Selective Α2-adrenoreceptor Agonist Research Articles

Effect of Dexmedetomidine Premedication on Sevoflurane Requirement using BIS during General Anaesthesia in Laparoscopic Cholecystectomy

Background: Dexmedetomidine is a highly selective α2-adrenoreceptor agonist with sedative, anxiolytic and analgesic properties without any respiratory depression. It decreases the requirement of volatile anaesthetics with better hemodynamic stability in surgical patients. We avoided the risk of awareness under anaesthesia by using Bispectral index. Aims: To evaluate the efficacy of Dexmedetomidine pre-medication on Sevoflurane requirement and to assess the haemodynamic stability during elective laparoscopic cholecystectomy surgeries. Methods: Randomized double-blind control study. Design: Forty eight patients were randomly allocated into two groups. Group A received saline infusion and Group 2 received Dexmedetomidine infusion in a dose of 1µg/kg over 15 min before induction. Vital parameters and bispectral index were noted throughout the surgery. Patients were induced and intubated as per the standard protocol and maintained with Oxygen & Nitrous oxide (1 litre Oxygen + 2 litre Nitrous oxide) with Sevoflurane concentration adjusted to achieve BIS values of 45–55. Demographic profile, hemodynamic parameters total Sevoflurane consumption were noted. Statistical Analysis: Statistical analysis was performed using SPSS software version 22.0. Percentage analysis was done for qualitative data. Parametric data were compared using an unpaired t-test. Nonparametric data were compared with Fisher’s exact test or Chi-square test. Results: Mean Sevoflurane consumption in Group A and Group B were 0.379 ± 0.10, 0.169 ± 0.05 ml/min respectively with P<0.001 which was statistically significant. A 55.4% reduction in Sevoflurane consumption was found in patients receiving Dexmedetomidine premedication. Conclusions: Dexmedetomidine premedication is useful to reducing Sevoflurane consumption during general anesthesia and it provides better haemodynamic stability.

Dexmedetomidine attenuates lipopolysaccharide-induced renal cell fibrotic phenotypic changes by inhibiting necroinflammation via activating α2-adrenoceptor: A combined randomised animal and in vitro study

BackgroundAcute kidney injury (AKI) was reported to be one of the initiators of chronic kidney disease (CKD) development. Necroinflammation may contribute to the progression from AKI to CKD. Dexmedetomidine (Dex), a highly selective α2-adrenoreceptor (AR) agonist, has cytoprotective and “anti-” inflammation effects. This study was designed to investigate the anti-fibrotic properties of Dex in sepsis models. MethodsC57BL/6 mice were randomly treated with an i.p. injection of lipopolysaccharides (LPS) (10 mg/kg) alone, LPS with Dex (25 μg/kg), or LPS, Dex and Atipamezole (Atip, an α2-adrenoreceptor antagonist) (500 μg/kg) (n=5/group). Human proximal tubular epithelial cells (HK2) were also cultured and then exposed to LPS (1 μg/ml) alone, LPS and Dex (1 μM), transforming growth factor-beta 1 (TGF-β1) (5 ng/ml) alone, TGF-β1 and Dex, with or without Atip (100 μM) in culture media. Epithelial-mesenchymal transition (EMT), cell necrosis, necroptosis and pyroptosis, and c-Jun N-terminal kinase (JNK) phosphorylation were then determined. ResultsDex treatment significantly alleviated LPS-induced AKI, myofibroblast activation, NLRP3 inflammasome activation, and necroptosis in mice. Atip counteracted its protective effects. Dex attenuated LPS or TGF-β1 induced EMT and also prevented necrosis, necroptosis, and pyroptosis in response to LPS stimulation in the HK2 cells. The anti-EMT effects of Dex were associated with JNK phosphorylation. ConclusionsDex reduced EMT following LPS stimulation whilst simultaneously inhibiting pyroptosis and necroptosis via α2-AR activation in the renal tubular cells. The “anti-fibrotic” and cytoprotective properties and its clinical use of Dex need to be further studied.

