亚麻醉剂量艾司氯胺酮对老年髋关节置换术患者血清基质金属蛋白酶-9及术后谵妄的影响

doi:10.12092/j.issn.1009-2501.2026.05.007

摘要/Abstract

摘要：

目的: 评估亚麻醉剂量艾司氯胺酮对老年髋关节置换术患者血清基质金属蛋白酶-9（MMP-9）及术后谵妄（POD）的影响。方法: 招募2024年2月至2025年3月于本院择期全身麻醉下行髋关节置换术的老年患者110例，年龄65～79岁，随机分为艾司氯胺酮组（E组，n=55）和对照组（C组，n=55）。E组患者给予艾司氯胺酮（负荷剂量0.2 mg/kg，随后以0.1 mg·kg^?1·h^?1的速度持续输注），而C组患者给予等容量的生理盐水（负荷剂量0.2 mL/kg，随后以0.1 mL·kg^?1·h^?1的速度持续输注）。术后3 d采用重症监护室（ICU）意识障碍评估法（CAM-ICU）评估POD。于术前、术后1 d及术后3 d通过静脉采血检测MMP-9、白细胞介素6（IL-6）和白细胞介素1β（IL-1β）的血清浓度。使用15项恢复质量问卷（QoR-15）在术后1 d和2 d评估恢复质量并记录首次下地活动时间及住院时间。结果: 与C组比较，E组POD发生率显著降低（9.1% vs. 23.6%，χ²=4.251，P=0.039），且POD严重程度[（3.1±1.1）vs.（4.2±1.6）分，t=4.201，P<0.001]和持续时长[（1.1±0.7）vs.（2.2±0.9）d，t=7.155，P<0.001]均显著改善。术后1 d和3 d，E组血清MMP-9、IL-6及IL-1β浓度均显著低于C组（P均<0.001）。与C组比较，E组QoR-15评分显著更高[术后1 d：（114.1±7.4）vs.（91.3±5.3）分；术后2 d：（126.1±8.5）vs.（103.2±6.3）分，P均<0.001），首次下地活动时间更短[（27.6±3.7）vs.（31.4±3.3）h，P<0.001]。两组术中及术后不良事件总发生率均相近（P>0.05）。结论: 亚麻醉剂量艾司氯胺酮可显著降低老年髋关节置换术患者POD发生率、血清MMP-9及IL-6、IL-1β水平，改善术后恢复质量，且不增加围术期不良事件风险，为优化老年患者麻醉管理提供了有效策略。

关键词: 艾司氯胺酮, 基质金属蛋白酶-9, 谵妄, 骨科手术, 老年

Abstract:

AIM: To evaluate the effects of subanesthetic dose of esketamine on serum matrix metalloproteinase-9 (MMP-9) and postoperative delirium (POD) in elderly patients undergoing hip replacement. METHODS: From February 2024 to March 2025, 110 elderly patients aged 65-79 years undergoing elective hip replacement under general anesthesia in our hospital were randomly divided into esketamine group (group E, n=55) and control group ( group C, n=55). Patients in group E were given esketamine (loading dose 0.2 mg/kg, followed by continuous infusion at a rate of 0.1 mg·kg^?¹·h^?¹), while patients in group C were given an equal volume of normal saline (loading dose 0.2 mL/kg, followed by continuous infusion at a rate of 0.1 mL·kg^?¹·h^?¹). POD was assessed by the confusion assessment method for the intensive care unit (CAM-ICU) at 3 days after operation. The serum concentrations of MMP-9, interleukin-6 (IL-6) and interleukin-1β (IL-1β) were detected by venous blood sampling before operation, 1 d and 3 d after operation. The quality of recovery was assessed using the 15-item quality of recovery questionnaire (QoR-15) at 1 and 2 days after surgery, and the time to first ambulation and length of hospital stay were recorded. RESULTS: Compared with Group C, Group E showed a significantly lower incidence of POD (9.1% vs. 23.6%, χ²=4.251, P=0.039), along with reduced severity (3.1±1.1 vs. 4.2±1.6 score, t=4.201, P<0.001) and shorter duration of POD (1.1±0.7 vs. 2.2±0.9 days, t=7.155, P<0.001). Serum concentrations of MMP-9, IL-6, and IL-1β in Group E were significantly lower than those in Group C at postoperative day 1 and day 3 (all P<0.001). Compared to Group C, Group E demonstrated significantly higher QoR-15 scores [postoperative day 1: (114.1±7.4) vs. (91.3±5.3) score; postoperative day 2: (126.1±8.5) vs. (103.2±6.3) score, both P<0.001] and earlier ambulation time (27.6±3.7 vs. 31.4±3.3 h, P<0.001). The total incidence of intraoperative and postoperative adverse events was similar between the two groups (P>0.05). CONCLUSION: Subanesthetic-dose esketamine significantly reduces the incidence of POD and serum levels of MMP-9, IL-6, and IL-1β, improves postoperative recovery quality, and does not increase perioperative adverse events in elderly patients undergoing hip replacement, providing an effective strategy for optimizing anesthesia management in geriatric populations.

