Effect of dexmedetomidine, an alpha2-adrenoceptor agonist, on human pupillary reflexes during general anaesthesia

AIMS: To test the hypothesis that the alpha2-adrenergic agonist, dexmedetomidine, dilates the pupil and does not alter the pupillary light reflex of anaesthetized patients. METHODS: Eight volunteers were administered general anaesthesia with propofol, nitrous oxide and alfentanil. One hour and 25 min after induction of anaesthesia, a 45 min infusion of dexmedetomidine was begun, targeting a plasma concentration of 0.6 ng x ml(-1). Pupil size, pupillary light reflex amplitude, light reflex recovery time, and reflex dilation were measured before and during dexmedetomidine infusion. RESULTS: Dexmedetomidine produced no change in pupil size and light reflex recovery time, increased the light reflex from 0.30 +/- 0.14 to 0.37 +/- 0.12 mm and significantly reduced pupillary reflex dilation by 72 +/- 62%. CONCLUSIONS: These pupillary effects of dexmedetomidine in humans are difficult to reconcile with the findings obtained in cats and rats that have demonstrated a direct inhibitory effect of alpha2-adrenergic agonists on the pupilloconstrictor nucleus. The increase in the magnitude of the light reflex in response to dexmedetomidine does not necessarily involve an anxiolytic mechanism.     

Dexmedetomidine: perioperative applications in children

Dexmedetomidine is a highly specific and selective alpha‐2‐adrenergic agonist with sedative, anxiolytic, and organ protective effects. Its clinical applications in children include premedication, prevention of emergence delirium, as part of multimodal anesthetic regimen and sedation in the pediatric intensive care unit. Its role in neuroprotection in children undergoing anesthesia should be explored. In this review, various uses of dexmedetomidine are discussed in detail.     

Effects of dexmedetomidine on propofol and remifentanil infusion rates during total intravenous anesthesia for spine surgery in adolescents

Introduction: Total intravenous anesthesia with propofol and a synthetic opioid is a frequently chosen anesthetic technique for posterior spinal fusion. Despite its utility, adverse effects may occur with high or prolonged propofol dosing regimens including delayed awakening. The current study investigated the propofol‐sparing effects of the concomitant administration of the α₂‐adrenergic agonist, dexmedetomidine, during spinal fusion surgery in adolescents. Methods: The surgical database of the department of orthopedic surgery was searched and patients (12–21 years of age) were identified who had undergone spinal fusion for either idiopathic or neuromuscular scoliosis during the past 24 months. Patients were assigned to two groups. Group 1 included patients anesthetized with propofol and remifentanil and group 2 included patients anesthetized with dexmedetomidine, propofol, and remifentanil. In the latter group, dexmedetomidine was administered as a continuous infusion of 0.5 μg·kg^?1·h^?1 started after the induction of anesthesia without a loading dose. Propofol was adjusted to maintain the bispectral index (BIS) number at 40–50 and remifentanil was adjusted to maintain the mean arterial pressure (MAP) at 50–65 mmHg. Labetolol or hydralazine was used if the MAP could not be maintained at 50–65 mmHg with remifentanil up to a maximum dose of 0.6 μg/kg/min. Statistical analysis included a nonpaired t‐test for parametric data (age, weight, remifentanil/propofol infusion requirements, and heart rate/blood pressure values). A nonparametric statistical analysis (Dunn) was used to compare BIS numbers. Parametric data are presented as the mean ± sd while nonparametric data are presented as the median and the 95th percentile confidence intervals. Results: Twelve patients received propofol–remifentanil–dexmedetomidine and 24 received propofol–remifentanil. There were no differences in the demographic data, BIS numbers or hemodynamic parameters between the two groups. There was a reduction in the propofol infusion requirements in patients who also received dexmedetomidine (71 ± 11 μg·kg^?1·min^?1) compared with those receiving only propofol–remifentanil (101 ± 33 μg·kg^?1·min^?1, P = 0.0045). No difference was noted in the remifentanil infusion requirements or the use of supplemental agents (hydralazine and labetolol) to maintain controlled hypotension. Conclusion: The concomitant use of dexmedetomidine in patients undergoing spinal fusion reduces propofol infusion requirements when compared with those patients receiving only propofol and remifentanil.     

