J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 7, Number 9, September 2015, pages 706-713

Procalcitonin Kinetics in the First 72 Hours Predicts 30-Day Mortality in Severely Ill Septic Patients Admitted to an Intermediate Care Unit

Figure 1. Receiver operating characteristic (ROC) curves of Δ-PCT% variation between day 0 and 72 h (black dotted line) and between 24 and 72 h (grey dotted line) for differentiating between 30-day survivors and non-survivors in 144 patients with severe sepsis syndromes, area under the ROC curve = 0.743 (0.055) for and 0.83 (0.046) (mean (standard deviation)), respectively (P = 0.052).

Figure 2. Kaplan-Meier estimation of probability of survival curves for different procalcitonin percentage variations (Δ-PCT) at different time intervals. (a) Δ-PCT percentage decrease between day 0 and 72 h greater or less than 15% in predicting survival; log rank test P < 0.000; 95% CI: 29.8 - 41.3. (b) Δ-PCT percentage decrease between 24 and 72 h greater or less than 20% in predicting survival; log rank test P < 0.0001; 95% CI: 11.4 - 27.8.

**Table 1.** Baseline Characteristics of the Overall Population and in the Two Groups of Patients Who Survived or Died at 30-Day Follow-Up
	Overall population (n = 144)	Death at 30 days	P
CHF: chronic heart failure; COPD: chronic obstructive pulmonary disease; MAP: mean arterial pressure; APACHE: Acute Physiology, Age and Chronic Health Evaluation; MEDS: mortality in emergency department sepsis score; SOFA: sepsis-related organ failure assessment score.
Age (years)	73 ± 14	72.3 ± 14.7	74.9 ± 12.9	0.32
Male	50 (34.7%)	37 (35.9%)	13 (31.7%)	0.70
Comorbidities
CHF (NYHA class III-IV)	35 (24.3%)	25 (24.3%)	10 (24.4%)	0.99
COPD	29 (20.1%)	21 (20.4%)	8 (19.5%)	0.99
Diabetes	30 (20.8%)	23 (22.3%)	7 (17.1%)	0.65
Chronic renal failure	26 (18.1%)	17 (16.5%)	9 (22.0%)	0.47
Active cancer	23 (16%)	13 (12.6%)	10 (24.4%)	0.12
Hematologic malignancy	18 (12.5%)	10 (9.7%)	8 (19.5%)	0.16
Chronic steroid therapy	27 (24.1%)	15 (18.8%)	12 (37.5%)	0.05
Age-adjusted Charlson comorbidity index	5.9 ± 2.3	5.7 ± 2.4	6.5 ± 1.8	0.07
Chronic total dependence	42 (29.2%)	29 (28.1%)	13 (31.7%)	0.40
Clinical parameters
Heart rate (bpm)	97 ± 20	96 ± 19	99 ± 20	0.42
Respiratory rate (bpm)	19.2 ± 6.6	18.6 ± 6.7	20.7 ± 6.4	0.82
MAP (mm Hg)	83.1 ± 15.5	83.2 ± 16.5	82.8 ± 13.0	0.89
Temperature (°C)	37.2 ± 1.0	37.2 ± 1.0	37.1 ± 0.9	0.34
PaO₂/FiO₂ (mm Hg)	243.8 ± 94.2	268.7 ± 85.6	192.2 ± 91.5	< 0.001
Indexes of severity
APACHE-II (points)	15.8 ± 5.9	14.9 ± 5.7	17.9 ± 6.2	< 0.05
MEDS (points)	9.3 ± 4.5	8.2 ± 4.1	12.2 ± 3.9	< 0.0001
SOFA (points)	5.7 ± 3.5	4.9 ± 3.3	7.6 ± 3.2	< 0.0001
Length of stay (days)	14.6 ± 11.2	15.7 ± 11.6	11.9 ± 9.9	0.52

Table 1. Baseline Characteristics of the Overall Population and in the Two Groups of Patients Who Survived or Died at 30-Day Follow-Up

Overall population (n = 144)

Death at 30 days

No (n = 103)

Yes (n = 41)

CHF: chronic heart failure; COPD: chronic obstructive pulmonary disease; MAP: mean arterial pressure; APACHE: Acute Physiology, Age and Chronic Health Evaluation; MEDS: mortality in emergency department sepsis score; SOFA: sepsis-related organ failure assessment score.

