Dexmedetomidine: a guide to its use for sedation in the US

Intravenous dexmedetomidine (Precedex(?)) provides both effective sedation in mechanically ventilated patients in an intensive care setting and effective procedural sedation. In these patient populations, it reduces the need for rescue sedation with intravenous propofol or intravenous midazolam and reduces opioid requirements. In addition, patients receiving dexmedetomidine are calm and easy to arouse and manage. Intravenous dexmedetomidine is generally well tolerated and is not associated with respiratory depression. Although the utilization of dexmedetomidine is associated with hypotension and bradycardia, both usually resolve without intervention.     

右美托咪定和咪达唑仑复合芬太尼对ICU术后机械通气患者镇静的影响

目的观察右美托咪定和咪达唑仑复合芬太尼用于ICU术后机械通气患者的镇静效果及安全性。方法选取150例ICU术后机械通气患者,采用信封法随机分为右美托咪定组和咪达唑仑组,每组75例,两组患者均给予芬太尼持续泵入。右美托咪定组采用右美托咪定0.2～0.6μg/(kg·h)持续泵入。咪达唑仑组采用0.08～0.10 mg/(kg·h)咪达唑仑持续泵入。采用Ramsay分级标准对两组患者镇静效果进行分级评分,观察两组患者的镇静效果。详细记录两组患者芬太尼用量、达到理想镇静所需的时间、停药后苏醒时间、镇静期间呼吸及循环系统功能的变化及其他不反应发生情况。结果右美托咪定组镇静满意率为97.33%,咪达唑仑组镇静满意率为96.00%,两组镇静满意率比较差异无统计学意义(P>0.05)。右美托咪定组芬太尼用量明显低于咪达唑仑组(P<0.05),达到理想镇静所需时间及停药后苏醒时间明显短于咪达唑仑组(P<0.05)。两组患者呼吸抑制、平均动脉压下降、SpO2下降及恶心发生率比较差异无统计学意义,但右美托咪定组谵妄发生率明显低于咪达唑仑组,两组比较差异有统计学意义(P<0.05)。结论右美托咪定复合芬太尼用于ICU术后机械通气患者的镇静治疗,镇静效果满意,可以达到理想镇静时间及易唤醒时间短,谵妄发生率低,可减少芬太尼用量,而且对患者呼吸及循环系统影响小,是一种较为理想的ICU镇静剂。     

Economic evaluation of dexmedetomidine relative to midazolam for sedation in the intensive care unit

Background

Dexmedetomidine is an α₂-receptor agonist administered by continuous infusion in the intensive care unit (ICU) for sedation of critically ill patients who are undergoing mechanical ventilation following intubation. Relative to ICU patients receiving midazolam (a γ-aminobutyric acid agonist) for sedation, those receiving dexmedetomidine spent less time on ventilation, had fewer episodes of delirium, and had a lower incidence of tachycardia and hypertension.

Objective

To assess the economic impact, in a Canadian context, of dexmedetomidine, relative to midazolam, for sedation in the ICU.

Methods

This economic evaluation was based on a cost–consequences analysis, from the perspective of the Canadian health care system. The selected time horizon was an ICU stay (maximum 30 days). Clinical data were obtained from a previously published prospective, randomized, double-blind trial comparing dexmedetomidine and midazolam. This evaluation considered the costs of the medications, mechanical ventilation, and delirium episodes, as well as costs associated with adverse events requiring an intervention. All costs were adjusted to 2010 and are reported in Canadian dollars.

Results

The average cost of the medication was higher for dexmedetomidine than midazolam ($1929.57 versus $180.10 per patient), but the average costs associated with mechanical ventilation and management of delirium were lower with dexmedetomidine than with midazolam ($2939 versus $4448 for ventilation; $2127 versus $3012 for delirium). The overall cost per patient was lower with dexmedetomidine than with midazolam ($7022 versus $7680). Deterministic sensitivity analysis confirmed the robustness of the difference.

Conclusions

The use of dexmedetomidine was, in most contexts, a more favourable strategy than the use of midazolam, in terms of clinical consequences and economic impact. Dexmedetomidine was less expensive than midazolam and was associated with lower occurrence of delirium and shorter duration of mechanical ventilation.     

