common among young patients, women, and people with negative experience of anesthesia or fear that arises just before the operation and anesthesia my lead to psychological trauma. Various agents such as phenothiazines, bezodiazepines, barbiturates, opioids, propofol, ketamine, dexmedetomidine or clonidine and antihistamines are used to relieve anxiety and provide sedation. Midazolam is a benzodiazepine,commonly used as an intravenous sedative agent for pre-operative sedation. Dexmedetomidine is an alpha-2 agonist which acts on adrenoreceptors in many tissues including the nervous, cardiovascular and respiratory systems. Unlike midazolam, dexmedetomidine does not affect the ventilatory response to carbon dioxide, it also produces analgesia which could potentially alleviate pain.

Comparison of preoperative sedation effect of dexmedetomidine via oral mucosa spray and nasal drip in children

Objective To evaluate the effects of dexmedetomidine (Dex) by oral mucosa spray versus nasal drip in preoperative sedation in children. Methods Sixty children underwent minor elective surgery in the inguinal region, aged 1 to 5 y, and American Society of Anesthesiologists (ASA) grade Ⅰ. They were divided into two groups according to the random number table method: the nasal drip group (group N) and the oral mucosa spray group (group B), 30 cases in each group. The children were given Dex 1.5 μg/kg by nasal drip or oral mucosa 40 min before surgery. Heart rate, pluse oxygen saturation(SpO2) and observer assessment of alertness and anxiety scale (OAA/S) were measured before and 10, 20, 30, 40 min after administration. The drug acceptance, parental separation anxiety scale and mask acceptance scale of the two groups were observed, and the occurrence of adverse events during the post-anesthesia care unit(PACU) was recorded. Results Drug acceptance satisfaction in group B was higher than in group N (P 0.05). Heart rate of group N and group B decreased significantly at 20, 30 min after medication respectively (P 0.05). No postoperative adverse reactions occurs in children during in the PACU. Conclusions A good sedative effect can be obtained by administration of Dex via oral mucosa spray or nasal drip route. The nasal drip mode works quickly, but it is more easily accepted by children during oral mucosa administration. Key words: Dexmedetomidine; Child; Oral mucosa spray; Nasal drip; Sedation

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.

Hemodynamic Stability of the Patients Receiving Intravenous Dexmedetomidine versus Intravenous Propofol Based Sedation in Cervical Disc Surgeries

Background: The sedative effect of dexmedetomidine is exercised subcortically and mimics natural sleep. The area of the brain with the highest concentration of alpha2-ARs is the locus coeruleus (LC) in the upper brainstem, which is responsible for arousal, sleep, anxiety, and withdrawal symptoms from drug addiction. It projects into two areas in the thalamus: the ventrolateral preoptic nucleus and the tuberomamillary nucleus. When the alpha2-AR is activated, it inhibits adenylyl cyclase. This results in the reduction of cAMP, with net efflux of K+ (through Ca2+-activated K+ channels) and inhibition of Ca2+ entry into nerve terminals. This hyperpolarises the neuron and suppresses the release of noradrenaline (NA) from the LC. Subjects and Methods: In this prospective study hundred ASA Grades I and II patients between the ages of 20 and 60 years undergoing elective cervical disc surgeries were enrolled after Ethical committee and Scientific committee approval meeting the below selection criteria. Results: The intergroup variation in the SBP during the intubation and till 5 mins after intubation showed a significant lower values in patients with the dexmedetomidine as compared with the propofol (P &lt; 0.001). Conclusion: Patients on dexmedetomidine had significantly better hemodynamic response to Fiberoptic bronchoscopy and intubation compared to propofol group. Heart rate, systolic, diastolic and mean arterial pressures were significantly lower in dexmedetomidine group as compared to propofol group during intubation and at various intervals post intubation.

The sedative effect of dexmedetomidine in outpatient undergoing dental surgery compared to several sedative drugs:a meta analysis

To evaluate the efficacy of dexmedetomidine and midazolam, ketamine or placebo administrated in outpatient dental surgery. PubMed, Embase, Cochrane Library and Web of Science were searched from inception to October 2017,to find all randomized controlled trials(RCTs) about the sedative effect of dexmedetomidine versus midazolam, ketamine or placebo during outpatient dental surgery. The quality of the studies was evaluated by the method recommended by Cochrane collaboration. Meta analysis was conducted using Review Manager 5.3 software. Twelve clinical trials with 678 patients were included. The results of meta analysis showed that the sedation score of children was lower in group of dexmedetomidine than that of group of normal saline (SMD=-1.73,95%CI:-2.70～-0.77,P=0.0004) and the sedation score of adults was also lower in group of dexmedetomidine than that of group of normal saline(SMD=-2.23,95%CI:-4.39～-0.08,P=0.04).There was no significant difference in sedation satisfaction of children between dexmedetomidine and ketamine(RR=1.14,95%CI:1.00-1.30,P=0.05).Dexmedetomidine provided more satisfactory sedation of children than midazolam(RR=1.38,95%CI:1.15-1.67,P=0.0006),and there was no significant difference in sedation satisfaction of adults between dexmedetomidine and midazolam (RR=1.42,95%CI:0.86-2.33,P=0.17). Moreover,dexmedetomidine provided more satisfactory behavior of children than ketamine (RR=1.19,95%CI:1.03-1.36,P=0.01) and midazolam (RR=1.28,95%CI:1.07-1.54,P=0.008). Compared with other sedative drugs, dexmedetomidine may be a better choice for moderate sedation during outpatient dental surgery.