Age (years)

73 ± 14

72.3 ± 14.7

74.9 ± 12.9

0.32

Male

50 (34.7%)

37 (35.9%)

13 (31.7%)

0.70

Comorbidities

CHF (NYHA class III-IV)

35 (24.3%)

25 (24.3%)

10 (24.4%)

0.99

COPD

29 (20.1%)

21 (20.4%)

8 (19.5%)

0.99

Diabetes

30 (20.8%)

23 (22.3%)

7 (17.1%)

0.65

Chronic renal failure

26 (18.1%)

17 (16.5%)

9 (22.0%)

0.47

Active cancer

23 (16%)

13 (12.6%)

10 (24.4%)

0.12

Hematologic malignancy

18 (12.5%)

10 (9.7%)

8 (19.5%)

0.16

Chronic steroid therapy

27 (24.1%)

15 (18.8%)

12 (37.5%)

0.05

Age-adjusted Charlson comorbidity index

5.9 ± 2.3

5.7 ± 2.4

6.5 ± 1.8

0.07

Chronic total dependence

42 (29.2%)

29 (28.1%)

13 (31.7%)

0.40

Clinical parameters

Heart rate (bpm)

97 ± 20

96 ± 19

99 ± 20

0.42

Respiratory rate (bpm)

19.2 ± 6.6

18.6 ± 6.7

20.7 ± 6.4

0.82

MAP (mm Hg)

83.1 ± 15.5

83.2 ± 16.5

82.8 ± 13.0

0.89

Temperature (°C)

37.2 ± 1.0

37.1 ± 0.9

0.34

PaO₂/FiO₂ (mm Hg)

243.8 ± 94.2

268.7 ± 85.6

192.2 ± 91.5

< 0.001

Indexes of severity

APACHE-II (points)

15.8 ± 5.9

14.9 ± 5.7

17.9 ± 6.2

< 0.05

MEDS (points)

9.3 ± 4.5

8.2 ± 4.1

12.2 ± 3.9

< 0.0001

SOFA (points)

5.7 ± 3.5

4.9 ± 3.3

7.6 ± 3.2

< 0.0001

Length of stay (days)

14.6 ± 11.2

15.7 ± 11.6

11.9 ± 9.9

0.52

**Table 2.** Baseline Laboratory Characteristics, Site and Type of Infection, and Isolated Microbiological Agent in the General Population and in the Groups of Patients Who Survived or Died at 30-Day Follow-Up
	Overall population (n = 144)	Death at 30 days	P
WBC: white blood cell count; ProBNP: pro-brain natriuretic peptide; PCT: procalcitonin.
Laboratory values
WBC count (1,000/mm³)	10.4 ± 9.3	10.9 ± 8.4	11.1 ± 11.3	0.54
Hemoglobin (g/dL)	10.7 ± 1.7	11.1 ± 2.2	10.7 ± 1.9	0.29
Platelet count (1,000/mm³)	210 ± 143	204 ± 136	223 ± 159	0.47
Creatinine (mg/dL)	1.7 ± 1.8	1.9 ± 1.7	1.3 ± 0.7	0.67
Lactate (mmol/L)	2.3 ± 1.6	2.4 ± 1.9	2.1 ± 1.0	0.38
Cardiac troponin I (μg/L)	0.3 ± 0.5	0.3 ± 0.6	0.1 ± 0.3	0.21
ProBNP (pg/mL)	9,244 ± 14,805	9,613 ± 16,604	7,998 ± 7,301	0.66
PCT on admission (ng/mL)	28.06 ± 63.29	34.1 ± 70.1	12.7 ± 33.7	0.07
PCT at 24 h (ng/mL)	29.09 ± 63.28	33.64 ± 70.05	16.81 ± 37.87	0.19
PCT at 72 h (ng/mL)	13.48 ± 29.04	13.31 ± 31.97	13.92 ± 20.21	0.91
Site and type of infection
Lung	74 (51.4%)	47 (45.6%)	27 (65.9%)	0.04
Urinary tract	32 (22.2%)	30 (29.1%)	2 (4.9%)	0.001
Gall bladder	6 (4.2%)	5 (4.9%)	1 (2.4%)	0.67
Other	32 (22.2%)	21 (20.4%)	11 (26.8%)	0.69
Septic shock	51 (35.4%)	25 (24.3%)	26 (63.4%)	< 0.0001
Nosocomial	33 (22.9%)	21 (20.4%)	12 (29.3%)	0.27
Community acquired	111 (77.1%)	82 (79.6%)	29 (70.7%)	0.27
Isolated agent
Positive blood cultures	67 (46.5%)	49 (47.6%)	18 (43.9%)	0.42
Gram-positive	27 (18.7%)	17 (16.5%)	10 (24.4%)	0.26
Gram-negative	30 (20.8%)	24 (23.3%)	6 (14.6%)	0.15
Fungi	3 (2.1%)	2 (1.9%)	1 (2.4%)	0.77
Polymicrobial	7 (4.9%)	11 (10.7%)	6 (14.6%)	0.63

