Title

Author(s)

Retrospective observational study of procalcitonin in oriental

intensive care unit patients with suspected nosocomial infection

Chan, Chin-pang, Ian;

Citation

Issued Date

URL

Rights

2012

http://hdl.handle.net/10722/173735

Creative Commons: Attribution 3.0 Hong Kong License

Retrospective Observational Study of Procalcitonin in Oriental

Intensive Care Unit Patients with Suspected Nosocomial Infection
by

Dr. Chan Chin Pang Ian

This work is submitted to

Faculty of Medicine of The University of Hong Kong
In partial fulfillment of the requirements for
The Postgraduate Diploma in Infectious Diseases, PDipID (HK)

Date: 12th August, 2012

Supervisor: Dr. Susanna K P Lau

Declaration
I,ChanChinPangIan,declarethatthisdissertationrepresentsmyownworkand
that it has not been submitted to this or other institution in application for a
degree,diplomaoranyotherqualifications.
I, Chan Chin Pang Ian also declare that I have read and understand the guideline
on What is plagiarism? published by The University of Hong Kong (available
at http://www.hku.hk/plagiarism/) and that all parts of this work complies with
the guideline.

Candidate: ChanChinPangIan

Signature:

Date:

Content
Acknowledgement

Abstract

Background

Study Objectives

10

Methodology

11

Results

19

Discussion

26

Reference Lists

34

Table and Figures

40

Appendix

46

Acknowledgement

I would like to express my sincerest thanks to Dr. LAW Kin Ip, Chief of Service,
Intensive Care Unit, Dr. FUNG Sau Chun, Kitty, Consultant (Microbiology),
Department of Pathology and Dr. LEE Kar Lung, Senior Medical Officer,
Intensive Care Unit of the United Christian Hospital, who enlightened me to
perform the current study.

They gave me a lot of inspiration during the

preparation of this study.

My thanks are also due to Dr. Susanna K.P. LAU, Associate Professor,
Department of Microbiology, the University of Hong Kong, who have given me
a lot of inspiration and valuable opinions for doing this project.

Abstract

Introduction

Procalcitonin (PCT) was one of the recently described bio-markers in rapid

diagnosis of severe sepsis.

However, the reported sensitivity and specificity of

PCT varied among studies and the results of Oriental population was scanty.
The objective of this study was to determine the usefulness of serum
procalcitonin level of the Oriental intensive care unit patients in diagnosis of
nosocomial infection

Materials and methods

This was a retrospective observational single-arm cohort review study, which

was conducted in a mixed medico-surgical Intensive Care Unit (ICU) of a
regional public hospital (United Christian Hospital) in Hong Kong SAR, China
between 1st January, 2009 and 30th June, 2009, to determine the blood
procalcitonin level at early diagnosis (and differentiation) in patients with SIRS
and hospital-acquired sepsis, in comparison with other parameters and markers.

Results

Total 33 patients were recruited in this study. The mean age was 61 years old
with nearly 1:1 male to female ratio.

The commonest offending organism and

involved system in nosocomial sepsis in ICU in this cohort was Gram negative
micro-organisms and respiratory tract respectively.

The positive likelihood

ratios (LR) of nosocomial sepsis in ICU were 4.242 (P = 0.032), 5.711 (P = 0.016)
and 8.550 (P = 0.023) with PCT > 0.1 ng/ml, PCT > 0.5 ng/ml and PCT > 5
ng/ml respectively.

Good discriminative power of PCT as a test in diagnosing

severe sepsis and septicaemia in ICU (AUC of ROC-curve 0.78-0.90) was also
demonstrated.

In patients with severe sepsis, at serum PCT cut-off point 1.23

ng/ml, the sensitivity and specificity was 89.5% and 71.4% respectively.

Conclusion

Our study demonstrated the consistent usefulness of PCT, including in diagnosis

of severe nosocomial sepsis and septicaemia in oriental ICU patients.

Background

Epidemiology of Severe Sepsis

The definitions of systemic inflammatory response syndrome (SIRS), sepsis,

severe sepsis, septic shock, and multiple organ dysfunction syndromes (MODS)
were first introduced by the American College of Chest Physicians (ACCP) and
the Society of Critical Care Medicine (SCCM) in 1992.
SIRS with infection.

Sepsis was defined as

Severe sepsis was sepsis complicated by organ

dysfunction, organ hypoperfusion or hypotension. [1]

Considerable health care burden was attributed by sepsis. Martin GS, et al

reviewed discharge data of approximately 750 million hospitalizations in the
United States over the 22-year period, 10,319,418 cases of sepsis were identified.
[2]

The trend of increasing incidence of sepsis from year 1979 to 2000 was

observed, from 83 cases per year per 100,000 populations to 240 cases per year
per 100,000 populations respectively. [2, 3]

The annual economic expenditure

in provision of care of patients with sepsis was more than $15 billion in the
United States. [4, 5]

Among public hospitals of the Hong Kong Hospital

Authority, the most frequent coded principal diagnosis in 2011 was pneumonia,
4

which contributed to nearly 25% of the coded principal diagnosis in the Clinical
Data and Reporting System (CDARS).

In year 2011, total number of Hospital

Authority hospital admissions with diagnosis of septicaemia was 21409. [6]

This finding probably underestimated the situation of Hong Kong, but already
reflected the substantial burden on the Hong Kong health care system.

Sepsis portends substantial mortality and morbidity.

The mortality rate

associated with severe sepsis and septic shock had been reported to be 25% to
30% and 40% to 70% respectively. [7, 8, 9] The mortality rate increased from
about 45% to 70% and 39% to 56% if the episodes were complicated by acute
renal failure (ARF) and new onset atrial fibrillation (AF) respectively. [9, 10]
Therefore, an effective early diagnosis and management of sepsis was crucial.

Management of Sepsis

International guidelines for the management of severe sepsis were published in

2004 by the Surviving Sepsis Campaign and condensed into two Care Bundles.
The management included early-goal directed therapy, [11] early initiation of
appropriate antibiotics, [12, 13]

control and removal of the septic foci, [14]

lung-protective ventilation strategy for mechanically ventilated patients with

5

acute respiratory distress syndrome (ARDS), [15] use of activated protein C

(APC) in selected high-risk cohort (APACHE II Score more than 24), [16-18]
consideration of relative adrenal insufficiency in vasopressor-refractory septic
shock and treatment with corticosteroid replacement [19, 20] and avoidance of
hyperglycaemia. [21, 22]

Pathophysiology of Severe Sepsis

Sepsis triggered cascades of complex interactions among the offending

microorganisms and the host immune, inflammatory and coagulatory systems.
[23]

The sepsis serial theory and sepsis parallel theory [24] described the

temporal relationship between systemic inflammatory response syndrome (SIRS)

and compensated anti-inflammatory response syndrome (CARS).

