乌司他丁对老年患者髋关节置换术后谵妄的影响

doi:10.3877/cma.j.issn.1674-134X.2019.03.007

中华关节外科杂志(电子版) ›› 2019, Vol. 13 ›› Issue (03) : 295 -301. doi: 10.3877/cma.j.issn.1674-134X.2019.03.007

所属专题：文献；

临床论著

乌司他丁对老年患者髋关节置换术后谵妄的影响

何颖宜¹, 罗程², 江伟航³, 詹鸿⁴^,^†(

)

^1. 510145　广州医科大学附属第三医院麻醉科；511400　广州市番禺区中心医院麻醉科
^2. 511400　广州市番禺区中心医院关节外科
^3. 511400　广州市番禺区中心医院麻醉科
^4. 510145　广州医科大学附属第三医院麻醉科

收稿日期:2019-02-22 出版日期:2019-06-01
通信作者: 詹鸿
基金资助:
广州市番禺区科技医疗卫生项目(2018－Z04－64)

Application of ulinastatin on postoperative delirium in elderly patients undergoing hip arthroplasty

Yingyi He¹, Cheng Luo², Weihang Jiang³, Hong Zhan⁴^,^†()

^1. Department of Anesthesiology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510145, China; Department of Anesthesiology, Panyu Central Hospital, Guangzhou 511400, China
^2. Department of Joint surgery, Panyu Central Hospital, Guangzhou 511400, China
^3. Department of Anesthesiology, Panyu Central Hospital, Guangzhou 511400, China
^4. Department of Anesthesiology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510145, China

Received:2019-02-22 Published:2019-06-01
Corresponding author: Hong Zhan
About author:
Corresponding author: Zhan Hong, Email: zhanh2@126.com

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引用本文：

何颖宜, 罗程, 江伟航, 詹鸿. 乌司他丁对老年患者髋关节置换术后谵妄的影响[J]. 中华关节外科杂志(电子版), 2019, 13(03): 295-301.

Yingyi He, Cheng Luo, Weihang Jiang, Hong Zhan. Application of ulinastatin on postoperative delirium in elderly patients undergoing hip arthroplasty[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2019, 13(03): 295-301.

目的

观察围术期应用乌司他丁对老年患者行髋关节置换术术后谵妄的影响。

方法

选取择期髋关节置换术老年患者120例，美国麻醉医师协会(ASA)分级Ⅰ～Ⅱ级，年龄在65～90岁，无神经、精神系统疾病，无长期服用镇静、抗抑郁药，术前沟通、依从性好；能配合完成术后随访。应用随机数字表法分成4组：乌司他丁组(U₁、U₂、U₃组)和对照组(C组)，每组30例，术中应用静吸复合全麻。手术切皮前分别予U₁组2 500 U/kg、U₂组5 000 U/kg、U₃组10 000 U/kg乌司他丁静脉维持1 h，术后第1、2天再继续静滴等量乌司他丁，C组等时静滴生理盐水。记录4组意识恢复时间、意识恢复后视觉模拟量表(VAS)评分、术后改良的警觉/镇静(OAA/S)评分和拔管后躁动评分；术后谵妄评定方法(CAM)评分；术后谵妄发生例数；记录术前和术后不同时点的白介素-6(IL-6)、S-100钙结合蛋白β亚单位(S-100β)和脑源性神经营养因子(BDNF)变化。一般情况、拔管时间及意识恢复质量评分采用单因素方差分析，CAM评分、IL-6、S-100β及BDNF数据采用重复测量资料方差分析，术后谵妄发生例数采用卡方检验进行统计学分析。

结果

U₂组、U₃组较C组、U1组拔管后躁动评分低(F ＝34.41，P<0.05)、意识恢复时间短(F ＝8.45，P<0.05)、术后改良OAA/S评分低(F ＝7.33，P<0.05)；术后3 d，乌司他丁组CAM评分均低于C组(F＝8.61，P<0.05)；术后C组出现谵妄例数多(χ²＝8.76，P<0.05)；术后6～24 h IL-6浓度U₁、U₂、U₃组低于C组(F＝16.84，P<0.05)；术后6～24 h的S-100β浓度U₁、U₂、U₃组低于C组(F ＝7.613，P<0.05)；术毕当时至术后12 h血清BDNF浓度U₁、U₂、U₃组明显高于C组(F ＝38.54，P<0.05)。