Table 2. Baseline Laboratory Characteristics, Site and Type of Infection, and Isolated Microbiological Agent in the General Population and in the Groups of Patients Who Survived or Died at 30-Day Follow-Up

Overall population (n = 144)

Death at 30 days

No (n = 103)

Yes (n = 41)

WBC: white blood cell count; ProBNP: pro-brain natriuretic peptide; PCT: procalcitonin.

Laboratory values

WBC count (1,000/mm³)

10.4 ± 9.3

10.9 ± 8.4

11.1 ± 11.3

0.54

Hemoglobin (g/dL)

10.7 ± 1.7

11.1 ± 2.2

10.7 ± 1.9

0.29

Platelet count (1,000/mm³)

210 ± 143

204 ± 136

223 ± 159

0.47

Creatinine (mg/dL)

1.7 ± 1.8

1.9 ± 1.7

1.3 ± 0.7

0.67

Lactate (mmol/L)

2.3 ± 1.6

2.4 ± 1.9

2.1 ± 1.0

0.38

Cardiac troponin I (μg/L)

0.3 ± 0.5

0.3 ± 0.6

0.1 ± 0.3

0.21

ProBNP (pg/mL)

9,244 ± 14,805

9,613 ± 16,604

7,998 ± 7,301

0.66

PCT on admission (ng/mL)

28.06 ± 63.29

34.1 ± 70.1

12.7 ± 33.7

0.07

PCT at 24 h (ng/mL)

29.09 ± 63.28

33.64 ± 70.05

16.81 ± 37.87

0.19

PCT at 72 h (ng/mL)

13.48 ± 29.04

13.31 ± 31.97

13.92 ± 20.21

0.91

Site and type of infection

Lung

74 (51.4%)

47 (45.6%)

27 (65.9%)

0.04

Urinary tract

32 (22.2%)

30 (29.1%)

2 (4.9%)

0.001

Gall bladder

6 (4.2%)

5 (4.9%)

1 (2.4%)

0.67

Other

32 (22.2%)

21 (20.4%)

11 (26.8%)

0.69

Septic shock

51 (35.4%)

25 (24.3%)

26 (63.4%)

< 0.0001

Nosocomial

33 (22.9%)

21 (20.4%)

12 (29.3%)

0.27

Community acquired

111 (77.1%)

82 (79.6%)

29 (70.7%)

0.27

Isolated agent

Positive blood cultures

67 (46.5%)

49 (47.6%)

18 (43.9%)

0.42

Gram-positive

27 (18.7%)

17 (16.5%)

10 (24.4%)

0.26

Gram-negative

30 (20.8%)

24 (23.3%)

6 (14.6%)

0.15

Fungi

3 (2.1%)

2 (1.9%)

1 (2.4%)

0.77

Polymicrobial

7 (4.9%)

11 (10.7%)

6 (14.6%)