Dexmedetomidine

Dexmedetomidine is a potent alpha2-adrenoceptor agonist with 8 times higher affinity for the alpha2-adrenoceptor than clonidine. Dexmedetomidine has shown sedative, analgesic and anxiolytic effects after intravenous administration to healthy volunteers or postsurgical patients in the intensive care unit. Dexmedetomidine produced a predictable haemodynamic decline (dose-dependently decreased arterial blood pressure and heart rate) in postsurgical patients coinciding with reductions in plasma catecholamines. In phase III clinical trials, dexmedetomidine 0.2 to 0.7 microg/kg/h produced clinically effective sedation and significantly reduced the analgesic requirements of postsurgical ventilated intensive care unit patients. There was no clinically apparent respiratory depression after cessation of assisted ventilation. Dexmedetomidine produced rapid and stable sedation in postsurgical ventilated patients while maintaining a high degree of patient rousability and anxiety reduction. Dexmedetomidine was well tolerated in phase III studies. The most frequently observed adverse events were hypotension, bradycardia and nausea.     

右美托咪定用于重症监护病房正颌外科术后留置气管插管患者的镇静

目的探讨右美托咪定用于重症监护病房(ICU)正颌外科术后留置气管插管患者镇静作用的有效性和安全性。方法 40例正颌外科术后入ICU留置气管插管患者,随机分为右美托咪定组和咪达唑仑组,每组20例。右美托咪定组予右美托咪定0.4μg·kg~(-1)·h~(-1)微泵静注,调整范围0.2～0.7μg·kg~(-1)·h~(-1);咪达唑仑组予咪达唑仑0.1 mg·kg~(-1)·h~(-1)微泵静注,调整范围0.05～0.2 mg·kg~(-1)·h~(-1)。采用Ramsay镇静深度评分系统,以Ramsay评分2～4分级为镇静目标,进行注射剂量的调整。记录用药前,用药后1、2、3、4、6、8、12、16 h的血压、心率、呼吸、脉搏血氧饱和度,观察镇静效果及不良反应。结果 2组患者用药后均可获得满意的镇静效果,Ramsay评分维持在2～4分级,良好耐受气管插管。2组用药前心率、平均动脉压(MAP)无显著差异(P>0.05),用药后心率和血压均有所下降,右美托咪定组各时点心率均低于咪达唑仑组(P<0.05),用药后1、2、3、4 h MAP低于咪达唑仑组(P<0.05)。2组呼吸频率、脉搏血氧饱和度无显著差异(P>0.05)。右美托咪定组需剂量调整的次数(2例1次)较咪达唑仑组(3例1次,4例2次)低。右美托咪定组发生2例心动过缓,予以阿托品治疗好转,2组均无严重不良反应发生。结论右美托咪定0.4μg·kg~(-1)·h~(-1)可安全用于ICU正颌外科术后留置气管插管患者的镇静,剂量调整发生率低于咪达唑仑。     

盐酸右美托咪定用于机械通气患者镇静的临床观察

目的探讨以盐酸右美托咪定为基础的镇静对重症监护病房（ICU）机械通气患者镇静效果的影响。方法 40例需机械通气的内科患者随机分为咪达唑仑组（A组）和盐酸右美托咪定＋咪达唑仑组（B组）,每组20例。记录镇静前的APACHEⅡ评分、Ramsay评分和PaO2/FiO2指标。记录镇静中4h、6h和12h的心率、血压和呼吸。镇静达12h时停止药物输注,每30min评估1次镇静深度,记录恢复时间,达到满意镇静深度的时间,镇静满意程度。结果 90%患者单独使用盐酸右美托咪定就能达到满意的镇静效果,如果联合使用咪达唑仑也只需要很低的剂量。比较咪达唑仑用量、调整泵速至镇静满意时间和恢复时间,B组均明显少于A组（P〈0.05）;B组的镇静满意程度明显高于A组（P〈0.05）。结论对机械通气的患者以盐酸右美托咪定为基础的镇静能提高咪达唑仑的镇静效果。     

