文章信息
- 范蒙蒙, 马晶茹
- FAN Mengmeng, MA Jingru
- 急性冠状动脉综合征患者经皮冠状动脉介入治疗术后谵妄的回顾性分析
- Retrospective Analysis of Delirium after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome
- 中国医科大学学报, 2019, 48(6): 519-524
- Journal of China Medical University, 2019, 48(6): 519-524
-
文章历史
- 收稿日期:2018-09-18
- 网络出版时间:2019-5-27 13:28
2. 沈阳医学院附属第二医院心血管内科, 沈阳 110035
2. Department of Cardiology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang 110035, China
近年来,随着经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)的广泛开展,PCI术后的并发症日益引起广泛关注。谵妄是急性发作的短暂精神障碍,特征为波动性意识水平降低、认知功能紊乱和睡眠-觉醒周期紊乱[1]。由于心内科医生对谵妄的认知不足,在临床上极易漏诊、误诊。谵妄的发生不仅延长住院时间,增加住院费用,消耗医疗成本,还与死亡率密切相关[2]。本研究拟回顾性分析沈阳医学院附属第二医院皇姑院区心血管内科2013年4月至2017年4月的相关资料,调查急性冠状动脉综合征(acute coronary syndrome,ACS)患者PCI术后谵妄的发生率,分析影响PCI术后谵妄的危险因素,从众多因素中筛选出相对可控因素,以便对可控因素采取适当的干预措施,降低谵妄的发生率。
1 材料与方法 1.1 研究对象选择2013年4月至2017年4月沈阳医学院附属第二医院皇姑院区心血管内科PCI术后的ACS患者878例。纳入标准:(1)行介入手术的ACS患者,ST段抬高型心肌梗死诊断参考2013年美国心脏病学会基金会/美国心脏协会(ACCF/AHA)制定的指南[3],非ST段抬高型心肌梗死和不稳定型心绞痛诊断参考2014年美国心脏协会/美国心脏病学会(AHA/ACC)制定的指南[4];(2)术前无精神障碍、痴呆、癫痫等病史;(3)近期未使用可显著影响精神活动的药物;(4)术前可正常交流。排除标准:(1)PCI术前发生谵妄;(2)合并脑外伤、精神病、痴呆、智力低下或其他神经疾病;(3)术前不能正常交流。
1.2 研究方法 1.2.1病历资料收集:收集患者的性别、年龄、诊断、体质量指数、既往史(高血压病、糖尿病、房颤、脑血管病、贫血等)、个人史等;冠状动脉病变程度;PCI手术时间、造影剂种类、造影剂用量;实验室检查资料(尿素、肌酐、离子)等,左心室射血分数(left ventricular ejection fraction,LVEF)。
1.2.2谵妄评估:由2名专科医师对PCI术后1周内的ACS患者进行谵妄评估,如2名医师评估结果不一致,则由第三名医师进行评估。谵妄的诊断标准参照美国精神疾病协会《精神疾病诊断和统计手册第五版》(Diagnostic and Statistical Manual-Ⅴ,DSM-Ⅴ)制定的标准[5]。
1.3 统计学分析采用SPSS 22.0软件进行统计分析。计量资料采用t检验或秩和检验,计数资料采用χ2检验,将单因素分析具有统计学差异的自变量代入二元logistic回归分析模型,得出PCI术后谵妄的独立危险因素。P < 0.05为差异有统计学意义。
2 结果 2.1 ACS患者PCI术后谵妄的临床特征纳入研究的878例患者中,15例在PCI术后1周内出现谵妄,发生率1.71%。15例患者均为急性起病,经过积极支持对症治疗后均康复出院,见表 1。
Case | Gender | Age (year) |
Diagnosis | Risk factors | Type and dosage of contrast agent(mL) | Time of delirium after PCI(h) | Clinical manifestations | Duration of delirium symptoms(h) | Coronary artery lesions(vessel) |
1 | Male | 80 | NSTEMI | Hypertension,diabetes,anemia,smoking,drinking | Iopromide,100 | 7.5 | Restlessness,irrelevant answer | 7.5 | 3 |
2 | Female | 77 | UA | Sleep disorders | Iohexol,270 | 38.0 | Indifferent,inattention | 7.5 | 1 |