Effect of ultrasound-guided femoral nerve block with dexmedetomidine and ropivacaine on postoperative analgesia in patients undergoing total knee arthroplasty: a randomized controlled trial

Background: Dexmedetomidine, a potent and highly selective α2-adrenoreceptor agonist, has become a popular adjuvant to local anesthetics. This study was designed to investigate the effect of dexmedetomidine with ropivacaine for femoral nerve block on postoperative analgesia after total knee arthroplasty. Methods: Forty-six patients after total knee arthroplasty received ultrasound-guided femoral nerve block with either 0.3% ropivacaine alone (group R) or 0.3% ropivacaine with 0.5 μg/kg dexmedetomidine (group RD). Total 24-h sufentanil consumption, visual analogue scale (VAS) pain scores, frequency of patient-controlled analgesia (PCA) pressed, Ramsay sedation score, the incidence of bradycardia and hypotension, and incidence of postoperative nausea and vomiting (PONV) were recorded. Results: Compared to group R, the total 24-h sufentanil consumption was significantly reduced (110.76 ± 11.56 vs. 99.09 ± 13.31; P<0.05), the VAS scores were lower at 10 and 12 h postoperatively [3(2–3) vs. 2(1–2) and 3(2–3) vs. 2(1–3), respectively; P<0.05], the frequency of PCA pressed was lower at 8–12 and 12–16-h time intervals [(5(3–6) vs. 2(1–3) and 4(3–4) vs. 2(1–3), respectively; P<0.05]. However, there were no differences in Ramsay’s sedation score and the incidence of PONV. Also, no patient experienced bradycardia and hypotension. Conclusions: 0.5 μg/kg dexmedetomidine with 0.3% ropivacaine for femoral nerve block significantly decreased the total 24-h sufentanil consumption, prolonged and enhanced the analgesic efficacy of ropivacaine, without clinically relevant cardiovascular depression or over-sedation in patients undergoing total knee arthroplasty.

Effect of interscalene brachial plexus block with dexmedetomidine and ropivacaine on postoperative analgesia in patients undergoing arthroscopic shoulder surgery: a randomized controlled clinical trial

BackgroundDexmedetomidine, a potent and highly selective α2-adrenoreceptor agonist has become a popular adjuvant to local anesthetics. The study was designed to explore the effect of dexmedetomidine added to ropivacaine for interscalene brachial plexus block (IBPB) on postoperative analgesia in patients undergoing arthroscopic shoulder surgery.MethodsForty-four adult patients undergoing arthroscopic shoulder surgery were randomly divided into 2 groups. Group R received 0.25% ropivacaine alone, whereas group RD received 0.25% ropivacaine and 0.5 μg/kg dexmedetomidine. A total volume of 15 ml was administered for ultrasound-guided IBPB in both groups. Duration of analgesia, visual analog scale (VAS) pain score, frequency of PCA pressed, first time of PCA pressed, sufentanil consumption, and patient satisfaction with analgesia quality were recorded.ResultsCompared with group R, the duration of analgesia was prolonged (8.25±1.76 vs. 11.55±2.41 h; P<0.05), the VAS pain scores were decreased at 8 and 10 h postoperatively (3 (2–3) vs. 0 (0–0) and 2 (2–3) vs. 0 (0–2.25), respectively; P<0.05), the frequencies of PCA pressed were decreased at 4–8 and 8–12 h time intervals (0 (0–0.25) vs. 0 (0–0) and 5 (1.75–6) vs. 0 (0–2), respectively; P<0.05), the time of first PCA pressed was prolonged (9.27±1.85 vs. 12.98±2.35 h; P<0.05), the total 24h sufentanil consumption was reduced (108.72±15.92 vs. 94.65±12.47 μg; P<0.05 ) and patient satisfaction score was also improved (3 (3–4) vs. 4 (4–5); P<0.05) in group RD.ConclusionWe concluded that adding 0.5 μg/kg dexmedetomidine to 0.25% ropivacaine for IBPB provided better postoperative analgesia, decreased the sufentanil consumption and improved the patient’s satisfaction in patients undergoing arthroscopic shoulder surgery.

Comparison of effects of dexmedetomidine and amifostine against X-ray radiation-induced parotid damage.

