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Bleeding-induced multiple organ dysfunction syndrome (MODS) is one of the major causes of death in pregnant women. MODS is thought to result from an inappropriate generalized host inflammatory response to a variety of acute insults. In this study we established a MODS model in postpartum rats, in which MODS was induced by the combination of induced hypotension for 60 min and clamping of the superior mesenteric artery for a period of 40 min. We sacrificed all the rats 24 h after dexmedetomidine (DEX) treatment. Thymus, spleen, and mesenteric lymph node tissue were collected to detect interferon-γ (IFN-γ) and interleukin-4 (IL-4) protein expression; lung and intestine tissue were collected to measure IFN-γ and IL-4 gene expression. In the present study, IFN-γ and IL-4 mRNA were increased in the lungs and intestines of the MODS rats. DEX administration decreased IFN-γ and IL-4 mRNA expression. IFN-γ and IL-4 expression for the thymus, spleen, and mesenteric lymph nodes were higher in the MODS postpartum rats relative to control rats, and these expression levels decreased upon DEX administration, But there were no significant differences between DEX doses. In conclusion DEX administration appeared to reduce IFN-γ and IL-4 protein expression in thymus, spleen, and mesenteric lymph node tissue and reduce IFN-γ and IL-4 gene expression in the lungs and intestines in the MODS postpartum rats but was not dose-dependent. [ABSTRACT FROM AUTHOR]

Objective: Anaesthetic agents used for magnetic resonance imaging (MRI) in paediatric patients should cause few adverse effects and allow fast anaesthetic induction and recovery. The administration route is also important and should be minimally invasive. In this study, we aimed to compare two different doses of intranasal dexmedetomidine applied to children for MRI sedation. Methods: Sixty patients between 1 and 10 years of age with American Society of Anesthesiologists Physical Status classification I or II who were scheduled for MRI were recruited into this prospective, randomized, double-blind study. Intranasal dexmedetomidine was administered at doses of 3 µg kg (Group 1) and 4 µg kg (Group 2) before imaging. Heart rate (HR), peripheral oxygen saturation, respiratory rate and Ramsay Sedation Scale (RSS) scores were recorded before the anaesthetic induction of sedation and every 10 min until discharge. If intranasal sedation failed, an intravenous cannula was placed and propofol was applied as a rescue anaesthetic. Bispectral Index (BIS) scores were also recorded before and after MRI. We recorded onset time of sedation, mood at separation from parents (defined as parental separation score), imaging quality, MRI duration, rescue anaesthetic requirement, total duration of sedation, recovery duration, parents' satisfaction and adverse effects. Results: The results related to age, weight and adverse effects were not statistically different between the groups. The parental separation score was significantly higher in Group 2 ( P = 0.003). Rescue anaesthetic requirement was significantly higher in Group 1 ( P = 0.002). The results related to recovery duration, MRI duration, parents' satisfaction, onset time of sedation and total duration of sedation were not statistically different. HR was significantly lower in all time intervals compared with basal values in both groups. In Group 2, RSS scores were significantly higher in the 30th, 40th and 50th min. The BIS scores in Group 2 were lower at the 50th min. Neither bradycardia nor oxygen desaturation were observed. Imaging studies were completed successfully in all patients. Conclusions: Based on lower rescue anaesthetic requirements, sufficient sedation and parental separation scores in Group 2, intranasal dexmedetomidine 4 µg kg was more efficient than intranasal dexmedetomidine 3 µg kg. The intranasal route may be an alternative noninvasive route to apply drugs for MRI sedation in paediatric patients. Trial registration ClinicalTrials.gov: NCT02299232. [ABSTRACT FROM AUTHOR]

Recent studies showed that the administration of dexmedetomidine relieved hyperalgesia in the presence of neuropathic pain. These findings have led to the hypothesis that the local administration of dexmedetomidine is useful for relieving acute inflammatory nociception, such as postoperative pain. Thus, we evaluated the inhibitory effect of locally injected dexmedetomidine on acute inflammatory nociception. Acute inflammatory nociception was induced by an intraplantar injection of 1% carrageenan into the hindpaws of rats, and dexmedetomidine was also injected combined with carrageenan. The paw withdrawal threshold based on von Frey filament stimulation was measured until 12 h after injection. We compared the area under the time-curve (AUC) between carrageenan and carrageenan with dexmedetomidine. To clarify that the action of dexmedetomidine was via α 2 -adrenoceptors, we evaluated the effect of yohimbine, a selective antagonist of α 2 -adrenoceptors, on the anti-nociception of dexmedetomidine. As the results, the intraplantar injection of carrageenan with over 10 μM dexmedetomidine significantly increased AUC, compared to that with only carrageenan injection. This effect of dexmedetomidine was reversed by the addition of yohimbine to carrageenan and dexmedetomidine. These results demonstrated that the locally injected dexmedetomidine was effective against carrageenan-induced inflammatory nociception via α 2 -adrenoceptors. The findings suggest that the local injection of dexmedetomidine is useful for relieving local acute inflammatory nociception. [ABSTRACT FROM AUTHOR]

The restraint of ferrets for physical examination and venipuncture often employs chemical means with parenteral drug injection or inhalant anesthetics. These methods often result in agitation, pain at the injection site, increased stress, and increased cost. A transmucosal (TM) detomidine gel has recently been evaluated for sedation to facilitate physical examination and common procedures in dogs and horses. The purpose of the present study was to evaluate TM detomidine in the domestic ferret for physical examination and venipuncture in a teaching laboratory setting. Detomidine was evaluated at 2 doses: 2 and 4 mg/m 2 . A total of 16 ferrets (8 female and 8 male) were randomly assigned to each dose group. Following the administration of detomidine, physiologic variables were collected (heart rate, respiratory rate, and rectal temperature) and sedation scoring was performed every 10 minutes. Owing to the rapid effect of the drug, time of onset was not consistently captured in the data recording protocol; the 8 males were used again in a subsequent laboratory and dosed at 3 mg/m 2 to refine the times of initial effect and dorsal recumbency. Venipuncture was attempted only after full physical examinations were completed and the ferrets could be placed in dorsal recumbency. Venipuncture was performed with detomidine sedation alone on 4 female and 5 male ferrets, with no significant difference based on dose group. Isoflurane was administered via face mask to the remaining ferrets due to insufficient sedation based on muscle movement and reaction to venipuncture. Heart rate significantly decreased following detomidine administration as compared with baseline values in both dose groups. There were no significant changes in respiratory rates. Sedation scores were significantly increased throughout the study period. Side effects of detomidine administration included piloerection of the tail in all ferrets and a second-degree atrioventricular block in one female ferret that resolved following reversal with atipamezole. Hyperglycemia was observed in 67% of the ferrets. TM detomidine effectively sedated domestic ferrets for physical examination and venipuncture. [ABSTRACT FROM AUTHOR]

