1、复旦学报(医学版)Fudan Univ J Med Sci2023 Mar.,50(2)硬膜外镇痛和静脉镇痛对结直肠癌根治术患者术后睡眠质量影响的比较石超 贾利红 杨礼 许平波 张军(复旦大学附属肿瘤医院麻醉科-复旦大学上海医学院肿瘤学系 上海 200032)【摘要】目的比较硬膜外镇痛和静脉镇痛对结直肠癌根治术患者术后睡眠质量的影响。方法选择择期行腹腔镜下结直肠癌根治术患者 70 例,性别不限,年龄 2565 岁,ASA 级,18.5 kg/m2BMI28 kg/m2。采用SPSS 19.0软件将患者随机分为硬膜外镇痛组(E组)和静脉镇痛组(V组)。E组全麻诱导前于 T12-L1或 T11-1
2、2节段旁侧入路穿刺置入硬膜外导管 46 cm,术中及术后镇痛以硬膜外镇痛为主。V 组未行硬膜外穿刺,术中及术后镇痛以静脉输注舒芬太尼为主。于术后 1、3、7、30 天时记录患者匹茨堡睡眠质量指数(Pittsburgh Sleep Quality Index,PSQI)和严重睡眠障碍的发生率;于术后 3、7、30 天记录患者术后恢复质量量表-15(Postoperative Quality of Recovery Scale-15,QoR-15)。记录患者切皮前和切皮时心率、收缩压和舒张压,麻醉后监护室(postanesthesia care unit,PACU)停留时间,PACU 呼吸机支持通
3、气时间和术后住院时间。观察患者住院期间主要不良事件的发生情况。结果2组患者术后 1、3、7、30天时 PSQI总分及严重睡眠障碍发生率差异无统计学意义;2组患者术后 3、7、30天的 QoR-15评分差异无统计学意义;2组患者 PACU 呼吸机支持通气时、术后住院时间、不良事件发生情况差异均无统计学意义。与 V 组比较,E 组患者 PACU 停留时间较短(P0.05),切皮时的收缩压和舒张压均较低(P0.05);与术前比较,两组患者术后 1、3、7、30天的 PSQI总分增高(P0.05);与术后 30天比较,两组患者术后 1、3、7天严重睡眠障碍发生率较高(P0.05)。结论结直肠癌根治术患
4、者术后 1周内严重睡眠障碍的发生率较高,不同的镇痛方法可能对患者睡眠质量及术后恢复无影响。硬膜外镇痛能较好地抑制手术刺激,加快患者从PACU转出。【关键词】匹茨堡睡眠质量指数(PSQI);结直肠癌;硬膜外镇痛;睡眠【中图分类号】R735.3,R614 【文献标志码】A doi:10.3969/j.issn.1672-8467.2023.02.010Comparison of effects of epidural analgesia and intravenous analgesia on postoperative sleep quality in patients undergoing r
5、adical resection of colorectal cancerSHI Chao,JIA Li-hong,YANG Li,XU Ping-bo,ZHANG Jun(Department of Anesthesiology,Fudan University Shanghai Cancer Center-Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China)【Abstract】Objective To compare the effects of epidural an
6、algesia and intravenous analgesia on postoperative sleep quality in patients undergoing radical resection of colorectal cancer.MethodsSeventy patients who underwent elective laparoscopic radical resection of colorectal cancer were selected,with no gender limitation,age of 25-65 years old,ASA-grade,1
7、8.5 kg/m2BMI28 kg/m2.Using SPSS19.0 software,they were randomly divided into two groups,epidural analgesia group(group E)and intravenous analgesia group(group V).In group E,an epidural catheter of 4-6 cm was placed by puncture SHI Chao and JIA Li-hong contributed equally to this work Corresponding a
8、uthor E-mail: 网络首发时间:2023-03-17 11 15 51 网络首发地址:https:/ the T12-L1 or T11-12 accessory approach before induction of general anesthesia,and intraoperative and postoperative analgesia was mainly based on epidural analgesia.In group V without epidural puncture,intravenous infusion of sufentanil was mai
9、nly used for analgesia during and after surgery.The Pittsburgh Sleep Quality Index(PSQI)and the incidence of severe sleep disorders were recorded on the 1,3,7,and 30 days after surgery,and the Postoperative Recovery Quality Scale-15(QoR-15)was recorded on the 3,7 and 30 days after the surgery.We rec
10、orded heart rate,systolic and diastolic blood pressure of the patients before and during the skin incision,postanesthesia care unit(PACU)stay time,PACU ventilator support ventilation time and postoperative hospital stay,and observe the occurrence of major adverse events during the patients hospitali
11、zation.ResultsThere was no significant difference in the total PSQI score and the incidence of severe sleep disorders on the 1,3,7 and 30 days after the operation between the two groups.There was no significant difference in QoR-15 score on the 3,7 and 30 days after operation between the two groups.
