Median Effective Dose of Dexmedetomidine Inducing Bradycardia in Elderly Patients Determined by Up-and-Down Sequential Allocation Method

Purpose: When dexmedetomidine is used in elderly patients, high incidence of bradycardia is reported. Given age-related physiological changes in this population, it is necessary to know the safety margin between the loading dose of dexmedetomidine and bradycardia. Therefore, we conducted this study to investigate the median effective dose (ED50) of dexmedetomidine causing bradycardia in elderly patients.Methods: Thirty patients with ages over 65 years undergoing elective general surgery were enrolled. The Dixon and Massay sequential method were applied to determine the loading dose of dexmedetomidine, starting from 1.0 µg/kg. The dose for the follow-up subjects increased or decreased according to the geometric sequence with the common ratio 1.2, based on the ''negative'' or ''positive'' response of the previous subject. Positive mean that the subject developed bradycardia during the test. Hemodynamic data including heart rate and systolic blood pressure were recorded. The level of sedation was assessed with the Observer Assessment of Alertness and Sedation Scale (OAA/S).Results: Bradycardia occurred in 13 patients (43.3%). The ED50 of dexmedetomidine causing bradycardia was 1.97 µg/kg (95% CI, 1.53-2.53 µg/kg). OAA/S scores at 10 min after the beginning of the dexmedetomidine infusion and 10 min after the termination of dexmedetomidine administration showed no significant differences between the positive and negative groups (P > 0.05).Conclusion: The ED50 of dexmedetomidine causing bradycardia in our cohort was higher than clinical recommended dose. A higher loading dose appears acceptable for a faster onset of sedation under careful hemodynamic monitoring.Trial registration: ChiCTR 15006368.     

Comparison of clonidine and dexmedetomidine for short-term sedation of intensive care unit patients

Background and Objectives:

Patients on mechanical ventilation in intensive care unit (ICU) are often uncomfortable because of anxiety, pain, and endotracheal intubation; therefore, require sedation. Alpha-2 agonists are known to produce sedation. We compared clonidine and dexmedetomidine as sole agents for sedation.

Study Design:

Prospective, randomized, controlled open-label study.

Materials and Methods:

A total of 70 patients requiring a minimum of 12 h of mechanical ventilation with concomitant sedation, were randomly allocated into two groups. Group C (n = 35) received intravenous (IV) clonidine (1 μg/kg/h titrated up to 2 μg/kg/h to attain target sedation), and Group D (n = 35) received IV dexmedetomidine for sedation (loading 0.7 μg/kg and maintenance 0.2 μg/kg/h titrated up to 0.7 μg/kg/h to achieve target sedation). A Ramsay Sedation Score of 3-4 was considered as target sedation. Additional sedation with diazepam was given when required to achieve target sedation. The quality of sedation, hemodynamic changes and adverse effects were noted and compared between the two groups.

Results:

Target sedation was achieved in 86% observations in Group D and 62% in Group C (P = 0.04). Additional sedation was needed by more patients in Group C compared with Group D (14 and 8 in Groups C and D, respectively, P = 0.034), mainly due to concomitant hypotension on increasing the dose of clonidine. Hypotension was the most common side-effect in Group C, occurring in 11/35 patients of Group C and 3/35 patients of Group D (P = 0.02). Rebound hypertension was seen in four patients receiving clonidine, but none in receiving dexmedetomidine.

Conclusion:

Both clonidine and dexmedetomidine produced effective sedation; however, the hemodynamic stability provided by dexmedetomidine gives it an edge over clonidine for short-term sedation of ICU patients.     

Systematic assessment of dexmedetomidine as an anesthetic agent: a meta-analysis of randomized controlled trials

Introduction

Here we aimed to study the effectiveness of dexmedetomidine as an anesthetic adjunct in surgery.

Material and methods

A systematic evaluation was performed on published clinical trials. Major databases such as Medline database were employed to search and identify relevant studies and then Rev.Man 5 was used for meta-analysis as well as forest plots. Mean difference (MD) was chosen as the effect size for measurement data, while odds ratio (OR) was calculated for enumeration data.

Results

A total of 18 studies met the inclusion criteria. The postoperative heart rate and mean arterial pressure for the dexmedetomidine group were significantly lower than the control group (combined MDs were –14.12 and –9.96). The incidence rates of postoperative nausea and vomiting, chills, and shivering of the dexmedetomidine group were lower than the control group (pooled ORs were 0.41, 0.21 and 0.14, respectively). However, the occurrence rates of bradycardia and hypotension in the dexmedetomidine group were higher than the control group (pooled ORs were 5.14 and 3.00).