Radiotherapy can be employed as a therapeutic modality alone in the early stages of cancer and is used together with other treatments such as surgery and chemotherapy in more advanced stages. However, exposure to ionizing radiation in association with radiotherapy affects several organs in the head and neck and can give rise to early and late side effects. Exposure to ionizing radiation used in radiotherapy is known to cause cell damage by leading to oxygen stress through the production of free oxygen radicals (such as superoxide radicals, hydroxyl radical, hydrogen peroxide, and singlet oxygen), depending on the total radiation dosage, the fractionation rate, radiosensitivity, and linear energy transfer. The purpose of the present study was to determine the potential protective role of a powerful and highly selective α2-adrenoreceptor agonist with a broad pharmacological spectrum against salivary gland damage induced by ionizing radiation exposure. Forty Sprague-Dawley rats were divided into five groups-control, ionizing radiation, ionizing radiation + dexmedetomidine (100µg/kg), ionizing radiation + dexmedetomidine (200µg/kg), and ionizing radiation + amifostine (200mg/kg). Following exposure to ionizing radiation, we observed necrosis, fibrosis, and vascular congestions in parotid gland epithelial cells. We also observed increases in malondialdehyde (MDA) and cleaved Caspase-3 levels and a decrease in glutathione (GSH). In groups receiving dexmedetomidine, we observed necrotic epithelial cells, fibrosis and vascular congestion in parotid gland tissue, a decrease in MDA levels, and an increase in GSH. Dexmedetomidine may be a promising antioxidant agent for the prevention of oxidative damage following radiation exposure.

The Comparison of the Efficacy of Early versus Late Administration of Dexmedetomidine on Postoperative Emergence Agitation in Children Undergoing Oral Surgeries: A Randomized Clinical Trial.

Background: Emergence Agitation (EA) is a dissociated state of consciousness characterized by irritability, uncompromising stance, and inconsolability. The etiology of EA is not completely understood. Dexmedetomidine is a highly selective α2-adrenoreceptor agonist with sedative and analgesic properties, which has been used to reduce the incidence of EA. We aimed to assess the efficacy of early versus late administration of dexmedetomidine on EA in children undergoing oral surgery.Methods: A randomized, parallel, double-blind clinical trial was conducted at Mofid Children’s Hospital affiliated to Shahid Beheshti University of Medical Sciences (Tehran, Iran) from November 2016 to March 2017. A total of 81 children, who underwent adenotonsillectomy or cleft palate repair surgery were enrolled in the study. Based on simple randomization, the children were assigned to two groups, namely early (group A, n=41) and late (group B, n=40) administration of dexmedetomidine. Intra-operative and postoperative hemodynamic variables, extubation time, post-anesthesia care unit (PACU) length of stay, and the scores on Ramsay sedation scale and FLACC pain scale were measured and compared. The data were analyzed using SPSS software (version 20.0), and P<0.05 were considered statistically significant.Results: The mean FLACC score was lower in the late group than in the early group (2.0±1.5 vs. 4.2±1.6, P<0.001). The mean Ramsay sedation score was higher in the late group than in the early group (3.5±1.4 vs. 1.8±0.8, P<0.001).Conclusion: Late administration of dexmedetomidine 1 µg/kg reduced the incidence of EA and PACU length of stay and improved postoperative pain management.Trial registration number: IRCT 2016122031497N1.

Effect of dexmedetomidine on hemodynamic and recovery responses during tracheal extubation

Endotracheal extubation is associated with cardiovascular and airway responses leading to tachycardia, hypertension, arrhythmias, myocardial ischemia, coughing, agitation, bronchospasm, increased bleeding, raised intracranial and intraocular pressure which may be life threatening especially in vulnerable patients. Dexmedetomidine, a highly selective α2-adrenoreceptor agonist is found to attenuate these effects and provide a smooth extubation. To assess the effect of dexmedetomidine on hemodynamic and ventilatory recovery during tracheal extubation. This comparative study was done in 42 patients who fulfilled the inclusion and exclusion criteria between the age group of 20 to 45 years from both sexes were randomly allocated in to two groups of 21 each. One group received 0.5mg Dexmedetomidine and the other group received 100 ml NS. Both groups were compared for the hemodynamic parameters at different time intervals during the whole procedure and were compared for differences if any. In the study group, parameters like Mean arterial pressure, Systolic Blood Pressure, Diastolic Blood Pressure and Heart Rate were under control than the control group. The extubation quality score between controls and dexmedetomidine group (2.14 vs. 1.24) is statistically significant (P&amp;#60;0.001). 14.28% of study group had cough compared to 52.39% in the control group. Bradycardia and Hypertension were significantly higher in the study population. Justbefore extubation, administration of dexmedetomidine ensures the smooth extubation of the trachea and reduces the cardiovascular responses. It also provides adequate sedation postoperatively.