Objective To investigate MK-467 as part of premedication in horses anaesthetized with isoflurane. Study design Experimental, crossover study with a 14 day wash-out period. Animals Seven healthy horses. Methods The horses received either detomidine (20 μg kg−1 IV) and butorphanol (20 μg kg−1 IV) alone ( DET) or with MK-467 (200 μg kg−1 IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg−1) and midazolam (0.06 mg kg−1) IV and maintained with isoflurane. Heart rate ( HR), mean arterial pressure ( MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO2) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index ( CI), systemic vascular resistance ( SVR), ratio of arterial oxygen tension to inspired oxygen (PaO2/FiO2) and tissue oxygen delivery ( DO2) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05. Results The induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+ MK, while SVR was higher with DET. Arterial oxygen tension and PaO2/FiO2 (40 minutes after induction), DO2 and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+ MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+ MK, the area under the plasma concentration time curve of butorphanol was smaller. Conclusions and clinical relevance MK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP. [ABSTRACT FROM AUTHOR]

Background and Aims: The use of propofol as the most common induction agent and the high prevalence of propofol injection pain (PIP) highlight the significance of finding the ideal combination of drug, dosage and mode of administration of premedicants to alleviate PIP. A number of bolus drugs with variable efficacy have been studied to reduce PIP. The aim of our study was to assess the efficacy of single dose intravenous (IV) infusion of dexmedetomidine 0.5 μg/kg compared with ketamine 0.5 mg/kg to alleviate PIP. Methods: In this prospective, randomised and double-blind study, 108 patients undergoing elective surgeries under general anaesthesia were randomly allocated to two groups: Group D to receive dexmedetomidine 0.5μg/ kg or Group K to receive ketamine 0.5 mg/kg in 20 ml of normal saline over 10 min. Immediately after the infusion, 1% propofol 2 mg/kg IV was injected over 25 s. The patients were assessed for pain every 5 s by asking the question 'does it hurt?' until the loss of consciousness. The pain scoring was done using McCririck and Hunter scale. Statistical analysis was done using SPSS 17.0. Results: The incidence of PIP and moderate-severe PIP was higher with Group D (79.6%; 16.7%) compared with Group K (40.7; 1.9%) (P < 0.001; 0.016). No patient in either group had arm withdrawal upon propofol injection. The incidence of hypertension and tachycardia was statistically significant in Group K as compared to Group D (P = 0.027). Conclusion: There was no difference in elimination of the arm withdrawal response and in incidence of moderate to severe PIP between the groups. [ABSTRACT FROM AUTHOR]

Dexmedetomidine (DEX) has been hypothesized to possess anti-oxidative properties that may mitigate the damage caused by ischemia-reperfusion (IR) injury. The aim of the present study was to examine the effects of DEX on intestinal contractile activity, inflammation and apoptosis following intestinal IR injury. Intestinal IR injury was induced in rats by complete occlusion of the superior mesenteric artery for 60 min, followed by a 60-min reperfusion period. Rats received an intraperitoneal injection of 25 µg/kg DEX at 30 min prior to the mesenteric IR injury. Following reperfusion, segments of the terminal ileum were rapidly extracted and transferred into an isolated organ bath. The contractile responses to receptor-mediated acetylcholine (Ach) and non-receptor-mediated potassium chloride (KCl) were subsequently examined. Nitric oxide (NO) levels were determined and the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, Bax and Bcl-2 were measured using an enzyme-linked immunosorbent assay. The levels of telomerase and caspase-3 were determined using reverse transcription-quantitative polymerase chain reaction. The results indicated that DEX treatment produced a significant reduction in the IR-induced contractile response to Ach and KCl in the intestinal tissue. Furthermore, DEX appeared to significantly ameliorate intestinal IR injury, in addition to reducing the production of NO. Similar reductions were observed in the intestinal expression levels of TNF-α and IL-6. In addition, DEX treatment resulted in a reduction in the expression levels of Bax in the intestinal tissues, while increasing those of Bcl-2, in addition to significantly increasing the mRNA levels of telomerase and caspase-3. Therefore, the present study indicated that NO, TNF-α and IL-6 may partially contribute to the pathogenesis of intestinal IR injury in addition to the increased expression levels of Bax, Bcl-2, telomerase and caspase-3. These findings suggest that DEX possesses beneficial anti-apoptotic and anti-inflammatory effects in intestinal tissue following bowel injury. [ABSTRACT FROM AUTHOR]

The aim of this questionnaire-based study was to identify which analgesics are currently prescribed to donkeys in clinical practice and to collect opinions from veterinary surgeons and donkey owners on the importance of different pain-related behaviours in donkeys. Questionnaires were completed by 143 veterinary surgeons and 93 donkey owners. Phenylbutazone, flunixin, detomidine and butorphanol were reported as the most frequently used analgesics in donkeys. Most veterinary surgeons reported administering these drugs at the horse dose rate and dosing interval, which may be inappropriate in the donkey. Four pain-related behaviours were identified as very important by veterinary surgeons and owners: dullness for colic-associated pain, keeping the foot lifted, and lameness for foot and limb pain and inability to chew properly for head and dental pain. This is a more limited behavioural repertoire than has recently been identified to be associated with pain in the donkey and suggests that the respondents were reporting perceived wisdom as to what people think are the behavioural signs associated with pain or were not interpreting pain-related behaviours correctly. [ABSTRACT FROM AUTHOR]

Background: In Sweden, scrotal or inguinal herniorrhaphy of livestock pigs in the field has traditionally been an important part of the surgical skills training of veterinary students. Few substances meet the legal requirements for field anaesthesia of production animals in the European Union but a protocol based on azaperone-detomidinebutorphanol- ketamine does. Unfortunately the anaesthesia is characterised by unpredictable duration and depth and of abrupt awakenings which is not acceptable from an animal welfare perspective and impedes surgical training. Lumbo-sacral epidural analgesia is proven to provide sufficient analgesia to allow abdominal surgery, but there are few reports on the field use of this loco-regional technique. The study aim was to evaluate whether lumbo-sacral anaesthesia can be safely and successfully used in the field by a veterinary student and whether the combination of dissociative and lumbo-sacral epidural anaesthesia improves analgesia and anaesthesia to guarantee animal welfare during herniorrhaphy in livestock pigs, enabling surgical skills training. Results: Pigs in the control-group (placebo) responded significantly stronger to surgery, with five out of 11 requiring additional doses of detomidine and ketamine. There were no significant differences between groups in respiratory rate, heart rate, blood pressure, SpO2 or blood gases. SpO2 levels <94 % were recorded in several pigs in both groups. No post-injection complications were reported at follow-up. Conclusions: The results from this study showed that lumbo-sacral epidural anaesthesia with lidocaine could successfully be administered during dissociative anaesthesia of livestock pigs by a veterinary student and without reported post-injection complications. It improved analgesia and anaesthesia during herniorrhaphy of sufficient duration to enable surgical skills training. The risks and consequences of hypoxaemia and hypoventilation should be considered. [ABSTRACT FROM AUTHOR]

Literature reports on the effect of sedative and anesthetic drugs on the first five peaks of brainstem auditory–evoked responses (BAERs) are somehow contradictory. In particular, no data are available on the effect of sedatives on BAER in horses. The objective of the study was to evaluate the influence of sedation with xylazine, detomidine, and detomidine–butorphanol combination on latencies of BAER peaks in horses. The absolute peak latencies of waves I, II, III, and V and interpeak latencies (IPLs) I–III, III–V, and I–V obtained in nine Bardigiano horses without sedation and with each of the sedation protocols were statistically compared. A statistically significant ( P < .05) increase of the latency of wave III and of the IPL I–III was present in horses sedated with detomidine compared with the subjects not sedated or sedated with xylazine. An effect of detomidine on conduction time along the auditory pathway is suspected. These results must be taken into account when using α2-agonists with greater affinity for specific receptors, such as detomidine, for sedation of animals undergoing BAER for clinical or research purposes. [ABSTRACT FROM AUTHOR]

