Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit

Balci Canan, Sungurtekin Hülya, Gürses Ercan, Sungurtekin Ugur, Kaptanoglu, Kaptanoglu Bünyamin

Description

The diagnosis of sepsis in critically ill patients is challenging because traditional markers of infection are often misleading. The present study was conducted to determine the procalcitonin level at early diagnosis (and differentiation) in patients with systemic inflammatory response syndrome (SIRS) and sepsis, in comparison with C-reactive protein, IL-2, IL-6, IL-8 and tumour necrosis factor-α. Method Thirty-three intensive care unit patients were diagnosed with SIRS, sepsis or septic shock, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria. Blood samples were taken at the first and second day of hospitalization, and on the day of discharge or on the day of death. For multiple group comparisons one-way analysis of variance was applied, with post hoc comparison. Sensitivity, specificity and predictive values of PCT and each cytokine studied were calculated. Results PCT, IL-2 and IL-8 levels increased in parallel with the severity of the clinical condition of the patient. PCT exhibited a greatest sensitivity (85%) and specificity (91%) in differentiating patients with SIRS from those with sepsis. With respect to positive and negative predictive values, PCT markedly exceeded other variables. Discussion In the present study PCT was found to be a more accurate diagnostic parameter for differentiating SIRS and sepsis, and therefore daily determinations of PCT may be helpful in the follow up of critically ill patients.

Sujets

• C-reactive protein
• Cytokine
• Diagnosis
• Procalcitonin
• Sepsis

Informations

• Publié par: biomed
• Publié le: 01 janvier 2002
• Nombre de lectures: 7
• Langue: English

