Systemic Administration Of Dexmedetomidine Research Articles

Efficacy and safety of dexmedetomidine in peripheral nerve blocks: A meta-analysis and trial sequential analysis.

The duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, several additives, including dexmedetomidine (DEX), have been investigated in order to prolong postoperative analgesia following single-shot regional anaesthesia. The aim of this meta-analysis was to assess the efficacy and safety of the addition of perineural DEX to local anaesthetics compared with local anaesthetics alone or local anaesthetics combined with systemic administration of DEX. A systematic review of randomised controlled trials (RCT) with meta-analysis, trial sequential analysis and assessment of the quality of evidence by the GRADE approach. The databases MEDLINE, CENTRAL and EMBASE (to May 2017) were systematically searched. All RCTs investigating the efficacy and safety of perineural DEX combined with local anaesthetics compared with local anaesthetics alone or local anaesthetics in combination with systemic DEX in peripheral nerve blocks of adults undergoing surgery were included. A total of 46 RCTs (3149 patients) were included. Patients receiving perineural DEX combined with local anaesthetics had a longer duration of analgesia than local anaesthetics alone [mean difference 4.87 h; 95% confidence interval (95% CI) 4.02 to 5.73; P < 0.001; I = 100%; moderate-quality evidence]. The most important adverse events in the DEX group were intraoperative bradycardia [risk ratio 2.83; 95% CI 1.50 to 5.33; P = 0.035; I = 40%; very low-quality evidence] and hypotension (risk ratio 3.42; 95% CI 1.24 to 9.48; P = 0.002; I = 65%; very low quality evidence). In contrast, there were no differences in the duration of analgesia between perineural or intravenous DEX combined with local anaesthetics (mean difference 0.98 h; 95% CI -0.12 to 2.08; P = 0.08; I = 0%). This meta-analysis demonstrated that DEX in combination with local anaesthetics increases postoperative analgesia for around 5 h. However, there are higher risks of intraoperative hypotension and bradycardia. Findings on side effects are associated with high uncertainty. Initial evidence suggests no difference in the duration of analgesia associated with systemic or perineural DEX. CRD42016042486.

Can Dexmedetomidine Influence Recovery Profiles from General Anesthesia in Nasal Surgery?

Objectives Dexmedetomidine has sympatholytic, sedative, anesthetic, and analgesic effects, as well as vasoconstrictive effects, which may help prevent hypotension under general anesthesia. This meta-analysis aimed to perform a systematic review of the literature and investigate the effect of dexmedetomidine on perioperative morbidity following nasal surgery and its adverse effects. Data Sources MEDLINE, SCOPUS, and the Cochrane database. Review Methods Two authors independently searched the databases from their inception to March 2017. Studies were selected that compared perioperative dexmedetomidine administration (dexmedetomidine groups) with a placebo or remifentanil (control groups) with regard to intraoperative morbidity, including surgical time, bleeding amount, hypotension, and bradycardia during operation, and postoperative morbidity, such as emergence agitation, nausea and vomiting, and sedation after operation. Results Surgical time, intraoperative blood loss, dose of inhaled anesthetic gas, dose of fentanyl, postoperative pain, and incidence of emergence agitation were significantly lower in the dexmedetomidine group versus the placebo group. In contrast, there were no significant differences in intraoperative hemodynamic stability and postoperative residual sedation and nausea and vomiting between groups. Additionally, compared with remifentanil (a currently widely used agent), dexmedetomidine was superior in view of postoperative pain and intraoperative blood pressure control. Conclusion This meta-analysis shows that the systemic administration of dexmedetomidine can decrease surgical time, intraoperative blood loss, and doses of intraoperative inhaled anesthetic gas and fentanyl as compared with placebo. It can also decrease postoperative pain and incidence of the emergence agitation. Due to the small number of studies, further clinical trials are needed to confirm these results.

Dexmedetomidine attenuates hypoxia/reoxygenation injury in primary neonatal rat cardiomyocytes.

Systemic administration of dexmedetomidine provides cardioprotection against ischemia/reperfusion (I/R) injury; however, the direct effects of dexmedetomidine on cardiomyocytes have not been clarified. The present study investigated the effects of dexmedetomidine on primary neonatal rat cardiomyocytes under hypoxic/reoxygenation (H/R) conditions. In order to simulate in vivo I/R injury, primary neonatal rat cardiomyocytes were cultured under hypoxic conditions for 1 h and subsequently reoxygenated for 24 h. The effects of preconditioning with dexmedetomidine 2 h before hypoxia and postconditioning during reoxygenation were also examined. Cellular viability and activity were analyzed by monitoring the dynamic response profile of living cells using a real-time cell analyzer system. A special scaled index, defined as the normalized cell index (NCI), was used to minimize the influence of inter-experimental variations. The dose-effect curve was generated from the area under the time-course curve values of NCI. H/R exposure markedly decreased cell viability and activity. Furthermore, no cytotoxicity was associated with a clinically relevant concentration of dexmedetomidine. Preconditioning with dexmedetomidine concentration-dependently ameliorated the reductions in NCI in cardiomyocytes following H/R injury. Additionally, postconditioning with dexmedetomidine improved the reductions in NCI at concentrations between 3 and 200 nM. Finally, the effect of 3–40 nM dexmedetomidine postconditioning was greater than preconditioning. These results indicated that preconditioning and postconditioning with dexmedetomidine attenuated H/R injury in primary neonatal rat cardiomyocytes at the cellular level.