12、There was no significant differences in the PACU ventilator support ventilation time,postoperative hospital stay,and adverse events between the two groups.Compared with group V,patients in group E had shorter PACU stay(P0.05),and lower systolic and diastolic blood pressure during skin incision(P0.05
13、).Compared with preoperation,the total PSQI scores of the two groups were increased on the 1,3,7 and 30 days after operation(P0.05).Compared with 30 days after operation,the incidence of severe sleep disturbance was higher in the two groups on the 1,3 and 7 days after operation(P0.05).ConclusionPati
14、ents undergoing radical resection of colorectal cancer have higher incidence of severe sleep disorders within 1 week after operation,and different methods of analgesia may have no effect on the sleep quality and postoperative recovery of patients.Epidural analgesia can better inhibit surgery stimula
15、tion,and accelerate the transfer of patients from PACU.【Key words】Pittsburgh sleep quality index(PSQI);colorectal neoplasms;epidural analgesia;sleep结直肠癌是男性第三大高发癌症,女性第二大高发癌症1。睡眠障碍在癌症患者中发生率较高,为 30%93%2。癌症患者会出现广泛的睡眠障碍,如入睡困难、睡眠维持困难和睡眠无法恢复3。研究表明,在癌症患者中观察到的睡眠问题对健康结局和生活质量具有重要影响,睡眠障碍与高血压、炎症以及代谢和内分泌功能受损相关4。手
16、术创伤、麻醉和复杂的应激反应均是造成术后睡眠障碍的重要原因6。阿片类药物通过同时作用于促进睡眠和促进觉醒的系统来影响睡眠,阿片类药物引起的睡眠障碍可能与桥脑网状结构和基底前脑中局部腺苷水平有关6。在健康成年人中快速给予阿片类药物时,会使深度睡眠(阶段 3 和 4)时间减少50%,浅睡眠(阶段 2)时间增加 33%,并可能导致长期使用成瘾者的深度睡眠不稳定,清醒时间增加,快速眼动时间减少7-8。硬膜外镇痛能够提供良好的镇痛效果,还可以大大减少阿片类药物的用量9。许多加速康复外科方案中,硬膜外镇痛较静脉镇痛有更好的镇痛效果,并且能加快患者的恢复11。因此,本研究拟比较硬膜外镇痛和静脉镇痛对结直肠癌
17、根治术患者术后睡眠质量的影响。资 料 和 方 法研究对象 本研究为单中心随机对照研究。经复旦大学附属肿瘤医院伦理委员会批准(伦理号:2107238-17),于中国临床试验注册中心注册(注册号:ChiCTR2100051980),并与患者及其家属签署知情同意书。选取 2020年 10月至 2021年 12月择期行腹腔镜下结直肠癌根治术患者 80 例。纳入标准:ASA 分级或级;年龄 2565 岁,性别不限,18.5 kg/m2BMI5,存在睡眠障碍,PSQI10,睡眠障碍12。通常 PSQI是评估 1 个月内的睡眠情况,但 Broderick 等13评价了不同周期长度(3、7、28 天)的 PS
18、QI 准确性,发现均能有效评估睡眠质量,其他研究4,14也有采用 PSQI评估术后 1 周内的睡眠情况。因此,本研究分别于术前 1天、术后 1、3、7和 30天时记录 PSQI。次要观察指标:术后 1、3、7、30 天严重睡眠障碍发生率,术后3、7 和 30 天 时 采 用 术 后 恢 复 质 量 量 表-15(Postoperative Recovery Quality Scale-15,QoR-15)15评估患者术后早期康复质量,并记录患者切皮前和切皮时心率、收缩压和舒张压,PACU 停留时 间,麻 醉 后 监 护 室(postanesthesia care unit,PACU)呼吸机支持
