ICU患者昼夜心率变异对近期和远期病死率的影响:基于MIMIC-Ⅱ数据库的回顾性队列研究

Effects of circadian heart rate variation on short-term and long-term mortality in intensive care unit patients:a retrospective cohort study based on MIMIC-Ⅱdatabase

目的探讨重症加强治疗病房(ICU)患者昼夜心率变异对近期和远期病死率的影响。方法采用回顾性队列研究方法,收集美国重症监护数据库(MIMIC-Ⅱv2.6)截至2011年4月发布的2001至2008年共32536例ICU患者的相关记录。暴露因素为昼夜心率变异,定义为夜间(23:00至次日07:00)平均心率与白天(07:00至23:00)平均心率的比值,即夜昼心率比;结局事件为28 d病死率和1年病死率。收集入选患者年龄、性别、种族、首次序贯器官衰竭评分(SOFA)、首次简化急性生理学评分Ⅰ(SAPSⅠ)、入ICU首个24 h内是否使用镇静药物及儿茶酚胺类药物、临床合并症〔高血压、慢性阻塞性肺疾病(COPD)、糖尿病合并并发症、糖尿病未合并并发症、充血性心力衰竭、肝脏疾病、肾衰竭等〕,以及患者入ICU首个24 h内完整的心率记录。采用Cox比例风险回归模型,并矫正相关混杂因素,探讨ICU患者昼夜心率变异对28 d病死率及1年病死率的影响,同时在不同首次SOFA评分患者中进行亚组分析。结果共纳入MIMIC-Ⅱ数据库中的15382例ICU患者,排除无心率记录、无死亡记录、使用心脏起搏器、心律失常、无SOFA和SAPSⅠ评分记录患者,最终共9439例患者进入研究队列。①整体患者Cox回归分析显示,ICU患者夜昼心率比升高与28 d病死率〔风险比(HR)=1.613,95%可信区间(95%CI)为1.338~1.943,P<0.001〕及1年病死率(HR=1.573,95%CI为1.296~1.908,P<0.001)增加有关。在调整了人口统计学因素(年龄、性别、种族)、疾病严重程度评分(SOFA、SAPSⅠ评分)、临床合并症(高血压、COPD、糖尿病合并并发症、糖尿病未合并并发症、充血性心力衰竭、肝脏疾病、肾衰竭等)和相关药物(镇静药物及儿茶酚胺类药物)后,ICU患者夜昼心率比与28 d病死率(HR=1.256,95%CI为1.018~1.549,P=0.033)及1年病死率(HR=1.249,95%CI为1.010~1.545,P=0.040)仍相关。②根据SOFA评分中位数5分将研究人群分为两组,SOFA评分≤5分组5478例,SOFA评分>5分组3961例。Cox回归亚组分析显示,在SOFA评分>5分组中,ICU患者夜昼心率比越高,28 d病死率(HR=1.430,95%CI为1.164~1.756,P=0.001)及1年病死率(HR=1.393,95%CI为1.123~1.729,P=0.003)越高。在调整了相关混杂因素后,随着夜昼心率比的升高,ICU患者的28 d病死率(HR=1.279,95%CI为1.032~1.584,P=0.025)及1年病死率(HR=1.255,95%CI为1.010~1.558,P=0.040)仍升高;但在SOFA评分≤5分组中,未显示出ICU患者夜昼心率比与28 d病死率和1年病死率存在关联。结论在ICU患者中,随着夜昼心率比的升高,28 d病死率及1年病死率均增加,提示重症患者昼夜心率变异与近期及远期病死率均呈正相关,尤其在病情相对较重的患者中关联更为显著。

Objective To investigate the effect of circadian heart rate variation on short-term and long-term mortality in intensive care unit(ICU)patients.Methods A retrospective cohort study was conducted.A total of 32536 ICU patients were recorded from 2001 to 2008 published by Multiparameter Intelligent Monitoring in Intensive CareⅡ(MIMIC-Ⅱv2.6)in April 2011.The circadian heart rate variation was defined as the ratio of mean nighttime(23:00 to 07:00)heart rate to mean daytime(07:00 to 23:00)heart rate.The 28-day mortality and 1-year mortality were defined as outcome events.The information such as age,gender,ethnicity,first sequential organ failure assessment(SOFA)score,first simplified acute physiology scoreⅠ(SAPSⅠ),usage of sedatives and catecholamines within 24 hours admission of ICU,clinical complications[hypertension,chronic obstructive pulmonary disease(COPD),diabetes with or without complications,congestive heart failure,liver disease,renal failure,etc.],and the complete heart rate records within 24 hours after ICU admission were collected.Cox proportional risk regression models were used to investigate the association between circadian heart rate variation and 28-day mortality and 1-year mortality in ICU patients.Besides,subgroup analysis was also performed in patients with different first SOFA scores.Results Totally 15382 ICU patients in MIMIC-Ⅱdatabase were enrolled,excluding the patients without heart rate records or death records,using pacemaker with arrhythmia,without SOFA or SAPSⅠscore records.Finally,9439 patients were enrolled in the study cohort.①Cox regression analysis of the whole patient showed that the higher circadian heart rate variation was correlated with the increased 28-day mortality[hazard ratio(HR)=1.613,95%confidence interval(95%CI)was 1.338-1.943,P<0.001]and 1-year mortality(HR=1.573,95%CI was 1.296-1.908,P<0.001).After adjustment for demographic factors(age,gender and ethnicity),severity of illness(SOFA and SAPSⅠscores),clinical complications(hypertension,COPD,diabetes with or without complications,congestive heart failure,liver disease,renal failure,etc.),and influence of medications(sedatives and catecholamines),the night-day heart rate ratio was also correlated with 28-day mortality(HR=1.256,95%CI was 1.018-1.549,P=0.033)and 1-year mortality(HR=1.249,95%CI was 1.010-1.545,P=0.040).②According to the SOFA score(median value of 5),the patients were divided into two subgroups,in which 5478 patients with SOFA score≤5 and 3961 patients with SOFA score>5.Cox regression subgroup analysis showed that circadian heart rate variation was related with higher 28-day mortality(HR=1.430,95%CI was 1.164-1.756,P=0.001)and 1-year mortality(HR=1.393,95%CI was 1.123-1.729,P=0.003)in patients with SOFA score>5.After adjustment for covariates,the 28-day mortality(HR=1.279,95%CI was 1.032-1.584,P=0.025)and 1-year mortality(HR=1.255,95%CI was 1.010-1.558,P=0.040)also increased with the increasing of night-day heart rate ratio in patients with SOFA score>5.However,the relationships did not exist in patients with SOFA score≤5.Conclusion In ICU patients,the 28-day mortality and 1-year mortality increase with the higher circadian heart rate variation,which indicates that the circadian heart rate variation in ICU patients is positively correlated with the short-term and long-term mortality,especially in patients with relatively severe illness.