Predictive Value of Combination of Procalcitonin and Predisposition, Infection, Response, and Organ Dysfunction (PIRO) System in Septic Patients with Positive Blood Cultures in the Emergency Department

Figures & data

Table 1 Criteria of the Howell-PIRO System (Not Included Malignancy)

Variable	0	1	2	3	4
Predisposition
Age (years)	<65	65 to 80	>80
COPD		Yes
Liver disease			Yes
Nursing home resident			Yes
Infection
Skin/soft tissue infection
Any other infection			Yes
Pneumonia					Yes
Response
Respiratory rate (bpm)				>20
Bands		>5%
Heart rate (bpm)			>120
Organ dysfunction
SBP (mmHg)	>90		70 to 90		<70
BUN (mmol/l)			>7.1
Respiratory failure/ hypoxemia				Yes
Lactate (mmol/l)				>4.0
Platelet count (x10^9/l)			<150

Abbreviations: COPD, chronic obstructive pulmonary disease; SBP, systolic blood pressure; BUN, blood urea nitrogen.

Figure 1 Flowchart of the study population.

Table 2 Characteristics of the Study Cohort

Characteristics	ICU (n = 284)	Non-ICU (n = 694)	P	MODS (n = 204)	Non-MODS (n =774)	P	Survivor (n =797)	Non-Survivors (n =181)	P
Age, years	78 (69,84)	70 (59,78)	0.040	82 (78,85)	66 (55,75)	0.001	66 (59,73)	84 (80,86)	0.001
Male, %	161 (56.7)	401 (57.8)	0.754	119 (58.3)	445 (57.5)	0.829	460 (57.7)	105 (58.0)	0.942
COPD, %	90 (31.7)	133 (19.2)	<0.001	57 (27.9)	178 (23.0)	0.142	151 (18.9)	42 (23.2)	0.194
Hypertension, %	147 (51.8)	278 (40.1)	0.001	103 (50.5)	342 (44.2)	0.108	372 (46.7)	80 (44.2)	0.546
CVD, %	63 (22.2)	117 (16.9)	0.051	46 (22.5)	134 (17.3)	0.086	141 (17.7)	34 (18.8)	0.729
CHF, %	137 (48.2)	270 (38.9)	0.007	89 (44.0)	336 (43.4)	0.956	299 (37.5)	93 (51.4)	0.001
CRD, %	40 (14.1)	68 (9.8)	0.052	24 (11.8)	85 (11.0)	0.752	78 (9.8)	20 (11.0)	0.609
DM, %	114 (40.1)	229 (33.0)	0.264	76 (37.3)	249 (32.2)	0.170	235 (29.5)	55 (30.4)	0.811
MAP, mmHg	77 (72,81)	85 (77,93)	<0.001	79 (75,83)	84 (76,92)	<0.001	87 (79,90)	82 (71,91)	<0.001
Temperature, °C	38.51±0.46	38.46±0.52	0.359	38.57±0.41	38.43±0.55	0.075	38.43±0.51	38.61±0.46	0.080
Heart rate, beats/min	102 (90,115)	98 (80,112)	<0.001	116 (104, 134)	90 (78,101)	<0.001	90 (80,100)	119 (107,126)	<0.001
Respiratory rate, bpm	24 (20,28)	24 (23,30)	0.555	30 (29,33)	23 (20,24)	<0.001	23 (20,25)	30 (29,34)	<0.001
WBC, °¡109/L	14.4 (12,18.8)	12.3 (10.8,14.9)	<0.001	15 (14.5,20.3)	11.2 (10.3,12.6)	<0.001	10.6 (10.2,12.1)	16.8 (14.9,20.3)	<0.001
Lac, mmol/L	3.7±1.4	2.4±1.4	<0.001	3.3±1.5	2.5±1.6	0.040	1.8±0.5	3.7±1.6	<0.001
PCT, ng/mL	8.6 (2.5, 12)	5 (2.2, 10.1)	<0.001	8.6 (2.8, 12.5)	3.5 (1.8, 10)	<0.001	2.4 (1.4, 7)	8.5 (3.6, 12.5)	<0.001
CRP	111±39	73±23	<0.001	115±38	70±21	<0.001	67±22	114±34	<0.001
ALB	29±6	33±7	<0.001	25±4	34±5	<0.001	34±6	25±4	<0.001
NLR	14 (8,24)	12 (8,20)	0.080	19 (10,25)	11 (8,19)	<0.001	9 (7,11)	19 (9,25)	<0.001
SOFA	6 (6,8)	4 (3,7)	<0.001	6 (5,9)	4 (4,7)	<0.001	4 (4,7)	6 (5,9)	<0.001
MEDS	11 (9,14)	8 (7,10)	<0.001	13 (10,16)	10 (8,10)	<0.001	10 (8,10)	12 (10,16)	<0.001
APACHE II	16.3±4.8	11.3±2.6	<0.001	15.6±4.2	12.4±2.5	<0.001	12.5±2.6	15.5±4.3	<0.001
PIRO	16 (12,20)	10 (8,12)	<0.001	16 (12,20)	10 (9,12)	<0.001	10 (9,12)	15 (12,20)	<0.001