19、通气时间和术后住院时间。观察患者住院期间主要不良事件的发生情况。统计学分析 样本量计算依据预实验结果(每组 10 例),静脉镇痛组和硬膜外阵痛组术后 7 天PSQI 评分分别为 10.403.24 和 8.502.27。设定 型 错 误 检 验 水 准 0.05(双 侧 检 验),检 验 效 能80%,失访率 10%;采用 PASS15.0 软件计算样本量,每组需要 40 例患者。采用 SPSS19.0 软件进行统计分析,正态分布的计量资料以 xs 表示,组间比较采用两样本 t 检验,组内比较采用重复测量设计的方差分析;偏态分布的计数资料以 M(P25,P75)表示,采用非参数检验(Mann-
20、Whitney U);计数资料比较采用 2检验或 Fisher 确切概率法。P0.05为差异有统计学意义。结 果一般资料数据比较 两组患者年龄、BMI、手术时间、麻醉时间、ASA 分级、性别比较差异无统计学意义(表 1)。术中用药比较 两组患者诱导舒芬太尼、丙泊酚、七氟烷用量比较差异无统计学意义;与 V 组比较,E组术中及术后舒芬太尼用量显著减少,差异有统计学意义(P0.001)。硬膜外镇痛相比静脉镇痛能减少术中和术后阿片类药物的用量,但不能减少术中镇静药物的用量(表 2)。心率血压比较 两组患者术前心率、切皮时心率、术前收缩压和舒张压差异均无统计学意义;与 V组比较,E组切皮收缩压和切皮舒张
21、压均较低,差异有统计学意义(P=0.003,0.013)。硬膜外镇痛相比静脉镇痛能更好的抑制手术切皮时的应激反应(表 3)。226石超,等.硬膜外镇痛和静脉镇痛对结直肠癌根治术患者术后睡眠质量影响的比较PACU 停留情况 两组患者 PACU 机械通气时间、拔管后 VAS 评分比较差异无统计学意义;与 V组比较,E组 PACU 停留时间较短,差异有统计学意义(P=0.004)。硬膜外镇痛相比静脉镇痛能减少阿片类药物的用量及阿片类药物带来的不良反应,因此 E组 PACU 停留时间较短(表 4)。表 1两组结直肠癌根治术患者一般资料比较Tab 1Comparison of general condi
22、tions in the patients undergoing radical resection of colorectal cancer between the two groupsM(P25,P75)or n(%)VariablesAge(y)BMI(kg/m2)Duration of surgery(min)Duration of anesthesia(min)GenderMaleFemaleASA Total(n=70)55.0(46.0,59.0)22.8(21.1,25.0)130.0(108.5,160.0)150.0(125.0,179.0)36.0(51.4)34.0(4
23、8.6)41.0(58.6)29.0(41.4)Group V(n=35)56.0(47.0,59.0)22.0(21.1,25.0)125.0(103.0,161.0)141.0(120.5,178.5)17(48.6)18(51.4)20(57.1)15(42.9)Group E (n=35)55.0(39.0,59.0)22.8(21.0,25.1)130.0(111.0,160.0)151.0(136.0,177.0)19(54.3)16(45.7)21(60.0)14(40.0)P0.5210.8010.5490.3440.6320.808ASA:American society o
24、f anesthesiologists;BMI:Body mass index.表 2两组结直肠癌根治术患者术中及术后用药情况Tab 2Intraoperative and postoperative medication in the patients undergoing radical resection of colorectal cancer between the two groupsM(P25,P75)VariablesSufentanil for induction(g)Sufentanil for operation(g)Sufentanil for postoperatio
25、n(g)Propofol(mg)Sevoflurane(mL)Total27.0(22.0,28.0)31.0(10.8,45.0)34.5(0.0,83.9)595.0(497.5,760.0)13.4(10.8,16.4)Group V25.0(20.0,30.0)41.0(37.5,54.0)83.9(76.4,85.9)600.0(490.0,760.0)12.8(9.8,16.2)Group E27.0(22.0,27.0)15.0(2.5,26.0)0(0,0)576.0(500.0,760.0)13.8(11.2,17.0)P0.7190.0010.0010.9200.267表
26、3两组结直肠癌根治术患者不同时点血压和心率比较Tab 3Comparison of blood pressure and heart rate in the patients undergoing radical resection of colorectal cancer between the two groups at different time points M(P25,P75)VariablesHR before operation(beat/min)HR during skin cutting(beat/min)SBP before operation(mmHg)SBP duri
