Alterations in whole-brain dynamic functional stability during memory tasks under dexmedetomidine sedation.

Purpose: This study aimed to explore the neurological effects of dexmedetomidine-induced sedation on memory using functional stability, a whole-brain voxel-wise dynamic functional connectivity approach. Methods: A total of 16 participants (10 men) underwent auditory memory task-related fMRI in the awake state and under dexmedetomidine sedation. Explicit and implicit memory tests were conducted 4 h after ceasing dexmedetomidine administration. One-sample Wilcoxon signed rank test was applied to determine the formation of explicit and implicit memory in the two states. Functional stability was calculated and compared voxel-wise between the awake and sedated states. The association between functional stability and memory performance was also assessed. Results: In the awake baseline tests, explicit and implicit memory scores were significantly different from zero (p < 0.05). In the tests under sedation, explicit and implicit memory scores were not significantly different from zero. Compared to that at wakeful baseline, functional stability during light sedation was reduced in the medial prefrontal cortex, left angular gyrus, and right hippocampus (all clusters, p < 0.05, GRF-corrected), whereas the left superior temporal gyrus exhibited higher functional stability (cluster p < 0.05, GRF-corrected). No significant associations were observed between functional stability and memory test scores. Conclusions: The distribution and patterns of alterations in functional stability during sedation illustrate the modulation of functional architecture by dexmedetomidine from a dynamic perspective. Our findings provide novel insight into the dynamic brain functional networks underlying consciousness and memory in humans.

The analgesic efficacy of ultrasound-guided transversus abdominis plane (TAP) block combined with oral multimodal analgesia in comparison with oral multimodal analgesia after caesarean delivery: a randomized controlled trial.

BACKGROUND: The transversus abdominis plane (TAP) block is used increasingly in parturients after caesarean delivery. This is a randomized controlled trial to evaluate the effectiveness of bilateral single-shot of TAP blocks in patients who received multimodal oral analgesia for postoperative pain relief. METHODS: Parturients who were scheduled for elective caesarean delivery under spinal anaesthesia were recruited and randomized to receive bilateral single-shot of TAP blocks or placebo in addition to multimodal oral analgesia which consisted of regular tramadol, celecoxib and paracetamol, with oral oxycodone used as a rescue for breakthrough pain. Only parturients in the TAP group would receive the TAP blocks with an injection of 15 ml (0.25%) ropivacaine on each side under aseptic techniques. All the parturients were evaluated for pain or related complications in the first 24 h after surgery. The primary outcome is the percentage of parturients who required oxycodone as a rescue analgesia. RESULTS: Eighty and 79 parturients were allocated to the TAP and placebo group respectively. Nine out of 79 (11.4%) parturients in the TAP group and 15 out of 73 (20.5%) parturients in the placebo group required oxycodone for breakthrough pain, P = 0.122. CONCLUSIONS: Bilateral single-shot of TAP blocks confer little additional benefit when a multimodal oral analgesic regimen is used for pain control after caesarean section under spinal anaesthesia. TRIAL REGISTRATION: Clinical Trial Registry of China ( http://www.chictr.org.cn ) identifier: ChiCTR-INR-16010130 , retrospectively registered on Dec 12, 2016.

A Comparison of Intranasal Dexmedetomidine and Dexmedetomidine Plus Buccal Midazolam for Non-painful Procedural Sedation in Children with Autism.

Children with autism often need sedation for diagnostic procedures and they are often difficult to sedate. This prospective randomized double-blind control trial evaluates the efficacy and safety using intranasal dexmedetomidine with and without buccal midazolam for sedation in children with autism undergoing computerized tomography and/or auditory brainstem response test. The primary outcome is the proportion of children attaining satisfactory sedation. One hundred and thirty-six children received intranasal dexmedetomidine and 139 received intranasal dexmedetomidine with buccal midazolam for sedation. Combination of intranasal dexmedetomidine and buccal midazolam was associated with higher sedation success when compared to intranasal dexmedetomidine. Since intranasal and buccal sedatives required little cooperation this could be especially useful technique for children with autism or other behavioral conditions.