The

pro-inflammatory cytokines and anti-inflammatory cytokines mediated the

responses respectively. [25]

An overwhelming SIRS led to peripheral

vasodilatation, myocardial dysfunction, microcirculatory hypo-perfusion and

mitochondrial dysfunction resulting in multi-organ failure (MOF).

The diagnosis of nosocomial infection in critical care patients was challenging

because there is no ideal markers to differentiate between infection and systemic
6

inflammatory response syndrome (SIRS). This might lead to either unnecessary

use of or delayed initiation of antibiotics, which would increase the risk of
antibiotic resistance or affect the prognosis of the patients.

Early administration of appropriate antimicrobial and early goal-directed therapy

were the keys of success in management of severe sepsis, so early recognition of
nosocomial infection in critically ill patients was of major importance.

Procalcitonin (PCT)

In order to enhance early diagnosis of nosocomial infection and avoid

unnecessary prescription of antibiotics, varies markers and parameters had been
investigated. However, the predictive values of vital signs, C-reactive protein
(CRP) and X-ray findings for diagnosing nosocomial infection, e.g. pneumonia
requiring antibiotics were low. [26, 27] Newer biomarkers e.g. Procalcitonin
and heparin-binding protein (HBP) were investigated in progress. [28]

Procalcitonin (PCT), a protein of 116-amino acid prohormone of calcitonin with

molecular weight 13 kDa in blood was discovered 35 years ago, which was
expressed by the CALC-1 gene on chromosome 11.
7

Whereas calcitonin was

released solely by the C-cells of the thyroid after hormonal stimulation, PCT was
produced

by

neuroendocrine

cells

in

the

lungs

and

intestine

after

pro-inflammatory cytokines stimulation, especially when caused by bacterial

infections. [29].

This phenomenon was first reported by Assicot, et al. (1993).

In healthy individuals, PCT levels were < 0.05 ng/mL, but could increase up to
1000 ng/mL in individuals suffering from severe sepsis or septic shock.
Increased PCT levels had been observed within 3 to 6 hours after infectious
challenge and correlated with the severity of infection, making PCT as one of the
potential early bio-markers for severe systemic bacterial infections and sepsis.
PCT level normalized with values of < 0.05 ng/mL as the severe bacterial
infection resolved.

The half-life of PCT was about 22-24 hours. [30-32] The

measurement of PCT in selected cases had been shown to significantly improve

diagnostic certainty and reduce the prescription and duration of antimicrobial
treatment in non-oriental studies. [33] However, PCT level would also increase
in non-infectious conditions with systemic inflammation response, such as
post-cardiac arrest, pancreatitis, trauma, OKT3 antibodies treatment and allergy
reactions.

PCT concentrations had been used to differentiate patients without infection from
patients with sepsis in clinical trials.

The general agreement on the cut-off

range of infection was PCT > 0.25 ng/mL (sensitivity 0.95; 95% CI: 0.89 to 0.98,
specificity 0.50; 95% CI: 0.46 to 0.55) [34] and > 0.1 ng/mL in
immunocompetent and immunocompromised patients respectively.

concentration < 0.5 ng/mL represented a low risk of severe sepsis and/or septic
shock.

On the other hand, a concentration > 2 ng/mL represented a high risk of

severe sepsis and/or septic shock. However, concentrations < 0.5 ng/mL could
not exclude infections, for instance, localized infections could be associated with
low PCT concentrations, or at initial stage of systemic infection (< 6 hours).
Higher mortality had been observed in patients who had elevated or persistently
high PCT concentrations, for instance, PCT > 5 ng/mL in severe sepsis and septic
shock. [35]

Despite intensive research, uncertainties still existed, including the role of

procalcitonin in diagnosis of nosocomial infection in Oriental Intensive Care
Unit (ICU) patients.

Study Objectives

The objectives of this study were to determine the usefulness of serum

procalcitonin level of the Oriental intensive care unit patients in diagnosis of
nosocomial infection and estimation of patient outcome, based on the hypothesis
of the association between elevation of serum procalcitonin level and severe
sepsis in ICU patients.

10

Methodology

Study Design

This was a retrospective observational non-interventional single-arm cohort

review study, which was conducted in a 14-bed mixed medico-surgical Intensive
Care Unit (ICU) and 6-bed High Dependency Unit (HDU) of a regional public
hospital (United Christian Hospital) in Hong Kong SAR, China between 1st
January, 2009 and 30th June, 2009, to determine the blood procalcitonin level at
early diagnosis (and differentiation) in patients with SIRS and hospital-acquired
sepsis, in comparison with other parameters and markers.

The study was

approved by the Hong Kong Hospital Authority - Research Ethics Committee

(Kowloon Central / Kowloon East), [Ref.: KC/KE-11-0052/ER-1].

Case records of ICU patients, who fulfilled the criteria of SIRS or sepsis as
suggested by Bone and coworkers [1] or the definition of nosocomial infection,
with available result of blood procalcitonin level at the time of suspected
nosocomial infection, recorded in the medical notes, Clinical Management

11

System (CMS) or Clinical Data and Reporting System (CDARS) of the United
Christian Hospital, were analyzed.

12

Inclusion Criteria
Patients would be included if they met all the following criteria:
1. Adult patients with age >/= 18 years old
2. Admission to ICU between 1st Jan, 2009 and 30th June, 2009
3. Body temperature >/= 38C for at least 2 readings 4 hours apart after 72-hour
hospitalization
4. Available serum procalcitonin level at the time of suspected nosocomial
infection
Exclusion Criteria
1. Terminal illnesses
2. Body temperature >/= 38C within 72-hour hospitalization
3. Disseminated malignancy
4. Long-term immunosuppressant

Measurements

The background demographic data and functional state of the patients were
recorded. The acute physiological parameters and chronic health status would
be evaluated.

The analysis would be focused on the relationship among serum

procalcitonin level, varies biomarkers and laboratory data, nosocomial infection

13

diagnosis and disease severity after Intensive Care Unit admission.