Conclusions

Dexmedetomidine can stabilize blood pressure and heart rate, and prevent postoperative adverse reactions. However, patients with original hypovolemia or heart block should be cautious. Besides, the quality of such studies should be improved in methodology to evaluate their efficacy and safety comprehensively.     

右美托咪定联合布托啡诺用于病毒性脑炎患者镇痛镇静的临床观察

目的 分析病毒性脑炎患者应用联合右美托咪定及布托啡诺治疗的临床效果.方法 将64例病毒性脑炎患者随机分为对照组及观察组,每组32例.以接受右美托咪定镇痛治疗者为对照组,以联合接受右美托咪定及布托啡诺镇痛治疗者为观察组,对比两组接受治疗后的镇痛镇静效果及药物副作用发生率.结果 观察组接受治疗后止痛起效时间、镇静起效时间、止痛持续时间及镇静持续时间分别为(10.12±2.77) min、(17.71 ±3.51)min、(766.61 ±86.12) min及(653.55±98.32) min明显短于对照组的(13.61 ±3.61)min、(21.67 ±3.26) min、(731.21 ±78.24) min及(610.27 ±86.38) min(P＜0.05);同时治疗前两组生活质量各项评分比较未见统计学差异(P＞0.05),经治疗后观察组生活质量各项评分改善较对照组更为明显(P＜0.05).此外两组药物副作用发生率比较未见统计学差异(P＞0.05).结论 联合右美托咪定及布托啡诺治疗可显著提高病毒性脑炎患者的镇痛镇静效果.     

Effects of Dexmedetomidine on Diaphragm Activity Measured by Ultrasonography in Spontaneously Breathing Patients

Background: Diaphragm movement is well correlated with inspired volume of the lung. Dexmedetomidine (DEX) has less effect on respiratory functions than other sedatives. The objective of this study was to investigate diaphragmatic movement using ultrasound (US) during DEX infusion for sedation in spontaneously breathing patients undergoing unilateral upper limb surgery.Methods: A total of 33 consecutive patients were enrolled in this study. Patients were sedated using DEX with ipsilateral axillary brachial nerve plexus block. Diaphragmatic activity was evaluated using diaphragmatic thickening at end-inspiration (TEI), diaphragmatic thickening at end-expiration (TEE), and diaphragmatic thickening fraction (DTF) measured by diaphragmatic US at three time-points; T0, baseline; T1, after DEX sedation; and T2, after DEX recovery. Supplementary oxygen was applied with a simple mask at 5 L/min. Peripheral oxygen saturation (SpO₂), end tidal CO₂ (EtCO₂), and respiratory rate (RR) were recorded.Results: TEI and TEE showed no significant changes during the study period (P = 0.394 and P = 0.205, respectively). DTF was maintained at both T0 and T1 (P = 1.000). At recovery after DEX infusion discontinued, DTF was increased by 3.85%, although such increase was not statistically significant (T0 vs. T2, P = 0.525). SpO₂ remained above 99% and EtCO₂ remained below 36 mmHg. Desaturation episodes were not observed during the study period.Conclusions: Results of this study showed that DEX sedation did not affect the diaphragmatic movement in situation of decreased RR induced by DEX. This finding implies that DEX-induced sedation does not result in clinically significant respiratory depression.     

右美托咪定对老年髋关节手术患者早期认知功能和炎症因子的影响

目的:观察右美托咪定对老年髋关节手术患者炎性细胞因子水平和术后认知功能的影响,为降低术后认知功能障碍(POCD)的发生提供理论参考.方法:60例择期在腰-硬联合阻滞麻醉下拟行全髋关节置换手术病人,按照术前给药方式的不同,随机分为观察组:静脉注射右美托咪定组(D组,30例)和对照组静脉注射等容量的生理盐水组(N组,30例...     