Pharmacokinetics and pharmacodynamics of dexmedetomidine.

Dexmedetomidine is an alpha-2 adrenoceptor agonist and has been used as a general anesthetic, sedative and analgesic for about 30 years. The aim of this paper is to review the pharmacokinetics and pharmacodynamics of dexmedetomidine, evaluate physiological factors that may affect the pharmacokinetics of dexmedetomidine, and summarize the pharmacodynamics of dexmedetomidine at different plasma levels. The pharmacokinetic parameters reported in previous studies according to noncompartmental analyses or population modeling results are compared. We concluded that the pharmacokinetic profile can be adequately described by a two-compartment model in population pharmacokinetic modeling. Body weight, height, albumin level, cardiac output, disease condition and other factors were considered to have significant influence on the clearance and/or distribution volume in different population pharmacokinetic models. The pharmacological effects of dexmedetomidine, such as sedation, heart rate reduction and biphasic change of blood pressure, vary at different plasma levels. These findings provide a reference for individualizing the dose of dexmedetomidine and achieving the desired pharmacological effects in clinical applications.

The effects of anaesthesia on the developing brain: a summary of the clinical evidence.

INTRODUCTION: There is data amassing in the literature regarding the potentially adverse effects of anaesthesia exposure on the developing human brain. The purpose of this article is to summarise current relevant data from clinical studies in this area. METHODS: Articles from journals written in English were searched for using PubMed, Ovid and Medline. Keywords used included: brain (newborn, infant, child and neonate), neurodegeneration, apoptosis, toxicity, neurocognitive impairment (developmental impairment and learning disorders) and anaesthesia (intravenous, inhalational and sedation). RESULTS: From the initial search, 23 articles were identified as potentially relevant, with publication dates spanning from 1978 to 2012.  Twelve studies were deemed irrelevant to the research questions. The results of neurocognitive assessment from eight of the remaining eleven studies had showed some differences in the performances of children exposed to anaesthesia. The control population in these studies was highly variable. The age at which the subjects were exposed to anaesthesia ranged from prenatal to 4 years in the majority of studies with one including children aged up to 12 years when exposed. DISCUSSION: Although there is clinical data suggesting a possible detrimental effect, the evidence is best considered preliminary and inconclusive at this stage. Many of the outcome measures were lacking in specificity and standardization in most cases. Parents should be counselled to not avoid necessary invasive procedures for fear of a currently ill-defined risk.  However, deferral of elective procedures beyond the first few years of life should be contemplated.

The effects of anaesthesia on the developing brain: a summary of the clinical evidence.

Introduction: There is data amassing in the literature regarding the potentially adverse effects of anaesthesia exposure on the developing human brain. The purpose of this article is to summarise current relevant data from clinical studies in this area. Methods: Articles from journals written in English were searched for using PubMed, Ovid and Medline. Keywords used included: brain (newborn, infant, child and neonate), neurodegeneration, apoptosis, toxicity, neurocognitive impairment (developmental impairment and learning disorders) and anaesthesia (intravenous, inhalational and sedation). Results: From the initial search, 23 articles were identified as potentially relevant, with publication dates spanning from 1978 to 2012.  Twelve studies were deemed irrelevant to the research questions. The results of neurocognitive assessment from eight of the remaining eleven studies had showed some differences in the performances of children exposed to anaesthesia. The control population in these studies was highly variable. The age at which the subjects were exposed to anaesthesia ranged from prenatal to 4 years in the majority of studies with one including children aged up to 12 years when exposed. Discussion: Although there is clinical data suggesting a possible detrimental effect, the evidence is best considered preliminary and inconclusive at this stage. Many of the outcome measures were lacking in specificity and standardization in most cases. Parents should be counselled to not avoid necessary invasive procedures for fear of a currently ill-defined risk.  However, deferral of elective procedures beyond the first few years of life should be contemplated.

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.