The blood

test results within 24 hours of suspected onset of nosocomial sepsis were

reviewed.

The severity of the disease, which was reflected by the use of

inotropes, organ failure and APACHE II score, would be also examined.

Procedures and Definitions

Sepsis work-up would be performed before commencement of antibiotics.

Blood cultures were obtained under strict aseptic technique by on-duty medical
officers and were analyzed using local standard microbiological methods.

At

least one set of 10 mL blood samples were taken and inoculated into aerobic and
anaerobic bottles (BACTEC) respectively. Bacteraemia was defined as positive
growth of any pathogens in the blood culture.

The isolation of

coagulase-negative staphylococci (CNS) from the blood culture was considered

contamination and thus absence of bacteraemia unless with evidence of persistent
bacteraemia or catheter-related bloodstream infection (CRBSI). [36]

Septic

shock was defined as severe sepsis with hypotension requiring vasopressor

support or mean arterial pressure <70 mm Hg for 30 minutes despite adequate
fluid resuscitation. [28]
14

Clean midstream urine (MSU) cultures were obtained before starting

antimicrobial therapy and were analyzed according to local standard
microbiological methods.

In cases of urinary catheters, the urine samples were

collected from fresh-catheterization urine (fresh-cath CSU).

A positive urine

culture was defined as bacterial growth over 103 CFU/ml urine or a bacterial
monoculture over 102 CFU/ml urine in the presence of pyuria (the finding of
greater than or equal to 10 leukocytes/mm3 of urine by either hemocytometry or
direct microscopy). [37]

Urine cultures revealing growth of two or more

different bacterial species reflecting mixed skin or gut flora were considered
contamination. [37]

The diagnosis of hospital-acquired pneumonia (HAP) was considered if the

patient had developed new or progressive radiographic infiltrate on Chest X-ray
(CXR), along with clinical features suggesting infection, which included the new
onset of fever, purulent sputum or tracheal aspirate, leukocytosis, and increase in
oxygen requirement, at least 48 h after hospital admission. [38, 39]

Sputum and

tracheal aspirate (TA) would be analyzed using local standard microbiological

methods.

Samples with profuse epithelial cells were considered contamination.

15

A wound infection was classified according to the anatomical site involvement

by the United States Centre for Disease Control and Prevention (CDC): [40]

Superficial incisional Surgical Site Infection (SSI) infection involved only skin
and subcutaneous tissue of incision.

Deep incisional SSI - infection involved deep tissues

Organ/space SSI - infection involved any part of the anatomy in organs and
spaces other than the incision, which was opened or manipulated during the
operation.

A surgical wound/site infection was diagnosed if infection occurred within 30

days of the surgical operation with at least one of the followings: [40]

- Purulent discharge from the surgical site

- Purulent discharge from wound or drain placed in wound

- Organisms isolated from aseptically obtained wound culture

- Signs and symptoms of infection, e.g. pain or tenderness, localised swelling, or

redness/heat
16

Hardware Description

The VIDAS BRAHMS PCT (PCT), which was an automated test for use
on the instruments of the VIDAS family for the determination of human
procalcitonin in human serum or plasma (lithium heparinate) using the ELFA
(Enzyme-Linked Fluorescent Assay) technique, was employed to check the PCT
level of the subjects.

Statistical Analysis

Statistical analyses were performed with IBM Statistical Package for the Social
Sciences (SPSS 19.0) Windows version 19.0.
variables were first performed.

Descriptive analyses for all

Normality of the data was checked by

one-sample Kolmogorov-Smirnov test, which indicated whether the data was

parametric or non-parametric one.

For univariate analysis, t-test and ANOVA

test were used for comparison of continuous variables and Pearsons chi-square
test or Fishers exact test for categorical variables.

A backward stepwise (Wald)

logistic regression model was used to identify independent risk factors of the
examined outcomes.

Baseline variables obtained with P value of less than 0.2

17

were entered into the logistic regression model, so as to identify the

corresponding independent predictors. [41]

Cox regression models with backward stepwise (Wald) were used to determine
the risk factors.

For evaluation of the association between serum procalcitonin

level and nosocomial sepsis, linear regression model was built and performed
analysis.

The receiver operating characteristic (ROC) curve and the respective

areas under the curve (AUCs) would be calculated. [42] The best cut-off value
of procalcitonin was chosen by using Youden's Index. [43]

All reported

p-values are two-sided and p-values less than 0.05 were regarded as statistically
significant.

18

Results

Discharge diagnoses of the 33 recruited patients were presented in Table 1.

Thirty-two (97%) patients enjoyed independent activity of daily living (ADL).
Their age and body weight ranged from 20 to 86 years (mean = 61 years, SD +/17) and from 35 to 90 kg (mean = 55.4kg, SD +/- 13.3) respectively.
accounted 55% (n = 18) of the cohort.

Males

Ten (30%) patients were smoker and 6

(18%) patients were drinker.

On evaluation of the chronic health status of the cohort (Figure 2), none was
suffering from congestive heart failure (CHF), dementia, peripheral vascular
disease (PVD) and haematological malignancy.

The common chronic illnesses

and past medical history included treated non-metastatic solid tumor (n=10;
33.3%), diabetes mellitus (DM) (n=11; 33.3%) and chronic pulmonary diseases
(n=4; 12.1%).

The mean APACHE II score was 19 (SD +/- 8) and the mean predicted death rate
(adjusted) [44] was 34.3% (SD +/- 20.0; Range 5.8-95.5). Four patients died
within 28-day hospitalization, giving a crude 28-day mortality rate of 12.1%.

19

One (3%) patient developed end-stage renal failure required long-term dialysis
(RRT Dependent) after the index episode. The median ICU length of stay (LOS)
and hospital LOS were 5 days (Range 1-49 days) and 16 days (Range 2-108 days)
respectively.

Twenty-three (69.7%) of the 33 patients were suffering from sepsis and 10

patients (30.3%) were not (Table 1). Among the whole cohort, the fulfilled
number of SIRS criteria was 2 (n=13; 39.4%), 3 (n=9; 27.3%) and 4 (n=11;
33.3%).

Nineteen (57.6%) patients were stratified as severe sepsis and 15

(45.5%) patients developed septic shock.

Five (15.2%) patients had positive

blood culture.