3 | Female | 85 | STEMI | Hypertension,diabetes,hypoxemia,atrial Fibrillation,cardiac insufficiency | Iopromide,170 | 16.5 | Restlessness,self-removal of trocar,unconsciousness,drowsiness | 72.0 | 1 |
4 | Male | 80 | NSTEMI | Hypertension | Iodixanol,90 | 1.0 | Restlessness,irritability | 2.0 | 2 |
5 | Female | 88 | NSTEMI | Hypertension,cardiac insufficiency | Iodixanol,110 | 12.5 | Restlessness,excited | 8.0 | 2 |
6 | Female | 86 | STEMI | Hypertension,diabetes,hyperlipidemia,previous cerebrovascular disease | Iodixanol,120 | 22.5 | Irrelevant answer,drowsiness | 12.0 | 1 |
7 | Male | 72 | STEMI | Hypertension,diabetes,previous cerebrovascular disease,sleep disorders | Iohexol,220 | 16.0 | Restlessness,noisy | 5.0 | 3 |
8 | Female | 73 | UA | Diabetes,hyperlipidemia | Iohexol,330 | 11.5 | Transient amnesia,visual changes,indifferent | 12.0 | 1 |
9 | Male | 69 | UA | Hypertension,diabetes,previous cerebrovascular disease | Ioversol,160 | Unknown | Excited,irritability | Unknown | 2 |
10 | Male | 74 | NSTEMI | Hypertension,diabetes,hyperlipidemia | Iopromide,120 | Unknown | Restlessness,irritability | Unknown | 2 |
11 | Male | 76 | NSTEMI | hypertension,Hyperlipidemia,cardiac insufficiency | Iopromide,180 | Unknown | Nonsense,noisy | Unknown | 3 |
12 | Female | 79 | UA | Hypertension,sleep disorders | Iohexol,150 | 16.0 | Drowsiness,unclear articulation,active thinking,nonsense | 7.0 | 1 |
13 | Male | 74 | NSTEMI | Diabetes | Iohexol,120 | 3.0 | Restlessness,irrelevant answer | 4.0 | 1 |
14 | Male | 80 | UA | Hypertension,sleep disorders | Ioversol,130 | 8.5 | Restlessness,excited,trance,irrelevant answer | 1.0 | 1 |
15 | Male | 85 | NSTEMI | Atrial fibrillation,cardiac insufficiency,smoking,sleep disorder,previous cerebrovascular disease | Ioversol,180 | Unknown | Excited,nonsense,inattention | Unknown | 3 |
UA,unstable angina;STEMI,ST-segment elevation myocardial infarction;NSTEMI,non-ST-segment elevation myocardial infarction. |
2.2 ACS患者PCI术后谵妄的相关因素
单因素分析显示,谵妄组患者与对照组患者(未出现谵妄)的年龄、睡眠障碍、肾小球滤过率(estimated glomerular filtration rate,eGFR)、冠状动脉病变程度具有统计学差异,见表 2。
Risk factors | Delirium group(n = 15) | Control group(n = 863) | t/Z/χ2 | P |
Age(year) | 78.47±5.66 | 64.23±10.45 | -4.992 | 0.000 |
BMI(kg/m2) | 26.29±3.25 | 25.07±3.40 | -1.325 | 0.183 |