Dexmedetomidine: sedation, analgesia and beyond

BACKGROUND: Dexmedetomidine is an alpha-2 adrenoreceptor agonist with sedative, analgesic and anxiolytic properties. Since its release in the US market in late 1999, it has gained remarkable attention in the adult, pediatric and geriatric populations, predominantly because of its minimal respiratory depression. However, beyond its well-known properties, dexmedetomidine has recently been investigated for its potential in many other clinical scenarios, including neuroprotection, cardioprotection and renoprotection, with promising results. OBJECTIVE: This review provides an outline of the current use of dexmedetomidine in adult and pediatric populations in several clinical settings, including operating room, intensive care unit, postsurgical patients and patients who need sedation and/or analgesia for invasive and noninvasive procedures. Our objectives were to examine the most up-to-date clinical evidence, describe the magnitude of effects, and shed some light on potential future applications. METHODS: Published, peer-reviewed studies, including preclinical data, were included in this review article. RESULTS/CONCLUSIONS: Dexmedetomidine is a novel agent with a wide safety margin and excellent sedative and moderate analgesic properties. Though its broadest use is currently in surgical and nonsurgical intensive care unit patients, dexmedetomidine appears to have promising future applications in the areas of neuroprotection, cardioprotection and renoprotection.     

右美托咪定用于机械通气患者镇静的疗效观察

目的观察右美托咪定对于机械通气患者镇静的疗效。方法将2012年ICU住院机械通气患者60例按随机、对照原则分为右美托咪定组(D)和丙泊酚组(P),分别记录两组患者用药前后Ramsay镇静评分、心率情况及用药前后血压的控制情况,对数据进行统计学分析。结果两组患者不同时间段Ramsay镇静评分、心率以及用药前后血压控制的差异具有统计学意义。结论右美托咪定的镇静效果好于丙泊酚,且血流动力学稳定。     

右美托咪定在重症监护患者镇静中的临床观察

目的研究右美托咪定在重症监护患者镇静中的效果及安全性。方法将2011年1月至2012年4月本院重症监护病房收治的需要镇静的60例患者随机分为右美托咪定组(30例)和咪达唑仑组(30例)。调整药物剂量使Ramsay评分控制在3～4分,分别记录镇静起效的时间、停用镇静药物后苏醒时间、谵妄发生率、机械通气时间、ICU留住时间及不良反应的发生率。结果与咪达唑仑组比较,右美托咪定组起效迅速,唤醒所需时间短,谵妄发生率低,治疗剂量内不诱发临床意义的呼吸抑制。两组患者的机械通气时间,ICU留住时间,血流动力学影响发生率相似。结论右美托咪定在重症监护病房是一种较为理想的镇静剂。     

Clinical pharmacokinetic monitoring of midazolam in critically ill patients

Midazolam is a commonly used sedative in critically ill, mechanically ventilated patients in intensive care unit (ICU) settings worldwide. We used a nine-step decision-making algorithm to determine whether therapeutic monitoring of midazolam in the ICU is warranted. Midazolam has a higher clearance and shorter half-life than other benzodiazepines, and prolonged sedation is achieved with continuous infusion. There appears to be very good correlation between plasma concentrations of both midazolam and its active metabolite, alpha1-hydroxymidazolam, and the degree of sedation. However, due to high interpatient variability, it is not possible to predict the level of sedation in any given individual based on plasma concentration of midazolam or its metabolites. Moreover, no simple and practical assay is available to quantitate midazolam plasma concentrations in the acute ICU setting. Many scales are available to assess the sedative effects of midazolam. Because the plasma concentration of midazolam required to achieve a constant level of sedation is highly variable, it is usually more prudent for the clinician to monitor for sedation with a validated clinical scale than by plasma concentrations alone. Various physiologic parameters, including age-related effects, compromised renal function, and liver dysfunction affect the pharmacokinetics of midazolam and alpha1-hydroxymidazolam. Although routine drug monitoring for all critically ill patients receiving midazolam is not recommended, this practice is likely beneficial in patients with neurologic damage in whom sedation cannot be assessed and in patients who have renal failure with a prolonged time to awakening.     

