Effect of Shenfu injection on immune function in elderly patients with sepsis

doi:10.16138/j.1673-6087.2024.03.01

Abstract

Abstract:

Objective To explore the effect of Shenfu injection on immune function in elderly patients with sepsis. Methods This study was a retrospective analysis. The elderly patients(n=126) with sepsis admitted to 4 hospitals including Shanghai Ruijin Hospital from January 2019 to December 2020 were divided into two groups according to whether Shenfu injection was used (61 cases in Shenfu group, 65 cases in control group). Basic data, comorbidities, relevant test results (including inflammatory factors, humoral immune indicators, cellular immune indicators, etc.), disease severity score, mortality rate, etc., were collected for statistical analysis. Results After seven days of Shenfu injection treatment, the indexes including the mean artery pressure (MAP), lactate (Lac), C-reactive protein (CRP), procalcitonin (PCT), prothrombin time (PT), activated partial thromboplastin time (APTT), interleukin-6(IL-6), IL-10, tumor necrosis factor-α(TNF-α), CD3 count, CD4 count, CD8 count, IgG, IgA and IgM of patients in 2 groups were significantly improved (all P<0.05). Compared with the control group, MAP(P=0.034), and the absolute count of CD3(P=0.002) and CD4(P=0.002) were significantly increased in the Shenfu treated group. Conclusions Shenfu injection combined with standard bundled regimen can improve the immune function and reduce inflammation in elderly patients with sepsis.

Key words: Elderly, Sepsis, Immune function, Inflammatory factors

CLC Number:

R631

LIU Di, QÜ Hongping, XÜ Zhihong, CAO Jiumei, ZHENG Lan, BAI Tingting. Effect of Shenfu injection on immune function in elderly patients with sepsis[J]. Journal of Internal Medicine Concepts & Practice, 2024, 19(03): 153-158.

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References 22

[1]	Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3)[J]. JAMA, 2016, 315(8):801-810. doi: 10.1001/jama.2016.0287 pmid: 26903338
[2]	Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update[J]. Crit Care Med, 2018, 46(6):997-1000. doi: 10.1097/CCM.0000000000003119 pmid: 29767636
[3]	Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017[J]. Lancet, 2020, 395(10219):200-211.
[4]	Mankowski RT, Anton SD, Ghita GL, et al. Older sepsis survivors suffer persistent disability burden and poor long-term survival[J]. J Am Geriatr Soc, 2020, 68(9):1962-1969.
[5]	Martín S, Pérez A, Aldecoa C. Sepsis and immunosenescence in the elderly patient[J]. Front Med (Lausanne), 2017, 4:20.
[6]	Hou X, Li C, Gu W, et al. Effect of Shenfu on inflammatory cytokine release and brain edema after prolonged cardiac arrest in the swine[J]. Am J Emerg Med, 2013, 31(8):1159-1164. doi: 10.1016/j.ajem.2013.03.020 pmid: 23806725
[7]	智屹惠, 王坤根, 王灵聪. 《中国严重脓毒症/脓毒性休克治疗指南(2014)》中医药部分解读[J]. 中华危重病急救医学, 2015, 27(6): 429-434.
[8]	高戈, 冯喆, 常志刚, 等. 2012国际严重脓毒症及脓毒性休克诊疗指南[J]. 中华危重病急救医学, 2013, 25(8): 501-505.
[9]	Markwart R, Condotta SA, Requardt RP, et al. Immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of naïve T-cells but no enduring cell-autonomous defects in T-cell function[J]. PLoS One, 2014, 9(12): e115094.
[10]	中国医师协会急诊医师分会中国研究型医院学会休克与脓毒症专业委员会. 参附注射液急重症临床应用专家共识[J]. 中国急救医学, 2018, 38(11): 925-931.
[11]	Huang P, Guo Y, Feng S, et al. Efficacy and safety of Shenfu injection for septic shock[J]. Am J Emerg Med, 2019, 37(12):2197-2204. doi: S0735-6757(19)30182-2 pmid: 30981461
[12]	奚小土, 朱满刚, 刘云涛, 等. 参附注射液对脓毒症患者免疫功能、炎症指标的影响[J]. 新中医, 2018, 50(6): 72-76.
[13]	Hotchkiss RS, Tinsley KW, Swanson PE, et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4⁺ T lymphocytes in humans[J]. J Immunol, 2001, 166(11):6952-6963. doi: 10.4049/jimmunol.166.11.6952 pmid: 11359857
[14]	McDunn JE, Turnbull IR, Polpitiya AD, et al. Splenic CD4⁺ T cells have a distinct transcriptional response six hours after the onset of sepsis[J]. J Am Coll Surg, 2006, 203(3):365-375.
[15]	Martin MD, Badovinac VP, Griffith TS. CD4 T cell responses and the sepsis-induced immunoparalysis state[J]. Front Immunol, 2020, 11:1364. doi: 10.3389/fimmu.2020.01364 pmid: 32733454
[16]	张文钊, 王志斌. 脓毒症免疫抑制相关效应T细胞亚群稳态失衡的研究进展[J]. 中华危重病急救医学, 2022, 34(1): 95-99.
[17]	Jensen IJ, Sjaastad FV, Griffith TS, et al. Sepsis-induced T cell immunoparalysis: the ins and outs of impaired T cell immunity[J]. J Immunol, 2018, 200(5):1543-1553. doi: 10.4049/jimmunol.1701618 pmid: 29463691
[18]	王静, 张毅, 高艳玲. 脓毒症患者免疫指标与预后的关系[J]. 中华危重病急救医学, 2022, 34(9): 931-934.
[19]	Zhang N, Liu J, Qiu Z, et al. Shenfu injection for improving cellular immunity and clinical outcome in patients with sepsis or septic shock[J]. Am J Emerg Med, 2017, 35(1): 1-6. doi: S0735-6757(16)30583-6 pmid: 28029485
[20]	Shankar-Hari M, Culshaw N, Post B, et al. Endogenous IgG hypogammaglobulinaemia in critically ill adults with sepsis[J]. Intensive Care Med, 2015, 41(8):1393-1401. doi: 10.1007/s00134-015-3845-7 pmid: 25971390
[21]	Venet F, Gebeile R, Bancel J, et al. Assessment of plasmatic immunoglobulin G, A and M levels in septic shock patients[J]. Int Immunopharmacol, 2011, 11(12):2086-2090. doi: 10.1016/j.intimp.2011.08.024 pmid: 21924385
[22]	Dietz S, Lautenschläger C, Müller-Werdan U, et al. Serum IgG levels and mortality in patients with severe sepsis and septic shock[J]. Med Klin Intensivmed Notfmed, 2017, 112(5):462-470. doi: 10.1007/s00063-016-0220-6 pmid: 27677760