Background: Endoscopic Retrograde Cholangio Pancreatography (ERCP) is routinely performed under propofol sedation. Adjuvant drugs have improved the quality of propofol sedation while minimizing complications. The aim of the study was to compare the propofol consumption, recovery and hemodynamic profiles of dexmedetomidine versus ketamine against a placebo control with BIS targeted in the sedative range for outpatient ERCP procedures. Materials and Methods: The study comprised of 72 patients undergoing ERCP, who were randomly allocated into one of the 3 groups: Group Dexmedetomidine (n =24) receiving a bolus and infusion of dexmedetomidine (1μg/kg and 0.5μg/kg/hr); Group Ketamine (n = 24) receiving a bolus and infusion of ketamine (0.25mg/kg and 5μg/kg/min) and Group Control (n =24) receiving saline placebo as a bolus and infusion with variable propofol boluses administered in all groups targeting BiSpectral Index between 60-70. Results: The total propofol consumption was significantly lower in both Dexmedetomidine (162.5 ± 71.7 mg ) and Ketamine groups (158.3 ± 66.89 mg) when compared with Control group (255.83 ± 114.12 mg)(p=0.001) .Time taken (minutes) to achieve Modified Aldrette Score (MAS) >9 and Observer Assessment of Alertness and Sedation (OAAS) score >4 was significantly prolonged in Dexmedetomidine group (MAS 16.6 ± 3.18 and OAAS 16.67 ± 2.82) compared to Ketamine (MAS 10 ± 4.17 and OAAS 8.75 ± 3.68) and Control (MAS 7.5 ± 3.29 and OAAS 6.88 ± 2.47) (p<0.001). Hemodynamic profiles were comparable although patients in dexmedetomidine had a statistically significant lower heart rate (p< 0.001) although without clinical significance. Conclusion: Low dose ketamine with background propofol boluses resulted in lesser propofol consumption, with earlier recovery and favourable hemodynamics when compared with Dexmedetomidine and control group in outpatient ERCP. [ABSTRACT FROM AUTHOR]

The objective of this article is to evaluate the effect of dexmedetomidine on emergence agitation (EA) and recovery profiles in children after sevoflurane anesthesia and its pharmacological mechanisms. Standard bibliographic databases, including MEDLINE, EMBASE, PsycINFP, Springer and ISI Web of Knowledge, were artificially searched to identify all randomized controlled trials (RCTs) comparing the impact of dexmedetomidine with placebo, fentanyl and midazolam on EA and recovery profiles after sevoflurane anesthesia in post-anesthesia care unit (PACU). Two authors assessed the quality of each study independently in accordance with strict inclusion criteria and extracted data. RevMan 5.0 software was applied for performing statistic analysis. The outcomes analyzed included: 1) incidence of EA, 2) emergence time, 3) time to extubation, 4) incidence of post-operation nausea and vomiting, 5) number of patients requiring an analgesic, and 6) time to discharge from PACU. A total of 1364 patients (696 in the dexmedetomidine group and 668 in the placebo, fentanyl and midazolam group) from 20 prospective RCTs were included in the meta-analysis. Compared with placebo, dexmedetomidine decreased the incidence of EA (risk ratio [RR] 0.37; 95% CI 0.30 to 0.46), incidence of nausea and vomiting (RR 0.57; 95% CI 0.38 to 0.85) and number of patients requiring an analgesic (RR 0.43; 95% CI 0.31 to 0.59). However, dexmedetomidine had a significantly delayed effect on the emergence time (weighted mean differences [WMD] 1.16; 95% CI 0.72 to 1.60), time to extubation (WMD 0.61; 95% CI 0.27 to 0.95), and time to discharge from recovery room (WMD 2.67; 95% CI 0.95 to 4.39). Compared with fentanyl (RR 1.39; 95% CI 0.78 to 2.48) and midazolam (RR 1.12; 95% CI 0.54 to 2.35), dexmedetomidine has no significantly difference on the incidence of EA. However, the analgesia effect of dexmedetomidine on postoperation pain has no significantly statistical differences compared with fentanyl (RR 1.12; 95% CI 0.66 to 1.91), which implied that its analgesia effect might play an important role in decreasing the incident of EA. No evidence of publication bias was observed. [ABSTRACT FROM AUTHOR]

Objective To assess the sedative and immobilization effect of intranasal administration ( INS) of midazolam ( MID) without or with INS dexmedetomidine ( DXM), and some physiological changes induced by the drugs. The ability of INS atipamezole to reverse the DXM component was also assessed. Study design Prospective 'blinded' experimental study. Animals In total, 15 pigeons. Methods Pigeons were sedated by INS MID alone at a dose of 5 mg kg−1 (group MID, n = 6) or in combination with INS DXM at a dose 80 μg kg−1 (group MID- DXM, n = 6). Measurements were made of heart rate ( HR), respiratory rate ( fR) and cloacal temperature ( CT). The degree of sedation was assessed at 15 minutes prior to, immediately after, and at intervals until 100 minutes after drug administrations. Following MID- DXM, INS atipamezole (250 μg kg−1) was administered and the same indices measured 5 and 10 minutes later. Results MID had no effect on HR and fR, and although CT decreased, it remained within physiological range. MID- DXM caused significant falls in HR, fR and CT that persisted until the end of sedation. Atipamezole antagonized sedation and cardiorespiratory side effects of MID- DXM within 10 minutes of application. In addition, for MID compared to MID- DXM, the lowest sedation scores [10 (7-14) and 10.5 (5-14) versus 2 (1-4) and 2 (1-5)] were achieved in the 10th and 20th minute versus the 20th and 30th minute of the sedation, respectively. Conclusions and clinical relevance MID alone, given INS had minimal side effects on vital functions but caused inadequate immobilization of pigeons for restraint in dorsal recumbency. MID - DXM caused an effective degree of immobilization from 20 to 30 minutes after administration, at which time birds tolerated postural changes without resistance. Atipamezole antagonized both side effects and sedation, but complete recovery had not occurred within 10 minutes after its application. [ABSTRACT FROM AUTHOR]

There is limited, useful, scientific information on detomidine in donkeys. This study compared the effects of intravenous saline, detomidine (10, 13.5, 17 and 20 µg/kg) and acepromazine (50 µg/kg) in donkeys by computing areas under the curve for 0-30, 30-60 and 60-120 minutes (AUC0-30, AUC30-60 and AUC60-120) for sedation scores, head heights and mechanical nociceptive thresholds (MNTs). For sedation scores, all detomidine treatments, except 10 µg/kg, increased AUC0-30 values compared with saline, and AUC0-30 values were larger for 17 µg/kg detomidine than for acepromazine. All head height AUC values were lower for detomidine than for saline (except AUC60-120 for 10 µg/kg detomidine) and acepromazine (except AUC0-30 for 10 and 20 µg/kg detomidine, and AUC60-120 for 10 µg/kg detomidine). For MNTs, all detomidine treatments increased AUC0-30 and AUC30-60 values compared with saline and acepromazine; AUC30-60 values were smaller for 10 µg/kg than for 17 and 20 µg/kg detomidine. MNT AUC60-120 values were larger for 20 µg/kg detomidine than for saline, 10 µg/kg detomidine and acepromazine. Detomidine induced sedation and antinociception, but only antinociception was dosage dependent. Selection of detomidine dosage for donkeys may depend on the required duration of sedation and/or degree of analgesia. [ABSTRACT FROM AUTHOR]