In the cohort with sepsis, 13 patients (56.5%) had identifiable etiological

microorganisms, and 5 patients (15.2%) had confirmed bacteraemia.
(23.1%) patients were infected by polymicroorganisms.

Three

Gram Negative

organisms (n=11; 33.3%) was the commonest offending agent. (Figure 4)

The

commonest septic focus was the lower respiratory tract (n=10; 30.3%), followed
by the peritoneum (n=5; 15.2%), surgical wounds and soft tissue (n=4; 12.1%),
the hepato-biliary system and urinary system (n=4; 12.1%) (Figure 3 and 4).
20

Concerning the acute physiological parameters of the whole cohort within 24

hours after the onset of fever, the mean body core temperature was 38.5C
(Range 38-41.7C).

Twenty-seven (81.8%), 21 (63.6%), 20 (60.6%) and 13

(39.3%) patients had tachycardia (Pulse>90/min), tachypnoea (Respiratory

Rate>20/min), refractory shock (mean arterial blood pressure (MAP) <65 despite
adequate fluid resuscitation) and impaired sensorium (GCS <15) respectively.

Among the 33 patients, 13 (39.4%) patients were complicated by acute kidney

injury (AKI) according to RIFLE (Risk, Injury, Failure, Loss of function, End
stage renal disease) criteria. (Figure 1) [45, 46]

Four patients had received

temporary renal replacement therapy with highest serum creatinine (Cr) 571
mol/l, urea 39.9 mmol/l and anuria. The mean peak total white cell count
(WBC) was 16.8 x10^9/L (SD +/- 9.5; Range 2.5-43.4) and the mean peak
neutrophil differential count was 13.2 x10^9/L (SD +/- 8.9).

The lowest

haematocrit (Hct) was 0.14 L/L (mean=0.30; SD +/- 0.08; range 0.14-0.52).
Seven (26.9%) and 6 (23.1%) patients white blood cells demonstrated left shift
and toxic granulation respectively in 26 samples, which film comments were
available.
21

On review of biochemical markers, C-reactive protein (CRP) was available in 16

cases, the mean CRP was 152.9 mg/l (SD +/- 102.5 mg/l; range 2-322 mg/l).
Serum lactate was checked in 6 cases, the mean lactate level was 5.03 mmol/l
(SD+/- 2.85 mmol/l; range 2.26-9.96 mmol/l). The median serum procalcitonin
(PCT) level was 2.62 ng/mL (range 0.00-200.00 ng/mL).

In the whole

33-patient cohort, the number of patients with serum PCT level >0.1 ng/mL, >0.5
ng/mL and >5 ng/mL were 27 (81.8%), 23 (69.7%) and 14 (42.4%) respectively.

On comparison of the acute physiological parameters within 24 hours of the

onset of fever between sepsis and non-sepsis patients, there were no significant
differences between two groups (highest temperature and heart rate, maximal
respiratory rate, fluid intake and urine output, worst Glasgow Coma scale (GCS)
and lowest MAP).

On analysis the blood parameters and admission severity scores between

nosocomial sepsis and non-sepsis cohorts within 24 hours of the onset of fever,
no significant differences were demonstrated (highest serum urea and creatinine
level, lowest albumin level, WBC, haematocrit and worst blood pH).

22

The CRP

levels and APACHE II scores in the sepsis cohort were not significantly higher
than the non-sepsis cohort.

The serum PCT levels strongly correlated with serum lactate levels ( r = 0.906; P
= 0.013), neutrophils count (r = 0.675; P < 0.001), WBC (r = 0.585; P < 0.001),
worst serum Cr ( r = 0.62; P < 0.001) and had medium correlation with APACHE
II score (r = 0.403; P = 0.02), urine output (r = -0.419; P = 0.015) and number of
SIRS criteria fulfillment (r = 0.451; P = 0.008). [47]

Higher serum PCT levels suggested higher probability of nosocomial sepsis.

The Likelihood Ratios (LR) of nosocomial sepsis required ICU care were 4.242
(P = 0.032), 5.711 (P = 0.016) and 8.550 (P = 0.023) with PCT > 0.1, PCT > 0.5
and PCT > 5 respectively.

This trend was also demonstrated in the severe

nosocomial sepsis subgroup (LR 12.172 (P = 0.02), 8.577 (P = 0.04) and 9.447 (P
= 0.014) with serum PCT levels > 0.1, > 0.5 and > 5 respectively.

The AUC of the ROC-curve of PCT in diagnosis of nosocomial sepsis in ICU

patients was 0.78 (95% CI: 0.62 to 0.94) indicating fair discriminative power
(Figure 5, Table 2). [48, 49] The sensitivity and specificity of predicting sepsis
was 82.6% and 40.0% when PCT cut-off level at 0.24 ng/ml was used.
23

If the

PCT cut-off level increased to 1.23 ng/ml, PCT results would be more specific
with fair sensitivity (sensitivity 78.3%; specificity 70%).

The PCT level demonstrated good discriminative power in diagnosing

nosocomial severe sepsis. (Figure 6, Table 3) The AUC of the ROC-curve of
PCT was 0.90 (95% CI: 0.79 to 1.00).

The sensitivity and specificity was

63.2% and 92.9% versus 84.2% and 78.6% if the PCT cut-off level was 5.16
ng/ml and 2.07 ng/ml respectively.

For detection of nosocomial septicaemia in ICU patients, the AUC of the

ROC-curve of PCT was 0.90 (95% CI: 0.75 to 1.00) indicating excellent
discriminative power.

To use 7.07 ng/ml as cut-off level for PCT to predict the

presence of bacteraemia, the specificity would be 78.6% with sensitivity 80%.

Higher serum PCT and lactate level associated with higher predicted mortality
rates (P = 0.006 and P = 0.043).

However, high serum CRP did not significantly

reflected higher predicted mortality rate. (P = 0.414)

On review the other biomarkers, CRP performed poor accuracy in differentiate

between sepsis and non-sepsis patients with AUC of the ROC-curve 0.67 (95%
24

CI: 0.31 to 1.00).

163 mg/l.

The specificity was only 50% even CRP cut-off level was

The inaccuracy of CRP was more significant in the diagnosis of

severe sepsis and septic shock (AUC of the ROC-curve 0.55 (95% CI: 0.23 to
0.87) and 0.33 (95% CI: 0.06 to 0.61) respectively).
demonstrated in WBC.