右美托咪啶上调sirtuin3减轻小鼠肾缺血-再灌注损伤

目的研究右美托咪啶(DEX)在肾缺血-再灌注(I/R)损伤小鼠中的保护作用及其机制。方法将小鼠分为假手术(sham)组、siRNA+sham组、肾I/R组(常规法)、DEX+I/R组(腹腔注射25μg/kg DEX)、siRNA+I/R组及siRNA+DEX+I/R组;siRNA+sham组、siRNA+I/R组、siRNA+DEX+I/R组术前3 d经尾静脉注射5×10^9TU/kg慢病毒-去乙酰化酶3(SIRT3) siRNA。生化分析仪测定肾功能;HE染色法观察肾组织形态学;Tunel染色法检测肾组织凋亡;Western blot检测SIRT3、亲环素D(Cyp D)和细胞色素C(Cyt C)表达。结果 DEX可降低小鼠肾I/R后肾脏损伤,上调SIRT3表达并下调Cyt C及乙酰化Cyp D蛋白表达水平(P<0. 05)。抑制SIRT3后可减轻DEX对肾脏的保护作用(P<0. 05)。结论 DEX减轻肾I/R损伤的作用可能与上调SIRT3相关。     

Comparison of Dexmedetomidine and Remifentanil on Airway Reflex and Hemodynamic Changes during Recovery after Craniotomy

PurposeDuring emergence from anesthesia for a craniotomy, maintenance of hemodynamic stability and prompt evaluation of neurological status is mandatory. The aim of this prospective, randomized, double-blind study was to compare the effects of dexmedetomidine and remifentanil on airway reflex and hemodynamic change in patients undergoing craniotomy.ResultsThe incidence of grade 2 and 3 cough at the point of extubation was 62.5% in the dexmedetomidine group and 53.1% in the remifentanil group (p=0.39). Mean arterial pressure (p=0.01) at admission to the PACU and heart rate (p=0.04 and 0.01, respectively) at admission and at 10 minutes in the PACU were significantly lower in the dexmedetomidine group. Respiration rate was significantly lower in the remifentanil group at 2 minutes (p<0.01) and 5 minutes (p<0.01) after extubation.ConclusionWe concluded that a single bolus of dexmedetomidine (0.5 µg/kg) and remifentanil infusion have equal effectiveness in attenuating coughing and hemodynamic changes in patients undergoing cerebral aneurysm clipping; however, dexmedetomidine leads to better preservation of respiration.     

Effect of Dexmedetomidine on Sevoflurane Requirements and Emergence Agitation in Children Undergoing Ambulatory Surgery

Purpose

Dexmedetomidine, a potent selective α2-adrenergic agonist, produces sedation and analgesia. This study was conducted to assess the effect of dexmedetomidine infusion on sevoflurane requirements, recovery profiles, and emergence agitation in children undergoing ambulatory surgery.

Materials and Methods

Forty children undergoing ambulatory hernioplasty or orchiopexy were randomized into two groups. The dexmedetomidine group (Group D, n=20) received dexmedetomidine 1 µg/kg, followed by 0.1 µg/kg/h until the end of surgery, whereas the saline group (Group S, n=20) received volume-matched normal saline. Sevoflurane was used for induction and maintenance of anesthesia and caudal block was performed in all children. End-tidal sevoflurane concentration (ET-sevo), the incidence of emergence agitation, pain scores, and sedation scores were recorded. Hemodynamic changes and other adverse effects were assessed in the perioperative period.

Results

ET-sevo of Group D was significantly reduced in 23.8-67% compared to Group S during surgery. The incidence of emergence agitation was lower in Group D than in Group S (5% vs. 55%, p=0.001). Postoperative pain was comparable, and discharge time was not different between the groups. Mean arterial pressure and heart rate were significantly lower in Group D during surgery.

Conclusion

Intraoperative infusion of dexmedetomidine reduced sevoflurane requirements and decreased emergence agitation without delaying discharge in children undergoing ambulatory surgery. However, caution should be taken in regard to bradycardia and hypotension.     

瑞芬太尼与右美托咪定用于预防全麻苏醒期呛咳反射及血流动力学波动的比较

目的 对比瑞芬太尼靶控输注和单次给予右美托咪定预防全麻苏醒期呛咳反射和稳定血流动力学的效果.方法 选择甲状腺切除手术患者90例,随机分为对照组(C组,n =30)、瑞芬太尼组(R组,n=30)和右美托咪定组(D组,n=30).术中以七氟烷和靶控输注瑞芬太尼维持麻醉.D组于手术结束前10 min经静脉缓慢滴注0.5 μg/kg右美托咪定.手术结束即刻,C组和D组同时停止输注瑞芬太尼;R组维持瑞芬太尼2 ng/mL靶控输注直至拔管结束.记录拔管期间患者呛咳评分、BP、HR、拔管后呼吸频率、镇静评分和咽痛评分.结果 拔管期间呛咳评分为0分(无呛咳)或1分(1次呛咳)的患者的比例在R组(73.3％)显著高于C组(40％)和D组(40％)(P＜0.05);R组MBP显著低于C组和D组(P＜0.05);R组和D组HR均低于C组(P＜0.05).结论 全麻醉苏醒期间,瑞芬太尼靶控输注在预防呛咳反射及血压升高方面效果优于单次给予右美托咪定;两者在稳定心率方面效果相当;拔管后两者均无明显呼吸抑制作用.     