Evaluation of Dexmedetomidine Dosing in Obese Critically Ill Patients

Background: Dexmedetomidine is a highly selective α2-adrenoreceptor agonist that produces dose-dependent sedation, anxiolysis, and analgesia without respiratory depression. Due to these ideal sedative properties, there has been increased interest in utilizing dexmedetomidine as a first-line sedative for critically ill patients requiring light sedation. Objective: To evaluate the ability to achieve goal intensive care unit (ICU) sedation before and after an institutional change of dosing from actual (ABW) to adjusted (AdjBW) body weight in obese patients on dexmedetomidine. Methods: This study included patients ≥ 18 years old, admitted to a surgical or medical ICU, required dexmedetomidine for at least 8 hours as a single continuous infusion sedative, and weighed ≥ 120% of ideal body weight. Percentage of RASS measurements within goal range (−1 to +1) during the first 48 hours after initiation of dexmedetomidine as the sole sedative agent or until discontinuation dosed on ABW compared to AdjBW was evaluated. Results: 100 patients were included in the ABW cohort and 100 in the AdjBW cohort. The median dosing weight was significantly higher in the ABW group (95.9 [78.9-119.5] vs 82.2 [72.1-89.8] kg; p = 0.001). There was no statistical difference in percent of RASS measurements in goal range (61.5% vs 69.6%, p = 0.267) in patients that received dexmedetomidine dosed based on ABW versus AdjBW. Conclusion: Dosing dexmedetomidine using AdjBW in obese critically ill patients for ongoing ICU sedation resulted in no statistical difference in the percent of RASS measurements within goal when compared to ABW dosing. Further studies are warranted.

Ultrasound-guided transversus abdominis plane block using ropivacaine and dexmedetomidine in patients undergoing caesarian sections to relieve post-operative analgesia: A randomized controlled clinical trial.

Dexmedetomidine, which is a highly selective α2 adrenoreceptor agonist, enhances the analgesic efficacy and prolongs the analgesic duration when administered in combination with local anesthetics. The current study aimed to evaluate the effects of dexmedetomidine combined with ropivacaine in ultrasound-guided transversus abdominis plane (TAP) block on post-operative analgesia following cesarean section (CS). A total of 70 patients scheduled for CS were divided randomly into 2 groups: The ropivacaine (R) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml 0.9% normal saline, and the dexmedetomidine (RD) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml dexmedetomidine (0.5 µg/kg). The primary outcome was pain-free duration, and secondary outcomes included heart rate (HR) and mean blood pressure (MBP) measurements, visual analogue scale (VAS) pain scores, number of patients who required rescue analgesic, time to first request for analgesia and patient satisfaction. There was no significant difference in HR and MBP between the two groups at 1 h post-surgery (P>0.05). However, VAS pain scores decreased at 6 and 8 h post-surgery [2 (1-2) vs. 0 (0-0.25) and 2 (2-3) vs. 0 (0-1), respectively; P<0.05], pain-free duration was prolonged (5.91±1.08 vs. 9.62±1.46 h; P<0.05), the number of patients who required rescue analgesic was reduced (19 vs. 9; P<0.05), the time to first request for analgesia was prolonged (7.10±1.21 vs. 11.60±2.11 h; P<0.05) and patient satisfaction was improved [3.5 (3-4) vs. 4 (4-5); P<0.05] in the RD group compared with the R group. Furthermore, no bradycardia or hypotension was observed. In conclusion, the results of the present study demonstrated that adding 0.5 µg/kg dexmedetomidine to 0.3% ropivacaine used in TAP block in patients undergoing CS prolonged pain-free duration, decreased VAS pain scores, reduced the number of patients who required rescue analgesic, prolonged the time to first request for analgesia and improved the patient satisfaction without serious side effects.