Similar findings were

On the other hand, the accuracy of adopting neutrophil

count in diagnosis of nosocomial infection was more reliable than total white cell
count.

The AUC of the ROC-curve 0.85 (95% CI: 0.71 to 1.00) in

differentiation between sepsis and non-sepsis patients.

The sensitivity and

specificity was 73.7% and 85.7% if the cut-off point at 10 x10^9/L. If the
neutrophil count increased to 11.25 x10^9/L, the specificity was 100% although
sensitivity was reduced to 63.2%.

25

Discussion

The diagnosis of nosocomial infection in seriously-ill intensive care unit patients

was often not simple and straightforward.

Infection, in contrast with

colonization, involved host local or systemic response. It was the host response
manifested the clinical pictures that triggered medical staff to suspect a patient
was suffering from sepsis, proceed to investigation of the septic foci and
administration of antimicrobial agents. In the elderly and immunocompromised
patients, however, the manifestations might be absent or atypical.

This patient

sub-group was the most vulnerable to complications of sepsis and associated

with higher morbidity. On the contrary, similar clinical manifestations might be
induced by non-infectious etiology (e.g. trauma, pancreatitis, cardiac arrest and
burn, etc.).

Commonly adopted routine laboratory tests were usually lack of sensitivity and
specificity to differentiate which patients should receive antibiotics.

The gold

standard confirmatory microbiological tests results were not immediately

available.

Nowadays, medical expenditure and antibiotic resistance were

escalating.

It warranted developing reliable quick investigation to identify

26

those patients in whom antimicrobial agents were likely beneficial.

In recent

years, much effort had invested into finding biochemical markers of infection.
The ideal biochemical marker of sepsis, should be sensitive to detect the
presence of infection at early phase, should be specific to discriminate sepsis
from other stimuli that might induce SIRS, should be rapidly and conveniently
used, and should preferably reflected the prognostic significance.

This retrospective case review on a cohort of ICU-patients, who developed fever

and SIRS after 72-hour hospitalization, demonstrated clinical implications of
PCT in diagnosis of nosocomial sepsis of oriental patients and overview the
usefulness of other routine laboratory tests. This cohort was represented by
Chinese case-mix while other studies concentrating on non-oriental populations.
The age and APACHE II score of our cohort was comparative with international
studies. [36, 50, 51, 52]
besides

diabetes

mellitus

Male-to-female ratio was nearly 1:1.

and

chronic

pulmonary

diseases,

Although
inactive

non-metastatic solid tumor history was the commonest past health in this cohort;
this would probably not bias the study results as the tumor was already treated
and not intervening PCT metabolism.
27

The results showed that PCT was useful marker in determination of nosocomial
sepsis and prediction of severity in oriental ICU patients, by demonstrating the
relationship between serum PCT level and the severity of the sepsis episodes.
(The positive likelihood ratios (LR) of nosocomial sepsis required ICU care were
4.242 (P = 0.032), 5.711 (P = 0.016) and 8.550 (P = 0.023) with PCT > 0.1 ng/ml,
PCT > 0.5 ng/ml and PCT > 5 ng/ml respectively.)

In cases of severe

nosocomial sepsis in ICU, the positive LRs were 12.172 (P = 0.02), 8.577 (P =
0.04) and 9.447 (P = 0.014) at serum PCT levels > 0.1 ng/ml, > 0.5 ng/ml and > 5
ng/ml respectively.

This was in line with the findings reported by P. Hausfater,

et al. although the cohort involved emergency department (ED) patients instead
of ICU patients and focused on community-acquired infections. [53] Huang DT
and colleagues, also showed positive LR by using PCT to determine
community-acquired pneumonia (CAP), but the LR was lower than our study
(1.41 versus 5.71).

This study also showed good discriminative power of PCT as a test in diagnosing
severe sepsis and septicaemia (AUC of ROC-curve 0.78-0.90).

This was

comparable with international data. M Pieri, et al. conducted a review study of

28

27 patients undergoing extracorporeal membrane oxygenation (ECMO) in Italy,

AUC of ROC-curve of PCT in diagnosis of sepsis was 0.681 (P = 0.0062). [55]
J Rebanda and P Povoa conducted a prospective observational study to assess the
usefulness of PCT in diagnosing post-operation infection after elective colonic
surgery.

PCT increased around 10 times the basal level and peaked at 24 to

48 hours. [56]

In cases of invasive candidaemia reported by A Cortegian and

colleagues, the ROC analysis showed that the best PCT cuto value was 4.57
ng/ml with AUC of 0.91 (CI 0.83 to 0.96, sensitivity 99%, specificity 80.39%).
[57] In a prospective observational multicenter cohort study of 581 patients in
the Netherlands with urinary tract infection (UTI), the AUC of the ROC-curve of
PCT diagnosing urosepsis-related bacteraemia was 0.81 (95% CI: 0.77 to 0.85).
[36] These results were consistent with our findings, in which the AUC of
ROC-curve was 0.90 (95% CI: 0.75 to 1.00) in nosocomial septicaemia
subgroup.

Concerning the sensitivity and specificity of serum PCT test as a diagnostic test
of sepsis, it varied among different studies, in which different PCT cut-off levels
and cohort characteristic, for example, infection source, were adopted.
29

P.

Hausfater and colleagues had reported the procalcitonin level had an overall
sensitivity 35% and specificity of 99% in detection of patients in emergency
departments (AED) with sepsis, with the use of a cutoff point of 0.5 ng/mL. [53]
However, if similar sensitivity and specificity was selected in our cohort, the
respective serum PCT cut-off point would be 15.5 ng/mL, which was much
higher than the findings of P. Hausfater, et al. In patients with severe sepsis,
required VA ECMO support, PCT had sensitivity = 87.8%, specificity = 50%
with 1.89 ng/ml as the cut-o. [55]

Our study demonstrated similar sensitivity

(89.5%) with higher specificity (71.4%) at a lower serum PCT cut-off point (i.e.
1.23ng/ml).

By Pearsons correlation coefficient, we tried to demonstrate correlation between

serum PCT level and clinical parameters.