Key words: esketamine, matrix metalloproteinase-9, postoperative delirium, orthopedic surgery, elderly

中图分类号:

R614
R687.3

靳广丽, 苏丽莎, 王利品, 王其敏. 亚麻醉剂量艾司氯胺酮对老年髋关节置换术患者血清基质金属蛋白酶-9及术后谵妄的影响[J]. 中国临床药理学与治疗学, 2026, 31(5): 631-638.

Guangli JIN, Lisha SU, Lipin WANG, Qimin WANG. Effects of sub-anesthetic dose esketamine on serum matrix metalloproteinase-9 and postoperative delirium in elderly patients undergoing hip replacement[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(5): 631-638.

图/表 6

参考文献 21

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Items	C group	E group	χ2 value/t value	P value
Gender (male/female, cases)	32/23	29/26	0.331	0.565
Age (years, $ \overline{x} $±s)	71.4±3.7	71.9±3.9	0.690	0.492
ASA grade (Ⅱ/Ⅲ, cases)	38/17	40/15	0.176	0.675
BMI (kg/m², $ \overline{x} $±s)	22.7±2.6	22.3±2.8	0.776	0.439
Smoking history [n(%)]	15(27.3)	13(23.6)	0.192	0.661
Drinking history [n(%)]	17(30.9)	19(34.5)	0.165	0.685
Hypertension [n(%)]	10(18.2)	9(16.4)	0.064	0.800
Diabetes [n(%)]	7(12.7)	10(18.2)	0.626	0.429
Coronary heart disease [n(%)]	3(5.5)	5(9.1)	0.539	0.463
LVEF (%, $ \overline{x} $±s)	64.5±4.6	64.9±5.2	0.427	0.670
Preoperative FEV₁/FVC (%, $ \overline{x} $±s)	75.7±5.5	76.0±5.6	0.284	0.777
Preoperative PaO₂ (mmHg, $ \overline{x} $±s)	95.9±4.8	96.2±4.6	0.335	0.739
Preoperative PaCO₂ (mmHg,$ \overline{x} $±s)	40.9±3.3	41.1±3.1	0.328	0.745
Basic oxygen saturation (%, $ \overline{x} $±s)	97.4±1.8	97.1±1.6	0.924	0.358
Years of education (years, $ \overline{x} $±s)	12.5±1.6	12.9±2.1	1.124	0.264
MMSE scale (score, $ \overline{x} $±s)	28.3±1.9	28.7±2.0	1.075	0.285
Operation time (min, $ \overline{x} $±s)	116.7±8.9	114.5±9.3	1.267	0.208
Duration of anesthesia (min, $ \overline{x} $±s)	130.6±8.6	132.6±8.6	1.220	0.225
Remifentanil consumption (mg, $ \overline{x} $±s)	2.1±0.6	2.2±0.5	0.950	0.345
Sufentanil consumption (μg, $ \overline{x} $±s)	154.0±19.5	150.9±21.1	0.800	0.425
Propofol consumption (mg, $ \overline{x} $±s)	685.5±89.3	678.2±92.1	0.422	0.674
Mean intraoperative BIS value (score, $ \overline{x} $±s)	48.2±3.5	49.1±3.8	1.292	0.199
Blood loss (mL, $ \overline{x} $±s)	145.6±28.1	141.6±27.8	0.751	0.455
Fluids intake (mL, $ \overline{x} $±s)	1238.5±322.8	1224.3±288.6	0.243	0.808
Duration of mechanical ventilation (h, $ \overline{x} $±s)	143.7±12.5	144.2±11.9	0.215	0.830
Awakening time (min, $ \overline{x} $±s)	9.5±4.0	9.8±3.8	0.403	0.688
PACU stay time (min, $ \overline{x} $±s)	56.5±6.2	57.0±8.5	0.352	0.725