Abbreviations: ICU, intensive care unit; MODS, multiple organ dysfunction syndrome; COPD, chronic obstructive pulmonary disease; CVD, cerebrovascular disease; CHF, congestive heart failure; CRD, chronic renal disease; DM, diabetes mellitus; MAP, mean arterial pressure; WBC, white blood cell; PCT, procalcitonin; Lac, lactate; CRP, C-reactive protein; ALB, albumin; NLR, neutrophils and lymphocytes ratio; SOFA, Sequential Organ Failure Assessment; APACHE II, Acute Physiology and Chronic Health Evaluation II; MEDS, Mortality in emergency department sepsis; PIRO, Predisposition, Infection, Response, and Organ dysfunction.

Figure 2 The median levels of SOFA, MEDS and PIRO scores, and mean level of APACHE II score in ICU-admission, developing of MODS and 28-day mortality groups. (A) The median level of SOFA score in ICU-admission, developing of MODS and 28-day mortality groups. (B) The median level of MEDS score in ICU-admission, developing of MODS and 28-day mortality groups. (C) The mean level of APACHE II score in ICU-admission, developing of MODS and 28-day mortality groups. (D) The median level of PIRO score in ICU-admission, developing of MODS and 28-day mortality groups.

Figure 3 Spearman correlations between 28-day mortality and SOFA score (A); MEDS score (B); APACHE II score (C); PIRO score (D) in patients with positive blood cultures.

Table 3 Binary Logistic Regression Analysis of Clinical Outcome for Septic Patients with Positive Blood Culture

Variables	Predictor	β	SE	Wald	P	OR (95% CI)
ICU-admission	WBC	0.176	1.453	5.632	0.018	1.192 (1.031–1.379)
	PCT	0.241	0.105	5.315	0.021	1.273 (1.037–1.563)
	Lac	1.261	0.325	15.055	<0.001	3.530 (1.867–6.676)
	ALB	−0.142	0.046	9.501	0.002	0.867 (0.792–0.949)
	NLR	0.077	0.034	5.205	0.023	1.080 (1.011–1.155)
	SOFA	0.220	0.142	2.414	0.120	2.701 (1.548–4.713)
	MEDS	0.895	0.215	17.369	<0.001	2.447 (1.607–3.728)
	APACHE II	0.623	0.144	18.644	<0.001	1.864 (1.405–2.474)
	PIRO	0.328	0.110	8.840	0.003	1.388 (1.118–1.723)
	Constant	−13.820	2.939	22.112	<0.001
MODS	WBC	0.362	0.129	7.861	0.005	1.436 (1.115–1.849)
	PCT	0.136	0.094	2.093	0.048	1.145 (0.953–1.377)
	Lac	0.177	0.299	0.351	0.554	1.194 (0.664–2.145)
	ALB	−0.665	0.192	11.967	0.001	0.514 (0.353–0.750)
	NLR	0.270	0.093	8.452	0.004	1.310 (1.092–1.572)
	SOFA	0.001	0.212	0.000	0.995	1.001 (0.660–1.518)
	MEDS	0.383	0.159	5.808	0.016	1.466 (1.074–2.001)
	APACHE II	0.372	0.162	5.286	0.022	1.450 (1.056–1.990)
	PIRO	0.196	0.084	5.461	0.019	1.216 (1.032–1.434)
	Constant	−18.945	4.468	19.978	<0.001
28-day-mortality	WBC	0.996	0.354	7.919	0.005	2.707 (1.353–5.417)
	PCT	0.306	0.098	9.764	0.002	1.358 (1.121–1.644)
	Lac	1.822	0.701	6.753	0.009	6.184 (1.565–24.436)
	ALB	−0.226	0.116	3.807	0.051	0.798 (0.636–1.001)
	NLR	0.128	0.153	0.701	0.402	1.136 (0.843–1.533)
	SOFA	0.092	0.157	0.340	0.560	1.096 (0.805–1.492)
	MEDS	0.440	0.147	8.922	0.003	1.553 (1.163–2.074)
	APACHE II	0.484	0.163	8.832	0.003	1.623 (1.179–2.234)
	PIRO	0.322	0.123	6.884	0.009	1.380 (1.085–1.754)
	Constant	−16.492	3.630	20.646	<0.001

Abbreviations: CI, confidence interval; OR, odds ratio; SE, standard error; WBC, white blood cell; PCT, procalcitonin; Lac, lactate; ALB, albumin; NLR, neutrophils and lymphocytes ratio; SOFA, Sequential Organ Failure Assessment; APACHE II, Acute Physiology and Chronic Health Evaluation II; MEDS, Mortality in emergency department sepsis; PIRO, Predisposition, Infection, Response, and Organ dysfunction.

