心脏手术患者术后谵妄预示认知风险高

《新英格兰医学杂志》7月4日在线发表的一项研究结果显示，心脏手术后谵妄患者面临认知功能总体下降以及术后1年内较长时间认知损害的风险。与未发生术后谵妄患者相比，术后谵妄患者6个月内恢复至术前认知表现水平的几率显著降低(N. Engl. J. Med. 2012 July 4 [doi:10.1056/NEJMoa1112923])。

在这项研究中，马萨诸塞大学渥斯特分校的Jane S. Saczynski博士及其同事对225例年龄≥60岁的CABG(冠脉旁路移植术)或瓣膜置换术患者随访1年，以评估术后谵妄对此后认知表现的影响。住院期间，研究者每日评估患者谵妄情况，并通过病历核实谵妄临床特征。出院后，分别在1、6和12个月评估患者认知功能。患者术后谵妄分层根据CAM(谵妄评定方法)结果而定，CAM包括4个关键特征：急性改变且呈波动性病程、注意力不集中、思维瓦解以及意识水平改变。上述评估得到MMSE(简易智力状态检查)、数字广度测试以及谵妄症状面谈结果的证实，患者还接受了查尔森合并症指数(CCI)评估。受试者平均年龄73岁，女性约占25%，多数为白人和非西班牙裔。

结果显示，46%的受试者出现术后谵妄，其中65%的患者持续1~2 d，余者持续时间≥3 d。谵妄患者年龄显著较大且受教育程度较低，并多有卒中或TIA(短暂脑缺血发作)史，CCI评分较高，术前认知功能水平较低。手术类型(无论是单纯CABG、单纯瓣膜置换术还是CABG+瓣膜置换术)与术后谵妄无显著关联。

就受试者总体而言，术后第2天认知功能与基线相比下降显著(MMSE评分下降4.6分)，术后3~5天认知功能恢复速度较快(1分/d)，然后改善速度非常缓慢，大约6个月时趋于稳定，此后无显著变化。但患者分层后上述情况有所变化，术后谵妄患者术后近期认知功能下降更为明显(7.7分 vs. 2.1分)，术后3~5天恢复迅速，此后6个月恢复情况也略好。非谵妄患者认知功能水平大约在术后1个月恢复至术前水平，而谵妄患者术后1年尚未恢复至术前水平。此外，术后6个月认知功能水平恢复至术前水平的非谵妄患者比例明显高于谵妄患者(40% vs.24%)，但在12个月时无显著差异(31% vs. 20%)。

研究者指出，谵妄是心脏手术之后的常见症状，估计可累及75%的患者。谵妄曾被认为是短期认知障碍，但上述结果表明，谵妄或许对心脏手术患者认知功能有长期影响。术后谵妄应与房颤、抑郁史、受教育水平较低以及既往患有脑血管疾病等因素一并列入心脏手术后长期损害的危险因素之列。研究者强调，谵妄是上述风险因素之中唯一可预防的因素。

这项研究中没有设立非手术对照组，研究者在多变量模型中也未充分解释术后谵妄组基线认知功能水平较低是否源于先前疾病负担较大。然而，研究者指出，在一项敏感性分析中，通过匹配受试者术前MMSE评分校正两组基线认知功能水平差异后，结果未见变化。

研究者认为，上述结果强调了诸如住院老年患者生活计划等主动干预措施预防谵妄以及减轻谵妄影响的重要性。此外，出院时认知筛查可确认出院后需要严密监测或个体化过渡期护理的高危患者，以改善其认知功能和临床结局。鉴于术后谵妄患者认知功能改善持续至术后6个月，应延长这类患者的物理和职业治疗等康复服务时间，因此研究结果还对心脏手术术后及康复护理也具有指导意义。

该研究由哈佛大学老年人自立中心(OAIC)、美国国立衰老研究所(NIA)、美国国立心肺血液研究所(NHLBI)和美国国立卫生研究院(NIH)资助。研究者报告无利益冲突。

爱思唯尔  版权所有

By: MARY ANN MOON, Cardiology News Digital Network
Patients who develop postoperative delirium after cardiac surgery are at risk for an overall decline in cognitive function and a prolonged period of impairment during the following year, according to a study published online July 4 in the New England Journal of Medicine.

Compared with cardiac surgery patients who do not develop postoperative delirium, those who do are significantly less likely to return to their preoperative level of cognitive performance within 6 months, said Jane S. Saczynski, Ph.D., of the division of geriatric medicine and Meyers Primary Care Institute at the University of Massachusetts, Worcester, and her associates.