0.63

**Table 3.** Factors Predictive of In-Hospital Death at Univariate and Multivariate Logistic Regression Analysis
	Univariate analysis	Multivariate analysis
*Age-adjusted Charlson comorbidity index [19]. COPD: chronic obstructive pulmonary disease; MDR: multiple drug-resistant; MAP: mean arterial pressure; MEDS: mortality in emergency department sepsis; SOFA: sepsis-related organ failure assessment; APACHE: acute physiology, age and chronic health evaluation; PCT: procalcitonin. Δ-PCT% variation is the ratio, expressed as percentage, of the difference between the second and the first measurement divided by the first measurement (see “Methods” section for more details).
Age	1.0	0.9 - 1.0	0.32
Age more than 75 years	1.0	0.5 - 2.1	0.98
Sex (male vs. female)	0.8	0.4 - 1.8	0.70
Diabetes	0.7	0.3 - 1.8	0.48
Chronic heart failure	1.0	0.4 - 2.3	0.98
COPD	0.9	0.4 - 2.3	0.90
Chronic renal failure	1.4	0.6 - 3.5	0.44
Cancer	2.2	0.9 - 5.6	0.87
Hematologic malignancy	2.2	0.8 - 6.2	0.11
Chronic total dependence	1.2	0.5 - 2.6	0.77
Corticosteroid therapy	2.6	1.0 - 6.4	0.04
Charlson index*	1.2	1.0 - 1.4	0.08
Pneumonia	2.3	1.1 - 4.9	0.03
Polymicrobial sepsis	2.5	1.1 - 5.9	< 0.05
MDR bacteria	2.4	0.9 - 6.3	0.08
Nosocomial acquired	1.6	0.7 - 3.7	0.27
Septic shock on presentation	5.4	2.5 - 11.8	< 0.001	5.3	2.3 - 12.4	< 0.0001
Antibiotic therapy within 6 h	0.4	0.1 - 1.3	0.19
MEDS	1.3	1.1 - 1.4	< 0.001	1.3	1.1 - 1.5	0.001
SOFA	1.3	1.1 - 1.4	< 0.001
SOFA 48 h	1.3	1.1 - 1.6	< 0.001
APACHE-II	1.1	1.0 - 1.1	0.02
PCT on admission	0.9	0.9 - 1.0	0.09
PCT at 24 h	0.9	0.9 - 1.0	0.22
PCT at 72 h	1.0	0.9 - 1.0	0.90
Δ-PCT % variation
Δ-0-72h decrease < 15%	6.1	2.7 - 13.6	< 0.0001	3.9	1.6 - 9.5	< 0.0001
Δ-24-72h decrease < 20%	5.9	2.5 - 14.1	< 0.0001	3.1	1.2 - 7.9	< 0.001

Table 3. Factors Predictive of In-Hospital Death at Univariate and Multivariate Logistic Regression Analysis

Univariate analysis

Multivariate analysis

95% CI

*Age-adjusted Charlson comorbidity index [19]. COPD: chronic obstructive pulmonary disease; MDR: multiple drug-resistant; MAP: mean arterial pressure; MEDS: mortality in emergency department sepsis; SOFA: sepsis-related organ failure assessment; APACHE: acute physiology, age and chronic health evaluation; PCT: procalcitonin. Δ-PCT% variation is the ratio, expressed as percentage, of the difference between the second and the first measurement divided by the first measurement (see “Methods” section for more details).

Age

1.0

0.9 - 1.0

0.32

Age more than 75 years

1.0

0.5 - 2.1

0.98

Sex (male vs. female)

0.8

0.4 - 1.8

0.70

Diabetes

0.7

0.3 - 1.8

0.48

Chronic heart failure

1.0

0.4 - 2.3

0.98

COPD

0.9

0.4 - 2.3

0.90

Chronic renal failure

1.4

0.6 - 3.5

0.44

Cancer

2.2

0.9 - 5.6

0.87

Hematologic malignancy

2.2

0.8 - 6.2

0.11

Chronic total dependence

1.2

0.5 - 2.6

0.77

Corticosteroid therapy

2.6

1.0 - 6.4

0.04

Charlson index*

1.2

1.0 - 1.4

0.08

Pneumonia

2.3

1.1 - 4.9

0.03

Polymicrobial sepsis

2.5

1.1 - 5.9

< 0.05

MDR bacteria

2.4

0.9 - 6.3

0.08

Nosocomial acquired

1.6

0.7 - 3.7

0.27

Septic shock on presentation

5.4

2.5 - 11.8

< 0.001

5.3

2.3 - 12.4

< 0.0001

Antibiotic therapy within 6 h

0.4

0.1 - 1.3

0.19

MEDS

1.3

1.1 - 1.4

< 0.001

1.3

1.1 - 1.5

0.001

SOFA

1.3

1.1 - 1.4

< 0.001

SOFA 48 h

1.3

1.1 - 1.6

< 0.001

APACHE-II

1.1

1.0 - 1.1

0.02

PCT on admission

0.9

0.9 - 1.0

0.09

PCT at 24 h

0.9

0.9 - 1.0

0.22

PCT at 72 h

1.0

0.9 - 1.0

0.90

Δ-PCT % variation

Δ-0-72h decrease < 15%

6.1

2.7 - 13.6

< 0.0001

3.9

1.6 - 9.5

< 0.0001

Δ-24-72h decrease < 20%

5.9

2.5 - 14.1

< 0.0001

3.1

1.2 - 7.9

< 0.001