结论

髋关节置换术围术期使用5 000 U/kg与10 000 U/kg乌司他丁量，可缩短意识恢复时间，减低拔管后躁动的发生，减轻老年人髋关节置换术后谵妄的发生；可能与乌司他丁影响炎症因子IL-6，从而减少S-100β和保持BDNF浓度有关。

关键词: 胰蛋白酶抑制剂, 关节成形术，置换，髋, 神经认知障碍

Objective

To explore the effect of perioperative ulinastatin on postoperative delirium in elderly patients undergoing hip arthroplasty.

Methods

A total of 120 elderly patients undergoing elective hip arthroplasty were recruited in the study, aged 65 to 90 years old, American Society of Anesthesiologists (ASA) I to II, without neurological or psychiatric diseases, no history of sedative or antidepressant drugs; with good communication and postoperative follow-up. The random number table method was divided into four groups: ulinastatin groups (group U₁, U₂, U₃) and control group (group C), 30 cases in each group, and the patients were used by Intraoperative intravenous inhalation combined with general anesthesia. Before the operation, the patients were given 2 500 U/kg ulinastatin in group U₁, 5 000 U/kg in group U2, 10 000 U/kg in group U₃ for 1 h, and continued intravenous infusion the same doses of ulinastatin on the first and second day after the operation. Group C received saline intravenously at the same time. The information including the time of consciousness recovery, visual analogue scale (VAS), the improved observer's assessment of alertness/sedation scale (OAA/S) and the confusion assessment method (CAM) score after operation, the number of delirium cases after operation, and the changes o interleukin-6 (IL-6)f, S-100 calcium binding protein beta subunit (S-100β) and brain-derived neurotrophic factor (BDNF)at different time points before and after the operation, were recorded. General condition, extubation time and consciousness recovery quality score data were analyzed by one-way analysis of variance. The CAM score, IL-6, S-100β and BDNF data were analyzed by repeated measures data analysis. The number of postoperative delirium cases was calculated by chi-square test.

Results

After extubation, the agitation scores in U₂ group and the U₃ group were lower than the group C and U₁(F=34.41, P <0.05), the recovery time of consciousness was shorter(F=8.45, P=0.008), and the postoperative modified OAA/S scale were lower( F=7.33, P <0.05). Three days after surgery, CAM score of ulinastatin groups were higher than group C (F=8.61, P<0.05); there were more cases of delirium in group C after the operation(χ²=8.76, P<0.05). After 6 h to 24 h, IL-6 concentration in group U₁, U₂, and U₃ were significantly lower than group C (F=16.84, P<0.05), S-100β group U₁, U₂, and U₃ were lower than group C (F=7.613, P<0.05). After surgery to 12h, serum BDNF concentration in group U₁, U₂, and U₃ were significantly higher than that in group C (F =38.54, P<0.05).

Conclusions

The use of 5, 000 U/kg and 10 000 U/kg ulinastatin in the perioperative period of hip arthroplasty can shorten the recovery time of consciousness and reduce the occurrence of agitation after extubation. It may be that the application of ulinastatin affects inflammation. Factor IL-6, which reduces S-100β and maintains BDNF concentration, is associated with the reduction of spasticity after hip arthroplasty in the elderly.

Key words: Trypsin inhibitors, Arthroplasty, replacement, hip, Neurocognitive disorders

表1 患者一般情况比较 (±s)

组别	例数	年龄(岁)	体重(kg)	麻醉时间(min)	手术时间(min)	丙泊酚用量(mg)
U₁组	30	74.3±7.6	21.3±2.2	156.3±36.7	120.26±32.8	435.4±139.5
U₂组	30	75.5±6.7	19.78±3.1	158.5±38.2	125.5±36.1	458.6±113.6
U₃组	30	76.6±5.6	20.8±2.4	160.2±37.5	24.4±34.4	446.9±128.7
C组	30	75.4±6.9	19.5±3.5	164.3±36.4	126.53±35.4	451.2±113.9
F值	?	0.3	0.2	0.25	0.2	1.6
P值	?	>0.05	>0.05	>0.05	>0.05	>0.05