项目	对照组 (n=65)	参附组 (n=61)	t/χ²	P
性别[n(%)]
男性	43(66.2)	39(63.9)	0.068	0.749
女性	22(33.9)	22(36.1)
年龄(岁)	72.85±8.39	73.95±7.57	0.768	0.444
主要合并症[n(%)]
高血压	43(66.2)	34(55.7)	1.437	0.231
肿瘤	32(49.2)	31(50.8)	0.032	0.859
糖尿病	21(32.3)	17(27.9)	0.294	0.587
COPD	4(6.2)	6(9.8)	0.189	0.664
冠心病	10(15.4)	14(23.0)	1.168	0.280
肝硬化	1(1.5)	3(4.9)	0.328	0.567
甲状腺功能减退	1(1.5)	1(1.6)	/	1.000
脏器功能[n(%)]
心功能不全	16(24.6)	25(41.0)	3.841	0.050
急性呼吸衰竭	45(69.2)	43(70.5)	0.024	0.878
肝功能不全	20(30.8)	16(26.2)	0.318	0.573
肾功能不全	37(56.9)	31(50.8)	0.472	0.492
凝血功能障碍	23(35.4)	24(39.3)	0.211	0.646
胃肠功能障碍	42(64.6)	40(65.6)	0.013	0.910
感染部位[n(%)]
呼吸道	20(30.8)	20(32.8)	0.059	0.808
腹腔	35(53.9)	29(47.5)	0.501	0.479
血液	10(15.4)	13(21.3)	0.741	0.389
胆道	7(10.8)	9(14.8)	0.451	0.502
皮肤	2(3.1)	1(1.6)	0.000	1.000
纵隔	4(6.2)	2(3.3)	0.115	0.735
中枢神经系统	0(0.0)	0(0.0)	/	/
泌尿道	0(0.0)	1(1.6)	/	/
病原学[n(%)]
革兰阴性菌	38(58.5)	37(60.7)	0.063	0.802
革兰阳性菌	16(24.6)	9(14.8)	1.924	0.165
真菌	7(10.8)	10(16.5)	0.853	0.356
病毒	1(1.5)	1(1.6)	/	1.000
病原未明确	14(21.5)	13(21.3)	0.001	0.975
血管活性药物
使用人数[n(%)]	47(72.3)	42(68.9)	0.181	0.670
使用天数(d)	5.51±6.41	4.57±4.69	0.255	0.318
机械通气
使用人数[n(%)]	48(73.9)	39(63.9)	1.447	0.229
使用天数(d)	7.06±7.58	7.57±8.14	0.422	0.788
APACHEⅡ评分(分)	23.25±7.81	23.71±7.97	0.428	0.669
SOFA评分(分)	8.95±4.15	8.23±4.30	0.829	0.409