The present study characterizes the pharmacokinetic ( PK) and pharmacodynamic ( PD) relationships of the α2-adrenergic receptor agonists detomidine ( DET), medetomidine ( MED) and dexmedetomidine ( DEX) in parallel groups of horses from in vivo data after single bolus doses. Head height ( HH), heart rate ( HR), and blood glucose concentrations were measured over 6 h. Compartmental PK and minimal physiologically based PK (m PBPK) models were applied and incorporated into basic and extended indirect response models ( IRM). Population PK/ PD analysis was conducted using the Monolix software implementing the stochastic approximation expectation maximization algorithm. Marked reductions in HH and HR were found. The drug concentrations required to obtain inhibition at half-maximal effect ( IC50) were approximately four times larger for DET than MED and DEX for both HH and HR. These effects were not gender dependent. Medetomidine had a greater influence on the increase in glucose concentration than DEX. The developed models demonstrate the use of mechanistic and m PBPK/ PD models for the analysis of clinically obtainable in vivo data. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD) is a frequent complication following major surgery in the elderly. However, the exact pathogenic mechanisms are still unknown. Dexmedetomidine, a selective alpha 2 adrenal receptor agonist, was revealed anesthesia and brain protective role. The present study aimed to examine whether dexmedetomdine protects against POCD induced by major surgical trauma under general anesthesia in aged mice. In the present study, cognitive function was assessed by Y-maze. Proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α), apoptosis-related factor caspase-3 and Bax were detected by real-time PCR, Western blot or immunohistochemistry. The results showed that anesthesia alone caused weak cognitive dysfunction on the first day after general anesthesia. Cognitive function in mice with splenectomy under general anesthesia was significantly exacerbated at the first and third days after surgery, and was significantly improved by dexmedetomidine administration. Splenectomy increased the expression of IL-1β, TNF-α, Bax and caspase-3 in hippocampus. These changes were significantly inversed by dexmedetomidine. These results suggest that hippocampal inflammatory response and neuronal apoptosis may contribute to POCD, and selective alpha 2 adrenal receptor excitation play a protective role. [ABSTRACT FROM AUTHOR]

Background and Aim Patients who undergo gastrointestinal endoscopy often require sedatives such as midazolam and the more recently developed alpha-2 agonist, dexmedetomidine. To assess the efficacy and safety of dexmedetomidine sedation for gastrointestinal endoscopy, we conducted a systematic review and meta-analysis of randomized controlled trials comparing dexmedetomidine with midazolam. Methods We searched Pub Med, the Cochrane library, and the Igaku-chuo-zasshi database in order to identify randomized trials eligible for inclusion in our meta-analysis. Data from the eligible studies were combined to calculate pooled odds ratios ( OR) or weighted mean differences ( WMD). Results We identified nine randomized trials from the database search. Compared to that of midazolam, the pooled OR for restlessness of dexmedetomidine was 0.078 (95% confidence interval [ CI]: 0.013-0.453, P < 0.0001), and there was no significant heterogeneity among the trial results. Dexmedetomidine significantly increased Ramsay sedation score compared with midazolam ( WMD: 0.401, 95% CI: 0.110-0.692, P = 0.0069), without significant heterogeneity. Compared with midazolam, the pooled OR for hypoxia, hypotension, and bradycardia with dexmedetomidine sedation were 0.454 (95% CI: 0.098-2.11), 1.370 (95% CI: 0.516-3.637), and 2.575 (95% CI: 0.978-6.785), respectively, with no significant differences detected between the groups. Conclusion This meta-analysis shows that dexmedetomidine is a safe and effective sedative agent for gastrointestinal endoscopy, especially endoscopic retrograde cholangiopancreatography and endoscopic submucosal dissection. [ABSTRACT FROM AUTHOR]

Objective To review the literature with regard to the use of different intravenous agents as supplements to inhalational anaesthesia in horses. The Part 2 of this review will focus in the use of opioids and α2-agonists. Databases used Pubmed and Web of Science. Search terms: horse, inhalant anaesthesia, balanced anaesthesia, partial intravenous anaesthesia, opioids, morphine, pethidine, butorphanol, methadone, fentanyl, alfentanil, remifentanil, sufentanil, xylazine, romifidine, detomidine, medetomidine and dexmedetomidine. Conclusions Different drugs and their combinations can be administered systemically in anaesthetized horses aiming to reduce the amount of the volatile agent while improving the recovery qualities and providing a multimodal analgesic approach. However, full studies as to whether these techniques improve cardiopulmonary status are not always available and potential disadvantages should also be considered. [ABSTRACT FROM AUTHOR]

The aims of this study were to evaluate the effects of the administration of a combination of tiletamine-zolazepam and detomidine (TZD) in 9 tigers ( Panthera tigris). Nine captive tigers were immobilized with tiletamine-zolazepam and detomidine administered intramuscularly. At the end of the procedure immobilization was partially reversed with atipamezole. Lateral recumbency was achieved in 15.6 ± 5.9 min. The median induction score [scored 1 (excellent) to 4 (poor)] was 1. The immobilization score [scored 1 (poor) to 6 (too deep)] was 5 (4-5) at all study times. After atipamezole administration, all tigers experienced severe ataxia and incoordination. Median recovery score [scored 1 (excellent) to 4 (poor)] was 2.5 (range 2-3). No neurologic and/or important adverse reactions were noticed within 5 days after recovery. The combination tiletamine-zolazepam with detomidine proved to be effective in immobilizing captive healthy tigers but it maybe associated with hypertension and ataxia during recovery. Zoo Biol. 34:40-45, 2015. © 2014 Wiley Periodicals Inc. [ABSTRACT FROM AUTHOR]