表1 患者一般情况比较 (±s)

组别	例数	年龄(岁)	体重(kg)	麻醉时间(min)	手术时间(min)	丙泊酚用量(mg)
U₁组	30	74.3±7.6	21.3±2.2	156.3±36.7	120.26±32.8	435.4±139.5
U₂组	30	75.5±6.7	19.78±3.1	158.5±38.2	125.5±36.1	458.6±113.6
U₃组	30	76.6±5.6	20.8±2.4	160.2±37.5	24.4±34.4	446.9±128.7
C组	30	75.4±6.9	19.5±3.5	164.3±36.4	126.53±35.4	451.2±113.9
F值	?	0.3	0.2	0.25	0.2	1.6
P值	?	>0.05	>0.05	>0.05	>0.05	>0.05

表2 术后拔管、意识恢复时间、意识恢复后VAS评分及拔管后躁动评分比较(±s)

组别	例数	拔管后躁动评分(分)	意识恢复时间(min)	意识恢复后VAS评分(分)	术后改良OAA/S评分(分)
U₁组	30	0.57±0.50^a	14.52±9.12^c	1.67±1.09	1.16±0.38^e
U₂组	30	0^ab	10.56±5.03^cd	1.77±1.30	1.06±0.25^e
U₃组	30	0^ab	10.06±6.84^cd	1.57±1.45	1.03±0.19^e
C组	30	0.87±0.62	19.42±9.60	1.93±1.11	1.47±0.63
F值	?	34.41	8.45	0.12	7.33
P值	?	<0.05	<0.05	>0.05	<0.05

表2 术后拔管、意识恢复时间、意识恢复后VAS评分及拔管后躁动评分比较(±s)

组别	例数	拔管后躁动评分(分)	意识恢复时间(min)	意识恢复后VAS评分(分)	术后改良OAA/S评分(分)
U₁组	30	0.57±0.50^a	14.52±9.12^c	1.67±1.09	1.16±0.38^e
U₂组	30	0^ab	10.56±5.03^cd	1.77±1.30	1.06±0.25^e
U₃组	30	0^ab	10.06±6.84^cd	1.57±1.45	1.03±0.19^e
C组	30	0.87±0.62	19.42±9.60	1.93±1.11	1.47±0.63
F值	?	34.41	8.45	0.12	7.33
P值	?	<0.05	<0.05	>0.05	<0.05

表3 患者CAM评分在术后3天的变化(±s)

组别	例数	CAM评分
组别	例数	术后第1天	术后第2天	术后第3天
U₁组	30	17.3±3.6^a	15.0±2.4	13.9±2.0^d
U₂组	30	16.6±3.8^ab	15.6±2.8	13.7±2.19^d
U₃组	30	16.7±3.0^ac	15.4±2.3	13.9±2.0^d
C组	30	20.8±4.4	15.9±3.4	15.5±2.7
F值	?	F_时间＝0.8，F_交互＝0.006, F_组间＝8.61
P值	?	P_时间>0.05, P_交互>0.05, P_组间<0.05

表3 患者CAM评分在术后3天的变化(±s)

组别	例数	CAM评分
组别	例数	术后第1天	术后第2天	术后第3天
U₁组	30	17.3±3.6^a	15.0±2.4	13.9±2.0^d
U₂组	30	16.6±3.8^ab	15.6±2.8	13.7±2.19^d
U₃组	30	16.7±3.0^ac	15.4±2.3	13.9±2.0^d
C组	30	20.8±4.4	15.9±3.4	15.5±2.7
F值	?	F_时间＝0.8，F_交互＝0.006, F_组间＝8.61
P值	?	P_时间>0.05, P_交互>0.05, P_组间<0.05

表4 血清IL-6在各时点的变化[ng/L，(±s)]

组别	例数	T₀	T₁	T₂	T₃	T₄	T₅
U₁组^a	30	20±8	27±8	33±8^b	40±7^c	45±6^d	20±8
U₂组^a	30	19±6	24±6	28±8^b	36±7^c	43±5^d	18±9
U₃组^a	30	19±6	23±6	27±6^b	35±6^c	43±6^d	18±7
C组	30	19±9	29±8	43±9	53±8	65±7	22±6
F值	?	F_时间＝25.3，F_交互＝1.85, F_组间＝16.84
P值	?	P_时间<0.05，P_交互>0.05，P_组间<0.05