Dexmedetomidine Protects against Ischemia and Reperfusion-Induced Kidney Injury in Rats.

Acute kidney injury (AKI), a clinical syndrome, is a sudden onset of kidney failure that severely affects the kidney tubules. One potential treatment is dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist that is used as an anesthetic adjuvant. It also has anti-inflammatory, neuroprotective, and sympatholytic qualities. The aim of this study was to establish whether DEX also offers protection against ischemia and reperfusion- (I/R-) induced AKI in rats. An intraperitoneal injection of DEX (25 μg/kg) was administered 30 min prior to the induction of I/R. The results indicate that in the I/R rats, DEX played a protective role by reducing the damage to the tubules and maintaining renal function. Furthermore, in response to I/R, the DEX treatment reduced the mRNA expression of TNF-α, IL-1β, IL-6, and MCP-1 in the kidney tissues and the serum levels of TNF-α, IL-1β, IL-6, and MCP-1. DEX also reduced the levels of oxidative stress and apoptosis in the tubular cells. These results indicate that in response to I/R kidney injury, DEX plays a protective role by inhibiting inflammation and tubular cell apoptosis, reducing the production of reactive oxygen species, and promoting renal function.

Dexmedetomidine attenuates endoplasmic reticulum stress-induced apoptosis and improves neuronal function after traumatic brain injury in mice

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide. Emerging studies have shown that endoplasmic reticulum (ER) stress plays an important role in the pathophysiology of TBI. Dexmedetomidine (Dex), a highly selective α2-adrenoreceptor agonist, has been shown to attenuate ER stress. However, there is no relevant research in the field of TBI. To study the effects of dexmedetomidine on TBI, we subjected mice to TBI with a controlled cortical impact (CCI) device. The expression levels of ER stress marker proteins and apoptosis-related proteins were evaluated by western blotting and immunofluorescence. Neuronal cell death was assessed by a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL) assay. Neurological and motor deficits were assessed by modified neurological severity scores (mNSSs) and beam balance and beam walking tests. Brain water content and EB leakage were also assessed. Our group found that ER stress was significantly activated 72 h after TBI. Dexmedetomidine significantly reduced ER stress and ER stress-related neuronal apoptosis induced by experimental TBI. In addition, dexmedetomidine significantly improved neurological function and alleviated brain oedema. These findings indicate that dexmedetomidine alleviates severe, post-traumatic ER stress and attenuates secondary brain damage.

Abstract 257: Ventricular Fibrillation Amplitude Spectral Area to Assess the Myocardial Effect of Hemodynamic and Metabolic Interventions During Cardiac Resuscitation in a Rat Model

Introduction: The amplitude spectral area (AMSA) of ventricular fibrillation (VF) has been shown to track the myocardial energy state and to predict the effect of defibrillation. We measured AMSA in a rat model of VF and assessed the effects of α-methylnorepinephrine (α-MNE) - a selective peripheral α 2 -adrenoreceptor agonist - given to increase the coronary perfusion pressure without myocardial β 1 -adrenoceptor stimulation and the effects of zoniporide (ZNP) - an inhibitor of the sodium-hydrogen exchanger isoform-1 - given to protect mitochondrial bioenergetic function from reperfusion injury. Methods: VF was electrically induced in 48 rats and left untreated for 8 minutes. Chest compression was then started and defibrillation attempted 8 minutes later. Rats were randomized to receive a 3-mg/kg bolus of ZNP or 0.9% NaCl control (Ctr) before starting chest compression and a 100-μg/kg bolus of α-MNE or 0.9% NaCl control (Ctr) at 2 minutes of chest compression yielding four groups of 12 rats each; ZNP/α-MNE, ZNP/Ctr, Ctr/α-MNE, and Ctr/Ctr. Results: AMSA (mV·Hz; mean±SEM) was 34.9±1.5 at minute one after induction of VF and decreased to 2.6±0.2 at minute eight. With chest compression, AMSA gradually increased attaining different levels among groups (p&lt;0.001). At minute seven of chest compression, AMSA was the highest with ZNP/α-MNE (29.9±2.5; p=0.012 vs Ctr/α-MNE and p&lt;0.001 vs Ctr/Ctr) followed by ZNP/Ctr (24.1±2.5; p=0.016 vs Ctr/Ctr), Ctr/α-MNE (18.9±2.3), and Ctr/Ctr (12.9±2.6). Survival at 240 minutes differed among groups (p=0.007) with the highest survival with ZNP/α-MNE. Analysis of the independent effects of the interventions revealed that AMSA at minute seven was significantly higher with ZNP (27.2±2.6 vs 16.2±1.6; p&lt;0.001) but not with α-MNE (22.9±2.1 vs 18.6±2.8; p=1.000). Survival was significantly higher with ZNP (18/24 vs 7/24; p=0.004) but not with α-MNE (12/24 vs 13/24; p=1.000). Conclusions: AMSA was the highest when ZNP was combined with α-MNE; a combination that also resulted in the highest 240-minute survival. This effect was primarily linked to ZNP without excluding a positive interaction with α-MNE. Accordingly, AMSA may also serve to assess the myocardial effects of metabolic interventions during cardiac resuscitation.