Table 4 Statistical Data of ROC Curve in Predicting ICU-Admission in Patients with Positive Blood Cultures

Variables	AUC (95% CI)	SE	P	Cut Off	Sensitivity	Specificity
WBC	0.725 (0.496–0.954)	0.117	0.075	12.75	0.800	0.750
PCT	0.620 (0.533–0.708)	0.045	0.009	6	0.294	0.977
Lac	0.637 (0.454–0.820)	0.093	0.125	2.25	0.500	0.913
ALB	0.759 (0.574–0.945)	0.095	0.015	26.35	0.875	0.636
NLR	0.615 (0.449–0.782)	0.085	0.225	5.03	0.950	0.353
MEDS	0.740 (0.663–0.817)	0.039	<0.001	8.5	0.646	0.759
APACHE II	0.780 (0.709–0.850)	0.036	<0.001	15.5	0.468	0.975
PIRO	0.751 (0.674–0.828)	0.039	<0.001	11.5	0.684	0.759
PCT+MEDS	0.772 (0.698–0.846)	0.038	<0.001	0.39	0.924	0.557
PCT+APACHE II	0.821 (0.757–0.885)	0.033	<0.001	0.37	0.899	0.608
PCT+PIRO	0.795 (0.723–0.867)	0.037	<0.001	0.45	0.911	0.633

Abbreviations: WBC, white blood cell; PCT, procalcitonin; Lac, lactate; ALB, albumin; NLR, neutrophils and lymphocytes ratio; APACHE II, Acute Physiology and Chronic Health Evaluation II; MEDS, Mortality in emergency department sepsis; PIRO, Predisposition, Infection, Response, and Organ dysfunction.

Table 5 Statistical Data of ROC Curve in Predicting MODS in Patients with Positive Blood Cultures

Variables	AUC (95% CI)	SE	P	Cut Off	Sensitivity	Specificity
WBC	0.879 (0.819–0.938)	0.030	<0.001	12.75	0.911	0.878
PCT	0.664 (0.584–0.745)	0.041	<0.001	1.01	0.911	0.426
ALB	0.789 (0.722–0.856)	0.034	<0.001	28.10	0.851	0.620
NLR	0.727 (0.653–0.801)	0.038	<0.001	7.32	0.873	0.511
MEDS	0.701 (0.622–0.779)	0.040	<0.001	12.5	0.43	0.957
APACHE II	0.761 (0.691–0.832)	0.036	<0.001	12.5	0.658	0.723
PIRO	0.811 (0.746–0.876)	0.033	<0.001	12.5	0.544	0.957
PCT+MEDS	0.758 (0.685–0.831)	0.037	<0.001	0.53	0.582	0.862
PCT+APACHE II	0.794 (0.727–0.862)	0.034	<0.001	0.47	0.684	0.787
PCT+PIRO	0.837 (0.776–0.898)	0.031	<0.001	0.48	0.696	0.883

Abbreviations: WBC, white blood cell; PCT, procalcitonin; Lac, lactate; ALB, albumin; NLR, neutrophils and lymphocytes ratio; APACHE II, Acute Physiology and Chronic Health Evaluation II; MEDS, Mortality in emergency department sepsis; PIRO, Predisposition, Infection, Response, and Organ dysfunction.

Table 6 Statistical Data of ROC Curve in Predicting 28-Day-Mortality in Patients with Positive Blood Cultures

Variables	AUC (95% CI)	SE	P	Cut Off	Sensitivity	Specificity
WBC	0.789 (0.673–0.905)	0.059	<0.001	14.05	0.767	0.896
PCT	0.782 (0.683–0.882)	0.051	<0.001	1.05	0.933	0.521
Lac	0.699 (0.561–0.838)	0.071	0.003	2.25	0.567	0.937
MEDS	0.745 (0.627–0.863)	0.060	<0.001	12.5	0.400	0.979
APACHE II	0.805 (0.707–0.904)	0.050	<0.001	15.5	0.633	0.875
PIRO	0.831 (0.742–0.920)	0.045	<0.001	11.5	0.867	0.708
PCT+MEDS	0.812 (0.705–0.919)	0.055	<0.001	0.50	0.667	0.937
PCT+APACHE II	0.866 (0.789–0.943)	0.039	<0.001	0.23	0.933	0.687
PCT+PIRO	0.885 (0.810–0.961)	0.039	<0.001	0.39	0.833	0.896

Abbreviations: WBC, white blood cell; PCT, procalcitonin; Lac, lactate; APACHE II, Acute Physiology and Chronic Health Evaluation II; MEDS, Mortality in emergency department sepsis; PIRO, Predisposition, Infection, Response, and Organ dysfunction.

Figure 4 The ROC curves of PCT combined with severe scores for predicting outcomes in septic patients with positive blood cultures for ICU-admission, developing of MODS and 28-day mortality. (A) The ROC curves of PCT combined with severe scores in septic patients with positive blood cultures for ICU-admission; (B) the ROC curves of PCT combined with severe scores in septic patients with positive blood cultures for developing of MODS; (C) the ROC curves of PCT combined with severe scores in septic patients with positive blood cultures for 28-day mortality.

Figure 5 Kaplan-Meier curves for 28-day survival categorized by the MEDS score (A), APACHE II score (B), PIRO score (C), and combination value of PCT+MEDS (D), PCT+APACHE II (E), and PCT+PIRO (F) in septic patients with positive blood cultures.