eGFR [mL/(min·1.73 m2)] | 65.60±22.62 | 89.52±25.09 | -3.433 | 0.001 |
K+(mmol/L) | 4.14±0.37 | 4.04±0.36 | -1.366 | 0.172 |
Na+(mmol/L) | 140.87±3.94 | 141.41±2.79 | -0.819 | 0.413 |
Cl-(mmol/L) | 102.60±5.79 | 103.21±3.10 | -0.031 | 0.975 |
Duration of PCI surgery(min) | 79.67±20.91 | 71.37±19.31 | -1.640 | 0.101 |
Dosage of contrast agent(mL) | 163.33±66.62 | 146.15±46.69 | -0.715 | 0.475 |
Lvef(%) | 60.75±6.54 | 61.09±7.27 | -0.269 | 0.788 |
Duration of hospital stay(d) | 14.80±4.04 | 13.26±4.16 | -1.575 | 0.115 |
Gender [n (%)] | 0.195 | 0.659 | ||
Male | 9(60.0) | 565(65.5) | ||
Female | 6(40.0) | 298(34.5) | ||
Diagnosis [n (%)] | 2.142 | 0.143 | ||
UA | 5(33.3) | 452(52.4) | ||
AMI | 10(66.7) | 411(47.6) | ||
Smoking [n (%)] | 0.187 | 0.666 | ||
No | 13(86.7) | 679(78.7) | ||
Yes | 2(13.3) | 184(21.3) | ||
Drinking [n (%)] | 0.089 | 0.765 | ||
No | 14(93.3) | 754(87.4) | ||
Yes | 1(6.7) | 109(12.6) | ||
Hypoxemia [n (%)] | 0.013 | 0.909 | ||
No | 14(93.3) | 839(97.2) | ||
Yes | 1(6.7) | 24(2.8) | ||
Hypertension [n (%)] | 0.923 | 0.337 | ||
No | 4(26.7) | 366(42.4) | ||
Yes | 11(73.3) | 497(57.6) | ||
Diabetes [n (%)] | 3.480 | 0.062 | ||
No | 7(46.7) | 597(69.2) | ||
Yes | 8(53.3) | 266(30.8) | ||
Hyperlipidemia [n (%)] | 0.001 | 0.972 | ||
No | 11(73.3) | 600(69.5) | ||
Yes | 4(26.7) | 263(30.5) | ||
Previous cerebrovascular disease [n (%)] | 1.626 | 0.202 | ||
No | 11(73.3) | 757(87.7) | ||
Yes | 4(26.7) | 106(12.3) | ||
Sleep disorders [n (%)] | 13.677 | < 0.001 | ||
No | 10(66.7) | 799(92.6) | ||
Yes | 5(33.3) | 64(7.4) | ||
Atrial fibrillation [n (%)] | 1.040 | 0.308 | ||
No | 13(86.7) | 825(95.6) | ||
Yes | 2(13.3) | 38(4.4) | ||
Anemia [n (%)] | < 0.001 | 1.000 | ||
No | 14(93.3) | 822(95.2) | ||
Yes | 1(6.7) | 41(4.8) | ||
Type of contrast agent [n (%)] | 3.855 | 0.050 | ||
Hypotonic | 13(80.0) | 819(94.9) | ||
Isotonic | 2(20.0) | 44(5.1) | ||
Cardiac insufficiency [n (%)] | 2.988 | 0.083 | ||
No | 11(73.3) | 779(90.3) | ||
Yes | 4(26.7) | 84(9.7) | ||
Coronary artery lesions [n (%)] | 13.364 | < 0.001 | ||
Single vessel | 7(46.7) | 716(83.0) | ||
Multivessel | 8(53.3) | 147(17.0) | ||
UA,unstable angina;AMI,acute myocardial infarction;LVEF,left ventricular ejection fraction;BMI,body mass index. |