"Our findings suggest that the development of postoperative delirium should be added to the list of risk factors for prolonged impairment after cardiac surgery, which includes the development of atrial fibrillation, a history of depression, a lower level of education, and preexisting cerebrovascular disease," they said.

Delirium is the only one of these factors that is potentially preventable, the investigators noted.

Delirium is common following cardiac surgery, affecting up to 75% of patients by some estimates. Dr. Saczynski and her colleagues followed 225 patients aged 60 years or older for 1 year after they underwent CABG (coronary artery bypass graft) or valve replacement, to assess the effect of postoperative delirium on later cognitive performance.

The study subjects were treated at two academic medial centers and a Veterans Affairs hospital. They were interviewed daily while they were hospitalized to assess delirium, and their records were reviewed for evidence of the clinical features of the condition. After discharge, the subjects were again interviewed in their residences at 1, 6, and 12 months to assess their cognitive function.

Delirium was rated as present or absent based on results of the CAM (Confusion Assessment Method), which evaluates four key features: acute change with a fluctuating course, inattention, disorganized thinking, and altered level of consciousness. This assessment was supported with results on the MMSE (Mini-Mental State Examination), the digit-span test, and the Delirium Symptom Interview.

The patients also were evaluated using the Charlson comorbidity index, which estimates the burden of illness based on the presence and severity of 17 medical conditions.

The mean age of the study subjects was 73 years; approximately 25% were women, and almost all were white and non-Hispanic.

Postoperative delirium developed in 46% of the study subjects. It lasted 1-2 days in 65% of these patients and for 3 or more days in the remaining 35%.

Subjects who developed delirium were significantly older and less educated than were those who did not; were more likely to have a history of stroke or TIA (transient ischemic attack); to have higher scores on the comorbidity index; and to have a lower level of cognitive function before the cardiac surgery.

Surgery type (whether CABG only, valve replacement only, or valve replacement with CABG) was not significantly associated with postoperative delirium.

In the study population as a whole, cognitive function declined significantly (by 4.6 points on the MMSE) between baseline and postoperative day 2. This initial drop was followed by significant increases in cognitive function, by 1 point per day, on days 3-5. The rate of improvement then slowed considerably and stabilized at approximately 6 months, showing no significant change thereafter.

However, this pattern changed when patients were stratified by the presence of delirium. Those who developed delirium showed a much greater decline in cognitive function in the immediate postoperative period, with a drop of 7.7 points vs. 2.1 points on the MMSE. They then showed more rapid recovery on days 3-5, and slightly greater recovery over the next 6 months.

"Patients without delirium returned to their preoperative level of cognitive function by approximately 1 month after surgery, whereas patients with delirium had not returned to their preoperative level of function by 1 year postoperatively," Dr. Saczynski and her associates said (N. Engl. J. Med. 2012 July 4 [doi:10.1056/NEJMoa1112923]).

"In addition, the proportion of patients who did not return to their preoperative level of function was significantly higher in the group with delirium than in the group without delirium through 6 months postoperatively (40% vs. 24%), but this proportion was not significantly different at 12 months (31% and 20%, respectively)," they noted.

This suggests that delirium, "which was once thought of as a short-term transient cognitive disorder, may have longer-term observed effects on cognitive function in patients who have undergone cardiac surgery," the investigators said.

The researchers did point out some potential caveats in their conclusions. The study did not have a nonsurgical group as a comparative control. In addition, the lower level of cognitive function at baseline in the group with postoperative delirium, as compared with those patients without postoperative delirium, could be caused by a trajectory of decline from a greater burden of preexisting disease that was not fully addressed in the multivariate models.

However, they added that in a sensitivity analysis, the baseline differences between the two study groups in cognitive function was controlled for by matching subjects’ preoperative MMSE scores and the results did not change.

The study results highlight the importance of proactive interventions such as the Hospital Elder Life Program to prevent delirium and to ameliorate its effects if it does develop. In addition, "cognitive screening at hospital discharge may identify high-risk patients who require close monitoring after discharge or tailored transitional care in order to enhance functional and clinical outcomes," they said.

The findings also have implications for postoperative and rehabilitative care after cardiac surgery. "Since patients with postoperative delirium continue to have improvements in cognitive function up to 6 months after surgery, rehabilitation services, such as physical and occupational therapy, may need to be extended for these patients," Dr. Saczynski and her colleagues said

This study was supported by the Harvard Older Americans Independence Center; the National Institute on Aging; the National Heart, Lung, and Blood Institute; and the National Institutes of Health. The authors reported no financial conflicts of interest relevant to the study.