As similar to the findings of

Fernando Rogelio Espinosa Lpez, et al, our study showed serum PCT levels in
nosocomial sepsis cases were medium correlated with APACHE II score (r =
0.403, P = 0.02 versus r = 0.523 p = 0.001;). [52]

We further demonstrated

strong correlation of serum PCT levels with serum lactate levels (r = 0.906; P =
0.013), neutrophils count (r = 0.675; P < 0.001), WBC (r = 0.585; P < 0.001) and
30

worst serum Cr (r = 0.62; P < 0.001), which had not been assessed in recent
studies.

This reflected the disease severity of our cohort and represented the

extent of organ damage.

Neutrophil count at cut-off point at 11.25 x10^9/L had

100% specificity on nosocomial sepsis differentiation in our study.

Our result

was different from Fernando, et al that higher serum PCT and lactate level were
associated with higher predicted mortality rates (P = 0.006 and P = 0.043;
PCT/mortality r = 0.303 P = 0.61). [52]

Limitations of this study involved restricted generalizability due to small sample

size and single-centred composition.

The study was retrospective in nature and

not blinded. Although HAP and ventilator-associated pneumonia (VAP) was

the commonest source of sepsis in our cohort and overseas reports, the diagnosis
of HAP and VAP was still difficult. This led to under or over estimation of the
disease burden. Indeed, Andrews CP and colleagues demonstrated that 29% of
clinically suspected VAP cases were disproved by autopsy results. [58] This
required cautious interpretation of the results.

In addition, serial measurement

of serum PCT was not performed in our study, which might give more
information of the usefulness and accuracy of PCT.

31

Conclusion

The diagnosis of nosocomial sepsis in ICU prior to culture results and invasive
procedures could help in initiating an early therapy and avoidance of unnecessary
antibiotics administration.

PCT had shown to be a useful marker in

differentiating nosocomial sepsis in ICU from those that were not.

Our study

demonstrated the consistent usefulness of PCT, particularly in diagnosis of severe

nosocomial sepsis and septicaemia in oriental ICU patients.

32

Reference Lists
1.

Bone RC, Balk RA, Cerra FB: Definitions for sepsis and organ failure and
guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM
Consensus Conference Committee. American College of Chest
Physicians/Society of Critical Care Medicine. Chest 1992; 101: 1644-1655

2.

Martin GS, Mannino DM, Eaton S: The epidemiology of sepsis in the

United States from 1979 through 2000. N Engl J Med 2003 Apr 17;
348(16): 1546-54

3.

Michael R Filbin, MD, et al: Shock, Septic. Emedicine 2006 Fev 23

4.

Chalfin DB, Holbein ME, Fein AM, Carlon GC. Cost-effectiveness of

monoclonal antibodies to gram-negative endotoxin in the treatment of
gram-negative sepsis in ICU patients. JAMA 1993;269:249-254.

5.

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky

MR. Epidemiology of severe sepsis in the United States: analysis of
incidence, outcome, and associated costs of care. Crit Care Med
2001;29:1303-1310.

6.

Clinical Data and Reporting System (CDARS), Hospital Authority, Hong

Kong

7.

Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of
recombinant human activated protein C for severe sepsis. N Engl J Med
2001;344:699-709.

8.

Annane D, Aegerter P, Jars-Guincestre MC, Guidet B. Current

epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit
Care Med 2003;168:165-172.

9.

Christopher H. Goss, MD, MSc, Shannon S. Carson, MD. Is Severe Sepsis

Associated With New-Onset Atrial Fibrillation and Stroke? JAMA.
2011;306(20):2264-2266.

10. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med
2004;351:159-169
11.

Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the

treatment of severe sepsis and septic shock. N Engl J Med
2001;345:1368-1377

12. Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of
33

inadequate antimicrobial treatment of bloodstream infections on patient

outcomes in the ICU setting. Chest 2000;118:146-155
13. Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik SD.
The benefit of appropriate empirical antibiotic treatment in patients with
bloodstream infection. J Intern Med 1998;244:379-386.
14. James A. Russell, M.D. Management of Sepsis. N Engl J Med Vol.
355:1699-1713 October 19, 2006 Number 16.
15. The Acute Respiratory Distress Syndrome Network. Ventilation with lower
tidal volumes as compared with traditional tidal volumes for acute lung
injury and the acute respiratory distress syndrome. N Engl J Med
2000;342:1301-1308.
16. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of
recombinant human activated protein C for severe sepsis. N Engl J Med
2001;344:699-709.
17. Bernard GR, Margolis BD, Shanies HM, et al. Extended Evaluation of
Recombinant Human Activated Protein C United States Trial (ENHANCE
US): a single-arm, phase 3B, multicenter study of drotrecogin alfa
(activated) in severe sepsis. Chest 2004;125:2206-2216.
18. Abraham E, Laterre PF, Garg R, et al. Drotrecogin alfa (activated) for
adults with severe sepsis and a low risk of death. N Engl J Med
2005;353:1332-1341.
19. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low
doses of hydrocortisone and fludrocortisone on mortality in patients with
septic shock. JAMA 2002;288:862-871.
20. Marik PE, Zaloga GP. Adrenal insufficiency during septic shock. Crit Care
Med 2003;31:141-145.
21/ Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in
critically ill patients. N Engl J Med 2001;345:1359-1367.
22. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in
the medical ICU. N Engl J Med 2006;354:449-461.
23. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N
Engl J Med 2003;348:138-150.
24. Claudio Ronco, Paola Inguaggiato, Vincenzo DIntini, Luise Cole, Rinaldo
Bellomo, Sonya Poulin, Valeria Bordoni1, Carlo Crepaldi, Fiorella
34