Os efeitos da acepromazina, detomidina e romifidina em eqüinos foram comparados, objetivando-se determinar qual o agente mais seguro e efetivo para a referida espécie animal. Foram utilizados 15 eqüinos hígidos, de ambos os sexos, idades e raças variadas e encaminhados ao setor de Cirurgia do Hospital Veterinário da FMVZ - USP. Os animais foram distribuídos em três grupos: grupo I, recebeu 0,1mg/kg de acepromazina; grupo II recebeu 20mcg/kg de detomidina e grupo III, o qual recebeu 80mcg/kg de romifidina, sendo todos os agentes administrados através da via intravenosa. Previamente à administração dos fármacos e aos 15, 30, 60 e 90 minutos, após sua aplicação, foram avaliadas a freqüência e ritmo cardíacos, freqüência respiratória, pressão arterial sistólica e diastólica, assim como foram coletadas amostras de sangue arterial para verificação do pH, pressão parcial de oxigênio e pressão parcial de dióxido de carbono. Os resultados foram submetidos à análise estatística através do teste de análise de variância (ANOVA), seguido do teste de Tukey. Não foi observada nenhuma alteração da freqüência respiratória nos grupos estudados. Verificou-se diminuição significativa dos valores da FC nos animais tratados com os agentes alfa-2 agonistas quando comparados com os valores obtidos no grupo I. Após a administração da acepromazina, observou-se diminuição significativa das pressões sistólica e diastólica em relação aos valores controle. Os animais do grupo I apresentaram valores pressóricos estatisticamente inferiores em relação aos valores obtidos nos grupos II e III. Os animais do grupo II demonstraram incremento da pressão arterial sistólica após 15 minutos da aplicação do agente, com subseqüente redução destes valores. O mesmo ocorreu no grupo III, porém, sem valor estatístico significativo. Com estes resultados, pode-se concluir que a romifidina e a detomidina promoveram alterações paramétricas de menor intensidade e duração quando comparadas à acepromazina.The effects of acepromazine, detomidine and romifidine were compared in horses in the present study, aiming to determine which agent is safer and more effective for the referred species of animal. Fifteen healthy horses of the same sex, age and breed varying, were sent to the Surgical Division of the Veterinarian Hospital of FMVZ-USP. The animals were distributed in three groups; group I - GI - received 0.1mg/kg of acepromazine; group II - GII - received 20mug/kg of detomidine; group III - GIII received 80mug/kg of romifidine, all agents delivered intravenously. Prior to administration of the agents and at 15, 30, 60 and 90 minutes after their application, the following parameters were evaluated: heart rate, respiratory rate, systolic and diastolic arterial pressure. Arterial blood samples were collected to verify pH, partial oxygen pressure and partial carbon dioxide pressure. The results were submitted to statistical analysis using the analysis of variance (ANOVA) followed by the Tukey test. No significant alteration was observed in respiratory rate of the studied groups. The heart rate significantly decreased in the animals treated with the alpha-2 agonist agents when compared to the values obtained in the GI. Following administration of acepromazine a significant decrease n systolic and diastolic blood pressures was observed in relation to control values. The animals of GI presented pressure values that were statistically inferior in relation to the values obtained for groups II and III. The animals in GII showed an increase in systolic arterial pressure after 15 minutes of agent administration, with subsequent reduction in this data. The same occurred in GIII however without statistically significant difference. With this results it can be concluded that romifidine and detomidine promoted alterations of less intensity and duration in the studied parameters when compared to acepromazine.

Twenty adult healthy quails (Coturnix coturnix) were divided into two equal groups. One group was administered detomidine (2.4 mg/kg, I/M) and other group was administered detomidine-ketamine cocktail (1.2 mg/kg + 30 mg/kg, I/M). Detomidine slowly and smoothly induced a light sedation accompanied by superficial analgesia, hypoventilation, hypothermia and bradycardia in all birds. Detomidine-ketamine cocktail rapidly and smoothly induced a deep anaesthesia accompanied by deep analgesia, hypoventilation, hypothermia and bradycardia and complete loss of all reflexes in all birds. In both groups, recovery from sedation and anaesthesia was smooth and of short duration. From this study it was concluded that for minor and least painful procedures in quails detomidine can be used alone, while for major and painful surgical procedures detomidine-ketamine combination should be preferred.

This study was conducted to determine the effects of intravenous detomidine on Schirmer tear test (STT) results in clinically normal horses. Eighteen adult horses were randomly divided into two groups of nine horses each. The treatment group was sedated with intravenous detomidine alone (20 μg/kg), and the control group received only intravenous saline (0.2 mL/100 kg). Schirmer tear test was performed just before intravenous administration of detomidine or saline in treatment and control groups, respectively. Schirmer tear tests were repeated 5, 20, 60, and 120 minutes later. Horses enrolled in this study consisted of nine males and nine females. Breeds were Arabian and Hanoverian, ranging from 3 to 6 years in age. In the treatment group, the pretreatment and subsequent posttreatment mean ± standard deviation values were 17.0 ± 6.9 (0 minutes), 11.8 ± 2.9 (5 minutes), 12.1 ± 2.0 (20 minutes), 12.1 ± 3.1 (60 minutes), and 15.0 ± 2.8 (120 minutes) mm wetting/min. In this group of horses, a significant reduction was observed in STT values at 5, 20, and 60 minutes after treatment with detomidine hydrochloride in comparison to the pretreatment values (analysis of variance with post hoc testing; P 5 = 0.004, P 20 = 0.007, P 60 = 0.006). There was no significant difference between baseline values and posttreatment values in the control saline group ( P ≥ .08). We conclude that intravenous detomidine causes a significant reduction in STT values in clinically normal horses. In horses, practitioners should measure STT values before intravenous administration of detomidine to accurately assess the results. [ABSTRACT FROM AUTHOR]

The locomotor pattern alterations produced after the administration of a sublingual detomidine gel was measured by an accelerometric method in horses. Using a randomized two-way crossover design, all animals (n?=?6) randomly received either detomidine gel or a placebo administered sublingually. A triaxial accelerometric device was used for gait assessment 15 minutes before (baseline) and every 10 minutes after each treatment for a period of 180 minutes. Eight different parameters were calculated, including speed, stride frequency, stride length, regularity, dorsoventral, propulsion, mediolateral, and total power. Force of acceleration and the three components of power were also calculated. Significant statistical differences were observed between groups in all the parameters but stride length. The majority of significant changes started between 30 and 70 minutes after drug administration and lasted for 160 minutes. This route of administration is definitely useful in horses in which a prolonged sedation is required, with stability being a major concern. [ABSTRACT FROM AUTHOR]

Background: Cardiac catheterization procedures produce challenges for the anesthetist because of the increased need to provide support in sedating and/or anesthetizing patients. Objective: To compare pulmonary and systemic hemodynamics of two anesthetic regimens: sevoflurane as volatile induction maintenance anesthesia and dexmedetomidine as total intravenous anesthesia in pediatric patients suffering from congenital heart disease with left-to-right intracardiac shunt. Design: A Prospective Randomized Study. Setting: Mansoura University Children Hospital (MUCH), Egypt. Method: Sixty pediatric patients of both sexes were referred for elective cardiac catheterization. Patients were randomly allocated into two equal groups, consisted of 30 patients. In the first group, the patients received volatile induction maintenance anesthesia (VIMA) with sevoflurane (GS group) while in the second, the patients received total intravenous anesthesia (TIVA) with dexmedetomidine (1 μg/kg) intravenous bolus dose over 10 minutes, anesthesia was maintained by intravenous infusion of dexmedetomidine at a rate of 1-2 μ/kg/hour (GD group). Result: The present study showed that the heart rate (HR), Pulmonary blood flow index (QpI), Systemic blood flow index (QsI) and Qp/Qs ratio were comparable in both groups. Pulmonary vascular resistance index (PVRI) and Systemic vascular resistance index (SVRI) were significantly lower in GS group after induction of general anesthesia (GA) if compared with the basal value maintaining PVR/SVR at baseline value. However, PVRI and SVRI were insignificantly higher in GD group after induction of GA if compared with the basal value; thus, maintaining PVR/SVR. The Systemic Mean arterial blood pressure (MAP) decreased in both groups. Conclusion: Total intravenous anesthesia with dexmedetomidine provided hemodynamic stability. It is comparable to volatile induction and maintenance of anesthesia with sevoflurane when administered to pediatric patients suffering from congenital heart disease with left-to-right intracardiac shunt during cardiac catheterization. [ABSTRACT FROM AUTHOR]

