Sun Shenghui, Sun Defeng, Yang Lin, Han Jun, Liu Ruochuan, Wang Lijie
Affiliated High School of Liaoning Normal University, Dalian, People's Republic of China.
Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, No.222 ZhongshanRoad, Xigang District, Dalian, 116011, Liaoning, People's Republic of China.
BMC Anesthesiol. 2017 Jun 9;17(1):75. doi: 10.1186/s12871-017-0367-6.
Postoperative cognitive dysfunction (POCD), common in elderly patients, is thought to be closely associated with intraoperative instability of hemodynamics and excessive excretion of tumor necrosis factor-α (TNF-α). Methoxamine is a blood-pressure increasing drug commonly used for maintaining intraoperative hemodynamics. Methoxamine potentially promotes TNF-α expression, leading to an increased risk of POCD. This study aimed to investigate the dose-dependent effect of methoxamine on the incidence of early POCD and blood TNF-α level.
This single-center prospective double-blind controlled clinical trial included a total of 300 adult patients (75-90 years old, American Society of Anesthesiologists class II-III) who underwent unilateral hip-joint replacement surgery under epidural anesthesia. Patients were randomly divided into three methoxamine groups (M1, M2, and M3), and one control group (n = 75 per group). During surgery, M1, M2, and M3 patients received intravenous infusion of methoxamine at 2, 3, or 4 μg·kg·min, respectively; the control group received saline of same volume at the same infusion rate. All patients received standard transfusion to maintain stable circulation. Hemodynamics, cardiovascular events, and serum TNF-α levels were monitored. Mini Mental State Examination was performed both before and after surgery to diagnose POCD.
The primary outcome of this study was the incidence of POCD, which was higher in the M3 group (18.7%) than in the control group (5.3%), the M1 group (6.7%), or the M2 group (6.7%) (all P < 0.05). The secondary outcomes were the postoperative blood TNF-α level and intraoperative hemodynamic parameters. The postoperative TNF-α level was found to be higher than baseline in all groups and was highest in M3 patients (P < 0.05). The intraoperative hemodynamic parameters showed improved stability in the M1 and M2 groups compared with the control group. However, in the M3 group, abnormally increased intraoperative blood pressure, cardiac output, and systolic stroke volume were observed.
Intravenous infusion of methoxamine at 2-3 μg·kg·min can maintain stable hemodynamics in elderly patients during epidural anesthesia for hip-joint replacement surgery, without increasing the incidence of POCD. Increasing the dose to 4 μg·kg·min provided no further advantages but induced adverse effects on the intraoperative hemodynamics.
Chinese Clinical Trial Register (Unique identifier: ChiCTR-INR-15007607 , retrospectively registered 18 Dec 2015).
术后认知功能障碍（POCD）在老年患者中很常见，被认为与术中血流动力学不稳定及肿瘤坏死因子-α（TNF-α）过度分泌密切相关。甲氧明是一种常用于维持术中血流动力学的升压药物。甲氧明可能会促进TNF-α表达，从而增加POCD的风险。本研究旨在探讨甲氧明对早期POCD发生率和血液TNF-α水平的剂量依赖性影响。
这项单中心前瞻性双盲对照临床试验共纳入300例成年患者（75 - 90岁，美国麻醉医师协会分级II - III级），这些患者在硬膜外麻醉下行单侧髋关节置换手术。患者被随机分为三个甲氧明组（M1、M2和M3）和一个对照组（每组n = 75）。手术过程中，M1、M2和M3组患者分别以2、3或4μg·kg·min的速度静脉输注甲氧明；对照组以相同的输注速度输注相同体积的生理盐水。所有患者均接受标准输血以维持循环稳定。监测血流动力学、心血管事件及血清TNF-α水平。术前和术后均进行简易精神状态检查以诊断POCD。
本研究的主要结局是POCD的发生率，M3组（18.7%）高于对照组（5.3%）、M1组（6.7%）和M2组（6.7%）（所有P < 0.05）。次要结局是术后血液TNF-α水平和术中血流动力学参数。发现所有组术后TNF-α水平均高于基线，且M3组患者最高（P < 0.05）。与对照组相比，M1组和M2组术中血流动力学参数显示稳定性有所改善。然而，在M3组中，观察到术中血压、心输出量和收缩期每搏量异常增加。
在髋关节置换手术硬膜外麻醉期间，以2 - 3μg·kg·min静脉输注甲氧明可维持老年患者血流动力学稳定，且不增加POCD的发生率。将剂量增加至4μg·kg·min并无进一步益处，反而会对术中血流动力学产生不良影响。
中国临床试验注册中心（唯一标识符：ChiCTR-INR-15007607，2015年12月18日追溯注册）