右美托咪定、咪达唑仑对择期手术病人认知功能的影响

目的 探讨右美托咪定、咪达唑仑对择期手术病人认知功能的影响.方法 选取行择期手术的区域麻醉病人90例,按数字均分法随机分成右美托咪定组、咪达唑仑组及对照组,每组30例.三组病人于麻醉前20 min分别给予静脉泵注右美托咪定、静注咪达唑仑和静注生理盐水.观察三组病人用药前后焦虑视觉模拟/焦虑状态问卷评分、警觉/镇静评分;比较术后24 h对水果图片的记忆情况.结果 组内用药前后比较,对照组用药后10 min脑电双频谱指数为(92.5±1.6),焦虑视觉模拟/焦虑问卷评分为(1.8±0.3)分,警觉/镇静评分为(4.9±0.1)分;右美托咪定组用药后10 min脑电双频谱指数为(86.1±2.4),焦虑视觉模拟/焦虑问卷评分为(0.2±0.4)分,警觉/镇静评分为(2.5±0.7);咪达唑仑组用药后10 min脑电双频谱指数为(87.3±1.3),焦虑视觉模拟/焦虑问卷评分为(0.4±0.6)分,警觉/镇静评分为(2.6±1.0)分;与对照组比较,右美托咪定组与咪达唑仑组病人用药后10 min脑电双频谱指数、焦虑视觉模拟/焦虑问卷评分、警觉/镇静评分较低(P<0.05).与咪达唑仑组相比,右美托咪定组用药后记忆正确率较高(P<0.05).结论 右美托咪定及咪达唑仑可明显改善病人麻醉前紧张焦虑情绪,提高记忆力,右美托咪定对病人的短期记忆功能影响小.     

右美托咪啶对重症治疗室患者镇静效果研究

目的观察盐酸右美托咪啶对重症治疗室患者的镇静效果及安全性。方法将50例重症创伤而需要机械通气的ICU患者随机分为两组;A咪达唑仑组（n=25）和B盐酸右美托咪啶组（n=25）。记录镇静前的APACHEⅡ评分、Ramsay评分。分别观察镇静中4、8、12h的心率,平均动脉血压,呼吸频率,氧饱和度等基本生命体征及用药后两药起效时间,恢复时间,镇静满意度,Ramsay评分和谵妄发生率等。结果B组血压、心率有明显下降但停药后马上恢复,而对呼吸氧饱和度影响均小于A组,安全性良好;且比较单纯咪达唑仑用量、调整泵速至镇静满意时间、镇静满意程度、恢复时间等,B组均明显少于A组（P〈0．05）。结论右美托咪啶用于重症治疗室患者镇静安全性好,能够提供良好的镇静。     

右美托咪定复合小剂量咪唑安定在慢诱导麻醉中对镇静程度的影响

目的比较右美托咪定(DEX)复合小剂量咪唑安定与单纯咪唑安定(MDZ)在慢诱导气管插管时对镇静程度的影响。方法 40例择期行气管插管全麻手术患者随机分为右美托咪定复合小剂量咪唑安定组(DEX-MDZ)和单用咪唑安定组(MDZ),每组20例。MDZ组静脉注射MDZ 0.05 mg/kg,增加量0.05 mg/kg,至警觉/镇静(OAA/S)评分2～4分;MDZ-DEX组静脉注射MDZ 0.02 mg/kg,然后于10 min内静注DEX负荷量1μg/kg,再持续泵注0.1μg/(kg.h)逐渐增量至0.7μg/(kg.h),直至镇静评分2～4分。记录重要时间点患者的血压(BP)、心率(HR)、OAA/S评分及反应;记录术后患者对慢诱导气管插管过程的记忆程度及满意度。结果两组患者BP、HR比较差异无统计学意义;DEX-MDZ患者在慢诱导气管插管期间较MDZ组更安静更配合,不良反应少;DEX-MDZ组患者慢诱导气管插管更舒适。结论右美托咪定复合小剂量咪唑安定较单用咪唑安定更适合于慢诱导气管插管。     

Propofol infusion for sedation in the intensive care unit: preliminary report.

Propofol (2,6,di-isopropylphenol) was given by continuous intravenous infusion to provide sedation after cardiac surgery in 30 patients and its effects compared with those of midazolam given to a further 30 patients. Propofol infusion allowed rapid and accurate control of the level of sedation, which was satisfactory for longer than with midazolam. Patients given propofol recovered significantly more rapidly from their sedation once they had fulfilled the criteria for weaning from artificial ventilation and as a result spent a significantly shorter time attached to a ventilator. There were no serious complications in either group. Both medical and nursing staff considered the propofol infusion to be superior to midazolam in these patients. These findings suggest that propofol is a suitable replacement for etomidate and alphaxalone-alphadolone for sedating patients receiving intensive care.     