项目	对照组 (n=65)	参附组 (n=61)	t/χ²	P
第7天APACHEⅡ(分)	12.57±3.61	12.34±4.21	0.230	0.822
第7天SOFA(分)	4.16±3.49	4.44±3.98	0.490	0.625
28 d病死率[n(%)]	13(20.0)	9(14.8)	0.601	0.490

项目	例数（n）	治疗前	治疗7 d后	差值	Z	P
MAP(mmHg)
对照组	65	77.9(69.7，87.5)	90.0(83.6，96.0)	3(-42，13.7)	3.659	<0.001
参附组	61	78.9(70.5，89.9)	95.0(84.7，100.5)	11.3(0，23.1)¹⁾	4.746	<0.001
Lac (mmol/L)
对照组	65	2.1(1.4，4.2)	1.7(1.3，2.4)	0.4(-0.3，2.2)	-2.567	<0.001
参附组	61	2.5(1.4，4.2)	1.8(1.1，2.4)	0.6(-0.1，2.5)	-2.829	0.010
CRP(mg/L)
对照组	65	144.0(21.1，228)	46.0(9.9，101.0)	41(1.27，123.8)	-4.863	<0.001
参附组	61	112.0(18.0，194.0)	40.6(12.0，82.5)	64(5.4，128.5)	-5.441	<0.001
PCT(μg/L)
对照组	65	4.2(1.2，24.7)	0.8(0.3，2.9)	3.4(-0.7，21.6)	-5.665	<0.001
参附组	61	5.2(1.0，29.6)	0.7(0.2，2.0)	3.4(0.9，27.7)	-6.213	<0.001
PT(s)
对照组	65	15.2(13.5，16.1)	13.7(12.8，15.5)	1.2(-0.5，3.8)	-2.567	<0.001
参附组	61	15.9(13.9，18.0)	14.0(13.1，16.3)	1(-0.3，2.5)	-3.406	0.010
APTT(s)
对照组	65	37.5(32.1，47.3)	35.4(30.1，42.2)	3.9(-3.3，10.2)	-2.514	<0.001
参附组	61	41.3(34.3，48.6)	37.4(30.2，42.3)	1(-0.6，12.3)	-2.668	0.012

项目	例数（n）	治疗前	治疗7 d后	差值	Z	P
IL-1β
对照组	65	5.0(5.0，11.8)	5.0(5.0，8.0)	0(0，6.4)	-1.704	0.088
参附组	61	5.0(5.0，18.0)	5.0(5.0，5.3)	0(0，2.7)	-1.690	0.091
IL-6
对照组	65	92.1(34.7，272.5)	29.6(17.5，86.2)	61.1(13.8，127.9)	-3.820	<0.001
参附组	61	79.5(40.3，221.8)	26.5(8.2，89.3)	25.5(3.4，175.0)	-3.661	<0.001
IL-8
对照组	65	200.0(83.4，761.5)	149.0(82.9，467.0)	39.7(-122.7，766.5)	-1.538	0.124
参附组	61	131.0(65.0，349.0)	117.0(47.5，315.5)	4(-125.6，141)	-0.988	0.323
IL-10
对照组	65	11.6(6.2，26.6)	8.0(5.0，14.9)	1.2(-0.1，19.4)	-2.514	0.012
参附组	61	7.7(5.6，23.2)	6.2(5.0，16.4)	1.4(-1.7，7)	-2.007	0.038
TNF-α
对照组	65	18.5(12.5，31.2)	15.6(11.3，26.2)	5.9(-5.3，25.9)	-2.072	0.038
参附组	61	17.3(11.1，26.4)	13.3(9.9，19.7)	4.7(-6.1，14.5)	-1.871	0.674

项目	例数（n）	治疗前	治疗7 d后	差值	Z	P
IgG
对照组	65	703.0(540.0，1 130.5)	1 070.0(774.5，1 486.0)	414.0(163.0，884.0)	5.565	0.001
参附组	61	893.0(593.0，1 080.0)	1 190.0(792.5，1 702.5)	425.0(155.0，640.1)	6.195	0.001
IgA
对照组	65	168.0(100.0，274.5)	234.0(160.0，339.5)	71.1(38.0，105.1)	4.879	0.001
参附组	61	179.0(106.0，264.0)	256.0(185.5，344.5)	61.0(21.5，116.0)	5.889	0.001
IgM
对照组	65	60.0(38.0，79.5)	79.0(53.0，122.0)	26.0(10.0，62.0)	5.343	0.015
参附组	61	59.0(40.0，93.5)	88.0(59.0，123.0)	27.0(14.5，54.5)	4.296	0.006