The effects of intravenous (IV) lidocaine, dexmedetomidine and their combination delivered as a bolus followed by a constant rate infusion (CRI) on the minimum alveolar concentration of isoflurane (MACISO) in dogs were evaluated. Seven healthy adult dogs were included. Anaesthesia was induced with propofol and maintained with isoflurane. For each dog, baseline MAC (MACISO/BASAL) was determined after a 90-minute equilibration period. Thereafter, each dog received one of the following treatments (loading dose, CRI): lidocaine 2 mg kg−1, 100 µg kg−1 minute−1; dexmedetomidine 2 µg kg−1, 2 µg kg−1 hour−1; or their combination. MAC was then determined again after 45- minutes of treatment by CRI. At the doses administered, lidocaine, dexmedetomidine and their combination significantly reduced MACISO by 27.3% (range: 12.5–39.2%), 43.4% (33.3–53.3%) and 60.9% (46.1–78.1%), respectively, when compared to MACISO/BASAL. The combination resulted in a greater MACISO reduction than the two drugs alone. Their use, at the doses studied, provides a clinically important reduction in the concentration of ISO during anaesthesia in dogs. [ABSTRACT FROM AUTHOR]

Dexmedetomidine, a highly selective α2-adrenergic agonist, has been reported to attenuate isoflurane-induced cognitive impairment and neuroapoptosis. However, the underlying molecular mechanisms remain poorly understood. The aim of this study was to investigate whether mitogen-activated protein kinase (MAPK) pathway was involved in dexmedetomidine-induced neuroprotection against isoflurane effects. Seven-day-old (P7) neonatal Sprague-Dawley rats were pretreated with various concentrations of dexmedetomidine, and then exposed to 0.75% isoflurane or air for 6 h. Terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL) was used to detect neuronal apoptosis in their hippocampus. Activated caspase-3, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinases (JNK), p38, phospho-ERK1/2, phospho-JNK and phospho-p38 proteins were detected by Western blotting in the hippocampus at the end of exposure. Also, P7 rats were pretreated with 75 μg/kg dexmedetomidine alone, or given the ERK inhibitor U0126 before dexmedetomidine pretreatment, or pretreated with the p38 MAPK inhibitor SB203580 or JNK inhibitor SP600125 alone, and then exposed to 0.75% isoflurane for 6 h. Isoflurane induced significant neuroapoptosis, increased the protein expression of phospho-JNK, phospho-c-Jun, phospho-p38 and phospho-nuclear factor-κB (NF-κB), decreased the level of phospho-ERK1/2 protein and reduced the ratio of Bcl-2/Bax in the hippocampus. Dexmedetomidine pretreatment inhibited isoflurane-induced neuroapoptosis and restored proteins expression of MAPK pathways and the Bcl-2/Bax ratio after isoflurane exposure. Moreover, SB203580 and SP600125 also partly attenuated the isoflurane-induced protein changes. However, U0126 did not reverse dexmedetomidine-induced neuroprotection. Our results indicate that the JNK and p38 pathways, not the ERK pathway are involved in dexmedetomidine-induced neuroprotection against isoflurane effects. [ABSTRACT FROM AUTHOR]

Objective To study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously ( IV) administered detomidine. Study design Randomised, prospective clinical study. Animals Twenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg. Methods Detomidine at 80 μg kg−1 was administered to ten calves sublingually ( GEL) and at 30 μg kg−1 to ten control calves IV ( V. jugularis). Meloxicam (0.5 mg kg−1) and local anaesthetic (lidocaine 3 mg kg−1) were administered before heat cauterization of horn buds. Heart rate ( HR), body temperature and clinical sedation were monitored over 240 minutes. Blood was collected from the V. cephalica during the same period for drug concentration analysis. Pharmacokinetic variables were calculated from the plasma detomidine concentration-time data using non-compartmental methods. Statistical analyses compared routes of administration by Student's t-test and linear mixed models as relevant. Results The maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng mL−1 (mean ± SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding. Conclusions and clinical relevance Oromucosally administered detomidine is an effective sedative agent for calves prior to disbudding. [ABSTRACT FROM AUTHOR]

Abstract: Microglia in the spinal cord is evidenced to play a crucial role in neuropathic pain. Spinal P2X4 receptors (P2X4Rs), which are mainly expressed in microglia, have been investigated for their roles in neuropathic pain. Dexmedetomidine (DEX), a highly selective agonist of α2-adrenergic receptors, is clinically applied to sedation and analgesia. Despite the proposed mechanisms underlying DEX-induced analgesia, the possible interactions between DEX and P2X4Rs at a molecular level have not been elucidated. We designated the spared nerve injury (SNI) to establish the neuropathic pain model. Mechanical paw withdrawal threshold (MWT) was measured to evaluate the sensitivity of neuropathic pain in rats. MWT was significantly decreased in SNI rats versus control rats. Expressions of spinal P2X4Rs, phosphorylated p38-mitogen-activated protein kinase (p-p38-MAPK) and brain-derived neurotrophic factor (BDNF) were upregulated in SNI rats. Immunofluorescence assay indicated higher densities of microglia and P2X4Rs, which appeared yellow in colour, suggesting they were co-labelled. Intraperitoneal injections of DEX 40μg/kg for 14 consecutive days markedly reversed the SNI-induced decline of MWT; the activation of microglia was markedly inhibited; in addition, the protein expressions of P2X4Rs, p-p38-MAPK and BDNF were significantly downregulated. Thus, DEX could attenuate the neuropathic pain in SNI rats, of which the mechanism might be related to the down-expressed P2X4Rs, p-p38 and BDNF in microglia of spinal dorsal horn. [Copyright &y& Elsevier]

Abstract: The present study aimed to investigate and evaluate the reversal of sedation, analgesia, ataxia, clinicophysiological findings, and hematobiochemical effects of detomidine by subsequent IV administration of tolazoline or atipamezole to improve safety and utility of detomidine in donkeys. Six mature donkeys weighing 250–300 kg and aged 4–6 years were used on three separate occasions. Each donkey received the following three treatments at the rate of one treatment per week in a randomized crossover study. The first group received 0.04 mg/kg bwt detomidine. The second group received 0.04 mg/kg bwt detomidine followed by 4.0 mg/kg bwt tolazoline. The third group received 0.04 mg/kg bwt detomidine followed by 0.4 mg/kg bwt atipamezole. Sedation, analgesia, ataxia, pulse rate, respiratory rate, and rectal temperature were recorded at 5 minutes before, then at 5, 15, 30, 60, and 90 minutes after injections. Red blood cell and white blood cell counts, Packed cell volume (%), hemoglobin, total protein, cholesterol, glucose, urea, aspartate amino transferase, alanine amino transferase, and gamma glutamyl transferase values were determined. Detomidine induced deep sedation, complete analgesia, and significant ataxia. Pulse and respiratory rates were decreased from the base line values, although rectal temperature was within the baseline value. The alterations in hematological and hematobiochemical parameters were mild and transient. [Copyright &y& Elsevier]