The effects of novel α2-adrenoreceptor agonist dexmedetomidine on shivering in patients underwent caesarean section.

Objective: Meperidine used to control shivering during perioperative period has associated side effects. The present study compared the safety of selective α2-adrenoreceptor agonist dexmedetomidine and meperidine for anti-shivering in primiparas after caesarean delivery under combined spinal-epidural anesthesia (CSEA).Methods: 100 primiparas scheduled for caesarean delivery were randomly allocated to dexmedetomidine group (Group D, n=50) and meperidine positive control group (Group M, n=50). Primiparas experienced shivering that continued to cord clamping were treated with dexmedetomidine (0.5 μg/kg) or meperidine (0.5 mg/kg) after cord clamping. The primary outcome measures were incidence of nausea, vomiting, and respiratory depression. Secondary outcome measures were shivering score, vital signs including blood pressure, heart rate and O2 saturation, tympanic temperature, and sedation score.Results: Dexmedetomidine provided similar anti-shivering effects as meperidine in patients after caesarean delivery under CSEA, evidenced as all shivering primiparas responded to either dexmedetomidine or meperidine treatment within 15 min. However, incidence of nausea and vomiting were significantly lower after dexmedetomidine treatment, accompanied with more stable blood pressure. Dexmedetomidine also provided well regulation of tympanic temperature and good sedation.Conclusion: Selective α2-adrenoreceptor agonist dexmedetomidine has a better safety profile compared with meperidine for anti-shivering in primiparas undergoing caesarean delivery. Dexmedetomidine could be a better choice for anti-shivering in patients requiring caesarean section. The mechanism of anti-shivering for dexmedetomidine may relate to well regulation of temperature and good sedation.

Practical potentials of using dexmedetomidine in oral and maxillofacial surgery

Dexmedetomidine is a selective α2 adrenoreceptor agonist. The drug has a set of useful properties due to wide prevalence of the receptors in a body. The article presents review of the literature of using dexmedetomidine in anesthetic practice of various surgery fields which positive results may be extrapolated to dentistry and maxillofacial surgery to solve important anesthesiologic problems. Inclusion of the drug in routine oral and maxillofacial surgery anesthesia can bring a significant amount of benefits: safe sedation for dental interventions, sedation for compromised airways without respiratory depression, improvement of intraoperative and postoperative analgesia, reduction of postoperative nausea, vomiting and postoperative shivering incidence, nephroprotection and stability of hypotensive hemodynamics, decrease of intraoperative blood loss. Thus, the dexmedetomidine may be a useful agent for anesthesia in oral and maxillofacial surgery that increases anesthesia safety and quality of medical care.

