Prognosis-related classification and dynamic monitoring of immune status in patients with sepsis: A prospective observational study

doi:10.5847/wjem.j.1920-8642.2021.03.004

Abstract

Abstract:

BACKGROUND: The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis. In this study, we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value.

METHODS: A prospective observational study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between July 2016 and December 2018. Blood samples were collected at days 1 and 3. Serum cytokine levels (e.g., tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10]) and CD14⁺ monocyte human leukocyte antigen-D-related (HLA-DR) expression were measured to serve as immune markers. Classification of each immune status, namely systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS), and mixed antagonistic response syndrome (MARS), was defined based on levels of immune markers. Changes of immune status were classified into four groups which were stabilization (SB), deterioration (DT), remission (RM), and non-remission (NR).

RESULTS: A total of 174 septic patients were enrolled including 50 non-survivors. Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors. Patients with MARS had the highest mortality rate. Immune status of 46.1% patients changed from day 1 to day 3. Among four groups of immune status changes, DT had the highest mortality rate, followed by NR, RM, and SB with mortality rates of 64.7%, 42.9%, and 11.2%, respectively.

CONCLUSIONS: Severe immune disorder defined as MARS or deterioration of immune status defined as DT lead to the worst outcomes. The preliminary model of the classification and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.

Key words: Infectious disease, Immune dysfunction, Immune status classification, Cytokine

Jun Yin, Yao Chen, Jun-ling Huang, Lei Yan, Zhong-shu Kuang, Ming-ming Xue, Si Sun, Hao Xiang, Yan-yan Hu, Zhi-min Dong, Chao-yang Tong, Chun-xue Bai, Zhen-ju Song. Prognosis-related classification and dynamic monitoring of immune status in patients with sepsis: A prospective observational study[J]. World Journal of Emergency Medicine, 2021, 12(3): 185-191.

Figures/Tables 4

Figure 1.

Table 1

Clinical and demographic characteristics of enrolled patients classified according to prognosis

Parameters	Survivors (n=124)	Non-survivors (n=50)	P-value
Age, years	67.5 (48.3-78.0)	67.0 (56.8-73.3)	0.703
Male, n (%)	78 (62.9)	31 (62.0)	0.911
Comorbidities, n (%)
Hypertension	58 (46.8)	25 (50.0)	0.700
Diabetes mellitus	33 (26.6)	15 (30.0)	0.651
Coronary heart disease	12 (9.7)	7 (14.0)	0.408
Chronic obstructive pulmonary disease	10 (8.1)	5 (10.0)	0.910
Hepatitis and cirrhosis	12 (9.7)	3 (6.0)	0.595
Renal insufficiency	14 (11.3)	7 (14.0)	0.620
Malignancy	11 (8.9)	6 (12.0)	0.729
Main site of infection, n (%)
Respiratory tract	80 (64.5)	37 (74.0)	0.707
Abdomen	30 (24.2)	8 (16.0)	0.311
Urinary tract	6 (4.8)	2 (4.0)	1.000
Skin and soft tissue	4 (3.2)	2 (4.0)	1.000
Blood stream	4 (3.2)	1 (2.0)	1.000
Index of severity of disease, median (25^th, 75^th)
APACHE II score
Day 1	12 (7, 16)	21 (12, 26)	<0.001
Day 3^a	9 (6, 13)	18 (14, 25)	<0.001
SOFA score
Day 1	3 (2, 4)	5 (4, 10)	<0.001
Day 3^a	2 (1, 4)	6 (4, 8)	<0.001
Inflammatory markers, median (25^th, 75^th)
WBC, ×10⁹/L
Day 1	10.85 (6.99, 14.50)	12.60 (8.16, 18.40)	0.024
Day 3^a	9.07 (6.90, 12.09)	13.15 (9.55, 19.79)	<0.001
CRP, mg/L
Day 1	90 (57, 96)	90 (63, 139)	0.353
Day 3^a	52 (15, 105)	90 (66, 144)	0.002
PCT, ng/L
Day 1	1.14 (0.29, 5.07)	1.47 (0.40, 10.40)	0.172
Day 3^a	0.56 (0.15, 1.98)	1.85 (0.60, 11.13)	<0.001
Interventions, n (%)
Glucocorticoids (prednisone >200 mg)	67 (54.0)	38 (76.0)	0.007
Mechanical ventilation	62 (50.0)	46 (92.0)	<0.001
Deep venous catheterization	54 (43.5)	38 (76.0)	<0.001
Urinary catheterization	57 (46.0)	43 (86.0)	<0.001
Adverse events, n (%)
Septic shock	16 (12.9)	20 (40.0)	<0.001
Secondary infection	36 (29.0)	14 (28.0)	0.019
Acute heart failure	26 (20.9)	22 (44.0)	0.002
Acute kidney injury	21 (16.9)	19 (38.0)	0.003
Acute liver injury	14 (11.3)	16 (32.0)	<0.001
Acute respiratory failure	37 (29.8)	28 (56.0)	<0.001
ICU length of stay (days)	14.0 (10.0, 21.8)	10.0 (5.0, 20.5)	<0.002

Table 1

Table 2

Figure 2.

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Parameters	Day 1			Day 3
Parameters	SIRS	CARS	MARS	SIRS	CARS	MARS
Survivors, n (%)^a	57 (98.3)	48 (68.6)	19 (41.3)	83 (94.3)	24 (60.0)	8 (30.7)
Non-survivors, n (%)^a	1 (1.7)	22 (31.4)	27 (58.7)	5 (5.7)	16 (40.0)	18 (69.2)
P_A/P_B^b	<0.001/<0.001			<0.001/<0.001

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