表4 血清IL-6在各时点的变化[ng/L，(±s)]

组别	例数	T₀	T₁	T₂	T₃	T₄	T₅
U₁组^a	30	20±8	27±8	33±8^b	40±7^c	45±6^d	20±8
U₂组^a	30	19±6	24±6	28±8^b	36±7^c	43±5^d	18±9
U₃组^a	30	19±6	23±6	27±6^b	35±6^c	43±6^d	18±7
C组	30	19±9	29±8	43±9	53±8	65±7	22±6
F值	?	F_时间＝25.3，F_交互＝1.85, F_组间＝16.84
P值	?	P_时间<0.05，P_交互>0.05，P_组间<0.05

表5 血清S-100β在各时点的变化[ng/L，(±s)]

组别	例数	T₀	T₁	T₂	T₃	T₄	T₅
U₁组^a	30	588±135	1095±18	1329±257^b	989±124^c	770±110^d	581±134
U₂组^a	30	583±139	1037±168	1318±242^b	968±175^c	767±127^d	568±126
U₃组^a	30	590±132	1063±131	1291±258^b	966±154^c	747±128^d	554±131
C组	30	5932±13	1151±276	1580±290	1088±149	840±128	626±154
F值	?	F_时间＝82.67，F_交互＝1.63, F_组间＝7.613
P值	?	P_时间<0.05, P_交互>0.05, P_组间<0.05

表5 血清S-100β在各时点的变化[ng/L，(±s)]

组别	例数	T₀	T₁	T₂	T₃	T₄	T₅
U₁组^a	30	588±135	1095±18	1329±257^b	989±124^c	770±110^d	581±134
U₂组^a	30	583±139	1037±168	1318±242^b	968±175^c	767±127^d	568±126
U₃组^a	30	590±132	1063±131	1291±258^b	966±154^c	747±128^d	554±131
C组	30	5932±13	1151±276	1580±290	1088±149	840±128	626±154
F值	?	F_时间＝82.67，F_交互＝1.63, F_组间＝7.613
P值	?	P_时间<0.05, P_交互>0.05, P_组间<0.05

表6 血清BDNF在各时点的变化[ng/L，(±s)]

组别	例数	T₀	T₁	T₂	T₃	T₄	T₅
U₁组^a	30	5.6±1.1	2.4±0.8^b	3.5±0.8^c	4.7±0.5^d	5.4±0.5	6.3±0.8
U₂组^a	30	5.7±1.1	2.5±0.7^b	3.5±0.9^c	4.8±0.7^d	5.7±0.9	6.3±0.9
U₃组^a	30	5.7±1.1	2.6±0.7^b	3.6±0.6^c	4.7±0.6^d	5.7±0.6	6.5±0.7
C组	30	5.6±1.0	1.8±0.8	2.9±0.8	4.2±0.7	5.2±0.6	6.1±0.8
F值	?	F_时间＝10.64, F_交互＝4.047, F_组间＝38.54
P值	?	P_时间<0.01，　 P_交互<0.01, P_组间<0.05

表6 血清BDNF在各时点的变化[ng/L，(±s)]

组别	例数	T₀	T₁	T₂	T₃	T₄	T₅
U₁组^a	30	5.6±1.1	2.4±0.8^b	3.5±0.8^c	4.7±0.5^d	5.4±0.5	6.3±0.8
U₂组^a	30	5.7±1.1	2.5±0.7^b	3.5±0.9^c	4.8±0.7^d	5.7±0.9	6.3±0.9
U₃组^a	30	5.7±1.1	2.6±0.7^b	3.6±0.6^c	4.7±0.6^d	5.7±0.6	6.5±0.7
C组	30	5.6±1.0	1.8±0.8	2.9±0.8	4.2±0.7	5.2±0.6	6.1±0.8
F值	?	F_时间＝10.64, F_交互＝4.047, F_组间＝38.54
P值	?	P_时间<0.01，　 P_交互<0.01, P_组间<0.05

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Application of ulinastatin on postoperative delirium in elderly patients undergoing hip arthroplasty

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Application of ulinastatin on postoperative delirium in elderly patients undergoing hip arthroplasty