27、ng skin cutting(mmHg)DBP before operation(mmHg)DBP during skin cutting(mmHg)Total78.0(67.3,82.0)70.0(60.0,80.0)142.5(134.3,160.0)138.0(125.0,140.5)75.0(70.0,80.0)76.5(70.0,85.0)Group V80.0(70.0,82.0)75.0(60.0,80.0)140.0(130,160.0)140.0(130.0,149.0)75.0(70.0,80.0)80.0(70.0,90.0)Group E78.0(65.0,80.0)
28、62.0(60.0,80.0)145.0(138.0,160.0)130.0(120.0,140.0)78.0(70.0,80.0)72.0(68.0,80.0)P0.7040.1420.5830.0030.4700.013HR:Heart reat;SBP:Systolic blood pressure;DBP:Diastolic blood pressure.表 4两组结直肠癌根治术患者 PACU停留情况Tab 4The recovery of pacu in the patients undergoing radical resection of colorectal cancer be
29、tween the two groups M(P25,P75)VariablesPACU length of stay(min)PACU length of ventilation time(min)VAS after extubationTotal40.0(31.0,49.3)5.0(0,17.8)0(0,1.0)Group V45.0(35.0,58.0)0(0,10.0)0(0,1.0)Group E33.0(30.0,43.0)5.0(0,20.0)0(0,0)P0.0040.6510.297PACU:Postoperative anesthesia care unit;VAS:Vis
30、ual Analog Score.227复旦学报(医学版)2023年 3月,50(2)PSQI比较 两组患者术前 1天,术后 1、3、7、30天 PSQI差异均无统计学意义;与术前比较,两组患者术后不同时段的 PSQI 值均升高,差异有统计学意义(P0.001)。两组患者术前 1 天,术后 3、7、30天的严重睡眠障碍发生率差异无统计学意义;与术后 30 天比较,两组患者术后 1、3、7 天严重睡眠障碍发生率较高,差异有统计学意义(P0.01)。硬膜外镇痛和静脉镇痛对结直肠癌根治术患者术后睡眠质量的影响无差异,但两组患者术后 1 个月内均出现了睡眠质量变差,术后 1 周内 2 组患者均有严重的
31、睡眠障碍(表 5、6)。QoR-15比较 两组患者术后 3、7、30天的 QoR-15比较差异无统计学意义(表 7)。住院天数及不良反应比较 两组患者住院天数、疼痛、发热、肠梗阻等不良反应差异无统计学意义(表 8)。讨 论睡眠是一种周期性的生理现象,对各种生物体的功能恢复都起到很大的作用,人类的睡眠包含两种时相:快动眼睡眠期(rapid eye movement,REM)和 非 快 动 眼 睡 眠 期(nonrapid eye movement,NREM)16。围术期的睡眠评估有多种方法,PSQI是 其 中 之 一,其 所 得 的 结 果 与 多 导 睡 眠 仪(polysomnography
32、,PSG)所测得的结果较为相符,在临床睡眠质量的评估及睡眠障碍的筛查等方面,其可靠性和有效性都得到了广泛证实17。因此本研究采用该量表进行睡眠的评估。围术期患者睡表 5两组结直肠癌根治术患者不同时点 PSQI总分比较Tab 5Comparison of PSQI in the patients undergoing radical resection of colorectal cancer between the two groups at different time pointsM(P25,P75)VariablesPrePSQIPos1PSQIPos3PSQIPos7PSQIPos30
33、PSQIPTotal3.5(2.0,5.0)9.0(8.0,10.0)(1)8.0(6.0,11.0)(1)8.0(7.0,10.0)(1)5.0(3.8,7.0)(1)0.001Group V4.0(2.0,5.0)9.0(8.0,10.0)(1)8.0(7.0,11.0)(1)8.0(8.0,12.0)(1)5.0(4.0,7.0)(1)0.001Group E3.0(2.0,5.0)9.0(8.0,10.0)(1)7.0(5.0,11.0)(1)8.0(7.0,10.0)(1)4.5(3.0,6.0)(1)0.001P0.5650.5510.0600.2320.153(1)vs.PreP