右美托咪定对口腔鳞癌细胞生长和运动能力的调节

目的 探究右美托咪定 ( dexmedetomidine, DEX) 对口腔鳞癌 ( oral squamous cell carcinoma, OSCC) 细胞生长和运动的调节作用。 方法 人 OSCC 细胞 CAL27 分为 DEX0、 5、 10 及 20 nmol / L 组。 运用 克隆形成实验和 BrdU 实验评估细胞增殖; Transwell 法检测细胞侵袭; 流式细胞术检测细胞凋亡率; ELISA 检测超氧化物歧化酶 (SOD) 和丙二醛 (MDA) 水平; 微管形成实验评估细胞微管形成能力; Western 印 迹检测血管内皮生长因子 (VEGF)、 纤连蛋白 ( FN)、 B 细胞淋巴瘤 2 ( Bcl-2) 和 Bcl-2 相关 X 蛋白 (Bax) 的表达。 结果 与对照组比较, DEX 处理可显著降低 CAL27 细胞克隆形成率和 BrdU 阳性细胞率, 减少侵袭细胞数和微管结节数, 下调 VEGF 和 FN 表达水平。 同时 DEX 处理可促进氧化应激, 提高 Bax / Bcl-2 比率。 结论 DEX 处理可抑制 CAL27 细胞增殖、 侵袭和微管形成能力, 并促进其氧化应激和凋亡。     

Novel Powdered Anti-adhesion Material: Preventing Postoperative Intra-abdominal Adhesions in a Rat Model

Background: Although laparoscopic surgery has decreased postoperative adhesions, complications induced by adhesions are still of great concern. The aim of this study was to investigate the anti-adhesive effects of a novel powdered anti-adhesion material that can be applied during laparoscopic surgery in comparison with other anti-adhesion materials. Methods:Our novel powdered anti-adhesion material is composed of aldehyde dextran and ε-poly(L-lysine). In 40 male rats, a 2.5×2.0-cm abdominal wall resection and cecum abrasion were performed. The rats were randomized into four groups based on the anti-adhesion treatments: normal saline; Seprafilm^®; Interceed^®; and novel powdered anti-adhesion material. The animals were euthanized on days 7 and 28 to evaluate the adhesion severity, area of adhesion formation, gross appearance, and pathological changes. Results: The adhesion severities on both days 7 and 28 were significantly lower for all anti-adhesion material groups compared with the normal saline group (p<0.05). Pathologically, all groups showed inflammatory cell infiltration on day 7 and complete regeneration of the peritoneum on day 28. Conclusions:Our novel powdered anti-adhesion material was found to be effective for reducing postoperative intra-abdominal adhesions and showed equivalent efficacy to commercial anti-adhesion materials.     

吡柔比星膀胱灌注预防浅表性膀胱癌术后复发的疗效观察

目的探讨吡柔比星（THP）膀胱内灌注预防浅表性膀胱癌术后复发的效果。方法患者随机分成两组,一组患者膀胱灌注卡介苗（BCG）（40例）,另一组膀胱灌注THP（40例）,随访6～24个月,观察两组复发情况及不良反应。结果BCG组和THP组2年复发率分别为12．5％（5／40）、14．0％（6／43）;两组间比较差异无统计学意义（x^2=0．038,P〉0．05）,而THP组不良反应发生率明显低于BCG组（x^2=9．565,P〈0．01）。结论膀胱灌注THP预防浅表性膀胱癌术后复发的疗效确切,不良反应小,安全性好。     

