Diagnostic and Prognostic Value of Interleukin-6 in Emergency Department Sepsis Patients

Figures & data

Table 1 Comparison of Baseline Patient Data Between the Non-Sepsis Group and Sepsis Group

Demographic Characteristics	Non-Septic (n=65)	Sepsis (n=63)	Total (n=128)	P value
Age, median (range)	70(30–90)	79(34–95)	72(30–95)	0.004**
Sex, Male, n (%)	44(67.7)	40(63.5)	84(65.6)	0.511
MAP (mmHg)	106.47(21.06)	92.14(23.07)	97.5(84.75–114)	0.000***
Comorbidities
Acute cerebrovascular disease, n (%)	19(29.2)	23(36.5)	42 (32.8)	0.686
Diabetes mellitus, n (%)	22(33.8)	20(31.7)	42 (32.8)	0.220
Cardiovascular disease, n (%)	28(43.1)	6(9.5)	34 (26.6)	0.001**
Chronic lung disease, n (%)	7(10.8)	14(22.2)	21 (16.4)	0.246
Use of vasopressors, n (%)	3(4.6)	19(30.2)	22 (17.7)	0.008**
Use of mechanical ventilation, n (%)	8(12.3)	24(38.1)	32 (25)	0.142
APHACHE II	29(16–39)	33.56(11.91)	33(20–41)	0.054
qSOFA	0(0–1)	1(0–1)	1(0–1)	0.006**
SOFA	1.75(1.5)	5(3–6)	3.3(2.36)	0.000***
GCS	15(15–15)	14(12–15)	15(13–15)	0.002**
Laboratory value
PCT (ng/mL)	0.03(0.01–0.1)	0.49(0.08–3.1)	0.09(0.02–0.57)	0.000***
CRP (mg/dl)	8.3(0.5–31.8)	39.8(10.3–98.6)	23.1(2.08–69.53)	0.000***
Lac (mmol/L)	1.25(0.83–1.88)	1.5(1–2.8)	1.4(0.9–2.2)	0.256
Creatinine (umol/L)	75.3(63–88.85)	88.8(55.5–124.7)	78.7(60.05–101.18)	0.170
Bilirubin (umol/L)	16.38 (14.63)	15.9(9.5–23)	14.95(9.7–21.73)	0.147
Platelets (× 1000/μL)	208.85 (60.59)	189(124–263)	206.5(150–255.75)	0.571
IL-6 (pg/mL)	10.84(4.41–27.01)	92.22(21.53–201.12)	23.09(8.32–115.41)	0.000***
WBC (×10^9个/L)	10.2 (4.25)	11.1(7–15.75)	10(6.85)	0.125
BUN (mmol/L)	7.01(4.90–11.74)	13.03(6.93–25.99)	9.71(5.45–19.19)	0.001**

Notes: **Means p < 0.01, ***Means p < 0.001. Normally distributed data are expressed as mean ± standard deviation; skewed distributed data are expressed as median and quartile.

Abbreviations: SD, Standard Deviation; MAP, Mean Arterial Pressure; qSOFA, Rapid Sequential Organ Failure Score; SOFA, Sequential Organ Failure Score; APHCHE II, Acute Physiology and Chronic Health Assessment II; GCS, Glasgow Coma Scale; PCT, procalcitonin; CRP, C-reactive protein; IL-6, interleukin-6; WBC, white blood cell count.

Table 2 Logistic Regression Analysis of Blood-Based Biomarkers for Predicting Sepsis

Independent Predictors	β	SE	Wald	P value	OR	95% CI
SOFA	1.326	0.503	6.944	0.008**	3.767	1.405	10.102
GCS	0.507	0.245	4.266	0.039*	1.66	1.026	2.684
IL-6	0.029	0.012	5.673	0.017*	1.029	1.005	1.054
qSOFA	0.807	0.928	0.757	0.384	2.241	0.364	13.811
D-D	−0.253	0.19	1.772	0.183	0.776	0.535	1.127
PCT	−0.03	0.43	0.005	0.944	0.97	0.418	2.254
BUN	0.079	0.039	3.999	0.046*	1.082	1.002	1.169
Constant	−13.237	5.054	6.859	0.009	0

Notes: *Means p < 0.05, **Means p < 0.01.

Abbreviations: CI, confidence interval; OR, odds ratio; IL-6, interleukin-6; PCT, procalcitonin; D-D, D-dimer; qSOFA, Quick Sequential Organ Failure Assessment; blank means none.

Table 3 Diagnostic Value of Serum IL-6, BUN and MAP for Sepsis

Independent Predictors	AUC	95% CI		P value	Cutoff	Sensitivity	Specificity	Youden Index	Positive Likelihood Ratio	Negative Likelihood Ratio
IL-6	0.764	0.668	0.861	0***	49.01	0.683	0.828	0.511	3.971	0.383
BUN	0.696	0.589	0.804	0.001**	14.015	0.489	0.864	0.353	3.596	0.591
MAP	0.685	0.575	0.795	0.003**	102.833	0.746	0.554	0.3	1.673	0.458
IL-6+ BUN	0.809	0.722	0.895	0***	0.74	0.511	1	0.511		0.489
IL-6+MAP	0.798	0.706	0.89	0***	0.358	0.825	0.734	0.559	3.102	0.238
BUN +MAP	0.786	0.692	0.881	0***	0.425	0.809	0.727	0.536	2.963	0.263
IL-6+ BUN +MAP	0.848	0.766	0.929	0***	0.467	0.809	0.791	0.6	3.871	0.241

Notes: **Means p < 0.01, ***Means p < 0.001.

