Intraoperative dexmedetomidine to prevent postoperative delirium: in search of the magic bullet.
Intraoperative dexmedetomidine to prevent postoperative delirium: in search of the magic bullet.
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术中右美托咪定预防术后谵妄：寻找灵丹妙药。
DOI：
10.1007/s12630-019-01300-3
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Whitlock,ElizabethL
中科院分区：
文献类型：
--
作者：
Donovan,AnneL;Whitlock,ElizabethL
由于筛查、诊断和管理过程的时间和资源密集性，躁动和谵妄是住院医疗机构质量改进的重要目标。在一般患者人群中，没有预防性药物治疗在预防谵妄方面显示出广泛的有效性。几项研究未能找到预防谵妄的神奇药物--氯胺酮和氟哌啶醇最近也没能给人留下深刻印象。1，2右美托咪定是一种有吸引力的药理学选择，因为它在改变几种已知的谵妄因素方面具有生物学可接受性，包括减弱炎症介质和儿茶酚胺，提供镇痛，减少谵妄诱导药物，促进自然睡眠-觉醒周期，以及其他合理的神经保护机制。关于术中右美托咪定给药后术后谵妄的数据相互矛盾，其可能发挥作用的多种机制促使在各种人群中采用各种剂量和给药方案进行试验。如果对接受常规治疗的不同患者组在术中提供右美托咪定无效，3在高度协议化、同质化的环境中使用右美托咪定是否会显示效果？在这个月的杂志上，Kim等报道了一项双盲随机疗效试验的结果，该试验对143名接受胸腔镜肺切除手术的患者进行了研究。患者随机接受七氟烷+右美托咪定0.5 μ g 4 kg-14 hr-1（在麻醉诱导前即刻开始，持续至手术结束）或七氟烷+安慰剂全身麻醉。滴定麻醉深度，以维持脑电双频指数为45±5，血压在基线的20%以内。在拔管后1分钟，然后每15分钟一次，直到从麻醉后恢复单元（PACU）出院，使用Riker镇静躁动量表测量紧急躁动。然后在PACU出院后开始使用意识模糊评估方法（CAM）或CAM-ICU对患者进行术后谵妄评估，重症监护室（ICU）患者每4小时一次，病房患者每天3次，直至术后第3天。作者显示右美托咪定组的苏醒期躁动减少（13% vs 35%;相对风险，0.38; 95%置信区间（CI），0.18 - 0.79; P= 0.011），而过度镇静没有相应增加，但令人惊讶的是，术后谵妄没有差异（25% vs 25%）。在ICU环境中基于特定镇静策略比较谵妄和其他不良神经认知结局发生率的研究发现，与苯二氮卓类5、6和丙泊酚相比，使用右美托咪定具有显著获益。7毫不奇怪，焦点已经转向研究术中使用右美托咪定是否也可以证明是有效的谵妄预防措施。结果是令人鼓舞的重点手术组，例如，在心脏8和骨科9，10手术，其中重大组织创伤是预期的。在最近的一项荟萃分析中，Wu等8发现，
Agitation and delirium are important targets for quality improvement across inpatient healthcare settings because of the time-and resource-intensive nature of the screening, diagnosis, and management processes. In the general patient population, no prophylactic pharmacologic treatment has shown widespread effectiveness in preventing delirium. Several studies have failed to find a magic pharmacologic bullet for preventing delirium—ketamine and haloperidol have recently failed to impress. 1, 2 Dexmedetomidine is an attractive pharmacologic option because of its biologic plausibility in modifying several known contributors to delirium, including attenuating inflammatory mediators and catecholamines, providing analgesia, reducing deliriuminducing medications, and promoting natural sleep-wake cycles, among other plausible neuroprotective mechanisms. Data on postoperative delirium after intraoperative dexmedetomidine administration are conflicting, and the diverse mechanisms by which it may act have prompted trials in a variety of populations, with a variety of doses and administration schema. If providing dexmedetomidine intraoperatively to a diverse group of patients otherwise receiving usual care has not been effective, 3 could its use in a highly protocolized, homogenous setting reveal an effect? In this month’s edition of the Journal, Kim et al. 4 report the results of a double-blind randomized efficacy trial of143 patients undergoing thoracoscopic lung resection surgery. Patients were randomized to receive general anesthesia with either sevoflurane plus dexmedetomidine at 0.5 μg4kg-14hr-1 (started immediately prior to anesthesia induction and continued until the end of surgery) or sevoflurane plus placebo. Anesthetic depth was titrated to maintain a bispectral index of 45±5 and a blood pressure within 20% of the baseline. Emergence agitation was measured with the Riker sedation agitation scale at one minute after extubation, then every 15 min until discharge from the postanesthesia recovery unit (PACU). Patients were then assessed for postoperative delirium with either the Confusion Assessment Method (CAM) or CAM-ICU starting after PACU discharge and every four hours for intensive care unit (ICU) patients or three times daily for ward patients until postoperative day 3. The authors showed a decrease in emergence agitation in the dexmedetomidine group (13% vs 35%; relative risk, 0.38; 95% confidence interval (CI), 0.18 to 0.79; P= 0.011) without a corresponding increase in oversedation but, disappointingly, no difference in postoperative delirium (25% vs 25%).There were reasons for optimism. Studies comparing the incidence of delirium and other adverse neurocognitive outcomes based on particular sedation strategies in the ICU setting have found significant benefit with use of dexmedetomidine compared with benzodiazepines 5, 6 and propofol. 7 Not surprisingly, focus has turned to investigation of whether intraoperative use of dexmedetomidine may also prove effective as a delirium prevention measure. Results were encouraging in focused surgical groups—for example, in cardiac 8 and orthopedic 9, 10 surgery—where significant tissue trauma is expected. In a recent meta-analysis, Wu et al. 8 found a significant reduction in postoperative delirium with