Gastaldon, Alessandra Brendolan, Pisitkun Trairak, Tiranathanagul

Khajohn. The role of extracorporeal therapies in sepsis. J NEPHROL
2003;16(suppl.7): S34-S41.
25. James A. Russell, M.D. Management of Sepsis. N Engl J Med Vol.
355:1699-1713 October 19, 2006 Number 16.
26. Stolz D, Christ-Crain M, Gencay MM, Bingisser R, Huber PR, Mller B,
Tamm M: Diagnostic value of signs, symptoms and laboratory values in
lower respiratory tract infection. Swiss Med Wkly 2006, 136:434-440.
27. Holm A, Nexoe J, Bistrup LA, Pedersen SS, Obel N, Nielsen LP, Pedersen
C: Aetiology and prediction of pneumonia in lower respiratory tract
infection in primary care. Br J Gen Pract 2007, 57:547-554.
28. Adam Linder1, Per kesson, Malin Inghammar, Carl-Johan Treutiger,
Anna Linnr and Jonas Sundn-Cullberg. Elevated plasma levels of
heparin-binding protein in intensive care unit patients with severe sepsis
and septic shock. Critical Care 2012, 16:R90
29. Jacobs JW, Lund PK, Potts JT Jr, Bell NH, Habener JF: Procalcitonin is a
glycoprotein. J Biol Chem 1981, 256:2803-2807.
30. Harbarth S, Holekova K, Froidevaux C, Pittet D, Ricou B, Grau GE, Vadas
L, Pugin J. Geneva Sepsis Network. Diagnostic value of procalcitonin,
interleukin-6, and interleukin-8 in critically ill patients admitted with
suspected sepsis. Am J Respir Crit Care Med. 2001; 164: 396-402
31. Mller B, Becker KL, Schadinger H, Rickenbacher PR, Huber PR,
Zimmerli W, Ritz R. Calcitonin precursors are reliable markers of sepsis in
a medical intensive care unit. Crit Care Med. 2000; 28: 977-983.
32. Meisner M. Procalcitonin: Experience with a new diagnostic tool for
bacterial infection and systemic inflammation. J Lab Med 1999; 23:
263-272.
33. Schuetz P, Christ-Crain M, Wolbers M, Schild U, Thomann R, Falconnier
C, Widmer I, Neidert S, Blum CA, Schnenberger R, Henzen C, Bregenzer
T, Hoess C, Krause M, Bucher HC, Zimmerli W, Mller B.
Procalcitonin-guided antibiotic therapy and hospitalization in patients with
lower respiratory tract infections: a prospective, multicenter, randomized
controlled trial. BMC Health Serv Res 2007; 7: 102 (ProHOSP study).
34. Cees van Nieuwkoop, Tobias N Bonten, Jan W vant Wout, Ed J Kuijper,
Geert H Groeneveld, et al. Procalcitonin reflects bacteremia and bacterial
35

load in urosepsis syndrome: a prospective observational study. Critical Care

2010, 14:R206
35. Christ-Crain M, Mller B. Procalcitonin in bacterial infections hype, hope
or more or less? Swiss Med Wkly 2005; 135: 451-460.
36. Cees van Nieuwkoop, Tobias N Bonten, Jan W vant Wout, Ed J Kuijper,
Geert H Groeneveld, et al. Procalcitonin reflects bacteremia and bacterial
load in urosepsis syndrome: a prospective observational study. Critical Care
2010, 14:R206.
37. Wilson ML, Gaido L: Laboratory diagnosis of urinary tract infections in
adult patients. Clin Infect Dis 2004, 38:1150-1158.
38. John G. Bartlett, MD. Hospital-Acquired Pneumonia, Merck Manual.
http://www.merckmanuals.com/professional/pulmonary_disorders/pneumo
nia/hospital-acquired_pneumonia.html
39. The ATS Board of Directors, December 2004 and the IDSA Guideline
Committee, October 2004. This official statement of the American Thoracic
Society and the Infectious Diseases Society of America was approved.
Guidelines for the Management of Adults with Hospital-acquired,
Ventilator-associated, and Healthcare-associated Pneumonia. Am J Respir
Crit Care Med Vol 171. pp 388416, 2005
40. http://dermnetnz.org/bacterial/wound-infection.html
41. Walker SH, Duncan DB: Estimation of the probability of an event as a
function of several independent variables. Biometrika 1967, 55:167-179.
42. Beck JR, Shultz EK: The use of receiver operating characteristic (ROC)
curves in test performance evaluation. Arch Pathol Lab Med 1986,
110:13-20.
43. Youden WJ: Index rating for diagnostic tests. Cancer 1950, 3:32-35.
44. http://www.sfar.org/scores2/apache22.html
45. Rinaldo Bellomo, Claudio Ronco, John A Kellum, et al. Acute renal
failure definition, outcome measures, animal models, fluid therapy and
information technology needs: the Second International Consensus
Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Critical
Care 2004, 8:R204-R212.
46. Bellomo, Ronco, et al. Criteria for Acute Renal Failure in Hospitalized
Patients. Crit Care Med. 2006;34(7):1913-1917.
47. http://en.wikipedia.org/wiki/Pearson_product-moment_correlation_coeffici
36

ent
48. http://gim.unmc.edu/dxtests/roc3.htm
49. Metz CE. Basic principles of ROC analysis. Sem Nuc Med.
1978;8:283-298.
50. Pierre Emmanuel Charles, Claire Tinel, Saber Barbar, Serge Aho, Sbastien
Prin, Jean Marc Doise, et al. Procalcitonin kinetics within the first days of
sepsis: relationship with the appropriateness of antibiotic therapy and the
outcome. Critical Care 2009, 13:R38
51. Philipp Schuetz, Werner Albrich and Beat Mueller. Procalcitonin for
diagnosis of infection and guide to antibiotic decisions: past, present and
future. Schuetz et al. BMC Medicine 2011, 9:107
52. Fernando Rogelio Espinosa Lpez, Abraham Emilio Reyes Jimnez,
Germn Carrasco Tobon, Jess Duarte Mote, and Octavio Novoa Faras.
Procalcitonin (PCT), C reactive protein (CRP) and its correlation with
severity in early sepsis. Clinical Reviews and Opinions Vol. 3(3), pp.
26-31, April 2011
53. P. Hausfater, S. Garric1, S. Ben Ayed, M. Rosenheim, M. Bernard, and B.
Riou. Usefulness of Procalcitonin as a Marker of Systemic Infection in
Emergency Department Patients: A Prospective Study. Clin Infect Dis.
(2002) 34 (7): 895-901.
54. Huang DT, Weissfeld LA, Kellum JA, Yealy DM, Kong L, Martino M,
Angus DC; GenIMS Investigators. Risk prediction with procalcitonin and
clinical rules in community-acquired pneumonia. Ann Emerg Med. 2008
Jul;52(1):48-58.e2. Epub 2008 Mar 17.
55. M Pieri, T Greco, AM Scandroglio, M De Bonis, G Maj, L Fumagalli,
A Zangrillo, F Pappalardo. Role of serum biomarkers in the diagnosis of
infection in patients undergoing extracorporeal membrane oxygenation.
Critical Care 2012, 16(Suppl 1):P26 (doi: 10.1186/cc10633)
56. J Rebanda, P Povoa. Usefulness of daily monitoring of procalcitonin and
C-reactive protein in the early diagnosis of infection after elective colonic
surgery. Critical Care 2012, 16(Suppl 1):P28 (doi: 10.1186/cc10635)
57. A Cortegiani, SM Raineri, F Montalto, MT Strano, A Giarratano.
Procalcitonin as a predictive marker for PCR test and blood culture results
in suspected invasive candidemia. Critical Care 2012, 16(Suppl 1):P29
(doi: 10.1186/cc10636)
37

58. Andrews CP, Coalson JJ, Smith JD, Johanson WG Jr: Diagnosis of
nosocomial bacterial pneumonia in acute, diffuse lung injury. Chest 1981,
80:254-258.