34、SQI,P0.05.PSQI:Pittsburgh Sleep Quality Index.表 6两组结直肠癌根治术患者不同时点严重睡眠障碍发生率Tab 6Incidence of severe sleep disorders in the patients undergoing radical resection of colorectal cancer between the two groups at different time pointsn(%)VariablePos1PSQI%Pos3PSQI%Pos7PSQI%Pos30PSQI%PTotal(n=70)30(42.9)(1)2
35、4(34.3)(1)25(35.7)(1)4(5.7)0.010Group V(n=35)14(40.0)(1)13(37.1)(1)14(40.0)(1)1(2.9)0.010Group E(n=35)16(45.7)(1)11(31.4)(1)11(31.4)(1)3(8.6)0.010P0.6290.6150.4540.614(1)vs.Pos30PSQI%,P0.05;Severe sleep disturbance:PSQI10.表 7两组结直肠癌根治术患者不同时点 QoR-15总分比较Tab 7Comparison of QoR-15 in the patients undergo
36、ing radical resection of colorectal cancer between the two groups at different time pointsM(P25,P75)VariablesPos3QoR-15Pos7QoR-15Pos30QoR-15Total115.0(108.0,119.0)120.5(116.8,125.0)128.5(124.0,132.3)Group V115.5(108.0,119.0)120.0(115.0,126.0)128.0(123.0,131.0)Group E115.0(108,119.0)122.0(117.0,125.0
37、)129.0(125.0,133.0)P0.8600.6130.451QoR-15:Postoperative Recovery Quality Scale-15.228石超,等.硬膜外镇痛和静脉镇痛对结直肠癌根治术患者术后睡眠质量影响的比较眠障碍的发生率较高18,睡眠障碍会对患者主观感觉、行为、免疫功能等方面均可产生不利影响,例如REM 在情绪调节和情感性记忆巩固中起着重要作用,REM 的延长和缩短与一系列系列精神症状和障碍(如抑郁、躁狂、自杀)有关19。阿片类药物对睡眠的影响在动物试验和临床试验都已经得到证明,如 Nelson等20向大鼠脑中注释阿片类药物,直接降低了桥脑网状结构和基底前脑
38、中调节睡眠区域的腺苷浓度,导致动物睡眠模式的严重中断。一项随机、对照、开放的多中心试验中,180 名拟行经腹子宫切除术的患者被随机分为两组(腰麻或全麻),全麻组术后第 1 晚的睡眠质量明显低于腰麻组(OR=2.45,P=0.03),术后第 1晚睡眠质量不良的危险因素为阿片类药物(OR=1.07,P=0.03)21。Arthu 等22比较了妇科手术患者硬膜外分别输注芬太尼和布比卡因进行镇痛的术后睡眠质量,发现术后早期 REM 睡眠和慢波睡眠(slow wave sleep,SWS)均有减少,但阿片类药物组 SWS减少程度较低。因此,本研究通过硬膜外镇痛来减少阿片类药物的用量进而来改善睡眠有较好的
39、科学性和创新性。本研究结果显示,硬膜外镇痛可以显著减少术中和术后舒芬太尼的的用量,与 V 组比较,E组患者切皮时的收缩压和舒张压更加稳定,说明硬膜外镇痛能更好地抑制手术的应激反应;与 V 组比较,E组患者 PACU 停留时间更短,可能与 E 组患者舒芬太尼用量少,拔管后呼吸抑制发生率低有关。本研究结果显示,两组患者术后 PSQI 评分和QoR-15评分差异无统计学意义,硬膜外镇痛并不能改善患者术后睡眠质量,也不利于术后恢复。这可能与睡眠受环境干扰因素较大有关,本研究术后随访过程中发现环境因素对患者的睡眠影响较大。本研究过程中以 PSQI10 为发生严重睡眠障碍,观察得到两组患者术后 1 周内均
40、有较高的严重睡眠障碍发生率;术后 30 天严重睡眠障碍率较低,可能说明阿片类药物对睡眠的影响存在剂量效应和时效性。本研究有一定的局限性:睡眠的环境干扰因素较多,无法做到两组统一;睡眠质量的评估缺乏客观指标;为单中心小样本研究,有待多中心大样本研究。结直肠癌根治术患者术后 1周内严重睡眠障碍的发生率较高,不同的镇痛方法可能对患者睡眠质量及术后恢复无影响。硬膜外镇痛能抑制手术的应激反应,加快患者 PACU 的转出。作者贡献声明石超,贾利红论文构思、撰写和修订,数据采集和分析。杨礼,许平波,张军论文构思、撰写和修订,数据分析。利益冲突声明所有作者均声明不存在利益冲突。参 考 文 献1 SIEGEL
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