右美托咪定辅助用于小儿尿道下裂修补术后镇痛的效果观察

观察右美托咪定复合芬太尼用于尿道下裂修补术患儿术后镇痛的效果及安全性。方法 选择全麻下择期行尿道下裂修补术的患儿60例,随机分为F组和D组,各30例。F组给予芬太尼0.3 μg/（kg·h）,D组给予右美托咪定0.05 μg/（kg·h）+芬太尼0.2 μg/（kg·h）,所有患者手术结束前30 min,给予芬太尼负荷剂量1 μg/kg。手术结束前即刻连接一次性恒速机械镇痛泵,泵注速率2 ml/h。记录连接镇痛泵后2、4、8、12、24及48 h的Wong-Baker脸谱疼痛评分和Ramsay镇静评分,补救镇痛次数以及术后心动过缓、低血压、恶心呕吐等不良反应发生情况。结果 与F组比较,D组患儿补救镇痛次数、恶心呕吐及躁动发生率降低,患儿2、4、8、12、24及48 h的Wong-Baker脸谱疼痛评分降低、而Ramsay镇静评分增高,差异有统计学意义（P＜0.05）,两组患者在镇痛过程中均未出现心动过缓及低血压。结论 右美托咪定辅助用于小儿尿道下裂术后镇痛能提供较好镇痛效果和较佳镇静舒适度,减少不良反应的发生。     

右美托咪定复合丙泊酚-瑞芬太尼用于轻度肝功能异常患者开胸术麻醉的适宜剂量

目的对轻度肝功能异常进行开胸手术的患者,研究使用右美托咪定复合丙泊酚、瑞芬太尼进行麻醉的效果及适宜剂量。方法选取150例我院2012年4月~2014年4月收治的轻度肝功能异常患者,所有患者均需要行开胸术。将以上患者随机分为观察组A、观察组B、对照组各50例。观察组A、观察组B患者在麻醉诱导前15min静脉滴注右美托咪定负荷剂量0.8μg/kg,并分别在麻醉诱导行气管插管后开始静脉泵注右美托咪定0.2μg/(kg·h)、0.5μg/(kg·h)维持直到手术结束前0.5h;对照组患者给予等量的生理盐水静脉注射。结果观察组B患者的HR情况和不良反应发生率与观察组A患者相比,明显较好,P<0.05;观察组A患者的HR情况和不良反应发生率与对照组患者,明显较好,P<0.05。结论可见丙泊酚-瑞芬太尼复合0.5μg/(kg·h)右美托咪定是最佳维持剂量。     

右美托咪定对骨巨细胞瘤细胞增殖、侵袭及迁移的影响

目的探究右美托咪定(dexmedetomidine,DEX)对骨巨细胞瘤细胞增殖、侵袭及迁移的影响.方法将细胞分Control、DEX 0.01、0.1及1μmol/L组.BrdU检测细胞增殖,transwell检测细胞侵袭,划痕实验检测细胞迁移,免疫印迹检测Ki67、PCNA、Bcl-2、VEGF、MMP-2、MMP-9、NF-κB p65及其下游蛋白表达水平、p38 MAPK表达及其下游蛋白磷酸化比值.结果与Control组比较,DEX 0.1、1μmol/L组BrdU阳性细胞百分比、侵袭细胞数、划痕闭合率和Ki67、PCNA、Bcl-2、VEGF、MMP-2、MMP-9表达水平显著降低,抑制p38 MAPK、NF-κB信号通路的激活.结论DEX通过调控p38 MAPK及NF-κB表达抑制骨巨细胞瘤细胞增殖、侵袭及迁移.     

The Effects of Anti-Adhesion Materials in Preventing Postoperative Adhesion in Abdominal Cavity (Anti-Adhesion Materials for Postoperative Adhesions)

Purpose The purpose of this study was to compare the effects of anti-adhesion materials in postoperative adhesions. Materials and Methods Rats were assigned to five groups: Group 1: Control. Group 2: chitin layers were used. Group 3: Na-hyaluronate / carboxymethylcellulose layers were used. Group 4: Na-hyaluronate gel was poured into the abdomen. Group 5: methylprednisolone was injected. The adhesion frequency and grade were scored according to Granat. Blood was taken for Hb, AST, BUN and albumin levels determination. Findings The adhesion frequencies (right and left) and grades were as follow in Groups; I: 82%, 91%, 2.63 ± 1.22; II: 8.3%, 25%, 0.58 ± 0.66; III: 17%, 33%, 1.08 ± 1.08; IV: 50%, 58%, 1.41 ± 1.44; V: 50%, 42%, 1.41 ± 1.50. The adhesion phase in all study groups was found significantly low compared to control group, p < 0.05. No difference was observed among serologic and hematological parameters in all groups. Conclusion All the materials used significantly lowered the adhesion frequency and grade.