38

Tables and Figures

Figure 1. RIFLE Criteria

A patient can fulfill the criteria through changes in serum creatinine (SCr) or
changes in urine output (UO), or both. The criteria that lead to the worst possible
classification should be used.

39

Patient
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33

Diagonosis 1
Hypokalaemia
Drug Overdose
Peptic ulcer disease
Cancer of Esophagus
Sepsis
Anastomotic Leakage
Cellulitis & Abscess
Urinary tract infection
Pulmonary tuberculosis
Drug Overdose
Pelvic Tumor
Ruptured HCC
COAD
Perforated peptic ulcer
Convulsion
Perforated duodenal ulcer
CA pancreas
hyponatraemia
Drug Overdose
Epiglottis
CA esophagus, Post-op
Hypokalaemia
ARF
Drug Overdose
Hypoakalaemia
Type I Respiratory failure
Septic Shock
Cholangitis
Perforated peptic ulcer
CA Tongue post-op
Perforated peptic ulcer
CA Esophagus Post-op
Strangulated inguinal hernia

Diagnosis 2
Aspiration
Deep vein thrombosis
Respiratory Failure
Pneumonia
Wound infection
Parapharyngeal Abscess
Septicaemia
DIC
Psychosis
Pelvic abscess
Post-arrest
Peritonitis
ARF
HAP
Hypokalaemia
Hyponatraemia
Epiglottic abscess
Respiratory failure
Hyponatraemia
Urinary tract infection
Periodental abscess
Acute chiolecystitis
Acute Cholangitis
Congestive heart failure
Peritonitis
HAP
Peritonitis
HAP
Respiratory failure

Table 1. Discharge diagnosis profiles of 33 patients

40

Diagnosis 3

VAP
Pneumonia
AMI

Pancytopenia
Pneumonia

Ketamine Overdose

Anorexia Nervosa
Mediastinitis
Cellulitis (drip site)

Pneumonia
CBD stones

Anastomotic leakage

Figure 3. Source of Nosocomial Infection

41

Figure 4. Etiological Microrganism in 13 Patients

42

Table 2. PCT cut-off level, sensitivity and specificity in diagnosis of

nosocomial sepsis in ICU
Positive if Greater Than or Equal To Sensitivity
0.235
0.826
0.430
0.783
0.760
0.783
1.225
0.783
2.485
0.652
3.245
0.652

43

1 - Specificity
0.600
0.500
0.400
0.300
0.200
0.100

Table 3. PCT cut-off level, sensitivity and specificity in diagnosis of severe

nosocomial sepsis in ICU
Positive if Greater Than or Equal To Sensitivity
0.100
1.000
0.235
0.947
0.430
0.895
0.760
0.895
1.225
0.895
2.065
0.842
2.485
0.789
3.245
0.789
11.025
0.421
15.500
0.421

44

1 - Specificity
0.571
0.500
0.429
0.357
0.286
0.214
0.143
0.071
0.071
0.000

Appendix

ACCP

American College of Chest Physicians

ADL

Activity of daily living

AF

Atrial fibrillation

AKI

Acute kidney injury

AMI

Acute myocardial infarction

APACHE II Score Acute Physiology and Chronic Health Evaluation II Score

APC

Activated Protein C

ARDS

Acute Respiratory Distress Syndrome

ARF

Acute renal failure

AUC

Area under the curve

BW

Body weight

CA

Cancer

CARS

Compensated anti-inflammatory response syndrome

CBD

Common bile duct

CDARS

Clinical data and reporting system

CDC

United States Centre for Disease Control and Prevention

CHF

Congestive heart failure

CI

Confidence interval

CMS

Clinical management system

CNS

Coagulase-negative staphylococci

COAD

Chronic obstructive airway disease

Cr

Creatinine

CRBSI

Catheter-related bloodstream infection

CRP

C-reactive Protein
45

CSU

Catheterized urine

CXR

Chest X-ray

DBP

Diastolic blood pressure

DIC

Disseminated intra-vascular coagulopathy

DM

Diabetes mellitus

DVT

Deep vein thrombosis

ECMO

Extracorporeal membrane oxygenation

ED

Emergency department

Fi O2

Fractions of inspired oxygen

GCS

Glasgow Coma scale

GFR

Glomerular filtration rate

HBP

Heparin-binding protein

HCC

Hepatocellular carcinoma

Hct

Haematocrit

HDU

High dependency unit

HR

Heart rate

HT

Hypertension

ICU

Intensive care unit

IHD

Ischaemic heart disease

IL

Interleukin

LR

Likelihood ratio

LOS

Length of stay

MAP

Mean arterial pressure

MODS

Multiple organ dysfunction syndrome

MOF

Multi-organ Failure

MSU

Midstream urine

PaCO2

Partial pressure of arterial carbon dioxide

46

PaO2

Partial pressure of arterial oxygen

PCT

Procalcitonin

PDU

Perforated duodenal ulcer

PPU

Perforated peptic ulcer

PTB

Pulmonary tuberculosis

PUD

Peptic ulcer disease

PVD

Peripheral vascular disease

ROC Curve

Receiver operating characteristic curve

RR

Respiratory rate

RRT

Renal replacement therapy

SAPS II Score

Simplified Acute Physiology Score II

SBP

Systolic blood pressure

SCCM

Society of Critical Care Medicine

SCr

Serum creatinine

SD

Standard deviation

SIRS

Systemic inflammatory response syndrome

SSI

Surgical Site Infection

TA

Tracheal aspirate

TNF

Tumor necrosis factor

UO

Urine output

UTI

Urinary tract infection

VA

Veno-arterial

VAP

Ventilator-associated pneumonia

WBC

Total white blood cell count

47