Synergistic Interaction Between Dexmedetomidine and Ulinastatin Against Vincristine-Induced Neuropathic Pain in Rats

Antimicrotubulin chemotherapeutic agents such as vincristine (VCR), often induce peripheral neuropathic pain. It is usually permanent and seriously harmful to cancer patients' quality of life and can result in the hampering of clinical treatments. Currently, there is no definitive therapy, and many of the drugs approved for the treatment of other neuropathic pain have shown little or no analgesic effect. It is therefore vital to find new and novel therapeutic strategies for patients suffering from chemotherapeutic agent-induced neuropathic pain to improve patients' quality of life. This study shows that intrathecal injections of dexmedetomidine (DEX), or intraperitoneally administered ulinastatin (UTI) significantly reduces Sprague Dawley rats' mechanical allodynia induced by VCR via upregulation of interleukin-10 expression and activating the α2-adrenergic receptor in dorsal root ganglion (DRG). Moreover, when combined there is a synergistic interaction between DEX and UTI, which acts against VCR-induced neuropathic pain. This synergistic interaction between DEX and UTI may be partly attributed to a common analgesic pathway in which the upregulation of interleukin -10 plays an important role via activating α2-adrenergic receptor in rat dorsal root ganglion. The combined use of DEX and UTI does not affect the rat's blood pressure, heart rate, sedation, motor score, spatial learning, or memory function. All of these show that the combined use of DEX and UTI is an effective method in relieving VCR-induced neuropathic pain in rats.

Effects of Perioperative Dexmedetomidine on Postoperative Mortality and Morbidity: A Systematic Review and Meta-analysis

Purpose

Major postoperative complications translate into increased health care resource utilization, prolonged hospital stays, and increased mortality. We aimed to assess the effects of perioperative dexmedetomidine use on postoperative mortality and the prevalence of major complications after cardiac and noncardiac surgery.

Dexmedetomidine Added to Local Anesthetic Mixture of Lidocaine and Ropivacaine Enhances Onset and Prolongs Duration of a Popliteal Approach to Sciatic Nerve Blockade

Purpose

A literature review of multiple clinical studies on mixing additives to improve pharmacologic limitation of local anesthetics during peripheral nerve blockade revealed inconsistency in success rates and various adverse effects. Animal research on dexmedetomidine as an adjuvant on the other hand has promising results, with evidence of minimum unwanted results. This randomized, double-blinded, contrastable observational study examined the efficacy of adding dexmedetomidine to a mixture of lidocaine plus ropivacaine during popliteal sciatic nerve blockade (PSNB).

Detecting a dexmedetomidine‐evoked reduction of noradrenaline release in the human brain with the alpha2C‐adrenoceptor PET ligand [11C]ORM‐13070

PET imaging can for some neurotransmitters be used to measure synaptic neurotransmitter concentrations. The objective of this study was to test whether the receptor binding of the α_2C‐AR antagonist PET tracer [¹¹C]ORM‐13070 would increase in response to reductions in synaptic noradrenaline, evoked by dexmedetomidine as a sympatholytic drug challenge. Six subjects underwent a control PET scan and two dexmedetomidine PET scans. Dexmedetomidine was infused with target plasma concentrations of 0.6 and 0.2 ng/ml. Tracer binding was measured by voxel‐based analysis of bound per free (B/F) images. ROI‐based analysis was performed in the dorsal striatum and in the thalamus. Vital signs and drug concentrations in plasma were measured and the sedative effect was estimated with the visual analog scale. In the voxel‐based analysis, dexmedetomidine administration was associated with a tendency to increased B/F tracer in the right thalamus (mean, +17%, P = 0.14, and +19%, P = 0.05, with the low and high dose, respectively). Tracer binding in the dorsal striatum was unaffected by dexmedetomidine. A cluster with significantly increased B/F tracer (+42%, P = 0.01) was seen in the right superior temporal gyrus with low‐dose dexmedetomidine, but not after the high dose. Brain uptake of [¹¹C]ORM‐13070 has previously been shown to be reduced in conditions of increased synaptic noradrenaline concentrations. In this study, tracer binding in the thalamus tended to increase in accordance with reduced activity of noradrenergic projections from the locus coeruleus, but statistical significance was not reached. Synapse 70:57–65, 2016. © 2015 Wiley Periodicals, Inc.     