Abbreviations: IL-6, interleukin-6; CI, confidence interval; OR, odds ratio; blank means no item.

Table 4 Pearson Correlation Analysis of IL-6 and Other Biomarkers

Variable	IL-6
	r	P
SOFA	0.341	<0.01
qSOFA	0.174	>0.05
PCT	−0.018	>0.05
CRP	0.221	<0.05
WBC	0.061	>0.05

Abbreviations: SOFA, Sequential Organ Failure Assessment; qSOFA, Quick Sequential Organ Failure Assessment; PCT, procalcitonin; CRP, C-reactive protein; IL-6, interleukin-6; WBC, white blood cell count; r, Pearson correlation coefficient.

Figure 1 Receiver operating characteristic (ROC) curves of biomarkers for the diagnosis of sepsis.

Table 5 Univariate Regression Analysis of Biomarkers for Predicting 28-Day Mortality in Patients with Sepsis

Independent Predictors	F	Significance	t	df	P value	Mean Difference	Sandard Error	95% CI
Age	1.81	0.183	2.368	61	0.021*	−8.694	3.671	−16.035	−1.354
Sex	0.485	0.489	0.257	61	0.798	−0.038	0.149	−0.337	0.26
MAP	0.289	0.593	0.138	61	0.89	0.913	6.601	−12.287	14.114
APHACHE II	0.056	0.814	0.705	43	0.485	−2.719	3.856	−10.496	5.058
qSOFA	23.236	0	4.554	41.207	0.000***	−0.604	0.133	−0.872	−0.336
SOFA	1.185	0.281	2.839	61	0.006**	−1.522	0.536	−2.593	−0.45
PCT	1.925	0.17	1.124	61	0.266	−1.215	1.081	−3.377	0.947
CRP	0.192	0.663	0.709	45	0.482	16.433	23.187	−63.133	30.268
Lac	2.392	0.128	1.879	51	0.066	−1.1	0.585	−2.274	0.075
Creatinine	1.013	0.318	1.044	61	0.3	27.855	26.672	−81.189	25.48
Bilirubin	0.296	0.589	0.28	61	0.78	1.496	5.334	−9.171	12.162
GCS	1.183	0.281	3.151	61	0.003**	2.398	0.761	0.876	3.919
IL-6	0.111	0.74	0.394	61	0.695	36.68	93.029	222.704	149.343
WBC	2.44	0.126	3.003	43	0.004**	−5.927	1.974	−9.908	−1.947
BUN	3.085	0.086	2.785	45	0.008**	15.551	5.584	−26.797	−4.304

Notes: *Means p < 0.05, **Means p < 0.01, ***Means p < 0.001.

Abbreviations: MAP, mean arterial pressure; qSOFA, Quick Sequential Organ Failure Assessment; SOFA, Sequential Organ Failure Score; APHCHE II, Acute Physiology and Chronic Health Assessment II; GCS, Glasgow Coma Scale; PCT, Procalcitonin; CRP, C-reactive protein; IL-6, interleukin-6; WBC, white blood cell count; Lac, lactate; CI, confidence interval.

Table 6 Logistic Regression Analysis of Biomarkers for Predicting 28-Day Mortality in Patients with Sepsis

Independent Predictors	β	SE	Wald	df	P value	OR	95% CI
SOFA	0.694	0.305	5.156	1	0.023*	2.001	1.1	3.641
IL-6	−0.001	0.001	0.57	1	0.45	0.999	0.996	1.002
Lac	0.519	0.218	5.64	1	0.018*	1.68	1.095	2.577
BUN	0.033	0.026	1.632	1	0.201	1.034	0.982	1.088
Agw	0.131	0.059	4.934	1	0.026*	1.14	1.016	1.28
Constant	−16.881	6.089	7.685	1	0.006	0

Note: *Means p < 0.05.

Abbreviations: SOFA, Sequential Organ Failure Assessment; IL-6, interleukin-6; Lac, lactate; CI, confidence interval; OR, odds ratio.

Table 7 Predictive Value of Lac, Age and SOFA Score in Predicting 28-Day Mortality in Patients with Sepsis

Independent Predictors	AUC	95% CI		P value	Cutoff	Sensitivity	Specificity	Youden Index	Positive Likelihood Ratio	Negative Likelihood Ratio
Age	0.626	0.461	0.791	0.149	80.5	0.706	0.674	0.38	2.166	0.436
SOFA	0.747	0.606	0.889	0.005**	2.5	0.941	0.13	0.071	1.082	0.454
Lac	0.679	0.524	0.834	0.040*	1.7	0.688	0.649	0.337	1.96	0.481
SOFA+Lac	0.748	0.607	0.889	0.004**	0.247	0.875	0.676	0.551	2.701	0.185
SOFA+ Age	0.785	0.656	0.915	0.001**	0.466	0.588	0.891	0.479	5.394	0.462
Lac+ Age	0.711	0.558	0.864	0.015*	0.281	0.813	0.568	0.381	1.882	0.329
SOFA+Lac+ Age	0.819	0.694	0.945	0.000***	0.44	0.625	0.892	0.517	5.787	0.42

Notes: *Means p < 0.05, **Means p < 0.01, ***Means p < 0.001.

Abbreviations: SOFA, Sequential Organ Failure Assessment; Lac, lactate; CI, confidence interval.

Figure 2 Receiver operating characteristic (ROC) curves of biomarkers for predicting 28-day mortality in sepsis patients.