Hemodynamic changes with intravenous dexmedetomidine and intravenous esmolol for attenuation of sympathomimetic response to laryngoscopy and tracheal intubation in neurosurgical patients: A comparative study

Background: Dexmedetomidine a highly selective α2-adrenoreceptor agonist and esmolol an ultra-short-acting β1-cardioselective adrenergic receptor blocker appear to be quite suitable to control the detrimental effects of laryngeal and tracheal stimulation. The study was conducted to compare the efficacy and safety of dexmedetomidine and esmolol for attenuation of hemodynamic responses to laryngoscopy and intubation in patients of elective neurosurgical procedures under general anesthesia. Materials and Methods: Sixty patients of age 20–60 years, the American Society of Anesthesiologists I and II posted for neurosurgical procedures, randomized into two groups of 30 each to receive dexmedetomidine (Group D): 1 μg/kg and esmolol (Group E): 1.5 mg/kg, both diluted to a total volume of 20 mL with 0.9% saline, infused intravenous over a period of 10 min, before 3 min of induction. Changes in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), rate pressure product (RPP), any side effects associated with the drugs during the study, i.e., 20 min of intubation, were observed and statistically analyzed. Result: There was no statistically significant difference (P = 0.195) in mean HR between Groups D and E during intubation but from the 1st min after intubation (T1) (0.0001) till 20th min (T20) (0.0041) a statistically significant difference in mean HR, mean SBP (P = 0.0001), mean DBP (P

Dexmedetomidine mitigates sevoflurane-induced cell cycle arrest in hippocampus.

Epidemiologic studies suggest the possibility of a modestly elevated risk of adverse neurodevelopmental outcomes in children exposed to anesthesia during early childhood. Sevoflurane is widely used in pediatric anesthetic practice because of its rapid induction and lower pungency. However, it is reported that sevoflurane leads to the long-term cognitive impairment. Some evidence revealed that the selective α2-adrenoreceptor agonist dexmedetomidine (DEX) exerts neuroprotective effects in various brain injury models of animals. But the role of DEX on sevoflurane-induced neuro-damage remains elusive. In our study, we isolated the hippocampal neuron cells from newborn neonatal rats and verified the purity of neurons by immunocytochemistry. We employed the flow cytometry and western blot to examine the effect of sevoflurane, DEX and α2-adrenergic receptor antagonist yohimbine on cell cycle distribution. Immunocytochemistry results showed the purity of neurons > 94%, which provided a good model for neural pharmacology experiments. The exposure of sevoflurane-induced cell cycle arrest at S phase and suppressed the expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB). The addition of DEX suppressed sevoflurane-induced cell cycle arrest and the inhibitory of BDNF and TrkB expression. But the function of DEX was partly blocked by a α2 adrenergic receptor blocker yohimbine. Sevoflurane suppressed neuron cell proliferation via inhibiting the expression of BDNF and TrkB, and DEX relieved the neurotoxicity induced by sevoflurane via α2 adrenergic receptor. These findings provided new evidence that DEX exerted as a neuroprotective strategy in sevoflurane-induced neuro-damage, and provided new basis for the clinical application of DEX.

Renoprotective effects of dexmedetomidine against ischemia-reperfusion injury in streptozotocin-induced diabetic rats.

BackgroundDiabetic patients are susceptible to renal ischemia-reperfusion injury, which leads to perioperative complications. Activation of NOD-like receptor protein 3 (NLRP3) inflammasome participates in the development of diabetes, and contributes to renal ischemia-reperfusion injury. Dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist, shows renoprotective effects against ischemia-reperfusion injury. We aimed to elucidate the effects, underlying mechanisms, and optimal timing of DEX treatment in diabetic rats.MethodsMale Sprague-Dawley rats (n = 12 per group) were randomly divided into normal-sham, diabetes-sham, diabetes-ischemia-reperfusion-control, diabetes-ischemia-reperfusion-DEX-pre-treatment, and diabetes-ischemia-reperfusion-DEX-post-treatment groups. Renal ischemia-reperfusion injury was induced in diabetic rats by occlusion of both renal arteries for 45 min, followed by reperfusion for 24 h. DEX (10 μg/kg) was administered intraperitoneally 1 h before ischemia (pre-treatment) or upon reperfusion (post-treatment). After reperfusion, renal tissue was biochemically and histopathologically evaluated.ResultsDEX treatment attenuated ischemia reperfusion-induced increase in NLRP3, caspase-1, IL-1β, phospho-AKT, and phospho-ERK signaling. Moreover, oxidative stress injury, inflammatory reactions, apoptosis, and renal tubular damage were favorably modulated by DEX treatment. Furthermore, post-reperfusion treatment with DEX was significantly more effective than pre-treatment in modulating NLRP3 inflammasome, AKT and ERK signaling, and oxidative stress.ConclusionsThis study shows that the protective effects of DEX in renal ischemia-reperfusion injury are preserved in diabetic conditions and may potentially provide a basis for the use of DEX in clinical treatment of renal ischemia-reperfusion injury.