Extrait

Available online http://ccforum.com/content/7/1/85
Open AccessResearch
Usefulness of procalcitonin for diagnosis of sepsis
in the intensive care unit
v v1 2 3 4 5Canan BalcI , Hülya Sungurtekin , Ercan Gürses , Ugur Sungurtekin and Bünyamin Kaptanoglu
1Specialist, Department of Anesthesiology and Reanimation, Pamukkale Unversity School of Medicine, Denizli, Turkey
2Associate Professor, Department of Anesthesiology and Reanimation, Pamukkale Unversity School of Medicine, Denizli, Turkey
3Assistant Professor, Department of Anesthesiology and Reanimation, Pamukkale Unversity School of Medicine, Denizli, Turkey
4Professor, Department of General Surgery, Pamukkale Unversity School of Medicine, Denizli, Turkey
5Associate Professor, Department of Biochemistry, Pamukkale Unversity School of Medicine, Denizli, Turkey
Correspondence: Hülya Sungurtekin, [e-mail]
Received: 10 June 2002 Critical Care 2003, 7:85-90 (DOI 10.1186/cc1843)
This article is online at http://ccforum.com/content/7/1/85Revisions requested: 31 July 2002
© 2003 BalcI et al., licensee BioMed Central Ltd
Revisions received: 28 August 2002 (Print ISSN 1364-8535; Online ISSN 1466-609X). This is an Open
Access article: verbatim copying and redistribution of this article areAccepted: 5 October 2002
permitted in all media for any non-commercial purpose, provided this
Published: 30 October 2002 notice is preserved along with the article's original URL.
Abstract
Introduction The diagnosis of sepsis in critically ill patients is challenging because traditional markers
of infection are often misleading. The present study was conducted to determine the procalcitonin level
at early diagnosis (and differentiation) in patients with systemic inflammatory response syndrome
(SIRS) and sepsis, in comparison with C-reactive protein, IL-2, IL-6, IL-8 and tumour necrosis factor-α.
Method Thirty-three intensive care unit patients were diagnosed with SIRS, sepsis or septic shock, in
accordance with the American College of Chest Physicians/Society of Critical Care Medicine
consensus criteria. Blood samples were taken on the first and second day of hospitalization, and on
the day of discharge or on the day of death. For multiple group comparisons one-way analysis of
variance was applied, with post hoc comparison. Sensitivity, specificity and predictive values for PCT
and each cytokine studied were calculated.
Results PCT, IL-2 and IL-8 levels increased in parallel with the severity of the clinical condition of the
patient. PCT exhibited a greatest sensitivity (85%) and specificity (91%) in differentiating patients with
SIRS from those with sepsis. With respect to positive and negative predictive values, PCT markedly
exceeded other variables.
Discussion In the present study PCT was found to be a more accurate diagnostic parameter for
differentiating SIRS and sepsis, and therefore daily determinations of PCT may be helpful in the follow
up of critically ill patients.
Keywords C-reactive protein, cytokine, diagnosis, procalcitonin, sepsis
tality rates in sepsis remain high [1,2]. Critical care physiciansIntroduction
have at their disposal a variety of data to serve as a guide in
The term ‘sepsis’ is used to define the systemic inflammatory discriminating infectious from noninfectious conditions in
response to an infectious agent (i.e. bacterial, viral, fungal or newly admitted patients. In a number of newly admitted
parasitic). Despite the use of new treatment modalities, patients the diagnosis of sepsis becomes clear after taking
improvements in technology and increased experience, mor- the medical history and completing the physical examination
APACHE = Acute Physiology and Chronic Health Evaluation; AUC = area under the receiver operating characteristic curve; CRP = C-reactive
protein; ICU = intensive care unit; IL = interleukin; PCT = procalcitonin; SIRS = systemic inflammatory response syndrome; TNF = tumour necrosis
factor. 85Critical Care February 2003 Vol 7 No 1 BalcI et al.
[3]. In other cases, in which noninfectious insults are respon- Blood samples were centrifuged at 1500g for 5 min (Rotina
sible for systemic inflammatory response syndrome (SIRS; 35; Cheftich Zentrifugen, Hennigsdorf, Berlin, Germany), and
e.g. trauma, burns, haemorrhages, hypothermia, pancreatitis serum for cytokine and PCT determination was collected in
and surgery) or in comatose patients, the diagnosis of sepsis sterile tubes. Serum samples were stored at –30°C until
remains difficult. assayed in Nu-6511E (Nuare, Tokyo, Japan). The treating
clinicians were blinded to the PCT results, and those per-
Prompt diagnosis and treatment with appropriate antimicro- forming the PCT assays were blinded to the clinical status of
bial chemotherapy is of the utmost importance in reducing the patient. The PCT results were not available during the
the morbidity and mortality associated with sepsis. The lack study period. Routine cultures of blood and urine, and of
of specific early markers of infection may be responsible in samples from trachea and suspected sites were obtained to
part for withholding of, or delaying or unnecessary antimicro- identify the organisms present and determine the degree of
bial treatment in critically ill patients [4]. Thus, there is an antibiotic resistance.
unmet need for clinical or laboratory tools that can distinguish
between SIRS and sepsis. Various markers of sepsis, includ- We attempted to maintain the patients’ haemoglobin level at
ing C-reactive protein (CRP), tumour necrosis factor (TNF)-α, 10–12 g/dl and central venous pressure at 8–12 mmHg in
IL-1β, IL-6 and IL-8, have all been studied for their ability to the ICU. If needed, blood products, intravascular fluid
differentiate SIRS from sepsis [4–7]. Several investigators replacement, and inotropic and/or vasopressor agents were
have questioned the diagnostic accuracy of procalcitonin administered.
(PCT) measurement, results with which have been inconsis-
tent and variable [4,6–10]. Thus, it may not be easy to dis- The American College of Chest Physicians/Society of Critical
criminate between SIRS and sepsis, even with the use of Care Medicine consensus classification was used for diagno-
PCT. sis of SIRS, sepsis and septic shock [11]. Patients were
assessed for the presence of infection at admission, on day 2,
The present study was conducted to determine the PCT level and on the day of discharge or on the day of death. Clinical
at early diagnosis (and differentiation) in patients with SIRS assessment was the first step in diagnosing infection. Cultures
and sepsis, in comparison with CRP, IL-2, IL-6, IL-8 and of urine, blood and tracheal aspirates were taken for diagno-
TNF-α in an unselected population of patients suffering from sis. Respiratory tract infection was assessed according to
a broad range of diseases in an intensive care unit (ICU). chest radiography and the presence or absence purulent tra-
cheal aspirates containing micro-organisms. Intra-abdominal
Method infection was suspected in the presence of contaminated or
The study was approved by the Institutional Ethics Commit- dirty surgical sites, and wound swabs were taken and ultra-
tees of the Pamukkale University Medical School. Written sound performed in such cases. Colonization was defined as
informed consent was obtained from all patients or their rela- microbiological evidence with no host response.
tives before enrollment. Over a 6-month period, all patients
Laboratory measurementsstaying for more than 24 hours in the ICU were consecutively
enrolled in the study. Patients who had chronic organ failure, CRP was measured using a routine turbidimetry assay (ILAD-
thyroid cancer or pancreatitis; who had received massive 900; Instrumentation Laboratory, Milan, Italy); a value greater
blood transfusion; or whose anticipated duration of stay was than 10mg/l was considered to be abnormally elevated.
under 24 hours were excluded from the study. TNF-α, and IL-2, IL-6 and IL-8 were measured using commer-
cially available cheluminescence kits (Immulite-One; DTC,
At admission, the patient’s age, sex, height and weight were Los Angeles, CA, USA). All cytokine samples were analyzed
recorded. Also, data were collected at admission, on day 2, in duplicate. PCT levels (normal range 0–0.5 ng/l) were
and on the day of discharge or on the day of death. These determined by means of a specific and ultrasensitive immuno-
data included the following: clinical status (SIRS, sepsis or luminometric assay (LUMI test PCT; Brahms Ag, Hennigs-
septic shock); Acute Physiology and Chronic Health Evalua- dorf/Berlin, Germany).
tion (APACHE)-II score; temperature; heart rate; respiratory
Statistical analysisrate; blood pressure; central venous pressure; laboratory
analysis (complete blood count, blood urea nitrogen, blood For multiple group comparisons of CRP, ILs and PCT, one-
sugar, serum sodium, potassium and calcium, aspartate way analysis of variance was applied, with least squares dif-
aminotransferase, alanine aminotransferase, prothrombin time, ference for post hoc comparison. The best cutoff value of
activated partial thromboplastin time, albumin, transferrin and parameters for the diagnosis of sepsis was determined
CRP); and arterial blood gas analysis. The final determination according to the Youden’s index method. The ability of PCT
of the patient’s status was done retrospectively, without to predict sepsis was evaluated by performing receiver