2.3 影响ACS患者PCI术后谵妄的二元logistic回归分析
将单因素分析具有统计学差异的自变量代入二元logistic回归分析模型,结果显示,年龄、睡眠障碍、冠状动脉病变程度为ACS患者PCI术后谵妄的独立危险因素,见表 3。
Risk factors | B | SE | Wald | P | Exp(B) | 95%CI |
Constant | -14.647 | 3.621 | 16.359 | < 0.001 | < 0.001 | |
Age | 0.156 | 0.043 | 13.300 | < 0.001 | 1.169 | 1.075-1.271 |
Sleep disorders | 1.945 | 0.629 | 9.551 | 0.002 | 6.993 | 2.037-24.006 |
egfr | -0.021 | 0.014 | 2.288 | 0.130 | 0.979 | 0.953-1.006 |
Coronary artery lesions | 1.510 | 0.572 | 6.969 | 0.008 | 4.527 | 1.475-13.890 |
eGFR,estimated glomerular filtration rate. |
3 讨论
谵妄是一种短暂的精神障碍,它以急性发作的觉醒水平变化和认知功能紊乱为主要特征,可累及患者的注意力、感受、思维、记忆、运动、睡眠周期等方面,如果不及时诊治或患者不能配合治疗,甚至会导致长期的认知功能障碍[6]。根据临床表现,谵妄可分为活动亢进型(约占25%)、活动抑制型(约占50%)和混合型(约占25%)[7]。活动亢进型表现为躁动、吵闹不安、易激惹、对亲友打骂、思维错乱、答非所问等;活动抑制型表现为精神活动抑制,常伴有回避、冷漠、反应减弱、注意力不集中、定向力障碍、嗜睡、不易唤醒等;混合型的患者则2种形式交替存在。PCI术后谵妄的发生不仅受疾病本身病理生理进程的影响,还是病情恶化的前兆,能明显增加PCI术后患者并发恶性心律失常及猝死的概率[6]。本研究中,15例PCI术后发生谵妄的患者中,8例表现为活动亢进型谵妄,2例表现为活动抑制型谵妄,5例表现为混合型谵妄,与MICHAUD等[8]的研究结果不一致,可能与本研究观察的病例数有限有关。
目前,PCI术后发生谵妄的发病机制尚未完全明确,文献报道的危险因素不尽相同,通常是多种因素相互作用的结果。本研究通过回归分析显示,年龄、睡眠障碍、冠状动脉病变程度为ACS患者PCI术后谵妄的独立危险因素。
研究[9]显示,70岁以上的患者发生谵妄的概率较70岁以下的患者高4倍。高龄患者的脑白质功能逐渐退化,导致乙酰胆碱和胆碱能受体逐渐减少,中枢神经传递功能的改变是导致术后谵妄的病理因素。另外,随着患者年龄的增高,衰老的脑细胞也逐渐增多,脑组织对缺氧的耐受力较差,因此,高龄患者发生谵妄的概率增加。研究[10]发现,年龄≥65岁的心肌梗死患者PCI术后1周内发生谵妄的概率为11.03%;JINNOUCHI等[11]研究发现,80岁以上老年ACS患者PCI术后发生谵妄的概率为29.8%。本研究中,未发生谵妄的患者平均年龄为(64.23±10.45)岁,而发生谵妄患者为(78.47±5.66)岁,明显高于对照组,与其他国内外研究一致。
睡眠障碍与术后谵妄发生密切相关,是发生术后谵妄的危险因素之一[6,12]。大量国外研究[13-15]报道,睡眠障碍会影响患者的精神状态,引起神经递质的传递和大脑中枢海马神经元的数量下降,导致记忆能力及空间认知能力降低、大脑功能失调,从而诱发谵妄。PCI术后有些患者需住进监护病房,监护病房机械辅助通气、制动、医疗设备多、噪音过大、护理操作频繁等均可导致患者睡眠被剥夺或者昼夜节律紊乱,容易诱发谵妄。LUETZ等[16]研究发现,降低监护病房的噪音可以明显减少谵妄的发生率。ARTEMIOU等[17]研究发现,在术前预防性地给予褪黑素,改善患者的睡眠,可降低术后发生谵妄的概率。本研究中,15例PCI术后发生谵妄的患者中有5例存在不同程度的睡眠障碍。
本研究中回归分析显示,冠状动脉多支病变是发生PCI术后谵妄的独立危险因素。冠状动脉多支病变的患者病情较重,病变波及范围广,合并症较多,心肌及脑组织缺血缺氧时间较长,PCI围术期可能出现紧张焦虑等,这些因素都可能诱发ACS患者PCI术后发生谵妄。
目前,基因易感性、生物标志物已成为谵妄研究的新热点[18],李晓晴等[19]首创性地观察了多巴胺受体基因多态性与术后谵妄的关联,发现rs6277的C等位基因是术后谵妄的危险因素。因此,未来本研究组将继续扩大样本量,进一步研究谵妄患者的基因多态性,更深入分析相关因素。
ACS患者PCI术后出现谵妄有增加心血管事件的风险,将给患者带来许多不良影响。因此,早期识别ACS患者PCI围术期诱发术后谵妄的危险因素,对高危患者及时采取针对性措施,制定合理的治疗方案,对进一步提升ACS的诊疗水平具有重要的意义。
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