A study of hemodynamics when different doses of dexmedetomidine is used with propofol as an inducing agent

Dexmedetomidine is a potent and highly selective α2 adrenoreceptor agonist which was approved for clinical use in 1999 and recently introduced in India. It has all the above mentioned properties and can impart significant benefits in the peri-operative use. In spite of the multiple desirable effects of dexmedetomidine, bradycardia and hypotension remain clinically significant adverse effects. High doses of dexmedetomidine can result in a decreased heart rate and cardiac output, with a biphasic dose response relation for BP. High doses of dexmedetomidine can also be a cause of systemic and pulmonary hypertension.

Dexmedetomidine protects against lipopolysaccharide-induced sepsis-associated acute kidney injury via an α7 nAChR-dependent pathway

Acute kidney injury (AKI) is a clinical syndrome that results in severe tubular damage with high morbidity and mortality. However, there is a lack of effective therapy strategies. Therefore, it is critical to develop effective drugs for AKI. Dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist, has neuroprotective, anti-inflammatory and sympatholytic properties. The present study aimed to investigate the effect DEX on attenuating the inflammatory reaction and apoptosis in the kidney tissues of septic mice and to explore its underlying mechanisms. Sepsis-induced AKI mice models were generated via intraperitoneal injection of lipopolysaccaride (LPS). DEX reduced LPS-induced local inflammation and tubular apoptosis, which was aggravated in the pathogenesis of renal dysfunction. Reverse transcription-quantitative polymerase chain reaction and western blot analysis results revealed that the expression of pro-apoptotic genes and inflammatory factors were markedly reduced by DEX pretreatment. Furthermore, the protective role of DEX was markedly inhibited by the α7 nicotinic acetylcholine receptor (nAChR) antagonist α-bungarotoxin. These findings provided novel evidence for the anti-apoptotic and anti-inflammatory effects of DEX in LPS-induced AKI mice through an α7 nAChR-dependent signaling pathway.

Comparison of effect of intrathecal dexmedetomidine and clonidine as an adjuvant to hyperbaric bupivacaine in patients undergoing surgery for fracture femur and tibia

Background: Spinal anaesthesia with bupivacaine is administered routinely for lower abdominal and lower limb surgeries. The ensuing nerve block is sufficient to ensure patient’s wellbeing, while motor block facilitates the surgeon’s work. Post-operative pain relief can be achieved by various methods namely systemic opioid and non-opioid peripheral nerve blocks and local wound infiltration, each with their own merits and demerits. the present study was undertaken to compare the effect of intrathecal dexmedetomidine and clonidine as an adjuvant to hyperbaric bupivacaine in patients undergoing surgery for fracture femur and tibia.Methods: 80 patients between 20-60 years, undergoing elective surgery for closed fracture shaft of femur and tibia with ASA physical status of 1 and 2 were included in the study. All the subjects were randomly allocated to one of the two groups (Group C and Group D) by a computer-generated randomization chart. Group C received 2.5ml of 0.5% hyperbaric bupivacaine with 50mcg clonidine and group D received 2.5ml of 0.5% hyperbaric bupivacaine with 5mcg dexmedetomidine.Results: 30 of the 40 patients in group C were of ASA I and 10 were ASA II, while in group D, 25 were ASA I and 15 were ASA II. A significant difference was found in the onset time for sensory and motor block, receding time for sensory and motor block and the need of the first rescue analgesia between the two groups, showing that Dexmedetomidine was more potent than clonidine.Conclusions: Dexmedetomidine is a potent, highly selective and specific α2-adrenoreceptor agonist that has both sedative and analgesic effects and is also a valuable adjuvant when regional anaesthesia is incorporated.