右美托咪定静脉泵注和鼻内给药两种方式对小儿口腔日间手术术后躁动的影响

目的比较右美托咪定静脉泵注和鼻内给药两种方法对七氟烷吸入麻醉下小儿口腔日间手术术后躁动的影响。方法随机纳入135例拟行口腔日间手术的患儿,年龄1~6岁,分为3组,每组45例,分别予麻醉诱导后右美托咪定1μg/kg静脉泵注(VD组)、麻醉诱导前15 min右美托咪定1μg/kg鼻内给药(ND组)或等量生理盐水对照(C组)。所有患儿采用七氟烷全凭吸入麻醉。术后每5 min进行一次躁动评分(PEDA)及疼痛评分(FLACC);记录麻醉诱导前(T0)、麻醉诱导后(T1)、手术开始时(T2)、手术结束时(T3)及苏醒时(T4)的HR、BP;记录苏醒时间、PACU停留时间及恶心呕吐、呼吸抑制、心动过缓等不良反应发生情况。结果 VD组和ND组术后躁动发生率明显低于C组(P0.01);T2和T3时VD组心率明显低于ND组和C组(P0.01),T3时ND组心率低于C组(P0.05);VD组和ND组苏醒时间长于C组(P0.01);3组患儿PACU停留时间没有差异;3组患儿最高疼痛评分没有差异。VD组有4例患儿出现心动过缓需使用阿托品治疗。3组患儿均未发生其他严重不良反应。结论右美托咪定静脉泵注和鼻内给药都能明显降低七氟烷麻醉后躁动的发生,右美托咪定鼻内给药对心率影响更小。     

Efficacy and Tolerability of Sufentanil,Dexmedetomidine, or Ketamine Added to Propofol-based Sedation for Gastrointestinal Endoscopy in Elderly Patients: A Prospective,Randomized, Controlled Trial

PurposeTo investigate the optimal agent combined with propofol for sedation in elderly patients undergoing gastrointestinal endoscopy.MethodsA total of 120 elderly patients scheduled for gastrointestinal endoscopy under propofol-based sedation were randomly allocated to receive propofol + saline (control group), propofol + sufentanil 0.1 μg/kg, propofol + dexmedetomidine 0.4 μg/kg, or propofol + ketamine 0.4 mg/kg. Mean arterial pressure, heart rate, pulse oximetry, pressure of end-tidal carbon dioxide, respiratory rate, and Ramsay sedation scale score were recorded. Induction time, procedure time, recovery time, propofol dose, and adverse events were also recorded.FindingsDuring the sedation procedure, the AUC of HR was lowest in the propofol + dexmedetomidine group (all, P < 0.05), and the AUC of pulse oximetry was significantly higher in the propofol + dexmedetomidine and propofol + ketamine groups compared to the other 2 groups (both, P < 0.05). The propofol + dexmedetomidine group had the highest prevalences of hypotension and bradycardia, and the control group experienced the largest number of hypoxia episodes (all, P < 0.05). The control group consumed the highest dose of propofol, while the propofol + ketamine group needed the lowest dose (all, P < 0.05).ImplicationsThe combination of propofol + ketamine 0.4 mg/kg maintained hemodynamic and respiratory stability, as evidenced by less hypotension, bradycardia, and hypoxia events, in elderly patients undergoing gastrointestinal endoscopy. China clinical trial registration (chictr.org.cn) ID: ChiCTR-INR-17013710.