Effect of Intrathecal Dexmedetomidine on Spinal Morphine Analgesia in Patients with Refractory Cancer Pain

Systemic administration of dexmedetomidine has been shown to reduce opioid consumption and improve analgesia satisfaction. The purpose of this study was to investigate the effect of intrathecal dexmedetomidine on spinal morphine analgesia in patients with refractory cancer pain. A double-blinded crossover study was designed and performed. Patients were randomly allocated in one of the two phases. Phase M received intrathecal morphine administration. Phase M+D received intrathecal morphine plus dexmedetomidine administration. All patients were monitored for 7 days and crossed over to alternate phase for another 1-week observation. Daily average visual analog scale (VAS) pain score, pain frequency, sleep deprivation, daily morphine consumption, bolus dose injection times, and side effects were all recorded. Pain intensity and frequency were significantly decreased in both phases compared with baseline. Daily morphine consumption and bolus dose injection times during phase M+D were significantly decreased compared with phase M. The incidences of constipation were significantly reduced in both phases compared with baseline administration, but nausea and vomiting were significantly increased. No serious side effects such as respiratory inhibition were observed in this study. Intrathecal administration of dexmedetomidine and morphine reduced the morphine consumption in patients with refractory cancer pain. There were no serious side effects.

Dexmedetomidine prolongs spinal anaesthesia induced by levobupivacaine 0.5% in guinea-pigs

Alpha-2 adrenoceptor agonists have been used in association with local anaesthetic to increase the duration of spinal anaesthesia. Intrathecal administration of clonidine prolonged motor blockade induced by local anaesthetic. Since the affinity of dexmedetomidine (DEX) to alpha-2 adrenoceptors is eight-times greater than clonidine, it is expected that DEX could be advantageous in clinical anaesthesia. We investigated the duration of motor nerve block induced by spinal injection of 0.5% levobupivacaine (LVB) associated with intrathecal or intraperitoneal administration of DEX. Seventy-two guinea-pigs were randomly divided in 12 groups, which were all treated with intrathecal injection of 50 microL of LVB. DEX was injected intrathecally with LVB in 6 groups or injected intraperitoneally after LVB in another 6 groups. Intrathecal DEX (0.1, 0.2 and 0.4 microg) increased the LVB-induced motor anaesthesia from 48 (41-66) min to 84.5 (52-91) min (P < 0.05), 101.5 (83-115) min (P < 0.05) and 105 (97-114) min (P < 0.05), respectively. Similarly, intraperitoneal DEX (20 and 40 microg kg(-1)) increased the motor blockade from 48.5 (33-59) min to 88 (71-114) min (P < 0.05) and 114.5 (103-156) min (P < 0.05), respectively. Pre-treatment with yohimbine reduced the duration of motor block from 101.5 (83-115) to 76.5 (68-86) min (P < 0.05) or from 114.5 (103-156) to 90 (83-93) min (P < 0.05) when DEX was administered by the intrathecal or intraperitoneal routes. Motor block induced by spinal injection of LVB was prolonged by intrathecal and systemic administration of DEX, which was partially dependent on activation of alpha-2 adrenoceptors.

Dexmedetomidine Does Not Increase the Incidence of Intracarotid Shunting in Patients Undergoing Awake Carotid Endarterectomy

Systemic administration of dexmedetomidine (DEX) decreases cerebral bloodflow (CBF) via direct alpha-2-mediated constriction of cerebral blood vessels and indirectly via its effect on the intrinsic neural pathway modulating vascular smooth muscle. Reduction in CBF without a concomitant decrease in cerebral metabolic rate has raised concerns that DEX may limit adequate cerebral oxygenation of brain tissue in patients with already compromised cerebral circulation (e.g., carotid endarterectomy [CEA]). In this study, we established the incidence of intraarterial shunting used as a sign of inadequate oxygen delivery in a consecutive series of 123 awake CEA performed in our institution using DEX as a primary sedative. Data were prospectively recorded in 151 patients who underwent CEA during the study period. Eighteen patients were sedated with midazolam and fentanyl (M/F) for medical or logistical reasons. Patients thought to be at risk of an intraoperative stroke were treated with a prophylactic intraarterial shunt. These patients, as well as those who required general anesthesia, were excluded from the final analysis. Five patients (4.3%) in the DEX group required intraarterial shunts. The incidence of shunting in patient undergoing awake CEA in our institution is 10% (historical control). No patients developed a stroke or other serious complications. It appears that the use of DEX as a primary sedative drug for CEA does not increase the incidence of intraarterial shunts.

Developmental Age Influences the Effect of Epidural Dexmedetomidine on Inflammatory Hyperalgesia in Rat Pups

Epidural alpha2-adrenergic agonists produce analgesic effects in children and adults, but efficacy and safety have not been established in neonates and infants. The aim of this study was to determine the effect of epidural dexmedetomidine on sensory processing, reversal of inflammatory hyperalgesia, and sedation during early development in rats. In rat pups aged 3, 10, and 21 postnatal days, mechanical withdrawal thresholds of the hind limbs were measured at baseline and after unilateral inflammation due to carrageenan. The effect of epidural dexmedetomidine on withdrawal thresholds was measured for 90 min after injection, and dose-response curves were constructed for each age group. The duration of the righting reflex was measured to assess sedation. The effects of epidural and systemic administration of dexmedetomidine were compared. At all ages, carrageenan-induced hyperalgesia was reversed by doses of epidural dexmedetomidine that did not affect the threshold of the contralateral paw or prolong the righting reflex. Higher doses of epidural dexmedetomidine affected baseline nociception in the contralateral paw and produced sedation but had no effect when given systemically. Reversal of hyperalgesia and sedation were produced by lower doses of epidural dexmedetomidine in the youngest pups. Spinally mediated selective reversal of inflammatory hyperalgesia by epidural dexmedetomidine can be achieved at all ages; relatively lower doses are effective in early life, but the therapeutic window is narrow. These data have implications for the use and dosing of epidural alpha2 agonists in neonates and infants.