右美托咪定在硬膜外麻醉下患者镇静中的效果观察

目的：观察右美托咪定在硬膜外麻醉下患者镇静中的效果,以探索更安全有效的临床麻醉辅助镇静方法。方法选择硬膜外麻醉下行下腹部手术的患者60例,随机均分为实验组和对照组,实验组给予静脉注射右美托咪定,对照组给予静脉注射咪达唑仑。硬膜外麻醉平面达到手术要求后进行镇静,根据镇静状态评分评估镇静深度,镇静目标值为镇静评分3～4分。监测和记录患者镇静药物使用前（T1）、镇静药物使用后25 min（T2）、术毕时（T3）以及术后10 min（T4）时的MAP和HR;观察患者术中不良反应的发生率,记录达到镇静目标的时间,评估术后24 h患者对手术过程的遗忘程度。结果对照组达到镇静目标时间明显短于实验组（P〈0.01）;实验组患者T2、T3时MAP低于对照组,HR慢于对照组（P〈0.05或P〈0.01）;对照组烦躁、呼吸抑制和对手术过程的遗忘程度达到2～3级的发生率明显高于实验组（P〈0.01）。结论硬膜外麻醉中静脉给予咪达唑仑能提供有效的镇静,但易出现烦躁、呼吸抑制、遗忘程度高,而静脉注射右美托咪定辅助镇静更安全舒适,可有效避免患者出现紧张和焦虑情绪,利于手术顺利进行。     

Spotlight on remifentanil: its analgesic and sedative use in the intensive care unit

Remifentanil (Ultivatrade), a 4-anilidopiperidine derivative of fentanyl, is an ultra-short-acting micro-opioid receptor agonist indicated to provide analgesia and sedation in mechanically ventilated intensive care unit (ICU) patients. Analgesia-based sedation with remifentanil is a useful option for mechanically ventilated patients in the ICU setting. Its unique properties (e.g. organ-independent metabolism, lack of accumulation, rapid offset of action) set it apart from other opioid agents. Remifentanil is at least as effective as comparator opioids such as fentanyl, morphine and sufentanil in providing pain relief and sedation in mechanically ventilated ICU patients. Moreover, it allows fast and predictable extubation, as well as being associated with a shorter duration of mechanical ventilation and quicker ICU discharge than comparators in some studies. In addition, remifentanil is generally well tolerated in this patient population. Thus, remifentanil is a welcome addition to the currently available pharmacological agents employed in the management of mechanically ventilated ICU patients.     

Remifentanil : a review of its analgesic and sedative use in the intensive care unit

Remifentanil (Ultiva), a 4-anilidopiperidine derivative of fentanyl, is an ultra-short-acting micro-opioid receptor agonist indicated to provide analgesia and sedation in mechanically ventilated intensive care unit (ICU) patients.Analgesia-based sedation with remifentanil is a useful option for mechanically ventilated patients in the ICU setting. Its unique properties (e.g. organ-independent metabolism, lack of accumulation, rapid offset of action) set it apart from other opioid agents. Remifentanil is at least as effective as comparator opioids such as fentanyl, morphine and sufentanil in providing pain relief and sedation in mechanically ventilated ICU patients. Moreover, it allows fast and predictable extubation, as well as being associated with a shorter duration of mechanical ventilation and quicker ICU discharge than comparators in some studies. In addition, remifentanil is generally well tolerated in this patient population. Thus, remifentanil is a welcome addition to the currently available pharmacological agents employed in the management of mechanically ventilated ICU patients.     