Subcutaneously administered dexmedetomidine is efficiently absorbed and is associated with attenuated cardiovascular effects in healthy volunteers.

Palliative care patients often need sedation to alleviate intractable anxiety, stress, and pain. Dexmedetomidine is used for sedation of intensive care patients, but there is no prior information on its subcutaneous (SC) administration, a route that would be favored in palliative care. We compared the pharmacokinetics and cardiovascular, sympatholytic, and sedative effects of SC and intravenously (IV) administered dexmedetomidine in healthy volunteers. An open two-period, cross-over design with balanced randomization was used. Ten male subjects were randomized to receive 1μg/kg dexmedetomidine both IV and SC. Concentrations of dexmedetomidine and catecholamines in plasma were measured. Pharmacokinetic variables were calculated with non-compartmental methods. In addition, cardiovascular and sedative drug effects were monitored. Eight subjects completed both treatment periods. Peak concentrations of dexmedetomidine were observed 15min after SC administration (median; range 15-240). The mean bioavailability of SC dexmedetomidine was 81% (AUC0-∞ ratio × 100%, range 49-97%). The mean (SD) peak concentration of dexmedetomidine in plasma was 0.3 (0.1) ng/ml, and plasma concentrations associated with sedative effects (i.e., > 0.2ng/ml) were maintained for 4h after SC dosing. Plasma noradrenaline concentrations were significantly lower (P< 0.001) within 3h after IV than after SC administration. Subjective scores for vigilance and performance were significantly lower 0-60min after IV than SC dosing (P< 0.001 for both). The onset of the cardiovascular, sympatholytic, and sedative effects of dexmedetomidine was clearly less abrupt after SC than IV administration. Dexmedetomidine is relatively rapidly and efficiently absorbed after SC administration. Subcutaneous dexmedetomidine may be a feasible alternative in palliative sedation, and causes attenuated cardiovascular effects compared to IV administration. CLINICALTRIALS. NCT02724098 . EUDRA CT number 2015-004698-34 .

Comparative, Sedative, and Analgesic Effects of Epidural Dexmedetomidine and Xylazine in Donkeys (Equus asinus)

In a prospective experimental crossover study, six clinically healthy donkeys were injected epidurally with normal saline (5 mL/animal), dexmedetomidine (5 μg kg−1), and xylazine (200 μg kg−1). Perineal analgesia, sedation, and degree of ataxia were evaluated preadministration and at 5, 10, 15, 30, 60, 90, 120, 150, and 180 minutes post-administrarion. Heart rate, respiratory rate, and rectal temperature were measured at the same time points. Epidural dexmedetomidine and xylazine produced complete bilateral perinea analgesia in all donkeys. The onset of analgesia was significantly rapid in dexmedetomidine-treated donkeys in comparison with xylazine (5.8 ± 2.04 vs. 14.2 ± 2.04 minutes, P = .004). Dexmedetomidine induced longer duration of perinea analgesia when compared with xylazine (160.0 ± 25.0 vs. 115.8 ± 14.97 minutes, P = .021). Both drugs induced moderate sedation (score 2). The sedative effect of dexmedetomidine was longer than that of xylazine (105 ± 10 vs. 80.83 ± 12 minutes, P = .017). All donkeys showed mild ataxia (score 1) after epidural xylazine and dexmedetomidine. Tail flaccidity was noticed in all donkeys at 15 and remained until 125 and 165 minutes postadministration of xylazine and dexmedetomidine, respectively. In conclusion, epidural dexmedetomidine induced faster and longer perinea analgesia with minimal cardiovascular effects than xylazine.

Sevoflurane sparing effect of dexmedetomidine in patients undergoing laparoscopic cholecystectomy: A randomized controlled trial.

Background and Aims:Sevoflurane is an excellent but expensive anesthetic agent for laparoscopic cholecystectomy. To decrease sevoflurane consumption during surgery adjuvants like dexmedetomidine may be used. Dexmedetomidine is a recently introduced drug which alleviates the stress response of surgery, produces sedation and analgesia. We aimed to evaluate sevoflurane sparing effect of dexmedetomidine in patients undergoing laparoscopic cholecystectomy under entropy-guided general anesthesia (GA).Material and Methods:In this prospective randomized control study, 100 American Society of Anesthesiologists physical status I–II adult surgical patients scheduled to undergo laparoscopic cholecystectomy were enrolled. Patients were randomly divided into two groups (n = 50). In dexmedetomidine group, patients received intravenous (IV) dexmedetomidine 0.5 μg/kg over 10 min before induction followed by 0.5 μg/kg/h infusion while in control group, patients received the same volume of normal saline.Results:Sevoflurane consumption was 41% lower in dexmedetomidine group as compared to control group (7.1 [1.6] vs. 12.1 [1.9] ml, P <0.001). A 40% reduction was observed in induction dose of propofol (83.0 [19.1] vs. 127.6 [24.8] mg, P <0.001). Mean Riker sedation-agitation score, visual analog score for pain and Aldrete's score were significantly lower in dexmedetomidine group as compared to control group. None of the patients experienced any significant side effects.Conclusion:A 41% reduction in sevoflurane consumption was observed in patients receiving IV dexmedetomidine as an adjuvant in patients undergoing laparoscopic cholecystectomy under GA.