Background To compare the safety and efficacy of dexmedetomidine/propofol (DP)-total i.v. anaesthesia (TIVA) vs remifentanil/propofol (RP)-TIVA, both with spontaneous breathing, during airway foreign body (FB) removal in children. Methods Seventy-seven children undergoing rigid bronchoscopy for FB removal were randomly allocated to receive either RP-TIVA and spontaneous ventilation (Group RP, n=38) or DP-TIVA and spontaneous ventilation (Group DP, n=39). Heart rate, arterial pressure, pulse oxygen saturation $(S{\hbox{p}_{{{\rm O}_2}}})$, respiratory rate, end-tidal CO2 $(\rm{\small E}{^{\prime}_{{\rm C}{{\rm O}_2}}})$, and induction time were recorded. Adverse events, the intervention for these events, and postoperative care duration were also assessed. Results The mean induction times were comparable between the two groups (Group RP 12.2 min vs Group DP 13.1 min, P>0.05). At the end of the procedure, the mean $\rm{\small E}{^{\prime}_{{\rm C}{{\rm O}_2}}}$ was higher in Group RP (Group RP 6.8 kPa vs Group DP 5.8 kPa, P<0.001), and respiratory rate was lower in Group RP (Group RP 20.4 vs Group DP 35.8, P<0.001). Additionally, the perioperative haemodynamic profile was more stable in Group DP than that in Group RP. The incidence rate of breath-holding and intervention were comparable between the two groups. In the post-anaesthesia care unit (PACU), no hypoxaemia was observed, and emergence time increased in Group DP (Group DP 65.1 min vs Group RP 23.8 min, P<0.0001). The incidence of cough in PACU was higher in Group RP (Group RP 55.3% vs Group DP 10.3%, P<0.0001). Conclusions Compared with RP-TIVA, DP-TIVA provided more stable respiratory and haemodynamic profiles, but required a longer recovery time. Clinical trial registration China Clinical Research Information Service, ChiCTR—TRC-13003018. [ABSTRACT FROM PUBLISHER]

The aim of this investigation was to determine and evaluate the sedative, analgesic, clinicophysiological and haematological effects of intravenous (i.v.) injection of detomidine, detomidine-butorphanol, romifidine and romifidine-butorphanol. Six standing donkeys were used. Each donkey received 4 i.v. treatments and the order of treatment was randomised with a one-week interval between each treatment. We found that i.v. injection of a combination of detomidine-butorphanol or romifidine-butorphanol produced potent neuroleptanalgesic effects thus providing better, safe and effective sedation with complete analgesia in standing donkeys compared with injection of detomidine or romifidine alone. The changes and reduction in pulse rate were within acceptable limits. The changes in clinicophysiological, haematological and biochemical values were mild and transient in these clinically healthy donkeys. [ABSTRACT FROM AUTHOR]

Background: Postoperative pain is very common distressing symptom after any surgical procedure. Different drugs in different routes have been used for controlling post-arthroscopic pain. No one proved to be ideal. We have compared the analgesic effect of ropivacaine, fentanyl, and dexmedetomidine when administered through the intra-articular route in arthroscopic knee surgery. Materials and Methods: From March 2008 to July 2010, 99 patients undergoing arthroscopic knee surgery were randomly assigned into three groups (A,B,C) in a prospective double-blinded fashion. Group A received 10 ml of 0.75% ropivacaine, where Group B received 50 μg fentanyl, and Group C received 100 μg of dexmedetomidine through the intra-articular route at the end of procedure. Pain assessed using visual analog scale and diclofenac sodium given as rescue analgesia when VAS >4. Time of first analgesia request and total rescue analgesic used in 24 hours were calculated. Results: Demographic profiles are quite comparable among the groups. Time for requirement of first postoperative rescue analgesia in Group A was 380.61 ± 22.973 min, in Group B was 326.82 ± 17.131 min and in Group C was 244.09 ± 20.096 minutes. Total rescue analgesia requirement was less in Group A (1.394 ± 0.496) compared to Group B (1.758 ± 0.435) and Group C (2.546 ± 0.546). Group A had higher mean VAS score at 6th and 24th postoperative hours. No side effects found among the groups. Conclusion: Therefore, it suggests that intra-articular ropivacaine gives better postoperative pain relief, with increased time of first analgesic request and decreased need of total postoperative analgesia compared to fentanyl and dexmedetomidine. [ABSTRACT FROM AUTHOR]

As per current recommendation, patients with acute ischemic stroke should be offered carotid endarterectomy (CEA) within 24-72 hours. The same applies to patients with recurrent transient ischemic attacks (TIA). This time is usually less for hemodynamic optimization of patients who've suffered acute ischemic stroke. Hence' they are hemodynamically labile and can have accelerated hypertension on induction/extubation. This can have disastrous outcomes. It is a common practice among anesthesiologists to avoid angiotensin converting enzyme(ACE) inhibitors or angiotensin receptor blockers on the day of surgery. This also adds to hypertensive issues perioperatively. Dexmedetomidine is a wonderful drug which can be used during CEA. Due to its centrally mediated sympatholytic effect, it confers good hemodynamic control during induction, intraoperatively, and during extubation. We did a search on PubMed and Google for carotid endarterectomies done under general and locoregional anesthesia during which dexmedetomidine was used. The keywords used by us during the search were as follows: anesthesia, carotid endarterectomy, anesthesia. We also searched for use of dexmedetomidine infusion to attenuate hypertensive response to intubation and for providing stability in major surgeries like CABG, craniotomies, bariatric surgeries, and valve replacements. [ABSTRACT FROM AUTHOR]

Background and Objectives: The present study was designed to evaluate the effect of intravenous dexmedetomidine on spinal anesthesia with 0.5% of hyperbaric bupivacaine. Materials and Methods: One hundred American Society of Anesthesiologists (ASA) physical status I/II patients undergoing elective surgeries under spinal anesthesia were randomized into two groups of 50 each. Immediately after subarachnoid block with 3 ml of 0.5% hyperbaric bupivacaine, patients in group D received a loading dose of 1 μg/kg of dexmedetomidine intravenously by infusion pump over 10 min followed by a maintenance dose of 0.5 μg/kg/h till the end of surgery, whereas patients in group C received an equivalent quantity of normal saline. Results: The time taken for regression of motor blockade to modified Bromage scale 0 was significantly prolonged in group D (220.7 ± 16.5 min) compared to group C (131 ± 10.5 min) (P < 0.001). The level of sensory block was higher in group D (T 6.88 ± 1.1) than group C (T 7.66 ± 0.8) (P < 0.001). The duration for two-dermatomal regression of sensory blockade (137.4 ± 10.9 min vs. 102.8 ± 14.8 min) and the duration of sensory block (269.8 ± 20.7 min vs. 169.2 ± 12.1 min) were significantly prolonged in group D compared to group C (P < 0.001). Intraoperative Ramsay sedation scores were higher in group D (4.4 ± 0.7) compared to group C (2 ± 0.1) (P < 0.001). Higher proportion of patients in group D had bradycardia (33% vs. 4%) (P < 0.001), as compared to group C. The 24-h mean analgesic requirement was less and the time to first request for postoperative analgesic was prolonged in group D than in group C (P < 0.001). Conclusion: Intravenous dexmedetomidine significantly prolongs the duration of sensory and motor block of bupivacaine spinal anesthesia. The incidence of bradycardia is significantly higher when intravenous dexmedetomidine is used as an adjuvant to bupivacaine spinal anesthesia. Dexmedetomidine provides excellent intraoperative sedation and postoperative analgesia. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine is an alpha 2 adrenergic agonist, prolongs analgesia when used in neuraxial and peripheral nerve blocks. We studied the effect of addition of dexmedetomidine to bupivacaine to perform transversus abdominis plane (TAP) block. Materials and Methods: A total of 50 patients scheduled for abdominal hysterectomy were divided into two equal groups in a randomized double-blinded way. Group B patients (n = 25) received TAP block with 20 ml of 0.25% bupivacaine and 2 ml of normal saline while Group BD (n = 25) received 0.5 mcg/kg (2 ml) of dexmedetomidine and 20 ml of 0.25% bupivacaine bilaterally. Time for first analgesic administration, totally used doses of morphine, pain scores, hemodynamic data and side-effects were recorded. Results: Demographic and operative characteristics were comparable between the two groups. The time for the first analgesic dose was longer in Group BD than Group B (470 vs. 280 min, P < 0.001) and the total doses of used morphine were less among Group BD patients in comparison to those in Group B (19 vs. 29 mg/24 h, P < 0.001). Visual analog scores were significantly lower in Group BD in the first 8 h post-operatively when compared with Group B, both at rest and on coughing (P < 0.001). In Group BD, lower heart rate was noticed 60 min from the induction time and continued for the first 4 h post-operatively (P < 0.001). Conclusions: The addition of dexmedetomidine to bupivacaine in TAP block achieves better local anesthesia and provides better pain control post-operatively without any major side-effects. [ABSTRACT FROM AUTHOR]