丙泊酚与咪唑安定在机械通气患者镇静中的应用

目的 对比观察丙泊酚和咪唑安定对机械通气患者的镇静效果和安全性.方法 将200例行机械通气的患者按入院顺序随机分为2组.丙泊酚组100例,采用丙泊酚镇静治疗;咪唑安定组100例,采用咪唑安定镇静治疗.两组患者均先给予镇静诱导,再给予微量泵持续滴注,采用Ramsay分级标准对两组患者镇静效果进行评估,其中Ⅰ级为镇静不够,Ⅱ~Ⅴ级为最佳镇静,Ⅵ级为镇静过度;观察患者用药期间呼吸频率、心率、平均动脉压及血气指标的变化,观察记录两组患者达到镇静目标时间、停用镇静剂至苏醒时间及拔管时间.同时比较两组患者镇静总费用及ICU住院时间.结果 丙泊酚组95例（95.00%）达最佳镇静程度,咪唑安定组93例（93.00%）达最佳镇静程度,两组镇静效果比较差异无统计学意义（P〉0.05）.丙泊酚组有4例（0.04%）发生平均动脉压下降,在停药后15 min左右循环稳定;咪唑安定组未见明显循环、呼吸系统等指标变化.丙泊酚组达到镇静目标时间、停用镇静剂至苏醒时间及拔管时间分别为（25.3±4.5）s、（23.4±4.5）min、（2.9±0.4）h,咪唑安定组分别为（45.5±6.7）s、（56.4±10.3）min、（6.2±1.2）h,前者均明显短于后者（P〈0.05）.丙泊酚组镇静费用明显高于咪唑安定组（P〈0.05）,两组ICU住院时间比较差异无统计学意义（P〉0.05）.结论 丙泊酚与咪唑安定均有显著的镇静效果,但丙泊酚起效快,咪唑安定镇静作用持续时间长,且丙泊酚价格相对较贵,临床上可根据实际需要合理选择.     

Addition of dexmedetomidine to standard sedation regimens after cardiac surgery: an outcomes analysis

STUDY OBJECTIVE: To characterize inpatient use of intravenous sedatives in the real-world setting, and to evaluate clinical and economic outcomes when dexmedetomidine was used with midazolam and propofol for select cardiovascular procedures. DESIGN: 12-month retrospective analysis. DATA SOURCE: An administrative claims database of operational data from a nationally representative sample of 250 medical and surgical hospitals. PATIENTS: Patients who received midazolam plus propofol (9996 patients) or dexmedetomidine, midazolam, plus propofol (356 patients) after cardiac valve or vessel surgery. MEASUREMENTS AND MAIN RESULTS: The source of patient demographics (e.g., age, sex, Charlson Comorbidity Index) and outcomes (e.g., charges, length of stay, mortality rate) was the hospital billing claim form. Patients in the dexmedetomidine-midazolam-propofol cohort tended to be younger and male and to have fewer comorbidities than those midazolam-propofol cohort. The primary outcomes for the three-drug cohort showed significant reductions in total charges/patient (approximately $18,000, p<0.05), total hospital length of stay (0.6 days, p<0.0001), days in the intensive care unit or cardiac care unit (3.87 days, p<0.0001), and mortality (2%, p=0.0142). Although pharmacy charges were higher (approximately $4000/patient), lower charges for the intensive care or cardiac care unit, operating room, room and board, and respiratory services were observed in the dexmedetomidinemidazolam-propofol cohort compared with the two-drug cohort. Also, mechanical ventilation was shorter by approximately 0.5 day in the three-drug cohort (p<0.01). CONCLUSION: These initial findings of a real-world assessment of dexmedetomidine use with other agents suggest favorable clinical and economic outcomes. Further research through randomized clinical trials of dexmedetomidine is warranted to better understand its optimum patient population, dosage, and the causality of the results, and to confirm the potential clinical and economic benefits observed in our patients.     

右美托咪定辅助全身麻醉患者的镇静及全身麻醉药物的节俭作用

目的探讨右美托咪定辅助全身麻醉患者的镇静及全身麻醉药物的节俭作用。方法对本院2012年2月～2013年1月收治的全身麻醉患者的临床治疗病例进行抽样,将40例全身麻醉患者按照抽签法随机分为对照组与观察组,每组各20例。对照组采用氯化钠注射液静脉注射治疗,然后使用丙泊酚进行全身麻醉诱导,观察组采用右美托咪定注射液静脉注射治疗。结果两组全身麻醉患者经过镇静治疗后的镇静效果及全身麻醉药物的使用情况差异有统计学意义（P〈0．05）。结论全身麻醉患者采用右美托咪定辅助全身麻醉的镇静及全身麻醉药物的使用量明显低于传统镇静治疗药物的使用情况,具有显著的节俭作用,能够有效缓解全身麻醉患者的痛苦。值得临床推广应用。