Items	C group	E group	χ2 value/t value	P value
Gender (male/female, cases)	32/23	29/26	0.331	0.565
Age (years, $ \overline{x} $±s)	71.4±3.7	71.9±3.9	0.690	0.492
ASA grade (Ⅱ/Ⅲ, cases)	38/17	40/15	0.176	0.675
BMI (kg/m², $ \overline{x} $±s)	22.7±2.6	22.3±2.8	0.776	0.439
Smoking history [n(%)]	15(27.3)	13(23.6)	0.192	0.661
Drinking history [n(%)]	17(30.9)	19(34.5)	0.165	0.685
Hypertension [n(%)]	10(18.2)	9(16.4)	0.064	0.800
Diabetes [n(%)]	7(12.7)	10(18.2)	0.626	0.429
Coronary heart disease [n(%)]	3(5.5)	5(9.1)	0.539	0.463
LVEF (%, $ \overline{x} $±s)	64.5±4.6	64.9±5.2	0.427	0.670
Preoperative FEV₁/FVC (%, $ \overline{x} $±s)	75.7±5.5	76.0±5.6	0.284	0.777
Preoperative PaO₂ (mmHg, $ \overline{x} $±s)	95.9±4.8	96.2±4.6	0.335	0.739
Preoperative PaCO₂ (mmHg,$ \overline{x} $±s)	40.9±3.3	41.1±3.1	0.328	0.745
Basic oxygen saturation (%, $ \overline{x} $±s)	97.4±1.8	97.1±1.6	0.924	0.358
Years of education (years, $ \overline{x} $±s)	12.5±1.6	12.9±2.1	1.124	0.264
MMSE scale (score, $ \overline{x} $±s)	28.3±1.9	28.7±2.0	1.075	0.285
Operation time (min, $ \overline{x} $±s)	116.7±8.9	114.5±9.3	1.267	0.208
Duration of anesthesia (min, $ \overline{x} $±s)	130.6±8.6	132.6±8.6	1.220	0.225
Remifentanil consumption (mg, $ \overline{x} $±s)	2.1±0.6	2.2±0.5	0.950	0.345
Sufentanil consumption (μg, $ \overline{x} $±s)	154.0±19.5	150.9±21.1	0.800	0.425
Propofol consumption (mg, $ \overline{x} $±s)	685.5±89.3	678.2±92.1	0.422	0.674
Mean intraoperative BIS value (score, $ \overline{x} $±s)	48.2±3.5	49.1±3.8	1.292	0.199
Blood loss (mL, $ \overline{x} $±s)	145.6±28.1	141.6±27.8	0.751	0.455
Fluids intake (mL, $ \overline{x} $±s)	1238.5±322.8	1224.3±288.6	0.243	0.808
Duration of mechanical ventilation (h, $ \overline{x} $±s)	143.7±12.5	144.2±11.9	0.215	0.830
Awakening time (min, $ \overline{x} $±s)	9.5±4.0	9.8±3.8	0.403	0.688
PACU stay time (min, $ \overline{x} $±s)	56.5±6.2	57.0±8.5	0.352	0.725

Group	Time points	MMP-9 concentration (ng/mL)	IL-6 concentration (pg/mL)	IL-1β concentration (pg/mL)
C	Preoperative 1 d	177.8±34.6	23.9±5.5	37.4±9.6
	Postoperative 1 d	467.3±56.7	60.8±9.6	75.6±13.8
	Postoperative 3 d	334.0±43.2	49.6±7.8	59.8±11.3
E	Preoperative1 d	183.5±37.3	24.4±5.2	38.7±10.7
	Postoperative 1 d	332.3±41.6	51.7±8.4	60.3±12.1
	Postoperative 3 d	220.3±39.7	41.3±7.6	48.5±8.6
	F_{between-group}/P_{between-group}	27.416/<0.001	18.953/<0.001	24.657/<0.001
	F_time/P_time	112.358/<0.001	89.247/<0.001	67.519/<0.001
	F_interaction/P_interaction	15.732/<0.001	9.846/<0.001	12.394/<0.001

Group	Time points	MMP-9 concentration (ng/mL)	IL-6 concentration (pg/mL)	IL-1β concentration (pg/mL)
C	Preoperative 1 d	177.8±34.6	23.9±5.5	37.4±9.6
	Postoperative 1 d	467.3±56.7	60.8±9.6	75.6±13.8
	Postoperative 3 d	334.0±43.2	49.6±7.8	59.8±11.3
E	Preoperative1 d	183.5±37.3	24.4±5.2	38.7±10.7
	Postoperative 1 d	332.3±41.6	51.7±8.4	60.3±12.1
	Postoperative 3 d	220.3±39.7	41.3±7.6	48.5±8.6
	F_{between-group}/P_{between-group}	27.416/<0.001	18.953/<0.001	24.657/<0.001
	F_time/P_time	112.358/<0.001	89.247/<0.001	67.519/<0.001
	F_interaction/P_interaction	15.732/<0.001	9.846/<0.001	12.394/<0.001

Group	Postoperative 1 d	Postoperative 2 d	Duration of first ambulation after operation (h)	Length of postoperative hospital stay (d)
C	91.3±5.3	103.2±6.3	31.4±3.3	9.2±1.9
E	114.1±7.4	126.1±8.5	27.6±3.7	9.0±1.4
t value	18.580	16.050	5.684	0.629
P value	<0.001	<0.001	<0.001	0.531