Background: One of the most commonly used regional anesthetic techniques in pediatric surgeries is the caudal epidural block. Its main disadvantage remains the short duration of action. Hence, different additives have been used. Dexmedetomidine is a potent as well as highly selective α2 adrenergic receptor agonist. The aim of this randomized, double-blinded, study was to compare the duration of postoperative analgesia of caudal dexmedetomidine versus morphine in combination with bupivacaine in pediatric patients undergoing lower abdominal or perineal surgery. Patients and Methods: A total of 50 pediatric patients 1-5 years old The American Society of Anesthesiologists status I, II scheduled for lower abdominal and perineal surgeries were included in the study. The patients were enrolled into 2 equal groups: Group A patients (n = 25) received dexmedetomidine with bupivacaine while Group B patients (n = 25) received morphine with bupivacaine. Patients were placed in a supine position then inhalational general anesthesia was induced, and laryngeal mask airway (LMA) was placed. Patients were then given caudal epidural analgesia. By the end of surgery reversal of muscle relaxation was done and the LMA was removed. Post-operatively, the sedation as well as pain score were observed and recorded. Results: The current study showed that minor complications were recorded in the post-anesthesia care unit; in addition, significantly longer periods of analgesia and sedation were detected in Group A. However, no significant differences in demographic data, as well as in the duration of surgery, and the time of emergence from anesthesia and patient condition during recovery were detected. Conclusion: The present study suggested that use of dexmedetomidine, during single dose injection, as an additive to the local anesthetic bupivacaine in caudal epidural analgesia prolongs the duration of post-operative analgesia following lower abdominal as well as perineal surgery compared with caudal morphine with no sideeffects on the vital signs. Postoperative side effects were seen with caudal morphine injection rather than with dexmedetomidine. [ABSTRACT FROM AUTHOR]

Recent studies have shown that dexmedetomidine exerts an anti-inflammatory effect by reducing serum levels of inflammatory factors, however, the up-stream mechanism is still unknown. The transcription factor NF-κB enters the nucleus and promotes the transcription of its target genes, including those encoding the pro-inflammatory cytokines IL-6 and TNF-a. In this study, we established a rat model that simulates a clinical surgical procedure to investigate the anti-inflammatory effect of perineural administration of dexmedetomidine and the underlying mechanism. Dexmedetomidine reduced the sciatic nerve levels of IL-6 and TNF-a at both the mRNA and protein level. Dexmedetomidine also inhibited the translocation of activated NF-κB to the nucleus and the binding activity of NF-κB. The anti-inflammatory effect is confirmed to be dose-dependent. Finally, pyrrolidine dithiocarbamate also reduced the levels of IL-6 and TNF-a and the activation of NF-κB. In conclusion, dexmedetomidine inhibited the nuclear translocation and binding activity of activated NF-κB, thus reducing inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Objective To describe the effects of alpha2-adrenergic receptor antagonists on the pharmacodynamics of sublingual ( SL) detomidine in the horse. Study design Randomized crossover design. Animals Nine healthy adult horses with an average age of 7.6 ± 6.5 years. Methods Four treatment groups were studied: 1) 0.04 mg kg−1 detomidine SL; 2) 0.04 mg kg−1 detomidine SL followed 1 hour later by 0.075 mg kg−1 yohimbine intravenously ( IV); 3) 0.04 mg kg−1 detomidine SL followed 1 hour later by 4 mg kg−1 tolazoline IV; and 4) 0.04 mg kg−1 detomidine SL followed 1 hour later by 0.12 mg kg−1 atipamezole IV. Each horse received all treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for yohimbine, atipamezole and tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume ( PCV) and plasma proteins were monitored. Results Chin-to-ground distance increased following administration of the antagonists, however, this effect was transient, with a return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia and increased incidence of atrioventricular blocks were either transiently or incompletely antagonized by all antagonists. PCV and glucose concentrations increased with tolazoline administration, and atipamezole subjectively increased urination frequency but not volume. Conclusions and clinical relevance At the doses administered in this study, the alpha2-adrenergic antagonistic effects of tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited by SL administration of detomidine are transient and incomplete. [ABSTRACT FROM AUTHOR]

Objectives To examine the effect of including buprenorphine with detomidine for sedation of horses undergoing clinical procedures. Study design Partially blinded, randomised, prospective clinical field trial. Animals Eighty four client-owned horses scheduled for minor surgery or diagnostic investigation under standing sedation. Methods The effects of buprenorphine (5 μg kg−1) (Group B, n = 46) or placebo (5% glucose solution) (Group C, n = 38) in combination with detomidine (10 μg kg−1) were compared in standing horses undergoing minor clinical procedures. The primary outcome measure was successful completion of the procedure. The degree of sedation and ataxia were scored using simple descriptive scales. Heart and respiratory rates were recorded at 15-30 minute intervals. Parametric data from each group were compared using anova or t-test and non parametric data using the Mann-Whitney U test. Results The procedure was carried out successfully in 91% of Group B and 63% of Group C ( p < 0.01). Repeat dosing was required in 24% of Group B and 32% of Group C ( p < 0.05). Sedation was more profound and lasted longer (60 versus 45 minutes) in Group B ( p < 0.01). Ataxia occurred after detomidine, increased after buprenorphine but not glucose administration, was more profound in group B and lasted longer (60 versus 30 minutes) p < 0.001). Heart and respiratory rates remained within normal limits in both groups and there were no serious adverse events. Conclusions and clinical relevance Buprenorphine 5 and 10 μg kg−1 enhanced the sedation produced by detomidine 10 and 20 μg kg−1 with minor side effects similar to other alpha2 agonist/opioid combinations. Detomidine-buprenorphine sedation is suitable for standing procedures in horses. [ABSTRACT FROM AUTHOR]