某些抗抑郁药可增加ICU患者死亡风险

Katherine M. Berg博士

旧金山(EGMN)——一项回顾性研究显示，在被收入重症监护病房时接受选择性5羟色胺再摄取抑制剂(SSRI)或5羟色胺去甲肾上腺再摄取抑制剂(SNRI)治疗的患者，发生院内死亡的几率较未接受上述抗抑郁症治疗的ICU患者增加73%。

麻省总医院和哈佛大学的肺科/重症医学科研究员Katherine M. Berg博士在美国胸科学会(ATS)年会上指出，抗抑郁药是2011年美国最常见的处方药物类型，而SSRI则是最常用的抗抑郁药类型。既往研究显示，SSRI的使用与出血、跌倒、心动过缓和卒中风险增高相关，而在冠心病患者中SSRI可能具有保护效应。

Berg博士及其合作者分析了2001~2008年间4个ICU的入院电子记录，以比较1,876例接受SSRI或SNRI治疗的患者与8,692例入院前未接受SSRI或SNRI治疗的对照患者的预后。

研究结果显示，在入住ICU后1,000天时，患者的死亡风险仍增高。如住院时正在接受SSRI或SNRI治疗，一些亚组发生院内死亡的风险甚至更高。如急性冠脉综合征或接受心脏手术者在入住ICU时正接受SSRI/SNRI治疗，则其死亡风险增加1倍以上。

死亡风险增高主要与5羟色胺再摄取抑制程度较高的药物治疗相关。“西酞普兰是一种较弱的药物，单独使用不会引起死亡风险增高，而舍曲林较强，可引起死亡风险增高。对这两种药物进行比较也可发现，使用舍曲林者较使用西酞普兰者死亡风险更高。”氟西汀、帕罗西汀和舍曲林与死亡率显著增高相关，但接受西酞普兰或依他普仑治疗者的死亡率与对照患者无显著差异。

在8,692例对照患者中，7%发生院内死亡，而在入住ICU时接受氟西汀治疗的286例患者、接受帕罗西汀治疗的320例患者和接受舍曲林治疗的426例患者中，院内死亡率分别为10%、13%和15%。其他844例患者接受其他抗抑郁药治疗。

这项研究中校正了每例患者的年龄、简化急性生理评分和联合Elixhauser共存疾病评分对院内死亡风险的影响。两组之间轻微但有统计学意义的差异包括：SSRI/SNRI组比对照组纳入更多女性患者(57% vs. 40%)；SSRI/SNRI组糖尿病(21% vs. 17%)或慢性阻塞性肺病(11% vs. 7%)的患病率更高；SSRI/SNRI组患者更常发生感染(11% vs. 8%)；但SSRI/SNRI组患者较少患急性冠脉综合征(8% vs. 10%)或心血管疾病(67% vs. 70%)。

该研究的数据来自重症监护的多参数智能监护Ⅱ数据库，这是一个去除了患者标识的公共数据集。Berg 博士披露无相关利益冲突。

爱思唯尔  版权所有

BY SHERRY BOSCHERT
Elsevier Global Medical News
Breaking News

SAN FRANCISCO (EGMN)–Patients on selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors when they were admitted to an intensive care unit were 73% more likely to die in the hospital, compared with ICU patients who were not on these antidepressants, a retrospective study found.

Dr. Katherine M. Berg and her associates analyzed electronic records from admissions to four ICUs in 2001-2008 to compare outcomes for 1,876 patients who were on a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) and 8,692 control patients who were not taking an SSRI or SNRI before admission.

The mortality risk remained elevated at 1,000 days after ICU admission, she reported in a late-breaking poster presentation and discussion session at an international conference of the American Thoracic Society.

Certain subgroups were at even greater risk of dying in the hospital if they were on an SSRI or SNRI when admitted to the ICU. Patients who had acute coronary syndrome or had undergone cardiac surgery were more than twice as likely to die if they were on an SSRI/SNRI when entering the ICU, compared with controls, said Dr. Berg, a pulmonary/critical care fellow at Massachusetts General Hospital and Harvard University, both in Boston.

The increased mortality risk appeared to be associated mainly with medications that have higher degrees of serotonin reuptake inhibition. “Citalopram, which is a lower-potency drug, by itself did not incur a higher mortality risk, but sertraline, which is one of the more potent drugs, did. Even comparing the two drugs to each other, if you were on sertraline, your mortality risk was higher” than if you were on citalopram, Dr. Berg said in an interview.

Fluoxetine, paroxetine, and sertraline were associated with significantly higher mortality, but no significant mortality differences were seen between patients on citalopram or escitalopram and control patients.

Of the 8,692 control patients, 7% died in the hospital, compared with in-hospital death rates of 10% in 286 patients on fluoxetine, 13% in 320 patients on paroxetine, and 15% in 426 patients on sertraline at the time of ICU admission. The remaining 844 patients were on other antidepressants.

The study adjusted for the effects of each patient’s age, Simplified Acute Physiology Score, and combined Elixhauser comorbidity score on in-hospital mortality risk.

Slight but statistically significant differences in the characteristics of the two groups included a greater proportion of women in the SSRI/SNRI group, compared with controls (57% vs. 40%), and a higher prevalence of diabetes (21% vs. 17%) or chronic obstructive pulmonary disease (11% vs. 7%) in patients on an SSRI/SNRI, compared with controls. Patients in the SSRI/SNRI group were more likely to have an infection than were controls (11% vs. 8%), but less likely to have acute coronary syndrome (8% vs. 10%) or cardiovascular disease (67% vs. 70%).

Further studies are needed to ascertain if this is a causal relationship or just an association between SSRI/SNRI use and mortality in ICU patients, she said. The findings are limited by the retrospective nature of the study, which also was unable to control for the effects of potentially important confounders such as smoking status or the presence of depression.

The data came from the Multiparameter Intelligent Monitoring in Intensive Care II database, a public collection of data with patient identifiers removed.

Antidepressants were the most commonly prescribed medication class in the United States in 2011, and SSRIs were the most common type of antidepressant, she said. SSRI use has been associated with increased risk of bleeding, falls, bradycardia, and stroke in previous studies, which also suggest a possible protective effect of SSRIs in patients with coronary artery disease.

Dr. Berg reported having no financial disclosures.